Background: Precision medicine focuses on the identification of therapeutic strategies that are effective for a group of patients based on similar unifying characteristics. The recent success of precision medicine in non-critical care settings has resulted from the confluence of large clinical and biospecimen repositories, innovative bioinformatics, and novel trial designs. Similar advances for precision

BACKGROUND Data from population-based cohorts suggest that symptom subtypes, and OSA-specific hypoxic burden (HB) could help to better identify patients with OSA at high cardiovascular (CV) risk. AIM We aimed to evaluate whether those new markers are associated with the risk of major adverse CV events (MACE) in clinical setting. METHODS Data from the Pays de la Loire cohort were linked to health administrative

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research

Rationale Infants born prematurely have impaired capacity to deal with oxidative stress shortly after birth. Objectives We hypothesize that the relative impact of exposure to air pollution on lung function is higher in preterm than in term infants. Methods In the prospective BILD-birth-cohort of 254 preterm and 517 term infants, we investigated associations of particulate matter (PM10) and nitrogen

The current definition of a chronic obstructive pulmonary disease (COPD) exacerbation (ECOPD) is based solely on worsening respiratory symptoms, with severity classified post hoc by the healthcare resource used to treat the event, which may vary among practitioners and healthcare systems. These shortcomings support a need to revise the ECOPD definition and severity classification to one that is useful

Rationale: Mechanical signaling through cell-matrix interactions plays a major role in progressive vascular remodeling in pulmonary arterial hypertension (PAH). Matrix metalloproteinase-8 (MMP-8) is an interstitial collagenase involved in regulating inflammation and fibrosis of the lung and systemic vasculature, but its role in PAH pathogenesis remains unexplored. Objectives: To evaluate MMP-8 as a

RATIONALE Use of severity of illness scores to classify patients for clinical care and research is common outside of the neonatal intensive care unit. Extremely premature (<29 weeks gestation), extremely low birth weight (<1000 grams) infants experience significant mortality and develop severe pathology during the protracted birth hospitalization. OBJECTIVE To measure at high resolution the changes

Rationale Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with COVID-19 is unknown. The objective of this study was to identify clinically relevant, novel subgroups in COVID-19-related ARDS, and compare them to previously described ARDS subphenotypes. Methods Eligible participants were adults with COVID-19

RATIONALE The continuous infusion of fentanyl or morphine is often prescribed to assist with analgesia and sedation (analgosedation) during mechanical ventilation. OBJECTIVES To compare the effect of fentanyl vs. morphine on patient-centered outcomes in ventilated patients. METHODS We conducted a cluster-randomized, cluster-crossover trial between July 2019 and August 2020 in two adult Intensive Care

RATIONALE Pulmonary sarcoidosis is generally presumed to be a T helper-1- and macrophage-driven disease. However, mouse models have recently revealed that chronically inflamed lung tissue can also comprise T follicular helper- (Tfh-) like cells and represents a site of active T cell / B cell cooperation. OBJECTIVES To assess the role of pulmonary Tfh- and germinal center-like lymphocytes in sarcoidosis

RATIONALE Alteration of human respiratory microbiota had been observed in COVID-19. How the microbiota is associated with the prognosis in COVID-19 is unclear. OBJECTIVES To characterize the feature and dynamics of the respiratory microbiota and its associations with clinical features in COVID-19 patients. Methods：We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens

Objectives We evaluated longitudinal kinetics of an 11-gene blood transcriptomic tuberculosis (TB) signature, RISK11, and effects of TB preventative therapy (TPT) and respiratory organisms on RISK11 signature score, in HIV-uninfected and HIV-infected individuals. Methods RISK11 was measured in a longitudinal study of RISK11-guided TPT in HIV-uninfected adults, a cross-sectional respiratory organisms

RATIONALE Population-based data regarding the consequences of very low birth weight (VLBW) and bronchopulmonary dysplasia (BPD) on adult exercise capacity is limited. OBJECTIVES To compare exercise capacity in a national VLBW cohort with term-born controls and explore factors contributing to the differences. METHODS At 26-30 years of age, 228 VLBW survivors and 100 controls underwent lung function

RATIONALE Mechanical ventilation (MV) is associated with hippocampal apoptosis and inflammation, and it is important to study strategies to mitigate them. OBJECTIVES Explore whether temporary transvenous diaphragm neurostimulation (TTDN) in association with MV mitigates hippocampal apoptosis and inflammation after 50 hours of MV. METHODS Normal-lung porcine study comparing apoptotic index, inflammatory

Ground-glass opacity (GGO)-associated lung cancers are common and radiologically distinct clinical entities known to have indolent clinical course and superior survival implying a unique underlying biology. However, the molecular and immune characteristics of GGO-associated lung nodules have not been systemically studied. Objectives Providing mechanistic insights for the treatment of these radiologically

RATIONALE. Metabolic Syndrome (MetSyn) increases the risk of World Trade Center-Lung Injury (WTC-LI). However, the temporal relationship of MetSyn, exposure intensity, and lung dysfunction is not well understood. We modeled the association of longitudinal MetSyn characteristics with WTC-lung disease to define modifiable risk. METHODS. Consented firefighters (N=5,738) were active-duty on 9/11/01 (9/11)

Rationale: For children with asthma, access to quick-relief medications is critical to minimizing morbidity and mortality. An innovative and practical approach to ensure access at school is to maintain a supply of stock albuterol that can be used by any student who experiences respiratory distress. To make this possible, state laws allowing for stock albuterol are needed to improve medication access

RATIONALE People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. OBJECTIVE Test differing durations of intravenous antimicrobials for CF exacerbations. METHODS STOP2 was a multi-center, randomized

Rationale Type 2 innate lymphoid cells (ILC2s) are significant sources of type 2 cytokines, which are implicated in the pathogenesis of asthma and asthma exacerbations. The role of ILC2s in virus-induced asthma exacerbations is not well-characterized. Objectives To characterize pulmonary ILC responses following experimental rhinovirus challenge in patients with moderate asthma and healthy subjects

RATIONALE Inhaled corticosteroids (ICS) are commonly prescribed with long-acting beta-2 agonists (LABA) in COPD. To date, the effects of ICS therapy on the airway microbiome in COPD are unknown. OBJECTIVES To determine the effects of ICS/LABA on the airway microbiome of COPD patients. METHODS Clinically stable COPD patients were enrolled into a 4-week run-in period during which ICS was discontinued

RATIONALE In acute respiratory distress syndrome (ARDS), the effect of positive end-expiratory pressure (PEEP) may depend on the extent to which multiorgan dysfunction contributes to risk of death, and the precision with which PEEP is titrated to attenuate atelectrauma without exacerbating overdistension. OBJECTIVE To evaluate whether multiorgan dysfunction and lung mechanics modified treatment effect

Rationale- Patients with indeterminate pulmonary nodules (IPNs) at risk of cancer undergo high rates of invasive, costly, and morbid procedures. Objectives: To train and externally validate a risk prediction model which combined clinical, blood, and imaging biomarkers to improve the noninvasive management of IPNs. Methods - In this prospectively collected, retrospective blinded evaluation (PRoBE) study

RATIONALE Determining whether an individual has obstructive or central sleep apnea is fundamental to selecting the appropriate treatment. OBJECTIVES Here we derive an automated breath-by-breath probability of obstruction, as a surrogate of gold-standard upper airway resistance, using hallmarks of upper airway obstruction visible on clinical sleep studies. METHODS From 5 NPSG signals (airflow, thoracic

RATIONALE Angiotensin-Converting Enzyme (ACE) 2, the entry receptor for severe acute respiratory syndrome-Coronavirus 2 (SARS-CoV2), is expressed in type 2 alveolar epithelial cells (AT2) that may play key roles in post-injury repair. Imbalance between ACE2 and ACE has also been hypothesized to contribute to lung injury. OBJECTIVES To characterize the expression and distribution of ACE2 and ACE and