THE ROLE OF T CELLS IN ASTHMA EXACERBATIONS

It is well known that corticosteroids are effective at treating asthma, but what happens when they are withdrawn? Castro et al studied 25 patients with moderate persistent asthma and found that when corticosteroid therapy is stopped, some patients experience an increase in T-cell levels—but not in the number of mast cells or eosinophils.

At study entry, the patients discontinued their usual medication and began using inhaled fluticasone propionate 1,760 µg/d for 30 days; albuterol was administered as needed to control symptoms. After 30 days, the patients underwent lung function testing and bronchoscopy with endobronchial biopsy and brushing. They then discontinued fluticasone but continued to use albuterol as needed.

The withdrawal period lasted for six weeks or until afternoon peak expiratory flow decreased by 25% and FEV1 declined by 15%. All tests were repeated at the end of the withdrawal period.

After fluticasone withdrawal, there was a significant increase in the patients’ mean T-cell levels, which correlated positively with increased albuterol use and airway hyperreactivity. However, only the patients with exacerbations experienced a significant increase in the number of T cells found in bronchial biopsies. Further examination revealed an increase in the number of CD4+ and CD8+ T cells that correlated with baseline asthma severity score.

The authors concluded that airway infiltration by T cells is sensitive to corticosteroid withdrawal and occurs more often during an asthma exacerbation than do increases in mast cell or eosinophil levels. These findings serve to set apart the inflammatory asthma phenotype from the typical allergic response linked with eosinophil and mast cell activation.

Castro M, Bloch SR, Jenkerson MV, et al. Asthma exacerbations after glucocorticoid withdrawal reflects T cell recruitment to the airway. Am J Respir Crit Care Med. 2004;169:842-849.

THREE DAYS OF AMOXICILLIN AS GOOD AS FIVE IN NONSEVERE PNEUMONIA

Antibiotics are recommended for the treatment of acute respiratory infections in children. However, the duration of treatment needed to eradicate the infection is a matter of debate. Recently, Agarwal et al compared a three-day regimen of amoxicillin with a five-day regimen for the treatment of nonsevere pneumonia in children. They found no difference in cure rates, but both costs and the incidence of resistance were lower in the three-day group.

The study was a double-blind, placebo-controlled, randomized trial conducted over two years. The trial included 2,188 children ages 2 months to 5 years who had a diagnosis of nonsevere pneumonia. All patients received amoxicillin three times a day for three days. Then patients were randomized to receive either two more days of amoxicillin or placebo. Follow-up evaluations were performed at three and five days after enrollment and again between 12 and 14 days.

No between-group differences were seen in either clinical cure rates or relapse rates. Results were also similar in the children who had presented with wheeze and in those who had not.

There was no change in rates of resistance to Haemophilus influenzae, but the proportion of Streptococcus pneumoniae isolates that were resistant to co-trimoxazole increased from 66.1% to 78.2% over two weeks in the five-day group. S pneumoniae resistance rates remained constant in the three-day group.

In this study, the average direct medical costs for treating 1,000 cases of nonsevere pneumonia were $1,100 for three days of treatment versus $1,250 for five days.

Agarwal G, Awasthi S, Kabra SK, et al, for the ISCAP Study Group. Three day versus five day treatment with amoxicillin for non-severe pneumonia in young children: a multicentre randomised controlled trial. BMJ. 2004;328:791-796.

IVIG HELPFUL IN CHILDREN WITH CYSTIC FIBROSIS

Some children with cystic fibrosis (CF) develop chest tightness, dry cough, and wheeze, accompanied by deteriorating lung function. These children are usually treated with oral corticosteroids, but their symptoms return when treatment is stopped.

Balfour-Lynn et al have reported on a retrospective case series review of the use of intravenous immunoglobulin (IVIG) therapy in such children. They found that IVIG improved symptoms and decreased the need for oral and inhaled corticosteroids.

Beginning in 1994, 16 children, all of whom had significant airway obstruction requiring treatment with corticosteroids, were given IVIG as a 12-hour infusion. The dosage used was 1 g/kg for two consecutive days, followed by 1 g/kg/month. The children also received IV corticosteroids and antihistamines before beginning IVIG treatment.

After IVIG therapy, FEV1 improved from a median of 50% of predicted to 54%, and FVC increased from 65% to 83%. Oral corticosteroids were stopped completely in eight patients, and the dosage was reduced in three. The total daily dose of inhaled corticosteroids was reduced from a median of 2,000 µg to 1,500 µg.

One drawback of IVIG is that it is a blood product derived from pooled donor plasma. Although there have been no cases of HIV transmission reported with IVIG use, in the mid-1990s there were several outbreaks of hepatitis C, and the potential for transmission of other bloodborne pathogens is unclear. Despite the risks, however, the authors recommended a trial of IVIG in select patients with severe CF-related obstructive lung disease.

Balfour-Lynn IM, Mohan U, Bush A, Rosenthal M. Intravenous immunoglobulin for cystic fibrosis lung disease: a case series of 16 children. Arch Dis Child. 2004;89:315-319.

NEW STATISTICS ON CHILDREN’S ASTHMA

The National Health Interview Survey, conducted by the Centers for Disease Control and Prevention, is an annual questionnaire distributed to a representative sample of civilian, noninstitutionalized households. The 2002 report, recently published by the US Department of Health and Human Services, included an update on the incidence of asthma in American children.

Nine million children younger than 18 have ever been given a diagnosis of asthma. As a child’s age increases, so does the likelihood that he or she has received an asthma diagnosis.
• The incidence of asthma was 14% in boys and 10% in girls.
• Children in poor families had an asthma incidence of 16% compared with 11% in families that were not poor.
• Children in single-parent families were more likely (17%) to have been given an asthma diagnosis than were those in two-parent families (11%).
• More than 4 million children (6%) reported having had an asthma attack in the past year, with boys having an incidence of 7%, compared with 5% for girls.
• Non-Hispanic black children were more than twice as likely to have had an asthma attack in the past year than were Hispanic children (9% vs 4%).
• Among children in fair or poor health, 29% reported having had an asthma attack in the past 12 months, compared with 4% of children with excellent or very good health.

Dey AN, Schiller JS, Tai DA. Summary Health Statistics for US Children: National Health Interview Survey, 2002. National Center for Health Statistics. Vital Health Stat 10(221). 2004.

HAVE STUDIES EXAGGERATED THE PREVALENCE OF CHRONIC SINUSITIS?

Chronic sinusitis has been reported to affect 14% to 16% of the population in the United States. However, these statistics come from the National Health Interview Survey and are based wholly on patients’ self-report. Suspecting that the prevalence of chronic sinusitis has been exaggerated, Shashy et al conducted a population-based study of residents of Olmsted County, Minnesota, and found the incidence of chronic sinusitis to be approximately 2%.

The study sample included all Olmsted County residents who were given a diagnosis of chronic sinusitis by their physicians in 2000. Chronic sinusitis was identified using ICD-9 codes.

In 2000, 2,405 patients had been given a diagnosis of chronic sinusitis. About two thirds of these patients were female; their mean age was 39.4 years. The overall prevalence of sinusitis, adjusted for both sex and age, was calculated to be 1,955 cases per 100,000 population. Almost all of these cases (94.8%) were diagnosed as “unspecified chronic sinusitis/chronic sinusitis not otherwise specified.”

Shashy et al pointed out that chronic sinusitis has very broad diagnostic criteria, and it can be confused with other similar conditions. They also acknowledged that their study population was from a predominantly white, Midwestern community, and therefore the results may not be generalizable to the US population.

Shashy RG, Moore EJ, Weaver A. Prevalence of the chronic sinusitis diagnosis in Olmsted County, Minnesota. Arch Otolaryngol Head Neck Surg. 2004; 130:320-323.

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