LITERATURE MONITOR:
A REVIEW OF RECENTLY PUBLISHED
CLINICAL ARTICLES

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.

SMOKING INCREASES RISK FOR PNEUMOCOCCAL DISEASE

Smoking has been linked to yet another adverse effect: invasive pneumococcal disease. In a recent study by Nuorti et al, cigarette smoking was associated with a fourfold increase in the risk for invasive pneumococcal disease and exposure to passive smoking was associated with a more than twofold increase.

The researchers interviewed 228 immunocompetent patients age 18 to 64 years with invasive pneumococcal disease (ie, isolation of Streptococcus pneumoniae from a normally sterile site) and 301 control subjects. Fifty-eight percent of the patients and 24% of the control subjects were current smokers.

Smoking was the strongest independent risk factor for pneumococcal disease, with 51% of the disease burden attributed to smoking and 17% attributed to passive smoking. Patients with the condition were 4.1 times more likely to be current smokers and 2.5 times more likely to be exposed to environmental tobacco smoke than were controls.

Nuorti et al also found a dose-response relationship between smoking and the risk for pneumococcal disease (Figure 2). In addition, the length of time since smoking cessation and the level of passive exposure among nonsmokers were positively correlated with the risk.

Figure 2 Dose-Response Relationship Between Cigarette Smoking and the Risk for Invasive Pneumococcal Disease

Data extracted from Nuorti et al. N Engl J Med. 2000.

The findings raise the question of whether all smokers should be vaccinated against pneumococci, noted John V. L. Sheffield, MD, and Richard K. Root, MD, in an accompanying editorial. While studies have shown that vaccination does not benefit older high-risk patients, the investigators suggested that immunocompetent, nonelderly smokers may have a better response.

Nuorti JP, Butler JC, Farley MM, et al. Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team. N Engl J Med. 2000;342:681-689.
Sheffield JVL, Root RK. Smoking and pneumococcal infection. N Engl J Med. 2000;342:732-734.

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.

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 in 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 a response to antiretroviral therapy. N Engl J Med. 2000;342:1085-1092.

PREDICTING OUTCOME OF SINUS SURGERY

An increased number of cells expressing interleukin 5 messenger RNA (IL-5 mRNA) in the ethmoid sinuses may be used to predict which allergic patients with chronic rhinosinusitis will not benefit from surgery, a recent study suggests.

Lavigne et al studied 15 allergic patients who underwent ethmoidectomy for chronic sinusitis. All of the patients had perennial rhinitis and extensive bilateral mucosal disease on computed tomography scans of the sinuses.

Biopsy of the inferior turbinate and of the most inflamed areas of the maxillary and ethmoid sinuses was used to determine the number of lymphocytes, mast cells and eosinophils, and cells expressing IL-4 and IL-5 mRNA in these areas at the time of surgery. These results were compared with two-year outcomes.

Symptoms were worse or unchanged after surgery in about half of the patients (53%). The only significant difference between responders and nonresponders was a higher number of cells expressing IL-5 mRNA at the time of surgery in the ethmoid sinuses of nonresponders.

Lavigne et al determined that a test using an arbitrary cutoff of 11 or more IL-5 mRNA-positive cells per high-power field in the ethmoid sinuses would have a sensitivity of 86% and a specificity of 88% in differentiating potential responders from nonresponders to surgery.

Lavigne F, Nguyen CT, Cameron L, et al. Prognosis and prediction of response to surgery in allergic patients with chronic sinusitis. J Allergy Clin Immunol. 2000;105:746-751.

EARLY EXPOSURE TO DUST MAY PREVENT ASTHMA

A little dust in the home may protect against asthma, Gereda et al reported. Their recent study suggests 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.

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 from September 1996 to December 1997. Specifically, the researchers 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.

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