Effects of respiratory muscle training (RMT) in patients with mild to moderate obstructive sleep apnea (OSA).

PURPOSE: Different forms of training focusing on the muscles of the upper airways showed limited effects on obstructive sleep apnea (OSA) and/or snoring. We investigated the effect of generalized respiratory muscle training (RMT) in lean patients with mild to moderate OSA. METHODS: Nine male subjects (52.0 ± 10.8 years, BMI 29.1 ± 2.1 kg/m2) with obstructive sleep apnea (apnea-hypopnea index (AHI) 9-29) participated in an open, single-arm pilot study. After a 1-week build-up phase, patients underwent 4 weeks of normocapnic hyperpnea RMT five times a week for 30 min each. The initial and final measurements comprised polysomnography, pulmonary function tests, Epworth sleepiness scale (ESS), and SF-36 questionnaire (quality of life (QoL) self-assessment). The investigational site was a university-affiliated hospital for pulmonary diseases and sleep medicine, Solingen/Germany. RESULTS: Patients trained effectively, seen by a significant (p < 0.01) increase of breathing frequency (23.3 ± 1.5 /min vs. 30.6 ± 2.9 /min) and minute volume (81.2 ± 13.7 L vs. 109.1 ± 21.9 L). AHI, snoring and ESS remained unchanged after training. QoL as measured by SF-36 significantly (p < 0.05) improved after the training in the subscales "bodily pain" (79 ± 21 vs. 90 ± 12) and "change of health" (3.1 ± 0.3 vs. 2.4 ± 0.5). CONCLUSIONS: There is no evidence that AHI, pulmonary function or daytime sleepiness are affected by 5 weeks of RMT. Nevertheless, there is an improvement of parameters of quality of life. TRIAL REGISTRATION: ClinicalTrials.gov , register no. NCT 00936286.

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 patient's 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.

Effect of a Heated Breathing Tube on Efficacy, Adherence and Side Effects during Continuous Positive Airway Pressure Therapy in Obstructive Sleep Apnea.

BACKGROUND: Heated breathing tubes were developed to improve heated humidification in continuous positive airway pressure (CPAP) therapy of patients with obstructive sleep apnea syndrome (OSAS). OBJECTIVES: We wanted to investigate the influence of a heated breathing tube on patients' satisfaction with the treatment, the rate of side effects and the adherence to treatment. METHODS: Eighty-eight patients with primarily diagnosed OSAS were treated in a randomized, controlled, single-blind trial for 12 months either with a CPAP system plus conventional heated humidifier or with a CPAP system plus heated humidifier and an integrated heated breathing tube. RESULTS: Both systems improved the respiratory disturbances and the quality of sleep in a similar manner. The difference in the overall satisfaction with the treatment (subscale 3 of the visual analogue scale) between the two treatment groups was not statistically significant (mean difference -14.1, 95% CI -28.7 to 0.6; p = 0.059). The rate of side effects and the quality of life did not differ significantly between the two groups. The patients with the heated breathing tube used the treatment on average 1 h longer, but this was not statistically significant (4.96 ± 1.95 vs. 3.90 ± 2.54 h/night; p = 0.06). CONCLUSIONS: Controlled heated breathing tube humidification as compared to conventional heated humidification improves neither the adherence to treatment, nor the rate of side effects, nor the quality of life in nonselected OSAS patients.

Parameters of Overnight Pulse Wave under Treatment in Obstructive Sleep Apnea.

BACKGROUND: Sleep-related breathing disorders may promote cardiovascular (CV) diseases. A novel and differentiated approach to overnight photoplethysmographic pulse wave analysis, which includes risk assessment and measurement of various pulse wave characteristics, has been evaluated in obstructive sleep apnea (OSA). OBJECTIVES: The purpose of this study was to assess if and which of the differentiated pulse wave characteristics might be influenced by OSA treatment with positive airway pressure (PAP). METHODS: The study included two protocols. In the case-control study (group A), pulse wave-derived CV risk indices recorded during PAP therapy were compared with those obtained in age, body mass index, and CV risk class-matched patients with untreated OSA (n = 67/67). In the prospective PAP treatment study (group B), 17 unselected patients undergoing a full-night sleep test at baseline and after 23 ± 19 weeks of treatment were analyzed. RESULTS: In untreated OSA patients (group A), the overnight hypoxic load was increased (SpO2 index 38.7 ± 17.5 vs. 24.0 ± 11.1, p < 0.001) and the pulse wave attenuation index (PWA-I) was lower (29.4 ± 9.2 vs. 33.5 ± 11.8, p = 0.022) than in treated patients. In group B, PAP therapy reduced the hypoxic load and increased the PWA-I significantly. The composite CV risk index was slightly but not significantly reduced. CONCLUSIONS: PAP therapy modified the hypoxic load and pulse wave-derived markers. The PWA-I - associated with sympathetic vascular tone - was most prominently modified by PAP. This novel approach to markers of CV function should be further evaluated in prospective studies.

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.

Long-term therapy with continuous positive airway pressure in obstructive sleep apnea: adherence, side effects and predictors of withdrawal - a 'real-life' study.

BACKGROUND: Long-term adherence to positive airway pressure (PAP) treatment is essential in patients with obstructive sleep apnea syndrome (OSAS). OBJECTIVES: The aim of the present study was to analyze treatment adherence under real-life conditions and factors associated with discontinuation of PAP therapy. METHODS: Patients newly diagnosed with OSAS and started on PAP therapy were contacted by telephone after a minimum of 1 year. Side effects, quality of life, subjective treatment adherence and Epworth Sleepiness Scale (ESS) scores were assessed. Objective treatment adherence was calculated by reading the built-in run time counter of the PAP device. Anthropometric parameters, level of education, apnea-hypopnea index (AHI), ESS score and the type of PAP therapy prescribed at the time of the first stay in the sleep lab were collected retrospectively. RESULTS: Median follow-up was 13 months (range 7-18 months). Of 303 patients (69 female, 234 male) available for this study, 191 patients (63%) still used the PAP device regularly ('users'), while 83 (27.4%) had definitively discontinued PAP treatment ('nonusers'). In the nonusers group, 29 patients (34.9%) discontinued PAP treatment within the first 3 months. In the users group, subjective PAP usage was 6.6 ± 1.5 h/night and objective adherence was 4.7 ± 2.3 h/night. Objective nightly use of PAP treatment correlated significantly with baseline AHI (r = 0.13, p = 0.041) but not with sex, age, body mass index, ESS score or education level. Patients with a low AHI and ESS score and patients without a coexisting medical condition or with more than two comorbidities tended to discontinue PAP therapy more frequently. CONCLUSIONS: PAP treatment adherence has to be optimized in OSAS patients. When initiating PAP therapy, clinicians have to focus on those patients at risk for discontinuing treatment. Education sessions and closer follow-up are possible strategies to improve treatment adherence and to avoid treatment discontinuation.

Choosing an Adequate Test to Determine Fitness for Air Travel in Obese Individuals.

BACKGROUND: Air travel is physically demanding and, because obesity is rising, physicians increasingly need to assess whether such patients can fly safely. Our aim was to compare the diagnostic accuracy of two routinely used exercise tests, 50-m walk test and 6-min walk test, and hypoxic challenge testing (HCT) in obese individuals. We further explored the diagnostic potential of perceived dyspnea as measured with the Borg scale because this is often recorded subsequent to walking tests. METHODS: In this prospective study, we examined 21 obese participants (10 women, age 51 ± 15 [mean  ±  SD], BMI 36 ± 5  kg/m2). The most prevalent comorbidity was COPD (n = 11). The reference standard for in-flight hypoxia, defined as oxygen saturation below 90%, was established in an altitude chamber. Diagnostic accuracy of each index test was estimated by area under the receiver operating characteristic curve (AUC). RESULTS: Of the 21 participants, 13 (9 with COPD) were identified with in-flight hypoxia. HCT was the only test separating the reference groups significantly with AUC 0.87 (95% CI,  0.62-0.96). Neither of the walking tests predicted noticeably above chance level: 50 m walk test had an AUC of 0.63 (0.36-0.84) and 6MWT had an AUC of 0.64 (0.35-0.86). We further observed good prognostic ability of subjective dyspnea assessment when recorded after 6MWT with an AUC of 0.80 (0.55-0.93). CONCLUSIONS: In-flight hypoxia in obese individuals can be predicted by HCT but not by simple walking tests.

CPAP therapy improves erectile function in patients with severe obstructive sleep apnea.

OBJECTIVES: Erectile dysfunction (ED) is highly prevalent in obstructive sleep apnea (OSA), however, the effect of continuous positive airway pressure (CPAP) therapy on erectile function has not yet been thoroughly investigated in these patients. METHODS: Ninety-four men with severe OSA (ie, with an apnea-hypopnea-index ≥ 30/h of sleep) were prospectively evaluated for the presence and severity of ED before and after 6-12 months of CPAP therapy. The abbreviated version of the International Index of Erectile Function, (the IIEF-5) was used to rate erectile function. Furthermore, all study participants responded to standard questionnaires of daytime sleepiness (Epworth Sleepiness Scale), quality of life (WHO Wellbeing 5 questionnaire) and depression (Major Depression Inventory). RESULTS: ED as defined by an IIEF-5 score of ≤21 was present in 64 patients (68.1%). CPAP treatment significantly improved erectile function in those patients suffering from moderate and severe ED. Additionally, a trend for a correlation between the improvement of erectile function under CPAP and the hours of its use was observed. Finally, this effect was associated with larger improvements of quality of life in affected patients. CONCLUSIONS: ED is very frequent in men with severe OSA and can at least partly be reversed by long-term CPAP therapy in most seriously affected patients. The beneficial effect on erectile function may depend on CPAP compliance and is accompanied by improvements of quality of life. Randomized controlled trials are needed to confirm these findings.

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.

Validation of transbronchial cryobiopsy in interstitial lung disease - interim analysis of a prospective trial and critical review of the literature.

BACKGROUND: Transbronchial Cryobiopsy (Cryo-TBB) represents a new approach for sampling lung tissue in interstitial lung disease (ILD). OBJECTIVES: Comparing the reliability of Cryo-TBB results and the procedure's complication rates with the procedure of surgical lung biopsy (SLB). METHODS: ILD subjects with the need of lung tissue sampling are analyzed in this prospective trial. To determine the relevance of procedure-related complications the pooled data from the ongoing and previous Cryo-TBB studies were compared with pooled data from previous SLB studies in an interim analysis. In our own cohort we analyzed how often Cryo-TBB results lead to a definite diagnosis without the need for a SLB. In subjects who underwent both procedures it was determined how often SLB confirmed Cryo-TBB findings. RESULTS: Analyzing the pooled data of the ongoing study (19 subjects) and our own retrospective study (32 subjects), in 38/51 subjects (75%) SLB was deemed to be unnecessary following Cryo-TBB. In 12/13 subjects an SLB was performed confirming Cryo-TBB results in 92%. 30 day-mortality was 1.9%, bleeding occurred in 78%, pneumothorax in 22%. 2 subjects showed a myocardial infarction. Complication rates are comparable to previous Cryo-TBB studies. Analysis of the pooled data from the literature showed an overall 30-day mortality of 0.7% for Cryo-TBB and 3.3% for SLB. CONCLUSIONS: Cryo-TBB may be a reliable diagnostic tool in ILD, dispensing the need for a SLB in most cases. Severe complications may occur less frequently than in SLB. Modifications of the procedure may lead to further risk reduction.

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.

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.

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

BACKGROUND AND AIMS: 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. METHODS: We analyzed 32 subjects with suspected ILD who underwent a TCB. Subjects' baseline characteristics, pathological findings after TCB and SLB, and complication rates were analyzed. The pathological inter-rater agreement was quantified statistically. RESULTS: The overall inter-rater agreement concerning TCB sample evaluation was good with a kappa value of 0.80. In 23/32 cases (72%), the findings from the TCB showed a strong congruence with all other clinical data, thereby enabling a definitive diagnosis. Eight of the remaining nine subjects gave their consent for an SLB, which led to a definitive histological diagnosis in six cases (75%). Following TCB, pneumothorax occurred in 6/32 subjects (19%) and endobronchial bleeding was moderate in 8/32 (25%) and was severe in 17/32 cases (53%). CONCLUSION: This is the first study to correlate histological results and complications following TCB and SLB in ILD subjects, some of whom underwent both procedures. TCB is a suitable diagnostic tool in ILD, potentially completely dispensing with the need for an SLB in some cases. In all cases, an interdisciplinary case evaluation is necessary as a final step.

Pulmonary Cytomegalovirus Replication in Renal Transplant Patients with Late Onset Pneumonitis.

BACKGROUND: In renal transplant patients, pneumonitis may be caused by cytomegalovirus (CMV pneumonitis). This condition is usually accompanied by CMV viremia. However, CMV may also reactivate locally in the lungs of renal transplant patients with pneumonitis due to other pathogens. The impact of local CMV replication/reactivation in the lungs is unknown. MATERIAL AND METHODS: All renal transplant patients at the Duesseldorf transplant center in the time from 01/2004 to 1/2008 were analyzed concerning pulmonary CMV replication in the setting of pneumonitis. RESULTS: Of 434 renal transplant recipients, 25 patients were diagnosed with pneumonitis. From these 25 patients with pneumonitis, 7 presented with isolated pulmonary CMV replication but without relevant CMV viremia 8±4.2 months after renal transplantation. Three of the 7 patients needed long-term respiratory support by invasive mechanical ventilation. Pulmonary opportunistic infections were diagnosed in 6 of the 7 patients. Therapy consisted of a reduction in immunosuppression, ganciclovir, and antibiotics. CONCLUSIONS: Our findings suggest that pulmonary CMV replication occurs in renal transplant patients with pneumonitis even at later phases after renal transplantation. This finding seems to be a frequent complication (7/25 patients). Clinicians should be aware of this condition because blood-based screening assays for CMV will remain negative.

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.

The use of overnight pulse wave analysis for recognition of cardiovascular risk factors and risk: a multicentric evaluation.

OBJECTIVES: Conventional methods for cardiovascular disease risk stratification are based on quantification of recognized risk factors or assessment of biomarkers during the wake period. We evaluated an algorithm on the basis of a photoplethysmographic pulse wave recording during sleep for cardiovascular risk assessment. METHODS: Five hundred and twenty individuals (346 men, age 55.0 ± 13.4 years, BMI 29.9 ± 6.  kg/m) with suspected sleep apnoea were randomly recruited at five sleep centres. Individual cardiovascular risk scores were calculated in accordance with established cardiovascular risk matrixes (ESH/ESC, Framingham, SCORE, PROCAM scores). A digital photoplethysmographic pulse wave signal was continuously recorded during the night using an oximeter sensor. An algorithm based on eight separate hypoxic and pulse wave derived parameters was trained in 130 individuals and validated in 390 individuals for low/high cardiovascular risk classification. RESULTS: All derived parameters were associated with elevated ESH/ESC risk in univariate analysis and five in the multiple logistic regression model [discrimination index C = 0.8, Chi-square (7) = 69, P < 0.0001]. The combined algorithm detected high-risk patients (validation set, ESH/ESC risk classes 4 and 5) with a sensitivity, specificity, positive predictive value and negative predictive value of 74.5, 76.4, 69.0 and 81.0%, respectively. Significant associations were also found for the Framingham, SCORE and PROCAM scores. The computed risk scores in individuals with/without (n = 34/356) a previous history of cardiovascular event (myocardial infarction, transitory ischemic attack or stroke) were 0.71 ± 0.27 and 0.42 ± 0.34 (P < 0.001), respectively. CONCLUSION: Parameters derived from modified pulse oximetry during sleep may provide information on cardiovascular function. Combined signal analysis may be used for recognition of individuals with established cardiovascular risk in a sleep laboratory cohort.

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.

A novel extracorporeal CO(2) 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.

Long-term auto-servoventilation or constant positive pressure in heart failure and coexisting central with obstructive sleep apnea.

BACKGROUND: The coexistence of obstructive sleep apnea (OSA) and central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR) is common in patients with heart failure (HF). While CPAP improves CSA/CSR by about 50%, maximal suppression is crucial in improving clinical outcomes. Auto-servoventilation (ASV) effectively suppresses CSA/CSR in HF, but few trials have been performed in patients with coexisting OSA and CSA/CSR. Our objective was to evaluate a randomized, controlled trial to compare the efficacy of ASV and CPAP in reducing breathing disturbances and improving cardiac parameters in patients with HF and coexisting sleep-disordered breathing. METHODS: Both modes were delivered using the BiPAP autoSV (Philips Respironics) over a 12-month period. Seventy patients (63 men, 66.3 ± 9.1 y, BMI 31.3 ± 6.0 kg/m(2)) had coexisting OSA and CSA/CSR, arterial hypertension, coronary heart disease, or cardiomyopathy and clinical signs of heart failure New York Heart Association classes II-III. Polysomnography, brain natriuretic peptide (BNP), spiroergometry, and echocardiography were performed at baseline and after 3 and 12 months of treatment. RESULTS: Both modes of therapy significantly improved respiratory disturbances, oxygen desaturations, and arousals over the study period. ASV reduced the central apnea hypopnea index (baseline CPAP, 21.8 ± 11.7; ASV, 23.1 ± 13.2; 12 months CPAP, 10.7 ± 8.7; ASV, 6.1 ± 7.8, P < .05) and BNP levels (baseline CPAP, 686.7 ± 978.7 ng/mL; ASV, 537.3 ± 891.8; 12 months CPAP, 847.3 ± 1848.1; ASV, 230.4 ± 297.4; P < .05) significantly more effectively as compared with CPAP. There were no relevant differences in exercise performance and echocardiographic parameters between the groups. CONCLUSIONS: ASV improved CSA/CSR and BNP over a 12-month period more effectively than CPAP.