Chronic obstructive pulmonary disease (COPD) is a common and potentially serious chronic
inflammatory respiratory disease. It has an estimated prevalence of 12% in Europe, making it
a major public health issue. It is currently the third leading cause of death worldwide and
affects a higher proportion of men (sex ratio 1.5:1.9). The main risk factor is cigarette
smoke exposure (whether active or passive), responsible for 80% of cases. Exposure to other
agents such as fine particles and fuel smoke can also lead to the development of the disease.
Finally, a favourable genetic background is now commonly accepted as a risk factor.
COPD diagnosis is based on lung function measurement : non-reversible obstructive respiratory
syndrome, i.e. a Tiffeneau coefficient (FEV1/FVC) < 70% after inhalation of a bronchodilator
agent. At the pulmonary level, it is characterized by bronchial remodeling associated with
parenchymal destruction, resulting on the one hand in peribronchial fibrosis, and on the
other hand in emphysema bullae related to the rupture of the alveolar walls.
Its management is global and combines a series of medicinal and non-medicinal measures: use
of bronchodilators and inhaled corticosteroids, smoking cessation (if applicable), prevention
strategies including vaccination, physical management such as respiratory rehabilitation and
management of comorbidities.
Indeed, COPD is currently considered a systemic disease with predominantly respiratory
involvement associated with numerous comorbidities. These include cardiovascular disease,
osteoporosis, depression, bronchopulmonary cancer and muscle dysfunction. The latter is
characterized by a decrease in muscle strength and volume and is also called sarcopenia.
Sarcopenia is present in 4 to 66% of patients and is associated with a particularly severe
patient profile, since patients with low muscle mass have a mortality 13 times higher than
patients with normal muscle mass (after adjustment for respiratory function).
Sarcopenia is defined by the loss of both muscle mass and strength, and extensive work has
been done in the geriatric population, leading to the drafting of European recommendations
which are considered applicable in the COPD population. Thus, sarcopenia can be defined by a
decrease in the appendicular muscle mass index (ASM or Appendicular Skeletal Muscle Mass
divided by height) measured by dexametry (or biphotonic X-ray absorptiometry), of less than
7.0 kg/m2 in men and 5.5 kg/m2 in women. However, although the measurement of lean body mass
is recommended by both the HAS (COPD care pathway guide) and the latest recommendations of
the Société de Pneumologie de Langue Française (French language lung society), this condition
is currently largely under-diagnosed in COPD patients. Moreover, there is no specific
treatment for sarcopenia: the only intervention that has been shown to be effective is
exercise training as part of respiratory rehabilitation.
Numerous studies have described the histological changes characterizing muscle damage in COPD
patients, particularly in the quadriceps. These include a decrease in the diameter and
vascularization of muscle fibers, associated with a change in fiber metabolism: disappearance
of type I fibers (predominantly oxidative metabolism) in favor of type II fibers (glycolytic
metabolism). Local inflammation is also observed, sometimes associated with necrosis and an
increase in the percentage of regenerating fibers. However, the originating mechanisms are
still largely unknown.
Fibrocytes are cells derived from blood monocytes and able to migrate from the blood flow to
different organs. They can exert pro-fibrotic functions by secreting collagen themselves or
activating collagen secretion by fibroblasts. This is notably the case in the lung of COPD
patients, where they play a key role in bronchial obstructive disease: they are recruited in
the blood during an acute exacerbation of COPD, and their density is increased at the
peribronchial level and negatively correlated with the parameters of lung function.
However, they may also play a pro-inflammatory role and influence the metabolism of resident
cells. It has recently been shown that their differentiation is accompanied by a metabolic
reprogramming that promotes oxidative phosphorylation. Moreover, recent data obtained in a
mouse model show their involvement in tissue repair after muscle injury.
Because of their capacity to secrete pro-inflammatory factors and their possible influence on
the metabolism of myofibers, studying their role in the development of sarcopenia in COPD
patients could therefore be a promising avenue. Moreover, due to their preferential
recruitment via a CXCL12/CXCR4 chemotactic axis, the migration of these cells towards damaged
tissues (lung, muscle) of COPD patients would potentially respond to a therapeutic strategy
by CXCR4 modulation.