Dad's the Link for Childhood Asthma

Researchers find genetic trail leads to fathers

THURSDAY, Sept. 1, 2005 (HealthDay News) -- Asthmatic children whose fathers have a history of the disease are at a greater risk of developing a severe asthma-related breathing difficulty than children whose fathers were always asthma-free, new research finds.

The breathing difficulty in question -- known as airway hyperresponsiveness, or AHR -- is a common feature of asthma, in which a patient's airways drastically narrow in reaction to allergens that range from dust mites and fungi to cold air, exercise and viral infections.

The extreme airway constriction characteristic of AHR can provoke wheezing and a prolonged bout of labored and painful breathing -- a condition known as dyspnea.

Reporting in the September issue of the American Journal of Respiratory and Critical Care Medicine, the researchers observe that this asthma-AHR parental connection appears to track along the paternal line, rather than from mother to child.

They add that the frequency, duration and strength of such AHR attacks serve as a good yardstick for measuring the severity of childhood asthma -- both as a snapshot of a child's current status and as a predictor of how well or poorly a child's asthmatic condition will progress over the long term.

"We have known for a long time that asthma has a strong genetic component, but our data suggest that certain asthma-related genes can also influence the severity of a child's asthma throughout their childhood," said the study's lead author, Dr. Benjamin A. Raby of the department of medicine at Brigham and Women's Hospital in Boston.

Raby and his colleagues pointed out that chronic and serious airway constriction can negatively impact on the development of a child's air passages and lung functions down the road.

According to the American Academy of Allergy, Asthma and Immunology, approximately 5 million children suffer from childhood asthma in the United States. About 80 percent of children who develop asthma do so before the age of 5, and the condition prompts nearly 3 million visits to doctors' offices -- and 200,000 hospitalizations -- every year.

There is no known cure for asthma, though the chronic illness can usually be managed and treated effectively and is not normally a progressively disabling disease. Children suffering from asthma may ultimately outgrow the disease as they enter adolescence or adulthood, although symptoms may recur down the road.

To assess the potential father-child asthma association, Raby and his team examined data on 1,041 boys and girls between the ages of 5 and 12. The children were enrolled in the Childhood Asthma Management Program (CAMP) -- the largest-to-date study of mild to moderate childhood asthma. None of the participants was diagnosed with severe asthma.

In the six months prior to the nearly four-year study -- which compared the long-term benefits of three inhaler asthma treatments -- all the children had manifested at least one of the following characteristics: asthma symptoms at least twice weekly; use of a bronchodilator at least twice weekly; and/or use of a daily asthma medication.

The children's parents completed family history questionnaires regarding asthma, smoking, educational background and socioeconomic status. As well, tests were conducted twice yearly to assess the amount of air entering and leaving the lungs.

To measure AHR severity, all the children completed a series of exams that calculated the presence of methacholine in their bodies. Methacholine is a bronchoconstrictor that can provoke a 20 percent decline in lung function.

Despite acknowledging prior research that had revealed evidence of a maternal asthma association, the researchers noted that no AHR severity and parental asthma correlation was found between mother and child.

However, Raby and his team found that the 208 children whose fathers had a history of asthma did demonstrate a history of more severe AHR. Air passage constriction problems were also more severe among children who had both an asthmatic mother and father.

The paternal-child connection existed regardless of nongenetic factors such as exposure to smoking, family wealth and parental education, the researchers said.

And they suggested that their work might help in the future identification of specific genes that are responsible for airway hyperresponsiveness. Further research, they said, might specifically reveal that the father-child association regarding asthma-associated AHR is in fact the function of AHR-specific genes that are passed on primarily through fathers.

Dr. Jonathan Corren, of the clinical faculty at the University of California, Los Angeles School of Medicine, viewed the study as interesting but problematic.

"I think it potentially sheds a little more light on some of the genetic mechanisms for how this disease is passed on, but it's probably not going to lead to difference, in terms of treatment or prevention," he said.

"It's not a modifiable issue," Corren cautioned. "People with asthma are going to have children, so we don't have any good mechanisms -- given the information that the father has asthma and he is going to have a baby -- to modify the risk. So while this work will help us dissect how this disease is passed on, it's always hard to stop the actual emergence of the disease."

Dr. Stephen Wasserman, a professor of medicine at the University of California, San Diego, went a step further.

"One would expect that there would be a relationship between a father or mother and the child," Wasserman said. "The question is what's one going to do about it? There's nothing you can do about it. You're either going to have asthma or not. We don't know how to prevent asthma from occurring in kids anyway, so really its identification as a marker for risk in children is not so important."

"What is important," Corren added, "is that this doesn't fuel concerns and fears. We don't want fathers to think 'oh my god, if I have asthma my child may have it bad.' That's not necessarily the case, and so this should all be viewed as just an interesting fact about the inheritability of this increasingly common disease."

Raby contended that while his team's research may not have short-term applications for patient treatment, the findings will prove useful down the road.

"They will certainly help our research efforts in how we look for the genes that cause airway twitchiness and asthma in population genetic studies," he said. "By knowing which parent to focus on for the different features of asthma, we may have an easier time identifying the genes that are most important in the development and progression of asthma."

More information

For more on childhood asthma, check out the American Academy of Allergy, Asthma and Immunology.

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