Longitudinal Imaging-Based Clusters in Former Smokers of the COPD Cohort Associate with Clinical Characteristics: The SubPopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS).

Purpose: Quantitative computed tomography (qCT) imaging-based cluster analysis identified clinically meaningful COPD former-smoker subgroups (clusters) based on cross-sectional data. We aimed to identify progression clusters for former smokers using longitudinal data.

Patients And Methods: We selected 472 former smokers from SPIROMICS with a baseline visit and a one-year follow-up visit.

Erratum: Structural and Functional Features on Quantitative Chest Computed Tomography in the Korean Asian versus the White American Healthy Non-Smokers.

This corrects the article on p. 20 in vol. 1236, PMID: 31270987.

The Effects of Rare Variants on Lung Function and Emphysema in SPIROMICS.

The role of PI (protease inhibitor) type Z heterozygotes and additional rare variant genotypes in the gene encoding alpha-1 antitrypsin, (serpin peptidase inhibitor, clade A, member 1), in determining chronic obstructive pulmonary disease risk and severity is controversial. To comprehensively evaluate the effects of rare variants on lung function and emphysema phenotypes in subjects with significant tobacco smoke exposure using deep gene resequencing and alpha-1 antitrypsin concentrations. DNA samples from 1,693 non-Hispanic white individuals, 385 African Americans, and 90 Hispanics with ≥20 pack-years smoking were resequenced for the identification of rare variants (allele frequency < 0.

Structural and Functional Features on Quantitative Chest Computed Tomography in the Korean Asian versus the White American Healthy Non-Smokers.

Objective: Considering the different prevalence rates of diseases such as asthma and chronic obstructive pulmonary disease in Asians relative to other races, Koreans may have unique airway structure and lung function. This study aimed to investigate unique features of airway structure and lung function based on quantitative computed tomography (QCT)-imaging metrics in the Korean Asian population (Koreans) as compared with the White American population (Whites).

Materials And Methods: QCT data of healthy non-smokers (223 Koreans vs.

Heterogeneous burden of lung disease in smokers with borderline airflow obstruction.

Background: The identification of smoking-related lung disease in current and former smokers with normal FEV is complex, leading to debate regarding using a ratio of forced expiratory volume in 1 s to forced vital capacity (FEV/FVC) of less than 0.70 versus the predicted lower limit of normal (LLN) for diagnosis of airflow obstruction. We hypothesized that the discordant group of ever-smokers with FEV/FVC between the LLN and 0.

Genome-wide association study of lung function and clinical implication in heavy smokers.

Background: The aim of this study is to identify genetic loci associated with post-bronchodilator FEV/FVC and FEV, and develop a multi-gene predictive model for lung function in COPD.

Methods: Genome-wide association study (GWAS) of post-bronchodilator FEV/FVC and FEV was performed in 1645 non-Hispanic White European descent smokers.

Results: A functional rare variant in SERPINA1 (rs28929474: Glu342Lys) was significantly associated with post-bronchodilator FEV/FVC (p = 1.

Sleep disruption as a predictor of quality of life among patients in the subpopulations and intermediate outcome measures in COPD study (SPIROMICS).

Study Objectives: Sleep quality is poor among patients with chronic obstructive pulmonary disease (COPD), and studies show that sleep disturbance is associated with low overall quality of life in this population. We evaluated the impact of patient-reported sleep quality and sleep apnea risk on disease-specific and overall quality of life within patients with COPD enrolled in the SPIROMICS study, after accounting for demographics and COPD disease severity.

Methods: Baseline data from 1341 participants [892 mild/moderate COPD (FEV1 ≥ 50% predicted); 449 severe COPD (FEV1 < 50%)] were used to perform three nested (blocks) regression models to predict quality of life (Short Form-12 mental and physical components and St.

Decreased Lung Function and All-Cause Mortality in HIV-infected Individuals.

Rationale: Human immunodeficiency virus (HIV) infection is associated with pulmonary disease and worse lung function, but the relationship of lung function with survival in HIV is unknown.

Objectives: To determine whether lung function is associated with all-cause mortality in HIV-infected individuals.

Methods: HIV-infected participants from cohorts in three locations underwent pre- and post-bronchodilator spirometry and determination of single-breath diffusing capacity of the lung for carbon monoxide (Dl) in 2008-2009, computed tomographic (CT) scanning of the chest for quantitative emphysema and airway measures, and echocardiography for estimated left ventricular systolic and diastolic function and tricuspid regurgitant velocity.

Variability in objective and subjective measures affects baseline values in studies of patients with COPD.

Rationale: Understanding the reliability and repeatability of clinical measurements used in the diagnosis, treatment and monitoring of disease progression is of critical importance across all disciplines of clinical practice and in clinical trials to assess therapeutic efficacy and safety.

Objectives: Our goal is to understand normal variability for assessing true changes in health status and to more accurately utilize this data to differentiate disease characteristics and outcomes.

Methods: Our study is the first study designed entirely to establish the repeatability of a large number of instruments utilized for the clinical assessment of COPD in the same subjects over the same period.

Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts.

Rationale: Chronic obstructive pulmonary disease exacerbations are associated with disease progression, higher healthcare cost, and increased mortality. Published predictors of future exacerbations include previous exacerbation, airflow obstruction, poor overall health, home oxygen use, and gastroesophageal reflux.

Objectives: To determine the value of adding blood biomarkers to clinical variables to predict exacerbations.

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD.

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts.

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial.

Background: 12 months of oral cyclophosphamide has been shown to alter the progression of scleroderma-related interstitial lung disease when compared with placebo. However, toxicity was a concern and without continued treatment the efficacy disappeared by 24 months. We hypothesised that a 2 year course of mycophenolate mofetil would be safer, better tolerated, and produce longer lasting improvements than cyclophosphamide.

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons.

Objective: Chronic obstructive pulmonary disease is a common comorbidity in HIV, with prevalence and severity of disease incompletely explained by risk factors such as smoking and age. Unique HIV-associated factors, including microbial translocation, monocyte activation, and endothelial dysfunction, have been described in other comorbidities, but have not been investigated in relation to pulmonary abnormalities in HIV. This study assessed the relationship of these pathologic processes to pulmonary function in HIV-infected and uninfected individuals and determined if relationships were unique to HIV.

Factors associated with abnormal spirometry among HIV-infected individuals.

Objective: HIV-infected individuals are susceptible to development of chronic lung diseases, but little is known regarding the prevalence and risk factors associated with different spirometric abnormalities in this population. We sought to determine the prevalence, risk factors and performance characteristics of risk factors for spirometric abnormalities among HIV-infected individuals.

Design: Cross-sectional cohort study.

Medicare Payment Policy Creates Incentives For Long-Term Care Hospitals To Time Discharges For Maximum Reimbursement.

Long-term care hospitals are postacute care facilities for patients requiring extended hospital-level care. These facilities are reimbursed by Medicare under a prospective payment system with a short-stay outlier policy, which results in substantially lower payments for patients discharged before a diagnosis-related group-specific short-stay threshold. Using Medicare data, we examined the impact of the short-stay policy on lengths-of-stay and Medicare reimbursement among patients in long-term care hospitals who require prolonged mechanical ventilation.

Pulmonary Function in HIV-Infected Recreational Drug Users in the Era of Anti-Retroviral Therapy.

Background: Individuals with HIV infection commonly have pulmonary function abnormalities, including airflow obstruction and diffusion impairment, which may be more prevalent among recreational drug users. To date, the relationship between drug use and pulmonary function abnormalities among those with HIV remains unclear.

Objective: To determine associations between recreational drug use and airflow obstruction, diffusion impairment, and radiographic emphysema in men and women with HIV.

Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease.

Rationale: Microbiome studies typically focus on bacteria, but fungal species are common in many body sites and can have profound effects on the host. Wide gaps exist in the understanding of the fungal microbiome (mycobiome) and its relationship to lung disease.

Objectives: To characterize the mycobiome at different respiratory tract levels in persons with and without HIV infection and in HIV-infected individuals with chronic obstructive pulmonary disease (COPD).

Differences between attendings' and fellows' perceptions of futile treatment in the intensive care unit at one academic health center: implications for training.

Purpose: Knowing when patients are too ill to benefit from intensive care is essential for clinicians to recommend aggressive or palliative care as appropriate. To explore prognostic ability among critical care fellows, the authors compared fellows' and attendings' assessments of futile critical care and evaluated factors associated with assessments.

Method: Thirty-six attendings and 14 fellows in intensive care units at the University of California, Los Angeles, were surveyed daily for three months (December 2011-March 2012) to identify patients perceived as receiving futile treatment.

Acute bronchodilator responses decline progressively over 4 years in patients with moderate to very severe COPD.

Background: We previously reported a progressive decline in absolute responses of FEV1 and FVC to a near-maximal dose of 2 different short-acting bronchodilators over 4 years. Since varying host factors and the method of expressing the response may impact the time trend of acute bronchodilator responses, we now examined the potential influence of salient host characteristics on changes in bronchodilator responses over time expressed in different ways.

Methods: As part of the 4-year, placebo-controlled Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) trial, pre- and post-bronchodilator spirometry was performed at baseline and 1 month and every 6 months thereafter.

Pulmonary symptoms and diagnoses are associated with HIV in the MACS and WIHS cohorts.

Background: Several lung diseases are increasingly recognized as comorbidities with HIV; however, few data exist related to the spectrum of respiratory symptoms, diagnostic testing, and diagnoses in the current HIV era. The objective of the study is to determine the impact of HIV on prevalence and incidence of respiratory disease in the current era of effective antiretroviral treatment.

Methods: A pulmonary-specific questionnaire was administered yearly for three years to participants in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS).

The opportunity cost of futile treatment in the ICU*.

Objective: When used to prolong life without achieving a benefit meaningful to the patient, critical care is often considered "futile." Although futile treatment is acknowledged as a misuse of resources by many, no study has evaluated its opportunity cost, that is, how it affects care for others. Our objective was to evaluate delays in care when futile treatment is provided.

Comparison of serum, EDTA plasma and P100 plasma for luminex-based biomarker multiplex assays in patients with chronic obstructive pulmonary disease in the SPIROMICS study.

Background: As a part of the longitudinal Chronic Obstructive Pulmonary Disease (COPD) study, Subpopulations and Intermediate Outcome Measures in COPD study (SPIROMICS), blood samples are being collected from 3200 subjects with the goal of identifying blood biomarkers for sub-phenotyping patients and predicting disease progression. To determine the most reliable sample type for measuring specific blood analytes in the cohort, a pilot study was performed from a subset of 24 subjects comparing serum, Ethylenediaminetetraacetic acid (EDTA) plasma, and EDTA plasma with proteinase inhibitors (P100).

Methods: 105 analytes, chosen for potential relevance to COPD, arranged in 12 multiplex and one simplex platform (Myriad-RBM) were evaluated in duplicate from the three sample types from 24 subjects.

Factors associated with palliative withdrawal of mechanical ventilation and time to death after withdrawal.

Background: In imminently dying patients, mechanical ventilation withdrawal is often a comfort measure and avoids prolonging the dying process.

Objective: The aim of the study was to identify factors associated with palliative withdrawal of mechanical ventilation and time to death after extubation.

Methods: Logistic regression models were used to identify factors associated with palliative withdrawal of mechanical ventilation.

The frequency and cost of treatment perceived to be futile in critical care.

Importance: Physicians often perceive as futile intensive care interventions that prolong life without achieving an effect that the patient can appreciate as a benefit. The prevalence and cost of critical care perceived to be futile have not been prospectively quantified.

Objective: To quantify the prevalence and cost of treatment perceived to be futile in adult critical care.

The impact of HAART on the respiratory complications of HIV infection: longitudinal trends in the MACS and WIHS cohorts.

Objective: To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART).

Design: Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women's Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively.

Methods: Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era.