How to deconstruct “race” and spirometry

To the Editor:In their recent Rostrum article, Ramsey et al1Ramsey N.B. Apter A.J. Israel E. Louisias M. Noroski L.M. Nyenhuis S.M. et al.Deconstructing the way we use pulmonary function test race-based adjustments.J Allergy Clin Immunol Pract. 2022; 10: 972-978Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar note that the Global Lung Initiative (GLI) found “that presumed normal lung function in ethnic groups is 13% to 14% less for Black, 0.7% to 2.7% less for North East Asian, and 9.7% to 13.7% less for South East Asian persons compared with White lung function.”1Ramsey N.B. Apter A.J. Israel E. Louisias M. Noroski L.M. Nyenhuis S.M. et al.Deconstructing the way we use pulmonary function test race-based adjustments.J Allergy Clin Immunol Pract. 2022; 10: 972-978Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar,2Quanjer P.H. Stanojevic S. Cole T.J. Baur X. Hall G.L. Culver B.H. et al.Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations.Eur Respir J. 2012; 40: 1324-1343Crossref PubMed Scopus (3519) Google Scholar More specifically, the GLI found that “FEV1 and FVC between ethnic groups differed proportionally from that in Caucasians, such that FEV1/FVC remained virtually independent of ethnic group.”2Quanjer P.H. Stanojevic S. Cole T.J. Baur X. Hall G.L. Culver B.H. et al.Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations.Eur Respir J. 2012; 40: 1324-1343Crossref PubMed Scopus (3519) Google Scholar Guidelines from the American Thoracic Society recommend that separate GLI predictive equations be used for those who identify as being in these groups.3Graham B.L. Steenbruggen I. Miller M.R. Barjaktarevic I.Z. Cooper B.G. Hall G.L. et al.Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement.Am J Respir Crit Care Med. 2019; 200: e70-e88Crossref PubMed Scopus (1305) Google Scholar Although all humans are much more genetically similar than different, some variability does correlate with “race” categories.4Bamshad M. Wooding S. Salisbury B.A. Stephens J.C. Deconstructing the relationship between genetics and race.Nat Rev Genet. 2004; 5: 598-609Crossref PubMed Scopus (264) Google Scholar It has been presumed that such genetic differences also explained the differences seen in lung volumes between those with ancestry from different parts of the world. Whether using separate predictive spirometry equations for subjects who identify as belonging to different racial groups is appropriate depends on the explanation for the observed difference in lung volumes. If the difference is due to external factors, it would not be appropriate to use separate equations, because doing so would mask a pathologic decline in lung function. There are many such extrinsic factors that might explain the lower lung volumes in those of African and Asian descent, such as nutrition, poverty, pollution, and access to medical care, all of which are different for those seen by society as White, Black, or Asian.1Ramsey N.B. Apter A.J. Israel E. Louisias M. Noroski L.M. Nyenhuis S.M. et al.Deconstructing the way we use pulmonary function test race-based adjustments.J Allergy Clin Immunol Pract. 2022; 10: 972-978Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar The extent to which these factors affect lung function is incompletely understood. Ramsey et al1Ramsey N.B. Apter A.J. Israel E. Louisias M. Noroski L.M. Nyenhuis S.M. et al.Deconstructing the way we use pulmonary function test race-based adjustments.J Allergy Clin Immunol Pract. 2022; 10: 972-978Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar describe as “fallacy—that lower lung function may be an inherent biological trait,” yet there is evidence to support an association between genetic ancestry and lung function.5Menezes A.M. Wehrmeister F.C. Hartwig F.P. Perez-Padilla R. Gigante D.P. Barros F.C. et al.African ancestry, lung function and the effect of genetics.Eur Respir J. 2015; 45: 1582-1589Crossref PubMed Scopus (34) Google Scholar,6Ortega V.E. Kumar R. The effect of ancestry and genetic variation on lung function predictions: what is "normal" lung function in diverse human populations?.Curr Allergy Asthma Rep. 2015; 15: 16Crossref PubMed Scopus (18) Google Scholar Before we abandon the notion that normal lung function may be different in persons who identify as belonging to different racial groups, we should consider the consequences. If we apply un-“adjusted” GLI equations to everyone, a greater proportion of patients of African or Asian descent will have a restrictive pattern on spirometry. This would warrant further evaluation and treatment only if this represents abnormal lung function. Furthermore, “low” lung function may disqualify these patients from some professions or therapies.1Ramsey N.B. Apter A.J. Israel E. Louisias M. Noroski L.M. Nyenhuis S.M. et al.Deconstructing the way we use pulmonary function test race-based adjustments.J Allergy Clin Immunol Pract. 2022; 10: 972-978Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Ramsey et al1Ramsey N.B. Apter A.J. Israel E. Louisias M. Noroski L.M. Nyenhuis S.M. et al.Deconstructing the way we use pulmonary function test race-based adjustments.J Allergy Clin Immunol Pract. 2022; 10: 972-978Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar propose using the “mixed/other” GLI equations (a composite of all groups) as “preferred over categorizing everyone as White.” However, if the lower lung volumes observed in non-White groups are due to these extrinsic factors as proposed, we would not want to incorporate these into predictive equations, just as we do not have separate equations for smokers, because that would conceal the detrimental effects of smoking. Rather, it would seem appropriate to use the White equations as un-“adjusted,” because subjects who identify as White would presumably have been least affected by these factors. Ramsey et al1Ramsey N.B. Apter A.J. Israel E. Louisias M. Noroski L.M. Nyenhuis S.M. et al.Deconstructing the way we use pulmonary function test race-based adjustments.J Allergy Clin Immunol Pract. 2022; 10: 972-978Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar conclude that we “consider our management plan considering both unadjusted and race-specific values.” Thus, it is appropriate to continue to ask patients to self-identify “race” and then generate one spirometry report using the White equations and, for those identifying as of African or Asian descent, another report using the GLI equations for those groups. For those whose un-“adjusted” report appears to show an abnormal (restrictive) pattern, the clinician can then decide whether additional evaluation is indicated. Future research should continue to investigate how social determinants of health adversely affect lung function so that these can be addressed. We also need to understand better any possible genetic contribution to lung function and how to apply such genetic information to individual patients rather than to “races.” Racism, including medical racism, is real. Every attempt must be made to find it, see it, and eliminate it. We do indeed need to deconstruct “race” and spirometry. Race may be a social construct, but ancestry is genetic.7Krainc T. Fuentes A. Genetic ancestry in precision medicine is reshaping the race debate.Proc Natl Acad Sci U S A. 2022; 119e2203033119Crossref PubMed Scopus (8) Google Scholar Until we determine that the lower lung volumes observed in patients who identify with certain “races” are not in some part due to common genetic ancestry, we should be careful regarding how we proceed. We want to avoid having “racial adjustments” mask underlying pathologic lung function, but also not have normal lung function interpreted as pathologic, abnormal, or inferior. Reply to “How to deconstruct ‘race’ and spirometry”The Journal of Allergy and Clinical Immunology: In PracticeVol. 10Issue 9PreviewThe authors appreciate the correspondence from Kelso1 regarding our Rostrum on deconstructing race-based reference equations in pulmonary function testing.2 Kelso raises several key points. Full-Text PDF