Obesity affects more than 650 million adults worldwide, with prevalence continuing to rise across all age groups and continents. This trend has important implications for asthma: individuals with obesity have a 30–50% higher risk of developing asthma, and obesity is highly prevalent among people with established disease. Mean body mass index in clinical trials and registries of adults with asthma consistently ranges from 28 kg·m ⁻² to 30 kg·m ⁻² , with up to 70% of patients being overweight or obese. These numbers highlight obesity as one of the most common comorbidities in asthma, consistently associated with poorer asthma control and a higher risk of exacerbations. Although obesity-associated asthma is often described as type-2 (T2)-low phenotype, it is increasingly recognised as a heterogeneous condition not restricted to a single phenotype. Excess adiposity influences asthma through multiple mechanisms, including dysregulated adipokine signalling, impaired innate lymphoid cells type 2 (ILC2)–eosinophil–macrophage cross-talk in adipose tissue, systemic low-grade inflammation, metabolic dysfunction, and mechanical effects on lung volumes. This diversity complicates diagnosis, endotyping, and treatment stratification. Obesity should therefore be considered a treatable trait in asthma. Weight reduction (through lifestyle interventions, pharmacotherapy or bariatric surgery) improves symptoms, lung function, and exacerbation risk across both T2-high and T2-low asthma. Importantly, patients with obesity experience similar reductions in exacerbations with anti-T2 biologics as their lean counterparts, though improvements in symptoms and lung function are variable. Future research should prioritise randomised, placebo-controlled trials evaluating glucagon-like peptide (GLP)-1 and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP)-agonist therapies specifically in patients with asthma and obesity, and elucidate how obesity modifies inflammatory endotypes and treatment responses.

Ataxia telangiectasia and Rad3-related (ATR) kinase and its interacting protein ATRIP orchestrate the replication stress response. Homozygous splice variants in the ATRIP gene, resulting in ATRIP deficiency, were identified in two patients of independent ancestry with microcephaly, primordial dwarfism, and recurrent infections. The c.829+5G>T patient exhibited lymphopenia, poor vaccine responses, autoimmune features with hemolytic anemia, and neutropenia. Immunophenotyping revealed reduced CD16+/CD56dim NK cells and absent naïve T cells, MAIT cells, and iNKT cells. Lymphocytic defects were characterized by TCR oligoclonality, abnormal class switch recombination, and impaired T cell proliferation. ATRIP deficiency resulted in low-grade ATR activation but impaired CHK1 phosphorylation under genotoxic stress. ATRIP-deficient cells inadequately regulated DNA replication, leading to chromosomal instability, compromised cell cycle control, and impaired cell viability. CRISPR-SelectTIME confirmed reduced cell fitness for both variants. This study establishes ATRIP deficiency as a monogenic cause of microcephalic primordial dwarfism, highlights ATRIP’s critical role in protecting immune cells from replication stress, and offers new insights into its canonical functions.

Background: Chronic pruritus (CP) and chronic cough (CC) are prevalent conditions with shared underlying mechanisms, including neuronal sensitisation and inflammation. While previous studies identified associations between pruritus and CC, limited data exist on their interplay when accounting for confounders such as smoking and asthma. Methods: This cross-sectional study analysed middle-aged and older participants from a population-based cohort, the Rotterdam Study. Logistic regression models assessed associations between demographic and lifestyle factors ( e.g. smoking), CC (categorised as new-onset or persistent based on longitudinal data), asthma, and CP, reported as odds ratios with 95% confidence intervals. Sensitivity analyses sequentially excluded participants with atopic dermatitis, asthma and a combination of atopic conditions. Results: In total, 4364 participants (age range 48–99 years, median age 71; 58.8% women) were included. Persistent CC was strongly associated with CP, doubling the odds in multivariable analyses (OR 2.07, 95% CI 1.43–3.00). Smoking was independently associated with CP, with the highest odds in current smokers (OR 1.46, 95% CI 1.10–1.92). The association between persistent CC and CP remained robust across all sensitivity analyses. Conclusions: Persistent CC is strongly associated with CP, emphasising shared pathogenic mechanisms. Smoking emerged as a modifiable risk factor for CP. Longitudinal studies are needed to establish causality and optimise therapeutic and management strategies.

Background/Objectives: Therapeutic adherence to asthma and COPD medications remains worryingly low and varies widely across patient groups, underscoring persistent challenges in chronic respiratory care. The aim of this nationwide study is to quantify real-world adherence and to identify its demographic and clinical determinants using the Belgian health care claims database of the National Institute for Health and Disability Insurance (NIHDI). Methods: Adherence was assessed using the Continuous Multiple Interval Measure of Medication Availability (CMA) among patients treated between 2020 and 2023. Mixed-effects logistic regression was applied to identify determinants of adherence. Results: Only 30.5% of patients achieved good adherence (CMA ≥ 0.8). Adherence varied substantially across pharmacological classes, ranging from 8.1% for inhaled corticosteroids to 66.4% for triple therapy. Age emerged as a major determinant, with adherence increasing steadily across age groups: only 4.0% of children and 15.7% of adolescents reached good adherence, compared with progressively higher rates in adults. Mixed-effects logistic regression confirmed age, sex, and pharmacological class as robust predictors of adherence. Conclusions: These findings highlight the magnitude of the therapeutic adherence gap in chronic respiratory diseases and clearly identify children, adolescents, and ICS or LABA + ICS users as the highest-risk groups. Recognizing these profiles has direct implications for clinical practice, as it provides concrete targets for future patient-centered interventions and guideline-concordant adherence-enhancing strategies.