Clinical trial NCT04521426: Ventilator-associated Injury (VAI) in Chronic Home Mechanical Ventilation
Official title: Ventilator-associated Injury (VAI) in Chronic Home Mechanical Ventilation: a Paradigm Switch in Order to Improve Ventilatory Support
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Respiratory Failure
Long-term Non-invasive Ventilation
Keywords: COPD
Lung fibrosis
non-invasive ventilation
respiratory muscles
diaphragm
lung inflammation
ventilator-induced lung injury
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2020-08-20
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: see above

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.

Eligibility criteria: Inclusion Criteria:

1. RLD: probable or confirmed diagnosis of interstitial pulmonary fibrosis (IPF) or other fibrotic lung disease of unknown origin.
2. COPD: GOLD stage III or IV
3. Being listed for lung transplantation

Exclusion Criteria:

1. Concomitant neuromuscular or systemic/collagen-vascular disease
2. Prior lung surgery (except for lung biopsies) or lung volume reduction treatment
3. Being unable to understand the patient information and consent for the study

Primary outcomes:
measure: Respiratory muscle morphology and functioning
timeFrame: during surgery
measure: Ventilator-associated lung injury serum TNF-alfa
timeFrame: during surgery
measure: Ventilator-associated lung injury serum IL-6
timeFrame: during surgery
measure: Ventilator-associated lung injury serum IL-1beta
timeFrame: during surgery
measure: Ventilator-associated lung injury serum IL-8
timeFrame: during surgery
measure: Ventilator-associated lung injury serum MIP-2
timeFrame: during surgery
measure: Ventilator-associated lung injury serum sRAGE
timeFrame: during surgery
measure: Ventilator-associated lung injury BAL TNF-alfa
timeFrame: during surgery
measure: Ventilator-associated lung injury BAL IL-6
timeFrame: during surgery
measure: Ventilator-associated lung injury BAL IL-1beta
timeFrame: during surgery
measure: Ventilator-associated lung injury BAL IL-8
timeFrame: during surgery
measure: Ventilator-associated lung injury BAL MIP-2
timeFrame: during surgery
measure: Ventilator-associated lung injury BAL sRAGE
timeFrame: during surgery
measure: Ventilator-associated lung injury basal membrane
timeFrame: during surgery
measure: Ventilator-associated lung injury alveolar cells
timeFrame: during surgery
measure: Ventilator-associated lung injury edema
timeFrame: during surgery
measure: Ventilator-associated lung injury fibrin
timeFrame: during surgery
measure: Ventilator-associated lung injury inflammatory cells
timeFrame: during surgery
measure: Ventilator-associated lung injury gene-expression
timeFrame: during surgery
Secondary outcomes:
measure: Ventilatory use
timeFrame: during surgery
measure: Ventilatory settings
timeFrame: during surgery
measure: Demographics_age
timeFrame: during surgery
measure: Demographics_gender
timeFrame: during surgery
measure: Demographics_BMI
timeFrame: during surgery
measure: Lung Function_FEV1
timeFrame: during surgery
measure: Lung Function_FVC
timeFrame: during surgery
measure: Blood gasses_PaCO2
timeFrame: during surgery
measure: Blood gasses_HCO3-
timeFrame: during surgery
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
References: