Multiorgan Pathology in Chronic Obstructive Pulmonary Disease (COPD)

There is increasing evidence in the literature that COPD should not be considered as a localised pulmonary disorder but as a systemic disease involving pathology in several extra pulmonary tissues. Well characterized systemic features are a chronic low grade systemic inflammation, altered body composition and a skeletal muscle fibre type shift. There are indications that an absolute or relative increase of fat mass puts COPD patients at increased risk for cardiovascular pathology while muscle atrophy is associated with a high prevalence of osteoporosis and with impaired physical function. The origin of systemic inflammation is poorly understood. Both endogenous and exogenous risk factors contribute to systemic inflammation and extra-pulmonary manifestations of COPD.

Overall objective of study 3:

To compare the pattern and severity of the systemic inflammatory profile in relation to skeletal muscle weakness and cardiovascular risk profile in COPD patients with mild to moderate disease compared to non-susceptible smokers.

Specific objectives:

To study the relative contribution of pulmonary and extra pulmonary factors on exercise capacity, skeletal muscle function and health status
To relate diet, physical activity and cardiovascular risk factors to body composition, skeletal muscle function and exercise capacity status
To study the influence of the emphysema phenotype on extra pulmonary pathology in COPD
To study muscle fibre type size and composition and to relate muscle oxidative phenotype with insulin sensitivity, inflammation (local and systemic) and molecular signatures of oxidative energy and protein metabolism.

Study design:

Cross-sectional study. Healthy smoking subjects and COPD patients will undergo extensive clinical, metabolic and inflammatory assessment at the university clinics in Groningen, Maastricht and CIRO Horn.

Study population:

Totally 60 subjects will be included

30 healthy subjects who after 20 pack years smoking have no signs of COPD (age 40-75 years)
30 COPD patients with GOLD stage II (age 40-75 years)

Primary study parameters/outcome of the study:

Smoking history and behaviour, diet and physical activity level assessed by questionnaire
Extensive lung function and CT scanning of the lung, ECG
Candidate genes for muscle dysfunction and CVD risk
Body composition (BIA, waist-hip ratio, DEXA-scan)
Systemic inflammation
Advanced Glycosylated Endproduct (AGE)
Glucose tolerance test
Risk factors of metabolic syndrome
6 minute walking distance
Handgrip strength
Skeletal muscle function by isokinetic dynamometry
Physical activity level and pattern by accelerometry
Muscle oxidative phenotype, fibre cross-sectional area and molecular signatures obtained in vastus lateralis muscle biopsies before and after incremental cycle ergometry

Nature and extent of the burden and risks associated with participation, benefit and group relatedness (if applicable):

Totally 22 hours will be spend in the hospital during 3 visits
CT-scanning of the lung is associated with a radiation burden of 0.8-1.6 mSv (dependent of body weight)
50 ml peripheral blood (v. cubiti)
Muscle biopsy may be associated with temporary pain and haematoma
Drawing of arterial blood from the radial artery rarely leads to bleeding and transitory nerve damage (numb feeling in wrist/hand area).

Eligibility

Relevant conditions:

Chronic Obstructive Pulmonary Disease

If you aren't sure if you meet the criteria above speak to your healthcare professional. Criteria may be updated but not reflected here, do not hesitate to contact the trial if you think are close to fitting criteria.

locations

Contact Information

Overall Contact

AMWJ Schols, Prof. dr. ir.

a.schols@pul.unimaas.nl

+31 43 387 5046

Data sourced from ClinicalTrials.gov