Severe Asthma Research Program
A National Institutes of Health/ National Heart, Lung & Blood Institute sponsored network


Key Recent SARP III Publications

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​1.     Peters MC, et al. National Heart Lung and Blood Institute Severe Asthma Research Program-3. Refractory Airway Type-2 Inflammation in a Large Subgroup of Asthmatics treated with Inhaled Corticosteroids. J Allergy Clin Immunol. 2018 Mar 7. pii: S0091-6749(18)30390-7.  doi: 10.1016/j.jaci.2017.12.1009. PubMed PMID: 29524537.

The goal of this project was to examine the baseline features of children and adults with severe and non-severe asthma enrolled in the SARP long-term study.  We thought it would be interesting to see how these features are different with age and whether or not there was an interaction between age and asthma severity in regards to any one feature.  We discovered that severe asthma in children is highly associated with inflammatory factors like allergy, blood eosinophils, and expired nitric oxide, but the degree of allergic sensitization was not different in children with severe compared to non-severe asthma.  At entry into the SARP program, adults with asthma had overall lower inflammatory factors compared to children, but with age those factors were relatively higher in adults with severe compared to non-severe asthma.  What was most different in adults compared to children with severe asthma was the amount of airflow limitation, and less improvement in air flow following inhaled albuterol, a bronchodilator which relaxes the muscle tone in the airways.  The most important result of the paper was that at entry into the SARP Study, children with severe asthma had relatively more allergy-related inflammation but normal lung function, whereas adults with severe asthma had more complex patterns of inflammation with reduced lung function.


Allergic inflammation, or type-2 inflammation, is increased in people with asthma but is typically improved with corticosteroid treatment. However, a group of people with severe asthma has persistent asthma symptoms despite treatment with inhaled corticosteroids. In this paper we used specialized techniques to measured allergic inflammation in sputum samples from subjects in the severe asthma research program who were taking inhaled corticosteroids. We found that a large group of severe asthma patients have increased airway allergic inflammation despite treatment with inhaled corticosteroids, and these allergic inflammation measurements remained high even after a corticosteroid injection. Furthermore, we found that these patients tended to be older in age and have more severe asthma. Finally, we also assessed whether we could use blood test measurements to predict whether a person would have airway allergic inflammation that was resistant to corticosteroids.

Conclusion:
-Inhaled or systemic corticosteroids do not fully suppress airway measures of allergic inflammation in a large sub-group of severe        asthma patients.
- Patients with steroid resistant allergic inflammation asthma are usually older with more severe disease.
- Increased body weight and age modify the performance of blood-based biomarkers of airway allergic inflammation
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2.     Teague WG, et al.Baseline Features of the Severe Asthma Research Program (SARP III) Cohort: Differences with Age, The Journal of Allergy and Clinical Immunology: In Practice, doi:10.1016/j.jaip.2017.05.032 PubMed PMID: 28866107. 

The goal of this project was to examine the baseline features of children and adults with severe and non-severe asthma enrolled in the SARP long-term study.  We thought it would be interesting to see how these features are different with age and whether or not there was an interaction between age and asthma severity in regards to any one feature.  We discovered that severe asthma in children is highly associated with inflammatory factors like allergy, blood eosinophils, and expired nitric oxide, but the degree of allergic sensitization was not different in children with severe compared to non-severe asthma.  At entry into the SARP program, adults with asthma had overall lower inflammatory factors compared to children, but with age those factors were relatively higher in adults with severe compared to non-severe asthma.  What was most different in adults compared to children with severe asthma was the amount of airflow limitation, and less improvement in air flow following inhaled albuterol, a bronchodilator which relaxes the muscle tone in the airways.  The most important result of the paper was that at entry into the SARP Study, children with severe asthma had relatively more allergy-related inflammation but normal lung function, whereas adults with severe asthma had more complex patterns of inflammation with reduced lung function.  
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3.     Denlinger LC, et al. Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations. Am J Respir Crit Care Med. 2017 Feb 1;195(3):302-313. doi: 10.1164/rccm.201602-0419OC. PubMed PMID: 27556234. 

This is a multicenter cohort study of adults and children with severe asthma. Blood eosinophils, bronchodilator responsiveness, body mass index, chronic sinusitis, and gastroesophageal reflux disease were found to be associated with exacerbation-prone asthma, after adjustment for age, sex, race, center, and medication adherence, with replication of these findings in a second cohort. Exacerbation-prone asthma is a distinct phenotype with prominent extrapulmonary features that may be modifiable.

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4.     Phipatanakul W, et al. Effects of Age and Disease Severity on Systemic Corticosteroid Responses in Asthma. Am J Respir Crit Care Med. 2017 Jun 1;195(11):1439-1448. doi: 10.1164/rccm.201607-1453OC. PMID: 27967215 

Adults, but not children remain different after a corticosteroid injection, suggesting that children may have more responsive disease. Regardless, 20% of children and adults with severe asthma, despite already being on high dose inhaled corticosteroids have a clinically important improvement in lung function. These findings suggest differences between children and adults with severe asthma and that following these patients over time will be important to furthering our understanding of the disease and its response to therapies.

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5.   Fitzpatrick AM, et al. Racial disparities in asthma-related healthcare utilization in the National Heart, Lung and Blood Institute’s Severe Asthma Research. 2019 Jan 8. pii: S0091-6749(18)31732-9. doi: 10.1016/j.jaci.2018.11.022. PubMed PMID: 30635198.


It is well known that asthma outcomes are worse in African American patients. The findings from our study suggest that
poorer asthma outcomes are not genetic or biological in nature, but are instead due to a number of socioeconomic and
environmental factors that impact asthma care. African American patients were more than twice as likely to visit the
emergency department for asthma, however, when controlling for community and family socioeconomic factors and
environmental exposure – the racial differences evened out. African American patients were also 43 percent less likely to
see a doctor in an outpatient setting for asthma. Thus, access to healthcare is one of the most important factors to
consider when seeking to address asthma disparities. It can be difficult to schedule preventive medical services, and
asthma medications can be expensive, even with adequate insurance coverage. In addition, controlling environmental
factors such as dust mites and molds, are an important factor for asthma management. These social and environmental
factors leading to disparities in outcomes can be modified and improved with the right interventions.