Allergen avoidance is not new in asthma. The first recorded incidence was way back in 1550. John Hamilton was an archbishop in Scotland who had bad asthma. Gerolamo Cardano was summoned to Scotland to see if he could help. He advised the archbishop to get rid of his feather bedding, feather pillows and cushions and replace them with elementary, hard stuff. Soon, there was a miraculous remission of his asthma.

Allergen exposure is a complex subject. Different things happen in the first or second year and later in childhood. The susceptibility to develop allergy and sensitisation to environmental allergens are genetically determined. There are some individuals who are more predisposed to developing allergy compared to others. This characteristic is described as ‘deviation'.

If someone is so inclined genetically, then he is likely to become sensitized to the allergens to which he is exposed. For example, a person from England is likely to become sensitized to house dust mite or to the cat if he has a pet cat. A person from Arizona is more likely to be sensitized to cockroaches. Some studies indicate that exposure to pets in very early life and indeed exposure to farm livestock may actually protect against the development of asthma. Perhaps, in some patients the exposure to an animal allergen in early life may induce immunotolerance. A more likely second mechanism could be that the greater exposure to microbes and infections in early life drives the immune reaction towards an infective type of reaction, thus protecting from developing allergy.

However, if a child becomes sensitized, it does not necessarily mean that he will develop asthma though he may show IgE or allergy mediated responses to the allergens. There are other factors, genetic or environmental, that contribute to the development of asthma. Once the child has got asthma then further allergen exposure is more likely to aggravate the condition and lead to persistent and perhaps more severe asthma.

Hence allergen avoidance is important. This can be achieved by reducing the allergen load. The load will depend on where the child lives. (Fig. 10)

 

Inhaled steroids are one of the most potent anti-inflammatory agents available to treat children with asthma. As many as 24 randomized controlled trials (RCTs) of inhaled steroid therapy were conducted around the world between 1973 and 1996. The trials revealed that inhaled steroids resulted in:

• 50 percent average improvement in symptoms
• 40 percent reduction in bronchodilator use
• 70 percent reduction in oral steroid use
• Good improvement in lung function, more than 10 percent or 38 L/min of predicted.

So there can be no doubt that inhaled steroids are highly effective in asthma and that too in low doses. (Fig. 11)

 

From the mid-1970s to the early 1990s, there was a relentless rise in the incidence of asthma attacks in children throughout the UK. Since 1992-93 there has been a fall in the frequency of asthma attacks. There can be two reasons for this fall:

• Increased use of inhaled steroids to treat early asthma in pre-school children
• Development of teams of highly trained respiratory nurses who train children and parents, the correct use of inhalers.

The fall is not only seen in the asthma attacks treated at home but also in the number of hospital admissions. (Fig. 12)

 

A study in Lester, a middle part of England, showed that the prevalence of diagnosed asthma and apparent wheezing in children aged between one and five years has doubled over the last ten years. Yet, there has been a reduction in asthma attacks and hospital admissions. (Fig. 13 & Fig. 14)

This provides indirect but powerful evidence that the change in treatment and the change in approach to teaching correct inhaler usage has influenced asthma outcome in children. Also the new evidence-based guidelines published by the British Thoracic Society say that inhaled steroids are the most effective controller drugs for children. The strongest possible evidence, covering children of all ages, backs this.

Between 1950 and 1960 steroids were first introduced to pre-school children. These were oral steroids, but were very costly. The children did not grow properly.

Systemic steroids seriously impair growth rate. This concern persists despite the change of delivery route from injection to oral to inhalation. This is a matter of concern to parents and doctors both.

 

Normal growth in children is divided into three phases:

Phase I: From infancy up to two years

• Growth is determined by the nutritional state in utero and often at birth.
• Not influenced by hormones such as steroids.

Phase II: Mild childhood growth

• In this phase, growth hormones, thyroid hormones and other hormones come into play.

Phase III: Pubertal growth

• Pulses of androgenic steroids drive the spurt in growth during this phase.

 

Henry Hyder Solter was a physician who had bad asthma. He practised in London and Edinburg. He wrote very wisely and almost prophetically about asthma in children. One of his most important statements was: “If asthma has come on young in a child he is generally below the average height.” This was 100 years before anyone thought about using steroids to treat asthma in children.

Asthma itself impairs growth. It has two important effects on the normal progression of growth in childhood:

a. Uncontrolled or inadequately treated asthma affects sleep and therefore the release of growth hormone during the night and early morning.

b. Children with asthma often go into puberty late, usually a year or two behind the normal child. Uncontrolled asthma impairs their attainment of normal final height.

 

 

Over the last 30 years, more than 360 studies conducted, have looked at growth systematically. These have provided certain criteria for inclusion while analysing the effect of inhaled steroid:

• Growth should be studied for at least one year.
• Measurements should be taken properly.
• Control group should be included.
• Confounders (Factors such as asthma severity and control) should be taken into account. (Fig. 15)

Applying these criteria, the number of eligible studies works out to 18.

 

Studies conducted by Rao and Kanisto compared 400 mcg of beclomethasone or budesonide with 200 mcg of fluticasone. The results indicated more rapid growth with fluticasone than with beclomethasone or budesonide. However, none of the inhaled corticosteroids appeared to affect final height. (Fig. 16)

We have been using inhaled steroids in children for the last 30 years and have not seen any retardation in the final adult height. In an analysis of five studies, all published in the recent five years, that used beclomethasone or budesonide but no fluticasone, children attained normal final height.

In another long-term prospective study, children received 400 mcg to 500 mcg of budesonide per day for an average of nine years. Compared to those who did not receive inhaled steroid, there was no difference in final height or in bone

density. This is very reassuring data. This study was longitudinal and measurements were done every year. Growth during the first years of inhaled steroid treatment showed a reduction. But then it caught up and accelerated. So, although there was a transient suppression of growth rate in the first year, the children caught up or continued growing for a longer period to achieve a normal final height. (Fig. 17)

Many children who have asthma tend to have other atopic diseases as well. Only about 60 percent of children have only asthma. A quarter of them have asthma and rhinitis. Nearly 10 percent of them have asthma and eczema while another 10 percent have all three atopic diseases.

All atopic diseases can be potentially treated with topical steroids. There is a transient reduction in growth rate with 400 mcg beclomethasone given into the lungs. There is a similar repressive effect when the same dose of inhaled steroid is given into the nose.

A study undertaken to assess the effects on growth of one year of treatment with intranasal beclomethasone, showed that the children grew more slowly than those who did not receive the steroid. Care must be taken while considering combinations of topical inhaled steroids in children with more than one atopic disease as the drugs can have a cumulative effect. (Fig. 18)

Fig. 19 shows growth rate in children receiving beclomethasone 400 mcg a day. If the dose is increased to 800 mcg a day, growth is slowed further. There should not be any second thought regarding the effects of a dose exceeding 400 mcg a day because there is hardly any. Nor is there any evidence of growth suppression at a dose of 200 mcg a day. However, the dose of 400 mcg a day must be exceeded with care.