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Abstract Background Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by excessive intra-alveolar accumulation of surfactant lipids and proteins. Therapeutic whole lung lavages are currently the principle therapeutic option in adults. Not much is known on the kinetics of the wash out process, especially in children. Methods In 4 pediatric and 6 adult PAP patients 45 therapeutic half lung lavages were investigated retrospectively. Total protein, protein concentration and, in one child with a surfactant protein C mutation, aberrant pro-SP-C protein, were determined during wash out. Results The removal of protein from the lungs followed an exponential decline and averaged for adult patients 2 – 20 g and Conclusion Following therapeutic half lung lavages by biochemical variables may help to estimate the degree of alveolar filling with proteinaceous material and to improve the efficiency of the wash out, especially in children.

Purpose Bilateral lung transplantation results in complete denervation of the lung and might impair hypercapnic ventilatory response (HCVR). However, experimental and clinical findings are scarce and conflicting. Therefore, this study investigated the relationship between HCVR and exercise capacity after long-term bilateral lung transplantation. Methods This cross-sectional analysis enrolled 46 bilateral lung transplant recipients between October 2011 and July 2012 who underwent cardiopulmonary exercise testing to evaluate maximum workload, and carbon dioxide (CO.sub.2) rebreathing. CO.sub.2 rebreathing was also evaluated in 35 control subjects. Results In lung transplant recipients age was 54 ± 11 years, body mass index (BMI) 25.4 ± 4.1 kg/m.sup.2, and time after transplantation 4.5 ± 2.5 years (range 9 months to 10 years). Controls were aged 41 ± 12 years and had a BMI of 24.9 ± 4.0 kg/m.sup.2. There were significant differences between lung transplant recipients and controls in forced expiratory volume in 1 s (76 ± 22 vs. 94 ± 12 % predicted, p < 0.001) and inspiratory vital capacity (91 ± 20 vs. 105 ± 14 % predicted, p = 0.001). Blood gases did not differ significantly in patients versus controls. HCVR in lung transplant recipients was 1.44 ± 1.07 L/min/mmHg compared with 2.09 ± 1.14 L/min/mmHg in controls (p = 0.001). Exercise capacity in lung transplant recipients (73 ± 24 W) was 49 % predicted. Linear regression analysis showed that exercise capacity was significantly associated with HCVR. A 1 L/min/mmHg decrease in HCVR decreased exercise capacity by 50 W. Conclusion HCVR is reduced in long-term bilateral lung transplant recipients and this might explain the observed impairment of exercise capacity., Author(s): Manuela J. Scherer[sup.1] , Gerhard Weinreich[sup.1] , Bjoern E. Kleibrink[sup.1] , Thomas Rabis[sup.1] , Markus Kamler[sup.2] , Helmut Teschler[sup.1] , Urte Sommerwerck[sup.1] [sup.3] Author Affiliations: (1) Department of Pneumology, [...]

Aims: Heart failure with preserved ejection fraction (HFpEF) is a condition with increasing prevalence. Sleep‐disordered breathing (SDB) is an important co‐morbidity in HFpEF. The SchlaHF‐XT registry evaluated the sex‐specific prevalence and predictors of SDB, including obstructive (OSA) and central sleep apnoea, in patients with HFpEF compared with heart failure with mildly reduced (HFmrEF) or reduced (HFrEF) ejection fraction. Methods and results: Consecutive adults with chronic heart failure treated according to current guidelines were enrolled. The presence of moderate‐to‐severe SDB (apnoea–hypopnoea index ≥15/h) was determined using Type 3 polygraphic devices. Of 3289 patients included, 2032 had HFpEF, 559 had HFmrEF, and 698 had HFrEF, of whom 34, 21, 23, and 42%, respectively, were female. Prevalence of SDB in HFpEF was high, but significantly lower than in HFmrEF or HFrEF (36% vs. 41 and 48%, respectively). Rates of SDB in males and females were 41 and 28% in HFpEF, 44 and 30% in HFmrEF, and 50 and 40% in HFrEF. The proportion of males and females with SDB who had OSA was significantly greater in those with HFpEF vs. HFrEF. Male sex, older age, higher body mass index, and New York Heart Association functional Class III/IV were significant predictors of moderate‐to‐severe SDB in HFpEF patients. Conclusions: Prevalence of SDB in HFpEF was high, but lower than in patients with HFmrEF or HFrEF. Moderate‐to‐severe SDB occurred more frequently in males than in females across the whole spectrum of heart failure. In both sexes, the proportion of OSA in SDB patients with HFpEF was higher than in those with HFrEF. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Background and objective: Increases in Cheyne–Stokes respiration (CSR) cycle length (CL), lung‐to‐periphery circulation time (LPCT) and time to peak flow (TTPF) may reflect impaired cardiac function. This retrospective analysis used an automatic algorithm to evaluate baseline CSR‐related features and then determined whether these could be used to identify patients with systolic heart failure (HF) who experienced serious adverse events in the Treatment of Sleep‐Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure (SERVE‐HF) substudy. Methods: A total of 280 patients had overnight diagnostic polysomnography data available; an automated algorithm was applied to quantify CSR‐related features. Results: Median baseline CL, LPCT and TTPF were similar in the control (n = 152) and adaptive servo‐ventilation (ASV, n = 156) groups. In both groups, CSR‐related features were significantly longer in patients who did (n = 129) versus did not (n = 140) experience a primary endpoint event (all‐cause death, life‐saving cardiovascular intervention or unplanned hospitalization for worsening HF): CL, 61.1 versus 55.1 s (P = 0.002); LPCT, 36.5 versus 31.5 s (P < 0.001); TTPF, 15.20 versus 13.35 s (P < 0.001), respectively. This finding was independent of treatment allocation. Conclusion: Patients with systolic HF and central sleep apnoea who experienced serious adverse events had longer CSR CL, LPCT and TTPF. Future studies should examine an independent role for CSR‐related features to enable risk stratification in systolic HF. [ABSTRACT FROM AUTHOR]