0
Communications to the Editor |

Apoptosis of Circulating Neutrophils in COPD Patients FREE TO VIEW

Mathias W. R. Pletz, MD; Hartmut Lode, MD
Author and Funding Information

Affiliations: Chest Hospital Heckeshorn, Berlin, Germany,  Hospital Universitari Son Dureta, Palma de Mallorca, Spain

Correspondence to: Mathias W. R. Pletz, MD, Department of International Health, Emory University, Atlanta, GA 30322; e-mail: mpletz@sph.emory.edu



Chest. 2005;127(4):1464-1465. doi:10.1378/chest.127.4.1464
Text Size: A A A
Published online

To the Editor:

We read with great interest the study by Noguera et al (May 2004)1 on the apoptosis of circulating neutrophils in COPD patients. Neutrophils exhibit a short half-life and are primarily removed by apoptosis. In contrast to apoptosis, neutrophil necrosis results in the release of aggressive enzymes, leading to tissue destruction and increased inflammation.

Noguera et al compared ex vivo the spontaneous apoptosis rates of circulating neutrophils from COPD patients in stable condition with those from smokers with normal lung function and healthy nonsmokers. Since it is known that spontaneous neutrophil apoptosis is decreased in various inflammatory conditions and that neutrophils are considered to play a crucial role in COPD pathogenesis, they expected to find a decreased or delayed apoptosis. They incubated the cells and measured spontaneous apoptosis rates after 2, 8, and 24 h by flow cytometry. Surprisingly, they were not able to find a difference between the COPD patients and the control subjects. Their conclusion was that neutrophil apoptosis in COPD patients occurred at a rate similar to that found in healthy individuals and smokers with normal lung function.

We agree with the methodology used; however, we believe that this conclusion is misleading. An increase in systemic cytokines (eg, interleukin-6), inhibiting the apoptosis of circulating neutrophils,2is present in stable-state COPD patients but is not as pronounced as in those with acute exacerbations.3In addition, the spontaneous apoptosis rates of circulating neutrophils show a high degree of interindividual variation.4 Therefore, a larger number of subjects than that investigated by Noguera et al might be needed to find a statistically significant difference between healthy volunteers and COPD patients in the stable state.

According to the guidelines of the Global Initiative for Chronic Obstructive Lung Disease,5 exacerbations are the main factor in the progression of COPD. Therefore, we performed a very similar study but enrolled only hospitalized patients who had experienced an acute exacerbation of COPD.4 Neutrophil apoptosis was measured at hospital admission, after 3 to 5 days, and at hospital discharge. In addition, we assessed spontaneous apoptosis rates in healthy volunteers. We were able to show that neutrophil apoptosis is significantly suppressed at the beginning of an acute exacerbation (p < 0.0001 [paired t test, and the parametric distribution of the data was confirmed by the Shapiro-Wilks test]), and that it increases progressively after treatment and clinical remission, reaching the values of healthy subjects on the day of hospital discharge. Therefore, we believe that delayed neutrophil apoptosis is an important key feature of COPD pathogenesis and deserves further investigation to avoid missing any potential new treatment options for COPD, which is a disease with a high burden.

Noguera, A, Sala, E, Pons, AR, et al (2004) Expression of adhesion molecules during apoptosis of circulating neutrophils in COPD.Chest125,1837-1842. [CrossRef] [PubMed]
 
Biffl, WL, Moore, EE, Moore, FA, et al Interleukin-6 delays neutrophil apoptosis.Arch Surg1996;131,24-29. [CrossRef] [PubMed]
 
Wedzicha, JA, Seemungal, TA, MacCallum, PK, et al Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels.Thromb Haemost2000;84,210-215. [PubMed]
 
Pletz, MW, Ioanas, M, de Roux, A, et al Reduced spontaneous apoptosis in peripheral blood neutrophils during exacerbation of COPD.Eur Respir J2004;23,532-537. [CrossRef] [PubMed]
 
Pauwels, RA, Buist, AS, Calverley, PM, et al Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary.Am J Respir Crit Care Med2001;163,1256-1276. [PubMed]
 
To the Editor:

We thank Drs. Pletz and Lode for their interest in our work (May 2004).1We agree with their comments and suggestions. Of course, in vivo conditions may differ very substantially from in vitro ones. Thus, the comments made by Drs. Pletz and Lode with respect to our work are well taken. We would like, however, to highlight another potential source of confusion. In the article by Pletz et al,2 patients were studied during exacerbations. As such, they were receiving intense steroid therapy, among other types of therapy. As is known by the authors, steroids can interfere both with systemic inflammation3and neutrophil apoptosis.4 We therefore fully agree with Drs. Pletz and Lode that the role of neutrophil apoptosis in COPD deserves further study.

References
Noguera, A, Sala, E, Pons, AR, et al Expression of adhesion molecules during apoptosis of circulating neutrophils in chronic obstructive pulmonary disease.Chest2004;125,1837-1842. [CrossRef] [PubMed]
 
Pletz, MW, Ioanas, M, de Roux, A, et al Reduced spontaneous apoptosis in peripheral blood neutrophils during exacerbation of COPD.Eur Respir J2004;23,532-537. [CrossRef] [PubMed]
 
Sin, DD, Lacy, P, York, E, et al Effects of fluticasone on systemic markers of inflammation in chronic obstructive pulmonary disease.Am J Respir Crit Care Med2004;170,760-765. [CrossRef] [PubMed]
 
Zhang, X, Moilanen, E, Kankaanranta, H Beclomethasone, budesonide and fluticasone propionate inhibit human neutrophil apoptosis.Eur J Pharmacol2001;431,365-371. [CrossRef] [PubMed]
 

Figures

Tables

References

Noguera, A, Sala, E, Pons, AR, et al (2004) Expression of adhesion molecules during apoptosis of circulating neutrophils in COPD.Chest125,1837-1842. [CrossRef] [PubMed]
 
Biffl, WL, Moore, EE, Moore, FA, et al Interleukin-6 delays neutrophil apoptosis.Arch Surg1996;131,24-29. [CrossRef] [PubMed]
 
Wedzicha, JA, Seemungal, TA, MacCallum, PK, et al Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels.Thromb Haemost2000;84,210-215. [PubMed]
 
Pletz, MW, Ioanas, M, de Roux, A, et al Reduced spontaneous apoptosis in peripheral blood neutrophils during exacerbation of COPD.Eur Respir J2004;23,532-537. [CrossRef] [PubMed]
 
Pauwels, RA, Buist, AS, Calverley, PM, et al Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary.Am J Respir Crit Care Med2001;163,1256-1276. [PubMed]
 
Noguera, A, Sala, E, Pons, AR, et al Expression of adhesion molecules during apoptosis of circulating neutrophils in chronic obstructive pulmonary disease.Chest2004;125,1837-1842. [CrossRef] [PubMed]
 
Pletz, MW, Ioanas, M, de Roux, A, et al Reduced spontaneous apoptosis in peripheral blood neutrophils during exacerbation of COPD.Eur Respir J2004;23,532-537. [CrossRef] [PubMed]
 
Sin, DD, Lacy, P, York, E, et al Effects of fluticasone on systemic markers of inflammation in chronic obstructive pulmonary disease.Am J Respir Crit Care Med2004;170,760-765. [CrossRef] [PubMed]
 
Zhang, X, Moilanen, E, Kankaanranta, H Beclomethasone, budesonide and fluticasone propionate inhibit human neutrophil apoptosis.Eur J Pharmacol2001;431,365-371. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543