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Sputum Inflammatory Patterns are Associated with Distinct Clinical Characteristics in Subjects with Occupational Asthma Independently from the Causal Agent

Migueres N1,2*, Vandenplas O3*, Walusiak-Skorupa J4, Wiszniewska M4, Munoz X5, Romero-Mesones C5, Suojalehto H6, Lindström I6, van Kampen V7, Merget R7, Mason P8, Maestrelli P8, Sastre J9, Quirce S10, Rifflart C3, Godet J2,11, de Blay F1, on behalf of the European network for the PHenotyping of OCcupational ASthma (E-PHOCAS)**

1Division of Pulmonology, Department of Chest Diseases, University Hospital of Strasbourg and Fédération de Médecine translationnelle, Strasbourg University, Strasbourg, France.
2UMR 7357 Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie ICUBE, Strasbourg, France.
3Service de Pneumologie, Centre Hospitalier Universitaire UCL Namur, Université Catholique de Louvain, Yvoir, Belgium.
4Department of Occupational Diseases and Environmental Health, Nofer Institute of Occupational Medicine, Lodz, Poland.
5Servei Pneumologia, Hospital Vall d’Hebron, Universitat Autonoma de Barcelona and CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
6Occcupational Health, Finnish Institute of Occupational Health, Helsinki, Finland.
7Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Ruhr University, Bochum, Germany.
8Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy.
9Department of Allergy, Fundacion Jimenez Dıaz, Universidad Autonoma de Madrid and CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
10Department of Allergy, La Paz University Hospital, IdiPAZ and CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
11Groupe Méthode Recherche Clinique, Pôle de Santé Publique, Strasbourg University, Strasbourg, France.
* These authors contributed equally.
** The E-PHOCAS investigators are listed in the onlince supplement.

J Investig Allergol Clin Immunol 2024; Vol. 34(2)
doi: 10.18176/jiaci.0868

Background: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated.
Objectives: To further characterize the interactions between induced sputum inflammatory patterns, asthma-related outcomes and the high- or low-molecular-weight category of causal agents in a large cohort of subjects with OA.
Methods: This multicenter, retrospective, cross-sectional study was conducted among 296 subjects with OA ascertained by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure.
Results: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (odds ratio [95% confidence interval], 1.31 [1.11-1.55] for each 250-µg increment in daily dose), short-acting b2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild: 2.48 [1.21-5.08]); moderate/severe: 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male gender (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), short-acting b2-agonist use once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the last 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the SIC (4.45 [1.85-11.59]).
Conclusion: The findings indicate that sputum inflammatory patterns in subjects with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with what has been reported in nonoccupational asthma and are not related to the type of causal agent.

Key words: Eosinophils, Induced sputum, Neutrophils, Occupational asthma, Phenotype