Pulmonary Therapy最新文献

Introduction: Gut microbiota modulate systemic anti-inflammatory and immune responses in the lungs, suggesting a potential to support lung health through probiotic supplementation. We hypothesized that a probiotic blend (Lactobacilli) combined with herbal extracts (resB^®) could improve quality of life in patients with chronic obstructive pulmonary disease (COPD).

Methods: We conducted a randomized, double-blinded, placebo-controlled study (NCT05523180) evaluating the safety and impact of resB^® on quality of life in volunteers with COPD. Participants took resB^® or placebo (two capsules daily) for 12 weeks. The primary endpoint was change in quality of life by Saint George's Respiratory Questionnaire (SGRQ). Secondary outcomes included safety, serum and sputum biomarkers, and microbiome analysis. resB^® was well tolerated with no related adverse events.

Results: Participants receiving resB^® showed significant improvement in SGRQ symptom scores (P < 0.05), while placebo recipients did not. In the resB^® group, serum and sputum levels of matrix metalloproteinase 9, C-reactive protein, and interleukin 6 decreased (P < 0.05), correlating with increased stool Lactobacilli. Additionally, Veillonella abundance increased in both stool and sputum.

Conclusion: These findings suggest that resB^® improves respiratory symptoms and reduces inflammation in patients with COPD, potentially by modulating gut and lung microbiota.

Trial registration: ClinicalTrials.gov identifier NCT05523180.

Introduction: Add-on treatment with amikacin liposome inhalation suspension (ALIS) to a multidrug antibiotic regimen is the only US Food and Drug Administration-approved treatment for adults with refractory Mycobacterium avium complex lung disease (MACLD). In real-world settings, other antibiotics may be added on to treat refractory MACLD. We analyzed healthcare resource utilization in a US patient population who received add-on treatment for refractory MACLD.

Methods: This was a retrospective claims analysis using Merative™ MarketScan® databases (January 2016 to December 2022). Two patient cohorts were defined: an ALIS and non-ALIS cohort. Index date was date of first prescription with ALIS or non-ALIS antibiotic for refractory MACLD. Hospitalizations (all-cause, respiratory-related, nontuberculous mycobacteria (NTM)-related) and emergency room (ER) visits at 0-6-month and 7-12-month post-index periods were compared with baseline (6-month pre-index period) per cohort. Multivariate logistic regression models compared the odds of hospitalizations or ER visits between cohorts.

Results: The ALIS and non-ALIS cohorts comprised 116 and 63 patients, respectively. The most common add-on treatments for refractory MACLD in the non-ALIS cohort were parenteral amikacin (41.3%) and moxifloxacin (27.0%). In the ALIS cohort, significant reductions from baseline, as compared with the 7-12-month post-index period, were observed in all-cause (12.1% vs 22.4%), respiratory-related (8.6% vs 20.7%), and NTM-related hospitalizations (9.5% vs 19.8%) (P < 0.05 for all comparisons). There were no significant changes from baseline in hospitalizations at follow-up in the non-ALIS cohort. No significant changes from baseline in ER visits or hospital length of stay were observed in either cohort. Adjusted odds ratios (ORs) of all-cause (OR [95% confidence interval, CI] 0.45 [0.21-0.96]) and respiratory-related hospitalizations (OR 0.44 [0.21-0.96]) were statistically significantly lower in the ALIS cohort compared with the non-ALIS cohort.

Conclusions: Add-on treatment with ALIS in refractory MACLD may lead to reductions in hospitalizations over time and lower odds of hospitalizations compared with add-on treatment with non-ALIS antibiotics.

Background: Insomnia disorder and obstructive sleep apnea (OSA) are two of the most common sleep disorders in the general population. Their coexistence, referred to as comorbid insomnia and sleep apnea (COMISA), exacerbates nighttime disturbances, increases daytime dysfunction, and further diminishes overall quality of life. COMISA is also associated with elevated cardiovascular and mental health risks, including resistant hypertension, heart failure, stroke, depression, and anxiety. Despite its clinical importance, COMISA often remains underdiagnosed, and its management poses notable challenges.

Objectives: This narrative review article aims to provide a comprehensive overview of the current understanding of COMISA, focusing on its definition, epidemiology, pathophysiological mechanisms, clinical presentation, diagnostic challenges and treatment approaches, including the diagnostic decision-making process and criteria for selecting appropriate therapeutic strategies.

Methods: Literature review of published studies with different designs, including peer-reviewed observational studies, randomized controlled trials, meta-analyses, and international clinical guidelines, was conducted. Databases used included PubMed, Scopus, and Web of Science, and they covered epidemiological, clinical, and therapeutic topics focusing on COMISA. Emphasis was placed on the cardiovascular, psychological, and therapeutic outcomes, as reported in the cited literature.

Results: Patients diagnosed with COMISA typically present with symptoms such as greater sleep fragmentation, prolonged sleep latency, persistent daytime fatigue, cognitive deficits, and elevated psychological distress, compared with individuals with insomnia or OSA alone. COMISA is also associated with a threefold increased risk of resistant hypertension and heightened cardiovascular mortality. Despite the fact that continuous positive airway pressure (CPAP) remains the cornerstone of OSA treatment, its effectiveness is often limited by comorbid insomnia, making combined cognitive behavioral therapy for insomnia (CBT-I) and CPAP interventions more promising, as well as emerging pharmacotherapies, such as dual orexin receptor antagonists. Patients with significant insomnia-related impairment or suboptimal CPAP adherence may benefit from these combined or alternative approaches.

Conclusions: COMISA represents a complex clinical entity that is associated with impairments in clinical outcomes and quality of life, requiring a multidisciplinary, personalized approach to simultaneously address sleep-disordered breathing and insomnia symptoms. Early recognition, individualized treatment strategies, and long-term monitoring are essential to improve prognosis and therapeutic success in this high-risk population.

Introduction: This study estimated the potential public health and economic impacts of different COVID-19 vaccination strategies in Malaysia using an updated COVID-19 vaccine.

Methods: A previously published Markov decision-tree model (2021-2022) was updated with the latest epidemiology data from Malaysia (October 2022-September 2023). This updated model was used to assess the outcomes of alternative vaccination strategies using the updated COVID-19 vaccine. Age-specific inputs were derived from Malaysian epidemiological data and published sources. The model projected health outcomes (cases, hospitalizations, and deaths) and economic outcomes (direct medical costs and productivity losses) across various age and risk categories.

Results: Vaccinating individuals aged 60 and above, as well as high-risk individuals aged 6 months to 59 years with vaccine coverage of 20%, was projected to prevent 91,824 infections, 1477 hospitalizations, and 53 deaths. The model estimated total savings of MYR 90.9 million in direct medical costs attributed to COVID-19 treatment and MYR 110.4 million in indirect costs attributed to COVID-19 illness. Expanding coverage among individuals aged 60 and above, as well as high-risk individuals of any age, to 50% could further increase the reduction in deaths, hospitalizations, infections, and costs by up to 150%.

Conclusions: When considering recent updated epidemiology data and expected vaccination coverage, vaccination strategies appear to have a smaller impact, largely caused by the reduction in vaccine coverage. However, despite this, using an updated COVID-19 vaccine could still reduce the health and economic burden of COVID-19 in terms of cases, hospitalizations, deaths, direct medical costs, and indirect productivity losses in Malaysia, especially among high-risk populations and older adults.

Introduction: Bronchiectasis is a chronic airway disease marked by recurrent infections, progressive inflammation, and declining pulmonary function. While pharmacologic therapies remain central to management, nonpharmacologic strategies-particularly nutrition and physical activity-are underutilized, despite growing evidence.

Objective: This review examines the role of nutritional support and physical activity in managing bronchiectasis, highlighting their impact on frailty, systemic inflammation, and functional outcomes.

Discussion: Frailty is increasingly recognized in bronchiectasis, particularly in patients with comorbid nontuberculous mycobacterial lung disease (NTM-LD), where prevalence may exceed 40%. Malnutrition, low body mass index (BMI), and sarcopenia are associated with poorer lung function, increased hospitalizations, and mortality. Meanwhile, physical inactivity-measured by low step count and prolonged sedentary time-is a strong predictor of exacerbation risk and healthcare utilization. Evidence supports the use of high-calorie, protein-rich diets and resistance-based exercise training to improve muscle mass, immune function, and quality of life. Synergistic effects are observed when nutritional interventions are combined with pulmonary rehabilitation. However, barriers to implementation remain, including a lack of access, under-referral, and limited emphasis on guidelines.

Conclusion: Nutritional and physical activity interventions offer measurable clinical benefits in bronchiectasis and should be integrated into routine multidisciplinary care. Future research should prioritize the validation of frailty screening tools, the implementation of effective strategies, and the development of policy mechanisms to expand coverage for dietetic and rehabilitation services.

Introduction: Up to 40% of patients with chronic obstructive pulmonary disease (COPD) exhibit elevated blood eosinophils, reflective of type 2 inflammation. Dupilumab and mepolizumab versus standard of care have demonstrated moderate-to-severe exacerbation reductions of 30-34% and 15-18%, respectively, over 52 weeks. This study compared their relative efficacy using indirect treatment comparison (ITC).

Methods: A Bucher ITC was performed on 52-week phase 3 trials of dupilumab (BOREAS/NOTUS) and mepolizumab (MATINEE/METREX/METREO). The primary ITC endpoint was annualized moderate-to-severe exacerbation rates in patients from BOREAS + NOTUS versus MATINEE + METREX (modified intention-to-treat high stratum cohort, representing an eosinophilic phenotype); sensitivity analyses were performed using different combinations of mepolizumab data including MATINEE + METREX + METREO (100-mg arm). Other 52-week endpoints included mean difference in pre-bronchodilator forced expiratory volume in 1 s (FEV₁), proportion of St. George's Respiratory Questionnaire (SGRQ) improvement ≥ 4 points, proportion of Evaluating Respiratory Symptoms in COPD (E-RS:COPD) improvement ≥ 2 points, and annualized severe exacerbation rate. Rate ratios (RRs)/odds ratios (ORs) with 95% confidence intervals (CIs) are reported.

Results: The primary ITC resulted in an RR of 0.82 (95% CI 0.66, 1.01), showing a numerical advantage for dupilumab versus mepolizumab in reducing moderate-to-severe exacerbation. Sensitivity analyses confirmed findings from the primary ITC (BOREAS + NOTUS vs. MATINEE + METREX + METREO: RR 0.83 [95% CI 0.68, 1.01]). Dupilumab demonstrated significantly greater FEV₁ improvement (mean difference 83.4 mL [95% CI 36.1, 130.7]) and proportion of E-RS:COPD improvement ≥ 2 points (OR 1.76 [95%CI 1.20, 2.54]), with a numerical difference favoring dupilumab for the proportion of SGRQ improvement ≥ 4 points (OR 1.16; [95% CI 0.86, 1.56]) and for annualized severe exacerbation rate (RR 0.61 [95% CI 0.33, 1.13]) versus mepolizumab.

Conclusion: This ITC suggests potential clinical benefits of dupilumab over mepolizumab in reducing exacerbations and improving lung function, respiratory symptoms, and quality of life in patients with COPD and type 2 inflammation. Direct head-to-head trials are necessary to confirm these results and better guide treatment choices.

Introduction: Preserved ratio impaired spirometry (PRISm) is an important phenotype of pulmonary function in clinical and public health practice. It is possible for some patients to have chronic obstructive pulmonary disease (COPD) at an early stage. At present there is little research on the association of PRISm with type 2 (T2) inflammation biomarkers. The blood eosinophilia and impairment of small airway function in PRISm have not been fully assessed. This study investigated the eosinophilic phenotype in PRISm.

Methods: Between January 2019 and September 2022, a retrospective assessment was conducted in a single pulmonary function unit in China. PRISm was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥ 70% and FEV1 < 80% predicted. Two groups were formed among the PRISm participants: eosinophilic PRISm, blood eosinophil count (BEC) ≥ 150/µL; non-eosinophilic PRISm, BEC < 150/µL. Differences were analyzed between eosinophilic and non-eosinophilic PRISm.

Results: The study included 313 participants, of whom 135 were assigned to the eosinophilic PRISm group. After adjusting for potential confounders, compared to non-eosinophilic PRISm, eosinophilic PRISm remained correlated with lower natural logarithm (ln) MEF25% predicted (- 0.161 [- 0.267, - 0.054], P = 0.003) and elevated fractional exhaled nitric oxide (FeNO) (10.616 [6.384, 14.849], P < 0.001).

Conclusion: Eosinophilic phenotype was common in individuals with PRISm. Compared to participants with non-eosinophilic PRISm, those with eosinophilic PRISm tended to have impaired MEF25% predicted and elevated FeNO.

Introduction: Sleep disorders are common yet often underdiagnosed in children with attention deficit/hyperactivity disorder (ADHD). These disturbances can exacerbate ADHD symptoms and negatively affect cognitive, emotional, and behavioral functioning. This study aimed to describe the prevalence of obstructive sleep apnea (OSA) and other sleep disorders in children with ADHD using standardized diagnostic criteria and to identify associated clinical and behavioral factors.

Methods: A cross-sectional study was conducted on 629 children aged 6-12 years (mean age: 7.8 ± 1.5 years) who were diagnosed with ADHD. Sleep disturbances were assessed using the Children's Sleep Habits Questionnaire (CSHQ), the Pediatric Sleep Questionnaire (PSQ), and respiratory polygraphy. Sleep disorders were classified on the basis of the International Classification of Sleep Disorders, Third Edition (ICSD-3). Multivariate logistic regression was used to identify associated risk factors.

Results: Sleep disorders were diagnosed in 70.0% of children with ADHD. The most common disorders were insomnia (40.2%), OSA (23.4%), parasomnias (27.8%), restless legs syndrome (10.5%), and delayed sleep-wake phase disorder (4.8%). The inattentive ADHD subtype, psychiatric comorbidities, tonsil and adenoid hypertrophy, iron-deficiency anemia, and sleep-related behaviors in children with ADHD were significantly associated with sleep disturbances.

Conclusions: Sleep disorders are highly prevalent and diverse in children with ADHD. Early identification and targeted management of sleep disturbances, particularly OSA and insomnia, are essential to improving sleep quality and optimizing ADHD outcomes. Routine sleep screening should be integrated into clinical ADHD evaluations. Graphical abstract available for this article.

An indwelling pleural catheter (IPC) is a valuable tool in the management of pleural effusions, allowing drainage strategies to be tailored to match patient-centred goals. Previously, IPCs were primarily utilised in malignant pleural effusion (MPE) in the presence of non-expandable lung (NEL) or after the failure of chemical pleurodesis. Several studies have compared IPC to intercostal chest drain (ICD) with talc pleurodesis (TP), as well as different drainage regimens, resulting in a transition of practice. Continued developments have led to novel adjuncts, such as digital drainage, which allow controlled flow rates. The emerging field of intrapleural therapy in MPE is gaining attention as a potential new treatment modality, possibly increasing the scope of IPCs further. This article will provide a narrative review of the role of IPCs and will be based on published evidence to date and highlight the importance of an individualised, patient-centred care approach.

Pleural infection encompasses a spectrum of disease that can present significant challenges in clinical practice. Despite better understanding of the underlying pathophysiology and microbiology, outcomes for patients remain poor. The use of antibiotics and chest tube drainage continue to be the mainstay of treatment, with surgery often reserved for those not responding to initial medical therapy. However, at present, the optimal management strategy for individual patients-including the role of early surgical and/or intrapleural therapy-is not clear. In this article, we provide an overview of the pathophysiology, diagnosis and management of pleural infection, highlighting current concepts and key practice points to aid the reader in caring for this important and often complex group of patients.