Isolated small airways obstruction predicts future chronic airflow obstruction: A multinational longitudinal study

Ben Knox-Brown, James Potts, Valentina Quintero Santofimio, Cosetta Minelli, Jaymini Patel, Najlaa Mohammed Abass, Dhiraj Agarwal, Rana Ahmed, Padukudru Anand Mahesh, Jayaraj Bs, Meriam Denguezli, Frits Franssen, Thorarinn Gislason, Christer Janson, Sanjay K. Juvekar, Parvaiz Koul, Andrei Malinovschi, Asaad Ahmed Nafees, Rune Nielsen, Stefanni Nonna M. ParaguasSonia Buist, Peter G.J. Burney, Andre F.S. Amaral

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2 Citations (Scopus)


Background Chronic airflow obstruction is a key characteristic of chronic obstructive pulmonary disease. We investigated whether isolated small airways obstruction is associated with chronic airflow obstruction later in life. Methods We used longitudinal data from 3957 participants of the multinational Burden of Obstructive Lung Disease study. We defined isolated small airways obstruction using the prebronchodilator mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FVC) (FEF 25-75) if a result was less than the lower limit of normal (<LLN) in the presence of a normal forced expiratory volume in 1 s to FVC ratio (FEV 1 /FVC). We also used the forced expiratory volume in 3 s to FVC ratio (FEV 3 /FVC) to define small airways obstruction. We defined chronic airflow obstruction as post-bronchodilator FEV 1 /FVC<LLN. We performed mixed effects regression analyses to model the association between baseline isolated small airways obstruction and chronic airflow obstruction at follow-up. We assessed discriminative and predictive ability by calculating the area under the receiver operating curve (AUC) and Brier score. We replicated our analyses in 26 512 participants of the UK Biobank study. Results Median follow-up time was 8.3 years. Chronic airflow obstruction was more likely to develop in participants with isolated small airways obstruction at baseline (FEF 25-75 less than the LLN, OR: 2.95, 95% CI 1.02 to 8.54; FEV 3 /FVC less than the LLN, OR: 1.94, 95% CI 1.05 to 3.62). FEF 25-75 was better than the FEV 3 /FVC ratio to discriminate future chronic airflow obstruction (AUC: 0.764 vs 0.692). Results were similar among participants of the UK Biobank study. Conclusion Measurements of small airways obstruction can be used as early markers of future obstructive lung disease.

Original languageEnglish
Article numbere002056
JournalBMJ Open Respiratory Research
Issue number1
Publication statusPublished - 20 Nov 2023


  • COPD epidemiology
  • Lung Physiology


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