BACKGROUND COPD ranks within the top three causes of mortality in the global burden of disease, yet it remains largely underdiagnosed. We assessed the underdiagnosis of COPD and its determinants in ...national and international surveys of general populations. METHODS We analyzed representative samples of adults aged ≥ 40 years randomly selected from well-defined administrative areas worldwide (44 sites from 27 countries). Postbronchodilator FEV1 /FVC < lower limit of normal (LLN) was used to define chronic airflow limitation consistent with COPD. Undiagnosed COPD was considered when participants had postbronchodilator FEV1 /FVC < LLN but were not given a diagnosis of COPD. RESULTS Among 30,874 participants with a mean age of 56 years, 55.8% were women, and 22.9% were current smokers. Population prevalence of (spirometrically defined) COPD ranged from 3.6% in Barranquilla, Colombia, to 19.0% in Cape Town, South Africa. Only 26.4% reported a previous lung function test, and only 5.0% reported a previous diagnosis of COPD, whereas 9.7% had a postbronchodilator FEV1 /FVC < LLN. Overall, 81.4% of (spirometrically defined) COPD cases were undiagnosed, with the highest rate in Ile-Ife, Nigeria (98.3%) and the lowest rate in Lexington, Kentucky (50.0%). In multivariate analysis, a greater probability of underdiagnosis of COPD was associated with male sex, younger age, never and current smoking, lower education, no previous spirometry, and less severe airflow limitation. CONCLUSIONS Even with substantial heterogeneity in COPD prevalence, COPD underdiagnosis is universally high. Because effective management strategies are available for COPD, spirometry can help in the diagnosis of COPD at a stage when treatment will lead to better outcomes and improved quality of life. CHEST 2015; 148(4):971-985
COPD is a treatable disease with increasing prevalence worldwide. Treatment aims to stop disease progression, to improve quality of life, and to reduce exacerbations. We aimed to evaluate the ...association of the stage of COPD on adherence to inhaled therapy and the relationship between adherence and COPD exacerbations.
A retrospective analysis of patients hospitalized for acute exacerbation of COPD in a tertiary care hospital in Upper Austria and discharged with a guideline conform inhaled therapy was performed. Follow-up data on medical utilization was recorded for the subsequent 24 months. Adherence to inhaled therapy was defined according to the percentage of prescribed inhalers dispensed to the patient and classified as complete (> 80%), partial (50-80%) or low (< 50%).
Out of 357 patients, 65.8% were male with a mean age of 66.5 years and a mean FEV
of 55.0%pred. Overall, 35.3% were current smokers, and only 3.9% were never-smokers. In 77.0% inhaled triple therapy (LAMA + LABA + ICS) was prescribed. 33.6% showed complete adherence to their therapy (33.2% in men, 34.4% in women), with a mean age of 67.0 years. Mean medication possession ratio by GOLD spirometry class I - IV were 0.486, 0.534, 0.609 and 0.755, respectively (p = 0.002). Hence, subjects with complete adherence to therapy had a significantly lower FEV
compared to those with low adherence (49.2%pred. vs 59.2%pred., respectively; p < 0.001). The risk of exacerbations leading to hospitalization was 10-fold higher in GOLD spirometry class IV compared to GOLD spirometry class I, which was even more evident in multivariate analysis (OR 13.62).
Complete adherence to inhaled therapy was only seen in 33.6% and was higher among those with more severe COPD.
Not applicable.
Background: The clinical spectrum of fibrotic interstitial lung diseases (ILDs) is highly heterogeneous. We aimed to evaluate the prognostic value of widely available baseline biomarkers for the ...improvement of lung function in patients with fibrotic ILDs. Methods: This registry-based study included 142 patients with fibrotic ILDs as defined by the presence of reticulation, traction bronchiectasis or honeycombing on initial high-resolution computed tomography (HRCT). Functional improvement at 1 year was defined as a relative increase of 5% in forced vital capacity (FVC) or of 10% in diffusion capacity for carbon monoxide (DLCO). The prognostic value of baseline biomarkers was evaluated for all patients and the subgroup with anti-inflammatory treatment. Results: At one year, 44 patients showed improvement while 73 showed disease progression. Multivariate analyses found prognostic significance for age < 60 years (OR 5.4; 95%CI 1.9–15.4; p = 0.002), lactate dehydrogenase (LDH) >250 U/L (OR 2.5; 95%CI 1.1–5.8; p = 0.043) and blood monocyte count < 0.8 G/L (OR 3.5; 95%CI 1.1–11.3; p = 0.034). In 84 patients undergoing anti-inflammatory treatment, multivariate analysis revealed age < 60 years (OR 8.5 (95%CI 2.1–33.4; p = 0.002) as the only significant variable. Conclusion: Younger age, a higher LDH and lower blood monocyte count predicted functional improvement in fibrotic ILD patients, while in those treated with anti-inflammatory drugs, only age had significant implications.
Purpose
To evaluate the association of peripheral blood (PBL) and broncho-alveolar lavage (BAL) biomarkers with inflammatory versus fibrotic high-resolution computed tomography (HRCT) findings in ...interstitial lung disease (ILD) patients.
Methods
HRCT findings of 127 consecutive ILD-board patients were semi-quantitatively evaluated: reticulation/honeycombing (RET), traction bronchiectasis (TBR) and emphysema (EMP) were classified as non-inflammatory/fibrotic; consolidations (CON), ground glass opacities (GGO), parenchymal nodules (NDL) and mosaic attenuation (MOS) as active inflammatory. Each HRCT finding was assessed in six distinct lung regions, resulting scores were graded as minimal (0–1 regions involved), medium (2–4) or extensive (5–6). Associations of routinely assessed PBL/BAL biomarkers with these HRCT scores were evaluated using Spearman correlation coefficients and graphical presentation; significance was tested by applying Kruskal–Wallis tests.
Results
Blood neutrophil, lymphocyte and eosinophil fraction, neutrophil to lymphocyte ratio (NLR) and BAL lymphocyte fraction consistently showed opposite correlations with inflammatory versus non-inflammatory/fibrotic HRCT finding scores. Blood lymphocyte fraction significantly differed by graded GGO (
p
= 0.032) and CON (
p
= 0.027) extent, eosinophil fraction by TBR (
p
= 0.006) and NLR by CON (
p
= 0.009). C-reactive protein was significantly related to GGO (
p
= 0.023) and CON (
p
= 0.004), BAL lymphocyte fraction to GGO (
p
= 0.017) extent.
Conclusion
Blood lymphocyte and eosinophil fraction, NLR, CRP and BAL lymphocyte fraction may aid to differentiate inflammatory from non-inflammatory/fibrotic ILD patterns.
Trial registration
This evaluation was based on data from the ILD registry of Kepler University Hospital Linz, as approved by the ethics committee of the Federal State of Upper-Austria (EK Number. I-26-17).
Cancer immunotherapy using immune-checkpoint inhibitors (ICI) has revolutionized the therapeutic landscape of various malignancies like non-small-cell lung cancer or melanoma. Pre-therapy response ...prediction and assessment during ICI treatment is challenging due to the lack of reliable biomarkers and the possibility of atypical radiological response patterns. Positron emission tomography/computed tomography (PET/CT) enables the visualization and quantification of metabolic lesion activity additional to conventional CT imaging. Various biomarkers derived from PET/CT have been reported as predictors for response to ICI and may aid to overcome the challenges clinicians currently face in the management of ICI-treated patients. In this narrative review, experts in nuclear medicine, thoracic oncology, dermatooncology, hemato- and internal oncology, urological and head/neck tumors performed literature reviews in their respective field and a joint discussion on the use of PET/CT in the context of ICI treatment. The aims were to give a clinical overview on present standards and evidence, to identify current challenges and fields of research and to enable an outlook to future developments and their possible implications. Multiple promising studies concerning ICI response assessment or prediction using biomarkers derived from PET/CT alone or as composite biomarkers have been identified for various malignancies and disease stages. Of interest, additional major incentives in the field may evolve from novel tracers specifically targeting immune-checkpoint molecules which could allow not only response assessment and prognosis, but also visualization of histological tumor cell properties like programmed death-ligand (PD-L1) expression in vivo. Despite the broad range of existing literature on PET/CT-derived biomarkers in ICI therapy, implications for daily clinical practice remain elusive. High-quality prospective data are urgently warranted to determine whether patients benefit from the application of PET/CT in terms of prognosis. At the moment, the lack of such evidence as well as the absence of standardized imaging methods and biomarkers still precludes PET/CT imaging to be included in the relevant clinical practice guidelines.
Reference values for lung volumes are necessary to identify and diagnose restrictive lung diseases and hyperinflation, but the values have to be validated in the relevant population. Our aim was to ...investigate the Global Lung Function Initiative (GLI) reference equations in a representative healthy Austrian population and create population-derived reference equations if poor fit was observed.
We analysed spirometry and body plethysmography data from 5371 respiratory healthy subjects (6-80 years) from the Austrian LEAD Study. Fit with the GLI equations was examined using z-scores and distributions within the limits of normality. LEAD reference equations were then created using the LMS method and the generalized additive model of location shape and scale package according to GLI models.
Good fit, defined as mean z-scores between + 0.5 and -0.5,was not observed for the GLI static lung volume equations, with mean z-scores > 0.5 for residual volume (RV), RV/TLC (total lung capacity) and TLC in both sexes, and for expiratory reserve volume (ERV) and inspiratory capacity in females. Distribution within the limits of normality were shifted to the upper limit except for ERV. Population-derived reference equations from the LEAD cohort showed superior fit for lung volumes and provided reproducible results.
GLI lung volume reference equations demonstrated a poor fit for our cohort, especially in females. Therefore a new set of Austrian reference equations for static lung volumes was developed, that can be applied to both children and adults (6-80 years of age).
There is no universal consensus on the best staging system for chronic obstructive pulmonary disease (COPD). Although documents (eg, the Global Initiative for Chronic Obstructive Lung Disease GOLD ...2007) have traditionally used forced expiratory volume in 1 s (FEV1) for staging, clinical parameters have been added to some guidelines (eg, GOLD 2011) to improve patient management. As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aimed to investigate how individual patients were categorised by GOLD 2007 and 2011, and compare the prognostic accuracy of the staging documents for mortality.
We searched reports published from Jan 1, 2008, to Dec 31, 2014. Using data from cohorts that agreed to participate and had a minimum amount of information needed for GOLD 2007 and 2011, we did a patient-based pooled analysis of existing data. With use of raw data, we recalculated all participant assignments to GOLD 2007 I-IV classes, and GOLD 2011 A-D stages. We used survival analysis, C statistics, and non-parametric regression to model time-to-death data and compare GOLD 2007 and GOLD 2011 staging systems to predict mortality.
We collected individual data for 15 632 patients from 22 COPD cohorts from seven countries, totalling 70 184 person-years. Mean age of the patients was 63·9 years (SD 10·1); 10 751 (69%) were men. Based on FEV1 alone (GOLD 2007), 2424 (16%) patients had mild (I), 7142 (46%) moderate (II), 4346 (28%) severe (III), and 1670 (11%) very severe (IV) disease. We compared staging with the GOLD 2007 document with that of the new GOLD 2011 system in 14 660 patients: 5548 (38%) were grade A, 2733 (19%) were grade B, 1835 (13%) were grade C, and 4544 (31%) were grade D. GOLD 2011 shifted the overall COPD severity distribution to more severe categories. There were nearly three times more COPD patients in stage D than in former stage IV (p<0·05). The predictive capacity for survival up to 10 years was significant for both systems (p<0·01) but area under the curves were only 0·623 (GOLD 2007) and 0·634 (GOLD 2011), and GOLD 2007 and 2011 did not differ significantly. We identified the percent predicted FEV1 thresholds of 85%, 55% and 35% as better to stage COPD severity for mortality, which are similar to the ones used previously.
Neither GOLD COPD classification schemes have sufficient discriminatory power to be used clinically for risk classification at the individual level to predict total mortality for 3 years of follow-up and onwards. Increasing intensity of treatment of patients with COPD due to their GOLD 2011 reclassification is not known to improve health outcomes. Evidence-based thresholds should be searched when exploring the prognostic ability of current and new COPD multicomponent indices.
None.
The clinical relevance of newly described nontuberculous mycobacteria is often unclear. We report a case of pulmonary infection caused by Mycobacterium hassiacum in an immunocompetent patient in ...Austria who had chronic obstructive pulmonary disease. Antimicrobial drug susceptibility testing showed low MICs for macrolides, aminoglycosides, fluoroquinolones, tetracyclines, imipenem, and linezolid.
Whether restricted spirometry, i.e. low Forced Vital Capacity (FVC), predicts chronic cardiometabolic disease is not definitely known. In this international population-based study, we assessed the ...relationship between restricted spirometry and cardiometabolic comorbidities.
A total of 23,623 subjects (47.5% males, 19.0% current smokers, age: 55.1 ± 10.8 years) from five continents (33 sites in 29 countries) participating in the Burden of Obstructive Lung Disease (BOLD) study were included. Restricted spirometry was defined as post-bronchodilator FVC < 5th percentile of reference values. Self-reports of physician-diagnosed cardiovascular disease (CVD; heart disease or stroke), hypertension, and diabetes were obtained through questionnaires.
Overall 31.7% of participants had restricted spirometry. However, prevalence of restricted spirometry varied approximately ten-fold, and was lowest (8.5%) in Vancouver (Canada) and highest in Sri Lanka (81.3%). Crude odds ratios for the association with restricted spirometry were 1.60 (95% CI 1.37-1.86) for CVD, 1.53 (95% CI 1.40-1.66) for hypertension, and 1.98 (95% CI 1.71-2.29) for diabetes. After adjustment for age, sex, education, Body Mass Index (BMI) and smoking, the odds ratios were 1.54 (95% CI 1.33-1.79) for CVD, 1.50 (95% CI 1.39-1.63) for hypertension, and 1.86 (95% CI 1.59-2.17) for diabetes.
In this population-based, international, multi-site study, restricted spirometry associates with cardiometabolic diseases. The magnitude of these associations appears unattenuated when cardiometabolic risk factors are taken into account.
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