Platinum-based, leukocyte-depleting chemotherapy does not alter induced sputum markers of neutrophilic inflammation in COPD patients with unresectable non-small cell lung cancer.
BACKGROUND
Neutrophilic inflammation is a major feature of chronic obstructive pulmonary disease (COPD), and several novel therapies aim at the suppression of neutrophils in COPD. Due to the abundance and redundancy of mediators involved in neutrophilic inflammation, there is an ongoing controversy about the feasibility of such anti-neutrophilic approaches. Systemic chemotherapy has broad side effects, including neutrophil toxicity.


OBJECTIVE
In this observational study, we have measured cellular and neutrophil-related inflammatory markers in induced sputum of COPD patients with unresectable non-small cell lung cancer (NSCLC) undergoing platinum-based chemotherapy.


METHODS
15 COPD/NSCLC patients were followed during their first course of chemotherapy with cisplatin (60 mg/m(2) days 1 and 7) and etoposide (100 mg/m(2) days 3, 4, and 5). Sputum induction was performed before, and 3 weeks after chemotherapy. Peripheral blood count, sputum total cells and differentials, and the concentrations of the inflammatory markers interleukin (IL)-8, and matrix metalloproteinase (MMP)-9 in sputum supernatant were analyzed.


RESULTS
Similar to COPD controls (n = 12), COPD/NSCLC patients had increased levels of absolute and relative sputum neutrophils, IL-8, and MMP-9 at baseline, when compared with healthy controls (n = 14, p < 0.001, all comparisons). After chemotherapy, there was a significant reduction in peripheral blood leukocytes (pre: 10,736 +/- 550, post: 6,536 +/- 1,064 cells/microl, p = 0.002) and log neutrophils (pre: 8.9 +/- 0.09, post: 8.1 +/- 0.2 cells/microl, p = 0.004), whereas log sputum neutrophils (pre: 0.3 +/- 0.37, post: 0.18 +/- 0.3 cells x 10(6)/ml, p = 0.1), IL-8 (pre 15.9 +/- 3.8, post: 17.7 +/- 3.6 ng/ml, p = 0.7), and log MMP-9 (pre: 5.3 +/- 0.57, post: 5.6 +/- 0.7 ng/ml, p = 0.33) remained unchanged.


CONCLUSIONS
A single course of platinum-based chemotherapy markedly decreases peripheral blood neutrophils, but has no effect on inflammatory patterns of induced sputum in COPD patients with unresectable NSCLC.
Beeh
K M
KM
Department of Internal Medicine, University Hospital of Mainz, Mainz, Germany. k.beeh@3-med.klinik.uni-mainz.de
Beier
J
J
Ernst
M
M
Kornmann
O
O
Buhl
R
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications* / Q000188:drug therapy; D002945:Cisplatin / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis*; D008175:Lung Neoplasms / Q000150:complications* / Q000188:drug therapy; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000503:physiopathology*; D013183:Sputum / Q000737:chemistry / Q000187:drug effects*
D016209:Interleukin-8; D005047:Etoposide; D020780:Matrix Metalloproteinase 9; D002945:Cisplatin