How wonderful that we have met with a paradox. Now we have some hope of making progress.—Niels Bohr

Chronic obstructive pulmonary disease (COPD) has recently risen to the third leading cause of death in the United States (1). While a wealth of important studies work to identify populations at risk for the development and progression of COPD, current research falls short in evaluating a group that is potentially protected from development of COPD: the U.S. Hispanic population. Hispanics, the fastest growing minority in the United States (2), have a heterogeneous ethnic ancestry comprised of American Indian, European, and African origin. Despite being the largest U.S. minority, Hispanics have traditionally fallen outside the scope of COPD clinical trials because of the relatively low prevalence of COPD and challenges of recruitment in this population. Ironically, it is these exclusions that may have delayed the understanding of genetic factors associated with protection against COPD development and progression, a key step in our understanding of the underlying susceptibility to COPD.

As early as 1969, it was recognized that U.S. Hispanics were using psychiatric resources at rates much lower than other minority groups (3). After reviewing additional clinical outcomes, including infant mortality and cardiovascular disease, Markides and Coreil codified the term “Hispanic paradox” to characterize the observation that health outcomes in U.S. Hispanics were more comparable to non-Hispanic whites than to African Americans, despite lower socioeconomic indices (4). The Hispanic paradox has been shown to apply to COPD. Samet and colleagues demonstrated that New Mexico Hispanics have reduced risk of physician-diagnosed COPD and chronic airflow obstruction compared with non-Hispanic whites (5). In addition, while the age-adjusted mortality for COPD increased in Hispanics from 1958 to 1982, the annual rates of death were lower than those for non-Hispanic whites for each year studied (6). Recently, the PLATINO study evaluated the prevalence of COPD in five Latin cities, finding the lowest prevalence in Mexico City, consistent with the Hispanic paradox (7). Theories explaining the better clinical outcomes in Hispanics include differential smoking habits (5), the effects of altitude on lung growth (7), a healthy immigrant effect (disproportionate migration of individuals with good health), and the “salmon bias” (less healthy Hispanics may return home where they die) (8). Although the etiology and validity of the Hispanic paradox remains unclear, the epidemiological literature suggests that Hispanics have improved COPD outcomes.

In this issue of the Journal, Bruse and colleagues (pp. 1254–1260) expand our understanding of the ethnic and genetic factors related to COPD prevalence and disease progression in Hispanic smokers (9). They accomplish this by examining nearly 2,000 participants of the Lovelace Smokers’ Cohort, a community-based longitudinal cohort of former and current smokers in Albuquerque, New Mexico. With these data, the risk of spirometry-defined COPD and risk of rapid decline in the forced expiratory volume in one second (FEV₁) is compared between Hispanic and non-Hispanic white smokers. Importantly, the authors use ancestry informative markers in addition to self-reported ethnicity to determine the relative effect of Native American ancestry on spirometric outcomes. At baseline, Hispanics were slightly younger and less likely to have a high school education than non-Hispanic whites. Smoking habits also differed between the ethnic groups, with Hispanics having more current smokers (77 versus 54%; P < 0.001), lower cumulative pack-years (34 versus 41; P < 0.001), and fewer packs smoked per day (1.10 versus 1.24; P < 0.001). After adjustment for relevant covariates, self-reported Hispanic ethnicity was associated with a 51% reduction in the odds of COPD compared with non-Hispanic whites (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.35–0.71). Hispanic ethnicity was also associated with a reduction in the odds of rapid (> 3% per year) decline in FEV₁ (OR, 0.48; 95% CI, 0.30–0.78). These findings persisted in models that adjusted for various measures of smoking intensity and duration. When exploring ancestry informative markers to define ethnicity, Hispanics in this cohort were composed of nearly 2/3 European markers and 1/3 American Indian markers. Higher American Indian ancestry was associated with a reduced odds of COPD (OR, 0.47; 95% CI, 0.33–0.69; P < 0.001) and rapid decline in FEV₁ (OR, 0.51; 95% CI, 0.32–0.83).

So how do these data contribute to unraveling the Hispanic paradox? First, the protective effect of Hispanic ethnicity does not appear to be solely related to smoking behavior in this cohort. The authors are to be commended for their multiple efforts to adjust for the effects of smoking. While it is always impossible to adjust for all potential confounders, it is reassuring that the reduced association between Hispanic ethnicity and COPD outcomes was resilient to several different models of smoking. Second, by defining ethnicity with ancestry informative markers, the authors have provided a more rigorous characterization of the relationship between COPD outcomes and specific genetic ancestry in Hispanics. The authors’ approach successfully quantifies the inherently qualitative and complicated concept of ethnicity. Finally, this report highlights the need to consider other populations of study in COPD. The Hispanic population is particularly understudied in COPD trials. To understand the factors related to disease susceptibility, populations protected from the disease should be evaluated just as rigorously as those known to be vulnerable to the disease. It is important that future population-based studies evaluating the genetic basis of COPD include Hispanics, as protective alleles may be more readily identified in this population. Ultimately, studies of the Hispanic paradox like this one may help to clarify our understanding of the paradoxes of COPD. Fortunately, we have some hope of making progress.

References

Section:

ChooseTop of pageReferences <<CITING ARTICLES