[Chronic cough]. / Chronischer Husten.

Coughing is an important protective reflex of the respiratory tract and primarily serves clearance of the bronchial system. It is also an exceptionally common symptom in outpatient care that can be an expression of a variety of diseases. Coughing duration of longer than 8 weeks is referred to as chronic cough. A structured, often interdisciplinary diagnostic process is essential. The aim here is to identify causal treatment options, avoiding overdiagnosis and simultaneously not overlooking severe illness. This article discusses current diagnostic procedures, important differential diagnoses and possible treatment options.

[Smoking-toxic substances and immunological consequences]. / Rauchen ­ Noxen und immunologische Folgen.

BACKGROUND: Tobacco smoke is the leading cause of morbidity and mortality in modern times. The combustion products in tobacco smoke contain a variety of toxic substances. FINDINGS: These substances have far-reaching effects on the immune system, altering both cell-mediated and humoral responses of the immune system. Hence, they affect the development, cytokine production, and effector function of both innate immune cells, including dendritic cells (DCs), macrophages, and natural killer (NK) cells, and adaptive immune cells, such as cytotoxic CD8+ T cells, CD4+ Th cells, regulatory T cells, and B cells, resulting in proinflammatory responses and/or immune cell dysfunction. CONCLUSION: However, although tobacco products have been shown to impair humoral and cell-mediated immunity, neither the extent of this impairment nor its mechanisms are clearly understood.

Position statement on endoscopic lung volume reduction in South Africa: 2022 update.

Chronic obstructive pulmonary disease (COPD) remains one of the most common causes of morbidity and mortality in South Africa. Endoscopic lung volume reduction (ELVR) was first proposed by the South African Thoracic Society (SATS) for the treatment of advanced emphysema in 2015. Since the original statement was published, there has been a growing body of evidence that a certain well-defined sub-group of patients with advanced emphysema may benefit from ELVR, to the point where the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines and the United Kingdom National Institute for Health and Care Excellence (NICE) advocate the use of endoscopic valves based on level A evidence. Patients aged 40 - 75 years with severe dyspnoea (COPD Assessment Test score ≥10) despite maximal medical therapy and pulmonary rehabilitation, with forced expiratory volume in one second (FEV1) 20 - 50%, hyperinflation with residual volume (RV) >175% or RV/total lung capacity (TLC) >55% and a six-minute walking distance (6MWD) of 100 - 450 m (post-rehabilitation) should be referred for evaluation for ELVR, provided no contraindications (e.g. severe pulmonary hypertension) are present. Further evaluation should focus on the extent of parenchymal tissue destruction on high-resolution computed tomography (HRCT) of the lungs and interlobar collateral ventilation (CV) to identify a potential target lobe. Commercially available radiology software packages and/or an endobronchial catheter system can aid in this assessment. The aim of this statement is to provide the South African medical practitioner and healthcare funders with an overview of the practical aspects and current evidence for the judicious use of the valves and other ELVR modalities which may become available in the country.

[Treatment recommendations for mechanical ventilation of COVID­19 patients]. / Behandlungsempfehlungen zur Beatmung von COVID­19-Patienten.

Background: Due to the novelty of COVID­19 there is lack of evidence-based recommendations regarding the mechanical ventilation of these patients. Objective: Identification and delineation of critical parameters enabling individualized lung and diaphragm protective mechanical ventilation. Material and methods: Selective literature search, critical evaluation and discussion of expert recommendations. Results: In the current literature a difference between ARDS in COVID­19 and classical ARDS is described; however, there are no evidence-based recommendations for dealing with this discrepancy. In the past parameters and approaches for a personalized mechanical ventilation strategy were already introduced and applied. Conclusion: Using the parameters presented here it is possible to individualize the mechanical ventilation of COVID­19 patients in order to adjust and increase its compatibility to the heterogeneous clinical presentation of the COVID­19 ARDS.

Risk stratification of EGFR+ lung cancer diagnosed with panel-based next-generation sequencing.

OBJECTIVE: Panel-based next-generation sequencing (NGS) is increasingly used for the diagnosis of EGFR-mutated non-small-cell lung cancer (NSCLC) and could improve risk assessment in combination with clinical parameters. MATERIALS AND METHODS: To this end, we retrospectively analyzed the outcome of 400 tyrosine kinase inhibitor (TKI)-treated EGFR+ NSCLC patients with validation of results in an independent cohort (n = 130). RESULTS: EGFR alterations other than exon 19 deletions (non-del19), TP53 co-mutations, and brain metastases at baseline showed independent associations of similar strengths with progression-free (PFS hazard ratios [HR] 2.1-2.3) and overall survival (OS HR 1.7-2.2), in combination defining patient subgroups with distinct outcome (EGFR+NSCLC risk Score, "ENS", p < 0.001). Co-mutations beyond TP53 were rarely detected by our multigene panel (<5%) and not associated with clinical endpoints. Smoking did not affect outcome independently, but was associated with non-del19 EGFR mutations (p < 0.05) and comorbidities (p < 0.001). Laboratory parameters, like the blood lymphocyte-to-neutrophil ratio and serum LDH, correlated with the metastatic pattern (p < 0.01), but had no independent prognostic value. Reduced ECOG performance status (PS) was associated with comorbidities (p < 0.05) and shorter OS (p < 0.05), but preserved TKI efficacy. Non-adenocarcinoma histology was also associated with shorter OS (p < 0.05), but rare (2-3 %). The ECOG PS and non-adenocarcinoma histology could not be validated in our independent cohort, and did not increase the range of prognostication alongside the ENS. CONCLUSIONS: EGFR variant, TP53 status and brain metastases predict TKI efficacy and survival in EGFR+ NSCLC irrespective of other currently available parameters ("ENS"). Together, they constitute a practical and reproducible approach for risk stratification of newly diagnosed metastatic EGFR+ NSCLC.

[Joint Statement of the German Radiological Society and the German Respiratory Society on a Quality-Assured Early Detection Program for Lung Cancer with Low-dose CT]. / Positionspapier der Deutschen Röntgengesellschaft und der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin zu einem qualitätsgesicherten Früherkennungsprogramm des Lungenkarzinoms mittels Niedrigdosis-CT.

Substantial new data on early detection of lung cancer with low-dose CT has become available since the last joint statement of the German Roentgenological Society and the German Respiratory Society was published in 2011. The German S3 guideline on lung cancer was revised in 2018 and now contains a weak recommendation towards early detection of lung cancer with low-dose CT in a quality-assured early detection program. These new developments required a repositioning of the involved professional societies. This present joint statement describes main features of a quality-assured program for early detection of lung cancer with low-dose CT in Germany.

[Interventional treatment of tracheopleural and bronchopleural fistulas]. / Interventionelle Versorgung tracheo-/bronchopleuraler Fisteln.

BACKGROUND: Interventional bronchoscopy is an indispensable option to manage bronchopleural and tracheopleural fistulas in patients in a poor general condition and at high risk for developing postoperative complications. METHODS: This article is based on a search in the PubMed database for relevant publications and own experiences as surgeons and pneumologists. RESULTS: Various interventional techniques can be used for the treatment of bronchopleural and tracheopleural fistulas. Currently, the insertion of stents or endobronchial valves is the most frequently used treatment. Ideally, the attending anesthesiologist will have experience with high frequency jet ventilation and the attending surgeon will have experience with rigid bronchoscopy, flexible bronchoscopy, and interventional bronchoscopy. DISCUSSION: Due to a lack of standardized treatment recommendations, individual treatment plans must be decided according to the location of the bronchopleural or tracheopleural fistula and taking existing comorbidities into account.

Successful treatment of a recurrent granulation polyp in the airways with high-dose-rate brachytherapy: a case report.

BACKGROUND: Benign central airway tumors are very rare diseases. Their unspecific symptoms are responsible for late diagnosis. Endoscopic interventions with different techniques and tools are widely used for their treatment. However, in certain cases interventional endoscopy might be unsuccessful and therefore other methods such as high-dose-rate brachytherapy could be a therapeutic option. CASE PRESENTATION: A 76-year-old white German woman was referred to our clinic for an endoscopic treatment of a recurrent granulation polyp in her left main bronchus. She had dyspnea, coughing, and mucus retention. Three times resections via bronchoscopy were performed within less than a year. After each intervention the polyp regrew inside her left main bronchus causing a repeat of the initial symptoms. She presented to our clinic less than 1 month since the last intervention. Twice we performed a rigid bronchoscopy in total anesthesia where we resected the granulation polyp with a snare wire loop and did an argon plasma coagulation of its base. Due to the recurrent growing of the granuloma, we performed a high-dose-rate brachytherapy in conscious sedation after another interventional bronchoscopy with a resection of the polyp and argon plasma coagulation of the base. Three months after brachytherapy our patient came to our clinic for a follow-up with none of the initial symptoms. Only a small remnant of the polyp without a significant occlusion of her bronchus was visualized by bronchoscopy. Furthermore, 6 months after brachytherapy she was not presenting any of the initial symptoms. CONCLUSIONS: This case report shows that high-dose-rate brachytherapy is a therapeutic option for the treatment of benign airway stenosis when other interventional treatments are not or are less than successful. However, further investigations are needed to prove the effectiveness and reliability of the method.

[Endoscopic interventions in pulmonology]. / Endoskopische Interventionen in der Pneumologie.

Bronchoscopy plays a significant role in the diagnosis and treatment of pulmonary diseases. Hemoptysis, or central airway obstruction, is a common indication for interventional bronchoscopy. In addition, the treatment of early lung cancer is the domain of bronchoscopy in inoperable patients. In recent years, endoscopic techniques have also been established as new therapeutic options in advanced chronic obstructive pulmonary disease and uncontrolled bronchial asthma.

Novel Endoscopic Approaches to Treating Chronic Obstructive Pulmonary Disease and Emphysema.

Chronic obstructive pulmonary disease (COPD) is a widespread disease associated with high morbidity and mortality. The principal aim of therapy is preventing disease progression. Besides rehabilitation and pharmacological treatment, different endoscopic approaches were developed in the past decade extending the therapeutic spectrum. Various endoscopic lung volume reduction (ELVR) techniques are available that differ in the implementation, mechanism of action, complication spectrum, and reversibility. So far, the data on efficacy and safety are variable and still very limited. The most comprehensive data are available for endoscopic valve therapy. This reversible technique leads to lobar atelectasis and thus significant lobar volume reduction in patients with severe emphysema and low collateral ventilation. Implantation of coils leading to parenchymal compression and bronchoscopic thermal vapor ablation inducing an inflammatory reaction are nonblocking ELVR techniques and thus independent of collateral ventilation. Besides ELVR techniques, targeted lung denervation has evolved as the latest development in the field of endoscopic therapy in COPD. The aim of this endoscopic method is sustainable bronchodilation by minimizing the influence of parasympathetic pulmonary nerves on smooth muscles of the airways. This review summarizes the different endoscopic procedures, their mechanism of action, and the results of the clinical trials including efficacy and safety.

[Preoperative pulmonary function analysis and cardiorespiratory risk assessment: the current standard]. / Präoperative Lungenfunktionsanalyse und kardiorespiratorische Risikoabschätzung, aktueller Standard.

The aim of preoperative lung function analysis and diagnostic cardiology is to identify patients with an increased risk of complications and to best inform the patients about treatment options and risks so that an informed treatment decision can be made. The identification of patients at increased peri-interventional risk by preoperative physiological diagnostics also forms the basis for further developments and improvements of interventions and intervention techniques in order to reduce the risk of complications. The acquisition of a detailed medical history, a thorough physical examination, and the diagnosis using ECG and spirometry may provide the first evidence for the presence of relevant comorbidities. In elective surgery a detailed preoperative evaluation of comorbidities must be done. The association of age and operative mortality is not only due to age alone, but also involves the spectrum of comorbidities. The algorithms for Germany are based on the "S3 Guidelines of the German Society of Pneumology of 2010". Both German and international guidelines recommend the discussion of each case before lung resections in an interdisciplinary case discussion with thoracic surgeons, oncologists, radio-oncologists and pulmonologists. Patients of advanced age should always be subjected to an extended preoperative cardiopulmonary investigation.

[Respiratory therapy with Ez-PAP for treatment of dynamic hyperinflation in patients with severe COPD and emphysema]. / Atemtherapie mit Ez-PAP zur Behandlung der dynamischen Überblähung bei Patienten mit schwerer COPD und Lungenemphysem.

BACKGROUND: Non-pharmacological respiratory physiotherapy in treatment of COPD with severe emphysema is achieving increasing importance. Ez-PAP, a compact CPAP- or flow-PEP system, supports inspiration by using the Coanda effect in addition to a PE(E)P-effect during expiration. METHODS AND PATIENTS: 30 patients with severe COPD and emphysema and hypercapnic respiratory failure under non-(NIV) (n = 28) and invasive ventilation (n = 2) were treated in ventilator-free intervals with Ez-PAP and analyzed retrospectively. Clinical courses such as ventilator-dependency, dyspnea by visual CR-10 Borg scale, results of six-minute walk tests (6MWT), lung function tests and recordings of transcutaneous CO2 measurements were evaluated where possible. RESULTS: Analyzed patients showed less ventilator dependancy (n = 9), reported a median decrease of shortness of breath by 3,3 points (n = 10) and improved by 50,4 m in the 6MWT (n = 5). A median increase of vital capacity by 544 ml (n = 5) was shown by spirometry. Combined with manual techniques for reducing air-trapping, treatment success was documented by a median reduction of pCO2 by 7,3 mmHg (n = 6) using transcutaneous pCO2 measurement. CONCLUSION: Ez-PAP is a simple mechanical method to reduce dynamic hyperinflation in severe COPD, thus achieving relief of respiratory muscles and more effective breathing. Prospective studies of this promising method are urgently required.

Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical reappraisal of its prognostic role.

BACKGROUND: Uncontrolled proliferation is a hallmark of malignant tumour growth. Its prognostic role in non-small cell lung cancer (NSCLC) has been investigated in numerous studies with controversial results. We aimed to resolve these controversies by assessing the Ki-67 proliferation index (PI) in three large, independent NSCLC cohorts. METHODS: Proliferation index was retrospectively analysed by immunohistochemistry in a cohort of 1065 NSCLC and correlated with clinicopathological data including outcome and therapy. RESULTS were validated in two independent cohorts of 233 squamous cell carcinomas (SQCC) and 184 adenocarcinomas (ADC). RESULTS: Proliferation index (overall mean: 40.7%) differed significantly according to histologic subtypes with SQCC showing a mean PI (52.8%) twice as high as ADC (25.8%). In ADC PI was tightly linked to growth patterns. In SQCC and ADC opposing effects of PI on overall (OS), disease-specific and disease-free survival were evident, in ADC high PI (optimised validated cut-off: 25%) was a stage-independent negative prognosticator (hazard ratio, HR OS: 1.56, P=0.004). This prognostic effect was largely attenuated by adjuvant radio-/chemotherapy. In SQCC high PI (optimised validated cut-off: 50%) was associated with better survival (HR OS: 0.65, P=0.007). CONCLUSIONS: Our data demonstrate that PI is a clinically meaningful biomarker in NSCLC with entity-dependent cut-off values that allow reliable estimation of prognosis and may potentially stratify ADC patients for the need of adjuvant therapy.

[Efficacy and sustainability of a smoking prevention program for pupils--"ohnekippe"]. / Wirksamkeit und Nachhaltigkeit eines Raucher-präventionsprogramm für Schüler--"ohnekippe"

BACKGROUND: Since 2000 the Thoraxklinik Heidelberg offers the primary smoking prevention program "ohnekippe" for children aged 12-14 years. This program was scientifically evaluated to test its efficacy and sustainability. METHODS: All pupils participating in this prevention program (n=1427) were asked to complete a written survey regarding their smoking behaviour at the time of intervention (baseline) and after one year. A control group (n=1412) without intervention from comparable schools and grades were questioned in parallel. Afterwards the program was modified with active involvement of schools and then data regarding smoking prevalence of young people were compared based on the microcensus 2005 and 2009. RESULTS: 187 (13,4 %) pupils in the intervention and 215 (15,4 %) pupils in the control group were smokers at baseline. One year after, the number of regular and occasional smokers had increased from 11.2 % to 21.2 % in both groups without significant differences. Besides age and initial smoking status the "peer group" had important influence on smoking behaviour of young people. After modifying the program the number of smoking young people in the catchment area of "ohnekippe" has decreased significantly (7.8 %). Overall smoking prevalence in this age group was much lower (11,8 %) than in the rest of Baden-Württemberg (16.0 %) and of Germany (17.5 %). CONCLUSION: Smoking prevention programs for young people can be effective if they are appropriately designed. Not only one prevention event, but intensive preparation and follow-up in schools as well as involvement of the "peer group" is essential for a successful intervention. After appropriate modification the smoking prevention program "ohnekippe" shows highly promising success.