Immune profile of adipose tissue from youth with obesity and asthma.

BACKGROUND: Obesity is a risk factor for paediatric asthma. Obesity-mediated systemic inflammation correlates with metabolic dysregulation; both are associated with asthma burden. However, adipose tissue inflammation is not defined in obesity-related asthma. OBJECTIVE: Define adipose tissue inflammation and its association with metabolic measures in paediatric obesity-related asthma. METHODS: Cellular profile of stromal vascular fraction from visceral adipose tissue (VAT) from youth with obesity-related asthma (n = 14) and obesity without asthma (n = 23) was analyzed using flow cytometry and correlated with metabolic measures. RESULTS: Compared to youth without asthma, VAT from youth with obesity-related asthma was enriched for leukocytes and macrophages, including M1 and dual M1M2 cells, but did not differ for CD4+ lymphocytes, and endothelial cells, their progenitors, and preadipocytes. M1 macrophage counts positively correlated with glucose, while M1M2 cells, CD4+ lymphocytes, and their subsets negatively correlated with high-density lipoprotein, in youth with obesity without asthma, but not among those with obesity-related asthma. CONCLUSIONS: Enrichment of macrophage-mediated inflammation in VAT from youth with obesity-related asthma supports its role in systemic inflammation linked with asthma morbidity. Lack of correlation of VAT cells with metabolic dysregulation in youth with obesity-related asthma identifies a need to define distinguishing factors associated with VAT inflammation in obesity-related asthma.

Clonally selected primitive endothelial cells promote occlusive pulmonary arteriopathy and severe pulmonary hypertension in rats exposed to chronic hypoxia.

One current concept suggests that unchecked proliferation of clonally selected precursors of endothelial cells (ECs) contribute to severe pulmonary arterial hypertension (PAH). We hypothesized that clonally selected ECs expressing the progenitor marker CD117 promote severe occlusive pulmonary hypertension (PH). The remodelled pulmonary arteries of PAH patients harboured CD117+ ECs. Rat lung CD117+ ECs underwent four generations of clonal expansion to enrich hyperproliferative ECs. The resulting clonally enriched ECs behaved like ECs, as measured by in vitro and in vivo angiogenesis assays. The same primitive ECs showed a limited ability for mesenchymal lineage differentiation. Endothelial differentiation and function were enhanced by blocking TGF-ß signalling, promoting bone morphogenic protein (BMP) signalling. The transplantation of the EC clones caused arterio-occlusive PH in rats exposed to chronic hypoxia. These EC clones engrafted in the pulmonary arteries. Yet cessation of chronic hypoxia promoted lung cell apoptosis and resolution of vascular lesions. In conclusion, this is to the best of our knowledge, the first report that clonally enriched primitive ECs promote occlusive pulmonary arteriopathy and severe PH. These primitive EC clones further give rise to cells of endothelial and mesenchymal lineage as directed by BMP and TGF-ß signaling.

Pediatric asthma comprises different phenotypic clusters with unique nasal microbiotas.

BACKGROUND: Pediatric asthma is the most common chronic childhood disease in the USA, currently affecting ~ 7 million children. This heterogeneous syndrome is thought to encompass various disease phenotypes of clinically observable characteristics, which can be statistically identified by applying clustering approaches to patient clinical information. Extensive evidence has shown that the airway microbiome impacts both clinical heterogeneity and pathogenesis in pediatric asthma. Yet, so far, airway microbiotas have been consistently neglected in the study of asthma phenotypes. Here, we couple extensive clinical information with 16S rRNA high-throughput sequencing to characterize the microbiota of the nasal cavity in 163 children and adolescents clustered into different asthma phenotypes. RESULTS: Our clustering analyses identified three statistically distinct phenotypes of pediatric asthma. Four core OTUs of the pathogenic genera Moraxella, Staphylococcus, Streptococcus, and Haemophilus were present in at least 95% of the studied nasal microbiotas. Phyla (Proteobacteria, Actinobacteria, and Bacteroidetes) and genera (Moraxella, Corynebacterium, Dolosigranulum, and Prevotella) abundances, community composition, and structure varied significantly (0.05 < P ≤ 0.0001) across asthma phenotypes and one of the clinical variables (preterm birth). Similarly, microbial networks of co-occurrence of bacterial genera revealed different bacterial associations across asthma phenotypes. CONCLUSIONS: This study shows that children and adolescents with different clinical characteristics of asthma also show different nasal bacterial profiles, which is indicative of different phenotypes of the disease. Our work also shows how clinical and microbial information could be integrated to validate and refine asthma classification systems and develop biomarkers of disease.