Chantale Diba

The effects of body weight on airway calibre

Increased wheeze and asthma diagnosis in obesity may be due to reduced lung volume with subsequent airway narrowing. Asthma (wheeze and airway hyperresponsiveness), functional residual capacity (FRC) and airway conductance (Gaw) were measured in 276 randomly selected subjects aged 28–30 yrs. Data were initially adjusted for smoking and asthma before examining relationships between weight and FRC (after adjustment for height), and between body mass index (BMI = weight·height−2) and Gaw (after adjustment for FRC) by multiple linear regression, separately for females and males. For males and females, BMI (±95% confidence interval) was 27.0±4.6 kg·m−2 and 25.6±6.0 kg·m−2 respectively, Gaw was 0.64±0.04 L·s−1·cmH2O−1 and 0.57±0.03 L·s−1·cmH2O−1, and FRC was 85.3±3.4 and 84.0±2.9% of predicted. Weight correlated independently with FRC in males and females. BMI correlated independently and inversely with Gaw in males, but only weakly in females. In conclusion, obesity is associated with reduced lung volume, which is linked with airway narrowing. However, in males, airway narrowing is greater than that due to reduced lung volume alone. The mechanisms causing airway narrowing and sex differences in obesity are unknown.

Airway re-narrowing following deep inspiration in asthmatic and nonasthmatic subjects.

After bronchoconstriction, deep inspiration (DI) causes dilatation followed by airway re-narrowing. Re-narrowing may be faster in asthmatic than nonasthmatic subjects. This study investigated the relationship between re-narrowing and the magnitude of both DI-induced dilatation and the volume-dependence of respiratory system resistance (Rrs) during tidal breathing. In 25 asthmatic and 18 nonasthmatic subjects the forced oscillation technique was used to measure Rrs at baseline and after methacholine challenge, during 1 min of tidal breathing, followed by DI to total lung capacity (TLC) and passive return to functional residual capacity (FRC). Dilatation was measured as the decrease in Rrs between end tidal inspiration and TLC, re-narrowing as Rrs at FRC immediately after DI, as per cent Rrs at end-tidal expiration, and volume dependent tidal fluctuation as the difference between mean Rrs at end-expiration and end-inspiration. Asthmatic subjects had greater re-narrowing, less dilatation, and greater tidal fluctuations both at baseline and after challenge. Re-narrowing correlated with baseline tidal fluctuation and inversely with dilatation. Both baseline tidal fluctuation and dilatation were significant independent predictors of re-narrowing. Following deep inspiration-induced dilatation, faster airway re-narrowing in asthmatic than nonasthmatic subjects is associated not only with reduced deep inspiration-induced dilatation but also with some property of the airways that is detectable prior to challenge as an increased volume dependence of resistance.

The Relationship Between Airflow Obstruction, Emphysema Extent, and Small Airways Function in COPD

BACKGROUND The severities of COPD (FEV(1) % predicted) and airflow obstruction (FEV(1)/FVC) are considered to be due to both emphysema and small airways disease. To our knowledge, this has not been previously confirmed by combined measurements of emphysema and of small airway function. We hypothesized that small airways disease and emphysema extent contribute independently to the severity of both COPD and airflow obstruction. METHODS Twenty-six subjects with COPD underwent measurements with forced oscillation technique (FOT) at 6 Hz and single-breath nitrogen washout. Respiratory system resistance, respiratory system reactance (Xrs), and expiratory flow limitation (EFL) index (measured as mean inspiratory Xrs − expiratory Xrs) were derived from FOT. Closing volume/vital capacity (CV/VC) was derived from the washout. Emphysema extent was measured as low attenuation areas < -910 Hounsfield units, expressed as a percentage of CT scan lung volume from multislice CT scans taken at total lung capacity. RESULTS Subjects were aged (mean ± SD) 69.6 ± 8.0 years. Postbronchodilator FEV(1) was 64.8 ± 19.8% predicted, and diffusing capacity of lung for carbon monoxide was 50.7 ± 15.8% predicted. Emphysema extent was 22.6% ± 15.0% CT scan volume. CV/VC was 16.9% ± 7.9%; Xrs, -3.72 ± 3.03 cm H(2)O/L/s; and EFL index, 3.88 ± 3.93 cm H(2)O/L/s. In multiple regression analyses, FEV(1)/FVC was predicted by both emphysema and CV/VC (model r(2) = 0.54, P < .0001) whereas FEV(1) % predicted was predicted by emphysema and EFL index (model r(2) = 0.38, P = .0014). CONCLUSIONS The severities of COPD and airflow obstruction are independently predicted by both small airways disease and emphysema extent.

Avoiding deep inspirations increases the maximal response to methacholine without altering sensitivity in non-asthmatics.

Airway hyperresponsiveness is characterised by a leftward shift of the dose-response curve (DRC) and an increase in the maximal response. Deep inspiration (DI) avoidance increases responsiveness in non-asthmatic, but not asthmatic, subjects. The aim was to determine the effect of DI avoidance on the sensitivity and maximal response of the FEV(1) DRC to methacholine. Thirteen non-asthmatic and ten asthmatic subjects underwent a standard cumulative high-dose methacholine challenge (0.1-200μmol). Subsequently, on separate days, increasing single doses of methacholine were administered after 10min of DI avoidance. A sigmoidal equation was fitted to the data to obtain values for α, the position constant, as a measure of sensitivity. The fall in FEV(1) at the highest common dose was used as a measure of the maximal response. The change in flow at 40% control vital capacity on the maximal (V˙40m) and partial (V˙40p) curves were calculated from the first manoeuvre after methacholine and the ratio of the values for V˙40m and V˙40p was calculated as a measure of the bronchodilator effect of DI (BD(DI)). In non-asthmatic subjects, avoiding DI increased the maximum fall in FEV(1) at the highest common dose (p=0.0001) but did not alter α (p=0.75). Avoiding DI before challenge did not alter BD(DI) (p=0.13). DI avoidance had no effect on airway responsiveness in asthmatic subjects. In non-asthmatic subjects, DI avoidance increases airway responsiveness by increasing the maximal response, but does not alter the sensitivity, suggesting that the loss of the effect of DI in asthma contributes to excessive bronchoconstriction.

Day-to-day variability of oscillatory impedance and spirometry in asthma and COPD

Variability in airway function may be a marker of disease activity in COPD and asthma. The aim was to determine the effects of repeatability and airway obstruction on day-to-day variability in respiratory system resistance (Rrs) and reactance (Xrs) measured by forced oscillation technique (FOT). Three groups of 10 subjects; normals, stable asthmatic and stable COPD subjects underwent daily FOT recordings for 7 days. Mean total and inspiratory Rrs and Xrs, and expiratory flow limitation (EFL) Index (inspiratory - expiratory Xrs), were calculated. The ICCs were high for all parameters in all groups. Repeatability, in terms of absolute units, correlated with airway obstruction and was therefore lowest in COPD. Day-to-day variability was due mostly to repeatability, with a small contribution from the mean value for some parameters. FOT measures are highly repeatable in health, stable asthma and COPD in relation to the wide range of measures between subjects. For home monitoring in asthma and COPD, either the coefficient of variation or individualized SDs could be used to define day-to-day variability.

Improved respiratory system conductance following bronchodilator predicts reduced exertional dyspnoea.

BACKGROUND In COPD, improvements in lung mechanics following bronchodilator, measured using the forced oscillation technique (FOT), are more sensitive than spirometry at detecting improvement in lung function following bronchodilator. The relationship between these improvements in lung mechanics and improvements in functional outcomes, such as exertional dyspnoea, following bronchodilator, in COPD is unknown. METHODS 17 COPD subjects were recruited into a double blind placebo controlled randomised cross over study. Dyspnoea was induced using a standardised six-minute walk test (6 MWT), and measured by borg score throughout the test. Measurement of respiratory system conductance (Grs), respiratory system reactance (Xrs), inspiratory capacity (IC) and spirometry were made at baseline and 1 h after a single dose of either 18 μg of tiotropium bromide plus 200 μg salbutamol, or placebo. RESULTS Subjects had a mean baseline FEV(1) of 45.5 ± 11.0% predicted. The bronchodilator induced reduction in exertional dyspnoea correlated significantly with the increase in Grs (r(s) = 0.59, p = 0.01) and approached significance with FEV(1) (r(s) = 0.45, p = 0.07) but not with FVC (r(s) = 0.30, p = 0.24), Xrs (r(s) = 0.19, p = 0.47) or IC (r(s) = -0.08, p = 0.78). Increase in Grs was the best and sole predictor of reduction in exertional dyspnoea, explaining 41% of the variance. There was no additional contribution to the model from the increase in FEV(1) or IC. CONCLUSION Bronchodilator induced improvements in exertional dyspnoea in moderate to severe COPD are predicted by improvements in Grs, measured by FOT, independent of improvements in spirometry or hyperinflation. The findings suggest that FOT may be useful for measuring response to bronchodilator in COPD.

Expiratory flow limitation relates to symptoms during COPD exacerbations requiring hospital admission.

Background Expiratory flow limitation (EFL) is seen in some patients presenting with a COPD exacerbation; however, it is unclear how EFL relates to the clinical features of the exacerbation. We hypothesized that EFL when present contributes to symptoms and duration of recovery during a COPD exacerbation. Our aim was to compare changes in EFL with symptoms in subjects with and without flow-limited breathing admitted for a COPD exacerbation. Subjects and methods A total of 29 subjects with COPD were recruited within 48 hours of admission to West China Hospital for an acute exacerbation. Daily measurements of post-bronchodilator spirometry, resistance, and reactance using the forced oscillation technique and symptom (Borg) scores until discharge were made. Flow-limited breathing was defined as the difference between inspiratory and expiratory respiratory system reactance (EFL index) greater than 2.8 cmH2O·s·L−1. The physiological predictors of symptoms during recovery were determined by mixed-effect analysis. Results Nine subjects (31%) had flow-limited breathing on admission despite similar spirometry compared to subjects without flow-limited breathing. Spirometry and resistance measures did not change between enrolment and discharge. EFL index values improved in subjects with flow-limited breathing on admission, with resolution in four patients. In subjects with flow-limited breathing on admission, symptoms were related to inspiratory resistance and EFL index values. In subjects without flow-limited breathing, symptoms related to forced expiratory volume in 1 second/forced vital capacity. In the whole cohort, EFL index values at admission was related to duration of stay (Rs=0.4, P=0.03). Conclusion The presence of flow-limited breathing as well as abnormal respiratory system mechanics contribute independently to symptoms during COPD exacerbations.