Occupational Tuberculosis in Denmark through 21 Years Analysed by Nationwide Genotyping.

Tuberculosis (TB) is a well-known occupational hazard. Based on more than two decades (1992-2012) of centralized nationwide genotyping of all Mycobacterium tuberculosis culture-positive TB patients in Denmark, we compared M. tuberculosis genotypes from all cases notified as presumed occupational (N = 130) with M. tuberculosis genotypes from all TB cases present in the country (N = 7,127). From 1992 through 2006, the IS6110 Restriction Fragment Length Polymorphism (RFLP) method was used for genotyping, whereas from 2005 to present, the 24-locus-based Mycobacterial Interspersed Repetitive Unit-Variable Number of Tandem Repeat (MIRU-VNTR) was used. An occupational TB case was classified as clustered if the genotype was 100% identical to at least one other genotype. Subsequently, based on genotype, time period, smear positivity, geography, susceptibility pattern, and any reported epidemiological links between the occupational cases and any potential source cases, the occupational case was categorized as confirmed, likely, possible or unlikely occupationally infected. Among the 130 notified presumed occupational cases, 12 (9.2%) could be classified as confirmed and 46 (35.4%) as unlikely, accounting for nearly half of all cases (44.6%). The remaining 72 cases (55.4%) were categorized as possible. Within this group, 15 cases (11.5%) were assessed to be likely occupational. Our study shows that genotyping can serve as an important tool for disentangle occupational TB in high-income low incidence settings, but still needs to be combined with good epidemiological linkage information

Echocardiographic predictors of exercise capacity and mortality in chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) reduces exercise capacity, but lung function parameters do not fully explain functional class and lung-heart interaction could be the explanation. We evaluated echocardiographic predictors of mortality and six minutes walking distance (6MWD), a marker for quality of life and mortality in COPD. METHODS: Ninety COPD patients (GOLD criteria) were evaluated by body plethysmography, 6MWD and advanced echocardiography parameters (pulsed wave tissue Doppler and speckle tracking). RESULTS: Mean 6MWD was 403 (± 113) meters. All 90 subjects had preserved left ventricular (LV) ejection fraction 64.3% ± 8.6%. Stroke volume decreased while heart rate increased with COPD severity and hyperinflation. In 66% of patients, some degree of diastolic dysfunction was present. Mitral tissue Doppler data in COPD could be interpreted as a sign of low LV preload and not necessarily an intrinsic impairment in LV relaxation/compliance. Tricuspid regurgitation (TR) increased with COPD severity and hyperinflation. Age (p < 0.001), BMI (p < 0.001), DLCO SB (p < 0.001) and TR (p 0.005) were independent predictors of 6MWD and a multivariable model incorporating heart function parameters (adjusted r(2) = .511) compared well to a model with lung function parameters alone (adjusted r(2) = .475). LV global longitudinal strain (p = 0.034) was the only independent predictor of mortality among all baseline, body plethysmographic and echocardiographic variables. CONCLUSIONS: Among subjects with moderate to severe COPD and normal LVEF, GLS independently predicted all-cause mortality. Exercise tolerance correlated with standard lung function parameters only in univariate models; in subsequent models including echocardiographic parameters, longer 6MWD correlated independently with milder TR, better DLCO SB, younger age and lower BMI. We extended the evidence on COPD affecting cardiac chamber volumes, LV preload, heart rate, as well as systolic and diastolic function. Our results highlight lung-heart interaction and the necessity of cardiac evaluation in COPD

Chest x-ray findings in tuberculosis patients identified by passive and active case finding: A retrospective study

Background: Chest x-ray is central in screening and diagnosis of tuberculosis. However, sputum culture remains gold standard for diagnosis. Aim: To establish the rate of normal chest x-rays in tuberculosis patients found by spot sputum culture screening, and compare them to a group identified through passive case finding. Method: Chest x-rays from 39 culture-positive patients, identified by spot sputum culture screening in Copenhagen from 2012 to 2014, were included in the study (spot sputum culture group(SSC)). 39 normal chest x-rays from persons screened by mobile x-ray, and 39 chest x-rays from tuberculosis-patients identified through passive case finding(PCF) were anonymised and randomised. Two respiratory physicians and two radiologists assessed the chest x-rays. Results: The normal chest x-ray rate was higher in the non-tuberculosis control group (median = 32 (82.1%), range = 74.4% – 100%), compared to the SSC group (median = 7 (17.9%), range = 10.3% – 33.3%), and the PCF controls (median = 3(7.7%), range = 2.6% – 15.4%). In the SSC group 14 (35.9%) were categorized as normal by at least one study participant. Conclusion: A substantial minority of patients diagnosed with tuberculosis by spot sputum culture screening, and through passive case finding would not have been identified with chest x-ray alone, highlighting that a normal chest x-ray does not exclude pulmonary tuberculosis. Keywords: Tuberculosis, Chest x-ray changes, Passive case finding, Active case finding, Chest x-ray assessment, Normal chest x-ra

Risk of Malignancy in Patients with Asthma-COPD Overlap Compared to Patients with COPD without Asthma

Chronic inflammation such as asthma may lead to higher risks of malignancy, which may be inhibited by anti-inflammatory medicine such as inhaled corticosteroids (ICS). The aim of this study was to evaluate if patients with asthma-Chronic Obstructive Pulmonary Disease (COPD) overlap have a higher risk of malignancy than patients with COPD without asthma, and, secondarily, if inhaled corticosteroids modify such a risk in a nationwide multi-center retrospective cohort study of Danish COPD-outpatients with or without asthma. Patients with asthma-COPD overlap were propensity score matched (PSM) 1:2 to patients with COPD without asthma. The endpoint was cancer diagnosis within 2 years. Patients were stratified depending on prior malignancy within 5 years. ICS was explored as a possible risk modifier. We included 50,897 outpatients with COPD; 88% without prior malignancy and 20% with asthma. In the PSM cohorts, 26,003 patients without prior malignancy and 3331 patients with prior malignancy were analyzed. There was no association between asthma-COPD overlap and cancer with hazard ratio (HR) = 0.92, CI = 0.78&ndash;1.08, p = 0.31 (no prior malignancy) and HR = 1.04, CI = 0.85&ndash;1.26, and p = 0.74 (prior malignancy) as compared to patients with COPD without asthma. ICS did not seem to modify the risk of cancer. In conclusion, in our study, asthma-COPD overlap was not associated with an increased risk of cancer events

Inclusion flow-chart of presumed occupational TB cases from 1992 through 2012.

<p>Inclusion flow-chart of presumed occupational TB cases from 1992 through 2012.</p

Sedating antihistamine treatment with promethazine in patients with severe COPD with and without asthma: death and severe exacerbations in a nationwide register study

ABSTRACTBackground Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without asthma despite limited knowledge of its effects and side effects. We evaluated if treatment with promethazine had a lower risk of harmful outcome.Methods Nationwide retrospective cohort study of Danish specialist diagnosed outpatients with COPD treated with promethazine or an active comparator (melatonin). Patients with collection of promethazine or melatonin were propensity score matched 1:1. The primary outcome was a composite of severe COPD exacerbations and death from all causes analyzed by Cox proportional hazards regression. We performed an interaction analysis for comorbid asthma.Results In our registry of 56,523 patients with COPD, 5,661 collected promethazine (n = 3,723) or melatonin (n = 1,938). A cohort of 3,290 promethazine- or melatonin-treated patients matched 1:1 was available for the primary analysis.Within 1-year patients treated with promethazine were at higher risk of the primary outcome than matched controls with a Hazard Ratio (HR) of 1.42 (CI 1.27–1.58, p < 0.0001). Similarly, the risk of death was higher for promethazine-treated patients (HR 1.53, CI 1.32–1.77, p < 0.0001). An interaction analysis for comorbid asthma showed no interaction between comorbid asthma and the likelihood of a primary outcome when collecting promethazine (p = 0.19). Adjusted Cox analysis on the entire population indicated a further increased risk with more promethazine (HR for primary outcome among patients collecting ≥ 400 promethazine tablets/year=2.15, CI 1.94–2.38, p<0.0001).Conclusions Promethazine-treated patients with COPD had a concerning excess risk of a composite outcome of severe exacerbations and death from all causes compared to melatonin