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Background: Chronic obstructive pulmonary disease (COPD) is a widespread chronic disease characterised by irreversible airway obstruction [1]. Features of clinical practice and healthcare systems for COPD patients can vary widely, even within similar healthcare structures. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy is considered the most reliable guidance for the management of COPD and aims to provide treating physicians with appropriate insight into the disease. COPD treatment adaptation typically mirrors the suggestions within the GOLD guidelines, depending on how the patient has been categorised. However, the present study posits that the reasons for adjusting COPD-related treatment are hugely varied., Objectives: The objective of this study was to assess the clinical symptoms that govern both pharmacological and non-pharmacological treatment changes in COPD patients. Using this insight, the study offers suggestions for optimising COPD management through the implementation of GOLD guidelines., Methods: In this observational cohort study, 24 general practitioners screened 260 COPD patients for eligibility from 2015-2019. General practitioners were asked to collect general information from patients using a standardised questionnaire to document symptoms. During a follow-up visit, the patient's symptoms and changes in therapy were assessed and entered into a central electronic database. Sixty-five patients were removed from the analysis due to exclusion criteria, and 195 patients with at least one additional visit within one year of the baseline visit were included in the analysis. A change in therapy was defined as a change in either medication or non-medical treatment, such as pulmonary rehabilitation. Multivariable mixed models were used to identify associations between given symptoms and a step up in therapy, a step down, or a step up and a step down at the same time., Results: For the 195 patients included in analyses, a treatment adjustment was made during 28% of visits. In 49% of these adjustments, the change in therapy was a step up, in 33% a step down and in 18% a step up (an increase) of certain treatment factors and a step down (a reduction) of other prescribed treatments at the same time. In the multivariable analysis, we found that the severity of disease was linked to the probability of therapy adjustment: patients in GOLD Group C were more likely to experience an increase in therapy compared to patients in GOLD Group A (odds ratio [OR] 3.43 [95% confidence interval {CI}: 1.02-11.55; p = 0.135]). In addition, compared to patients with mild obstruction, patients with severe (OR 4.24 [95% CI: 1.88-9.56]) to very severe (OR 5.48 [95% CI: 1.31-22.96]) obstruction were more likely to experience a therapy increase (p <0.0001). Patients with comorbidities were less likely to experience a treatment increase than those without (OR 0.42 [95% CI: 0.24-0.73; p = 0.002]). A therapy decrease was associated with both a unit increase in COPD Assessment Test (CAT) score (OR 1.07 [95% CI: 1.01-1.14; p = 0.014]) and having experienced an exacerbation (OR 2.66 [95% CI: 1.01-6.97; p = 0.047]). The combination of steps up as well as steps down in therapy was predicted by exacerbation (OR 8.93 [95% CI: 1.16-68.28; p = 0.035]) and very severe obstruction (OR 589 [95% CI: 2.72 - >999; p = 0.109])., Conclusions: This cohort study provides insight into the management of patients with COPD in a primary care setting. COPD Group C and airflow limitation GOLD 3-4 were both associated with an increase in COPD treatment. In patients with comorbidities, there were often no treatment changes. Exacerbations did not make therapy increases more probable. The presence of neither cough/sputum nor high CAT scores was associated with a step up in treatment.

Objectives: Patients with severe COVID-19 may be at risk of longer term sequelae. Long-term clinical, immunological, pulmonary and radiological outcomes of patients treated with anti-inflammatory drugs are lacking., Methods: In this single-centre prospective cohort study, we assessed 90-day clinical, immunological, pulmonary and radiological outcomes of hospitalised patients with severe COVID-19 treated with tocilizumab from March 2020 to May 2020. Criteria for tocilizumab administration were oxygen saturation &lt;93%, respiratory rate &gt;30/min, C-reactive protein levels &gt;75 mg/l, extensive area of ground-glass opacities or progression on computed tomography (CT). Descriptive analyses were performed using StataIC 16., Results: Between March 2020 and May 2020, 50 (27%) of 186 hospitalised patients had severe COVID-19 and were treated with tocilizumab. Of these, 52% were hospitalised on the intensive care unit (ICU) and 12% died. Eleven (22%) patients developed at least one microbiologically confirmed super-infection, of which 91% occurred on ICU. Median duration of hospitalisation was 15 days (interquartile range [IQR] 10&ndash;24) with 24 days (IQR 14&ndash;32) in ICU patients and 10 days (IQR 7&ndash;15) in non-ICU patients. At day 90, 41 of 44 survivors (93%) were outpatients. No long-term adverse events or late-onset infections were identified after acute hospital care. High SARS-CoV-2 antibody titres were found in all but one patient, who was pretreated with rituximab. Pulmonary function tests showed no obstructive patterns, but restrictive patterns in two (5.7%) and impaired diffusion capacities for carbon monoxide in 11 (31%) of 35 patients, which predominated in prior ICU patients. Twenty-one of 35 (60%) CT-scans at day 90 showed residual abnormalities, with similar distributions between prior ICU and non-ICU patients., Conclusions: In this cohort of severe COVID-19 patients, no tocilizumab-related long-term adverse events or late-onset infections were identified. Although chest CT abnormalities were highly prevalent at day 90, the majority of patients showed normal lung function., Trial Registration: ClinicalTrials.gov NCT04351503.

Background: Sarcoidosis is a disorder of unknown aetiology. Most patients have steroid-responsive disease, but side effects and steroid resistance may necessitate alternative treatments. Endothelin has in-vitro fibrogenic activity and the endothelin system is activated in sarcoidosis., Objectives: We studied the efficacy and safety of the endothelin receptor antagonist bosentan in sarcoidosis patients., Methods: In a prospective 12-month, double-blind, 1:1-randomised, placebo-controlled phase II trial, we assessed the effect of bosentan in patients with steroid-resistant sarcoidosis and with impaired exercise capacity and/or resting lung function. Primary endpoints were safety and overall response rate of total lung capacity, diffusion capacity, peak oxygen uptake, 6-minute walking distance and chest computed tomography score. Secondary endpoints included adverse events and quality of life., Main Results: Twenty patients were randomised. Three patients discontinued the study medication prematurely. No serious drug-related adverse events occurred. At 12 months no statistically significant differences were observed in the primary endpoints including total lung capacity, diffusion capacity, 6-minute walking distance, peak oxygen uptake, and computed tomography-score. Sixty-three percent of the patients treated with bosentan showed an increase of 10% in at least one of the primary endpoints, compared with 67% in the placebo group (p = 1)., Conclusions: There is no evidence to support efficacy of bosentan as an antifibrotic treatment for patients with steroid-resistant pulmonary sarcoidosis. Bosentan was well tolerated and no drug-related adverse effects were observed within the study population., Trial Registration: ISRCTN registry, ISRCTN73579020.

Principles: A decrease in plasma lipids occurs during severe sepsis and has prognostic implications in critical illness. Whether lipids have prognostic implications or could help to differentiate community-acquired pneumonia from other lower respiratory tract infections remains unknown., Methods: We analysed data from patients with lower respiratory tract infections enrolled in four prospective trials. We studied the time courses of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) and compared them with the underlying diagnosis and medical outcomes., Results: Of 572 patients included, 372 had community-acquired pneumonia and 200 acute and exacerbations of chronic obstructive bronchitis. We found significantly lower concentrations of TC, LDL-C and HDL-C in all patients on admission as compared to hospital discharge, particularly in community-acquired pneumonia. A multivariate logistic regression analysis including HDL-C, CRP, age and diabetes showed that HDL-C (OR: 0.18 [95%CI 0.11-0.3]) and CRP (OR: 1.01 [95%CI 1.01-1.02]) were independent predictors of community-acquired pneumonia. TC levels were significantly lower in non-survivors than in survivors (3.26 mmol/L [95%CI 2.58-3.96] vs 3.78 mmol/L [95%CI 3.01-4.65]). The prognostic accuracy, defined as the area under the receiver operator characteristic curve of TC to predict mortality, was 0.63 (95%CI 0.53-0.72) in all patients and increased to 0.94 (95%CI 0.86-1.00) in patients with bacteraemic community-acquired pneumonia., Conclusions: In conclusion, low lipid levels, particularly low HDL-C, pointed to bacterial infection and low TC was predictive of adverse outcomes in patients with lower respiratory tract infections. Reflecting the severity of disease, plasma lipid levels may be a complementary tool in the diagnostic and prognostic workup of patients with lower respiratory tract infections.

Background: since 1999 data from pulmonary hypertension (PH) patients from all PH centres in Switzerland were prospectively collected. We analyse the epidemiological aspects of these data., Methods: PH was defined as a mean pulmonary artery pressure of >25 mm Hg at rest or >30 mm Hg during exercise. Patients with pulmonary arterial hypertension (PAH), PH associated with lung diseases, PH due to chronic thrombotic and/or embolic disease (CTEPH), or PH due to miscellaneous disorders were registered. Data from adult patients included between January 1999 and December 2004 were analysed., Results: 250 patients were registered (age 58 +/- 16 years, 104 (41%) males). 152 patients (61%) had PAH, 73 (29%) had CTEPH and 18 (7%) had PH associated with lung disease. Patients <50 years (32%) were more likely to have PAH than patients >50 years (76% vs. 53%, p <0.005). Twenty-four patients (10%) were lost to followup, 58 patients (26%) died and 150 (66%) survived without transplantation or thrombendarterectomy. Survivors differed from patients who died in the baseline six-minute walking distance (400 m [300-459] vs. 273 m [174-415]), the functional impairment (NYHA class III/IV 86% vs. 98%), mixed venous saturation (63% [57-68] vs. 56% [50-61]) and right atrial pressure (7 mm Hg [4-11] vs. 11 mm Hg [4-18])., Discussion: PH is a disease affecting adults of all ages. The management of these patients in specialised centres guarantees a high quality of care. Analysis of the registry data could be an instrument for quality control and might help identify weak points in assessment and treatment of these patients.

Background: Although airway obstruction, as defined by improvement of forced expiratory volume in one second (FEV1) and/or forced vital capacity (FVC), is irreversible in patients with COPD, they clearly seem to benefit from treatment with inhaled bronchodilators., Aims: To assess the response pattern of residual volume (RV) compared to FEV1 after bronchodilation in patients with reversible and irreversible airway obstruction., Methods: Changes in static lung volumes were compared with improvement in dynamic lung volumes in 396 consecutive patients undergoing reversibility testing with repeat bodyplethysmography. Reversibility was defined as improvement of FEV1 >200 ml and >12% after inhalation of fenoterol hydrobromide., Results: Irreversibility was found in 297 out of 396 patients with airway obstruction. Except for total lung capacity (TLC), all parameters (residual volume [RV], vital capacity [VC], forced inspiratory vital capacity [IVC], forced vital capacity [FVC], forced expiratory volume in one second [FEV1] and the FEV1/VC ratio) showed statistically significant changes after bronchodilation in 396 patients. The multiple linear regression model adjusted for age, sex and BMI showed a non-linear relationship between DeltaFEV1 or DeltaVC compared to DeltaRV after bronchodilation. If the increase in DeltaFEV1 is lower than 0.1 L, DeltaRV remains constant. However, if the increase in DeltaFEV1 is more than 0.1 L, DeltaRV decreases too. The same is found at an increase in VC of 0.3 L., Conclusion: In summary, in patients with irreversible airway obstruction DeltaRV cannot be predicted by DeltaFEV1 or DeltaVC after bronchodilation. Therefore, spirometric assessment should be complemented by bodyplethysmography.

Background: Lower respiratory tract infections (LRTI) account for the majority of all antibiotics prescribed in the clinical practice, irrespective of the fact that most cases are self-limiting. Using the outcome and microbiology findings as gold standard, we determined sensitivity, specificity, positive and negative predictive values of common used signs and symptoms of bacterial LRTI requiring antibiotic therapy., Patients: 243 consecutive patients with suspected LRTI admitted to a tertiary care hospital., Results: Bacterial LRTI requiring antibiotic therapy and self-limiting LRTI were diagnosed in 32 and 86 patients, respectively. Assessing these two groups, sputum, dyspnea, crackles, fever and leukocytes (WBC) were insensitive and unspecific parameters for the diagnosis of bacterial LRTI requiring antibiotic therapy. Cough was sensitive (93.8%) but unspecific (5.8%). The sensitivity of infiltrates, C-reactive protein (CRP) >50 mg/L and procalcitonin (PCT) >0.1 ng/mL was 96.9%, 93.8% and 93.8%, respectively. PCT >0.25 ng/mL showed the highest specificity (97.7%), followed by WBC >16 x 109/L (94.2%) and CRP >100 mg/L (91.9%). The sensitivity of WBC >16 x 109/L was low (37.5%)., Conclusion: The overall sensitivity and specificity of signs and symptoms for bacterial LRTI requiring antibiotic therapy was poor. Obtaining a chest-X-ray with infiltrates and determining CRP at a cut-off value of 50 mg/L or PCT at a cutoff value of 0.1 ng/mL was required to ascertain the need for antibiotics in LRTI.

Background: Flexible bronchoscopy is a procedure commonly performed for diagnostic and therapeutic purposes. The aim of this study was to assess the diagnostic yield and the safety of routine bronchoscopy techniques including transbronchial needle aspiration and transbronchial biopsy at a university hospital in Switzerland., Methods: 616 consecutive bronchoscopies performed at the Pulmonary Medicine Department (University Hospital Basel) over a period of 6 months were analysed retrospectively using bronchoscopy reports and hospital charts. Diagnostic procedures included bronchial washings, bronchoalveolar lavage, bronchial brushings, transbronchial needle aspiration and transbronchial biopsies., Results: 430 bronchoscopies had a diagnostic, 186 a therapeutic indication. The overall diagnostic yield was 57% (245/430). Bronchoscopy performed for suspected tumours confirmed malignancy in 43% of cases. Bronchoscopy in suspected infection and tuberculosis identified pathogenic organisms in 46% and 27% of cases, respectively. The diagnostic yield for central and peripheral TBNA was 37.8 and 43.6%, respectively. Complications were very rare (n = 10, 1.6%) and were only minor., Conclusion: This study demonstrates that routine bronchoscopy techniques including transbronchial needle aspiration and transbronchial biopsy are safe and have a high diagnostic yield.

The Asthma Quality of Life Questionnaire (University of Sydney [AQLQ-Sydney]) is a self-administered questionnaire that has been developed in Australia and validated in different languages in Australia, the USA and Spain. We developed a German translation of this questionnaire by applying a sequential forward and backward translation approach. The objective of this study was to validate a German translation of the AQLQ-Sydney questionnaire in an outpatient population of asthmatic patients in Switzerland. Outpatients were assessed for a diagnosis of asthma and those who consented were selected for the validation study. All patients had spirometry, methacholine challenge testing, fractional exhaled nitric oxide recorded and answered the German AQLQ-Sydney. A subgroup of 17 patients answered the questionnaire for a second time after receiving asthma treatment with combined steroids and bronchodilators for two months. Test-retest-reliability was tested in 12 stable asthmatic patients without treatment modification. Of 90 patients assessed, 57 were diagnosed with asthma and participated in the validation study. The total score did not significantly correlate with any of the objective measures of severity of asthma. However, the "Breathlessness" subscale score correlated weakly with PD20 methacholine. Internal consistency was high with Cronbach's alpha of 0.97 for the total score and 0.91-0.97 for the subscale scores. Test-retest reliability was also high for the total score and the subscale scores. The questionnaire detected a significant improvement in total quality of life score and "Breathlessness" and "Mood" subscale scores after a period of combined treatment with inhaled steroids and long acting bronchodilators. The German translation of the AQLQ-Sydney had a good internal consistency and test-retest-reliability in stable asthmatic patients. It shows responsiveness to treatment. Some correlations with objective markers were detected.

Questions Under Study: Evaluation of cardiopulmonary capacity and work ability is often done by cardiopulmonary exercise testing under laboratory conditions. Mobile CPET devices allow measurements under specific real-life conditions, i.e.: at the patient's workplace. We investigated the feasibility and validity of mobile CPET in healthy controls., Method: We compared oxygen uptake measured by mobile CPET (MCPET) with that by standard CPET (LCPET), and we compared oxygen uptake with markers of self-reported physical exhaustion. Twenty-two healthy subjects (15 male, 21-49 years) underwent LCPET and 6 outdoors 12-min running tests (MCPETs) at different intensities. Physical exhaustion and the time they could continue exercising (T(EX)) was reported for each level. Standard descriptive statistics were applied., Results: Of 132 MCPETs, performed in 22 subjects, 128 (97%) were of suitable quality. The facemask was well tolerated and nobody felt uncomfortable at any time. On average VO2 [peak] was 21% (SD 9%) higher with MCPET compared to LCPET (median 3.60, range [2.22, 5.14] versus median 2.63, range [1.67, 4.16] L*min(-1)), but showed a strong correlation (r2 = 0.90). MCPET-VO2 at steady state correlated with subjectively rated physical exhaustion, and with TEX., Conclusions: Out-of-laboratory MCPET was feasible, correlated with parameters of standard CPET, and correlated with markers of physical exhaustion. After validation in patients, MCPET could be used for a rational evaluation of cardiopulmonary capacity and work ability in selected patients.

For many years asthma has been regarded as an inflammatory disease of the airway mucosa leading to bronchial hyperreactivity. Recent studies showed marked abnormalities in airway smooth muscle behaviour in patients with asthma. The pathogenesis of asthma seems to consist of airway inflammation combined with airway smooth muscle remodelling. The latter pathology is linked to a lack of the ant-proliferative transcription factor C/EBP-alpha in this specific cell type.

Background: In daily routine, physicians use history, physical examination and technology-based information such as laboratory tests and imaging studies to diagnose the patients' disease. We determined the diagnostic value of lung auscultation in patients admitted to the Medical emergency room with chest symptoms., Methods: Two-hundred-and forty-three consecutive patients (137 males), mean age 59.2 years were included. Internal Medicine registrars had to make a presumptive diagnosis, 1) after having taken the history and 2) after having auscultated the lungs. Thereafter, routine diagnostic procedures were performed. The estimated diagnosis was compared with the final diagnosis based on the written report to the Family Practitioner., Results: Two-hundred-eighty-seven diagnoses were made. Eighteen percent of patients suffered from left heart failure, 13% from unexplained chest pain, 10.5% from chest wall pain, and 10.5% from pneumonia. Forty-one percent of the diagnoses were already correct when based only on the patient's history. Lung auscultation improved the diagnostic yield only in 1% and worsened it in another 3%. By multiple logistic regression, normal lung auscultation (OR 0.12 [95CI% 0.053-0.29]) was the independent predictor for not having a lung or heart disease. However, elevation of B-type natiuretic peptide (BNP) (OR 1.16 per 100 pg/ml (95CI% 1.004-1.35), wheezing (OR 0.023 [0.002-0.33]) and pCO2 (OR 0.25 (0.10-0.621) were independent predictors for having a heart disease, whereas wheezing (OR 7.41 [3.26-16.83]) and CRP (OR 1.008 per 10 units [1.003-1.014]) were risk factors for having a lung disease., Conclusion: In contrast to history taking, abnormal lung auscultation does not appear to contribute considerably to the final diagnosis in patients presenting with chest symptoms in an emergency room setting. However, normal lung auscultation is a valuable predictor for not having a lung or heart disease, whereas wheezing is a predictor for having a lung disease and not having a heart disease.

The association of leukotriene receptor antagonists and Churg-Strauss Syndrome (CSS) has been recognised for several years. However, whether these drugs have a direct pathogenic role remains controversial. The present case describes an asthmatic patient, who developed severe obstructive symptoms and progressive heart failure after two sequential exposures to montelukast. As the patient exhibited a markedly raised blood eosinophil count with diffuse infiltrates on chest x-ray and signs of myocarditis, CSS was suspected. The disease was confirmed by open lung biopsy. The symptoms improved rapidly after administration of high dose immunosuppression with methylprednisolone and cyclophosphamide. This case is noteworthy because the time course of events strongly suggests a direct aetiological role for montelukast in the development of CSS. The pathophysiological mechanism of the association remains unknown.

Background: Atopic disorders have been associated with a Th-2 cytokine predominance. This study investigated Th1- and Th2-related gene expression in asthmatics, atopics and healthy individuals., Methods: We compared Th1- and Th2-related in vivo-signals using gene expression arrays in 18 atopic asthmatics, 8 atopic non-asthmatic and 14 healthy control subjects. Purified mRNA from peripheral blood mononuclear cells was reverse-transcribed and hybridised to cDNA membranes. Group differences were assessed after standardisation with Mann-Whitney U-test., Results: Atopic individuals had upregulated lymphotoxin-alpha and downregulated IFNGR1. On the other hand, they had particularly high IL-4, IL-5 and IL4R levels, together with significantly upregulated IL10. Asthmatic individuals had normal Th1-gene expression, but an upregulation og Th-2 genes. Atopic individuals had high, asthmatic individuals excessively high IL12RB1-levels. No Th-2 gene was downregulated in both atopic phenotypes. The expression of IL6R correlated with the daily dose of inhaled corticosteroids., Conclusions: Atopic individuals had a down regulation of key TH1- and Th2-genes, resulting in a balanced upregulation of Th-specific genes. In contrast, asthmatic subjects had normal Th1-gene expression but a constant upregulation of Th2-specific genes, leading to Th2-predominance.

Principles: Current asthma management employing inhaled corticosteroids (ICS) and longacting b2-agonists (LABA) aims to rapidly achieve and then maintain overall asthma control including symptoms with minimal medication. This study compared self-guided adjustable maintenance dosing with budesonide/formoterol in a single inhaler with fixed dosing., Methods: In an open-label, parallel-group, multicentre study, 127 asthmatic patients, well controlled on ICS and LABA, were treated with budesonide/formoterol (Symbicort) Turbuhaler) 200/6 mg (equivalent to 160/4.5 mg delivered dose) 2 inhalations bid for 4 weeks, and were then randomised to budesonide/formoterol adjustable dosing (n = 69) (guided self-adjustment of dose: 1 inhalation bid or 2 inhalations at night with interim step ups to 2 inhalations bid and if not sufficient up to 4 inhalations bid for 14 days) or fixed dosing (2 inhalations bid) (n = 58) for 12 weeks., Results: Patients used adjustable dosing effectively; >50% used a decreased maintenance dose on >50% of the days. Seventy-two percent (50/69) from the adjustable-dosing group reduced their maintenance dose within the first 2 treatment weeks. Thirteen adjustable-dose patients (18.8%) never reduced their dose and 4 (5.8%) stepped up their dose. Symptom severity (NHLBI severity grade) decreased in both groups; however, the decrease was only statistically significant (p = 0.004) in the adjustable-dosing group. Treatment failures occurred in 17% and 24% of patients (adjustable and fixed dosing, respectively p = 0.35). Nocturnal awakenings (0.057 vs. 0.067/night, p = 0.006) and rescue medication use (0.15 vs. 0.23 inhalations/day, p <0.0001) were significantly less frequent with adjustable dosing, and the average daily medication dose was significantly reduced (3.0 vs. 3.9, p <0.0001) compared with fixed dosing. Lung function measurements (FEV1 and PEF) were not significantly different between groups during the study. There were no asthma-related hospital admissions., Conclusion: Asthma patients on adjustable maintenance dosing with budesonide/ formoterol maintained control of symptoms using significantly less medication overall than fixed dosing. Thus, adjustable maintenance dosing achieved guideline goals of effective asthma control at an appropriately low maintenance dose. However, larger studies on adjustable maintenance dosing are needed.

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.

Background: Degradation of extracellular matrix (ECM) and basement membranes is required for tumour cell invasion and metastasis. The ECM is degraded by matrix metalloproteinases (MMP) which are counteracted by tissue inhibitors of metalloproteinases (TIMP). In aggressive tumours the balance of proteolysis and antiproteolysis is disrupted, resulting in fast tumour progression and invasiveness. We examined MMP and TIMP expression patterns in bronchial washings of 58 consecutive lung tumour patients and 10 controls. Pathohistological investigations revealed squamous cell carcinoma (n = 23), adenocarcinoma (n = 18), small cell lung carcinoma (n = 9), and pulmonary metastases of extrapulmonary tumours (n = 8). MMP/TIMP expression was correlated to histology, location, or staging of tumours., Methods: Expression and activity of MMP was identified by zymography and Western blotting. Expression of TIMP-1 and TIMP-2 was analysed by Western blotting and enzyme-linked immunosorbent assays., Results: We identified MMP-1, MMP-2 and MMP-9, but not MMP-3 or MMP-8 in bronchial washings. All MMPs were expressed in the tumour-affected and the tumour-free parts of the lung. While MMP-1 and MMP-9 were present in all samples, the inactive precursor of MMP-2 was specifically expressed in adenocarcinoma or lung metastases of extrapulmonary tumours. No MMP-2 was found in controls. While TIMP-1 was expressed in all samples, TIMP-2 was not detectable., Conclusion: The tumour type-specific expression of the MMP-2 precursor in adenocarcinoma and lung metastases suggests that MMP-2 in the absence of TIMP-2 correlates with aggressive tumour progression and may serve as an indicator for poor prognosis.