EARLY EXPOSURE TO DUST MAY PREVENT ASTHMA

A little dust in the home may protect against asthma, Gereda et al have found. Results from their recent study suggest that exposure to environmental endotoxin--which is part of the cell wall of common bacteria--early in life enhances development of the immune system.

The researchers studied the homes of 61 infants (age 9 to 24 months) who had at least three episodes of wheezing. Skin-prick testing was used to measure the infants' sensitivity to dust mite, cat, dog, cockroach, mouse, milk, egg, and soy allergens. In addition, house-dust samples were collected from the infants' homes and were used to measure the concentration of house-dust endotoxin and allergens.

Ten of the infants tested positive to at least one of the allergens. The concentration of house-dust endotoxin was significantly lower in the homes of the infants with positive skin-test results than in the homes of those with negative results (mean, 468 vs 1,035 endotoxin units/mL).

Furthermore, endotoxin concentrations positively correlated with the proportion of interferon-gamma--producing CD4 T cells, suggesting that endotoxin exposure during infancy may enhance type 1 immunity.

"This may be an important clue in the development of effective and safe asthma prevention," said Andy Liu, MD, co-author of the study.

Gereda JE, Leung DYM, Thatayatikom A, et al. Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitization in infants at high risk of asthma. Lancet. 2000;355:1680-1683.

HIGH-DOSE INHALED CORTICOSTEROIDS EFFECTIVE FOR COPD

Support for the widespread practice of using high-dose inhaled corticosteroids in patients with moderate to severe chronic obstructive pulmonary disease (COPD) was found in a randomized, placebo-controlled study.

Burge et al examined data on 751 nonasthmatic patients (age 40 to 75 years) with COPD who were enrolled in the Inhaled Steroids in Obstructive Lung Disease in Europe study. The patients were randomized to 500 µg fluticasone propionate or placebo twice daily for three years.

While fluticasone administration did not affect the annual rate of decline in forced expiratory volume in one second (FEV1), the mean FEV1 following bronchodilator use at three and 36 months was significantly higher in the fluticasone group than in the placebo group.

Patients in the fluticasone group had fewer exacerbations per year (median rate, 0.99 vs 1.32) and a smaller decline in health status per year than did the placebo group.

The number of serious side effects in the fluticasone group was similar to that in the placebo group, Burge et al reported. Patients who received fluticasone showed a small decrease in mean cortisol concentration and had a slightly higher incidence of inhaled glucocorticoid-related adverse events than did the placebo group.

Burge PS, Calverley PM, Jones PW, et al. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ. 2000;320:1297-1303.

HYPERRESPONSIVE AIRWAY IN ATHLETES LINKED TO AIR CONTENT

Elite athletes have a significantly higher prevalence of airway hyperresponsiveness (AHR) than do sedentary individuals, according to a recent study. The findings suggest that "it is not only exercise itself that predisposes to AHR but possibly the content and the physical characteristics of inhaled air during training," reported Langdeau et al.

One hundred competitive athletes and 50 sedentary people completed a questionnaire on exercise-induced symptoms and underwent spirometry, methacholine challenge, allergen skin-prick tests, and heart rate variability recording for evaluation of parasympathetic tone. All subjects were age 18 to 55 years and were nonsmokers. The athletes were subdivided according to the characteristics of the ambient air inhaled during training (ie, dry air, cold air, humid air, and mixed air).

The athletes had a higher prevalence of cough with exercise than did the sedentary group (38% vs 12%), with most of this difference accounted for by the prevalence among athletes who exercised in cold air (76%). In addition, the prevalence of rhinorrhea and pharyngeal secretions with exercise was significantly higher among the athletes than among the sedentary subjects (40% vs 20%).

As shown in Figure 1, the prevalence of AHR was also significantly higher among the athletes than among the sedentary group. Here, the difference was due mostly to the prevalence among athletes who exercised in humid air (ie, swimmers) and, secondarily, among the cold-air subgroup.

The athletes had a significantly higher estimated parasympathetic tone, but this measurement showed only a weak correlation with AHR and could not explain the difference in AHR prevalence among the subgroups of athletes.

Langdeau JB, Turcotte H, Bowie DM, et al. Airway hyperresponsiveness in elite athletes. Am J Respir Crit Care Med. 2000;161:1479-1484.

APPETITE SUPPRESANTS STRONGLY LINKED TO PULMONARY HYPERTENSION

Strong new evidence confirms the link between the use of fenfluramine appetite suppressants in the mid 1990s and the reported increase in cases of primary pulmonary hypertension in the United States.

Rich et al prospectively collected data on 579 patients diagnosed with pulmonary hypertension during the period of September 1996 to December 1997. Specifically, the investigators examined the patients' exposure to antidepressants, anorexigens, and amphetamines.

They found that 16.1% of the 205 patients with primary pulmonary hypertension and 11.4% of the 376 patients with secondary pulmonary hypertension had taken anorexigens. Of the medications surveyed, only fenfluramine and dexfenfluramine were used significantly more often among patients with primary as opposed to secondary pulmonary hypertension (11.2% vs 4.9%).

Furthermore, patients with primary pulmonary hypertension were more likely to have used fenfluramines for six months or longer and more recently (in relation to the onset of symptoms) than were patients with secondary pulmonary hypertension.

The quick withdrawal of fenfluramines from the market in 1997 "may well have aborted an incipient epidemic in the United States," Rich et al believe.

Rich S, Rubin L, Walker AM, et al. Anorexigens and pulmonary hypertension in the United States: results from the surveillance of North American pulmonary hypertension. Chest. 2000;117:870-874.

AZITHROMYCIN PROPHYLAXIS CAN BE WITHDRAWN IN HIV-INFECTED PATIENTS

Azithromycin prophylaxis against Mycobacterium avium can be discontinued in patients with human immunodeficiency virus (HIV) infection whose CD4+ cell counts have increased to more than 100 cells/mm3 in response to antiretroviral therapy, new findings suggest.

El-Sadr et al randomized 520 patients infected with HIV to 1,200 mg azithromycin once weekly or placebo. In addition, all patients were receiving retroviral therapy; as a result, their CD4+ cell counts had increased from less than 50 to more than 100 cells/mm3. The patients were followed for a median of 12 months.

No cases of confirmed M avium complex disease were reported. Only a small percentage of patients in the azithromycin and placebo groups developed confirmed or probable bacterial pneumonia (1.2% and 1.9%, respectively). Furthermore, the groups had similar rates of HIV disease progression and mortality.

The rate of adverse events leading to discontinuation of the study drug was significantly higher among patients treated with azithromycin than in the placebo group (7.4% vs 1.1%).

"These findings contribute to the efforts to simplify treatment regimens and improve adherence to them, decrease the risk of antimicrobial resistance, and avoid adverse events associated with additional medications," El-Sadr et al reported.

El-Sadr WM, Burman WJ, Grant LB, et al. Discontinuation of prophylaxis for Mycobacterium avium complex disease in HIV-infected patients who have a response to antiretroviral therapy. N Engl J Med. 2000;342:1085-1092.

SMOKING LINKED TO PHYSICAL INJURIES

Smokers were 1.5 times more likely to suffer fractures, sprains, and other physical injuries during an eight-week basic training program than were nonsmokers, according to findings from a study of army recruits.

"Soldiers or others do not have to wait 10 to 30 years for heart disease or cancer in order to experience the detrimental effects of smoking," explained study co-author John W. Gardner, MD, DrPH. "These data show that at least some of the detrimental effects of cigarette smoking may occur at an early age and have immediate consequences," he added.

Dr. Gardner and colleagues prospectively examined smoking and injury rates among 915 female and 1,087 male army recruits undergoing an eight-week basic military training program. During this period, 33% of the men and 50% of the women had at least one clinic visit for injury.

Subjects who reported smoking in the month prior to beginning basic training had significantly higher injury rates than did nonsmokers (40% vs 29% for men and 56% vs 46% for women). Smokers also had a greater number of previous injuries, more prior illnesses, and lower levels of physical activity and physical fitness than did nonsmokers.

Altarac M, Gardner JW, Popovich RM, et al. Cigarette smoking and exercise-related injuries among young men and women. Am J Prev Med. 2000;18:96-102.

COAGULATION FACTOR IX: A RISK FACTOR FOR VENOUS THROMBOSIS

The risk of deep venous thrombosis is more than twice as high in patients with high levels of coagulation factor XI than in patients with normal levels, according to a recent study. Because 10% of the population has high factor XI levels, Meijers et al believe that this variable is "an important contributor to the overall burden of venous thrombosis."

These researchers determined factor XI antigen levels in 474 patients with a first episode of deep venous thrombosis and 474 control subjects enrolled in the population-based Leiden Thrombophilia Study. They found a dose-response relationship between factor XI levels and the risk for deep venous thrombosis.

This association remained significant even after the researchers controlled for oral-contraceptive use, sex, age, and genetic risk factors. Subjects who had factor XI levels above the 90th percentile had an odds ratio for deep venous thrombosis of 2.2, compared with patients who had levels at or below the 90th percentile.

The findings also suggest that 11% of all cases of thrombosis may be attributable to high factor XI levels. "We postulate that a high level of factor XI causes thrombosis through sustained generation of thrombin, which leads to the protection of fibrin from proteolysis," Meijers et al reported.

Meijers JC, Tekelenburg WLH, Bouma BN, et al. High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med.2000;342:696-701.