Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial.

BACKGROUND: Safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear. RESEARCH QUESTION: What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19? STUDY DESIGN AND METHODS: Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on < 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or ICU transfer. Using a Bayesian statistical approach, the posterior probability of superiority within each treatment arm (superiority threshold 95%) was calculated. RESULTS: The trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention-to-treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n = 139 [70 intervention, 69 usual care]), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean, 24.7%; 95% credible interval, 18.6-31.4) receiving usual care and 32 participants (posterior mean, 22.1%; 95% credible interval, 16.6-28.1) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and in 11.9% of participants in the intervention arm. INTERPRETATION: Among nonintubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04344587; URL: www. CLINICALTRIALS: gov.

Optimal NIV Medicare Access Promotion: Patients With COPD: A Technical Expert Panel Report From the American College of Chest Physicians, the American Association for Respiratory Care, the American Academy of Sleep Medicine, and the American Thoracic Society.

This document summarizes the work of the COPD Technical Expert Panel working group. For patients with COPD, the most pressing current coverage barriers identified were onerous diagnostic requirements focused on oxygenation (rather than ventilation) and difficulty obtaining bilevel devices with backup rate capabilities. Because of these difficulties, many patients with COPD were instead sometimes prescribed home mechanical ventilators. Critical evidence supports changes to current policies, including randomized controlled trial evidence suggesting a mortality benefit from bilevel positive airway pressure with backup rate and updated clinical practice guidelines from the American Thoracic Society as well as the European Respiratory Society. To achieve optimal access to noninvasive ventilation for patients with COPD, we make the following key recommendations: (1) removal of the need for overnight oximetry testing; (2) the ability to initiate therapy using bilevel devices with backup rate capability; and (3) increased duration of time to meet adherence criteria (ie, a second 90-day trial period) in those patients actively engaged in their care. Clear guidelines based on medical necessity are also included for patients who require initiation of or switch to a home mechanical ventilator. Adoption of these proposed recommendations would result in the right device, for the right type of patient with COPD, at the right time. Finally, we emphasize the need for adequate clinical support during initiation and maintenance of home noninvasive ventilation in such patients.

Noninvasive Ventilation in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease involving upper and lower motor neurons and has limited treatment options. The weakness progresses to involve the diaphragms, resulting in respiratory failure and death. Home noninvasive ventilation has been shown to improve survival and quality of life, especially in those with intact bulbar function. Once initiated, close monitoring with nocturnal oximetry, remote downloads from the home noninvasive ventilation machine, and measurement of serum bicarbonate should be conducted. Additionally, transcutaneous CO2 monitoring can be considered if available. This article discusses the indications, timing, initiation, and management of noninvasive ventilation in amyotrophic lateral sclerosis.

Current Approach to Diagnosis and Management of Pulmonary Eosinophilic Syndromes: Eosinophilic Pneumonias, Eosinophilic Granulomatosis with Polyangiitis, and Hypereosinophilic Syndrome.

Eosinophils play a key role in orchestrating the complex clinicopathological pulmonary and extrapulmonary disease features in patients with eosinophilic syndromes. Eosinophilic pulmonary syndromes consist of a heterogeneous group of disorders characterized by the presence of peripheral blood eosinophilia and/or eosinophilic-related pulmonary impairment. These disorders can present with varying degrees of organ involvement, and while their presentation may be similar, it is important to define the disease state, as management and prognosis differ. In this article, we discuss acute and chronic eosinophilic pneumonias, eosinophilic granulomatosis with polyangiitis, and the hypereosinophilic syndromes. The mainstay of therapy for these disorders has been corticosteroids; however, recent and ongoing studies have provided strong grounds for optimism for specific targeted treatment approaches.

Advances in the treatment of idiopathic pulmonary fibrosis.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a lung limited, progressive fibrotic disease with a poor prognosis. The cause is unknown, and currently there is no treatment that reverses the disease or stops progression. This combination of a poor prognosis and the absence of curative therapy has prompted a sustained investigative effort to identify beneficial treatments. Recently released trial results suggest progress. AREAS COVERED: Although the mechanism of disease is poorly understood, a number of compounds that influence pathways thought to play a mechanistic role have been studied for use in IPF. This article discusses a number of these landmark trials. EXPERT OPINION: From these studies we conclude that the future treatment of IPF will include expanding pharmacological options. Recent studies have identified two agents that appear to slow disease progression and may offer a window into pathogenesis and future drug targets.

Mitogen-activated protein kinase phosphatase-1 modulates regional effects of injurious mechanical ventilation in rodent lungs.

RATIONALE: Mechanical ventilation induces heterogeneous lung injury by mitogen-activated protein kinase (MAPK) and nuclear factor-κB. Mechanisms regulating regional injury and protective effects of prone positioning are unclear. OBJECTIVES: To determine the key regulators of the lung regional protective effects of prone positioning in rodent lungs exposed to injurious ventilation. METHODS: Adult rats were ventilated with high (18 ml/kg, positive end-expiratory pressure [PEEP] 0) or low Vt (6 ml/kg; PEEP 3 cm H(2)O; 3 h) in supine or prone position. Dorsal-caudal lung mRNA was analyzed by microarray and MAPK phosphatases (MKP)-1 quantitative polymerase chain reaction. MKP-1(-/-) or wild-type mice were ventilated with very high (24 ml/kg; PEEP 0) or low Vt (6-7 ml/kg; PEEP 3 cm H(2)O). The MKP-1 regulator PG490-88 (MRx-108; 0.75 mg/kg) or phosphate-buffered saline was administered preventilation. Injury was assessed by lung mechanics, bronchioalveolar lavage cell counts, protein content, and lung injury scoring. Immunoblotting for MKP-1, and IκBα and cytokine ELISAs were performed on lung lysates. MEASUREMENTS AND MAIN RESULTS: Prone positioning was protective against injurious ventilation in rats. Expression profiling demonstrated MKP-1 20-fold higher in rats ventilated prone rather than supine and regional reduction in p38 and c-jun N-terminal kinase activation. MKP-1(-/-) mice experienced amplified injury. PG490-88 improved static lung compliance and injury scores, reduced bronchioalveolar lavage cell counts and cytokine levels, and induced MKP-1 and IκBα. CONCLUSIONS: Injurious ventilation induces MAPK in an MKP-1-dependent fashion. Prone positioning is protective and induces MKP-1. PG490-88 induced MKP-1 and was protective against high Vt in a nuclear factor-κB-dependent manner. MKP-1 is a potential target for modulating regional effects of injurious ventilation.

A novel model of rheumatoid arthritis-associated interstitial lung disease in SKG mice.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is associated with increased mortality in up to 10% of patients with rheumatoid arthritis. Lung exposure to cigarette smoke has been implicated in disease development. Little is known about the mechanisms underlying the development of RA-ILD, in part due to the lack of an appropriate mouse model. The objectives of this study were (i) to test the suitability of SKG mice as a model of cellular and fibrotic interstitial pneumonia in the setting of autoimmune arthritis, and (ii) to determine the role of lung injury in the development of arthritis in SKG mice. Lung tissues were evaluated in arthritic SKG mice by quantifying cell accumulation in bronchoalveolar lavage, static compliance, collagen levels, and infiltrating cell phenotypes by flow cytometry and histology. Lung injury was induced by exposure to cigarette smoke or bleomycin. Arthritic SKG mice developed a patchy cellular and fibrotic interstitial pneumonia associated with reduced static compliance, increased collagen levels, and accumulation of inflammatory cells. Infiltrating cells comprised CD4+ T cells, B cells, macrophages, and neutrophils. Chronic exposure to cigarette smoke or initiation of lung injury with bleomycin did not cause arthritis. The pattern of lung disease suggests that arthritic SKG mice represent an authentic model of nonspecific interstitial pneumonia in RA-ILD patients. The lack of arthritis development after cigarette smoke or lung injury suggests that a model where breaches in immunologic tolerance are induced by lung inflammation and injury alone may be overly simplistic.

Wnt signaling pathway and lung disease.

The Wnt pathway plays an important role in development and in regulating adult stem cell systems. A variety of cellular processes is mediated by Wnt signaling, which includes cellular proliferation, differentiation, survival, apoptosis, and cell motility. Loss of regulation of these pathways can lead to tumorigenesis, and the Wnt pathway has been implicated in the development of several types of cancers, including colon, lung, leukemia, breast, thyroid, and prostate. The Wnt pathway has also been associated with other lung diseases such as interstitial lung disease (ILD) and asthma. Our increasing understanding of the Wnt pathway offers great hope that new molecular-based screening tests and pharmaceutical agents that selectively target this pathway will be developed to diagnose and treat these diseases in the future.