| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Medicine, Pneumology, Physiology and Nutrition (DIMPEPINU), University of Palermo; Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Palermo; Department of Clinical Medicine, University "La Sapienza"; and National Institute of Health (ISS), Rome, Italy
Correspondence and requests for reprints should be addressed to Maria R. Bonsignore, M.D., Department of Medicine, Pneumology, Physiology and Nutrition (DIMPEPINU), University of Palermo, Via Trabucco 180, 90146 Palermo, Italy. E-mail: m.bonsignore{at}unipa.it
Small numbers of bone marrow–derived multipotent progenitors (CD34+ cells) normally circulate in peripheral blood. They indirectly reflect hematopoiesis, but may also be involved in tissue repair processes, either by engrafting in damaged areas, or by promoting angiogenesis and improving oxygen and nutrient supply to damaged tissue. In subjects with chronic ischemic heart disease, bone marrow–derived CD34+ cell counts were normal, but their proliferation was decreased compared with normal subjects (1). Low circulating CD34+ cells have also been found in patients with stroke (2) or other chronic diseases, such as rheumatoid arthritis (3), suggesting that bone marrow–derived progenitors may be involved in different pathologic states. Because no data are available for chronic obstructive pulmonary disease (COPD), we hypothesized that circulating CD34+ cells may be decreased in patients with COPD, and the change in CD34+ cells may be proportional to disease severity.
We studied 12 patients with moderate to severe COPD (mean age ± SD: 67.6 ± 7.7 yr; FEV1: 49.4 ± 12.3% of predicted; PaO2: 76 ± 8 mm Hg; and 
O2peak: 20.2 ± 2.2 ml · kg–1 · min–1) and eight age-matched control subjects (age: 65.4 ± 5.3 yr; FEV1: 109.0 ± 14.5% predicted; PaO2: 91 ± 3 mm Hg; and O2peak: 27.4 ± 3.1 ml · kg–1 · min–1). All subjects were clinically stable and none of the patients had been on systemic steroids in the 6 wk preceding the study. Venous blood samples were obtained under sterile conditions at baseline in both groups. Peripheral blood mononuclear cells (PBMCs) were obtained by standard Ficoll gradient, and labeled with anti-CD34 antibody for flow cytometric analysis (Cell Quest Software; Becton-Dickinson, Franklin Lakes, NJ). Colony assays were obtained by standard methods (PBMCs seeded at 3 x 105 cells · ml–1 per dish, and supplemented with growth factors according to erythrocyte or granulocyte-monocyte series). For statistical analysis, data obtained in patients with COPD and control subjects were compared by unpaired t test or Mann-Whitney test; simple linear regression was used to assess relationships between variables (p < 0.05 for all tests).
Red blood cell and white blood cell (WBC) counts were in the normal range in both groups. WBC counts were 6.9 ± 1.4 · 103 cells/µl in patients with COPD, and 6.6 ± 1.2 · 103 cells/µl in control subjects (not significant). Slightly increased neutrophil differential counts were found in patients with COPD (63.9 ± 6.0 vs. 57.7 ± 7.4% of WBCs, p = 0.05). Circulating CD34+ cell counts were threefold lower in patients with COPD compared with control subjects (0.19 ± 0.19 vs. 0.57 ± 0.31% of lymphocytes; absolute counts: 3.1 ± 2.6 vs. 10.1 ± 4.3 cells/µl; p < 0.0001). The number of erythrocyte burst-forming units (BFU-E) and granulocyte-monocyte colony–forming units (GM-CFU) was also reduced in patients with COPD (BFU-E/ml: 129 ± 33 vs. 172 ± 16 [p < 0.01]; GM-CFU/ml: 92 ± 24 vs. 188 ± 17 [p 
0.001]). In the entire sample, resting CD34+ cell counts significantly correlated with PaO2 (r = 0.52, p < 0.05), FEV1/FVC ratio (r = 0.63, p < 0.01), and O2peak (r = 0.56, p < 0.01).
In summary, we found that patients with moderate to severe COPD showed (1) normal blood cell counts, (2) decreased circulating CD34+ cell counts and lower number of hematopoietic colonies, and (3) a trend for decreasing circulating progenitors with increasing COPD severity.
Although these preliminary data need to be confirmed in larger COPD patient samples, they strongly suggest that the bone marrow is involved in COPD. Besides lung damage, repair mechanisms may also be impaired in COPD. The bone marrow should be considered as a previously unrecognized systemic target of COPD.
FOOTNOTES
Supported by the Italian National Council of Research, Agenzia 2000 (CNRC005114), and the National Institute of Health (ISS), Rome, Italy.
Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
(Received in original form March 20, 2006; accepted in final form March 26, 2006)
REFERENCES
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
