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 â\u89¥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 (Î\u94(Formula Presented.)), 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 Î\u94(Formula Presented.) of the healthy controls in the study; 6MWDs were compared according to Î\u94(Formula Presented.), as normal, â\u89¥ ULN < EFLT, or â\u89¥ 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 Î\u94(Formula Presented.) below the ULN (0.09 kPa·s·L-1), 6MWD was stable. 6MWD declined significantly in patients with Î\u94(Formula Presented.) â\u89¥ ULN. Worse lung function and more exacerbations were found in patients with COPD with Î\u94(Formula Presented.) â\u89¥ ULN, and patients with Î\u94(Formula Presented.) â\u89¥ ULN had shorter time to first exacerbation and hospitalization. A significantly higher mortality was found in patients with Î\u94(Formula Presented.) â\u89¥ ULN and FEV1.50%. Conclusion: Patients with baseline Î\u94(Formula Presented.) â\u89¥ ULN had a deterioration in exercise performance, more exacerbations, and greater hospitalizations, and, among those with moderate airway obstruction, a higher mortality. Î\u94(Formula Presented.) is a novel independent marker of outcome in COPD

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

<p>Abstract</p> <p>Background</p> <p>The reported diagnostic yield from bronchoscopies in patients with lung cancer varies greatly. The optimal combination of sampling techniques has not been finally established.</p> <p>The objectives of this study were to find the predictors of diagnostic yield in bronchoscopy and to evaluate different combinations of sampling techniques.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Drengenes_LaboratoryContamination_DRYAD_fastq

Fastq files generated by Illumina MiSeq sequencing of the bacterial 16S rRNA gene region V3V4 (164 samples, paired-end reads)

Inflammatory cytokine response to exercise in alpha-1-antitrypsin deficient COPD patients 'on' or 'off' augmentation therapy.

BackgroundThere is still limited information on systemic inflammation in alpha-1-antitrypsin-deficient (AATD) COPD patients and what effect alpha-1-antitrypsin augmentation therapy and/or exercise might have on circulating inflammatory cytokines. We hypothesized that AATD COPD patients on augmentation therapy (AATD + AUG) would have lower circulating and skeletal muscle inflammatory cytokines compared to AATD COPD patients not receiving augmentation therapy (AATD-AUG) and/or the typical non-AATD (COPD) patient. We also hypothesized that cytokine response to exercise would be lower in AATD + AUG compared to AATD-AUG or COPD subjects.MethodsArterial and femoral venous concentration and skeletal muscle expression of TNFα, IL-6, IL-1β and CRP were measured at rest, during and up to 4-hours after 50% maximal 1-hour knee extensor exercise in all COPD patient groups, including 2 additional groups (i.e. AATD with normal lung function, and healthy age-/activity-matched controls).ResultsCirculating CRP was higher in AATD + AUG (4.7 ± 1.6 mg/dL) and AATD-AUG (3.3 ± 1.2 mg/dL) compared to healthy controls (1.5 ± 0.3 mg/dL, p &lt; 0.05), but lower in AATD compared to non-AATD-COPD patients (6.1 ± 2.6 mg/dL, p &lt; 0.05). TNFα, IL-6 and IL-1β were significantly increased by 1.7-, 1.7-, and 4.7-fold, respectively, in non-AATD COPD compared to AATD COPD (p &lt; 0.05), and 1.3-, 1.7-, and 2.2-fold, respectively, compared to healthy subjects (p &lt; 0.05). Skeletal muscle TNFα was on average 3-4 fold greater in AATD-AUG compared to the other groups (p &lt; 0.05). Exercise showed no effect on these cytokines in any of our patient groups.ConclusionThese data show that AATD COPD patients do not experience the same chronic systemic inflammation and exhibit reduced inflammation compared to non-AATD COPD patients. Augmentation therapy may help to improve muscle efflux of TNFα and reduce muscle TNFα concentration, but showed no effect on IL-6, IL-1β or CRP

Drengenes_LaboratoryContamination_DRYAD_Metadata

Metadata file needed to rerun the bioinformatics analyses performed in Laboratory Contamination in Airway Microbiome Studies

TNF-alpha is associated with loss of lean body mass only in already cachectic COPD patients

Abstract Background Systemic inflammation may contribute to cachexia in patients with chronic obstructive pulmonary disease (COPD). In this longitudinal study we assessed the association between circulating C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels and subsequent loss of fat free mass and fat mass in more than 400 COPD patients over three years. Methods The patients, aged 40–76, GOLD stage II-IV, were enrolled in 2006/07, and followed annually. Fat free mass and fat mass indexes (FFMI &amp; FMI) were calculated using bioelectrical impedance, and CRP, TNF-α, IL-1ß, and IL-6 were measured using enzyme immunoassays. Associations with mean change in FFMI and FMI of the four inflammatory plasma markers, sex, age, smoking, FEV1, inhaled steroids, arterial hypoxemia, and Charlson comorbidity score were analyzed with linear mixed models. Results At baseline, only CRP was significantly (but weakly) associated with FFMI (r = 0.18, p &lt; 0.01) and FMI (r = 0.27, p &lt; 0.01). Univariately, higher age, lower FEV1, and use of beta2-agonists were the only significant predictors of decline in FFMI, whereas smoking, hypoxemia, Charlson score, and use of inhaled steroids predicted increased loss in FMI. Multivariately, high levels of TNF-α (but not CRP, IL-1ß or IL-6) significantly predicted loss of FFMI, however only in patients with established cachexia at entry. Conclusion This study does not support the hypothesis that systemic inflammation is the cause of accelerated loss of fat free mass in COPD patients, but suggests a role for TNF-α in already cachectic COPD patients

Vitamin D, vitamin D binding protein, and longitudinal outcomes in COPD

Background Associations between Vitamin D3 [25(OH)D], vitamin D binding protein (VDBP) and chronic obstructive pulmonary disease (COPD) are previously reported. We aimed to further investigate these associations on longitudinal outcomes. Methods 426 COPD patients from western Norway, GOLD stage II-IV, aged 40–76, were followed every six-month from 2006 through 2009 with spirometry, bioelectrical impedance measurements and registration of exacerbation frequency. Serum 25(OH)D and VDBP levels were determined at study-entry by high-performance liquid chromatography coupled with mass spectrometry and enzyme immunoassays respectively. Yearly change in lung function and body composition was assessed by generalized estimating equations (GEE), yearly exacerbation rate by negative binomial regression models, and 5 years all-cause mortality by Cox proportional-hazard regression. Results 1/3 of the patients had vitamin D deficiency (<20ng/mL) and a greater decline in both FEV1 and FVC, compared to patients with normal levels; for FEV1 this difference only reached statistical significance in the 28 patients with the lowest levels (<10ng/mL, p = 0.01). Neither 25(OH)D nor VDBP levels predicted exacerbation rate, change in fat free mass index or risk of death. Conclusion Severe vitamin D deficiency may affect decline in lung function parameters in COPD. Neither 25(OH)D nor VDBP levels did otherwise predict markers of disease progression