Therapeutic Advances in Respiratory Disease最新文献

Background: Nintedanib and pirfenidone are preferred pharmacological therapies for patients with idiopathic pulmonary fibrosis (IPF). However, evidence favoring antifibrotic therapy in patients with non-IPF fibrosing interstitial lung diseases (ILD) is limited.

Objective: To investigate the effects of antifibrotic therapy on disease progression, all-cause mortality, and acute exacerbation (AE) risk in patients with non-IPF fibrosing ILDs.

Design: Meta-analysis.

Data sources and methods: Electronic databases were searched for articles published before 28 February 2023. Studies that evaluated the efficacy of antifibrotic agents in patients with fibrosing ILDs were selected. The primary outcome was the disease progression risk, and the secondary outcomes included all-cause mortality and AE risk. The GRADE criteria were used for the certainty of evidence assessment.

Results: Nine studies with 1990 participants were included. Antifibrotic therapy reduced the rate of patients with disease progression (five trials with 1741 subjects; relative risk (RR), 0.56; 95% CI, 0.42-0.75; p < 0.0001; I² = 0; high-certainty evidence). Antifibrotic therapy did not significantly decrease all-cause mortality (nine trials with 1990 subjects; RR, 0.76; 95% CI, 0.55-1.03; p = 0.08; I² = 0; low-certainty evidence). However, in patients with progressive fibrosing ILDs (PF-ILD), antifibrotic therapy decreased all-cause mortality (four trials with 1100 subjects; RR, 0.69; 95% CI, 0.48-0.98; p = 0.04; I² = 0; low-certainty evidence).

Conclusion: Our study supports the use of antifibrotic agents in patients with PF-ILDs, which could slow disease progression and decrease all-cause mortality.

Trial registration: This study protocol was registered with PROSPERO (registration number: CRD42023411272).

Background: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation.

Objectives: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm.

Design: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated.

Methods: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery.

Results: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 (p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy (p = 0.010).

Conclusion: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.

Background: The latest guidelines discourage the use of long-acting beta₂-agonists/inhaled corticosteroids (LABA/ICS) for chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the optimal subsequent treatment after discontinuing LABA/ICS.

Objectives: To compare the effectiveness and safety of switching from LABA/ICS to triple therapy (LABA/long-acting muscarinic antagonists (LAMA)/ICS) or to dual bronchodilators (LABA/LAMA) in COPD patients.

Design: This was a new-user, active-comparator, and propensity score-matched cohort study analyzing the Taiwanese nationwide healthcare insurance claims.

Methods: We recruited COPD patients switching from LABA/ICS to triple therapy or to dual bronchodilators from 2015 to 2019. The primary effectiveness outcome was the annual rate of exacerbations, and safety outcomes included severe pneumonia and all-cause mortality. Stratification by prior exacerbations was conducted.

Results: After matching, each group comprised 1892 patients, 55% of whom experienced no exacerbations in the prior year. Treatment with LABA/LAMA/ICS versus LABA/LAMA showed comparable annual rate of moderate-to-severe exacerbations (incidence rate ratio, 1.04; 95% confidence interval (CI), 0.91-1.19). However, switching to LABA/LAMA/ICS was associated with increased risks of severe pneumonia (hazard ratio (HR), 1.65; 95% CI, 1.30-2.09) and all-cause death (HR, 1.39; 95% CI, 1.09-1.78). In patients with⩾2 prior exacerbations, LABA/LAMA/ICS versus LABA/LAMA was related to a 21% reduced rate of exacerbations but with a twofold increased pneumonia risk and a 49% elevated risk of all-cause mortality.

Conclusion: Switching from LABA/ICS to triple therapy versus dual bronchodilators in COPD patients was associated with similar rates of annual exacerbations but was related to elevated risks of severe pneumonia and all-cause mortality. Among frequent exacerbators, triple therapy was associated with lower rates of exacerbation but was accompanied by increased risks of pneumonia and mortality compared to LABA/LAMA. Careful consideration of the examined safety events is necessary when switching from LABA/ICS to triple therapy in COPD management.

Background: High-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) are important respiratory support strategies for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the results are conflicting for the risk of intubation with HFNC as compared to COT.

Objectives: We systematically synthesized the outcomes of HFNC relative to COT in COVID-19 patients with AHRF and evaluated these outcomes in relevant subpopulations.

Design: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources and methods: We searched PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, medRxiv, BioRxiv, and the Cochrane Central Register of Controlled Trials for randomized controlled trials and observational studies that compared the efficacy of HFNC with COT in patients with COVID-19-related AHRF. Primary outcomes were intubation rate and mortality rate. Secondary outcomes were the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO₂/FiO₂), respiratory rate, hospital length of stay, intensive care unit (ICU) length of stay, and days free from invasive mechanical ventilation.

Results: In total, 20 studies with 5732 patients were included. We found a decreased risk of requiring intubation in HFNC compared to COT [odds ratio (OR) = 0.61, 95% confidence interval (CI): 0.46-0.82, p = 0.0009, I² = 75%]. Similarly, we found HFNC was associated with lower risk of intubation rate compared to COT in the subgroup of patients with baseline PaO₂/FiO₂ < 200 mmHg (OR = 0.69, 95% CI: 0.55-0.86, p = 0.0007, I² = 45%), and who were in ICU settings at enrollment (OR = 0.57, 95% CI: 0.38-0.85, p = 0.005, I² = 80%). HFNC was associated with an improvement of PaO₂/FiO₂ and respiratory rate compared to COT. The use of HFNC compared to COT did not reduce the mortality rate, days free from invasive mechanical ventilation, hospital length of stay, or ICU length of stay.

Conclusion: Compared to COT, HFNC may decrease the need for tracheal intubation in patients with COVID-19-related AHRF, particularly among patients with baseline PaO₂/FiO₂ < 200 mmHg and those in ICU settings.

Trial registration: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022339072).

Background: Radial probe endobronchial ultrasound (radial EBUS) is widely used to diagnose pulmonary lesions; however, the diagnostic value of radial EBUS-guided transbronchial biopsy (TBB) varies, and its complications (especially the risk of bleeding) are not properly understood.

Objectives: In this study, we evaluated the diagnostic performance and rate of complication of this procedure, and investigated the risk factors associated with the procedure-related bleeding events.

Design: A retrospective cohort study.

Methods: This was a retrospective study that included consecutive patients who underwent radial EBUS-guided TBB. Radial EBUS was performed under moderate sedation in inpatients or outpatients. The severity of bleeding was graded using the standardized definitions of bleeding.

Results: Of 133 patients (median age, 69 years; men 57.1%) included, 41 were outpatients (30.8%). The diagnostic accuracy, sensitivity, and specificity for malignancy were 76.1% (89/117), 71.1% (69/97), and 100% (20/20), respectively. The diagnostic accuracy ranged from 66.9% to 79.0%, depending on the classification of undiagnosed cases as either false negatives or true negatives. Twenty-seven patients (20.3%) developed complications (pneumothorax, 3; pneumonia, 5; complicated pleural effusion, 2; bleeding event grade 2 or higher, 21). Of the 41 outpatients, two developed complications (pneumothorax without intervention, 1; grade 2 bleeding event, 1). Of the 21 patients (15.8%) with procedure-related bleeding events, 18 had grade 2, and three had grade 3 bleeding complications. In multivariate analysis, a large size of ⩾30 mm (adjusted odds ratio (OR), 5.09; p = 0.03) and central lesion (adjusted OR, 3.67; p = 0.03) were significantly associated with the risk of grade 2 or higher bleeding events.

Conclusion: Our results suggest that radial EBUS-guided TBB is an accurate and safe method for diagnosing pulmonary lesions. Clinically significant procedure-related bleeding was rare. The central location and larger size (⩾30 mm) of pulmonary lesions were risk factors for grade 2 or higher bleeding events.

Background: Perioperative heparin-free anticoagulation extracorporeal membrane oxygenation (ECMO) for lung transplantation is rarely reported.

Objective: To evaluate the impact of a heparin-free strategy on bleeding and thrombotic events, blood transfusion, and coagulation function during the early perioperative period and on prognosis, and to observe its effect on different ECMO types.

Design: A retrospective cohort study.

Methods: Data were collected from 324 lung transplantation patients undergoing early perioperative heparin-free ECMO between August 2017 and July 2022. Clinical data including perioperative bleeding and thrombotic events, blood product transfusion, coagulation indicators and 1-year survival were analysed.

Results: Patients were divided in venovenous (VV; n = 251), venoarterial (VA; n = 40) and venovenous-arterial (VV-A; n = 33) groups. The VV group had the lowest intraoperative bleeding and thoracic drainage within 24 h postoperatively. Vein thrombosis occurred in 30.2% of patients within 10 days postoperatively or 1 week after ECMO withdrawal, and no significant difference was found among the three groups. Double lung transplantation, increased intraoperative bleeding, and increased postoperative drainage were associated with vein thrombosis. Except for acute myocardial infarction in one patient, no other serious thrombotic events occurred. The VV-ECMO group had the lowest demand for blood transfusion. The highest prothrombin time and the lowest fibrinogen levels were observed in the VA group during ECMO run, while the highest platelet counts were found in the VV group. Both intraoperative bleeding and thoracic drainage within 24 h postoperatively were independent predictors for 1-year survival, and no thrombosis-related deaths occurred.

Conclusion: Short-term heparin-free anticoagulation, particularly VV-ECMO, did not result in serious thrombotic events or thrombosis-related deaths, indicating that it is a safe and feasible strategy for perioperative ECMO in lung transplantation.

Background: It remains unclear whether erythrocyte sedimentation rate (ESR) accurately predicts prognosis during treatment and how ESR changes.

Objectives: We aimed to assess the predictive values of ESR as a prognostic factor of Mycobacterium avium complex pulmonary disease (MAC-PD) while on anti-mycobacterial treatment and its changes according to the treatment responses.

Design: This study is a retrospective cohort study.

Methods: This study included patients aged 18 years or older who initiated anti-mycobacterial treatment for MAC-PD at Seoul National University Hospital between January 1, 2009 and March 31, 2022. ESR should be measured at least twice, with a minimum interval of 3 months, during the initial 12 months from the commencement of antibiotic treatment. A mixed linear regression and Cox proportional-hazards models were used to analyze repeated ESR data and the association with patient survival.

Results: Of a total of 825 patients who initiated antibiotic treatment for MAC-PD, 369 patients were included in the analysis. Increased levels of ESR during the treatment process were associated with a higher risk of mortality (adjusted hazard ratio 1.03; 95% confidence interval, 1.02-1.03) after adjusting age, sex, comorbidities, presence of cavity, acid-fast bacilli smear positivity, and culture conversion at 12 months. During the treatment, ESR at 12 months of treatment significantly decreased compared to baseline ESR in both the culture-converted and not-converted groups, which was categorized based on whether the culture conversion was achieved within the 12 months after treatment initiation.

Conclusion: ESR predicted mortality during treatment and decreased over time, regardless of treatment outcomes. Our results underscore the importance of administering anti-mycobacterial treatment even in patients who did not achieve a microbiological cure.

Robotic-assisted bronchoscopy (RAB) was recently added to the armamentarium of tools used in sampling peripheral lung nodules. Protocols and guidelines have since been published advocating use of large oral artificial airways, use of confirmatory technologies such as radial endobronchial ultrasound (R-EBUS), and preferably limiting sampling to pulmonary parenchymal lesions. We present three clinical cases where RAB was used unconventionally to sample pulmonary nodules in unusual locations and in patients with challenging airway anatomy. In case 1, we introduced the ion catheter through a nasal airway in a patient with trismus. In case 2, we established a diagnosis by sampling a station 5 lymph node, and in case 3, we sampled a lesion located behind an airway stump from previous thoracic surgery. All three patients would have presented significant challenges for alternative biopsy modalities such as CT-guided needle biopsy or video-assisted thoracic surgery.

Background: Real-world data on the use, healthcare resource utilization (HCRU), and associated costs of antifibrotic therapies in patients with idiopathic pulmonary fibrosis (IPF) are limited.

Objectives: To assess the prevalence of antifibrotic treatment, characteristics of patients receiving treatment, discontinuation rates, and HCRU and costs associated with treatment.

Design: This retrospective study analyzed de-identified longitudinal and cross-sectional data, respectively, from two US claims databases: Optum's de-identified Clinformatics^® Data Mart Database (CDM; commercial claims, Medicare Advantage) and the Veterans Health Administration (VHA) database. The study periods were October 1, 2013-March 31, 2019 and October 1, 2014-September 30, 2019, respectively. Eligible individuals were adults with ⩾1 diagnosis claim for IPF.

Methods: Antifibrotic prevalence, patient demographics, treatment discontinuation rates, and HCRU and costs were determined separately for each cohort and described using summary statistics. Bivariate comparisons were analyzed using Chi-square and Student's t-tests for categorical and continuous variables, respectively.

Results: Overall, 4223 and 4459 eligible patients were identified in the CDM and VHA databases, respectively. Prevalence of antifibrotic uptake was 9.2% and 29.1% and the rate of index treatment discontinuation was 47% and 66% during follow-up in the CDM and VHA cohorts, respectively. Antifibrotic-treated patients were significantly younger (p < 0.0001) with lower mean Charlson Comorbidity Index scores at baseline versus untreated patients in both cohorts. In the CDM cohort, the number of outpatient and pharmacy visits was significantly higher in treated versus untreated patients during follow-up (both p < 0.0001). A similar trend was observed for the VHA cohort. Total follow-up costs in both cohorts were significantly higher in treated versus untreated patients due to higher pharmacy costs (CDM; p < 0.0001) or higher outpatient and pharmacy costs (VHA; p < 0.0001).

Conclusion: The low prevalence of antifibrotic usage in both cohorts, together with the high rate of antifibrotic discontinuation, and increased HCRU and costs in treated versus untreated patients, support the need for novel treatment options for IPF.

Trial registration: Not applicable.

Nanoparticles have attracted extensive attention due to their high degree of cell targeting, biocompatibility, controllable biological activity, and outstanding pharmacokinetics. Changing the size, morphology, and surface chemical groups of nanoparticles can increase the biological distribution of agents to achieve precise tissue targeting and optimize therapeutic effects. Examples of their use include nanoparticles designed for increasing antigen-specific immune responses, developing vaccines, and treating inflammatory diseases. Nanoparticles show the potential to become a new generation of therapeutic agents for regulating inflammation. Recently, many nanomaterials with targeted properties have been developed to treat acute lung injury/acute respiratory distress syndrome (ALI/ARDS). In this review, we provide a brief explanation of the pathological mechanism underlying ALI/ARDS and a systematic overview of the latest technology and research progress in nanomedicine treatments of ALI, including improved nanocarriers, nanozymes, and nanovaccines for the targeted treatment of lung injury. Ultimately, these nanomedicines will be used for the clinical treatment of ALI/ARDS.