Yasuo To

Purpose: Asthma is a heterogeneous disease, and identifying phenotypes associated with an increased exacerbation burden is clinically important. Preserved ratio impaired spirometry (PRISm) has been linked to adverse health outcomes; however, its clinical impact on asthma remains incompletely defined. The aim of this study was to determine whether asthma with PRISm represents a distinct clinical phenotype characterised by an increased exacerbation burden. Patients and Methods: We retrospectively analysed data from 1,411 adult patients with asthma. The patients were categorised into three groups according to %FEV₁ and FEV₁/FVC: control (n=1102), PRISm (n=133), and airflow obstruction groups (n=176). Clinical characteristics and asthma exacerbation profiles were compared among the groups. Results: Age, sex, smoking status, and body mas index (BMI) significantly differed among the groups. The PRISm group had a significantly higher frequency of severe acute exacerbations than the control group, whereas no significant difference was observed between the PRISm and airflow obstruction groups. Severe asthma was more frequent in the PRISm group than in the control group, but its frequency was comparable between the PRISm and airflow obstruction groups. In multinomial logistic regression analysis, relative to the control group, the PRISm group was characterised by higher BMI (1.08 (1.03– 1.13), adjusted odds ratio (95% confidence interval)), longer asthma duration (1.02 (1.00– 1.03)), and higher severe acute exacerbation (2.31 (1.46– 3.64)). Relative to the airflow obstruction group, the PRISm group was characterised by higher BMI (1.15 (1.07– 1.24)) and shorter asthma duration (0.97 (0.96– 0.99)), while the frequency of severe acute exacerbations (1.39 (0.78– 2.48)) did not differ significantly between them. Conclusion: Asthma with PRISm may represent a distinct and clinically relevant phenotype associated with a substantial exacerbation burden. Its clinical importance lies not merely in its spirometric profile, but in the identification of a subgroup of patients who may require closer surveillance and earlier optimisation of management.

Asthma is a heterogeneous condition influenced by multiple clinical and biological factors, and obesity has emerged as a major modifier that worsens symptoms and increases the risk of exacerbations. This review aimed to examine the mechanisms by which obesity contributes to reduced responsiveness to corticosteroids, which remain the cornerstone of guideline-based asthma management. We reviewed evidence from clinical and experimental studies describing how adipose tissue dysfunction, chronic low-grade inflammation, oxidative stress, and systemic comorbidities alter glucocorticoid receptor signalling and downstream pathways. Particular attention was given to immune mechanisms such as neutrophilic inflammation and interleukin-17 signalling, as well as metabolic disturbances including hyperleptinaemia and vitamin D deficiency. We also considered the role of lifestyle factors, such as physical inactivity and dietary patterns, in sustaining corticosteroid insensitivity. Based on these insights, we evaluated both established and emerging therapeutic strategies, including weight loss, structured exercise, dietary modification, and drug repurposing with agents such as metformin, low-dose theophylline, and glucagon-like peptide-1 receptor agonists. A comprehensive synthesis of these findings highlights the need for integrated lifestyle and pharmacological interventions, and provides a framework for the development of targeted treatments to improve outcomes in patients with obesity-associated, corticosteroid-insensitive asthma.

Although the effectiveness of vaccination at preventing hospitalization and severe coronavirus disease (COVID-19) has been reported in numerous studies, the detailed mechanism of innate immunity occurring in host cells by breakthrough infection is unclear. One hundred forty-six patients were included in this study. To determine the effects of vaccination and past infection on innate immunity following SARS-CoV-2 infection, we analyzed the relationship between anti–SARS-CoV-2 S Abs and biomarkers associated with the deterioration of COVID-19 (IFN-λ3, C-reactive protein, lactate dehydrogenase, ferritin, procalcitonin, and D-dimer). Anti-S Abs were classified into two groups according to titer: high titer (≥250 U/ml) and low titer (<250 U/ml). A negative correlation was observed between anti–SARS-CoV-2 S Abs and IFN-λ3 levels (r = −0.437, p < 0.001). A low titer of anti–SARS-CoV-2 S Abs showed a significant association with oxygen demand in patients, excluding aspiration pneumonia. Finally, in a multivariate analysis, a low titer of anti–SARS-CoV-2 S Abs was an independent risk factor for oxygen demand, even after adjusting for age, sex, body mass index, aspiration pneumonia, and IFN-λ3 levels. In summary, measuring anti–SARS-CoV-2 S Abs and IFN-λ3 may have clinical significance for patients with COVID-19. To predict the oxygen demand of patients with COVID-19 after hospitalization, it is important to evaluate the computed tomography findings to determine whether the pneumonia is the result of COVID-19 or aspiration pneumonia.