American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jan 2022
Comparative StudyVentilatory Drive Withdrawal Rather Than Reduced Genioglossus Compensation as a Mechanism of Obstructive Sleep Apnea in REM.
Rationale: REM sleep is associated with reduced ventilation and greater obstructive sleep apnea (OSA) severity than non-REM (nREM) sleep for reasons that have not been fully elucidated. Objectives: Here, we use direct physiological measurements to determine whether the pharyngeal compromise in REM sleep OSA is most consistent with 1) withdrawal of neural ventilatory drive or 2) deficits in pharyngeal pathophysiology per se (i.e., increased collapsibility and decreased muscle responsiveness). Methods: Sixty-three participants with OSA completed sleep studies with gold standard measurements of ventilatory "drive" (calibrated intraesophageal diaphragm EMG), ventilation (oronasal "ventilation"), and genioglossus EMG activity. ⋯ Drive withdrawal was exacerbated in phasic REM sleep. Conclusions: In patients with OSA, the pharyngeal compromise characteristic of REM sleep appears to be predominantly explained by ventilatory drive withdrawal rather than by preferential decrements in muscle activity or responsiveness. Preventing drive withdrawal may be the leading target for REM sleep OSA.
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Am. J. Respir. Crit. Care Med. · Jan 2022
Comparative StudyEfficacy of Inhaled Treprostinil on Multiple Disease Progression Events in Patients with Pulmonary Hypertension Due to Parenchymal Lung Disease in the INCREASE Trial.
Rationale: The INCREASE study of inhaled treprostinil met its primary endpoint of change in 6-minute-walk distance at Week 16. In addition, there were significantly fewer clinical worsening events in patients receiving inhaled treprostinil. However, the incidence of multiple events in the same patient is unknown. ⋯ Fewer patients receiving inhaled treprostinil had multiple progression events compared with those receiving the placebo (35 vs. 58, 22% vs. 36%; P = 0.005). Conclusions: Patients who received inhaled treprostinil were significantly less likely to experience further disease progression events after an initial event compared with patients receiving placebo. These results support the continuation of inhaled treprostinil despite the occurrence of disease progression in clinical practice.
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Am. J. Respir. Crit. Care Med. · Jan 2022
Development of A Blood-Based Transcriptional Risk Score for Chronic Obstructive Pulmonary Disease.
Rationale: The ability of peripheral blood biomarkers to assess chronic obstructive pulmonary disease (COPD) risk and progression is unknown. Genetics and gene expression may capture important aspects of COPD-related biology that predict disease activity. Objectives: Develop a transcriptional risk score (TRS) for COPD and assess the contribution of the TRS and a polygenic risk score (PRS) for disease susceptibility and progression. ⋯ In ECLIPSE cases, we replicated the association with FEV1 change (β, -8.2; 95% CI, -15 to -1; P = 0.025) and the majority of other COPD-related traits. Models including PRS, TRS, and clinical factors were more predictive of COPD (area under the receiver operator characteristic curve, 0.84) and annualized FEV1 change compared with models with one risk score or clinical factors alone. Conclusions: Blood transcriptomics can improve prediction of COPD and lung function decline when added to a PRS and clinical risk factors.