Inflammatory Phenotypes Of Asthma Research Articles

To investigate the function of age-related genes in different subtypes of asthma based on bioinformatics analysis

Asthma is a heterogeneous airway inflammatory disease that can be classified according to the inflammatory phenotype. The pathogenesis, clinical features, response to hormone therapy, and prognosis of different inflammatory phenotypes differ significantly. This condition also refers to age-related chronic ailments. Here, we intend to identify the function of aging-related genes in different inflammatory phenotypes of asthma using bioinformatic analyses. Initially, the research adopted the GSEA analysis to understand the fundamental mechanisms that govern different inflammatory phenotypes of asthma pathogenesis and use the CIBERSORT algorithm to assess the immune cell composition. The differentially expressed genes (DEGs) of eosinophilic asthma (EA), neutrophilic asthma (NA), and paucigranulocytic asthma (PGA) were identified through the limma R package. Aging-related genes, screened from multiple databases, were intersected with DEGs of asthma to obtain the asthma-aging-related DEGs. Then, the GO and KEGG pathway enrichment analyses showed that the NA- and EA-aging-related DEGs are involved in the various cytokine-mediated signaling pathways. PPI network and correlation analysis were performed to identify and evaluate the correlation of the hub genes. Further, the clinical characteristics of asthma-aging-related DEGs were explored through ROC analysis. 3 and 12 aging-related DEGs in EA and NA patients show high diagnostic accuracy, respectively (AUC >0.7). This study provided valuable insights into aging-related gene therapy for phenotype-specific asthma. Moreover, the study suggests that effective interventions against asthma may operate by disrupting the detrimental cycle of “aging induces metabolic diseases, which exacerbate aging".

Exploring Inflammatory Asthma Phenotypes: Proteomic Signatures in Serum and Induced Sputum.

Asthma drug responses may differ due to inflammatory mechanisms triggered by the immune cells in the pulmonary microenvironment. Thus, asthma phenotyping based on the local inflammatory profile may aid in treatment definition and the identification of new therapeutic targets. Here, we investigated protein profiles of induced sputum and serum from asthma patients classified into eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma, according to inflammatory phenotypes. Proteomic analyses were performed using an ultra-performance liquid chromatography (ultra-HPLC) system coupled to the Q Exactive Hybrid Quadrupole Orbitrap Mass Spectrometer. Fifty-two (52) proteins showed significant differences in induced sputum among the groups, while only 12 were altered in patients' sera. Five proteins in the induced sputum were able to discriminate all phenotypic groups, while four proteins in the serum could differentiate all except the neutrophilic from the paucigranulocytic inflammatory pattern. This is the first report on comparative proteomics of inflammatory asthma phenotypes in both sputum and serum samples. We have identified a potential five-biomarker panel that may be able to discriminate all four inflammatory phenotypes in sputum. These findings not only provide insights into potential therapeutic targets but also emphasize the potential for personalized treatment approaches in asthma management.

Phenotyping of Severe Asthma in the Era of Broad-Acting Anti-Asthma Biologics

Severe asthma is associated with significant morbidity and mortality despite maximal use of inhaled corticosteroids and additional controller medications, and has a high economic burden. Biologic therapies are recommended for the management of severe, uncontrolled asthma to help prevent exacerbations and to improve symptoms and health-related quality of life. Effective management of severe asthma requires consideration of clinical heterogeneity that is driven by varying clinical and inflammatory phenotypes, which are reflective of distinct underlying disease mechanisms. Phenotyping patients using a combination of clinical characteristics such as age of onset or comorbidities and biomarker profiles, including blood eosinophil counts, and levels of fractional exhaled nitric oxide and serum total immunoglobulin E, is important for the differential diagnosis of asthma. Additionally, phenotyping is beneficial for risk assessment, selection of treatment, and monitoring of treatment response in patients with asthma. This review describes the clinical and inflammatory phenotypes of asthma, provides an overview of biomarkers routinely used in clinical practice and those that have recently been explored for phenotyping, and aims to assess the value of phenotyping in severe asthma management in the current era of biologics.

Asthma Inflammatory Phenotypes: How Can We Distinguish Them?

induced sputum is used to assess different inflammatory phenotypes in asthma, but is not used routinely. We aimed to determine the proportion of inflammatory asthma phenotypes based on induced sputum, to find biomarkers that can discriminate between phenotypes, and to evaluate biomarkers in patients with and without biological therapy in different inflammatory asthma phenotypes. this cross-sectional study investigated clinical characteristics, asthma control tests, skin prick test, impulse oscillometry (IOS), spirometry, induced sputum, biomarkers (IgE, eosinophils, fractional exhaled nitric oxide (FeNO), serum periostin, IL-5, IL-6, IL-8, IL-17A, IL-33) in 80 asthmatics. A total of 17/80 patients were treated with biologics (10 with omalizumab, 7 with benralizumab). a total of 31% of patients had eosinophilic asthma (EA), 30% had mixed granulocytic asthma (MGA), 24% had paucigranulocytic asthma (PGA), and 15% had neutrophilic asthma (NA). The difference was found in blood eosinophils (p = 0.002), the highest observed in EA. The cut-off ≥ 240/μL eosinophils, with 64% sensitivity and 72.7% specificity, identified EA (AUC = 0.743, p = 0.001). A higher IL-8 level was associated with NA (p = 0.025). In 63 non-biologic asthma group, eosinophils were higher in EA than in NA, MGA, and PGA (p = 0.012, p = 0.028, and p = 0.049, respectively). A higher IL-17A was associated with EA without biologics (p = 0.004). A significantly higher IL-5 was found in EA treated with biologics, in comparison with EA without biologics (p = 0.043). The number of leucocytes and neutrophils was higher in MGA without biologics (p = 0.049, p = 0.019), while IL-5, IL-6, and IL-8 levels were higher in MGA treated with biologics (p = 0.012, p = 0.032, p = 0.038, respectively). EA and MGA were the most prevalent asthma phenotypes. Blood eosinophils can identify EA, both in patients with and without biologics. Apart from the clinical profile, a broad spectrum of biomarkers for assessing inflammatory phenotypes is necessary for an adequate therapy approach to patients with asthma.

Airway Microbiome Composition and Co-Occurrence Network Are Associated with Inflammatory Phenotypes of Asthma

Introduction: The composition and co-occurrence network of the airway microbiome might influence the asthma inflammatory phenotype. Airway microbiota change with asthma phenotypes, and the structure of the bacterial community in the airway might differ between different asthma inflammatory phenotypes and may also influence therapy results. Identifying airway microbiota can help to investigate the role that microbiota play in the asthma inflammatory process. Methods: Induced sputum from 55 subjects and 12 healthy subjects from Beijing, China, was collected and analyzed for bacterial microbiota. Microbiome diversity, composition, co-occurrence networks, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were predicted and compared between the study groups. Results: Significant differences in the sputum microbiome composition, co-occurrence network, and predicted functional pathways were observed between the two inflammatory phenotypes. Asthmatics in the low FeNO group exhibited lower α-diversity in the sputum microbiota and had higher abundance of the phylum Proteobacteria compared with that of the high FeNO group. The network in the high FeNO group was more “closed” and “connected” compared with that of the low FeNO group, and an alteration in the abundance of keystone species T. socranskii was found. Significantly different predicted metabolic subfunctions including nucleotide metabolism, lipid metabolism, energy metabolism, replication and repair, and drug resistance antimicrobial and carbohydrate metabolism between the two studied phenotypes were also observed. Conclusion: Our findings confirm that the airway microbiota is associated with the asthma inflammation process. The differences in the airway microbiome composition and co-occurrence network may affect distinct asthma inflammatory phenotypes, suggesting the possibility that more targeted therapies could be applied based on the airway bacterial genera.

Asthma Prevalence and Phenotyping in the General Population: The LEAD (Lung, hEart, sociAl, boDy) Study.

Asthma is a chronic heterogeneous respiratory disease involving differential pathophysiological pathways and consequently distinct asthma phenotypes. In the LEAD Study, a general population cohort (n=11.423) in Vienna ranging from 6-82 years of age, we addressed the prevalence of asthma and explored inflammatory asthma phenotypes that included allergic and non-allergic asthma, and within these phenotypes, an eosinophilic (eosinophils ≥300 cells/µL, or ≥150 cells/µL in the presence of ICS medication) or non-eosinophilic (eosinophils <300 cells/µL, or <150 cells/µL in the presence of ICS) phenotype. In addition, we compared various factors related to biomarkers, body composition, lung function, and symptoms in control subjects versus subjects with current asthma (current doctor's diagnosis of asthma). An overall prevalence of 4.6% was observed for current asthma. Furthermore, an age-dependent shift from allergic to non-allergic asthma was found. The non-eosinophilic phenotype was more prominent. Obesity was a prevalent condition, and body composition including visceral adipose tissue (VAT), is affected in current asthma versus controls. This broad-aged and large general population cohort identified differential patterns of inflammatory asthma phenotypes that were age-dependent. The presence of eosinophilia was associated with worse asthma control, increased asthma medication, increased VAT, and lower lung function, the opposite was found for the presence of an allergic asthma.

Effect Of Tezepelumab In Patients With Severe, Uncontrolled Asthma By Age Of Onset, Allergic Status, And Eosinophilic Phenotype

Biologic efficacy for severe asthma varies depending on age of asthma onset and inflammatory phenotype. This post hoc analysis assessed the effect of tezepelumab in patients with severe, uncontrolled asthma with childhood-onset and current allergic or non-eosinophilic disease and adult-onset and current eosinophilic or non-allergic disease using pooled data from the phase 2b PATHWAY and phase 3 NAVIGATOR studies.

SPUTUM NEUTROPHILIA IN ACUTE EXACERBATION OF BRONCHIAL ASTHMA

Background : Asthma is a common respiratory condition that affects an estimated 358 million people worldwide. Neutrophilic asthma is an asthma inflammatory phenotype associated with exacerbation,airflow limitation,and steroid resistance. Objective : The aim of the study was to observe the severity of Bronchial asthma in patients with Sputum Neutrophilia .Methods:This is a prospective cross sectional study by Department of Pulmonary Medicine including 50 patients with Acute Exacerbation of Bronchial Asthma as determined by ACQ. Results: Patients with sputum neutrophilia were seen to have higher ACQ scores,poor bronchodilator reversibility ,low expiratory volumes and poor response to inhaled corticosteroids with a higher risk of exacerbation.The correlation between sputum Neutrophilia and Bronchodilator reversibility using spirometry is statistically significant(p value = 0.0001) with a greater incidence of hospitalization for asthma.Conclusion:Neutrophilic asthma is associated with less atopy and these patients have lower levels of exhaled nitric oxide (FeNO), greater incidence of hospitalization for asthma and higher incidence of steroid resistance.Sputum neutrophilia has a positive correlation with smoking and is more often seen in older males

Asthma inflammatory phenotypes on four continents: most asthma is non-eosinophilic.

Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK). We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016-20. All centres studied children and adolescents (age range 8-20 years), except the UK centre which involved 26-27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum. Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37-2.94) with lower odds in the LMICs: Brazil (0.73, 0.42-1.27), Ecuador (0.40, 0.24-0.66) and Uganda (0.62, 0.37-1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda. This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally.

TIPE2 May Target the Nrf2/HO-1 Pathway to Inhibit M1 Macrophage-Related Neutrophilic Inflammation in Asthma.

PurposeAlthough recent studies have highlighted the link of TIPE2 and asthma airway inflammation, its roles and molecular mechanisms in different asthma inflammatory phenotypes remain largely unknown. We evaluated sputum TIPE2 expression level and its correlation with different asthma phenotypes. Additionally, we explored the roles and mechanism of TIPE2 in M1 polarization of macrophages.MethodsA total of 102 asthma patients who underwent sputum induction were enrolled to evaluate the expression level of TIPE2 and its association with different asthma phenotypes. To explore the roles and mechanism of TIPE2 in M1 polarization of macrophages, THP-1 monocytes stimulated with phorbol-12-myristate-13-acetate, were used as a model of undifferentiated (M0) macrophages, and M0 macrophages were treated with lipopolysaccharide to induce M1 macrophages.ResultsThe sputum TIPE2 level was significantly lower in patients with neutrophilic asthma (NA) and higher in patients with eosinophilic asthma (EA) compared with patients with paucigranulocytic asthma. The levels of IL-1β, TNF-α and IL-6 were highest in NA compared with other groups. TIPE2 levels in sputum negatively correlated with IL-1β and TNF-α levels but positively correlated with IL-4, IL-5, IL-13, and IL-10 levels (P < 0.05). In vitro, TIPE2 enhanced Nrf2/HO-1 pathway activation in macrophages and inhibited LPS-induced M1 macrophage differentiation and related cytokine release. Further analysis showed that the Nrf2 inhibitor ML385 weakened TIPE2-induced activation of the Nrf2/HO-1 pathway, as well as TIPE2-induced suppression in M1 polarization of macrophage and inflammatory cytokines secretion.ConclusionsTIPE2 expression level was highly down-regulated in NA and was negatively correlated with inflammatory factors (IL-1β and TNF-α). Aberrant expression of TIPE2 may target the Nrf2/HO-1 pathway to inhibit M1 macrophage–related neutrophilic inflammation in asthma.

Blood inflammatory phenotypes were associated with distinct clinical expressions of asthma in adults from a large population-based cohort.

SummaryBackgroundAsthma is an inflammatory heterogeneous disease. Asthma inflammatory phenotypes based on blood eosinophil and neutrophil counts have never been identified and characterized in population-based studies.MethodsAdults with current asthma and available blood eosinophil and neutrophil counts from the French population-based CONSTANCES cohort were included. Current asthma was defined by reports of asthma attacks, symptoms or treatments in the last 12 months. Inflammatory phenotypes were based on low (L) and high (H) blood (B) eosinophil (E) (LBE/HBE: </⩾0·25 × 109/L, respectively) and neutrophil (N) (LBN/HBN: </⩾5 × 109/L, respectively) cut-offs. Associations between inflammatory phenotypes and the clinical expressions of asthma were studied using logistic models adjusted for age, sex, smoking status, body mass index, education level, French deprivation index and treatment. Other cut-offs were applied. Stratified analyses according to age or sex were performed.FindingsAmong 15,019 adults with asthma (56% women, 59%≥40 years), the LBE/LBN (reference), LBE/HBN, HBE/LBN and HBE/HBN phenotypes accounted for 57%, 6%, 33% and 4% respectively. The LBE/HBN phenotype was associated with being awaken by an attack of coughing, chronic bronchitis, and dyspnoea (adjusted(a)OR ranging from 1·21 to 1·42). The HBE/LBN and HBE/HBN phenotypes were associated with asthma attacks (aOR=1·31[1·20-1·42], 1·25[1·02-1·53]) and asthma symptom score (p for trend<0·0001, p for trend=0·001, respectively). The HBE/LBN phenotype was also associated with being awaken with chest tightness (aOR=1·30[1·20-1·40]). Results were unchanged whatever the cut-offs used. No statistically significant heterogeneity was observed according to age or sex.InterpretationDifferences in the clinical expressions of asthma were found between the phenotypes, reproducible whatever the cut-offs used, and similar to those observed in case-control and clinical studies. Such phenotypes are of interest to improve asthma management and study its environmental risk factors.FundingThe CONSTANCES cohort receives grants from ANR (ANR-11-INBS-0002), the Caisse nationale d'assurance maladie-CNAM and the Ministry of research. CONSTANCES also receives funding from MSD, AstraZeneca, Lundbeck and L'Oréal, managed by INSERM-Transfert. T.Tsiavia is supported by a PhD grant from the Fondation pour le Recherche Médicale (ECO202006011654).

Sputum Metabolomic Profiling Reveals Metabolic Pathways and Signatures Associated With Inflammatory Phenotypes in Patients With Asthma.

PurposeThe molecular links between metabolism and inflammation that drive different inflammatory phenotypes in asthma are poorly understood. We aimed to identify the metabolic signatures and underlying molecular pathways of different inflammatory asthma phenotypes.MethodsIn the discovery set (n = 119), untargeted ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to characterize the induced sputum metabolic profiles of asthmatic patients with different inflammatory phenotypes using orthogonal partial least-squares discriminant analysis (OPLS-DA), and pathway topology enrichment analysis. In the validation set (n = 114), differential metabolites were selected to perform targeted quantification. Correlations between targeted metabolites and clinical indices in asthmatic patients were analyzed. Logistic and negative binomial regression models were established to assess the association between metabolites and severe asthma exacerbations.ResultsSeventy-seven differential metabolites were identified in the discovery set. Pathway topology analysis uncovered that histidine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism as well as phenylalanine, tyrosine and tryptophan biosynthesis were involved in the pathogenesis of different asthma phenotypes. In the validation set, 24 targeted quantification metabolites were significantly expressed between asthma inflammatory phenotypes. Finally, adenosine 5′-monophosphate (adjusted relative risk [adj RR] = 1.000; 95% confidence interval [CI] = 1.000–1.000; P = 0.050), allantoin (adj RR = 1.000; 95% CI = 1.000–1.000; P = 0.043) and nicotinamide (adj RR = 1.001; 95% CI = 1.000–1.002; P = 0.021) were demonstrated to predict severe asthma exacerbation rates.ConclusionsDifferent inflammatory asthma phenotypes have specific metabolic profiles in induced sputum. The potential metabolic signatures may identify therapeutic targets in different inflammatory asthma phenotypes.

Unraveling the Relationship of Asthma and COVID-19.

Viral infections are one of the main causes of asthma exacerbations. During the COVID-19 era, concerns regarding the relationship of SARS-CoV2 with asthma have been raised. The concerns are both for COVID severity and asthma exacerbations. Many studies on COVID-19 epidemiology and comorbidities have assessed whether asthma represents a risk factor for SARS-CoV2 infection and/or more severe course of the disease. This review covers the current evidence on the prevalence of asthma in COVID-19 and its association with susceptibility to and severity of SARS-CoV2 infection. It will examine the possible role of underlying asthma severity in COVID-19 related outcomes as well as the molecular mechanisms involved in the co-existence of these entities. The possible role of asthma inflammatory phenotypes will also be evaluated. Finally, the impact of asthma comorbidities and the implications of asthma medication on COVID-19 will be addressed.

Distribution of inflammatory phenotypes among patients with asthma in Jilin Province, China: a cross-sectional study

BackgroundThe inflammatory phenotypes of asthma predict the treatment response and prognosis. The phenotype distributions differ depending on the geographical region. This study aimed to assess the distribution of different inflammatory phenotypes among asthma patients in Jilin Province, China.MethodsA total of 255 patients with asthma were recruited from Jilin Province, China for this cross-sectional study. Each patient underwent sputum induction following clinical assessment and peripheral blood collection. Inflammatory phenotypes were classified according to the inflammatory cell counts in the sputum.ResultsPaucigranulocytic asthma (PGA) was the most common inflammatory phenotype (52.2%), followed by eosinophilic asthma (EA, 38.3%), mixed granulocytic asthma (MGA, 5.2%), and neutrophilic asthma (NA, 4.3%). NA was more common among patients over 45 years old and those who were treated with higher doses of inhaled corticosteroids (ICS), but was less common following antibiotics treatment (p < 0.05). The proportion of patients with EA decreased as the ICS treatment dose and time increased (p = 0.038). Patients with uncontrolled asthma had higher numbers of sputum eosinophils and neutrophils (p < 0.05). Patients with severe asthma had a higher percentage of sputum neutrophils (p < 0.05). A greater proportion of patients with NA had severe asthma (60%) compared to those with EA (18.2%) (p = 0.016).ConclusionsThe most common asthma inflammatory cell phenotype in Jilin Province, China is PGA, followed by EA, MGA, and NA. The low prevalence of NA in Jilin Province compared to other countries and also other regions in China might be due to excessive antibiotic use and irregular ICS treatment in this region.

Characteristics of inflammatory phenotypes among patients with asthma: relationships of blood count parameters with sputum cellular phenotypes

BackgroundThere is a need to identify the asthma inflammatory phenotypes of patients to facilitate personalized asthma treatment. Sputum induction is time-consuming and requires expert clinical technique. This study aimed to assess the distribution and characteristics of asthma inflammatory phenotypes in Jilin Province, China; it also aimed to identify an easier method for characterization of an asthma phenotype, rather than sputum cellular analysis.MethodsIn this study, 232 asthma patients underwent sputum induction following clinical assessment and blood collection. Inflammatory cell counts in sputum were used to classify asthma inflammatory phenotypes. Receiver operating characteristic curve and Spearman correlation coefficient analyses were used to identify correlations between clinical parameters.ResultsAmong the included patients, there had 52.1% paucigranulocytic, 38.4% eosinophilic, 4.3% neutrophilic, and 5.2% mixed granulocytic asthma phenotypes, respectively. In total, 129 (55.6%) patients had asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO); these patients had higher proportion of smokers, higher sputum neutrophil count, worse lung function, and worse asthma control, compared with patients who had asthma alone (p < 0.05). Sputum eosinophil/neutrophil counts were positively correlated with blood eosinophil/neutrophil counts (p < 0.01). To identify the presence of sputum eosinophil proportion ≥ 3%, optimal cut-off values for blood eosinophil count and fractional exhaled nitric oxide (FeNO) were 0.2 × 109/L and 30.25 ppd (area under the curve (AUC) = 0.744; AUC = 0.653, p < 0.001). AUCs did not significantly differ between FeNO and blood eosinophil count (p = 0.162), but both exhibited poor specificity (57% and 49%, respectively). To identify the presence of sputum neutrophil proportion ≥ 61%, the optimal cut-off value for blood neutrophil proportion was 69.3% (AUC = 0.691, p = 0.0003); however, this exhibited poor sensitivity (50%).ConclusionsPaucigranulocytic asthma was the most common phenotype, followed by eosinophilic asthma. Higher proportion of smokers, poor patient compliance, insufficient treatment, and poor asthma control may have been the main causes of high ACO proportion among patients in this study. Blood eosinophil/neutrophil counts exhibited poor specificity and sensitivity for prediction of airway eosinophilic/neutrophilic inflammation.

Chronic oral corticosteroids use and persistent eosinophilia in severe asthmatics\xa0from the Belgian severe asthma registry

BackgroundSevere asthma (SA) may require frequent courses or chronic use of oral corticosteroids (OCS), inducing many known side effects and complications. Therefore, it is important to identify risk factors of chronic use of OCS in SA, considering the heterogeneity of clinical and inflammatory asthma phenotypes. Another aim of the present analysis is to characterize a subpopulation of severe asthmatics, in whom blood eosinophil counts (BEC) remain elevated despite chronic OCS treatment.MethodsIn a cross-sectional analysis of 982 SA patients enrolled in the Belgian Severe Asthma Registry (BSAR) between March 2009 and February 2019, we investigated the characteristics of the OCS treated patients with special attention to their inflammatory profile.ResultsAt enrollment, 211 (21%) SA patients were taking maintenance OCS (median dose: 8 [IQR: 5–10]) mg prednisone equivalent). BEC was high (> 400/mm3) in 44% of the OCS treated population. Multivariable logistic regression analysis showed that risk factors for chronic use of OCS in SA were late-onset asthma (i.e. age of onset > 40 yr), frequent exacerbations (i.e. ≥2 exacerbations in the previous year) and non-atopic asthma. Late-onset asthma was also a predictor for persistently high BEC in OCS treated SA patients.ConclusionThese data showed a significant association between a persistently high BEC and late-onset asthma in OCS treated SA patients. Whether it is poor compliance to treatment or corticosteroid insensitivity the reasons for this association warrants further investigation.

Relationship between sputum periostin level and inflammatory asthma phenotypes in Egyptian patients

Introduction Asthma is a common chronic inflammatory air way disease which poses a high disease burden worldwide. Asthma is a heterogenous disease with various phenotypes and endotypes. Refractory asthma requires new and personalized approaches to manage it effectively. Periostin is a promising biomarker that may help in predicting severity, prognosis and could be a therapeutic target. We aimed in this study to investigate periostin levels in the sputum of asthmatic Egyptian patients of inflammatory phenotypes and its relation to asthma severity. Subjects and methods This study included 96 adult asthmatic patients; 48 patients with mild-to-moderate bronchial asthma, 48 patients with severe bronchial asthma according to ATS criteria and 10 healthy controls. All participants were subjected to full history taking and clinical examination; pulmonary function tests; skin prick test; induced-sputum analysis for inflammatory cells and periostin. Results Sputum periostin concentrations were significantly higher in patients with asthma than in controls. Sputum periostin is strongly correlated with age and sputum TLC and inversely correlated with FEV1. It is correlated with sputum neutrophil count and sputum eosinophil percentage. Best cut off value for sputum periostin is >528.25 ng/ml to differentiate between mild-to-moderate and severe asthma. Conclusion Sputum periostin levels provide a satisfying diagnostic accuracy in severe asthmatic with persistent airflow limitation than mild-to-moderate asthmatic adults. There is a modest positive correlation between sputum periostin and sputum eosinophilia

Expression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype

BackgroundMore than 300 million people carry a diagnosis of asthma, with data to suggest that they are at a higher risk for infection or adverse outcomes from severe acute respiratory syndrome coronavirus 2. Asthma is remarkably heterogeneous, and it is currently unclear how patient-intrinsic factors may relate to coronavirus disease 2019.ObjectiveWe sought to identify and characterize subsets of patients with asthma at increased risk for severe acute respiratory syndrome coronavirus 2 infection.MethodsParticipants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to angiotensin-converting enzyme-2 (ACE2) expression within bronchial epithelium. ACE-2–correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets.ResultsStratifying by type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the severe acute respiratory syndrome coronavirus 2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with type 1 and 2 IFN signatures, normally induced by viral infections. T-cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe coronavirus disease 2019, including male sex, history of hypertension, low peripheral blood, and elevated bronchoalveolar lavage lymphocytes.ConclusionsACE2 expression is linked to upregulation of viral response genes in a subset of type 2–low patients with asthma with characteristics resembling known risk factors for severe coronavirus disease 2019. Therapies targeting the IFN family and T-cell–activating factors may therefore be of benefit in a subset of patients.

Predictors of a good response to inhaled corticosteroids in obesity-associated asthma

IntroductionAsthma in obese subjects is poorly understood. According to GINA guidelines, pulmonologists increase ICS in case of poor asthma control but lung volume restriction may also worsen respiratory symptoms in obese asthmatics leading to overtreatment in this subpopulation. MethodsWe conducted a retrospective study on 1217 asthmatics recruited from University Hospital of Liege. 92 patients with a BMI ≥30 came at least two times at the asthma clinic (mean interval: 335 days). In this obese population, we identified predictors of good (decrease in ACQ ≥0.5) versus poor response (rise in ACQ ≥0.5) to ICS step-up therapy. ResultsObese asthmatics had a poorer asthma control and quality of life as compared to non-obese and exhibited reduced FVC, higher levels of blood leucocytes and markers of systemic inflammation. The proportion of asthma inflammatory phenotypes was similar to that observed in a general population of asthmatics. Among uncontrolled obese asthmatics receiving ICS step-up therapy, 53% improved their asthma control while 31% had a worsening of their asthma. Uncontrolled obese asthmatics showing a good response to increase in ICS had higher ACQ, lower CRP levels, higher sputum eosinophil counts and higher FeNO levels at visit 1. Uncontrolled obese asthmatics that worsened after increasing the dose of ICS had lower FVC, lower sputum eosinophil counts and higher sputum neutrophil counts. ConclusionWe observed poorer asthma control in obese asthmatics despite similar bronchial inflammation. Managing obese asthmatics according to ACQ alone seems to underestimate asthma control and the contribution of restriction to dyspnea. Increasing the dose of ICS in the absence of sputum eosinophilic inflammation or in the presence of restriction or bronchial neutrophilia led to poorer asthma control. In those patients, management of obesity should be the first choice.

Ceramide/sphingosine-1-phosphate imbalance is associated with distinct inflammatory phenotypes of uncontrolled asthma.

Asthma is associated with inflammatory dysregulation, but the underlying metabolic signatures are unclear. This study aimed to classify asthma inflammatory phenotypes based on cellular and metabolic features. To determine cellular and metabolic profiles, we assessed inflammatory cell markers using flow cytometry, sphingolipid (SL) metabolites using LC-MS/MS, and serum cytokines using ELISA. Targeted gene polymorphisms were determined to identify genetic predispositions related to the asthma inflammatory phenotype. In total, 137 patients with asthma and 20 healthy controls (HCs) were enrolled. Distinct cellular and metabolic profiles were found between them; patients with asthma showed increased expressions of inflammatory cell markers and higher levels of SL metabolites compared to HCs (P<.05 for all). Cellular markers (CD66+ neutrophils, platelet-adherent eosinophils) and SL metabolic markers (C16:0 and C24:0 ceramides) for uncontrolled asthma were also identified; higher levels were observed in uncontrolled asthma compared to controlled asthma (P<.05 for all). Asthmatics patients with higher levels of CD66+ neutrophils had lower FEV1(%), higher ACQ (but lower AQLO) scores, and higher sphingosine and C16:0 ceramide levels compared to those with low levels of CD66+ neutrophils. Asthmatics patients with higher levels of platelet-adherent eosinophils had higher S1P levels compared to those with lower levels of platelet-adherent eosinophils. Patients carrying TT genotype of ORMDL3 had more CD66+ neutrophils; those with AG/ GG genotypes of SGMS1 exhibited higher platelet-adherent eosinophils. Patients with uncontrolled asthma possess distinct inflammatory phenotypes including increased CD66+ neutrophils and platelet-adherent eosinophils, with an imbalanced ceramide/S1P rheostat, potentially involving ORMDL3 and SGMS1 gene polymorphisms. Ceramide/S1P synthesis could be targeted to control airway inflammation.