Lars Hagmeyer

A Novel Extracorporeal CO2 Removal System: Results of a Pilot Study of Hypercapnic Respiratory Failure in Patients With COPD

BACKGROUND Hypercapnic respiratory failure in patients with COPD frequently requires mechanical ventilatory support. Extracorporeal CO2 removal (ECCO2R) techniques have not been systematically evaluated in these patients. METHODS This is a pilot study of a novel ECCO2R device that utilizes a single venous catheter with high CO2 removal rates at low blood flows. Twenty hypercapnic patients with COPD received ECCO2R. Group 1 (n = 7) consisted of patients receiving noninvasive ventilation with a high likelihood of requiring invasive ventilation, group 2 (n = 2) consisted of patients who could not be weaned from noninvasive ventilation, and group 3 (n = 11) consisted of patients on invasive ventilation who had failed attempts to wean. RESULTS The device was well tolerated, with complications and rates similar to those seen with central venous catheterization. Blood flow through the system was 430.5 ± 73.7 mL/min, and ECCO2R was 82.5 ± 15.6 mL/min and did not change significantly with time. Invasive ventilation was avoided in all patients in group 1 and both patients in group 2 were weaned; PaCO2 decreased significantly (P < .003) with application of the device from 78.9 ± 16.8 mm Hg to 65.9 ± 11.5 mm Hg. In group 3, three patients were weaned, while the level of invasive ventilatory support was reduced in three patients. One patient in group 3 died due to a retroperitoneal bleed following catheterization. CONCLUSIONS This single-catheter, low-flow ECCO2R system provided clinically useful levels of CO2 removal in these patients with COPD. The system appears to be a potentially valuable additional modality for the treatment of hypercapnic respiratory failure.

Definition, discrimination, diagnosis and treatment of central breathing disturbances during sleep

The complexity of central breathing disturbances during sleep has become increasingly obvious. They present as central sleep apnoeas (CSAs) and hypopnoeas, periodic breathing with apnoeas, or irregular breathing in patients with cardiovascular, other internal or neurological disorders, and can emerge under positive airway pressure treatment or opioid use, or at high altitude. As yet, there is insufficient knowledge on the clinical features, pathophysiological background and consecutive algorithms for stepped-care treatment. Most recently, it has been discussed intensively if CSA in heart failure is a “marker” of disease severity or a “mediator” of disease progression, and if and which type of positive airway pressure therapy is indicated. In addition, disturbances of respiratory drive or the translation of central impulses may result in hypoventilation, associated with cerebral or neuromuscular diseases, or severe diseases of lung or thorax. These statements report the results of an European Respiratory Society Task Force addressing actual diagnostic and therapeutic standards. The statements are based on a systematic review of the literature and a systematic two-step decision process. Although the Task Force does not make recommendations, it describes its current practice of treatment of CSA in heart failure and hypoventilation. Description of the actual approach to differential diagnosis and treatment options in central breathing disturbances http://ow.ly/QsE9304Jt8f

The role of transbronchial cryobiopsy and surgical lung biopsy in the diagnostic algorithm of interstitial lung disease

It is not yet known if transbronchial cryobiopsy (TCB) is a reliable and safe diagnostic tool in the investigation of interstitial lung disease (ILD). To date, there have been no studies directly comparing the value of TCB with that of surgical lung biopsy (SLB). The study was initiated to determine whether the samples taken by TCB lead to a reliable diagnosis and whether SLB can be avoided in a relevant percentage of cases.

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.

Insights from the German Compassionate Use Program of Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis.

Background: Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and has been shown to slow disease progression by reducing annual lung function decline. Objective: To evaluate the results of a large cohort of IPF patients treated with nintedanib within a compassionate use program (CUP) in Germany (9 centers). Methods: Patients (≥40 years) were required to have a confirmed diagnosis of IPF, a forced vital capacity (FVC) ≥50% predicted (pred.) and a carbon monoxide diffusing capacity (DLCO) 30-79% pred. and not to be eligible for pirfenidone treatment. Clinical data, pulmonary function tests and adverse events were recorded up to July 2015. Results: Sixty-two patients (48 male/14 female) with moderate IPF (FVC 64 ± 17% pred. and DLCO 40 ± 10% pred.) were treated with nintedanib. 77% of patients switched from pirfenidone (mean treatment duration 14 ± 2 months) mostly due to disease progression (mean decline in FVC 7.4 ± 3% pred. in the 6 months prior to nintedanib intake). Initiation of nintedanib treatment occurred 69 ± 29 months after IPF diagnosis, and mean treatment duration was 8 ± 4 months. Most patients (63%) stabilized 6 months after treatment start (mean FVC decline 3 ± 1 vs. -17 ± 2% in patients with disease progression; p < 0.01). The most common adverse events were diarrhea (63%) and weight loss (50%). Dose reduction occurred in 34% of cases and treatment discontinuation in 10%. Conclusion: Nintedanib treatment was generally well tolerated and was associated with FVC stabilization in the majority of IPF patients in this CUP setting where most patients were not treatment naïve. Our data are in agreement with the previously published data.

Transbronchial Cryobiopsies for the Diagnosis of Diffuse Parenchymal Lung Diseases: Expert Statement from the Cryobiopsy Working Group on Safety and Utility and a Call for Standardization of the Procedure

Transbronchial cryobiopsies (TBCB) have recently been introduced as a promising and safer alternative to surgical lung biopsy in the diagnostic approach to diffuse parenchymal lung diseases (DPLD). Despite a substantial and expanding body of literature, the technique has not yet been standardized and its place in the diagnostic algorithm of DPLD remains to be defined. In part, this reflects concerns over the diagnostic yield and safety of the procedure, together with the rapid spread of the technique without competency and safety standards; furthermore, there is a substantial procedural variability among centers and interventional pulmonologists. We report this expert statement proposed during the third international conference on “Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease” (Ravenna, October 27–28, 2016), which formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure. The following 5 domains were reviewed: (1) what is the role of TBCB in the diagnostic evaluation of DPLD: patient selection; (2) pathological considerations; (3) contraindications and safety considerations; (4) how should TBCB be performed and in what procedural environment; and (5) who should perform TBCB. Finally, the existence of white paper recommendations may also reassure local hospital credentialing committees tasked with endorsing an adoption of the technique.

Successful Concomitant Therapy with Pirfenidone and Nintedanib in Idiopathic Pulmonary Fibrosis: A Case Report

Pirfenidone and nintedanib are both pleiotropic anti-fibrotic agents approved for the treatment of idiopathic pulmonary fibrosis (IPF) as monotherapy. To date, evidence supporting their efficacy as concomitant therapy has not been reported. Here, we present the first case of a Caucasian male patient with IPF treated with both pirfenidone and nintedanib following 2 years of treatment with pirfenidone monotherapy. Over a 24-month period, there was a clear decline in the patients forced vital capacity from 3.5 liter before initiation of treatment to 2.5 liter after 24 months. Concomitant nintedanib treatment was initiated in March 2015. Lung function stabilized, and the two treatments were well tolerated. Treatment with pirfenidone and nintedanib has currently been ongoing for nearly 12 months. This is the first report of a successful long-term treatment with pirfenidone and nintedanib and suggests that in selected cases, concomitant anti-fibrotic therapy may represent a safe and therapeutically valuable escalation option after pirfenidone monotherapy.

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

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.

Smoking-Related Interstitial Lung Disease

BACKGROUND Smoking-related interstitial lung diseases (SR-ILDs) are a heterogeneous group of diseases with major clinical significance. Reliable epidemiological data are not yet available. METHOD Review of pertinent literature retrieved by a selective search in PubMed. RESULTS The available data on many aspects of SR-ILDs are sparse, but recent studies on the pathophysiology and targeted treatment of these conditions have revealed ways in which clinical outcomes can be improved. Highresolution computerized tomography should be used for differential diagnosis; lung biopsy is often unnecessary. Oncogenic mutations play a role in the pathogenesis of pulmonary Langerhans-cell histiocytosis (PLCH). In the future, cladribine and vemurafenib may be treatment options for PLCH. Desquamative interstitial pneumonia (DIP) may be difficult to distinguish from respiratorybronchiolitis-associated interstitial lung disease (RB-ILD); DIP is treated with steroids and sometimes with immune suppressants. In idiopathic pulmonary fibrosis (IPF), the antifibrotic drugs pirfenidone and nintedanib can delay disease progression. Smoking is also a risk factor for combined pulmonary fibrosis and emphysema (CPFE), rheumatoid-arthritis-associated interstitial lung disease (RA-ILD), pulmonary alveolar proteinosis (PAP), acute eosinophilic pneumonia (AEP), and diffuse alveolar hemorrhage (DAH) in Goodpasture syndrome. CONCLUSION In smokers with exertional dyspnea and/or a nonproductive cough, SR-ILDs must be considered in the differential diagnosis. If an SR-ILD is suspected, the patient should be referred to a pulmonary specialist. Early treatment and smoking cessation can improve clinical outcomes, particularly in the acute and chronically progressive types of SR-ILD.

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.