[Refractory Dyspnea in Advanced COPD: Palliative Treatment with Opioids]. / Refraktäre Dyspnoe bei fortgeschrittener COPD: Palliative Therapie mit Opioiden.

Dyspnea is a leading symptom in COPD. Bronchodilators (long acting anticholinergics and long acting beta agonists) are the mainstay of medical treatment. Non pharmacological therapies like pulmonary rehabilitation, long-term oxygen therapy or lung volume reduction can help to further improve dyspnea. Nevertheless, patients with advanced disease may develop refractory dyspnea. Randomized controlled trials demonstrated that the palliative treatment with low-dose systemic opioids is an effective treatment option in these patients. A low starting dose (e. g. 1.0 mg morphine, immediate release) is recommended. Subsequent doses are titrated to achieve the lowest effective dose based on whether dyspnea relief has been achieved and whether any side effects have developed. This low-dose opioid treatment has been demonstrated to be safe for symptom reduction in severe COPD and is not associated with increased hospital admissions or deaths. Physicians should offer a trial of low-dose oral opioids to patients with refractory dyspnea that affects their daily activities and quality of life.

[Rebiopsy for Patients with Lung Cancer - Joint Opinion from both the Endoscopic and Thoracic Oncology Sections of the German Society of Pneumology (DGP)]. / Empfehlung der Sektionen 2 und 11 der DGP zur Rebiopsie bei Lungenkarzinomen.

Performing rebiopsies for primary lung cancer and/or their metastases is becoming more and more prominent in daily practice, as the therapeutical spectrum increases and some newer strategies are dependent on immunohistochemical and/or molecular factors. In general, nearly all recurrent lesions or metastases can be reached. However, frequently invasive procedures are necessary with the need to carefully weigh risks and benefits of rebiopsies for the patient in each case. In this review indications for recurrent and progressive disease as well as risks are discussed and alternatives to rebiopsies are shown. This work is the joint opinion from both the endoscopic and thoracic oncology sections of the German Society of Pneumology (DGP).

Obstructive sleep apnea (OSA) and clinical depression-prevalence in a sleep center.

BACKGROUND: This study aimed to determine the prevalence of clinical depression as defined by ICD-10 criteria in all patients with obstructive sleep apnea (OSA) referred to a sleep center. METHODS: Prospective general and sleep evaluations were conducted in 447 consecutive patients referred to our sleep center during the first quarter of 2008. Inclusion criteria were Apnea Hypopnea Index (AHI) > 9, completion of the Beck Depression Inventory (BDI-II) with a score ≥14 and World Health Organization WHO-5 Well-Being Index (WHO-5) ≤ 13. The subsequent psychiatric examination according to ICD-10 criteria was performed by in-house clinical sleep specialists. RESULTS: A total of 447 patients were surveyed, of whom 322 had an AHI > 9. Out of these, 85 met the combined screening criterion BDI II ≥ 14 and WHO-5 ≤ 13. Eighty-one patients underwent a psychiatric examination by psychiatric sleep specialists. In 21.5 % of the sample, clinical depression was diagnosed. Other complaints existed in 12 % (n = 10); 7 % (n = 6) of patients had a different psychiatric diagnosis. CONCLUSIONS: The prevalence of clinical depression according to ICD-10 criteria in a selected clinical sample (referred to the sleep center) was 21.5 %. Mood scales tend to overestimate complaints as compared to psychiatric consultation. Interdisciplinary cooperation is recommended for both OSA patients with symptoms of depression and depressed patients with treatment resistance.

[Liquid Biopsy: Detection of Molecular Markers for Treatment Decisions in Lung Cancer]. / "Liquid biopsy": Analyse molekularer Marker aus Blutproben zur Therapiesteuerung beim Lungenkarzinom.

Personalized, individualized, targeted therapy has successfully found entrance in the palliative treatment of lung cancer as they enable a personalized and individualized strategy going ahead with biomarker testing. Due to the crescending amount of predictive molecular and immunhistochemical analyses at different time points during therapy the need for more and actual tumor tissue increases; however these samples cannot always be obtained without major discomfort for the patients. Therefore, analyses from blood, the so called "liquid biopsy", is an alternative or additional method. Activating mutations in the EGFR gene and the inhibitory mutation T790 M can already be detected from blood during clinical routine. This review presents the status of liquid biopsy for diagnosis, prognosis and as predictive parameter during the course of therapy in lung cancer and gives an outlook on future developments.

[Haemoptysis : Intensive care management of pulmonary hemorrhage]. / Hämoptoe : Intensivmedizinisches Management von Lungenblutungen.

There is a wide spectrum of severities in patients with pulmonary bleeding with a range from mild haemoptysis to severe bleeding with an acute risk of asphyxiation. For the management of acute pulmonary haemorrhage, it is essential to identify the underlying cause in order to initiate a target-oriented or causal therapy. The most common causes of localized pulmonary bleeding are lung cancer as well as infections, anticoagulant therapy or bronchiectasis. Diffuse alveolar haemorrhage is mostly due to pulmonary vasculitis or connective tissue disease, but may also occur in pulmonary metastasis, congestive heart failure, coagulation disorders and from many other causes. In a case of severe pulmonary bleeding it is essential to secure the airways and ensure sufficient ventilation, i. e. by intubation with a double-lumen endotracheal tube and by appropriate positioning of the patient. Stabilizing haemodynamics is crucial. Simultaneously basic diagnostic measures, i. e. appropriate laboratory tests, chest X­ray, computed tomography scan of the chest and bronchoscopy, are performed. Localized pulmonary bleeding usually requires local treatment, like bronchoscopic therapy, bronchial artery embolization or surgery. Diffuse alveolar haemorrhage must be treated systemically, i. e. by immunosuppressive therapy in cases of vasculitis or by medical treatment of coagulation disorders. Even with optimal interdisciplinary management the in-hospital mortality of severe pulmonary bleeding remains high. There is a significant risk of recurrent bleeding depending on the cause of haemorrhage. In patients with "cryptogenic" haemoptysis there is an increased rate of lung cancer within the following years and follow-up of these patients is recommended.

[Estrogen Receptors and their Impact for Prognosis and Therapy of Lung Cancer - New Insights to an Underestimated Mechanism]. / Östrogenrezeptoren und ihre Bedeutung für die Prognose und Therapie des Lungenkarzinoms - neue Erkenntnisse zu einem bisher unterschätzten Mechanismus.

Though tobacco smoking is the leading cause of lung cancer, during the last decades the prevalence increased in never smoking patients, especially in women. Sex steroid hormones and particularly the estrogen receptors (ERs) seem to play an important but still underestimated role in non-small cell lung cancer (NSCLC). Beside long existing hints that hormone replacement therapy (HRT) increases the risk of lung tumors recent analyses on cell lines, xenografts and human tumors of both sexes gave clear evidence of ER expression and proliferation in NSCLC. Most recently, the expression of ERs apparently has prognostic and predictive value. Recently, an intracellular "cross-talk" between the ER and the epithelial growth factor receptor (EGFR) could be demonstrated. EGFR are important targets of approved tyrosinkinases (TKIs), like gefitinib, erlotinib or afatinib. Currently, clinical studies are enrolling lung tumor patients for combination treatment with EGFR TKI and antihormonal drugs, e. g. fulvestrant.

EGFR mutational status in a large series of Caucasian European NSCLC patients: data from daily practice.

BACKGROUND: The prognosis of metastatic non-small cell lung cancer (NSCLC) is still poor. Activating epithelial growth factor receptor (EGFR) mutations are important genetic alterations with dramatic therapeutical implications. Up to now, in contrast to Asian populations only limited data on the prevalence of those mutations are available from patients with Caucasian and especially European ethnicity. METHODS: In this multicentre study, 1201 unselected NSCLC patients from Southern Germany were tested in the daily clinical routine for EGFR mutation status. RESULTS: Activating EGFR mutations were found in 9.8% of all tumours. Mutations in exons 18, 19 and 21 accounted for 4.2%, 61.9% and 33.1% of all mutations, respectively. Non-smokers had a significantly higher rate of EGFR mutations than smokers or ex-smokers (24.4% vs 4.2%; P<0.001). Non-lepidic-non-mucinous adenocarcinomas (G2) accounted for 45.5% of all activating EGFR mutations and 3.5% of all squamous cell carcinomas were tested positive. Thyroid transcription factor 1 protein expression was significantly associated with EGFR mutational status. CONCLUSION: These comprehensive data from clinical routine in Germany add to the knowledge of clinical and histopathological factors associated with EGFR mutational status in NSCLC.

Infected mediastinal bronchogenic cyst in a 12 year old girl.

Bronchogenic cysts are an uncommon congenital malformation deriving from the primitive foregut. They are mainly unilocular, and respiratory distress is the most common presentation in pediatric patients. We describe the case of a 12-year-old girl with a huge infected mediastinal bronchogenic cyst which was resected via an axillary muscle-sparing thoracotomy.

[Recommendations for training courses in bronchoscopy]. / Empfehlungen zu Trainingskursen in der Bronchoskopie.

Bronchoscopic training courses are an essential part of the education in bronchoscopy for all kinds of specialisations and professions performing such investigations. All aspects of the application should be mentioned during a course. These recommendations are necessary because the number of bronchoscopies performed in the last years has increased due to the increasing number of patients, improved equipment and better availability. Courses should provide the basic knowledge including main points of indications, preconditions for the procedure and decisions of consequence after bronchoscopy. Participants should be trained in the skills of correct handling and performing flexible bronchoscopies in training dummies. Necessary competence requirements on the course instructor are adequate professional qualifications, paedagogic skills and the availability of appropriate teaching material. Quality assurance of the course should be achieved by consequent evaluation. A widely spread field of bronchoscopic applications can improve patient care in many medical specialisations.

[Sleep related breathing disorders]. / Schlafbezogene Atmungsstörungen.

Sleep related breathing disorders are common conditions and the management of patients with sleep apnea is an essential component of routine patient care. Daytime sleepiness is the leading symptom of sleep apnea but not mandatory. Especially patients with cardiac, pulmonary or metabolic comorbidities can benefit from treatment of sleep apnea and those patients should be considered for cardio-respiratory screening even with mild clinical symptoms. Continuous positive airway pressure therapy is still the most efficient treatment for sleep apnea and standard treatment for severe forms. With patient education, training and close follow-up a reasonably good compliance can be achieved in adequately selected patients. In mild forms of sleep apnea oral appliances may be efficient and in highly selected lean patients with anatomic risk factors upper airway surgery may be considered. Central sleep apnea, especially Cheyne-Stokes respiration, is highly prevalent in patients with severe cardiac insufficiency. If this disorder persists after cardiac treatment special ventilation modes like adaptive servo ventilation can be used.

Two most common diagnoses among myriads of cystic lung diseases.

BACKGROUND: Diffuse cystic lung diseases are a group of heterogeneous pathophysiological processes and include neoplastic, inflammatory, and infectious etiologies. This manuscript focuses on manifestations of pulmonary Langerhans cell histiocytosis (PLCH) and lymphangioleiomyomatosis (LAM). Description of the cases: Three female patients with LAM and one with PLCH are described. Stress dyspnea was a key symptom. There were similar cyst patterns in more than one lung lobe with a slow, progressive course. Histopathology confirmed the LAM diagnosis resulting from the nodular proliferate and the cyst wall that strongly expressed Human Melanoma Black-45 (HMB-45). A typical constellation for PLCH was demonstrated in high-resolution computed tomography (HRCT). It was found to be disseminated and relatively thick-walled cysts, mainly in the upper and middle parts. An individualized therapy was applied. Three patients with mild symptoms were followed up, including HRCT evaluations. Sirolimus was administered to one patient with a severe manifestation of LAM. CONCLUSION: LAM and PLCH are rare. High-resolution computed tomography is an essential diagnostic tool. Lung emphysema as misdiagnosis should be avoided. The characteristics of pulmonary cysts, the cyst's wall regularity, and identification of associated pulmonary lesions, should be evaluated. A promising new therapy concept are mTOR inhibitors are, especially in LAM. The most important recommendation in PLCH is the cessation of cigarette smoking. HIPPOKRATIA 2021, 25 (2):83-86.

[Current status of erlotinib and gefitinib in palliative therapy for NSCLC--does the EGF-R mutation state have any significance?]. / Aktueller Stellenwert von Erlotinib und Gefitinib in der palliativen Therapie des NSCLC--welche Bedeutung hat der EGF-R-Mutationsstatus?

In spite of intensive research and a huge amount of chemotherapy trials, the prognosis of metastastic non-small cell lung cancer (NSCLC) is still poor. Erlotinib and Gefitinb are tyrosine kinase inhibitors (TKIs) which act against the EGF receptor (EGF-R). Activation of mutations in the tyrosine kinase domain leads to an increase in effectiveness. What is the clinical impact of EGF-R mutation screening? What value do TKIs in 1st, 2nd and 3rd line have in therapy for metastatic NSCLC? Which treatment options exist after failure of TKI in the 1st line? These and other clinically relevant questions in the context of TKIs are discussed in the present comprehensive review.

[Physiology and pathophysiology of bronchial secretion]. / Physiologie und Pathophysiologie der bronchialen Sekretion.

The mechanisms of bronchial secretion are an important part of the innate defense system that protects the airways against pathogens and environmental toxins. Bronchial secretions are mainly produced by goblet cells and submucosal glands but also small amounts of surfactant from clara cells and some other fluids are part of the airway epithelium fluid. Together with the ciliary system the bronchial secretions are essential for the bronchial clearance ("mucociliary clearance"). Cilia beat within a periciliary layer with low viscosity ("sol-phase"). They move the overlying mucous sheet ("gel-phase") by their tips towards the nose to remove those mucous particles together with foreign material and pathogens from the airways. The gel-layer of the airway epithelium fluid is formed mainly by water, mucins (MUC) and free proteins. Mucins are highly glycosylated macromolecules, to date more than 18 different MUC-genes have been described. In addition the airway epithelium fluids contains many antibacterial proteins and peptides including lysozyme, lactoferrin, secretory IgA, complement, beta-defensines as well as many others. Acute inflammatory or toxic stimuli can promote hypersecretion of mucins mediated by a large variety of cytokines and chemokines or even directly like some toxins. Chronic inflammatory conditions like asthma or COPD are associated with hyperplasia of goblet cells and submucosal glands thus increasing the secretory capacity of the airways. The system of mucociliary clearance forms a functional unit together with the coughing mechanisms discussed elsewhere in this journal.

Arthropathy and cutaneous manifestations in a 28-year-old patient with cystic fibrosis.

We report on a 28-year-old man with known cystic fibrosis who presented with pain and cutaneous nodules in the elbow joints. His symptoms had appeared episodically in the previous months, they were always self-limiting, and independent of pulmonary exacerbations. A radiograph of the joints was unremarkable. These findings fit well with a special form of CF-related arthritis. As in the case of classical CF arthritis, the treatment to be considered is, in particular, symptomatic administration of non-steroidal anti-inflammatory drugs and possibly glucocorticoids. Also under discussion as a further possibility is the use of antibiotics. Our patient has always refused medication. The condition again proved to be self-limiting. In contrast to the classical form of CF arthritis, the special form is not associated with either joint swelling or local warmth. In the presence of arthritic symptoms in CF patients, consideration must always be given to a hypertrophic pulmonary osteoarthropathy. The latter, however, shows typical radiological changes and is exacerbated by lung infections. The presence of arthritic pathologies in a patient with CF further underscores the fact that CF is a multiorgan morbid condition.