Military Inhalational Exposures Outside the Theater of Conflict and Chronic Respiratory Symptoms.

Importance: Deployment to Afghanistan and Southwest Asia has been associated with adverse respiratory health outcomes. However, the impact of inhalational exposures (eg, vapor, dust, gas, fumes), which are known correlates of reduced lung function and future chronic lung disease, during military service time outside this deployment period has not been assessed.

Objective: To assess military inhalational exposures during nonwartime routine activities and their associations with chronic respiratory symptoms.

Increased exacerbations and hospitalizations among PI*MZ compared to PI*MM individuals: an electronic health record analysis.

Background: The best described endotype of COPD is alpha-1 antitrypsin (AAT) deficiency, due to a genetic abnormality in the SERPINA1 gene. Common deficient PI variants are the Z and S variants. Homozygotes for the Z allele (PI*ZZ individuals) carry the genotype most commonly associated with severe AAT deficiency (AATD), but a highly prevalent endotype is the heterozygous state (PI*MZ individuals).

Extensions of Heterogeneity in Integration and Prediction (HIP) With R Shiny Application.

Multiple data views measured on the same set of participants are becoming more common and have the potential to deepen our understanding of many complex diseases by analyzing these different views simultaneously. Equally important, many of these complex diseases show evidence of subgroup heterogeneity (e.g.

Sinusitis and rhinitis among US veterans deployed to Southwest Asia and Afghanistan after September 11, 2001.

Background: Post-9/11 veterans were exposed to environmental and occupational pollutants during deployment.

Objective: Our aim was to determine associations between deployment-related exposures and sinusitis and rhinitis.

Methods: Between April 2018 and March 2020, veterans with land-based deployment after 9/11 who were living within 25 miles of 6 Department of Veteran Affairs medical centers were randomly chosen by using a Defense Manpower Data Center roster.

Dynamic and prognostic proteomic associations with FEV decline in chronic obstructive pulmonary disease.

Rationale: Identification and validation of circulating biomarkers for lung function decline in COPD remains an unmet need.

Objective: Identify prognostic and dynamic plasma protein biomarkers of COPD progression.

Methods: We measured plasma proteins using SomaScan from two COPD-enriched cohorts, the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene), and one population-based cohort, Multi-Ethnic Study of Atherosclerosis (MESA) Lung.

Individual Risk Factors of PM Associated With Wintertime Mortality in Urban Patients With COPD.

Background: Air pollution contributes to premature mortality, but potential impacts differ in populations with existing disease, particularly for individuals with multiple risk factors. Although COPD increases vulnerability to air pollution, individuals with COPD and other individual risk factors are at the intersection of multiple risks and may be especially susceptible to the effect of acute outdoor air pollution.

Research Question: What is the association between wintertime air pollution and mortality in patients with COPD and the modifying role of individual risk factors?

Study Design And Methods: This study evaluated 19,243 deceased veterans with prior COPD diagnosis who had resided in 25 US metropolitan regions (2016-2019).

Lifestyle Intervention and Excess Weight in Chronic Obstructive Pulmonary Disease (COPD): INSIGHT COPD Randomized Clinical Trial.

Being overweight or obese is common among patients with chronic obstructive pulmonary disease (COPD), but whether interventions targeted at weight loss improve functional impairments is unknown. INSIGHT (Intervention Study in Overweight Patients with COPD) tested whether a pragmatic low-intensity lifestyle intervention would lead to better physical functional status among overweight or obese participants with COPD. The trial was a 12-month, multicenter, patient-level pragmatic clinical trial.

An optimized workflow for MS-based quantitative proteomics of challenging clinical bronchoalveolar lavage fluid (BALF) samples.

Background: Clinical bronchoalveolar lavage fluid (BALF) samples are rich in biomolecules, including proteins, and useful for molecular studies of lung health and disease. However, mass spectrometry (MS)-based proteomic analysis of BALF is challenged by the dynamic range of protein abundance, and potential for interfering contaminants. A robust, MS-based proteomics compatible sample preparation workflow for BALF samples, including those of small and large volume, would be useful for many researchers.

sJIVE: Supervised Joint and Individual Variation Explained.

Analyzing multi-source data, which are multiple views of data on the same subjects, has become increasingly common in molecular biomedical research. Recent methods have sought to uncover underlying structure and relationships within and/or between the data sources, and other methods have sought to build a predictive model for an outcome using all sources. However, existing methods that do both are presently limited because they either (1) only consider data structure shared by all datasets while ignoring structures unique to each source, or (2) they extract underlying structures first without consideration to the outcome.

Robust integrative biclustering for multi-view data.

In many biomedical research, multiple views of data (e.g. genomics, proteomics) are available, and a particular interest might be the detection of sample subgroups characterized by specific groups of variables.

Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function.

Background: Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking.

Methods: We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV] to forced vital capacity [FVC] ≥0.

Biomarkers and the microbiome in the detection and treatment of early-stage non-small cell lung cancer.

Lung cancer is one of the most common and deadly cancers in the world. However, over the last several years, research into lung cancer screening and novel therapeutic approaches have provided promise that earlier detection combined with new treatment strategies may result in significantly improved outcomes. Biomarkers will most certainly play a major role in identifying those who may benefit from, and how to apply, these new treatment strategies.

Network Analysis to Identify Multi-Omic Correlations in the Lower Airways of Children With Cystic Fibrosis.

The leading cause of morbidity and mortality in cystic fibrosis (CF) is progressive lung disease secondary to chronic airway infection and inflammation; however, what drives CF airway infection and inflammation is not well understood. By providing a physiological snapshot of the airway, metabolomics can provide insight into these processes. Linking metabolomic data with microbiome data and phenotypic measures can reveal complex relationships between metabolites, lower airway bacterial communities, and disease outcomes.

Plasma Metabolomic Signatures of Chronic Obstructive Pulmonary Disease and the Impact of Genetic Variants on Phenotype-Driven Modules.

Small studies have recently suggested that there are specific plasma metabolic signatures in chronic obstructive pulmonary disease (COPD), but there have been no large comprehensive study of metabolomic signatures in COPD that also integrate genetic variants. Fresh frozen plasma from 957 non-Hispanic white subjects in COPDGene was used to quantify 995 metabolites with Metabolon's global metabolomics platform. Metabolite associations with five COPD phenotypes (chronic bronchitis, exacerbation frequency, percent emphysema, post-bronchodilator forced expiratory volume at one second [FEV]/forced vital capacity [FVC], and FEV percent predicted) were assessed.

Prone Positioning of Patients With Coronavirus Disease 2019 Who Are Nonintubated in Hypoxic Respiratory Distress: Single-Site Retrospective Health Records Review.

Introduction: In March and April 2020 of the coronavirus disease 2019 pandemic, site clinical practice guidelines were implemented for prone positioning of patients with suspected coronavirus disease 2019 in hypoxic respiratory distress who are awake, alert, and spontaneously breathing. The purpose of this pandemic disaster practice improvement project was to measure changes in pulse oximetry associated with prone positioning of patients with coronavirus disease 2019 infection in adult acute respiratory distress or adult respiratory distress syndrome, who are awake, alert, spontaneously breathing, and nonintubated.

Methods: A retrospective chart review of patients who were coronavirus disease 2019 positive in the emergency department from March 30, 2020 to April 30, 2020 was conducted for patients with a room air pulse oximetry <90% and a preprone position pulse oximetry ≤94% who tolerated prone positioning for at least 30 minutes.

Morphological and functional properties of the conducting human airways investigated by in vivo computed tomography and in vitro MRI.

The accurate representation of the human airway anatomy is crucial for understanding and modeling the structure-function relationship in both healthy and diseased lungs. The present knowledge in this area is based on morphometric studies of excised lung casts, partially complemented by in vivo studies in which computed tomography (CT) was used on a small number of subjects. In the present study, we analyzed CT scans of a cohort of healthy subjects and obtained comprehensive morphometric information down to the seventh generation of bronchial branching, including airway diameter, length, branching angle, and rotation angle.

Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease.

Rationale: Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown.

Objectives: To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up.

Ambient air pollution and lung disease in China: health effects, study design approaches and future research.

Ambient air pollution in China has worsened following dramatic increases in industrialization, automobile use and energy consumption. Particularly bothersome is the increase in the PM2.5 fraction of pollutants.