[Lung function test in advanced age]. / Lungenfunktionsprüfung im höheren Lebensalter.

Advanced age is not an obstacle to carring out a lung function test. In most cases a lung function test is necessary due to the fact that about 20% of older persons are affected by an obstructive respiratory disorder. Standard values for the lung function test are available up to advanced ages. The experience of the examiner and a calm environment for the lung function test have an impact on the quality of the measurement results. Severe cognitive impairments and severe immobility make the performance of a lung function test impossible. Simple geriatric assessments can help to reliably identify these patients. Alternative lung function test procedures have to be validated in order to adequately diagnose this vulnerable subgroup of patients at risk.

Exploring the potential of taurolidine in inducing mobilization and detachment of colon cancer cells: a preliminary in-vitro study.

BACKGROUND: Recently, taurolidine has been intensively studied on a variety of in-vitro cancer cell-lines and first data exhibit encouraging antitumoral effects. While the clinical use of taurolidine is considered, some studies with in-vivo experiments contradict this beneficial effect and even indicate advanced cancer growth. The aim of this study is to further investigate this paradox in-vivo effect by taurolidine and closely analyze the interaction of cancer cells with the surrounding environment following taurolidine exposure. METHODS: HT-29 (ATCC® HTB-38™) cells were treated with taurolidine at different concentrations and oxaliplatin using an in-vitro model. Morphological changes with respect to increasing taurolidine dosage were visualized and monitored using electron microscopy. Cytotoxicity of the agents as well as extent of cellular detachment by mechanical stress was measured for each substance using a colorimetric MTS assay. RESULTS: Both taurolidine and oxaliplatin exhibit cell toxicity on colon cancer cells. Taurolidine reshapes colon cancer cells from round into spheric cells and further induces cluster formation. When exposed to mechanical stress, taurolidine significantly enhances detachment of adherent colon carcinoma cells compared to the control (p < 0.05) and the oxaliplatin group (p < 0.05). This effect is dose dependent. CONCLUSIONS: Beside its cytotoxic effects, taurolidine could also change mechanical interactions of cancer cells with their environment. Local cancer cell conglomerates could be mechanically mobilized and may cause metastatic growth further downstream. The significance of changes in cellular morphology caused by taurolidine as well as its interaction with the microenvironment must be further addressed in clinical cancer therapies. Further clinical studies are needed to evaluate both the safety and efficacy of taurolidine for the treatment of peritoneal surface malignancies.

Exploring Insulin Production Following Alveolar Islet Transplantation (AIT).

Recent studies have demonstrated the feasibility of islet implantation into the alveoli. However, until today, there are no data on islet behavior and morphology at their transplant site. This study is the first to investigate islet distribution as well insulin production at the implant site. Using an ex vivo postmortem swine model, porcine pancreatic islets were isolated and aerosolized into the lung using an endoscopic spray-catheter. Lung tissue was explanted and bronchial airways were surgically isolated and connected to a perfusor. Correct implantation was confirmed via histology. The purpose of using this new lung perfusion model was to measure static as well as dynamic insulin excretions following glucose stimulation. Alveolar islet implantation was confirmed after aerosolization. Over 82% of islets were correctly implanted into the intra-alveolar space. The medium contact area to the alveolar surface was estimated at 60 +/- 3% of the total islet surface. The new constructed lung perfusion model was technically feasible. Following static glucose stimulation, insulin secretion was detected, and dynamic glucose stimulation revealed a biphasic insulin secretion capacity during perfusion. Our data indicate that islets secrete insulin following implantation into the alveoli and display an adapted response to dynamic changes in glucose. These preliminary results are encouraging and mark a first step toward endoscopically assisted islet implantation in the lung.

[Pneumonia in old age]. / Pneumonie im hohen Lebensalter.

Pneumonia is a common and severe disease in older people. In this group of patients pneumonia is among the four most frequent diseases leading to death. The diagnosis can often be difficult due to an atypical clinical presentation. Therefore, pneumonia should always be considered as the cause of any deterioration in an older person. Geriatric problems, such as frailty, physical and psychological limitations should be recorded as well as the social situation, as all these factors are of prognostic importance. Pneumonia acquired in a nursing home or by people in need of long-term care has a less favorable prognosis. Although this type of pneumonia is considered to be community acquired, special attenion is required. The treatment of pneumonia does not fundamentally differ from the treatment of younger patients but should take special situations into account, such as the patient's wishes documented in a living will when planning therapy. Older people in particular often show atypical clinical pictures with a coronavirus disease 2019 (COVID-19) infection. Therefore, in any acute change in the health condition of an older person COVID-19 should be considered.

[Aging of the lungs and immune system as hellmark in the pathogenesis of idiopathic pulmonary fibrosis and COVID-19]. / Alterung von Lunge und Immunsystem als Meilensteine in der Pathogenese von idiopathischer Lungenfibrose und COVID-19.

Idiopathic pulmonary fibrosis (IPF) does not occur in younger persons. Therefore, it is not surprising that the nine hallmarks of biological aging can all be found in the pathomechanism of IPF. In this respect the homeostasis of cellular protein synthesis, degradation and recycling becomes unbalanced, which causes a dysregulation of repair mechanisms in the case of lung damage. Severve acute respiratory syndrome coronarvius type 2 (SARS-CoV-2) infections may also predominantyl seen in aged persons. In this situation cellular aging of the lungs also plays a role but additionally, the aging of the immune system is also of great importance. Immunosenescence is associated with a loss of naïve T­cells. Moreover, there are gender-specific differences with a loss of B­cells only in men but not in women, which partly explains the more severe course of COVID-19 pneumonia in older men.

Treatment of Cheyne-Stokes respiration with adaptive servoventilation-analysis of patients with regard to therapy restriction.

PURPOSE: The SERVE-HF study revealed no benefit of adaptive servoventilation (ASV) versus guideline-based medical treatment in patients with symptomatic heart failure, an ejection fraction (EF) ≤45% and a predominance of central events (apnoea-hypopnea Index [AHI] > 15/h). Because both all-cause and cardiovascular mortality were higher in the ASV group, an EF ≤ 45% in combination with AHI 15/h, central apnoea-hyponoea index [CAHI/AHI] > 50% and central apnoea index [CAI] > 10/h were subsequently listed as contraindications for ASV. The intention of our study was to analyse the clinical relevance of this limitation. METHODS: Data were analysed retrospectively for patients treated with ASV who received follow-up echocardiography to identify contraindications for ASV. RESULTS: Echocardiography was conducted in 23 patients. The echocardiogram was normal in 10 cases, a left ventricular hypertrophy with normal EF was found in 8 patients, there was an EF 45-50% in 2 cases and a valvular aortic stenosis (grade II) with normal EF was found in 1 case. EF <45% was present in just 2 cases, and only 1 of these patients also had more than 50% central events in the diagnostic night. CONCLUSION: The population typically treated with ASV is entirely different from the study population in SERVE-HF, as nearly half of the patients treated with ASV showed a normal echocardiogram. Thus, the modified indication for ASV has little impact on the majority of treated patients. The current pathomechanistic hypothesis of central apnoea must be reviewed.

Assessment of sleep and sleep disorders in geriatric patients.

Sufficient and refreshing sleep is important for good health, physical and cognitive functioning as well as quality of life. An assessment of sleep quality and sleep disorders is therefore mandatory in geriatric patients. Despite a variety of clinical assessment tools for screening and diagnosing sleep disorders, only some of them have been validated in older subjects and nearly none in geriatric patients or in individuals with dementia. Therefore, the aim of this review is to present a concise overview of assessment tools for sleep disorders that are widely used in sleep medicine and to briefly discuss the suitability and limitations in geriatric patients and subjects with dementia.

Noninvasive ventilation: education and training. A narrative analysis and an international consensus document.

Noninvasive ventilation (NIV) is an increasingly used method of respiratory support. The use of NIV is expanding over the time and if properly applied, it can save patients' lives and improve long-term prognosis. However, both knowledge and skills of its proper use as life support are paramount. This systematic review aimed to assess the importance of NIV education and training. Literature search was conducted (MEDLINE: 1990 to June, 2018) to identify randomized controlled studies and systematic reviews with the results analyzed by a team of experts across the world through e-mail based communications. Clinical trials examining the impact of education and training in NIV as the primary objective was not found. A few studies with indirect evidence, a simulation-based training study, and narrative reviews were identified. Currently organized training in NIV is implemented only in a few developed countries. Due to a lack of high-grade experimental evidence, an international consensus on NIV education and training based on opinions from 64 experts across the twenty-one different countries of the world was formulated. Education and training have the potential to increase knowledge and skills of the clinical staff who deliver medical care using NIV. There is a genuine need to develop structured, organized NIV education and training programs, especially for the developing countries.

Cost-utility of non-invasive mechanical ventilation: Analysis and implications in acute respiratory failure. A brief narrative review.

The growing interest in the quality of patient care at the levels of the health care managers, insurance companies, and health professionals is evident. Further, the growing population requires good quality health services. In this review, we analyzed the cost-effectiveness of noninvasive ventilation (NIV) in an acute setting for the treatment of respiratory failure. The strength of this review is that it identified and summarized the most relevant studies regarding various aspects of the cost-utility of NIV in an acute setting. This is the first review that focuses on the importance of the skills and training of the team in the reduction of costs associated with NIV. However, the small number of studies, heterogeneity of quality, and different outcomes of the different studies are the greatest limitations of this review. In conclusion, although there is great variation in the data drawn from the literature, NIV seems to be a cost-effective tool, especially in specific patients (those with chronic obstructive pulmonary disease) for whom the addition of NIV improves outcomes and has a positive impact on this expenditure.

Emergencies and outcome in invasive out-of-hospital ventilation: An observational study over a 1-year period.

OBJECTIVES: The number of ventilated patients is further increasing which leads to an increasing number of patients with weaning failure. In Germany, the treatment of patients with invasive out-of-hospital becomes more and more common. The aim of the study was to observe the outcome, the frequency and character of emergencies of patients with invasive out-of-hospital ventilation. METHODS: We conducted a prospective study over 1 year. Fifty-nine invasively ventilated patients living either at home or at nursing homes specialized in ventilator medicine were included. RESULTS: Forty-one (71%) of the patients were living in a nursing home. Chronic obstructive pulmonary disease (COPD) was the most common underlying disease (52.5%). Duration of daily ventilation did not change over the 1-year period. 52.8% of the months went without a documented emergency. The most common emergencies were oxygen desaturation (29.6%), increase of secretion (12.2%) and dyspnea (8.7%). We found no difference in the frequency of emergencies between patients cared for in their own home compared with residential care. Ten patients died during the observation period. Fewer emergencies (P = .02, CI 0.03-0.85) was the only parameter associated with a reduced mortality. Frequency of emergencies as well as survival showed no difference regarding the way patients were cared for. CONCLUSIONS: In patients with invasive home mechanical ventilation survival for more than 1 year seems to be common. Only the rate of emergencies affected survival.

Fiducial marker placement via conventional or electromagnetic navigation bronchoscopy (ENB): an interdisciplinary approach to the curative management of lung cancer.

BACKGROUND AND AIMS: Conventional and electromagnetic navigation bronchoscopy (ENB) is generally used as a diagnostic tool in suspicious pulmonary nodules. The use of this technique for the placement of fiducial markers in patients with inoperable but early-stage lung cancer could present an innovative approach enabling risk-reduced therapy. METHODS: We present seven clinical cases where conventional bronchoscopy and ENB were used as part of an experimental interdisciplinary approach to clinical management and therapy planning. In each case, we analyzed the clinical indication, endoscopic procedures and post-interventional outcome. RESULTS: In six patients (three females, three males) with peripheral non-small cell lung cancer (NSCLC), stage cT1cN0cM0, surgery and conventional stereotactic radiation therapy was not possible because of end-stage chronic obstructive pulmonary disease. ENB was used for fiducial marker placement prior to cyberknife radiotherapy. No procedure-related complications were observed. Complete remission could be achieved in four cases, partial remission in two cases and no relevant complications induced by radiotherapy were observed. In one male patient, an endoluminal relapse in the right lower lobe was diagnosed following a right upper lobe resection for a NSCLC. The tumor could not be clearly identified by computerized tomography, so that the bronchoscopic placement of a fiducial marker in the tumor was performed in order to allow stereotactic radiochemotherapy, by which complete remission could be achieved. CONCLUSION: Fiducial marker placement may be an interesting bronchoscopic technique in the interdisciplinary therapeutic approach to inoperable early-stage lung cancer. In the described cases, therapy planning was successful and no procedure-related complications were observed.

Comparison of Transcutaneous and Capillary Measurement of PCO2 in Hypercapnic Subjects.

BACKGROUND: Measurement of PCO2 is vital in determining effective alveolar ventilation. However, obtaining capillary PCO2 by a skin prick of the earlobe is painful, and nocturnal measurements disturb sleep. End-expiratory measurement of PCO2 is also well established, but there is a low precision in predicting arterial or capillary CO2. The purpose of the study was to evaluate nocturnal measurement of noninvasive, transcutaneous PCO2 (PtcCO2 ) measurement in hypercapnic subjects. METHODS: In this prospective study, 31 subjects with chronic hypercapnic failure--in a stable phase of the underlying disease--and a control group of 12 healthy volunteers were included. Transcutaneous measurements were taken by the Tosca sensor (Radiometer, Copenhagen, Denmark) over a period of at least 6 h during the night. A capillary blood gas was measured at midnight and 4:00 am. RESULTS: The mean nocturnal capillary PCO2 (PcapCO2 ) of subjects was 50.6 ± 10.2 mm Hg. In the 31 subjects with known hypercapnic respiratory failure, the correlation between PtcCO2 and PcapCO2 at midnight was 0.86 and at 4:00 am r = 0.80. The bias of the hypercapnic subjects was d = + 4.5 with a limit(s) of agreement of 2 SD = 13.0. The process of blood sampling caused no significant change in PtcCO2 . CONCLUSIONS: Our study evaluated transcutaneous capnography as a continuous nocturnal measurement in hypercapnic subjects. We found a good agreement between the methods. Because CO2 is not constant in patients with respiratory failure, but instead fluctuates, we would recommend the continuous transcutaneous measurement of PCO2 as our method of choice in the diagnosis of nocturnal hypercapnia.

Anticyclic modulated ventilation versus continuous positive airway pressure in patients with coexisting obstructive sleep apnea and Cheyne-Stokes respiration: a randomized crossover trial.

BACKGROUND: Although coexisting obstructive sleep apnea (OSA) and Cheyne-Stokes respiration (CSR) occur frequently in patients with heart diseases, optimal treatment remains unclear. Positive airway pressure (PAP) effectively treats OSA and adaptive servo-ventilation (ASV) has been shown to improve CSR. We compared a new treatment algorithm combining automatic continuous positive airway pressure (APAP) and ASV (anticyclic modulated ventilation, ACMV) versus continuous positive airway pressure (CPAP). METHODS: Thirty-nine patients (35 male, four female; aged 65.5±9.7 years; body mass index, 31.0±5.9 kg/m2) with underlying heart disease and coexisting OSA and CSR were enrolled. After diagnostic polysomnography (PSG) and CPAP titration, patients were randomized either to CPAP or to ACMV for four weeks of treatment in a crossover design. RESULTS: Total apnea-hypopnea index (AHI) was 49.0±18.8/h at baseline, 12.3±14.6/h with CPAP (P<0.001 vs baseline), and 3.7±5.6/h with ACMV (P<0.001 vs. baseline and vs. CPAP). Obstructive AHI was 20.7±14.4/h at baseline, 5.1±9.3/h with CPAP (P<0.001 vs. baseline), and 0.4±0.4/h with ACMV (P<0.001 vs. baseline and vs. CPAP). Central AHI was 28.3±13.4/h at baseline, 7.2±9.7/h with CPAP (P<0.001 vs baseline) and 3.3±5.4/h with ACMV (P<0.001 vs. baseline and vs. CPAP). Ejection fraction was increased significantly (from 38.6±15.6 to 44.4±12.2%) only with ACMV. Subjective sleepiness significantly improved only with CPAP whereas objective sleep quality and treatment adherence were not different between both treatment modalities. CONCLUSION: ACMV is an effective treatment option in patients with coexisting OSA and CSR. It is superior to CPAP in reducing total AHI as well as obstructive and central AHI.

Successful weaning and decannulation after interventional bronchoscopic recanalization of tracheal stenosis.

PURPOSE: Early posttracheostomy tracheal stenosis (PTTS) may cause weaning and decannulation failure. Although bronchoscopic recanalization offers an effective treatment, it is not known how successfully patients can be weaned and decannulated after recanalization. The aims of this study were to determine the incidence of PTTS in a modern weaning center and to elucidate the benefit of interventional recanalization in terms of weaning and decannulation success. MATERIALS AND METHODS: A total of 722 patients admitted within a 24-month period were examined. Patients' baseline characteristics, incidence of weaning and decannulation failure, incidence of PTTS, and rate of postinterventional weaning and decannulation success were determined. RESULTS: Of 722 patients, 450 were deemed suitable for weaning from invasive ventilation. Two hundred eighty-eight patients showed initial weaning and decannulation failure, and 14 of these 288 patients (4.9%) were found to have a PTTS. Recanalization was performed in all cases without procedure-associated complications. Ten (71%) of 14 patients could be successfully weaned and decannulated. Seven of these 10 patients were discharged, 3 patients died during the hospital stay, and 4 (29%) of 14 patients could not be weaned. CONCLUSIONS: Posttracheostomy tracheal stenosis remains a relevant cause of weaning and decannulation failure. Bronchoscopic recanalization is safe and facilitates weaning and successful decannulation in about half of the cases.

Frequency and management of respiratory incidents in invasive home ventilation.

There has been a rise in the number of patients requiring long-term ventilation, both in the in-hospital and the out-of-hospital setting. Despite this, little is known about the subsequent clinical course of these patients following hospital discharge. The purpose of this study was to determine the frequency and management of respiratory incidents in patients with invasive out-of-hospital ventilation living in a nursing home allied to a weaning centre. We evaluated retrospectively the protocols that are used to monitor the patients over a period of 2 months. The average time from hospital discharge was 386 ± 330 days. Of the total 17 patients, 9 (53%) patients remained free from any respiratory incidents, while the remaining 8 (47%) patients were responsible for a total of 95 respiratory incidents. Patients that suffered respiratory incidents had been ventilated at home for an average of 194 days, while the others were receiving out-of-hospital ventilation for an average of 557 days. Desaturation (17), dyspnoea (17) and reduced general condition (10) were the most common respiratory incidents. Also, the use of an Ambu bag (bag valve mask; 17), request for a pneumologist review (12) and replacement of the tracheal cannula (7) were the most common interventions. Respiratory incidents are common in invasive home mechanical ventilation, and so home mechanical ventilation needed to be organized safely. Being allied to a weaning centre helps to organize invasive home mechanical ventilation in a safe manner over the long-term ventilation.

Evaluation of a noninvasive algorithm for differentiation of obstructive and central hypopneas.

STUDY OBJECTIVES: The clear discrimination of central and obstructive hypopneas is highly relevant to avoid misinterpretation and inappropriate treatment of complicated breathing patterns. Esophageal manometry is the accepted standard for the differentiation of the phenotypes of sleep apnea. However, it is limited in its use due to poor acceptance by patients and therefore rarely performed in routine clinical practice. Flattening of the inspiratory airflow curve, paradoxical breathing, arousal position, sleep stages, and breathing pattern at the end of the hypopnea can each give hints for the classification of hypopnea. The aim of this study was to evaluate a standardized algorithm combining these polysomnographic parameters for the discrimination of hypopneas in everyday practice. METHODS: Polysomnography (PSG) and esophageal manometry were performed in 41 patients suspected of having sleep apnea (33 male, 52.3 ± 15.9 yr, body mass index 28.6 ± 4.5 kg/m(2)). Hypopneas were independently discriminated by blinded investigators based on esophageal pressure and the PSG-based algorithm. Only those hypopneas that could be differentiated with both methods were evaluated. RESULTS: There were 1,175 of 1,837 hypopneas (64%) that could be defined by esophageal pressure, 1,812 (98.6%) by the PSG-based algorithm. Using esophageal pressure as a reference, the new algorithm correctly defined 76.9% of central and 60.5% of obstructive hypopneas. The overall accuracy was 68%. The isolated analysis of single PSG parameters revealed a lower accuracy compared with the combined algorithm. CONCLUSIONS: The PSG-based algorithm allows for discrimination of most hypopneas. It is advantageous in comparison with esophageal pressure because it is noninvasive and less impaired by artefacts. Therefore, it is a potentially helpful tool for sleep specialists. CITATION: Randerath WJ; Treml M; Priegnitz C; Stieglitz S; Hagmeyer L; Morgenstern C. Evaluation of a noninvasive algorithm for differentiation of obstructive and central hypopneas. SLEEP 2013;36(3):363-368.