Economic burden of bronchiectasis in Germany.

Estimates of healthcare costs for incident bronchiectasis patients are currently not available for any European country.Out of a sample of 4 859 013 persons covered by German statutory health insurance companies, 231 new bronchiectasis patients were identified in 2012. They were matched with 685 control patients by age, sex and Charlson Comorbidity Index, and followed for 3 years.The total direct expenditure during that period per insured bronchiectasis patient was EUR18 634.57 (95% CI EUR15 891.02-23 871.12), nearly one-third higher (ratio of mean 1.31, 95% CI 1.02-1.68) than for a matched control (p<0.001). Hospitalisation costs contributed to 35% of the total and were >50% higher in the bronchiectasis group (ratio of mean 1.56, 95% CI 1.20-3.01; p<0.001); on average, bronchiectasis patients spent 4.9 (95% CI 2.27-7.43) more days in hospital (p<0.001). Antibiotics expenditures per bronchiectasis outpatient (EUR413.81) were nearly 5 times higher than those for a matched control (ratio of mean 4.85, 95% CI 2.72-8.64). Each bronchiectasis patient had on average 40.5 (95% CI 17.1-43.5) sick-leave days and induced work-loss costs of EUR4230.49 (95% CI EUR2849.58-5611.20). The mortality rate for bronchiectasis and matched non-bronchiectasis patients after 3 years of follow-up was 26.4% and 10.5%, respectively (p<0.001). Mortality in the bronchiectasis group was higher among those who also had chronic obstructive lung disease than in patients with bronchiectasis alone (35.9% and 14.6%, respectively; p<0.001).Although bronchiectasis is considered underdiagnosed, the mortality and associated financial burden in Germany are substantial.

Value of flexible bronchoscopy in the pre-operative work-up of solitary pulmonary nodules.

The diagnostic value of flexible bronchoscopy in the pre-operative work-up of solitary pulmonary nodules (SPN) is still under debate among pneumologists, radiologists and thoracic surgeons. In a prospective observational manner, flexible bronchoscopy was routinely performed in 225 patients with SPN of unknown origin. Of the 225 patients, 80.5% had lung cancer, 7.6% had metastasis of an extrapulmonary primary tumour and 12% had benign aetiology. Unsuspected endobronchial involvement was found in 4.4% of all 225 patients (or in 5.5% of patients with lung cancer). In addition, flexible bronchoscopy clarified the underlying aetiology in 41% of the cases. The bronchoscopic biopsy results from the SPN were positive in 84 (46.5%) patients with lung cancer. Surgery was cancelled due to the results of flexible bronchoscopy in four cases (involvement of the right main bronchus (impaired pulmonary function did not allow pneumonectomy) n=1, small cell lung cancer n=1, bacterial pneumonia n=2), and the surgical strategy had to be modified to bilobectomy in one patient. Flexible bronchoscopy changed the planned surgical approach in five cases substantially. These results suggest that routine flexible bronchoscopy should be included in the regular pre-operative work-up of patients with SPN.

Old ideas to innovate tuberculosis control: preventive treatment to achieve elimination.

The introduction of new rapid diagnostic tools for tuberculosis (TB) and the promising TB drugs pipeline together with the development of a new World Health Organization Strategy post 2015 allows new discussions on how to direct TB control. The European Respiratory Society's European Forum for TB Innovation was created to stimulate discussion on how to best take advantage of old and new opportunities, and advances, to improve TB control and eventually progress towards the elimination of TB. While TB control is aimed at reducing the incidence of TB by early diagnosis and treatment of infectious cases of TB, TB elimination requires focus on sterilising the pool of latently infected individuals, from which future TB cases would be generated. This manuscript describes the three core components that are necessary to implement the elimination strategy fully. 1) Improve diagnosis of latent TB infected individuals. 2) Improve regimens to treat latent TB infection. 3) ensure public health commitment to make both 1) and 2) possible. Old and new evidence is critically described, focusing on the European commitment to reach elimination and on the innovative experiences and best practices available.

Negative and positive predictive value of a whole-blood interferon-γ release assay for developing active tuberculosis: an update.

RATIONALE: only limited data are available on the predictive value of interferon-γ release assays for progression from latent tuberculosis infection to active tuberculosis (TB). OBJECTIVES: to build on our initial study comparing the QuantiFERON-TB Gold in-tube assay (QFT) with the tuberculin skin test (TST) in close contacts of patients with TB and evaluating progression to active TB for up to 4 years. METHODS: a cohort of close contacts of smear-positive index cases established between May 2005 and April 2008 was tested with QFT and TST. Through April 2010, progressors to active TB were consecutively recorded. MEASUREMENTS AND MAIN RESULTS: of the 1,414 contacts (141 children), 1,033 were still resident in Hamburg at the end of the study period, and results of both tests were available for 954. QFT, but not TST, results were associated with exposure time (P < 0.0001). For QFT, 198 of 954 (20.8%) were positive; 63.3% (604) were TST positive at greater than 5 mm and 25.4% at greater than 10 mm. Nine hundred and three contacts refused chemoprevention and 19 developed active TB. All 19 (100%) had been QFT positive with a progression rate of 12.9% (19 of 147) over the observation period. Corresponding values for the TST were significantly lower: 89.5% (17 of 19) and 3.1% (17 of 555) at greater than 5 mm, and 52.6% (10 of 19) and 4.8% (10 of 207) at greater than 10 mm, respectively. The progression rate of 28.6% (6 of 21) for QFT-positive children was significantly higher than 10.3% (13 of 126) for adults (P = 0.03). CONCLUSIONS: results suggest that QFT is more reliable than the TST for identifying those who will soon progress to active TB, especially in children.

Predictive value of a whole blood IFN-gamma assay for the development of active tuberculosis disease after recent infection with Mycobacterium tuberculosis.

RATIONALE: Numerous studies have been published on the new Mycobacterium tuberculosis (MTB)-specific IFN-gamma release assays. However, their prognostic value for progression from latent tuberculosis infection (LTBI) to active TB has yet to be established. OBJECTIVES: To compare the QuantiFERON-TB Gold In-Tube assay (QFT) with the tuberculin skin test (TST) in recently exposed close contacts of active TB cases with respect to their development of TB disease within 2 years. METHODS: Close contacts (n = 601) of MTB-positive source cases underwent both TST and QFT testing and were subsequently observed for 103 (+/-13.5) weeks. Risk factors for MTB infection were evaluated by multivariate analysis. MEASUREMENTS AND MAIN RESULTS: For the TST, 40.4% (243/601) of contacts were positive at a 5-mm cutoff, whereas only 66 (11%) were QFT positive. QFT positivity, but not TST, was associated with exposure time (P < 0.0001). Six contacts progressed to TB disease within the 2-year follow-up. All were QFT positive and had declined preventive treatment, equating to a progression rate of 14.6% (6/41) among those who were QFT positive. The progression rate for untreated TST-positive subjects was significantly lower (P < 0.003), at 2.3% (5 of 219), and one subject who progressed was TST negative. CONCLUSIONS: Results suggest that QFT is a more accurate indicator of the presence of LTBI than the TST and provides at least the same sensitivity for detecting those who will progress to active TB. The high rate of progression to active TB of those who are QFT positive (14.6%), which is far greater than the 2.3% found for those who are TST positive, has health and economic implications for enhanced TB control, particularly if this higher progression rate is seen in studies of other at-risk populations.

Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study.

BACKGROUND: Talc is the most effective chemical pleurodesis agent for patients with malignant pleural effusion. However, concerns have arisen about the safety of intrapleural application of talc, after reports of development of acute respiratory distress syndrome in 1-9% of treated patients. Our aim was to establish whether use of large-particle-size talc is safe in patients with malignant pleural effusion. METHODS: We did a multicentre, open-label, prospective cohort study of 558 patients with malignant pleural effusion who underwent thoracoscopy and talc poudrage with 4 g of calibrated French large-particle talc in 13 European hospitals, and one in South Africa. The primary endpoint was the occurrence of acute respiratory distress syndrome after talc pleurodesis. FINDINGS: No patients developed acute respiratory distress syndrome (frequency 0%, one-sided 95% CI 0-0.54%). 11 (2%) patients died within 30 days. Additionally, seven patients had non-fatal post-thoracoscopy complications (1.2%), including one case of respiratory failure due to unexplained bilateral pneumothorax. INTERPRETATION: Use of large-particle talc for pleurodesis in malignant pleural effusion is safe, and not associated with the development of acute respiratory distress syndrome.

Microbiologic Outcome of Interventions Against Mycobacterium avium Complex Pulmonary Disease: A Systematic Review.

OBJECTIVE: Pulmonary disease (PD) caused by Mycobacterium avium complex (MAC) is increasing worldwide. We conducted a systematic review of studies that include microbiologic outcomes to evaluate current macrolide-based treatment regimens. METHODS: We searched literature published before April 2017 by using the MEDLINE, Cochrane, and Embase databases. Risk of bias in randomized trials was assessed using the Cochrane tool. RESULTS: We retrieved 333 citations and evaluated 42 studies including 2,748 patients: 18 studies were retrospective chart reviews, 18 were prospective, and six were randomized. The weighted average proportion of sputum culture conversions in macrolide-containing regimens after subtracting posttreatment microbiologic recurrences was 52.3% (95% CI, 44.7%-59.9%). Using the triple-drug regimens recommended by the American Thoracic Society (ATS) achieved treatment success in 61.4% (95% CI, 49.7%-72.5%), which further increased to 65.7% (95% CI, 53.3%-77.4%) when drugs were taken for at least 1 year by patients who were macrolide susceptible and had previously untreated MAC. The overall risk of bias was low in five of the six randomized trials. However, selective outcome reporting because of a posteriori exclusion of initially included patients (14.0%), uncompleted treatment (17.6%), and inconsistent use of outcome parameters (17 definitions of treatment success) hampered the comparison of nonrandomized trials. CONCLUSIONS: To date, randomized studies on treatment outcome in patients with MAC PD are scarce. Long-term treatments with ATS-recommended regimens for patients who are macrolide susceptible are superior to other macrolide-based therapies. A standardized definition of treatment success and genotypic distinction between reinfection and relapse by means of pretreatment and posttreatment identification of MAC species in cases of microbiologic recurrences may help to optimize evaluation of treatment regimens in the future.

Cost-effectiveness of interferon-gamma release assay screening for latent tuberculosis infection treatment in Germany.

OBJECTIVES: To assess the cost-effectiveness of the new QuantiFERON-TB Gold In-Tube (QFT-G) [Cellestis; Carnegie, VIC, Australia] assay for screening and treating of persons who have had close contact with tuberculosis (TB) patients and are suspected of having latent tuberculosis infection (LTBI) [hereafter called close-contacts] in Germany. METHODS: The health and economic outcomes of isoniazid treatment of 20-year-old close-contacts were compared in a Markov model over a period of 20 years, using two different cutoff values for the tuberculin skin test (TST), the QFT-G assay alone, or the QFT-G assay as a confirmatory test for the TST results. RESULTS: QFT-G assay-based treatment led to cost savings of $542.9 and 3.8 life-days gained per LTBI case. TST-based treatment at a 10-mm induration size cutoff gained $177.4 and 2.0 life-days gained per test-positive contact. When the cutoff induration size for the TST was reduced to 5 mm, the incremental cost-effectiveness ratio fell below the willingness-to-pay threshold ($30,170 per life-years gained) but resulted in unnecessary treatment of 77% of contacts owing to false-positive TST results. Combination with the 5-mm induration size TST cutoff value compared to the results of the QFT-G assay alone reduced the total costs per 1,000 contacts by 1.8% to $222,869. The number treated to prevent 1 TB case was 22 for the two QFT-G assay-based procedures, 40 for the TST at a cutoff induration size of 10 mm, and 96 for the TST at a cutoff induration size of 5 mm. When the sensitivity rates of the TST and the QFT-G assay were compounded, the QFT-G assay strategy alone was slightly less costly (0.6%) than the two-step approach. CONCLUSIONS: Using the QFT-G assay, but especially combining the QFT-G assay following the TST screening of close-contacts at a cutoff induration size of 5 mm before LTBI treatment is highly cost-effective in reducing the disease burden of TB.

Consequences of tuberculosis among asylum seekers for health care workers in Germany.

BACKGROUND: Immigrants have been contributing to the incidence of tuberculosis (TB) in Germany for many years. The current wave of migration of asylum seekers to Germany may increase that figure. Healthcare workers (HCW) who look after refugees not only in hospitals and medical practices but also in aid projects may be exposed to cases of TB. METHODS: The incremental TB cases arising from imported TB as well as from TB cases that developed later in refugees were calculated in a Markov model over a period of 5 years. Infectious and non-infectious susceptible TB and multidrug-resistant TB (MDR-TB) cases were determined separately. In addition, the total amount of latent TB in contact persons and the risk of infection by HCW were estimated. Due to uncertainty of future refugee flows to Europe, different scenarios were considered in univariate and multivariate sensitivity analysis. RESULTS: Assuming a decrease in immigration by half each year to the bottom line of 2014, and in light of the current number of 800,000 asylum seekers, we calculated an additional 10,090 TB cases by the end of the fifth year (5976 cases of infectious pulmonary TB and 143 cases of pulmonary MDR-TB). In case of an unchanging influx of asylum seekers over the 5-year period, 19,031 TB cases would arise, 377 of which infectious MDR-TB. Eighty -seven ensuing TB cases would develop in HCW in the same period, 3 of which MDR-TB cases. CONCLUSIONS: Although the total number of TB cases in HCW expected to ensue from the current influx of asylum seekers is rather small, the 3 MDR-TB cases we calculated have to be taken seriously. We consider it essential to increase awareness of protective measures such as respiratory masks and, in the event of documented exposure, of supply-oriented occupational health screening.

Clinical Aspects of Adult Tuberculosis.

Tuberculosis (TB) in adults can present in a large number of ways. The lung is the predominant site of TB. Primary pulmonary TB should be distinguished from postprimary pulmonary TB, which is the most frequent TB manifestation in adults (70%-80% cases). Cough is common, although the chest radiograph often raises suspicion of disease. Sputum sampling is a key step in the diagnosis of TB, and invasive procedures such as bronchoscopy may be necessary to achieve adequate samples for diagnosis. Extrapulmonary involvement, which may present many years after exposure, occurs in a variable proportion of cases (20%-45%). This reflects the country of origin of patients and also the frequency of associated human immunodeficiency virus (HIV) coinfection. In the latter case, the presentation of TB is often nonspecific, and care needs to be taken to not miss the diagnosis. Anti-TB therapy should be given in line with proven (or assumed) drug resistance. In extrapulmonary TB, adjunctive therapeutic measures may be indicated; although in all cases, support is often required to ensure that people are able to complete treatment with minimal adverse events and maximal adherence to the prescribed regimen, and so reduce risk of future disease for themselves and others.

Screening of COPD patients for abdominal aortic aneurysm.

PURPOSE: Screening for abdominal aortic aneurysm (AAA) in "men aged over 65 years who have ever smoked" is a recommended policy. To reduce the number of screenings, it may be of value to define subgroups with a higher prevalence of AAA. Since chronic obstructive pulmonary disease (COPD) and AAA are associated with several common risk factors, this study investigates the prevalence of AAA in COPD patients. PATIENTS AND METHODS: Patients with COPD were identified via the hospital information system. Inclusion criteria were: COPD stage I-IV, ability to give full consent, and age >18 years; exclusion criteria were: patient too obese for an ultrasound check, previously diagnosed AAA, prior surgery for AAA, or ethical grounds such as concomitant advanced malignant or end-stage disease. The primary endpoint of the study was an aortic diameter measured by ultrasound of ≥30 mm. Defined secondary endpoints were evaluated on the basis of medical records and interviews. RESULTS: Of the 1,180 identified COPD patients, 589 were included in this prospective study. In 22 patients (3.70%), the aortic diameter was ≥30 mm, representing an AAA prevalence of 6.72% among males aged >65 years. The risk of AAA increased with the following comorbidities/risk factors: male sex (odds ratio [OR] 2.98), coronary heart disease (OR 2.81), peripheral arterial occlusive disease (OR 2.47), hyperlipoproteinemia (OR 2.77), AAA in the family history (OR 3.95), and COPD stage I/II versus IV (OR 1.81). CONCLUSION: The overall AAA prevalence of 3.7% in our group of COPD patients is similar to that of the general population aged >65 years. However, the frequency of AAA in male COPD patients aged >65 years is considerably higher (6.72%) and increased further still in those individuals with additional comorbidities/risk factors. Defining subgroups with a higher risk of AAA may increase the efficiency of screening.

Talc pleurodesis: basic fibroblast growth factor mediates pleural fibrosis.

STUDY OBJECTIVES: Patients with recurrent pleural effusions secondary to malignancy are subjected to pleurodesis if clinically indicated. Pleurodesis involves the introduction of a sclerosing agent into the pleural space. Talc is one of the most commonly used sclerosing agents in treating patients with recurrent, symptomatic malignant pleural effusions. However, the mechanisms whereby talc mediates pleural fibrosis remain unclear. We hypothesized that the intrapleural instillation of talc induces the pleural mesothelial production of basic fibroblast growth factor (bFGF), which is responsible for pleural fibrosis. METHODS: Samples of pleural fluid collected from 23 patients with malignant pleural effusions and 6 patients with congestive heart failure (control group) were included in this study. A tumor grading scale (1 to 9) was used to demonstrate the extent of the tumor. In vitro pleural mesothelial cells (PMCs) were activated with talc, and the conditioned medium was collected to evaluate bFGF levels by enzyme-linked immunosorbent assay. The bFGF-induced proliferation of fibroblasts was studied by [(3)H]thymidine incorporation. The messenger RNA expression of bFGF in talc-activated PMCs was determined by Northern analysis. RESULTS: In this study, we demonstrated that patients who have undergone successful pleurodesis following intrapleural talc insufflation have significantly higher levels of bFGF in their pleural fluid compared to those who do not respond to pleurodesis. In addition, we found a significant negative correlation between bFGF levels and tumor size. Talc-activated PMCs produce significantly higher levels of bFGF compared to control, which correlates with bFGF messenger RNA expression in PMCs stimulated with talc. The neutralization of pleural fluids and conditioned medium from talc-stimulated PMCs with bFGF antibodies significantly inhibits the bFGF-induced proliferation of pleural fibroblasts. CONCLUSIONS: An important outcome of this study was the finding that patients with extensive tumor involvement of the pleural mesothelium have a significantly lower pleural fluid bFGF response to talc compared to those who have limited involvement. Patients with limited pleural disease and higher bFGF responses go on to have successful pleurodesis, demonstrating that the presence of a mesothelium that is free of tumor enhances the possibility of success. In vitro PMCs stimulated with talc release biologically active bFGF.