Frequent exacerbators – a distinct phenotype of severe asthma

Abstract

SummaryBackground Exacerbations represent a major source of morbidity and mortality in asthma and are a prominent feature of poorly controlled, difficult-to-treat disease. Objective The goal of our study was to provide a detailed characterization of the frequent exacerbator phenotype and to identify risk factors associated with frequent and seasonal exacerbations. Methods Ninety-three severe asthmatics (SA) and 76 mild-to-moderate patients (MA) were screened and prospectively followed up for 1 year (NCT00555607). Medical history, baseline clinical data and biomarkers were used to assess risk factors for frequent exacerbations. Results During the study, 104 exacerbations were recorded in the SA group and 18 in the MA. Frequent exacerbators were characterized by use of higher doses of inhaled (1700 vs. 800 lg) and oral (6.7 vs. 1.7 mg) glucocorticosteroids, worse asthma control (ACQ score 2.3 vs. 1.4), lower quality of life (SGRQ score 48.5 vs. 33.3), higher sputum eosinophils (25.7% vs. 8.2%) and a more rapid decline in FEV 1 /FVC ratio (À0.07 vs. À0.01 DFEV 1 / FVC, frequent vs. non-frequent, respectively, P < 0.05). Exhaled NO > 45 p.p.b. and a history of smoking were associated with an increased risk of frequent exacerbations (odds ratios: 4.32 and 2.90 respectively). Conclusion and Clinical Relevance We were able to distinguish and characterize a subphenotype of asthma subjects -frequent exacerbators -who are significantly more prone to exacerbations. Patients with FeNO > 45 p.p.b. and a history of smoking are at increased risk of frequent exacerbations and require careful monitoring in clinical practice.

Allergy in severe asthma

“…Recently, a new distinct phenotype of severe asthma has been identified in frequent exacerbators, and history of smoking seems to be a risk factor for this phenotype (130). A novel risk score for asthma exacerbations developed and validated by Bateman et al (131) supports the evidence that smoking status is a main predictor for uncontrolled asthma.…”

Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease

“…BIOAIR is a European multicenter study (9)(10)(11). Briefly, subjects were between 18 and 80 years of age and were divided into three groups: patients with mild to moderate asthma, patients with severe asthma, and patients with COPD (Table 1).…”

“…It was therefore our aim in this study to provide a more detailed evaluation of serum chitinase levels in airway disease by investigating both serum YKL-40 levels and chitotriosidase activity in parallel in patients taking part in the European multicenter BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) study (9)(10)(11). The design of this study enabled us, for the first time, to examine in the same study the repeatability of chitinase measurements over a 1-year period, the effect of oral steroid treatment, and the effect of spontaneous exacerbations in both patients with asthma and patients with COPD.…”

Advances in asthma pathophysiology: stepping forward from the Maurizio Vignola experience

“…A variety of parameters have been identified for this definition: functional parameters, frequency of exacerbations, age of patients, presence of allergy, geographical localisation [49] and biomarkers. In a recent pan-European study, the stability of phenotypes in adults with controlled and severe asthma has been analysed in the BIOAIR cohort (longitudinal assessment of clinical course and BIOmarkers in severe chronic AIRway disease study), to compare phenotypes defined either by biomarkers (the "Hastie approach") or by physiological variables (the "Moore approach") over 1 year of observation [50]. There are still conflicting data on the repeatability of inflammatory phenotypes defined by sputum analysis.…”