Asthma needs to be treated with anti-inflammatories

January 2005

Although pediatricians seem to be doing a good job of prescribing asthma drugs that relieve airway hyperresponsiveness, such as albuterol, they are coming up short as far as treatment of the underlying inflammation.

Asthma continues to occupy the top position among common chronic disorders in children and adolescents, with some 5 million U.S. children affected as of 2001. About three-fourths of these children have persistent asthma.

“We are ignoring the fact that the key to asthma is chronic inflammation in the lung, and it really should be treated with anti-inflammatory drugs,” said Theresa Guilbert, MD, assistant professor of pediatrics at the Arizona Respiratory Center, University of Arizona, at the AAP 2004 National Conference and Exhibition in San Francisco.

Inhaled steroids are the only medications that have been shown to reduce inflammation, illness and deaths in patients with persistent asthma. Even in children, the benefits of low- to medium-dose inhaled steroids outweigh the risks.

Of those patients with severe-persistent asthma, the most serious form, only about 20% are taking inhaled corticosteroids, which the AAP, the American Academy of Family Physicians and the NIH concur should be the preferred drug for anyone with that type of asthma. In the pediatric arena, the lack of prescription of inhaled steroids might be ascribed to the perception that most children have mild disease and are not at risk for adverse outcomes. But that is not the case, said Guilbert, citing an Australian study of 51 children who died from asthma between 1986 and 1989, which found that equal percentages would have been classified as having mild-persistent asthma, moderate-persistent asthma or severe-persistent asthma at the time of death. There has been concern that steroids may affect growth in children, but a number of studies have now dispelled that association, provided the steroids are used rationally in low or medium doses.

Aggressive treatment needed

Data now affirm that the earlier asthma is diagnosed and treated, the better the children do later in life. The Children’s Respiratory Study, an important investigation that assessed more than 1,000 newborns enrolled at birth and followed over time, identified an asthma predictive index, which seems to correlate with children who wheeze during their school years and may prove to be a useful tool in the clinic. Another consideration is whether a child already has persistent asthma at a young age. “Even if they are only 2 or 3 years of age, if they have persistent asthma, they should be treated the same way they would be if they were older,” Guilbert emphasized. “If they are using an albuterol inhaler more than twice weekly, or waking up due to asthma symptoms more than twice per month, they may have persistent asthma and need a controller medication.”

It is important to stabilize patients and keep them on the first round of anti-asthma medications chosen for two to three months, according to Guilbert. If they are doing well, stepping down therapy is an option. For those patients who have environmental changes, a step up in therapy might be mandated.

When the therapeutic program is effective, children with asthma should be nearly symptom free, with few absences from school. They should be running and playing, not sitting quietly on the couch to avoid activity.

Usually young children are brought to the office because of exacerbations, whereas older children see the doctor because of symptoms that occur when they participate in sports. For these patients, spirometry is an important diagnostic tool to assess pulmonary function. Of particular concern are patients with low peak flow in the morning, which signals low pulmonary function at night — a feature commonly linked with death.

Even specialists do not routinely measure airway hyperresponsiveness, but certain features of the disease can serve as clues about airway status. For example, nighttime problems or exercise-induced asthma suggests twitchy airways. Inflammation similarly is not routinely measured; knowing the levels of peripheral eosinophils and immunoglobulin E (IgE) is useful. The presence of atopic dermatitis and parental history of asthma should raise a red flag that a child may be at risk for developing asthma.

There is now some evidence of different phenotypes related to genotypes, which can trigger different thoughts about treatment. For example, patients respond to steroids in different ways. Although patients who are not doing well may not be taking the prescribed inhaled steroid or may be taking it incorrectly, some have alterations in steroid-receptor binding, which can block the effect of the drug. Markers of inflammation, such as exhaled nitric oxide, are being studied as predictors of response to inhaled steroids. Finally, the dose may be inadequate, or the patient may not be administering the drug properly.

Among the newer treatment options for patients with severe asthma is combination therapy including an inhaled steroid and a long acting b2-agonist. Macrolide antibiotics are receiving renewed interest because Chlamydia and Mycoplasma are appearing in lung biopsies of severe asthmatics.

For more information:

• Szefler S, Guilbert T. Asthma therapy, new and coming. Presented at the 2004 AAP National Conference and Exhibition. Oct. 9-13, 2004. San Francisco.