Airway and Serum Biochemical Correlates of Refractory Neutrophilic Asthma

Publication date: Available online 3 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Rafeul Alam, James Good, Donald Rollins, Mukesh Verma, HongWei Chu, Tuyet-Hang Pham, Richard J. Martin
BackgroundDespite the progress in diagnosis and management of asthma, many patients have poorly controlled or refractory asthma. The mechanism of this refractory asthma is not well understood.ObjectiveExplore the relationship between neutrophils and other biomarkers of refractory asthma.MethodSixty subjects with refractory asthma (RA), 30 with non-refractory asthma (NRA) and 20 healthy subjects were enrolled. We performed a comprehensive characterization of these study subjects, which included laboratory and pulmonary function studies, chest CT, and bronchoscopy with bronchoalveolar lavage. We analyzed BAL and serum for a total of 244 biomolecules by multiplex assay and correlated them with the clinical and other laboratory parameters.ResultsRA was significantly different from NRA with regard to pulmonary function indices, bronchial basement membrane thickness, and BAL neutrophils and lymphocytes but not eosinophils. BAL neutrophils negatively and positively correlated with the forced vital capacity and age, respectively. Of the 244 biomolecules studied, 52 and 14 biomolecules from BAL and serum, respectively, were significantly different among the study groups. Thirteen of these 52 molecules correlated with BAL neutrophils. BAL from 40% of RA patients was positive for a pathogenic microbe. Infection-negative neutrophilic RA was associated with an increase in select biomarkers of inflammation in the serum suggesting the presence of systemic inflammation.ConclusionsRA was associated with increased number of neutrophils and proneutrophilic biomolecules in the airways. Subclinical infection was present in 40% of RA patients, which likely contributed to neutrophilic inflammation. A subgroup of non-infected neutrophilic RA was associated with systemic inflammation.

Teaser

Through a comprehensive analysis of bronchoalveolar lavage and blood this paper identified neutrophils and proneutrophilic biomolecules as strong correlates of refractory asthma.


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