Severe Asthma Research Program
A National Institutes of Health/ National Heart, Lung & Blood Institute sponsored network
Key Recent SARP III Publications
1. 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.
2. Choi S, et al. Quantitative computed tomography imaging-based clustering differentiates asthmatic subgroups with distinctive clinical phenotypes. J Allergy Clin Immunol. 2017 Jan 28. pii: S0091-6749(17)30146-X. doi: 10.1016/j.jaci.2016.11.053. PubMed PMID: 28143694.
The unique structural and functional alterations observed in each imaging cluster provide a basis for new insights for the existing pathophysiology of asthma. The clustering membership can be used for a basis for the development of effective interventions for asthmatics in the future.
Severe asthma can be quite different from patient to patient – a new approach to “cluster” these patients into groups to understand their disease better has been done. The SARP imaging cluster study added CT scans of the chest to the information we gathered on our patients. We found unique changes in the windpipes and lungs of the patients in these clusters. Our hope is this information can be used to target treatment better in the future.
3. 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.
4. Luyster FS, et al. Association Between Insomnia and Asthma Burden in the Severe Asthma Research Program (SARP) III. Chest. 2016 Dec;150(6):1242-1250. doi: 10.1016/j.chest.2016.09.020. PubMed PMID: 27720882.
Our study found over a third of adults with asthma have insomnia. Those with insomnia had more depression and anxiety, poorer quality of life, and had more frequent asthma-related health care use in the past year than those without insomnia. Patients with asthma should be evaluated for insomnia and provided insomnia treatment if needed by their healthcare provider.
Insomnia is an inability to get a good night’s sleep on a regular basis . It was found in 37% of adults with asthma. Those with insomnia had more symptoms of depression and anxiety and worse quality of life than those without insomnia. Also, patients who reported insomnia had more frequent doctor visits, emergency room visits, and hospitalizations because of their asthma than those without insomnia. These findings suggest patients with asthma should be asked about sleep problems and provided treatment for insomnia if needed by their doctor.
5. Peters MC, et al. Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts. Lancet Respir Med. 2016 Jul;4(7):574-84. doi: 10.1016/S2213-2600(16)30048-0. PubMed PMID: 27283230; PubMed Central PMCID: PMC5007068.
Severe asthma is a complex disease frequently associated with older age and obesity. Low grade systemic inflammation often occurs in obesity and is associated with insulin resistance, atherosclerosis, type-2 diabetes and hypertension. However, the role of systemic inflammation and metabolic dysfunction as a risk factor for having severe asthma is poorly understood. In this study, we measured blood levels of interleukin-6 (IL-6) a protein commonly increased in patients with obesity. We found that increased blood IL6 levels were strongly associated with severe asthma and that subjects with high IL6 levels had other markers of metabolic dysfunction, including higher rates of hypertension and diabetes. This work suggests that obesity and IL6 related systemic inflammation could be a unique mechanism in severe asthma and that inflammation originating outside the lung can play a critical role in triggering disease pathology inside the lung.
6. Altes TA, et al. Clinical correlates of lung ventilation defects in asthmatic children. J Allergy Clin Immunol. 2016 Mar;137(3):789-96.e7. doi: 10.1016/j.jaci.2015.08.045. PubMed PMID: 26521043.
This study showed that a new method using inhaled hyperpolarized helium-3 gas can be safely used to image by MRI the pattern of ventilation in the lungs of children with asthma. This method has significant advantages over standard chest CT in that there is no exposure to ionizing radiation. We learned that children with severe asthma have greater regions of the lung which do not get enough air, and that the volume of these poorly ventilated regions correlates significantly with many of the features of asthma.
7. Duvall MG, et al. Natural Killer Cell-Mediated Inflammation Resolution Is Disabled In Severe Asthma. Sci. Immunol. 2, eaam5446 (2017) doi: 10.1126/sciimmunol.aam5446
Anti-inflammatory corticosteroids are a first line of defense against many types of asthma, but patients with severe asthma do not frequently respond to this therapy. We determined that this lack of response may be due in part to defects in natural killer (NK) cells, which are important mediators of inflammation resolution. We found that NK cells from patients with severe asthma had impaired killing and that corticosteroid exposure further inhibited the function of these cells, whereas the proresolving mediator LXA4 preserved NK cell effector mechanisms. Therefore, corticosteroids may be a counterproductive therapy in patients with severe asthma, and specifically activating NK cells may provide an alternate therapeutic target.