Pulmonary Therapy最新文献

Pneumothorax, defined by the presence of air in the pleural cavity, is a potentially life-threatening condition requiring prompt diagnosis and tailored management. Rapid and accurate diagnosis is primarily achieved through radiological imaging. Management strategies for pneumothorax vary according to severity and aetiology. Conservative care, involving vigilant observation and supplemental oxygen, is suitable for small, stable pneumothoraxes. Needle aspiration can be an effective first-line treatment, although it may fail in some instances, necessitating escalation. Ambulatory devices facilitate outpatient care and reduce the length of hospital stays. Chest drainage remains a cornerstone therapy. Indwelling pleural catheters may be implemented in selective cases. Endobronchial treatments, including valves and spigots, offer minimally invasive options for reducing the flow of air leaks. Medical thoracoscopy with talc poudrage provides both diagnostic and therapeutic benefits in patients unsuitable for surgery, while surgical intervention represents the gold standard for definitive treatment. Adjunctive interventions include talc slurry pleurodesis and autologous blood patch pleurodesis for patients unsuitable for surgery. Effective management necessitates individualized treatment plans, incorporating risk factor modification, pain management, and physiotherapy. This practical approach aims to update the reader on the treatment modalities that can be used in all forms of pneumothorax in clinical practice.

Introduction: Elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to substantially improve clinical outcomes among people living with cystic fibrosis (pwCF). The impact of ETI on health care resource utilization in the context of universal health care is largely unknown. We aimed to assess the impact of ETI on hospital and non-hospital health care resource utilization in a national cohort of pwCF up to 2 years after ETI initiation.

Methods: We included all pwCF aged 12 years or older in the Danish Cystic Fibrosis Cohort initiating ETI therapy between 1 September 2020 and 31 December 2022. The following health care contacts were reported: acute and elective hospitalizations, acute and elective outpatient contacts, general practitioner (GP) visits, other specialist visits, physiotherapist/chiropractor visits, pharmacy visits, and blood sampling appointments. Pre- and post-ETI data were analyzed using logistic and linear regression models estimating number of visits, days in hospital, and odds ratios (ORs) for one monthly contact.

Results: A total of 283 pwCF initiated ETI in the study period. At 24 months post-ETI, utilization of the following health care resources was reduced: elective hospitalizations [OR 0.20 (95% CI: 0.08; 0.50)], elective outpatient hospital contacts [0.70 (0.57; 0.86)], pharmacy visits [0.56 (0.45; 0.71)], and blood sampling appointments [0.61 (0.49; 0.77)]. Number of contacts per month was reduced for the aforementioned outcomes, as well as number of days in hospital for elective hospitalizations. A downward but not statistically significant trend was observed for acute hospitalizations. No significant change was observed for acute outpatient visits, GP visits, other specialist visits, or visits to a physiotherapist/chiropractor.

Conclusion: In a national cohort of pwCF, ETI was associated with substantial reductions in elective hospitalizations, elective outpatient contacts, duration of elective hospitalizations, pharmacy visits, and blood sampling appointments, sustained 2 years post-ETI initiation. These findings highlight the real-world effectiveness of ETI in the context of a universal health care system.

Pleural mesothelioma (PM) is a rare incurable disease, predominantly linked to asbestos exposure. Not only is diagnosis difficult, but treatment choices are often limited to systemic anti-cancer treatment with chemotherapy or immunotherapy. Surgery has been employed for decades, but its application has been fiercely debated despite some randomized controlled trials such as the recent Mesothelioma and Radical Surgery 2 (MARS 2) study. We provide a commentary on this controversial topic.

Introduction: This post hoc analysis assessed the ability of tezepelumab treatment to restore normal lung function in patients with severe, uncontrolled asthma with abnormal lung function at baseline pooled from the PATHWAY and NAVIGATOR studies.

Methods: PATHWAY and NAVIGATOR were multicentre, randomized, double-blind, placebo-controlled studies. Patients (12-80 years old) included in this analysis received tezepelumab 210 mg subcutaneously every 4 weeks or matched placebo for 52 weeks. Patients had a percent predicted pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV₁) of < 80% (< 90% for adolescents in NAVIGATOR) at screening. The change from baseline to week 52 in pre-BD FEV₁ was assessed by baseline percent predicted pre-BD FEV₁ subgroup [abnormal (< 80%) and normal (≥ 80%)]. The proportion of patients with abnormal lung function at baseline who achieved normal lung function at week 52 was assessed overall and by biomarker level and disease duration subgroups.

Results: Of the 665 and 669 patients who received tezepelumab or placebo, respectively, 564 and 569 had abnormal lung function at baseline. Tezepelumab improved the pre-BD FEV₁ from baseline to week 52 versus placebo by 0.14 L [95% confidence interval (CI) 0.09-0.19] and 0.13 L (95% CI 0.01-0.24) in patients with abnormal and normal lung function at baseline, respectively. A higher proportion of tezepelumab than placebo recipients with abnormal lung function at baseline achieved normal lung function at week 52 (17.2% vs. 9.9%, respectively). Among tezepelumab recipients, those with higher levels of type 2 inflammatory biomarkers and a shorter duration of disease at baseline were more likely to achieve normal lung function at week 52.

Conclusion: In patients with severe, uncontrolled asthma, a greater proportion of tezepelumab than placebo recipients with abnormal lung function at baseline achieved normal lung function at week 52.

Trial registration: PATHWAY: NCT02054130; NAVIGATOR: NCT03347279.

Idiopathic pulmonary fibrosis (IPF) represents a clinical and therapeutic challenge characterized by progressive fibrosis and destruction of the lung architecture. The pathogenesis of IPF has been long debated; while it is generally believed that repeated lung injury and abnormal wound repair are the main pathogenetic mechanisms, clear understanding of disease development and efficacious treatment remain important unmet needs. Indeed, current standard of care (i.e., the antifibrotic drugs pirfenidone and nintedanib) can slow down lung function decline and disease progression without halting the disease. In the last 2 decades, several clinical trials in IPF have been completed mostly with negative results. Yet, unprecedented numbers of clinical trials of pharmacological interventions are currently being conducted. In this review, we summarize and critically discuss the current and future treatment landscape of IPF, with emphasis on the most promising developmental molecules.

Chronic obstructive pulmonary disease (COPD) is a common and complex disease characterized by persistent airflow limitation and the presence of exacerbations, resulting in significant morbidity and mortality. Although the pathogenesis of COPD is multifactorial, airway inflammation plays a significant role in disease progression. Despite the advantages of non-pharmaceutical and pharmaceutical interventions that have significantly improved the symptom burden and exacerbation frequency in COPD, there is a lack of disease-modifying therapies that target the underlying disease mechanisms. Monoclonal antibodies (mAbs), a drug class that has improved treatment in severe asthma by blocking mediators of the type 2 (Th2) and allergic inflammatory cascades, are currently under investigation for their efficacy in COPD. Our review summarizes the evidence for the use of monoclonal antibodies in COPD and discusses current limitations and promising advances. Although targeting Th1 inflammation has failed to improve COPD outcomes, recent clinical trials have shown beneficial effects of monoclonal antibodies targeting Th2 inflammation, providing evidence for a personalized approach in COPD treatment.

Introduction: Pulmonary hypertension (PH) is a rare and severe disorder that significantly affects patients' lives. However, a comprehensive picture of the diagnosis and treatment of this condition in Japan remains unclear. This study aimed to elucidate these aspects by conducting a nationwide survey targeting patients with PH and treating physicians.

Methods: A cross-sectional survey was conducted among 160 patients with PH (119 with pulmonary arterial hypertension [PAH] and 41 with chronic thromboembolic pulmonary hypertension [CTEPH]), of whom 121 were female (75.6%), and 211 physicians across Japan. The questionnaires assessed patients' diagnostic journey, employment status, communication with physicians regarding treatment goals, health-related quality of life (HRQoL), and medication adherence.

Results: Patients visited a mean of 2.3 medical facilities before receiving a PH diagnosis (PAH patients: 2.2 visits; CTEPH patients: 2.3 visits), with a mean time from symptom onset to diagnosis of 18.0 months (PAH: 20.2 months; CTEPH: 12.2 months). Employment and school attendance rates declined from 68.8% before diagnosis to 44.4% immediately after diagnosis, and further to 36.9% at the time of the survey. Discrepancies in communication about treatment goals were observed between patients and physicians, particularly in patients with CTEPH (82.9% of patients reported such discussions vs. 41.2% of treating physicians). Median HRQoL scores, as assessed by the emPHasis-10 questionnaire, indicated impairment (PAH: 21.5; CTEPH: 18.0), which worsened with increasing disease severity.

Conclusion: This nationwide study provides a comprehensive overview of the challenges faced by patients with PH in Japan. The findings suggest the essential need for earlier diagnosis, support for employment and education among patients, and improved patient-physician communication to reduce the burden of PH and enhance patient outcomes. Graphical abstract avaliable for this article.

Introduction: Human respiratory syncytial virus (RSV) infections can result in hospitalization and/or death among vulnerable populations. Molnupiravir is a prodrug of ß-D-N4-hydroxycytidine, which has broad-spectrum preclinical activity against RNA viruses. We conducted a pilot trial evaluating molnupiravir for RSV infection.

Methods: Double-blind, placebo-controlled, phase 2a human challenge study in healthy adults (≥ 18 to ≤ 55 years old). Eligible participants were randomized 1:1:1 to molnupiravir prophylaxis (5 days, 800 mg twice daily; followed by placebo), molnupiravir treatment (5 days, 800 mg twice daily; started on day 5, unless triggered earlier by positive PCR test; preceded and followed by placebo), or placebo. Study intervention was administered for 11 days, from day -1 (evening), prior to inoculation with RSV on day 0 (morning). For 10 days, quarantined participants reported symptoms thrice daily and underwent nasal wash sample collection twice daily. Primary efficacy endpoints (assessed by quantitative viral culture on plaque assay) were peak viral load (PVL) in all participants (for prophylaxis) and area under the viral-load time curve (VL-AUC) in participants with confirmed infection (for treatment). Adverse events were assessed from day 0 to day 28.

Results: Forty participants each were randomized to prophylaxis and placebo and 36 to treatment. Molnupiravir was not statistically significant from placebo in either primary endpoint: with prophylaxis, the difference in mean log₁₀ PVL was - 0.29 plaque-forming units (PFU)/ml (90% CI - 1.16, 0.58; p = 0.578), and with treatment, the difference in mean log₁₀ VL-AUC was - 2.69 day*PFU/ml (90% CI - 6.17, 0.79; p = 0.201). Molnupiravir treatment resulted in significantly faster symptom resolution: 6.0 days versus 8.5 days with placebo (hazard ratio: 2.24 [95% CI: 0.99, 5.07]; p = 0.0459). Adverse event rates were comparable between arms.

Conclusions: Although the primary endpoints were not met, modest, non-significant benefits with molnupiravir treatment were seen across virologic endpoints, along with significantly faster symptom resolution.

Clinical trial registration: ClinicalTrials.gov NCT05559905.

Introduction: Long-acting muscarinic antagonist (LAMA) addition to inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) dual therapy is recommended for severe asthma, but its real-world effectiveness is not well established.

Methods: A systematic literature review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to investigate clinical outcomes in US adults with asthma receiving ICS + LABA + LAMA as multiple-/single-inhaler triple therapy (MITT/SITT). Real-world/observational studies published in English in Embase/MEDLINE databases (2014-2024) and conference abstracts presented 2022-2024 were eligible for inclusion.

Results: From 588 identified records, only 8 articles reporting 6 unique studies were included; 2 assessed SITT and 4 assessed MITT, and 4 treatments were investigated. Exacerbation rates reported in two studies were significantly reduced with tiotropium (TIO) + ICS + LABA MITT versus high-dose ICS + LABA within 6 (64% lower) and 12 months (73%), and fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg SITT versus pre-treatment after 12 months (41%). Oral corticosteroid (OCS) use was reported in two studies. The proportion of patients with ≥ 1 rescue OCS dispensing decreased with TIO 1.25 mcg + ICS + LABA MITT, with greatest reductions for MITT ± leukotriene receptor antagonist (pre-treatment: 68.4%, post treatment: 54.2%). Mean number of OCS dispensings/patient/year significantly decreased (29%, p < 0.001) following FF/UMEC/VI 100/62.5/25 mcg SITT initiation. Treatment adherence/persistence was reported in three studies. Mean (standard deviation) proportion of days covered was significantly higher (p < 0.001) for FF/UMEC/VI SITT versus MITT after 6 (0.56 [0.31] versus 0.46 [0.31]) and 12 months (0.46 [0.33] versus 0.35 [0.30]). Persistence at 12 months was 25.9% and 12.0%, respectively. Lung function, clinical remission, quality of life, and safety outcomes were not reported in any study.

Conclusions: This brief communication reports a systematic review that identified few sources of SITT or MITT in US patients with asthma. Although inclusion of observational studies can result in reporting/selection bias, we identified greater clinical benefits with triple therapies versus dual therapies.

The latest advances in asthma treatment have highlighted the significance of eosinophilia and the possible role of some pro-eosinophilic mediators, like interleukins (IL) IL-5, IL-4/IL-13, and IL-33 in the disease's pathogenesis. Considering that a subgroup of patients with chronic obstructive pulmonary disease (COPD) may have blood eosinophilia akin to that seen in asthma, numerous studies in the last decade have suggested that eosinophilic COPD is a separate entity. While the exact role of blood eosinophils in the pathophysiology of COPD remains unclear, eosinophilia seems to increase the effectiveness of corticosteroid therapy. Currently, monoclonal antibodies targeting the interleukins (IL-5, IL-4, IL-13, and IL-33) or their receptors are being investigated in patients with COPD belonging in T2-high endotype. This review focuses on the mechanisms of eosinophilia in COPD, the effects of eosinophilia on disease outcome, and examines the most recent data on the use of peripheral blood eosinophilia in treating patients with COPD. Finally, we emphasize the current implication of monoclonal antibodies in COPD in the context of eosinophilic airway inflammation.