Haemoglobin as a biomarker for clinical outcomes in chronic obstructive pulmonary disease.

In COPD, anaemia is associated with increased morbidity, but the relationship between haemoglobin over its entire observed range and morbidity is poorly understood. Such an understanding could guide future therapeutic targeting of haemoglobin in COPD management. Leveraging the COPDGene study, we conducted a cross-sectional analysis of haemoglobin from COPD participants, examining symptoms, quality of life, functional performance, and acute exacerbations of COPD (AECOPD). Haemoglobin was analysed both as a continuous variable and categorised into anaemia, normal haemoglobin, and polycythaemia groups. Fractional polynomial modelling was used for continuous analyses; categorical models were multivariable linear or negative binomial regressions. Covariates included demographics, comorbidities, emphysema, diffusing capacity, and airflow obstruction. From 2539 participants, 366 (14%) were identified as anaemic and 125 (5%) as polycythaemic. Compared with normal haemoglobin, anaemia was significantly associated with increased symptoms (COPD Assessment Test score: p=0.006, modified Medical Research Council (mMRC) Dyspnoea Score: p=0.001); worse quality of life (St. George's Respiratory Questionnaire (SGRQ) score: p<0.001; Medical Outcomes Study Short Form 36-item Questionnaire (SF-36) General Health: p=0.002; SF-36 Physical Health: p<0.001), decreased functional performance (6-min walk distance (6MWD): p<0.001), and severe AECOPD (p=0.01), while polycythaemia was not. Continuous models, however, demonstrated increased morbidity at both ends of the haemoglobin distribution (p<0.01 for mMRC, SGRQ, SF-36 Physical Health, 6MWD, and severe AECOPD). Evaluating interactions, both diffusing capacity and haemoglobin were independently associated with morbidity. We present novel findings that haemoglobin derangements towards either extreme of the observed range are associated with increased morbidity in COPD. Further investigation is necessary to determine whether haemoglobin derangement drives morbidity or merely reflects systemic inflammation, and whether correcting haemoglobin towards the normal range improves morbidity.

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Copyright ©The authors 2021.

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Conflict of interest: A. Balasubramanian has nothing to disclose. Conflict of interest: R.J. Henderson has nothing to disclose. Conflict of interest: N. Putcha reports grants from the NIH outside the submitted work. Conflict of interest: A. Fawzy has nothing to disclose. Conflict of interest: S. Raju has nothing to disclose. Conflict of interest: N.N. Hansel reports grants from the NIH and the COPD Foundation, grants and personal fees from AstraZeneca and GSK, grants from Boehringer Ingelheim, and personal fees from Mylan during the conduct of the study. Conflict of interest: N.R. MacIntyre reports personal fees from Inspirx, Ventec and Hillrom outside the submitted work. Conflict of interest: R.L. Jensen has nothing to disclose. Conflict of interest: G.L. Kinney has nothing to disclose. Conflict of interest: W.W. Stringer reports grants from AstraZeneca, and personal fees from Medical Director (Pulmonary Rehabilitation Program), Pulmonary and Critical Care Physician, and Medical Director (Blood Gas Laboratories), outside the submitted work. Conflict of interest: C.P. Hersh reports grants from the NHLBI during the conduct of the study; and grants from Bayer, Boehringer Ingelheim, Novartis and Vertex, outside the submitted work. Conflict of interest: R.P. Bowler has nothing to disclose. Conflict of interest: R. Casaburi has nothing to disclose. Conflict of interest: M.K. Han reports grants from the NHLBI during the conduct of the study; and personal fees from GSK, AZ, BI, Teva, Merck, Verona and Mylan, and research support from Sunovion and Novartis, outside the submitted work. Conflict of interest: J. Porszasz has nothing to disclose. Conflict of interest: B.J. Make reports grants, nonfinancial support and other support from AstraZeneca, nonfinancial support from Spiration, grants, nonfinancial support and other support from GlaxoSmithKline and Sunovion, other support from Mt Sinai, Web MD, National Jewish Health, Novartis, the American College of Chest Physicians, Projects in Knowledge and Hybrid Communications, grants from Pearl Research, other support from Medscape, Verona, Boehringer Ingelheim, Theravance and Ultimate Medical Academy, nonfinancial support and other support from Circassia, personal fees and nonfinancial support from Third Pole, nonfinancial support and other support from Phillips, other support from the Eastern Pulmonary Society, Catamount Medical, Science 24/7, Eastern VA Medical Center and Academy Continued Health Care Learning, grants from the NHLBI, personal fees from Takeda, and other support from Wolters Kluwer Health, outside the submitted work. Conflict of interest: M.C. McCormack has a patent with UpToDate with royalties paid, a patent with GSK pending, and a patent with Celgene pending. Conflict of interest: R.A. Wise reports personal fees from AstraZeneca/Medimmune/Pearl, grants and personal fees from Boehringer Ingelheim, personal fees from Contrafect, Roche-Genentech, Merck, Circassia, Pneuma, Verona, Mylan/Theravance and Propeller Health, grants from Sanofi-Aventis, personal fees from AbbVie, grants and personal fees from GSK, and personal fees from ChemRx, Kiniksa, Bristol Myers Squibb, Galderma, Kamada, Pulmonx, Kinevant and PureTech, outside the submitted work.