Asthma Phenotypes Research Articles

Nasal virus infection induces asthma exacerbation through B-cell-dependent recruitment of inflammatory monocytes.

Upper respiratory viral infections (URVIs) are responsible for 80% of asthma exacerbation episodes. However, the underlying mechanisms remain poorly understood. In this study, we used a mouse model of URVI and examined the impact of URVI on asthma phenotypes and the underlying mechanisms. Previously, we have reported that nasal-restricted infection with respiratory syncytial virus (RSV) only produces mild sino-nasal inflammation and mucus production, without causing direct lung infection. However, such nasal-restricted infection dramatically enhanced TH2 and TH17 inflammatory responses in the lungs and increased airway hyperresponsiveness (AHR) in mice with house dust mite (HDM)-induced asthma. Additionally, nasal-restricted infection with RSV recruited Ly6C+ inflammatory monocytes (IMs) into the lungs of mice with and without HDM-induced asthma. The expression of monocyte chemokines, including CCL2 and CCL7, also increased. Interestingly, nasal virus infection-induced AHR was abolished in mice depleted of IMs and in CCR2-/- mice, indicating that the recruited IMs play a key role in nasal virus infection-induced asthma exacerbations in mice. Lastly, we observed that recruitment of Ly6C+ IMs following URVI was abolished in mice lacking B cells and that nasal-restricted infection with RSV increased numbers of CCL2+CCL7+ B cells in the lungs of mice as compared to controls. Taken together, our data have shown that URVI enhances the allergic inflammatory response and AHR through a B cell‒monocyte regulatory axis.

Therapeutic effect of long-acting muscarinic antagonist for treating uncontrolled asthma assessed using impulse oscillometry

BackgroundIn recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS.MethodsOf a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV1 or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA.ResultsOf the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV1 or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV1, %MMEF, %PEF, and all IOS parameters.ConclusionICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases.

Level of education, but not occupation, is differentially associated with asthma phenotypes in adults.

Education, but not occupation, was differentially associated with adult asthma phenotypes in the general population. Further research into socioeconomic status variation in various asthma phenotypes is warranted.

Identification of severe acute pediatric asthma phenotypes using unsupervised machine learning.

More targeted management of severe acute pediatric asthma could improve clinical outcomes. To identify distinct clinical phenotypes of severe acute pediatric asthma using variables obtained in the first 12 h of hospitalization. We conducted a retrospective cohort study in a quaternary care children's hospital from 2014 to 2022. Encounters for children ages 2-18 years admitted to the hospital for asthma were included. We used consensus k means clustering with patient demographics, vital signs, diagnostics, and laboratory data obtained in the first 12 h of hospitalization. The study population included 683 encounters divided into derivation (80%) and validation (20%) sets, and two distinct clusters were identified. Compared to Cluster 1 in the derivation set, Cluster 2 encounters (177 [32%]) were older (11 years [8; 14] vs. 5 years [3; 8]; p < .01) and more commonly males (63% vs. 53%; p = .03) of Black race (51% vs. 40%; p = .03) with non-Hispanic ethnicity (96% vs. 84%; p < .01). Cluster 2 encounters had smaller improvements in vital signs at 12-h including percent change in heart rate (-1.7 [-11.7; 12.7] vs. -7.8 [-18.5; 1.7]; p < .01), and respiratory rate (0.0 [-20.0; 22.2] vs. -11.4 [-27.3; 9.0]; p < .01). Encounters in Cluster 2 had lower percentages of neutrophils (70.0 [55.0; 83.0] vs. 85.0 [77.0; 90.0]; p < .01) and higher percentages of lymphocytes (17.0 [8.0; 32.0] vs. 9.0 [5.3; 14.0]; p < .01). Cluster 2 encounters had higher rates of invasive mechanical ventilation (23% vs. 5%; p < .01), longer hospital length of stay (4.5 [2.6; 8.8] vs. 2.9 [2.0; 4.3]; p < .01), and a higher mortality rate (7.3% vs. 0.0%; p < .01). The predicted cluster assignments in the validation set shared the same ratio (~2:1), and many of the same characteristics. We identified two clinical phenotypes of severe acute pediatric asthma which exhibited distinct clinical features and outcomes.

Research progress on the relationship between phenotype and signaling pathways of pulmonary macrophages and asthma

Objective The purpose of this study is to systematically investigate the different phenotypes and functional analyses of macrophages in lung tissue. Data sources A search was performed using three databases (Web of Science, Science Direct, and MEDLINE) for all relevant studies published from January 1, 2019, to December 31, 2023. Study selections This systematic review complied with the PRlSMA document’s requirements, including studies related to the signaling pathway relationship between pulmonary macrophages and asthma phenotype. The search includedstudies published in English or French lanquage, and was based on title, abstract, and complete textDocuments not meeting inclusion requirements were excluded Results We have identified studies published within the past five years that meet the criteria for inclusion in this review. We found that asthma is a heterogeneous chronic inflammatory lung disease, and lung tissue macrophages are important immune cells in the respiratory tract. Pulmonary macrophages are also heterogeneous, as they have different subgroups with varying effector functions depending on the environment. They have different phenotypes and biological functions in different disease environments. The phenotypic changes of pulmonary macrophages occur during asthma, and the study of the different phenotypes and functions of macrophages in lung tissue is of great significance for treatment. Conclusions This review summarizes current literature and provides a detailed introduction to the role of macrophages as key inflammatory mediators in the pathogenesis of asthma, as well as existing knowledge gaps. In addition, we propose that regulatory macrophages may prevent the development of asthma by producing IL-10, and regulating the polarization of pulmonary macrophages may be a new direction for asthma treatment.

Hedgehog signaling pathway regulates Th17 cell differentiation in asthma via IL-6/STAT3 signaling

Asthma is the most prevalent chronic inflammatory disease of the airways in children. The most prevalent phenotype of asthma is eosinophilic asthma, which is driven by a Th2 immune response and can be effectively managed by inhaled corticosteroid therapy. However, there are phenotypes of asthma with Th17 immune response that are insensitive to corticosteroid therapy and manifest a more severe phenotype. The treatment of this corticosteroid-insensitive asthma is currently immature and requires further attention. The objective of this study is to elucidate the regulation of the Hedgehog signaling pathway in Th17 cell differentiation in asthma. The study demonstrated that both Smo and Gli3, key components of the Hedgehog signaling pathway, were upregulated in Th17 polarization in vitro and in a Th17-dominant asthma model in vivo. Inhibiting Smo with a small molecule inhibitor or genetically knocking down Gli3 was found to suppress Th17 polarization. Smo was found to increase in Th1, Th2, Th17 and Treg polarization, while Gli3 specifically increased in Th17 polarization. ChIP-qPCR analyses indicated that Gli3 can directly interact with IL-6 in T cells, inducing STAT3 phosphorylation and promoting Th17 cell differentiation. Furthermore, the study demonstrated a correlation between elevated Gli3 expression and IL-17A and IL-6 expression in children with asthma. In conclusion, the study demonstrated that the Hedgehog signaling pathway plays an important role in the pathogenesis of asthma, as it regulates the differentiation of Th17 cells through the IL-6/STAT3 signaling. This may provide a potential therapeutic target for corticosteroid-insensitive asthma driven by Th17 cells.

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".

Clinical and Economic Burden of Severe Asthma With Low Blood Eosinophil Counts

BackgroundType 2 (T2) low severe asthma phenotype is often a result of corticosteroid-overtreated T2-disease due to persistent symptoms, often not related to asthma, and unlikely to respond to high-dose corticosteroid treatment. ObjectiveThis study aimed to characterise severe asthma patients with low eosinophil counts (<300 cells/μl) and describe their disease burden and treatment across healthcare settings in the UK. MethodsA retrospective cohort study of severe asthma patients using linked Clinical Practice Research Datalink (CPRD) Aurum-Hospital Episode Statistics (HES) and UK Severe Asthma Registry (UKSAR) data indexed patients on latest blood eosinophil count (BEC). Clinical characteristics, treatment patterns, outcomes, and healthcare resource use (HCRU) were described by baseline BEC (≤150 and >150 to <300 cells/μl). ResultsAnalysis included 701 (CPRD-HES) and 1,546 (UKSAR) patients; with 60.5% and 59.4% having BECs ≤150 cells/μl at baseline, respectively. Across BEC groups, the proportion with uncontrolled asthma (≥2 exacerbations) at follow-up (12-months post-index) was 5.4% in CPRD-HES and 45.2% in UKSAR. Maintenance OCS use remained high across BEC groups (CPRD-HES: 29.4%; UKSAR: 51.7%), symptom control remained poor (>200 μg SABA or >500 μg terbutaline/day in CPRD-HES: 48.8%; median ACQ-6 score in UKSAR: 2.0 [1.0-3.3]). HCRU were similar across BEC groups. ConclusionMost patients managed in primary care were infrequent exacerbators, whilst UKSAR patients exacerbated frequently. Large proportions of both patient groups had poor symptom control and continued to receive high levels of maintenance OCS, increasing risk of corticosteroid-induced morbidity. These data highlight the need for rigorous assessment of underlying disease pathology to guide appropriate treatment.

Genetic aspects of the realization of the severity of the bronchial asthma phenotype in children

Genetic aspects of the realization of the severity of the bronchial asthma phenotype in children

COVID-19 Infection in a Group of Egyptian Children with Bronchial Asthma: A Single Center Study

Abstract Background Impact of asthma on COVID-19 severity and outcome in infants is not well investigated. Therefore, we sought to assess the presentation, severity and outcome of COVID-19 infection in a group of Egyptian asthmatic children. Patients and Methods We conducted an observational follow up study on 30 asthmatic children with probable/confirmed COVID-19, aged 6-10 years, who were enrolled consecutively from the Emergency department and Isolation Ward, Children`s Hospital, Ain Shams University, Egypt. COVID-19 clinical manifestations, severity and outcome were studied. Results The median age of the children was 9 years (IQR: 6-18 years). Out of the 30 studied patients, we had 9 boys and 21 girls. COVID-19 was asymptomatic in 2/30 (6.7%), mild in 20/30 (66.7%), and severe in 8/30 (26.7%). Clinical manifestations of COVID-19 included constitutional (22,73.3%), respiratory (21, 70%), gastrointestinal (7, 23%), cardio- vascular (5, 16.7%), and dermatological (1, 3.3%) manifestations. Multisystem inflammatory syndrome (MIS-c) was diagnosed in only one patient. Chest X-ray abnormalities were found in (36.7%). The median duration of hospital stay was 10 days, Complete resolution was the final outcome of all patients. Conclusion Asthma does not represent a risk of severe COVID-19 or poor outcome and COVID-19 course, and the outcome in asthmatic children is similar to the general pediatric population. However, our study is limited by the small sample size and short duration of follow-up. Further longitudinal studies are needed to investigate the exact impact of different SARS-CoV-2 variants with respect to asthma phenotypes and asthma biological treatments and allergen immunotherapies in children.

Viral and non-viral episodes of wheezing in early life and the development of asthma and respiratory phenotypes among urban children.

Viral wheezing is an important risk factor for asthma, which comprises several respiratory phenotypes. We sought to understand if the etiology of early-life wheezing illnesses relates to childhood respiratory and asthma phenotypes. Data were collected prospectively on 429 children in the Urban Environment and Childhood Asthma (URECA) birth cohort study through age 10 years. We identified wheezing illnesses and the corresponding viral etiology (PCR testing of nasal mucus) during the first 3 years of life. Six phenotypes of respiratory health were identified at 10 years of age based on trajectories of wheezing, allergic sensitization, and lung function. We compared the etiology of early wheezing illnesses to these wheezing respiratory phenotypes and the development of asthma. In the first 3 years of life, at least one virus was detected in 324 (67%) of the 483 wheezing episodes documented in the study cohort. Using hierarchical partitioning we found that non-viral wheezing episodes accounted for the greatest variance in asthma diagnosed at both 7 and 10 years of age (8.0% and 5.8% respectively). Rhinovirus wheezing illnesses explained the most variance in respiratory phenotype outcome followed by non-viral wheezing episodes (4.9% and 3.9% respectively) at 10 years of age. Within this high-risk urban-residing cohort in early life, non-viral wheezing episodes were frequently identified and associated with asthma development. Though rhinovirus wheezing illnesses had the greatest association with phenotype outcome, the specific etiology of wheezing episodes in early life provided limited information about subsequent wheezing phenotypes.

Contribution of Gestational Weight Gain to Childhood Asthma Phenotypes: A Prospective Cohort Study

BackgroundThe contribution of prenatal anthropometric measures to the development of specific childhood asthma phenotypes is not known. ObjectiveWe aimed to evaluate associations between prepregnancy body mass index (BMI) and gestational weight gain (GWG) with allergic and non-allergic asthma phenotypes in childhood. MethodsOur study population included term, healthy infants in the middle Tennessee region of the United States. Prepregnancy BMI and GWG were ascertained from questionnaires administered during early infancy and categorized based on World Health Organization (WHO) and Institute of Medicine (IOM) recommendations, respectively. Allergic asthma was defined as 5-year current asthma and a positive skin test or specific IgE to aeroallergen(s). We used multivariable logistic regression models for asthma and multinomial logistic regression models for non-asthma, allergic asthma, and non-allergic asthma. ResultsA total of 1,266 children were included. At the 5-year follow-up, 194 (15.3%) had asthma; among them, 102 (52.6%) had allergic asthma. Both inadequate and excessive GWG, compared to adequate GWG, were associated with increased odds of asthma (inadequate: aOR 1.76 [95% CI: 1.03–2.98]; excessive: aOR 1.70 [95% CI: 1.12–2.57]) and increased odds of allergic asthma compared to no asthma (inadequate: aOR 3.49 [95% CI: 1.66–7.32]; excessive: aOR 2.55 [95% CI: 1.34–4.85]). Prepregnancy BMI was not associated with asthma nor with asthma phenotypes. ConclusionBoth inadequate and excessive GWG were associated with allergic asthma risk. These results support the benefits of optimal GWG during pregnancy on child health outcomes.

Frequency of Severe Asthma and Its Clinical Phenotypes at the Asthma Clinic in One of the Largest Sudanese Tertiary Pediatric Hospitals: A Cross-Sectional Hospital-Outpatient-Based Study.

Asthma is one of the most common non-communicable diseases. Childhood asthma has been increasing in Sudan, with a 13-16% prevalence among Khartoum school children. To achieve and maintain good asthma control, proper diagnosis, assessment of severity, and appropriate medication administration are crucial, with phenotyping being a key factor in determining patients' specific treatment. To study the frequency of severe asthma and the distribution of its different phenotypes and to investigate associations between age and gender and different phenotypes of asthma. This descriptive cross-sectional hospital-based study was conducted in the Asthma Clinic of Mohamed Al-Amin Hamid Pediatrics Hospital. It included 229 patients who were presented to the clinic from September 2021 to April 2022. Data were collected from the patients and/or their caregivers using a modified validated standard questionnaire and were analyzed using SPSS version 26.0. A p-value of 0.05 or less was considered statistically significant. In this study of 229 participants, 14.4% had severe asthma, with 44.5% and 41% exhibiting mild and moderate asthma, respectively. Most were effectively managed in steps 2 or 3. The cohort, primarily aged 5 or younger (40.2%) with a male majority (62%), showed a mean diagnosis age of 2.9 ± 2.8 years. Impressively, 90% maintained well-controlled asthma. Within severe asthma cases (87% atopic), 39.4% represented a severe allergic asthma phenotype. Elevated eosinophil counts were noted in 45.5% (serum) and 78.8% (sputum cytology), while 57.6% had normal serum IgE levels. The predominant symptom pattern in severe asthma was episodic multi-trigger wheezing (48.5%). Age and gender displayed no significant association with severe asthma phenotype. This study reveals a concerning rise in childhood asthma prevalence in Sudan, emphasizing the importance of tailored treatment strategies. Severe asthma, characterized by atopic eosinophilic involvement, necessitates targeted interventions in pediatric asthma care for specific phenotypes.

Endotypes of severe neutrophilic and eosinophilic asthma from multi-omics integration of U-BIOPRED sputum samples.

Clustering approaches using single omics platforms are increasingly used to characterise molecular phenotypes of eosinophilic and neutrophilic asthma. Effective integration of multi-omics platforms should lead towards greater refinement of asthma endotypes across molecular dimensions and indicate key targets for intervention or biomarker development. To determine whether multi-omics integration of sputum leads to improved granularity of the molecular classification of severe asthma. We analyzed six -omics data blocks-microarray transcriptomics, gene set variation analysis of microarray transcriptomics, SomaSCAN proteomics assay, shotgun proteomics, 16S microbiome sequencing, and shotgun metagenomic sequencing-from induced sputum samples of 57 severe asthma patients, 15 mild-moderate asthma patients, and 13 healthy volunteers in the U-BIOPRED European cohort. We used Monti consensus clustering algorithm for aggregation of clustering results and Similarity Network Fusion to integrate the 6 multi-omics datasets of the 72 asthmatics. Five stable omics-associated clusters were identified (OACs). OAC1 had the best lung function with the least number of severe asthmatics with sputum paucigranulocytic inflammation. OAC5 also had fewer severe asthma patients but the highest incidence of atopy and allergic rhinitis, with paucigranulocytic inflammation. OAC3 comprised only severe asthmatics with the highest sputum eosinophilia. OAC2 had the highest sputum neutrophilia followed by OAC4 with both clusters consisting of mostly severe asthma but with more ex/current smokers in OAC4. Compared to OAC4, there was higher incidence of nasal polyps, allergic rhinitis, and eczema in OAC2. OAC2 had microbial dysbiosis with abundant Moraxella catarrhalis and Haemophilus influenzae. OAC4 was associated with pathways linked to IL-22 cytokine activation, with the prediction of therapeutic response to anti-IL22 antibody therapy. Multi-omics analysis of sputum in asthma has defined with greater granularity the asthma endotypes linked to neutrophilic and eosinophilic inflammation. Modelling diverse types of high-dimensional interactions will contribute to a more comprehensive understanding of complex endotypes. Unsupervised clustering on sputum multi-omics of asthma subjects identified 3 out of 5 clusters with predominantly severe asthma. One severe asthma cluster was linked to type 2 inflammation and sputum eosinophilia while the other 2 clusters to sputum neutrophilia. One severe neutrophilic asthma cluster was linked to Moraxella catarrhalis and to a lesser extent Haemophilus influenzae while the second cluster to activation of IL-22.

Association between specific IgE to staphylococcal enterotoxin B and the eosinophilic phenotype of asthma.

Sensitization to staphylococcal superantigens (SAgs) could contribute to asthma severity. However, its relevance with eosinophilic phenotype has not yet been clarified. This study aimed to investigate associations between serum specific IgE levels to SAg and eosinophilic airway inflammation in adult asthmatics. The serum specific IgE levels to 3 SAgs, including staphylococcal enterotoxin A (SEA) and B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured by ImmunoCAP in 230 adult asthmatic patients and 50 healthy controls (HCs). Clinical characteristics and laboratory parameters, including serum total/free IgE, and 2 eosinophil-activation markers, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), were analyzed according to blood eosinophil counts (BEC; 150 cells/μL) and serum specific IgE levels to 3 SAgs (0.35 kU/L). Asthmatic patients showed higher serum specific IgE levels to 3 SAgs than HCs (p < 0.05 for all). The serum total/clinfree IgE levels were significantly higher in asthmatics with positive IgE responses to 3 SAgs than those without (p < 0.05 for all). There were no significant differences in clinical parameters including age, asthma severity, comorbidities, or smoking according to IgE responses to 3 SAgs. Patients with positive IgE responses to SEB (not to SEA/TSST-1) had higher serum specific IgE levels to house dust mites and ECP/EDN as well as higher BEC with positive correlations between serum SEB-specific IgE levels and BEC/ECP/EDN (p < 0.05 for all). These findings suggest that serum SEB-specific IgE levels could contribute to eosinophil activation as well as IgE production in adult asthma.

Comparison of Asthma Phenotypes in Severe Asthma Cohorts (SARP, U-BIOPRED, ProAR and COREA) From 4 Continents.

Asthma is a clinical syndrome with various underlying pathomechanisms and clinical phenotypes. Genetic, ethnic, and geographic factors may influence the differences in clinical presentation, severity, and prognosis. We compared the characteristics of asthma based on the geographical background by analyzing representative cohorts from the United States, Europe, South America, and Asia using the Severe Asthma Research Program (SARP), Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED), Program for Control of Asthma in Bahia (ProAR), and Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), respectively. The clinical characteristics and medications for the SARP (n = 669), U-BIOPRED (n = 509), ProAR (n = 996), and COREA (n = 3,748) were analyzed. Subgroup analysis was performed for severe asthma. The mean age was highest and lowest in the COREA and SARP, respectively. The asthma onset age was lowest in the ProAR. The mean body mass index was highest and lowest in the SARP and COREA, respectively. Baseline pulmonary function was lowest and highest in the U-BIOPRED and COREA, respectively. The number of patients with acute exacerbation in the previous year was highest in U-BIOPRED. The mean blood eosinophil count was highest in COREA. The total immunoglobulin E was highest in the ProAR. The frequency of atopy was highest in the SARP. The principal component analysis plot revealed differences among all cohorts. The cohorts from 4 different continents exhibited different clinical and physiological characteristics, probably resulting from the interplay between genetic susceptibility and geographical factors.

Inflammasome-Mediated Mechanisms Of Systemic Inflammation In COVID-19 And Asthma

The review examines the formation of inflammasome-mediated mechanisms of systemic inflammation in asthma after COVID-19. It provides insight into the clinical and pathophysiological relationship between asthma and COVID-19. The review summarizes information about the role of the NLRP3 inflammasome in the pathogenesis of asthma and describes in detail its manifestations in various asthma phenotypes. Emphasizing the significance of the inflammatory-mediated immune response during coronavirus infection in patients with bronchopulmonary pathology, the review outlines the consequences of hyperactivation of the NLRP3 pathway, leading to increased production of cytokines, the appearance of neutrophil and monocyte-derived traps, induction of pyroptosis and the development of complications.

Association of Obesity and Severe Asthma in Adults.

The incidence of obesity and asthma continues to enhance, significantly impacting global public health. Adipose tissue is an organ that secretes hormones and cytokines, causes meta-inflammation, and contributes to the intensification of bronchial hyperreactivity, oxidative stress, and consequently affects the different phenotypes of asthma in obese people. As body weight increases, the risk of severe asthma increases, as well as more frequent exacerbations requiring the use of glucocorticoids and hospitalization, which consequently leads to a deterioration of the quality of life. This review discusses the relationship between obesity and severe asthma, the underlying molecular mechanisms, changes in respiratory function tests in obese people, its impact on the occurrence of comorbidities, and consequently, a different response to conventional asthma treatment. The article also reviews research on possible future therapies for severe asthma. The manuscript is a narrative review of clinical trials in severe asthma and comorbid obesity. The articles were found in the PubMed database using the keywords asthma and obesity. Studies on severe asthma were then selected for inclusion in the article. The sections: 'The classification connected with asthma and obesity', 'Obesity-related changes in pulmonary functional tests', and 'Obesity and inflammation', include studies on subjects without asthma or non-severe asthma, which, according to the authors, familiarize the reader with the pathophysiology of obesity-related asthma.

Clinical and allergological characteristics of patients with severe bronchial asthma in the regional registry and phenotyping principles for the targeted therapy choice

Introduction. Severe asthma targeted therapy effectiveness depends on precise targeting of the selected drug to the key link in pathogenesis. Therefore, severe asthma phenotyping in real clinical practice is relevant.Aim. To determine main clinical and allergological characteristics of patients with severe asthma and to establish important phenotyping signs determined choice of a targeted drug for severe asthma treatment.Materials and methods. The prospective and retrospective study involved patients (n = 198) of the Sverdlovsk region registry receiving targeted therapy of severe asthma. Considering clinical and allergological picture, allergic, non-allergic eosinophilic and mixed severe asthma phenotypes were identified. Clinical and laboratory characteristics of phenotypes were described. A phenotyping algorithm was developed.Results. In the register of patients (n = 198) with severe asthma, non-allergic eosinophilic asthma was 46.5%, allergic – 34.8%, mixed – 18.7%. Significant signs for phenotyping were identified: age of asthma onset, proven allergy, Phadiatop ImmunoCAP level and blood eosinophils on baseline, concomitant allergic rhinitis, chronic rhinosinusitis with nasal polyps and hyper-sensitivity to NSAIDs. The main signs of allergic severe asthma determined: early onset, proven allergy and a positive result of Phadiatop ImmunoCAP (the probability of allergic phenotype increases with Phadiatop ≥ 1.53 PAU/l). Signs of non-allergic eosinophilic asthma were eosinophilia ≥ 150 cells/µl, absence of allergy, concomitant chronic rhinosinusitis with nasal polyps and hypersensitivity to NSAIDs, late onset (after 30 years). Signs were identified for mixed asthma: presence of proven allergy or latent sensitization in combination with high level of Phadiatop ImmunoCAP, late onset, eosinophilia ≥ 300 cells/µl, chronic rhinosinusitis with nasal polyps, hypersensitivity NSAIDs.Conclusions. The algorithm for severe asthma phenotyping based on the isolation of eosinophilia of allergic and non-allergic origin is proposed. Severe asthma phenotyping, which can be carried out in real clinical practice, should facilitate the selection of an initial targeted drug.

Real-World Data on Tezepelumab in Patients With Severe Asthma in Germany

Tezepelumab is a novel biologic blocking thymic stromal lymphopoetin, approved for severe asthma irrespective of biomarker levels or phenotype. To characterize a real-world tezepelumab patient cohort and the efficacy among various asthma phenotypes. We performed a retrospective, multicenter study on patients with severe asthma initiating tezepelumab. Clinical response was evaluated at 3 and 6 months. We included 129 patients with an average age of 52.5 ± 13.1 years, 59.7% were female. The majority (86.0%) had increased type 2 (T2) biomarkers, 68.2% an allergic and 31.8% an eosinophilic phenotype. 23.3% of patients were biologic-naive. 22 (18.2%) patients discontinued tezepelumab therapy owing to suspected side effects or insufficient efficacy. At 6 months' follow-up, median reduction in annualized exacerbation rate was-1 [25th percentile; 75% percentile {-2.9; 0.0}], the reduction of oral corticosteroid dose among patients with long-term oral corticosteroid therapy was -5 mg [-10; 0] and the Asthma Control Test (ACT) improved by 2 [0; 5] points. A treatment response according to Biologic Asthma Response Score of 80.8% was demonstrated. There were no significant differences in treatment response between T2-high versus T2-low, early- versus adult-onset and eosinophilic versus non-eosinophilic asthma. Prior treatment with other biologics was associated with inferior treatment response. In this real-life cohort, including a large proportion of patients with history of previous biologic use and encompassing various subgroups, the majority responded to tezepelumab. Our data further suggest a steroid-sparing effect of tezepelumab.