No abstract

α1-Antitrypsin (AAT) is the archetype member of the serine protease inhibitor (SERPIN) supergene family. The AAT deficiency is most often associated with the Z mutation, which results in abnormal Z AAT folding in the endoplasmic reticulum of hepatocytes during biogenesis. This causes intra-cellular retention of the AAT protein rather than efficient secretion with consequent deficiency of circulating AAT. The reduced serum levels of AAT contribute to the development of chronic obstructive pulmonary disease (COPD) and the accumulation of abnormally folded AAT protein increases risk for liver diseases. In this review we show that with the discovery of AAT deficiency in the early 60s as a genetically determined predisposition to the development of early-onset emphysema, intensive investigations of enzymatic mechanisms that produce lung destruction in COPD were pursued. To date, the role of AAT in other than lung and liver diseases has not been extensively examined. Current findings provide new evidence that, in addition to protease inhibition, AAT expresses anti-inflammatory, immunomodulatory and antimicrobial properties, and highlight the importance of this protein in health and diseases. In this review co-occurrence of several diseases with AAT deficiency is discussed.

Today, invasive and non-invasive home mechanical ventilation have become a well-established treatment option. Consequently, in 2010 the German Society of Pneumology and Mechanical Ventilation (DGP) has leadingly published the guidelines on "Non-Invasive and Invasive Mechanical Ventilation for Treatment of Chronic Respiratory Failure". However, continuing technical evolutions, new scientific insights, and health care developments require an extensive revision of the guidelines.For this reason, the updated guidelines are now published. Thereby, the existing chapters, namely technical issues, organizational structures in Germany, qualification criteria, disease specific recommendations including special features in pediatrics as well as ethical aspects and palliative care, have been updated according to the current literature and the health care developments in Germany. New chapters added to the guidelines include the topics of home mechanical ventilation in paraplegic patients and in those with failure of prolonged weaning.In the current guidelines different societies as well as professional and expert associations have been involved when compared to the 2010 guidelines. Importantly, disease-specific aspects are now covered by the German Interdisciplinary Society of Home Mechanical Ventilation (DIGAB). In addition, societies and associations directly involved in the care of patients receiving home mechanical ventilation have been included in the current process. Importantly, associations responsible for decisions on costs in the health care system and patient organizations have now been involved.The currently updated guidelines are valid for the next three years, following their first online publication on the home page of the Association of the Scientific Medical Societies in German (AWMF) in the beginning of July 2017. A subsequent revision of the guidelines remains the aim for the future.

No abstract

Trefoil factor family (TFF)-domain peptides (formerly P-domain peptides, trefoil factors) represent major mucin-associated peptides of the gastrointestinal tract. Here, the first localization studies on TFF3 in the lower respiratory tract of human material are presented. Immunohistochemistry revealed significant accumulation of TFF3 to mucous cells in the acini of submucosal glands and varying amounts in goblet cells at the ductular portions and the surface epithelium. TFF3 appears also as a component of the mucus, for example from patients with chronic bronchitis. Expression of TFF3 was also shown by use of the polymerase chain reaction. In contrast, TFF1 and TFF2 transcripts were hardly detectable in the human respiratory tract. Thus, a structural function of TFF3 for the airway mucus is discussed, possibly together with the mucins MUC5B and MUC5AC.

The non-invasive ventilation (NIV) is widespread in the clinical medicine and has attained meanwhile a high value in the clinical daily routine. The application of NIV reduces the length of ICU stay and hospitalization as well as mortality of patients with hypercapnic acute respiratory failure. Patients with acute respiratory failure in context of a cardiopulmonary edema should be treated in addition to necessary cardiological interventions with continuous positive airway pressure (CPAP) or NIV. In case of other forms of acute hypoxaemic respiratory failure it is recommended the application of NIV to be limited to mild forms of ARDS as the application of NIV in severe forms of ARDS is associated with higher rates of treatment failure and mortality. In weaning process from invasive ventilation the NIV reduces the risk of reintubation essentially in hypercapnic patients. A delayed intubation of patients with NIV failure leads to an increase of mortality and should therefore be avoided. With appropriate monitoring in intensive care NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency. Furthermore NIV can be useful within palliative care for reduction of dyspnea and improving quality of life. The aim of the guideline update is, taking into account the growing scientific evidence, to outline the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.

Patients with chronic congestive cardiac failure (CCF) frequently suffer from central sleep apnoea syndrome (CSAS). Continuous positive airway pressure (CPAP) has been suggested as a treatment. The authors hypothesised that bilevel ventilation might be easier to initiate and superior to CPAP at correcting the sleeprelated abnormality of breathing in patients with CCF.After excluding those with a history suggestive of obstructive sleep apnoea, 35 patients with CCF (left ventricular ejection fraction v35%) were screened with overnight oximetry and the diagnosis of CSAS was established with polysomnography in 18. Two 14-day cycles of CPAP (0.85 kPa (8.5 mbar)) or bilevel ventilation (0.85/0.3 kPa (8.5/3 mbar)) in random order, were compared in a crossover study.Sixteen patients (13 males), mean age 62.0 ¡ 7.4 yrs completed the study. The pretreatment apnoea/hypopnoea index of 26.7¡10.7 was significantly reduced by CPAP and bilevel ventilation to 7.7¡5.6 and 6.5¡6.6, respectively. The arousal index fell from 31.1¡10.0 per hour of sleep to 15.7¡5.4 and 16.4¡6.9, respectively. Significant and equal improvements with CPAP and bilevel ventilation were found for sleep quality, daytime fatigue, circulation time and New York Heart Association class.The authors conclude that continuous positive airway pressure and bilevel ventilation equally and effectively improve Cheyne-Stokes respiration in patients with congestive cardiac failure. Eur Respir J 2002; 20: 934-941.

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. Young children and the elderly are disproportionately affected by CAP. Lower respiratory tract infections (LRTIs), including CAP, were ranked third in a list of the 30 leading causes of death worldwide in 1990. Mortality rates are low (< 2%) in CAP patients treated as outpatients, but are higher (5 to 20%) among patients hospitalized for CAP, and are highest (up to 50%) in patients admitted to the intensive care unit. Several risk factors are known to be associated with increases in mortality, the most important of which are age > 65 years, male gender, and comorbidities such as chronic heart failure, advanced chronic obstructive pulmonary disease, neurological diseases, and liver cirrhosis. Patients living in nursing homes may have a special risk for multiresistant bacterial infection. The incidence of CAP varies worldwide by country, age, and gender. Further, data about epidemiology, etiology, morbidity, mortality, and economical burden of diseases differ between countries. In this review, we present recent data regarding the incidence, etiology, and rate of antibiotic resistance among CAP patients from the German Network for Community Acquired Pneumonia (CAPNETZ) registry and review data from several European countries.