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 →Signal transduction and targeted therapy
Acute hemodynamic effects of TPN171H in pulmonary arterial hypertension: a randomized, controlled, phase 2a trial
Pulmonary arterial hypertension (PAH) has a poor prognosis despite available treatments. TPN171H, structurally modified from traditional Chinese medicine (Epimedium), was reported to have a high affinity for phosphodiesterase type 5 and exhibited anti-inflammatory and vasodilatory effects in preclinical studies. This phase 2a randomized trial (NCT04483115) evaluated the hemodynamic effects and safety of TPN171H in PAH. Sixty patients with PAH were randomly assigned to receive placebo, TPN171H (2.5, 5, or 10 mg) or tadalafil (20 or 40 mg) and evaluated for hemodynamic changes for 24 h. The primary endpoint was the maximum change (%) in pulmonary vascular resistance (PVR) from baseline. The key secondary endpoint was the change (%) in PVR to systemic vascular resistance (SVR) ratio at each observation point from baseline. Compared to the placebo group, the least square mean differences in the maximum change in PVR were -16.8% (95% CI, -29.1 to -4.5, p = 0.008) in TPN171H 5 mg, -15.4% (95% CI, -28.2 to -2.7, p = 0.019) in tadalafil 20 mg, and -13.3% (95% CI, -25.6 to -0.9, p = 0.036) in the tadalafil 40 mg group. Moreover, TPN171H 5 mg, but none of the tadalafil doses, showed a significant reduction in PVR/SVR ratio at 2 h (p = 0.026), 3 h (p = 0.030), and 5 h (p = 0.046) compared to the placebo group. No serious adverse events occurred. TPN171H 5 mg demonstrated favorable acute hemodynamic effects and an acceptable short-term safety profile in this exploratory trial, supporting further evaluation in adequately powered trials.
11 May 2026
Read appraisal →The European respiratory journal
Impact of positive airway pressure therapy on pulmonary arterial pressures in obstructive sleep apnoea or obesity hypoventilation syndrome: a systematic review and meta-analysis
BACKGROUND: There is limited and conflicting evidence on the impact of obstructive sleep apnoea (OSA) and its treatment with positive airway pressure (PAP) therapy on pulmonary hypertension (PH). Our research question was: does treatment of OSA and obesity hypoventilation syndrome (OHS) with PAP therapy improve pulmonary arterial pressures? METHODS: A systematic review and random effects meta-analysis was performed (PROSPERO: CRD42024595312). PubMed, Embase, Scopus, Web of Science, EBSCO, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov were searched using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Studies reporting pulmonary arterial pressure in patients with OSA and OHS pre- and post-PAP therapy were included. The primary outcome was post-PAP therapy change in pulmonary arterial pressures, with separate analyses on pulmonary arterial systolic pressure and mean pulmonary arterial pressure. Sensitivity analysis was performed to assess the impact of PAP therapy in patients with only OSA or OHS. RESULTS: 23 studies (20 observational and three randomised controlled trials) with 733 patients were included (19 with OSA (n=518) and four with OHS and concomitant OSA (n=215)). Most patients had severe OSA. PAP therapy was associated with a mean reduction in pulmonary arterial pressure of 5.96 (95% CI 3.20-8.73) mmHg; p<0.0001. In patients with baseline PH (n=233), the reduction was 11.41 (95% CI 8.66-14.15) mmHg; p<0.00001. The beneficial effect of PAP therapy was similar in OSA and OHS. There was no sex difference in the impact of PAP therapy. Heterogeneity was high across studies (I2>85%), reflecting differences in study design, patient populations and methodologies. CONCLUSIONS: PAP therapy reduces pulmonary arterial pressures in patients with mostly severe OSA or OHS, with a more pronounced effect in those with baseline PH. As such, our findings may not apply to patients with milder degrees of OSA. While reductions in pulmonary arterial pressures were observed in all groups, the low certainty necessitates cautious application of these findings in clinical practice.
5 Apr 2026
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