Biological clustering supports both “Dutch” and “British” hypotheses of asthma and chronic obstructive pulmonary disease

Abstract

BackgroundAsthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases.ObjectiveWe sought to determine, in terms of their sputum cellular and mediator profiles, the extent to which they represent distinct or overlapping conditions supporting either the “British” or “Dutch” hypotheses of airway disease pathogenesis.MethodsWe compared the clinical and physiological characteristics and sputum mediators between 86 subjects with severe asthma and 75 with moderate-to-severe COPD. Biological subgroups were determined using factor and cluster analyses on 18 sputum cytokines. The subgroups were validated on independent severe asthma (n = 166) and COPD (n = 58) cohorts. Two techniques were used to assign the validation subjects to subgroups: linear discriminant analysis, or the best identified discriminator (single cytokine) in combination with subject disease status (asthma or COPD).ResultsDiscriminant analysis distinguished severe asthma from COPD completely using a combination of clinical and biological variables. Factor and cluster analyses of the sputum cytokine profiles revealed 3 biological clusters: cluster 1: asthma predominant, eosinophilic, high TH2 cytokines; cluster 2: asthma and COPD overlap, neutrophilic; cluster 3: COPD predominant, mixed eosinophilic and neutrophilic. Validation subjects were classified into 3 subgroups using discriminant analysis, or disease status with a binary assessment of sputum IL-1β expression. Sputum cellular and cytokine profiles of the validation subgroups were similar to the subgroups from the test study.ConclusionsSputum cytokine profiling can determine distinct and overlapping groups of subjects with asthma and COPD, supporting both the British and Dutch hypotheses. These findings may contribute to improved patient classification to enable stratified medicine.

Serum cytokine profiles as predictors of asthma control in adults from the EGEA study

“…These results are consistent with the positive association between IL-8 levels and neutrophil counts found in sputum (28) and in blood [14]. However, we found no association between "pro-inflammatory cytokine profile" and blood eosinophil counts or total IgE level, in contrast with previous studies on IL-5 and IL-13 in sputum (18,(29)(30)(31). The "proinflammatory cytokine profile" was not correlated with asthma control outcomes, allergic diseases, and lung function.…”

Strategies targeting the IL-4/IL-13 axes in disease

“…The Th2 high COPD patients had no association with asthma history, airway reversibility, reduced hyperinflation following ICS treatment together with lower lung function, increased blood and lung wall eosinophils as compared to non-Th2 high COPD patients [269]. Asthma-COPD overlap syndrome (ACOS) is now well recognized as a disease with key aspects of both asthma and COPD [270,271].…”

Clinically relevant subgroups in COPD and asthma

“…Recent evidence suggests it may be identified by sputum cytokine profile [68]. Nevertheless, trials focussing on such patients have been published and suggest that steroids are more beneficial in this group than in other COPD patients [25].…”