Why a gender gap in cystic fibrosis care?

A new study of the well-established “gender gap” in cystic fibrosis has shown, for the first time, that females are diagnosed with CF significantly later than males are – and that the difference cannot be explained by gender differences in common CF symptoms, chest X-rays or the age at which youngsters are infected with pseudomonas aeruginosa, the bacterium implicated in up to 90 percent of CF deaths.

The research team from the UW Medical School points out, however, that it’s currently impossible to know if the delay in diagnosis causes the higher mortality rate seen in female patients with CF.

The findings are published in the July 15 American Journal of Epidemiology. Lead author of the study is Hui-Chuan Lai, assistant professor in the nutritional sciences department at UW–Madison.

CF is the most common potentially lethal genetic disease among Caucasians. Its symptoms and the severity of the disease vary greatly among patients, but most have gastrointestinal problems and nearly all develop serious lung disease.

The topic of newborn screening for the disease has been controversial for years, and the Wisconsin CF Neonatal Screening Project began in 1985 to assess the benefits and risks to patients of the practice. The American Journal of Epidemiology findings are based in part on data from the Wisconsin study.

CF scientists and physicians have recognized for many years that females with CF do not live as long, on average, as males with the disease, but the reason why has never been clear. In the current study, the Wisconsin research team examined the age and condition of CF patients at the time of diagnosis. The goal was to find out if there are significant differences between males and females as to when they are diagnosed and whether one gender has more serious disease than the other at the same age.

The research team used CF Foundation Registry data on 11,275 patients diagnosed between 1986 and 1998. They found that, on average, females were diagnosed four months later than males were; the median age for females at diagnosis was 12.7 months, for males 8.7 months.

The researchers also found the delay in diagnosis for girls was most pronounced for patients with respiratory symptoms only (such as coughing and wheezing). In that group, girls were diagnosed a median of 18 months later than boys were.

Finally, the researchers compared the severity of symptoms, chest X-rays and the age at which the patient acquired a respiratory infection. They found no significant differences in such factors between males and females.

“When we discovered that females are diagnosed on average four months later than males are, we speculated that girls perhaps had less severe respiratory problems at diagnosis than boys did,” says lead author Lai. “But that isn’t the case. There were no differences between boys and girls in terms of their cough, their chest X-ray, or the age when they got their first respiratory infection. We have to look elsewhere for an explanation.”

Philip Farrell, M.D., principal investigator of the Wisconsin Neonatal Screening Project and dean of UW Medical School, says although a four-month delay in diagnosis may not seem significant, the period from six months of age to one year is a critical time for CF symptoms to appear and worsen. Patients can become very seriously ill in a matter of weeks. Taking a cue from recent cardiovascular studies, the authors suggest that both physicians and parents may have an “unconscious bias” that is producing this disparity. They note that the prevalence of recurrent wheezing is 1.5 times higher in males than in females and that boys younger than 10 are at higher risk for developing asthma. Physicians may be relying on such perceptions in deciding whether to refer children with respiratory problems to diagnostic tests such as the sweat test for CF.

They also suggest a cultural factor. Boys traditionally are encouraged to be more physically active than girls are, and perhaps parents may notice breathing or stamina problems sooner in boys.

While there is no hard evidence proving that later diagnosis in girls is responsible for their higher CF mortality rate, Farrell says some research suggests that early diagnosis is associated with greater longevity. Those studies, however, are still in progress and the definitive answer is likely years away. He suggests that neonatal screening – whose benefits are only now becoming clear – may be the only way to ensure consistently early diagnosis of both girls and boys with CF.

The National Institutes of Health funded the study.