Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking

Jonas Eriksson Ström, Jamshid Pourazar, Robert Linder, Anders Blomberg, Anne Lindberg, Anders Bucht, Annelie F Behndig, Jonas Eriksson Ström, Jamshid Pourazar, Robert Linder, Anders Blomberg, Anne Lindberg, Anders Bucht, Annelie F Behndig

Abstract

Background: Cytotoxic lymphocytes are increased in the airways of COPD patients. Whether this increase is driven primarily by the disease or by smoking is not clear, nor whether it correlates with the rate of decline in lung function.

Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study according to pre-determined criteria; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry.

Results: In BAL fluid, the proportions of NK, iNKT and NKT-like cells all increased with pack-years. Within the COPD group, NK cells - but not iNKT or NKT-like cells - were significantly elevated also in subjects that had quit smoking. In contrast, current smoking was associated with a marked increase in iNKT and NKT-like cells but not in NK cells. Rate of lung function decline did not significantly affect any of the results.

Conclusions: In summary, increased proportions of NK cells in BAL fluid were associated with COPD; iNKT and NKT-like cells with current smoking but not with COPD. Interestingly, NK cell percentages did not normalize in COPD subjects that had quit smoking, indicating that these cells might play a role in the continued disease progression seen in COPD even after smoking cessation.

Trial registration: Clinicaltrials.gov identifier NCT02729220 .

Keywords: Bronchoalveolar lavage; Chronic obstructive pulmonary disease; Disease mechanisms; Lung function decline; Smoking habits.

Conflict of interest statement

Ethics approval and consent to participate

Informed consent was obtained from all volunteers after verbal and written information and the study was approved by the local Ethics Committee at Umeå University, Sweden, and performed according to the declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study design
Fig. 2
Fig. 2
Part 1, 2 and 3: NK, iNKT and NKT-like cell populations in BAL fluid. Data shown as median and IQR. LF: lung function. Shown p-values calculated using the Mann-Whitney U-test. See Additional file 1 for corresponding data in tables
Fig. 3
Fig. 3
Part 2: NKT-like cell subpopulations in BAL fluid. Data shown as median and IQR. LF: lung function. Shown p-values calculated using the Mann-Whitney U-test. See Additional file 1 for corresponding data in tables

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Source: PubMed

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