Therapeutic Advances in Respiratory Disease最新文献

Background: Non-idiopathic pulmonary fibrosis interstitial lung diseases (non-IPF ILDs) comprise a broad spectrum of pathologies with varying degrees of inflammation and fibrosis. Progressive fibrosing ILD is associated with significant mortality and limited treatment options. Standard regimens employ multimodal immunosuppression, most commonly prolonged courses of oral corticosteroids (OCS), that are associated with a high risk of adverse effects and limited proven efficacy.

Objectives: This study investigates the safety, tolerability, and effectiveness of monthly intravenous pulse methylprednisolone (PMP) for the treatment of patients with progressive non-IPF ILD.

Design: Retrospective single-center cohort study of patients at an academic tertiary referral center for ILD between October 2019 and September 2022.

Methods: All non-IPF ILD patients who received intravenous PMP (1000 mg daily for three consecutive days/month) between October 2019 and September 2022 were included. The decision to treat was based on a multidisciplinary consensus diagnosis following ATS/ERS/JRS/ALAT guidelines and confirmed or at high risk for ILD progression. Treatment continuation was contingent upon pulmonary function test (PFT) improvement (assessed approximately every 3 months), tolerable adverse events, and shared decision making with patients. Effectiveness was measured by a change in forced vital capacity (FVC) and diffusion limit of carbon monoxide (DLCO), with improvement being defined as an absolute increase in either FVC >5% or DLCO >10% from baseline.

Results: Thirty-three patients received PMP at our center. One patient died of an acute exacerbation of ILD. Of the 32 patients included for analysis, 17 (53%) exhibited improved lung function with PMP between PFTs, which was maintained for a median follow-up of 209 days. The regimen was generally well-tolerated, with the most common adverse effects being insomnia and restlessness on infusion days. Advanced disease, indicated by lower FVC, traction bronchiectasis, and oxygen dependence, predicted poor response.

Conclusions: PMP may offer a safer, better-tolerated, and more effective treatment for progressive non-IPF ILD than prolonged OCS. Notably, a third of fibrotic hypersensitivity pneumonitis patients showed improved FVC after 3 months of PMP, defying expectations of steroid non-responsiveness. However, further well-designed controlled prospective clinical trials are needed to confirm our findings and establish long-term safety.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease marked by airway inflammation and obstruction. Ensifentrine is a novel inhaled PDE3 and PDE4 inhibitor with both bronchodilator and anti-inflammatory effects.

Objectives: Comprehensively review the available evidence on ensifentrine and its potential role in COPD management.

Design: Systematic review and meta-analysis with trial sequential analysis of randomized clinical trials.

Data sources and methods: We systematically searched PubMed, Scopus, ScienceDirect, Cochrane Library, and Medline for clinical trials published between 2018 and August 2024 that evaluated the safety and efficacy of ensifentrine in patients with COPD. We assessed study quality using the RoB 2 tool and conducted the meta-analysis with the "meta" package in R (version 4.3.2), using the mean difference with a 95% confidence interval to evaluate changes in outcomes.

Results: Five studies met the predefined inclusion criteria with 2519 participants. At week 12, the pooled analysis indicated that forced expiratory volume in 1 s (FEV₁) and trough FEV₁ were significantly increased in the ensifentrine group (mean difference (MD): 91.32; 95% CI: 69.63 to 113.01) and (MD: 40.90; 95% CI: 19.65 to 62.15), respectively. At week 24, the pooled analysis indicated that the evaluating respiratory symptoms total score was significantly decreased in the ensifentrine group (MD: -0.81; 95% CI: -1.36 to -0.27), transition dyspnea index score was significantly increased in the ensifentrine group (MD: 0.96; 95% CI: 0.62 to 1.29), no significant difference was observed in rescue medication use (MD: -0.30; 95% CI: -0.60 to 0.00), and no significant difference was observed in St. George's Respiratory Questionnaire total score (MD: -1.46; 95% CI: -3.22 to 0.30). Based on subgroup analysis, higher doses were associated with more favorable results.

Conclusion: In conclusion, owing to its dual effects, ensifentrine has a significant impact on improving pulmonary function and quality of life with minimal side effects. Promising results are expected if implied by synergizing with other drugs, however, more studies are needed to study the long-term effect on disease progression.

Trial registration: The study protocol was published via PROSPERO: International Prospective Register of Systematic Reviews (#CRD42024570799).

Background: Patients with chronic obstructive pulmonary disease (COPD) who survive sepsis remain immunocompromised and are at increased risk of subsequent viral infections, including influenza and respiratory syncytial virus (RSV).

Objective: This study aimed to address the 1-year risk of viral infections after sepsis in patients with COPD through the use of a federated database, TriNetX.

Design: A propensity score-matched (PSM) retrospective cohort study.

Methods: We used data of 903,683 COPD patients and identified 113,589 who experienced sepsis. The risk of distinct viral infections, including herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), RSV and influenza, within 1 year post-sepsis was analyzed, with the employment of PSM to minimize confounding. The effect of vaccination was also assessed to determine its protective efficacy.

Results: A total of 98,883 COPD patients with sepsis and 1:1 matched COPD without sepsis were eligible for analyses. COPD patients with sepsis had consistently higher risk for viral infections within 1 year after the sepsis compared with COPD patients without sepsis. The hazard ratios (HRs) were as follows: HSV 1.936 (95% CI: 1.775-2.112), VZV 3.050 (2.489-3.737), CMV 2.101 (1.832-2.410), RSV 3.297 (3.158-3.443), and Influenza 3.197 (3.071-3.328). Sensitivity analysis demonstrated the consistently elevated risks across sepsis with varying severities. We further explored the protective effect of vaccinations among patients with COPD and found the significant protective effect of VZV glycoprotein E (HR 0.724, 95% CI: 0.595-0.882), RSV prefusion F protein-based vaccine (HR 0.676, 95% CI: 0.563-0.812) and influenza vaccine (HR 0.709, 95% CI: 0.649-0.776).

Conclusion: COPD patients recovering from sepsis remain at increased risk of viral infections, highlighting the importance of targeted preventive strategies, including vaccination.

Bronchiectasis is a chronic disease characterised by permanent dilatation of the bronchi, which leads to the development of chronic airways inflammation and clinical sequelae such as cough, sputum production, and recurrent infections. The clinical syndrome is typically associated with reduced quality of life and greater healthcare utilisation. Prevalence data for bronchiectasis remain limited in many parts of the world, and the available studies report heterogeneous results with overall prevalence rates reported between 52.5 and 1248.7 per 100,000. Over the past 25 years, the prevalence has steadily increased, likely due to increased awareness and improved diagnostic techniques. Bronchiectasis is most prevalent in older age groups, and it is more commonly found in females. It is associated with multiple comorbidities, including chronic obstructive pulmonary disease, chronic rhinosinusitis, asthma, hypertension, cardiovascular disease and symptoms of anxiety and depression. First Nations populations experience a disproportionately high burden of disease. Bronchiectasis is more common in First Nations patients living in rural or remote communities and in those with socioeconomic disadvantage. It is associated with a lower age at diagnosis than the general population, more frequently associated with higher smoking rates and childhood respiratory tract infections, including a higher prevalence of human T-cell lymphotropic virus 1 in Australian Indigenous populations. These factors contribute to more extensive bronchiectasis on imaging, higher exacerbation rates and greater mortality. The introduction of lung cancer screening programmes is likely to increase the incidental detection of asymptomatic bronchiectasis patients, whose consequences are likely to burden healthcare systems. It would be beneficial to determine risk factors for those likely to develop clinically significant disease and, therefore, to prioritise referrals for further assessment.

Background: Joubert syndrome (JS) is an autosomal recessive disorder with a distinctive mid-hindbrain malformation known as the "molar tooth sign" which involves the breathing control center and its connections with other structures. Literature has reported significant respiratory abnormalities which included hyperpnea interspersed with apneic episodes during wakefulness. Larger-scale studies looking at polysomnographic findings or subjective reports of sleep problems in this population have not yet been published.

Objectives: The primary objectives were (1) compare a large group of children with JS and their unaffected siblings for caregiver-reported sleep difficulties. Secondary objectives were (1) present new polysomnography (PSG) data on our JS cohort; (2) review sleep disordered breathing (SDB) in other rare congenital hindbrain anatomic abnormalities.

Design: We conducted a cross-sectional study on a cohort of 109 families affected by JS.

Methods: Pediatric Sleep Questionnaire (PSQ) and the Children's Sleep Habits Questionnaire (CSHQ) along with general medical health information focused on respiratory and sleep problems were mailed to all patients and families. Caregivers were asked to complete the survey for both children with JS and unaffected siblings, if any. Baseline diagnostic PSG was retrospectively reviewed for those with available studies, and the sleep parameters were compared to a referent cohort.

Results: Study participants with JS were older than their unaffected siblings (p = 0.02). Genetic mutations were available for 41 out of 118 individuals, with the most common mutation being MKS3 (31.4%). Patients with JS had higher scores in the PSQ compared to their unaffected siblings (p < 0.001). PSG data showed severe SDB with apnea-hypopnea index (AHI) of 23 ± 15 events/h in patients with JS. Events were primarily obstructive (obstructive AHI 18 ± 15 events/h vs central AHI 4 ± 4 events/h). Abnormal sleep architecture with increased arousal indices, decreased efficiency, and more time awake and in light sleep or wakefulness when compared to the referent data.

Conclusion: SDB is common and severe in patients with JS, and the significantly greater obstructive component reported in this cohort makes it necessary to perform complete PSG studies to address or prevent clinical manifestations in this at-risk population. PSQ could represent a viable method to screen for SDB in JS.

Background: The role of the gut-lung axis in respiratory disease is increasingly recognised. Much emphasis has been placed on gastro-oesophageal reflux disease; however, oesophageal dysmotility may also play a significant role. Azithromycin, a known prokinetic, has been shown to be of major benefit in a number of respiratory diseases, but the relationship between oesophageal function and the lung has not been examined.

Objectives: We assessed the feasibility of performing continuous cough monitoring and repeated high-resolution oesophageal manometry (HROM) in patients with chronic respiratory disease.

Design: We conducted an open-label, single-arm, feasibility trial.

Methods: Azithromycin 250 mg once daily was given to patients with chronic respiratory disease who reported a chronic cough. All participants were monitored continually for at least 1 week prior to and 4 weeks after azithromycin with the Hyfe Cough Tracker. Participants also had HROM performed at two time-points, immediately before and 4 weeks after initiation of azithromycin. Feasibility outcomes pertaining to recruitment, data quality, and acceptability of trial processes were assessed. Exploratory outcome data for metrics of oesophageal function were also analysed.

Results: A total of 30 participants (57% female, mean age 65.2 (SD = 11.3)) were recruited over a 10-month period, giving a recruitment rate of three patients per month in a single centre. A total of 87% (n = 26) of participants completed all three study visits. All pre-specified data quality outcomes met their 'green' traffic light stop-go criteria. HROM demonstrated that the majority (52%) of participants had abnormal oesophageal function, as defined by the Chicago Classification, at baseline. Changes in oesophageal function were not significantly associated with changes in objective or subjective cough measures, except for a weakly negative correlation with the Hull Airway Reflux Questionnaire score.

Conclusion: A large-scale trial examining the effect of azithromycin on the relationship between oesophageal function and cough in respiratory disease is feasible and acceptable to patients.

Trial registration: This trial was prospectively registered ClinicalTrials.gov ID: NCT05469555.

Background: Pulmonary function tests offer crucial parameters for evaluating lung health and predicting clinical outcomes. Hyperlipidemia, a prevalent metabolic disorder, has been linked to declining pulmonary function. Statins are an essential therapy for lowering lipid levels in hyperlipidemia.

Objectives: This study aims to investigate the therapeutic potential of statins in mitigating the decline in pulmonary function.

Design: This is a retrospective cohort study.

Methods: Out of 8286 patients who underwent spirometry testing from January 2018 to December 2020, 492 patients were included in the final analysis. The relationship between statin usage, dosage, along with other biometric indices and spirometry parameters were evaluated. Multivariate logistic regression analyses were employed to assess the association between statin use and the decline in pulmonary function.

Results: In patients with persistent hyperlipidemia, the use of statins was associated with a higher predicted percentage of forced expiratory volume in 1 second (FEV1) compared to non-users (84.0% vs 78.0%, p = 0.015). Logistic regression models further revealed that statin use independently prevented FEV1 decline, irrespective of dosage (adjusted OR 0.036, 95% CI: 0.002-0.618 in lower statins dose group and adjusted OR 0.170, 95% CI: 0.019-1.552 in higher statins dose group).

Conclusion: The findings suggested that statin usage, regardless of dosage, independently mitigated the decline in pulmonary function among patients with persistent hyperlipidemia. Early initiation of statin therapy may hold promise for individuals experiencing hyperlipidemia and declining pulmonary function.

Background: Malignant pleural effusion (MPE) affects approximately 150,000 patients in the United States each year and usually signifies advanced-stage cancer. The optimal treatment remains a challenge but indwelling pleural catheters (IPC) offer several advantages and may help achieve spontaneous pleurodesis (SP) in some patients.

Objectives: We aim to investigate the predictors of SP among patients with MPE, particularly in a resource-limited community-based safety net hospital.

Design: This is a retrospective cohort study done at a community-based safety net hospital.

Methods: Adults diagnosed with or suspected of having MPE between January 2015 and December 2023 who underwent IPC placement were included. Data was collected retrospectively from December 2023 to June 2024. Data encompassed demographics, imaging, post-procedural complications, pleural fluid analysis, oncology treatment history, and utilization of medical thoracoscopy without chemical pleurodesis (MTWCP) for diagnosis.

Results: A total of 173 patients underwent IPC insertion. Most of our patients were women (64.2%), and Latin American (65.9%), with a mean age of 55.3 years. The most common type of primary cancer was breast (28.9%) followed by lung (23.1%) and lymphoma (6.9%). Pleural fluid characteristics such as glucose, eosinophils, Lactate Dehydrogenase (LDH), and protein concentration were not significantly associated with SP. Most patients had low Eastern Cooperative Oncology Group scores of 0-2 (64.6%) and low LENT (Lactate Dehydrogenase (L), Eastern Cooperative Oncology Group (E) Performance Score, Neutrophil-to-Lymphocyte Ratio (N), and Tumor type (T) score) scores of 0-4 (59%). Lower scores (better functional status) were significantly associated with SP. Post-IPC chemotherapy and/or radiotherapy and immunotherapy were significantly associated with SP, adjusted odds ratio (OR) 7.295 (95% CI: 3.05-17.4, p = 0.001) and adjusted OR 6.261 (95% CI: 2.73-14.36, p = 0.001) respectively. MTWCP was also a predictor of SP with an adjusted OR of 4.031 (95% CI: 1.452-11.19, p = 0.007).

Conclusion: Our study is the first to assess predictors of SP in a resource-limited safety net hospital representing under-represented and underserved patients. We identify several factors associated with higher rates of SP such as higher functional status, MTWCP, chemotherapy, immunotherapy, and radiation post-IPC placement. The study findings can help clinicians consider IPC placement and guide them regarding the duration and possible complications of IPC. MTWCP appears to improve the success of SP. Further studies are needed to assess these findings further.

Background: Prevention of lung attacks (LAs)/exacerbation is an important treatment goal in both asthma and chronic obstructive pulmonary disease (COPD). However, LAs are often not registered as such in medical records.

Objectives: Development and evaluation of CodeX Asthma and COPD.

Design: An electronic medical record-based algorithm to identify LAs in Dutch primary care patients with asthma or COPD was developed. The algorithms were evaluated in nine general practices in the Netherlands.

Results: A total of 479 LAs (in 1164 patients) were identified with CodeX Asthma in the past year, of which only 16% were registered. CodeX COPD identified 321 LAs (in 242 patients) in the past 3 years, of which two were registered.

Conclusion: CodeX algorithms are capable of identifying unrecorded LAs and high-risk/uncontrolled patients in an easy way. This offers primary care providers a simple solution to easily identify and closely manage high-risk patients with asthma or COPD by identifying LAs' frequency and potential under- or overtreatment.