Non-eosinophilic Phenotypes Research Articles

Prospective Real-World Analysis of Asthma Patients With Preserved and Reduced Physical Activity.

Asthma is a highly heterogeneous airway disease, and the clinical characteristics of patients with asthma with preserved and reduced physical activity are poorly understood. We aimed to investigate the risk factors and clinical phenotypes associated with reduced physical activity in a wide range of patients with asthma. We conducted a prospective observational study of 138 patients with asthma, including patients with asthma without chronic obstructive pulmonary disease (COPD) (n= 104) and asthma-COPD overlap (n= 34), and 42 healthy controls. Physical activity levels were measured for 2 weeks using a triaxial accelerometer at baseline and 1 year later. Higher eosinophils and body mass index (BMI) were associated with reduced physical activity in patients with asthma without COPD. Cluster analysis of asthma without COPD revealed 4 asthma phenotypes. We identified a cluster with preserved physical activity (n= 43) that was characterized by good symptom control and lung function and included a high proportion of biologics users (34.9%). Multivariate regression analysis revealed that patients with late-onset eosinophilic (n= 21), high-BMI noneosinophilic (n= 14), and symptom-predominant asthma phenotypes (n= 26) had lower levels of physical activity than controls. Patients with asthma-COPD overlap also had significantly lower physical activity levels than controls. Similar trends in physical activity levels were observed in each asthma group at 1-year follow-up. This study showed the clinical features of patients with asthma with preserved and reduced physical activity. Reduced physical activity was observed in various asthma phenotypes and in asthma-COPD overlap.

Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation.

Patients with eosinophilic asthma react well to conventional treatment of asthma while individualized therapy for non-eosinophilic endotypes have yet to be developed. Dysregulated sphingosine metabolites are associated with the pathophysiology of different asthma endotypes with their receptors involved. However, whether the sphingosine-1-phosphate receptor 4 (S1PR4) contributes to disease progression of asthma remains underappreciated. In this study, we demonstrated that sphingosine metabolism was disturbed in asthma while it could not be used to distinguish between different endotypes of asthma. S1PR4, a vital receptor of bioactive sphingosine metabolites and mainly expressed in macrophages, exhibited lower expression both in patients and experimental mice with neutrophilic airway inflammation. Additionally, S1pr4 deficiency aggravated the OVA/LPS-induced pulmonary inflammation in mice along with a significant up-regulation in M1 macrophage activation. Mechanistic studies showed that S1PR4 was strongly connected to bioactive oxylipins concurrent with bounding to formyl peptide receptor 2 to influence the phosphorylation of JNK and contributed to the macrophage M1 program, which in turn secreted amounts of inflammatory cytokines associated to the inflammatory response of neutrophilic asthma. Furthermore, treating mice with S1PR4 agonist CYM50308 was characterized by less pulmonary inflammatory infiltration. Our research indicates S1PR4 a promising therapeutic target for non-eosinophilic phenotypes of asthma.

Quantitative assessment of emphysema and bronchial wall thickness in patients with stable chronic obstructive pulmonary disease: comparison between the eosinophilic and non-eosinophilic phenotypes.

ObjectiveTo perform a quantitative assessment of bronchial wall thickening and the emphysema score in patients with stable chronic obstructive pulmonary disease (COPD), comparing the eosinophilic and non-eosinophilic COPD phenotypes.Materials and MethodsThis was a retrospective observational study of patients with COPD followed between August 2018 and July 2019. The patients were divided into two groups by the eosinophil count in peripheral blood: eosinophilic (≥ 300 cells/µL); and non-eosinophilic (< 300 cells/µL). Quantitative, automated assessments of emphysema and bronchial wall thickness were performed by evaluating computed tomography scans of the chest.ResultsWe evaluated the records of 110 patients diagnosed with COPD: 28 (25.5%) in the eosinophilic group; and 82 (74.5%) in the non-eosinophilic group. The demographic, clinical, functional, and therapeutic variables were comparable between the two groups. There were no significant differences between the two groups in terms of the emphysema score or bronchial wall thickness (p > 0.05 for both).ConclusionPatients with eosinophilic COPD do not appear to have lower emphysema scores or greater bronchial wall thickening than do those with non-eosinophilic phenotypes of the disease.

Astımda uzun süreli makrolid tedavisi

Macrolides are antibiotics with antiviral, anti-inflammatory and immunomodulatory effects in together with their bacteriostatic effects. In addition to its beneficial effects on chronic respiratory diseases such as COPD, cystic fibrosis, diffuse panbronchiolitis, and bronchiectasis, its effects on uncontrolled severe asthma and asthma exacerbations have been the subject of research in recent years. In randomized controlled trials, azithromycin, a macrolide, has been shown to reduce asthma exacerbations and significantly improve asthma-related quality of life in both eosinophilic and non-eosinophilic asthma phenotypes. However, there are also differences such as doses, durations and some studies not showing its effectiveness in severe eosinophilic asthma. In the GINA report, azithromycin can be recommended as an add-on therapy in patients with uncontrolled non-T2 severe asthma despite high-dose inhaled corticosteroid/ long-acting beta2-agonist/long-acting antimuscariniric treatments, or in T2 severe asthma patients whose asthma is not under control despite biologic therapy. In this review, the use of macrolides, especially azithromycin, in the treatment of asthma, immunomodulatory activities and safety profiles are discussed on the basis of current studies and guidelines.

Metabolic Phenotypes in Asthmatic Adults: Relationship with Inflammatory and Clinical Phenotypes and Prognostic Implications.

Bronchial asthma is a chronic disease that affects individuals of all ages. It has a high prevalence and is associated with high morbidity and considerable levels of mortality. However, asthma is not a single disease, and multiple subtypes or phenotypes (clinical, inflammatory or combinations thereof) can be detected, namely in aggregated clusters. Most studies have characterised asthma phenotypes and clusters of phenotypes using mainly clinical and inflammatory parameters. These studies are important because they may have clinical and prognostic implications and may also help to tailor personalised treatment approaches. In addition, various metabolomics studies have helped to further define the metabolic features of asthma, using electronic noses or targeted and untargeted approaches. Besides discriminating between asthma and a healthy state, metabolomics can detect the metabolic signatures associated with some asthma subtypes, namely eosinophilic and non-eosinophilic phenotypes or the obese asthma phenotype, and this may prove very useful in point-of-care application. Furthermore, metabolomics also discriminates between asthma and other “phenotypes” of chronic obstructive airway diseases, such as chronic obstructive pulmonary disease (COPD) or Asthma–COPD Overlap (ACO). However, there are still various aspects that need to be more thoroughly investigated in the context of asthma phenotypes in adequately designed, homogeneous, multicentre studies, using adequate tools and integrating metabolomics into a multiple-level approach.

Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort

Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). One thousand seven hundred sixteen patients with prospective data were included; 83.8%were identified as most likely (grade 3), 8.3%were identified as likely (grade 2), and 6.3%identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6%of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs6.7 years; P< .001) and worse lung function (postbronchodilator %predicted FEV1, 76.1%vs89.3%; P= .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5%vs62.9%; P= .047), to have eczema (20.8%vs8.5%; P= .003), and to use anti-IgE (32.1%vs13.4%; P= .004) and leukotriene receptor antagonists (50.0%vs28.0%; P= .011) add-on therapy. According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.

Diagnostic value of thymus and activation-regulated chemokine and of periostin in eosinophilic asthma: A prospective study

Background: Serum thymus and activation-regulated chemokine (TARC) and periostin are reliable biomarkers in eosinophilic asthma. Objective: This study was carried out to determine the use of periostin and TARC as biomarkers in asthma and to compare the superiority of one over the other, especially in asthma with an eosinophilic phenotype. Methods: The study was conducted with 87 patients with asthma and 42 healthy control subjects. Patients with asthma were also divided into eosinophilic and non-eosinophilic phenotypes. A pulmonary function test was performed in all the participants, and serum and induced sputum TARC, periostin concentrations, eosinophils, and total immunoglobulin E values were examined. Results: TARC and periostin levels were significantly higher in the asthma group than in the control group (p < 0.001). The serum TARC level in the eosinophilic group was significantly higher than in the non-eosinophilic and control groups (p < 0.001). The induced sputum TARC level was significantly higher in the non-eosinophilic group than in the control group (p < 0.001). The TARC and periostin levels of the patients were evaluated by using receiver operator characteristic analysis. The cutoff value for TARC was determined to be 1415.39 ng/L; likewise, the cutoff value for periostin was 107.60 ng/L. The present study detected that serum levels of TARC correlated to serum levels of periostin (r = 0.54; p = 0.032). Furthermore, when evaluating correlations between serum and sputum levels, there was a correlation detected between TARC and periostin in serum, whereas this correlation was stronger in sputum: r = 0.66, p = 0.020; and r = 0.62, p = 0.028, respectively. Conclusion: Serum and sputum TARC and periostin may contribute for monitoring the improvement of patients, particularly those with asthma. Furthermore, TARC was a more reliable biomarker than periostin for patients with eosinophilic asthma.

Diagnostic value of thymus and activation-regulated chemokine and of periostin in eosinophilic asthma: A prospective study.

Serum thymus and activation-regulated chemokine (TARC) and periostin are reliable biomarkers in eosinophilicasthma. This study was carried out to determine the use of periostin and TARC as biomarkers in asthma and to comparethe superiority of one over the other, especially in asthma with an eosinophilic phenotype. The study was conducted with 87 patients with asthma and 42 healthy control subjects. Patients with asthma were also divided into eosinophilic and non-eosinophilic phenotypes. A pulmonary function test was performed in all the participants,and serum and induced sputum TARC, periostin concentrations, eosinophils, and total immunoglobulin E valueswere examined. TARC and periostin levels were significantly higher in the asthma group than in the control group (p < 0.001). The serum TARC level in the eosinophilic group was significantly higher than in the non-eosinophilic and control groups(p < 0.001). The induced sputum TARC level was significantly higher in the non-eosinophilic group than in the control group(p < 0.001). The TARC and periostin levels of the patients were evaluated by using receiver operator characteristic analysis.The cutoff value for TARC was determined to be 1415.39 ng/L; likewise, the cutoff value for periostin was 107.60 ng/L. Thepresent study detected that serum levels of TARC correlated to serum levels of periostin (r = 0.54; p = 0.032). Furthermore,when evaluating correlations between serum and sputum levels, there was a correlation detected between TARC and periostinin serum, whereas this correlation was stronger in sputum: r = 0.66, p = 0.020; and r = 0.62, p = 0.028, respectively. Serum and sputum TARC and periostin may contribute for monitoring the improvement of patients, particularly those with asthma. Furthermore, TARC was a more reliable biomarker than periostin for patients with eosinophilic asthma.

Eosinophil extracellular trap formation is closely associated with disease severity in chronic rhinosinusitis regardless of nasal polyp status

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory airway disease involving non-eosinophilic and eosinophilic phenotypes, which translate to various endotypes. Activated eosinophils and neutrophils are known to generate extracellular traps consisting of DNA and cytotoxic granule proteins. We sought to investigate the presence of eosinophil and neutrophil extracellular traps (EETs and NETs, respectively) in human CRS tissues and to clarify the associations with their clinical features. Nasal polyp (NP) or ethmoid tissue slides of 43 subjects from endoscopic sinus surgery for CRS were analysed. Quantitative analysis of EETs and NETs was performed by confocal microscopy using immunofluorescent staining. For correlation study, the presence of NPs, number of infiltrating tissue eosinophils, preoperative Lund–Mackay scores, and other comorbidities were analysed. EET formation was observed to varying degrees in all CRS groups and was correlated with the number of tissue eosinophils (r = 0.83, p < 0.001) regardless of the presence of NPs. Patients with more EETs demonstrated higher Lund–Mackay scores (r = 0.51, p = 0.009), blood eosinophilia (r = 0.80, p < 0.001), and decreased olfactory function (r = −0.65, p < 0.001). No correlation between the extent of EET formation and the presence of atopy or asthma was apparent. However, none of the CRS groups containing neutrophils formed NETs in this study. Eosinophilic CRS indicates the presence of EETs. Formation of EETs could have a role in clinical decision-making and prediction of treatment outcome of CRS, regardless of NP status.

Diagnosis and Management of Severe Asthma.

Severe therapy-resistant asthma has been defined as "asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming 'uncontrolled' or which remains 'uncontrolled' despite this therapy". Patients who usually present with 'difficult-to-treat asthma' should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.

Two inflammatory phenotypes of nasal polyps and comorbid asthma

BackgroundNasal polyps and comorbid asthma (NPCA) is a common united airway disease. However, the inflammatory phenotyes of NPCA are not clear. ObjectiveTo identify inflammatory phenotypes of NPCA. MethodsA total of 106 patients diagnosed with NPCA were recruited from rhinologic clinics. A combined method of biopsies from nasal polyps and fractional exhaled nitric oxide (FeNO) was used to explore inflammatory phenotyes of NPCA. Patients were evaluated with respect to clinical, functional, and inflammatory parameters. Clinical outcomes after medical treatment were also assessed. ResultsTwo distinct inflammatory phenotypes (eosinophilic [64.15%] and noneosinophilic phenotypes [35.85%]) were identified. Inflammatory patterns of upper and lower airways were consistent in NPCA. Patients with eosinophilic NPCA had a higher nasal polyps recurrence rate than did patients with noneosinophilic NPCA, a more severe asthma phenotype (P < .001), higher exhaled nitric oxide levels (P < .001), higher IgE levels (P < .001), higher Lund-Mackay scores (P < .05), and more blood eosinophilia (P < .001). In addition, eosinophilic NPCA was associated with worse pulmonary function and responded well to an 8-week course of medical treatment based on computed tomographic findings and the ratio of forced expiratory volume in 1 second to forced vital capacity. The total IgE concentration was a marker for eosinophilic NPCA (optimal cutoff, >55.5 kU/L; sensitivity, 86.2%; specificity, 85.4%). ConclusionPatients with NPCA had 2 inflammatory phenotypes with distinct clinical profiles. Total IgE is a marker of eosinophilic NPCA.

Phenotyping asthma using an unsupervised prediction model based on blood granulocyte responsiveness

Method Clinical parameters, activation of blood granulocytes and sputum phenotypes were assessed in 115 adult asthma patients (NCT01611012). Blood granulocytes were stained with antibodies against the active FcgRII receptor (CD32, clones A17/A27) and a-chain of MAC-1 (CD11b) in the presence or absence of fMLF, and analysed by flow cytometry. NLPCA was used to reduce dimensions in a combined cellular and clinical dataset, followed by discriminant analysis to generate a prediction model. Phenotypes identified by the model were cross-validated by inflammatory sputum phenotypes based on sputum induction (reference test). Results Peripheral blood eosinophil count, FeNO (Fraction of Exhaled Nitric Oxide), ACQ (Asthma Control Questionnaire), medication use, nasal polyposis, aspirin sensitivity and neutrophil/eosinophil responsiveness upon stimulation, are important parameters to differentiate between eosinophilic and non-eosinophilic phenotypes. The combinations of these parameters lead to an accurate prediction model for eosinophilic asthma with 90.5% sensitivity and 91.5% specificity.

Azithromycin for Prevention of Exacerbations in Severe Asthma: A Multicentre Randomized Double Blind Placebo-controlled Trial: Brusselle GG, VanderStichele C, Jordens P, et al. Thorax 2013;68:322–9.

Severe asthma increases the risk of lower respiratory tract infections and frequent asthma exacerbations. Two types of severe asthma exist: eosinophilic phenotypes and noneosinophilic (neutrophilic) phenotypes.

Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial

BackgroundPatients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic...

Airway Activation of Formyl Peptide Receptors Inhibits Th1 and Th17 Cell Responses via Inhibition of Mediator Release from Immune and Inflammatory Cells and Maturation of Dendritic Cells

Formyl peptide receptors (FPRs) are chemoattractant receptors that mediate inflammatory cell responses to infection. Recent evidence indicates that noneosinophilic asthma phenotypes can be developed by both Th1 and Th17 cell responses when exposed to LPS-containing allergens. In this study, we evaluated the effects of airway activation of FPRs by their synthetic agonist, Trp-Lys-Tyr-Met-Val-D-Met (W-peptide), on the development of Th1 and Th17 cell responses in a noneosinophilic asthma mouse model. A noneosinophilic asthma mouse model was generated by intranasal sensitization with 10 μg of LPS plus 75 μg of OVA on days 0, 1, 2, and 7. Mice were then challenged with 50 μg of OVA alone on days 14, 15, 21, and 22. W-peptide was administered during the sensitization period, and immune and inflammatory responses were evaluated after OVA challenge. Lung inflammation after OVA challenge was partly abolished by airway activation of FPRs during sensitization. Maturation of dendritic cells (DCs) and migration of DCs from the lung to lung-draining lymph nodes were inhibited by FPR activation. In addition, airway activation of FPRs inhibited allergen-specific T cell proliferation in the lymph nodes. Production of IL-12 and IL-6 (Th1- and Th17-polarizing cytokines) from lung DCs was decreased by airway activation of FPRs. This effect resulted in the inhibition of allergen-specific Th1 and Th17 cell responses. Airway activation of FPRs during sensitization effectively prevents the development of Th1 and Th17 cell responses induced by LPS-containing allergens via multiple mechanisms, such as inhibition of DC maturation and migration and the production of Th1- and Th7-polarizing cytokines.

Eosinophil and neutrophil extracellular DNA traps in human allergic asthmatic airways

Asthma is a heterogeneous inflammatory airway disorder that involves eosinophilic and noneosinophilic phenotypes. Unlike in healthy lungs, eosinophils are often present in atopic asthmatic airways, although a subpopulation of asthmatic subjects predominantly experience neutrophilic inflammation. Recently, it has been demonstrated that eosinophils and neutrophils generate bactericidal extracellular traps consisting of DNA and cytotoxic granule proteins. We sought to explore whether living eosinophils and neutrophils infiltrating human atopic asthmatic airways actively form extracellular DNA traps in vivo. Quantitative analysis of eosinophils releasing DNA was performed in endobronchial biopsy specimens from 20 human subjects with mild atopic asthma at baseline and after local allergen challenge and 10 healthy subjects. DNA was stained with propidium iodine and major basic protein with specific antibody. Differential cell counts and cytokines/chemokines were assessed in bronchoalveolar lavage fluid. Asthmatic airways were infiltrated with a significantly higher number of eosinophils than healthy airways (39.3 ± 4.6 vs 0.4 ± 0.9, P< .0001). All asthmatic subjects but only 1 control subject expressed eosinophils releasing DNA that colocalized with major basic protein (33.65 ± 20.33 vs 0.3 ± 0.9 per high-power field, P< .0001). Four asthmatic subjects mostly expressed neutrophilic inflammation and neutrophil DNA traps. Allergen challenge had no significant quantitative effect on eosinophil or neutrophil DNA traps. Airway eosinophils or DNA traps did not correlate with either bronchoalveolar lavage levels of IL-5, IFN-γ, or eotaxin or the provoking doses of methacholine or allergen in asthmatic subjects. Extracellular DNA traps are generated by eosinophils and neutrophils in human atopic asthmatic airways in vivo. The mechanism and role of this new finding will necessitate further investigation.

Differential gene expression and cytokine production from neutrophils in asthma phenotypes

Asthma is characterised into eosinophilic and non-eosinophilic phenotypes based on inflammatory cell patterns in airway secretions. Neutrophils are important in innate immunity, and are increased in the airways in non-eosinophilic asthma. The present study investigated the activity of neutrophils in asthma phenotypes. Participants with eosinophilic (n = 8) and non-eosinophilic asthma (n = 9) and healthy controls (n = 11) underwent sputum induction and blood collection. Neutrophils were isolated and cultured with or without lipopolysaccharide. Cytokines were measured by ELISA, and gene expression was analysed using a gene expression microarray and quantitative PCR. In non-eosinophilic asthma, blood neutrophils released significantly higher levels of interleukin-8 at rest. Cytokine gene expression and sputum neutrophil protein production did not differ between asthma subtypes. Microarrays demonstrated closely related expression profiles from participants with non-eosinophilic asthma that were significantly distinct from those in eosinophilic asthma. A total of 317 genes were significantly altered in resting neutrophils from participants with non-eosinophilic asthma versus eosinophilic asthma, including genes related to cell motility and regulation of apoptosis. Non-eosinophilic and eosinophilic asthma are associated with specific gene expression profiles, providing further evidence that these phenotypes of asthma involve different molecular mechanisms of disease pathogenesis at the systemic level. The mechanisms of non-eosinophilic asthma may involve enhancement of blood neutrophil chemotaxis and survival.

Pro-con debate: Inhaled corticosteroids should not be prescribed in primary care to children under two years of age — the case for

Inhaled corticosteroids (ICS) are effective treatment for older children and adults with asthma. Pathological studies have established that eosinophilic inflammation is important especially in mild to moderate asthma, thus providing a rationale for ICS treatment. However, we have wrongly concluded in the past that early and aggressive treatment of asthma is needed to prevent irreversible scarring and airflow obstruction. We have increasing evidence from all age groups that there are non-eosinophilic asthma phenotypes, that remodelling is independent of inflammation, and that steroids do not prevent children developing progressive airflow obstruction. Asthma treatments that are valuable in adults may not be effective in children, and safe prescribing requires paediatric clinical trials. In young preschool children, the evidence for any eosinophilic airway inflammation is scant, the symptomatic benefit of inhaled steroids is meagre, and there is clear evidence that ICS do not modify the natural history. There is also the potential for steroids to interfere with the developing lung. Thus, we believe that ICS should not be prescribed in primary care for children under two years of age, and that if these children are thought to need more than intermittent therapy with beta-agonists or possibly leukotriene antagonists, specialist referral is mandatory.

Proportion of eosinophilic and non-eosinophilic inflammation phenotypes in patients with mild to severe bronchial asthma, its influence on main clinical and functional outcomes and efficacy of inhaled steroid treatment

Proportion of eosinophilic and non-eosinophilic inflammation phenotypes in patients with mild to severe bronchial asthma, its influence on main clinical and functional outcomes and efficacy of inhaled steroid treatment

Airway inflammation assessed by invasive and noninvasive means in severe asthma: Eosinophilic and noneosinophilic phenotypes

Airway inflammation assessed by bronchial biopsies demonstrates distinct eosinophilic and noneosinophilic phenotypes in severe asthma, but their relationship to other biomarkers of disease (induced sputum and nitric oxide [NO]) is not clear. We sought to compare airway inflammation using noninvasive (induced sputum, exhaled NO), and invasive (bronchial biopsies) methods in moderate and severe asthma and to assess whether induced sputum and exhaled NO would allow the identification of eosinophilic and noneosinophilic phenotypes in severe asthma. We performed a cross-sectional study of 32 subjects with severe asthma and 35 subjects with moderate asthma, from whom we obtained bronchial biopsies, induced sputum, and exhaled NO measurements. Among subjects with severe asthma, we identified eosinophilic and noneosinophilic phenotypes using both bronchial biopsies and sputum cell counts. However, the vast majority of subjects with high sputum eosinophil counts did not have high mucosal eosinophil counts. Exhaled NO was increased in the eosinophilic phenotype as judged from bronchial biopsy findings, but not on the basis of induced sputum. Subjects with high sputum eosinophil counts experienced more asthma exacerbations than the subjects with low sputum eosinophil counts. In contrast, we did not find any differences in the clinical characteristics between eosinophilic and noneosinophilic phenotypes that were identified by bronchial biopsies. The use of sputum cell counts allowed the identification of a subgroup of subjects with severe asthma who were at risk of more frequent asthma exacerbations. Monitoring sputum eosinophil counts in subjects with severe asthma may allow identifying the subjects with the greatest disease activity.