"Atopic cough" is a new clinical entity that presents with isolated chronic bronchodilator-resistant cough accepted in the Japanese Respiratory Society Guidelines for Management of Cough. The essential features are eosinophilic tracheobronchitis, increased cough reflex sensitivity and an atopic constitution. It has been suggested that activated helper T lymphocytes and the cytokines which are produced by these cells are involved in the pathogenesis, but the relationship between helper T cell-derived cytokines and the airway cough reflex sensitivity remains unknown.
The effect of an orally active Th2 cytokine inhibitor, suplatast tosilate (CAS 94055-76-2, IPD; 300 mg/day), on the cough response to inhaled capsaicin (CAS 404-86-4) was examined in ten patients with atopic cough. The capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. The serum total immunoglobulin E (IgE) level and the peripheral blood eosinophil count were also determined after treatment with suplatast tosilate.
The cough threshold measured after four weeks of treatment with suplatast tosilate was significantly increased compared to the value obtained with placebo, along with a decrease of the serum IgE level and peripheral eosinophil count.
Th2 cytokines may increase the airway cough reflex sensitivity in patients with atopic cough. Oral administration of suplatast tosilate may be a novel therapy for atopic cough.
"Suplatast tosilate is an oral agent that has been shown to inhibit the synthesis of both IL-4 and IL-5.11 Suplatast has been shown in early clinical trials to decrease serum IgE and peripheral blood eosinophil counts.12 "
[Show abstract][Hide abstract] ABSTRACT: New information regarding the molecular mechanisms of allergic disorders has led to a variety of novel therapeutic approaches. This article briefly reviews the pathogenesis of asthma and allergic diseases, discusses the rationale behind using immunomodulators in these diseases; and examines the therapeutic effects of immunomodulators on allergic diseases. There are a number of immunomodulators that have been developed for the treatment of allergic disorders. Some have looked very promising in pre-clinical trials, but have not shown significant benefits in human clinical trials thus indicating the disparity between mouse models and human asthma. This review focuses on immunomodulators that are in human clinical trials and not molecules in pre-clinical development.
[Show abstract][Hide abstract] ABSTRACT: New developments in the field of allergy and immunology have yielded a variety of novel therapeutic approaches in recent years, and more agents are at the clinical trial stage. Among the therapeutic approaches discussed in this review are Toll-like receptor agonists, immunostimulatory oligodeoxynucleotides, orally and parenterally administered cytokine blockers, and specific cytokine receptor antagonists. Transcription factor modulators targeting syk kinase, peroxisome proliferator-activated receptor-gamma, and nuclear factor-kappaB are also being evaluated in the treatment of asthma. The anti-IgE monoclonal antibody omalizumab has established effectiveness in patients with allergic asthma, but the criteria for selecting patients who are most likely to benefit from it are less clear. This review summarizes data from human clinical trials with immunomodulators to discuss the rationale for their use, their efficacy, and adverse events associated with them.
Current Allergy and Asthma Reports 11/2009; 9(6):475-83. DOI:10.1007/s11882-009-0070-x · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Capsaicin, the pungent extract of red peppers, has been used in clinical research for almost three decades. Capsaicin has gained favor as the provocative agent of choice to measure cough reflex sensitivity, as it induces cough in a safe, reproducible, and dose-dependent manner. One of the major uses of capsaicin cough challenge testing has been to evaluate the effect of a pharmacological intervention on the human cough reflex. The current review summarizes the published experience with capsaicin inhalation challenge in the evaluation of drug effects on cough reflex sensitivity. A notable contrast evident between studies demonstrating a drug effect (inhibition of cough reflex sensitivity) and those that do not, is the predominance of healthy volunteers as subjects in the latter. This observation suggests that subjects with pathological cough, rather than normal volunteers, comprise the optimal group in which to evaluate the effect of potential antitussive agents on human cough reflex sensitivity.
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