Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
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PloS one
Inhaled nitric oxide in fibrotic and advanced interstitial lung disease: A systematic review and meta-analysis of randomized controlled trials.
PURPOSE: Interstitial lung disease (ILD) can lead to pulmonary hypertension (PH), contributing to reduced exercise capacity in patients with ILD. Inhaled nitric oxide (iNO) reduces pulmonary artery pressure and pulmonary vascular resistance and may improve exercise capacity in this population; however, the available evidence remains limited. Therefore, we conducted a systematic review and meta-analysis to compare the efficacy and safety of iNO versus placebo in patients with ILD. METHODS: We systematically searched PubMed, Embase, Cochrane databases, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing iNO with placebo in patients with ILD. The primary endpoint was 6-minute walk distance (6MWD). Secondary endpoint was moderate-to-vigorous physical activity (MVPA). Safety endpoint was any adverse events. Continuous endpoints were reported using mean differences (MDs) or standardized mean differences (SMDs), and binary endpoints were reported using risk ratios (RRs), all with 95% confidence intervals (CIs). RESULTS: Four RCTs, including one crossover trial, enrolling 274 patients were analyzed. Of these, 172 received iNO. The median follow-up period was 12 weeks. In the pooled analyses, iNO likely results in little to no difference in 6MWD compared with placebo (MD 1.83m; 95% CI -12.98 to 16.64; p = 0.81), and may result in little to no difference in any adverse events (RR 1.12; 95% CI 0.97 to 1.30; p = 0.12) and MVPA (SMD 0.32; 95% CI -0.93 to 1.56; p = 0.39). CONCLUSION: INO did not demonstrate improvements in 6MWD or MVPA. These findings do not support routine use of iNO in this population.
23 June 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
The burden of autoimmune pulmonary alveolar proteinosis: a systematic review
BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is characterised by abnormal alveolar surfactant accumulation and reduced pulmonary gas transfer. Disease severity and progression depend on pulmonary surfactant accumulation, the rate of which varies widely among patients. Currently, whole-lung lavage (WLL) is the most widely accepted therapy. This review addresses the burden of aPAP on patients, caregivers and society. METHODS: MEDLINE and Embase databases were systematically searched for reports on the manifestations, treatment burden, caregiver impact and healthcare costs of aPAP published after 2000. RESULTS: Out of 1023 publications identified, 50 reported relevant data (for 2855 aPAP patients), including 43 observational studies and seven phase 2/3 trials. Commonly reported symptoms included dyspnoea, cough and sputum production. Clinical manifestations included progressive hypoxaemia, reduced exercise capacity, reduced quality of life, and an increased rate of serious infections. Low prevalence and nonspecific signs and symptoms contributed to delayed diagnosis of aPAP, frequent misdiagnoses, use of multiple tests with nondiagnostic results, and therapies that were inappropriate or exacerbated the disease. WLL was the most frequently administered therapy, and many patients required repeat procedures. Medical care costs were higher for PAP patients than for non-PAP control patients. CONCLUSIONS: The results highlight the multifactorial and substantial burden of aPAP on patients. Significant unmet needs remain, particularly in achieving timely and accurate diagnosis and in providing effective, well-tolerated therapies that address the underlying pathophysiology of the disease.
10 Apr 2026
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