Home noninvasive ventilatory support for patients with chronic obstructive pulmonary disease:patient selection and perspectives

Long-term or home mechanical noninvasive ventilation (Home-NIV) has become a well-established form of therapy over the last few decades for chronic hypercapnic COPD patients in European countries. However, meta-analyses and clinical guidelines do not recommend Home-NIV for COPD patients on a routine basis. In particular, there is ongoing debate about Home-NIV in chronic hypercapnic COPD regarding the overall effects, the most favorable treatment strategy, the selection of eligible patients, and the time point at which it is prescribed. The current review focuses on specific aspects of patient selection and discusses the various scientific as well as clinical-guided perspectives on Home-NIV in patients suffering from chronic hypercapnic COPD. In addition, special attention will be given to the topic of ventilator settings and interfaces

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Living conditions and autonomy levels in COPD patients receiving non-invasive ventilation: impact on health related quality of life

Background!#!Research on health-related quality of life (HRQL) has become increasingly important in recent decades. However, the impact of both living conditions and the level of autonomy impairments on HRQL in COPD patients receiving non-invasive ventilation (NIV) is still unclear.!##!Methods!#!The Severe Respiratory Insufficiency Questionnaire (SRI) was used to measure HRQL in a prospective cohort of COPD patients in whom home NIV was already established. Data on sociodemographics, clinical characteristics and standardized levels of autonomy impairment were evaluated. A multiple linear regression analysis was performed to identify the factors associated with a reduced HRQL.!##!Results!#!A total of 137 patients (67.0 ± 7.8 years, 45% female) were assessed. The mean SRI Summary Score was 54.1 ± 16.9 (95%CI: 51.1-57.1; N = 127). Regular ambulatory care was provided in 76% of patients, but only 37% underwent pulmonary rehabilitation. Overall, 69% of patients lived with family members, while 31% lived alone (family situation). Autonomy impairment levels were most serious in 3%, serious in 14%, and significant in 29% of patients, while 54% had no impairments at all. Of note, higher levels of autonomy impairment were markedly associated with lower SRI scores (regression coefficient - 6.5 ± 1.1 per level; P &amp;lt; 0.001). In contrast, family situation (0.2 ± 3.0; P = 0.959), ambulatory care by a respiratory specialist (1.7 ± 3.6; P = 0.638), and pulmonary rehabilitation (- 0.8 ± 3.1; P = 0.802) did not appear to influence HRQL. Possible subgroup effects were evident for the factors 'impaired autonomy' and 'living in a nursing home' (P = 0.016).!##!Conclusion!#!A higher level of autonomy impairment has been identified as the major determinant of reduced HRQL in COPD-patients receiving long-term NIV, particularly in those living in a nursing home. Trial Registration German Clinical Trials Register (DRKS00008759)

Clinical evidence for respiratory insufficiency type II predicts weaning failure in long-term ventilated, tracheotomised patients: a retrospective analysis

Abstract Background Patients who require a prolonged weaning process comprise a highly heterogeneous group of patients amongst whom the outcome differs significantly. The present study aimed to identify the factors that predict whether the outcome for prolonged weaning will be successful or unsuccessful. Methods Data from tracheotomised patients who underwent prolonged weaning on a specialised weaning unit were assessed retrospectively via an electronic and paper-bound patient chart. Factors for weaning success were analysed by univariate and multivariate analyses. Results Out of the 124 patients examined, 48.4% were successfully weaned (n = 60). Univariate analysis revealed that long-term home mechanical ventilation prior to current weaning episode; time between intubation and the first spontaneous breathing trial (SBT); time between intubation and the first SBT of less than 30 days; lower PaCO2 prior to, and at the end of, the first SBT; and lower pH values at the end of the first SBT were predictors for successful weaning. Following multivariate analysis, the absence of home mechanical ventilation prior to admission, a maximum time period of 30 days between intubation and the first SBT, and a non-hypercapnic PaCO2 value at the end of the first SBT were predictive of successful weaning. Conclusions The current analysis demonstrates that the evidence for respiratory insufficiency type II provided by clinical findings serves as a predictor of weaning failure

The Impact of Non-Invasive Ventilation on Sleep Quality in COPD Patients

Background: Non-invasive ventilation (NIV) has been shown to be the most appropriate therapy for COPD patients with chronic respiratory failure. While physiological parameters and long-term outcome frequently serve as primary outcomes, very few studies have primarily addressed the impact of NIV initiation on sleep quality in COPD. Methods: This single-center prospective cohort study comprised NIV-naïve patients with COPD. All patients underwent polysomnographic evaluation both at baseline and at 3 months follow-up, accompanied by the assessment of health-related quality of life (HRQL) using the Severe Respiratory Insufficiency Questionnaire (SRI) and the Epworth Sleepiness Scale (ESS). A subgroup evaluation was performed to address the impact of comorbid obstructive sleep apnea syndrome (OSAS). Results: Forty-six patients were enrolled and twenty-five patients completed the follow-up period (66.7 ± 7.4 years). NIV resulted in an increase in slow-wave sleep (+2% (−3.5/7.5), p = 0.465) and rapid eye movement sleep (+2.2% (−1.0/5.4), p = 0.174), although no statistical significance could be detected. ESS (−1.7(−3.6/0.1), p = 0.066) also showed a positive trend. Significant improvements in the Respiratory Disturbance Index (RDI) (−12.6(−23.7/−1.5), p = 0.027), lung function parameters, transcutaneous PCO2 and the SRI summary scale (4.5(0.9/8), p = 0.016) were observed. Conclusion: NIV therapy does not decrease sleep quality and is even capable of improving HRQL, transcutaneous PaCO2, daytime sleepiness and RDI, and the latter especially holds true for patients with comorbid OSAS