Duchenne muscular dystrophy (DMD) is a fatal genetic neuromuscular disorder, characterised by progressive decline in skeletal muscle function due to the secondary consequences of dystrophin deficiency. Weakness extends to the respiratory musculature, and cardiorespiratory failure is the leading cause of death in men with DMD. Intermittent hypoxia has emerged as a potential therapy to counteract ventilatory insufficiency by eliciting long-term facilitation of breathing. Mechanisms of sensory and motor facilitation of breathing have been well delineated in animal models. Various paradigms of intermittent hypoxia have been designed and implemented in human trials culminating in clinical trials in people with spinal cord injury and amyotrophic lateral sclerosis. Application of therapeutic intermittent hypoxia to DMD is considered together with discussion of the potential barriers to progression owing to the complexity of this devastating disease. Notwithstanding the considerable challenges and potential pitfalls of intermittent hypoxia-based therapies for DMD, we suggest it is incumbent on the research community to explore the potential benefits in pre-clinical models. Intermittent hypoxia paradigms should be implemented to explore the proclivity to express respiratory plasticity with the longer-term aim of preserving and potentiating ventilation in pre-clinical models and people with DMD.

Toward a safe home: Experiencing the transition to an outpatient setting with home mechanical ventilation. A thematic analysis Abstract. Background: With the progress in medical options, the need for home mechanical ventilation increases. The transition from long-term ventilation in an institution to home mechanical ventilation in an outpatient setting is a difficult phase in terms of setting up the network of care, coordination of care for those with the ventilatory insufficiency and the financing. Aim: The study describes how patients with ventilatory insufficiency and family caregivers experience the transition from an institution to an ambulatory setting with invasive or non-invasive home mechanical ventilation. Methods: A qualitative research design with a social-constructivist approach was adopted using thematic analysis according to Braun and Clarke. We included seven German-speaking patients (≥ 18 years old) with ventilatory insufficiency and home mechanical ventilation (> 6 h/day) from the German part of Switzerland, with discharge from an institution to home, and five family caregivers who care for patients with the described criteria. Results: The institution was seen as a safe place. Affected persons and their family caregivers had to create a safe environment at home. Three themes were formed inductively: To gradually build trust with each other, to become experts as family caregivers, to align their own network with the new care needs.Conclusions: The transition home succeeds in the interplay of gaining trust, building expertise, and creating sustainable networks. Professionals can use this knowledge to provide targeted support to patients with home mechanical ventilation and their family caregivers.
Zusammenfassung. Hintergrund: Mit dem Fortschritt an medizinischen Möglichkeiten erfolgt ein erhöhter Bedarf an Heimbeatmung. Der Übergang von stationärer Langzeitbeatmung in ambulante Heimbeatmung ist eine schwierige Phase in Bezug auf den Aufbau des Netzwerks zur Betreuung, die Koordination der Pflege und die Finanzierung. Ziel: Die Studie beschreibt, wie Betroffene mit ventilatorischer Insuffizienz und pflegende Angehörige den Übergang von einer Institution ins ambulante Setting mit invasiver oder nichtinvasiver Heimbeatmung erleben. Methode: Es wurde ein qualitatives Forschungsdesign mit sozialkonstruktivistischem Ansatz gewählt mit einer Auswertung nach der thematischen Analyse von Braun und Clarke. Eingeschlossen wurden sieben deutschsprachige Betroffene (≥ 18 Jahre) mit ventilatorischer Insuffizienz und Heimbeatmung (> 6 h/Tag) aus der Deutschschweiz, mit Austritt von einer Institution nach Hause, sowie fünf pflegende Angehörige, welche Betroffene mit den beschriebenen Kriterien betreuen. Ergebnisse: Die Institution wurde als sicherer Ort erlebt. Betroffene und Angehörige mussten nach dem Übergang zu Hause ein sicheres Umfeld schaffen. Drei Themen wurden induktiv gebildet: Miteinander schrittweise Vertrauen gewinnen, als Angehörige Expert_innen werden und das eigene Netzwerk auf die neuen Betreuungsbedürfnisse ausrichten. Schlussfolgerungen: Der Übergang nach Hause gelingt im Zusammenspiel von Vertrauen gewinnen, Expertise aufbauen und tragfähige Netzwerke schaffen. Fachpersonen können mit diesem Wissen Betroffene mit Heimbeatmung und ihre Angehörigen gezielt begleiten.

BACKGROUND: Non-invasive ventilation (NIV) is a recommended treatment for COPD patients suffering from chronic hypercapnic respiratory failure. Prolonged dyspnea after mask removal in the morning, often referred to as deventilation syndrome, is a common side effect but has been poorly characterized yet. This study aimed to explore the pathomechanism, identify risk factors and possible treatment strategies for the deventilation syndrome.
METHODS: A prospective, controlled, non-blinded study was conducted. After a night with established NIV therapy, the patients underwent spirometry, blood gas analyses and 6-min walking tests (6MWT) directly, at 2 and 4 h after mask removal. Dyspnea was measured by the modified Borg scale. Bodyplethysmography and health-related quality of life (HRQoL) questionnaires were used. Patients suffering from deventilation syndrome (defined as dyspnea of at least three points on the Borg scale after mask removal) were treated with non-invasive pursed lip breathing ventilation (PLBV) during the second night of the study.
RESULTS: Eleven of 31 patients included (35%) met the given criteria for a deventilation syndrome. They reported significantly more dyspnea on the Borg scale directly after mask removal (mean: 7.2 ± 1.0) compared to measurement after 2 h (4.8 ± 2.6; p = 0.003). Initially, mean inspiratory vital capacity was significantly reduced (VCmax: 46 ± 16%) compared to 2 h later (54 ± 15%; p = 0.002), while no changes in pulse oximetry or blood gas analysis were observed. Patients who suffered from a deventilation syndrome had a significantly higher mean airway resistance (Reff: 320 ± 88.5%) than the patients in the control group (253 ± 147%; p = 0.021). They also scored significantly lower on the Severe Respiratory Insufficiency Questionnaire (SRI; mean: 37.6 ± 10.1 vs 50.6 ± 16.7, p = 0.027). After one night of ventilation in PLBV mode, mean morning dyspnea decreased significantly to 5.6 ± 2.0 compared to 7.2 ± 1.0 after established treatment (p = 0.019) and mean inspiratory vital capacity increased from 44 ± 16.0% to 48 ± 16.3 (p = 0.040).
CONCLUSIONS: The deventilation syndrome is a serious side effect of NIV in COPD patients, characterized by increase of dyspnea. It is associated with decrease in vital capacity, exercise tolerance after mask removal and lower HRQoL. Patients with high airway resistance are at greater risk of suffering from morning dyspnea. Ventilation in PLBV mode may prevent or improve the deventilation syndrome.
BACKGROUND: The study was registered in the German Clinical Trials Register (DRKS00016941) on 09 April 2019.

BACKGROUND: Home ventilation is an effective treatment option for obesity hypoventilation syndrome (OHS). This therapy is still controversial for stable chronic obstructive pulmonary disease (COPD). A recent study showed reduced mortality for COPD patients receiving home ventilation with high inflation pressures and back-up respiratory rates [so called High Intensity non-invasive ventilation (NIV)].
OBJECTIVE: The purpose of this study is whether High Intensity NIV applied in the routine care of COPD and OHS patients can lead to CO2 reduction and survival data comparable to data from controlled studies.
METHODS: In this prospective non interventional study fifty-one patients with COPD (FEV1 0.95l, corr. 32.8%) and 34 patients with OHS (VC 1.74l, corr. 50.7%) with chronic hypercapnic respiratory failure, who were treated with NIV were followed up for four years.
RESULTS: Elevated CO2 values before NIV in COPD patients (8.6kPa), and in OHS patients (8.3kPa), could be lowered significantly to the upper normal range (COPD: 5.9kPa; OHS: 5.85kPa). The one-, two-, and three-year survival rates for COPD patients were 83%, 73%, and 55%, respectively. The one-, two-, and three-year survival rates for OHS patients were 85%, 72%, and 68%, respectively.
CONCLUSIONS: High intensity NIV within routine care is effective in reducing blood CO2 levels in COPD- and in OHS- related chronic respiratory insufficiency. The survival rates obtained here are comparable to data from controlled clinical trials on COPD.

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Pompe disease is an inherited disorder due to a mutation in the gene that encodes acid α-glucosidase (GAA). Children with infantile-onset Pompe disease develop progressive hypotonic weakness and cardiopulmonary insufficiency that may eventually require mechanical ventilation (MV). Our team conducted a first in human trial of diaphragmatic gene therapy (AAV1-CMV-GAA) to treat respiratory neural dysfunction in infantile-onset Pompe. Subjects (aged 2-15years, full-time MV: n=5, partial/no MV: n=4) underwent a period of preoperative inspiratory muscle conditioning exercise. The change in respiratory function after exercise alone was compared to the change in function after intramuscular delivery of AAV1-CMV-GAA to the diaphragm with continued exercise. Since AAV-mediated gene therapy can reach phrenic motoneurons via retrograde transduction, we hypothesized that AAV1-CMV-GAA would improve dynamic respiratory motor function to a greater degree than exercise alone. Dependent measures were maximal inspiratory pressure (MIP), respiratory responses to inspiratory threshold loads (load compensation: LC), and physical evidence of diaphragm activity (descent on MRI, EMG activity). Exercise alone did not change function. After AAV1-CMV-GAA, MIP was unchanged. Flow and volume LC responses increased after dosing (p<0.05 to p<0.005), but only in the subjects with partial/no MV use. Changes in LC tended to occur on or after 180days. At Day 180, the four subjects with MRI evidence of diaphragm descent had greater maximal voluntary ventilation (p<0.05) and tended to be younger, stronger, and use fewer hours of daily MV. In conclusion, combined AAV1-CMV-GAA and exercise training conferred benefits to dynamic motor function of the diaphragm. Children with a higher baseline neuromuscular function may have greater potential for functional gains.