Fractional Exhaled Nitric Oxide as an Inflammatory Biomarker in Chronic Obstructive Pulmonary Disease (COPD) with or without Concurrent Diagnosis of Asthma: The Canadian Cohort Obstructive Lung Disease (CanCOLD)

Abstract

We studied whether fractional exhaled nitric oxide (F_ENO) can differentiate chronic obstructive pulmonary disease (COPD) with concurrent diagnosis of asthma from COPD-only as well as its ability to predict disease severity and progression.

This study was embedded in the Canadian Cohort Obstructive Lung Disease (CanCOLD). Subjects of ≥40 years old completed F_ENO measurements were subdivided into four groups, including COPD (N = 86 [COPD-only (N = 35) and COPD with concurrent diagnosis of asthma (N = 51)], healthy (N = 72), and at risk (N = 151). Three of the most common clinical definitions were used for characterizing COPD with concurrent diagnosis of asthma: 1) atopy and self-reported physician diagnosis of asthma, 2) ≥12% and ≥200 ml post-bronchodilator FEV1; 3) self-reported physician diagnosis of asthma. F_ENO values were classified using quartiles and the American Thoracic Society (ATS) guideline 2011.

Compared to COPD-only, more COPD with concurrent diagnosis of asthma had a significant F_ENO50 level of $\ge$ 33.5 ppb (fourth quartile) than COPD-only (p = 0.045, 0.011, and 0.006, for definition 1, 2, and 3, respectively). Considering the ATS guideline 2011, fewer COPD with concurrent diagnosis of asthma had F_ENO50 < 25 than COPD-only, which was statistically significant with definition 1 and 3 (p = 0.038 and 0.026, respectively).

F_ENO as a biomarker has the potential to be used as a complementary value for differentiating COPD with concurrent diagnosis of asthma from COPD-only. Further studies should be conducted on validated definitions of COPD with concurrent diagnosis of asthma, which may include a reference to the type of airway inflammation in addition to the clinical definition.

Keywords:

• Fractional exhaled nitric oxide
• chronic obstructive pulmonary disease (COPD)
• asthma
• Canadian Cohort Obstructive Lung Disease (CanCOLD)

Declaration of interest

SMY Mostafavi-PourManshadi, Nafiseh Naderi, Palmina Mancino, and Pei Zhi Li have no conflict of interest. Wan Tan reports grants from WCT reports grants from Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants- 93326) with industry partners Astra Zeneca Canada Ltd., Boehringer-Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd., during the conduct of the study., during the conduct of the study. Jean Bourbeau reports grants from CIHR, grants from Canadian Respiratory Research Network (CRRN), personal fees from Canadian Thoracic Society, personal fees from CHEST, grants from Foundation of the MUHC, grants from Aerocrine, grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Grifols, grants and personal fees from GlaxoSmithKline, grants and personal fees from Novartis, grants and personal fees from Trudell, outside the submitted work.

Acknowledgments

The authors thank Circassia (formerly Aerocrine) for its support and providing the measurement instrument, Niox Mino. We also thank the men and women who participated in the study and individuals in the CanCOLD Collaborative research Group: Executive Committee: Jean Bourbeau, (Mcgill University, Montreal, QC, Canada); Wan C Tan, J Mark FitzGerald; D D Sin. (UBC, Vancouver, BC, Canada); D D Marciniuk (University of Saskatoon, Saskatoon, SASK, Canada) D E O’Donnell (Queen’s University, Kingston, ON, Canada); Paul Hernandez (University of Halifax, Halifax, NS, Canada); Kenneth R Chapman (University of Toronto, Toronto, ON, Canada); Robert Cowie (University of Calgary, Calgary, AB, Canada); Shawn Aaron (University of Ottawa, Ottawa, ON, Canada); F Maltais (University of Laval, Quebec City, QC, Canada); International Advisory Board: Jonathon Samet (the Keck School of Medicine of USC, California, USA); Milo Puhan (John Hopkins School of Public Health, Baltimore, USA) ; Qutayba Hamid (McGill University, Montreal, Qc, Canada); James C Hogg (UBC James Hogg Research Center, Vancouver, BC, Canada). Operations Center: Jean Bourbeau (PI), Carole Baglole, Carole Jabet, Palmina Mancino, Yvan Fortier, (University of McGill, Montreal, QC, Canada); Wan C Tan (co-PI), Don Sin, Sheena Tam, Jeremy Road, Joe Comeau, Adrian Png, Harvey Coxson, Miranda Kirby, Jonathon Leipsic, Cameron Hague (University of British Columbia James Hogg Research Center, Vancouver, BC, Canada). Economic Core: Mohsen Sadatsafavi (University of British Columbia, Vancouver, BC). Public Health core: Teresa To, Andrea Gershon (University of Toronto) Data management and Quality Control: Wan C Tan, Harvey Coxson, (UBC, Vancouver, BC, Canada); Jean Bourbeau, Pei-Zhi Li, Jean-Francois Duquette, Yvan Fortier, Andrea Benedetti, Denis Jensen (Mcgill University, Montreal, QC,Canada), Denis O’Donnell (Queen’s University, Kingston, ON, Canada. Field Centers: Wan C Tan (PI), Christine Lo, Sarah Cheng, Cindy Fung, Nancy Ferguson, Nancy Haynes, Junior Chuang, Licong Li, Selva Bayat, Amanda Wong, Zoe Alavi, Catherine Peng, Bin Zhao, Nathalie Scott-Hsiung, Tasha Nadirshaw (UBC James Hogg Research Center, Vancouver, BC); Jean Bourbeau (PI), Palmina Mancino, David Latreille, Jacinthe Baril, Laura Labonte (McGill University, Montreal, QC, Canada); Kenneth Chapman (PI), Patricia McClean, Nadeen Audisho, (University of Toronto, Toronto, ON, Canada); Brandie Walker, Robert Cowie (PI), Ann Cowie, Curtis Dumonceaux, Lisette Machado(University of Calgary,Calgary, AB, Canada); Paul Hernandez (PI), Scott Fulton, Kristen Osterling (University of Halifax, Halifax, NS, Canada); Shawn Aaron (PI), Kathy Vandemheen, Gay Pratt, Amanda Bergeron (University of Ottawa, Ottawa, ON, Canada); Denis O’Donnell (PI), Matthew McNeil, Kate Whelan (Queen’s University, Kingston, ON, Canada); Francois Maltais (PI), Cynthia Brouillard (University of Laval, Quebec City, QC, Canada); Darcy Marciniuk (PI), Ron Clemens, Janet Baran (University of Saskatoon, Saskatoon, SK, Canada).

Additional information

Funding

This project was specifically funded Circassia (formerly Aerocrine). The Canadian Cohort Obstructive Lung Disease (CanCOLD) study is currently funded by the Canadian Respiratory Research Network (CRRN); industry partners: Astra Zeneca Canada Ltd; Boehringer Ingelheim Canada Ltd; GlaxoSmithKline Canada Ltd; Novartis. Researchers at RI-MUHC Montreal and Icapture Center Vancouver lead the project. Previous funding partners are the CIHR (CIHR/Rx&D Collaborative Research Program Operating Grants- 93326); the Respiratory Health Network of the FRQS; industry partners: Almirall; Merck Nycomed; Pfizer Canada Ltd; and Theratechnologies. The funders/sponsors had no role in the study design, data collection and analysis, or preparation of the manuscript.