Blood Institute Severe Asthma Research Articles

Racial disparities in asthma-related health care use in the National Heart, Lung, and Blood Institute's Severe Asthma Research Program

Despite advances in asthma care, disparities persist. Black patients are disproportionally affected by asthma and also have poorer outcomes compared with white patients. We sought to determine associations between black and white patients and asthma-related health care use, accounting for complex relationships. This study was completed as part of the National Heart, Lung, and Blood Institute's Severe Asthma Research Program, a prospective observational cohort. Between November 2012 and February 2015, it enrolled 579 participants 6years and older with 1year of observation time and complete data. Inverse probability of treatment weighting was used to balance racial groups with respect to community and family socioeconomic variables and environmental exposure variables. The primary outcome was emergency department (ED) use for asthma. Secondary outcomes included inhaled corticosteroid use, outpatient physician's office visits for asthma, and asthma-related hospitalization. Black patients had greater odds of ED use over 1year (odds ratio, 2.19; 95% CI, 1.43-3.35) but also differed in the majority (>50%) of baseline variables measured. After statistical balancing of the racial groups, the difference between black and white patients with respect to ED use no longer reached the level of significance. Instead, in secondary analyses black patients were less likely to see an outpatient physician for asthma management (adjusted odds ratio, 0.57; 95% CI, 0.38-0.85). The disparity in ED use was eliminated after consideration of multiple variables. Social and environmental policies and interventions tailored to black populations with a high burden of asthma are critical to reduction (or elimination) of these disparities.

Severe Asthma Phenotypes — How Should They Guide Evaluation and Treatment?

Although patients with "severe" asthma tend to be characterized by ongoing symptoms and airway inflammation despite treatment with high doses of inhaled and systemic corticosteroids, there is increasing recognition of marked phenotypic heterogeneity within affected patients. Although "precision medicine" approaches for patients with severe asthma are needed, there are many hurdles that must be overcome in daily practice. The National Heart, Lung and Blood Institute's Severe Asthma Research Program (SARP) has been at the forefront of phenotype discovery in severe asthma for the past decade. SARP, along with other international groups, has described clinical severe asthma phenotypes in both adults and children that can be evaluated in the clinical setting. Although these clinical phenotypes provide a good "starting point" for addressing disease heterogeneity in severe asthma in everyday practice, more efforts are needed to understand how these phenotypes relate to underlying disease mechanisms and pharmacological treatment responses. This review highlights the clinical asthma phenotypes identified to date, their associations with underlying endotypes and potential biomarkers, and remaining knowledge gaps that must be addressed before precision medicine can become a reality for patients with severe asthma.

Severe Asthma in Children: Lessons Learned and Future Directions

Severe asthma in children is a complicated and heterogeneous disorder that is extremely challenging to treat. Although most children with asthma derive clinical benefit from daily administration of low-to-medium-dose inhaled corticosteroid (ICS) therapy, a small subset of children with "severe" or "refractory" asthma require high doses of ICS and even systemic corticosteroids to maintain symptom control. These children with severe asthma are at increased risk for adverse outcomes including medication-related side effects and recurrent and life-threatening exacerbations that significantly impair quality of life. This review highlights findings on severe asthma in school-age children (age 6-17 years) from the National Heart, Lung and Blood Institute's Severe Asthma Research Program (SARP) over a 10-year period, between 2001 and 2011. Although SARP has advanced knowledge of the unique clinical, biological, and molecular attributes of severe asthma in children, considerable gaps remain for which additional studies are needed.

Asymmetric Dimethylarginine

Asymmetric Dimethylarginine

Severe Asthma in Children: Insights from the National Heart, Lung, and Blood Institute's Severe Asthma Research Program

Severe asthma in children is a complicated disorder characterized by ongoing symptoms and persistent airway inflammation despite treatment with high doses of inhaled and oral corticosteroids. Although knowledge of asthma and its associated mechanisms has increased substantially over the past decade, significant gaps remain about the determinants of severe asthma in children and the progression of the disorder across the lifespan. This review highlights recent insights into severe asthma in children derived from the National Heart, Lung, and Blood Institute's Severe Asthma Research Program (SARP), with an emphasis on age-specific findings and differences from severe asthma in adults. While the existence of a true severe asthma phenotype in children is subject to some debate, given the results of SARP and other investigators, we conclude that there is indeed a subgroup of children with severe asthma who have extreme morbidity and differentiating clinical features that are identifiable very early in life. However, unlike adults with severe asthma, children with severe asthma are more likely to fall in a more narrow cluster that is characterized by marked atopy and reversible airflow obstruction. While SARP has advanced knowledge of severe asthma in children, considerable gaps remain for which additional studies are needed.

Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program

Severe asthma causes the majority of asthma morbidity. Understanding mechanisms that contribute to the development of severe disease is important. The goal of the Severe Asthma Research Program is to identify and characterize subjects with severe asthma to understand pathophysiologic mechanisms in severe asthma. We performed a comprehensive phenotypic characterization (questionnaires, atopy and pulmonary function testing, phlebotomy, exhaled nitric oxide) in subjects with severe and not severe asthma. A total of 438 subjects with asthma were studied (204 severe, 70 moderate, 164 mild). Severe subjects with asthma were older with longer disease duration (P < .0001), more daily symptoms, intense urgent health care utilization, sinusitis, and pneumonia (P < or = .0001). Lung function was lower in severe asthma with marked bronchodilator reversibility (P < .001). The severe group had less atopy by skin tests (P = .0007), but blood eosinophils, IgE, and exhaled nitric oxide levels did not differentiate disease severity. A reduced FEV(1), history of pneumonia, and fewer positive skin tests were risk factors for severe disease. Early disease onset (age < 12 years) in severe asthma was associated with longer disease duration (P < .0001) and more urgent health care, especially intensive care (P = .002). Later disease onset (age > or = 12 years) was associated with lower lung function and sinopulmonary infections (P < or = .02). Severe asthma is characterized by abnormal lung function that is responsive to bronchodilators, a history of sinopulmonary infections, persistent symptoms, and increased health care utilization. Lung function abnormalities in severe asthma are reversible in most patients, and pneumonia is a risk factor for the development of severe disease.