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Original Research: Asthma |

Granule Cytotoxic Activity and Oxidative DNA Damage in Smoking and Nonsmoking Patients With AsthmaCytotoxic Immune Response and DNA Damage in Asthma

Athanasia Proklou, MD; Nikolaos Soulitzis, PhD; Eirini Neofytou, PhD; Nikoletta Rovina, MD, PhD; Eleftherios Zervas, MD, PhD; Mina Gaga, MD, PhD; Nikolaos M. Siafakas, MD, PhD, FCCP; Eleni G. Tzortzaki, MD, PhD, FCCP
Author and Funding Information

From the Department of Thoracic Medicine, University Hospital of Heraklion (Drs Proklou, Siafakas, and Tzortzaki), and the Laboratory of Molecular and Cellular Pulmonology (Drs Soulitzis, Neofytou, Siafakas, and Tzortzaki), Medical School, University of Crete, Heraklion, Crete; and the First University Department of Respiratory Medicine (Dr Rovina), and the Seventh Respiratory Medicine Department and Asthma Center (Drs Zervas and Gaga), Chest Diseases Hospital “Sotiria,” Athens, Greece.

Correspondence to: Eleni G. Tzortzaki, MD, PhD, FCCP, Department of Thoracic Medicine, Medical School, University of Crete, 71003 Heraklion, Crete, Greece; e-mail: tzortzaki@med.uoc.gr


Drs Proklou and Soulitzis contributed equally to this research.

Funding/Support: This study was supported by a competitive research grant from the Hellenic Thoracic Society [Grant 2009/05].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(4):1230-1237. doi:10.1378/chest.13-0367
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Background:  Lung cytotoxic mechanisms trigger the release of perforin and granzymes, causing oxidative DNA damage that ultimately leads to apoptosis. These effects, although demonstrated in COPD, have not been investigated in patients with asthma and in particular in patients with asthma who smoke. Our aim was to measure perforin, granzyme A, granzyme B, and 8-OHdG expression in sputum from smoking and nonsmoking patients with asthma, compared with smoking and nonsmoking control subjects.

Methods:  Perforin, granzyme A, granzyme B, and 8-OHdG expression levels were detected by enzyme-linked immunosorbent assays in induced sputum specimens.

Results:  Perforin expression was increased in 40% of smokers and 45% of smoking patients with asthma and in only 7% of nonsmoking patients with asthma (P = .004), compared with control subjects’ values. In contrast, granzymes A and B levels were increased in > 40% of patients in all three groups vs control subjects. Finally, 8-OHdG levels were elevated in 35% of smoking patients with asthma, in 20% of smokers, and in only 10% of nonsmoking patients with asthma. Statistical analysis revealed a positive correlation between granzyme A (P < .001) and granzyme B (P = .006) expression levels and the number of pack-years in smoking patients with asthma.

Conclusions:  Asthma cytotoxic immune response is mainly represented by granzymes A and B, whereas in smoking patients with asthma perforin and 8-OHdG are additionally involved, resembling the immune response in COPD.

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