Extramacular drusen are highly associated with age-related macular degeneration, but not with CFH and ARMS2 genotypes.

BACKGROUND: To evaluate the association of extramacular drusen (EMD) with age-related macular degeneration (AMD) and with complement factor H (CFH rs1061170) and age-related maculopathy susceptibility 2 (ARMS2 rs10490924) polymorphisms in individuals with and without AMD. METHODS: In this case-control study, AMD staging was performed in 622 individuals. EMD were defined as ≥10 drusen (including ≥1 intermediate drusen) outside the Early Treatment of Diabetic Retinopathy Study Grid within field 2. Genotype associations for CFH and ARMS2 variants were assessed using logistic regression analysis. RESULTS: EMD (n=213) showed a strong association with AMD (OR=3.85; p=1.66×10(-13)). AMD (n=316) was strongly associated with CFH (p=1.78×10(-7)) and ARMS2 genotypes (p=1.67×10(-8)). After adjustment for AMD, age and gender, EMD were neither associated with CFH (p=0.11) nor with ARMS2 (p=0.45) genotypes. In individuals without AMD, the groups with and without EMD showed no differences regarding both genetic variants. CONCLUSIONS: The strong association between drusen within and outside of the macula suggests a common pathogenesis. However, EMD were not AMD-independently associated with CFH or ARMS2 genotypes. Our results indicate that patients without AMD but with EMD can serve as controls in studies evaluating AMD risk factors. Further studies are required to elucidate the aetiology and clinical relevance of EMD.

Safety of fexofenadine in children treated for seasonal allergic rhinitis.

BACKGROUND: The incidence of allergic rhinitis in children is increasing. OBJECTIVE: To evaluate the safety of fexofenadine HCI in children ages 6 through 11 years for treatment of seasonal allergic rhinitis. METHODS: Two large, double-blind, randomized, placebo-controlled, parallel studies with identical protocols included patients with a positive skin test to fall allergen(s) and allergic rhinitis symptoms. Patients were randomized to receive fexofenadine 15, 30, or 60 mg or placebo twice daily for 2 weeks after a 1-week placebo lead-in. Safety was evaluated through adverse event reporting, electrocardiograms, and pre- and posttreatment laboratory panels and physical examinations. RESULTS: A total of 875 patients from both studies were eligible for safety analyses. Ten patients (5 on placebo, 5 on fexofenadine) discontinued because of an adverse event; no event that resulted in discontinuation was judged to be caused by study medication. Incidence of adverse events was similar in active and placebo groups, and did not increase with increasing fexofenadine dose: 36.2% (83 of 229) in the placebo group versus 35.3% (79 of 224), 36.8% (77 of 209), and 34.7% (74 of 213) in the 15, 30, and 60 mg twice-daily fexofenadine groups, respectively. Headache was the most commonly reported adverse event (6.6%, 8.0%, 7.2%, and 9.4% in the placebo, 15, 30, 60 mg twice-daily fexofenadine groups, respectively). Clinical, vital sign, electrocardiogram, and laboratory measures were similar in active and placebo groups. There was no statistically significant mean change from baseline in any electrocardiogram parameter after fexofenadine treatment. CONCLUSIONS: Fexofenadine, 15, 30, and 60 mg twice daily, was safe and well tolerated in this large pediatric patient population.

Mometasone furoate: efficacy and safety in moderate asthma compared with beclomethasone dipropionate.

BACKGROUND: Mometasone furoate (MF) is a new inhaled glucocorticoid administered by dry powder inhaler (DPI). OBJECTIVE: MF-DPI was evaluated for safety and efficacy and compared with placebo DPI and beclomethasone dipropionate (BDP) administered by metered dose inhaler (MDI) in the treatment of patients with moderate persistent asthma. METHODS: Eligible patients (n = 227), 13 to 75 years of age, maintained on inhaled glucocorticoids before entering the trial, were randomized to receive: MF-DPI, 100 microg, twice daily, MF-DPI, 200 microg, twice daily, BDP MDI, 168 microg, twice daily, or placebo in a 12-week, multicenter, double-blind study. RESULTS: At endpoint, FEV1 (primary efficacy variable) significantly improved for all three active treatments compared with placebo (P < .01, all comparisons). The response to MF-DPI, 200 microg, twice daily treatment was approximately twice as large as the response to MF-DPI, 100 microg, twice daily or BDP MDI treatment, although the differences between these groups did not reach statistical significance. Secondary efficacy variables including PEFR, asthma symptoms, nocturnal awakenings, and albuterol use showed similar trends. The MF-DPI, 100 microg, twice daily and BDP MDI, 168 microg, twice daily treatment groups produced comparable results for all efficacy variables. CONCLUSIONS: MF-DPI, 100 microg and 200 microg, twice daily were well-tolerated and significantly improved lung function and symptom control in the treatment of patients with moderate persistent asthma. In this study, MF-DPI, 200 microg, twice daily seemed to be the most effective dosage.

Inhaled mometasone furoate reduces oral prednisone requirements while improving respiratory function and health-related quality of life in patients with severe persistent asthma.

BACKGROUND: Inhaled corticosteroid therapy in severe persistent asthma has been shown to reduce or eliminate oral corticosteroid (OCS) use while retaining effective asthma control. OBJECTIVE: We sought to evaluate the ability of mometasone furoate (MF) delivered by means of dry powder inhaler to reduce daily oral prednisone requirements in OCS-dependent patients with severe persistent asthma. METHODS: We performed a 12-week, double-blind, placebocontrolled trial (21 centers, 132 patients) comparing 2 doses of MF (400 and 800 microg administered twice daily) with placebo, followed by a 9-month open-label phase in which 128 patients received treatment with MF. RESULTS: At the endpoint of the double-blind trial, MF 400 and 800 mg twice daily reduced daily OCS requirements by 46.0% and 23.9%, respectively, whereas placebo increased OCS requirements by 164.4% (P <.01). Oral steroids were eliminated in 40%, 37%, and 0% of patients in the MF 400 and 800 mg twice daily and placebo groups, respectively. Pulmonary function and quality of life significantly increased for MF-treated patients. Further reductions in OCS requirements were achieved with long-term MF treatment in the open-label phase. CONCLUSION: MF inhaled orally as a dry powder is an effective alternative to systemic corticosteroids in patients with severe persistent asthma.

Venom immunotherapy: when to start, when to stop.

Over the past 25 years, major advances have been made in the diagnosis and treatment of insect sting allergy. Controlled clinical trials have demonstrated the efficacy of venom immunotherapy (VIT) in the prevention of subsequent systemic reactions in allergic individuals. We have refined our criteria for selection of patients for VIT. Studies on selections of venoms, rush immunotherapy, and interval between VIT injections have been performed. Finally, much work has been done to try to define criteria for the discontinuation of VIT.

New therapies for allergic rhinitis.

New therapies for allergic rhinitis are more effective and have fewer side effects than older medications. Antihistamines, decongestants, and cromolyn sodium nasal sprays are often tried first. Second generation prescription antihistamines have fewer side effects than over-the-counter ones. Steroid nasal sprays are extremely effective and safe for the entire range of allergy symptoms. Immunotherapy requires a lengthy course of injections, but it can bring long-term relief for severe allergies.

A controlled trial of twice daily triamcinolone oral inhaler in patients with mild-to-moderate asthma.

BACKGROUND: National and international guidelines recommend inhaled anti-inflammatory medications for patients with all but the mildest forms of asthma. Patients may also be more compliant with twice daily dosing. OBJECTIVE: To evaluate the efficacy and safety of triamcinolone acetonide (triamcinolone acetonide), 400 microg bid, in mild-to-moderate asthma patients. METHODS: A multicenter, randomized, double-blind, placebo-controlled study with a 7- to 21-day baseline and 6-week treatment period. Adult mild-to-moderate asthma patients poorly controlled by beta2-agonists alone were randomized to receive placebo (48) or triamcinolone acetonide (53). Patients recorded daytime and nighttime asthma symptoms, albuterol use, and morning and evening peak expiratory flow (PEF) rates on diary cards. Clinic spirometry measures included FEV1, FEF25-75%, FVC, FEV1/FVC, and PEF. RESULTS: Triamcinolone acetonide treatment resulted in improvement from baseline of 17% for FEV1 (P < .0001); 44% for albuterol use (P = .0009); 9% for FVC (P = .0185); 19% for PEF (P = .0011); 42% for FEF25-75% (P < .0001); 8% for FEV1/FVC (P = .0016); 36% for daytime, 39% for nighttime, and 38% for total asthma symptoms (P < or = .0001); and 12% for morning, and 10% for evening PEF (P < or = .001). These changes were highly significant when compared with placebo (P < or = .0185). Significant improvement for all variables was demonstrated within 1 to 2 weeks of active treatment, and maintained for most variables over the 6-week treatment phase. Both treatments were well tolerated. Respiratory adverse events occurred more frequently with placebo; pharyngitis was reported more frequently with triamcinolone acetonide. CONCLUSIONS: Triamcinolone acetonide, administered twice daily, can effectively and safely treat patients with milder forms of asthma. In these patients, triamcinolone acetonide improves asthma symptoms and decreases the need for as-needed beta2-agonists.

Dose ranging study of mometasone furoate (Nasonex) in seasonal allergic rhinitis.

BACKGROUND: Topical nasal corticosteroids are rapidly gaining acceptance as first-line therapy for seasonal allergic rhinitis, but there is a desire for effective corticosteroids with an improved safety profile over existing products. OBJECTIVE: A multicenter, double-blind dose ranging study was conducted to compare the activity and tolerance of four doses of mometasone furoate nasal spray (tradename Nasonex) and placebo in adult patients with seasonal allergic rhinitis. METHODS: Four hundred eighty patients with seasonal allergic rhinitis were enrolled and randomized to receive mometasone furoate nasal spray 50 micrograms (n = 96), 100 micrograms (n = 95), 200 micrograms (n = 98) or 800 micrograms (n = 95), or placebo vehicle (n = 95) once daily for 28 days. RESULTS: All of the doses of mometasone furoate nasal spray showed activity in reducing the severity of rhinitis. The 200-microgram dose reduced total nasal symptom scores and total symptom scores throughout the study (P < .05 versus placebo vehicle). The 50-microgram dose and the 100-microgram dose showed less consistent activity at early timepoints (days 3 and 7), while the 800 microgram dose did not provide significant additional benefits over the 200-microgram dose. All dose levels were well tolerated CONCLUSION: The results of this trial indicate that 200 micrograms once daily is the optimum dose of mometasone furoate nasal spray for the treatment of seasonal allergic rhinitis.

Stinging insect hypersensitivity in children.

In the past two decades, many advances have been made in the treatment of patients with insect venom sensitivity. An effective treatment (venom immunotherapy) has been developed and indications for therapy refined. In the past year, reports concerning fatal toxic reactions to multiple stings, Africanized ("killer") bees, bumblebee venom allergy and treatment, and reactions to fire ant stings have been published. Papers have also appeared on the use of sting challenges in the diagnostic evaluation of insect sting allergy, laboratory investigations of the mechanism of action of venom immunotherapy, and the outcome of discontinuing venom treatment after 5 years in insect-allergic patients.

A placebo- and active-controlled randomized trial of prophylactic treatment of seasonal allergic rhinitis with mometasone furoate aqueous nasal spray.

BACKGROUND: Topical nasal corticosteroids have become a mainstay of treatment for the symptoms of seasonal allergic rhinitis (SAR). It is likely that topical corticosteroids, by blocking an initial influx of inflammatory cells in the nasal mucosa induced by aeroallergens, may have a preventive effect on nasal allergy symptoms when administered before the pollen season. OBJECTIVE: This study was designed to assess the efficacy and safety of an 8-week course of mometasone furoate nasal spray (MFNS), 200 micrograms once daily, in the treatment of SAR compared with beclomethasone dipropionate aqueous nasal spray (BDP), 168 micrograms twice daily, and placebo vehicle, when treatment is initiated before the anticipated onset of the ragweed season. METHODS: Three hundred forty-nine patients with SAR to ragweed pollen from nine centers in the Northeast and Midwest of the United States were randomized to one of the three intranasal study medications (MFNS, 200 micrograms once daily, BDP, 168 micrograms twice daily, or placebo vehicle), starting 4 weeks before the estimated start of the ragweed season. RESULTS: The proportion of "minimal symptom" days (total nasal symptom score < or = 2) was statistically significantly higher in both the MFNS and BDP groups when compared with the placebo vehicle group (p < 0.01). The two active treatment groups were not statistically significantly different from each other. MFNS and BDP displayed a similar safety profile that did not differ from placebo. CONCLUSIONS: This suggests that MFNS, 200 micrograms (once daily), is a useful therapy in the prophylactic treatment of SAR.

Allergic and nonallergic rhinitis. Directing medical therapy at specific symptoms.

Rhinitis is a common complaint, especially during the allergy season. Physicians can often identify the probable allergen or irritant with history taking, and skin tests may be helpful in confirming the clinical impression. Often, environmental control measures can provide significant relief. Successful drug treatment hinges on selection of the proper class of medication for a given patient's type and severity of symptoms. Antihistamines remain a mainstay for reducing sneezing, itching, and nasal discharge. New oral agents are nonsedating, and an eyedrop form is available for bothersome eye symptoms. Decongestants reduce nasal blockage and are often especially beneficial when used in combination with antihistamines, In moderate to severe rhinitis, intranasal corticosteroids are the most effective treatment.

Comparison of triamcinolone acetonide nasal inhaler with astemizole in the treatment of ragweed-induced allergic rhinitis.

BACKGROUND: Few clinical trials have directly compared the efficacy of antihistamines with topical nasal corticosteroids. OBJECTIVE: The study was performed to compare the efficacy and safety of triamcinolone acetonide nasal spray at a dose of 110 micro g in each nostril once daily with 10 mg of oral astemizole once daily for the treatment of seasonal allergic rhinitis. METHODS: A multicenter, double-blind, parallel-group study was conducted in 239 patients who were randomized to receive either triamcinolone acetonide or astemizole. A 5-day, drug-free, lead-in period was followed by 4 weeks of double-blind treatment. One hundred four patients treated with triamcinolone acetonide and 105 patients treated with astemizole could be evaluated. RESULTS: Overall, triamcinolone acetonide was more effective than astemizole in reducing total nasal symptoms, nasal stuffiness, nasal itching, and sneezing (p

Tilarin in combination with astemizole.

This multicentre double-blind, placebo controlled study had a practical objective, based on the expectation that many patients with seasonal allergic rhinitis will be prescribed oral antihistamine monotherapy by their primary care physician, whereas allergy specialists are more likely to prescribe combination therapy including antiinflammatories. The specific question was, "Will the addition of nedocromil sodium 1% nasal spray to astemizole tablets improve control of symptoms of seasonal allergic rhinitis induced by ragweed pollen, as compared to astemizole therapy alone?'. Following a one-week baseline, planned to coincide with the start of the local ragweed pollen season, patients (aged 12-64) were randomly assigned to four weeks' double-blind test treatment with either nedocromil sodium 1% nasal spray four times daily (QID) + astemizole (n = 146) or placebo nasal spray + astemizole (n = 148) or double-dummy (nasal spray + capsules) placebo (n = 71). Patient diary cards were kept throughout the five weeks, and clinic visits were made before and after baseline and after one and four weeks' treatment. During the 10-day peak pollen period, the diary card rhinitis symptom summary score (0-4 severity scale) was significantly reduced in patients receiving either astemizole alone (p < 0.001) or the combination therapy (p < 0.001) as compared with placebo. Direct comparison of the active treatments further showed that symptoms were significantly less severe (p < 0.01) with the combined therapy than with astemizole alone, and this despite significantly greater reliance on permitted rescue medications (p < 0.05 for pseudoephedrine usage) in the astemizole group. Clinical assessments of rhinitis made during the peak pollen visit, after the first week of test treatment, were also significantly (p < 0.05 - p < 0.01) in favour of combined therapy with nedocromil sodium 1% nasal spray + astemizole rather than astemizole alone, and at the same time this preference was confirmed by physician (p = 0.011) and patient (p = 0.003) opinions of symptom control. In conclusion, this antiinflammatory + antihistamine treatment proved superior to antihistamine alone for effective management of allergic rhinitis. The combined therapy worked quickly and was well-tolerated, with no serious adverse events or untoward effects on blood or urine variables.

Insect sting allergy: analysis of a cohort of patients who initiated venom immunotherapy from 1978 to 1986.

BACKGROUND: The proper duration of venom immunotherapy remains uncertain. OBJECTIVE: We report our experience with a cohort of patients who started venom immunotherapy from 1978 to 1986. METHODS: In a midwestern allergy practice, the cohort of 204 stinging insect-allergic patients who commenced venom immunotherapy from 1978 to 1986 were identified and evaluated by retrospective chart analysis and patient telephone inquiry. RESULTS: Only 12 patients remain on venom treatment. The majority of patients have discontinued venom immunotherapy either by self-determination (35 patients) or upon physician advice (80 patients). There was no relationship between the severity of the initial sting reaction and the length of time patients received therapy. After cessation of venom treatment, there were 148 re-stings in 117 patients with only two re-sting reactions, both of which occurred in patients with severe initial sting reactions. CONCLUSIONS: Most patients who have received four to 6 years of venom immunotherapy continue to tolerate insect stings after cessation of treatment.

Detection of beta-blocker use in people with asthma.

Although there have been numerous reports of adverse outcomes for people with asthma who are placed on beta-blockers, there has been no description of how often people with asthma receive prescriptions for beta-blockers. Despite the fact that pharmacy claims are available and can be used for clinical evaluation, there has been no description of a practical surveillance or warning system to recognize and reduce the rate of beta-blocker use in people with asthma. This study used administrative claims data to estimate the prevalence of patients with asthma who also had prescriptions for beta-blockers. Chart audit was used to supplement our understanding of the causes of the problem and its consequences. In the calendar year 1989, in a large midwestern group practice that contracts with a single health maintenance organization (HMO), 3,170 HMO patients presumed to have asthma were identified. Of those 3,170 patients, 44 or 1.4% also had filled prescriptions for beta-blockers. The occurrence of beta-blocker use varied by age group: from less than 1% in patients below 30 years of age, rising to 8.9% in patients aged 60 to 69. Two of the patients with asthma who had prescriptions for beta-blockers were hospitalized for asthma in the study period. In 61% of the cases, different physicians managed the asthma care from those who prescribed the beta-blockers. In the remaining 39%, one physician was responsible for both the asthma care and beta-blocker prescription. We conclude prescribing beta-blockers for individuals with asthma is not uncommon. Current systems of administrative claims data permit the development of warning systems to help avert adverse outcomes.

The value of immunotherapy with venom in children with allergy to insect stings.

BACKGROUND: The treatment of patients allergic to insect stings with insect-venom injections has been shown to be 97 percent effective in reducing the risk of sting-induced anaphylaxis. However, the frequency of systemic reactions to subsequent stings in unimmunized adults with previous reactions is approximately 60 percent. To determine which factors, in addition to a history of reaction and evidence of venom-specific IgE antibody, predispose patients to future insect-sting reactions, we studied a venom-sensitive group of children who were deemed to be at relatively low risk for severe reactions; 28 percent of them received venom therapy. METHODS: We studied 242 children, 2 through 16 years of age, each of whom had had a systemic allergic reaction, affecting only the skin, to an insect sting. Each child had a positive skin-test reaction to one or more of five hymenopteran venoms. Sixty-eight children received immunotherapy with insect venom and 174 did not; about half were randomly assigned to treatment groups, and the rest were assigned on the basis of the patient's (or the parents') choice. The results of accidental stings during four years of observation were evaluated. RESULTS: In the treated group, 84 stings in 36 patients resulted in one systemic reaction (1.2 percent of stings). In contrast, 196 stings in 86 untreated children resulted in 18 systemic reactions (9.2 percent of stings, P less than 0.001). Sixteen of these 18 reactions were judged to be milder than the patient's reaction to the first sting, 2 were similar in severity, and none were more severe. CONCLUSIONS: These data confirm that immunotherapy with insect venom prevents recurrences of systemic reactions after subsequent insect stings. Because of the surprisingly low rate of reactions among untreated children, we could not identify any characteristics that were predictive of repeat reactions. Since only 9.2 percent of stings in the untreated children led to a systemic reaction and since there was no progression to a more severe reaction, we conclude that venom immunotherapy is unnecessary for most children who are allergic to insect stings.

Stinging insect allergy. How management has changed.

The state of the art for insect allergy has undergone significant changes over the last two decades. Epinephrine, which is indispensable to treat all but the mildest reactions, is available in portable kits and can be used by the patient when medical help is not readily available. Venom immunotherapy has proven to be safe and effective for those patients who require it, and the concern that lifelong therapy would be necessary is likely to be unwarranted.