Ventilator-associated Injury (VAI) in Chronic Home Mechanical Ventilation

NCT04521426 | Completed

• 1 other identifier: VAI-HMV
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Respiratory Failure; Long-term Non-invasive Ventilation

Keywords

COPD; Lung fibrosis; non-invasive ventilation; respiratory muscles; diaphragm; lung inflammation; ventilator-induced lung injury

Outcome Measures

Primary Outcomes (19)

• Respiratory muscle morphology and functioning

  Biopsies of the diaphragm and intercostal muscles will be taken during surgery

  during surgery

• Ventilator-associated lung injury serum TNF-alfa

  serum TNF-alfa

  during surgery

• Ventilator-associated lung injury serum IL-6

  serum IL-6

  during surgery

• Ventilator-associated lung injury serum IL-1beta

  serum IL-1beta

  during surgery

• Ventilator-associated lung injury serum IL-8

  serum IL-8

  during surgery

• Ventilator-associated lung injury serum MIP-2

  serum MIP-2

  during surgery

• Ventilator-associated lung injury serum sRAGE

  serum sRAGE

  during surgery

• Ventilator-associated lung injury BAL TNF-alfa

  BAL TNF-alfa

  during surgery

• Ventilator-associated lung injury BAL IL-6

  BAL IL-6

  during surgery

• Ventilator-associated lung injury BAL IL-1beta

  BAL IL-1beta

  during surgery

• Ventilator-associated lung injury BAL IL-8

  BAL IL-8

  during surgery

• Ventilator-associated lung injury BAL MIP-2

  BAL MIP-2

  during surgery

• Ventilator-associated lung injury BAL sRAGE

  BAL sRAGE

  during surgery

• Ventilator-associated lung injury basal membrane

  histopathological changes to the basal membrane

  during surgery

• Ventilator-associated lung injury alveolar cells

  histopathological changes to type I alveolar cells

  during surgery

• Ventilator-associated lung injury edema

  edema in the alveoli and interstitium

  during surgery

• Ventilator-associated lung injury fibrin

  interstitial fibrin

  during surgery

• Ventilator-associated lung injury inflammatory cells

  Inflammatory cells influx in the alveoli

  during surgery

• Ventilator-associated lung injury gene-expression

  Gene-expression profiling of epithelial cells with regard to inflammatory factors

  during surgery

Secondary Outcomes (9)

• Ventilatory use

  during surgery

• Ventilatory settings

  during surgery

• Demographics_age

  during surgery

• Demographics_gender

  during surgery

• Demographics_BMI

  during surgery

Study Arms (3)

Lung Fibrosis

1. probable or confirmed diagnosis of interstitial pulmonary fibrosis (IPF) or other fibrotic lung disease of unknown origin. 2. being listed for lung transplantation

Other: No other than standard care

COPD standard therapy

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

Other: No other than standard care

COPD with long-term NIV

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).

Other: No other than standard care

Interventions

No other than standard care OTHER

No other than standard care.

COPD standard therapy; COPD with long-term NIV; Lung Fibrosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

see above

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, Netherlands

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

1. Blood samples 2. BAL fluid 3. Explanted lungs 4. Respiratory muscle biopsies

MeSH Terms

Conditions

Respiratory Insufficiency; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Pneumonia; Ventilator-Induced Lung Injury

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases, Interstitial; Fibrosis; Respiratory Tract Infections; Infections; Lung Injury

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 29, 2020
• First Posted: August 20, 2020
• Study Start: October 1, 2020
• Primary Completion: October 1, 2022
• Study Completion: September 1, 2023
• Last Updated: November 29, 2023

Record last verified: 2023-11

Locations

NL (1)