Impact of the Arg 16 allele of the B2AR gene on the effect of withdrawal of LABA in patients with moderate to severe asthma.

INTRODUCTION: Long-acting beta agonists (LABAs) are effective for controlling asthma, however questions about their safety have led to concerns over use. Genetic polymorphisms at the 16 amino acid position of the beta-2 adrenergic receptor gene (B2AR) may be associated with increased risk. METHODS: A randomized, double blind study was conducted in patients with moderate to severe asthma being treated with combined inhaled corticosteroids/LABA (ICS/LABA), comparing the effect of LABA continuation versus withdrawal on asthma outcomes among patients stratified by B2AR genotype (Arg/Arg vs. Gly/Gly at the 16th amino acid position). RESULTS: 67 participants (31 Arg/Arg, 36 Gly/Gly) were randomized to receive fluticasone alone (F) or continue combined fluticasone/salmeterol (F/S) after a run-in period on F/S. Among Gly/Gly subjects, those in the F/S treatment group showed improvement in AM PEFR (+ 8.4 L/s) whereas those receiving F alone experienced a reduction in AM PEFR over the study period (-14.4 L/s), (p = 0.06). There was no significant difference in morning peak expiratory flow rate (AM PEFR) in Arg/Arg participants randomized to receive F/S (-15.7L) vs F alone (-5.6 L/s) (p = 0.61). There was no significant difference in exacerbations in the Arg/Arg subjects treated with F/S compared with those treated with F (p = 0.65). CONCLUSIONS: Withdrawal of LABA therapy in asthmatics with the Arg/Arg genotype at the 16th amino acid position of B2AR did not lead to significant improvement in AM PEFR. LABA withdrawal in the Gly/Gly genotype however led to a borderline significant decline in AM PEFR.

A multi-center, retrospective review of patch testing for contact dermatitis in allergy practices.

BACKGROUND: Studies assessing patch testing (PT) in allergy practices are limited. OBJECTIVES: To determine whether PT results using a limited panel of allergens such as in the Thin-Layer Rapid-Use Epicutaneous Test (TT) as compared with an expanded panel, such as the addition of supplemental allergens (North American Contact Dermatitis [NACD] Panel, Dormer Cosmetics, hairdressing series, corticosteroid series, and personal products) will miss a significant number of positive PTs. To compare our PT results with published data from dermatology practices. METHODS: This is a 5-year multicenter retrospective chart review of PT at 3 separate allergy practices. RESULTS: Four hundred twenty-seven patients (mean age, 49.8 years) were patch tested. Eighty-two percent were female; 54% reported an atopic history. Of the standardized allergens, the 5 most common positives were nickel sulfate, fragrance mix I, p-phenylenediamine (PPD), thimerosal, and cobalt chloride. Two hundred eighteen (56.9%; 95% CI = 51.9-61.8%) patients were positive to at least 1 TT allergen. Ninety-eight (25.6%; 95% CI = 21.5-30.2%) patients were positive to both a TT and a supplemental allergen. Forty-eight (12.5%; 95% CI = 9.6-16.2%) patients were negative to a TT allergen but positive to a supplemental allergen. CONCLUSION: Positive allergens would have been missed in 12.5% of patients when evaluating with TT allergens alone, whereas 25.6% would be partially evaluated. Patch test performance characteristics for these allergy practices appear to parallel that seen for dermatology. The TT remains an adequate screening tool in an allergy practice, but a more comprehensive panel may be needed to fully evaluate contact dermatitis.

Rituximab in the treatment of acquired factor VIII inhibitors.

Autoantibodies against factor VIII (FVIII) are rare but can cause life-threatening bleeding requiring costly factor replacement and prolonged immunosuppression. We report 4 consecutively treated patients whose acquired FVIII inhibitors responded rapidly to immunosuppressive regimens that included rituximab, a monoclonal antibody against CD20(+) B cells. Three patients had spontaneously occurring inhibitors. The fourth, a patient with mild hemophilia A, developed both an autoantibody and an alloantibody following recombinant FVIII treatment. Pretreatment FVIII activities ranged from less than 1% to 4% and inhibitor titers from 5 to 60 Bethesda units (BU). One patient with polymyalgia rheumatica who developed the inhibitor while receiving prednisone responded to single agent rituximab. The hemophilia patient had rapid resolution of the autoantibody, whereas the alloantibody persisted for months. Responses continue off treatment from more than 7 to more than 12 months. This report adds to the growing evidence that rituximab has efficacy in immune disorders resulting from autoantibody formation.