Search

This SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure) sub study analysis evaluated polysomnography (PSG) data in patients with heart failure with reduced ejection fraction (HFrEF) and predominant central sleep apnea (CSA) randomised to guideline-based medical therapy, with or without adaptive servo ventilation (ASV). Patients underwent full overnight PSG at baseline and at 12 months. All PSG recordings were analysed by a core laboratory. Only data for patients with baseline and 3- or 12-month values were included. The sub study included 312 patients; the number with available PSG data differed for each variable (94–103 in the control group, 77–99 in the ASV group). After 12 months, baseline-adjusted respiratory measures were significantly better in the ASV group versus control. Although some between-group differences in sleep measures were seen at 12 months (e.g., better sleep efficiency in the ASV group), these were unlikely to be clinically significant. The number of periodic leg movements during sleep (PLMS) increased in the ASV group (p = 0.039). At 12 months, the respiratory arousal index was significantly lower in the ASV versus control group (p < 0.001), whilst the PLMS-related arousal index was significantly higher in the ASV group (p = 0.04 versus control). ASV attenuated the respiratory variables characterising sleep apnea in patients with HFrEF and predominant CSA in SERVE-HF. Sleep quality improvements during ASV therapy were small and unlikely to be clinically significant. The increase in PLMS and PLMS-related arousals during ASV warrants further investigation, particularly relating to their potential association with increased cardiovascular risk. in press

A commonly used approach to study the association between a time-varying biomarker, such as forced vital capacity (FVC), and a time-to-event outcome, such as new onset of chronic obstructive pulmonary disease (COPD), is to incorporate the biomarker as a time-dependent covariate in a Cox model. This approach, which is known as the time-dependent Cox model (TDCM), requires knowledge of the value of the time-varying biomarker at all time points at which the event of interest occurs [1]. However, in clinical studies, longitudinal biomarker measurements are taken intermittently during scheduled (and sometimes unscheduled) visits, meaning that imputation of missing values is required for those event times at which the biomarker is not observed. In practical application of the TDCM, this is achieved by carrying forward the most recent biomarker measurement. While the use of last observation carried forward (LOCF) is easy to understand and implement, the resulting step function (see fig. 1, panel C for an example) is unlikely to provide a good approximation of the true biomarker trajectory. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Chen has nothing to disclose. Conflict of interest: Dr. Postmus has nothing to disclose. Conflict of interest: Dr. Cowie has nothing to disclose. Conflict of interest: Dr. Woehrle has nothing to disclose. Conflict of interest: Dr. Wegscheider has nothing to disclose. Conflict of interest: Dr. Simonds has nothing to disclose. Conflict of interest: Dr. Boezen has nothing to disclose. Conflict of interest: Dr. Somers reports other from Steering Committee SERV HF, outside the submitted work. Conflict of interest: Dr. Teschler has nothing to disclose. Conflict of interest: Dr. Eulenburg has nothing to disclose.

International audience; Aims: The Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients with Heart Failure trial investigated the effects of adaptive servo-ventilation (ASV) (vs. control) on outcomes of 1325 patients with heart failure and reduced ejection fraction (HFrEF) and central sleep apnoea (CSA). The primary outcome (a composite of all-cause death or unplanned HF hospitalization) did not differ between the two groups. However, all-cause and cardiovascular (CV) mortality were higher in the ASV group. Circulating biomarkers may help in better ascertain patients’ risk, and this is the first study applying a large set of circulating biomarkers in patients with both HFrEF and CSA.Methods and results: Circulating protein-biomarkers (n = 276) ontologically involved in CV pathways, were studied in 749 (57% of the trial population) patients (biomarker substudy), to investigate their association with the study outcomes (primary outcome, CV death and all-cause death). The mean age was 69 ± 10 years, and > 90% were male. The groups (ASV vs. control and biomarker substudy vs. no biomarker) were well balanced. The “best” clinical prognostic model included male sex, systolic blood pressure < 120 mmHg, diabetes, loop diuretic, cardiac device, 6-min walking test distance, and N-terminal pro BNP as the strongest prognosticators. On top of the “best” clinical prognostic model, the biomarkers that significantly improved both the discrimination (c-index) and the net reclassification index (NRI) of the model were soluble suppression of tumorigenicity 2 for the primary outcome; neurogenic locus notch homolog protein 3 (Notch-3) for CV-death and all-cause death; and growth differentiation factor 15 (GDF-15) for all-cause death only.Conclusions: We studied 276 circulating biomarkers in patients with HFrEF and central sleep apnoea; of these biomarkers, three added significant prognostic information on top of the best clinical model: soluble suppression of tumorigenicity 2 (primary outcome), Notch-3 (CV and all-cause death), and GDF-15 (all-cause death).

Introduction: Recent data suggested that different ASV devices are associated with different outcomes based on a physiological experiment in complex sleep apnoea patients with preserved ejection fraction (n=14). Due to changes in technology over time, two different ASV devices were used in the SERVE-HF study of heart failure patients with reduced ejection fraction (Cowie et al. NEJM 2015;373:1095–105). Aim: To compare outcomes by ASV device used in SERVE-HF (n=1325). Methods: Outcome data from the SERVE-HF study were retrospectively analysed based on stratification by ASV device used (AutoSet CS2 at trial start [2009], moving to AutoSet S9SC from 2011; trial end 2013). CS2 was the only device used in 2009 and 2010, and S9SC was the only device used in 2013; in 2011 and 2012 the number of patients using CS2 and S9SC was 65 and 54, and 5 and 145, respectively. Control group patients who started ASV were also included in the analysis. Results: There was no effect of ASV device type on the primary endpoint (left figure), the rate of cardiovascular death (right figure), or on the rate of non-cardiovascular death. No significant interactions were found between device type and the primary endpoint (p=0.572), cardiovascular death (p=0.674) or non-cardiovascular death (p=0.071). Conclusion: Data from the large, randomised, SERVE-HF trial did not show any differential effects of ASV on outcome based on device type.

Polysomnography (PSG) is the gold standard for sleep analysis and the diagnosis of sleep-disordered breathing (SDB). As PSG is time-consuming and labor-intensive, it is the last step in a stepwise diagnostic workup. An early preliminary diagnosis can be obtained by a novel single-channel minimal-contact device which is placed under the patient’s mattress topper. This study assessed the diagnostic accuracy of the novel minimal-contact device VitaLog (SWG Sportwerk GmbH & Co. KG, Dortmund, Germany) for sleep–wake classification and measurement of heart rate (HR). The results were compared to PSG. VitaLog is a minimal-contact sensor that does not restrict sleep. The diagnostic accuracy of VitaLog was studied in 49 patients referred to our sleep research unit due to suspected SBD. Results obtained by VitaLog were compared to those of a simultaneous PSG to assess the diagnostic accuracy of VitaLog for sleep–wake classification and measurement of HR. Compared to PSG, the accuracy of HR determined by VitaLog was excellent (r = 0.99) with a bias of 0.15 beats per min (bpm). Regarding total sleep time (TST), we found a good correlation of r = 0.8 and a bias of 14 min. For sleep efficiency (SE) estimated by VitaLog, the correlation was moderate with r = 0.6 with a bias of 4.0%. Sleep latency (SL) and wake after sleep onset (WASO) were underestimated by 1 and 12 min, respectively. VitaLog is a promising approach for the estimation of the sleep-related parameters TST, SE, SL, and WASO based on a minimal-contact sensor. In addition, it measures HR with excellent accuracy. However, algorithm modifications are desired to provide appropriate diagnostic accuracy in all sleep disorder cohorts.

BACKGROUND: Dental status has been implicated in several systemic inflammatory diseases and is a potential focus for systemic infections. Therefore, most lung-transplant centers have recommendations regarding pre-transplant dental care and follow-up, but there are no official clinical guidelines. To date there is little information on oral health status in lung transplant (LTx) recipients. The aim of this study was to systematically assess oral health status in LTx recipients. OBJECTIVES: The aim of this study was to assess oral health status, including periodontal disease, oral health behavior, and awareness of the need for good oral health after LTx. METHODS: LTx recipients were recruited during follow-up outpatient visits at a university clinic transplant unit. Oral health status was quantified using the count of Decayed, Missing and Filled Teeth (DMF-T) and the grade of periodontal disease was measured by probing depth. Patients' oral health behavior was assessed using a questionnaire. RESULTS: Seventy-three patients were included at 5.8±3.4 years after lung transplantation. The mean DMF-T was 21.9±5.5. Patients with cystic fibrosis as the indication for transplantation had a significantly lower DMF-T than patients with chronic obstructive pulmonary disease as the transplant indication. Of the 66 patients with teeth, 97% had moderate or severe periodontal disease. The prevalence of moderate or severe periodontal disease was significantly higher in LTx recipients (mean age 55.9 years) compared with older individuals (age 65-74 years) from the German general population (p

BACKGROUND:There is a lack of robust data about factors predicting continuation (or termination) of positive airway pressure therapy (PAP) for sleep apnea. This analysis of big data from a German homecare provider describes patients treated with PAP, analyzes the therapy termination rate over the first year, and investigates predictive factors for therapy termination. METHODS:Data from a German homecare service provider were analyzed retrospectively. Patients who had started their first PAP therapy between September 2009 and April 2014 were eligible. Patient demographics, therapy start date, and the date of and reason for therapy termination were obtained. At 1 year, patients were classified as having compliance-related therapy termination or remaining on therapy. These groups were compared, and significant predictors of therapy termination determined. RESULTS:Of 98,329 patients included in the analysis, 11,702 (12%) terminated PAP therapy within the first year (after mean 171 ± 91 days). There was a U-shaped relationship between therapy termination and age; therapy termination was higher in the youngest (

This on-treatment analysis was conducted to facilitate understanding of mechanisms underlying the increased risk of all-cause and cardiovascular mortality in heart failure patients with reduced ejection fraction and predominant central sleep apnoea randomised to adaptive servo ventilation versus the control group in the SERVE-HF trial. Time-dependent on-treatment analyses were conducted (unadjusted and adjusted for predictive covariates). A comprehensive, time-dependent model was developed to correct for asymmetric selection effects (to minimise bias). The comprehensive model showed increased cardiovascular death hazard ratios during adaptive servo ventilation usage periods, slightly lower than those in the SERVE-HF intention-to-treat analysis. Self-selection bias was evident. Patients randomised to adaptive servo ventilation who crossed over to the control group were at higher risk of cardiovascular death than controls, while control patients with crossover to adaptive servo ventilation showed a trend towards lower risk of cardiovascular death than patients randomised to adaptive servo ventilation. Cardiovascular risk did not increase as nightly adaptive servo ventilation usage increased. On-treatment analysis showed similar results to the SERVE-HF intention-to-treat analysis, with an increased risk of cardiovascular death in heart failure with reduced ejection fraction patients with predominant central sleep apnoea treated with adaptive servo ventilation. Bias is inevitable and needs to be taken into account in any kind of on-treatment analysis in positive airway pressure studies., SERVE-HF on-treatment results showed increased cardiovascular risk similar to the intention-to-treat analysis http://ow.ly/hoO130dx4s9

Summary Background Purified α1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe α1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT. Methods Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open-label extension trial (RAPID-OLE). Patients from 22 hospitals in 11 countries outside of the USA received 60 mg/kg per week A1PI. The primary endpoint was annual rate of adjusted 15th percentile lung density loss measured using CT in the intention-to-treat population with a mixed-effects regression model. This trial is registered with ClinicalTrials.gov, number NCT00670007. Findings Between March 1, 2006, and Oct 13, 2010, 140 patients from RAPID-RCT entered RAPID-OLE: 76 from the early-start group and 64 from the delayed-start group. Between day 1 and month 24 (RAPID-RCT), the rate of lung density loss in RAPID-OLE patients was lower in the early-start group (−1·51 g/L per year [SE 0·25] at total lung capacity [TLC]; −1·55 g/L per year [0·24] at TLC plus functional residual capacity [FRC]; and −1·60 g/L per year [0·26] at FRC) than in the delayed-start group (−2·26 g/L per year [0·27] at TLC; −2·16 g/L per year [0·26] at TLC plus FRC, and −2·05 g/L per year [0·28] at FRC). Between months 24 and 48, the rate of lung density loss was reduced in delayed-start patients (from −2·26 g/L per year to −1·26 g/L per year), but no significant difference was seen in the rate in early-start patients during this time period (−1·51 g/L per year to −1·63 g/L per year), thus in early-start patients the efficacy was sustained to month 48. Interpretation RAPID-OLE supports the continued efficacy of A1PI in slowing disease progression during 4 years of treatment. Lost lung density was never recovered, highlighting the importance of early intervention with A1PI treatment. Funding CSL Behring.

Aims Central sleep apnoea/Cheyne–Stokes respiration (CSA/CSR) is a risk factor for increased mortality and morbidity in heart failure (HF). Adaptive servo-ventilation (ASV) is a non-invasive ventilation modality for the treatment of CSA/CSR in patients with HF. Methods SERVE-HF is a multinational, multicentre, randomized, parallel trial designed to assess the effects of addition of ASV (PaceWave™, AutoSet CS™; ResMed) to optimal medical management compared with medical management alone (control group) in patients with symptomatic chronic HF, LVEF ≤45%, and predominant CSA. The trial is based on an event-driven group sequential design, and the final analysis will be performed when 651 events have been observed or the study is terminated at one of the two interim analyses. The aim is to randomize ∼1200 patients to be followed for a minimum of 2 years. Patients are to stay in the trial up to study termination. The first patient was randomized in February 2008 and the study is expected to end mid 2015. The primary combined endpoint is the time to first event of all-cause death, unplanned hospitalization (or unplanned prolongation of a planned hospitalization) for worsening (chronic) HF, cardiac transplantation, resuscitation of sudden cardiac arrest, or appropriate life-saving shock for ventricular fibrillation or fast ventricular tachycardia in implantable cardioverter defibrillator patients. Perspectives The SERVE-HF study is a randomized study that will provide important data on the effect of treatment with ASV on morbidity and mortality, as well as the cost-effectiveness of this therapy, in patients with chronic HF and predominantly CSA/CSR. Trial registration ISRCTN19572887

Obstructive sleep apnea (OSA) is a common disorder of breathing but is probably underappreciated as a perioperative risk factor.This review is based on pertinent articles, published up to 15 August 2015, that were retrieved by a selective search in PubMed based on the terms "sleep apnea AND anesthesia" OR "sleep apnea AND pathophysiology." The guidelines of multiple specialty societies were considered as well.OSA is characterized by phases of upper airway obstruction accompanied by apnea/hypoventilation, with hypoxemia, hypercapnia, and recurrent overactivation of the sympathetic nervous system. It has been reported that 22% to 82% of all adults who are about to undergo surgery have OSA. The causes of OSA are multifactorial and include, among others, an anatomical predisposition and /or a reduced inspiratory activation of the bronchodilator muscles, particularly when the patient is sleeping or has taken a sedative drug, anesthetic agent, or muscle relaxant. OSA is associated with arterial hypertension, coronary heart disease, and congestive heart failure. It can be assessed before the planned intervention with polysomnography and structured questionnaires (STOP/STOP-BANG), with sensitivities of 62% and 88%. The utility of miniaturized screening devices is debated. Patients with OSA are at risk for perioperative problems including difficult or ineffective mask ventilation and/or intubation, postoperative airway obstruction, and complications arising from other comorbid conditions. They should be appropriately monitored postoperatively depending on the type of intervention they have undergone, and depending on individually varying, patient-related factors; postoperative management in an intensive care unit may be indicated, although no validated data on this topic are yet available.OSA patients need care by specialists from multiple disciplines, including anesthesiologists with experience in recognizing OSA, securing the airway of OSA patients, and managing them postoperatively. No randomized trials have yet compared the modalities of general anesthesia for OSA patients with respect to postoperative complications or phases of apnea or hypopnea.

Scarce evidence suggests that ambient air pollution and temperature might play a role in incidence and severity of sleep disordered breathing (SDB). We investigated the association of short-term exposure to fine particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 μm (PM10)), ozone and temperature with SDB in the general population.Between 2006 and 2008, 1773 participants (aged 50–80 years) of the Heinz Nixdorf Recall study underwent screening for SDB, as defined by the apnoea–hypopnoea index (AHI). We assessed daily exposure to PM10, ozone, temperature and humidity. We used multiple linear regression to estimate associations of daily PM10, ozone levels and temperature on the day of screening, adjusting for relative humidity, season, age, sex, body mass index, education, smoking habits, alcohol consumption and physical activity.In the study population, the mean±sdAHI was 11.2±11.4 events·h−1. Over all seasons, an interquartile range increase in temperature (8.6°C) and ozone (39.5 µg·m−3) was associated with a 10.2% (95% CI 1.2–20.0%) and 10.1% (95% CI 2.0–18.9%) increase in AHI, respectively. Associations for temperature were stronger in summer, yielding a 32.4% (95% CI 0.0–75.3%) increase in AHI per 8.6°C (p-value for season–temperature interaction 0.08). We observed that AHI was not associated with PM10.This study suggests that short-term variations in ozone concentration and temperature are associated with SDB.

BACKGROUND Central sleep apnea is associated with poor prognosis and death in patients with heart failure. Adaptive servo-ventilation is a therapy that uses a noninvasive ventilator to treat central sleep apnea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure. We investigated the effects of adaptive servo-ventilation in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea. METHODS We randomly assigned 1325 patients with a left ventricular ejection fraction of 45% or less, an apnea–hypopnea index (AHI) of 15 or more events (occurrences of apnea or hypopnea) per hour, and a predominance of central events to receive guideline-based medical treatment with adaptive servo-ventilation or guidelinebased medical treatment alone (control). The primary end point in the time-toevent analysis was the first event of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure. RESULTS In the adaptive servo-ventilation group, the mean AHI at 12 months was 6.6 events per hour. The incidence of the primary end point did not differ significantly between the adaptive servo-ventilation group and the control group (54.1% and 50.8%, respectively; hazard ratio, 1.13; 95% confidence interval [CI], 0.97 to 1.31; P = 0.10). All-cause mortality and cardiovascular mortality were significantly higher in the adaptive servo-ventilation group than in the control group (hazard ratio for death from any cause, 1.28; 95% CI, 1.06 to 1.55; P = 0.01; and hazard ratio for cardiovascular death, 1.34; 95% CI, 1.09 to 1.65; P = 0.006). CONCLUSIONS Adaptive servo-ventilation had no significant effect on the primary end point in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea, but all-cause and cardiovascular mortality were both increased with this therapy. (Funded by ResMed and others; SERVE-HF ClinicalTrials.gov number, NCT00733343.) abstr act

Background: Recent studies found that the non-contact type IV screening device SleepMinder (ResMed Sensor Technologies, Dublin, Ireland) detects sleep-disordered breathing (SDB) with high diagnostic accuracy in cohorts suspected of obstructive sleep apnoea (OSA). However, it was reported that in patients with periodic limb movement (PLM) Sleepminder overestimates the apnoea-hypopnoea index (AHI). Aims and objectives: We aimed to overcome this limitation by introducing the novel sleep disorder index (SDI) which is the sum of the AHI and the period limb movement index (PLMI). This study tested the hypothesis whether using the SDI is associated with high diagnostic accuracy for detecting SDB and/or PLM. Methods: Between January 2011 and December 2013 we studied a mixed cohort of 57 patients (31 OSA, 19 PLM). The easy-to-use device SleepMinder emits a very low electromagnetic radiation and detects body movement by measuring the Doppler effect. We interpreted the device-generated movement index as the SDI and validated the diagnostic accuracy against simultaneous application of PSG. Results: The SDI of SleepMinder correlated well with the sum of AHI and PLMI derived from PSG (r=0.79, p=0.01). For PSG-SDI cut-off ≥15/h, sensitivity was 92.2% and specificity was 95.8%. We found a positive predictive value of 97.2% and a negative predictive value of 95.8%. Positive likelihood ratio was 23.3 and negative likelihood ratio was 0.03. Conclusions: The non-contact type IV screening device SleepMinder detects accurately the combination of the sleep disorders SDB and/or PLM. Thus, this easy-to-use method provides a high pre-test probability for further specific, diagnostic testing.

Background Accumulating evidence suggests a role of obstructive sleep apnoea (OSA) as a risk factor for coronary atherosclerosis. This study aimed i) to assess the prevalence of OSA in the general population and ii) to analyse the association of this disorder with traditional cardiovascular disease risk factors and subclinical coronary atherosclerosis. Methods In a cross-sectional analysis of the Heinz Nixdorf Recall study a subgroup of 1604 subjects (791 men, age 50–80 years) underwent OSA screening. Furthermore, coronary artery calcium (CAC) was measured. OSA was defined as apnoea-hypopnoea index (AHI) ≥ 15/h. Results OSA was observed in 29.1% of men and 15.6% of women. In a multiple linear regression analysis adjusted for risk factors AHI was associated with CAC in men aged ≤65 years (estimated log-transformed increase of CAC = 0.25, 95% confidence interval (CI) = −0.001–0.50, p = 0.051) and in women of any age (estimated log-transformed increase = 0.23, 95% CI = 0.04–0.41, p = 0.02). Doubling of the AHI was associated with a 19% increase of CAC in men aged ≤65 years and with a 17% increase in women of any age. Conclusions In the general population aged ≥50 years OSA is associated with subclinical atherosclerosis in men aged ≤65 years and in women of any age, independent of traditional cardiovascular risk factors.

Tracheal stenosis due to either benign or malignant disease is a situation that the pulmonary physicians and thoracic surgeons have to cope in their everyday clinical practice. In the case where tracheal stenosis is caused due to malignancy mini-interventional interventions with laser, apc, cryoprobe, balloon dilation or with combination of more than one equipment and technique can be used. On the other hand, in the case of a benign disease such as; tracheomalacia the clinician can immediately upon diagnosis proceed to the stent placement. In both situations however; it has been observed that the stents induce formation of granuloma tissue in both or one end of the stent. Therefore a frequent evaluation of the patient is necessary, taking also into account the nature of the primary disease. Evaluation methodologies identifying different types and extent of the trachea stenosis have been previously published. However; we still do not have an effective adjuvant therapy to prevent granuloma tissue formation or prolong already treated granuloma lesions. There have been proposed many mechanisms which induce the abnormal growth of the local tissue, such as; local pressure, local stress, inflammation and vascular endothelial growth factor overexpression. Immunomodulatory agents inhibiting the mTOR pathway are capable of inhibiting the inflammatory cascade locally. In the current mini-review we will try to present the current knowledge of drug eluting stents inhibiting the mTOR pathway and propose a future application of these stents as a local anti-proliferative treatment.

Background: Conventional pulmonary rehabilitation programs improve exercise tolerance but have no effect on pulmonary function in patients with chronic obstructive pulmonary disease (COPD). The role of controlled breathing using respiratory biofeedback during rehabilitation of patients with COPD remains unclear. Objectives: To compare the effects of a conventional 4-week pulmonary rehabilitation program with those of rehabilitation plus controlled breathing interventions. Methods: A randomized controlled trial was performed. Pulmonary function (FEV1), exercise capacity (6-min walking distance, 6MWD), health-related quality of life (chronic respiratory questionnaire, CRQ) and cardiac autonomic function (rMSSD) were evaluated. Results: Forty COPD patients (mean ± SD age 66.1 ± 6.4, FEV1 45.9 ± 17.4% predicted) were randomized to rehabilitation (n = 20) or rehabilitation plus controlled breathing (n = 20). There were no statistically significant differences between the two groups regarding the change in FEV1 (mean difference –0.8% predicted, 95% CI –4.4 to 2.9% predicted, p = 0.33), 6MWD (mean difference 12.2 m, 95% CI –37.4 to 12.2 m, p = 0.16), CRQ (mean difference in total score 0.2, 95% CI –0.1 to 0.4, p = 0.11) and rMSSD (mean difference 2.2 ms, 95% CI –20.8 to 25.1 ms, p = 0.51). Conclusions: In patients with COPD undergoing a pulmonary rehabilitation program, controlled breathing using respiratory biofeedback has no effect on exercise capacity, pulmonary function, quality of life or cardiac autonomic function.

Chronic obstructive pulmonary disease (COPD) is associated with impaired exercise tolerance, but it has not been established to what extent cardiac autonomic function impacts on exercise capacity.To evaluate whether there is an association between airflow limitation and cardiac autonomic function and whether cardiac autonomic function plays a role in exercise intolerance and daily physical activity (PA) in patients with COPD.Univariate and multivariate analyses were performed to evaluate the association between both 6-minute walking test (6MWT) and PA (steps per day) and pulmonary function, cardiac autonomic function (HR at rest, HRR and heart rate variability, HRV) in patients with COPD.In 154 COPD patients (87 females, mean [SD]: age 62.5 [10.7] years, FEV(1) %predicted (43.0 [19.2]%), mean HR at rest was elevated (86.4 [16.4] beats/min) and HRV was reduced (33.69 [28.96] ms) compared to published control data. There was a significant correlation between FEV(1) and HR at rest (r = -0.32, p0.001), between HR at rest and 6MWD (r = -0.26, p = 0.001) and between HR at rest and PA (r = -0.29, p = 0.010). No correlation was found between HRV and 6MWD (r = 0.089, p = 0.262) and PA (r = 0.075, p = 0.322). In multivariate analysis both HR and FEV(1) were independent predictors of exercise capacity in patients with COPD.In patients with COPD the degree of airflow limitation is associated with HR at rest. The degree of airflow limitation and cardiac autonomic function, as quantified by HR at rest, are independently associated with exercise capacity in patients with COPD.

Diseases of the lung, e. g. chronic obstructive pulmonary disease (COPD), interstitial lung diseases, bronchiectasis or cystic fibrosis, often lead to recurrent severe respiratory infections that cause exacerbations of the underlying disease. These acute or chronic inflammatory processes can result in a progressive destruction of the lung and in an ongoing decline in lung function. Therefore longer inpatient stays for intravenous antibiotic treatment are necessary and the quality of life in these patients is severely limited. A rapid detection of infectious agents in human lungs is often crucial, because the choice of the appropriate therapeutic regime depends at first on the identification of the infecting species. Standard methods for detection and identification are either time consuming, of low sensitivity or expensive. It is known that bacteria, and also mitosporic fungi, produce volatile organic compounds (VOCs) that can be detected in exhaled breath by ion mobility spectrometry (IMS), were a distinct detection of a specific VOC is related to a “peak”. We investigated, whether the detection and characterisation of VOCs by Multi-capillary column coupled to IMS in exhaled breath of patients whose airways are either infected or colonized by Pseudomonas aeruginosa compared to healthy non-smoker controls is capable of identifying those infectious agents. To realize a non invasive identification of pathogens, the exhaled breath of 53 persons (24 patients suffering chronic or infectious on Pseudomonas and 29 healthy controls) was investigated using an ion mobility spectrometer type BioScout. In total 224 different signals were found. Actually, 21 different signals are able to differentiate the two groups, Control and Pseudomonas, with rank sum values less than 0.2. For all 224 signals Box-and-Wisker plots were realized. The peaks with the lowest rank sum values F (0,107) and PS0 (0,112) show rather good separation of both groups. Our preliminary results demonstrate that distinct patterns of a small number of IMS-peaks are sufficient for the identification of these infectious agents. Therefore MCC-IMS seems to be a promising method for the non-invasive identification of patients which are colonized or infected with bacteria such as Pseudomonas aeruginosa.

Objectives: Prediction of histopathological response with PET/CT scans after neoadjuvant chemoradiotherapy is limited by confounding factors which have been evaluated in this analysis. Methods:18F-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT findings [standard uptake value (SUV), residual tumor volume] were correlated with histopathological parameters of the resection specimens (tumor cell density, necrosis, scar, macrophage infiltration) in patients with locally advanced non-small cell lung cancer (stage IIIA/IIIB) after neoadjuvant induction chemotherapy (platinum-based doublet) and concurrent chemoradiotherapy (cisplatin/vinorelbine/45 Gy). Results: Sixty patients [40 male/20 female, median age 56 years (34–78)] completed induction therapy, 46 patients (stage IIIA/IIIB: 16/30; squamous cell carcinoma 41%, adenocarcinoma 48%, large cell carcinoma 11%) were resected. Pathologic complete response of the primary tumor was observed in 19 patients (41%) with a broad range of SUVmean (0.4–9.8, mean 3.0) after neoadjuvant therapy. A high rate of histopathological complete remissions (44%) was observed in tumors with a postinduction SUV >2.5 and volumes larger than the median (7.9 cm3) before resection. SUVmean was positively correlated with the macrophage score (r = 0.39, p = 0.007) and tumor cell density (r = 0.32, p = 0.03). Conclusions: These observations suggest that postinduction FDG uptake should be interpreted with caution in larger residual tumor volumes, since high SUV levels may be due to macrophage infiltration and not viable tumor tissue.

Purpose To investigate the role of prophylactic cranial irradiation (PCI) within a trimodality protocol (chemotherapy, chemoradiotherapy, surgery) for patients with operable stage IIIA non–small-cell lung cancer (NSCLC). Patients and Methods After mediastinoscopic staging, patients with operable stage IIIA NSCLC were enrolled to a German multicenter trial and randomly assigned to receive either primary resection followed by adjuvant thoracic radiation therapy (50 to 60 Gy; arm A) or preoperative chemotherapy (cisplatin/etoposide [PE]; three cycles) followed by concurrent chemoradiotherapy (PE plus 45 Gy; 1.5 Gy twice per day) and definitive surgery (arm B), respectively. Patients in arm B were scheduled to receive PCI (30 Gy; 2 Gy daily fractions). Results One hundred twelve patients were randomly assigned between November 1994 and July 2001. One hundred six patients were eligible (arm A: 51, arm B: 55), 90 males and 16 females, 50 with squamous cell, 16 with large cell, five with adenosquamous, and 35 with adenocarcenoma (median age, 57 years; range, 37 to 71 years). Forty-three patients received PCI as scheduled in arm B. Eleven long-term survivors (arm A: four; arm B: seven) underwent a comprehensive neuropsychological examination. PCI significantly reduced the probability of brain metastases as first site of failure (7.8% at 5 years v 34.7%; P = .02), the overall brain relapse rate was reduced comparably (9.1% at 5 years v 27.2%; P = .04). A slightly reduced neurocognitive performance in comparison with the age-matched normal population was found for patients in both treatment groups. No significant difference between patients who were treated with or without PCI could be noted. Conclusion PCI is effective in preventing brain metastases following this aggressive trimodality approach. Neurocognitive late effects are not significantly different between patients treated with or without PCI.

Background: Sleep disordered breathing (SDB) is common in neuromuscular diseases but its relationship to respiratory function is poorly defined. A study was undertaken to identify distinct patterns of SDB, to clarify the relationships between SDB and lung and respiratory muscle function, and to identify daytime predictors for SDB at its onset, for SDB with continuous hypercapnic hypoventilation, and for diurnal respiratory failure. Methods: Upright and supine inspiratory vital capacity (IVC, % predicted), maximal inspiratory muscle pressure (PImax), respiratory drive (P0.1), respiratory muscle effort (P0.1/PImax), and arterial blood gas tensions were prospectively compared with polysomnography and capnometry (PtcCO2) in 42 patients with primary myopathies. Results: IVC correlated with respiratory muscle function and gas exchange by day and night. SDB evolved in three distinct patterns from REM hypopnoeas, to REM hypopnoeas with REM hypoventilation, to REM/non-REM (continuous) hypoventilation, and preceded diurnal respiratory failure. SDB correlated with IVC and PImax which yielded highly predictive thresholds for SDB onset (IVC

PURPOSE: Relapse pattern and late toxicities in long-term survivors were analyzed after the introduction of prophylactic cranial irradiation (PCI) into a phase II trial on trimodality treatment of locally advanced (LAD) non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Seventy-five patients with stage IIIA(N2)/IIIB NSCLC were treated with induction chemotherapy, preoperative radiochemotherapy, and surgery. PCI was routinely offered during the second period of study accrual. Patients were given a total radiation dose of 30 Gy (2 Gy per daily fraction) over a 3-week period starting 1 day after the last chemotherapy cycle. RESULTS: Introduction of PCI reduced the rate of brain metastases as first site of relapse from 30% to 8% at 4 years (P = .005) and that of overall brain relapse from 54% to 13% (P < .0001). The effect of PCI was also observed in the good-prognosis subgroup of 47 patients who had a partial response or complete response to induction chemotherapy, with a reduction of brain relapse as first failure from 23% to 0% at 4 years (P = .01). Neuropsychologic testing revealed impairments in attention and visual memory in long-term survivors who received PCI as well as in those who did not receive PCI. T2-weighted magnetic resonance imaging revealed white matter abnormalities of higher grades in patients who received PCI than in those who did not. CONCLUSION: PCI at a moderate dose reduced brain metastases in LAD-NSCLC to a clinically significant extent, comparable to that in limited-disease small-cell lung cancer. Late toxicity to normal brain was acceptable. This study supports the use of PCI within intense protocols for LAD-NSCLC, particularly in patients with favorable prognostic factors.

Bronchiolitis obliterans with organising pneumonia (BOOP) is a distinct clinical pathologic syndrome. Most patients experience a good response to therapy, and death from progressive BOOP is uncommon. This report describes the clinical features, etiologic factors, pathologic findings, and outcome of 10 patients with rapidly progressive BOOP that was characterised by severe respiratory failure. The major clinical manifestations were dyspnea, cough, fever, crackles on chest examination, and hypoxemia at rest. Underlying conditions or exposures included connective-tissue disease, exposure to birds, and chronic nitrofurantoin therapy. All patients had the characteristic histopathologic findings of BOOP. However, at autopsy in six patients, the predominant histologic pattern was that of alveolar septal inflammation and fibrotic honeycombing. Seven patients died and three patients survived but had persistent pulmonary dysfunction despite aggressive care. In two patients BOOP has progressed, with severe chronic respiratory decompensation. Thus, there is a subset of patients with BOOP who present with a fulminant course leading to death or chronic severe fibrosis and marked impairment of lung function. In addition, the histologic picture of BOOP may be a manifestation of early lung injury that can resolve or progress rapidly to alveolar septal inflammation, end-stage fibrosis, and honeycombing. (Am J Respir Crit Care Med 1994 ;149 :1670-5)