STUDY OBJECTIVES: Although obesity, asthma, and sleep-disordered breathing are interrelated, there is limited understanding of the independent contributions of body-mass index and pulmonary function on polysomnography in children with asthma. METHODS: We conducted a retrospective chart review on 448 7- to 18-year-old children with asthma who had undergone polysomnography testing between 1/2007-12/2011 to elucidate the association between spirometry variables, body-mass index, and polysomnography parameters, adjusting for asthma and antiallergic medications. RESULTS: Obese children had poorer sleep architecture and more severe gas exchange abnormalities compared to healthy weight children. Multivariate analysis revealed an independent association of body-mass index with sleep efficiency, with more light and less deep sleep in both obese and healthy-weight children, and with baseline oxygen saturation and oxygen nadir in obese children. In obese children, forced vital capacity was independently associated with less deep sleep (time in N3 sleep) as well as with oxygen nadir, while among healthy-weight children, forced expiratory volume directly correlated but forced vital capacity inversely correlated with deep sleep. In obese children, inhaled corticosteroid was associated with baseline oxygen saturation, and montelukast was associated with lower end-tidal carbon dioxide. In healthy-weight children, inhaled corticosteroid was associated with arousal awakening index, and montelukast was associated with light sleep. Antiallergic medications were not independently associated with polysomnography parameters. CONCLUSIONS: Pulmonary function, body-mass index, and asthma medications have independent and differing influences on sleep architecture and gas exchange polysomnography parameters in obese and healthy-weight children with asthma. Asthma medications are associated with improved gas exchange in obese children and improved sleep architecture in healthy-weight children with asthma. CITATION: Conrad LA, Nandalike K, Rani S, Rastogi D. Associations between sleep, obesity, and asthma in urban minority children. J Clin Sleep Med. 2022;18(10):2377-2385.

Rationale

Obesity-related asthma is associated with higher disease burden than normal-weight asthma among Hispanics. Adiposity, metabolic dysregulation, and inflammation are all implicated in pathogenesis of obesity-related asthma, but their independent contributions are poorly understood.

Objective

To examine the independent contributions of body fat distribution, metabolic abnormalities and inflammation on asthma symptoms and pulmonary function among Hispanics.

Methods

Participants of the Hispanic Community Health Study/Study of Latinos with doctor-diagnosed asthma who completed an asthma symptom questionnaire and performed a valid spirometry were included in the analysis (n = 1126). Multivariate analysis was used to examine the independent association of general adiposity (assessed using body mass index), truncal adiposity (assessed by waist circumference), metabolic dysregulation (presence of insulin resistance and low HDL) and inflammation (high-sensitivity C-Reactive Protein≥3 mg/L) with reported asthma symptoms or pulmonary function measures (FEV₁, and FVC) while adjusting for demographic and clinical covariates.

Results

Of the 1126 participants, 334 (29.5%) were overweight, and 648 (57.8%) were obese. FEV₁ and FVC were lower in obese compared to normal-weight asthmatics. In analyses controlling for metabolic and adiposity factors, high hs-CRP (>7 mg/L) was associated with more symptoms (prevalence-ratio 1.27 (95%CI 1.05, 1.54), and lower FVC (β -138 ml (95%CI -27 ml, -249 ml)) and FEV₁ (β -155 ml (95% CI -38 ml, -272 ml). Low HDL was also associated with lower FVC (β -111 ml (-22 ml, -201 ml) and FEV₁ (β -100 ml (-12 ml, -188 ml)). Results were similar in men and women.

Conclusions

Our findings suggest that hs-CRP and low HDL, rather than general and truncal adiposity, are associated with asthma burden among overweight and obese Hispanic adults.

Puerto Ricans are disproportionately affected with asthma in the USA. In this study, we aim to identify genetic variants that confer susceptibility to asthma in Puerto Ricans.We conducted a meta-analysis of genome-wide association studies (GWAS) of asthma in Puerto Ricans, including participants from: the Genetics of Asthma in Latino Americans (GALA) I-II, the Hartford-Puerto Rico Study and the Hispanic Community Health Study. Moreover, we examined whether susceptibility loci identified in previous meta-analyses of GWAS are associated with asthma in Puerto Ricans.The only locus to achieve genome-wide significance was chromosome 17q21, as evidenced by our top single nucleotide polymorphism (SNP), rs907092 (OR 0.71, p=1.2×10^-12) at IKZF3 Similar to results in non-Puerto Ricans, SNPs in genes in the same linkage disequilibrium block as IKZF3 (e.g. ZPBP2, ORMDL3 and GSDMB) were significantly associated with asthma in Puerto Ricans. With regard to results from a meta-analysis in Europeans, we replicated findings for rs2305480 at GSDMB, but not for SNPs in any other genes. On the other hand, we replicated results from a meta-analysis of North American populations for SNPs at IL1RL1, TSLP and GSDMB but not for IL33Our findings suggest that common variants on chromosome 17q21 have the greatest effects on asthma in Puerto Ricans.

De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains <1% of variation. While we are underpowered to see small differences, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, we did find significantly fewer DNMs in Amish individuals, even when compared with other Europeans, and even after accounting for parental age and sequencing center. Specifically, we found significant reductions in the number of C→A and T→C mutations in the Amish, which seem to underpin their overall reduction in DNMs. Finally, we calculated near-zero estimates of narrow sense heritability (h²), which suggest that variation in DNM rate is significantly shaped by nonadditive genetic effects and the environment.