Detailed analysis of sputum and systemic inflammation in asthma phenotypes: are paucigranulocytic asthmatics really non-inflammatory?

Abstract

BackgroundThe technique of induced sputum has allowed to subdivide asthma patients into inflammatory phenotypes according to their level of granulocyte airway infiltration. There are very few studies which looked at detailed sputum and blood cell counts in a large cohort of asthmatics divided into inflammatory phenotypes. The purpose of this study was to analyze sputum cell counts, blood leukocytes and systemic inflammatory markers in these phenotypes, and investigate how those groups compared with healthy subjects.MethodsWe conducted a retrospective cross-sectional study on 833 asthmatics recruited from the University Asthma Clinic of Liege and compared them with 194 healthy subjects. Asthmatics were classified into inflammatory phenotypes.ResultsThe total non-squamous cell count per gram of sputum was greater in mixed granulocytic and neutrophilic phenotypes as compared to eosinophilic, paucigranulocytic asthma and healthy subjects (p < 0.005). Sputum eosinophils (in absolute values and percentages) were increased in all asthma phenotypes including paucigranulocytic asthma, compared to healthy subjects (p < 0.005). Eosinophilic asthma showed higher absolute sputum neutrophil and lymphocyte counts than healthy subjects (p < 0.005), while neutrophilic asthmatics had a particularly low number of sputum macrophages and epithelial cells. All asthma phenotypes showed an increased blood leukocyte count compared to healthy subjects (p < 0.005), with paucigranulocytic asthmatics having also increased absolute blood eosinophils compared to healthy subjects (p < 0.005). Neutrophilic asthma had raised CRP and fibrinogen while eosinophilic asthma only showed raised fibrinogen compared to healthy subjects (p < 0.005).ConclusionsThis study demonstrates that a significant eosinophilic inflammation is present across all categories of asthma, and that paucigranulocytic asthma may be seen as a low grade inflammatory disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0208-2) contains supplementary material, which is available to authorized users.

Clinical phenotypes in asthma during childhood

“…Herr et al 89 also described wheezer phenotypes in very young children in a French birth cohort including a mild episodic viral wheeze, which was very similar to our EVW group. 91 93 poor disease prognosis is attached to particular severe phenotypes. This is also consistent with findings from Tucson where children with early transient wheeze were less likely than persistent wheezers to have frequent episodes of wheeze or wheeze apart from colds in infancy.…”

Small Airways Disease and Asthma Management: Is there a Connection?

“…Epithelial cells may also release thymic stromal BARCELONA RESPIRATORY NETWORK lymphopoietin (TSLP) and IL-33, which stimulate innate lymphoid cells to release cytokines like IL-5 46 . Whichever the type of lymphocyte involved in this immunological process, eosinophilic asthmatics display greater sputum lymphocyte and epithelial cell counts, supporting the concept of a close interaction between lymphocytes and eosinophils leading to epithelial injury and shedding 28 . What seems clear is that eosinophilic asthma appears to be determined by different molecular mechanisms and gene expression as compared to other asthma phenotypes.…”

“…The IgE-mediated sensitisation to animal dander has recently been shown to be particularly associated with the eosinophilic phenotype. However, sputum eosinophilia may be present in asthma irrespective of the atopic status 28 . Though it has been shown that non-atopic asthmatics may sometimes have airway IgE production directed towards some aeroallergens 45 , there is currently great interest in epithelial cells and innate lymphoid cells as key players in driving eosinophilic inflammation in nonatopic subjects 46 .…”

Eosinophilia and Chronic Airway Diseases

“…Several large cohort studies including more than 100 patients have reported the proportion of eosinophilic asthmatics. Though differences may appear between the studies based on the disease severity, treatment with inhaled corticosteroids (ICS), and the proportion of atopic patients in the different asthma cohorts, it is reasonable to conclude that eosinophilic asthma represents approximately half of the patients and that this figure is possibly increasing with disease severity 13,17,22,[27][28][29][30][31][32][33] (Table 1). There is more controversy regarding the neutrophilic threshold that defines a neutrophilic asthma phenotype.…”

“…Thresholds ranging from 49 to 93% have been proposed by different research groups. What is well established is that neutrophil count, in contrast to eosinophil count, increases with age 34 and cumulative smoking history 28 . Our threshold value for sputum neutrophil counts based on large series of healthy subjects, whose mean age is around 40 years, is as high as 76%.…”