Gender differences in small airways function


Dr Surya Kant, Professor and Head, Dept. of Respiratory Medicine, KGMU, UP, Lucknow. National Vice Chairman IMA-AMS    14 January 2023

Women with mild asthma have worse small airway dysfunction compared to men and their lung function declined more rapidly with age, according to a study published in Annals of Allergy, Asthma & Immunology.1


This cross-sectional, observational study compared the gender differences in the small airway function - measured by forced expiratory flow at 50% (FEF50%), at 75% (FEF75%) and between 25% and 75% (FEF25%-75%) - and FeNO level in 1609 patients (600 men and 1009 women) with mild asthma between February 2017 and December 2020. Spirometry, methacholine challenge tests (MCTs), fractional exhaled nitric oxide (FeNO) and impulse oscillometry measurements were performed for the participants.


Nearly 30% of the male patients had small airway disorder compared to ~47% of female study subjects. Out of the 600 men, 205 had bronchial hyperresponsiveness (BHR+) and 395 did not have BHR (BHR -).  Among women, 400 were BHR+ and 609 were BHR-.


In the age-matched participants, small airway function was better among males than in females; the FEF50% for men was 78.6% vs 72% for women; FEF75% was 67.5% vs 60.15%, respectively and FEF25%-75% was 73.7% vs. 67.4%, respectively. Men also had higher FeNO levels than the women participants; 42.0 ppb vs 29.0 ppb, respectively. Similar observations were noted on impulse oscillometry. FeNO levels were much lower among men who were current smokers (26 ppb) vs nonsmokers (46 ppb) vs ex-smokers (64 ppb). Among nonsmokers, the decline in small airway function and FeNO values occurred more quickly among women with asthma compared to men with asthma.


Researchers also determined the optimal cut-off values for small airway function and FeNO level for predicting a positive methacholine challenge test (MCT). The overall FEF values were 87.2% for FEF50%, 77.1% for FEF75% and 81.6% for FEF25%-75%. The FeNo cut-off was greater than 40 ppb for all patients. A gender difference was also observed for these values. For FEF25%-75%, the cut-off was 81.5% for males and 73.7% for females; for FEF50%, the values were 86.4% vs 76.9%, respectively. The cut-off for FeNO was 41.0 ppb in males and 35.0 ppb in females.


Several factors account for poorly-controlled asthma including history of acute exacerbations, incorrect inhaler use, failure to adhere to prescribed treatment. Recently, persistent uncontrolled inflammation in the peripheral small airways (≤ 2 mm), hithertho recognized as the “quiet zone” of the lung, leading to small airways dysfunction has been implicated as a factor contributing to uncontrolled asthma. It is better measured by impulse oscillometry than the routine spirometry.2


According to the authors, this is the first study to highlight the gender differences in small airway function and FeNO level in patients with mild asthma. The identification of cut-off values could further enhance the diagnostic accuracy.




  1. Zhang X, et al. Sex differences of small airway function and fractional exhaled nitric oxide in patients with mild asthma. Ann Allergy Asthma Immunol. 2022 Nov 16;S1081-1206(22)01916-0.  doi: 10.1016/j.anai.2022.11.010.
  2. Cottini M, et al. Small airway dysfunction and poor asthma control: a dangerous liaison. Clin Mol Allergy. 2021 May 29;19(1):7. doi: 10.1186/s12948-021-00147-8.

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