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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., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)