Therapeutic Advances in Respiratory Disease最新文献

Background: It has been shown that asthma is potentially linked to a higher risk of cardiovascular disease (CVD) and cardiovascular mortality (CVM).

Objectives: This study aims to systematically review and summarize epidemiological evidence on the relationship between asthma and these cardiovascular outcomes.

Design: Systematic review and meta-analysis.

Data sources and methods: This meta-analysis, registered with PROSPERO (CRD 42024576126), utilized data from PubMed, Embase, the Cochrane Library, and references from included studies. The search covered literature from the inception of these databases until July 17, 2024. We included observational studies examining the link between asthma and CVD and CVM. Bias risk was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). We calculated pooled relative risk (RR) with a 95% confidence interval (CI) using a random-effects model.

Results: A total of 29 studies encompassing 11,380,027 participants were included. The overall risk for CVD in asthma patients was 1.30 (95% CI: 1.20-1.42). Specific CVD risks were elevated for coronary heart disease (CHD, RR 1.35; 95% CI: 1.27-1.42), angina pectoris (AP, RR 1.48; 95% CI: 1.16-1.89), myocardial infarction (MI, RR 1.33; 95% CI: 1.25-1.41), and heart failure (HF, RR 1.53; 95% CI: 1.04-2.23). Asthma was also associated with a higher risk of CVM (RR 1.26; 95% CI: 1.05-1.51).

Conclusion: Asthma is associated with a higher risk of developing CVD, including specific types such as CHD, AP, MI, and HF. In addition, asthma patients face an increased risk of cardiovascular mortality compared to non-asthmatics.

Background: The role of preoperative conditioning on postoperative outcomes in thoracic surgery is of growing interest. There is a paucity of data on understanding compliance with a patient-led walking program and its impact on quality of life.

Objectives: To understand the feasibility of patient-driven data collection of daily steps via pedometers and to understand the impact of preoperative conditioning on quality of life.

Design: A prospective single-institution quality improvement study.

Methods: The study included patients who underwent thoracic surgery between 2020 and 2022 who were and were selected to receive a pedometer at their preoperative clinic appointment. A daily step goal was determined, and patients were instructed to record their daily steps. Quality of life was assessed at baseline and at presentation for surgery. Clinical data and postoperative outcomes were derived from the institutional Society of Thoracic Surgery General Thoracic Surgery Database.

Results: There were 167 patients provided with pedometers at their presurgical clinic appointment, of whom 43 returned pedometer data (utilization rate 26%). Of the 104 who underwent lung resection, 74 (44.3%) did not record step data, 15 had <6000 median daily steps, and 15 had >6000 median daily steps. Pre-intervention self-perceived outcomes were similar. Post-pedometer data demonstrated higher scores in the domains of general health (p = 0.016), quality of life (p = 0.03), general physical health (p = 0.002), physical performance (p = 0.03), social health (p = 0.009), social performance (p=0.01), and fatigue level (p = 0.01) for patients with higher median step counts. There were no significant differences in postoperative outcomes based on survival, length of stay (p = 0.77), or respiratory complications (p = 0.52).

Conclusion: A patient-led walking program using pedometers is feasible for a minority of patients. Higher recorded daily step counts are associated with improved self-perceived quality of life in patients prior to lung surgery.

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous lung condition characterised by chronic respiratory symptoms, fixed airway obstruction and persistent inflammation that leads to a progressive airflow limitation. Although COPD has traditionally been linked to neutrophilic inflammation, recent studies have identified a subset of patients - approximately 20%-40% - with elevated eosinophil levels in blood and sputum. Emerging evidence suggests that eosinophilic inflammation has a pivotal role in a subset of COPD patients and may influence disease progression, exacerbation frequency and therapeutic responses. This narrative review provides a comprehensive analysis of the role of eosinophils in COPD with particular attention to their role as biomarkers in blood and sputum. We evaluate the prevalence of eosinophilic inflammation in COPD exanimating different thresholds used in blood and in sputum to define it. In addition, we focus on eosinophilic COPD phenotype as a treatable trait, emphasising recent evidence that supports the effectiveness of biological target therapy.

Background: The 2018 guidelines on the diagnosis of idiopathic pulmonary fibrosis (IPF) conditionally recommend multidisciplinary discussion (MDD) for diagnostic decision-making. However, limited data concerning the diagnostic impact of MDD on interstitial lung diseases (ILDs) are available.

Objectives: The objective of this prospective study was to assess the impact of MDD at a tertiary referral ILD center on diagnostic trajectories, prognosis, and identification of potential treatable traits in ILD management.

Design: This prospective study enrolled all consecutive adult ILD patients referred for MDD to a tertiary academic center in San Antonio, TX, USA from January 2017 to May 2020. The subjects were followed during a 3-year follow-up period after the MDD.

Methods: Patients were stratified into three groups according to the pre-MDD diagnosis: unspecified ILD, IPF, and not IPF, and compared to the re-stratification post-MDD diagnosis into: unclassifiable ILD, IPF, and not IPF. The primary outcome was the percentage change in diagnostic trajectories after the MDD discussion.

Results: A total of 201 ILD patients (61.7% male; mean (DS) age: 67.2 (10.4) years) were included in the study. The total diagnostic trajectory change occurred in 122 (60.7%) patients. The diagnostic trajectories changed in 40 (46.5%) patients in the IPF group and 8 (19.5%) in the non-IPF group (p-value = 0.0003). Patients with pre-MDD unspecified-ILD were classified as not-IPF in 32.4% (n = 24), IPF in 23% (n = 17), and unclassifiable-ILD in 44.6% (n = 33) post-MDD. Considering the post-MDD diagnosis, differences in mortality were detected among the three groups (p = 0.037).

Conclusion: Our results suggest that MDD has a significant impact not only on the diagnostic trajectories (DT) but also on the prognosis of patients with ILDs.

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality in systemic sclerosis, marked by complex immunopathogenic mechanisms and progressive fibrosis. Recent advances have illuminated key cellular players as T cells, macrophages, dendritic cells, and profibrotic mediators such as TGF-β, PDGF, and CTGF, alongside emerging roles for epigenetic reprogramming in sustaining fibroblast activation. This narrative review synthesizes current understanding of immune-fibrotic crosstalk and critically evaluates both established therapies (e.g., mycophenolate mofetil, nintedanib, tocilizumab, and rituximab) and novel targeted approaches. Particular attention is given to emerging immunomodulatory, antifibrotic, and cell-based therapies, including CAR-T and mesenchymal stem cell treatments, as well as the potential of epigenetic modulators repurposed from oncology. By bridging basic science and clinical practice, this review outlines the evolving therapeutic landscape of SSc-ILD and highlights opportunities for future research and personalized intervention.

Background: Noninvasive ventilation (NIV) is frequently employed for acute hypoxemic respiratory failure, yet optimal intubation timing for high-risk NIV failure patients remains uncertain.

Objectives: To investigate mortality outcomes associated with early versus late intubation in high-risk NIV failure patients.

Design: Secondary analysis of a multicenter observational cohort study.

Methods: Patients with high NIV failure risk (updated HACOR score ⩾11 after 1-2 h of NIV) were enrolled. We defined that intubation was needed in these high-risk patients. Intubation occurring within 12 h of NIV initiation was classified as early intubation, while intubation after 12 h was designated as late intubation. Primary outcomes were intensive care unit (ICU) and hospital mortality. In sensitivity analyses, patients who achieved NIV success were categorized into the late-intubation group. Due to baseline imbalances, propensity score matching was performed with covariate adjustment.

Results: Among the study population, 171 patients underwent early intubation and 222 underwent late intubation. Despite greater baseline severity in the early intubation group, ICU mortality (36% vs 58%, p < 0.001) and hospital mortality (38% vs 58%, p < 0.001) were significantly lower compared to the late-intubation group. In sensitivity analyses, 190 patients with NIV success were included in the late-intubation group, further accentuating the severity disparity between groups. After propensity matching (220 patients: 110 per group), most of the baseline characteristics were comparable. The early intubation group had a 100% intubation rate versus 71% in the late-intubation group, with the latter exhibiting higher mortality (ICU: 46% vs 32%, p = 0.052; hospital: 50% vs 34%, p = 0.020).

Conclusion: In patients at high risk for NIV failure, early intubation is associated with reduced mortality.

Background: Acute exacerbations of bronchiectasis (AEB) are frequently caused by bacterial and/or viral infections. Rapid multiplex polymerase chain reaction (PCR) panels in respiratory specimens have significantly advanced microbial evaluation in patients with pneumonia. However, their clinical utility in patients with AEB remains unknown.

Objectives: To investigate the microbial characteristics of AEB using FilmArray Pneumonia plus Panel (FAPP) and explore its clinical impact in a real-world setting.

Design: A cross-sectional study.

Methods: Spontaneous sputum samples of patients hospitalized for AEB were tested using FAPP in addition to standard-of-care testing. Microbial characteristics of AEB and the clinical impact of FAPP were evaluated.

Results: Among 83 patients, FAPP detected ⩾1 bacterial pathogen(s) in 68 samples (81.9%), identifying 101 bacteria, with high abundance (10⁶ to ⩾10⁷ copies/ml) observed in 48 patients (57.8%). The most commonly detected bacteria were Pseudomonas aeruginosa (Pa) (37/83, 44.6%), Staphylococcus aureus (21/83, 25.3%), and Haemophilus influenzae (13/83, 15.7%). Respiratory viruses were identified in 21 patients (25.3), with Influenza A and Respiratory syncytial virus being the most common. Culture detected bacteria in significantly fewer samples (n = 25 [30.1%], p < 0.001). FAPP demonstrated 100% positive percent agreement and negative predictive value for all cultured bacteria, except for Corynebacterium striatum (n = 2), which was not included in the panel. FAPP shortened the time to bacterial results (mean: 10.8 h vs 70.8 h by culture, p < 0.001), and led to antimicrobial changes in 25 patients (30.1%) before the culture results were available. In multivariate analysis, chronic Pa infection (odds ratio (OR) 14.71), underweight status (OR 5.84), and cystic bronchiectasis (OR 5.26) were independent predictors of Pa detection by FAPP.

Conclusion: The sputum multiplex PCR panel (FAPP) enables rapid identification of bacterial and viral pathogens in AEB, supporting early antimicrobial decision-making. Our findings highlight the potential utility of sputum multiplex PCR panels in improving the management of bronchiectasis exacerbations.

Background: Initial regimen selection is critical for pulmonary arterial hypertension (PAH) management and survival. Since 2015, guidelines have recommended upfront combination therapy as the standard of care in newly diagnosed patients.

Objectives: To highlight real-world treatment patterns and predictors of initial combination therapy.

Design: Retrospective cohort analysis of U.S. administrative claims from 01 January 2013 (Optum's de-identified Clinformatics^® Data Mart Database [CDM]) or 01 July/2015 (IQVIA PharMetrics^® Plus) through 30 September 2020.

Methods: Patients initiating PAH medications (phosphodiesterase-5 inhibitors (PDE5i), soluble guanylate cyclase stimulators (SGCS), endothelin receptor antagonists (ERA), or prostacyclin analogues (PCY)) were identified and indexed on the first medication date. All PAH medications identified between index and 365 days post-index were identified and classified as PDE5i/SGCS/ERA monotherapy, PDE5i/SGCS + ERA dual therapy, or PCY-containing regimen. Treatment regimens were analyzed by index year, physician specialty, and among physician specialists associated with a Pulmonary Hypertension Care Center. Multivariable regression was conducted to identify patient characteristics predictive of the first-line regimen.

Results: 1754 (CDM) and 1107 (IQVIA PharMetrics Plus) met selection criteria. The most initiated first-line regimen was PDE5i/SGCS/ERA monotherapy (CDM: 61.2%; IQVIA PharMetrics Plus: 50.9%). The proportion of CDM patients initiating PDE5i/SGCS + ERA dual therapy increased from 13.1% in 2013 to 21.9% in 2019; for IQVIA PharMetrics Plus, PDE5i/SGCS + ERA dual therapy remained consistent (24.4% in 2015, 23.7% in 2019). More pulmonologists prescribed PDE5i/SGCS + ERA dual therapy (CDM: 30.2%; IQVIA PharMetrics Plus: 38.6%) than cardiologists (CDM: 18.3%; IQVIA PharMetrics Plus: 24.3%). PHCC patients were prescribed first-line dual therapy (35.7% vs 26.9%) and PCY-containing regimens (30.3% vs 21.7%) more frequently than non-PHCC patients, respectively. Females (vs males) were more likely to receive dual therapy and PCY-containing regimens; Black (vs White) patients were less likely to receive PCY-containing regimens.

Conclusion: Additional research is needed to better understand barriers to optimal initial treatment regimen selection and to quantify the impacts of therapeutic delay.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder caused by defects in lysosome-related organelles (LROs). Eleven HPS subtypes have been identified, each associated with mutations in distinct genes, with HPS-4 being among the rarer forms. Here, we present a 38-year-old Chinese woman with oculocutaneous albinism (OCA), bleeding tendency, and progressive pulmonary fibrosis, ultimately diagnosed with HPS through platelet transmission electron microscopy. The patient received nintedanib, an antifibrotic agent, which appeared to stabilize pulmonary function for approximately 18 months. Genetic testing revealed a novel homozygous splice site variant in HPS4 (NM_022081.6 c.1713+1delG), predicted to result in splice disruption and nonsense-mediated mRNA decay. Based on in silico analysis, the variant was considered pathogenic. To contextualize this case, we reviewed all published HPS4-related cases and identified 51 reported patients carrying 37 unique mutations, including 16 nonsense, 8 frameshift, 7 splice-site, 5 missense, and 1 gross insertion variant. Our findings broaden the mutational spectrum of HPS4 and support the utility of nintedanib in managing HPS-associated interstitial lung disease. It also underscores the potential for pharmacologic intervention to alter the disease trajectory in HPS, particularly in resource-limited settings where lung transplantation is not widely accessible.

Background: Cystic fibrosis (CF) outcomes are influenced by a myriad of genetic, microbiological, and environmental factors, as well as socioeconomic constraints. Studies have shown that low socioeconomic status is associated with a higher risk of death, lower body weight and height, worsened pulmonary function, and increased pulmonary exacerbation in children with CF. Screening for social risk factors (SRFs) is one possible approach to help mitigate unmet social needs in people with CF (PwCF).

Objectives: Does a positive screening response for SRF correlate with health outcomes in PwCF?

Design: This is a single-center, retrospective analysis of outcomes in adult PwCF. The study includes data from 2021 to 2022.

Methods: A social needs screening tool was administered to identify SRF in PwCF in eight domains: housing, food, transportation, utilities, healthcare cost, medication cost, income/employment, and education. A total of 121 PwCF were included in the analysis. Linear mixed-effects models, Poisson regression, and mixed-effects Cox regression were used for analyses of multivariate models.

Results: When adjusted for multiple covariables, PwCF who screened positive for SRF had similar lung function and BMI as PwCF who reported no SRF and an increased CF exacerbation rates per person/per year when compared to their peers, 1.700 (1.275, 2.266) versus 0.829 (0.608, 1.130) (p = 0.006). Adjusted models showed that the median time to exacerbation was significantly lower in PwCF who screened positive for SRF (210 days vs 389 days).

Conclusion: PwCF who responded positively for SRF experienced an increased rate of CF exacerbation, and this finding remained significant when adjusted for multiple variables, including new CF medications. Medication cost, income/employment concerns, and food insecurity emerged as the most significant predictors of exacerbation rates and time to the next exacerbation. Further studies are needed to evaluate effective interventions and resources to mitigate SRF.