Is there a correlation between the changes in airway inflammation and the changes in respiratory mechanics after vaping in patients with asthma?

Abstract

BACKGROUND

Electronic cigarettes (ECs) have been promoted as alternatives to traditional cigarettes.

AIM

To investigate ECs’ effects on respiratory system, especially in patients with respiratory diseases.

METHODS

We randomly selected 25 smokers with stable moderate asthma and matched them with 25 healthy smokers. All were subjucted to pulmonary function tests (PFTs), impulse oscillometry (IOS), fraction exhaled Nitric Oxide (FeNO), exhaled breathe condensate (EBC) and biomarker measurements before and after vaping one nicotine-containing EC.

RESULTS

The increase in FeNO 30 minutes after EC, reflecting airway inflammation, significantly correlated with increase of residual volume (RV), total lung capacity, respiratory impedance at 5 Hz (Z5Hz) and respiratory resistance at 5 and 20 Hz (R5Hz and R20Hz). No significant correlations were found between EBC biomarkers' changes and respiratory mechanics.

CONCLUSION

This is the first study demonstrating that the changes in airway inflammation caused by EC have direct effects in respiratory mechanics of asthmatic patients.

Key Words: Asthma, Electronic cigarette, Airway inflammation, Lung function, Impulse oscillometry, FeNO

Core Tip: This is the first study that correlates the acute changes in pulmonary function and in airway inflammation in patients with asthma after vaping one electronic cigarette.

INTRODUCTION

Electronic cigarette (EC) is a novel smoking product promoted to replace tobacco cigarette in smokers' daily habits. However, despite the fact that the effects of the tobacco cigarette have been investigated thoroughly the last decades, this is not the case for EC. There is evidence that EC have several acute effects on lung function of healthy individuals[1-6], and on lung function and airway inflammation of patients with asthma[4-6] and chronic obstructive pulmonary disease (COPD)[6,7]. In a previous study, we have evaluated the acute effects of EC on lung function and airway inflammation in patients with asthma compared to healthy individuals[4]. However, we did not evaluate the possible correlations of the changes on airway inflammation with the acute effects of EC on lung function.

With this study we investigate the correlations between the changes in airway inflammation, reflected by the changes in fraction exhaled Nitric Oxide (FeNO) and exhaled breathe condensate (EBC) biomarkers, with the changes in pulmonary function tests (PFTs) and impulse oscillometry after vaping one nicotine-containing EC.

MATERIALS AND METHODS

Ethical approval

The protocol of this study was approved by the Ethics Committee of the Medical School, Aristotle University of Thessaloniki, reference 369-8/22.2.2017, before the initiation of enrolment and all participants gave their written informed consent. The protocol of the study was also registered in ISRCTN-registry (ISRCTN89151172).

Data collection process

The participants in this study[4] were divided into two groups: (1) The “asthmatic group” which consisted of asthmatic patients with moderate persistent stable asthma well controlled by receiving “step 3” treatment according to global initiative for asthma (GINA) guidelines[8]; and (2) the “control group” which consisted of healthy individuals. The participants of both groups were current every day smokers[9]. Exclusion criteria for the asthmatic group were: (1) Age under 18 years; (2) an acute asthma exacerbation the last month before enrollment; (3) a change in the asthma medication the last month before enrollment; and (4) another acute or chronic disease apart from asthma the last two weeks before enrollment. Out of 87 eligible patients, 25 were recruited by using a random number generator. Exclusion criteria for the control group were: (1) Age under 18 years; and (2) the existence of any acute or chronic disease the last two weeks before enrollment. The recruitment of the 25 participants of the control group was made after matching them with those of the asthmatic group for gender, age, body mass index and smoking history (number of packyears).

Methodology

All participants were subjected to PFTs (spirometry, static lung volumes and Diffusion Lung Capacity for Carbon Monoxide)[10], total respiratory resistances measurement with an impulse oscillometry system (IOS)[11], FeNO measurement[12] and EBC gathering[13] for measurement of pH[13] and of concentrations of Interleukins 1b, 4, 5, 6, 8, 10, 13 and 17A and tumor necrosis factor-alpha with flow cytometry and of concentrations of 8-Isoprostane and leukotriene B4 with enzyme-linked immunosorbent assay[13]. Subsequently, participants vaped an EC, which had the same concentration of nicotine in the cartridge (medium nicotine content) and was of the same company. The composition of the e-liquid had been analyzed in a previous study[1]. Participants of both groups vaped the EC for five minutes (10 puffs with 30-second intervals between puffs). A new cartridge and atomiser were used for every participant. During EC inhalation two asthmatic patients presented mild cough and wheezing, which resolved automatically after a few minutes without necessitate reliever medication usage. Fifteen minutes after vaping the participants were subjected again to PFTs and IOS measurements and 30 min after vaping they were subjected to a new FeNO measurement and EBC gathering.

Data monitoring

Statistical analysis was performed using the SPSS software. All variables were continuous. To investigate for correlations between the changes in airway inflammation and the changes in respiratory mechanics linear regression was used between the difference in FeNO and in EBC biomarkers and the difference in PFTs and in IOS before and after the vaping of the EC in both groups.

RESULTS

There were no significant correlations between the changes in FeNO and the changes in respiratory mechanics before and after EC in the control group (Table 1). On the other hand, the difference in FeNO before and after EC in the asthmatics was significantly correlated with the corresponding differences in residual volume (RV), total lung capacity and respiratory impedance at 5 Hz (Z5Hz) (Table 1). Furthermore, the difference in FeNO before and after EC in the asthmatics was correlated with the corresponding differences in respiratory resistance at 5 and 20 Hz (R5Hz and R20Hz) at the limit of significance, where the number 0.000 was the lowest limit of the 95% of the confidence intervals (Table 1). However no significant correlations were found between the changes in the EBC biomarkers and the changes in respiratory mechanics before and after EC neither in the asthmatic nor in the control group.

Table 1 Linear regression between the difference in fraction exhaled Nitric Oxide (particles per billion) and the difference in pulmonary function tests and in impulse oscillometry before and after the vaping of one electronic cigarette.

Conrol group (n = 25)
Variable	Unstandardized coefficients (B) (95%CI)	Standardised coefficients (r)	P value
diff_FEV1 (L)	0.004 (-0.009–0.016)	0.131	0.53
diff_FVC (L)	-0.004 (-0.021–0.014)	-0.089	0.67
diff_FEV1/FVC (%)	0.096 (-0.216–0.407)	0.131	0.53
diff_PEF (L/s)	-0.065 (-0.166–0.035)	-0.269	0.19
diff_FEF25-75 (L/s)	0.000 (-0.053–0.054)	0.004	0.99
diff_RV (L)	0.010 (-0.005–0.025)	0.281	0.17
diff_TLC (L)	0.001 (-0.018–0.019)	0.015	0.94
diff_Z5Hz (kPa/L/s)	0.000 (-0.006–0.006)	-0.012	0.96
diff_R5Hz (kPa/L/s)	-0.001 (-0.007–0.004)	-0.112	0.59
diff_R20Hz (kPa/L/s)	-0.001 (-0.006–0.000)	-0.044	0.84
Asthma group (N = 25)
diff_FEV1 (L)	-0.007 (-0.016–0.002)	-0.327	0.11
diff_FVC (L)	0.005 (-0.005–0.015)	0.203	0.33
diff_FEV1/FVC (%)	-0.027 (-0.173–0.119)	-0.080	0.71
diff_PEF (L/sec)	-0.010 (-0.087–0.066)	-0.059	0.78
diff_FEF25-75 (L/s)	-0.007 (-0.033–0.020)	-0.110	0.60
diff_RV (L)	0.027 (0.005–0.049)	0.465	0.019
diff_TLC (L)	0.018 (0.005–0.031)	0.519	0.008
diff_Z5Hz (kPa/L/s)	0.005 (0.000–0.010)	0.402	0.046
diff_R5Hz (kPa/L/s)	0.005 (0.000–0.010)	0.386	0.057
diff_R20Hz (kPa/L/s)	0.003 (0.000–0.006)	0.358	0.078

FeNO: Fractional exhaled Nitric Oxide; ppb: Particles per billion; EC: Electronic cigarette; N: Number; CI: Confidence intervals; diff: Difference; FEV1: Forced expiratory volume in 1 second; L: Liters; FVC: Forced vital capacity; PEF: Peak expiratory flow; sec: Second; FEF25-75: Forced expiratory flow between 25% and 75% of FVC; RV: Residual volume; TLC: Total lung capacity; Z5Hz: Respiratory impedance at 5 Hz; Hz: Hertz; kPa: Kilopascal, R5Hz; R20Hz: Respiratory resistance at 5, 20 Hz.

DISCUSSION

FeNO has been associated with Th2 regulated asthma, reflecting eosinophilic inflammation[14]. Z5Hz is increased in worsening asthma[4,5], and the same applies for both R20Hz and R5Hz which reflect large and total airway resistance respectively[4,5]. The association between the changes in FeNO and in Z5Hz, R5Hz and R20Hz in the asthmatics after vaping could be attributed to the aggravation of airway inflammation in these patients (increase of FeNO), leading to bronchoconstriction (increase in impulse oscillometry indices), something that was not the case for the control group.

The increase of RV and TLC indicates the existence of air trapping and hyperinflation in obstructive lung diseases[15,16]. The correlation between the difference in FeNO before and after EC and the corresponding differences in RV and TLC in the asthmatic patients means that the deterioration of the airway inflammation is significantly associated with air trapping and hyperinflation, something not observed in the control group. This is particularly interesting since these defects are not as common in asthma as in COPD and when they are observed in asthma, they are associated with longer disease duration and fixed airflow obstruction[17,18].

Study limitations

The main limitation of this study is the relatively small number of participants in each group. Perhaps, this is the reason why the correlation between the difference in FeNO and the difference in R5Hz and R20Hz were at the limit of significance and there was no statistically significant correlation between the difference in FeNO and the differences in other key asthma indices such as forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow and forced expiratory flow between 25% and 75% of FVC (FEF25-75). Possibly for the same reason there were no significant correlations between the changes in the EBC biomarkers and the changes in respiratory mechanics. Additional limitations of the study are that the measurements during the follow up were assessed only in one timepoint after EC, and only a specific brand of EC was used. Asthma is a chronic inflammatory airway disease that requires a long period of time for treatment and evaluation. Evaluating only the changes in lung function related indices or markers after a single inhalation of EC might not illustrate the effect of EC on asthma lung function. Additionally, only well controlled asthmatic patients of GINA “step-3” were evaluated. All the asthmatic patients studied were receiving treatment with inhaled corticosteroids (ICS) and it is possible that the presence of ICS could have implicated with the changes in lung function and airway inflammation[19,20], after the use of the EC.

CONCLUSION

In conclusion, this study demonstrates that there is a direct association between airway inflammation and respiratory mechanics in patients with asthma after the use of EC, even in patients receiving ICS. As EC becomes more popular, there is an urgent need for studies which will assess its effects in human health, especially in certain group of respiratory patients as those with asthma.

ARTICLE HIGHLIGHTS

Research background

Electronic cigarette (EC) is a novel smoking product promoted to replace tobacco cigarette in smokers' daily habits. However, despite the fact that the effects of the tobacco cigarette have been investigated thoroughly the last decades, this is not the case for EC. There is evidence that EC have several acute effects on lung function of healthy individuals, and on lung function and airway inflammation of patients with asthma and chronic obstructive pulmonary disease. In a previous study, we have evaluated the acute effects of EC on lung function and airway inflammation in patients with asthma compared to healthy individuals. However, we did not evaluate the possible correlations of the changes on airway inflammation with the acute effects of EC on lung function.

Research motivation

With this study we investigate the correlations between the changes in airway inflammation, reflected by the changes in fraction exhaled Nitric Oxide (FeNO) and exhaled breathe condensate (EBC) biomarkers, with the changes in pulmonary function tests (PFTs) and impulse oscillometry after vaping one nicotine-containing EC.

Research objectives

With this study we investigate the correlations between the changes in airway inflammation, reflected by the changes in FeNO and EBC biomarkers, with the changes in PFTs and impulse oscillometry after vaping one nicotine-containing EC.

Research methods

The protocol of this study was approved by the Ethics Committee of the Medical School, Aristotle University of Thessaloniki, reference 369-8/22.2.2017, before the initiation of enrolment and all participants gave their written informed consent. The protocol of the study was also registered in ISRCTN-registry (ISRCTN89151172).

Research results

There were no significant correlations between the changes in FeNO and the changes in respiratory mechanics before and after EC in the control group. On the other hand, the difference in FeNO before and after EC in the asthmatics was significantly correlated with the corresponding differences in residual volume, total lung capacity and respiratory impedance at 5 Hz. Furthermore, the difference in FeNO before and after EC in the asthmatics was correlated with the corresponding differences in respiratory resistance at 5 and 20 Hz (R5Hz and R20Hz) at the limit of significance, where the number 0.000 was the lowest limit of the 95% of the confidence intervals. However no significant correlations were found between the changes in the EBC biomarkers and the changes in respiratory mechanics before and after EC neither in the asthmatic nor in the control group.

Research conclusions

In conclusion, this study demonstrates that there is a direct association between airway inflammation and respiratory mechanics in patients with asthma after the use of EC, even in patients receiving inhaled corticosteroids.

Research perspectives

As EC becomes more popular, there is an urgent need for studies which will assess its effects in human health, especially in certain group of respiratory patients as those with asthma.