Lower airway microbiota in COPD and healthy controls.

BACKGROUND: The lower airway microbiota in patients with chronic obstructive pulmonary disease (COPD) are likely altered compared with the microbiota in healthy individuals. Information on how the microbiota is affected by smoking, use of inhaled corticosteroids (ICS) and COPD severity is still scarce. METHODS: In the MicroCOPD Study, participant characteristics were obtained through standardised questionnaires and clinical measurements at a single centre from 2012 to 2015. Protected bronchoalveolar lavage samples from 97 patients with COPD and 97 controls were paired-end sequenced with the Illumina MiSeq System. Data were analysed in QIIME 2 and R. RESULTS: Alpha-diversity was lower in patients with COPD than controls (Pielou evenness: COPD=0.76, control=0.80, p=0.004; Shannon entropy: COPD=3.98, control=4.34, p=0.01). Beta-diversity differed with smoking only in the COPD cohort (weighted UniFrac: permutational analysis of variance R2=0.04, p=0.03). Nine genera were differentially abundant between COPD and controls. Genera enriched in COPD belonged to the Firmicutes phylum. Pack years were linked to differential abundance of taxa in controls only (ANCOM-BC (Analysis of Compositions of Microbiomes with Bias Correction) log-fold difference/q-values: Haemophilus -0.05/0.048; Lachnoanaerobaculum -0.04/0.03). Oribacterium was absent in smoking patients with COPD compared with non-smoking patients (ANCOM-BC log-fold difference/q-values: -1.46/0.03). We found no associations between the microbiota and COPD severity or ICS. CONCLUSION: The lower airway microbiota is equal in richness in patients with COPD to controls, but less even. Genera from the Firmicutes phylum thrive particularly in COPD airways. Smoking has different effects on diversity and taxonomic abundance in patients with COPD compared with controls. COPD severity and ICS use were not linked to the lower airway microbiota.

Clinical information predicting severe obstructive sleep apnea: A cross-sectional study of patients waiting for sleep diagnostics.

INTRODUCTION: Obstructive sleep apnea (OSA) is highly prevalent with serious health consequences. Demand for diagnostic studies is high, in many countries exceeding capacity. PURPOSE: The objective of this cross-sectional study was to identify predictors of severe OSA among patients on waiting lists for sleep studies, to better prioritize time to examinations. METHODS: The sample comprised 3646 patients (30.3% women) referred to a university clinic in Western Norway with suspected OSA. All patients underwent respiratory polygraphy. Severe OSA was defined by an apnea-hypopnea index ≥30. Information on symptoms (snoring, breathing cessations, daytime sleepiness) and medical history was collected with questionnaires, including prior diagnosis of angina, myocardial infarction, stroke, hypertension, depression or diabetes. Blood pressure was measured with thresholds of 90 and 140 mmHg defining diastolic and systolic hypertension. RESULTS: 15.7% had severe OSA. In multivariate logistic regression analysis, factors positively associated with severe OSA were increasing age, male sex, snoring, breathing cessations, BMI ≥30, diastolic hypertension, self-reported history of hypertension, and self-reported myocardial infarction. A prediction score (range 0-5) devised from 5 of these items (age ≥50, snoring, breathing cessations, BMI ≥30, and self-reported hypertension) had a sensitivity of 96.2% and a negative predictive value of 97.1% for severe OSA, when a score ≥2 was set as cut-off. CONCLUSIONS: Based on a prediction score derived from simple, easily available data, patients unlikely to suffer from severe OSA can be identified, and thus facilitate more urgent consideration of patients more likely to have severe OSA.

The association of tidal EFL with exercise performance, exacerbations, and death in COPD.

BACKGROUND: Tidal expiratory flow limitation (EFLT) is frequently found in patients with COPD and can be detected by forced oscillations when within-breath reactance of a single-breath is ≥0.28 kPa·s·L-1. The present study explored the association of within-breath reactance measured over multiple breaths and EFLT with 6-minute walk distance (6MWD), exacerbations, and mortality. METHODS: In 425 patients, spirometry and forced oscillation technique measurements were obtained on eight occasions over 3 years. 6MWD was assessed at baseline and at the 3-year visit. Respiratory symptoms, exacerbations, and hospitalizations were recorded. A total of 5-year mortality statistics were retrieved retrospectively. We grouped patients according to the mean within-breath reactance [Formula: see text], measured over several breaths at baseline, calculated as mean inspiratory-mean expiratory reactance over the sampling period. In addition to the established threshold of EFLT, an upper limit of normal (ULN) was defined using the 97.5th percentile of [Formula: see text], of the healthy controls in the study; 6MWDs were compared according to [Formula: see text], as normal, ≥ ULN < EFLT, or ≥ EFLT. Annual exacerbation rates were analyzed using a negative binomial model in the three groups, supplemented by time to first exacerbation analysis, and dichotomizing patients at the ULN. RESULTS: In patients with COPD and baseline [Formula: see text] below the ULN (0.09 kPa·s·L-1), 6MWD was stable. 6MWD declined significantly in patients with [Formula: see text]. Worse lung function and more exacerbations were found in patients with COPD with [Formula: see text], and patients with [Formula: see text] had shorter time to first exacerbation and hospitalization. A significantly higher mortality was found in patients with [Formula: see text] and FEV1 >50%. CONCLUSION: Patients with baseline [Formula: see text] had a deterioration in exercise performance, more exacerbations, and greater hospitalizations, and, among those with moderate airway obstruction, a higher mortality. [Formula: see text] is a novel independent marker of outcome in COPD.

Systemic mannose-binding lectin is not associated with Chronic Obstructive Pulmonary Disease.

Mannose-binding lectin (MBL) deficiency is associated with increased susceptibility to airways infections and autoimmunity. We examined whether MBL deficiency was more common in COPD patients, and whether MBL deficiency was associated with COPD severity. 415 COPD patients and 231 healthy subjects, aged 40-75, were examined in 2006/07. Plasma MBL levels were determined by ELISA. Low or deficient MBL levels were defined as plasma levels below 500ng/mL or 100ng/mL respectively. Logistic regression models determined factors associated with MBL deficiency; with explanatory variables study category, sex, age, smoking, comorbid heart disease, and CRP. For COPD severity, explanatory variables were FEV1, exacerbation history, hypoxia, respiratory symptoms, inhaled steroids, and CRP. 18.2% of healthy subjects and 22.2% of patients had MBL levels below 100ng/mL (p=0.23); 42.9% of healthy subjects and 49.6% of patients had levels below 500ng/mL (p=0.10). After adjustment for co-variables, patients had an OR (95% CI) of 1.26 (0.7, 2.2) for having MBL levels below 100ng/mL compared with healthy subjects, and an OR (95% CI) of 1.06 (0.7, 1.7) for having levels below 500ng/mL. Among the COPD patients, none of the disease variables were associated with MBL deficiency. No association was found between MBL deficiency and COPD or COPD severity.

Occupational exposure and incidence of respiratory disorders in a general population.

OBJECTIVE: To study the effect of occupational exposure on the incidence of adult asthma and six respiratory symptoms using a job exposure matrix (JEM). METHODS: From 1985, we conducted an 11-year community cohort study on the incidence of asthma and respiratory symptoms in Western Norway (N=2401, aged 15-70 years at baseline). The analyses in the current study were based on subjects < or =65 years at baseline, since those >65 years were unlikely to experience significant occupational exposures within the follow-up period. RESULTS: More women than men were exposed to biological dust (38% versus 29%), while more men were exposed to mineral dust (48% versus 19%), and gas or fumes (58% versus 53%). After adjusting for age, educational level, smoking, and previous occupational exposures, we found that high exposure to biological dust exposure was significantly related to a higher incidence of chronic and morning cough in men; for women, low exposure was related to attacks of dyspnea. Low exposure to workplace gas or fumes was significantly related to incident phlegm cough and attacks of dyspnea for women, while for men, high exposure was related to dyspnea grade 2. For the incidence of asthma and phlegm cough, after adjusting for all confounders, we found a significant interaction between workplace exposures and gender, where women had a higher risk of disease. CONCLUSIONS: Assessed by a JEM, occupational airborne exposure was weakly related to the incidence of asthma and respiratory symptoms, significantly more so for women than for men.

Predictors of diagnostic yield in bronchoscopy: a retrospective cohort study comparing different combinations of sampling techniques.

BACKGROUND: The reported diagnostic yield from bronchoscopies in patients with lung cancer varies greatly. The optimal combination of sampling techniques has not been finally established. The objectives of this study were to find the predictors of diagnostic yield in bronchoscopy and to evaluate different combinations of sampling techniques. METHODS: All bronchoscopies performed on suspicion of lung malignancy in 2003 and 2004 were reviewed, and 363 patients with proven malignant lung disease were included in the study. Sampling techniques performed were biopsy, transbronchial needle aspiration (TBNA), brushing, small volume lavage (SVL), and aspiration of fluid from the entire procedure. Logistic regression analyses were adjusted for sex, age, endobronchial visibility, localization (lobe), distance from carina, and tumor size. RESULTS: The adjusted odds ratios (OR) with 95% confidence intervals (CI) for a positive diagnostic yield through all procedures were 17.0 (8.5-34.0) for endobronchial lesions, and 2.6 (1.3-5.2) for constriction/compression, compared to non-visible lesions; 3.8 (1.3-10.7) for lesions > 4 cm, 6.7 (2.1-21.8) for lesions 3-4 cm, and 2.5 (0.8-7.9) for lesions 2-3 cm compared with lesions <= 2 cm. The combined diagnostic yield of biopsy and TBNA was 83.7% for endobronchial lesions and 54.2% for the combined group without visible lesions. This was superior to either technique alone, whereas additional brushing, SVL, and aspiration did not significantly increase the diagnostic yield. CONCLUSION: In patients with malignant lung disease, visible lesions and larger tumor size were significant predictors of higher diagnostic yield, after adjustment for sex, age, distance from carina, side and lobe. The combined diagnostic yield of biopsy and TBNA was significant higher than with either technique alone.