Bronchodilator responsiveness varies by time of day and season, with a decline throughout the day and higher rates in winter, according to a retrospective study analyzing data from 1,620 patients at Cambridge University Hospitals NHS Foundation Trust.
The findings, published in Thorax, showed that for every one-hour increment in the workday, the odds of a positive bronchodilator response decreased by 8%. Under the ATS/ERS 2005 criteria, 28% of patients tested in the morning (08:30-12:30) showed responsiveness compared to 22% in the afternoon (13:30-16:30). The effect was most pronounced in patients referred for asthma or suspected asthma.
Seasonal variation was also significant, with winter months showing the highest bronchodilator responsiveness. Compared to winter, patients tested in autumn had significantly lower odds of having bronchodilator responsiveness, but only for those with bronchodilator responsiveness according to the ATS/ERS 2005 definition.
The SPIROTIMETRY study analyzed spirometry data from adults tested between January 2016 and December 2023. Testing was conducted between 08:30 and 16:30 using the MasterScreen-PFT-Pro system, with a standardized 400 µg salbutamol dose administered via a metered-dose inhaler and spacer. Statistical analyses adjusted for age, sex, BMI, smoking history, and prebronchodilator FEV₁/FVC.
Of the participants, 62% were female, with a mean age of 53.2 years (SD 16.1) and BMI of 29.4 kg/m² (SD 7.1). Fifty-eight percent were referred for asthma or suspected asthma, and these patients had significantly higher odds of bronchodilator responsiveness.
The results are consistent with the recently published RADicA study, which found that patients self-reported their worst symptoms in the morning and night. Previous research has indicated that the clock protein REV-ERBα controls airway hyperresponsiveness at different times of day, and that knocking down the Rev-erbα gene abolishes the time-of-day effect.
The findings suggest that spirometry test timing may influence diagnostic outcomes, particularly in asthma assessments. The authors emphasize the importance of documenting test timing for consistency and suggest further research to confirm whether adjusting testing schedules could improve diagnostic accuracy.
"It is important that prospective studies are conducted to confirm our findings, with particular focus on repeated measurements of the same individuals at different times of the day," said Ben Knox-Brown, from Royal Papworth Hospital NHS Foundation Trust and Cambridge University Hospitals NHS Foundation Trust.
One author reported receiving consultation fees from ndd Medical Technologies. All other authors declared no conflicts of interest. Dr. Akhilesh Jha was funded by an MRC Clinician Scientist Fellowship (Reference MR/Y000935/1).
The authors reported no conflicts of interest.
