Seasonal variability of lung function and Asthma Quality of Life Questionnaire Scores in adults with uncontrolled asthma

Abstract

Introduction: Asthma exacerbations spike in the spring and autumn months, yet the seasonal variation of asthma symptoms and lung function is poorly studied.

Methods: Seasonal variation of lung function, rescue medication use and patient-reported symptoms was evaluated by post hoc analyses of the Phase III lebrikizumab (anti-IL-13) LAVOLTA I and II studies in 2148 subjects with uncontrolled asthma. Lung function measurements (prebronchodilator FEV1, forced vital capacity (FVC) and peak expiratory flow (PEF)), rescue medication use and Standardised Asthma Quality of Life Questionnaire (AQLQ(S)) were measured every 4 weeks over 52 weeks. By-month estimates normalised by hemispheric season were based on mixed-effect models with repeated measures (MMRM), adjusted by study stratification factors as covariates when appropriate. The dependency of clinical outcomes with seasonal variability was assessed by employing linear contrasts comparing hemisphere normalised December versus July group means from an MMRM regression and presented as the difference in means (adjusted 95% CI).

Results: FEV1, FVC and PEF, rescue medication use and AQLQ(S) progressively worsened towards winter, unlike spring and autumn surges in asthma exacerbations. The December versus July mean differences were: (1) PEF=-6.5 (-8.7 to -4.2) L/min, 2) prebronchodilator FEV1=-42 (-57 to -27) mL, (3) FVC=-41 (-59 to -23) mL and (4) AQLQ(S)=-0.15 (-0.19 to -0.1) units. Among AQLQ questions, discomfort or distress related to cough was most variable with respect to season (-0.33 (-0.42 to -0.24) units).

Discussion: Interpretation of interventional studies biased by seasonal exposures may be confounded by seasonal variability.

Trials registration numbers: NCT01867125 and NCT01868061.

Keywords: asthma; asthma epidemiology.

Conflict of interest statement

Competing interests: RB, XY, TS, JO, CTJH, JA and DFC are employees of Genentech, Inc and hold Roche stocks and/or options. JGM was previously an employee of Genentech at the time of this study.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Seasonal analysis of lung function and AQLQ outcomes. Hemisphere normalised (see Methods section) per-month least-squares means (lsmeans±SE) are plotted for (A) PEF, (B) pre-BD FEV1, (C) FVC, (D) rescue medication use (puffs) and (E) AQLQ(S). AQLQ(S), Standardised Asthma Quality of Life Questionnaire Scores; BD, bronchodilator; FVC, forced vital capacity; PEF, peak expiratory flow.