Value of Cardiopulmonary Exercise Testing in the Prognosis Assessment of Chronic Obstructive Pulmonary Disease Patients: A Retrospective, Multicentre Cohort Study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases associated with high mortality. Previous studies suggested a prognostic role for peak oxygen uptake (VO2peak) assessed during cardiopulmonary exercise testing (CPET) in patients with COPD. However, most of these studies had small sample sizes or short follow-up periods, and despite their relevance, CPET parameters are not included in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) tool for assessment of severity. OBJECTIVES: We therefore aimed to assess the prognostic value of CPET parameters in a large cohort of outpatients with COPD. METHODS: In this retrospective, multicentre cohort study, medical records of patients with COPD who underwent CPET during 2004-2017 were reviewed and demographics, smoking habits, GOLD grade and category, exacerbation frequency, dyspnoea score, lung function measurements, and CPET parameters were documented. Relationships with survival were evaluated using Kaplan-Meier analysis, Cox regression, and receiver operating characteristic (ROC) curves. RESULTS: Of a total of 347 patients, 312 patients were included. Five-year and 10-year survival probability was 75% and 57%, respectively. VO2peak significantly predicted survival (hazard ratio: 0.886 [95% confidence interval: 0.830; 0.946]). The optimal VO2peak threshold for discrimination of 5-year survival was 14.6 mL/kg/min (area under ROC curve: 0.713). Five-year survival in patients with VO2peak <14.6 mL/kg/min versus ≥ 14.6 mL/kg/min was 60% versus 86% in GOLD categories A/B and 64% versus 90% in GOLD categories C/D. CONCLUSIONS: We confirm that VO2peak is a highly significant predictor of survival in COPD patients and recommend the incorporation of VO2peak into the assessment of COPD severity.

[MDR tuberculosis, Alpha-1-anti-trypsin Deficiency, Cough in a Geriatric Nurse]. / MDR-Tuberkulose, Alpha-1-Antitrypsin-Mangel, Husten bei Altenpflegerin.

Multidrug-resistant tuberculosis (MDR-TB) is of low proportion in comparison to the total number of TB patients, however, due to the necessity of a complex medication with potentially severe and life threatening adverse reactions, long term sequelae, and unfavorable outcome special attention is essential. We report the case of a 30-year-old geriatric nurse with a history of chronic cough and hereditary alpha-1-anti-trypsin deficiency (AATD), who suffered from MDR-TB and experienced a number of severe adverse reactions.

Prevalence Of Chronic Hypercapnia In Severe Chronic Obstructive Pulmonary Disease: Data From The HOmeVent Registry.

Background: Non-invasive ventilation (NIV) has been shown to improve survival and quality of life in COPD patients with chronic hypercapnic respiratory failure. However, the proportion of COPD patients with chronic hypercapnia is not yet known and clinical data enabling better identification of patients are scarce. The HOmeVent registry was initiated to determine the prevalence of chronic hypercapnia in COPD in an outpatient setting and to evaluate the predictors of hypercapnia. Methods: HOmeVent is a multicenter, prospective, observational, non-interventional patient registry that includes COPD patients in GOLD stage 3 or 4. Eligible patients were identified and enrolled in an outpatient setting during routine clinic visits. Assessments included blood gas analyses, pulmonary function testing and quality of life assessment. Results: Ten outpatient clinics in Germany enrolled 231 COPD patients in the registry (135 in GOLD stage 3 (58%) and 96 in GOLD stage 4 (42%)). Arterial carbon dioxide pressure (PaCO2) was ≥45 mmHg in 58 patients (25%); of these, 20 (9%) had PaCO2 ≥50 mmHg. The prevalence of hypercapnia at both cut-off values was numerically higher for patients in GOLD stage 4 versus 3. An increased body mass index, a decreased forced vital capacity and an increased bicarbonate level were significant independent predictors of hypercapnia. The proportion of patients who received NIV was 6% overall and 22% of those with hypercapnia. Conclusion: A relevant proportion of COPD patients in GOLD stage 3 and 4 exhibits chronic hypercapnia and might, therefore, be candidates for long-term domiciliary NIV treatment.

[Spectrum of tuberculous diseases in a pulmonary outpatient clinic]. / Spektrum tuberkulöser Erkrankungen in der pneumologischen Praxis.

BACKGROUND: Although the incidence of 6.6 newly diagnosed tuberculosis (TB) cases per 100,000 inhabitants is in decline in Germany, TB remains a disease of significant epidemiologic importance. PATIENTS AND METHODS: From 04/2001 to 07/2008, a total of 75 TB patients of an internal-pulmonary outpatient clinic had been treated (0.5% of all patients). 58 (77.3%) patients fulfilled the criteria of an active TB, 17 (22.7%) of latent tuberculous infection (LTBI). 68.0% were male (average age men 39.3 +/- 16.9 years [mean +/- standard deviation], women 46.8 +/- 21.5 years; p = not significant). 69.3% of the patients were born in Germany, 30.7% abroad. 84.5% patients had isolated pulmonary, 8.6% additional organ involvement, and 6.9% isolated extrapulmonary TB. 62.1% of active TB cases were microbiologically proven (51.7% microscopically, 43.1% in addition culturally, 6.9% exclusively culturally, 19.0% by polymerase chain reaction [PCR]). RESULTS: Of 23 tests, 52.2% were fully sensitive against the most important first-line drugs ethambutol (M), isoniazid (H), rifampicin (R), pyrazinamide (Z), und streptomycin (S). 13.0% had an isolated resistance against H (4.4%) or S (8.6%), 4.4% a multiple drug resistance (MDR) against R und H, 30.4% a polyresistance (S and H). Symptoms were quite often unspecific, not taken care of, or misinterpreted. CONCLUSION: Diagnosis and therapy of an active or latent TB illness remains, an important task and challenge, necessitating an effective cooperation of outpatient, hospital, and health authority institutions.

Breath condensate nitrite correlates with hyperinflation in chronic obstructive pulmonary disease.

Estimating the degree of pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) is not always straight forward. Standard pulmonary function tests provide only a crude estimate of this important aspect of COPD. In addition, good patient cooperation cannot always be achieved and therefore adds to the uncertainties with regard to the extent of hyperinflation of the lung. The aim of this investigation was to characterize exhaled breath condensate nitrite in volunteers, healthy smokers, and stable COPD (GOLD-stages 0-4) and to compare this parameter with inflammatory markers in exhaled breath condensate and with lung function in order to test the hypothesis that elevated exhaled breath condensate nitrite reflects hyperinflation in COPD. We found a logarithmic correlation of exhaled breath condensate nitrite to residual volume (r=0.75, p<0.0001), total lung capacity (r=0.51, p<0.0001), and thoracic gas volume (r=0.71, p<0.0001) but no correlation of exhaled breath condensate nitrite concentrations with levels of inflammatory cytokines in exhaled breath condensate (interleukin (IL)-8, IL-1beta, IL-6, IL-10, IL-12, and tumor necrosis factor-alpha). Analysis of COPD subgroups revealed a logarithmic correlation of EBC nitrite to residual volume, total lung capacity, and intrathoracic gas volume exclusively for patients characterized by GOLD classes 2, and higher. Our results confirm a relation of exhaled breath condensate nitrite levels and hyperinflation measured by conventional pulmonary function tests. Investigations using isolated lung models and cells stretched in culture also provide insight into this relation. Exhaled breath condensate nitrite may be a biochemical indicator of pulmonary overdistension.

[New perspectives in GINA Asthma Guideline 2006]. / Paradigmenwechsel in der Therapieempfehlung des Asthma bronchiale.

The GINA (Global Initiative for Asthma) 2006 guideline contains far-reaching innovations in asthma management and control. The dose and choice of recommended medication depend on the degree of asthma severity and the quality of asthma control, rather than using the known stepwise severity approach. This flexible scheme gives the treating physician great freedom in the choice of substance used. However, the coexistence of the nonetheless valid four-degree severity grading with the new five-degree therapy scheme may cause confusion. The asthma control-guided new treatment recommendations are based on the experience with the GOAL (Gaining Optimal Asthma controL) trial. Altogether, the GINA 2006 guideline represents a shift of paradigm in asthma management. The efficacy of these recommendations and their practicability, however, have still to be proven. The aim of this review is, first, to introduce these new aspects and, second, to critically discuss advantages and potential disadvantages.

[Diagnostics and therapy of idiopathic pulmonary hemosiderosis]. / Die idiopathische pulmonale Hämosiderose.

Idiopathic pulmonary hemosiderosis (IPH) is a rare clinical entity characterized by recurrent episodes of diffuse alveolar hemorrhage. The disease--also called Ceelen's syndrome--was subsequently defined as a clinical entity comprising the triade of hemoptysis, opacities in X-ray, and anemia, in which the etiology is still unknown. Intensive search for a specific etiology ends up negative, and there are no features, which are specifically pathognomonic for IPH. Therefore, the diagnosis relies solely on the exclusion of other disorders in which diffuse alveolar hemorrhage is a cardinal sign. Acute episodes may occur frequently, eventually leading to lung fibrosis in the chronic stage. Usually, the therapy consists of high doses of corticosteroids, which can be combined with immunosuppressive drugs. In addition to this review, a case having Ceelen's syndrome is presented. After a complicated clinical course, the patient could finally be stabilized with a combination therapy of prednisolone and azathioprine.

[Severe acute respiratory syndrome (SARS)]. / Schweres akutes respiratorisches Syndrom (SARS).

The sudden appearance of the severe acute respiratory syndrome (SARS) in 2003 demonstrated to the world at large that despite the high standard of medical care in affected countries, a highly contagious emerging infectious disease could spread rapidly worldwide. By application and improvement of stringent infection control measures, a further spread of SARS could be stopped and the disease could so far be defeated. In the meantime, decisive progress in the knowledge about the structure and further characteristics of the SARS coronavirus (SARS-CoV) have been made, including the likely virus reservoir and the ways of spread. Validated diagnostic tests are now available and are further being improved. Effective vaccines and antiviral agents are being developed. Of imminent importance to prepare against a resurgence of SARS, remain, besides an exact knowledge about the viral pathogen and its possible further behavior, constant vigilance, early recognition, and instant isolation of suspected cases of SARS.

Exhaled breath condensate cytokine patterns in chronic obstructive pulmonary disease.

Differences in cytokine patterns in stable chronic obstructive pulmonary disease (COPD), exacerbated COPD, smokers without apparent COPD, and healthy volunteers should be of interest for pathophysiological and therapeutic reasons. Methods including lavage, biopsy and sputum have been employed to investigate cytokines in the lung. For asystematic comparison, exhaled breath condensate (EBC) appears to be well suited. We investigated healthy volunteers, smokers without apparent COPD, stable and exacerbated COPD patients (+/- inhalative steroids) and finally those whose exacerbation made mechanical ventilation inevitable, for a more complete picture of inflammatory cytokines in COPD. We chose EBC because it is non-invasive and can be used repeatedly in spontaneous breathing individuals and during mechanical ventilation. EBC cytokines (IL-1 beta, IL-6, IL-8, IL-10, IL-12 p 70, TNF-alpha) were assayed from a single sample using a multiplex array test kit. We observed a significant increase of all cytokines in acute exacerbation compared to stable COPD, smokers, and volunteers. Stable COPD and volunteers exhibited only small differences in cytokine pattern with respect to IL-1 beta and IL-12 (P<0.01). Smokers had increased levels of all investigated cytokines (P<0.01) compared to non-smokers and, with the exception of IL-1 beta, to stable COPD. Inhaled steroids resulted in reduced levels of IL-1 beta, IL-6, IL-8, IL-10, and IL-12 (all: P<0.01) in stable COPD (all: ex-smokers) with dose dependency for IL-8, IL-1 beta and IL-12. EBC analysis successfully characterized important differences in stable COPD compared to exacerbation or smoking and non-smoking healthy individuals.

Differential diagnosis of pleural effusions by fuzzy-logic-based analysis of cytokines.

Pleural effusions can be caused by highly different underlying diseases and are characterized by complex interactions of various local and circulating cells as well as numerous soluble parameters like interleukins (IL). Knowledge about this complex network could help to indicate underlying disease. Therefore, we have investigated immunoreactive concentrations of IL-4, IL-6, IL-11, IL-15, IL-17, IL-18, and tumor necrosis factor-alpha (TNF-alpha) in pleural effusions and peripheral blood from patients with tuberculosis, bronchial carcinoma and other carcinomas as well as congestive heart failure (CHF) and pneumonias. To determine the value of cytokine measurement for differential diagnosis, statistical and fuzzy-logic methods were applied. Quantitative analysis showed high concentrations of IL-6 and IL-11 only in pleural effusions. IL-15, IL-17, IL-18 and TNF-alpha could be detected also in blood plasma. Lowest amounts were detected in CHF indicating the non-inflammatory origin of effusions. Statistical analysis did not provide evidence for diagnostic relevance of singular cytokines. Fuzzy-logic analysis was able to assign patients to the correct diseases with 80% accuracy using IL-6 and IL-15 measurement. Our results confirm the pathogenetic role of these cytokines in pleural effusions. Fuzzy-logic-based procedures may help to characterize and distinguish effusions of unknown origin even in small patient groups.

[Pulmonary and pleural tuberculosis in the elderly]. / Tuberkulose der Lunge und Pleura im Alter.

With the increase of the proportion of the elderly in the total population more cases of pulmonary and extrapulmonary tuberculosis (TB) are observed in this age group as well. Symptoms of TB are unspecific, often less apparent in the elderly, and may therefore cause a delay in the diagnostic process. A history of TB and comorbidities are more common in elder as compared to younger TB patients. The tuberculin skin test is less frequently positive. The interferon-gamma-release assay is complementary and together with clinical, radiologic, and bacteriologic test results helpful for the diagnosis or the exclusion of an active or latent TB infection. Medical treatment of TB in the elderly follows the established guidelines in the same way as for younger patients. The likelihood of drug-induced side effects and interactions with concomitant medications, however, is increased. Comorbidity and age-related immunosuppression may lead to a delay in the healing process. Higher age, comorbidity, and immunosuppression are predictors of an increased TB mortality. Even in a low-incidence country like Germany, TB should be recognized as an explanation for clinical symptoms particularly in the elderly patient group in order to allow an early diagnosis and therapy and thus a reduction of mortality and prevention of a further spread of this disease.