Benefits and Risks for Inhaled Corticosteroids in Children: An Expert Interview With David B. Allen, MD

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David Allen, MDFor children who have persistent asthma of any degree, inhaled corticosteroid (ICS) treatment is recommended. However, there is ongoing debate with regard to the potential adverse systemic effects and safety of long-term use of these agents, particularly in children. This concern mainly stems from the findings from studies assessing the effects of ICS on lower-leg growth rate or the hypothalamic-pituitary-adrenal axis.[1] The current consensus is that ICS are highly effective and, because their benefits clearly exceed potential risks, can be used safely in children who have persistent asthma.[2,3]

In this Expert Interview conducted by Helen Fosam, PhD, Medscape Allergy & Clinical Immunology, David B. Allen, MD, summarizes the current issues and evidence surrounding the risks and benefits of using ICS to treat asthma in children. David B. Allen, MD, is Professor of Pediatrics at the University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Dr. Allen is also the Director of Endocrinology and Residency Training at the University of Wisconsin Children's Hospital, Madison, Wisconsin.

Dr. Allen: Hello; my name is David Allen. I'm Professor of Pediatrics at the University of Wisconsin Children's Hospital. I'm Director of Endocrinology there, as well as the Director of the Pediatric Residency Program at the University of Wisconsin School of Medicine and Public Health.

Medscape: What are the current challenges in regard to the safety of corticosteroids in treating children with asthma?

Dr. Allen: One of the issues that arises in the care of a child with any type of chronic disease is accepting the fact that chronic medication is going to be necessary. It is a normal tendency for most clinicians, especially pediatricians, to be somewhat reluctant to make a diagnosis that's going to be long-lasting in a child and to prescribe a chronic medication. That's a challenge that remains the treatment of asthma.

Specifically in the areas of inhaled corticosteroids, concerns remain about the effects of these medications on different systems in a child's body, namely, the adrenal gland system, the growth system, and the bone density and bone metabolism area. Clearly, these medications are being prescribed earlier in life than they were, and so we're looking at longer and longer term treatment. I think that that also gives us all pause about the potential complications of many years of these medications compared with just episodic use.

The etiology of asthma clearly involves an inflammatory component, and I think the number of expert panels over the last 10 years has clearly shown that the use of an anti-inflammatory medication is necessary, and recommended as first-line treatment, for control of persistent asthma.

Medscape: From a safety standpoint, are inhaled corticosteroids the therapy of choice for the optimal management of asthma in children?

Dr. Allen: As a premise for this type of discussion, we have to agree that the treatment of persistent asthma requires chronic medication, and then the question becomes: What is the safest way to apply that anti-inflammatory medication?

The question about safety really relates to the different effects that the drugs have on the lung -- the organ of interest -- vs the rest of the body. The principle behind inhaled corticosteroid treatments vs oral glucocorticoids to treat the inflammation of asthma is the principle of targeting the medication toward the specific part of the body that we want to get an anti-inflammatory effect, and minimizing the effect on other parts of the body. From this standpoint, there really is no question that inhaled forms of corticosteroid treatment are going to be more safe for the child than reliance on oral glucocorticoids. The important role that inflammation has to play in persistent asthma has clearly brought inhaled corticosteroids, at least at this point, as our most effective anti-inflammatory agent and should be considered first-line treatment.

Medscape: What are the major systemic effects of inhaled corticosteroids, particularly with long-term use?

Dr. Allen: When people think about treatment of diseases with corticosteroids, the systems of the body that are adversely affected by these medications include the growth system, the bone mineralization system, and the effects on the adrenal gland system itself, which is responsible for the body's own production of cortisol.[2]

There are other side effects that occur locally with regard to the steroid effects on the mouth -- the mucosa that it comes into contact with. There's also been some concern about ocular side effects because we know that individuals who are treated with high doses of oral glucocorticoids can have problems with side effects in the eye, such as glaucoma or cataracts. But those have not been the important areas of focus in children. So for the purposes of our discussion today, I'd like to focus on linear growth, bone mineralization, and what's called the hypothalamic-pituitary-adrenal axis.

Effect on Growth

With regard to growth, we know that it takes little oral glucocorticoid administration to exceed the normal production of cortisol in the body, and therefore to exert a suppressive effect on the growth system. The growth axis of a child is very sensitive to the effects of glucocorticoids on a number of levels, including the production of growth hormone, the response to growth hormone peripherally, the bioactivity of growth hormone's major second messenger (called the IGF-1 [insulin-like growth factor 1], and detrimental effects on collagen synthesis. So, it is natural to be concerned about the effects of inhaled corticosteroids on linear growth, and this area has really received intense study over the last 15 years.

When careful studies were done in the mid-1990s looking at inhaled beclomethasone, they were able to show that there was a demonstrable and significant effect on growth of children who were in the school-age years, that is, prior to puberty. The amount of growth suppression that was seen was about 1.5 cm/year, and this was repeated in a number of studies. This may not sound like very much growth inhibition, but because a normal child only grows about 5-6 cm/year during those ages, it's about a 25% reduction in growth.

Most of that effect from the beclomethasone probably related to its relatively high bioavailability through the intestinal system, which added to the glucocorticoid burden in addition to the drug that was absorbed through the lungs.

A number of medications have been developed since that time, which have reduced the percentage of the drug that gets absorbed into the body through the gastrointestinal tract where it's really not exhibiting any therapeutic effect. Those medications, such as budesonide, fluticasone and mometasone, and (most recently) ciclesonide, have shown reduced effects on linear growth in children compared with the older studies of beclomethasone.[4,5] It doesn't mean that they're completely free of any growth effects, but they have been reduced.

The advantage of medications that get access to the body almost exclusively through the lung is that they avoid an unnecessary, nontherapeutic glucocorticoid burden and allow one to titrate dosages to what is necessary to control the disease. Now it takes work to do this. It takes frequent disease control assessments to practice effective dose titration. With this approach to asthma management, it is quite possible to use these medications very safely with minimal or no effects on the short-term growth of the child.

Looking toward the long term, despite the 1- or 2-year studies that have shown detectable effects on the growth of children, the long-term studies have not shown that inhaled corticosteroid treatment alone has any detectable effect on the final adult height of people who grew up with asthma. So that's very reassuring that most of what is happening during the childhood years is a delay in the growth process and not a permanent stunting of the growth. The delay in the growth process seems to diminish with more prolonged treatment, and any height deficits are largely made up during the pubertal growth spurt.

Effect on Adrenal Gland

With regard to the adrenal gland system, this is more of a concern about the ability of the body -- in a situation of a severe illness or a stressor -- to mount a cortisol response endogenously that will maintain blood pressure, glucose levels, and mental status to be maintained.

Whenever there's exogenous glucocorticoid administered to the body, beginning with the brain, this system senses the presence of exogenous glucocorticoids and reduces its own production of endogenous cortisol. If this is of sufficient magnitude and goes on for a long enough period of time, in the absence of those signals that would normally come from the brain, it leads to atrophy of the adrenal gland and the ability of the person to respond to a stressor by raising his/her cortisol level -- what we call adrenal insufficiency.

Studies suggest that patients who require long-term treatment with high-dose ICS may have abnormal morning plasma cortisol levels and reduced responsiveness to ACTH [adrenocorticotrophic hormone] stimulation.[2,6]

On the other hand, studies have also shown repeatedly that although it's possible to detect the presence of inhaled corticosteroids in the bloodstream, and detect suppression of the endogenous cortisol production, over time this does not lead -- with rare exceptions -- to sufficient suppression of the adrenal axis to cause risk for adrenal insufficiency. Of course, this is related to the dose and the adherence to treatment of the individual. In individuals who require high-dose inhaled corticosteroid therapy in which they definitely would require oral glucocorticoids, I recommend in those situations that monitoring be done periodically to assess the hypothalamic-pituitary-adrenal axis.

Several studies on individuals treated with inhaled corticosteroids alone, for up to 3 years, have shown that it is a very rare occurrence for these patients to be at risk for adrenal insufficiency.

So the bottom line, when it comes to the hypothalamic-pituitary-adrenal axis, is that moderate- to low-dose inhaled corticosteroids used alone without oral glucocorticoids poses very little risk for adrenal insufficiency. However, individuals who are on chronically high-dose inhaled corticosteroids, receiving supplemental oral glucocorticoids to their inhaled therapy for their exacerbations, or might be using glucocorticoids for other atrophic diseases require occasional monitoring of their fasting morning plasma cortisol level preferably drawn between 6:00 am and 8:00 am. If the cortisol level is above 11 mcg [micrograms]/dL, it almost excludes the possibility of clinically significant adrenal insufficiency. If it's less than that, then consultation with an expert for a low-dose ACTH stimulation test would be advisable.

Effect on Bone Mineralization

Lastly, with regard to bone mineralization, this is another system of the body that is exquisitely sensitive to the effects of glucocorticoids. We know that glucocorticoids are used therapeutically, and when they're present in the body in excess of the body's normal production, have a negative effect on bone mineralization at a number of sites.[2,7,8]

Glucocorticoids interfere with the intestinal absorption of calcium by exhibiting an antivitamin D effect. They promote the renal excretion of calcium so that the combination of those 2 effects creates a negative calcium balance in the body.

In some cases this calcium imbalance results in elevations of parathyroid hormone and the development of secondary hyperparathyroidism, although this is often difficult to demonstrate biochemically in many people who are on glucocorticoids.

More recently, it has been shown that there are direct effects of glucocorticoids on the bone metabolism itself, specifically inducing the apoptosis of osteoblasts and other important cells, such as osteocytes, which damages the overall health of the bone. These effects, even with relatively modest doses of glucocorticoids over long periods of time, can interfere with normal bone metabolism.

Medscape: What is the evidence for the safety of inhaled corticosteroids in children, particularly with regard to bone integrity?

Dr. Allen: When it comes to children, this is actually an extremely difficult area to analyze. This is because the skeletons of children are changing so fast that the bone mineral content is going up rapidly, and the bone mineral density, particularly in adolescence, is increasing at a very rapid rate. So whenever we're trying to analyze the health of bones with regard to bone mineral density in children, we're looking at a moving target that is very influenced by the child's size, by where they are in their puberty status, and so on.

Nevertheless, I think that it is appropriate for us to have some concern about the long-term effects of these inhaled corticosteroids, because we know from experience that oral glucocorticoids have clearly demonstrated adverse effects on bone mineralization.

So what do we know so far? Every cross-sectional study that has been done of children using inhaled corticosteroids alone has failed to show that there is any demonstrable adverse effect on bone mineralization, that is, the bone mineral density of those individuals falls within the normal range for children their age. In certain situations, again, when high doses of inhaled corticosteroids are used, or the treatment of the child is punctuated by periods of oral glucocorticoid use, it is possible to see adverse effects on bone mineralization.

We have important challenges ahead of us in terms of the techniques that we use to examine bone mineral density in children. The commonly used DEXA [dual-energy x-ray absorptiometric] scan actually gives us a 2-dimensional view of the bone mineral density -- what's called areal bone mineral density.

If one thinks about it for a minute, you can see that that reading is influenced by the bone size of the child, so that larger bones in larger children actually have an exaggerated apparent bone mineral density, and smaller bones in smaller children have an artificially lower bone mineral density. Consequently, it is extremely complicated to try to interpret a bone mineral density by DEXA in a child. This test should be performed by an expert who is able to correct for the child's size, their pubertal status, and their developmental stage as might be assessed by a bone-age film at the same time.

Other techniques are coming along: different types of CT [computerized tomographic] scans that can be done on peripheral bones, which are probably going to offer us the advantage of more accurately looking at the true bone mineral density of children. But for now, those are really not available for routine use.

From what we know so far with regard to bone mineral density, inhaled corticosteroids seem to be safe, particularly when they're used alone and in moderate doses. There is no study at this point that demonstrates an adverse effect on bone mineral density during childhood when treated with moderate-dose inhaled corticosteroids. It is also appropriate to be cautious because most of those studies have been done in school-age children. In this age group, bone mineral content is increasing rapidly because the size of the bones is increasing, but the bone mineral density is not changing very much until adolescence when there is a rapid and very profound increase in bone mineral density. We need more studies of inhaled corticosteroid effects in the adolescent population to see whether we can detect any changes in the rapid bone accretion that normally would occur during those years.

Medscape: Are new therapeutic approaches for inhaled corticosteroids in development, and do they offer an advantage over current therapies?

Dr. Allen: The challenge with using a glucocorticoid at any time is to try to target the effect of that medication on the organ itself while minimizing the exposure of the rest of the body to the glucocorticoid. Inhaled corticosteroids have already brought us a long way toward that goal, but the drugs still get absorbed through the lung quite efficiently -- and to some extent through the intestinal route -- and gain access to the glucocorticoid receptors throughout the body.

So one can imagine that therapeutic challenges with new medications would include even more efficient delivery of the drug to the lung without any absorption through the intestinal tract, and then some adaptations that would, for instance, confine the glucocorticoid effect to the lung and eliminate or further minimize its effect after it was absorbed into the circulation.

When we look at the newer medications, we've largely accomplished the goal of better targeting the medication to the lung, thus minimizing the absorption through the gastrointestinal tract. A number of modifications also have been made with the drug delivery device combination to maximize the particle size that can be delivered in the airway to the distal lung where it needs to have its major anti-inflammatory effect. So those 2 challenges have largely already been met to increase the delivery of the inhaled corticosteroid to the target part of the body.

What's in development right now are adaptations to inhaled corticosteroids that would further limit their activity to the lung -- for instance, conversion to an active form within the lung, greater retention of the active drug in the lung, and further reduction in accessibility of absorbed drug to the glucocorticoid receptor. The first step is actually something that has been known for a long time; the beclomethasone molecule itself as delivered from the device is not a particularly active glucocorticoid and is converted by the body to an active form in the lung and other tissues. The problem with that particular corticosteroid is that it has fairly high intestinal absorption, so it was difficult to avoid systemic exposure to the drug that really wasn't coming into the body through the lung.

A newer inhaled corticosteroid -- ciclesonide -- is also activated in the lung to its active form, but offers this advantage similar to beclomethasone without the intestinal absorption.

Another potential area where inhaled corticosteroids could be improved would be how they're handled in the bloodstream after they're absorbed into the body. Keeping a glucocorticoid tightly bound to a protein limits its access to its receptor, so the development of compounds that have high protein binding and limited access to receptors outside the lung would improve their safety profile. One can also think about trying to make modifications to these steroids that would enhance their clearance and reduce their storage in fat tissues throughout the body -- what we call "reduce the lipophylicity" of these drugs -- so that once they got into the bloodstream they would be excreted quite rapidly.

Going one step further would be to try to find something that exhibited a similar anti-inflammatory effect without giving the side effects associated with glucocorticoids. In the area of transplant medicine, of course, there have been tremendous advancements made in the last several years in drugs that inhibit cytokine production and are potent anti-inflammatories without acting through the glucocorticoid pathway, and are not associated with the systemic side effects of glucocorticoids. So that would be another area where antiasthma drugs could be developed that would avoid the possible systemic effects of inhaled corticosteroids.

Medscape: From a patient perspective, what are the treatment challenges that might have an impact on adherence and optimal outcomes?

Dr. Allen: When we think about the challenges related to the issue of the safety of inhaled corticosteroids, it doesn't only involve the occurrence of adverse effects that we need to monitor, but also the perceptions that people have about the adverse effects and how those affect the prescribing of these medications as well as adherence to the treatment. Surveys continue to show that physicians have concerns about using glucocorticoids on a chronic basis. I think much of this derives appropriately from our education about the risks for glucocorticoids, particularly when they're used orally. It's important that we always keep in mind that, when using any type of glucocorticoid therapeutically, that titration to the lowest effective dose is always a primary goal of the treatment. This requires careful monitoring; it requires seeing patients back; it requires doing inventories about how they're doing with their disease management. The pace of clinical practice is now so busy that having to educate patients about their medications, and also to arrange for careful follow-ups, is often an impediment to prescribing.

From the patient's standpoint, they're very aware of the possible side effects of inhaled corticosteroids, particularly in this age of easy access to information. I think we should presume that many of our patients will either already be conversant in these possible side effects or will have accessed the Internet to read about potential side effects of inhaled corticosteroids. Particularly with parents, we find that concern about potential side effects is an important factor that limits their adherence to the treatment.

I would recommend strongly a discussion about the risks and benefits of inhaled corticosteroids when they're prescribed, particularly their effect on growth. In the United States parents are particularly concerned about the normal growth and development of their children. They're very reluctant to administer a medication that they think is going to interfere with the growth of their child. It's important to sit down with them and discuss the rationale for prescribing an inhaled corticosteroid to treat their child's inflammatory disease, and to review the evidence that shows that use of moderate-dose inhaled corticosteroids has no expected effect on their child's growth, and that their child's growth with be closely monitored. These discussions will help to alleviate unrealistic fears that they might have about steroids in general. Many times families are also confused about whether there are any differences between anabolic steroids and anti-inflammatory steroids.

It is also important to indicate to patients an awareness of the rare possible side effects that can occur with these medications, and that you are interested in seeing their child back perhaps in 3 or 4 months to carefully monitor his or her growth and to do a careful assessment of the disease to see whether the dose can be reduced. I think with that kind of assurance -- that there's going to be careful monitoring for any potential side effects, that the doses can be reduced, and that the doses that are being used are very safe -- parents are more likely to buy into the concept of treating their child protectively with these medications, even when symptoms aren't apparent. In the absence of that, I think concern about growth, particularly in our parents, severely limits their adherence to the treatment plan.

Medscape: From the evidence and from your clinical experience, what would be your treatment recommendation for a child with asthma?

Dr. Allen: I think the evidence is convincing that chronic asthma is an inflammatory disease and requires anti-inflammatory treatment. Presently, glucocorticoids are our most effective anti-inflammatory treatment for asthma. From an endocrinologist's standpoint, my concern is about the potential side effects of these medications; and there's clearly an advantage to using targeted therapy to provide anti-inflammatory treatment rather than reliance on systemic glucocorticoid therapy via the oral route. It is important to reiterate that message because I think it's difficult sometimes to accept prescribing a chronic medication for a child when intermittent treatment will sometimes do.

Studies have shown that most children who have repeated exacerbations of wheezing during the year and require more than 3-4 short courses of prednisone have abnormal lung function, that is, they continue to experience some ongoing inflammation with mild asthma. That is a situation in which the child's quality of life could be improved by good control of the inflammation. Many of these children appear to be sort of bumping along dealing with their symptoms rather than having their symptoms alleviated.

Given the reality that persistent anti-inflammatory treatment is necessary for the control of the asthma, the choice is clear between inhaled vs oral glucocorticoids. We've talked about some of the different characteristics of inhaled corticosteroids that affect their safety profiles. I think the general principles are that current preparations that have very, very low bioavailability when given via the oral route are the preferred therapies. Medications that are effectively delivered to the lung also offer an advantage because they allow us to titrate the dose to what's needed to control the disease. But physicians also need to be alert to the fact that whatever drug is delivered to the lung will get absorbed into the systemic circulation. So particularly when children require moderate-to-high doses of inhaled corticosteroids over long periods of time, it's important to be aware of monitoring for potential side effects.

Medscape: What type of tests and monitoring should be performed, particularly when treating children with corticosteroids?

Dr. Allen: When it comes to monitoring for linear growth, this requires every office to have a quality stadiometer, that is, a wall-mounted device that can accurately assess a child's height. When we're in the position of trying to accurately determine whether a child has had a slowing in their growth velocity over a 4- to 6-month period of time, it requires very accurate measures. So this requires a good instrument in the clinic.

I recommend when children begin on inhaled corticosteroids that they be seen back again for a careful height measurement, about 4 months or so after the first visit and then perhaps every 6 months after that for a careful visit, plotting the growth measurements on the growth curve so that not only the physician, but also the family, can be reassured that the child's growth rate is normal.

Now there are many things that can adversely affect a child's growth, and particularly late in the school-age years, it's normal for there to be crossing of percentile lines, depending on when puberty occurs. So a slowing of growth rate particularly at that age doesn't always mean that this is an adverse effect of inhaled corticosteroids. So my recommendation if a slowing of growth rate is detected with growth monitoring is that an expert, such as a pediatric endocrinologist, be consulted to examine the child's growth pattern and to determine whether other factors, such as constitutional growth delay as well as a delay in puberty, are affecting the growth of the child rather than just simply trying to take the child off of inhaled corticosteroids, which he or she may badly need.

When it comes to bone mineral density, it is hard to provide any evidence-based guidelines for monitoring at this point. Currently, DEXA scans in childhood cannot predict fracture risk later in life, unlike the adult situation in which there is a fairly good relationship between DEXA scan findings and fracture risk.

My recommendation with regard to bone mineral density is really confined to children who are on very high-dose inhaled corticosteroids chronically or are requiring intermittent oral glucocorticoids or glucocorticoids by other routes. These are children who physicians like myself see in consultation and occasionally consider medications, such as bisphosphonates, as bone stabilizers in an attempt to limit further bone loss. So I don't think there really should be any recommendations for routine DEXA scanning in these children.

Finally, with regard to the adrenal axis, this is an area in which the literature can be very confusing because many of the studies for adrenal function are very sensitive to the presence of glucocorticoid circulating in the body, which does not translate necessarily into a clinically important adverse effect. So it is important to be aware of how the different studies of the hypothalamic-pituitary-adrenal axis relate to the risk for adrenal insufficiency.

As a general rule, very sensitive studies, such as urinary cortisol or repeated serum sampling of the blood for cortisol, provide a good idea of how much glucocorticoid is gaining access to the systemic circulation. They're exquisitely sensitive indicators of exogenous glucocorticoid exposure, but they have limited predictive value for the clinically significant adverse effect of adrenal insufficiency. For that we rely on either studies of plasma cortisol obtained during a normal endogenous stimulation test, which would be the early-morning fasting plasma cortisol, or an ACTH stimulation test, and the most modern one, which I think has the most applicability to the situation of inhaled corticosteroids, would be what is called a low-dose ACTH stimulation test.

My advice to the practitioner, again, is that children who are on low-dose inhaled corticosteroids do not need routine monitoring of their hypothalamic-pituitary-adrenal axis unless another possible side effect of the glucocorticoids, such as growth suppression, is being detected. For children who are on moderate-to-high doses of inhaled corticosteroids, it probably is reasonable to do an occasional, perhaps every 6 months, monitoring of an early-morning fasting plasma cortisol. I still think in real life that this is a useful screen to rule out the presence of adrenal insufficiency. It is not a sensitive indicator of the presence of adrenal insufficiency, but if you get a fasting morning plasma cortisol level, preferably drawn before 8:00 am, if the value is greater than 11 mcg/dL, it essentially excludes clinically significant adrenal insufficiency and provides assurance that normal nighttime endogenous production of ACTH is occurring in that individual.

If the morning plasma cortisol level falls below 11 mcg/dL on repeated sampling, then the patient could have hypothalamic-pituitary-adrenal axis suppression and requires a low-dose ACTH stimulation test. This is a test that can be done in the office and involves an IV [intravenous] injection of 1 mcg of cosyntropin and evaluating the cortisol level 30 minutes later. A value that is above 18 mcg/dL 30 minutes after administration of the cosyntropin would be considered a normal response, indicating that the adrenal gland has its anatomic integrity and is still responding to ACTH. If the value falls below 18 mcg/dL, then it is advisable to consult with an expert to advise on possible management strategies.

References
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  2. Allen DB. Effects of inhaled steroids on growth, bone metabolism, and adrenal function. Adv Pediatr. 2006;53:101-110. Abstract
  3. Peters SP. Safety of inhaled corticosteroids in the treatment of persistent asthma. J Natl Med Assoc. 2006;98:851-861. Abstract
  4. Becker AB, Kuznetsova O, Vermeulen J, et al; Pediatric Montelukast Linear Growth Study Group. Linear growth in prepubertal asthmatic children treated with montelukast, beclomethasone, or placebo: a 56-week randomized double-blind study. Ann Allergy Asthma Immunol. 2006;96:800-807. Abstract
  5. Ferguson AC, Van Bever HP, Teper AM, et al. Comparison of the relative growth velocities with budesonide and fluticasone propionate in children with asthma. Respir Med. 2006 May 27; [Epub ahead of print].
  6. White M, Crisalida T, Li H, et al. Effects of long-term inhaled corticosteroids on adrenal function in patients with asthma. Ann Allergy Asthma Immunol. 2006;96:437-444. Abstract
  7. Mortimer KJ, Harrison TW, Tattersfield AE. Effects of inhaled corticosteroids on bone. Ann Allergy Asthma Immunol. 2005;94:15-21. Abstract
  8. El O, Gulbahar S, Ceylan E, et al. Bone mineral density in asthmatic patients using low dose inhaled glucocorticosteroids. J Investig Allergol Clin Immunol. 2005;15:57-62. Abstract
Funding Information

Supported by an independent educational grant from ALTANA Pharma.

David B. Allen, MD, Professor of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Director of Endocrinology and Residency Training, University of Wisconsin Children's Hospital, Madison, Wisconsin

Disclosure for interviewer: Helen Fosam, PhD, has disclosed no relevant financial relationships.

Disclosure for interviewee: David B. Allen, MD, has disclosed no relevant financial relationships.

 ©2006 Medscape