Ar Koczulla

Exercise training leads to physiological left ventricular hypertrophy in COPD

Patients with chronic obstructive pulmonary disease (COPD) are affected by dyspnoea, limited exercise capacity and reduced quality of life [1,2]. COPD is associated with increased pulmonary vascular resistance, which leads to increased load of the right heart and decreased filling pressure and stroke volume of the left ventricle (LV). Cardiac involvement is usually considered as occurrence of cor pulmonale. Dedicated changes of the LV are less known. Since pulmonary rehabilitation was shown to provide beneficial effects, current COPD guidelines recommend exercise training in patients ranging from mild to severe disease (www.goldcopd.org) [3,4]. It is expected that the rate of hospitalizations and the perceived intensity of breathlessness is reduced. Pulmonary rehabilitation was shown to improve peripheral metabolism and breathing pattern, e.g. by reduced hyperinflation and increased respiratorymuscle endurance. It should be taken into account, that typical symptoms primarily attributed to COPD can also result, at least in part, from concomitant heart failure. Since exercise training is known to improve symptomsof heart failure, it is hypothesized thatmoderate exercise training exhibits beneficial effects on LV morphology and function in COPD. A total of 10 patients with stable COPD (Table 1) in accordance to the GOLD criteria based on spirometry [1] were enrolled into this prospective study. Spirometry was performed in standardized manner including the forced expiratory volume in the first second (FEV1), vital capacity (VC), the Tiffeneau ratio and carbon monoxide diffusion capacity (DLCO). Capillary blood gas analysis was performed under resting conditions. Medical treatment consisted of inhalation therapy and oral medication of hypertension. An intensive physical exercise training was initiated and follow up examinations were performed after 6 months of continued training. Spirometry, echocardiographyand concentration of Btype natriuretic peptide (BNP) was assessed at time of enrolment and at follow up [5]. The study was approved by the local institutional ethics committee and written informed consent was obtained from all study participants. Echocardiography was used to measure LV enddiastolic and endsystolic cavity diameters, interventricular septum and posterior wall thickness. LV enddiastolic volume (LVEDV), endsystolic volume (LVESV), strokevolume (LVSV), ejection fraction (LVEF) and LVmasswas obtained based on the Penn-cube convention [6–8]. LV enddiastolic and endsystolic wall stress was calculated using a thick-walled spheremodel and the wall stress index as described [9]. Although we have previously shown that an echocardiography based approach overestimates LV mass and underestimates LVwall stress when comparedwith cardiacmagnetic resonance imaging [8], the present study is valid since similar methods were used at time of enrolment and follow up. An individualized structured training program includingwarming up, strength and endurance components twice a week was initiated and continued over 6 months. Within the first 3 months, training for the improvement of maximal strength and endurance was done. In the second half, it was aimed to maintain the achieved physical status. Strength training consisted of consecutive exercises of the upper and lower limbs (rowing, pulling down forces, rope pulling, knee bends). Subsequently, 12 min of cycle ergometer endurance training was performed. Every 3 weeks, the maximal individual force development was measured and exercise intensity was increased from 35% at the beginning up to 80% within the first 3 months. In parallel, endurance intensity was continuously increased from 60% to 125% of the maximal

Reduction of glutamate-induced excitotoxicity in murine primary neurons involving calpain inhibition

Excessive glutamate secretion leads to excitotoxicity, which has been shown to underlie neurodegenerative disorders. Excitotoxicity is in part exerted by overactivation of calpains, which promote neuronal cell death via induction of limited proteolysis of the cellular proteins p35, regulatory subunit of cyclin-dependent kinase 5, and αII-spectrin. We used primary murine neuronal cells in a model of glutamate toxicity. The protease inhibitor α1-antitrypsin was able to prevent glutamate toxicity as determined by MTT assay and immunofluorescence. Calpain and caspase 3 activity were reduced following α1-antitrypsin treatment, as assessed by calpain and caspase 3 activity assays. In addition we could observe a modulation of cleavage of the calpain/caspase substrates αII-spectrin and p35 in Western blots. In summary, α1-antitrypsin shows inhibitory effects on excitotoxicity of primary neurons involving the inhibition of calpain activity. The advantage of using α1-antitrypsin is that the substance is already in clinical use for the treatment of patients with hereditary α1-antitrypsin deficiency. Further experiments are required in animal models of neurodegenerative disorders to assess the suitability of this substance in patients suffering from Alzheimers disease or Parkinsons disease.

[Chronic obstructive pulmonary disease : new pharmacotherapeutic options].

Data about the clinical presentation of chronic obstructive pulmonary disease (COPD) have resulted in a new classification of the disease. The degree of airflow limitation has been amended by symptoms and exacerbation rate. The standard pharmacotherapy of stable COPD is in transition, as fixed combinations of long acting beta agonists and long acting anticholinergics are in the late stages of clinical development. On this background inhaled corticosteroids will need to be re-evaluated. Roflumilast is a recently approved therapeutic option that primarily diminishes exacerbation frequency in patients with chronic bronchitis and severe airflow obstruction (FEV(1) < 50%). In COPD patients with acute exacerbations procalcitonin levels can be used to guide antibiotic therapy. Comparable clinical outcomes can be achieved while using significantly less amounts of antibiotics.ZusammenfassungDaten über die klinische Präsentation der chronisch-obstruktiven Lungenerkrankung (COPD) haben zu einer neuen Klassifikation der Erkrankung geführt. Außer der spirometrischen Schweregradeinteilung werden das Ausmaß der Symptome sowie die Exazerbationsrate berücksichtigt. Die Standardtherapie der stabilen COPD befindet sich im Umbruch, da in naher Zukunft Fixkombinationen aus langwirksamen Betamimetika und langwirksamen Anticholinergika eingesetzt werden können. Damit wird der Stellenwert von inhalativen Steroiden neu zu bewerten sein. Die Zulassung von Roflumilast hat die medikamentöse Therapie um eine Option erweitert, mit Hilfe derer bei Patienten mit schwerer Obstruktion (FEV1 <50%) und den Symptomen einer chronischen Bronchitis eine Senkung der Exazerbationsfrequenz erreicht werden kann. Bezüglich des Managements der COPD-Exazerbation hat sich die Neuerung ergeben, dass unter Zuhilfenahme des Prokalzitoninspiegels bei gleichem klinischem Outcome ein sparsamerer Antibiotikaeinsatz erreicht werden kann.AbstractData about the clinical presentation of chronic obstructive pulmonary disease (COPD) have resulted in a new classification of the disease. The degree of airflow limitation has been amended by symptoms and exacerbation rate. The standard pharmacotherapy of stable COPD is in transition, as fixed combinations of long acting beta agonists and long acting anticholinergics are in the late stages of clinical development. On this background inhaled corticosteroids will need to be re-evaluated. Roflumilast is a recently approved therapeutic option that primarily diminishes exacerbation frequency in patients with chronic bronchitis and severe airflow obstruction (FEV1 < 50%). In COPD patients with acute exacerbations procalcitonin levels can be used to guide antibiotic therapy. Comparable clinical outcomes can be achieved while using significantly less amounts of antibiotics.

Spezielle Trainingstherapie zur Reduktion der Inflammation bei Anti-Jo-1-Syndrom

A 46-year-old patient was frequently seen with a medically treated Anti-Jo-1 syndrome. The patient had already been treated with azathioprine and oral corticosteroids on account of decreasing lung function, dyspnoea, fatigue, and beginning signs of myositis. Although high doses of steroids and azathioprine were administered, the muscleskeletal syndromes increased steadily. The patient used to be an active long-distance runner (20 km), but now was unable to perform that kind of physical exercise. It was decided to start a treatment with the GalileoTM training device for active muscle training of the lower extremities. Before and after three months of training the following assessment was performed: measurement of health-related quality of life (St. Georges respiratory questionnaire, SGRQ), ultrasound measurement of the cross-sectional area of the quadriceps muscle, 6 minute walk test (6 MWT), lung function testing, and assessment of serum markers of inflammation (TNF-alpha, interleukin-8, CRP, CK, myoglobin). After only two months, training with the GalileoTM five times a week has improved the patients conditions dramatically. The training will be continued.

Successful Treatment of Severe Pneumonia Caused by Burkholderia cenocepacia With Intravenous Antibiotics and Immunosuppression Under Extracorporal Membrane Oxygenation

Purulent destruction–complicated pneumonia is a rare and serious disease of multifactorial genesis. In many cases, the diagnosis cannot be established by microbiological analysis of bronchial aspirates or transbronchial biopsies. In our present case, isolation of the pathogen was only possible by collecting specimens via open surgical lung biopsy. A 57-year-old otherwise healthy man was transferred to our department from another hospital. He presented with progressive respiratory failure while computed tomographic scan showed severe bilateral necrotising pneumonia. With open surgical lung biopsy, we could prove evidence of Burkholderia cenocepacia as causative pathogen. As the patients pulmonary condition deteriorated and he developed septic multiorgan failure, we initiated extracorporeal membrane oxygenation (ECMO) and commenced aggressive treatment with 4 intravenous antibiotics, cyclosporine, and corticosteroids. With this therapy, the patients situation rapidly improved; and he was successfully weaned from ECMO andmechanical ventilation. Pneumonia caused by B cenocepaciawithout underlying pulmonary disease such as cystic fibrosis is an absolute rarity. According to the severity of cepacia syndrome, an interdisciplinary approach including ECMO aggressive antibiotic treatment and immunosuppression was decisive for a successful therapy.

Chronisch obstruktive Lungenerkrankung (COPD)

What is emphysema? Emphysema is a condition that involves damage to the walls of the air sacs (alveoli) of the lung. Normally there are more than 300 million alveoli in the lung. The alveoli are normally stretchy and springy, like little balloons. Like a balloon, it takes effort to blow up normal alveoli; however, it takes no energy to empty the Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease that makes it difficult to empty air out of the lungs. This difficulty in emptying air out of the lungs (airflow obstruction) can lead to shortness of breath or feeling tired because you are working harder to breathe. COPD is a term that is used to include chronic bronchitis, emphysema, or a combination of both conditions. Asthma is also a disease where it is difficult to empty the air out of the lungs, but asthma is not included in the definition of COPD. It is not uncommon, however for a patient with COPD to also have some degree of asthma.

Allergische Reaktionen der Lunge

Allergic diseases of the lungs may affect the airways, the pulmonary parenchyma and the pulmonary vessels. The most relevant representatives are allergic asthma, hypersensitivity pneumonitis, bronchopulmonary aspergillosis and the Churg-Strauss syndrome. The type of allergic reaction and the pathophysiological consequences vary considerably between these entities. New drugs target specific mechanisms based on new insights into the pathogenetic processes of the underlying disease.ZusammenfassungAllergische Erkrankungen der Lunge können die Atemwege, das Lungenparenchym und die Gefäße der Lunge betreffen. Dazu gehören das exogen-allergische Asthma bronchiale, die exogen-allergische Alveolitis, die allergische bronchopulmonale Aspergillose und das Churg-Strauss-Syndrom. In Bezug auf die Art der allergischen Reaktion und deren pathophysiologische Konsequenzen unterscheiden sich die Krankheitsentitäten stark. Das therapeutische Vorgehen hängt von der vorliegenden Erkrankung ab. In diesem Zusammenhang werden Biologika, die spezifisch und kausal in die Erkrankung eingreifen, zukünftig möglicherweise eine größere Rolle spielen.AbstractAllergic diseases of the lungs may affect the airways, the pulmonary parenchyma and the pulmonary vessels. The most relevant representatives are allergic asthma, hypersensitivity pneumonitis, bronchopulmonary aspergillosis and the Churg-Strauss syndrome. The type of allergic reaction and the pathophysiological consequences vary considerably between these entities. New drugs target specific mechanisms based on new insights into the pathogenetic processes of the underlying disease.

Allergische Reaktionen der Lunge@@@Pulmonary allergic reactions

Allergic diseases of the lungs may affect the airways, the pulmonary parenchyma and the pulmonary vessels. The most relevant representatives are allergic asthma, hypersensitivity pneumonitis, bronchopulmonary aspergillosis and the Churg-Strauss syndrome. The type of allergic reaction and the pathophysiological consequences vary considerably between these entities. New drugs target specific mechanisms based on new insights into the pathogenetic processes of the underlying disease.ZusammenfassungAllergische Erkrankungen der Lunge können die Atemwege, das Lungenparenchym und die Gefäße der Lunge betreffen. Dazu gehören das exogen-allergische Asthma bronchiale, die exogen-allergische Alveolitis, die allergische bronchopulmonale Aspergillose und das Churg-Strauss-Syndrom. In Bezug auf die Art der allergischen Reaktion und deren pathophysiologische Konsequenzen unterscheiden sich die Krankheitsentitäten stark. Das therapeutische Vorgehen hängt von der vorliegenden Erkrankung ab. In diesem Zusammenhang werden Biologika, die spezifisch und kausal in die Erkrankung eingreifen, zukünftig möglicherweise eine größere Rolle spielen.AbstractAllergic diseases of the lungs may affect the airways, the pulmonary parenchyma and the pulmonary vessels. The most relevant representatives are allergic asthma, hypersensitivity pneumonitis, bronchopulmonary aspergillosis and the Churg-Strauss syndrome. The type of allergic reaction and the pathophysiological consequences vary considerably between these entities. New drugs target specific mechanisms based on new insights into the pathogenetic processes of the underlying disease.

Pulmonary allergic reactions

Allergic diseases of the lungs may affect the airways, the pulmonary parenchyma and the pulmonary vessels. The most relevant representatives are allergic asthma, hypersensitivity pneumonitis, bronchopulmonary aspergillosis and the Churg-Strauss syndrome. The type of allergic reaction and the pathophysiological consequences vary considerably between these entities. New drugs target specific mechanisms based on new insights into the pathogenetic processes of the underlying disease.ZusammenfassungAllergische Erkrankungen der Lunge können die Atemwege, das Lungenparenchym und die Gefäße der Lunge betreffen. Dazu gehören das exogen-allergische Asthma bronchiale, die exogen-allergische Alveolitis, die allergische bronchopulmonale Aspergillose und das Churg-Strauss-Syndrom. In Bezug auf die Art der allergischen Reaktion und deren pathophysiologische Konsequenzen unterscheiden sich die Krankheitsentitäten stark. Das therapeutische Vorgehen hängt von der vorliegenden Erkrankung ab. In diesem Zusammenhang werden Biologika, die spezifisch und kausal in die Erkrankung eingreifen, zukünftig möglicherweise eine größere Rolle spielen.AbstractAllergic diseases of the lungs may affect the airways, the pulmonary parenchyma and the pulmonary vessels. The most relevant representatives are allergic asthma, hypersensitivity pneumonitis, bronchopulmonary aspergillosis and the Churg-Strauss syndrome. The type of allergic reaction and the pathophysiological consequences vary considerably between these entities. New drugs target specific mechanisms based on new insights into the pathogenetic processes of the underlying disease.