Effect of prednisone on woodsmoke-induced sputum inflammation in healthy volunteers: A randomized, placebo-controlled pilot study.

Background: Inhalation of biomass smoke is associated with adverse respiratory effects in those with chronic pulmonary conditions. There are few published data regarding the effects of anti-inflammatory interventions on these outcomes.

Objective: Our aim was to assess the effects of postexposure prednisone on woodsmoke (WS)-induced sputum neutrophilia.

Loss of Airway Phylogenetic Diversity Is Associated with Clinical and Pathobiological Markers of Disease Development in Chronic Obstructive Pulmonary Disease.

The airway microbiome has the potential to shape chronic obstructive pulmonary disease (COPD) pathogenesis, but its relationship to outcomes in milder disease is unestablished. To identify sputum microbiome characteristics associated with markers of COPD in participants of the Subpopulations and Intermediate Outcome Measures of COPD Study (SPIROMICS). Sputum DNA from 877 participants was analyzed using 16S ribosomal RNA gene sequencing.

Proximal and Distal Bronchioles Contribute to the Pathogenesis of Non-Cystic Fibrosis Bronchiectasis.

Non-cystic fibrosis bronchiectasis (NCFB) may originate in bronchiolar regions of the lung. Accordingly, there is a need to characterize the morphology and molecular characteristics of NCFB bronchioles. Test the hypothesis that NCFB exhibits a major component of bronchiolar disease manifest by mucus plugging and ectasia.

A pilot randomized clinical trial of γ-tocopherol supplementation on wood smoke-induced neutrophilic and eosinophilic airway inflammation.

Background: Air pollutants, including particulates from wood smoke, are a significant cause of exacerbation of lung disease. γ-Tocopherol is an anti-inflammatory isoform of vitamin E that has been shown to reduce allergen-, ozone-, and endotoxin-induced inflammation.

Objective: The objective of this study was to determine whether γ-tocopherol would prevent experimental wood smoke-induced airway inflammation in humans.

Application of artificial intelligence in quantifying lung deposition dose of black carbon in people with exposure to ambient combustion particles.

Background: Understanding lung deposition dose of black carbon is critical to fully reconcile epidemiological evidence of combustion particles induced health effects and inform the development of air quality metrics concerning black carbon. Macrophage carbon load (MaCL) is a novel cytology method that quantifies lung deposition dose of black carbon, however it has limited feasibility in large-scale epidemiological study due to the labor-intensive manual counting.

Objective: To assess the association between MaCL and episodic elevation of combustion particles; to develop artificial intelligence based counting algorithm for MaCL assay.

Eosinophils-from cradle to grave: An EAACI task force paper on new molecular insights and clinical functions of eosinophils and the clinical effects of targeted eosinophil depletion.

Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti-inflammatory, regulatory).

Indoor Pollution and Lung Function Decline in Current and Former Smokers: SPIROMICS AIR.

Indoor pollutants have been associated with chronic obstructive pulmonary disease morbidity, but it is unclear whether they contribute to disease progression. We aimed to determine whether indoor particulate matter (PM) and nitrogen dioxide (NO) are associated with lung function decline among current and former smokers. Of the 2,382 subjects with a history of smoking in SPIROMICS AIR, 1,208 participants had complete information to estimate indoor PM and NO, using individual-based prediction models, in relation to measured spirometry at two or more clinic visits.

Air Pollution and Diet: Potential Interacting Exposures in Asthma.

Purpose Of Review: To provide a review of emerging literature describing the impact of diet on the respiratory response to air pollution in asthma.

Recent Findings: Asthma phenotyping (observable characteristics) and endotyping (mechanistic pathways) have increased the specificity of diagnostic and treatment pathways and opened the doors to the identification of subphenotypes with enhanced susceptibility to exposures and interventions. Mechanisms underlying the airway immune response to air pollution are still being defined but include oxidative stress, inflammation, and activation of adaptive and innate immune responses, with genetic susceptibility highlighted.

Potential mechanisms mediating PM-induced alterations of H3N2 influenza virus infection and cytokine production in human bronchial epithelial cells.

Exposure to particulate matter (PM) has been associated with increased hospital admissions for influenza. Airway epithelial cells are a primary target for inhaled environmental insults including fine PM (PM) and influenza viruses. The potentiation of PM exposure on the effects of influenza virus on airway epithelial cells has not been adequately elucidated.

A blood and bronchoalveolar lavage protein signature of rapid FEV decline in smoking-associated COPD.

Accelerated progression of chronic obstructive pulmonary disease (COPD) is associated with increased risks of hospitalization and death. Prognostic insights into mechanisms and markers of progression could facilitate development of disease-modifying therapies. Although individual biomarkers exhibit some predictive value, performance is modest and their univariate nature limits network-level insights.

Plasma sterols and vitamin D are correlates and predictors of ozone-induced inflammation in the lung: A pilot study.

Background: Ozone (O3) exposure causes respiratory effects including lung function decrements, increased lung permeability, and airway inflammation. Additionally, baseline metabolic state can predispose individuals to adverse health effects from O3. For this reason, we conducted an exploratory study to examine the effect of O3 exposure on derivatives of cholesterol biosynthesis: sterols, oxysterols, and secosteroid (25-hydroxyvitamin D) not only in the lung, but also in circulation.

Airway and Systemic Prostaglandin E2 Association with COPD Symptoms and Macrophage Phenotype.

Background: Polymorphisms and products of the cyclooxygenase (COX) pathway have been associated with the development of chronic obstructive pulmonary disease (COPD) and adverse outcomes. COX-produced prostaglandin E2 (PGE-2) may play a role in the inflammation observed in COPD, potentially through deleterious airway macrophage polarization. A better understanding of the role of PGE-2 in COPD morbidity may inform trials for therapeutics targeting the COX pathway or PGE-2.

Expanded characterization of in vitro polarized M0, M1, and M2 human monocyte-derived macrophages: Bioenergetic and secreted mediator profiles.

Respiratory macrophage subpopulations exhibit unique phenotypes depending on their location within the respiratory tract, posing a challenge to in vitro macrophage model systems. Soluble mediator secretion, surface marker expression, gene signatures, and phagocytosis are among the characteristics that are typically independently measured to phenotype these cells. Bioenergetics is emerging as a key central regulator of macrophage function and phenotype but is often not included in the characterization of human monocyte-derived macrophage (hMDM) models.

Black carbon content in airway macrophages is associated with increased severe exacerbations and worse COPD morbidity in SPIROMICS.

Background: Airway macrophages (AM), crucial for the immune response in chronic obstructive pulmonary disease (COPD), are exposed to environmental particulate matter (PM), which they retain in their cytoplasm as black carbon (BC). However, whether AM BC accurately reflects environmental PM exposure, and can serve as a biomarker of COPD outcomes, is unknown.

Methods: We analyzed induced sputum from participants at 7 of 12 sites SPIROMICS sites for AM BC content, which we related to exposures and to lung function and respiratory outcomes.

Clinical Implications of Low Absolute Blood Eosinophil Count in the SPIROMICS COPD Cohort.

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) considers blood eosinophil counts < 100 cells/μL (BEC) in people with COPD to predict poor inhaled corticosteroid (ICS) responsiveness. However, the BEC phenotype is inadequately characterized, especially in advanced COPD.

Research Question: Are there differences between GOLD group D patients with high BEC and those with low BEC regarding baseline characteristics and longitudinal outcomes?

Study Design And Methods: We used multivariable mixed models and logistic regression to contrast clinical characteristics and outcomes of BEC vs BEC > 100 (BEC) in all subjects with COPD (n = 1,414) and GOLD group D subjects (n = 185) not receiving ICS.

Prolonged, physiologically relevant nicotine concentrations in the airways of smokers.

Nicotine from cigarette smoke is a biologically active molecule that has pleiotropic effects in the airway, which could play a role in smoking-induced lung disease. However, whether nicotine and its metabolites reach sustained, physiologically relevant concentrations on airway surfaces of smokers is not well defined. To address these issues, concentrations of nicotine, cotinine, and hydroxycotinine were measured by mass spectrometry (MS) in supernatants of induced sputum obtained from participants in the subpopulations and intermediate outcome measures in COPD study (SPIROMICS), an ongoing observational study that included never smokers, former smokers, and current smokers with and without chronic obstructive pulmonary disease (COPD).

Fish oil blunts lung function decrements induced by acute exposure to ozone in young healthy adults: A randomized trial.

Background: Over one-third of the U.S. population is exposed to unsafe levels of ozone (O).

Biomarkers of Airway Immune Homeostasis Differ Significantly with Generation of E-Cigarettes.

Numerous studies have demonstrated that e-cigarettes can impact respiratory immune homeostasis; however, the extent of these effects remains an active area of investigation, and most previous studies were conducted with model systems or subjects exposed to third-generation e-cigarettes, such as vape pens and box mods. Given the rise in popularity of nicotine-salt-containing pods and disposable e-cigarettes (fourth generation), we set out to better understand the respiratory effects of these newer e-cigarettes and compare their effects to early-generation devices. We collected induced sputum samples from a cohort of nonsmokers, smokers, third-generation e-cigarette users, and fourth-generation e-cigarette users ( = 20-30 per group) and evaluated the cellular and fluid-phase composition for markers of inflammation, host defense, and lung injury.

Dibutyl phthalate exposure alters T-cell subsets in blood from allergen-sensitized volunteers.

Phthalates are ubiquitous environmental contaminants associated with allergic disease in epidemiological and animal studies. This investigation aims to support these associations by interrogating systemic immune effects in allergen-sensitized volunteers after controlled indoor air exposure to a known concentration of dibutyl phthalate (DBP). The phthalate-allergen immune response (PAIR) study enrolled 16 allergen-sensitized participants to a double-blinded, randomized, crossover exposure to two conditions (DBP or control air for 3 hr), each followed immediately by inhaled allergen challenge.

Mucus and mucus flake composition and abundance reflect inflammatory and infection status in cystic fibrosis.

Background: Mucus hyperconcentration in cystic fibrosis (CF) lung disease is marked by increases in both mucin and DNA concentration. Additionally, it has been shown that half of the mucins present in bronchial alveolar lavage fluid (BALF) from preschool-aged CF patients are present in as non-swellable mucus flakes. This motivates us to examine the utility of mucus flakes, as well as mucin and DNA concentrations in BALF as markers of infection and inflammation in CF airway disease.