The rs2601796 variant in ADCY9 gene is associated with severe asthma and less bronchodilator response.

Asthma is a respiratory disease caused by the interaction of genetic and environmental factors. The adenylyl cyclase type 9 (ADCY9) enzyme produces the cyclic-adenosinemonophosphate (cAMP), important mediator involved in bronchodilation and immunomodulatory response. The aim of this study was to investigate if rs2601796 and rs2532019 variants in the ADCY9 gene are associated with asthma and lung function. The study comprised 1,052 subjects. Logistic regressions were done using PLINK 1.9 adjusted by sex, age, BMI, smoke and principal components. Bronchodilator responsiveness was assessed using the percentage of difference in FEV1 before and after the bronchodilator use. The in silico analysis for gene expression was performed in the GTEx Portal. The variant rs2601796 (AA/AG genotype) was positively associated with asthma severity (OR: 1.60 IC95%: 1.08-2.39) and with obstruction in individuals with severe asthma (OR: 3.10, IC95%: 1.11-8.62). Individuals with severe asthma and the AA/AG genotype of rs2601796 had less responsiveness to bronchodilators and also a lower expression of ADCY9 in lung and whole blood. The variant rs2532019 (TT/GT genotype) also downregulated the ADCY9 gene expression, but no significant association with the studied phenotypes was found. Thus, the variant in ADCY9 was associated with worse asthma outcomes, including a lower response to bronchodilators, likely due to the impact on its gene expression rate. This variant may be useful in the future to assist in personalized management of patients with asthma.

Handgrip strength as a diagnostic tool for frailty risk in elderly patients with moderate to severe asthma / Força de preensão manual como ferramenta diagnóstica de risco de fragilidade em pacientes idosos com asma moderada a grave

ABSTRACT Objective: To evaluate handgrip strength (HGS) as a diagnostic tool for frailty risk in elderly patients with asthma, as well as to investigate the prevalence of frailty in this population. Methods: This was a cross-sectional study including 96 patients ≥ 60 years of age diagnosed with moderate to severe asthma and treated at a tertiary referral center in Brazil. We measured HGS using a calibrated hydraulic hand dynamometer. We used a frailty scale and the AUC to assess the diagnostic accuracy of the HGS test. Results: The median age of participants was 67 years. Most (78%) were women and non-White (91%) of low socioeconomic status. HGS identified those at risk for frailty, with an AUC of 71.6% (61.5-80.4%; p < 0.002), as well as a sensitivity of 73.58% and a specificity of 67.53%, on the basis of a cutoff of ≤ 19 kgf. Conclusions: HGS appears to be a simple, reliable tool for clinicians to determine frailty risk in older asthma patients in a point-of-care setting.

RESUMO Objetivo: Avaliar a força de preensão manual (FPM) como ferramenta diagnóstica de risco de fragilidade em pacientes idosos com asma e investigar a prevalência de fragilidade nessa população. Métodos: Estudo transversal com 96 pacientes com idade ≥ 60 anos e diagnóstico de asma moderada a grave, atendidos em um centro terciário de referência no Brasil. Medimos a FPM com um dinamômetro hidráulico manual calibrado. Usamos uma escala de fragilidade e a ASC para avaliar a precisão diagnóstica do teste de FPM. Resultados: A mediana da idade dos participantes foi de 67 anos. A maioria eram mulheres (78%) não brancas (91%) cujo nível socioeconômico era baixo. O ponto de corte de FPM ≤ 19 kgf identificou os participantes que apresentavam risco de fragilidade, com ASC = 71,6% (61,5-80,4%; p < 0,002), sensibilidade = 73,58% e especificidade = 67,53%. Conclusões: A FPM parece ser uma ferramenta simples e confiável para determinar, no próprio local de atendimento médico, o risco de fragilidade em pacientes idosos com asma.