Mono Therapy with Inhaled Steroids: The New Standard for Asthma?
By William T. Elliott, MD, FACP
The standard of care for the treatment of mild asthma is moving to mono therapy with inhaled steroids. A study from the University of Helsinki compared inhaled steroid treatments to inhaled terbutaline, a beta agonist, in patients with mild asthma. At the end of six weeks of treatment, patients who used inhaled steroids had significant improvements in symptom scores, peak expiratory flow rates, and eosinophil counts compared to those who used terbutaline (Allergy 2000;55:505-509). In a separate study from New Zealand, researchers compared the use of budesonide, an inhaled corticosteroid, to the use of budesonide with an inhaled beta agonist. At the end of six weeks, the researchers found that the use of budesonide alone was at least as effective as the combination of the two drugs in preventing symptoms. They concluded that short- acting bronchodilators should only be used as needed for symptoms (Am J Respir Crit Care Med 2000;161:1459-1464).
The Centers for Disease Control have issued guidelines for the treatment of community-acquired pneumonia. Suitable regimens include a macrolide (erythromycin, clarithromycin, or azithromycin), doxycycline, or a beta-lactam with good activity against pneumococci. Hospitalized patients should receive an intravenous beta-lactam (cefuroxime, ceftriaxone, cefotaxime, or ampicillin/sulbactam) plus a macrolide. The newer fluoroquinolones are effective against drug resistant Streptococcus pneumoniae, but should be considered second line for initial therapy to limit the development of pneumococcal resistance to these drugs. Fluoroquinolones should be given if the patient fails other regimens, or if the strain of S. pneumoniae is highly drug resistant. Vancomycin is not routinely indicated for drug resistant S. pneumoniae (Arch Intern Med 2000;160:1399-1408).
Cardiovascular
Could lowering cholesterol with drugs or diet affect cognition? English researchers looked at the effects of low-fat diet, a Mediterranean diet, or control diet on psychological well-being and cognitive function of volunteers at six and 12 weeks. Both active dietary interventions reduced serum cholesterol levels significantly. And while all three groups showed improvement in psychological well-being over the treatment period, the two groups that lowered their cholesterol levels did significantly worse on at least one measure of cognitive function (Am J Med 2000;108:547-553). The second study looked at cholesterol lowering with lovastatin (Mevacor). More than 200 healthy volunteers were randomized to six months therapy with 20 mg/d of lovastatin or placebo. At the end of six months, assessments of cognitive function and psychological well-being were performed. The placebo-treated patients showed improvement in all five neuropsychological tests, which is to be expected when tests are repeated over time. The lovastatin-treated group showed improvement only in the memory recall test. Although psychological well-being did not seem to be affected by lovastatin, the treated individuals showed small decrements in psychomotor speed and attention (Am J Med 2000;108:538-546).
It is a given that early administration of thrombolytic therapy for acute myocardial infarction results in better outcomes. Now researchers from Canada are suggesting that the best time to administer these drugs may be before the patient gets to the hospital. The pooled data from six randomized trials were the subject of a meta-analysis on the timing of thrombolytic therapy and outcomes. The results showed that pre-hospital administration of thrombolytic therapy was associated with a significant reduction in all-cause hospital mortality. The meta-analysis was of insufficient power to demonstrate a difference at one or two years (JAMA 2000;283:2686-2692).
Oncology
The FDA reports that the recently approved breast cancer drug trastuzumab (Herceptin) is associated with severe adverse reactions in women with advanced metastatic breast cancer, including 15 deaths. Most of the fatal reactions have occurred in women with underlying lung disease, usually within 12 hours of the initial dose, and often during the initial infusion. The FDA still regards the drug safe for use in breast cancer patients but only with appropriate monitoring.
COX-2 inhibition may do more than reduce inflammation—it may also inhibit the growth of solid tumors. Investigators from Vanderbilt University have shown that the growth of lung tumors is inhibited when the gene for COX-2 is removed from mice, or in mice that are treated with a COX-2 inhibitor. The investigators have shown that the production of endothelial growth factor is dependent on COX-2. Mice without the gene showed a 94% reduction in the growth factor while mice treated with a COX-2 inhibitor showed 92% reduction. Endothelial growth factor is thought to be responsible for the development of blood vessels in solid tumors (J Clin Invest 2000;105:1589-1594).
Men’s Health
Many physicians are reluctant to prescribe sildenafil (Viagra) to men with known coronary artery disease (CAD). A study from the University of Pennsylvania looked at the hemodynamic effect of the drug on 14 men with severe coronary disease. Sildenafil caused a small decrease in system blood pressure but had minimal effect on other hemodynamics. The authors conclude that the drug was not associated with adverse cardiovascular effects in men with CAD. They still caution against the concomitant use of sidenafil and nitrate-containing medications (N Engl J Med 2000;342:1622-1626).
Saw palmetto is a reasonable first-line therapy for men with uncomplicated benign prostatic hypertrophy (BPH) according to researchers from UCLA. In a placebo-controlled study of 44 men, the herbal preparation was shown to cause a involution of the prostatic epithelium as shown on prostate biopsy. Clinical measures of the drug’s effect were only slightly better than placebo and did not reach statistical significance over the six-month study period. Still, the researchers suggest that there is some evidence of a mechanism of action of saw palmetto, and that there were no side effects seen. They also suggest that clinical effects may occur over a longer period of time (J Urol 2000;163:1451-1456).
Rheumatology
COX-2 inhibitors are associated with lower rates of gastrointestinal irritation than non selective NSAIDs. Now there is evidence that celecoxib (Celebrex) may also have less adverse effect on the kidney as well. NSAIDs generally cause reduced renal perfusion and glomerular filtration rate (GFR), especially the high-dose, long acting NSAIDs. Researchers from Maryland looked at 29 healthy elderly individuals, comparing renal function on maximal doses of celecoxib (400 mg b.i.d.) and maximal doses of naproxen (500 mg b.i.d.). Naproxen resulted in a significantly greater decrease in GFR by day 6 of treatment compared to celecoxib. The authors suggest that COX-1 may play a bigger role in renal hemo dynamics than previously thought, COX-1 seems to be responsible for preserving GFR, while COX-2 is important in regulating a sodium and water balance (Arch Intern Med 2000;160:1465-1470).
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