Respiratory Infections May Drive Puerto Rico’s High Asthma Burden

Early-life respiratory viruses may play an outsize role in Puerto Rico’s sky-high rates of childhood asthma, according to a collaborative study led by researchers from UC San Francisco and the City University of New York (CUNY).

Puerto Ricans have the highest asthma rates in the world, with the disease affecting roughly 14.2 percent of Puerto Ricans at some point in their lives. In contrast, 9.6 percent of African-Americans, 8.2 percent of non-Hispanic whites, and 4.8 percent of Mexican-Americans report that they have experienced asthma at some point in their lives according to data from the U.S. Centers for Disease Control and Prevention. Puerto Ricans are also four times more likely to die of the disease than non-Hispanic whites.

Asthma risk is an interplay of genetic and environmental factors, and researchers have hypothesized that respiratory viruses endemic to the island are a key contributor to Puerto Rico’s high asthma rates.

“The alarmingly high rate of asthma in the Puerto Rican population has been a mystery to scientists since its discovery decades ago,” said Eric M. Wohlford, MD, PhD, a UCSF pediatric allergy and immunology fellow in the Asthma Collaboratory in the UCSF School of Pharmacy, and lead author of the new study. “Our lab and others have previously discovered population-based differences in asthma genetics, response to medications, and environmental factors that may contribute, but there has been an open question as to whether common respiratory viral infections may differentially predispose some groups to asthma more than others.”

The new study, published May 5, 2020, in PLOS ONE, was overseen by corresponding author Luisa Borrell, DDS, PhD, a distinguished professor in CUNY’s Graduate School of Public Health & Health Policy, and senior author Esteban Burchard, MD, MPH, a pulmonologist and professor in the UCSF departments of Medicine and of Bioengineering and Therapeutic Sciences who directs the UCSF Asthma Collaboratory. The work is part of a collaboration with study co-author José R. Rodríguez-Santana, MD, at Centro de Neumologia Pediátrica in Caguas, Puerto Rico, among other collaborators.

The research team collected socio-demographic information and medical histories for 2,842 Puerto Rican, Mexican-American, and African-American children.

Study participants were drawn from the GALA II and SAGE studies, two parallel case-control studies of asthma led by the Burchard lab, which were conducted between 2006 to 2014 in Latino (Mexican-American and Puerto Rican) and African-American children aged 8 to 21, respectively. SAGE participants were recruited from the San Francisco Bay Area and GALA II participants were recruited from across the continental United States (Chicago, Houston, New York City, and the San Francisco Bay Area) and Puerto Rico.

The researchers split the children into 1,091 with an asthma diagnosis and 1,733 without a diagnosis and determined how much more often children with asthma had experienced a handful of common respiratory infections before the age of two – including upper respiratory infection, pneumonia, bronchitis, and bronchiolitis / respiratory syncytial virus (RSV).

The research confirmed the higher rates of early life respiratory infections among Puerto Ricans – finding that rates of early life RSV infections or bronchiolitis in particular were four- to nine-fold higher in Puerto Rican children than in Mexican-Americans and African-American children.

They also showed the consequences of these high rates of early-life infection for later asthma risk were also especially severe in Puerto Rican children.

Compared to children without asthma, Mexican-American children with asthma were three times more likely to have had at least one of a handful of common early life respiratory infections, and African-American children with asthma were four times more likely to have had such an infection, but Puerto Rican children with asthma were more than six times more likely to have had at least one these infections before the age of 2.

“Our results suggest that while all groups have greater odds of asthma after respiratory infections, some groups are more affected than others,” Borrell noted. “Particularly in the Puerto Rican population, we note that viral infections may be a major driver of childhood asthma compared to other groups.”

“Our current study gives us a glimpse at the association between early-life respiratory infections and asthma in Puerto Ricans, but it is not able to establish causation,” Wohlford added. “To do that, longitudinal studies that follow patients over time during and after viral infections to monitor for asthma development are needed. Our group is actively enrolling a large longitudinal birth cohort study of 3,000 Puerto Rican mother–infant pairs, called PRIMERO, to do exactly that.”

PRIMERO, Puerto Rican Infant Metagenomic and Epidemiologic Study of Respiratory Outcomes, is an NIH/NHLBI funded longitudinal birth cohort designed to study respiratory viral infections and early life origins of asthma.

Authors: Additional authors on the study were Jennifer R. Elhawary, Brian Plotkin, Sam Oh, Thomas Nuckton, Celeste Eng, and Sandra Salazar of UCSF; Michael LeNoir of Bay Area Pediatrics; Kelley Meade of UCSF Benioff Children’s Hospital Oakland; Harold J. Farber of Baylor College of Medicine and Texas Children’s Hospital in Houston; Denise Serebrisky of Jacobi Medical Center in the Bronx; Emerita Brigino-Buenaventura of Kaiser Permanente-Vallejo Medical Center; William Rodriguez-Cintron of Veterans Caribbean Health Care System in San Juan, Puerto Rico; Rajesh Kumar of The Ann and Robert H. Lurie Children’s Hospital of Chicago; Shannon Thyne of UCLA; and Max A. Seibold of National Jewish Health in Denver.

Funding: This work was supported in part by the Sandler Family Foundation, the American Asthma Foundation, the RWJF Amos Medical Faculty Development Program, Harry Wm. and Diana V. Hind Distinguished Professor in Pharmaceutical Sciences II, National Institutes of Health (NIH) (R01HL117004, R01HL128439, R01HL135156, 1X01HL134589, R01HL141992, 5T32GM007546, 1U01HL138626-01A1), National Institute of Health and Environmental Health Sciences (R01ES015794, R21ES24844), the National Institute on Minority Health and Health Disparities (P60MD006902 RL5GM118984, R01MD010443) and the Tobacco-Related Disease Research Program (24RT-0025, 27IR-0030).

Disclosures: The authors declare that they have no relevant conflicts of interest.

The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes UCSF Health, which comprises three top-ranked hospitals, as well as affiliations throughout the Bay Area.