Allergic Rhinitis Ebook

Hay Fever and Allergies

This eBook addressed the real causes of seasonal allergies like hay fever and other irritating health problems, and provides more informed solutions based on recent research into how to stop allergies at the system level. It doesn't take much now to be able to get rid of allergies, without having to see a doctor, pay huge medical and pharmaceutical bills, or fill your body with chemicals that do more harm than good to your system. However, if you are a doctor or run a clinic of any kind, you can learn things that you can apply to your own clinic to provide maximum benefit to you and your patients. Keep yourself informed with real research! When you find the underlying causes of allergic rhinitis (the medical term for hay fever) you will be far more informed on how to fight this in your own body. Take the natural way to heal yourself!

Hay Fever and Allergies Summary

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Classification Of Allergic Rhinitis

Traditionally, allergic rhinitis has been separated into perennial allergic rhinitis (responsible allergens found indoors, such as dust mites, dogs, and cats) with year-round symptoms or seasonal allergic rhinitis (responsible pollen allergens found seasonally outdoors, such as trees in the spring, grass in the summer, and weeds in the fall in temperate climates in the Northern Hemisphere). The Allergic Rhinitis and its Impact

Allergic Rhinitis Overview

Many randomized, double-blinded controlled trials for allergic rhinitis in reaction to airborne pollens, animal allergens, and house dust mite aeroallergens demonstrate efficacy of allergen immunotherapy based on subjective symptoms scores and medication diaries. Favorable immunological changes include decreased basophil histamine release, Nasal challenges also confirm that such therapy attenuates both the immediate- and late-phase allergic responses by decreasing mucosal membrane cellular influx and mediator production. Ragweed immunotherapy for 3-5 yr is required to achieve clinical remission. Both mixed- and single-grass pollen immunotherapy studies for hay fever result in significantly decreased symptom-medication scores during the grass pollen season and responses to grass skin testing and nasal challenge testing. Increases in grass-specific IgG-blocking antibody occurs in subjects successfully treated with mixed-grass immunotherapy. The size of both the immediate- and late-phase...

Future Therapeutic Options for Allergic Rhinitis

Future therapies for allergic rhinitis may include immunomodulators such as monoclonal anti-IgE (omalizumab), inhibitors of inflammatory cell immigration into the nasal mucosa, and anti-inflammatory therapies. Omalizumab binds to soluble IgE and also results in a reduction in the high-affinity receptor for IgE on mast cells and basophils and possibly on select dendritic cells. If dosed according to the recommendation of 0.16 mg kg U IgE, the free plasma IgE concentration is reduced to approx 15 U mL. This results in reduced allergic rhinitis symptoms and improvement in asthma. The necessity for injecting this compound and the cost are the major limitations on the eventual application of omalizumab for allergic rhinitis. A variety of anti-inflammatory therapies or immunomodulators have been considered or tried for rhinitis. Syk-kinase inhibitor is an example of such therapeutic approaches. Syk-kinase is a signaling protein important for mast cell and basophil degranulation. By applying...

Differential Diagnosis Allergic Rhinitis

Allergic rhinitis is the most prevalent form of rhinitis and should be considered in any individual presenting with nasal complaints. Other possible diagnoses are listed in Table 1. The principal factors utilized in distinguishing allergic rhinitis from the other conditions are summarized in Tables 5 and 6, with history being the most important. The diagnosis of allergic rhinitis is presumptive until specific allergic sensitivity is identified by epicutaneous or percutaneous testing or in vitro specific IgE testing. Immediate wheal and flare skin tests remain the most cost-effective means of identifying specific IgE. The value of intradermal allergy testing is primarily to exclude the diagnosis with negative results, with positive intradermal results providing only tenuous support of a diagnosis of allergic rhinitis. The evidence of specific IgE should be correlated with exposure and symptoms to support the diagnosis. Identifying environmental factors that trigger nasal symptoms is...

Perennial Nonallergic Rhinitis

Perennial nonallergic rhinitis (PNAR) is a term used to designate a heterogeneous group of disorders that share clinical features. The pathophysiology is not completely defined, and nasal histology does not correlate with symptoms. PNAR is common, representing 30-60 of subjects referred to an allergy immunology or otolaryngology clinic for evaluation. PNAR coexists with allergic rhinitis in more than 50 of adults with allergic rhinitis, a condition referred to as mixed rhinitis. Mucosal inflammation is less evident in PNAR than in allergic rhinitis, making the term rhinitis sometimes a misnomer. However, the symptoms are consistent with other inflammatory nasal disease, and inflammation may be present in a subset of PNAR. The typical presentation of PNAR is complaints of nasal obstruction, with or without rhinorrhea or postnasal drip, exacerbated by physical stimuli such as odor (particularly floral smells), air temperature changes, air movement, body position change, food, beverage...

Nonallergic Rhinitis with Eosinophilia

Nasal polyp view from the rhinoscope in the left nostril. The septum is on the left and the polyp is the pale soft tissue between the middle and inferior turbinate. Nasal polyps are associated with chronic inflammatory sinus disease, usually eosinophilic. Nasal polyps are not consistently found in subjects with allergic rhinitis but could explain persistent congestion. Cystic fibrosis is also associated with nasal polyps, although not generally with eosinophilic inflammation. Fig. 4. Nasal polyp view from the rhinoscope in the left nostril. The septum is on the left and the polyp is the pale soft tissue between the middle and inferior turbinate. Nasal polyps are associated with chronic inflammatory sinus disease, usually eosinophilic. Nasal polyps are not consistently found in subjects with allergic rhinitis but could explain persistent congestion. Cystic fibrosis is also associated with nasal polyps, although not generally with eosinophilic inflammation. Allergic rhinitis and...

Allergic Rhinitis

Both nedocromil and cromolyn are effective agents in the therapy of both seasonal and perennial forms of allergic rhinitis. However, this discussion will be limited to the use of cromolyn because nasal preparations of nedocromil are not commercially available in the United States. Cromolyn is available in an aqueous form, both with and without prescription, for the therapy of allergic rhinitis. As with asthma, cromolyn administration prevents both the early and late nasal responses to allergen and decreases both activated and indolent eosinophils found in nasal secretions and biopsies. As in asthma, nasal cromolyn should be administered once the rhinitis is reasonably controlled and it should be given prior to exposure. Thus, therapy for seasonal allergic rhinitis should be initiated before the allergy season begins. This drug can be highly effective in blocking symptoms resulting from isolated allergy exposure when it is administered immediately before mowing the lawn or visiting a...

H3 antagonists with a dual mechanism

Activity was reported for a series of tacrine analogs to treat the cognitive deficits in Alzheimer's disease 82 . Compound 34 (FUB833) (hH3 K 0.33 nM) had an IC5o of 2.6 nM for AChE. The series also showed activity for BuChE and HNMT, the main histamine metabolizing enzyme in brain. A series of compounds with dual H3 antagonist HNMT activity was reported 83 . Compound 35 had sub-nanomolar affinity for H3 and an IC50 of 51 nM for HNMT. Schering-Plough reported dual H H3 antagonists prepared by linking chloropheniramine with imidazole alkyl amines for allergic rhinitis 84 .

Potential Therapeutic Applications

Rhinitis and Nasal Congestion - Nasal obstruction and rhinorrhea present in allergic rhinitis are at least partly influenced by neuropeptides released from sensory, parasympathetic, and sympathetic nerves. NPY is co-localized with norepinephrine in sympathetic perivascular nerves. NPY is released with norepinephrine on sympathetic nerve stimulation and produces long lasting vasoconstriction of the nasal vascular bed through postsynaptic NPY Y1 receptors (35). In addition to direct vasoconstriction, there is evidence to suggest that NPY modulates the release of transmitters originating from parasympathetic and sensory nerves by acting on prejunctional NPY Y2 receptors. This would then attenuate the vasodilator response to the subsequent parasympathetic nerve stimulation in the nasal mucosa via non-adrenergic and non-cholinergic mechanisms (36). Putative therapeutic application of NPY in rhinitis has been recently suggested because intranasal administration of exogenous NPY in human...

Bronchial Hyperresponsiveness

One of the absolute features of asthma is exaggerated nonspecific airway reactivity to a variety of irritating stimuli. Thus, asthmatics develop airway obstruction in response to natural exposures (cold air, exercise, irritating chemicals, laughing, and coughing) or to provocations in the laboratory (histamine, methacholine, cold air hyperventilation) (Table 9). Airway hyperresponsiveness is found universally in asthmatics, in a portion of subjects with chronic bronchitis, in some subjects with allergic rhinitis, and in 3-8 of otherwise normal subjects. There is a close correlation between the degree of increased responsiveness and disease severity patients with the most reactive airways often require oral CCSs for control, whereas milder degrees of abnormality predict the requirement for fewer medications. Hyperresponsiveness increases after allergen exposure, late-phase allergic reactions, viral infections (especially influenza-type infections), and ozone exposure. Conversely,...

Pathophysiology And Specific

The pathophysiology is well defined for allergic, infectious, some medication-related, and select systemic disease-associated rhinitis syndromes. The pathophysiology of allergic rhinitis stems from the degranulation of mast cells and the subsequent mucosal recruitment of inflammatory cells, particularly eosinophils (Table 2, Fig. 1). Mast cell degranulation has been established by nasal allergen challenge, nasal lavage with analysis of mediators, nasal cytology, and nasal biopsy. Inflammation, characterized by recruitment of eosinophils into the nasal mucosa, is an essential component of the pathology of allergic rhinitis. The symptoms of allergic rhinitis are a composite of the effects of mediators on receptors, for example, histamine with H1 receptor or leukotrienes (LTD4 specifically) with cysteinyl-leukotriene receptor 1, and of cell recruitment with inflammation. The mediators released from mast cells are responsible for the acute symptoms of allergic rhinitis, primarily itching...

Allergen Immunotherapy

Specific allergen immunotherapy provides a 50 reduction in medication and symptoms if sufficient doses of the major allergens are administered to significantly (epicutaneous or percutaneous positive skin tests) allergic subjects. This improvement is confirmed by the majority of controlled trials with immunotherapy in both seasonal and perennial allergic rhinitis. Laboratory tests and challenge studies, in general, correlate with the clinical findings. The most consistent humoral change is an increase in specific IgG, with some studies showing a switch from specific IgG1 to IgG4 (Table 10). However, the many exceptions indicate that there is not a specific confir­ matory test to Stepwise Approach to the Treatment of Seasonal Allergic Rhinitis Perennial allergic rhinitis in adults Intermittent disease Advantages of allergen immunotherapy in addition to symptom improvement are that the treatment may reduce the future development of additional sensitivities and minimize the occurrence...

Otitis Media With Effusion

OME is a common cause of mild hearing loss in children, most often between the ages of two and seven years. The middle ear contains fluid that varies from a thin transudate to a very thick consistency (glue ear). Eustachian tube obstruction is usually caused by primary congenital tube dysfunction. Other possible contributing factors are allergic rhinitis, adenoidal hyperplasia, supine feeding position, or a submucous cleft. Middle-ear effusion was found to persist for at least one month in up to 40 of children who had suffered from AOM, and for at least three months in 10 of afflicted children (27).

Evaluation Of Pde4 Inhibitors In Animal Models

Respiratory Disorders - The efficacy of PDE4 inhibitors in animal models of asthma and COPD is well documented. A large number of structurally diverse, selective PDE4 inhibitors have demonstrated their ability to inhibit bronchoconstriction and airway hyper-responsiveness, eosinophil infiltration and local cytokine recruitment in a variety of models involving a range of stimuli. Efficacy has been shown in mice, rats, guinea pigs, dogs and monkeys, and the therapeutic potential of PDE4 inhibitors in asthma, allergic rhinitis and COPD has been extensively reviewed (7-9,36-39). The activity of recently disclosed PDE4 inhibitors in these models will be discussed in the Medicinal Chemistry Developments section in this chapter.

Acute Allergic Conjunctivitis

Ocular disorders mediated by mast cells are the most common hypersensitivity responses of the eye. AC is a result of direct exposure of the ocular mucosal surfaces to environmental allergens such as pollens from trees, grasses, and weeds interacting with the pollen-specific immunoglobulin (Ig)E found on the mast cells of the eye. Of all the various pollens, ragweed has been identified as the cause in approx 75 of cases of allergic rhinoconjunctivitis in the United States. Common conjunctival symptoms are itching, tearing, and perhaps burning. Involvement of the cornea is rare, with blurring of the vision being the most common corneal symptom. Clinical signs include a milky or pale pink conjunctiva with vascular congestion that may progress to conjunctival swelling (chemosis). A white exudate may form during the acute state, which becomes stringy in the chronic form. Although ocular signs are typically mild, the conjunctiva frequently takes on a pale, boggy appearance that often...

CCR3 Antagonists for the Treatment of Respiratory Diseases

Introduction - Bronchial asthma and allergic rhinitis are chronic inflammatory diseases characterized by the selective migration of leukocyte subtypes from the vasculature into the bronchial epithelium and nasal mucosa, respectively. One of the most striking aspects of these diseases is the accumulation of the eosinophil leukocyte (1). It was this observation that led to the search for, and subsequent identification of the molecular entities responsible for this phenomenon. One such molecule, designated eotaxin, was isolated from the bronchoalveolar lavage fluid from allergen-challenged guinea pigs, and early results demonstrated that this protein was an eosinophil-selective p-chemokine (2). Chemokines, or chemotactic cytokines, are members of a large family ( 50) of small molecular weight proteins (-8-10 kD). These proteins were initially characterized by their ability to stimulate migration of distinct subsets of leukocytes in the direction of a molecular gradient (chemotaxis)....

Skin Anomalies Pathological Noninfective

Classically this condition is the end-result of intense, chronic pruritus that results from repetitive rubbing or scratching. The skin responds by thickening and the increase in skin markings is referred to as lichenification. This occurs mostly in individuals with a history of allergies, eczema, hay fever or asthma. They have sensitive and easily irritated skin.

Immunological Diseases

Selective IgA deficiency is the most common immune deficiency disorder, affecting approx 1 in 400 individuals. It is characterized by decreased mucosal immunity, resulting in recurrent sinopulmonary, gastrointestinal and genitoureteral infections. Some patients remain asymptomatic while others manifest evidence of disease. IgA deficiency may be seen in association with atopic disease in some patients. These patients may develop asthma, allergic rhinitis or atopic dermatitis. The dermatitis is more typical of AD, both in character and distribution.

Natural History of Clinical Reactions to Food Allergy

Some patients with allergic rhinitis who are allergic to tree or grass pollens also react upon contact of the mouth with fresh fruits or vegetables. This is called the oral allergy syndrome (OAS) and is frequently a result of cross-reactions between the proteins in the foods and pollen (e.g., melons or bananas and ragweed pollen) (Tables 2 and 3). The natural history of such a food reaction is not entirely clear, but it may correlate with the degree of clinical reactivity to pollens.

Targeting Nonhepatic Hmgcoa Reductase

Diminish, both through empirical observation and directed trials. This factor may already account for the variability in the results from some clinical trials. Taken together, these previous data suggest that there may be further opportunity for chemistry optimisation of statin class drugs achieving higher systemic exposure, to exploit these potential novel mechanisms, assuming that the mechanism behind muscle toxicity can be understood and avoided. Alternatively, there exists the possibility of delivering statins at high relative concentrations to local sites and optimising the structure of the statin to ensure it is rapidly metabolised to an inactive form, either on exposure to the systemic circulation, or through efficient clearance on first pass metabolism, i.e., a 'soft statin' approach. Clinical conditions amenable to this strategy include asthma, allergic rhinitis or dermatitis, psoriasis, or even arthritis.

Vivian P Hernandez TrujiUo md and Phil Lieberman md

Histamine is widely distributed throughout the body, with the highest concentrations in the lung, skin, and gastrointestinal tract. H1 receptors are the most important in producing allergic symptoms. Most first-generation antihistamines have a structural resemblance to histamine. The most important side effect of first-generation antihistamines is sedation. As a consequence, increasing numbers of second-generation antihistamines have become available. The activities of second-generation antihistamines are probably related to the fact that each of these mediators act through a G proteincoupled receptor that is analogous in structure to the receptor for histamine. The advantages of second-generation antihistamines include lack of sedation and ease of use (i.e., once-daily dosing). Antihistamines are important in the treatment of various allergic diseases. Antihistamines are the first-line therapy in the treatment of allergic rhinitis. Antihistamines are also becoming increasingly...

Clinically Investigated Isozymeselective Pi3k Inhibitors

Selectivity of these compounds (and also the PIK-39, PIK-293, PIK-294 analogs) is postulated to arise due to a conformational rearrangement of Met752 (Met804 in PI3Kg), which is distal to the highly homologous adenine binding pocket 22 . CAL-101 is being evaluated as an oral therapeutic in two phase I clinical trials in a recently completed trial as a treatment for allergic rhinitis (presumably as an anti-inflammatory agent) 92 and in an on-going trial as a treatment for cancer, focused on patients with hematologic malignancies 88,93-95 . CAL-101 inhibits p110d-mediated basophil activation in whole blood with an IC50 of 30-70 nM and has demonstrated well-tolerated, sustained plasma concentrations of 500-5000 nM in a 7-day multidose healthy human volunteer study, indicating a viable therapeutic index 88,94 . Although data on preclinical PI3Kd-selective inhibitors other than IC-87114 is limited, recent patent disclosures suggest that this area remains active 96-98 .

IgE ss a Mediator for Many Types of Allergic Diseases

The state of atopy of a person toward certain antigens is created by the generation of IgE-specific antibodies for those antigenic substances, but not all IgE in a person reflects specific sensitization. IgE is well known for playing a central role in the pathogenesis of allergic rhinitis and anaphylactic reactions to foods, drugs, and insect stings. In many studies carried out on patients living in communities in the Western world, elevated IgE levels have been shown to be associated with the risk of developing asthma, although its exact role in the pathogenesis of asthma is not clear. A series of clinical trials demonstrated that anti-IgE effectively attenuates the early- and late-phase reactions and improves symptoms of asthmatic patients. These studies have unambiguously confirmed the association of the IgE antibody and asthma.

IgE Acting Upstream in the Allergic Pathway

The symptoms of an allergic disease may be caused by multiple hypersensitivity reactions involving IgE, other classes of antibodies, and effector T cells. In some allergic states, such as contact skin hypersensitivity, IgE is not the central mechanism. It is understood, however, that in most cases of allergic rhinitis, anaphylactic reactions to foods and drugs, and probably in the majority of cases of allergic asthma (now that anti-IgE has been shown to alleviate the symptoms of allergic asthma in clinical studies), type I hypersensitivity is responsible for the pathogenesis of the disease using IgE as the major mediator.

Human Experience With Antiige Therapy Clinical Studies

Three forms of anti-IgE antibodies have been studied in human clinical trials, with the majority of studies using omalizumab. Multiple phase 2 and 3 studies were performed on adult and adolescent patients with asthma, pediatric patients with asthma, patients with seasonal allergic rhinitis, patients with perennial allergic rhinitis, and patients with concomitant allergic asthma and persistent allergic rhinitis. Phase 3 studies were done on allergic rhinitis patients with both tree pollen sensitivity in the spring and weed sensitivity in the fall, investigating the effect of anti-IgE in combination with specific immuno-therapy. A phase 2 trial was done on patients with severe sensitivity to peanuts and another on patients with sensitivity to latex.

FDA Approval of AntiIgE for Adults with Moderate to Severe Asthma

Mens that may bring about a long-term remission are developed, perhaps less severe patients may also benefit considering overall pharmaco-economic equations. Finally, since the involvement of IgE in the pathogenesis of allergic rhinitis is firmly established, a concept being adopted by increasing numbers of allergists is that those asthma patients with concomitant allergic rhinitis are very suitable patients. This rationale has been backed up by the positive results of a phase 3 trial investigating the effects of omalizumab on patients with both asthma and allergic rhinitis.

Combined With Desensitization Immunotherapy

Desensitization immunotherapy is perhaps the most used treatment for patients with severe allergic rhinitis and allergic asthma, offering the possibility of creating a long-term remission with successful therapy. The major limiting factor of specific immunotherapy includes a limitation of dosage to assure safety. A growing interest among allergists is the use of anti-IgE to achieve both an attenuation of symptoms and a tolerable state for allowing accelerated or more vigorous regimens of immunotherapy.

Roger W Fox md and Richard F Lockey md

Allergen immunotherapy is appropriate and effective treatment in patients who have symptoms of allergic rhinitis and or allergic asthma with natural exposure to allergens and who demonstrate specific IgE antibodies (by skin tests or in vitro tests) to relevant allergens. Allergen immunotherapy is medically indicated in patients with respiratory allergies when symptoms are not controlled adequately by pharmacotherapy and avoidance measures, or when there is a need to avoid adverse effects of pharmacotherapy or a wish to reduce long term use of pharmacotherapy. Randomized, double-blind, placebo-controlled studies show that immunotherapy is effective for the treatment of allergic rhinitis and or asthma. in patients with moderate to severe respiratory allergies, immunotherapy should be considered. Allergen immunotherapy, a series of allergen vaccine injections over a defined period, results in decreased sensitivity or tolerance to inhaled or injected allergens, which can be measured both...

Indications For Allergen Immunotherapy

Allergen avoidance, pharmacotherapy, and patient education form the basis for treating allergic rhinitis, conjunctivitis, and asthma. Allergen immunotherapy is indicated for patients with these diseases who have demonstrated evidence of specific IgE antibodies to clinically relevant allergens and in whom environmental control and pharmacotherapy have failed. The absolute indication for prescribing allergen immunotherapy depends on the degree to which symptoms can be reduced by allergen avoidance, by medication and the amount, type, and length of time medications are required to control symptoms. Immunotherapy, when appropriate, should be used adjunctively with continued environmental control measures and appropriate pharmacotherapy. For stinging-insect-induced anaphylaxis, specific Hymenoptera venom immunotherapy is the treatment of choice. Allergic Rhinitis

Future Trends In Immunotherapy

New technology and advancement of knowledge in the basic mechanisms and patho-physiology of allergic diseases will completely change allergen immunotherapy in the future. These advances should result in new, safer, and substantially more effective methods of manipulating the human immune response. Several approaches may be used (1) novel delivery systems, such as sublingual immunotherapy (the World Health Organization accepts this type of immunotherapy as a valid alternative to the subcutaneous route for allergic rhinitis and asthma) (2) allergen fragments or peptides (devoid of anaphylactic potential) for active immunotherapy (3) IgE-binding haptens of major allergens for passive saturation of effector cells and induction of blocking antibodies (4) plasmid DNA immunization (5) allergen-specific antibodies and antibody fragments for Bousquet J, Michel FB. Specific immunotherapy in allergic rhinitis and asthma. In Busse WW, Holgate ST, eds. Rhinitis and Asthma. Boston, Blackwell...

The Immunodeficiency Disorders

Secondary causes of immune dysfunction must be considered when one is evaluating for immunodeficiency, since secondary disorders occur much more commonly than the primary disorders (Table 2). For the individual with recurrent sinusitis and pneumonia, disorders resulting in impairment of mucus clearance from the respiratory tract such as cystic fibrosis and ciliary dysfunction should be considered. Similarly, the chronic congestion associated with perennial allergic rhinitis can predispose to URI. Opportunistic infection and wasting are hallmark findings of AIDS however, recurrent bacterial infection is common in HIV infection, especially in children. Immunodeficiency related to a single site that is associated with loss of protein in the stool or urine should trigger an

Causes Of Bronchial Asthma Allergic Asthma

About 90 of asthmatics between the ages of 2 and 16 yr are allergic, 70 less than 30 yr are allergic, and about 50 of patients older than 30 yr are concomitantly allergic (Table 2). Thus, coincidental allergies are far and away the most common underlying condition associated with the development of asthma. One should suspect allergy as a contributing factor when (1) there is a family history of allergic diseases, (2) the clinical presentation includes seasonal exacerbations or exacerbations related to exposures to recognized allergens, (3) there is concomitant allergic rhinitis or other allergic disease, (4) a slight-to-moderate eosinophilia is present (300-1000 mm3) or eosinophilia in the sputum is observed, or (5) the patient is less than 40 yr old. Skin testing can be used to confirm immunoglobulin (Ig)E directed against incriminated allergens but does not establish a cause-and-effect relationship. Thus, patients may have a positive skin test but not have clinical symptoms of...

Indole acetic acid derivatives and related compounds

Compound Acid

Numerous 1-indole acetic acid derivatives compounds have been reported as CRTH2 antagonists. These include the tetrahydrocarbazole derivative 17, Rama-troban (BAY U3405), which is currently marketed in Japan for allergic rhinitis 51 . Ramatroban was developed as a thromboxane A2 receptor (TP) antagonist later it was also shown to be a CRTH2 antagonist. Ramatroban has been reported to reduce antigen-induced early and late-phase allergic responses in mice, rats and guinea pigs. In humans, Ramatroban has been reported to attenuate PGD2-induced bronchial hyper-responsiveness 52,53 . It has been postulated that the efficacy observed with Ramatroban in humans cannot be fully explained by its action on TP and that Ramatroban's efficacy in humans is due in part to its CRTH2 antagonist activity 23 . The affinities of Ramatroban and its close analogs, 18 and 19, for the CRTH2 receptor were determined using a 3H -PGD2 binding assay (K values for Ramatroban, 18 and 19 were 4.3, 0.5 and 0.6 nM,...

Targeting BCells Expressing IgE

A 52 week treatment, multicenter, randomized, double blinded, parallel group controlled study to investigate the effect of Omalizumab on intestinal geohelmith reinfection in adolescent patients with allergic asthma and or perennial allergic rhinitis previously treated with an anti-intestinal geohelmith treatment regimen. Brazilan Ascariasis Reinfection Trial CIGE025a 2303. Novartis data on file. Adelroth E, Rak S, Haahtela T, et al. Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis. J Allergy Clin Immunol 2000 106 253-259. Casale TB, Condemi J, LaForce C, et al. Omalizumab Seasonal Allergic Rhinitis Trial Group. Effect of omalizumab on symptoms of seasonal allergic rhinitis a randomized controlled trial. JAMA 2001 286 2956-2967. Chervinsky P, Casale T, Townley R, et al. Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol 2003 91 160-167. Kuehr J,...

Uses of Antihistamines

It is quite clear that nonsedating second-generation antihistamines are the recommended first line of therapy for patients with allergic rhinitis (Table 5). They are usually sufficient to treat symptoms of sneezing, rhinorrhea, and itching associated with mild to moderate allergic rhinitis. They are also helpful for ocular symptoms. However, with the exception of azelastine, little effect on nasal congestion is seen. There is no distinct difference in the efficacy between first- and second-generation antihistamines for the therapy of allergic rhinitis. However, the lack of effect on performance makes second-generation antihistamines the drugs of choice. As with allergic rhinitis, antihistamines are the drug of choice in patients with urticaria. The primary symptom in urticaria is pruritus. Antihistamines exert their major suppressive activities on this symptom. They are usually less effective in reducing wheal size. For patients with chronic urticaria, daily administration may be most...

Coclusion Of Allergic Diseases

Both nedocromil sodium and cromolyn sodium are useful anti-inflammatory drugs in the therapy of allergic diseases. These diseases include asthma, allergic rhinitis, and allergic ocular disorders. Additional therapeutic uses have been proposed. Nedocromil and cromolyn are both available in the United States for asthma therapy, but only cromolyn is available for the treatment of the other conditions.

Pathogenesis Role of Allergens

There is a strong correlation of atopic dermatitis with other atopic conditions such as asthma and allergic rhinitis. The term atopic march has been coined to define the natural history of atopic diseaases characterized by a sequence of progression in the clinical signs of atopic disease with some manifestations becoming more prominent while others subside. Typically, the cutaneous manifestations represented by AD represent the beginning of the atopic march, with approx 50 of patients with AD (especially severe AD) developing asthma and approx 66 developing allergic rhinitis. Because of earlier historical observations of AD associated with other atopic diseases, investigators have explored the role of various allergens as causal factors in these diseases (Table 1). Two other types of aeroallergens are felt to play a role in the pathogenesis of AD animal dander and cockroach allergens. Both of these allergen groups have been studied in association with asthma and allergic rhinitis and...

Antileukotrienes Where Do They Fit In Your Practice

In the 2002 NAEPP guidelines, antileukotrienes are recommended for therapy in patients who have mild or moderate persistent asthma. In the 2002 Global Initiative for Asthma guidelines, antileukotrienes are recommended for therapy in patients who have mild, moderate, or severe persistent asthma. Montelukast is indicated for use in patients aged 12 mo and older, and zafirlukast is indicated for use in patients aged 5 yr and older with chronic asthma. Montelukast is also indicated for use in patients aged 2 yr and older with seasonal allergic rhinitis.

Reasons For Lack Of Benefit From Immunotherapy

Specific allergen immunotherapy is effective treatment for specific patients with allergic rhinitis and allergic asthma. Careful selection of the patient and the relevant allergen(s) for immunotherapy requires expertise and knowledge about the pathophysiology of allergic diseases and regional outdoor and indoor allergen sources. Allergen immunotherapy is indicated for symptomatic patients in whom an adequate trial of environmental control and avoidance and appropriate pharmacotherapy has failed. Reduction of symptoms and the amount of medications required occurs in patients who received optimal maintenance doses of specific immunotherapy for a 3- to 5-yr period. Systemic reactions occur rarely they may range from mild, manifested as generalized pruritus, urticaria, or symptoms of allergic rhinitis and conjunctivitis, to life threatening, with upper and lower airway obstruction and or anaphylactic shock. Fatalities are rare but do occur. A retrospective survey by questionnaire of...

Adjuvant Therapies Acute Bacterial Sinusitis

Patients with a viral URTI may benefit from symptomatic therapy, aimed at improving their quality of life during the acute illness. The use of normal saline as a spray or lavage can provide symptomatic improvement by liquefying secretions to encourage drainage. The short-term (three days) use of topical alpha-adrenergic decongestants can also provide symptomatic relief, but their use should be restricted to older children and adults due to the potential for undesirable systemic effects in infants and young children. Topical glucocorticosteroids may also be useful in reducing nasal mucosal edema, mostly in those cases where a patient who has seasonal allergic rhinitis develops the complication of an acute URTI. The antipyretic and analgesic effects of nonsteroidal anti-inflammatory agents can relieve or ameliorate the associated symptoms of fever, headache, generalized malaise, and facial tenderness. Until the clinical diagnosis of acute bacterial sinusitis is established, management...

Rhinitis Associated With Systemic Diseases or Anatomical Defects

The presence of systemic findings or the persistence of nasal symptoms despite treatment should prompt consideration of systemic diseases or anatomical problems resulting in nasal symptoms. Structural problems typically will present with a predominance of unilateral symptoms or initially unilateral symptoms. Nasopharyngoscopy, paranasal computed tomography, and or otolaryngological consultation are major considerations with lateralizing nasal complaints or bleeding noted from one nasal airway or unremitting congestion (Fig. 5). Nasal septal deviations are the most common anatomical nasal variants noted, but often septal deviation is not primarily responsible for the symptoms unless very severe or coupled with mucosal disease such as allergic rhinitis or PNAR. Profuse rhinorrhea should prompt testing of the secretions for glucose or for p2-transferrin (p-trace protein) to exclude cerebrospinal fluid rhinorrhea. The treatment of allergic rhinitis is three-pronged allergen exposure...

Immunological Changes Induced By Allergen Immunotherapy

The hallmark of asthma and allergic rhinitis is allergic inflammation of the mucosa and submucosa, predominantly caused by eosinophils. TH2 lymphocytes amplify and prolong allergic inflammation and late-phase reactions. TH1 cytokines, i.e., IFN-y and IL-2, inhibit production of TH2 cytokines. Successful immunotherapy is associated with a shift in IL-4 IFN-y production (from IL-4 to IFN-y) either as a consequence of downregulation of the TH2 response or increase in the TH1 response by regulatory T cells screting interleukin (IL)-10 and transforming growth factor (TGF)-p. Not all immunological changes associated with effective immunotherapy occur in all subjects, although there is general correlation between clinical improvement and favorable alterations from baseline immunological parameters. Reduction in biological sensitivity to specific allergens has been demonstrated in allergen immunotherapy trials to such allergens as ragweed, mixed grasses, birch and mountain cedar pollen...

Stacie M Jones MD Ariana Buchanan md and A Wesley Burks MD

Atopic dermatitis is a complex, multifactorial disorder that first develops in most patients before the age of five. The diagnosis relies on information compiled from all aspects of clinical history, physical examination, and laboratory data. Strong correlations exist between atopic dermatitis and other atopic conditions such as asthma and allergic rhinitis. Underlying IgE-mediated sensitivitiy to both aeroallergens and foods have been shown to be strong triggering factors in atopic dermatitis. In addition, Staphylococcus aureus can exacerbate atopic dermatitis both by causing secondary infection of compromised skin and by secreting exotoxins that function as superantigens directly stimulating T-cell proliferation. Successfut treatment of atopic dermatitis involves a multifaceted approach that addresses avoidance of underlying triggering factors, proper care of dry skin, and pharmacologic management, including oral antipruritic agents, topical corticosteroids, and oral antibiotics...

Syk kinase inhibitors which have progressed to clinical studies

R112 (8) is the first small molecule inhibitor of Syk kinase that has advanced to Phase 2 clinical trials 22,65 . Compound 8 inhibited Syk kinase with Ki 0.096 mM, selectively inhibited tryptase release from human mast cells induced by anti-IgE cross-linking, histamine from basophils, and dust mite allergen induced histamine release from human basophils with EC50s 0.353, 0.28 and 0.49 mM, respectively. One advantage of compound 8 was its rapid onset of action since rapidly effective treatment is highly desirable during an allergic attack. Compound 8 also inhibited leukotriene C4 (LTC4), proinflammatory cytokines, including tumor necrosis factor a (TNFa), GM-CSF and IL-8, with EC50s 0.115, 2.01,1.58 and 1.75 mM, respectively. Compound 8 was advanced to a Phase 2, double-blind, randomized, placebo-controlled, parallel-group seasonal allergic rhinitis trial in a park environment over a period of 2 days at two sites 65 . Patients received 6mg of compound 8 b.i.d via metered spray pump...

Diagnosis

For many infants and young children, it is common to wheeze with viral respiratory infections. For some of these children, the symptoms may subside in the preschool years, whereas others will have more chronic symptoms. There are prognostic indicators that may help the clinician in identifying preschool-aged children with recurrent wheezing who are at risk for developing persistent asthma. These prognostic indicators include having a parent with asthma or the wheezing child having eczema, allergic rhinitis, wheezing episodes apart from colds, and or eosinophilia greater than 4 . Children and their parents often ask whether they will outgrow asthma and whether asthma will return after remission. Sensitization to house dust mite airway hyperresponsiveness, female sex, smoking, and early age of asthma onset are associated with asthma persistence and relapse, as shown in Table 1. On physical examination, findings may be subtle or absent. Wheezing may or may not be present. Evidence of...

Occupational Asthma

In 1951, Churg and Strauss described a vasculitic process that had pathological findings and clinical features warranting the designation of a separate disease entity, allergic angiitis and granulomatosis. The disease is characterized pathologically by necrotizing vasculitis, tissue infiltration by eosinophils, and extravascular granulomas. The disease has three phases, beginning with a prodrome of allergic asthma and allergic rhinitis that may exist for many years. The second phase includes eosinophilia along with the development of pulmonary eosinophilic infiltrates resembling Loffler's syndrome, eosino-philic pneumonia, or eosinophilic gastroenteritis. The third phase is the vasculitic phase involving pulmonary vessels (96 ), skin (67 ), peripheral nerves (63 ), the gastrointestinal tract (42 ), heart (38 ), and kidney (38 ). The syndrome affects males and females equally the onset of first stage involving allergic rhinitis and asthma occurs around the age of 30 yr, while the...

Trpm2trpm5trpm8

TRPM8 knockdown data indicate that it could represent an important neuronal axis that can be exploited in chronic sensitized pain states 59 . Additionally, modulators of TRPM8 have potential utility for the treatment of asthma, chronic obstructive pulmonary disease, and allergic rhinitis 60 . Based on expression patterns, TRPM8 modulators could even play an important role in prostate cancer. Recently, menthol-based TRPM8 agonists (33) have been reported to significantly inhibit the growth of TRPM8 positive tumors in mice by as much as 77 at well-tolerated doses 61,62 .

Dennis K Ledford md

Classification of Allergic Rhinitis Differential Diagnosis Treatment of Allergic Rhinitis Conclusion Suggested Reading Allergic rhinitis is a common condition with a diverse differential diagnosis and multiple therapeutic options. Optimizing treatment by verifying the diagnosis and directing therapy to the most bothersome symptoms will result in improved quality of life. Key Words Nasal polyp antihistamine corticosteroid rhinitis allergic rhinitis nonallergic rhinitis immunotherapy. atrophic, polypoid or hyperplastic rhinitis, and rhinitis associated with systemic diseases (Table 1). Some authorities divide nonallergic rhinitis into subgroups based on triggers,for example, weather, odor, alcohol ingestion, or irritants, but the symptoms and physical findings of these rhinitis subgroups tend to be more alike than dissimilar, prompting others to classify all into one category. Occupational rhinitis is a classification sometimes used, referring to irritant, nonallergic rhinitis or...

Medical Therapy

Topical and oral decongestants reduce nasal congestion associated with acute sinusitis and may reduce ostial edema, allowing for improved sinus drainage. Older antihistamines with strong anticholinergic effects such as diphenhydramine and hydroxyzine may cause mucous inspissation and make it more difficult to clear secretions. However, the newer second- and third-generation antihistamines such as loratadine, cetirizine, and fexofenadine have virtually no anticholinergic effects and can be continued in patients who require these agents for concomitant allergic rhinitis.

Adjunctive Therapy

Antihistamines are used in patients with underlying allergic rhinitis. They can relieve symptoms of itching, rhinorrhea, and sneezing in allergic patients, but in nonallergic patients they can cause thickening of secretions, which may prevent needed drainage of the sinus ostia.

Disorders

Azelastine is a second-generation H1 receptor antagonist that was first shown to be clinically effective in relieving the symptoms of allergic rhinitis following oral or intranasal administration and is presently approved for allergic conjunctivitis. Pemirolast potassium, a pyridopirimidine compound, is approved in Japan for use in the treatment of bronchial asthma, allergic rhinitis, and allergic vernal conjunctivitis. Although its mechanism is not entirely understood, it appears from available data that pemirolast prevents mast cell degranulation and subsequent release of histamine (and 5-hydroxytryptamine in some species), perhaps through inhibition of phospholipid by-products involved in intracellular signal transduction.

Genetic Associations

Like other atopic conditions, AD has a strong genetic predisposition. As many as 6080 of patients with AD have a family history of a first-degree relative with AD, asthma or allergic rhinitis. In studies of twins, Rajka reported a much higher concordance for atopy in monozygotic twins, whereas AD alone revealed only a 50 concordance in both monozygotic and dizygotic twins. Rajka's data cast doubt on the strictly hereditary influence, yet underscore the importance of the combination of hereditary and environmental factors in the disease process. Numerous reports have suggested HLA associations among families with atopic disease in general and AD specifically. Based on genomic studies assessing for susceptibility loci for atopic dermatitis, multiple pathophysiologically relevant candidate genes have been identified including areas on chromosome 3q21, 1q21, 17q25, and 20p. An area on chromosome 5q31-33 that contains a clustered family of Th2 cytokine genes has been of particular...

Skin Test Reactions

Have strict clinical relevance and must be analyzed in light of the clinical history. For aeroallergen sensitivity, findings of seasonal distribution of other associated disease, such as allergic rhinitis and asthma, may provide additional clues for interpreting positive skin tests and instituting appropriate avoidance procedures. In the case of food allergen sensitivity, sampson found prick skin tests to have an excellent negative predictive accuracy of 82-100 , but a poor, highly variable, positive predictive accuracy of 2575 when compared to blinded food challenge. Positive results must be correlated with the clinical history and dietary assessment and then confirmed with a trial of an allergen-elimination diet and subsequent food challenge.

Phototherapy

Recently, omalizumab, a humanized IgG1 monoclonal antibody against IgE has been shown to be effective in treatment of allergic asthma and allergic rhinitis. As such, this therapy could potentially decrease the effects of IgE in AD, but the high serum IgE levels seen in AD may limit its utility. However, omalizumab may have a role in treatment of food-induced AD. In a population of peanut-allergic patients, the threshold of sensitivity to peanuts on oral food challenge was significantly increased after treatment wiht anti-IgE, suggesting protection against unintented ingestion of the food allergen.

Immunotherapy

Although allergen immunotherapy has been useful in some atopic conditions (i.e., allergic rhinitis), its role in the treatment of AD has been limited. In clinical practice, immunotherapy will frequently exacerbate the condition of AD rather than provide relief. Some clinicians advocate the use of immunotherapy, especially in older patients with significant aeroallergen hypersensitivity, but recommend initiating therapy with a much smaller dilution of allergen extract than in standard therapy for allergic rhinitis. The dose of extract needed to induce tolerance is often greater than the dose tolerated by the patient with AD, thereby precluding its use in most patients.

Prognosis

Currently there are no prospective, longitudinal studies evaluating the prognosis and disease remission of AD. Vickers retrospectively evaluated 2000 children with AD after 20 yr and noted an overall clearance rate of 84 . Vowles likewise evaluated 84 patients after 13 yr and found only 45 resolution of disease. These and other studies reflect the difficulty in assessing prognosis with reports of disease resolution ranging from 37 to 84 in various retrospective surveys. In addition, no specific disease factors are predictive of the disease severity or course. Some patients are noted to have spontaneous resolution of their disease during infancy and early childhood. Improvement may also be seen during puberty in some patients, but exacerbations noted in others. Cases in adults will often resolve or significantly improve after the second decade of life. As is common with atopic diseases, some cases of AD resolve, but patients develop other forms of atopy such as allergic rhinitis and...

John A Anderson md

Adverse reactions to foods can be divided into those that are allergic and those resulting from food intolerance. Allergic food reactions are IgE-mediated and are usually limited to individuals with other atopic diseases such as allergic rhinitis, atopic dermatitis, and allergic asthma. The serious form of IgE-mediated reactions to food is anaphylaxis. The most common foods to cause this are peanuts, shellfish, and tree nuts. Acute urticaria from foods is also most commonly caused by these three agents. Atopic dermatitis can be related to food allergy as well.

Atopic Dermatitis

Atopic dermatitis (AD) is an inherited genetic skin disorder that involves both IgE- and cell-mediated immune mechanisms. After allergen-induced mast cell activation, the skin is infiltrated by monocytes, lymphocytes, and finally eosinophils and their by-products. Severe purities precedes the eczema, which has a characteristic distribution in infancy, childhood, and adult life. In allergic families, this condition begins in early infancy, often as breast-feeding is discontinued, and usually begins to clear by 3-5 yr of age. By this time the child often has additional symptoms of allergic rhinitis, asthma or both leading to the use of the term dermo-respiratory syndrome.

History

Most individuals who develop food allergies have other manifestations of allergy or have family members with allergic disease. This includes atopic dermatitis, urticaria, asthma, and allergic rhinitis conjunctivitis. A history of asthma in a food-allergic individual should be considered a risk factor for possible serious life-threatening reactions of an anaphylactic nature to that food.

Allergic disorders

4.1.1 Allergic rhinitis, asthma and atopic dermatitis Allergic rhinitis is characterized by IgE-mediated hypersensitive immune responses to seasonal or perennial allergens in the upper airways. Current therapies include anti-histamines and anti-cysteinyl leukotrienes, but most effective, albeit showing slow onset of action, are locally applied corticosteroids that owe their broad anti-inflammatory effects to their potent blocking of chemokine and cytokine production 4 . It has been reported that the glucocorticoid dexamethasone could inhibit Syk via inhibiting IgE-dependent cell activation by inducing the expression of Src-like adapter protein (SLAP), a negative regulator of Syk action 20 . Syk inhibitors are expected to elicit broad symptom control since genetic or pharmacologic Syk inhibition blocks the production and release of all IgE-mediated inflammatory mediators by mast cells and basophils

IgE Receptors

IgE is known as the main antibody involved in allergic inflammatory processes such as asthma, atopic dermatitis, and allergic rhinitis. Two distinct receptors have been demonstrated for IgE the high-affinity IgE receptor (FceRI), and the low-affinity IgE receptor (FceRII).

Stephen F Kemp md

Allergic Rhinitis Allergic Eye Disease Both nedocromil sodium and cromolyn sodium are anti-inflammatory drugs that may be used in the therapy of allergic diseases. These diseases include asthma, allergic rhinitis, and allergic ocular disorders. Additional therapeutic uses have been proposed. Nedocromil and cromolyn are both available in the United States for asthma therapy, but only cromolyn is available for the treatment of the other conditions. Recent publications in the evidence-based literature have upheld the safety profile of nedocromil and cromolyn but increasingly suggest that other topical anti-inflammatory agents are more effective and have comparable safety at recommended doses. Nedocromil sodium and cromolyn sodium both can be used prophylactically prior to isolated allergen exposures and must be used regularly for maintenance therapy. No consistent, severe adverse reactions occur with either drug. Cromolyn sodium and nedocromil sodium are two nonsteroidal...

Atopic Eczema

Atopic eczema is a recurrent inflammatory skin condition that produces redness, itching, and scaly patches. People who have atopic eczema also often have other allergic conditions, such as allergic rhinitis (see page 379) or asthma (see page 245), or are allergic to penicillin or sulfa. Atopic eczema is a very common condition that affects about 3 percent of Americans. The disorder can occur at any age but typically appears between infancy and young adulthood. The condition often improves on its own before puberty but also can persist throughout life.

Robert Q Lanier md

The development of a drug to affect the basic cause of allergic disease has invigorated practicing allergists' interest in the intricate molecular and cellular processes occurring in allergic reactions. An anti-immunoglobulin (Ig)E antibody is not merely a chemical blocking agent, but possesses potential multiple immunoregulatory effects. A lead product, omalizumab, a recombinant humanized IgG1 antibody with a unique set of binding specificities toward human IgE, has been approved in the United States and Australia for treating adult and adolescent patients with moderate to severe asthma. Applications of this biopharmaceutical in treating allergic rhinitis and for protecting against anaphylactic reactions to peanuts are in active development. It may also have an important role in protection against anaphylaxis during standard antigen specific immunotherapy, providing safety and the ability to more aggressively extend this traditional therapy

Infection Control

In 1996, the Hospital Infection Control Practices Advisory Committee (HICPAC) recommended a number of isolation and barrier precaution practices for HCWs when caring for patients with MRSA (Garner 1996). The most fundamental measure to reduce cross-infection is hand hygiene. It is amazing how low compliance to this important and simple measure is. However, hand hygiene alone is not enough to control MRSA. The Centers for Disease Control and Prevention (CDC) published a guideline in 2002, recommending a number of new strategies for improving hand hygiene among HCWs (Boyce and Pittet 2002). The Society for Healthcare Epidemiology of America (SHEA) published a further reaching guideline in 2003 to prevent transmission of multidrug-resistant strains of S. aureus and enterococci (Muto et al. 2003). Most basic infection control meausures are widely agreed upon, including identification and isolation of patients infected or colonized with MRSA in a single room with toilet and hand-washing...

Ocular Conditions

Other ocular conditions seen in association with AD include conjunctivitis, keratitis and keratoconus (elongation of the corneal surface). Conjunctivitis is frequently a year-round complication of AD, but may also be seen in a seasonal distribution in association with allergic rhinitis in patients with aeroallergen hypersensitivity. Vernal conjunctivitis, characterized by a cobblestone pattern of papules on the inner eyelid, may be especially troublesome, requiring prompt treatment to prevent corneal abrasion. The association of AD and keratoconus is unexplained, yet of concern in approx 1 of patients with AD. Corneal erosions may also be seen in patients with secondary herpetic infections that go undiagnosed and untreated.

Tryptase inhibitors

RWJ-58643 (4) was discontinued from an allergic rhinitis trial (phase Ila) due to its taste 26 . In this single center, randomized and double-blind study, single topical nasal doses of 4 (100, 300, and 600 mg) or placebo were given to 16 male patients with grass pollen allergic rhinitis followed by a nasal allergen challenge. Significant reductions of symptoms, as well as eosinophil and IL-5 levels were found in the two lower dose groups, however, the efficacy was not dose responsive. Futhermore, late eosinophilia was observed in the higher dose groups 27 .

Allergic Disease

The incidence of asthma and allergic disease is rising. However, primary care physicians have dealt with allergic conditions far more often than they may expect even before the development of these recent epidemiological trends. Some examples of immunological disease that the primary care physician has encountered include asthma, allergic rhinitis, and atopic dermatitis. The incidence of asthma and allergic disease is rising. However, primary care physicians have dealt with allergic conditions far more often than they may expect even before the recent increase in allergic conditions. Some examples of immunological disease that the primary care physician sees include asthma, allergic rhinitis, and atopic dermatitis. To illustrate the importance of allergic disorders in clinical medicine, consider that physicians obtain an allergy history before prescribing any antibiotic because of the high incidence of drug reactions in the population. Just as IgE production and mast cell activation...

Analgesia

The pyrazine benzazepine analog 15 (GSK207040) had subnanomolar affinity for human (Ki 0.21 nM) and rat receptors (Ki 0.83 nM) and was a full inverse agonist (EC50 0.63 nM) 51 . The rat oral bioavailability of GSK207040 was 88 with an i.v. t1 2 of 2.6 h. GSK207040 p.o. inhibited ex vivo 3H -R-a-methyl-histamine binding (ED50 0.03 mg kg) and was also active in the rat dipsogenia model. In pathophysiologically relevant pharmacodynamic models, GSK207040 reversed scopolamine-induced amnesia in a passive avoidance paradigm and reversed capsaicin-induced reductions in paw-withdrawal threshold 51 . GSK has also disclosed pyrazolo 3,4-d azepines 52 and thiazolo 4,5-d azepines 53 heterocyclic azepine cores. Incorporation of the basic nitrogen into a diazepine ring is represented by 16 (GSK334429) 51 . GSK334429 displayed subnanomolar affinity for human and rat receptors and had good oral bioavailability and intrinsic pharmacokinetic properties in rat. GSK207040 and GSK334429 produced...

Dust Mite Allergen

However, two high-profile publications in the New England Journal of Medicine suggested that the clinical benefit of using bed covers alone is limited. The first of these studies was a randomized trial of mite impermeable vs control bed covers in 1122 adult patients with asthma requiring inhaled corticosteroids. Although there was an effect on the mite content of mattress dust, there was no difference in peak flow rates or asthma medication requirements after a year. Interestingly, both treatment and control groups had equal improvement over the yearlong trial. A similar randomized trial was conducted among 279 patients with allergic rhinitis. This trial again reported lower mite content in mattress dust, but no discernible clinical improvement. When taking into consideration the available data, one realizes that there are many potentially effective methods to decrease mite exposure. Unfortunately, few single methods or combinations of methods have been tested in randomized,...

Acute Sinusitis

Optimal duration of therapy for acute bacterial sinusitis has not been well-defined, but most textbooks recommend a 7- to 14-day course (6,28). Problems include the uncertainty of diagnosis using clinical assessment, radiography, ultrasound or computerized tomography, and difficulty differentiating bacterial sinusitis from viral or allergic rhinitis. In addition, most studies have involved acute maxillary sinusitis and it is not clear that these data can be applied to frontal, ethmoid, and sphenoid sinusitis.

Epidemiology

The prevalence of atopic disease in general and of allergic rhinitis in particular has increased during the past century. Currently, the prevalence of allergic rhinitis is approx 30 , increased from approx 10-15 at the mid-point of the 20th century. The increase is more apparent in affluent socioeconomic circumstances, particularly western Europe, North America, Australia, and New Zealand. Explanation for this increase remains elusive, with a variety of hypotheses (summarized in Table 4). The hygiene hypothesis, as first suggested by Salzman and colleagues in 1979, is probably the most widely accepted explanation. This hypothesis proposes that reduced infections and endotoxin exposure in infancy diminishes the stimuli to convert the TH2-like immune response (allergic-like with a predominance of interleukin IL -4 and IgE production) present at birth to a TH1-like response (nonallergic with interferon-y production and reduced IgE). The endotoxin association suggests that the innate...