Identification and Dynamics With Cerebral Functional Magnetic Resonance Imaging (CHAOSBOLD)

Central Control of Breathing in Patients With Chronic Obstructive Pulmonary Disease: Identification and Dynamics With Cerebral Functional Magnetic Resonance Imaging

Chronic obstructive pulmonary disease (COPD) is a chronicle inflammatory disease with a non reversible diminution of the airway flow. COPD is caused most commonly from tobacco smoking, which triggers an abnormal inflammatory response in the lung. Worldwide, COPD ranked as the sixth leading cause of death in 1990. It is projected to be the fourth leading cause of death worldwide by 2030 due to an increase in smoking rates and demographic changes in many countries. COPD is responsible for 16000 deaths per year in France, 100 000 hospitalizations per year and the health care expenditure of COPD in France is 3.5 billion of Euros. Classical markers of the disease severity, the forced expiratory volume in one second, poorly correlates with dyspnea and prognosis. Therefore, many studies focused on the control of breathing in an attempt to understand the pathophysiological mechanisms involved in the progression of the disease. Breathing control is enhanced in patients with COPD due to the progressive failure of respiratory muscles (airflow obstruction, static and dynamic hyperinflation, positive intrinsic end expiratory pressure), the ventilation/ perfusion ratio abnormalities leading to the loss of the gaz exchange efficiency. Inspiratory command depends on the medulla automatic pathway and the voluntary corticospinal command. Indirect method of breathing control estimation suggested in COPD patients an increased excitability of neurons involved in the voluntary diaphragm activation and a reduced cortical reserve. This may represent an increase risk factor for acute respiratory failure. Until now, no study reported the central breathing control with cerebral fMRI in COPD patients.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Other: cerebral fMRI; Other: cerebral fMRI

Detailed Description

Chronic obstructive pulmonary disease (COPD) is a chronicle inflammatory disease with a non reversible diminution of the airway flow. COPD is caused most commonly from tobacco smoking, which triggers an abnormal inflammatory response in the lung. Worldwide, COPD ranked as the sixth leading cause of death in 1990. It is projected to be the fourth leading cause of death worldwide by 2030 due to an increase in smoking rates and demographic changes in many countries. COPD is responsible for 16000 deaths per year in France, 100 000 hospitalizations per year and the health care expenditure of COPD in France is 3.5 billion of Euros. Classical markers of the disease severity, the forced expiratory volume in one second, poorly correlates with dyspnea and prognosis. Therefore, many studies focused on the control of breathing in an attempt to understand the pathophysiological mechanisms involved in the progression of the disease. Breathing control is enhanced in patients with COPD due to the progressive failure of respiratory muscles (airflow obstruction, static and dynamic hyperinflation, positive intrinsic end expiratory pressure), the ventilation/ perfusion ratio abnormalities leading to the loss of the gaz exchange efficiency. Inspiratory command depends on the medulla automatic pathway and the voluntary corticospinal command. Indirect method of breathing control estimation suggested in COPD patients an increased excitability of neurons involved in the voluntary diaphragm activation and a reduced cortical reserve. This may represent an increase risk factor for acute respiratory failure. Until now, no study reported the central breathing control with cerebral fMRI in COPD patients. This pilot study also aims in estimating if the absence or diminution of the cortical reserve is a marker of disease severity. In addition correlations will be performed between activated neuronal signals with fMRI and ventilatory flow output recordings (chaotic analysis).

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75018
    • Hôpital Bichat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA for Patient:

• Informed patients with written consent,
• More than eighteen years old,
• Patients having a social insurance
• A previous medical examination
• Patients, half with moderate (GOLD II) and half with severe (GOLD III) COPD will be included. These patients will be clinically in a steady state situation for at least one month (no acute exacerbation). GOLD grading of COPD patients will be performed according to the American Thoracic Society.

EXCLUSION CRITERIA for patient:

• Long-term oxygen therapy
• Previous cerebral vascular accident
• Central neurological disease (tumor, Parkinson, etc.)
• Nobody benefiting from a particular protection: pregnant woman, minor person, major person under guardianship and under guardianship, the persons hospitalized without their consent and protected by the law, or the private persons of freedom.
• Contraindication in the functional intellectual MRI:
• Port of a biomedical device like cardiac simulator
• Cardiac defibrillator
• Insulin pump or neurostimulating,
• Claustrophobia,
• Impossibility to remain lengthened
• Presence of cerebral vascular clips, metallic foreign body intra-ocular, not compatible cardiac valve
• Pregnancy

INCLUSION CRITERIA for Healthy Volunteers:

• Informed healthy volunteer with written consent,
• More than eighteen years old,
• Healthy volunteer having a social insurance
• A previous medical examination
• Non-smoker
• Non pathology and medicinal treatment

EXCLUSION CRITERIA for healthy volunteers:

• Nobody benefiting from a particular protection: pregnant woman, minor person, major person under guardianship and under guardianship, the persons hospitalized without their consent and protected by the law, or the private persons of freedom.
• Contraindication in the functional intellectual MRI:
• Port of a biomedical device like cardiac simulator
• Cardiac defibrillator
• Insulin pump or neurostimulating,
• Claustrophobia,
• Impossibility to remain lengthened
• Presence of cerebral vascular clips, metallic foreign body intra-ocular, not compatible cardiac valve
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PATIENT; Patients, half with moderate (GOLD II) and half with severe (GOLD III) COPD	Other: cerebral fMRI; the central breathing control with cerebral fMRI in COPD patients; Other Names: the central breathing control with cerebral fMRI; Other: cerebral fMRI; the central breathing control with cerebral fMRI in Accepts Healthy Volunteers; Other Names: the central breathing control with cerebral fMRI
Other: Accepts Healthy Volunteers; Control arm with the same intervention	Other: cerebral fMRI; the central breathing control with cerebral fMRI in COPD patients; Other Names: the central breathing control with cerebral fMRI; Other: cerebral fMRI; the central breathing control with cerebral fMRI in Accepts Healthy Volunteers; Other Names: the central breathing control with cerebral fMRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Central ventilatory control	Evaluation of the central ventilatory control at the patients COPD during the application of an inspiratory resistance.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the neuronal activation	Evaluation of the neuronal activation bulbo-pontique and corticospinal during the application of an inspiratory resistance.	1 month
Chaotic analysis	The correlations will be performed between activated neuronal signals with fMRI and ventilatory flow output recordings (chaotic analysis).	1 month

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Laurence MANGIN, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: April 4, 2011
• First Submitted That Met QC Criteria: April 6, 2011
• First Posted (Estimate): April 7, 2011

Study Record Updates

• Last Update Posted (Estimate): August 14, 2013
• Last Update Submitted That Met QC Criteria: August 13, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Chronic obstructive pulmonary disease (COPD)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: P100136; AOM10010 (Other Identifier: French Ministry)