Idiopathic Pulmonary Fibrosis Among Young Patients: Challenges in Diagnosis and Management.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is considered a disease of older patients, being rare in patients ≤ 50 years. Still, IPF can occur in younger patients, but this particular patient group is not well characterised so far. The aim of this study was to compare the diagnostic certainty, clinical features, comorbidities and survival in young versus older IPF patients. METHODS: We reviewed our medical records from February 2011 until February 2015, to identify IPF patients, who were then classified as young (≤ 50 years) or older IPF (> 50 years). Radiographic and histological findings, lung function parameters, comorbidities, disease progression and survival were analysed and compared between the two groups. RESULTS: Of 440 patients with interstitial lung disease, 129 patients with IPF were identified, including 30 (23.3%) ≤50 years and 99 (76.7%) > 50 years. There were no differences between age groups in baseline demographics; younger patients were less likely to have a confirmed diagnosis by high-resolution computed tomography (p = 0.014), more likely to require a biopsy (p = 0.08) and less likely to have received antifibrotic therapy (p = 0.006). Despite an overall limited prognosis, younger patients had a significantly better median survival after diagnosis (p = 0.0375), with a significantly higher proportion of older patients dying due to respiratory failure (p = 0.0383). CONCLUSION: IPF patients under the age of 50 years have similar features and clinical course compared to older IPF patients. These patients should be diagnosed by adopting a multidisciplinary team approach, potentially benefitting from earlier intervention with effective antifibrotic therapy.

Comparing Azole Plasma Trough Levels in Lung Transplant Recipients: Percentage of Therapeutic Levels and Intrapatient Variability.

BACKGROUND: This study compared therapeutic azole plasma trough levels (APL) of the azole antimycotics itraconazole (ITR), voriconazole (VOR), and posaconazole (POS) in lung transplant recipients and analyzed the influencing factors. In addition, intrapatient variability for each azole was determined. METHODS: From July 2012 to July 2015, 806 APL of ITR, VOR, posaconazole liquid (POS-Liq), and posaconazole tablets (POS-Tab) were measured in 173 patients of the Munich Lung Transplantation Program. Therapeutic APL were defined as follows: ITR, ≥700 ng/mL; VOR, 1000-5500 ng/mL; and POS, ≥700 ng/mL (prophylaxis) and ≥1000 ng/mL (therapy). RESULTS: VOR and POS-Tab reached the highest number of therapeutic APL, whereas POS-Liq showed the lowest percentage (therapy: ITR 50%, VOR 70%, POS-Liq 38%, and POS-Tab 82%; prophylaxis: ITR 62%, VOR 85%, POS-Liq 49%, and POS-Tab 76%). Risk factors for subtherapeutic APL of all azoles were the azole dose (ITR, P < 0.001; VOR, P = 0.002; POS-Liq, P = 0.006) and age over 60 years (ITR, P = 0.003; VOR, P = 0.002; POS-Liq, P = 0.039; POS-Tab, P < 0.001). Cystic fibrosis was a significant risk factor for subtherapeutic APL for VOR and POS-Tab (VOR, P = 0.002; POS-Tab, P = 0.005). Double lung transplantation (LTx) was significantly associated with less therapeutic APL for VOR and POS-Liq (VOR, P = 0.030; POS-Liq, P < 0.001). Concomitant therapy with 80 mg pantoprazole led to significantly fewer therapeutic POS APL as compared to 40 mg (POS-Liq, P = 0.015; POS-Tab, P < 0.001). VOR displayed the greatest intrapatient variability (46%), whereas POS-Tab showed the lowest (32%). CONCLUSIONS: Our study showed that VOR and POS-Tab achieve the highest percentage of therapeutic APL in patients with LTx; POS-Tab showed the lowest intrapatient variability. APL are significantly influenced by azole dose, age, cystic fibrosis, type of LTx, and comedication with proton-pump inhibitors. Considering the high number of subtherapeutic APL, therapeutic drug monitoring should be integrated in the post-LTx management.

Suspected pulmonary embolism in patients with pulmonary fibrosis: Discordance between ventilation/perfusion SPECT and CT pulmonary angiography.

BACKGROUND AND OBJECTIVE: Pulmonary embolism (PE) is a common differential diagnosis in patients with pulmonary fibrosis presenting with a clinical deterioration. Both ventilation/perfusion (V/Q)-single photon emission computed tomography (SPECT) and computed tomographic pulmonary angiography (CTPA) are routinely used to detect PE. However, the value of V/Q-SPECT and CTPA in this scenario has not been studied so far. We aimed to investigate the concordance of V/Q-SPECT and CTPA in patients with pulmonary fibrosis and suspicion of pulmonary embolism. METHODS: A total of 22 consecutive patients with pulmonary fibrosis and clinical deterioration who underwent both V/Q-SPECT and CTPA were included in the study and analyzed for the presence of pulmonary embolism. RESULTS: Nine of 22 patients (41%) had evidence for pulmonary embolism in V/Q-SPECT, and two of these patients had matching evidence for pulmonary embolism in CTPA. In the other seven patients with positive findings in V/Q-SPECT, no evidence of pulmonary embolism was found in CTPA. None of the 13 patients with a negative V/Q-SPECT had evidence for pulmonary embolism in CTPA. CONCLUSION: In patients with pulmonary fibrosis and suspected pulmonary embolism, pulmonary embolism is detected more frequently by V/Q-SPECT than by CTPA. Thromboembolic disease is identified on CTPA only in a minority of patients with positive findings on V/Q-SPECT. When making treatment decisions, clinicians should be aware of the high rate of discordant findings in V/Q-SPECT and CTPA in this specific patient population.

Haemodynamic changes in pulmonary hypertension in patients with interstitial lung disease treated with PDE-5 inhibitors.

BACKGROUND AND OBJECTIVE: Interstitial lung diseases (ILD) are often associated with pulmonary hypertension (PH). This study aimed to evaluate the therapeutic benefit of phosphodiesterase-5 (PDE-5) inhibitors in pulmonary hypertension secondary to ILD. METHODS: Patients with ILD and PH were treated with sildenafil or tadalafil. Right heart catheterization was performed before and after a minimum of 3-month treatment. In addition, lung function, 6-min walk distance (6MWD) and plasma brain natriuretic peptide (BNP) concentration were assessed. RESULTS: Ten ILD patients (three female, mean age 64.4 ± 9.0 years, six with idiopathic pulmonary fibrosis (IPF), four with hypersensitivity pneumonitis, (HP)) with significant precapillary PH (mean pulmonary artery pressure (PAPm) ≥ 25 mmHg, pulmonary vascular resistance (PVR) > 280 dyn*s*cm(-5) ; pulmonary artery wedge pressure (PAWPm) ≤ 15 mmHg) were treated with either sildenafil (n = 5) or tadalafil (n = 5). Pulmonary haemodynamics were severely impaired at baseline (PAPm 42.9 ± 5.4 mmHg; cardiac index (CI) 2.7 ± 0.6 L/min/m2; PVR 519 ± 131 dyn × sec × cm(-5)). After mean follow-up of 6.9 ± 5.8 months an increase in CI (2.9 ± 0.7 L/min/m2 , P = 0.04) and a decrease in PVR (403 ± 190 dyn × sec × cm(-5) , P = 0.03) were observed. 6MWD and BNP did not change significantly. CONCLUSIONS: Our data suggest that treatment with PDE-5 inhibitors improves pulmonary haemodynamic patients with PH secondary to ILD.

Impact of asthma in Europe: A comparison of web search data in 21 European countries.

Background: Asthma is a chronic inflammatory disorder of the airways and one of the most important non-communicable diseases worldwide. Analyzing crowdsourced data can help understand public interest and unmet needs as well as potential factors influencing search behavior. Objective: The study aimed to investigate asthma-related web search data in Europe to identify possible regional and seasonal variations and to assess public interest. Methods: Google Ads Keyword Planner was used to measure search volume for search terms related to asthma, allergic asthma, and bronchial asthma in 21 European countries between January 2018 and December 2021. The top 10 keywords of each country were categorized qualitatively. Search volume per 100 000 inhabitants was descriptively assessed in terms of regional and seasonal trends. Spearman correlations between search volume and pollen concentration as well as coronavirus disease (COVID-19) cases were investigated. Results: The median search volume per 100 000 inhabitants for asthma and allergic asthma was highest in Northern and Western Europe, while the highest search volume for bronchial asthma was observed in Western and Eastern regions. A seasonal trend was identified for all search terms and in all regions. Correlations were found between search frequency and pollen load and search behavior and COVID-19 cases. Overall, Europeans were most interested in the diseases in general, their treatment options, and symptoms. Conclusion: These results highlighted the need for reliable and region-specific information about the disease and for public campaigns to improve asthma control. The study also emphasizes the importance of using crowdsourced data for a more encompassing overview beyond conventional healthcare data.

The Munich-LTX-Score: predictor for survival after lung transplantation.

BACKGROUND: The purpose of this study was to create a prognostic score calculated one yr after LTX based on post-transplant factors inclusive of donor and recipient characteristics that could be used to predict long-term survival in patients after lung transplantation (LTX). METHODS: Uni- and multivariate analysis in 206 consecutive LTX patients identified independent risk factors for post-transplant mortality and onset of bronchiolitis obliterans syndrome. Munich-LTX-Score is devised by summing up each identified risk factor. RESULTS: Multivariate analyses revealed acute rejection, lymphocytic bronchiolitis, donor age ≥ 55 yr, and HLA-A ≥ 2-/DR ≥ 2 mismatch and single LTX to be independent negative predictors for long-term survival (p < 0.05). Munich-LTX-Score identified three discrete groups: low-, moderate-, and high risk. The actuarial five-yr survival after score calculation one yr after LTX of the entire cohort was 58%, compared with 91% in low-, 54% in moderate-, and 0% in the high-risk group (p < 0.001). CONCLUSION: Within our cohort of patients calculation of the Munich-LTX-Score, consisting of donor-, recipient-, and post-transplant characteristics, one yr after LTX allowed to predict long-term survival of lung transplant recipients. After prospective validation, this score could identify patients who may benefit from intensified surveillance after LTX.

Computed Tomography Imaging in ILD: New Trends for the Clinician.

Today, radiological methods are an integral part of diagnostics in lung diseases, and they provide important information regarding the evaluation of interstitial lung diseases (ILDs) [...].

Dark-field chest x-ray imaging: first experience in patients with alpha1-antitrypsin deficiency.

BACKGROUND: Spirometry and conventional chest x-ray have limitations in investigating early emphysema, while computed tomography, the reference imaging method in this context, is not part of routine patient care due to its higher radiation dose. In this work, we investigated a novel low-dose imaging modality, dark-field chest x-ray, for the evaluation of emphysema in patients with alpha1-antitrypsin deficiency. METHODS: By exploiting wave properties of x-rays for contrast formation, dark-field chest x-ray visualises the structural integrity of the alveoli, represented by a high signal over the lungs in the dark-field image. We investigated four patients with alpha1-antitrypsin deficiency with a novel dark-field x-ray prototype and simultaneous conventional chest x-ray. The extent of pulmonary function impairment was assessed by pulmonary function measurement and regional emphysema distribution was compared with CT in one patient. RESULTS: We show that dark-field chest x-ray visualises the extent of pulmonary emphysema displaying severity and regional differences. Areas with low dark-field signal correlate with emphysematous changes detected by computed tomography using a threshold of -950 Hounsfield units. The airway parameters obtained by whole-body plethysmography and single breath diffusing capacity of the lungs for carbon monoxide demonstrated typical changes of advanced emphysema. CONCLUSIONS: Dark-field chest x-ray directly visualised the severity and regional distribution of pulmonary emphysema compared to conventional chest x-ray in patients with alpha1-antitrypsin deficiency. Due to the ultra-low radiation dose in comparison to computed tomography, dark-field chest x-ray could be beneficial for long-term follow-up in these patients.

Is sirolimus a therapeutic option for patients with progressive pulmonary lymphangioleiomyomatosis?

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM. METHODS: Sirolimus (trough level 5 - 10 ng/ml) was administered to ten female patients (42.4 ± 11.9 years) with documented progression. Serial pulmonary function tests and six-minute-walk-distance (6-MWD) assessments were performed. RESULTS: The mean loss of FEV1 was -2.30 ± 0.52 ml/day before therapy and a significant mean gain of FEV1 of 1.19 ± 0.26 ml/day was detected during treatment (p = 0.001). Mean FEV1 and FVC at baseline were 1.12 ± 0.15 l (36.1 ± 4.5%pred.) and 2.47 ± 0.25 l (69.2 ± 6.5%pred.), respectively. At three and six months during follow-up a significant increase of FEV1 and FVC was demonstrated (3 months ΔFEV1: 220 ± 82 ml, p = 0.024; 6 months ΔFEV1: 345 ± 58 ml, p = 0.001); (3 months ΔFVC: 360 ± 141 ml, p = 0.031; 6 months ΔFVC: 488 ± 138 ml, p = 0.006). Sirolimus was discontinued in 3 patients because of serious recurrent lower respiratory tract infection or sirolimus-induced pneumonitis. No deaths and no pneumothoraces occurred during therapy. CONCLUSIONS: Our data suggest that sirolimus might be considered as a therapeutic option in rapidly declining LAM patients. However, sirolimus administration may be associated with severe respiratory adverse events requiring treatment cessation in some patients. Moreover, discontinuation of sirolimus is mandatory prior to lung transplantation.

Increased Pericardial Adipose Tissue in Smokers.

BACKGROUND: Pericardial adipose tissue (PAT), a visceral fat depot directly located to the heart, is associated with atherosclerotic and inflammatory processes. The extent of PAT is related to the prevalence of coronary heart disease and might be used for cardiovascular risk prediction. This study aimed to determine the effect of smoking on the extent of PAT. METHODS: We retrospectively examined 1217 asymptomatic patients (490 females, age 58.3 ± 8.3 years, smoker n = 573, non-smoker n = 644) with a multislice CT scanner and determined the PAT volume. Coronary risk factors were determined at inclusion, and a multivariate analysis was performed to evaluate the influence of smoking on PAT independent from accompanying risk factors. RESULTS: The mean PAT volume was 215 ± 107 mL in all patients. The PAT volume in smokers was significantly higher compared to PAT volume in non-smokers (231 ± 104 mL vs. 201 ± 99 mL, p = 0.03). Patients without cardiovascular risk factors showed a significantly lower PAT volume (153 ± 155 mL, p < 0.05) compared to patients with more than 1 risk factor. Odds ratio was 2.92 [2.31, 3.61; p < 0.001] for elevated PAT in smokers. CONCLUSION: PAT as an individual marker of atherosclerotic activity and inflammatory burden was elevated in smokers. The finding was independent from metabolic risk factors and might therefore illustrate the increased inflammatory activity in smokers in comparison to non-smokers.

Early Bronchoscopy Improves Extubation Rates after Out-of-Hospital Cardiac Arrest: A Retrospective Cohort Analysis.

BACKGROUND: Patients suffering from out-of-hospital cardiac arrest (OHCA) frequently receive a bronchoscopy after being admitted to the ICU. We investigated the optimal timing and the outcome in these patients. METHODS: All patients who suffered from OHCA and were treated in our ICU from January 2013 to December 2018 were retrospectively analyzed. The data were collected from the patients' medical files, and included duration of mechanical ventilation, antibiotics, microbiological test results and neurological outcome. The outcome was the effect of early bronchoscopy (≤48 h after administration) on the rate of intubated patients on day five and day seven. RESULTS: From January 2013 to December 2018, 190 patients were admitted with OHCA. Bronchoscopy was performed in 111 patients out of the 164 patients who survived the first day. Late bronchoscopy >48 h was associated with higher rates of intubation on day five (OR 4.94; 95% CI 1.2-36.72, 86.7% vs. 55.0%, p = 0.036) and day seven (OR 4.96; 95% CI 1.38-24.69; 80.0% vs. 43.3%, p = 0.019). CONCLUSION: This study shows that patients who suffered from OHCA might have a better outcome if they receive a bronchoscopy early after hospital admission. Our data suggests an association of early bronchoscopy with a shorter intubation period.

Longitudinal Assessment of Health and Quality of Life of COVID-19 Patients Requiring Intensive Care-An Observational Study.

Long-term health consequences in survivors of severe COVID-19 remain unclear. Eighteen COVID-19 patients admitted to the intensive care unit at the University Hospital Rechts der Isar, Munich, Germany, between 14 March and 23 June 2020, were prospectively followed-up at a median of 36, 75.5, 122 and 222 days after discharge. The health-related quality of life (HrQoL) (36-item Short Form Health Survey and St. George's Respiratory Questionnaire, SGRQ), cardiopulmonary function, laboratory parameters and chest imaging were assessed longitudinally. The HrQoL assessment revealed a reduced physical functioning, as well as increased SGRQ impact and symptoms scores that all improved over time but remained markedly impaired compared to the reference groups. The median radiological severity scores significantly declined; persistent abnormalities were found in 33.3% of the patients on follow-up. A reduced diffusion capacity was the most common abnormal pulmonary function parameter. The length of hospitalization correlated with role limitations due to physical problems, the SGRQ symptom and the impact score. In conclusion, in survivors of severe COVID-19, the pulmonary function and symptoms improve over time, but impairments in their physical function and diffusion capacity can persist over months. Longer follow-up studies with larger cohorts will be necessary to comprehensively characterize long-term sequelae upon severe COVID-19 and to identify patients at risk.

X-ray dark-field chest imaging for detection and quantification of emphysema in patients with chronic obstructive pulmonary disease: a diagnostic accuracy study.

BACKGROUND: Although advanced medical imaging technologies give detailed diagnostic information, a low-dose, fast, and inexpensive option for early detection of respiratory diseases and follow-ups is still lacking. The novel method of x-ray dark-field chest imaging might fill this gap but has not yet been studied in living humans. Enabling the assessment of microstructural changes in lung parenchyma, this technique presents a more sensitive alternative to conventional chest x-rays, and yet requires only a fraction of the dose applied in CT. We studied the application of this technique to assess pulmonary emphysema in patients with chronic obstructive pulmonary disease (COPD). METHODS: In this diagnostic accuracy study, we designed and built a novel dark-field chest x-ray system (Technical University of Munich, Munich, Germany)-which is also capable of simultaneously acquiring a conventional thorax radiograph (7 s, 0·035 mSv effective dose). Patients who had undergone a medically indicated chest CT were recruited from the department of Radiology and Pneumology of our site (Klinikum rechts der Isar, Technical University of Munich, Munich, Germany). Patients with pulmonary pathologies, or conditions other than COPD, that might influence lung parenchyma were excluded. For patients with different disease stages of pulmonary emphysema, x-ray dark-field images and CT images were acquired and visually assessed by five readers. Pulmonary function tests (spirometry and body plethysmography) were performed for every patient and for a subgroup of patients the measurement of diffusion capacity was performed. Individual patient datasets were statistically evaluated using correlation testing, rank-based analysis of variance, and pair-wise post-hoc comparison. FINDINGS: Between October, 2018 and December, 2019 we enrolled 77 patients. Compared with CT-based parameters (quantitative emphysema ρ=-0·27, p=0·089 and visual emphysema ρ=-0·45, p=0·0028), the dark-field signal (ρ=0·62, p<0·0001) yields a stronger correlation with lung diffusion capacity in the evaluated cohort. Emphysema assessment based on dark-field chest x-ray features yields consistent conclusions with findings from visual CT image interpretation and shows improved diagnostic performance than conventional clinical tests characterising emphysema. Pair-wise comparison of corresponding test parameters between adjacent visual emphysema severity groups (CT-based, reference standard) showed higher effect sizes. The mean effect size over the group comparisons (absent-trace, trace-mild, mild-moderate, and moderate-confluent or advanced destructive visual emphysema grades) for the COPD assessment test score is 0·21, for forced expiratory volume in 1 s (FEV1)/functional vital capacity is 0·25, for FEV1% of predicted is 0·23, for residual volume % of predicted is 0·24, for CT emphysema index is 0·35, for dark-field signal homogeneity within lungs is 0·38, for dark-field signal texture within lungs is 0·38, and for dark-field-based emphysema severity is 0·42. INTERPRETATION: X-ray dark-field chest imaging allows the diagnosis of pulmonary emphysema in patients with COPD because this technique provides relevant information representing the structural condition of lung parenchyma. This technique might offer a low radiation dose alternative to CT in COPD and potentially other lung disorders. FUNDING: European Research Council, Deutsche Forschungsgemeinschaft, Royal Philips, and Karlsruhe Nano Micro Facility.

Potential functional and survival benefit of double over single lung transplantation for selected patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a frequent indication for lung transplantation (LTX) with pulmonary hypertension (PH) negatively affecting outcome. The optimal procedure type remains a debated topic. The aim of this study was to evaluate the impact of pretransplant PH in IPF patients. Single LTX (SLTX, n = 46) was the standard procedure type. Double LTX (DLTX, n = 30) was only performed in cases of relevant PH or additional suppurative lung disease. There was no significant difference for pretransplant clinical parameters. Preoperative mean pulmonary arterial pressure was significantly higher in DLTX recipients (22.7 +/- 0.8 mmHg vs. 35.9 +/- 1.8 mmHg, P < 0.001). After transplantation, 6-min-walk distance and BEST-FEV(1) were significantly higher for DLTX patients (6-MWD: 410 +/- 25 m vs. 498 +/- 23 m, P = 0.02; BEST-FEV(1): 71.2 +/- 3.0 (% pred) vs. 86.2 +/- 4.2 (% pred), P = 0.004). Double LTX recipients demonstrated a significantly better 1-year-, overall- and Bronchiolitis obliterans Syndrome (BOS)-free survival (P < 0.05). Cox regression analysis confirmed SLTX to be a significant predictor for death and BOS. Single LTX offers acceptable survival rates for IPF patients. Double LTX provides a significant benefit in selected recipients. Our data warrant further trials of SLTX versus DLTX stratifying for potential confounders including PH.

Coronary calcium scoring assessed on native screening chest CT imaging as predictor for outcome in COVID-19: An analysis of a hospitalized German cohort.

BACKGROUND: Since the outbreak of the COVID-19 pandemic, a number of risk factors for a poor outcome have been identified. Thereby, cardiovascular comorbidity has a major impact on mortality. We investigated whether coronary calcification as a marker for coronary artery disease (CAD) is appropriate for risk prediction in COVID-19. METHODS: Hospitalized patients with COVID-19 (n = 109) were analyzed regarding clinical outcome after native computed tomography (CT) imaging for COVID-19 screening. CAC (coronary calcium score) and clinical outcome (need for intensive care treatment or death) data were calculated following a standardized protocol. We defined three endpoints: critical COVID-19 and transfer to ICU, fatal COVID-19 and death, composite endpoint critical and fatal COVID-19, a composite of ICU treatment and death. We evaluated the association of clinical outcome with the CAC. Patients were dichotomized by the median of CAC. Hazard ratios and odds ratios were calculated for the events death or ICU or a composite of death and ICU. RESULTS: We observed significantly more events for patients with CAC above the group's median of 31 for critical outcome (HR: 1.97[1.09,3.57], p = 0.026), for fatal outcome (HR: 4.95[1.07,22.9], p = 0.041) and the composite endpoint (HR: 2.31[1.28,4.17], p = 0.0056. Also, odds ratio was significantly increased for critical outcome (OR: 3.01 [1.37, 6.61], p = 0.01) and for fatal outcome (OR: 5.3 [1.09, 25.8], p = 0.02). CONCLUSION: The results indicate a significant association between CAC and clinical outcome in COVID-19. Our data therefore suggest that CAC might be useful in risk prediction in patients with COVID-19.

Anti-inflammatory effects of antibacterials on human Bronchial epithelial cells.

BACKGROUND: Human Bronchial epithelial cells (hu-BEC) have been claimed to play a significant role in the pathogenesis of chronic inflammatory airway diseases like COPD. In this context IL-8 and GM-CSF have been shown to be key cytokines. Some antibiotics which are routinely used to treat lower respiratory tract infections have been shown to exert additional immunomodulatory or anti-inflammatory effects. We investigated whether these effects can also be detected in hu-BEC. METHODS: Hu-BEC obtained from patients undergoing lung resections were transferred to air-liquid-interface (ALI) culture. These cultures were incubated with cefuroxime (CXM, 10-62.5 mg/l), azithromycin (AZM, 0.1-1.5 mg/l), levofloxacin (LVX, 1-8 mg/l) and moxifloxacin (MXF, 1-16 mg/l). The spontaneous and TNF-alpha (10 ng/ml) induced expression and release of IL-8 and GM-CSF were measured using PCR and ELISA in the absence or presence of these antibiotics. RESULTS: The spontaneous IL-8 and GM-CSF release was significantly reduced with MXF (8 mg/l) by 37 +/- 20% and 45 +/- 31%, respectively (both p < 0.01). IL-8 release in TNF-alpha stimulated hu-BEC decreased by 16 +/- 8% (p < 0.05) with AZM (1.5 mg/l). With MXF a concentration dependent decrease of IL-8 release was noted up to 39 +/- 7% (p < 0.05). GM-CSF release from TNF-alpha stimulated hu-BEC was maximally decreased by 35 +/- 24% (p < 0.01) with MXF (4 mg/l). CONCLUSION: Using ALI cultures of hu-BEC we observed differential effects of antibiotics on spontaneous and TNF-alpha induced cytokine release. Our data suggest that MXF and AZM, beyond bactericidal effects, may attenuate the inflammatory process mediated by hu-BEC.

Predictive value of coronary calcifications for future cardiac events in asymptomatic patients: underestimation of risk in asymptomatic smokers.

Coronary calcification (CAC) is an established marker for coronary atherosclerosis and has a highly specific predictive value for cardiovascular events. This study aimed to determine the predictive value in the specific group of asymptomatic smokers in comparison to non-smokers. We included 1432 asymptomatic individuals (575 women, 857 men, age 59.2 ± 7.7 years.) in this study. Coronary calcification was calculated by multi-slice computed tomography following a standardized protocol including calcium score (CS). Coronary risk factors were determined at inclusion. After mean observation time of 76.3 ± 8.5 months the patients were contacted and evaluated for cardiovascular events (myocardial infarction, cardiac death and revascularisation). Mean CS was 231 ± 175 in smokers and 239 ± 188 in non-smokers. Cardiovascular events were found in 14.9% of our patients and there were significantly more events in smokers (119 events, 8.3%) than in non-smokers (94 events, 6.6%, p = 0.001). CS > 400 showed a hazard ratio for future cardiac events of 5.1 (95% CI 4.3-7.6) in smokers and 4.4 (95% CI 3.4-6.2) in non-smokers, p = 0.01. Also in smokers determination of CAC is a valuable predictor of future cardiovascular events. In our study smokers showed throughout all score groups a significantly higher risk compared to non-smokers with equal CS. Therefore, CS may underestimate the risk for future cardiac events in smokers compared to non-smokers.

Discerning the Primary Carcinoma in Malignant Peritoneal and Pleural Effusions Using Imaging Mass Spectrometry-A Feasibility Study.

PURPOSE: Malignant effusions challenge diagnostic accuracy due to cytomorphologic overlaps between various malignant primaries. Workup of this material to establish a correct diagnosis is time consuming and limited by the sparsity of material. In order to circumvent these drawbacks, the use of MALDI imaging MS (IMS) as a diagnostic platform has been explored. EXPERIMENTAL DESIGN: Cytology cell blocks from malignant effusions (serous ovarian carcinoma and several non-ovarian carcinomas including gastric adenocarcinoma) containing at least 30% neoplastic cells are selected for generation of cytology microarrays (CMA). CMA sections are transferred to conductive glass slides, subjected to on-tissue tryptic digestion, and matrix application for MALDI-IMS analysis. RESULTS: Supervised classification analysis identifies serous ovarian carcinomas as the source of malignant effusions with a sensitivity of 85.7% when compared to samples from all other included primary sites. When compared to gastric adenocarcinoma, serous ovarian carcinoma samples can be delineated with a sensitivity of 97.3%. CONCLUSION AND CLINICAL RELEVANCE: These preliminary results highlight that MALDI-IMS allows subtyping of malignant effusions to identify the precise origin of neoplastic cells. While achieving similar results compared to classical approaches such as immunocytology, more material is conserved that will be available for further tests.

Effect of inpatient rehabilitation on quality of life and exercise capacity in long-term lung transplant survivors: a prospective, randomized study.

BACKGROUND: The purpose of this study was to examine the effect of an inpatient rehabilitation program on health-related quality of life (HRQOL) and exercise capacity (EC) in long-term (>1 year after lung transplantation) survivors (LTSs) in comparison to a control group (CG). METHODS: Sixty LTSs, 4.5 ± 3.2 years after lung transplantation (LTx), were randomly assigned to two equally sized groups that were stratified for gender and underlying disease. Thirty LTSs (age 49 ± 13 years, 13 male and 17 females, 19 double LTxs, 7 BOS Stage ≥ 1) attended an inpatient rehabilitation program (intervention group, IG) for 23 ± 5 days. The CG (age 50 ± 12 years, 13 males and 17 females, 20 double LTxs, 2 BOS Stage ≥ 1) received medical standard therapy (physiotherapy). Patients were evaluated by cardiopulmonary exercise testing, 6-minute walk test (6MWT), SF-36, SGRQ and the Quality of Life Profile for Chronic Diseases questionnaire before and after (18 ± 3 days) the program. RESULTS: The groups were statistically indistinguishable in terms of clinical data. Each treatment group significantly improved their sub-maximal EC (6MWT: IG, 493 ± 90 m vs 538 ± 90 m, p < 0.001; CG, 490 ± 88 m vs 514 ± 89 m, p < 0.001) and maximal EC (VO(2peak): IG, 17.0 vs 18.5 ml/min/kg, p = 0.039; CG, 18.0 vs 19.5 ml/min/kg, p = 0.005), without reaching statistical significance between the groups. In both study groups, patients HRQOL tended to improve. Significant correlations were found between EC parameters and HRQOL scales. CONCLUSIONS: Our data suggest that structured physical training may improve exercise tolerance in LTS. Our study results did not demonstrate a significant benefit of an inpatient over an outpatient exercise program.