Dr. Qaadri

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Childhood Asthma Interview

By Dr. Shafiq Qaadri, MD

How many children in Canada have asthma and why does the incidence seem to be increasing exponentially?
Asthma is the most common chronic disease in childhood, and the most common chronic disease for which children and their families are seen in emergency. Depending on the age group, anywhere up to 15 per cent of children have asthma.

What are the official theories about why the rate is increasing?
We are trying to understand why asthma begins in early life…Most asthma starts in early life, in the preschool years and early school age years. Because of that, it is really very important that we recognize that control of asthma in early life may prove to be very important in terms of long-term outcomes.

There is a hygiene hypothesis, which has some appeal in helping us tease apart the mechanisms by which this may be occurring but it is not quite as simplistic as that would suggest. We do know that asthma is a complex disease involving gene and environmental interaction.

What exactly is this sterile hypothesis, the boy-in-the-bubble idea, of ‘too clean’ living from 0 to age 5?
This is put forward probably best by David Strachan. The Western obsession with cleanliness and avoidance of infections in early life is associated with an immune deprivation syndrome wherein the children who’s basic immune vent is toward the allergy asthma phenotype is not educated in a manner that helps to provide a balanced type of immune response. That would be the thesis that lies behind that.

It is as valid as any other hypothesis. Epidemiologic studies that look at various populations and mechanistic studies that attempt to tease apart how these things may impact us at the cellular and physiologic levels have been underway for some time…I think we have some years ahead of us yet before we will truly understand all these issues, especially how do we prevent this disease and potentially how can we cure asthma.

What are some of the challenges of both making the diagnosis of asthma in kids and then getting parental buy-in?
The challenge that I put out to my colleagues is to realize that most asthma that ever occurs begins in childhood….In the child with an immediate family history of asthma, in the child with allergic eczema, in the child with early-life food or inhalant allergy, the probability of recurrent wheezing or coughing type of syndromes truly being asthma is greatly increased.

Recognizing that then is important in terms of thinking about early interventions which can help to effectively control the asthma.

Are there statistics with regard to, for example, time to diagnosis--how long it actually takes for a family doctor to diagnose pediatric asthma?
There are no good data which I am aware of in terms of how long that delay is although we repeatedly hear from patients and their families that this has been a problem going on for not just months but typically years before it was believed to be asthma.

The other side of the picture these days is that there is also the increasing potential to diagnose asthma when in fact it does not exist. And because we do not have a biologic gold standard to help us make the diagnosis, it is not a simple problem.

What are the medications to treat mild to moderate pediatric asthma?
The most important factor to recognize first is that environmental control and appropriate education are critical pieces of any intervention strategy. That really is something that is important for all patients and families where the child has asthma.

In terms of medications, there are two basic categories: the controller-preventer medications and the symptom-reliever medications. While the group of controller medications has been fairly broad in the past, guidelines increasingly have focused on inhaled corticosteroids as the best first option, as an anti-inflammatory-controller therapy for the treatment of asthma.

The problem has been that studies in young children have not given us as much information as we need and there are some real issues that parents have about the use of inhaled corticosteroids. We try and deal with these regularly but parents are concerned and because of their concerns often do not follow through with regular treatment. We believe that regular treatment in children with persistent asthma is important.

Are we winning the battle of increasing the amount of controller-preventer therapy or are people still using their rescue beta-2 agonists too much?
We are still seeing a lot of intermittent use of both symptom-relief and controller medications. It is important to recognize that in persistent disease, control is one of the features that may present long term changes from developing, and because these long term changes in the airways appear to begin in early life, we think that regular compliance with a controller medication is an important factor.

What were the highlights of the article published recently in the Annals of Allergy, Asthma and Immunology—the study of steroids and montelukast?
The main focus of the study was to look at the safety of montelukast in younger children and to compare it to the inhaled corticosteroids as a specific issue relating to growth in children. That is the greatest concern brought up by parents of children with asthma and clearly the study shows that regular use of montelukast did not affect children’s growth whereas with all of the other studies that have looked at the use of other inhaled corticosteroids there is some small but significant impact on growth during that year of therapy.

What are the numbers involved?
The average depends on how old the children are. One of the important things about this study was that we really were careful to look at children during probably the most stable growth periods: for males, that is between 6 to 8 years of age; for females, 6 to 7 years of age.

What was the actual numerical effect on annualized growth rate?
The effect was that compared to the placebo group. The montelukast group grew actually slightly better, 0.3 cm more over the 56 week period of treatment whereas, compared to the placebo group, the steroid group grew, on average, 0.78 cm less than the placebo group.

Given this effect on velocity of growth, an effect on the HPA (hypothalamic-pituitary-adrenal axis), are you suggesting that there may be other effects that we have yet to track?
There are systemic markers of the effect of the inhaled corticosteroids and in this study we measured the two biochemical markers for bone reabsorption and deposition…There are some changes there that are of statistical significance, but at this concentration of steroid used in this study, we did not go looking for other potential effects because it would not have been likely.

Is there a difference in the effect on one-year growth between the various steroids--fluticasone, budesonide, and the new one, cyclesonide?
In general the inhaled corticosteroid effect seems to be roughly the same in most of the one year and longer studies that have been undertaken. Again part of the problem with studies are looking at a very defined group and a lot of them have had disparate ages and we are just now beginning to see some very good studies in the younger children, in the preschool children where it is clear that we need to be able to recognize the disease and treat the disease early in hopes that we will have some long term impact.

In the US, the FDA have required labelling of all of the corticosteroids, noting that they have all had some reduction in growth velocity. I think it is important to put that in context. We are talking about an average from most of the studies that is about the 1 cm mark and that becomes important.

It does not seem to worsen beyond that. So I think it is important not to raise additional concerns on the part of patients… We do need long term outcome studies that track use of the inhaled corticosteroids from early life. We need long term studies tracking the benefit of any controller medicine and safety.

Is it fair to say that the leukotriene inhibitors are basically a kind of allergy tablet, knocking out particular pathways in the allergy cascade?
The cysteinyl leukotrienes, which are blocked by montelukast, play an important role in asthma and they play an important role in allergic responses. But you also have to remember that with viral triggers we see an increase in the cysteinyl leukotrienes in a variety of biological fluids and therefore they cross over between not just allergy but other conditions, such as RSV infections.

Leukotriene inhibitors basically refers to montelukast (Singulair). What happened to Accolate, its companion?
As far as I know, it is still possible to have that medication dispensed in Canada. But it has not been approved for use in children under the age of 12, and so it is really not a compound that I have had much to do with.

What is the main message that family physicians and pediatricians treating kids with asthma should be aware of?
The key is that parents really want to know two things when physicians talk about introducing a trial of a new medication. They want to know if it will work and is it safe. The key message in this study is that here is a safe and effective approach to the management of asthma in younger children.

What is this idea that there is a ‘recapture’ of that one-year growth?
There are very few studies that have followed children over a long period of time, and one of the longest studies by Soren Pederson was a nonrandomized, non-controlled observational study that followed kids from an average 10 years of age until their adult height. This study showed by that point that the children reached the height that was anticipated or calculated that they should reach.

Having said that, that was not a randomized controlled study and we do need longer-term studies that will help to look at that.

Do you use much combination therapy?
In younger children, we do not have data that the combination of an inhaled corticosteroid and a long-acting beta-agonist have any benefits over the inhaled corticosteroid alone. As a result, with the first really focused iteration of asthma guidelines for children, our recommendation is that if the children were not controlled on a moderate dose of corticosteroids to consider add on therapy such as a leukotriene receptor antagonist or long-acting beta agonist.

How would you counsel parents in this scenario—the husband reads that the inhaled corticosteroid is one of the preferred anti-inflammatory treatments, and if you allow the inflammation to simmer, you may lead to chronic lung damage, irreversible remodeling and so on? And the mother who reads about the steroid impact, and wonders if you are going to adversely impact her child’s growth and health?
I think the important thing of our linear growth study is that it now provides a safe and effective alternative approach to steroid controller therapy in younger children. As with any introduction of any new treatment, it really needs to be considered a trial of therapy. One of the things we again encourage in the Canadian Pediatric Asthma guidelines is that when medications are introduced that each physician should consider this a trial of therapy and in some period of time, whether it is four weeks, six weeks or eight weeks, that the patient should be reassessed to ensure that the medication is in fact effective and safe.

So what is your final message to physicians with respect to pediatric asthma?
I think the important thing is to recognize that when children do have asthma that it begins early in life and that there now is an alternative for safe and effective therapy of asthma in younger children.

Dr. Shafiq Qaadri is a Toronto family physician and Continuing Medical Education (CME) lecturer. www.doctorQ.ca

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