American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2020
Editorial CommentIdentifying a Neuro-Phenotype in Severe Asthma.
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Am. J. Respir. Crit. Care Med. · May 2020
Randomized Controlled Trial Comparative StudyThrombomodulin alfa for Acute Exacerbation of Idiopathic Pulmonary Fibrosis: A Randomized, Double-blind, Placebo-controlled Trial.
Rationale: Acute exacerbation during the course of idiopathic pulmonary fibrosis causes a poor prognosis. Coagulation abnormalities and endothelial damage are involved in its pathogenesis. Thrombomodulin alfa, a recombinant human soluble thrombomodulin, has anticoagulant and antiinflammatory effects. ⋯ Conclusions: Thrombomodulin alfa did not improve the 90-day survival proportion. The present results suggest that the use of thrombomodulin alfa for the treatment of acute exacerbation of idiopathic pulmonary fibrosis not be recommended. Clinical trial registered with www.clinicaltrials.gov (NCT02739165).
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Am. J. Respir. Crit. Care Med. · May 2020
Randomized Controlled TrialPitolisant for Daytime Sleepiness in Obstructive Sleep Apnea Patients Refusing CPAP: A Randomized Trial.
Rationale: Excessive daytime sleepiness is a common disabling symptom in obstructive sleep apnea syndrome. Objectives: To evaluate the efficacy and safety of pitolisant, a selective histamine H3 receptor antagonist with wake-promoting effects, for the treatment of daytime sleepiness in patients with moderate to severe obstructive sleep apnea refusing continuous positive airway pressure treatment. Methods: In an international, multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was individually titrated at up to 20 mg/d over 12 weeks. ⋯ Adverse event incidence, mainly headache, insomnia, nausea, and vertigo, was similar in the pitolisant and placebo groups (29.5% and 25.4%, respectively), with no cardiovascular or other significant safety concerns. Conclusions: Pitolisant significantly reduced self-reported daytime sleepiness and fatigue and improved patient-reported outcomes and physician disease severity assessment in sleepy patients with obstructive sleep apnea refusing or nonadherent to continuous positive airway pressure. Clinical trial registered with www.clinicaltrials.gov (NCT01072968) and EU Clinical Trials Register (EudraCT 2009-017251-94).
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Am. J. Respir. Crit. Care Med. · May 2020
Comparative StudyAirway Occlusion Pressure as an Estimate of Respiratory Drive and Inspiratory Effort During Assisted Ventilation.
Rationale: Monitoring and controlling respiratory drive and effort may help to minimize lung and diaphragm injury. Airway occlusion pressure (P0.1) is a noninvasive measure of respiratory drive. Objectives: To determine 1) the validity of "ventilator" P0.1 (P0.1vent) displayed on the screen as a measure of drive, 2) the ability of P0.1 to detect potentially injurious levels of effort, and 3) how P0.1vent displayed by different ventilators compares to a "reference" P0.1 (P0.1ref) measured from airway pressure recording during an occlusion. ⋯ Bench experiments showed a low mean bias for P0.1vent compared with P0.1ref for most ventilators but precision varied; in patients, precision was lower. Ventilators estimating P0.1vent without occlusions could underestimate P0.1ref. Conclusions: P0.1 is a reliable bedside tool to assess respiratory drive and detect potentially injurious inspiratory effort.
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Am. J. Respir. Crit. Care Med. · May 2020
rhIGF-1/BP3 Preserves Lung Growth and Prevents Pulmonary Hypertension in Experimental BPD.
Rationale: Antenatal factors, such as chorioamnionitis, preeclampsia, and postnatal injury, are associated with an increased risk for bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH) after preterm birth. IGF-1 (insulin-like growth factor-1) is markedly decreased in normal preterm infants, but whether IGF-1 treatment can prevent BPD or PH is unknown. Objectives: To evaluate whether postnatal treatment with rhIGF-1 (recombinant human IGF-1)/BP3 (binding peptide 3) improves lung growth and prevents PH in two antenatal models of BPD induced by intraamniotic exposure to endotoxin (ETX) or sFlt-1 (soluble fms-like tyrosine kinase 1), and in a postnatal model due to prolonged hyperoxia. ⋯ In both models, postnatal rhIGF-1/BP3 treatment restored RAC and RVH to normal values when compared with placebo injections. rhIGF-1/BP3 treatment also preserved lung structure and prevented RVH after postnatal hyperoxia. In vitro studies showed that rhIGF-1/BP3 treatment increased lung endothelial cell and alveolar type 2 cell proliferation. Conclusions: Postnatal rhIGF-1/BP3 treatment preserved lung structure and prevented RVH in antenatal and postnatal BPD models. rhIGF-1/BP3 treatment may provide a novel strategy for the prevention of BPD in preterm infants.