Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation

BACKGROUND: The lung microbiome of healthy individuals frequently harbors oral organisms. Despite evidence that microaspiration is commonly associated with smoking-related lung diseases, the effects of lung microbiome enrichment with upper airway taxa on inflammation has not been studied. We hypothesize that the presence of oral microorganisms in the lung microbiome is associated with enhanced pulmonary inflammation. To test this, we sampled bronchoalveolar lavage (BAL) from the lower airways of 29 asymptomatic subjects (nine never-smokers, 14 former-smokers, and six current-smokers). We quantified, amplified, and sequenced 16S rRNA genes from BAL samples by qPCR and 454 sequencing. Pulmonary inflammation was assessed by exhaled nitric oxide (eNO), BAL lymphocytes, and neutrophils. RESULTS: BAL had lower total 16S than supraglottic samples and higher than saline background. Bacterial communities in the lower airway clustered in two distinct groups that we designated as pneumotypes. The rRNA gene concentration and microbial community of the first pneumotype was similar to that of the saline background. The second pneumotype had higher rRNA gene concentration and higher relative abundance of supraglottic-characteristic taxa (SCT), such as Veillonella and Prevotella, and we called it pneumotype(SCT). Smoking had no effect on pneumotype allocation, α, or β diversity. Pneumotype(SCT) was associated with higher BAL lymphocyte-count (P= 0.007), BAL neutrophil-count (P= 0.034), and eNO (P= 0.022). CONCLUSION: A pneumotype with high relative abundance of supraglottic-characteristic taxa is associated with enhanced subclinical lung inflammation

Increased production of IL-4 and IL-12p40 from bronchoalveolar lavage cells are biomarkers of Mycobacterium tuberculosis in the sputum

BACKGROUND: Tuberculosis (TB) causes 1.45 million deaths annually world wide, the majority of which occur in the developing world. Active TB disease represents immune failure to control latent infection from airborne spread. Acid-fast bacillus (AFB) seen on sputum smear is a biomarker for contagiousness. METHODS: We enrolled 73 tuberculosis patients with extensive infiltrates into a research study using bronchoalveolar lavage (BAL) to sample lung immune cells and assay BAL cell cytokine production. All patients had sputum culture demonstrating Mycobacterium tuberculosis and 59/73 (81%) had AFB identified by microscopy of the sputum. Compared with smear negative patients, smear positive patients at presentation had a higher proportion with smoking history, a higher proportion with temperature >38.5 0 C, higher BAL cells/ml, lower percent lymphocytes in BAL, higher IL-4 and IL-12p40 in BAL cell supernatants. There was no correlation between AFB smear and other BAL or serum cytokines. Increasing IL-4 was associated with BAL PMN and negatively associated with BAL lymphocytes. Each 10-fold increase in BAL IL-4 and IL-12p40 increased the odds of AFB smear positivity by 7.4 and 2.2-fold, respectively, in a multi-variable logistic model. CONCLUSION: Increasing IL-4 and IL-12p40 production by BAL cells are biomarkers for AFB in sputum of patients who present with radiographically advanced TB. They likely reflect less effective immune control of pathways for controlling TB, leading to patients with increased infectiousness

Microlayer enrichment in natural treatment systems:linking the surface microlayer to urban water quality

Natural treatment systems (NTS), such as constructed wetlands and stormwater ponds, are multibenefit, multidisciplinary approaches to sustaining water resources and reducing contaminant loading to urban streams. Surficial thin films (called surface microlayers) are not well characterized in NTS, but may have important implications for ecosystems, public health, and pollutant fate and transport. We present results from a case study evaluating microlayer contaminant partitioning across 4 NTS in Melbourne, Australia. To our knowledge, this study provides the first direct evidence for microlayer formation and contaminant enrichment (total petroleum hydrocarbons and trihalomethanes) in NTS. Contaminated microlayers were detected in the three most stable NTS, with stability defined relative to wind speed. Fluorescent-dissolved organic matter profiles differed between microlayer and subsurface water in these systems, suggesting that fluorescence-based techniques are useful for microlayer detection. Although individual fluorophores were not consistently associated with specific contaminants, fluorescence ratios were useful for identifying likely contaminant source waters, including road-runoff and irrigation water from nearby green spaces. We evaluate our case study in light of what is known about surface microlayers in analogous systems (e.g., oceans, estuaries, and lakes), in order to identify existing research gaps and future opportunities. WIREs Water 2016, 3:269–281. doi: 10.1002/wat2.1128. This article is categorized under: Engineering Water > Sustainable Engineering of Water Engineering Water > Water, Health, and Sanitation Science of Water > Water Quality.</p

Early elevation of serum MMP-3 and MMP-12 predicts protection from World Trade Center-lung injury in New York City Firefighters: a nested case-control study.

After 9/11/2001, some Fire Department of New York (FDNY) workers had excessive lung function decline. We hypothesized that early serum matrix metalloproteinases (MMP) expression predicts World Trade Center-Lung Injury (WTC-LI) years later.This is a nested case-control analysis of never-smoking male firefighters with normal pre-exposure Forced Expiratory Volume in one second (FEV1) who had serum drawn up to 155 days post 9/11/2001. Serum MMP-1, 2,3,7,8, 9, 12 and 13 were measured. Cases of WTC-LI (N = 70) were defined as having an FEV1 one standard deviation below the mean (FEV1 ≤ 77%) at subspecialty pulmonary evaluation (SPE) which was performed 32 months (IQR 21-53) post-9/11. Controls (N = 123) were randomly selected. We modeled MMP's ability as a predictor of cases status with logistic regression adjusted for time to blood draw, exposure intensity, weight gain and pre-9/11 FEV1.Each log-increase in MMP-3 and MMP-12 showed reduced odds of developing WTC-LI by 73% and 54% respectively. MMP-3 and MMP-12 consistently clustered together in cases, controls, and the cohort. Increasing time to blood draw significantly and independently increased the risk of WTC-LI.Elevated serum levels of MMP-3 and MMP-12 reduce the risk of developing WTC-LI. At any level of MMP-3 or 12, increased time to blood draw is associated with a diminished protective effect

Models of Susceptibility to Lung Injury.^*

*<p>Each Model Includes: ΔBMI between MME and SPE, Exposure Group, Pre-9/11 FEV₁% Predicted, Time to MME (days) and MMP (Log₁₀pg/mL).</p><p>OR, Odds Ratio; CI, Confidence Interval; AUC, Area Under the Curve; HL, Hosmer Lemeshow.</p

Longitudinal Lung Function Assessment of Cohort.

*<p>Median (IQR).</p><p>FEV₁, Forced Expiratory Volume in one second; FVC, Forced Vital capacity; BDR, Bronchodilator Response; MCT, Methacholine Challenge Testing; PC₂₀, Provocative concentration of methacholine that results in a 20% drop in FEV₁; TLC, Total Lung Capacity; RV, Residual Volume; DL_co, Diffusing Capacity of the Lung for Carbon Monoxide; VA, Alveolar Ventilation; BWT, Bronchial Wall Thickening.</p

Serum Biomarkers.

*<p>p<0.05; All values shown as median (IQR).</p

Demographics of Cohort.

*<p>Median (IQR).</p><p>WTC, World Trade Center; MME, Medical Monitoring Exam; SPE, Subspecialty Pulmonary Exam; PFT, Pulmonary Function Test; BMI, Body Mass Index.</p