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

Chronic and Acute Exposures to the World Trade Center Disaster and Lower Respiratory Symptoms: Area Residents and Workers

Objectives. We assessed associations between new-onset (post–September 11, 2001 [9/11]) lower respiratory symptoms reported on 2 surveys, administered 3 years apart, and acute and chronic 9/11-related exposures among New York City World Trade Center–area residents and workers enrolled in the World Trade Center Health Registry. Methods. World Trade Center–area residents and workers were categorized as case participants or control participants on the basis of lower respiratory symptoms reported in surveys administered 2 to 3 and 5 to 6 years after 9/11. We created composite exposure scales after principal components analyses of detailed exposure histories obtained during face-to-face interviews. We used multivariate logistic regression models to determine associations between lower respiratory symptoms and composite exposure scales. Results. Both acute and chronic exposures to the events of 9/11 were independently associated, often in a dose-dependent manner, with lower respiratory symptoms among individuals who lived and worked in the area of the World Trade Center. Conclusions. Study findings argue for detailed assessments of exposure during and after events in the future from which potentially toxic materials may be released and for rapid interventions to minimize exposures and screen for potential adverse health effects

Case-Control Study of Lung Function in World Trade Center Health Registry Area Residents and Workers

Rationale: Residents and area workers who inhaled dust and fumes from the World Trade Center disaster reported lower respiratory symptoms in two World Trade Center Health Registry surveys (2003–2004 and 2006–2007), but lung function data were lacking. Objectives: To examine the relationship between persistent respiratory symptoms and pulmonary function in a nested case–control study of exposed adult residents and area workers 7–8 years after September 11, 2001. Methods: Registrants reporting post September 11th onset of a lower respiratory symptom in the first survey and the same symptom in the second survey were solicited as potential cases. Registrants without lower respiratory symptoms in either Registry survey were solicited as potential control subjects. Final case–control status was determined by lower respiratory symptoms at a third interview (the study), when spirometry and impulse oscillometry were also performed. Measurements and Main Results: We identified 180 cases and 473 control subjects. Cases were more likely than control subjects to have abnormal spirometry (19% vs. 11%; P,0.05), and impulse oscillometry measurements of elevated airway resistance (R5; 68% vs. 27%; P,0.0001) and frequency dependence of resistance (R5–20; 36% vs. 7%; P , 0.0001). When spirometry was normal, cases were more likely than control subjects to have elevated R5 and R5–20 (62% vs. 25% and 27% vs. 6%, respectively; both P , 0.0001). Associations between symptoms and oscillometry held when factors significant in bivariate comparisons (body mass index, spirometry, and exposures) were analyzed using logistic regression. Conclusions: This study links persistent respiratory symptoms and oscillometric abnormalities in World Trade Center–exposed residents and area workers. ElevatedR5andR5–20 in cases despite normal spirometry suggested distal airway dysfunction as a mechanism for symptoms

Bronchodilator Response Predicts Longitudinal Improvement in Small Airway Function in World Trade Center Dust Exposed Community Members

The evolution of lung function, including assessment of small airways, was assessed in individuals enrolled in the World Trade Center Environmental Health Center (WTC-EHC). We hypothesized that a bronchodilator response at initial evaluation shown by spirometry or in small airways, as measured by forced oscillation technique (FOT), would be associated with improvement in large and small airway function over time. Standardized longitudinal assessment included pre and post bronchodilator (BD) spirometry (forced vital capacity, FVC; forced expiratory volume in 1 second, FEV1) and FOT (resistance at 5 Hz, R5; resistance at 5 minus 20 Hz, R5–20). Longitudinal changes were assessed using linear mixed-effects modelling with adjustment for potential confounders (median follow-up 2.86 years; 95% measurements within 4.9 years). Data demonstrated: (1) parallel improvement in airflow and volume measured by spirometry and small airway function (R5 and R5–20) measured by FOT; (2) the magnitude of longitudinal improvement was tightly linked to the initial BD response; and (3) longitudinal values for small airway function on FOT were similar to residual abnormality observed post BD at initial visit. These findings suggest presence of reversible and irreversible components of small airway injury that are identifiable at initial presentation. These results have implications for treatment of isolated small airway abnormalities that can be identified by non-invasive effort independent FOT particularly in symptomatic individuals with normal spirometry indices. This study underscores the need to study small airway function to understand physiologic changes over time following environmental and occupational lung injury