Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis

Abstract

Background Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified five asthma subphenotypes that represent the severity spectrum of early onset allergic asthma, late onset severe asthma and severe asthma with COPD characteristics. Analysis of induced sputum from a subset of SARP subjects showed four sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophils (≥2%) and neutrophils (≥40%) had characteristics of very severe asthma. Objective To better understand interactions between inflammation and clinical subphenotypes we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Methods Participants in SARP at three clinical sites who underwent sputum induction were included in this analysis (n=423). Fifteen variables including clinical characteristics and blood and sputum inflammatory cell assessments were selected by factor analysis for unsupervised cluster analysis. Results Four phenotypic clusters were identified. Cluster A (n=132) and B (n=127) subjects had mild-moderate early onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of Cluster C (n=117) and D (n=47) subjects who had moderate-severe asthma with frequent health care utilization despite treatment with high doses of inhaled or oral corticosteroids, and in Cluster D, reduced lung function. The majority these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophils were the most important variables determining cluster assignment. Conclusion This multivariate approach identified four asthma subphenotypes representing the severity spectrum from mild-moderate allergic asthma with minimal or eosinophilic predominant sputum inflammation to moderate-severe asthma with neutrophilic predominant or mixed granulocytic inflammation.

Pediatric Obesity-Related Asthma: The Role of Metabolic Dysregulation

“…108 As noted in normal-weight asthma, although classic asthma is atopic, involving eosinophils and Th2 cells, severe asthma, even among normal-weight individuals, is nonatopic, mediated by neutrophils. 117 Whether similar variability in the involvement of innate immune pathways comprising Th1 cells, M1 macrophages, and neutrophils occurs in the pathogenesis of obesity-related asthma needs further investigation. Recent literature highlighting the role of metabolic dysregulation in obesity-related asthma 118 may begin to clarify these issues because differential inflammation among obese individuals with or without metabolic dysregulation may partly underlie the heterogeneity of the obese asthma phenotype.…”

Phenotyping Asthma: Linking Clinical Features to Biomolecular Pathways

“…A similar report from the cohort in Newcastle, Australia, described that patients with neutrophilic inflammation had a greater frequency of primary care doctor visits for asthma exacerbations and a high prevalence of chest infections in the previous 12 months, of rhinosinusitis and of gastro-oesophageal reflux symptoms when compared to eosinophilic asthma 62 .…”

“…In the SARP cohort, use of the inflammatory phenotypes assessed by sputum cell counts led to the identification of four phenotypic clusters with two clusters of mild-to-moderate early onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns, and two other clusters with either neutrophilic or mixed inflammatory patterns with moderate-to-severe asthma with frequent healthcare use despite treatment with high doses of inhaled or oral corticosteroids and also reduced lung function 62 . A similar report from the cohort in Newcastle, Australia, described that patients with neutrophilic inflammation had a greater frequency of primary care doctor visits for asthma exacerbations and a high prevalence of chest infections in the previous 12 months, of rhinosinusitis and of gastro-oesophageal reflux symptoms when compared to eosinophilic asthma 62 .…”

Asthma-COPD overlap szindróma

“…Azok az asthmás betegek, akiknél súlyosabb és később kezdődő betegség vagy krónikus infekciók, vagy dohányzás igazolható, ott neutrofil gyulladás is megfigyelhető volt a légutakban [25,26]. A köpet neutrofilszáma összefüggést mutatott a súlyosabb asthmafenotípusokkal, amelyek magas dózi-sú inhalációs vagy orális kortikoszteroidhasználat ellené-re is több egészségügyi kezeléssel és csökkent légzés-funkciós értékekkel párosultak [27]. A másik fontos megfigyelés, hogy a COPD-betegek 20-40%-ánál a kö-pet eozinfilszintje emelkedett [28], illetve 15-40%-ban a sejtek jelen voltak a bronchoalveolaris lavage és tüdőszö-veti mintákban is [29].…”