Ventilator-associated Injury (VAI) in Chronic Home Mechanical Ventilation
- Conditions
- Long-term Non-invasive VentilationRespiratory Failure
- Interventions
- Other: No other than standard care
- Registration Number
- NCT04521426
- Lead Sponsor
- University Medical Center Groningen
- Brief Summary
Rationale:
The pathophysiological changes in respiratory muscle morphology and functioning in patients with end-stage pulmonary disease are not very well known. Furthermore, in COPD, long-term high-intensity NIV is applied without knowing the exact consequences on the lungs and respiratory muscles.
Objective: The aims of the study are to get insight in:
A. changes respiratory muscles in end-stage respiratory disease, comparing COPD with restrictive lung disease (RLD) due to pulmonary fibrosis B. the effects of long-term HI-NIV in severe COPD patients on the respiratory muscles and the lungs; by comparing COPD patients that had been treated with long-term NIV to COPD patients that were not treated with long-term NIV.
Study design: In order to investigate this, the investigators will include in a small pilot cohort study patients being lung transplanted. In these patients there is lung tissue available and respiratory muscle biopsies will be performed during lung-transplant surgery.
Study population: Patients that are listed for lung transplantation for an underlying diagnosis of COPD or RLD will be asked to participate. Three groups will be included: patients with a RLD due to pulmonary fibrosis, COPD patients that had been treated with long-term NIV prior to being lung transplanted and COPD patients that were not treated with long-term NIV. Patients will be included definitely once being lung transplanted.
Main study parameters/endpoints: The study is an exploratory pilot study. Both contractile strength and the structure of single diaphragm and intercostal muscle fibres as well as lung injury; i.e. alveolar structure and damage and inflammation in the alveoli, will be investigated.
- Detailed Description
Rationale:
Chronic Obstructive Pulmonary Disease (COPD) is a progressive inflammatory disease characterised by airway and lung parenchyma damage. At end-stage disease patients may develop chronic hypercapnic respiratory failure, a disease characteristic that is however not uniformly seen in other end-stage lung diseases, such as in patients with pulmonary fibrosis. The underlying process for the development of chronic hypercapnic respiratory failure is incompletely understood and the role of respiratory muscle alterations is unclear.
Home noninvasive ventilation with high-intensity ventilatory settings (HI-NIV) has been shown to be effective in these severe COPD patients. However, in patients being mechanically ventilated on the intensive care unit for diverse reasons, high-intensity ventilation, especially high tidal volumes, has been shown to result in ventilator associated lung and diaphragm injury. Whether this occurs in home high-intensity NIV, is however completely unknown.
Objective: The aims of the study are to get insight in:
A. changes respiratory muscles in end-stage respiratory disease, comparing COPD with restrictive lung disease (RLD) due to pulmonary fibrosis B. the effects of long-term HI-NIV in severe COPD patients on the respiratory muscles; i.e. the contractile strength and the structure of single diaphragm and intercostal muscle fibres and the lungs; i.e. alveolar structure and damage and inflammation, by comparing COPD patients that had been treated with long-term NIV to COPD patients that were not treated with long-term NIV.
Study design: In order to investigate this, the investigators will include in a small pilot cohort study patients being lung transplanted. In these patients there is lung tissue available and respiratory muscle biopsies will be performed during lung-transplant surgery.
Study population: Patients that are listed for lung transplantation for an underlying diagnosis of COPD or RLD will be asked to participate. Three groups will be included: patients with a RLD due to pulmonary fibrosis, COPD patients that had been treated with long-term NIV prior to being lung transplanted and COPD patients that were not treated with long-term NIV. Patients will be included definitely once being lung transplanted.
Main study parameters/endpoints: The study is an exploratory pilot study. The study aims to get data on respiratory muscle and lung and airway pathology in order to, if important results are observed, set up a larger prospective trial investigating both clinical outcomes and pathology of the respiratory muscles/lungs. Both contractile strength and the structure of single diaphragm and intercostal muscle fibres as well as lung injury; i.e. alveolar structure and damage and inflammation in the alveoli, will be investigated.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15
- RLD: probable or confirmed diagnosis of interstitial pulmonary fibrosis (IPF) or other fibrotic lung disease of unknown origin.
- COPD: GOLD stage III or IV
- Being listed for lung transplantation
- Concomitant neuromuscular or systemic/collagen-vascular disease
- Prior lung surgery (except for lung biopsies) or lung volume reduction treatment
- Being unable to understand the patient information and consent for the study
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Lung Fibrosis No other than standard care 1. probable or confirmed diagnosis of interstitial pulmonary fibrosis (IPF) or other fibrotic lung disease of unknown origin. 2. being listed for lung transplantation COPD standard therapy No other than standard care 1. COPD: GOLD stage III or IV 2. being listed for lung transplantation 3. did not underwent LVR surgery or endoscopic LVR 4. not being treated with chronic NIV COPD with long-term NIV No other than standard care 1. COPD: GOLD stage III or IV 2. being listed for lung transplantation 3. did not underwent LVR surgery or endoscopic LVR 4. being treated with chronic NIV before lung transplantation (at least 1 months, at least 4 hours per day).
- Primary Outcome Measures
Name Time Method Ventilator-associated lung injury gene-expression during surgery Gene-expression profiling of epithelial cells with regard to inflammatory factors
Ventilator-associated lung injury serum sRAGE during surgery serum sRAGE
Ventilator-associated lung injury fibrin during surgery interstitial fibrin
Ventilator-associated lung injury BAL MIP-2 during surgery BAL MIP-2
Ventilator-associated lung injury alveolar cells during surgery histopathological changes to type I alveolar cells
Ventilator-associated lung injury BAL sRAGE during surgery BAL sRAGE
Ventilator-associated lung injury inflammatory cells during surgery Inflammatory cells influx in the alveoli
Ventilator-associated lung injury serum IL-1beta during surgery serum IL-1beta
Respiratory muscle morphology and functioning during surgery Biopsies of the diaphragm and intercostal muscles will be taken during surgery
Ventilator-associated lung injury BAL IL-1beta during surgery BAL IL-1beta
Ventilator-associated lung injury serum TNF-alfa during surgery serum TNF-alfa
Ventilator-associated lung injury serum IL-6 during surgery serum IL-6
Ventilator-associated lung injury serum IL-8 during surgery serum IL-8
Ventilator-associated lung injury BAL TNF-alfa during surgery BAL TNF-alfa
Ventilator-associated lung injury BAL IL-6 during surgery BAL IL-6
Ventilator-associated lung injury serum MIP-2 during surgery serum MIP-2
Ventilator-associated lung injury BAL IL-8 during surgery BAL IL-8
Ventilator-associated lung injury basal membrane during surgery histopathological changes to the basal membrane
Ventilator-associated lung injury edema during surgery edema in the alveoli and interstitium
- Secondary Outcome Measures
Name Time Method Lung Function_FVC during surgery FVC
Blood gasses_PaCO2 during surgery PaCO2
Ventilatory settings during surgery Settings of the NIV
Blood gasses_HCO3- during surgery HCO3-
Demographics_age during surgery age
Demographics_gender during surgery gender
Demographics_BMI during surgery BMI
Lung Function_FEV1 during surgery FEV1
Ventilatory use during surgery Duration of usage (longitudinally and use per day)
Trial Locations
- Locations (1)
University Medical Center Groningen
🇳🇱Groningen, Netherlands