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Introduction: A significant number of patients with moderate asthma remain symptomatic despite treatment with inhaled corticosteroids (ICS). These patients do not yet meet the criteria for oral corticosteroids (OCS) and monoclonal antibodies. The new anti-chemokine oral drug XC8 could represent an alternative treatment option for these patients. The objective of this trial was to evaluate the effect of different doses of the XC8 in patients with partly controlled asthma in a phase 2a clinical trial., Methods: A double-blind, parallel-group, randomized, multicenter, phase 2a trial was conducted at 12 sites in Russia. Patients with asthma were randomized into four groups (n = 30 each) to receive XC8 at 2 mg, 10 mg, 100 mg or placebo once-daily for 12 weeks in addition to low-dose ICS with or without LABA. Efficacy and safety parameters were evaluated at weeks 0, 2, 6, and 12., Results: No statistically significant difference between the treatment arms in the number of patients with adverse events was observed. The primary endpoint, improvement of forced expiratory volume in 1 s (FEV 1 ) % predicted over 12 weeks compared to placebo, was not statistically significant. The treatment of patients with XC8 (100 mg) resulted in statistically and clinically significant improvements in FEV 1 compared to baseline (7.40% predicted, p < 0.001). Patients with elevated peripheral blood eosinophil count (PBEC, > 300 cells/μl) or serum interferon-γ (IFN-γ) level (> 100 pg/mL) treated with XC8 (100 mg) achieved a statistically significant improvement in FEV 1 (11.33% predicted or 8.69% predicted, respectively, p < 0.05) as compared to the baseline versus the placebo. The strongest effect was observed in patients with both high PBEC and IFN-γ level. Pharmacodynamic engagement was demonstrated through the reduction of serum levels of C-C motif ligand 2 (CCL2) and C-X-C motif chemokine 10 (CXCL10). Treatment with XC8 (100 mg) alleviated resistance to maintenance ICS therapy in patients with elevated IFN-γ level., Conclusions: Given the high safety, oral route of administration, and efficacy, XC8 may provide a promising treatment option for patients with mild-to-moderate asthma., Trial Registration: 795-30/12/2015 (Ministry of Health Russian Federation), NCT03450434 (ClinicalTrials.gov).

Scientific Members of the Austrian Society of Pneumology describe the expected development in respiratory health and provide guidance towards patient-oriented and cost-efficient respiratory care in Austria.Methods: In November 2017, respiratory care providers (physicians, nurses, physiotherapists) together with patient's advocacy groups and experts in health development, collaborated in workshops on: respiratory health and the environment, bronchial asthma and allergy, COPD, pediatric respiratory disease, respiratory infections, sleep disorders, interventional pneumology, thoracic oncology and orphan diseases.Results: Respiratory disease is extremely prevalent and driven by ill-health behavior, i.e. cigarette smoking, over-eating and physical inactivity. For the majority of respiratory diseases increased prevalence, but decreased hospitalizations are expected.The following measures should be implemented to deal with future challenges:1. Screening and case-finding should be implemented for lung cancer and COPD.2. E-health solutions (telemedicine, personal apps) should be used to facilitate patient management.3. Regional differences in respiratory care should be reduced through E‑health and harmonization of health insurance benefits across Austria.4. Patient education and awareness, to reduce respiratory health illiteracy should be increased, which is essential for sleep disorders but relevant also for other respiratory diseases.5. Respiratory care should be inter-professional, provided via disease-specific boards beyond lung cancer (for ILDs, sleep, allergy)6. Programs for outpatient's pulmonary rehabilitation can have a major impact on respiratory health.7. Increased understanding of molecular pathways will drive personalized medicine, targeted therapy (for asthma, lung cancer) and subsequently health care costs.

Treatment of malignant pleural mesothelioma (MPM) depends on performance status of the patient, tumor stage, and histological differentiation. Chemotherapy (CHT) can be administered as first- and second-line treatment in unresectable MPM or as neoadjuvant or adjuvant treatment before or after surgery. A combination of an antifolate and platinum-based CHT is the only approved standard of care. Several targeted and immunotherapies are in evaluation and further studies are warranted to determine the therapeutic value of these new treatment options. Radiotherapy (RT) can be considered either as adjuvant treatment after surgery or for palliation of pain-related tumor growth. Recent data support the use of RT in a neoadjuvant setting. Macroscopic complete resection by pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP) is indicated in selected patients with good performance status. Surgery should only be applied as part of a multimodality treatment (MMT) in combination with chemo- and/or radiotherapy. In a large number of cases, palliative attempts are needed to improve quality of life and to achieve symptom control., Competing Interests: Conflict of interestM.A. Hoda, T. Klikovits, M. Arns, K. Dieckmann, S. Zöchbauer-Müller, C. Geltner, B. Baumgartner, P. Errhalt, B. Machan, W. Pohl, J. Hutter, J. Eckmayr, M. Studnicka, M. Flicker, P. Cerkl, W. Klepetko, on behalf of the Austrian Mesothelioma Interest Group (AMIG) declare that they have no competing interests.

Background: Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor originating from the pleural cavity with a strong link to previous asbestos exposure. In order to determine the demographics, diagnostics, therapeutic strategies, and prognosis of MPM patients in Austria, the Austrian Mesothelioma Interest Group (AMIG) was founded in 2011. In this report the data from the AMIG MPM database collected to date are reported., Methods: A prospective observational registry was initiated, including patients with histologically verified MPM diagnosed and treated at specialized centers in Austria. Patient inclusion started in January 2011 and follow-up was completed until September 2015., Results: A total number of 210 patients were included. There were 167 male and 43 female patients with a mean age of 67.0 years (SD ± 11.3) at the time of diagnosis. Asbestos exposure was confirmed in 109 (69.4 %) patients. The histological subtype was epithelioid in 141 (67.2 %), sarcomatoid in 16 (7.6 %), biphasic in 28 (13.3 %), and MPM not otherwise specified in 25 (11.9 %) patients. Of the patients, 30 (14.3 %) received best supportive care (BSC) only, 71 (33.8 %) chemotherapy (CHT) alone, four (1.9 %) radiotherapy (RT) alone, 23 (11.9 %) CHT/RT, two (0.9 %) surgery alone, and 76 (36.2 %) curative surgery within a multimodality treatment (MMT), which was more frequently performed for patients younger than 65 years and with early-stage disease (I + II). Median overall survival (OS) was 19.1 months (95 % CI 14.7-23.5). The 1‑, 3‑, and 5‑year OS rates were 66 %, 30 %, and 23 %, respectively, and OS was significantly better in patients undergoing surgery within MMT (5-year survival 5 % vs. 40 %, p = 0.001)., Conclusion: Patients with earlier disease stages, younger age, good performance status, and epithelioid histology were more likely to undergo MMT including surgery, which resulted in a more favorable outcome., Competing Interests: Conflict of interestT. Klikovits, M.A. Hoda, Y. Dong, M. Arns, B. Baumgartner, P. Errhalt, C. Geltner, B. Machan, W. Pohl, J. Hutter, J. Eckmayr, M. Studnicka, M. Flicker, P. Cerkl, K. Kirchbacher and W. Klepetko declare that they have no competing interests.

This statement was written by a group of pulmonologists and pediatric pulmonologists belonging to the corresponding professional associations ÖGP (Austrian Society for Pulmonology) and ÖGKJ (Austrian Society for pediatric and adolescent medicine) to provide a concise overview of the latest updates in the 2015 GINA Guidelines and to include aspects that are specific to Austria., Competing Interests: Conflict of interestF. Horak received lecture fees and congress-support from thermofisher, MEDA, HAL, Bencard, Allergopharma as well as sponsoring for organizing national seminars from HAL, Allergopharma, Bencard and Stallergenes. D. Doberer received financial support for the ASA-net (Austrian Severe Asthma Net) from Novartis. F. Wantke received lecture fees or congress-support from ALK, Thermofisher, Meda, Chiesi, Glaxo, Mundipharma and Novartis. M. Studnicka received lecture fees and congress support from Chiesi, Novartis, GSK, Boehringer-Ingelheim, Menarini, Astra-Zeneca. A. Zacharasiewicz received congress support from Chiesi, Gilead, AOP Orphan and Actavis and received lecture fees from Astra Zeneca and financial support and lecture fees for the ASA-net (Austrian Severe Asthma Net) from Novartis. W. Pohl has given presentations at symposia and/or served on scientific advisory boards sponsored by Almirall, Astra Zeneca, Boehringer Ingelheim, Chiesi, Mundipharma, Meda, Novartis, Teva. E. Eber received lecture fees and congress support from Actavis, AOP Orphan, AstraZeneca, Chiesi, Forest, Gilead, MSD, Novartis, and Pari. Z. Szepfalusi and E. Horak declare that they have no competing interests.

Idiopathic bronchiolitis obliterans organizing pneumonia (idiopathic BOOP) and idiopathic CD4+ T lymphocytopenia are syndromes of unknown origins which have been characterized in recent years. An important feature of both syndromes is the good prognosis. The clinical and histological features of idiopathic BOOP are unspecific but characteristic, whereas the clinical features of idiopathic CD4+ T lymphocytopenia are not homogeneous. We present a report on the first patient in whom both syndromes were found simultaneously. Initially the chest x-ray showed bilateral patchy opacities and the peripheral blood showed a severe CD4+ T cell depletion. The diagnosis of BOOP was verified by open lung biopsy, which demonstrated the histological features of BOOP. No evidence was found of congenital or acquired reasons associated with CD4+ T cell depletion or with the histological features of BOOP, which implies the diagnosis of idiopathic CD4+ T lymphocytopenia and idiopathic BOOP. Within a follow-up period of 14 months the pulmonary opacities disappeared completely and the CD4+ T cells increased, but did not reach normal values.

We report on two patients with idiopathic CD4+ T cell depletion. A 26 year-old woman presented to us with acute respiratory failure requiring mechanical ventilation. Despite combined antibiotic therapy parenterally the opacities increased in the chest X-ray. An open lung biopsy was performed and led to the histological diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP). Respiratory function was improved impressively by high dose parenteral cortisone administration. This patient showed a general lymphocytopenia with severe CD4+ T cell depletion (60(37%)/mm3 blood). The CT4+ T cell concentration increased during a follow up period of 14 months, but did not reach normal values. The second patient was a 33 year-old homosexual. He was admitted with a mucocutaneous fungal infection which was successfully treated by antifungal drugs. This patient demonstrated a transient CD4+ T cell depletion (350(32%)/mm3 blood). In both patients HIV type 1 and 2 infections were excluded by antibody- and p 24-antigen testing, polymerase chain reaction and virus culture. CONCLUSION. Idiopathic CD4+ T lymphocytopenia differs from HIV infection in immunological profile, in the tendency to reversal of the CD4+ T cell depletion over time and in its better prognosis. It is unclear if this is a new syndrome and whether a transmissible agent, or possibly a genetically-determined reaction to noxious agents is responsible.

Vitronectin is a multifunctional glycoprotein which is involved in several of the processes of inflammation and repair. In previous studies we demonstrated that increased concentrations of vitronectin can be detected in bronchoalveolar lavage fluids (BAL) of patients with interstitial lung disease (e.g. sarcoidosis). The outcome of sarcoidosis is generally favorable, however, some patients progress to pulmonary fibrosis. There is a need for markers indicating early fibrotic changes in the lung in patients with sarcoidosis. The present study was designed to evaluate the potential of BAL-vitronectin measurements for the assessment of disease activity in subjects with sarcoidosis. BAL-vitronectin concentrations were determined in 19 patients with biopsy proven sarcoidosis and sequential analysis of BAL-vitronectin levels were performed in 11 patients before and after therapy. Patients with active sarcoidosis had higher BAL-vitronectin concentrations (1.56 +/- 0.89 microgram/ml) than patients with inactive disease (0.68 +/- 0.33 microgram/ml; p < 0.01). Patients with active sarcoidosis received high-dose glucocorticoid treatment for four weeks followed by low-dose glucocorticoid therapy for eleven months. After high-dose medication BAL-vitronectin concentrations fell significantly (1.08 +/- 0.9 microgram/ml; p < 0.01). A further decrease in vitronectin levels resulted when therapy was continued for a year (0.75 +/- 0.48 micrograms/ml). Clinical deterioration correlated with an increase in BAL-vitronectin concentrations. Thus, measurement of BAL-vitronectin levels might be a useful marker for assessing disease activity and response to therapy in patients with sarcoidosis, but does not provide prognostic information.

In 176 patients with acute myocardial infarction (AMI) serum magnesium concentration (MGK) and serum potassium concentration (KK) were analysed during the first 48 hours after AMI. The patients rhythm was continuously recorded. In a subgroup of 70 patients a signal averaging-ECG was performed. 4.5% of the patients had a low, 55.7% a normal and 39.8% a high MGK. 14.8% of the patients had a low, 80.1% a normal and 5.1% a high KK. Ventricular arrhythmias > or = Lown IV b were found in 25% of the patients with low MGK, in 38.8% with normal and in 52.9% with high MGK. 50% of the patients with low, 62.2% with normal and 61.3% with high MGK had late potentials. There was no relation between hypomagnesemia and ventricular arrhythmias as between hypomagnesemia and late potentials. Thus, hypomagnesemia in AMI patients is rare and does not correlate with ventricular arrhythmia or delayed ventricular potentials.

Idiopathic pulmonary fibrosis (IPF) is characterized by a chronic inflammatory process in the lower respiratory tract of unknown etiology and poor prognosis. There is evidence that cytotoxic mediators released by neutrophils and eosinophils, such as myeloperoxidase (MPO) and eosinophil cationic protein (ECP) play a central role in the pathogenesis of this disease. The aim of this study was to assess disease activity in patients with IPF by measuring MPO and ECP concentrations in bronchoalveolar lavage (BAL). 14 patients with IPF had significantly higher concentrations of BAL-MPO and ECP (median = 117.2 micrograms/l, range: 4-217 micrograms/l and median = 16 micrograms/l, range: 4-34 micrograms/l, respectively) than patients with sarcoidosis (n = 9) (median = 6.5 micrograms/l, range: 4-12 micrograms/l and median = 7.1 micrograms/l, range: 2-13 micrograms/l, respectively) or pneumonia (n = 13) (median = 10.8 micrograms/l, range: 5-14 micrograms/l and median = 7.6 micrograms/l, range: 3-10 micrograms/l, respectively) (p < 0.01). Follow-up of MPO and ECP concentrations in BAL was performed in 8 patients with IPF before and after 4 weeks high-dose and 12 months low-dose corticosteroid therapy. Changes in MPO and ECP levels paralleled the clinical course and successful treatment resulted in a significant decrease of both MPO and ECP concentrations (p < 0.05), while clinical deterioration or treatment failure was associated with an increase of BAL-MPO and ECP levels. Increased MPO and ECP concentrations in BAL seem to reflect ongoing disease activity and may be useful prognostic markers in the management of patients with IPF.

Synostosing ankylosis of lower limb joints was investigated radiologically and clinically in approximately 2000 patients with ankylosing spondylitis. Ankylosis was found in 8 hip joints and in 4 of the joints of the foot skeleton. Most commonly the initial picture of these diseases is that of an arthritis (sometimes specifically misinterpreted as such) years and decades before the manifestation of ankylosing spondylitis appears. The ossifying potential of the disease can apparently manifest itself early in limited areas. The radiological morphology with destruction and reconstruction is found mainly as the well known vertebral changes. Immobilization can at the most be regarded as a favourable factor in a predominantly immunological-inflammatory patho-mechanism. Additional local abnormalities of the vascular or enzymatic systems of the joints can be assumed.

Biopsy of the ear lobule in inflammatory rheumatic and collagen diseases is not a suitable method for detecting vascular involvement. A perivascular cell infiltration van often be found but it non-specific. The intensity of cell infiltration did not correlate with duration, severity or activity of the disease process.

278 patients with ankylosing spondylitis have been studied in order to find a basis for prognosis by setting a mobility function index of the vertebral column. This index does not depend on manifestation age or on the blood sedimentation rate. It increases with progression of x-ray findings. A coincidence of impaired mobility and overweight is relatively frequent and function index and electrophoresis are correlated. In contrary to this study a study of the course gives probably more prognostic indications.

200 in-patients with rheumatoid arthritis (RA) were examined with regard to the diagnostic criteria for early recognition of rheumatoid heart involvement. 75 patients showed some evidence (37.5%). The criteria are: subjectively, reduced general state, feeling of oppression, disproportional tachycardia and dyspnea: objectively, changes in the electrocardiogram (tachycardia, T-inversions sometimes resembling to infarct pictures, disturbances of repolarization, extrasystoles and AV blocks). The severity of the change may alter rapidly. Severe myocarditides may manifest as heart failure and dilatation of rapid onset. For prognostic and therapeutic reasons the recognition of a heart involvement, despite these often minimal appearances, is important. It is remarkable that there was no correlation between the activity of rheumatoid process, the titre of rheumatoid factor, and the degree of heart involvement. Age and age of onset, duration of disease and sex also showed no correlation with rheumatoid heart involvement.

Statistical reports of the "Bundesversicherungsanstalt für Angestellte" and from an affiliated rheumatological rehabilitation clinic show that within the general term of "rheumatism" inflammatory rheumatic diseases are only a few per cents. Myalgic syndromes of the vertebral column without obvious changes of the skeleton rank first. They are followed by degenerative diseases of the vertebral column and peripheral joints. While the number of treatment courses of cardiovascular disorders for men and women (male predominance) remained relatively constant from 1968-1974 and in 50% of the cases lead to pensioning-off, treatment courses of bone and joint diseases have clearly increased with a female predominance; pensioning-off is necessary only in a few cases. There is no correlation between morbidity and number of treatment courses; the importance of economical and social factors for the therapeutic regimen is pointed out. Rehabilitation clinics of the pension-paying institutions offer optimal possibilities of a long term treatment of rheumatic diseases, as single or repeat treatment. The activities of a league against rheumatism should concentrate on the clinically and sociomedically most severe joint diseases.

The frequency and preferred localisation of overt subchondral osteonecrosis in large joints have been studied in a roentgenological and clinical study. Among 619 patients (454 female, 165 male) a severe subchondral osteonecrosis was found 44 times on one or more (maximum 3) large joints of 30 patients. The hip and shoulder joints were most frequently attacked, while patients with an advanced stage or longer duration of the disease and those in the middle age groups showed this most often. Osteonecrosis did not necessarily correlate with the activity of the disease process and with the presence of a positive rheumatoid factor. Radiologically, osteolytic appearances are seen most often in the elbow and osteochondritis dissecans in the knee joint. In the hip and shoulder joint the appearances are those of reparative states with a distinct demarcation, more rarely a severe osteolysis also involving the adjacent skeletal parts, occasionally a diffuse irregular lytic osteoporosis and necrosis. The pathogenesis is discussed in detail.

In order to investigate the possible stimulation of antibodies in the genital tract by immunization female NMRI-mice were given orally a live influenza vaccine (A/PR/8/34, H1N1) on two occasions which were 10 days apart. Subsequently, virus specific IgA antibodies measured by an enzyme immunoassay in homogenates of urinary bladder, uterus and vagina and also in uterine washings. Specific IgA antibodies were not detectable in the sera of immunized mice. The high IgA titer in uterine washings, and in the homogenates suggests enhancement by vaccine of IgA antibody production in the genital tract.