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Stafler P, Rothschild B, Gendler Y, Seguier-Lipszyc E, Tyroler S, Waisbourd-Zinman O, Mei-Zahav M, Prais D, Shkalim Zemer V. Lung clearance index: A sensitive measure of airway function improvement in adolescents after weight loss from bariatric surgery. Respir Med 2025; 237:107950. [PMID: 39818344 DOI: 10.1016/j.rmed.2025.107950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 01/10/2025] [Accepted: 01/11/2025] [Indexed: 01/18/2025]
Abstract
BACKGROUND Morbid obesity in adolescents impacts respiratory function, often leading to reduced lung volume and obstructive ventilatory defects. However, standard spirometric values frequently remain within normal ranges. OBJECTIVES We hypothesized that Lung Clearance Index (LCI) is a more sensitive marker for detecting airway dysfunction in adolescents with morbid obesity than conventional lung function tests. METHODS A prospective single-center cohort study evaluated adolescents with morbid obesity undergoing laparoscopic sleeve gastrectomy (LSG). Assessments included fractional exhaled nitric oxide, multiple breath washout, spirometry, plethysmography, diffusion capacity, and a 6-min walk test, conducted pre- and post-surgery. RESULTS Seventeen adolescents (mean age 17.1 years, BMI 45.5 kg/m2) were studied. Pre-surgery, LCI was slightly elevated (mean 7, SD ± 0.7), other lung function measures were normal. LCI correlated with BMI (r = 0.637, p = 0.014), no correlation was found between FEV1 and BMI (r = -0.083, p = 0.752). Post-surgery, mean LCI fell from 7 (±0.7) to 6.5 (±0.7), p = 0.009. The pre-operatively observed correlation between LCI and BMI was no longer present post-operatively (r = 0.362, p = 0.225). LCI changes (r = 0.676, p = 0.011) correlated with BMI changes, whilst FEV1 did not (r = 0.160, p = 0.540). CONCLUSIONS LCI appeared to be a more sensitive marker than conventional spirometry for detecting airway dysfunction in adolescents with morbid obesity. Significant post-surgery improvements suggested enhanced ventilation homogeneity. LCI may detect subtle airway changes in this population, and be potentially valuable for both clinical assessment and research.
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Affiliation(s)
- Patrick Stafler
- Pulmonary Institute, Schneider Children's Medical Center of Israel, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Benjamin Rothschild
- Pulmonary Institute, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
| | - Yulia Gendler
- Department of Nursing, School of Health Sciences, Ariel University, Ariel, Israel.
| | - Emmanuelle Seguier-Lipszyc
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Pediatric Surgery, Meir Medical Center, Kfar Saba, Israel.
| | - Simona Tyroler
- Department of Pediatric and Adolescent Surgery, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
| | - Orith Waisbourd-Zinman
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Institute for Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
| | - Meir Mei-Zahav
- Pulmonary Institute, Schneider Children's Medical Center of Israel, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Dario Prais
- Pulmonary Institute, Schneider Children's Medical Center of Israel, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Vered Shkalim Zemer
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Clalit Health Services, Dan Petah Tikva District, Petah Tikva, Israel.
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Escobar NS, Ratjen F. An update on multiple breath washout in children with cystic fibrosis. Expert Rev Respir Med 2024; 18:1061-1071. [PMID: 39709582 DOI: 10.1080/17476348.2024.2445683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 12/18/2024] [Indexed: 12/23/2024]
Abstract
INTRODUCTION Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane regulator (CFTR) gene, leading to progressive lung disease and systemic complications. Lung disease remains the primary cause of morbidity and mortality, making early detection of lung function decline crucial. The Lung Clearance Index (LCI), derived from the multiple breath washout (MBW) test, has emerged as a sensitive measure for identifying early airway disease. AREAS COVERED This review examines the technical aspects and clinical relevance of LCI, its advantages over traditional lung function tests, and its application in CF clinical trials. A focused literature review highlights LCI's utility in evaluating treatment efficacy and its potential integration into routine CF care. EXPERT OPINION LCI is more sensitive than spirometry for detecting early lung function decline and is predominantly used in pediatric settings. Its use is expanding in adult CF populations as advances in treatment allow adults to maintain stable lung function. In clinical trials, LCI is widely recognized as an outcome measure. While implemented into clinical care in many centers in Europe, this is not yet the case in North America. Faster testing protocols and point-of-care interpretation tools will support LCI's integration into routine CF monitoring.
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Affiliation(s)
- Natalia S Escobar
- Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Felix Ratjen
- Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
- Translational Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
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Modaresi M, Rafizadeh B, Eftekhari K, Shirzadi R, Tarighatmonfared F, Mirlohi SH. Correlation Between Lung Clearance Index (LCI) and Forced Expiratory Volume (FEV1) in Children with Cystic Fibrosis (CF): A Cross-sectional Study. JOURNAL OF COMPREHENSIVE PEDIATRICS 2024; 15. [DOI: 10.5812/jcp-144672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 02/10/2024] [Accepted: 03/05/2024] [Indexed: 01/05/2025]
Abstract
Background: The Lung Clearance Index (LCI) serves as a non-uniform ventilation index utilized for monitoring pulmonary function in patients with cystic fibrosis (CF). Lung Clearance Index exhibits higher sensitivity compared to forced expiratory volume in 1 second (FEV1) for early detection of lung disease and does not necessitate active patient cooperation, as required for FEV1 measured through spirometry. Presently, FEV1 is the standard parameter employed for monitoring lung function in CF patients. Objectives: The objective of this study was to assess the correlation between LCI and FEV1 in patients with cystic fibrosis. Methods: This cross-sectional study enrolled children aged 6 to 18 years with confirmed CF diagnosis, who were referred to the CF clinic at Children's Medical Center Hospital (Tehran, Iran). Participants completed consent forms and subsequently underwent pulmonary function tests. Lung Clearance Index was calculated using the exhaling-D device via the Multiple Breath Washout (MBW) method, followed by FEV1 assessment through spirometry. Results: The study included 52 patients with an average age of 12 years, among whom 52% were males. The mean ± standard deviation of FEV1 and LCI were 80.2% ± 25.3 and 8.9 ± 2.8, respectively. A significant inverse relationship was observed between these two parameters in the study (r = -0.49, P = 0.001). Conclusions: These findings further underscore the potential utility of LCI, which offers ease of administration and demonstrates high reliability and accuracy compared to FEV1 for monitoring pulmonary function in CF patients.
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Gut G, Bar-Yoseph R, Hanna M, Brandl N, Alisha I, Rizik S, Pollak M, Hakim F, Amirav I, Bentur L, Gur M. Pulmonary functions, nasal symptoms, and quality of life in patients with primary ciliary dyskinesia (PCD). Pediatr Pulmonol 2024; 59:688-694. [PMID: 38116904 DOI: 10.1002/ppul.26814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 10/24/2023] [Accepted: 12/03/2023] [Indexed: 12/21/2023]
Abstract
BACKGROUND Several factors may influence quality of life (QOL) for patients with primary ciliary dyskinesia (PCD). We aimed to evaluate the association between pulmonary functions, nasal symptoms and QOL in PCD patients. METHODS A prospective single center study. Patients performed spirometry, whole body plethysmography, forced oscillation technique (FOT), lung clearance index (LCI), 6-min walk test (6MWT), and filled two questionnaires: a specific PCD QOL questionnaire (PCD-QOL) and Sino-nasal outcome test (SNOT-22) questionnaire, assessing symptoms of chronic rhinosinusitis and health related QOL. RESULTS Twenty-seven patients (56% females), age 19.4 ± 10.5 years were included; their, FEV1 was 74.6 ± 22.7%, and RV/TLC was (157.3 ± 39.3% predicted). Health perception and lower respiratory symptoms domains of PCD-QOL had the lowest score (median [IQR]: 50 [33.3-64.6] and 57.1 [38.9-72.2], respectively). FOT parameters correlated with several PCD-QOL domains. R5 z-score (indicating total airway resistance) and AX z-score (indicating airway reactance) correlated negatively with physical domain (r = -0.598, p = .001, and r = -0.42, p = .03, respectively); R5 z-score also correlated negatively with hearing domain (r = -0.57, p = .002). R5-20 z-score (indicating small airway resistance) correlated negatively with role domain (r = -0.49, p = .03). SNOT-22 score correlated negatively with several PCD-QOL domains (lower respiratory symptoms r = -0.77, p < .001; physical r = -0.72, p < .001; upper respiratory symptoms r = -0.66, p < .001). No correlations were found between spirometry values, LCI, 6MWT, and PCD-QOL. CONCLUSIONS FOT suggested small airway dysfunction, and correlated negatively with several PCD-QOL domains. Nasal symptoms had strong negative correlations with PCD-QOL. Larger longitudinal studies will further elucidate factors affecting QOL in PCD.
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Affiliation(s)
- Guy Gut
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Ronen Bar-Yoseph
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Moneera Hanna
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Noa Brandl
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Irit Alisha
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Suha Rizik
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Mordechai Pollak
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Fahed Hakim
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Israel Amirav
- Pediatric Pulmonology Unit, Dana-Dwek Children's Hospital, Tel-Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Lea Bentur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Michal Gur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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Gur M, Manor E, Hanna M, Simaan N, Gut G, Toukan Y, Hakim F, Bar-Yoseph R, Bentur L. The effect of inspiratory muscle training in PCD and CF patients: A pilot study. Pediatr Pulmonol 2023; 58:3264-3270. [PMID: 37646121 DOI: 10.1002/ppul.26655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 08/01/2023] [Accepted: 08/22/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND Effective work of breathing and bronchial hygiene requires synergy of inspiratory and expiratory muscles. Inspiratory muscle training (IMT) is a part of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD). There is some evidence of its efficacy in cystic fibrosis (CF) and, recently, in long COVID-19. We are not aware of studies on IMT in primary ciliary dyskinesia (PCD). Our aim was to assess the effect of IMT on respiratory muscle strength and pulmonary function in PCD and CF patients. METHODS A single center pilot study. Spirometry, lung clearance index (LCI), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were measured at baseline (visit 1), after a month of IMT with ®POWERbreathe (visit 2), and at follow-up (visit 3). RESULTS The cohort included 27 patients (19 PCD, 8 CF); mean age 18.4 ± 9.8 years. After a month of IMT, there was a significant increase in MIP and MIP% (6.19-7.44, p = .015; and 81.85%-100.41%, p = .046, respectively), which was sustained at visit 3. Compliance ≥90% led to higher improvement in MIP. In sub-group analysis, improvement in MIP and MIP% remained significant for PCD patients (p = .026 and p = .049, respectively). No significant changes were found in spirometry, MEP or LCI. CONCLUSIONS IMT was well-tolerated and led to improved inspiratory muscle strength in PCD patients. The clinical implication of improved MIP should be further investigated. Larger, long-term studies are needed to evaluate long-term effects of IMT on pulmonary function, respiratory muscle strength, pulmonary exacerbations, and quality of life.
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Affiliation(s)
- Michal Gur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Eynav Manor
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Moneera Hanna
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Nadeen Simaan
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Guy Gut
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Yazeed Toukan
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Fahed Hakim
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Ronen Bar-Yoseph
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Lea Bentur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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Appelt D, Steinkamp G, Sieber S, Ellemunter H. Early and sustained improvements of lung clearance index from two to sixteen weeks of elexacaftor/tezacaftor/ivacaftor therapy in patients with cystic fibrosis-a real world study. Front Pharmacol 2023; 14:1125853. [PMID: 36969845 PMCID: PMC10030732 DOI: 10.3389/fphar.2023.1125853] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 02/21/2023] [Indexed: 03/11/2023] Open
Abstract
Since the introduction of CFTR modulator therapies, longitudinal real-life data of lung clearance index (LCI) during treatment is scarce. In this single-centre, post-approval setting, we report data of 51 patients with different stages of lung disease, age 2-52 years with repeated measurements of forced expiratory volume as a percentage of the predicted value (ppFEV₁) and LCI after 2, 4, and 16 weeks of CFTR modulator treatment and at baseline. In 25 patients during elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) treatment, significant improvements of LCI (median -1.4) and ppFEV₁ (median +8.3%) were observed after only 2 weeks, and were maintained after 4 and 16 weeks of treatment (LCI: -2.0, -2.2; ppFEV₁: +7.2%, +11.8%). We observed a significant correlation between LCI improvement at week 16 and lower baseline LCI. In 26 younger and healthier patients receiving lumacaftor/ivacaftor (LUM/IVA) treatment, no significant changes of LCI and ppFEV₁ occured. With ELX/TEZ/IVA, our data shows rapid, significant improvements of LCI and ppFEV₁ already after 2 weeks. Early LCI measurements can help to assess the patient's response to this high-cost therapy.
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Affiliation(s)
- Dorothea Appelt
- Cystic Fibrosis Centre Innsbruck, Department of Paediatrics III, Medical University of Innsbruck, Innsbruck, Austria
| | | | - Sarah Sieber
- STAT-UP Statistical Consulting & Data Science GmbH, Munich, Germany
| | - Helmut Ellemunter
- Cystic Fibrosis Centre Innsbruck, Department of Paediatrics III, Medical University of Innsbruck, Innsbruck, Austria
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Gur M, Bar-Yoseph R, Hanna M, Abboud D, Keidar Z, Palchan T, Toukan Y, Masarweh K, Alisha I, Zuckerman-Levin N, Bentur L. Effect of Trikafta on bone density, body composition and exercise capacity in CF: A pilot study. Pediatr Pulmonol 2023; 58:577-584. [PMID: 36372909 PMCID: PMC10100338 DOI: 10.1002/ppul.26243] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 10/26/2022] [Accepted: 11/05/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND While the positive effect of Trikafta on cystic fibrosis (CF) pulmonary disease is well established, there is limited data about its effect on bone mineral density (BMD), body composition and exercise capacity. METHODS A pilot single center study. BMD and body composition were measured three months after the initiation of Trikafta (study group) and compared to values obtained 2 years earlier. CF patients not treated with Trikafta, for whom BMD was measured 2 years apart, served as controls. Spirometry, lung clearance index (LCI), sweat test, six-min walk test (6MWT) and cardio-pulmonary exercise test (CPET) were performed before and three months after the initiation of Trikafta. RESULTS Nine study patients, aged 18.6 ± 4.7 years, and nine controls. For the study group, BMI and hip and spine BMD increased significantly (19.4 ± 2.6 to 20.3 ± 2.19 BMI, p = 0.05; 0.73 ± 0.098 to 0.81 ± 0.12 gr/cm2 hip, p = 0.017; 0.76 ± 0.14 to 0.82 ± 0.14 gr/cm2 spine, p = 0.025). For the control group, there was no difference in hip or spine BMD. Lean body mass, %fat z-score and fat mass/height2 z-score increased significantly (34770.23 ± 10521.21 to 37430.16 ± 10330.09gr, p = 0.017; -0.8 ± 0.75 to 0.46 ± 0.58, p = 0.012; and -0.98 ± 0.66 to -0.04 ± 0.51, p = 0.025, respectively). 6MWT improved from 541.1 ± 48.9 to 592.9 ± 54.5 m (p = 0.046). As expected, FEV1%pred increased (p = 0.008) and sweat chloride decreased significantly (p = 0.017). In CPET, VE/VCO2 improved, indicating better ventilatory efficiency. CONCLUSIONS To the best of our knowledge, this is the first study evaluating the metabolic effects of Trikafta. The results are encouraging and offer hope beyond the well-established effect on pulmonary disease. Larger long-term studies are warranted to unpin the underlying physiological mechanisms.
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Affiliation(s)
- Michal Gur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Ronen Bar-Yoseph
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Moneera Hanna
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Dana Abboud
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Zohar Keidar
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.,Nuclear Medicine Institute, Rambam Health Care Campus, Haifa, Israel
| | - Tala Palchan
- Nuclear Medicine Institute, Rambam Health Care Campus, Haifa, Israel
| | - Yazeed Toukan
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Kamal Masarweh
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Irit Alisha
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Nehama Zuckerman-Levin
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.,Pediatric Diabetes Unit, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Lea Bentur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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Bowerman C, Ratjen F, Stanojevic S. Estimating the minimum sample size for interventional and observational studies using the lung clearance index as an endpoint✰. J Cyst Fibros 2022; 22:356-362. [PMID: 36402729 DOI: 10.1016/j.jcf.2022.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 10/16/2022] [Accepted: 11/10/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND With the increasing availability of highly effective modulators for people living with cystic fibrosis (CF), there is a need to re-design research studies to reflect the changing epidemiology of the CF population. The lung clearance index (LCI), a sensitive physiological measure of lung function, may be ideally suited as an endpoint in the era of CF modulator therapies. In this study we describe study design considerations for implementing LCI into interventional and observational research. METHODS Simulations were used to estimate the required sample size to detect a range of treatment effects for interventional studies (including cross-over trials) and to track lung disease progression in observational studies. RESULTS Using published treatment effects to inform the design of prospective studies can lead to inefficient study designs. Large improvements in LCI for a few individuals can skew results and can influence interpretations of treatment effects. Adjusting for baseline LCI can help to improve the efficiency of a study. Compared to the forced expiratory volume in 1 second (FEV1), analysis using LCI as an endpoint requires as little as one third of the total sample size. CONCLUSIONS Planning of prospective studies that include LCI as an endpoint need to consider baseline LCI and disease severity of the study population; whereas interpretation of results needs to consider whether a few individuals skew the overall treatment effect.
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Herrmann J, Kollisch-Singule M, Satalin J, Nieman GF, Kaczka DW. Assessment of Heterogeneity in Lung Structure and Function During Mechanical Ventilation: A Review of Methodologies. JOURNAL OF ENGINEERING AND SCIENCE IN MEDICAL DIAGNOSTICS AND THERAPY 2022; 5:040801. [PMID: 35832339 PMCID: PMC9132008 DOI: 10.1115/1.4054386] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 04/13/2022] [Indexed: 06/15/2023]
Abstract
The mammalian lung is characterized by heterogeneity in both its structure and function, by incorporating an asymmetric branching airway tree optimized for maintenance of efficient ventilation, perfusion, and gas exchange. Despite potential benefits of naturally occurring heterogeneity in the lungs, there may also be detrimental effects arising from pathologic processes, which may result in deficiencies in gas transport and exchange. Regardless of etiology, pathologic heterogeneity results in the maldistribution of regional ventilation and perfusion, impairments in gas exchange, and increased work of breathing. In extreme situations, heterogeneity may result in respiratory failure, necessitating support with a mechanical ventilator. This review will present a summary of measurement techniques for assessing and quantifying heterogeneity in respiratory system structure and function during mechanical ventilation. These methods have been grouped according to four broad categories: (1) inverse modeling of heterogeneous mechanical function; (2) capnography and washout techniques to measure heterogeneity of gas transport; (3) measurements of heterogeneous deformation on the surface of the lung; and finally (4) imaging techniques used to observe spatially-distributed ventilation or regional deformation. Each technique varies with regard to spatial and temporal resolution, degrees of invasiveness, risks posed to patients, as well as suitability for clinical implementation. Nonetheless, each technique provides a unique perspective on the manifestations and consequences of mechanical heterogeneity in the diseased lung.
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Affiliation(s)
- Jacob Herrmann
- Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242
| | | | - Joshua Satalin
- Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210
| | - Gary F. Nieman
- Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210
| | - David W. Kaczka
- Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242; Department of Anesthesia, University of Iowa, Iowa City, IA 52242; Department of Radiology, University of Iowa, Iowa City, IA 52242
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10
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Gur M, Zuckerman-Levin N, Masarweh K, Hanna M, Laghi L, Marazzato M, Levanon S, Hakim F, Bar-Yoseph R, Wilschanski M, Bentur L. The effect of probiotic administration on metabolomics and glucose metabolism in CF patients. Pediatr Pulmonol 2022; 57:2335-2343. [PMID: 35676769 PMCID: PMC9796051 DOI: 10.1002/ppul.26037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 05/23/2022] [Accepted: 06/08/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND OBJECTIVES Cystic fibrosis (CF)-related diabetes (CFRD) affects 50% of CF adults. Gut microbial imbalance (dysbiosis) aggravates their inflammatory response and contributes to insulin resistance (IR). We hypothesized that probiotics may improve glucose tolerance by correcting dysbiosis. METHODS A single-center prospective pilot study assessing the effect of Vivomixx® probiotic (450 billion/sachet) on clinical status, spirometry, lung clearance index (LCI), and quality of life (QOL) questionnaires; inflammatory parameters (urine and stool metabolomics, blood cytokines); and glucose metabolism (oral glucose tolerance test [OGTT]), continuous glucose monitoring [CGM], and homeostasis model assessment of IR (HOMA-IR) in CF patients. RESULTS Twenty-three CF patients (six CFRD), mean age 17.7 ± 8.2 years. After 4 months of probiotic administration, urinary cysteine (p = 0.018), lactulose (p = 0.028), arabinose (p = 0.036), mannitol (p = 0.041), and indole 3-lactate (p = 0.046) significantly increased, while 3-methylhistidine (p = 0.046) and N-acetyl glutamine (p = 0.047) decreased. Stool 2-Hydroxyisobutyrate (p = 0.022) and 3-methyl-2-oxovalerate (p = 0.034) decreased. Principal component analysis, based on urine metabolites, found significant partitions between subjects at the end of treatment compared to baseline (p = 0.004). After 2 months of probiotics, the digestive symptoms domain of Cystic Fibrosis Questionnaire-Revised improved (p = 0.007). In the nondiabetic patients, a slight decrease in HOMA-IR, from 2.28 to 1.86, was observed. There was no significant change in spirometry results, LCI, blood cytokines and CGM. CONCLUSIONS Changes in urine and stool metabolic profiles, following the administration of probiotics, may suggest a positive effect on glucose metabolism in CF. Larger long-term studies are needed to confirm our findings. Understanding the interplay between dysbiosis, inflammation, and glucose metabolism may help preventing CFRD.
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Affiliation(s)
- Michal Gur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Nehama Zuckerman-Levin
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.,Pediatric Diabetes Unit, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Kamal Masarweh
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Moneera Hanna
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Luca Laghi
- Department of Agricultural and Food Sciences, University of Bologna, Cesena, Italy.,Interdepartmental Centre for Industrial Agrofood Research, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Massimiliano Marazzato
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Shir Levanon
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Fahed Hakim
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Ronen Bar-Yoseph
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Michael Wilschanski
- Department of Pediatric Gastroenterology, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Lea Bentur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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11
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Koucký V, Komárek A, Pohunek P. Repeatability of lung clearance index in infants with cystic fibrosis and recurrent wheeze. Pediatr Pulmonol 2022; 57:1608-1617. [PMID: 35419996 DOI: 10.1002/ppul.25921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 04/06/2022] [Accepted: 04/10/2022] [Indexed: 11/12/2022]
Abstract
OBJECTIVES To describe the short- and medium-term repeatability of lung clearance index at 2.5% (LCI2.5 ) in infants and calculate the number of patients needed to enroll in a study (N) using LCI2.5 as a primary outcome. METHODS An 8-month follow-up observational study was employed for assessing short-term [coefficient of repeatability (CR) and intraclass correlation (ICC)] and medium-term repeatability (Bland-Altman method) of LCI2.5 in infants with cystic fibrosis (CF) or recurrent wheeze (RW) measured by the nitrogen multiple-breath washout test (N2 -MBW). Using these variability data, the N to reach 90% test power at the level of statistical significance (0.05) was calculated. RESULTS Forty infants with CF and 21 with RW were enrolled. Initial N2 -MBW testing was successful in 33 and 17 patients, respectively. Follow-up data were available for 23 and 11 infants, respectively. Short-term repeatability of LCI2.5 was high (CR = 1.10 and 1.04 in CF and RW patients, respectively; ICC = 0.88 and 0.83 in CF and RW patients, respectively). The between-subject standard deviation was <13% of the actual LCI2.5 value. In clinically stable patients, LCI2.5 did not significantly change during the 8-month follow-up. Mean LCI2.5 change was -0.08 (1% of baseline) in CF and -0.05 (0.6%) in RW, with 95% limits of agreement being (-1.70; 1.53) in CF and (-1.51; 1.40) in RW patients. N = 23 infants if both intragroup differences of LCI2.5 and minimal difference to be detected would be 2.0. CONCLUSION N2 -MBW may be a reproducible tool with reasonable test power to detect differences in infant studies.
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Affiliation(s)
- Václav Koucký
- Department of Pediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
| | - Arnošt Komárek
- Department of Probability and Mathematical Statistics, Faculty of Mathematics and Physics, Charles University, Prague, Czech Republic
| | - Petr Pohunek
- Department of Pediatrics, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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12
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Ciuca IM, Pop LL, Dediu M, Stoicescu ER, Marc MS, Manea AM, Manolescu DL. Lung Ultrasound in Children with Cystic Fibrosis in Comparison with Chest Computed Tomography: A Feasibility Study. Diagnostics (Basel) 2022; 12:diagnostics12020376. [PMID: 35204467 PMCID: PMC8871437 DOI: 10.3390/diagnostics12020376] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/28/2022] [Accepted: 01/30/2022] [Indexed: 01/15/2023] Open
Abstract
Background: Cystic fibrosis (CF) lung disease determines the outcome of this condition. For lung evaluation processes, computed tomography (CT) is the gold standard, but also causes irradiation. Lately, lung ultrasound (LUS) has proven to be reliable for the diagnosis of consolidations, atelectasis, and/or bronchiectasis. The aim of our study was to evaluate the value of a newly conceived LUS score by comparing it to the modified Bhalla CT score. A further aim was to evaluate the correlation between the score and the lung clearance index (LCI). Methods: Patients with CF were screened by LUS, followed by a CT scan. Spearman’s test was used for correlations. Results: A total of 98 patients with CF were screened, and 57 were included in the study; their mean age was 11.8 ± 5.5 (mean ± SD) years. The mean LUS score was 5.88 ± 5.4 SD. The LUS CF score had a very strong correlation with the CT score of rs = 0.87 (p = 0.000). LUS showed a good sensibility for detecting atelectasis (Se = 83.7%) and consolidations (Se = 94.4%). A lower Se (77.7%) and Sp (9%) were found for cylindrical bronchiectasis. Conclusion: Our study shows that LUS and the lung CF score are parameters that can be used with a complementary role in the diagnosis and monitoring of CF lung disease in children.
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Affiliation(s)
- Ioana Mihaiela Ciuca
- Pediatric Department, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (I.M.C.); (L.L.P.); (M.D.)
| | - Liviu Laurentiu Pop
- Pediatric Department, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (I.M.C.); (L.L.P.); (M.D.)
| | - Mihaela Dediu
- Pediatric Department, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (I.M.C.); (L.L.P.); (M.D.)
| | - Emil Robert Stoicescu
- Radiology Department, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (E.R.S.); (D.L.M.)
- Research Center for Pharmaco-Toxicological Evaluations, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Monica Steluta Marc
- Pulmonology Department, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- Correspondence: ; Tel.: +40-721434044
| | - Aniko Maria Manea
- Neonatology and Puericulture Department, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania;
| | - Diana Luminita Manolescu
- Radiology Department, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (E.R.S.); (D.L.M.)
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13
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Marpole R, Ohn M, O'Dea CA, von Ungern-Sternberg BS. Clinical utility of preoperative pulmonary function testing in pediatrics. Paediatr Anaesth 2022; 32:191-201. [PMID: 34875135 DOI: 10.1111/pan.14356] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 11/30/2021] [Accepted: 12/01/2021] [Indexed: 11/28/2022]
Abstract
Perioperative respiratory adverse events pose a significant risk in pediatric anesthesia, and identifying these risks is vital. Traditionally, this is assessed using history and examination. However, the perioperative risk is multifactorial, and children with complex medical backgrounds such as chronic lung disease or obesity may benefit from additional objective preoperative pulmonary function tests. This article summarizes the utility of available pulmonary function assessment tools as preoperative tests in improving post-anesthetic outcomes. Currently, there is no evidence to support or discourage any pulmonary function assessment as a routine preoperative test for children undergoing anesthesia. In addition, there is uncertainty about which patients with the known or suspected respiratory disease require preoperative pulmonary function tests, what time period prior to surgery these are required, and whether spirometry or more sophisticated tests are indicated. Therefore, the need for any test should be based on information obtained from the history and examination, the child's age, and the complexity of the surgery.
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Affiliation(s)
- Rachael Marpole
- Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, WA, Australia.,Division of Paediatrics, School of Medical, University of Western Australia, Crawley, WA, Australia
| | - Mon Ohn
- Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, WA, Australia.,Division of Paediatrics, School of Medical, University of Western Australia, Crawley, WA, Australia.,Perioperative Medicine Team, Telethon Kids Institute, Nedlands, WA, Australia
| | - Christopher A O'Dea
- Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, WA, Australia
| | - Britta S von Ungern-Sternberg
- Perioperative Medicine Team, Telethon Kids Institute, Nedlands, WA, Australia.,Division of Emergency Medicine, Anaesthesia and Pain Medicine, School of Medical, University of Western Australia, Crawley, WA, Australia.,Department of Anaesthesia and Pain Management, Perth Children's Hospital, Nedlands, WA, Australia
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14
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Cherrez-Ojeda I, Robles-Velasco K, Osorio MF, Calderon JC, Bernstein JA. Current Needs Assessment for Using Lung Clearance Index for Asthma in Clinical Practice. Curr Allergy Asthma Rep 2022; 22:13-20. [DOI: 10.1007/s11882-022-01025-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/13/2021] [Indexed: 11/03/2022]
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15
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Schranc Á, Balogh ÁL, Diaper J, Südy R, Peták F, Habre W, Albu G. Flow-controlled ventilation maintains gas exchange and lung aeration in a pediatric model of healthy and injured lungs: A randomized cross-over experimental study. Front Pediatr 2022; 10:1005135. [PMID: 36160799 PMCID: PMC9500311 DOI: 10.3389/fped.2022.1005135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 08/24/2022] [Indexed: 11/30/2022] Open
Abstract
Flow-controlled ventilation (FCV) is characterized by a constant flow to generate active inspiration and expiration. While the benefit of FCV on gas exchange has been demonstrated in preclinical and clinical studies with adults, the value of this modality for a pediatric population remains unknown. Thus, we aimed at observing the effects of FCV as compared to pressure-regulated volume control (PRVC) ventilation on lung mechanics, gas exchange and lung aeration before and after surfactant depletion in a pediatric model. Ten anesthetized piglets (10.4 ± 0.2 kg) were randomly assigned to start 1-h ventilation with FCV or PRVC before switching the ventilation modes for another hour. This sequence was repeated after inducing lung injury by bronchoalveolar lavage and injurious ventilation. The primary outcome was respiratory tissue elastance. Secondary outcomes included oxygenation index (PaO2/FiO2), PaCO2, intrapulmonary shunt (Qs/Qt), airway resistance, respiratory tissue damping, end-expiratory lung volume, lung clearance index and lung aeration by chest electrical impedance tomography. Measurements were performed at the end of each protocol stage. Ventilation modality had no effect on any respiratory mechanical parameter. Adequate gas exchange was provided by FCV, similar to PRVC, with sufficient CO2 elimination both in healthy and surfactant-depleted lungs (39.46 ± 7.2 mmHg and 46.2 ± 11.4 mmHg for FCV; 36.0 ± 4.1 and 39.5 ± 4.9 mmHg, for PRVC, respectively). Somewhat lower PaO2/FiO2 and higher Qs/Qt were observed in healthy and surfactant depleted lungs during FCV compared to PRVC (p < 0.05, for all). Compared to PRVC, lung aeration was significantly elevated, particularly in the ventral dependent zones during FCV (p < 0.05), but this difference was not evidenced in injured lungs. Somewhat lower oxygenation and higher shunt ratio was observed during FCV, nevertheless lung aeration improved and adequate gas exchange was ensured. Therefore, in the absence of major differences in respiratory mechanics and lung volumes, FCV may be considered as an alternative in ventilation therapy of pediatric patients with healthy and injured lungs.
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Affiliation(s)
- Álmos Schranc
- Unit for Anesthesiological Investigations, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University of Geneva, Geneva, Switzerland
| | - Ádám L Balogh
- Unit for Anesthesiological Investigations, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University of Geneva, Geneva, Switzerland
| | - John Diaper
- Unit for Anesthesiological Investigations, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University of Geneva, Geneva, Switzerland
| | - Roberta Südy
- Unit for Anesthesiological Investigations, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University of Geneva, Geneva, Switzerland
| | - Ferenc Peták
- Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary
| | - Walid Habre
- Unit for Anesthesiological Investigations, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University of Geneva, Geneva, Switzerland.,Pediatric Anesthesia Unit, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University Hospitals of Geneva, Geneva, Switzerland
| | - Gergely Albu
- Unit for Anesthesiological Investigations, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University of Geneva, Geneva, Switzerland.,Division of Anesthesiology, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University Hospitals of Geneva, Geneva, Switzerland
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16
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Marczak H, Peradzyńska J, Seidl E, Griese M, Urbankowski T, Lange J, Bogusławski S, Krenke K. The improved clinical course of persistent tachypnea of infancy with inhaled bronchodilators and corticosteroids. Pediatr Pulmonol 2021; 56:3952-3959. [PMID: 34520130 DOI: 10.1002/ppul.25674] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 07/31/2021] [Accepted: 09/11/2021] [Indexed: 01/28/2023]
Abstract
BACKGROUND Persistent tachypnea of infancy (PTI) is the most common interstitial lung disease in young children. As no standardized therapeutic guidelines exist, different pharmaceuticals are used to treat PTI; inhaled corticosteroids (ICS) and bronchodilators being mostly used. This observation assessed the effectiveness of bronchodilators and ICS in children with PTI enrolled in the children's interstitial lung diseases (chILD)-EU Register. METHODS Symptomatic children with PTI were observed according to a predetermined stepwise protocol including bronchodilators as the first choice treatment (6 weeks). In patients with incomplete response, additionally, ICS was given (12 weeks). Signs, symptoms, and pulmonary function were evaluated at three time points: at baseline, 6 (±1) weeks after initiation of bronchodilators, and 12 (±1) weeks after bronchodilators/ICS. RESULTS Thirty-one children (median age: 44 months, interquartile range [IQR]: 15-67) were included. The therapy was associated with a significant reduction of tachypnea (53.3% of patients, p = 0.02), exercise intolerance (52.2% of patients, p < 0.001), chest retractions (43.8% of patients, p = 0.04), and crackles (29.2% of patients, p = 0.02). Also, a significant improvement in forced expiratory volume in 1 s (FEV1 ) (median z score: -2.21 vs. -0.47, p = 0.03), residual volume (RV) (median z score 5.28 vs. 1.07, p = 0.007), RV% total lung capacity (TLC) (median z score: 6.05 vs. 1.48, p = 0.01), sRaw (median z score: 6.6 vs. 4.64, p = 0.01), R5 (median z score: 1.27 vs. 0.31, p = 0.009), and R5-R20 (median: 0.58 vs. 0.26 kPa/(l/s), p = 0.002) was demonstrated. CONCLUSIONS Inhaled bronchodilators and ICS may exert a positive effect on the severity of symptoms and pulmonary function test (PFT) in symptomatic children with PTI. However, a randomized control trial should be conducted to confirm their effectiveness.
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Affiliation(s)
- Honorata Marczak
- Department of Pediatric Pneumology and Allergy, Medical University of Warsaw, Warsaw, Poland
| | - Joanna Peradzyńska
- Department of Epidemiology and Biostatistics, Medical University of Warsaw, Warsaw, Poland
| | - Elias Seidl
- Department of Pediatric Pneumology, Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany
| | - Matthias Griese
- Department of Pediatric Pneumology, Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany
| | | | - Joanna Lange
- Department of Pediatric Pneumology and Allergy, Medical University of Warsaw, Warsaw, Poland
| | - Stanisław Bogusławski
- Department of Pediatric Pneumology and Allergy, Medical University of Warsaw, Warsaw, Poland
| | - Katarzyna Krenke
- Department of Pediatric Pneumology and Allergy, Medical University of Warsaw, Warsaw, Poland
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17
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Lung Clearance Index in Children with Cystic Fibrosis during Pulmonary Exacerbation. J Clin Med 2021; 10:jcm10214884. [PMID: 34768401 PMCID: PMC8584600 DOI: 10.3390/jcm10214884] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 10/13/2021] [Accepted: 10/19/2021] [Indexed: 11/16/2022] Open
Abstract
(1) Background: Pulmonary exacerbation (PEx) is one of the main factors affecting the quality of life and life expectancy in patients with cystic fibrosis (CF). Our study aimed to evaluate the change in selected pulmonary function parameters, including lung clearance index (LCI), in patients with CF diagnosed with PEx. (2) Methods: We enrolled 40 children with CF aged 6–17. They performed spirometry and multiple breath nitrogen washout (MBNW) tests during a stable condition period at the beginning and the end of intravenous antibiotic treatment. (3) Results: LCI increased by 65% and FEV1 decreased by ≥10% in 40% of patients with CF during PEx. An absolute change in LCI between a stable condition period and PEx was 1.05 (±1.92) units, which corresponds to a relative change of 11.48% (±18.61) of the baseline. The relative decrease in FEV1 was −9.22% (±12.00) and the z-score was −0.67 (±1.13). After the PEx treatment, FEV1 increased by 11.05% (±9.04) on average, whereas LCI decreased by 1.21 ± 1.59 units on average, which represented 9.42% ± 11.40 compared to the value at the beginning of PEx. (4) Conclusions: The change in LCI captures a higher proportion of events with functional impairment than FEV1 in school-age children with CF.
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18
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Gur M, Ben-David Y, Hanna M, Ilivitzki A, Weichhendler A, Bar-Yoseph R, Toukan Y, Masarweh K, Bentur L. The Association between IgG and Disease Severity Parameters in CF Patients. J Clin Med 2021; 10:jcm10153316. [PMID: 34362100 PMCID: PMC8347508 DOI: 10.3390/jcm10153316] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/22/2021] [Accepted: 07/27/2021] [Indexed: 11/18/2022] Open
Abstract
Assessing disease severity in patients with cystic fibrosis (CF) is essential when directing therapies. Serum immunoglobulin G (IgG) levels increase with disease severity. Lung clearance index (LCI) is recognized as an outcome measure for CF clinical trials. Our aim was to evaluate the correlations between IgG and disease severity markers. This was a single-center retrospective study, evaluating association between IgG and markers of severity in CF patients (including clinical characteristics, lung spirometry, LCI, clinical scores and computed tomography (CT) scores) during stable conditions. There were 69 patients, age 20.5 ± 11.6 years. Nineteen (27.5%) patients had elevated IgG. IgG correlated positively with LCI (r = 0.342, p = 0.005). IgG was higher in pancreatic insufficient (PI) and patients with liver disease (1504.3 ± 625.5 vs. 1229 ± 276.1 mg/dL in PI vs. PS, p = 0.023, and 1702.6 ± 720.3 vs. 1256.2 ± 345.5 mg/dL with vs. without liver disease, p = 0.001, respectively). IgG also correlated positively with CRP, CT score, and days with antibiotics in the previous year (r = 0.38, p = 0.003; r = 0.435, p = 0.001; and r = 0.361, p = 0.002, respectively), and negatively with FEV1% and SK score (r = −0.527, p < 0.001 and r = −0.613, p < 0.001, respectively). IgG correlated with clinical parameters, pulmonary functions, and imaging. However, this is still an auxiliary test, complementing other tests, including lung function and imaging tests. Larger multi-center longitudinal studies are warranted.
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Affiliation(s)
- Michal Gur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children’s Hospital, Rambam Health Care Campus, Haifa 3109601, Israel; (M.G.); (Y.B.-D.); (M.H.); (A.W.); (R.B.-Y.); (Y.T.); (K.M.)
- Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Efron St 1, Haifa 3525422, Israel;
| | - Yael Ben-David
- Pediatric Pulmonary Institute and CF Center, Rappaport Children’s Hospital, Rambam Health Care Campus, Haifa 3109601, Israel; (M.G.); (Y.B.-D.); (M.H.); (A.W.); (R.B.-Y.); (Y.T.); (K.M.)
| | - Moneera Hanna
- Pediatric Pulmonary Institute and CF Center, Rappaport Children’s Hospital, Rambam Health Care Campus, Haifa 3109601, Israel; (M.G.); (Y.B.-D.); (M.H.); (A.W.); (R.B.-Y.); (Y.T.); (K.M.)
| | - Anat Ilivitzki
- Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Efron St 1, Haifa 3525422, Israel;
- Pediatric Radiology Unit, Ruth Rappaport Children’s Hospital, Rambam Health Care Campus, Haifa 3109601, Israel
| | - Adi Weichhendler
- Pediatric Pulmonary Institute and CF Center, Rappaport Children’s Hospital, Rambam Health Care Campus, Haifa 3109601, Israel; (M.G.); (Y.B.-D.); (M.H.); (A.W.); (R.B.-Y.); (Y.T.); (K.M.)
| | - Ronen Bar-Yoseph
- Pediatric Pulmonary Institute and CF Center, Rappaport Children’s Hospital, Rambam Health Care Campus, Haifa 3109601, Israel; (M.G.); (Y.B.-D.); (M.H.); (A.W.); (R.B.-Y.); (Y.T.); (K.M.)
- Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Efron St 1, Haifa 3525422, Israel;
| | - Yazeed Toukan
- Pediatric Pulmonary Institute and CF Center, Rappaport Children’s Hospital, Rambam Health Care Campus, Haifa 3109601, Israel; (M.G.); (Y.B.-D.); (M.H.); (A.W.); (R.B.-Y.); (Y.T.); (K.M.)
- Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Efron St 1, Haifa 3525422, Israel;
| | - Kamal Masarweh
- Pediatric Pulmonary Institute and CF Center, Rappaport Children’s Hospital, Rambam Health Care Campus, Haifa 3109601, Israel; (M.G.); (Y.B.-D.); (M.H.); (A.W.); (R.B.-Y.); (Y.T.); (K.M.)
| | - Lea Bentur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children’s Hospital, Rambam Health Care Campus, Haifa 3109601, Israel; (M.G.); (Y.B.-D.); (M.H.); (A.W.); (R.B.-Y.); (Y.T.); (K.M.)
- Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Efron St 1, Haifa 3525422, Israel;
- Correspondence: ; Tel.: +972-4-7774360; Fax: +972-4-7774395
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19
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Kurz JM, Ramsey KA, Rodriguez R, Spycher B, Biner RF, Latzin P, Singer F. Association of lung clearance index with survival in individuals with cystic fibrosis. Eur Respir J 2021; 59:13993003.00432-2021. [PMID: 34289977 DOI: 10.1183/13993003.00432-2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 06/28/2021] [Indexed: 11/05/2022]
Abstract
BACKGROUND The lung clearance index (LCI) assesses global ventilation inhomogeneity and is a sensitive biomarker of airway function in cystic fibrosis (CF) lung disease. OBJECTIVES We examined the association of LCI with the risk of death or lung transplantation (LTX) in individuals with CF. METHODS We performed a retrospective analysis in a cohort of individuals with CF aged≥5 years with LCI and FEV1 measurements performed between 1980 and 2006. The outcome was time until death or LTX. We used the earliest available LCI and FEV1 values in a Cox proportional hazard regression adjusted for demographic and clinical variables. For sensitivity analyses, we used the mean of the first three LCI and FEV1 measurements, stratified the cohort based on age, and investigated individuals with normal FEV1. RESULTS In total, 237 individuals with CF with a mean (range) age of 13.9 (5.6-41.0) years were included. The time-to-event analysis accrued 3813 person-years and 94 (40%) individuals died or received LTX. Crude hazard ratios [95% CI] were 1.04 [1.01-1.06] per one z-score increase in LCI and 1.25 [1.11-1.41] per one z-score decrease in FEV1. After adjusting LCI and FEV1 mutually in addition to sex, age, BMI and the number of hospitalisations, hazard ratios were 1.04 [1.01-1.07] for LCI, and 1.12 [0.95-1.33] for FEV1. Sensitivity analyses yielded similar results and using the mean LCI strengthened the associations. CONCLUSIONS Increased ventilation inhomogeneity is associated with greater risk of death or LTX. Our data support LCI as novel surrogate of survival in individuals with CF.
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Affiliation(s)
- Johanna Manuela Kurz
- Division of Respiratory Medicine, Department of Paediatrics, Inselspital University Hospital Bern, University of Bern, Bern, Bern, Switzerland.,Graduate School for Health Sciences, University of Bern, Bern, Switzerland
| | - Kathryn Angela Ramsey
- Division of Respiratory Medicine, Department of Paediatrics, Inselspital University Hospital Bern, University of Bern, Bern, Bern, Switzerland
| | - Romy Rodriguez
- Division of Respiratory Medicine, Department of Paediatrics, Inselspital University Hospital Bern, University of Bern, Bern, Bern, Switzerland
| | - Ben Spycher
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | | | - Philipp Latzin
- Division of Respiratory Medicine, Department of Paediatrics, Inselspital University Hospital Bern, University of Bern, Bern, Bern, Switzerland
| | - Florian Singer
- Division of Respiratory Medicine, Department of Paediatrics, Inselspital University Hospital Bern, University of Bern, Bern, Bern, Switzerland
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20
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Hildebrandt J, Rahn A, Kessler A, Speth F, Fischer DC, Ballmann M. Lung clearance index and diffusion capacity for CO to detect early functional pulmonary impairment in children with rheumatic diseases. Pediatr Rheumatol Online J 2021; 19:23. [PMID: 33676536 PMCID: PMC7937245 DOI: 10.1186/s12969-021-00509-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 02/19/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND In adults with rheumatic diseases pulmonary complications are relevant contributors to morbidity and mortality. In these patients diffusion capacity for CO (DLCO) is an established method to detect early pulmonary impairment. Pilot studies using DLCO indicate that early functional pulmonary impairment is present even in children with rheumatic disease albeit not detectable by spirometry and without clinical signs of pulmonary disease. Since the lung clearance index (LCI) is also a non-invasive, feasible and established method to detect early functional pulmonary impairment especially in children and because it requires less cooperation (tidal breathing), we compared LCI versus DLCO (forced breathing and breath-holding manoeuvre) in children with rheumatic diseases. FINDINGS Nineteen patients (age 9-17 years) with rheumatic disease and no clinical signs of pulmonary disease successfully completed LCI and DLCO during annual check-up. In 2 patients LCI and DLCO were within physiological limits. By contrast, elevated LCI combined with physiological results for DLCO were seen in 8 patients and in 9 patients both, the LCI and DLCO indicate early functional pulmonary changes. Overall, LCI was more sensitive than DLCO to detect early functional pulmonary impairment (p = 0.0128). CONCLUSIONS Our findings suggest that early functional pulmonary impairment is already present in children with rheumatic diseases. LCI is a very feasible and non-invasive alternative for detection of early functional pulmonary impairment in children. It is more sensitive and less cooperation dependent than DLCO. Therefore, we suggest to integrate LCI in routine follow-up of rheumatic diseases in children.
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Affiliation(s)
- Julia Hildebrandt
- grid.10493.3f0000000121858338Department of Pediatrics, Rostock University Medical Centre, Ernst-Heydemann Strasse 8, DE 18057 Rostock, Germany
| | - Anja Rahn
- grid.10493.3f0000000121858338Department of Pediatrics, Rostock University Medical Centre, Ernst-Heydemann Strasse 8, DE 18057 Rostock, Germany
| | - Anja Kessler
- grid.10493.3f0000000121858338Department of Pediatrics, Rostock University Medical Centre, Ernst-Heydemann Strasse 8, DE 18057 Rostock, Germany
| | - Fabian Speth
- grid.10493.3f0000000121858338Department of Pediatrics, Rostock University Medical Centre, Ernst-Heydemann Strasse 8, DE 18057 Rostock, Germany
| | - Dagmar-Christiane Fischer
- grid.10493.3f0000000121858338Department of Pediatrics, Rostock University Medical Centre, Ernst-Heydemann Strasse 8, DE 18057 Rostock, Germany
| | - Manfred Ballmann
- Department of Pediatrics, Rostock University Medical Centre, Ernst-Heydemann Strasse 8, DE 18057, Rostock, Germany.
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21
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Trinkmann F, Maros M, Roth K, Hermanns A, Schäfer J, Gawlitza J, Saur J, Akin I, Borggrefe M, Herth FJF, Ganslandt T. Multiple breath washout (MBW) testing using sulfur hexafluoride: reference values and influence of anthropometric parameters. Thorax 2021; 76:380-386. [PMID: 33593931 DOI: 10.1136/thoraxjnl-2020-214717] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 01/07/2021] [Accepted: 01/20/2021] [Indexed: 11/04/2022]
Abstract
BACKGROUND Multiple breath washout (MBW) using sulfur hexafluoride (SF6) has the potential to reveal ventilation heterogeneity which is frequent in patients with obstructive lung disease and associated small airway dysfunction. However, reference data are scarce for this technique and mostly restricted to younger cohorts. We therefore set out to evaluate the influence of anthropometric parameters on SF6-MBW reference values in pulmonary healthy adults. METHODS We evaluated cross-sectional data from 100 pulmonary healthy never-smokers and smokers (mean 51 (SD 20), range 20-88 years). Lung clearance index (LCI), acinar (Sacin) and conductive (Scond) ventilation heterogeneity were derived from triplicate SF6-MBW measurements. Global ventilation heterogeneity was calculated for the 2.5% (LCI2.5) and 5% (LCI5) stopping points. Upper limit of normal (ULN) was defined as the 95th percentile. RESULTS Age was the only meaningful parameter influencing SF6-MBW parameters, explaining 47% (CI 33% to 59%) of the variance in LCI, 32% (CI 18% to 47%) in Sacin and 10% (CI 2% to 22%) in Scond. Mean LCI increases from 6.3 (ULN 7.4) to 8.8 (ULN 9.9) in subjects between 20 and 90 years. Smoking accounted for 2% (CI 0% to 8%) of the variability in LCI, 4% (CI 0% to 13%) in Sacin and 3% (CI 0% to 13%) in Scond. CONCLUSION SF6-MBW outcome parameters showed an age-dependent increase from early adulthood to old age. The effect was most pronounced for global and acinar ventilation heterogeneity and smaller for conductive ventilation heterogeneity. No influence of height, weight and sex was seen. Reference values can now be provided for all important SF6-MBW outcome parameters over the whole age range. TRIAL REGISTRATION NUMBER NCT04099225.
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Affiliation(s)
- Frederik Trinkmann
- 1st Department of Medicine, University Medical Centre Mannheim, Mannheim, Baden-Württemberg, Germany .,Department of Pneumology and Critical Care Medicine, Thoraxklinik at University Hospital Heidelberg, Translational Lung Research Centre Heidelberg (TLRC), Member of German Centre for Lung Research (DZL), Heidelberg, Baden-Württemberg, Germany.,Department of Biomedical Informatics, Centre for Preventive Medicine & Digital Health Baden-Württemberg, University Medical Centre Mannheim, Mannheim, Germany
| | - Máté Maros
- Department of Biomedical Informatics, Centre for Preventive Medicine & Digital Health Baden-Württemberg, University Medical Centre Mannheim, Mannheim, Germany.,Department of Neuroradiology, University Medical Centre Mannheim, Mannheim, Germany
| | - Katharina Roth
- 1st Department of Medicine, University Medical Centre Mannheim, Mannheim, Baden-Württemberg, Germany
| | - Arne Hermanns
- 1st Department of Medicine, University Medical Centre Mannheim, Mannheim, Baden-Württemberg, Germany
| | - Julia Schäfer
- 1st Department of Medicine, University Medical Centre Mannheim, Mannheim, Baden-Württemberg, Germany
| | - Joshua Gawlitza
- Institute for Clinical Radiology and Nuclear Medicine, University Medical Centre Mannheim, Mannheim, Germany
| | - Joachim Saur
- 1st Department of Medicine, University Medical Centre Mannheim, Mannheim, Baden-Württemberg, Germany
| | - Ibrahim Akin
- 1st Department of Medicine, University Medical Centre Mannheim, Mannheim, Baden-Württemberg, Germany.,DZHK (German Centre for Cardiovascular Research), Mannheim, Germany
| | - Martin Borggrefe
- 1st Department of Medicine, University Medical Centre Mannheim, Mannheim, Baden-Württemberg, Germany.,DZHK (German Centre for Cardiovascular Research), Mannheim, Germany
| | - Felix J F Herth
- Department of Pneumology and Critical Care Medicine, Thoraxklinik at University Hospital Heidelberg, Translational Lung Research Centre Heidelberg (TLRC), Member of German Centre for Lung Research (DZL), Heidelberg, Baden-Württemberg, Germany
| | - Thomas Ganslandt
- Department of Biomedical Informatics, Centre for Preventive Medicine & Digital Health Baden-Württemberg, University Medical Centre Mannheim, Mannheim, Germany
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22
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Frauchiger BS, Carlens J, Herger A, Moeller A, Latzin P, Ramsey KA. Multiple breath washout quality control in the clinical setting. Pediatr Pulmonol 2021; 56:105-112. [PMID: 33058570 DOI: 10.1002/ppul.25119] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 10/08/2020] [Accepted: 10/10/2020] [Indexed: 01/21/2023]
Abstract
BACKGROUND Multiple breath washout (MBW) is increasingly used in the clinical assessment of patients with cystic fibrosis (CF). Guidelines for MBW quality control (QC) were developed primarily for retrospective assessment and central overreading. We assessed whether real-time QC of MBW data during the measurement improves test acceptability in the clinical setting. METHODS We implemented standardized real-time QC and reporting of MBW data at the time of the measurement in the clinical pediatric lung function laboratory in Bern, Switzerland, in children with CF aged 4-18 years. We assessed MBW test acceptability before (31 tests; 89 trials) and after (32 tests; 96 trials) implementation of real-time QC and compared agreement between reviewers. Further, we assessed the implementation of real-time QC at a secondary center in Zurich, Switzerland. RESULTS Before the implementation of real-time QC in Bern, only 58% of clinical MBW tests were deemed acceptable following retrospective QC by an experienced reviewer. After the implementation of real-time QC, MBW test acceptability improved to 75% in Bern. In Zurich, after the implementation of real-time QC, test acceptability improved from 38% to 70%. Further, the agreement between MBW operators and an experienced reviewer for test acceptability was 84% in Bern and 93% in Zurich. CONCLUSION Real-time QC of MBW data at the time of measurement is feasible in the clinical setting and results in improved test acceptability.
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Affiliation(s)
- Bettina S Frauchiger
- Pediatric Respiratory Medicine, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Julia Carlens
- Pediatric Respiratory Medicine, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.,Clinic for Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Andreas Herger
- Division of Respiratory Medicine and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
| | - Alexander Moeller
- Division of Respiratory Medicine and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
| | - Philipp Latzin
- Pediatric Respiratory Medicine, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Kathryn A Ramsey
- Pediatric Respiratory Medicine, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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23
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Gur M, Bar-Yoseph R, Diab G, Hanna M, Rozen G, Daud F, Keidar Z, Toukan Y, Masarweh K, Nir V, Gut G, Hakim F, Bentur L. Understanding the interplay between factors that influence bone mineral density in CF. Pediatr Pulmonol 2020; 55:2667-2673. [PMID: 32584478 DOI: 10.1002/ppul.24925] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Accepted: 06/23/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVES Multiple factors affect bone mineral density (BMD) in cystic fibrosis (CF). Our aim was to perform comprehensive analyses of parameters potentially contributing to BMD. METHODS A prospective single-center study assessing BMD, and correlations with multiple parameters including pancreatic status, lung functions, 6-minute walk test (6MWT), clinical score (modified Shwachman-Kulczycki [SK] score), vitamin D, nutritional intake, hand grip strength (HGS), habitual physical activity (smart watches), and quality of life (SF-36 questionnaire). RESULTS Forty CF patients, mean age 18.3 ± 8.1 years, forced expiratory volume in 1 second 74.7% ± 17.9% predicted. Fifteen (37.5%) and 11 (27.5%) had osteopenia and osteoporosis, respectively. BMD was similar in pancreatic sufficient (pancreatic sufficient [PS], n = 15) and insufficient (pancreatic insufficient [PI], n = 25); median hip z score -1.5 ((-2.7)-(+0.2)) vs -1.5 ((-3.5)-(+0.7)), P = .79; spine -0.8 ((-2.2)-(+2)) vs -1.2 ((-4.4)-(+1.5)), P = .39 in PS vs PI, respectively. BMD correlated with HGS (r = .72, P < .001 hip; r = .52, P = .001 spine) and fat-free mass index (r = .81, P < .001 hip; r = .63, P < .001 spine). BMD z score correlated weakly with SK score and moderately with SF-36 general health. Data from smart watches, nutrition questionnaires, and 6MWT did not correlate with BMD. In a multivariate model, age and SK score predicted spine z score BMD. CONCLUSIONS A substantial number of CF patients have low BMD. Similar rates in PS and PI suggest that other factors, such as disease severity, may contribute to low BMD. SK and age, which can easily be obtained even with limited resources, were the best predictors of low BMD. Further larger multicenter studies are warranted to evaluate the contribution of multifactorial etiologies to low BMD in CF.
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Affiliation(s)
- Michal Gur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Ronen Bar-Yoseph
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Giselle Diab
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Clinical Nutrition Unit, Rambam Health Care Campus, Haifa, Israel
| | - Moneera Hanna
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Geila Rozen
- Clinical Nutrition Unit, Rambam Health Care Campus, Haifa, Israel
| | - Faten Daud
- Nuclear Medicine Institute, Rambam Health Care Campus, Haifa, Israel
| | - Zohar Keidar
- Nuclear Medicine Institute, Rambam Health Care Campus, Haifa, Israel
| | - Yazeed Toukan
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Kamal Masarweh
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Vered Nir
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Guy Gut
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Fahed Hakim
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Lea Bentur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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24
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Karlsson J, Fodor GH, Santos Rocha A, Lin N, Habre W, Wallin M, Hallbäck M, Peták F, Lönnqvist P. End-expiratory lung volume assessment using helium and carbon dioxide in an experimental model of pediatric capnoperitoneum. Acta Anaesthesiol Scand 2020; 64:1106-1113. [PMID: 32314349 DOI: 10.1111/aas.13607] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Revised: 02/08/2020] [Accepted: 04/08/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Capnoperitoneum during laparoscopy leads to cranial shift of the diaphragm, loss in lung volume, and risk of impaired gas exchange. Infants are susceptible to these changes and bedside assessment of lung volume during laparoscopy might assist with optimizing the ventilation. Thus, the primary aim was to investigate the monitoring value of a continuous end-expiratory lung volume (EELV) assessment method based on CO2 dynamics ( EELV CO 2 ) in a pediatric capnoperitoneum model by evaluating the correlation and trending ability against helium washout (EELVHe ). METHODS Intra-abdominal pressure (IAP) was randomly varied between 0, 6, and 12 mm Hg with CO2 insufflation, while positive end-expiratory pressure (PEEP) levels of 3, 6, and 9 cm H2 O were randomly applied in eight anesthetized and mechanically ventilated chinchilla rabbits. Concomitant EELV CO 2 and EELVHe and lung clearance index (LCI) were obtained under each experimental condition. RESULTS Significant correlations were found between EELV CO 2 and EELVHe before capnoperitoneum (r = .85, P < .001), although increased IAP distorted this relationship. The negative influence of IAP was counteracted by the application of PEEP 9, which restored the correlation between EELV CO 2 and EELVHe and resulted in 100% concordance rate between the methods regarding changes in lung volume. EELVHe and LCI showed a curvilinear relationship, and an EELVHe of approximately 20 mL kg-1 , determined with a receiver operating characteristic curve, was associated with near-normal LCI values. CONCLUSION In this animal model of pediatric capnoperitoneum, reliable assessment of changes in EELV based on EELV CO 2 requires an open lung strategy, defined as EELV above approximately 20 mL kg-1 .
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Affiliation(s)
- Jacob Karlsson
- Department of Physiology and Pharmacology (FYFA) Eriksson I Lars group‐Section of Anesthesiology and Intensive Care Karolinska Institute Stockholm Sweden
- Pediatric Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden
| | - Gergely H. Fodor
- Unit for Anaesthesiological Investigations Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine University of Geneva Geneva Switzerland
| | - Andre Santos Rocha
- Unit for Anaesthesiological Investigations Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine University of Geneva Geneva Switzerland
| | - Na Lin
- Unit for Anaesthesiological Investigations Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine University of Geneva Geneva Switzerland
| | - Walid Habre
- Unit for Anaesthesiological Investigations Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine University of Geneva Geneva Switzerland
- Pediatric Anesthesia Unit Geneva Children's Hospital Geneva Switzerland
| | - Mats Wallin
- Department of Physiology and Pharmacology (FYFA) Eriksson I Lars group‐Section of Anesthesiology and Intensive Care Karolinska Institute Stockholm Sweden
- Maquet Critical Care AB Solna Sweden
| | | | - Ferenc Peták
- Departmenet of Medical Physics and Informatics University of Szeged Szeged Hungary
| | - Per‐Arne Lönnqvist
- Department of Physiology and Pharmacology (FYFA) Eriksson I Lars group‐Section of Anesthesiology and Intensive Care Karolinska Institute Stockholm Sweden
- Pediatric Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden
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25
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Isaac SM, Jensen R, Anagnostopoulou P, Davies JC, Gappa M, Latzin P, Saunders C, Short C, Singer F, Stanojevic S, Zwitserloot A, Ratjen F. Evaluation of a multiple breath nitrogen washout system in children. Pediatr Pulmonol 2020; 55:2108-2114. [PMID: 32437013 DOI: 10.1002/ppul.24862] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 05/13/2020] [Indexed: 11/10/2022]
Abstract
INTRODUCTION The multiple breath nitrogen washout (MBW) test offers a sensitive measure of airway function. In this study we aim to (a) assess the validity of the EasyOne Pro LAB (MBWndd ) in an in vitro lung model, (b) assess the feasibility, repeatability, and reproducibility of MBWndd and (c) compare outcomes with the Exhalyzer D (MBWEM ) and body plethysmography. METHODS In vitro, functional residual capacity (FRC) measurements were assessed using a lung model under quasi-physiological conditions and compared to measured FRC. In vivo plethysmography and MBW were performed in a prospective study of children at two visits (n = 45 healthy; n = 41 cystic fibrosis [CF]). Bland-Altman plots were used to compare agreement between FRC and lung clearance index (LCI) measurements. RESULTS In vitro FRCndd measurements were repeatable but lung volumes were underestimated (mean relative difference -5.4% (limits of agreement [LA] -9.6%; -1.1%), 95% confidence interval (CI) -6.27; -4.45). In vivo, compared to plethysmography, FRCndd was consistently lower (-19.3% [-40.5; 1.9], 95% CI [-23.9; -14.7]), and showed a volume dependency. LCIndd values were also higher in children with smaller lung volumes. The within-test coefficient of variation of the FRCndd and LCIndd were 4.9% in health, and 5.6% and 6.9% in CF respectively. LCIndd was reproducible between-visits (mean relative difference [LA] -3.7% [-14.8, -7.5; 95% CI -6.6; -0.73] in health [n = 17] and 0.34% [-13.2, 22.8; 95% CI -5.0; 5.69] in CF [n = 23]). When calculated using the same algorithm, LCIndd was similar to LCIEM in health. CONCLUSIONS MBWndd measurements are feasible, repeatable, and reproducible, however, MBW-derived outcomes are not interchangeable with MBWEM .
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Affiliation(s)
- Sarah M Isaac
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada
| | - Renee Jensen
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada
| | - Pinelopi Anagnostopoulou
- Division of Respiratory Medicine, Department of Pediatrics, University Children's Hospital of Bern, University of Bern, Bern, Switzerland.,Institute of Anatomy, University of Bern, Bern, Switzerland
| | - Jane C Davies
- National Heart & Lung Institute, Imperial College London and Royal Brompton Hospital, London, UK
| | - Monika Gappa
- Evangelisches Krankenhaus Düsseldorf, Formerly Marienhospital Wesel, Germany
| | - Philipp Latzin
- Division of Respiratory Medicine, Department of Pediatrics, University Children's Hospital of Bern, University of Bern, Bern, Switzerland
| | - Clare Saunders
- National Heart & Lung Institute, Imperial College London and Royal Brompton Hospital, London, UK
| | - Christopher Short
- National Heart & Lung Institute, Imperial College London and Royal Brompton Hospital, London, UK
| | - Florian Singer
- Division of Respiratory Medicine, Department of Pediatrics, University Children's Hospital of Bern, University of Bern, Bern, Switzerland
| | - Sanja Stanojevic
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.,University of Toronto, Toronto, Ontario, Canada
| | - Annelies Zwitserloot
- University Medical Centre Groningen, Beatrix Children's Hospital, The Netherlands
| | - Felix Ratjen
- Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, Canada.,University of Toronto, Toronto, Ontario, Canada.,Division of Respiratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
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26
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Ring AM, Carlens J, Bush A, Castillo-Corullón S, Fasola S, Gaboli MP, Griese M, Koucky V, La Grutta S, Lombardi E, Proesmans M, Schwerk N, Snijders D, Nielsen KG, Buchvald F. Pulmonary function testing in children's interstitial lung disease. Eur Respir Rev 2020; 29:29/157/200019. [PMID: 32699025 DOI: 10.1183/16000617.0019-2020] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 04/11/2020] [Indexed: 12/17/2022] Open
Abstract
The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease. A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, whole-body plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome.PFTs may be useful in different stages of management of children with suspected or confirmed chILD, but the chILD spectrum is diverse and includes a heterogeneous patient group in all ages. Research studies in well-defined patient cohorts are needed to establish which PFT and outcomes are most relevant for diagnosis, evaluation of disease severity and course, and monitoring individual conditions both for improvement in clinical care and as end-points in future randomised controlled trials.
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Affiliation(s)
- Astrid Madsen Ring
- Paediatric Pulmonary Service, Dept of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Danish PCD & chILD Centre, CF Centre Copenhagen, Copenhagen, Denmark.,Joint first authors
| | - Julia Carlens
- Clinic for Paediatric Pneumology, Allergology and Neonatology, Medizinische Hochschule Hannover Zentrum fur Kinderheilkunde und Jugendmedizin, Hannover, Germany.,Joint first authors
| | - Andy Bush
- Paediatrics and Paediatric Respiratory Medicine, Imperial College London, London, UK.,Paediatric Respiratory Medicine, Royal Brompton and Harefield NHS Foundation Trust, London, UK
| | - Silvia Castillo-Corullón
- Unidad de Neumología infantil y Fibrosis quística, Hospital Clínico Universitario de Valencia, Valencia, Spain
| | - Salvatore Fasola
- Institute of Biomedical Research and Innovation, National Research Council of Italy, Palermo, Italy
| | - Mirella Piera Gaboli
- Neumologia Infantil y Unidad de Cuidados Intensivos Pediatricos, Hospital Universitario Salamanca, Salamanca, Spain
| | - Matthias Griese
- University Hospital of Munich, Dr. von Hauner Children's Hospital, German Center for Lung Research (DZL), Munich, Germany
| | - Vaclav Koucky
- Dept of Paediatrics, Univerzita Karlova v Praze 2 lekarska fakulta, Prague, Czech Republic
| | - Stefania La Grutta
- Institute of Biomedical Research and Innovation, National Research Council of Italy, Palermo, Italy
| | - Enrico Lombardi
- Pediatric Pulmonary Unit, Anna Meyer Pediatric University-Hospital, Florence, Italy
| | | | - Nicolaus Schwerk
- Clinic for Paediatric Pneumology, Allergology and Neonatology, Medizinische Hochschule Hannover Zentrum fur Kinderheilkunde und Jugendmedizin, Hannover, Germany
| | | | - Kim Gjerum Nielsen
- Paediatric Pulmonary Service, Dept of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Danish PCD & chILD Centre, CF Centre Copenhagen, Copenhagen, Denmark.,Joint last authors
| | - Frederik Buchvald
- Paediatric Pulmonary Service, Dept of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Danish PCD & chILD Centre, CF Centre Copenhagen, Copenhagen, Denmark .,Joint last authors
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Voldby C, Green K, Kongstad T, Ring AM, Sandvik RM, Skov M, Buchvald F, Pressler T, Nielsen KG. Lung clearance index-triggered intervention in children with cystic fibrosis - A randomised pilot study. J Cyst Fibros 2020; 19:934-941. [PMID: 32576447 DOI: 10.1016/j.jcf.2020.06.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 05/29/2020] [Accepted: 06/05/2020] [Indexed: 01/21/2023]
Abstract
HYPOTHESIS Using increase in the lung clearance index (LCI) as a trigger for bronchoalveolar lavage (BAL) and associated antimicrobial treatment might benefit clinical outcomes in children with cystic fibrosis (CF). METHODS A 2-year, longitudinal, interventional, randomized, controlled pilot study with quarterly visits in 5-18 years old children with CF. LCI and z-scores for the forced expired volume in 1 s (zFEV1) and body mass index (zBMI) were obtained at every visit, CF Questionnaire-revised (CFQ-R) yearly and BAL and chest computed tomography at first and last visit. Children in the intervention group had BAL performed if LCI increased >1 unit from a fixed baseline value established at first visit. If the presence of a pathogen was documented in the BAL fluid, treatment was initiated/altered accordingly. RESULTS Twenty-nine children with CF were randomized to the control (n = 14) and intervention group (n = 15). The median (interquartile range) number of BAL procedures per child was 2.5 (2.0; 3.0) and 6.0 (4.0; 7.0) in the control and intervention group, respectively. There was no significant difference between groups in slope for the primary outcome LCI; difference was 0.21 (95% confidence interval: -0.45; 0.88) units/year. Likewise, there was no significant difference between groups in slope for the secondary outcomes zFEV1, zBMI, CFQ-R respiratory symptom score and the proportion of total disease and trapped air on chest computed tomography. CONCLUSIONS LCI-triggered BAL and associated antimicrobial treatment did not benefit clinical outcomes in a small cohort of closely monitored school-age children with CF.
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Affiliation(s)
- Christian Voldby
- CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
| | - Kent Green
- CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
| | - Thomas Kongstad
- CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
| | - Astrid Madsen Ring
- CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
| | - Rikke Mulvad Sandvik
- CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
| | - Marianne Skov
- CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
| | - Frederik Buchvald
- CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
| | - Tacjana Pressler
- CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark; CF Centre Copenhagen, Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
| | - Kim Gjerum Nielsen
- CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
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Eddy RL, Serajeddini H, Knipping D, Landman ST, Bosma KJ, Mackenzie CA, Dhaliwal I, Parraga G. Pulmonary Functional MRI and CT in a Survivor of Bronchiolitis and Respiratory Failure Caused by e-Cigarette Use. Chest 2020; 158:e147-e151. [PMID: 32544490 DOI: 10.1016/j.chest.2020.06.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 06/03/2020] [Accepted: 06/06/2020] [Indexed: 11/16/2022] Open
Abstract
Although nearly 3,000 e-cigarette-related hospitalizations have been reported in North America, the long-term outcomes in these patients have not been described. We followed an 18-year-old boy who survived acute critical illness and respiratory failure related to 5 months of e-cigarette use. Chronic irreversible airflow obstruction and markedly abnormal 129Xe MRI ventilation heterogeneity was observed and persisted 8 months after hospital discharge, despite improvement in quality-of-life and chest CT findings. Lung clearance index and oscillometry measures were also highly abnormal at 8 months postdischarge. Although 129Xe MRI ventilation abnormalities were dominant in the lung apices and central lung regions, the pattern of ventilation defects was dissimilar to ventilation heterogeneity observed in patients with obstructive lung disease, such as asthma and COPD. Our findings underscore the long-term functional impacts of e-cigarette-related lung injury in survivors of critical illness; longitudinal evaluations may shed light on the pathophysiologic mechanisms that drive e-cigarette-related lung disease.
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Affiliation(s)
- Rachel L Eddy
- Robarts Research Institute, Department of Medicine, Western University, London, ON, Canada; Department of Medical Biophysics, Department of Medicine, Western University, London, ON, Canada
| | - Hana Serajeddini
- Divisions of Respirology, Department of Medicine, Western University, London, ON, Canada
| | - Danielle Knipping
- Robarts Research Institute, Department of Medicine, Western University, London, ON, Canada
| | - Simon T Landman
- Divisions of Respirology, Department of Medicine, Western University, London, ON, Canada
| | - Karen J Bosma
- Critical Care, Department of Medicine, Western University, London, ON, Canada
| | - Constance A Mackenzie
- Divisions of Respirology, Department of Medicine, Western University, London, ON, Canada; Clinical Pharmacology and Toxicology, Department of Medicine, Western University, London, ON, Canada; Nunavut Poison Centre, Ontario, MB, Canada
| | - Inderdeep Dhaliwal
- Divisions of Respirology, Department of Medicine, Western University, London, ON, Canada
| | - Grace Parraga
- Robarts Research Institute, Department of Medicine, Western University, London, ON, Canada; Divisions of Respirology, Department of Medicine, Western University, London, ON, Canada.
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Multiple Breath Washout for Diagnosing Asthma and Persistent Wheeze in Young Children. Ann Am Thorac Soc 2020; 16:599-605. [PMID: 30580555 DOI: 10.1513/annalsats.201807-503oc] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Rationale: There is an unmet need for sensitive lung function tests for young children to aid in the diagnosis of asthma and wheezy disorders. We hypothesized that multiple breath washout (MBW) could be a valuable tool for such a purpose. Objectives: To compare the ability of MBW lung clearance index with traditional lung function measurements to discriminate between preschool children with well-controlled asthma/persistent wheeze and healthy children. Methods: We investigated 646 children from the COPSAC2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) mother-child cohort, who completed MBW testing with nitrogen, spirometry, and plethysmography before age 6 years. Asthma/persistent wheeze was prospectively diagnosed according to a validated symptom-based algorithm at the COPSAC clinic. Student's t tests and receiver operating characteristic curves were applied to analyze the discriminative ability of the lung function indices. Results: A total of 144 (22.3%) children were diagnosed with asthma/persistent wheeze during their first 6 years of life. Lung clearance index from MBW was not significantly different in children with versus those without asthma/persistent wheeze (mean standard deviation [SD] = 6.96 [1.14] vs. 6.95 [0.93], mean difference [95% confidence interval] = 0.02 [-0.18 to 0.22], P = 0.86, area under the curve [AUC] = 0.48), whereas significant differences were observed for specific airway resistance from plethysmography (1.21 kPa/s [0.31] vs. 1.14 kPa/s [0.25]; +0.07 kPa/s [0.02-0.13]; P < 0.01; AUC = 0.56) and spirometry forced expiratory volume in 1 second (FEV1) % predicted (99.4% [12.0] vs. 102.6% [12.5]; -3.2% [-5.6 to -0.9]; P < 0.01; AUC = 0.56) and forced expiratory flow at 25-75% (1.55 L/s [0.44] vs. 1.68 L/s [0.46]; -0.14 L/s [-0.22 to -0.05]; P < 0.01; AUC = 0.58). FEV1 (L/s) and FEV1/forced vital capacity ratio were not significantly different (P > 0.4). Conclusions: MBW, spirometry, and plethysmography are not sensitive tools for diagnosing mild asthmatic disease in young children.
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Heidenreich JF, Weng AM, Metz C, Benkert T, Pfeuffer J, Hebestreit H, Bley TA, Köstler H, Veldhoen S. Three-dimensional Ultrashort Echo Time MRI for Functional Lung Imaging in Cystic Fibrosis. Radiology 2020; 296:191-199. [PMID: 32343212 DOI: 10.1148/radiol.2020192251] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background In cystic fibrosis (CF), recurrent imaging and pulmonary function tests (PFTs) are needed for the assessment of lung function during disease management. Purpose To assess the clinical feasibility of pulmonary three-dimensional ultrashort echo time (UTE) MRI at breath holding for quantitative image analysis of ventilation inhomogeneity and hyperinflation in CF compared with PFT. Materials and Methods In this prospective study from May 2018 to June 2019, participants with CF and healthy control participants underwent PFTs and functional lung MRI by using a prototypical single breath-hold three-dimensional UTE sequence. Fractional ventilation (FV) was calculated from acquired data in normal inspiration and normal expiration. FV of each voxel was normalized to the whole lung mean (FVN), and interquartile range of normalized ventilation (IQRN; as a measure of ventilation heterogeneity) was calculated. UTE signal intensity (SI) was assessed in full expiration (SIN, normalized to aortic blood). Obtained metrics were compared between participants with CF and control participants. For participants with CF, MRI metrics were correlated with the standard lung clearance index (LCI) and PFT. Mann-Whitney U tests and Spearman correlation were used for statistical analysis. Results Twenty participants with CF (mean age, 17 years ± 9 [standard deviation]; 12 men) and 10 healthy control participants (24 years ± 8; five men) were included. IQRN was higher for participants with CF than for control participants (mean, 0.66 ± 0.16 vs 0.50 ± 0.04, respectively; P = .007). In the 20 participants with CF, IQRN correlated with obstruction markers forced expiratory volume in 1 second-to-forced vital capacity ratio (r = -0.70; 95% confidence interval [CI]: -0.92, -0.28; P < .001), mean expiratory flow 25% (r = 0.78; 95% CI: -0.95, -0.39; P < .001), and with the ventilation inhomogeneity parameter LCI (r = 0.90; 95% CI: 0.69, 0.96; P < .001). Mean SIN in full expiration was lower in participants with CF than in control participants (0.34 ± 0.08 vs 0.39 ± 0.03, respectively; P = .03). Conclusion Three-dimensional ultrashort echo time MRI in the lungs allowed for functional imaging of ventilation inhomogeneity within a few breath holds in patients with cystic fibrosis. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Wielpütz in this issue.
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Affiliation(s)
- Julius F Heidenreich
- From the Department of Diagnostic and Interventional Radiology (J.F.H., A.M.W., C.M., T.A.B., H.K., S.V.) and Department of Pediatrics (H.H.), University Hospital Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany; and Department of Application Development, Siemens Healthcare GmbH, Erlangen, Germany (T.B., J.P.)
| | - Andreas M Weng
- From the Department of Diagnostic and Interventional Radiology (J.F.H., A.M.W., C.M., T.A.B., H.K., S.V.) and Department of Pediatrics (H.H.), University Hospital Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany; and Department of Application Development, Siemens Healthcare GmbH, Erlangen, Germany (T.B., J.P.)
| | - Corona Metz
- From the Department of Diagnostic and Interventional Radiology (J.F.H., A.M.W., C.M., T.A.B., H.K., S.V.) and Department of Pediatrics (H.H.), University Hospital Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany; and Department of Application Development, Siemens Healthcare GmbH, Erlangen, Germany (T.B., J.P.)
| | - Thomas Benkert
- From the Department of Diagnostic and Interventional Radiology (J.F.H., A.M.W., C.M., T.A.B., H.K., S.V.) and Department of Pediatrics (H.H.), University Hospital Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany; and Department of Application Development, Siemens Healthcare GmbH, Erlangen, Germany (T.B., J.P.)
| | - Josef Pfeuffer
- From the Department of Diagnostic and Interventional Radiology (J.F.H., A.M.W., C.M., T.A.B., H.K., S.V.) and Department of Pediatrics (H.H.), University Hospital Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany; and Department of Application Development, Siemens Healthcare GmbH, Erlangen, Germany (T.B., J.P.)
| | - Helge Hebestreit
- From the Department of Diagnostic and Interventional Radiology (J.F.H., A.M.W., C.M., T.A.B., H.K., S.V.) and Department of Pediatrics (H.H.), University Hospital Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany; and Department of Application Development, Siemens Healthcare GmbH, Erlangen, Germany (T.B., J.P.)
| | - Thorsten A Bley
- From the Department of Diagnostic and Interventional Radiology (J.F.H., A.M.W., C.M., T.A.B., H.K., S.V.) and Department of Pediatrics (H.H.), University Hospital Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany; and Department of Application Development, Siemens Healthcare GmbH, Erlangen, Germany (T.B., J.P.)
| | - Herbert Köstler
- From the Department of Diagnostic and Interventional Radiology (J.F.H., A.M.W., C.M., T.A.B., H.K., S.V.) and Department of Pediatrics (H.H.), University Hospital Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany; and Department of Application Development, Siemens Healthcare GmbH, Erlangen, Germany (T.B., J.P.)
| | - Simon Veldhoen
- From the Department of Diagnostic and Interventional Radiology (J.F.H., A.M.W., C.M., T.A.B., H.K., S.V.) and Department of Pediatrics (H.H.), University Hospital Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany; and Department of Application Development, Siemens Healthcare GmbH, Erlangen, Germany (T.B., J.P.)
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Horsley AR, Alrumuh A, Bianco B, Bayfield K, Tomlinson J, Jones A, Maitra A, Cunningham S, Smith J, Fullwood C, Pandyan A, Gilchrist FJ. Lung clearance index in healthy volunteers, measured using a novel portable system with a closed circuit wash-in. PLoS One 2020; 15:e0229300. [PMID: 32097445 PMCID: PMC7041809 DOI: 10.1371/journal.pone.0229300] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 02/03/2020] [Indexed: 11/18/2022] Open
Abstract
Introduction Lung clearance index (LCI) is a sensitive measure of early lung disease, but adoption into clinical practice has been slow. Challenges include the time taken to perform each test. We recently described a closed-circuit inert gas wash-in method that reduces overall testing time by decreasing the time to equilibration. The aim of this study was to define a normative range of LCI in healthy adults and children derived using this method. We were also interested in the feasibility of using this system to measure LCI in a community setting. Methods LCI was assessed in healthy volunteers at three hospital sites and in two local primary schools. Volunteers completed three washout repeats at a single visit using the closed circuit wash-in method (0.2% SF6 wash-in tracer gas to equilibrium, room air washout). Results 160 adult and paediatric subjects successfully completed LCI assessment (95%) (100 in hospital, 60 in primary schools). Median coefficient of variation was 3.4% for LCI repeats and 4.3% for FRC. Mean (SD) LCI for the analysis cohort (n = 53, age 5–39 years) was 6.10 (0.42), making the upper limit of normal LCI 6.8. There was no relationship between LCI and multiple demographic variables. Median (interquartile range) total test time was 18.7 (16.0–22.5) minutes. Conclusion The closed circuit method of LCI measurement can be successfully and reproducibly measured in healthy volunteers, including in out-of-hospital settings. Normal range appears stable up to 39 years. With few subjects older than 40 years, further work is required to define the normal limits above this age.
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Affiliation(s)
- Alex R. Horsley
- Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom
- Manchester Adult CF Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom
- * E-mail:
| | - Amnah Alrumuh
- Institute of Applied Clinical Science, Keele University, Newcastle-under-Lyme, United Kingdom
- Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, United Kingdom
| | - Brooke Bianco
- Manchester Adult CF Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom
- NIHR Manchester Clinical Research Facility, Manchester, United Kingdom
| | - Katie Bayfield
- NIHR Manchester Clinical Research Facility, Manchester, United Kingdom
| | - Joanne Tomlinson
- Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, United Kingdom
| | - Andrew Jones
- Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom
- Manchester Adult CF Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom
| | - Anirban Maitra
- Royal Manchester Children’s Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
| | - Steve Cunningham
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
| | - Jaclyn Smith
- Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Catherine Fullwood
- Research and Innovation, Manchester University NHS Foundation Trust, Manchester, United Kingdom
- Centre for Biostatistics, Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Anand Pandyan
- Institute of Applied Clinical Science, Keele University, Newcastle-under-Lyme, United Kingdom
| | - Francis J. Gilchrist
- Institute of Applied Clinical Science, Keele University, Newcastle-under-Lyme, United Kingdom
- Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, United Kingdom
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Anagnostopoulou P, Latzin P, Jensen R, Stahl M, Harper A, Yammine S, Usemann J, Foong RE, Spycher B, Hall GL, Singer F, Stanojevic S, Mall MA, Ratjen F, Ramsey KA. Normative data for multiple breath washout outcomes in school-aged Caucasian children. Eur Respir J 2019; 55:13993003.01302-2019. [DOI: 10.1183/13993003.01302-2019] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Accepted: 12/10/2019] [Indexed: 12/19/2022]
Abstract
BackgroundThe multiple breath nitrogen washout (N2MBW) technique is increasingly used to assess the degree of ventilation inhomogeneity in school-aged children with lung disease. However, reference values for healthy children are currently not available. The aim of this study was to generate reference values for N2MBW outcomes in a cohort of healthy Caucasian school-aged children.MethodsN2MBW data from healthy Caucasian school-age children between 6 and 18 years old were collected from four experienced centres. Measurements were performed using an ultrasonic flowmeter (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) and were analysed with commercial software (Spiroware version 3.2.1, Eco Medics AG). Normative values and upper limits of normal (ULN) were generated for lung clearance index (LCI) at 2.5% (LCI2.5%) and at 5% (LCI5%) of the initial nitrogen concentration and for moment ratios (M1/M0 and M2/M0). A prediction equation was generated for functional residual capacity (FRC).ResultsAnalysis used 485 trials from 180 healthy Caucasian children aged from 6 to 18 years old. While LCI increased with age, this increase was negligible (0.04 units·year–1 for LCI2.5%) and therefore fixed ULN were defined for this age group. These limits were 7.91 for LCI2.5%, 5.73 for LCI5%, 1.75 for M1/M0 and 6.15 for M2/M0, respectively. Height and weight were found to be independent predictors of FRC.ConclusionWe report reference values for N2MBW outcomes measured on a commercially available ultrasonic flowmeter device (Exhalyzer D, Eco Medics AG) in healthy school-aged children to allow accurate interpretation of ventilation distribution outcomes and FRC in children with lung disease.
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Nuttall AGL, Velásquez W, Beardsmore CS, Gaillard EA. Lung clearance index: assessment and utility in children with asthma. Eur Respir Rev 2019; 28:28/154/190046. [PMID: 31748419 DOI: 10.1183/16000617.0046-2019] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Accepted: 07/26/2019] [Indexed: 11/05/2022] Open
Abstract
There is increasing evidence that ventilation heterogeneity and small airway disease are significant factors in asthma, with evidence suggesting that the small airways are involved from an early stage in childhood asthma. Spirometry is commonly used to monitor lung function in asthmatics; however, it is not sensitive to small airway disease. There has been renewed interest in multibreath washout (MBW) tests, with recognition of the lung clearance index (LCI) as a global index of abnormality in gas mixing of the lungs that therefore also reflects small airway disease. This review summarises the technical and practical aspects of the MBW/LCI in children, and the differences between commercially available equipment. Children with severe asthma are more likely to have an abnormal LCI, whereas most children with mild-to-moderate asthma have an LCI within the normal range, but slightly higher than age-matched healthy controls. Monitoring children with asthma with MBW alongside standard spirometry may provide useful additional information.
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Affiliation(s)
- Amy G L Nuttall
- Institute for Lung Health, NIHR Leicester Respiratory Biomedical Research Unit and Dept of Infection Immunity and Inflammation, University of Leicester, Leicester, UK.,Children's Hospital, University Hospitals Leicester, Leicester, UK
| | - Werner Velásquez
- Hospital de Especialidades Rodolfo Robles, Quetzaltenango, Guatemala
| | - Caroline S Beardsmore
- Institute for Lung Health, NIHR Leicester Respiratory Biomedical Research Unit and Dept of Infection Immunity and Inflammation, University of Leicester, Leicester, UK.,Children's Hospital, University Hospitals Leicester, Leicester, UK
| | - Erol A Gaillard
- Institute for Lung Health, NIHR Leicester Respiratory Biomedical Research Unit and Dept of Infection Immunity and Inflammation, University of Leicester, Leicester, UK .,Children's Hospital, University Hospitals Leicester, Leicester, UK
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New severity assessment in cystic fibrosis: signal intensity and lung volume compared to LCI and FEV1: preliminary results. Eur Radiol 2019; 30:1350-1358. [DOI: 10.1007/s00330-019-06462-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 07/30/2019] [Accepted: 09/16/2019] [Indexed: 10/25/2022]
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Ellemunter H, Steinkamp G. Lung clearance index to detect the efficacy of Aztreonam lysine inhalation in patients with cystic fibrosis and near normal spirometry - A single-centre feasibility study. PLoS One 2019; 14:e0221673. [PMID: 31498805 PMCID: PMC6733506 DOI: 10.1371/journal.pone.0221673] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 08/10/2019] [Indexed: 12/29/2022] Open
Abstract
Comparing the efficacy of inhaled antibiotics can be difficult in small groups of patients with cystic fibrosis and mild lung disease. In a feasibility study we compared Aztreonam lysine for inhalation solution (AZLI; Cayston®) to standard inhaled antibiotic therapy in patients with cystic fibrosis and near normal spirometry. To detect treatment responses we used both lung clearance index (LCI) and forced expiratory volume in one second (FEV1). At baseline, median FEV1 was 87% pred. and median LCI was 8.6 (upper limit of normal: 7.0). After 4 weeks, LCI improved by -0.36 after AZLI and deteriorated by +0.12 after tobramycin treatment (p = 0.039). No significant differences between treatments (p = 0.195) were observed using FEV1. These results suggest that lung clearance index can be used to detect treatment induced changes in subjects with mild lung disease.
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Affiliation(s)
- Helmut Ellemunter
- Cystic Fibrosis (CF) Centre at the Medical University of Innsbruck, Innsbruck, Austria
| | - Gratiana Steinkamp
- Cystic Fibrosis (CF) Centre at the Medical University of Innsbruck, Innsbruck, Austria
- Clinical Research and Medical Scientific Writing, Schwerin, Germany
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Yaacoby-Bianu K, Plonsky MT, Gur M, Bar-Yoseph R, Kugelman A, Bentur L. Effect of late preterm birth on lung clearance index and respiratory physiology in school-age children. Pediatr Pulmonol 2019; 54:1250-1256. [PMID: 31091024 DOI: 10.1002/ppul.24357] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Revised: 04/06/2019] [Accepted: 04/26/2019] [Indexed: 01/09/2023]
Abstract
BACKGROUND We hypothesized that former late preterm (LP) children have abnormal pulmonary physiology parameters, including uneven ventilation distribution, due to premature disruption of normal lung development. METHODS A cross-sectional study evaluating former LP children at the age of 6 to 12 years as compared to term controls. Demographics and child's and family history of asthma/atopy/smoking were recorded. The outcome parameters were spirometry, multiple breath washout (MBW) measurement by lung clearance index (LCI), 6-minute walk test (6MWT), symptoms related to asthma and allergy, and Godin Leisure-Time Exercise Questionnaire. RESULTS Twenty-nine former LP were compared to 30 term-control children (mean age, 8.2 ± 1.7 and 8.8 ± 1.8 years, respectively). LP had reduced forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) compared to term controls (FEV1 1.59 ± 0.48 vs 1.80 ± 0.39 L, P = 0.005 and FVC 1.73 ± 0.45 vs 1.99 ± 0.49 L, P = 0.009). There were no differences between the two groups regarding FEV1/FVC, forced expiratory flow between 25 and 75 (FEF25-75), LCI (7.10 ± 0.79 vs 6.96 ± 0.75, P = 0.50), 6MW distance, and weekly leisure-activity score. Former LP children had more episodes of wheezing and greater use of asthma medication. CONCLUSIONS This pilot study suggests that LP have lower pulmonary function tests (PFTs) but not ventilation inhomogeneity measured by LCI or functional disturbance. It is unclear if the differences in PFTs are due to late prematurity by itself or are the consequence of maternal and neonatal factors associated with LP. Further larger studies are required to assess the long-term respiratory consequences of LP birth.
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Affiliation(s)
- Karin Yaacoby-Bianu
- Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Moran T Plonsky
- Department of Pediatrics B, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Michal Gur
- Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Ronen Bar-Yoseph
- Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Amir Kugelman
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.,Department of Neonatal Intensive Care, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Lea Bentur
- Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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Fretzayas A, Douros K, Moustaki M, Loukou I. Applications of lung clearance index in monitoring children with cystic fibrosis. World J Clin Pediatr 2019; 8:15-22. [PMID: 31041164 PMCID: PMC6477151 DOI: 10.5409/wjcp.v8.i2.15] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 02/03/2019] [Accepted: 02/19/2019] [Indexed: 02/06/2023] Open
Abstract
A sensitive, reproducible and feasible measure of lung function for monitoring the respiratory health is a prerequisite for the optimization of management of the patients with cystic fibrosis (CF). Spirometry has been considered the method of choice, although it is applicable only in children older than 6 years of age, as good cooperation is necessary for its proper performance. However, over the last 15 years, scientific interest in gas dilution techniques and particularly in multiple breath wash out (MBW) method has been revived. The most commonly reported index of MBW is lung clearance index (LCI). The aim of this review is to present the most recent developments in the application of LCI as a monitoring index of respiratory status of CF patients. LCI is a sensitive and reproducible marker of ventilation inhomogeneity. It is more sensitive than spirometry and, unlike spirometry; it can be performed across the whole pediatric age range. Since it is dependent on body size, until at least the age of 6 years, the relative and not the absolute changes are more appropriate for providing clinically meaningful conclusion on ventilation inhomogeneity. Until now, MBW has been mainly used as a research tool. Based on the currently available data LCI cannot safely predict high-resolution computed tomography findings in children with CF, especially in infants. It can be used as an end-point measure for the assessment of beneficial effect of interventions. However, its utility as an outcome measure for the efficacy of therapeutic interventions seems to be dependent on the pathophysiologic mechanisms that underlie each intervention. It seems that more studies, especially longitudinal ones, are required in order to fully clarify the clinical usefulness of LCI, not only in the research setting, but also in every day practice of CF clinic.
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Affiliation(s)
- Andrew Fretzayas
- School of Medicine, University of Athens, Athens 11527, Greece
- Department of Pediatrics, Athens Medical Center, Athens University Medical School, Maroussi 15125, Greece
| | - Konstantinos Douros
- Respiratory Unit, Third Department of Pediatrics, Athens University Medical School, “Attikon” University Hospital, Haidari 12464, Greece
| | - Maria Moustaki
- Department of Cystic Fibrosis, “Agia Sofia”, Children’s Hospital, Athens 11527, Greece
| | - Ioanna Loukou
- Department of Cystic Fibrosis, “Agia Sofia”, Children’s Hospital, Athens 11527, Greece
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Gur M, Masarweh K, Toukan Y, Nir V, Bar-Yoseph R, Hanna M, Manor E, Hakim F, Bentur L. Six-minute walk, lung clearance index, and QOL in bronchiolitis obliterans and cystic fibrosis. Pediatr Pulmonol 2019; 54:451-456. [PMID: 30575341 DOI: 10.1002/ppul.24223] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 11/18/2018] [Accepted: 11/21/2018] [Indexed: 11/07/2022]
Abstract
INTRODUCTION The 6-min walk test (6MWT) predicts outcome in pulmonary hypertension. Recently, its use was reported in both cystic fibrosis (CF) and bronchiolitis obliterans (BO). While the 6MWT is a simple, non-invasive and inexpensive tool, lung clearance index (LCI) measurement requires expensive equipment and expertise. We aimed to evaluate 6MWT in BO and CF, and to compare to MBW (multiple breath washout), pulmonary function tests and quality of life (QOL). METHODS A prospective single center study assessing 6MWT, MBW, spirometry, whole-body plethysmography and QOL (SF-36 questionnaire) in BO and CF patients and correlations between them. RESULTS Thirty-three BO patients and 37 CF patients. LCI was significantly higher in BO (12.4 ± 4.2 vs 10.5 ± 3.4, P = 0.044) while FEF 25-75% was significantly lower in BO (43.9 ± 24.4 vs 60.8 ± 30.8, P = 0.014). 6MWD was 474.8 ± 76.3 in BO and 506.6 ± 70 in CF (P > 0.05). There was no correlation between 6MWD and LCI in these small study groups There were few correlation between spirometry prameters and 6MWD. In CF, SF-36 scores correlated with pulmonary functions. CONCLUSIONS The 6MWT is an easy-to-perform test that may be helpful in chronic lung diseases in regions with limited resources. However,with the current limited data, 6MWT cannot replace LCI or spirometry as a marker of disease progression. Is is suggested that, together with QOL, the 6MWT may provide a global estimation of the physiological and general well-being of these patients. Further larger multi-center studies are warranted to evaluate the correlations of 6MWT with pulmonary physiology parameters in various chronic diseases.
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Affiliation(s)
- Michal Gur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Kamal Masarweh
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Yazeed Toukan
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Vered Nir
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Ronen Bar-Yoseph
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Moneera Hanna
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Eynav Manor
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Fahed Hakim
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Lea Bentur
- Pediatric Pulmonary Institute and CF Center, Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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Metrock LK, Qayed M, Simon D, Cash T, O'Connor MG, Johnson S, Esiashvili N, Katzenstein HM. Respiratory Difficulties in Children With Underlying Asthma During Immunotherapy for High-risk Neuroblastoma. J Pediatr Hematol Oncol 2017; 39:e450-e453. [PMID: 28121746 DOI: 10.1097/mph.0000000000000782] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Treatment of high-risk neuroblastoma now includes antibody based antitumor immunotherapy as part of standard care. Although this therapy has resulted in dramatic improvements in survival, it is associated with significant side effects. Children with underlying respiratory issues, and in particular asthma, may be more susceptible to immunotherapy associated respiratory compromise and pulmonary complications. Early routine involvement of pulmonology care is warranted for these patients in an effort to allow maximal delivery of immunotherapy and minimize acute and long-term complications.
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Affiliation(s)
- Laura K Metrock
- *Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta †Division of Pediatric Pulmonology ∥Division of Radiation Oncology, Emory University, Atlanta, GA ‡Division of Pediatric Allergy, Immunology, and Pulmonology Medicine §Division of Pediatric Hematology/Oncology, Vanderbilt University School of Medicine, and Monroe Carell Jr Children's Hospital, Nashville, TN
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Oude Engberink E, Ratjen F, Davis SD, Retsch-Bogart G, Amin R, Stanojevic S. Inter-test reproducibility of the lung clearance index measured by multiple breath washout. Eur Respir J 2017; 50:50/4/1700433. [PMID: 28982773 PMCID: PMC5898949 DOI: 10.1183/13993003.00433-2017] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 07/06/2017] [Indexed: 01/15/2023]
Abstract
The lung clearance index (LCI) has strong intra-test repeatability; however, the inter-test reproducibility of the LCI is poorly defined. The aim of the present study was to define a physiologically meaningful change in LCI in preschool children, which discriminates changes associated with disease progression from biological variability. Repeated LCI measurements from a longitudinal cohort study of children with cystic fibrosis and age-matched controls were collected to define the inter-visit reproducibility of the LCI. Absolute change, the coefficient of variation, Bland–Altman limits of agreement, the coefficient of repeatability, intra-class correlation coefficient, and percentage changes were calculated. LCI measurements (n=505) from 71 healthy and 77 cystic fibrosis participants (aged 2.6–6 years) were analysed. LCI variability was proportional to its magnitude, such that reproducibility defined by absolute changes is biased. A physiologically relevant change for quarterly LCI measurements in health was defined as exceeding ±15%. In clinically stable cystic fibrosis participants, the threshold was higher (±25%); however, for measurements made 24 h apart, the threshold was similar to that observed in health (±17%). A percentage change in LCI greater than ±15% in preschool children can be considered physiologically relevant and greater than the biological variability of the test. Biological variability of lung clearance index is dependent on magnitude; % change is better for tracking patientshttp://ow.ly/tgbX30dBbCX
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Affiliation(s)
- Esther Oude Engberink
- Division of Respiratory Medicine, Dept of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada.,Division of Respiratory Medicine and Allergy, Dept of Pediatrics, Radboud University Medical Center Amalia Children's Hospital, Nijmegen, The Netherlands
| | - Felix Ratjen
- Division of Respiratory Medicine, Dept of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada.,Dept of Medicine, University of Toronto, Toronto, ON, Canada
| | - Stephanie D Davis
- Section of Pediatric Pulmonology, Allergy and Sleep Medicine, Dept of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA
| | - George Retsch-Bogart
- Division of Pediatric Pulmonology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Reshma Amin
- Division of Respiratory Medicine, Dept of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada.,Dept of Medicine, University of Toronto, Toronto, ON, Canada
| | - Sanja Stanojevic
- Division of Respiratory Medicine, Dept of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada .,Dept of Medicine, University of Toronto, Toronto, ON, Canada
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O'Neill K, Elborn JS, Tunney MM, O'Neill P, Rowan S, Martin S, Bradley JM. Training in multiple breath washout testing for respiratory physiotherapists. Physiotherapy 2017; 104:61-66. [PMID: 28822601 DOI: 10.1016/j.physio.2017.04.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Accepted: 04/13/2017] [Indexed: 11/26/2022]
Abstract
INTRODUCTION The development of multiple breath washout (MBW) testing in respiratory disease highlights the need for increased awareness amongst respiratory physiotherapists and a potential opportunity for professional development in the use of an important outcome measure for clinical trials. OBJECTIVES To rationalise how MBW may be a useful assessment tool for respiratory physiotherapists and to describe a local MBW training and certification programme for physiotherapists. RESULTS The respiratory Multidisciplinary Team in the Belfast Health and Social Care Trust (BHSCT) identified a need for MBW testing to be available to facilitate clinical research and assessment. A 2day training programme consisting of prereading preparation, self-directed learning, theory presentations, practical demonstrations and hands-on practice was developed and delivered. All participants underwent a certification process. CONCLUSION We have demonstrated the successful training and certification of clinical and research physiotherapists and encourage other respiratory physiotherapists to consider MBW test training.
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Affiliation(s)
- Katherine O'Neill
- Centre for Experimental Medicine, Queen's University Belfast, United Kingdom.
| | - J Stuart Elborn
- Centre for Experimental Medicine, Queen's University Belfast, United Kingdom
| | | | - Philip O'Neill
- Office for Digital Learning, Ulster University, United Kingdom
| | - Stephen Rowan
- South Eastern Health and Social Care Trust, United Kingdom
| | - Susan Martin
- Northern Ireland Clinical Trials Unit, Belfast Health and Social Care Trust, United Kingdom
| | - Judy M Bradley
- Northern Ireland Clinical Research Facility, Queen's University Belfast, United Kingdom
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Utility of Lung Clearance Index Testing as a Noninvasive Marker of Deployment-related Lung Disease. J Occup Environ Med 2017; 59:707-711. [DOI: 10.1097/jom.0000000000001058] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Grosse-Onnebrink J, Mellies U, Olivier M, Werner C, Stehling F. Chest physiotherapy can affect the lung clearance index in cystic fibrosis patients. Pediatr Pulmonol 2017; 52:625-631. [PMID: 28125158 DOI: 10.1002/ppul.23670] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 11/12/2016] [Accepted: 12/28/2016] [Indexed: 11/06/2022]
Abstract
OBJECTIVES The lung clearance index (LCI) is determined by multiple-breath washout lung function (MBW). It is increasingly used as an endpoint in clinical trials. Chest physiotherapy (CP) is part of routine cystic fibrosis (CF) care. Whether the LCI is useful in detecting short-term treatment effects of CP has not been sufficiently investigated. We assessed the short-term influence of CP with highly standardized high-frequency chest wall oscillation (HFCWO) on the LCI in CF patients. METHODS In this randomized controlled study, the LCI was obtained in 20 CF patients (7-34 years) hospitalized for infective pulmonary exacerbation prior to and immediately after a single treatment of HFCWO. Twenty-one control group CF patients (7-51 years) received no treatment. We calculated the coefficient of repeatability (CR) to estimate the clinical relevance of possible treatment effects. RESULTS HFCWO improved (ie, decreased) the LCI by a median of 0.9 (range -0.45; 3.47; P = 0.002); the LCI decreased in 15 of 20 intervention group patients. In five patients the decrease in LCI exceeded the CR (2.15), indicating a clinically relevant treatment effect; in five patients the LCI increased but did not exceed the CR. The LCI did not change significantly in the control group patients. CONCLUSIONS HFCWO can have a short-term decreasing effect on the LCI, but the treatment response is heterogeneous. In future trials using LCI as an endpoint, the timing of CP in relation to MBW should be considered a possible bias.
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Affiliation(s)
- Joerg Grosse-Onnebrink
- Department of General Pediatrics, Pediatric Respiratory Medicine Unit, University Children's Hospital Muenster, Muenster, Germany
| | - Uwe Mellies
- Department of Pediatric Pulmonology, University of Duisburg-Essen, Children's Hospital, Essen, Germany
| | - Margarete Olivier
- Department of Pediatric Pulmonology, University of Duisburg-Essen, Children's Hospital, Essen, Germany
| | - Claudius Werner
- Department of General Pediatrics, Pediatric Respiratory Medicine Unit, University Children's Hospital Muenster, Muenster, Germany
| | - Florian Stehling
- Department of Pediatric Pulmonology, University of Duisburg-Essen, Children's Hospital, Essen, Germany
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Saunders C, Bayfield K, Irving S, Short C, Bush A, Davies JC. Developments in multiple breath washout testing in children with cystic fibrosis. Curr Med Res Opin 2017; 33:613-620. [PMID: 27931123 DOI: 10.1080/03007995.2016.1268999] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND Lung clearance index (LCI) is becoming recognized as an important addition in the monitoring of pediatric cystic fibrosis (CF). The non-invasive technique is easy to perform in all ages, reproducible and increasingly being used in clinical trials. There is interest in utilizing it within the clinic setting but its current use is mostly as a research tool. The procedure is highly dependent on skilled operators and a relaxed testing environment is key to obtaining good quality measurements. CONCLUSIONS Standardization of LCI is part of an ongoing collaborative, multicenter process. This review describes the background to LCI, discusses technical issues and limitations and provides examples of its utility in clinical and research contexts.
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Affiliation(s)
- Clare Saunders
- a NHLI, Imperial College London , UK
- b Royal Brompton and Harefield NHS Foundation Trust , London , UK
| | - Katie Bayfield
- a NHLI, Imperial College London , UK
- b Royal Brompton and Harefield NHS Foundation Trust , London , UK
| | - Samantha Irving
- a NHLI, Imperial College London , UK
- b Royal Brompton and Harefield NHS Foundation Trust , London , UK
| | - Christopher Short
- a NHLI, Imperial College London , UK
- b Royal Brompton and Harefield NHS Foundation Trust , London , UK
| | - Andrew Bush
- a NHLI, Imperial College London , UK
- b Royal Brompton and Harefield NHS Foundation Trust , London , UK
| | - Jane C Davies
- a NHLI, Imperial College London , UK
- b Royal Brompton and Harefield NHS Foundation Trust , London , UK
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Gur M, Yaacoby-Bianu K, Ilivitzki A, Bar-Yoseph R, Nir V, Hakim F, Toukan Y, Bentur L. Lung Clearance Index (LCI) in Patients with Bronchiolitis Obliterans: A Preliminary Report and Comparison to Cystic Fibrosis Patients. Lung 2016; 194:1007-1013. [PMID: 27645685 DOI: 10.1007/s00408-016-9934-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2016] [Accepted: 08/17/2016] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Bronchiolitis obliterans (BO) is a chronic airway disease following an insult to the lower respiratory tract. Lung clearance index (LCI) measures ventilation inhomogeneity and has been studied in cystic fibrosis (CF). We aimed to evaluate LCI in BO and to compare it to LCI in CF patients. METHODS LCI was measured in BO patients, compared to CF patients, and correlated with spirometry and CT findings. RESULTS Twenty BO patients and 26 CF patients (with similar mean age and BMI) underwent evaluation. FEV1 % and FEF25-75 % predicted were significantly lower in the BO group (60.5 ± 17.8 vs. 72.7 ± 20.7, p = 0.041, and 42.8 ± 22.8 vs. 66.4 ± 37.4, p = 0.017, respectively). In both groups, LCI was inversely correlated with FVC %, FEV1 %, and FEF25-75 % predicted. LCI % was slightly higher (190.4 ± 63.5 vs. 164.9 ± 39.4, p = 0.1) and FRC gas % (measured by multiple breath washout) was significantly higher in the BO group (92.5 ± 35.9 vs. 71.3 ± 18, p = 0.014). The strength of statistical association between the lower FEF25-75 % values and the higher LCI values was stronger in BO patients. CONCLUSIONS Similar to CF, LCI may provide estimation of ventilation inhomogeneity in BO. The results indicate greater small airway involvement and air trapping in BO. Further prospective longitudinal studies evaluating the correlation of LCI measurements with multiple clinical and physiological parameters should be performed to assess the clinical benefit of LCI measurement in BO.
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Affiliation(s)
- Michal Gur
- Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, PO Box 9602, 31092, Haifa, Israel
| | - Karin Yaacoby-Bianu
- Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, PO Box 9602, 31092, Haifa, Israel
| | - Anat Ilivitzki
- Pediatric Radiology Unit, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Ronen Bar-Yoseph
- Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, PO Box 9602, 31092, Haifa, Israel
| | - Vered Nir
- Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, PO Box 9602, 31092, Haifa, Israel
| | - Fahed Hakim
- Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, PO Box 9602, 31092, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Yazeed Toukan
- Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, PO Box 9602, 31092, Haifa, Israel.,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Lea Bentur
- Pediatric Pulmonary Institute and CF Center, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, PO Box 9602, 31092, Haifa, Israel. .,Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
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Downing B, Irving S, Bingham Y, Fleming L, Bush A, Saglani S. Feasibility of lung clearance index in a clinical setting in pre-school children. Eur Respir J 2016; 48:1074-1080. [PMID: 27390277 DOI: 10.1183/13993003.00374-2016] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 05/24/2016] [Indexed: 01/26/2023]
Abstract
Lung function testing in pre-school children in the clinical setting is challenging. Most cannot perform spirometry and many infant lung function tests require sedation. Lung clearance index (LCI) derived from the multiple-breath washout (MBW) test has been shown to be sensitive to early disease changes but may be time consuming and so a shortened test (LCI0.5) may be more feasible in young children. We sought to establish feasibility of MBW in unsedated pre-school children in a clinic setting and hypothesised use of LCI0.5 would increase success rates.116 pre-school children (28 healthy controls and 88 with respiratory disease), median age 4.0 years (range 2-6 years), underwent MBW tests unsedated in a clinic setting, using sulfur hexafluoride as a tracer gas and an adapted photoacoustic gas analyser.81 (70%) out of 116 children completed LCI and 72% completed LCI0.5 measurement. Test success increased significantly in patients over 3 years (0% at <2.5 years, 33% at 2.5-3 years and 70% at >3 years, p<0.0001). LCI was elevated in those with respiratory disease compared with healthy controls.MBW is feasible in a clinic setting in unsedated pre-schoolers, particularly in those >3 years old, and LCI is raised in those with respiratory disease. Use of LCI0.5 did not increase success rate in pre-schoolers.
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Affiliation(s)
- Barrett Downing
- NHLI, Imperial College London, and Royal Brompton and Harefield NHS Foundation Trust, London, UK
| | - Samantha Irving
- NHLI, Imperial College London, and Royal Brompton and Harefield NHS Foundation Trust, London, UK
| | - Yvonne Bingham
- NHLI, Imperial College London, and Royal Brompton and Harefield NHS Foundation Trust, London, UK
| | - Louise Fleming
- NHLI, Imperial College London, and Royal Brompton and Harefield NHS Foundation Trust, London, UK
| | - Andrew Bush
- NHLI, Imperial College London, and Royal Brompton and Harefield NHS Foundation Trust, London, UK
| | - Sejal Saglani
- NHLI, Imperial College London, and Royal Brompton and Harefield NHS Foundation Trust, London, UK
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Grønbæk J, Hallas HW, Arianto L, Pedersen K, Thomsen A, Chawes BL, Bisgaard H. New time-saving predictor algorithm for multiple breath washout in adolescents. Pediatr Res 2016; 80:49-53. [PMID: 27002983 DOI: 10.1038/pr.2016.57] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 01/19/2016] [Indexed: 01/14/2023]
Abstract
BACKGROUND Multiple breath washout (MBW) is an informative but time-consuming test. This study evaluates the uncertainty of a time-saving predictor algorithm in adolescents. METHODS Adolescents were recruited from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC2000) birth cohort. MBW trials were performed at 13 y of age with Innocor model Inn00400 using sulfur hexafluoride (SF6) as tracer gas. Measurements were analyzed using a mixed model focusing on two prediction points doubling (t5%) and quadrupling (t10%) the standard end point (t2.5%). RESULTS One hundred and seventy-two MBW trials conducted in 78 adolescents with and without asthma from COPSAC2000 were included. At t10%, the washout time (WoT) was reduced by 41%, and an uncertainty of 0.159 lung clearance index (LCI) units was introduced (±2 SD), ±1.27). At t5%, the WoT was reduced by 25%, with an uncertainty of 0.083 LCI units (±0.558). The optimal prediction point, which led to most saved time and least uncertainty was t5%. CONCLUSION The predictor algorithm is capable of shortening the MBW test time but introduces an increasing uncertainty with earlier prediction points. This first-of-a-kind prediction algorithm holds promise in shortening the MBW test in children but should be used with caution in subjects with normal LCI values.
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Affiliation(s)
- Jonathan Grønbæk
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Henrik Wegener Hallas
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Lambang Arianto
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | | | | | - Bo Lund Chawes
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Hans Bisgaard
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
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Fuchs SI, Schwerk N, Pittschieler K, Ahrens F, Baden W, Bals R, Fähndrich S, Gleiber W, Griese M, Hülskamp G, Köhnlein T, Reckling L, Rietschel E, Staab D, Gappa M. Lung clearance index for monitoring early lung disease in alpha-1-antitrypsin deficiency. Respir Med 2016; 116:93-9. [PMID: 27296827 DOI: 10.1016/j.rmed.2016.04.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 03/23/2016] [Accepted: 04/26/2016] [Indexed: 11/28/2022]
Abstract
Patients with alpha-1-antitrypsin deficiency (AATD) and a PI-ZZ genotype are at high risk to develop severe emphysema during adulthood. However, little is known about early stages of emphysema and disease manifestation in other PI-types. Spirometry is commonly used for monitoring although early manifestation of emphysema is suspected within the peripheral airways that are not accessible by forced expiratory manoeuvres. We hypothesized that the Lung Clearance Index (LCI) derived from multiple breath nitrogen-washout (N2-washout) is useful to bridge this diagnostic gap. Patients from age 4 years onward and different PI-types performed N2-washout and spirometry. Results were compared to controls. 193 patients (4-79 years, 75% PI-ZZ) and 33 controls (8-60 years) were included. Mean (SD) LCI in patients was 9.1 (3.1) and 6.3 (0.6) in controls (p ≤ 0.001). 47% of adult patients with other than PI-ZZ genotypes and 39% of all patients with normal spirometry had abnormal LCIs. The LCI measured by N2-washout discriminates between patients with AATD and controls, reflects AATD related lung disease in all stages and appears to identify early peripheral lung changes in younger age than spirometry. We conclude that a normal spirometry does not exclude presence of AATD related lung disease even in genotypes other than PI-ZZ.
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Affiliation(s)
- Susanne I Fuchs
- Department of Paediatrics and Research Institute, Marien Hospital Wesel, Germany.
| | - Nicolaus Schwerk
- Paediatric Pulmonology, Allergology and Neonatology, Medical University Hannover, Germany
| | | | | | | | - Robert Bals
- Department 5, University of Saarland, Homburg, Germany
| | | | | | - Matthias Griese
- Dr. von Haunersches Kinderspital, Medical University Munich, Germany
| | - Georg Hülskamp
- Department of Paediatrics, Clemenshospital Münster, Germany
| | | | | | - Ernst Rietschel
- Cystic Fibrosis Centre, University Hospital of Cologne, Germany
| | - Doris Staab
- Paediatric Pulmonologie and Allergology, Charité Berlin, Germany
| | - Monika Gappa
- Department of Paediatrics and Research Institute, Marien Hospital Wesel, Germany
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