CIGARETTES AND ALCOHOL ELEVATE ALT LEVELS IN HEPATITIS C

Alcohol consumption and hepatitis C virus (HCV) may have a synergistic effect on alanine aminotransferase (ALT) levels. However, the effect of smoking on ALT activity among people with HCV or hepatitis B (HBV) infection is not well understood.

To investigate these issues, Wang et al surveyed a community with hyperendemic HBV and HCV, using a questionnaire that included demographics, frequency of cigarette and alcohol use, and history of blood transfusion. Serum samples were obtained and tested for hepatitis B surface antigen (HBsAg), anti-HCV markers, and ALT levels.

Of the 6,095 participants, 9.2% had elevated ALT concentrations. In comparison to seronegative subjects, HBsAg-seropositive subjects were three times more likely to have elevated ALT levels; anti-HCV–seropositive subjects were 11 times more likely.

Among the seronegative subjects, male gender, frequent alcohol consumption, and a history of blood transfusion all increased the likelihood of elevated ALT levels. None of the risk factors studied was shown to influence this likelihood among HBsAg-seropositive subjects. In contrast, among the anti-HCV–seropositive subjects, both frequent alcohol consumption and cigarette smoking conferred an increase in risk, and the effects of the two were additive (Figure 1).

Wang et al admit that levels of cigarette and alcohol consumption were self-reported, which could have resulted in a bias toward underestimation. These investigators conclude that alcohol use and cigarette smoking should be avoided by anti-HCV–seropositive individuals because they may exacerbate hepatic dysfunction.

Wang C-S, Wang S-T, Chang T-T, et al. Smoking and alanine aminotransferase levels in hepatitis C virus infection. Arch Intern Med. 2002;162:811-815.

Figure 1 How Smoking and Drinking Increase the Risk of Liver Damage in Anti-HCV–Seropositive Subjects*

* Heavy smoking was defined as more than one pack per day; light smoking as less than that amount. Definitions of alcohol consumption were not included in the study. HCV, hepatitis C virus; ALT, alanine aminotransferase. Adapted from Wang et al. Arch Intern Med. 2002.

VORICONAZOLE AN ACCEPTABLE ALTERNATIVE FOR PERSISTENT FEVER

In patients with neutropenia and persistent fever, voriconazole may be an acceptable antifungal alternative to amphotericin B preparations. In an international, multicenter trial, voriconazole was shown to reduce the number of complications, the incidence of renal dysfunction, and the frequency of breakthrough infections.

Walsh et al randomly assigned 415 patients to voriconazole and 422 patients to liposomal amphotericin B between March 1998 and September 1999. The patients were 12 years or older; all were neutropenic because they had undergone transplantation of hematopoietic stem cells or had received chemotherapy for leukemia, lymphoma, or other cancers. In addition, all patients had persistent fever despite having been given more than 96 hours of systemic antibacterial therapy.

Five criteria were used to define treatment success: The patient did not suffer a breakthrough fungal infection, did not have to prematurely discontinue therapy, and survived seven days after therapy’s end; the fever resolved despite ongoing neutropenia; and the baseline fungal infection was eliminated.

The researchers found that the two treatments’ efficacy was equal for four of these five outcome criteria. However, breakthrough fungal infections developed in eight of the patients receiving voriconazole and in 21 of those given liposomal amphotericin B.

Furthermore, the amphotericin B group was more likely to have elevated serum bilirubin levels, azotemia, or moderate or severe hypokalemia. Infusion-related toxic effects were less common with voriconazole.

The researchers conclude that this second-generation triazole could be used for early antifungal therapy in place of amphotericin B in neutropenic patients with persistent fever.

Walsh TJ, Pappas P, Winston DJ, et al. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med. 2002;346:225-234.

FREE-RUNNING CHALLENGE A BETTER TEST FOR EIA?

Undiagnosed asthma, including exercise-induced asthma (EIA), is present in many high school athletes. To evaluate methods of screening for asthma or EIA, Hammerman et al studied 801 Pittsburgh high school athletes ranging in age from 13 to 18 years. The athletes were given brief questionnaires, had their peak expiratory flow rates (PEFR) measured, and took part in a free-running exercise challenge.

Forty-six athletes identified themselves as having asthma, which was confirmed by the free-running test. (This test requires the athlete to run for eight minutes; PEFR measurements are taken immediately after the run and then again three and six minutes later.) Of the remaining 755 athletes, 49 were diagnosed with EIA after a positive free-running test. PEFR had a negative predictive value of 95% but a positive predictive value of only 8% when used alone as a screen for EIA.

Of the athletes with self-reported asthma, 39 had a greater than 15% drop in their PEFR after the free-running test even though they had used their asthma medication beforehand. This indicated that some athletes’ asthma was not under adequate control.

The free-running challenge test was determined to be an important tool for diagnosing EIA, which can be missed using laboratory challenges alone. The investigators also recommend that athletes with asthma be monitored to ensure effectiveness of prescribed medication.

Hammerman SI, Becker JM, Rogers J, et al. Asthma screening of high school athletes: identifying the undiagnosed and poorly controlled. Ann Allergy Asthma Immunol. 2002;88:380-384.

METERED-DOSE INHALERS VERSUS NEBULIZERS IN ACUTE ASTHMA

Studies have shown that nebulizers often dispense more medication than do metered-dose inhalers (MDIs) and spacers but with no added therapeutic benefit. Nebulizers are also more expensive to own and maintain and require the use of peripheral equipment. Newman et al undertook a large, 2.5-year, prospective, open-label study to compare albuterol administered via MDI/spacer with albuterol administered via nebulizer in an urban emergency department.

During the study period, 2,342 emergency department patients received treatment for acute asthma. Department personnel administered albuterol by nebulizer for 12 months (phase 1) then switched to MDI/spacer for 18 months (phase 2). Significant differences were noted in favor of the MDI/spacer. Peak expiratory flow rates were 11% higher when patients used MDI/spacers than when they used nebulizers. There were also lower relapse rates in patients using the MDI/spacers; they spent 6.5% less time in the emergency department. A highly significant between-group difference was found in the amount of albuterol used during treatment. On average, more than six times as much albuterol was dispensed from nebulizers as from MDI/spacers.

Using MDI/spacers reduces the need for medication as well as for labor and supplies. Thus, Newman et al conclude that the MDI/spacer is an alternative to nebulizer therapy in the treatment of acute asthma in an emergency department setting.

Newman KB, Milne S, Hamilton C, Hall K. A comparison of albuterol administered by metered-dose inhaler and spacer with albuterol by nebulizer in adults presenting to an urban emergency department with acute asthma. Chest. 2002;121:1036-1041.

TOPICAL STEROIDS COMPARED FOR CHILDREN WITH ECZEMA

Atopic eczema is often treated with topical corticosteroids. However, few studies have evaluated an optimal treatment protocol. Thomas et al performed a randomized double-blind study to compare a potent topical corticosteroid used for three days with a milder one administered for seven days.

One hundred seventy-four children ranging in age from 1 to 15 years were assigned to one of two groups and followed for 18 weeks. The mild group used 1% hydrocortisone ointment twice daily for seven days. The potent group used 0.1% betamethasone twice daily for three days. Outcomes were based on self-reported scratching frequency rated on a scale of 1 (none) to 5 (all the time). A score of 2 or less was considered scratch-free. A relapse was defined by a scratch score higher than 2 for at least three consecutive days.

The median number of scratch-free days was 118 in the mild group and 117.5 in the potent group. There were no between-group differences in secondary outcomes.

Both mild and potent topical corticosteroids are safe and effective, conclude Thomas et al; thus, the final choice of treatment can be left to the patient.

Thomas KS, Armstrong S, Avery A, et al. Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema. BMJ. 2002;324:768-771.