Faculty Bibliography

BACKGROUND: Unlike many antihistamines, desloratadine can reduce nasal congestion in patients with seasonal allergic rhinitis (SAR). OBJECTIVE: We compared the effects of 5 mg of desloratadine and placebo on nasal airflow and SAR symptoms, including nasal congestion, in response to grass pollen in an allergen-exposure unit. METHODS: In a randomized, double-blind, placebo-controlled, crossover trial, 47 subjects with histories of SAR received desloratadine or placebo every morning for 7 days and, after a 10-day washout period, were crossed over to the other treatment arm for 7 days. Subjects underwent a 6-hour allergen exposure on day 7 of each treatment period. Nasal airflow and nasal secretion weights were measured before and every 30 minutes during allergen exposure; SAR symptoms (including nasal congestion) were scored before exposure and every 15 minutes thereafter. RESULTS: Nasal obstruction, as measured by nasal airflow, was less severe with desloratadine than with placebo (P <.02). Individual and combined SAR symptom severity scores, including nasal congestion and sneezing, were significantly lower with desloratadine than with placebo (all P < or =.003). Within 30 minutes of allergen exposure, less severely decreased nasal airflow (P <.02), less nasal secretions (P <.001), and less severe symptoms, including nasal congestion (P <.002), rhinorrhea, and sneezing, occurred with desloratadine compared with placebo, and this continued throughout (0-6 hours) allergen exposure. Desloratadine was well tolerated, with an adverse event profile similar to that of placebo. CONCLUSION: In subjects with allergen-induced SAR symptoms, desloratadine significantly reduced the severity of nasal obstruction and accompanying complaints of nasal congestion and other SAR symptoms compared with the effects of placebo.

BACKGROUND:Nonsedating antihistamines are well-established treatment for seasonal allergic rhinitis (SAR), but patients do not always respond to the first antihistamine prescribed. OBJECTIVE:This double-blind, double-dummy, randomized, 2-phase, multicenter study was designed primarily to compare the therapeutic responses to loratadine and fexofenadine in patients who failed initial therapy with the other drug. METHODS:Male and female patients aged 12 to 60 years received loratadine 10 mg once daily (n = 331) or fexofenadine 60 mg twice daily (n = 328) for 14 days (phase 1); nonresponders (ie, those who had <25% reduction in the sum of 5 SAR symptoms rated by the investigator on a 4-point scale) subsequently received the alternate medication for 14 days (phase 2). The investigator's rating of relief (complete, marked, moderate, or slight relief of symptoms or treatment failure) at the end of phase 2 was the primary efficacy measure; changes in total symptom severity (TSS) assessed by the investigator (4-point scale) and the patient (11-point visual analog scale) were secondary measures. RESULTS:Mean decreases in TSS were significantly greater with loratadine than with fexofenadine for the 659 patients who completed phase 1 (-12.7 vs -10.2, respectively; P = 0.019; patient assessment) and for the 389 patients who responded to initial therapy (-6.6 vs -6.1, respectively; P = 0.037; investigator assessment). Of the 389 patients who responded to initial therapy, 61.0% had received loratadine and 57.0% had received fexofenadine. More nonresponders to initial therapy had moderate, marked, or complete relief of symptoms after switching to loratadine than after switching to fexofenadine (62.4% vs 51.2%, respectively; P = 0.005) and treatment failure in 10.6% vs 21.7%, respectively (P = 0.011). CONCLUSION/CONCLUSIONS:Overall, ioratadine provided significantly better therapeutic response than fexofenadine in patients who failed to respond to initial therapy with the other drug.

BACKGROUND:The impact of long-acting nitrates on the extent and severity of stress-induced myocardial ischemia is not well described, especially after long-term treatment. METHODS:Forty patients with chronic stable angina and reversible ischemia on an exercise stress myocardial perfusion single photon emission computed tomography (ex-SPECT) were prospectively studied in a 6-week period. At baseline, rest thallium-201/exercise stress technetium 99m sestamibi SPECT was performed, followed by treatment with extended-release isosorbide 5-mononitrate (5-ISMN, Imdur). Follow-up ex-SPECT was performed 5 days and 6 weeks after the initiation of therapy with extended-release 5-ISMN. The exercise treadmill testing (ETT) protocol and exercise duration of the follow-up studies were the same as that of the baseline ETT. Defect extent and severity were analyzed both by means of an automated quantitative method, with CEqual software, and visually, with a 20-segment scoring system (which was also used to derive a summed stress score [SSS]). RESULTS:In the 6-week study period, significant reductions occurred in both the extent and the severity of exercise-induced ischemia by means of quantitative SPECT (13.8% [P<.0003] and 12.7% [P<.0003], respectively). There was no significant change in these variables between stages 2 (day 5) and 3 (6 weeks), indicating no development of tolerance to the nitrate effect. Similar reductions were noted by means of the visual analysis (SSS reduction of 13.0% [P<.002]) in the entire study period. CONCLUSIONS:Patients with chronic-stable-angina treated with a long-acting nitrate demonstrate improvement in myocardial perfusion defect extent and severity in an extended period by means of both visual and quantitative analysis of sequential exercise testing to the same rate-pressure product end point.

Cholelithiasis leads to 80,000 cholecystectomies being performed every year in France, but its prevalence is still unknown. The aim of this study was to assess the prevalence and risk factors of cholelithiasis in a random population of 1027 women and 727 men over the age of 30 in a small town in the southeast of France. Detailed clinical history, dietary investigation, and gallbladder ultrasound were collected for each subject and assessed by univariate analysis. A regression model was used in the multivariate analysis to detect the relative risk of cholelithiasis. Cholelithiasis was found in 130 individuals (global prevalence 13.9%). The relative risk for lithiasis was higher in women compared to men (1.89). Age (P<0.0001) and body mass index (BMI) >25 (P = 0.013) were also significant risk factors. Neither pregnancy nor oral contraceptive use proved to be risk factors. Typical biliary colic pain was the only symptom significantly associated with cholelithiasis (P<0.0001). These results show that the prevalence of gallstones in France is similar to that in Denmark and Italy.

Although equally potent at blocking the H1 receptor, first- and second-generation antihistamines can be distinguished with respect to their different effects on the central nervous system (CNS). First-generation antihistamines readily cross the blood-brain barrier leading to significant drowsiness, altered mood, reduced wakefulness, and impaired cognitive and psychomotor performance. This paper reviews of studies CNS functioning conducted with loratadine, a second-generation H1-receptor antagonist, at its therapeutic dose of 10 mg per day. Studies employing self-report measures, such as diary cards, visual analogue scales, rating scales, and mood inventories have shown that the effect of loratadine on somnolence, fatigue, and mood was comparable to those found with placebo. In studies exploring physiological indices of CNS functioning, such as EEG-evoked potentials, and sleep latency tests, loratadine has been shown to be free of CNS effects. In addition, studies have investigated the effects of loratadine on actual driving performance, and on tests of cognitive and psychomotor functioning. On all of these performance measures, loratadine has been shown to have effects comparable to placebo. In contrast, diphenhydramine, a common first-generation antihistamine, usually available without a doctor's prescription, has significant adverse effects on vigilance, divided attention, working memory and psychomotor performance. Impairment has been shown to occur even in the absence of self-reported sleepiness.

BACKGROUND:The effect of H1-blockers may differ depending on the target organ. OBJECTIVE:A double-blind, placebo-controlled study was carried out to compare the effect of a 7-day treatment with loratadine (10 mg daily) or cetirizine (10 mg daily) on nasal challenge with grass pollen grains and skin tests with allergen or histamine. METHODS:Twenty-four patients were enrolled, but the analysis was carried out on 23. Nasal challenge was carried out by using 5-fold increasing numbers of pollen grains. Skin prick tests were done with serial concentrations of allergens and 1 concentration of histamine. Patients were tested in a cross-over design, with each treatment being administered for the previous 7 days and with a 2-week washout period. RESULTS:By comparison with placebo, loratadine and cetirizine increased significantly the threshold number of pollen grains required to induce a positive nasal challenge (P <.001). There was no difference between loratadine and cetirizine. Skin test responses to allergen were significantly reduced by loratadine and cetirizine by comparison with placebo. Skin test responses to histamine were significantly decreased by the 2 H1-blockers, but they were more profoundly decreased by cetirizine than by loratadine. CONCLUSIONS:Both H1-blockers reduced similarly allergen-induced skin test and nasal challenge responses. Cetirizine was more effective on histamine skin test responses.

BACKGROUND:Asthma is a common and costly condition. Concomitant asthma and allergic rhinitis (AR) have been shown to increase the medication costs for people with asthma. No studies have compared medical care costs of those with and without concomitant AR. OBJECTIVES/OBJECTIVE:We sought to determine the prevalence and incremental medical care costs of concomitant AR. METHODS:For each member of a population-based asthma cohort, we used all their medical charts within Olmsted County to record age at first diagnosis of asthma; the presence and age of any diagnosis of AR; and the total, ambulatory, and respiratory care-related costs of medical care. Costs were compared for age- and sex-specific strata of people with asthma who did and did not have AR. RESULTS:AR was most commonly diagnosed in people whose asthma was diagnosed before age 25 (prevalence of 59%) and uncommonly diagnosed in anyone after age 40 (prevalence <15%). Yearly medical care charges were on average 46% higher for those with asthma and concomitant AR than for persons with asthma alone, controlling for age and sex. We were unable to assess the impact of treatment of AR on medical care charges. CONCLUSIONS:Physicians should consider the diagnosis of AR (prevalence >50%) in all symptomatic children and young adults with asthma. Further evaluation is necessary to evaluate the ability of treatment to decrease the incremental costs of AR in persons with asthma.