Asthma phenotypes in Turkey: a multicenter cross-sectional study in adult asthmatics; PHENOTURK study

Dursun, A. Berna/0000-0002-6337-6326; Gemicioglu, Bilun/0000-0001-5953-4881; Dilsad, Mungan/0000-0001-8806-2764; yorgancioglu, arzu/0000-0002-4032-0944; Bayram, Hasan/0000-0002-5236-766XWOS: 000395446700009PubMed: 26073091Background and AimsTo evaluate asthma phenotypes in patients with asthma from different regions of Turkey. MethodsA total of 1400 adult asthmatic patients (mean (SD) age: 44.0 (13.9) years, 75% females) from 14 centers across Turkey were included in this study and a standard questionnaire was applied between the time period of February 2011-January 2012. ResultsThe disease onset40 years of age was higher percentage in obese vs. normal/overweight patients and nonallergic vs. allergic patients (P<0.01). the percentage of patients who had FEV1 values over 80% was higher in allergic than nonallergic and normal/overweight than obese patients (P<0.01). Uncontrolled asthmatics have more severe disease (P<0.01). There were more frequent hospital admissions in nonallergic and uncontrolled asthmatics (P<0.01). Chronic rhino-sinusitis was the leading comorbid disorder in normal/overweight and allergic asthma, while gastroesophageal reflux disorder was more frequent in nonallergic and uncontrolled asthma (P<0.01). Asthma control rate was the highest (39.0%) in patients from Marmara region among all geographical regions (P<0.05). ConclusionIn conclusion, our findings revealed existence of clinical/trigger related phenotypes based on BMI, allergic status, control level and geographical region with more frequent respiratory dysfunction and/or adverse health outcomes in uncontrolled, obese and nonallergic phenotypes.Turkish Thoracic Society, Asthma-Allergy Working GroupThis study was funded by the Turkish Thoracic Society, Asthma-Allergy Working Group. We would also like to thank KAPPA Consultancy Training Research Ltd, Istanbul for providing editorial support and Alpha Medical, Istanbul for providing support in statistical analysis

Near-fatal asthma phenotype in the ENFUMOSA Cohort.

BACKGROUND: Near-fatal asthma (NFA) is characterized by severe asthma attacks usually requiring intensive care unit admission. This phenotype of asthma has been studied mainly in acute conditions. METHODS: The aim of our study was to compare the clinical, functional and inflammatory characteristics of NFA patients with mild to severe asthmatics in stable conditions. We recruited 155 asthmatic patients from five centres of the European Network for Understanding Mechanisms of Severe Asthma: 67 patients with mild-to-moderate asthma controlled by low/medium doses of inhaled corticosteroids; 64 with severe asthma that, despite treatment with high doses of inhaled corticosteroids, long-acting beta2-agonists and for 1/3 also with regular oral corticosteroids, had at least one asthma exacerbation in the previous year; 24 with an NFA episode in the previous 5 years in the absence of inclusion criteria for the previous groups. All the patients were examined in stable conditions. RESULTS: NFA patients were taking less corticosteroids and were less compliant to prescribed asthma medications than the other two groups of patients. Lung function, blood gases, atopic status, sputum and blood inflammatory cell count of NFA patients were similar to mild-to-moderate, but not severe, asthmatic patients. CONCLUSIONS: In stable conditions patients with an NFA attack in the previous 5 years cannot be distinguished from patients with mild-to-moderate asthma, while they are different from severe asthmatics both in terms of lung function and of airway inflammation. The risk factor that characterizes this group of patients is reduced usage of prophylactic corticosteroids

Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial

Background: Increased numbers of neutrophils are reported in the airways of patients with severe asthma. It is not clear if they contribute to the lack of control and severity. There are currently no strategies to investigate this by decreasing neutrophil numbers in the airways.Objective: To investigate the safety and efficacy of SCH527123, a selective CXCR2 receptor antagonist, in patients with severe asthma and increased number of neutrophils in sputum.Methods: In a randomized, double-blind, parallel study, patients with severe asthma and sputum total cell count &lt; 10 9 106/g and neutrophils &gt; 40% were randomized to SCH527123, 30 mg daily PO (n = 22) or placebo (n = 12) for 4 weeks. Primary end-points were safety and change in sputum and blood neutrophil counts. Secondary end-points were change in asthma control questionnaire (ACQ) score, minor and major exacerbations, spirometry and sputum neutrophil activation markers.Results: The SCH 527123 caused a mean reduction of 36.3% in sputum neutrophil percentage compared to a 6.7% increase in the placebo arm (P = 0.03). The mean absolute neutrophil count in blood was reduced by 14% at the end of 4 weeks, but recovered by the 5th week. There were no differences in the overall rates of adverse events among the groups. There were fewer mild exacerbations (1.3 vs. 2.25, P = 0.05) and a trend towards improvement in the ACQ score (mean difference between groups of 0.42 points,P = 0.053). No statistically significant changes were observed in forced expiratory volume in 1 s (FEV1), sputum myeloperoxidase, IL8 or elastase.Conclusions: The SCH527123 is safe and reduces sputum neutrophils in patients with severe asthma.Clinical Relevance: This new treatment provides an opportunity to investigate the role of neutrophils in severe asthma with potential clinical benefits. Larger studies of longer duration are needed to evaluate the impact on other outcomes of asthma including exacerbations

Frequent exacerbators - a distinct phenotype of severe asthma

BACKGROUND: 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 μg) 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 FEV1 /FVC ratio (-0.07 vs. -0.01 ΔFEV1 /FVC, frequent vs. non-frequent, respectively, P 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

RItA: The Italian severe/uncontrolled asthma registry

Background: The Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care. Methods: Four hundred and ninety three adult patients from 27 Italian centers (recruited in 2011-2014) were analyzed. Results: Mean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV1% pred of 75.1%, median values of 300/mm3of blood eosinophil count, 323 kU/L of serum total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3% hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95% CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30-borderline), nasal polyps (1.86, 0.88-3.89-borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67-borderline), and anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicenter studies and available registries showed data consistency across European and American populations. Conclusions: An international effort in the implementation of SUA patients' registries could help to better understand the clinical features and to manage severe asthma, representing a non-negligible socioeconomic burden for health services