Exhaled nitric oxide (FENO) has been proposed as a marker of asthmatic inflammation, but it is unclear whether FENO in clinical use selects patients primarily according to their atopic or asthmatic status. The aim of this study was to investigate the determinants of increased FENO in patients with suspected asthma, by means of multinomial logistic regression analysis. The FENO of 132 patients referred because of symptoms suggestive of asthma were studied, and the explanatory factors tested included atopy according to prick skin tests, clinical asthma according to lung function tests, sputum eosinophilia and bronchial hyperresponsiveness (BHR). Slightly elevated FE(NO) levels were significantly explained only by sputum eosinophilia (OR: 3.7; 95% CI: 1.1-13.1; P=0.04), but for high levels of FE(NO) (> or =3 SD of predicted), clinical asthma (OR: 16.3; 95% CI: 5.4-49.7; P <0.0001) and sputum eosinophilia (OR: 12.0; 95% CI: 4.1-35.0; P >0.0001) were the characteristics with the highest prediction, followed by atopy and BHR. A significant interaction between asthma and atopy was observed relating to the effect on high FENO, but further analyses stratified by atopy showed significant associations between asthma and high FENO both in atopic and nonatopic patients. We conclude that in patients with symptoms suggesting asthma, slightly elevated and high levels of FENO are associated with sputum eosinophilia, whereas asthma is significantly associated only with high levels of FENO, irrespective of atopy. The results suggest that FENO is primarily a marker of airway eosinophilia, and that only high values of FENO may be useful to identify patients with atopic or nonatopic asthma.
Background
Nonsteroidal anti‐inflammatory drug (NSAID) exacerbated respiratory disease (N‐ERD) is a triad with asthma, chronic rhinosinusitis with nasal polyps, and NSAID intolerance. Uncontrolled N‐ERD forms a major public health problem due to frequent and difficult‐to‐treat exacerbations and/or requiring putatively frequent endoscopic sinus surgeries (ESS). Our aim was to study factors affecting control of N‐ERD.
Methods
Retrospective patient record data (patient characteristics, prior sinus surgeries, follow‐up data in 2020) from 167 N‐ERD patients undergoing consultation at three tertiary hospitals from 2001 to 2017 was used. Outcome measurements reflecting uncontrolled N‐ERD were revision ESS, corticosteroids/biological therapy, and antibiotic courses during 2016–2020. Associations were analyzed by using nonparametric tests, Cox's proportional hazard, and binary logistic regression models.
Results
Nasal polyp eosinophilia increased the risk of revision surgery during the follow‐up (adjusted hazard ratio [aHR] 3.21, confidence interval 1.23–8.38). Also baseline oral corticosteroids (OCS; HR, 1.73, 1.04–2.89) and baseline surgery without total ethmoidectomy increased the risk of revision ESS (HR, 2.17, 1.07–4.42) in unadjusted models. In addition, both baseline OCS (adjusted odds ratio [aOR] 2.78, 1.23–6.26) and a history of ≥4 previous ESS (aOR, 2.15, 0.98–4.70) were associated with the use of OCS/biological therapy during the follow‐up, but not with high number of antibiotics.
Conclusions
Nasal polyp eosinophilia, baseline OCS, and a history of recurrent ESS predict uncontrolled N‐ERD. These factors might be clinically useful in risk‐estimation of uncontrolled disease and for organizing follow‐ups. Prospective cohort studies with larger sample size are needed to further study the factors affecting the upper airway control of N‐ERD.
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