Arformoterol tartrate in the treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease.

Arformoterol tartrate inhalational solution is a nebulized bronchodilator that has been approved for long-term, twice-daily maintenance therapy for bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD). It is a single-isomer ([R,R]-formoterol), selective, long-acting, full beta(2)-agonist with affinity for both subtypes of beta-adrenergic receptor, and 2-fold higher affinity for the beta(2) receptor versus racemic formoterol. It is 1,000-fold more potent in receptor-binding affinity compared to (S,S)-enantiomer of formoterol. More than 2,000 COPD patients have participated in 16 completed clinical trials, including phase III pivotal and open-label trials to evaluate the efficacy and safety of arformoterol at doses ranged from 15 to 50 microg. These studies demonstrated that treatment with arformoterol significantly improved various lung function parameters, overall clinical status and ability to function, as well as significantly reduced COPD exacerbations and use of rescue medication. In terms of safety, arformoterol was found to be well tolerated in doses up to 50 microg/day with no reports of significant clinical, laboratory or cardiovascular adverse events, such as changes in QTc interval or cardiac arrhythmias. Recent asthma literature has alluded to caution with the use of long-acting beta-agonists (LABAs) (except probably in combination with inhaled corticosteroids) citing possible increase in the risk of asthma-related mortality. However, there is no comparable data available with regards to the use of LABAs in COPD patients.

Pimecrolimus reduces eosinophil activation associated with calcium mobilization.

BACKGROUND: Pimecrolimus is a calcineurin inhibitor that inhibits T cell and mast cell activation and effectively treats atopic dermatitis. However, its effects on eosinophils, a cell type implicated in allergic disease pathology, are unknown. Therefore, we examined the effects of pimecrolimus on eosinophil superoxide anion production, degranulation and survival. METHODS: Purified eosinophils from normal or atopic donors were incubated with serial dilutions of pimecrolimus (microM to nM) and then stimulated with platelet activating factor (PAF), interleukin 5 (IL5), secretory immunoglobulin A (sIgA) or Alternaria alternata (Alt) fungus extract. Eosinophil activation was monitored by cytochrome c reduction resulting from superoxide anion production and by a 2-site immunoassay for eosinophil-derived neurotoxin (EDN) in cellular supernatants, as a marker of degranulation. Eosinophil survival was measured by propidium iodide exclusion using flow cytometry after 4 days in culture. RESULTS: Normal and atopic eosinophil superoxide anion production induced by PAF, and associated with increased intracellular calcium, was inhibited up to 37% with 1 microM pimecrolimus. However, superoxide anion production induced by IL5 and sIgA was not consistently inhibited. EDN release, which ultimately depends on calcium, was inhibited about 30% with PAF, IL5 and sIgA stimulation for normal and atopic donor eosinophils. Furthermore, calcium-dependent Alt-induced EDN release was inhibited up to 49% with nanomolar pimecrolimus. Finally, increased eosinophil survival promoted by IL5 and sIgA was not influenced by pimecrolimus. CONCLUSION: Pimecrolimus moderately inhibits eosinophil superoxide anion production and EDN release associated with calcium mobilization, which may contribute to its efficacy in treating atopic dermatitis.

Epiceram for the treatment of atopic dermatitis.

EpiCeram consists of a specific combination of ceramides, cholesterol and fatty acids that mimics those naturally found in the skin. EpiCeram was approved by the FDA in April 2006 for use as a nonsteroidal lipid barrier emulsion to manage symptoms of burning and itching associated with dry skin conditions such as atopic dermatitis, irritant contact dermatitis, radiation dermatitis and other dermatoses. EpiCeram has shown comparable efficacy to a mid-strength topical corticosteroid in a clinical study involving 113 children with moderate to severe atopic dermatitis. Unlike topical steroids and immunomodulators such as calcineurin inhibitors that have clinically well-recognized undesirable side effects and usage restrictions (including FDA black box warning for the latter), current data suggests that EpiCeram has a favorable safety profile. Additionally, EpiCeram does not appear to have substantial restrictions associated with its use, especially with regards to the duration of use or patient age, compared to the other classes of prescription products.

Two puffs of 90 microg albuterol prior to 3% saline sputum induction results in less FEV-1 decline than single concentration 25 mg/ml methacholine challenge.

BACKGROUND: Assessment of sputum eosinophilia has shown benefit in the diagnosis and monitoring of asthma. However, the possibility of bronchospasm related to the hypertonic saline used in sputum induction appears to have limited this procedure's acceptance in clinical practice. OBJECTIVE: Because the methacholine (MCH) challenge has been widely accepted as safe in the diagnosis of mild asthma, we sought to compare the safety of SI with 3% hypertonic saline following pretreatment with 2 puffs of 90 microg albuterol to that of a single concentration 25 mg/mL MCH challenge. METHODS: We performed a retrospective review of 152 consecutive subjects, 57 with mild asthma and the remaining with other respiratory problems who had undergone both a SI and a MCH challenge at our single site tertiary care referral center. RESULTS: Median reduction of FEV-1 in subjects with and without asthma (n=152) was 9.95% in the MCH group compared to 35% in the SI group (p value < 0.0001). FEV-1 was reduced in excess of 20% in 33 of 152 (21.7%) MCH challenge tests compared to 1 of 152 (0.66%) SI. Median reduction of FEV-1 in asthmatic subjects (n=57) was 17.86% in the MCH group compared to 32% in the SI group (p value < 0.0001). CONCLUSIONS: With regard to potential bronchoconstriction, we conclude that 2 puffs of 90 microg albuterol administered prior to 3% saline sputum induction results in less FEV-1 decline than single concentration 25 mg/mL MCH.

Cephalosporin allergy.

Allergic reactions to cephalosporins may occur because of sensitization to cephalosporin determinants shared with penicillin or to unique cephalosporin haptens. The exact nature of the haptenic determinants resulting from the degradation of currently available cephalosporins is incompletely understood. Cephalosporin skin testing or specific IgE immunoassays have limited clinical utility. Patients with a history of allergy to cephalosporins or penicillin may be at increased risk for a reaction to cephalosporins. Skin testing for an allergy to penicillin may be helpful in patients with a history of penicillin allergy who have a clinical indication for cephalosporin use. Most of these patients have negative tests and should not be at increased risk for a reaction to cephalosporins.

Nebulized salbutamol vs salbutamol and ipratropium combination in asthma.

OBJECTIVE: To see the additional benefit of combined frequent nebulization with salbutamol and ipratropium bromide in acute attack of asthma with moderate severity. METHODS: Fifty asthmatic children in the age range of 6-14 years were divided into two equal groups. Group I children were nebulized with three doses of Salbutamol alone (0.03 ml/kg/dose) and Group II children were given combined nebulization of Salbutamol (dose as in group I) and Ipratropium bromide (250 microgm/dose for three doses) at 20 minutes interval. Children were observed at 15, 30, 60, 120, 180 and 240 minutes interval. RESULTS: A significant improvement in % of PEFR starting at 30 minutes and lasting the entire study period of 4 hours was noted in both the groups. However on analysis of varience the results were better in group II. CONCLUSION: Frequent combined nebulization with Salbutamol and Ipratropium bromide is beneficial in acute asthma of moderate severity.

Vaccine allergy: diagnosis and management.

As a group, vaccines provide a safe and effective way of preventing infectious and allergic illness. Allergic reactions to vaccines and drug products have become important and common features of practice and demand heightened awareness. Serious adverse effects of vaccines are rare but have been reported to various components of different vaccines. Although there are few precise diagnostic tests available, patients usually can be diagnosed accurately after careful attention to the history and physical findings. Better understanding of these reactions can lead to proper vaccine selection and can improve immunization acceptance rates in the community. Prevention, avoidance, use of alternative agents, desensitization, and premedication remain the mainstays of therapy, even as more refined diagnostic and management tools are developed. VAERS data, in addition to the traditional uses (signal detection, large registry of rare vaccine adverse events), can serve as a source of cases for epidemiologic (eg, case-control) studies that evaluate biologic factors that may be related to vaccine-related adverse reactions. Additional studies that are aimed at identifying other causes of immediate hypersensitivity after immunization with live virus vaccines are warranted.