Incidence rates of childhood asthma with recurrent exacerbations in the US Environmental influences on Child Health Outcomes (ECHO) program.

BACKGROUND: Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse. OBJECTIVES: This study hypothesized that IRs for ARE would vary by time, geography, age, and race and ethnicity, irrespective of parental asthma history. METHODS: The investigators leveraged data from 17,246 children born after 1990 enrolled in 59 US with 1 Puerto Rican cohort in the Environmental Influences on Child Health Outcomes (ECHO) consortium to estimate IRs for ARE. RESULTS: The overall crude IR for ARE was 6.07 per 1000 person-years (95% CI: 5.63-6.51) and was highest for children aged 2-4 years, for Hispanic Black and non-Hispanic Black children, and for those with a parental history of asthma. ARE IRs were higher for 2- to 4-year-olds in each race and ethnicity category and for both sexes. Multivariable analysis confirmed higher adjusted ARE IRs (aIRRs) for children born 2000-2009 compared with those born 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR = 15.36; 95% CI: 12.09-19.52), and for males versus females (aIRR = 1.34; 95% CI 1.16-1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR = 2.51; 95% CI 2.10-2.99; and aIRR = 2.04; 95% CI: 1.22-3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than those born in the West (P < .01 for each comparison). Children with a parental history of asthma had rates nearly 3 times higher than those without such history (aIRR = 2.90; 95% CI: 2.43-3.46). CONCLUSIONS: Factors associated with time, geography, age, race and ethnicity, sex, and parental history appear to influence the inception of ARE among children and adolescents.

Long-term future risk of severe exacerbations: Distinct 5-year trajectories of problematic asthma.

BACKGROUND: Assessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short- but not long-term risk. Problematic asthma patients with unfavorable long-term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment. AIM: To identify distinct trajectories of severe exacerbation rates among "problematic asthma" patients and develop a risk score to predict the most unfavorable trajectory. METHODS: Severe exacerbation rates over five years for 177 "problematic asthma" patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group-based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory. RESULTS: Three distinct trajectories were found: 58.5% had rare intermittent severe exacerbations ("infrequent"), 32.0% had frequent severe exacerbations at baseline but improved subsequently ("nonpersistently frequent"), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near-fatal asthma ("persistently frequent"). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near-fatal asthma (+1 point), body mass index ≥25kg/m2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the "persistently frequent" trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort. CONCLUSIONS: Patients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently frequent severe exacerbations in the future.

Socioeconomic status, diet, and recurrent severe asthma exacerbations in Puerto Rican youth.

Background: Why Puerto Rican youths have higher rates of severe asthma exacerbations (SAEs) than their non-Hispanic White peers is unclear. Objective: We aimed to identify risk factors associated with recurrent SAEs in Puerto Rican youths with asthma. Methods: We performed cross-sectional and longitudinal analyses of recurrent SAEs in 209 Puerto Rican youths with asthma who participated in 2 cross-sectional studies approximately 5.2 years apart: the Puerto Rico Genetics of Asthma and Lifestyle study (visit 1, participants aged 6-14 years) and the Epigenetic Variation and Childhood Asthma in Puerto Ricans study (visit 2, participants aged 9-20 years). Recurrent SAEs were defined as at least 2 SAEs in the previous year. Results: Of the youths in our study, there were 80 (38.3%) and 47 (22.4%) with recurrent SAEs at visit 1 and visit 2, respectively, and 31 participants (14.8%) had persistent recurrent SAEs (ie, recurrent SAEs at both visits). In multivariable analyses, low household income was significantly associated with 2.4 to 12.3 times increased odds of recurrent SAEs in all analyses, with stronger longitudinal associations. Low parental education level, nonprivate or employer-based health insurance, overweight or obesity, residential proximity to a major road, and low or moderate level of outdoor activity were each significantly associated with recurrent SAEs in at least 1 analysis. Further, persistence of low parental numeracy level, low household income, and an unhealthy diet were each associated with persistent recurrent SAEs. Conclusion: In this study of Puerto Rican youths with asthma, persistence of low parental numeracy level, a low household income, and an unhealthy diet were associated with persistent recurrent SAEs. Our findings support policies promoting equity and healthy lifestyles for Puerto Rican children and their families.

Benralizumab Prevents Recurrent Exacerbations in Patients with Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis.

Exacerbations in chronic obstructive pulmonary disease (COPD), which tend to occur in clusters and increase with disease severity, come with high societal and economic burdens. Prevention and delay of recurrent exacerbations is an unmet and significant therapeutic need for patients with COPD. GALATHEA (NCT02138916) and TERRANOVA (NCT02155660) were trials assessing efficacy of benralizumab in patients with frequent COPD exacerbations despite treatment. Although these studies found that benralizumab given as an add-on treatment did not significantly reduce annual rates of COPD exacerbations after 56 weeks of treatment, in the following exploratory post hoc analysis of the GALATHEA and TERRANOVA trials we identified a potential responder population in which treatment with benralizumab prevents recurrent COPD exacerbations during 30- and 90-day periods following an initial exacerbation, a vulnerable period for an exacerbation to occur. This responder population was characterized by high blood eosinophil counts and frequent previous exacerbations despite optimized triple therapy. These results highlight the importance of targeted therapies for high-risk populations and merit further research into the benefits of biologic therapies for COPD exacerbations.

Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer from acute exacerbations. Our objective was to describe recurrent exacerbations in a GP-based Swiss COPD cohort and develop a statistical model for predicting exacerbation. METHODS: COPD cohort demographic and medical data were recorded for 24 months, by means of a questionnaire-based COPD cohort. The data were split into training (75%) and validation (25%) datasets. A negative binomial regression model was developed using the training dataset to predict the exacerbation rate within 1 year. An exacerbation prediction model was developed, and its overall performance was validated. A nomogram was created to facilitate the clinical use of the model. RESULTS: Of the 229 COPD patients analyzed, 77% of the patients did not experience exacerbation during the follow-up. The best subset in the training dataset revealed that lower forced expiratory volume, high scores on the MRC dyspnea scale, exacerbation history, and being on a combination therapy of LABA + ICS (long-acting beta-agonists + Inhaled Corticosteroids) or LAMA + LABA (Long-acting muscarinic receptor antagonists + long-acting beta-agonists) at baseline were associated with a higher rate of exacerbation. When validated, the area-under-curve (AUC) value was 0.75 for one or more exacerbations. The calibration was accurate (0.34 predicted exacerbations vs 0.28 observed exacerbations). CONCLUSION: Nomograms built from these models can assist clinicians in the decision-making process of COPD care.