Growing out of asthma
“Boys are more likely than girls to grow out of childhood asthma when they hit their teenage years”, BBC News announced today. It said that research of more than 1,000 children over an average of nine years, found that although boys were more likely to wheeze than girls, the symptoms were also more likely to disappear when boys reached adolescence. It reported Asthma UK experts as saying “sex hormones might play a role in the symptoms of asthma and its severity” and that this research points to an unknown mechanism behind the development of asthma.
This study used statistical modelling to deduce that, compared to boys, girls’ airways were more likely to give a pronounced asthmatic response when exposed to provocative stimuli. However, it also found that both sexes were susceptible to a number of other factors that influenced airway responsiveness, such as a history of hayfever and allergies, and it could not be put down to one factor alone. This study will probably promote further research into the processes involved in the development of asthma and the possible reasons why gender difference may influence its prognosis.
Where did the story come from?
Dr Kelan G. Tantisira and colleagues from the Brigham and Women’s Hospital and Harvard Medical School, John Hopkins University, and the Washington University School of Medicine, US, carried out the research. The study was funded by the National Heart, Lung and Blood Institute, the General Clinical Research Center, and the National Center for Research Resources. The study was published in the peer-reviewed medical journal: American Journal of Respiratory and Critical Care Medicine.
What kind of scientific study was this?
This cohort study aimed to examine the factors that are responsible for the persistence of increased airway responsiveness, a characteristic of asthma, in asthmatic children.
This study used all the participants from an earlier randomised controlled trial, the Childhood Asthma Management Programme (CAMP). Between December 1993 and September 1995, CAMP enrolled 1,041 children between five and 12 years of age who had mild to moderate asthma. The children’s asthma was confirmed with measures of PC20, a recognised measure of asthma severity. This is the concentration of methacholine, a substance known to challenge the airways of people with asthma, needed to produce a 20% reduction in FEV1 (the volume of air that can be forcibly exhaled in the first second after a maximal inspiration).
The children were randomly assigned to receiving a steroid inhaler (200mg of budesonide (311 children), 8mg of nedocromil, an asthma medication with a different mechanism of action (312 children), or a placebo (418 children) twice daily. The participants were treated for four to six years until the treatment phase ended in 1999.
The children underwent methacholine testing again eight months after they began treatment, and then annually throughout the rest of the treatment and observation periods (the observational phase being a five-year period commencing in 1999 at the end of the treatment phase).
Statistical methods were used to examine the change in PC20 in each child over time, and the difference between boys and girls. The analyses took into account numerous potential confounding factors including asthma severity, other allergies, family history and socio-environmental variables such as household smoking and pets. The researchers also examined physical sexual maturity in both boys and girls using a recognised staging system.
What were the results of the study?
Of the original sample, 60% were boys, who, compared to girls, were diagnosed at a significantly younger age. It included a larger proportion of children at an earlier stage of sexual maturation, and had significantly poorer lung function as shown by lower predicted lung function measures.
Of the original sample, 90% completed the observational phase of the study. Boys and girls had comparable PC20 values up until about the age of 11, but after this age through to 18 years, boys required a significantly larger concentration of methacholine to achieve a 20% reduction in FEV1 compared to girls (i.e. boys had reduced responsiveness of the airways). The PC20 of girls also increased as they aged but by a much smaller amount. This occurred when several factors were taken into account, including ethnicity, duration of asthma and severity at start of the study, and continued corticosteroid use, responsiveness to allergy skin testing, and lung function measures prior to the test. When the researchers looked at differences in PC20 by sexual maturity staging, they found that the PC20 for boys increased with each increase in stage towards maturity, while the PC20 for girls remained largely unchanged as they matured.
The researchers carried out analyses to look at other variables that can affect airway responsiveness. Through this, they found that males had significantly lower PC20 (increased responsiveness of the airways) if diagnosed at a younger age, if they had had any positive allergy skin test, had higher blood concentration of the antibody IgE and another blood cell involved in the allergic immune response, and had reduced response to inhaled bronchodilator treatment.
Girls had significantly reduced PC20 with these same factors (apart from allergy skin test response, which made no difference), and also with previous history of hayfever or allergy, and mother smoking while pregnant. In both sexes, PC20 was significantly increased (reduced responsiveness of the airways) by higher BMI, increased duration of asthma, and improved predicted lung function variables.
What interpretations did the researchers draw from these results?
The researchers concluded that increased airway responsiveness, as indicated by a lower PC20, is more severe in postpubertal females with asthma than postpubertal males with asthma. They acknowledge that there are other factors associated with airway responsiveness in both sexes.
What does the NHS Knowledge Service make of this study?
This study has strengths in that it followed a large group of asthmatic children with yearly lung function tests over a 10-year period, and that it gave a clear indication of how responsiveness of the airways can alter with aging and maturation. The study identified clear differences between the two sexes and this will promote further research into the underlying mechanisms.
The authors acknowledge that there is a variety of additional factors that also affected responsiveness of the airways in both sexes. These included duration of asthma, age at diagnosis and other allergic markers. However, as they say, these could not explain the overall differences seen between the sexes. The reduced airway responsiveness in males coinciding with increased physical sexual maturity suggests possible structural differences within the body (for example, boys having larger airways than girls), or that hormonal mechanisms may play a role.
There are two important potential limitations to consider:
- All of the children were taking part in a separate clinical trial of their response to two different preventative medications, and these treatments may have affected the responsiveness of the children’s airways. The researchers do address this limitation and say that there was no apparent difference between the groups at the end of the treatment period.
- Only airway responsiveness to a provocative stimulus was measured. No assessment is given in the report of asthma symptoms to see how these findings correlate with disease severity and impact upon health, in other words, whether there was any actual difference in the experienced condition between boys and girls.
This study will probably promote further research into the processes involved in the development of asthma and the possible reasons why gender difference may influence its prognosis. It is not yet clear how new targeted treatments for asthma can make use of this finding.
Sir Muir Gray adds...
Good to see that boys do better at something.
