Can exhaled nitric oxide differentiate causes of pulmonary fibrosis?

Abstract

Background: Interstitial lung diseases (ILD) comprise a heterogeneous group of disorders, and when diagnosed at the stage of pulmonary fibrosis, the underlying lung disease can sometimes be difficult to identify. The aim of the present study was to determine whether there are differences in FENO (fraction of exhaled nitric oxide) between different subtypes of fibrotic ILD.

Methods: Sixty-one patients, with honeycombing on computed tomography (CT) scan, and whose FENO levels had been measured during chronic dyspnoea evaluation, were divided into four groups based on pulmonary fibrosis aetiology: idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis (HP), connective tissue disease-associated ILD disorders (CTD-ILD), drug-induced pneumonia. The FENO values of each group were compared and CT scan features were analysed to identify the mechanisms involved in FENO change.

Results: The median FENO value of patients with chronic HP was 51 ppb (IQR 36-74), higher than that of the other groups (22 ppb (IQR 17-30) in IPF, 19 ppb (IQR 17-21) in drug-induced pneumonia, and 25 ppb (IQR 17-37) for CTD-ILD; p = 0.008). At the cut-off value of 41 ppb, the optimal sensitivity and specificity to diagnose HP with FENO were respectively 76.9% and 85.4%. On CT scans, only extensive lobular areas with decreased attenuation, a recognized marker of bronchiolar disease, were associated with high FENO values (p = 0.0002).

Conclusion: FENO could be a tool for differentiating chronic HP from other types of pulmonary fibrosis. The mechanism involved seems to be bronchiolar disease.

Keywords: 25–75% Forced Expiratory Flow; Bronchiolar disease; CANO; CTD-ILD; DIP; Exhaled nitric oxide; FE(NO); FEF 25–75; FEV(1); Forced Expiratory Volume in 1 s; GGO; HP; Hypersensitivity pneumonitis; ILD; IPF; IQR; Idiopathic pulmonary fibrosis; J'aw(NO); SSC; TLC; Total Lung Capacity; VC; alveolar concentration of exhaled NO; conducting airway flux; connective tissue disease-associated ILD disorders; drug induced pneumonia; fractional exhaled nitric oxide; ground-glass opacities; hypersensitivity pneumonitis; idiopathic pulmonary fibrosis; interquartile range; interstitial lung disease; systemic sclerosis; vital capacity.