CF Carriers at Higher Risk of Childhood Asthma: Study

Children who carry certain mutations associated with cystic fibrosis (CF), but do not have the disease — called CF carriers — may be more likely to develop asthma than children who don’t carry a mutation, a California study found.

In particular, inheriting one copy of the most common CF-causing mutation, F508del, from one parent and one of two other variants not likely to be CF-causing from the other, was linked to a higher asthma risk.

The association was further increased, although not significantly, among children in areas with high air pollution.

The findings “have implications for the design of CF screening programs, referrals, educational materials, and the study of alternative treatment options,” for asthmatic CF carriers, the researchers wrote.

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The study, “CFTR gene variants, air pollution, and childhood asthma in a California Medicaid population,” was published in Pediatric Pulmonology. 

CF carriers typically inherit one CF-causing mutation in the CFTR gene. Since two mutations are required for CF to develop, these patients do not have the disease, but can pass it along to their children.

Sometimes carriers might also have other CFTR mutations that are not known to cause disease. While having these extra mutations does not mean the patient will develop CF, they could dictate in part how much functional CFTR protein — the product of the CFTR  gene — a carrier has.

Research suggests that carriers might be at an increased risk for some health conditions, with one study showing they are more likely to develop asthma, a condition characterized by episodes of wheezing, breathlessness, and chest tightness.

Environmental factors like air pollution or exposure to tobacco smoke might also influence asthma or risk its exacerbations.

CF carriers and asthma

The researchers investigated the CFTR carrier status and asthma prevalence among children born in California between July 2007 and June 2017 who were on Medicaid, a U.S. governmental program that provides health insurance to low-income families.

CFTR genetic status was determined from CF newborn screening records. At birth, newborns in California are screened for the presence of immunoreactive trypsinogen (IRT), a protein elevated in CF. Babies with IRT above a certain cutoff are referred for genetic testing to look for CF-causing mutations.

Asthma incidence (newly diagnosed cases) was compared between CF carriers — babies in whom a CF-causing mutation was found — and two different control groups. The first included babies with IRT below the cutoff, babies not referred for genetic testing but presumed unlikely to carry CFTR mutations and the second included those with IRT at or above the cutoff but for whom no mutations were revealed in the genetic screen.

Across 5,746 children, 941 were carriers, with F508del being the most frequently observed mutation. At the last follow-up, the participants had a mean age of 4.7 years.

Data showed carriers were at greater risk of developing asthma compared to low IRT controls. Carriers who had multiple mutations, that is, one known CF-causing mutation and another not known to cause CF, had a lower risk of asthma than those with a single variant.

The carrier subgroups at the highest risk of asthma had inherited one copy of the F508del mutation from one parent and either a (TG) 11T5 or T7 variant from the other.

(TG) 11T5 or T7 variants are known to reduce CFTR function. Carriers with F508del plus one of these variants are thought to have CFTR function between 25-45% of normal levels, the researchers noted.

Air pollution data from the California Environmental Protection Agency were used to determine whether environmental exposures might interact with genetic carrier status to elevate risk.

The relationship between F508del/(TG) 11T5 or T7 genetic status and asthma was increased, but not significantly, for children born in areas with pollution at or above air quality standards set by California’s environmental agency.

“This finding is consistent with the importance of environmental factors in the pathogenesis [development] of asthma, especially among those with high-risk CFTR genotypes [genetic makeup],” the researchers wrote.

While the findings suggest carriers of certain CFTR mutations may be at an increased risk of asthma, that study predominately included Black and Hispanic children from low-income families, limiting the generalizability of the findings, the team noted.

The researchers also pointed out that it’s possible, though unlikely, that children in the two controls groups have a CFTR mutation that was not identified, since some children did not undergo genetic screening and the screen included just 40 known mutations.

“We encourage others to attempt replication of our findings and to explore the possible mechanisms of action,” the research team wrote.