|
1
|
Huang LY, Huang B, Lv Z, Lu XD. Effects of acetylcysteine on micro-inflammation and pulmonary ventilation in chronic obstructive pulmonary disease exacerbation. World J Clin Cases 2024; 12:3482-3490. [PMID: 38983436 PMCID: PMC11229918 DOI: 10.12998/wjcc.v12.i18.3482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 04/22/2024] [Accepted: 04/23/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a serious complication of chronic obstructive pulmonary disease, often characterized by increased morbidity and mortality. In traditional Chinese medicine, AECOPD is linked to phlegm-heat and blood-stasis, presenting symptoms like thick sputum, fever, and chest pain. It has been shown that acetylcysteine inhalation in conjunction with conventional therapy significantly reduced inflammatory markers and improved lung function parameters in patients with AECOPD, suggesting that acetylcysteine may be an important adjunctive therapy for patients with phlegm-heat-blood stasis type AECOPD. AIM To investigate the effect of acetylcysteine on microinflammation and lung ventilation in patients with phlegm-heat and blood-stasis-type AECOPD. METHODS One hundred patients with phlegm-heat and blood-stasis-type AECOPD were randomly assigned to two groups. The treatment group received acetylcysteine inhalation (10% solution, 5 mL, twice daily) along with conventional therapy, whereas the control group received only conventional therapy. The treatment duration was 14 d. Inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor-alpha) in the serum and sputum as well as lung function parameters (forced expiratory volume in one second, forced vital capacity, and peak expiratory flow) were assessed pre- and post-treatment. Acetylcysteine inhalation led to significant reductions in inflammatory markers and improvements in lung function parameters compared to those in the control group (P < 0.05). This suggests that acetylcysteine could serve as an effective adjunct therapy for patients with phlegm-heat and blood-stasis-type AECOPD. RESULTS Acetylcysteine inhalation significantly reduced inflammatory markers in the serum and sputum and improved lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD compared with the control group. These differences were statistically significant (P < 0.05). The study concluded that acetylcysteine inhalation had a positive effect on microinflammation and lung ventilation function in patients with this type of AECOPD, suggesting its potential as an adjuvant therapy for such cases. CONCLUSION Acetylcysteine inhalation demonstrated significant improvements in reducing inflammatory markers in the serum and sputum, as well as enhancing lung ventilation function parameters in patients with phlegm-heat and blood-stasis type AECOPD. These findings suggest that acetylcysteine could serve as a valuable adjuvant therapy for individuals with this specific type of AECOPD, offering benefits for managing microinflammation and optimizing lung function.
Collapse
Affiliation(s)
- Li-Yuan Huang
- Department of Integration of Traditional Chinese and Western Medicine, School of Clinical Medicine, Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, China
| | - Bin Huang
- Department of Infectious Diseases, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu Province, China
| | - Zheng Lv
- Department of Zoology, School of Life Sciences, Changchun Normal University, Changchun 130032, Jilin Province, China
| | - Xiao-Dan Lu
- Precision Medical Center, Jilin Province General Hospital, Changchun 130021, Jilin Province, China
| |
Collapse
|
|
2
|
Ng D, Kerwin EM, White MV, Miller SD, Haughie S, Ward JK, Allan R. Clinical Bioequivalence of Wixela Inhub and Advair Diskus in Adults With Asthma. J Aerosol Med Pulm Drug Deliv 2020; 33:99-107. [PMID: 31634023 PMCID: PMC7133441 DOI: 10.1089/jamp.2019.1547] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 08/27/2019] [Indexed: 01/12/2023] Open
Abstract
Background: Wixela® Inhub® is a dry powder inhaler approved as a generic equivalent to Advair® Diskus® (fluticasone propionate [FP]/salmeterol fixed-dose combination) for patients with asthma or chronic obstructive pulmonary disease (COPD). This study aimed at confirming the local (lung) therapeutic equivalence of both the FP and salmeterol components of Wixela Inhub (test [T]) to Advair Diskus (reference [R]) after inhalation. Methods: This randomized, double-blind, double-dummy, placebo-controlled, parallel-group study in patients ≥18 years with mild-to-moderate persistent asthma compared the local therapeutic equivalence (using forced expiratory volume in 1 second [FEV1]) of FP/salmeterol (100/50 μg) after inhaled delivery via T and R. Results: Randomized patients (N = 1127) received T (n = 512), R (n = 512), or placebo (n = 103). T and R significantly increased day 1 FEV1 area under the effect curve over 12 hours of the change from baseline (AUC[0-12]) and day 29 trough FEV1 over placebo, indicating that these endpoints were sufficiently sensitive for evaluation of bioequivalence. On day 1, T and R each increased FEV1 AUC(0-12) over placebo (3.134 L•h [T], 2.677 L•h [R]; each p < 0.0001). Following twice-daily dosing for 28 days, T and R also each increased trough FEV1 (measured on day 29) over placebo (235 mL [T], 215 mL [R]; each p < 0.0001). Least-squares mean T/R ratios (90% confidence intervals) for day 1 FEV1 AUC(0-12) and day 29 trough FEV1 were 1.120 (1.016-1.237) and 1.069 (0.938-1.220), respectively, indicating that T and R were bioequivalent for both co-primary endpoints. FP/salmeterol was well tolerated when administered via either T or R. Conclusions: These results demonstrate that the therapeutic effects of Wixela Inhub are bioequivalent to Advair Diskus in the lung. Wixela Inhub represents a therapeutically equivalent new FP/salmeterol treatment option for use in the treatment of asthma and COPD.
Collapse
Affiliation(s)
- Dik Ng
- Mylan Pharma UK Ltd., Sandwich, Kent, United Kingdom
| | | | | | - S. David Miller
- Northeast Medical Research Associates, Inc., North Dartmouth, Massachusetts
| | - Scott Haughie
- Mylan Pharma UK Ltd., Sandwich, Kent, United Kingdom
| | | | - Richard Allan
- Mylan Pharma UK Ltd., Sandwich, Kent, United Kingdom
| |
Collapse
|
|
3
|
Haughie S, Allan R, Wood N, Ward J. Equivalent Systemic Exposure to Fluticasone Propionate/Salmeterol Following Single Inhaled Doses from Advair Diskus and Wixela Inhub: Results of Three Pharmacokinetic Bioequivalence Studies. J Aerosol Med Pulm Drug Deliv 2020; 33:34-42. [PMID: 31364911 PMCID: PMC7041328 DOI: 10.1089/jamp.2019.1537] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 06/17/2019] [Indexed: 01/07/2023] Open
Abstract
Background: Wixela® Inhub® was developed to deliver inhaled fluticasone propionate/salmeterol (FP/S) combination as a substitutable generic equivalent to Advair® Diskus®. These studies aimed to confirm the pharmacokinetic bioequivalence (BE) of FP/S after single doses of Wixela Inhub (test [T]) and Advair Diskus (reference [R]). Methods: Three open-label, randomized, two-way crossover, single-dose studies in healthy subjects (N = 66 each) compared the systemic exposure of FP and salmeterol after inhalation from three dose strengths of FP/S (100/50, 250/50, or 500/50 μg) delivered from T and R. Primary BE endpoints were the area under the plasma concentration-time curve from time = 0 to the last measurable concentration (AUC(0-t)) and the maximum observed plasma concentration (Cmax) for both FP and S. The BE acceptance criteria specified that the 90% confidence intervals (CIs) of the geometric mean T/R ratios for AUC(0-t) and Cmax can be contained within 0.80-1.25 for both FP and salmeterol. Results: Wixela Inhub met the acceptance criteria for BE for FP and salmeterol at each dose strength. Estimated AUC(0-t) and Cmax geometric mean ratios (T/R [90% CI]) for FP were, respectively, 1.04 (1.00-1.08) and 0.92 (0.87-0.96) for 100/50 μg FP/S, 1.07 (1.02-1.13) and 1.01 (0.95-1.07) for 250/50 μg, and 0.97 (0.92, 1.00) and 0.90 (0.86-0.93) for 500/50 μg. Estimated AUC(0-t) and Cmax ratios for salmeterol were, respectively, 1.08 (1.04-1.11) and 1.00 (0.94-1.04) for 100/50 μg FP/S, 1.03 (0.99-1.07) and 0.93 (0.87-1.00) for 250/50 μg, and 1.00 (0.96-1.04) and 0.86 (0.81-0.91) for 500/50 μg. FP/S at all doses via both T and R was comparably well tolerated. Conclusions: Wixela Inhub was bioequivalent to Advair Diskus at all three dose strengths for both FP and S, providing direct evidence of equivalent systemic safety and indirect evidence for equivalent pulmonary deposition.
Collapse
Affiliation(s)
| | | | | | - Jon Ward
- Mylan Pharma UK Ltd., Sandwich, United Kingdom
| |
Collapse
|
|
4
|
Singh D, Worsley S, Zhu CQ, Hardaker L, Church A. Umeclidinium/vilanterol versus fluticasone propionate/salmeterol in COPD: a randomised trial. BMC Pulm Med 2015; 15:91. [PMID: 26286141 PMCID: PMC4545560 DOI: 10.1186/s12890-015-0092-1] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Accepted: 08/04/2015] [Indexed: 11/10/2022] Open
Abstract
Background Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD). This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment. Methods Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg. Endpoints included 0–24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety. Results Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046–0.113; wmFEV1) and 0.090 L (0.055–0.125; trough FEV1) (both p < 0.001). UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL. Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George’s Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks. The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common. Conclusions Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment. Trial Registration NCT01822899 Registration date: March 28, 2013 Electronic supplementary material The online version of this article (doi:10.1186/s12890-015-0092-1) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Dave Singh
- University of Manchester, Medicines Evaluation Unit, Langley Building, University Hospital of South Manchester Foundations Trust, Southmoor Road, Manchester, M23 9QZ, UK.
| | - Sally Worsley
- Respiratory Medicines Development Centre, GSK, London, UK.
| | | | - Liz Hardaker
- Global Clinical Safety and Pharmacovigilance, GSK, London, UK.
| | - Alison Church
- Respiratory Medicines Development Center, GSK, Research Triangle Park, North Carolina, USA.
| |
Collapse
|
|
5
|
Asai K, Kobayashi A, Makihara Y, Johnson M. Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg combination therapy in Japanese patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2015; 10:803-11. [PMID: 25945045 PMCID: PMC4407765 DOI: 10.2147/copd.s79842] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
PURPOSE Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250) in Japanese patients with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26) or placebo (n=26) for 12 weeks. At the start and end of treatment, inflammation biomarkers (sputum and serum), lung function, and health status (COPD Assessment Test [CAT] questionnaire) were measured. RESULTS Although a numerical decrease in differential neutrophil count was observed from baseline, SFC 250 did not significantly reduce sputum neutrophils compared with placebo, nor were there significant changes from baseline in the other biomarkers (sputum or serum), lung function, or CAT, versus placebo. Squamous epithelial cell contamination in some sputum samples rendered them unacceptable for analysis, which reduced the sample size to n=19 (SFC 250) and n=10 (placebo). However, inclusion of contaminated samples did not affect the overall trend of the outcome. Ad hoc bootstrap statistical analysis showed a 27.9% (SFC 250) and 1.3% (placebo) decrease in sputum neutrophils. Sputum IL-8 decreased by 43.2% after SFC 250 but increased by 48.3% with placebo. Responder analyses showed 42% of patients had ≥20% decrease in neutrophils from baseline; and 47% of patients had a ≥200 pg/mL change in sputum IL-8 following SFC 250 versus 20% after placebo; both changes are considered clinically relevant. CONCLUSION This study provides additional information about inflammation in Japanese COPD patients and is the first to study the anti-inflammatory effects of SFC 250 in this context and population. In the primary analysis, SFC 250 did not produce significant changes from baseline in sputum neutrophil levels or other sputum or serum inflammatory markers compared with placebo. Secondary ad hoc statistical analysis showed that SFC 250 reduced the number of sputum neutrophils and IL-8 compared with placebo.
Collapse
Affiliation(s)
- Kazuhisa Asai
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | | | - Yukio Makihara
- Medical Affairs Respiratory Department, GlaxoSmithKline, Tokyo, Japan
| | | |
Collapse
|
|
6
|
Patel JG, Nagar SP, Dalal AA. Indirect costs in chronic obstructive pulmonary disease: a review of the economic burden on employers and individuals in the United States. Int J Chron Obstruct Pulmon Dis 2014; 9:289-300. [PMID: 24672234 PMCID: PMC3964024 DOI: 10.2147/copd.s57157] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Objective To review and summarize existing literature on the indirect burden of chronic obstructive pulmonary disease (COPD) in the US. Methods Medline, Scopus, and OvidSP databases were searched using defined search terms to identify relevant studies. Eligible studies were published in English between January 2000 and April 2012 and calculated the indirect burden of COPD in a US population in terms of prevalence, incidence or costs of productivity loss, disability, morbidity, or mortality. Results Of 53 studies identified, eleven met eligibility criteria, with data years spanning 1987–2009. Estimates of workforce participation range from 56% to 69% among individuals with COPD and from 65% to 77% among individuals without COPD. Approximately 13%–18% of those with COPD are limited in the amount or type of work they can do and one-third or more experience general activity limitation. Estimates of restricted activity days range from 27–63 days per year. Estimates of mean annual sick leave and/or disability days among employed individuals with COPD range from 1.3–19.4 days. Estimates of bed confinement range from 13–32 days per year. Estimated mean annual indirect costs were $893–$2,234/person (US dollars) with COPD ($1,521–$3,348 in 2010 [US dollars]) and varied with the population studied, specific cost outcomes, and economic inputs. In studies that assessed total (direct and indirect) costs, indirect costs accounted for 27%–61% of total costs, depending on the population studied. Conclusions COPD is associated with substantial indirect costs. The disease places a burden on employers in terms of lost productivity and associated costs and on individuals in terms of lost income related to absenteeism, activity limitation, and disability. Consideration of indirect as well as direct costs is necessary to gain a more complete view of the societal burden of COPD.
Collapse
Affiliation(s)
- Jeetvan G Patel
- Pharmacy Administration and Public Health, University of Houston, Houston, TX, USA ; US Health Outcomes, GlaxoSmithKline, Durham, NC, USA
| | | | - Anand A Dalal
- US Health Outcomes, GlaxoSmithKline, Durham, NC, USA
| |
Collapse
|