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Abstract
Exhaled nitric oxide (FENO) is a marker of type-2 inflammation in asthma and is used in its management. However, smokers and ex-smokers have lower FENO values, and the clinical use of FENO values in COPD patients is unclear. Therefore, we investigated if FENO had a relationship to different COPD characteristics in smoking and ex-smoking subjects. Patients with COPD (n = 533, 58% females) were investigated while in stable condition. Measurements of FENO50, blood cell counts, IgE sensitisation and lung function were performed. Medication reconciliation was used to establish medication usage. Smokers (n = 150) had lower FENO50 9 (8, 10) ppb (geometric mean, 95% confidence interval) than ex-smokers did (n = 383) 15 (14, 16) ppb, p < 0.001. FENO50 was not associated with blood eosinophil or neutrophil levels in smokers, but in ex-smokers significant associations were found (r = 0.23, p < 0.001) and (r = –0.18, p = 0.001), respectively. Lower FENO values were associated with lower FEV1% predicted in both smokers (r = 0.17, p = 0.040) and ex-smokers (r = 0.20, p < 0.001). Neither the smokers nor ex-smokers with reported asthma or IgE sensitisation were linked to an increase in FENO50. Ex-smokers treated with inhaled corticosteroids (ICS) had lower FENO50 14 (13, 15) ppb than non-treated ex-smokers 17 (15, 19) ppb, p = 0.024. This was not found in smokers (p = 0.325). FENO is associated with eosinophil inflammation and the use of ICS in ex-smoking COPD subjects, but not in smoking subjects suggesting that the value of FENO as an inflammatory marker is more limited in smoking subjects. The association found between low FENO values and low lung function requires further investigation.
Acknowledgments
The authors are grateful to the research nurses/technicians at the three study sites: Dalarna, Gävle and Uppsala. The authors wish to thank Robin Quell for proofreading and editing this manuscript.
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Notes on contributors
M. Högman
MH, BS, KL, KB, CJ and AM participated in the study design and together with AT collected and analysed the data. MH prepared the initial draft. All authors have discussed the draft, and have read and approved the final manuscript.
A. Thornadtsson
MH, BS, KL, KB, CJ and AM participated in the study design and together with AT collected and analysed the data. MH prepared the initial draft. All authors have discussed the draft, and have read and approved the final manuscript.
K. Bröms
MH, BS, KL, KB, CJ and AM participated in the study design and together with AT collected and analysed the data. MH prepared the initial draft. All authors have discussed the draft, and have read and approved the final manuscript.
C. Janson
MH, BS, KL, KB, CJ and AM participated in the study design and together with AT collected and analysed the data. MH prepared the initial draft. All authors have discussed the draft, and have read and approved the final manuscript.
K. Lisspers
MH, BS, KL, KB, CJ and AM participated in the study design and together with AT collected and analysed the data. MH prepared the initial draft. All authors have discussed the draft, and have read and approved the final manuscript.
B. Ställberg
MH, BS, KL, KB, CJ and AM participated in the study design and together with AT collected and analysed the data. MH prepared the initial draft. All authors have discussed the draft, and have read and approved the final manuscript.
H. Hedenström
MH, BS, KL, KB, CJ and AM participated in the study design and together with AT collected and analysed the data. MH prepared the initial draft. All authors have discussed the draft, and have read and approved the final manuscript.
A. Malinovschi
MH, BS, KL, KB, CJ and AM participated in the study design and together with AT collected and analysed the data. MH prepared the initial draft. All authors have discussed the draft, and have read and approved the final manuscript.