Pulmonary Therapy最新文献

Purpose of review: This review aims to summarize the latest evidence on how climate change has altered the environmental exposures and their influence on the epidemiology, pathophysiology, and outcomes of interstitial lung diseases (ILD). Rising global temperatures are exacerbating environmental threats (like heatwaves, floods, and dust storms) and worsening air quality. This burden disproportionately affects certain vulnerable groups, accelerating the decline of their ILD. Epigenetic modifications play a vital role in explaining the interaction between the environmental factors and development and progression of ILD. Establishment of strong policies is critical for both reducing the rate of climate change and implementing better adaptation strategies to protect the vulnerable group from its ongoing consequences.

Obstructive sleep apnea (OSA) is increasingly recognized as a major comorbidity in chronic respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD). The coexistence of OSA with asthma or COPD significantly complicates the clinical course, leading to poorer disease control, more frequent exacerbations, reduced lung function, impaired sleep quality, and increased cardiovascular and overall mortality. In asthma, OSA exacerbates airway inflammation, enhances bronchial hyperresponsiveness, and decreases responsiveness to standard therapies. In COPD, the "overlap syndrome" is associated with profound nocturnal hypoxemia, chronic hypercapnia, pulmonary hypertension, and a markedly elevated risk of hospitalization and death. Underlying mechanisms include chronic airway inflammation, oxidative stress induced by intermittent hypoxia, instability of ventilatory control (high loop gain), structural upper-airway alterations, and the burden of obesity and metabolic dysfunction. These interactions highlight the urgent need for integrated and proactive management strategies. Thus, we propose an Asthma-COPD-OSA Outpatient Unit (ACOSOU)-a care-delivery model, not a disease entity-designed to integrate systematic screening, diagnosis, treatment initiation, and long-term follow-up of OSA in patients with asthma and COPD. Optimal care requires systematic screening in respiratory outpatient settings, appropriate diagnostic pathways using polysomnography or home sleep apnea testing, and individualized treatment approaches. Continuous positive airway pressure (CPAP) remains the cornerstone therapy for OSA-asthma and OSA-COPD overlap, improving gas exchange, reducing exacerbations, and enhancing disease control. Comprehensive management also includes optimization of inhaled therapies, pulmonary rehabilitation, weight reduction, sleep hygiene, and multidisciplinary collaboration. This review proposes an integrated ACOSOU model to streamline screening, diagnosis, CPAP titration, and long-term follow-up. However, implementation in low- and middle-income countries faces challenges including limited trained sleep-medicine personnel, unequal access to diagnostic tools, and high CPAP costs without insurance coverage. Strengthening infrastructure, training, and policy support will be essential to improve outcomes for patients with chronic respiratory diseases and OSA comorbidity.

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive lung condition associated with high morbidity and mortality. Single-inhaler triple therapy (SITT), such as budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF), is recommended for patients with COPD who are not adequately controlled by dual therapy (DT). Escalation from DT or switching from triple therapy (TT)-SITT or multiple-inhaler TT (MITT)-are key real-world treatment pathways.

Methods: The observational, retrospective, multicenter ORESTES study included adults (≥ 40 years) with COPD initiating BGF in routine clinical practice. This secondary analysis focuses on the following treatment pathways: escalation from DT and switch from TT. Patients' characteristics, exacerbations, additional COPD treatments, and healthcare resource utilization (HCRU) were assessed.

Results: A total of 295 patients escalated from DT and 356 switched from TT (SITT: 147; MITT: 209) to BGF. 66.8% of patients escalating from DT and 78.5% switching from TT showed a high-risk GesEPOC phenotype; 77.9% and 80.0% had mMRC grade ≥ 2, and 91.2% and 96.1% had ≥ 3 comorbidities. Following BGF initiation, the annualized exacerbation rate decreased by 11.6% (from 1.06 to 0.94) in patients escalating from DT and by 15.5% (from 1.60 to 1.35) in patients switching from TT (after SITT: 17.8% reduction; after MITT: 14.1%). Rescue medication use declined overall, and specifically short-acting beta-2 agonists (SABA) use declined by 23.2% and 19.4% (SITT: 21.9%; MITT: 18.4%). Emergency room visits and hospitalizations decreased by 19.7% and 19.0% in patients escalating from DT, and by 29.4% and 25.5% among those switching from TT (SITT: 25.0%/18.3%; MITT: 32.4%/29.9%).

Conclusions: In this real-world Spanish cohort of patients with COPD not adequately controlled with DT or TT, reductions in exacerbations, rescue medication use, and HCRU were observed after BGF initiation, supporting the potential value of earlier introduction of BGF in patients with persistent symptoms and/or frequent exacerbations despite high-intensity therapy.

Clinical trial registration: NCT06321731.

Introduction: This study estimated the potential public health impact of alternative COVID-19 vaccination strategies in Singapore.

Methods: The outcomes of alternative vaccination strategies using a Pfizer-BioNTech COVID-19 vaccine updated to the latest circulating strain were estimated using a combined decision tree-Markov cohort model. The model was previously used to estimate the impact of vaccination based on epidemiological data from 2021/22 and vaccine coverage data from 2022/23. It has now been updated with epidemiology data from 2023/24 and an assumed vaccine coverage of 20%. Age-specific inputs were derived from local epidemiological data and published sources. The model projected health outcomes (cases, hospitalizations, and deaths) and economic outcomes (direct medical costs and productivity losses) across different age and risk subgroups.

Results: Vaccinating individuals aged 60 and above, as well as individuals aged 6 months to 59 years with comorbidities, making them at high risk for severe COVID-19 outcomes, with a vaccine coverage of 20%, is projected to result in 14,099 fewer infections, 2668 fewer hospitalizations, and 21 fewer deaths in 1 year. This leads to a total estimated savings of SGD 21.3 million in direct medical costs and SGD 24.8 million in indirect costs. Increasing coverage to 50% has the potential to further increase deaths, hospitalizations, infections, and costs averted by 150%.

Conclusions: Although vaccination has a smaller impact on public health compared to the previous evaluation because of the updated epidemiology and lower estimated coverage, an updated vaccine can still have a public health and economic impact in Singapore.

Drug-induced interstitial lung disease (DI-ILD) has emerged as a clinically significant complication associated with a broadening spectrum of therapeutic agents. DI-ILD can result in significant morbidity and mortality if not promptly diagnosed and treated. In this review, we synthesize current evidence concerning the epidemiology, risk factors, pathophysiological mechanisms, clinical manifestations, diagnostic approaches, and management strategies of DI-ILD, with focused emphasis on three major therapeutic groups: immune checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell (CAR-T) therapies, and biological agents; adding other commonly used drugs known for causing DI-ILD as well, such as: amiodarone, methotrexate, and nitrofurantoin. Early recognition, drug discontinuation, tailored immunosuppression, and supportive care are pivotal to improving outcomes. Enhanced medical awareness and a multidisciplinary care approach are essential to mitigate morbidity and mortality. By synthesizing current knowledge, this review aims to enhance awareness and understanding of DI-ILD, thereby facilitating earlier diagnosis and more effective management strategies for this potentially severe adverse drug event.

Emerging evidence demonstrates the evolving role of fungi in the pathophysiology and disease progression observed in bronchiectasis. Fungal-associated traits are linked to disease severity, exacerbation frequency and airway inflammation. Structural abnormalities and impaired mucociliary clearance, characteristic of bronchiectasis, predispose to fungal colonisation, with subsequent immunopathogenic responses dependent on underlying host immunity. The diagnosis of fungal infection remains challenging in clinical settings, owing to the limitations of existing diagnostic modalities; however, the development of culture-independent molecular techniques shows promise. The use of next-generation sequencing has significantly advanced our understanding of the fungal microbiome in bronchiectasis, identifying fungi that are challenging to culture. Integrative microbiomics further elucidates the intricate and dynamic role of fungi in relation to other microbial kingdoms, and across distant organs such as the gut, revealing important relationships with bacterial pathogens including Pseudomonas aeruginosa. Airway inflammatory profiling has shown fungal-associated inflammatory endotypes which may serve as treatable traits. Environmental influences on fungi and bronchiectasis-exacerbated by air pollution and climate change-underscore the key role of the exposome in fungal-associated endotypes in bronchiectasis. This review outlines the clinical significance of fungi in bronchiectasis, the current diagnostic and treatment challenges, and emerging fungal-associated endotypes in the context of environmental influence on disease.

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive pulmonary hypertension characterized by chronic fibrotic thrombi. Treatment includes surgical, endovascular, and pharmaceutical options. With varied treatments, it is essential to understand how they are deployed across real-world settings. We aimed to describe clinical characteristics, treatment patterns, and quality of life across real-world settings in the USA.

Methods: Data were drawn from the Adelphi Real World CTEPH Disease Specific Program™, a cross-sectional survey of US physicians and patients, conducted September 2023-May 2024. Physicians recruited by local fieldwork agents using a short screening questionnaire provided demographics, clinical characteristics, and treatment patterns for 1-6 consecutively consulting patients with right heart catheterization confirmed CTEPH. These patients self-completed a form containing the EQ-5D-5L, visual analog scale (EQ-VAS), workplace and activity impairment scale (WPAI), pulmonary arterial hypertension symptom and impact scale. Data were stratified by treatment setting (accredited or nonaccredited pulmonary hypertension center). Analyses were descriptive.

Results: In total, 98 physicians provided data on 153 patients, of whom 53 completed the patient self-complete form. Mean (standard deviation) patient age was 59.2 years, 59.5% female, and 73.2% considered operable. Of those who had undergone a surgery/procedure (n = 68), 82.1% had undergone pulmonary thromboendarterectomy (PTE), and 19.1% balloon pulmonary angioplasty (BPA). Overall, 82.4% were prescribed any pharmaceutical medication for their CTEPH; of those treated, 81.0% were prescribed anticoagulants. Monotherapy (45.7%) was the most reported regimen in nonaccredited settings; for accredited settings, this was dual therapy (45.5%). EQ-5D-5L scores were low with nearly a quarter of patients reporting problems with usual activities and mobility, and 26.4% needing to change work patterns.

Conclusions: Though treatment patterns generally followed guidelines, BPA was potentially underutilized. Dyspnea was common, despite treatment, with patients experiencing reduced quality of life, highlighting an unmet need.

Introduction: Fractional exhaled nitric oxide (FeNO) is an important type 2 (T2) asthma biomarker. Home-based FeNO monitoring can provide longitudinal data better reflecting the variable nature of T2 inflammation versus single-point data. We sought to compare longitudinal mean FeNO and variability (CV) in relation to asthma control, and to compare detection rate of T2_FeNO inflammation at diagnostic (≥ 40 ppb in GINA 1) and on-treatment (≥ 25 ppb in GINA 2-5) cutoffs during home versus clinic measurements.

Methods: This was an observational study with once-daily home-based FeNO (Vivatmo me) and symptom diary in patients with asthma of different GINA steps performed over 3 months. Clinic FeNO, forced expiratory volume in 1 s (FEV₁), and 5-item asthma control questionnaire (ACQ-5) scores were also collected at two visits (enrolment/study end).

Results: We enrolled 85 patients (n = 23 step 1, n = 37 steps 2-3, and n = 25 steps 4-5). Mean FeNO over 3 months was highest in uncontrolled steps 4-5 (p = 0.006), and FeNO variability in steps 2-3 (p = 0.046). Subjects with optimal control (ACQ < 0.75 both visits) had comparable mean FeNO values, but fewer patients with CV above the median vs. suboptimally controlled patients (39.1% vs. 54.1%; p = 0.03). In GINA 1, FeNO CV was lower in optimally controlled patients (p = 0.10). Mean FeNO was higher on symptomatic asthma days, particularly in step 1 (p = 0.002), with similar trends during loss of asthma control phases. Home FeNO increased the detection rate of T2_FeNO inflammation at a diagnostic cutoff (≥ 40 ppb, step 1) from 8.7% (clinic FeNO) to 47.8% of subjects, and of on-treatment T2_FeNO inflammation in GINA steps 2-3 and 4-5 from 58.3% to 83.3%, and 64% to 96%, respectively.

Conclusion: Home-based FeNO provides important information about airway inflammation, distinct and complementary to symptom control. Detection of T2_FeNO inflammation is facilitated at all GINA steps at diagnostic and predictive/prognostic cutoffs, with important implications for management and diagnosis.

Trial registration: German Clinical Trial Register (DRKS) DRKS00029118, registered July 1, 2022.

Introduction: In Italy, elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) in combination with ivacaftor was reimbursed starting July 2021 for use in people with cystic fibrosis (CF) aged ≥ 12 years homozygous for F508del mutation or heterozygous with at least one F508del allele and with a minimal function mutation. This study assessed the impact of ELX/TEZ/IVA on real-world outcomes among this population in Italy.

Methods: This observational study used data from Verona CF Center from October 2018 to December 2022 to describe the impact of ELX/TEZ/IVA on individuals aged ≥ 12 years with ≥ 1 F508del allele on lung function and healthcare resource utilization (HCRU). Lung function (percent predicted forced expiratory volume in 1 s [ppFEV₁]), hospitalizations, outpatient visits, pulmonary exacerbations (PEx), and prescribed medications were analyzed during baseline and follow-up periods (12 months pre- and post-ELX/TEZ/IVA initiation, respectively) and reported as change from baseline.

Results: A total of 149 individuals were included (mean [standard deviation, SD] age: 32.6 [12.25] years). A mean improvement in ppFEV₁ of +14.38 percentage points (95% confidence interval [CI] 12.65; 16.10) was observed during the follow-up period. An 87.2% reduction in the annualized PEx rate (rate ratio: 0.128 [95% CI 0.085; 0.187]) and an 85.4% reduction in the annualized hospitalization rate (rate ratio: 0.146 [95% CI 0.096; 0.213]) were observed during follow-up compared to baseline. Reductions in the proportion of individuals requiring prescription medications, including intravenous antibiotics, mucolytic agents, and bronchodilators, were observed.

Conclusion: Substantial improvements in lung function and reductions in HCRU were observed after treatment with ELX/TEZ/IVA in the Verona CF Center. Results contribute to the growing evidence of country-specific real-world data on the positive impact of ELX/TEZ/IVA.

Introduction: Dry powder inhalers (DPIs) have a 20-40-fold lower carbon footprint compared to pressurized metered-dose inhalers (pMDIs). Switching from pMDI to DPI is therefore beneficial from an environmental perspective, but many health care professionals are concerned that this may worsen treatment outcomes in asthma and chronic obstructive pulmonary disease (COPD).

Methods: We analyzed patient outcomes and carbon footprints of switching inhaler treatment from pMDI to DPI. We performed a post hoc analysis on clinical outcomes data from a 12-week real-world, non-interventional study of adult patients with asthma or COPD who switched treatment from pMDI to the budesonide-formoterol Easyhaler DPI. Clinical end points included asthma control test (ACT), Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ), lung function tests, and reliever use (asthma), and COPD assessment test (CAT), and modified Medical Research Council dyspnea scale (mMRC) (COPD). In the carbon footprint calculation, we used estimates from the Montreal Protocol for pMDI and for DPI the estimate as reported.

Results: Among all 237 patients (142 asthma, 95 COPD) by switching their treatment clinical improvements were observed in all the outcome measures (p < 0.001). Furthermore, the need for reliever medication decreased among patients with asthma (p < 0.001). The amount of estimated kg CO₂e emissions per year for maintenance treatment was 97.0% lower for the DPI than for pMDI. For reliever medication among patients with asthma, it was 99.6% lower. Among them, the emission savings could amount to approximately 131 kg CO₂e annually. This is of similar magnitude, as individual high-impact environmental actions such as eating a plant-based diet or purchasing green energy.

Conclusions: Our results show that disease control was maintained among patients with asthma or COPD when they switched from pMDI to DPI, while the carbon footprint of inhaler treatment was reduced.