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Distinct Asthma Phenotypes Among Older Adults with Asthma.

ABSTRACT: BACKGROUND:Older adults have high rates of asthma morbidity and mortality. Asthma is now recognized as a heterogeneous disease, yet the distinct phenotypes among older adults are unknown. OBJECTIVE:The objective of this study was to identify asthma phenotypes in a diverse population of elderly patients with asthma. METHODS:Using cluster analysis, 180 older adults with persistent asthma were analyzed. Subjects completed detailed questionnaires, skin prick testing, and spirometry with reversibility. Twenty-four core variables were analyzed. RESULTS:Four groups were identified. Subjects in cluster 1 (n = 69) typically had asthma diagnosed after the age of 40 and the shortest duration of asthma. Cluster 2 (n = 40) had the mildest asthma defined by spirometry, Asthma Control test (ACT), and Asthma Quality of Life Questionnaire (AQLQ). They also had the lowest body mass index (BMI), lowest depression score, and least number of comorbidities. Cluster 3 (n = 46) had the longest duration of asthma (56 years) and the highest atopic skin test sensitization (74%). Cluster 4 (n = 25) had the most severe asthma, with extremely low FEV1% predicted (37.8%), lowest ACT, and lowest AQLQ scores. They were more likely to be black and had the highest comorbidities. Using BMI, posttreatment FEV1% predicted, and duration of asthma, 95.6% of subjects were able to be correctly classified. CONCLUSIONS:In older adults with asthma, distinct phenotypes vary on key features that are more pronounced among the elderly, including comorbidities, fixed airway obstruction, and duration of asthma ?40 years. Further work is required to determine the clinical and therapeutic implications for different asthma phenotypes in older adults.

SUBMITTER: Baptist AP

PROVIDER: S-EPMC5897052 | biostudies-literature | 2018 Jan - Feb

REPOSITORIES: biostudies-literature

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Distinct Asthma Phenotypes Among Older Adults with Asthma.

Baptist Alan P AP Hao Wei W Karamched Keerthi R KR Kaur Bani B Carpenter Laurie L Song Peter X K PXK

The journal of allergy and clinical immunology. In practice 20170727 1

<h4>Background</h4>Older adults have high rates of asthma morbidity and mortality. Asthma is now recognized as a heterogeneous disease, yet the distinct phenotypes among older adults are unknown.<h4>Objective</h4>The objective of this study was to identify asthma phenotypes in a diverse population of elderly patients with asthma.<h4>Methods</h4>Using cluster analysis, 180 older adults with persistent asthma were analyzed. Subjects completed detailed questionnaires, skin prick testing, and spirom ...[more]

PMID: 28757370

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Project description:BackgroundBronchial thermoplasty regulates structural abnormalities involved in airway narrowing in asthma. In the present study we aimed to investigate the effect of bronchial thermoplasty on histopathological bronchial structures in distinct asthma endotypes/phenotypes.MethodsEndobronchial biopsies (n = 450) were collected from 30 patients with severe uncontrolled asthma before bronchial thermoplasty and after 3 sequential bronchial thermoplasties. Patients were classified based on blood eosinophils, atopy, allergy and smoke exposure. Tissue sections were assessed for histopathological parameters and expression of heat-shock proteins and glucocorticoid receptor. Proliferating cells were determined by Ki67-staining.ResultsIn all patients, bronchial thermoplasty improved asthma control (p < 0.001), reduced airway smooth muscle (p = 0.014) and increased proliferative (Ki67 +) epithelial cells (p = 0.014). After bronchial thermoplasty, airway smooth muscle decreased predominantly in patients with T2 high asthma endotype. Epithelial cell proliferation was increased after bronchial thermoplasty in patients with low blood eosinophils (p = 0.016), patients with no allergy (p = 0.028) and patients without smoke exposure (p = 0.034). In all patients, bronchial thermoplasty increased the expression of glucocorticoid receptor in epithelial cells (p = 0.018) and subepithelial mesenchymal cells (p = 0.033) and the translocation of glucocorticoid receptor in the nucleus (p = 0.036). Furthermore, bronchial thermoplasty increased the expression of heat shock protein-70 (p = 0.002) and heat shock protein-90 (p = 0.001) in epithelial cells and decreased the expression of heat shock protein-70 (p = 0.009) and heat shock protein-90 (p = 0.002) in subepithelial mesenchymal cells. The effect of bronchial thermoplasty on the expression of heat shock proteins -70 and -90 was distinctive across different asthma endotypes/phenotypes.ConclusionsBronchial thermoplasty leads to a diminishment of airway smooth muscle, to epithelial cell regeneration, increased expression and activation of glucocorticoid receptor in the airways and increased expression of heat shock proteins in the epithelium. Histopathological effects appear to be distinct in different endotypes/phenotypes indicating that the beneficial effects of bronchial thermoplasty are achieved by diverse molecular targets associated with asthma endotypes/phenotypes.

Project description:BackgroundAsthma 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).

Dataset Information

Distinct Asthma Phenotypes Among Older Adults with Asthma.

Publications

Distinct Asthma Phenotypes Among Older Adults with Asthma.

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