American journal of respiratory and critical care medicine最新文献

Rationale: Cough is a key symptom in patients with fibrotic interstitial lung disease (ILD). Objectives: This study evaluated the prevalence, longitudinal change, associations, and prognostic significance of cough severity in patients with fibrotic ILD. Methods: We included consecutive patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD who completed the 100-mm Cough Severity Visual Analog Scale from the prospective multicenter Canadian Registry for Pulmonary Fibrosis. Baseline cough severity and associations with patient demographics and clinical factors were determined. Relationships between baseline cough severity and health outcomes were evaluated. Measurements and Main Results: Patients with IPF (n = 1,061) had higher median baseline cough severity than those with non-IPF fibrotic ILD (n = 2,825) (24 vs. 20 mm; P < 0.001), with worse cough associated with gastroesophageal reflux disease for both cohorts. Worse cough severity was independently associated with worse health-related quality of life at baseline, larger annualized decline in Dl_CO, development of disease progression, and reduced transplant-free survival in both IPF and non-IPF fibrotic ILD cohorts. The IPF cohort (2.2 mm; 95% confidence interval, 1.6-2.9 mm) had larger annualized increments in cough severity than the non-IPF fibrotic ILD cohort (1.1 mm; 95% confidence interval, 0.8-1.4 mm; P = 0.004). There was no difference in worsening cough over time comparing those receiving and not receiving ILD-targeted therapy or with and without lung function decline. Conclusions: Cough is common in patients with IPF and non-IPF fibrotic ILD, with increasing cough severity over time irrespective of ILD-targeted therapy. Patient-reported cough severity has prognostic implications on health-related quality of life, disease progression, and survival in fibrotic ILD.

Rationale: Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) have high morbidity and mortality; thus, novel treatments are needed.

Objectives: Assess efficacy and safety of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with IPF and PPF.

Methods: This phase 2, randomized, double-blind, placebo-controlled trial included parallel cohorts of patients with IPF (n = 278 randomized, n = 276 treated) or PPF (n = 125 randomized, n = 123 treated) who received 30-mg admilparant, 60-mg admilparant, or placebo (1:1:1) twice daily for 26 weeks. Background antifibrotics (both cohorts) and immunosuppressants (PPF only) were permitted.

Measurements and main results: Rates of change in percentage of predicted forced vital capacity (ppFVC) over 26 weeks for IPF were -2.7% (placebo), -2.8% (30-mg), and -1.2% (60-mg) and for PPF were -4.3% (placebo), -2.9% (30-mg), and -1.1% (60-mg). Treatment differences between 60-mg admilparant and placebo were 1.4% (95% CI, -0.1 to 3.0) for IPF and 3.2% (95% CI, 0.7 to 5.7) for PPF. Treatment effect was observed with or without background antifibrotics in both cohorts. Diarrhea occurred at similar frequencies in admilparant arms versus placebo. Transient day 1 post-dose blood pressure reductions were observed in all arms in both cohorts but greater with admilparant. Treatment discontinuations due to adverse events were similar across IPF arms and lower with admilparant (2.5% [30-mg]; 0% [60-mg]) versus placebo (17.1%) for PPF.

Conclusions: In this first phase 2 study to evaluate antifibrotic treatment in parallel IPF and PPF cohorts, 60-mg admilparant slowed lung function decline and was safe and well tolerated, supporting further evaluation in phase 3 trials. Clinical trial registration available at www.

Clinicaltrials: gov, ID: NCT04308681.

Rationale: Due to effects of aging on the respiratory system, it is conceivable that the association between driving pressure and mortality depends on age.

Objective: We endeavored to evaluate whether the association between driving pressure and mortality of patients with acute respiratory distress syndrome (ARDS) varies across the adult lifespan, hypothesizing that it is stronger in older, including very old (≥80 years), patients.

Methods: We performed a secondary analysis of individual patient-level data from seven ARDS Network and PETAL Network randomized controlled trials ("ARDSNet cohort"). We tested our hypothesis in a second, independent, national cohort ("Hellenic cohort"). We performed both binary logistic and Cox regression analyses including the interaction term between age (as a continuous variable) and driving pressure at baseline (i.e., the day of trial enrollment) as the predictor, and 90-day mortality as the dependent variable.

Findings: Based on data from 4567 patients with ARDS included in the ARDSNet cohort, we found that the effect of driving pressure on mortality depended on age (p=0.01 for the interaction between age as a continuous variable and driving pressure). The difference in driving pressure between survivors and non-survivors significantly changed across the adult lifespan (p<0.01). In both cohorts, a driving pressure threshold of 11 cmH₂O was associated with mortality in very old patients.

Interpretation: Data from randomized controlled trials with strict inclusion criteria suggest that the effect of driving pressure on mortality of patients with ARDS may depend on age. These results may advocate for a personalized age-dependent mechanical ventilation approach.