Exhaled Nitric Oxide and Sputum Eosinophils Are Complementary Tools for Diagnosing Occupational Asthma

• Published in: Allergy (Copenhagen) Vol. 80; no. 4; pp. 1015 - 1024
• Main Authors: Doyen, Virginie, Migueres, Nicolas, Kampen, Vera, Suojalehto, Hille, Mason, Paola, Munoz, Xavier, Sastre, Joaquin, Quirce, Santiago, Svanes, Cecilie, Walters, Gareth, Moore, Vicky, Jacobsen, Iben Brock, Folletti, Ilenia, Preisser, Alexandra M., Walusiak‐Skorupa, Jolanta, Rifflart, Catherine, Blay, Frédéric, Vandenplas, Olivier
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.04.2025
• Subjects: Adult; Asthma; Asthma, Occupational - diagnosis; Asthma, Occupational - metabolism; Biomarkers; breathing; confidence interval; eosinophils; Eosinophils - immunology; Eosinophils - metabolism; Exhalation; Female; fractional exhaled nitric oxide; Humans; inflammation; Inhalation; Leukocyte Count; Leukocytes (eosinophilic); Male; Middle Aged; Nitric oxide; Nitric Oxide - metabolism; occupational asthma; Occupational exposure; Respiratory tract diseases; Retrospective Studies; ROC Curve; specific inhalation challenge; Sputum; Sputum - cytology; Sputum - immunology; sputum eosinophils; sputum eosinophils; occupational asthma; fractional exhaled nitric oxide; specific inhalation challenge
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.16447

ABSTRACT Background Exposure‐related changes in exhaled nitric oxide (FeNO) and sputum eosinophils have not been thoroughly compared in the investigation of occupational asthma. Objective This study aimed at comparing the accuracies of the changes in FeNO concentrations and sputum eosinophil counts in identifying asthmatic reactions induced by occupational agents during specific inhalation challenges (SICs). Methods This retrospective multicenter study included 321 subjects who completed an assessment of FeNO and sputum eosinophils before and 24 h after SICs with various occupational agents, of whom 156 showed a positive result. Results Post‐challenge changes in FeNO and sputum eosinophils showed similar accuracies, with areas under the receiver operating characteristics curve of 0.78 (95% confidence interval [95% CI], 0.72–0.83) and 0.81 (95% CI, 0.76–0.86), respectively. Increases in FeNO level ≥ 13 ppb and sputum eosinophils ≥ 1.25% were identified as the optimal threshold values for differentiating positive from negative SICs. Using these thresholds, the changes in FeNO and sputum eosinophils each achieved a ≥ 95% specificity but a low sensitivity (55% and 62%, respectively). FeNO and sputum eosinophils showed discordant increases in 38% of subjects with a positive SIC. Combining either a rise in FeNO ≥ 13 ppb or an increase in sputum eosinophils ≥ 1.25% increased the sensitivity to 77%. Conclusions Increases in FeNO concentration and/or sputum eosinophils after exposure to occupational agents strongly support a diagnosis of occupational asthma. The assessment of both markers of airway inflammation should be regarded as a reliable complementary tool to spirometry for identifying bronchial responses to occupational agents. This retrospective multicenter cohort showed that the changes in FeNO and sputum eosinophils after challenge exposure to occupational agents have a similarly high accuracy in differentiating positive from negative SICs. The ROC‐based optimal thresholds of 13 ppb and 1.25% for the post‐challenge changes in FeNO and sputum eosinophils, respectively, provided a high specificity in identifying asthmatic reactions. In addition, combining both inflammatory markers substantially increased the sensitivity to 77% (95% CI, 70%–83%). CI, confidence interval; FeNO, fractional exhaled nitric oxide; ppb, parts per billion; SIC, specific inhalation challenge.