Race is associated with differences in airway inflammation in patients with asthma

Abstract

Background African-Americans have a greater burden from asthma compared to Caucasians. Whether the pattern of airway inflammation differs between African-Americans and Caucasians is unclear. Objective To compare sputum airway inflammatory phenotypes of African-Americans and Caucasians treated or not treated with ICS (ICS+ and ICS-, respectively). Methods We performed a secondary analysis of self-identified African-Americans and Caucasians with asthma enrolled in clinical trials conducted by the National Heart, Lung, and Blood Institute-sponsored Asthma Clinical Research Network and AsthmaNet. Demographics, clinical characteristics, and sputum cytology following sputum induction were examined. We utilized a sputum eosinophil 2% cut point to define individuals with either an eosinophilic (≥2%) or non-eosinophilic (<2%) inflammatory phenotype. Results Among 1,018 participants, African-Americans (n=264) had a lower FEV1% predicted (80 vs. 85%, p<0.01), greater total IgE (197 vs. 120, p<0.01) and a greater proportion with uncontrolled asthma (43% vs. 28%, p<0.01) compared to Caucasians (n=754). There were 922 subjects in the ICS+ group (248 African-Americans, 674 Caucasians) and 298 subjects in the ICS− group (49 African-Americans, 249 Caucasians). Eosinophilic airway inflammation was not significantly different between African-Americans and Caucasians in either group (% with eosinophilic phenotype: ICS+ group: 19% vs. 16%, p=0.28; ICS− group: 39% vs. 35%, p=0.65; respectively). However, when adjusted for confounding factors, African-Americans were more likely to exhibit eosinophilic airway inflammation than Caucasians in the ICS+ group (OR:1.58; CI:1.01–2.48; p=0.046), but not in the ICS− group (p=0.984). Conclusion African-Americans exhibit greater eosinophilic airway inflammation, which may explain the greater asthma burden in this population.

Exacerbation-prone asthma in the context of race and ancestry in Asthma Clinical Research Network trials

“…25,[44][45][46] Like most variation throughout the genome, these genetic risk loci have varying allele frequencies between subjects from different ancestral backgrounds that could influence asthma severity and therapeutic responsiveness to commonly used asthma therapies in subjects of African descent. 5,14,15,25,[44][45][46][47][48] In African American and Puerto Rican asthma cohorts, greater African ancestry has consistently been shown to be inversely associated with baseline lung function measures consistent with observations from large general populations. 20,23,45,49 Three prior ancestry-based genetic studies have tested for associations between global genetic ancestry and asthma exacerbations in cohorts of African descent, 2 in African American and 1 in Puerto Rican subjects.…”

“…[10][11][12][13] Post hoc analyses of National Heart, Lung, and Blood Institute (NHLBI)-sponsored Asthma Clinical Research Network (ACRN) and AsthmaNet clinical trial cohorts have shown that African American subjects have lower lung function, a greater proportion of uncontrolled asthma, and a greater likelihood of treatment failure compared with their white counterparts. 14,15 Race and ethnic designations do not sufficiently capture the ancestral genetic, cultural, geographic, or socioeconomic contexts that underlie differences in asthma severity between racial groups. 16 Ancestry-based studies leveraging genome-wide genotyping technologies have demonstrated that whole-genome African ancestry is associated with higher risk of asthma, lower lung function, and poor symptom control in African American subjects and Hispanic groups of African descent.…”

Pharmacogenetics of inhaled long‐acting beta2‐agonists in asthma: A systematic review

“…In conclusion, there is considerable variability in pharmacogenetic LABA studies due to differences in study design and characteristics of included patients. Environmental conditions, such as socioeconomic factors (income, education), ethnic genetic variants, environmental allergen exposure, psychosocial stressors, behavioral risk factors (smoking, obesity), poor medication adherence, and lack of access to medicines or evidence‐based care, can influence gene expression . ADRB2 rs1042713 has been shown to influence LABA response in children in observational studies.…”

Impact of Historic Migrations and Evolutionary Processes on Human Immunity

“…Variation in TLR1-TLR6-TLR10 is the major genetic determinant of human interindividual differences in TLR1/2-mediated responses, including cytokine production to a number of clinically relevant pathogens such as Staphylococcus aureus and Listeria monocytogenes [30] (Table 1). This inheritance from archaic humans may have also left some human individuals more prone than others to developing asthma, hay fever, and other allergies (of 58 SNPs associated with susceptibility to allergic disease, 12 had a Neanderthal or Denisovan origin) [26], although these associations remain to be fully demonstrated [31].…”

“…In the absence of regular pathogen challenges that require maintained modulation of the balance between inflammation and suppression of the immune response, the organism can overreact to inflammatory stimuli and trigger exacerbated responses. For instance, descendants of African populations generally present higher susceptibility to a variety of autoimmune syndromes such as inflammation-associated carcinomas, lupus, asthma, and multiple sclerosis (MS), the overall prevalence of which is up to three times higher in individuals with African ancestry relative to individuals with European ancestry [31,49,50]. relative to other populations might be beneficial to combatting infections, but might also increase the chances of developing inflammatory and autoimmune disorders, which warrants further investigation.…”