Telehealth mitigates COPD disease progression compared to standard of care: a randomized controlled crossover trial.

BACKGROUND: We showed excellent adherence and satisfaction with our telehealth care (TC) approach for COPD. Here, the results of a consecutive randomized controlled trial are presented. METHODS: Patients were randomly assigned to TC or standard care (SC). During TC, patients answered six daily questions online, and focused on the early recognition of exacerbations, in addition to SC. RESULTS: The mean increase in COPD assessment test (CAT) was 1.8 vs. 3.6 points/year in the TC and SC groups, respectively (P = 0.0015). Satisfaction with care (VAS) at baseline was 8.2; at the end of SC, 8.5 (P = 0.062); and after TC, 8.8 (P < 0.001). We detected significantly more moderate exacerbations during TC. CONCLUSION: Whilst receiving TC, the slope of the CAT increase - an indicator of the naturally progressive course of COPD - was reduced by 50%. Satisfaction with care increased with TC. The higher number of detected moderate exacerbations probably indicates a higher diagnostic sensitivity than without TC.

Length of hospital stay for TB varies with comorbidity and hospital location.

BACKGROUND: Although most guidelines overwhelmingly recommend outpatient TB treatment, hospitalisations are common. We investigated the proportion of TB patients hospitalised and determined factors associated with length of stay (LOS) in Switzerland.METHODS: Cases with TB as the primary diagnosis were retrieved from a nation-wide hospitalisation database and compared to TB notifications. Month and year of admission, hospital site, type of TB, age, sex, LOS and up to 50 ICD-10 coded comorbidities were compared with controls matched for age, sex and admission date.RESULTS: From 2002 to 2015, the estimated TB hospitalisation rate was 81%. The median LOS of 6,234 TB patients was stable at 14 days (IQR 6-22), but increased in patients with miliary TB, old patients and with hospital location. TB-associated comorbidities included HIV, liver disease, anaemia, malnutrition and genitourinary tract diseases. LOS was associated with three comorbidity clusters: 1) malnutrition, cachexia and anaemia (median LOS 20 days, IQR 13-31); 2) toxic liver disease and hepatitis (median LOS 23 days, IQR 14-37.5); and 3) adverse drug events (median LOS 20 days, IQR 13-30).CONCLUSION: Most TB patients were hospitalised. LOS was related to TB type, comorbidities and hospital location. Promoting outpatient care is a priority to improve TB management in Switzerland.

[ARDS after Incidental Aspiration of Petroleum in an Adult]. / ARDS nach akzidentieller Aspiration von Petroleum bei einem Erwachsenen.

Petroleum aspiration as a reason for lipid pneumonia is a rare complication. Mostly children are affected and mortality rates are low. In most case series, virtually every subject survived.We describe here the case of a patient who developed ARDS and pneumatoceles with a fatal outcome. Due to the undulant nature of the disease, multipe thoracic CT were performed, enabling us to describe the precise radiologic course of the disease.

Characteristics of medically and surgically treated empyema patients: a retrospective cohort study.

BACKGROUND: The role of drainage, intrapleural fibrinolytics, and/or surgery in the management of thoracic empyema is controversial. OBJECTIVES: We aimed to investigate the operational practice of empyema management at our hospital. METHODS: Between January 2001 and December 2008, all patients with thoracic empyema were retrieved. After exclusion of patients with malignant effusion, traumatic or iatrogenic empyema, and a history of pleurodesis or tuberculosis, we compared the characteristics of medically versus surgically treated empyema patients. RESULTS: Seventy-eight of 215 retrieved patients were acute bacterial empyema cases. All received intravenous antibiotics. Fifty-eight (74.4%) initially received tube thoracostomy, 34 (43.6%) were treated with intrapleural urokinase, and 30 (38.5%) were operated on. Of 20 patients without initial tube thoracostomy, 15 (75%) were operated on, compared to 9 (37.5%) who were initially treated by tube thoracostomy without intrapleural fibrinolytics (OR 5; 95% CI 1.4-18.5, p = 0.01) and 6 (17.7%) who were initially treated with tube thoracostomy and intrapleural urokinase (OR 14; 95% CI 3.6-53.6, p < 0.001). The surgery patients were not different in demographic and clinical characteristics but were more likely to describe significant chest pain 12 months after discharge. CONCLUSIONS: In this retrospective cohort study of thoracic empyema patients, initial chest tube insertion and intrapleural fibrinolytics were associated with less surgical therapy. Other predictors of the need for surgery could not be identified. Surgery patients were more likely to suffer from residual chest pain 12 months after discharge. Initial treatment with IV antibiotics, chest tube, and intrapleural fibrinolytics was successful in the majority of patients.

Prevalence of sarcoidosis in Switzerland is associated with environmental factors.

The current study aimed to investigate incidence, prevalence and regional distribution of sarcoidosis in Switzerland with respect to environmental exposures. All sarcoidosis patients hospitalised between 2002 and 2005 were identified from the Swiss hospital statistics from the Swiss Federal Office for Statistics (Neuchâtel, Switzerland). Regional exposure characteristics included the regional distribution of different industrial sectors, agriculture and air quality. Co-inertia analysis, as well as a generalised linear model, was applied. The prevalence of "ever-in-life" diagnosed sarcoidosis, currently active sarcoidosis and sarcoidosis requiring hospitalisation was 121 (95% CI 93-149), 44 (95% CI 34-54) and 16 (95% CI 10-22) per 100,000 inhabitants, respectively. The mean annual incidence of sarcoidosis was 7 (95% CI 5-11) per 100,000 inhabitants. The regional workforce in the metal industry, water supply, air transport factories and the area of potato production, artificial meadows (grassland) and bread grains were positively associated with the frequency of sarcoidosis. The prevalence of sarcoidosis was higher than assumed based on former international estimates. Higher frequency was found in regions with metal industry and intense agriculture, especially production of potatoes, bread grains and artificial meadows.

B-type natriuretic peptide and C-terminal-pro-endothelin-1 for the prediction of severely impaired peak oxygen consumption.

OBJECTIVE: To assess the utility of B-type natriuretic peptide (BNP) and C-terminal-pro-endothelin-1 (CT-proET-1) to predict a severely impaired peak oxygen consumption (peak VO(2), < 14 mL kg(-1) min(-1)) in patients referred for cardiopulmonary exercise testing. DESIGN: Cross-sectional study. SETTING: Tertiary care center. METHODS: Peak VO(2), BNP and CT-proET-1 were assessed in 141 consecutive patients referred for cardiopulmonary exercise testing. RESULTS: B-type natriuretic peptide [median (interquartile range) 48 (38-319) vs. 33 (15-86) pg mL(-1); P = 0.002] and CT-proET-1 [87 (76-95) vs. 60 (52-74) pmol L(-1); P < 0.001] were higher in patients with a peak VO(2) < 14 mL kg(-1) min(-1) (n = 30) than in those with a peak VO(2) > or = 14 mL kg(-1) min(-1) (n = 111). CT-pro-ET-1 had a higher area under the receiver-operator-characteristics curve (AUC) to predict a peak VO(2) < 14 mL kg(-1) min(-1) than BNP (0.79 vs. 0.68; P = 0.04). The optimal BNP cut-off of 37.2 pg mL(-1) had a sensitivity of 80% and a specificity of 56%. The optimal CT-proET-1 cut-off of 74.4 pmol L(-1) had a sensitivity of 80% and specificity of 76%. A five-item score composed of body mass index, diabetes, forced expiratory volume within the first second, alveolo-arterial oxygen pressure difference, and BNP had an AUC of 0.88 to predict a peak VO(2) < 14 mL kg(-1) min(-1). Adding CT-proET-1 to the score resulted in an AUC of 0.92. CONCLUSIONS: C-terminal-pro-endothelin-1 is superior to BNP for the prediction of a peak VO(2) < 14 mL kg(-1) min(-1) in patients referred for CPET. A score incorporating body mass index, diabetes status, spirometry, blood gases, BNP and CT-proET-1 improves the prediction of a peak VO(2) < 14 mL kg(-1) min(-1) based on single biomarkers.

Bronchial hyperresponsiveness and the development of asthma and COPD in asymptomatic individuals: SAPALDIA cohort study.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is a common feature of asthma. However, BHR is also present in asymptomatic individuals and its clinical and prognostic significance is unclear. We hypothesised that BHR might play a role in the development of chronic obstructive pulmonary disease (COPD) as well as asthma. METHODS: In 1991 respiratory symptoms and BHR to methacholine were evaluated in 7126 of the 9651 participants in the SAPALDIA cohort study. Eleven years later 5825 of these participants were re-evaluated, of whom 4852 performed spirometric tests. COPD was defined as an FEV1/FVC ratio of <0.70. RESULTS: In 1991 17% of participants had BHR, of whom 51% were asymptomatic. Eleven years later the prevalence of asthma, wheeze, and shortness of breath in formerly asymptomatic subjects with or without BHR was, respectively, 5.7% v 2.0%, 8.3% v 3.4%, and 19.1% v 11.9% (all p<0.001). Similar differences were observed for chronic cough (5.9% v 2.3%; p = 0.002) and COPD (37.9% v 14.3%; p<0.001). BHR conferred an adjusted odds ratio (OR) of 2.9 (95% CI 1.8 to 4.5) for wheezing at follow up among asymptomatic participants. The adjusted OR for COPD was 4.5 (95% CI 3.3 to 6.0). Silent BHR was associated with a significantly accelerated decline in FEV1 by 12 (5-18), 11 (5-16), and 4 (2-8) ml/year in current smokers, former smokers and never smokers, respectively, at SAPALDIA 2. CONCLUSIONS: BHR is a risk factor for an accelerated decline in FEV1 and the development of asthma and COPD, irrespective of atopic status. Current smokers with BHR have a particularly high loss of FEV1.

Pulmonary (99m)Tc-DTPA aerosol clearance and survival in usual interstitial pneumonia (UIP).

BACKGROUND: Clearance of inhaled technetium 99m-labelled diethylenetriamine penta-acetic acid ((99m)Tc-DTPA) from the lungs is a potential indicator of disease progression in patients with idiopathic pulmonary fibrosis (IPF). METHODS: We prospectively analysed the usefulness of this technique for predicting survival in 106 non-smoking patients with usual interstitial pneumonia (UIP) pattern IPF diagnosed by high resolution CT (HRCT) scanning or histological examination (M/F 65/41, mean (SD) age 61 (11) years). DTPA clearance was analysed according to both mono-exponential and bi-exponential models. Half times for the fast (t(0.5)F) and slow (t(0.5)S) components of clearance, the percentage contribution of the fast component (fF), and half time for mono-exponential approximation to the early part of the clearance curve (t(0.5)) were calculated. RESULTS: The patients had substantially faster t(0.5) (mean 23.9 (9.6) minutes) than normal values (>45 minutes). Thirty seven patients (35%) died during follow up (median 15 months). Univariate Cox regression analysis identified significant predictors of survival as age, forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC), % predicted TLC, carbon monoxide transfer factor (TLCO), % predicted TLCO, arterial oxygen tension (PaO(2)), oxygen saturation, t(0.5)F, and HRCT fibrosis score. Multiple stepwise Cox regression analysis identified t(0.5)F (p=0.03, hazard ratio 0.747, 95% CI 0.578 to 0.964), % predicted TLC (p=0.02, hazard ratio 0.976, 95% CI 0.956 to 0.995), % predicted TLCO (p=0.003, hazard ratio 0.960, 95% CI 0.935 to 0.986), and age (p=0.003, hazard ratio 1.062, 95% CI 1.021 to 1.104) as independent predictors of survival. CONCLUSION: These data suggest that (99m)Tc-DTPA clearance t(0.5)F measurement may predict survival in patients with UIP pattern IPF.

Functional genomics in sarcoidosis--reduced or increased apoptosis?

BACKGROUND: A variety of studies have stressed the importance of the control of inflammatory cell longevity and the balance of pro-survival and pro-apoptotic signaling pathways. The aim of the study was to investigate the systemic activation of apoptosis pathways using cDNA array technology in patients with acute onset sarcoidosis. METHOD: We have performed a comprehensive genomic analysis, applying high-density human GeneChip probe arrays (HGU95A, Affymetrix) for RNA expression profiling from peripheral blood mononuclear cells from patients with acute pulmonary sarcoidosis and matched healthy controls. Twelve patients and 12 controls were assessed, mean age 36 +/- 12 and 33 +/- 10 years respectively. Results focus on apoptosis-related gene products. Group differences were assessed with the Mann-Whitney U-test. RESULTS: Seven patients had self-limited disease (all type I sarcoidosis) and 5 progressive disease requiring immunosuppression (all type II or III sarcoidosis). We found 53 of 112 (47%) apoptosis-related gene products dysregulated in sarcoidosis compared to controls. Particular growth factors, especially heparin-binding EGF-like GF, EGF, PDEGF, SISPDGF2 and VEGF, were upregulated in patients consistent with a pro-survival profile. The Bcl-2 family of genes also showed a net pro-survival profile in sarcoidosis patients. In contrast, alterations in the TNF-pathway were compatible with increased apoptosis signals in both, type I and type II/III sarcoidosis patients. Other cell death receptors were equally expressed, as were caspases and p53-associated genes. In contrast to patients with type I-sarcoidosis, patients with progressive type II or III disease showed an upregulation of NFKB and a leak of downregulation of inhibitor of apoptosis 1. CONCLUSION: Significant differences in the expression of apoptosis-related genes were found in peripheral blood of patients with acute onset sarcoidosis. Gene expression did not show a definite pattern that was suggestive of pro-survival or proapoptosis. However, the number of genes whose altered expression would be predicted to favour increased survival exceeded that of genes likely to reduce survival. Protein-based confirmation of the differences in the activity of apoptosis-pathways needs to be done in further studies.

Pulmonary function in idiopathic pulmonary fibrosis and referral for lung transplantation.

Of patients awaiting lung transplantation, the death rates are highest in those with idiopathic pulmonary fibrosis (IPF), suggesting that many IPF patients are referred late for transplantation. Therefore this study was undertaken to evaluate baseline pulmonary function test (PFT) and high-resolution computed tomography (HRCT) fibrosis scores, and the relationship to survival in IPF patients younger than 65 yr of age. A total of 115 patients with usual interstitial pneumonia (UIP) were studied. At presentation to a tertiary referral center, PFT and HRCT data were collected and analyzed for prognostic significance: the primary outcome measure was patient death. Based on the length of the waiting list for transplantation, prediction of 2-yr survival was examined. DL(CO) percent predicted and HRCT-fibrosis score were found to be independent predictors of survival and in combination gave the best prognostic prediction. The optimal points on the receiver operating characteristic (ROC) curves for discriminating between survivors and nonsurvivors corresponded to 39% DL(CO) percent predicted, and to a HRCT-fibrosis score of 2.25. The combination of these parameters yielded an optimal point with a specificity and a sensitivity of 84% and 82%, respectively. A model based on a combination of DL(CO) percent predicted and HRCT-fibrosis score may optimize the timing of referral for transplantation.

B-cell isotype control in atopy and asthma assessed with cDNA array technology.

B-cell isotype switching and the production of IgE is regulated by a variety of gene products through different mechanisms. A better understanding of these processes has the potential to identify markers of disease and new therapeutic targets. The aim of the study was to investigate human B-cell isotype control and IgE production in atopy and asthma with cDNA array technology. Eighteen atopic asthmatic, eight atopic nonasthmatic, and fourteen healthy control subjects were included. Peripheral blood mononuclear cells were separated by gradient centrifugation, mRNA was purified, and the reverse-transcribed probes were hybridized to cDNA membranes. Group differences were assessed with the Mann-Whitney U-test. Twenty-three of seventy-eight tested IgE-related genes had significantly altered expression in atopy and asthma compared with that in the healthy subjects. The differentially expressed genes include surface molecules involved in T- and B-cell interaction and activation, cytokines, intracellular signaling products, and transcription factors. In conclusion, both atopic nonasthmatic and atopic asthmatic individuals had activated proinflammatory pathways, a minimal requirement for B-cell isotype switching, and a clear net pro-IgE cytokine climate.

Apoptosis signals in atopy and asthma measured with cDNA arrays.

A variety of studies have stressed the importance of the control of inflammatory cell longevity and the balance of pro-survival and pro-apoptotic signalling. Recently, asthma was found to be associated with reduced apoptosis of inflammatory cells in lung tissue. The aim of the study was to investigate the systemic activation of apoptosis pathways using cDNA array technology in atopy and asthma. Eighteen atopic asthmatics (AA), eight atopic non-asthmatic (AN) and 14 healthy control subjects (C) were included in the study. Peripheral blood mononuclear cells were separated with gradient centrifugation, mRNA purified and the reverse-transcribed probes hybridized to cDNA arrays. The signals were compared by standardizing to the 100 most expressed genes and group differences assessed with the Mann-Whitney U-test. We found a concerted up-regulation of several pro-survival cytokines and growth factors in AN and AA. FAS and FASL were not differentially expressed, but FAST kinase was over-expressed in AN and AA. The tumour necrosis factor pathway was activated in AN and AA with increased cytokine and receptor levels and increased TRAF2, an intracellular signalling product. There were indications of a down-regulated p53 system. In contrast, the Bcl-2 family of genes showed a net pro-apoptotic profile in AN and AA. The group of caspases showed a constant gene expression pattern in all groups. In conclusion, significant differences in the expression of apoptosis-related genes were found in peripheral blood of atopic individuals with and without asthma. cDNA array technology proved to be useful and may be complementary to DNA-based studies in order to analyse interactive and multidimensional pathways as shown here for apoptosis.

Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: a randomised crossover study.

BACKGROUND: Inhaled corticosteroids are currently the cornerstone of asthma treatment. Some studies of high-dose fluticasone propionate in patients with no or mild asthma have, however, suggested substantial systemic absorption. We investigated the pharmacokinetics of fluticasone propionate in patients with asthma receiving appropriate doses for severity. METHODS: We did a double-blind, randomised, crossover study in 11 patients with asthma and 13 matched healthy controls (age 20-65 years; asthma patients forced expiratory volume in 1 s <75% and stable on high-dose inhaled corticosteroids). Patients received one 1000 microg intravenous dose or 1000 microg daily for 7 days inhaled (via spacer device) fluticasone propionate. In the 12 h after dosing, we monitored plasma fluticasone propionate and cortisol concentrations by mass spectrometry and competitive immunoassay with use of direct chemiluminescence. Analysis was by intention to treat. FINDINGS: After inhalation, geometric mean values were significantly lower in the asthma group than in controls for fluticasone propionate plasma area under curve (1082 [95% CI 850-1451] vs 2815 pg mL(-1) h(-1) [2262-3949], -62% difference [45-72]; p<0.001), maximum concentrations (117 [91-159] vs 383 pg/mL [302-546], -68% [-50 to -81]; p<0.001), and systemic bioavailability (10.1 [7.9-14.0] vs 21.4% [15.4-32.2], -54% [-27 to -70]; p=0.001). Intravenous-dose clearance, volume of distribution at steady state, plasma half-life, and mean residence time, were similar in the two groups. Less suppression of plasma cortisol concentrations was seen in the asthma group than in controls 4-12 h after inhaled fluticasone propionate. INTERPRETATION: Systemic availability of fluticasone propionate is substantially less in patients with moderate to severe asthma than in healthy controls. Inhaled corticosteroids that are absorbed through the lungs need to be assessed in patients who are receiving doses appropriate for disease severity, and not in normal volunteers.

Exercise capacity and extent of resection as predictors of surgical risk in lung cancer.

Lung resection remains the most effective treatment for non-small cell lung cancer (NSCLC). However, there is no consensus about reliable operative risk assessment in these patients. The aim of this study was to identify predictors of postoperative complications and death after lung resection for NSCLC. In this prospective trial, 125 of 142 (88%) consecutive NSCLC patients from 1990 to August 1997 had complete data sets. All underwent functional assessment including spirometry and cardiopulmonary exercise tests and lung resection via thoracotomy. Complications occurred in 31 of 125 (25%) patients including 2 (1.6%) deaths. On logistic regression analysis, only maximal oxygen uptake (V'O2,max) x kg body weight(-1) expressed as a percentage of the predicted value (p<0.0001) and the estimated extent of lung tissue resection (p=0.02) were independent predictors of postoperative complications. Six of seven patients with a V'O2,max x kg body weight(-1) of <60% pred, but only eight of 65 with values >90% pred, exhibited postoperative complications. Maximal oxygen uptake and the estimated extent of lung tissue resection are independent predictors of postoperative complications. These simple parameters should be integrated into the preoperative decision analysis for operability in patients undergoing lung resection for lung cancer.

End-stage cystic fibrosis: improved diabetes control 2 years after successful isolated pancreatic cell and double-lung transplantation.

Over a period of years, insulin-dependent diabetes and respiratory insufficiency developed in a 35-year-old patient with end-stage cystic fibrosis. After waiting more than 4 years while receiving maintenance treatment with continuous liquid O2 and nasal ventilation, the patient underwent double-lung and pancreatic islet cell transplantation. Subsequently, the patient has enjoyed a normal life with full employment and much better control of his diabetes. Pancreatic islet cell transplantation is a simple and innocuous technique easily added to the end of lung transplantation. These new pancreatic cells, although locally injected, are still secreting more than 2 years later as assessed by repeated C-peptide measurements.

Variable radiomorphologic data of high altitude pulmonary edema. Features from 60 patients.

The purpose of the study was to collect radiomorphologic data of a large population of subjects with high altitude pulmonary edema. A blinded retrospective analysis of 60 patients severe enough to warrant hospital admission is reported. Immediately after rescue to low altitude, the severity of HAPE was graded using a quadrant-based scoring system (0-4 each quadrant). Its distribution and the morphologic features were noted. HAPE was more severe in the base, and specifically, the right lower quadrant, as compared to the other quadrants. It was often located both centrally and peripherally (60 percent) and in 92 percent was characterized by air space disease of homogeneous (n = 40) rather than patchy distribution (n = 15). In recurrent HAPE (n = 13), radiomorphologic data were as variable as among different HAPE patients. We conclude that HAPE does not have one common radiomorphologic condition. Based on the literature, earlier experience, and follow-up observations, we hypothesize that it may start patchy and peripheral, supporting the concept of uneven vasoconstriction with overperfusion and/or permeability leak. Later on, such as in the severe cases studied, it becomes homogeneous. Recurrent episodes generally do not show an identical distribution of HAPE, suggesting that structural abnormalities are not involved in the pathogenesis of HAPE.