Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen.
In allergic asthma patients development of prolonged airway inflammation after allergen challenge is associated with intravascular platelet activation.
Measurements of EBT with the device we constructed are not significantly influenced by changes within the accepted range of a standard indoor environment. EBT represents a different characteristic of the human organism than otic and axillary temperatures. EBT is increased in uncontrolled asthmatics and decreases under anti-inflammatory treatment.
Background: Asthma and seasonal allergic rhinitis (SAR) are recognized as manifestations of a single airway disease. Desloratadine has demonstrated efficacy in treating SAR symptoms, including nasal obstruction. Methods: Safety and efficacy of desloratadine and montelukast each were assessed in a double-blind, placebo-controlled trial of patients with SAR and symptoms of asthma, who were assigned randomly to once-daily treatment with desloratadine 5 mg, montelukast 10 mg, or placebo for 4 weeks. Change from baseline of AM/PM reflective total asthma symptom severity scores (TASS), FEV1, individual asthma symptom scores, and β2-agonist usage were assessed. Results: Desloratadine and montelukast each were associated with statistically significant reductions from baseline in the mean TASS averaged over the 4-week period (p ≤0.022 vs. placebo). Individual asthma symptom scores also improved significantly for both therapies (p ≤ 0.05). Patients treated with desloratadine or montelukast demonstrated improvement from baseline in FEV1 versus placebo; significant improvement was seen in a subset of patients with baseline FEV1 <80% of predicted normal (both p < 0.05). Both active therapies significantly reduced β2-agonist use (both p < 0.01). Improvements for both therapies were comparable for all efficacy parameters; they were tolerated well with adverse event profiles similar to placebo. Conclusions: Asthma symptoms and β2-agonist were improved significantly in patients with concomitant SAR and asthma treated with desloratadine 5 mg as well as montelukast 10 mg once daily. Both therapies significantly improved FEV1 in a subset of patients with FEV1 <80% of predicted normal at entry. Improvements in asthma symptoms were comparable for both active treatment groups.
Specific immunotherapy is a well-established treatment for allergic rhinoconjunctivitis; conventional regimens are lengthy, however, reducing convenience and cost-effectiveness. This study evaluated the efficacy and safety of an ultrashort course (four doses) of the immunotherapy Grass Modified Allergen Tyrosine Adsorbate (Allergy Therapeutics, Worthing, U.K.) monophosphoryl lipid A (MATA MPL). Subjects were randomized to receive four injections of either Grass MATA MPL (n = 514; 300-2000 standardized units/injection) or placebo (n = 514) before the grass pollen season. They used electronic diaries to record allergy symptoms and medication use during the pollen season. The primary end point was the difference between the mean combined symptom and medication scores in the Grass MATA MPL and placebo groups during the 4 local peak pollen weeks. The injection course was completed by 95.3 and 97.7% of the Grass MATA MPL and placebo groups, respectively, and was well tolerated. Grass MATA MPL treatment afforded a 13.4% benefit over placebo in the 4 peak pollen weeks (p = 0.0038). The benefit in subjects with 28 complete diary entries during the 4 peak pollen weeks was 26.9% (p = 0.0031). Significant benefits over placebo were observed in subjects with severe symptoms (17.1%; p = 0.0023), in those who had a history of allergic rhinoconjunctivitis for up to 35 years (up to 37.2%; p = 0.0059) and at sites with a higher burden of disease (38.3%; p < 0.0001). The ultrashort course of Grass MATA MPL was well tolerated and provided a significant benefit over placebo in relieving allergy symptoms.
The use of polytherapy in clinical practice necessitates an appreciation and understanding of the potential for drug interactions. Recent publications provide insight into the role of the active transport systems P-glycoprotein (P-gp) and human organic anion-transporting polypeptides (OATPs) in drug interactions. Active drug transporters influence the bioavailability of a number of drugs by controlling their movement into, and out of, cells. The active transport systems P-gp and OATP play an important role in drug elimination. The activity of these transport systems is controlled, in part, by genetic factors; however, drugs and foods also influence the activity of these systems. It appears that interference with P-gp or OATP, either as upregulation or inhibition, may affect plasma drug concentrations by altering intestinal absorption, proximal renal-tubular excretion or biliary excretion. Overall, the net bioavailability of a drug or substance is affected by the relative contributions of cellular efflux (P-gp) and influx (OATP) mechanisms and to what extent these systems are active during phases of uptake and absorption versus removal and excretion from the body. Many of the drugs and foods that affect active drug transport activity are known to interact with the cytochrome P450 enzyme system; therefore, the net effect of concomitant drug administration is complex. One must now consider the impact of metabolism (CYP-mediated drug biotransformation), P-gp-mediated drug efflux and OATP-mediated uptake when making assessments of drug absorption and distribution.
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