Combined analysis of five non-interventional studies of the effectiveness, tolerability, and safety of the extrafine fixed dose beclomethasone/formoterol combination in the treatment of asthma in Austria.

OBJECTIVE: The real-world effectiveness and tolerability of an extrafine fixed dose beclomethasone/formoterol (BDP/FF) treatment of patients with partially or non-controlled asthma was evaluated in five non-interventional studies (NISs) from Austria. METHODS: Asthma patients enrolled in these five NISs were treated with beclomethasone/formoterol (Foster® or Foster® Nexthaler®) as maintenance and reliever over 12 weeks. Asthma control, lung function and symptom scores were assessed at baseline, after 4-8 weeks and at the end of the investigations in week 12. In addition, tolerability and handling of the devices were evaluated by questionnaires. RESULTS: The combined analysis included 891 patients (53% female, aged 49.3 years) demonstrating significant improvements in asthma control, lung function parameters (PEF, FEV1 and FVC) and symptom scores (reduction of breathlessness, wheezing, chest tightness and cough). These changes were already detectable after 4-8 weeks. The treatment was effective irrespective of smoking status, exercise, or previous medication. Tolerability of the therapy with extrafine BDP/FF was rated as "very good" or "good" in 98% of the patients. 95% of the patients intended to continue the treatment, and nearly all (99%) rated the handling of the device as "very good" or "good". No serious adverse reactions were reported. CONCLUSIONS: This combined analysis of five non-interventional studies confirms the effectiveness and tolerability of the extrafine fixed-dose BDP/FF combination (Foster® and Foster® Nexthaler®) in a heterogenous patient population suffering from partially or non-controlled asthma. Therapy was associated with a high patient satisfaction and the absence of serious adverse reactions.

[COVID-19 Vaccination in Asthma Patients Treated with Biologicals - Statement of the Austrian Society of Pneumology and German Respiratory Society]. / COVID-19-Impfungen bei Biologika-Therapie von Asthma bronchiale.

Patients with asthma should be vaccinated against COVID-19. This includes patients with severe asthma. Treatment with a biological for asthma is no contra-indication for vaccination against COVID-19.

[Efficiency as a new parameter of physical fitness of patients in 6-minute-walk-test]. / Effizienz als ein neuer Parameter zur Objektivierung der körperlichen Leistungsfähigkeit mittels 6-Minuten-Gehtest.

UNLABELLED: AIMS OF THE INVESTIGATION: The 6-minute-walk-test (6-MWT) is an effective tool for measuring physical fitness in elderly patients. The increased walking distance is taken as a parameter for improved physical conditions. Frequently an unaltered walking distance is found after participation in a rehabilitation measure, but heart rate is significantly lower in the second challenge, indicating an improved physical fitness. This positive effect is not recognized when only the walking distance is considered. METHODS: We therefore carried out a retrospective analysis of the 6-MWT tests performed by 303 male patients (69.2 ± 8.7 years) before and after 3-4 weeks of clinical rehabilitation. Instrumented by a mobile pulse oximeter for recording oxygen saturation and heart rate, patients were instructed at the outset and at the end of their rehabilitation stay to walk as fast as they could during 6 min. Measurements were performed every 30 s and printed. A new parameter, efficiency (E = S/6/f (C)) was introduced: the ratio of the walking distance, S, divided by 6 min and divided by the mean heart frequency, f (C) (beats/minute). RESULTS: The patients group walked 351 ± 79 m at 106.2 ± 12.7 beats/min in the initial 6-MWT and 362 ± 76.0 m at a heart rate of 104.0 ± 12.2 beats/min in the final test. Along with the increase in walking distance, efficiency E increased from 0.56 ± 0.13 m/beat to 0.59 ± 0.12 m/beat. Efficiency significantly correlates with the walking distance (p < 0.01). 54 patients (18%) had an increased efficiency in the final test at the end of rehabilitation although they walked a shorter distance compared to the initial test value: they walked with a lower heart frequency. CONCLUSIONS: The patient's performance of the second walk test with an unchanged distance at a lower heart frequency reveals an improved physical fitness. This is solely described by an increase of the parameter of efficiency, E. Calculation of this parameter delivers a quantification of the effect of exercise training irrespective of the patient's cooperation. Efficiency, hence, is a meaningful complement to the sole consideration of the distance walked in the assessment of physical fitness as a benefit of rehabilitation.

Impact of chronic obstructive pulmonary disease (COPD) on attention functions.

The present study investigates the influence of COPD on attention functions, learning, and logical thinking. Therefore, 60 COPD patients and 60 healthy controls were recruited into a cross-sectional study and underwent extensive neuropsychological testing. The Attention Network Test was used for assessment of tonic and phasic alertness, orienting, and executive attention. Logical thinking and learning were determined with the Standard Progressive Matrices and the Verbal and Nonverbal Learning Test, respectively. Significant group differences were found in phasic alertness (p=0.001) and orienting (p=0.01) but not in executive attention. In addition overall reaction time was significantly slower in the COPD group (p=0.001). Further group differences were found in verbal (p<0.001) and visual learning (p<0.001) and logical thinking (p<0.001). Regression analysis revealed significant correlations for age (p=0.024) and blood carbon dioxide levels (p=0.043) in reaction time, a correlation for age and orienting (p=0.019) and finally for age (p=0.011) as well as for blood carbon dioxide values (p=0.048) and performance in logical thinking. Results are indicating a global impairment in cognitive functions of COPD patients which is negatively influenced by accelerated aging and increasing with disease severity.

Idiopathic diaphragmatic paralysis--satisfactory improvement of inspiratory muscle function by inspiratory muscle training.

Daily inspiratory muscle strength and endurance training (IMT) was performed in a 44-year-old patient with idiopathic bilateral diaphragmatic paralysis (BDP) in addition to nocturnal non-invasive ventilation (NIV). After 4 months of training inspiratory muscle function improved satisfactorily whereas phrenic nerve latency remained pathological. Due to the improvement of inspiratory muscle capacity nocturnal NIV could be stopped without inducing nocturnal respiratory insufficiency.

Product development for weaning in respiratory care.

This paper describes the development of a therapeutical device for the support of the weaning process in respiratory care, following the decannulation of the breathing tube. The new product is to enhance the healing of a temporary, percutaneous tracheostoma by the provision of visual contact to the stoma or the wound respectively, allowing to intervene at an early stage if required. Interventions are facilitated by the new device by means of variable adaptors, in particular for (tracheal) suctioning, (temporal) insertion of a placeholder cannula or contribution of oxygen and by the reinsertion of a breathing tube if necessary. As the overall benefit, the new product will shorten the healing process of the tracheostoma and support wound management for the benefit of patients.

Lung disease 35 years after aspiration of activated charcoal in combination with pulmonary lymphangioleiomyomatosis. A histological and clinicopathological study with scanning electron microscopic evaluation and element analysis.

Activated charcoal provides effective treatment for most toxic ingestions. Accidental aspiration of activated charcoal is rare. Previously, there have been a few single cases reported on charcoal-related pulmonary complications. We describe an unusual case of pulmonary lesions 35 years after accidental aspiration of activated charcoal. The 38-year-old female patient presented with recurrent pneumothorax. A routinely performed chest roentgenogram revealed pulmonary lesions, highly suggestive to lymphangioleiomyomatosis (LAM). Histopathological investigation of the lung tissue demonstrated some features of LAM but showed prominent pneumoconiotic lesions with cystic tissue destruction. The pneumoconiotic reaction was characterized by prominent black deposits accompanied by foreign-body granuloma formation and minimal fibrosis. Scanning electron microscopic investigation of these deposits showed particles measuring up to 300 microm in greatest diameter. Energy-dispersive X-ray spectra of these particles revealed carbon-rich material, presumably charcoal. The aspiration event was confirmed by the clinical history. To our knowledge, this is the first report not only on a long-term follow-up after aspiration of activated charcoal but also on charcoal-related pulmonary lesions in combination with LAM.

Adjustable maintenance dosing with budesonide/formoterol or budesonide: double-blind study.

Adjustable maintenance dosing with either budesonide/formoterol or budesonide was compared in asthma patients. This double-blind trial randomized 133 patients (mean forced expiratory volume in 1s 66% predicted) to receive 2 inhalations twice daily of budesonide/formoterol 160/4.5 microg (640/18 microg/day) or budesonide 320 microg (1280 microg/day) for 4 weeks. The study drug was adjusted in both groups according to symptoms to 2-4 inhalations daily during Weeks 5-8 and 1-4 inhalations daily during Weeks 9-20. Asthma was well controlled in both groups, with minimal levels of treatment failure (5 budesonide/formoterol vs. 2 budesonide patients; P=NS) and minimal use of reliever therapy. Clinically important improvements in health-related quality of life (HRQL) occurred in the physical functioning and emotional role functioning domains (both P<0.05) for the budesonide/formoterol group compared with budesonide. Physician and patient treatment satisfaction favored budesonide/formoterol (both P<0.05). Budesonide/formoterol patients used fewer daily inhalations of study drug (P=0.024). The median average daily inhaled corticosteroid dose during the study was 448 microg with budesonide/formoterol and 1152 microg with budesonide. Adjustable maintenance dosing with budesonide/formoterol and budesonide resulted in high levels of asthma control. Adjustable budesonide/formoterol treatment achieved greater HRQL benefits and patient satisfaction, with lower overall drug use.

Body weight of mares and foals, estrous cycles and plasma glucose concentration in lactating and non-lactating Lipizzaner mares.

This study summarizes weight development, plasma glucose concentrations and reproductive parameters in lactating (n = 46) and non-lactating Lipizzaner mares (n = 11) throughout the breeding season. It was the aim of the study to analyse if an energy deficit with possible effects on reproductive functions occurs at any time during the first 4 months of gestation. Mean gestation length was 334.3 +/- 7.3 days. Gestation of foals born in May/June was shorter (P < 0.01) than for foals born in March/April. Out of the 46 lactating mares, 44 ovulated between Days 8 and 18 postpartum and two mares ovulated on days 30 and 145, respectively. Pregnant mares were significantly (P < 0.001) heavier (600.1 +/- 5.3 kg) than non-pregnant mares (521.8 +/- 10.0 kg) at the beginning of the study. Birth resulted in weight reduction of 64.8 +/- 2.4 kg. During the first 2 weeks postpartum mares lost on average 3.0 +/- 1.8 kg and in the following 2 weeks gained 3.6 +/- 1.4 kg of weight. Thereafter, weight increased slightly but continuously (P < 0.01). At no time after foaling, weight differed significantly between groups. Weight of the foals three days after birth varied between 29 and 67 kg (53.7 +/- 1.1 kg). Average daily weight gain of foals was relatively constant throughout the study period (1.15 +/- 0.17 kg). Although lactation at no time was associated with a major weight loss, it had clear effects on energy metabolism as shown by constantly lower plasma glucose concentrations in lactating mares. Glucose concentrations decreased after foaling and were significantly lower in lactating mares from Weeks 3 to 16 after foaling than at corresponding times in non-lactating mares (P < 0.01). However, glucose concentrations were still within the physiological range. Mares seem to be able to compensate energy losses during lactation mainly by increasing feed intake and not by mobilisation of body fat.

Alveolar macrophages of patients with adult respiratory distress syndrome express high levels of heat shock protein 72 mRNA.

Adult respiratory distress syndrome (ARDS), a multifactorial disease with poor prognosis, is characterized by an accumulation of inflammatory cells within the airspaces of the lungs. There is evidence that alveolar macrophages (AM) are involved in the pathogenesis of this pulmonary disease. It has been demonstrated that AM synthesize heat shock proteins (HSPs) after exposure to certain stress factors. Increasing evidence suggests that HSPs could confer protection against oxidative injury, noxious molecules, and bacterial toxins. In stressed cells HSP 72 appears to be essential for survival during and after exposure to cellular injury. The aim of this study was to evaluate the magnitude of HSP 72 expression by human AM of patients with ARDS and correlate that with respiratory burst activity. Bronchoalveolar lavage was performed in six ARDS patients, 10 patients with high risk for developing ARDS, and two patients who underwent bronchoscopy for other reasons. Spontaneous ex vivo expression of HSP 72 in AM could be demonstrated by immunocytochemistry. Total RNA as well as poly(A)-rich mRNA were extracted from recovered AM and analyzed by Northern blot and slot blot using a human HSP 72-specific probe. Signals of slot blot were analyzed by densitometry and expressed as relative levels of HSP 72 mRNA of stressed (42 degrees C) HT 1080 control cells. Significantly (p < .001) higher levels of HSP 72 mRNA were measured in patients with ARDS (96.2 +/- 9.5 relative levels) in comparison to those not developing this syndrome (46.0 +/- 4.2). With regard to respiratory burst activity of AM in patients with ARDS, there was a negative correlation between HSP 72 expression and reactive oxygen species production. The AM of patients with ARDS with high relative levels of HSP 72 expression showed low respiratory burst activity. A predictive value for disease severity of high level of HSP 72 mRNA in AM in patients at risk for ARDS has to be evaluated by future studies. This demonstration of HSP 72 expression ex vivo suggests a protective role of HSP response against endo/exogenously generated stress factors in AM.

[Practicability, effectiveness and tolerance of a standardized prepared theophylline infusion]. / Praktikabilität, Wirksamkeit und Verträglichkeit einer standardisierten Theophyllin-Fertiginfusion.

The practicality, efficacy, and tolerance of a standardized, ready-to-use theophylline solution (Eloasthmin, Leopold Pharma, Graz) was studied on 33 patients with bronchial asthma and/or chronic obstructive bronchitis (COPD) (19 males, 14 females) aged 19 to 79 (median 50) years. Eloasthmin a ready-to-use pure theophylline solution containing no auxilliary substances, contains one gram theophyllin per liter in a hypotonic (2/3) NaCl solution. The infusion therapy was carried out in patients in an acute stage of their chronic obstructive ventilation dysfunction. The therapy was carried out for 2 to 4 days at a dose of 400 to 1000 mg theophylline per day, so that theophylline blood levels remained within the therapeutic range of 8 to 20 mg/ml. A highly significant improvement (p < 0.001) of lung function parameters was seen during treatment: VC before therapy = 2.46 l, after therapy = 3.36 l; FEV 1 before therapy = 1.34 l, after therapy = 2.04 l; and PEF before therapy = 3.48 l/s after therapy = 5.13 l/s. Since most patients also received concomittant medication (beta 2-sympathomimetica and/or glucocorticoids), it was difficult to differentiate the specific efficacy of the theophylline.

[A patient with idiopathic bronchiolitis obliterans with organizing pneumonia and idiopathic CD4+ T-lymphocytopenia]. / Ein Patient mit einer idiopathischen Bronchiolitis obliterans mit organisierender Pneumonie und einer idiopathischen CD4+ T-Lymphozytopenie.

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.

[Idiopathic CD4+ T-lymphocytopenia in 2 patients without indications for HIV infection]. / Idiopathische CD4+ T-Lymphozytopenie bei zwei Patienten ohne Hinweis auf eine HIV-Infektion.

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.

Bronchoalveolar lavage procollagen-III-peptide in recent onset hypersensitivity pneumonitis: correlation with extracellular matrix components.

Hypersensitivity pneumonitis (HP) is characterized by the accumulation of inflammatory cells in the lung parenchyma, and may progress to fibrosis. The content of the fibroblast derived collagen metabolite procollagen-III-peptide (PCP-III) in bronchoalveolar lavage (BAL) fluid of HP patients has been found to be increased. Previous studies have shown elevation of the fibroblast adhesion molecules, vitronectin and fibronectin in the BAL fluid of recent onset HP. In view of these observations, it was hypothesized that increases in PCP-III would be associated with increases in vitronectin and fibronectin in the BAL fluid of subjects with untreated recent onset HP. BAL was performed in 14 patients with HP and nine normal controls. The aminoterminal domain of PCP-III was measured by radioimmunoassay, and vitronectin and fibronectin by enzyme-linked immunosorbent assay. Detectable amounts of BAL PCP-III were seen in all HP patients but not in the normal controls (mean +/- SEM 5.1 +/- 1.2 versus < 0.2 ng.ml-1; i.e. below the limit of detection of the PCP-III assay). The BAL fluid concentration of PCP-III correlated well with the amount of vitronectin (r = 0.638) and fibronectin (r = 0.710). Except for PCP-III and mast cells, no significant correlations were found between PCP-III, vitronectin, fibronectin and the cellular parameters. The findings suggest that an increased turnover of collagens and proteoglycans is present in the lower respiratory tract of patients with recent onset HP, possibly reflecting remodelling of the extracellular matrix.

Elevated levels of bronchoalveolar lavage vitronectin in hypersensitivity pneumonitis.

Vitronectin is an adhesive glycoprotein that is present in plasma and the extracellular matrix. Hypersensitivity pneumonitis (HP) is characterized by pulmonary inflammation and damage to the extracellular matrix. Perhaps reflecting this, fibronectin has been found to be elevated in the lower respiratory tract of subjects with HP. Vitronectin, like fibronectin, binds to both extracellular matrix components and cells and may mediate tissue remodeling. Thus, it was investigated whether vitronectin might be increased in bronchoalveolar lavage (BAL) fluid of patients with HP. Vitronectin and, for comparison, fibronectin were measured in BAL fluid from 16 patients with HP and nine healthy control subjects by enzyme-linked immunosorbent assay. Vitronectin was significantly increased in the HP group (658.4 +/- 121.8 ng/ml) compared with the controls (58.4 +/- 11.1 ng/ml, p < 0.001) and was found to be positively correlated with fibronectin. Patients whose last antigenic exposure was 4 or fewer days before the BAL had statistically significantly higher BAL vitronectin and fibronectin than did patients whose last exposure was 5 or more days before the BAL. The serum vitronectin levels did not differ. There was no significant relationship between the lavage fluid vitronectin and fibronectin levels and the BAL cell profile in HP. This study confirms that vitronectin, like fibronectin, is a normal constituent of the lower respiratory tract, and demonstrates that vitronectin is elevated in the lower respiratory tract of patients with HP and may play a role in tissue remodeling and fibrosis in this disease.

[Vitronectin in bronchoalveolar lavage--a parameter of disease activity in sarcoidosis]. / Vitronectin in der bronchoalveolären Lavage--ein Aktivitätsparameter bei Sarkoidose.

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.

[Serum magnesium, serum potassium and arrhythmia profile in patients with acute myocardial infarct]. / Serummagnesium, Serumkalium und Arrhythmieprofil bei Patienten mit akutem Myokardinfarkt.

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.