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

Chronic Obstructive Pulmonary Disease Is Associated with Low Levels of Vitamin D

Introduction: COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported. Methods: Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40–76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls. Levels <20 ng/mL defined deficiency. Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO2), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models. Results: COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI. Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = −6.63), current smoking ( = −4.02), GOLD stage III- IV ( = −4.71, = −5.64), and depression ( = −3.29). Summertime decreased the risk of vitamin D deficiency (OR = 0.22). Conclusion: COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels

VII Scandinavian Copd Research Symposium, Holmenkollen, Oslo 18th-19th November 2016

Peer reviewe

Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis.

Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs) contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease

Predictive equations for spirometric reference values in a healthy adult suburban population in Tanzania

This study was conducted in Kinondoni district, Dar es Salaam, Tanzania, with the objectives to generate prediction equations for forced expiratory volume in 1 second (FEV1), forced expiratory volume in 6 seconds (FEV6), FEV1/FEV6 ratio and peak expiratory flow (PEF) from a nonsymptomatic sample of the population, and to compare these equations to published reference values. The study included adults aged ≥15 years who were recruited by use of community based, multistage cluster random sampling. Participants performed spirometry and answered questionnaires regarding respiratory symptoms and socioeconomic conditions. Anthropometric data were collected. Selection of subjects for generation of reference values followed American Thoracic Society (ATS) recommendations. Data were analyzed using multiple regression techniques. Fifty two men and 98 women were selected to the reference value group. FEV1, FEV6, FEV1/FEV6 and PEF were regressed against age, height and weight. For men a curvilinear model was chosen when predicting FEV1, FEV6 and PEF, and a linear model predicted FEV1/FEV6. For women a linear model was used in the regression equations. The reference values generated from our study were lower than in several previously published studies. Our study suggests that assessment of respiratory function should be based on reference values generated from the same population as those being assessed

The prevalence of undiagnosed renal failure in a cohort of COPD patients in western Norway

SummaryPatients with COPD are at risk for other comorbid diseases, like heart failure, coronary heart disease, and depression. However, little is known about COPD phenotypes and prevalence of sub-clinical renal failure.433 COPD patients and 233 subjects without COPD, from Western Norway, age 40–75, GOLD stage II–IV, were examined in 2006/07 upon entry to the Bergen COPD Cohort Study. Plasma creatinine was measured in 422 of the COPD patients. The Glomerular Flow Rate (GFR) was determined with the Cockcroft Gault formula, and having a GFR < 60 was defined as renal failure. Examined explanatory factors were sex, age, smoking habits, GOLD stage, hypoxemia, exacerbation history, cachexia, use of daily inhaled steroids, Charlson comorbidity score, use of ACE inhibitors and/or ARBs, and the inflammatory plasma markers C-reactive protein (CRP), soluble tumor necrosis factor receptor 1 (sTNF-R1) and neutrophil gelatinase associated lipocalin (NGAL). Associations between explanatory variables and renal failure were examined by a logistic regression analysis.The prevalence of having GFR < 60 was 9.6% in female COPD patients and 5.1% in male COPD patients (p = 0.08). In multivariable analysis, female sex, higher age, cachexia, and the inflammatory markers sTNF-R1 and NGAL were all independently associated with a higher risk for renal failure, whereas use of inhaled steroids, Charlson score, GOLD stage, respiratory failure, and exacerbation frequency were not.Undiagnosed renal failure is a concern particularly in elderly COPD patients and COPD patients with cachexia

Effect of stimulating waveform and of data processing on respiratory impedance measurement

Several commercial and custom-made forced oscillation technique (FOT) devices are used to assess respiratory system impedance. The impulse oscillometry system (IOS) is a widespread device, which yields similar, but not identical results to those provided by other FOT systems. Differences may be related to the forcing waveform, the device hardware, or the data processing algorithms. We evaluated the agreement between resistance (Rrs) and reactance (Xrs) measurements while alternating between different forcing waveforms and data processing algorithms