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P189 Mitochondrial dysfunction in muscle and airway compartments in COPD: preliminary findings
  1. G Haji,
  2. C Wiegman,
  3. M Patel,
  4. P Kemp,
  5. I Adcock,
  6. F Chung,
  7. M Polkey
  1. Royal Brompton Hospital/Imperial College, London, England

Abstract

Introduction & Rationale Oxidative stress may underlie both pulmonary and non-pulmonary manifestations of COPD and may result from mitochondrial dysfunction. We hypothesised that if oxidative stress arose from the lung and ‘spilled over’ to cause non-pulmonary disease (e.g. skeletal muscle weakness) then greater evidence of mitochondrial dysfunction should be evident in the lung.

Objectives We measured mitochondrial function in endobronchial and skeletal muscle biopsies from COPD patients and healthy smokers matched for smoking history, age and sex.

Methods and Measurements We have so far biopsied 4 control smokers with normal FEV1 and FEV1/FVC ratio, and 4 GOLD II COPD patients out of a planned total of 40. Bronchoscopy with endobronchial biopsies (EB) and percutaneous muscle biopsy of the vastus lateralis (VL) were obtained on the same day; additional phenotypic measurements included lung function, quadriceps strength and 6-minute walk (6MW) distance. Mitochondria were isolated and mitochondrial reactive oxygen species (ROS) and membrane potential (MP) were measured using MitoSOX Red and the carbocyanine dye JC-1 respectively and intracellular ROS determined by 2’-7’-dichlorofluorescin diacetate (DCF) staining.

GOLD stage II COPD patients had reduced lung function, quadriceps strength and 6MW test despite a similar smoking history. There was increased mitochondrial and intracellular ROS in both skeletal muscle and bronchial biopsies of COPD patients compared to controls. There was a trend for reduced MP in COPD EB mitochondria.

Conclusion The presence of excessive ROS in cells from a lung and a non-lung compartment support the existence of a generalised dysfunction of mitochondria in established COPD resulting in increased mitochondrial oxidative stress.

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