The purpose of this study was to determine the incidence and the high-resolution computed tomography findings of air-leak syndromes in a large group of hematopoietic stem cell (HSC) transplant recipients with proved chronic graft versus host disease (cGVHD). High-resolution computed tomography scans of 9 allogeneic HSC transplant recipients (8 men, 1 woman; 19 to 45 years of age; median 28 y), with a proven diagnosis of cGVHD-related bronchiolitis obliterans syndrome (BOS) were reviewed for the presence, appearance, and distribution of abnormalities. Nine patients with cGVHD developed 10 episodes of spontaneous air-leak syndromes secondary to cGVHD-related BOS during the study period analyzed; for a 2-year estimated cumulative incidence of 2.1% (95% confidence interval 0.2% to 3.8%) its prevalence was 5.7% (95%CI: 2.6% to 10.5%). All cases were allogeneic HSC transplant recipients with cGVHD who acquired new respiratory symptoms and/or radiologic abnormalities. Pneumomediastinum and pneumothorax were present in 6 patients. Subcutaneous emphysema was identified in 3 patients and pulmonary interstitial emphysema in 2 patients. A combination of different air-leak syndromes was observed in 6 patients. Air-leak syndromes represent an uncommon late complication in HSC transplant recipients with cGVHD-related BOS.

Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi‐ancestry meta‐analysis of genome‐wide association studies (meta‐GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression.Methods: A meta‐GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10⁻⁵) were assessed for replication in 36,477 European and 1078 non‐European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico.Results: One hundred and twenty‐six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule‐1/exostosin like glycosyltransferase‐2 (VCAM1/EXTL2) (discovery: odds ratio (OR_{T allele}) = 0.82, p = 9.05 × 10⁻⁶ and replication: OR_{T allele} = 0.89, p = 5.35 × 10⁻³) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR_{C allele} = 0.85, p = 3.10 × 10⁻⁵ and replication: OR_{C allele} = 0.89, p = 1.30 × 10⁻²). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood.Conclusions: This multi‐ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.

Background: The Spanish registry of α₁-antitrypsin deficiency (AATD) integrated in the European Alpha-1 Research Collaboration (EARCO) provides information about the characteristics of patients, in particular those with the PI*SZ genotype, which is frequent in Spain.Method: Individuals with severe AATD defined as proteinase inhibitor (PI) genotypes PI*ZZ, PI*SZ and other rare deficient variants were included from February 1, 2020, to February 1, 2022. The analysis focused on a comparison of the characteristics of PI*ZZ and PI*SZ patients.Results: 409 patients were included (53.8% men) with a mean±sdage of 53.5±15.9 years. Genotypes were PI*ZZ in 181 (44.7%), PI*SZ in 163 (40.2%), PI*SS in 29 (7.2%) and other in 32 (7.9%). 271 (67.4%) had lung disease: 175 chronic obstructive pulmonary disease (43.5%), 163 emphysema (40.5%) and 83 bronchiectasis (20.6%). Patients with the PI*SZ genotype were younger, more frequently non-index cases and had a lower frequency of respiratory diseases except asthma compared with PI*ZZ patients. Among patients with respiratory diseases, PI*SZ individuals were significantly older both at onset of symptoms and at diagnosis; only asthma was more frequent in PI*SZ than in PI*ZZ individuals. Twelve PI*SZ patients (15.4%) received augmentation therapy compared with 94 PI*ZZ patients (66.2%; p<0.001).Conclusions: There is a high prevalence of PI*SZ in Spain. Patients with the PI*SZ genotype were older at symptom onset and diagnosis and had less severe lung disease compared with PI*ZZ patients. The prevalence of asthma was higher in PI*SZ, and up to 15% of PI*SZ patients received augmentation therapy.