Diagnosing Type 2 Inflammation in COPD: Comparison of Blood and Sputum Eosinophil Assessment in the University of California Los Angeles COPD Phenotyping Study.

Background: COPD phenotyping is an approach for developing tailored therapies. The eosinophilic phenotype is associated with exacerbation risk and response to specific treatments. This study evaluates the relationship between sputum and blood eosinophilia, hypothesizing that sputum eosinophil percentage (SpE%) better reflects disease severity and exacerbation risk than blood eosinophil counts (BEC).

Re-envisioning clinical trial design in systemic sclerosis.

Introduction: Systemic sclerosis (SSc) is a progressive autoimmune rheumatic disease with high morbidity and mortality and few effective treatment options. Increased biopharmaceutical investment in therapeutic development for rare diseases has created new opportunities for drug discovery in SSc. However, despite the increased pipeline activity in SSc, success rates remain dismally low.

Impact of quantitative radiological features of interstitial lung disease on immunomodulatory treatment response in three autoimmune interstitial lung disease cohorts.

Background: The defining radiological features of autoimmune interstitial lung disease (ILD) are ground glass opacification (GGO) and fibrosis. The associations between these features and physiological response to immunomodulation remain unclear.

Methods: This study leveraged three autoimmune ILD cohorts: two with systemic sclerosis (SSc) and one with rheumatoid arthritis (RA) which were selected for inherent differences in fibrotic extents/patterns.

Characteristics Associated with Lung Function Trajectories: An Analysis of the SPIROMICS Cohort.

Discovering the biological basis of progression in chronic obstructive pulmonary disease (COPD), especially of rapid decline (RD) in forced expiratory volume in 1 second, is essential to the development of precision therapies. First, we sought to define baseline characteristics of RD (⩾100 ml/yr), relative to participants with stable-to-improved (S/I) status or with intermediate decline (D)-categories based on spirometric data from the Framingham Offspring cohort. Second, we sought to examine these categories as predictors of longitudinal COPD outcomes, adjusting for baseline characteristics.

Longitudinal Outcomes in Pi*MZ Alpha-1 Antitrypsin-Deficient Individuals with Tobacco Smoking History from the SPIROMICS Cohort.

Reliable data about the natural history of lung function decline in alpha-1 antitrypsin (AAT)-deficient Pi*MZ heterozygotes is largely missing. We hypothesized that, in adults with a tobacco smoking history, lung function deteriorates faster in Pi*MZ compared with the Pi*MM genotype. We identified 1,856 Pi*MM and 79 Pi*MZ participants with ⩾20 pack-years tobacco smoking history from the SPIROMICS (Subpopulations and Intermediate Outcomes Measures in COPD Study) cohort by DNA sequencing and followed them over a median of 4.

Biological correlates of radiological features of systemic sclerosis interstitial lung disease.

Background And Objectives: The extent and pattern of radiological features ( fibrosis and ground glass) can influence treatment approaches for systemic sclerosis-related interstitial lung disease (SSc-ILD). However, the pathobiology underlying these radiological features is poorly understood and warrants further investigation.

Methods: 68 proteins were measured in bronchoalveolar lavage (BAL) fluid from 103 SSc-ILD participants in Scleroderma Lung Study I.

Treatment Response Biomarkers for Systemic Sclerosis-Associated Interstitial Lung Disease.

Objective: This study investigated whether changes in circulating biomarkers predict progressive pulmonary fibrosis (PPF) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) receiving treatment.

Methods: Participants of the Scleroderma Lung Study II, which compared receiving mycophenolate mofetil (MMF) versus cyclophosphamide (CYC) for treating SSc-ILD, who had blood samples at baseline and 12 months were included. Levels for C-reactive protein (CRP), interleukin-6, C-X-C motif chemokine ligand (CXCL) 4, CCL18, and Krebs von den Lungen (KL)-6 were measured, and a logistic regression model evaluated relationships between changes in these biomarkers and the development of PPF by 24 months.

Relationship between high-resolution computed tomography quantitative imaging analysis and physiological and clinical features in antisynthetase syndrome-related interstitial lung disease.

Objectives: To explore the association between the extent of CT abnormalities by quantitative imaging analysis (QIA) and clinical/physiological disease parameters in patients with antisynthetase syndrome associated interstitial lung disease (ARS-ILD).

Methods: We analysed 20 patients with antisynthetase antibodies and active ILD enrolled in the Abatacept in Myositis-Associated Interstitial Lung Disease study. High-resolution chest CT was obtained at weeks 0, 24 and 48 and QIA scored the extent of ground glass (quantitative score for ground glass), fibrosis (quantitative score for lung fibrosis, QLF) and total ILD (quantitative ILD, QILD).

Phenotypes and Trajectories of Tobacco-exposed Persons with Preserved Spirometry: Insights from Lung Volumes.

Among tobacco-exposed persons with preserved spirometry (TEPSs), we previously demonstrated that different lung volume indices-specifically, elevated total lung capacity (TLC) versus elevated ratio of functional residual capacity to TLC (FRC/TLC)-identify different lung disease characteristics in the COPDGene cohort. We sought to determine differential disease characteristics and trajectories associated with lung volume indices among TEPSs in the SPIROMICS cohort. We categorized TEPSs ( = 814) by tertiles (low, intermediate, and high) of TLC or residual volume-to-TLC ratio (RV/TLC) derived from baseline computed tomography images and then examined clinical and spirometric disease trajectories in mutually exclusive categories of participants with high TLC without high RV/TLC ([TLC]) versus high RV/TLC without high TLC ([RV/TLC]).

Duration and Frequency of Spirometry Needed to Accurately Reflect Annualized Change of FEV in Chronic Obstructive Pulmonary Disease.

The slope of decline in forced expiratory volume in 1 second (FEV) is commonly used to reflect the rate of disease progression for descriptive studies and therapeutic trials in chronic obstructive pulmonary disease (COPD). The frequency and duration of spirometric testing needed to report the true slope are unknown. We sought to define the minimum frequency and follow-up duration needed to accurately describe the annualized rate of FEV change among patients with moderate to very severe COPD.

Association of bronchial disease on CT imaging and clinical definitions of chronic bronchitis in a single-center COPD phenotyping study.

Introduction: Chronic Bronchitis (CB) represents a phenotype of chronic obstructive pulmonary disease (COPD). While several definitions have been used for diagnosis, the relationship between clinical definitions and radiologic assessment of bronchial disease (BD) has not been well studied. The aim of this study was to evaluate the relationship between three clinical definitions of CB and radiographic findings of BD in spirometry-defined COPD patients.

Impact of Marijuana Use on Lung Health.

The widespread use of marijuana in the context of increasing legalization has both short- and long-term health implications. Although various modes of marijuana use-smoked, vaped, or ingested-may lead to a wide scope of potential systemic effects, we focus here on inhalational use of marijuana as the most common mode with the lung as the organ that is most directly exposed to its effects. Smoked marijuana has been associated with symptoms of chronic bronchitis and histopathologic changes in airway epithelium, but without consistent evidence of long-term decline in pulmonary function.

Prevalence and Management of Chronic Obstructive Pulmonary Disease in the Gulf Countries with a Focus on Inhaled Pharmacotherapy.

Chronic obstructive pulmonary disease (COPD) is a preventable, progressive disease and the third leading cause of death worldwide. The epidemiological data of COPD from Gulf countries are very limited, as it remains underdiagnosed and underestimated. Risk factors for COPD include tobacco cigarette smoking, water pipe smoking (Shisha), exposure to air pollutants, occupational dusts, fumes, and chemicals.

The Effect of Chronic Altitude Exposure on Chronic Obstructive Pulmonary Disease Outcomes in the SPIROMICS Cohort: An Observational Cohort Study.

Individuals with chronic obstructive pulmonary disease (COPD) have airflow obstruction and maldistribution of ventilation. For those living at high altitude, any gas exchange abnormality is compounded by reduced partial pressures of inspired oxygen. Does residence at higher altitude exposure affect COPD outcomes, including lung function, imaging characteristics, symptoms, health status, functional exercise capacity, exacerbations, and mortality? From the SPIROMICS (Subpopulation and Intermediate Outcome Measures in COPD Study) cohort, we identified individuals with COPD living below 1,000 ft (305 m) elevation ( = 1,367) versus above 4,000 ft (1,219 m) elevation ( = 288).

Association between ambient exposure to PM and upper aerodigestive tract cancer in Los Angeles.

Fine particulate matter (PM ) contains carcinogens similar to those generated by tobacco smoking, which may increase the risks of developing smoking-related cancers, such as upper aerodigestive track (UADT) cancers, for both smokers and never-smokers. Therefore, it is imperative to understand the relation between ambient PM exposure and risk of UADT cancers. A population-based case-control study involving 565 incident UADT cancer cases and 983 controls was conducted in Los Angeles County from 1999 to 2004.

Sex differences in clinical outcomes and biological profiles in systemic sclerosis-associated interstitial lung disease: a post-hoc analysis of two randomised controlled trials.

Background: Observational studies have shown that men with systemic sclerosis have an increased risk of interstitial lung disease (ILD) and mortality compared with women. However, previous studies have not controlled for treatment effect or evaluated the biological mechanism or mechanisms underlying this sex difference. We aimed to compare ILD progression and long-term morbidity and mortality outcomes in male and female participants of two randomised controlled trials for systemic sclerosis-associated ILD.

Eosinophil recovery in hospitalized COVID-19 patients is associated with lower rates of ICU admission and in-hospital mortality: An observational cohort analysis.

Background: Admission eosinopenia (<100 cells/μL) is associated with poor clinical outcomes in hospitalized COVID-19 patients. However, the effects of eosinophil recovery (defined as reaching ≥50 eosinophils/μL) during hospitalization on COVID-19 outcomes have been inconsistent.

Methods: The study included 1,831 patients admitted to UCLA hospitals between February 2020 and February 2021 with PCR-confirmed COVID-19.

Combining Clinical and Biological Data to Predict Progressive Pulmonary Fibrosis in Patients With Systemic Sclerosis Despite Immunomodulatory Therapy.

Objective: Progressive pulmonary fibrosis (PPF) is the leading cause of death in systemic sclerosis (SSc). This study aimed to develop a clinical prediction nomogram using clinical and biological data to assess risk of PPF among patients receiving treatment of SSc-related interstitial lung disease (SSc-ILD).

Methods: Patients with SSc-ILD who participated in the Scleroderma Lung Study II (SLS II) were randomized to treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CYC).

Longitudinal Follow-Up of Participants With Tobacco Exposure and Preserved Spirometry.

Importance: People who smoked cigarettes may experience respiratory symptoms without spirometric airflow obstruction. These individuals are typically excluded from chronic obstructive pulmonary disease (COPD) trials and lack evidence-based therapies.

Objective: To define the natural history of persons with tobacco exposure and preserved spirometry (TEPS) and symptoms (symptomatic TEPS).