Small airway function, fractional exhaled oxide differ in men, women with mild asthma
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Women with mild asthma have worse small airway function, lower fractional exhaled nitric oxide and more prominent declines in these parameters with age than men, according to a study published in Annals of Allergy, Asthma & Immunology.
Sex-based stratification with different cutoff values could improve diagnoses, Xue Zhang, PhD, of the department of respiratory and critical care medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine in Shanghai, China, and colleagues wrote.
The cross-sectional, double-centered, observational study examined 600 men and 1,009 women aged 18 to 75 years with FEV1 of 80% or higher and suspected asthma symptoms between February 2017 and December 2020.
Patients underwent high-resolution CT, spirometry, methacholine challenge tests (MCTs) and FeNO measurements, with 458 men and 764 women also receiving blood tests and 227 men and 382 women undergoing measurement for impulse oscillometry (IOS).
Overall, 205 of the men and 400 of the women were positive for bronchial hyperresponsiveness (BHR+), comprising 37.6% of the total study population.
Women had worse small airway function — measured by forced expiratory flow at 50% (FEF50%), at 75% (FEF75%) and between 25% and 75% (FEF25%-75%) — than age-matched men among patients with BHR+, the researchers found.
Specifically, BHR+ men had significantly higher FEF50% (78.6% vs. 72%), FEF75% (67.5% vs. 60.15%) and FEF25%-75% (73.7% vs. 67.4%; P < .001 for all) than BHR+ women, with similar trends noted on IOS measurements.
The researchers considered patients to have small airway disorder (SAD) if two of their FEF50%, FEF75% or FEF25%-75% were less than 65% of the predicted values, which occurred in fewer men (29.27% vs. 46.75%; P = .001).
However, BHR+ women had better large airway function as measured by the ratio of FEV1 to forced vital capacity (FVC) than men (81.22% vs. 79.94%).
FeNO levels also were significantly higher among BHR+ men vs. women (42 ppb vs. 29 ppb; P <. 001), with 43.9% of BHR+ men vs. 31.75% of BHR+ women showing FeNO levels exceeding 50 ppb.
Also in the BHR+ population, current smokers had lower FeNO levels (26 ppb) than ex-smokers (64 ppb; P < .001) and never smokers (46 ppb; P = .001). When smoking was eliminated as a cofounder, the researchers found even more significant differences between the sexes in small airway function and FeNO.
Analysis of the nonsmoking patients also revealed that women with asthma experienced lower small airway function and higher FeNO levels with increasing age, along with more rapid declines in FEFs and FeNO levels compared with men.
Optimal cutoff values for predicting a positive MCT result included 87.2% for FEF50%, 77.1% for FEF75%, and 81.6% for FEF25%-75% for all patients. Among men, these values included 86.4%, 76.3%, and 81.5%. For women, they were 76.9%, 66.8%, and 73.7% (P < .001 for all).
Similarly, the optimal FeNO level cutoff level was greater than 40 ppb for all patients, greater than or equal to 41 ppb for men and greater than or equal to 35 ppb for women (P < .001 for all). Based on these differences, the researchers suggested that women may benefit from sex-specific cutoff values during diagnosis.
The researchers called their findings evidence of sex-based differences in small airway function and FeNO levels in patients with mild asthma, which current international guidelines do not address in their preventive, diagnostic or therapeutic approaches. The researchers recommended multicenter, large-scale, prospective studies to validate their studies and set optimal cutoff values for men and women.
Perspective
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Andrew M. Namen, MD, FCCP, FAASM
These results are significant. FeNO has not been fully accepted in adult asthma management due to the lack of consistent results when implementing diagnostic testing or as a guide in treatment management of adults with asthma. The authors discussed how FeNO may be a safe alternative to methacholine challenges in identifying patients with clinically relevant mild asthma, which is difficult to diagnose.
The importance of this study is that, in part, it explains gender and environmental differences such as smoking and provides gender-specific FeNO thresholds with improved testing performance in identifying asthma, especially when FeNO is combined with pulmonary function testing results.
Also, this study highlights the challenge of using FeNO alone. It suggests that one FeNO threshold is not enough and that FeNO alone is not a strong diagnostic test for mild asthma. But in combination with small-airway pulmonary function testing parameters, it shows promise.
The sensitivity of the combination of gender-specific and environmental-specific FeNO thresholds with pulmonary function testing and small-airway disorder parameters may help exclude patients from asthma diagnosis, especially among patients in which methacholine challenge is discouraged.
As stated by the authors, these FeNO thresholds and pulmonary function testing metrics should be studied prospectively in a multicenter trial among patients with features of asthma but not yet defined.
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