Overcoming Heterogeneity in Pediatric Asthma: Tobacco Smoke and Asthma Characteristics Within Phenotypic Clusters in an African American Cohort

Abstract

Objective Asthma in children and adolescents is a heterogeneous syndrome comprised of multiple subgroups with variable disease expression and response to environmental exposures. The goal of this study was to define homogeneous phenotypic clusters within a cohort of children and adolescents with asthma and to determine overall and within-cluster associations between environmental tobacco smoke (ETS) exposure and asthma characteristics. Methods A combined hierarchical/k-means cluster analysis of principal component variables was used to define phenotypic clusters within a cohort of 6 to 20 year-old urban and largely minority subjects. Results Among the 154 subjects, phenotypic cluster analysis defined three independent clusters (Cluster 1 [n=57]; Cluster 2 [n=33]; Cluster 3 [n=58]). A small fourth cluster (n=6) was excluded. Patients in Cluster 1 were predominantly males with a relative abundance of neutrophils in their nasal washes. Patients in Cluster 2 were predominantly females with high body mass index percentiles and later-onset asthma. Patients in Cluster 3 had higher eosinophil counts in their nasal washes and lower Asthma Control Test™ (ACT) scores. Within-cluster regression analysis revealed several significant associations between ETS exposure and phenotypic characteristics that were not present in the overall cohort. ETS exposure was associated with a significant increase in nasal wash neutrophils (Beta Coefficient = 0.73 [95%CI: 0.11 to 1.35]; P=0.023) and a significant decrease in ACT score (−5.17 [−8.42 to −1.93]; P=0.003) within Cluster 1 and a significant reduction in the bronchodilator-induced % change in FEV1 (−36.32 [−62.18 to −10.46]; P=0.009) within Cluster 3. Conclusions Clustering techniques defined more homogeneous subgroups allowing for the detection of otherwise undetectable associations between environmental tobacco smoke exposure and asthma characteristics.

Extracellular Cyclophilin Levels Associate with Parameters of Asthma in Phenotypic Clusters

“…The 154 AsthMaP participants were grouped into four phenotypic clusters based on groupings of clinical variables as we previously described (26). One cluster consisted of six subjects displaying a mild asthma phenotype, and was excluded from further analyses.…”

Airway Platelet Activation is Associated with Airway Eosinophilic Inflammation in Asthma

“…8 One of the clusters was characterized by an allergic asthma phenotype with increased nasal wash eosinophils and worse asthma control. Nasal washes were available for 25 participants within this cluster.…”

The investigation of asthma phenotypes

“…Benton et al [22 ] conducted a cluster analysis in an African-American asthma cohort aged 6-20 years (Asthma Severity Modifying Polymorphisms) recruited in an emergency department (n ¼ 154). The cluster analysis on seven variables (Asthma Control Test (ACT) score, postbronchodilator FEV1% predicted, eosinophils from nasal washes, total serum IgE, gender, age of onset, and BMI) identified four groups including cluster 0 composed of six individuals with an extremely mild phenotype, cluster 1 composed mainly of men with high neutrophils counts in their nasal washes (n ¼ 57), cluster 2 predominantly composed of women with high BMI and later-onset asthma (n ¼ 33), and cluster 3 including children with high eosinophil counts in their nasal washes and lower ACT scores (n ¼ 58).…”