Rationale: Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined.Objectives: To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA.Methods: Baseline data from the NHLBI Severe Asthma Research Program (SARP)-3 were analyzed. An exacerbation was defined as a burst of systemic corticosteroids lasting 3 days or more. Patients were classified by their number of exacerbations in the past year: none, few (one to two), or exacerbation prone (>3). Replication of a multivariable model was performed with data from the SARP-1 1 2 cohort.Measurements and Main Results: Of 709 subjects in the SARP-3 cohort, 294 (41%) had no exacerbations and 173 (24%) were exacerbation prone in the prior year. Several factors normally associated with severity (asthma duration, age, sex, race, and socioeconomic status) did not associate with exacerbation frequency in SARP-3; bronchodilator responsiveness also discriminated exacerbation proneness from asthma severity. In the SARP-3 multivariable model, blood eosinophils, body mass index, and bronchodilator responsiveness were positively associated with exacerbation frequency (rate ratios [95% confidence interval],

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Inhaled corticosteroids are the mainstay of asthma treatment using a step-up approach with incremental dosing and additional controller medications in order to achieve symptom control and prevent exacerbations. While most patients respond well to this treatment approach, some patients remain refractory despite high doses of inhaled corticosteroids and a long-acting β-agonist. The problem lies in the heterogeneity of severe asthma, which is further supported by the emergence of severe asthma phenotypes. This heterogeneity contributes to the variability in treatment response. Randomized controlled trials involving add-on therapies in poorly controlled asthma have challenged the idea of a "one size fits all" approach targeting specific phenotypes in their subject selection. This review discusses severe asthma phenotypes from unbiased clustering approaches and the most recent scientific evidence on novel treatments to provide a guide in personalizing severe asthma treatment.

OBJECTIVES This study aims to investigate the impact of respiratory symptoms in current and former smokers with and without obstructive lung disease (OLD) on all‐cause mortality. DESIGN Secondary analysis in a prospective cohort (the Health, Aging and Body Composition study). SETTING Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS Black and white men and women with a history of current and former smoking (N = 596; 63% male and 37% female) aged 70‐79 years followed for 13 years. Participants were categorized into 4 mutually exclusive groups based on symptom profile and forced expiratory volume in the 1st second to forced vital capacity ratio. The groups were Less Dyspnea‐No OLD (N = 196), More Dyspnea‐No OLD (N = 104), Less Dyspnea‐With OLD (N = 162), and More Dyspnea‐With OLD (N = 134). MEASUREMENTS All‐cause mortality. RESULTS Overall, 53% in Less Dyspnea‐No OLD, 63% in More Dyspnea‐No OLD, 67% in Less Dyspnea‐With OLD, and 84% in More Dyspnea‐With OLD died within the 13‐ year follow up period (log‐rank χ2 = 44.4, P < .0001). The hazard ratio was highest for participants with OLD, both with (HR =1.91, 95% CI 1.44 ‐ 2.54; P < .0001) and without dyspnea (HR = 1.52, 95% CI 1.15 ‐ 2.02; p = .004). Participants without OLD but with dyspnea had a similar risk of death to subjects who had OLD but fewer symptoms. CONCLUSIONS OLD is associated with high risk of death with different risk profiles based on symptom group. Patients with symptoms of shortness of breath without OLD should be considered an at‐risk group given their similar mortality to those with OLD with minimal symptoms. J Am Geriatr Soc 67:2116–2122, 2019

Background Adiposity-related ventilatory constraints in older adults can potentially contribute to greater risk of exercise intolerance and mobility disability. This study investigated whether ventilatory limitation, measured by breathing reserve (BR) at peak exercise, is associated with body composition and physical function in older adults with obesity. Methods This study was a cross-sectional analysis of data from a community-based cohort (N = 177) of older men and women (65–79 years) with obesity (body mass index = 30–45 kg/m2). All participants underwent cardiopulmonary exercise testing on a treadmill, dual-energy X-ray absorptiometry for body composition, and physical function assessments. We examined relationships between BR and body composition and physical function using multiple linear regression and compared a subset with (BR ≤ 30%; BR-low; n = 56) and without (BR ≥ 45%; BR-high, n = 48) ventilatory limitation using unpaired Student’s t test and analysis of covariance. Results BR was inversely related to total body mass, lean mass, fat mass, % body fat, and waist circumference (p < 0.05 for all). BR was positively related to 400 m walk time (p = .006) and inversely related to usual gait speed (p = .05) and VO2peak (p < .0001), indicative of worse physical function. BR-low had greater adiposity, but also greater lean mass, higher VO2peak, and faster 400 m walk time, compared to BR-high (p < .05, for all). Conclusions Older adults with obesity who also have ventilatory limitation have overall higher measures of adiposity, but do not have lower peak exercise capacity or physical function. Thus, ventilatory limitation does not appear to be a contributing factor to obesity-related decrements in exercise tolerance or mobility.