Rhinitis Ebook

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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 on Asthma (ARIA) Workshop, in collaboration with the World Health Organization, recommended a different classification, using the terms intermittent and persistence and the severity classifications of mild, moderate, and severe. Intermittent is defined as having symptoms for less than 4 wk of the year. Mild is defined as not affecting quality of life. Most subjects who seek medical care are expected to be in the moderate to severe persistent category, because over-the-counter products are available for treatment of less severe disease. Published studies report...

Nonallergic Rhinitis with Eosinophilia

Nonallergic rhinitis with eosinophilia (NARES) is a syndrome that is generally distinguished from PNAR by the presence of eosinophils in the nasal secretions or mucosa. The symptoms cannot be distinguished from PNAR, and the family history is generally negative, increasing the clinical confusion between NARES and PNAR. Affected subjects are 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. 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...

The Common Cold and the

The common cold and the flu (influenza) are both caused by viruses. The viruses that cause colds and the flu are transmitted when an infected person coughs or sneezes into the air and another person inhales the infected droplets. You can also catch a cold or the flu by kissing an infected person or by touching your mouth after touching the other person's hands or an object he or she has touched. Each cold is caused by a different virus, and there are nearly 200 different cold viruses. Adults average about two to four colds per year. The virus that causes the flu changes from year to year that is why a flu immunization is good for only a year. When these viruses enter your body, they multiply rapidly. Your immune system tries to fight them, producing symptoms that include coughing, sneezing, and a runny nose. Many people confuse the common cold with the flu, but there is one easy way to tell the difference the flu usually causes a fever, while a cold does not. Also, a cold causes nasal...

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,

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...

Rhinitis Induced by Drugs or Hormones Rhinitis Medicamentosa

Topical use of a-adrenergic decongestant sprays for more than 5-7 d in succession may result in a rebound nasal congestion upon discontinuation of treatment or after the immediate effects have waned. Continued use of the decongestant to control withdrawal congestion can lead to an erythematous, congested nasal mucosa termed rhinitis medicamentosa. Regular intranasal cocaine use will have the same effect and should be considered in the differential diagnosis. Other systemic medications or hormone changes may also be associated with nasal symptoms, although the nasal mucosa may not always appear the same with each medication. The mechanisms responsible for nasal symptoms associated with medications or hormones are variable. Antihypertensive therapies with p-blockers and a-adrenergic antagonists probably affect regulation of nasal blood flow. Oral a-adrenergic antagonists are also commonly utilized for symptom relief of prostate enlargement. Topical ophthalmic p-blocker therapy may also...

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. Wegener's granulomoatosis may present initially with upper airway...

Atrophic Rhinitis

Atrophic rhinitis usually occurs in late middle-aged to elderly patients. The cause of atrophic rhinitis is unknown, with the leading theory being age-related mucosal atrophy, sometimes complicated by secondary bacterial infection. Primary atrophic rhinitis resembles the rhinitis associated with Sjogren's syndrome or previous nasal surgery, including extensive turbinectomy. Examination generally reveals a patent nasal airway with atrophic, erythematous turbinates, despite the symptoms of congestion. Some subjects with atrophic rhinitis report nasal congestion, crusting of the nasal airway, and a bad smell (ozena). Ozena is associated with bacterial overgrowth of the mucosa, particularly Klebseilla ozaenae and Pseudomonas aeruginosa. The appearance of ozena may resemble chronic granulomatous disease, such as Wegener's granulomatosis or sarcoidosis, or the effects of previous local irradiation. The prevalence of ozena is variable, with a greater occurrence in select geographic areas,...

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...

Rhinitis

Rhinitis (common cold) is an inflammation of the nasal mucous membrane or lining. Depending on the host response and the etiologic agent rhinitis is characterized BOX 54-1 Viral Agents That Can Cause Rhinitis by variable fever, increased mucous secretions, inflammatory edema of the nasal mucosa, sneezing, and watery eyes. With rare exceptions, rhinitis is caused by viruses some of these agents are listed in Box 54-1. Rhinitis is common because of the large number of different causative viruses, and reinfections may occur with same virus type.

The Virus And The Host

The pathogenesis can in most cases be ascribed to degeneration and death of the infected cells. This may be mediated directly by the virus or by the immune clearance mechanisms. Denatured proteins elicit local inflammatory and systemic reactions. The local inflammatory response dominates the clinical picture in some infections, such as common colds, croup and bronchiolitis, while cell and organ failure or dysfunction is typical in poliomyelitis and hepatitis. Some infections are particularly dangerous to the fetus (CMV infection, rubella) or to the child in the perinatal period (herpes simplex, coxsackie B, varicella-zoster, hepatitis B and HIV infections). Bronchiolitis is seen only in the first 2 years of life, and croup mostly in children below school age. Otherwise the clinical course is not markedly different in children compared with adults.

How Are New Antivirals Discovered

Once a molecule binding to a viral protein has been located, a more efficient molecule can be 'designed' by the chemists. Excellent examples of semi-designed antivirals are inhibitors of the common cold virus, which bind tightly to the viral capsid protein and which can be visualized by X-ray crystallography in the binding pocket on the virion surface, and also inhibitors of the influenzavirus neuraminidase enzyme. In the latter case the enzyme-active site had been identified as a saucer-like depression on the top of the viral

The Nature Of Virus Reservoirs

A significant number of human viruses leading to either mild or life-threatening disease are maintained in human populations. The list runs the gamut from colds caused mainly by rhi-noviruses, warts caused by papillomaviruses, to AIDS caused by HIV. The mode of passage of viruses between humans (i.e., the vector) is intimately involved with human behavior. This behavior can be modified by the disease symptoms themselves. Thus, a respiratory infection leads to coughing and sneezing, which spreads an aerosol of droplets containing virus. HSV is spread in saliva requiring direct transfer of an aqueous suspension by contrast, the closely related varicella zoster (chicken pox) virus (VZV) is spread by inhalation of a virus-loaded aerosol. Warts are spread by direct physical contact between the virus-loaded source (another wart or a passive reservoir) and layers of the skin below the keratinized epidermis exposed by small cuts or abrasions. Poliovirus is spread only by virus-containing...

Relenza And Tamiflu Inhibitors Of Influenza A And B Neuraminidase

Both drugs bind to a group of 11 or so amino acids in the active site of the NA enzyme. These amino acids are constant in all current influenza A and B viruses and so the drugs inhibit all these viruses. Even previous pandemic viruses such as the Great Pandemic of 1918 have a near identical active site and are inhibited. Drug-resistant mutants have been described but to date appear less pathogenic and less infectious than the wild-type virus and thereby would not be expected to spread in the community. Although research is continuing with anti-common cold drugs none to date has shown strong enough clinical effects to warrant extensive use and virtually no drugs exist for the remaining important respiratory viruses, namely adenoviruses, parainfluenzaviruses or coronaviruses.

The Most Recent Past And The Future

Scientifically, major drug discoveries are most likely to emerge from a judicious mixture of biology and X-ray crystallography whereby existing compounds are closely analysed for their binding or target interactions at the molecular level. Already this approach has led to the refinement of the two drugs binding to influenza A and B neuraminidase, protease inhibitor of HIV and a drug against the common cold virus. Virologists are anticipating a new influenza pandemic and therefore antivirals with a broad antiviral spectrum would be comforting to have. Amantadine itself does inhibit most, if not all, of the influenza A subtypes known to exist in humans, birds, pigs and horses and so might be expected to inhibit even a new pandemic influenza A virus. The new neuroaminidase inhibitors would also act against pandemic influenza A virus.

The Glorious Pastand The New Challenges

Great optimism followed the successful smallpox programme, but not all infectious diseases of viral aetiology may be so amenable to control. In particular, a vaccine against HIV may be more difficult to develop than at first anticipated. Nevertheless, there is a range of virus diseases within reach of being controlled by vaccination at least in developed countries. Poliomyelitis is for all practical purposes eliminated from many countries through extensive use of either live (attenuated) or killed (inactivated) vaccines among children. In some developed countries measles is now close to eradication or is an extremely rare disease, and through continued mass vaccination mumps and rubella may also become infections of the past. On the other hand, influenza is difficult to control by vaccination since the virus changes its antigenic properties and previously acquired immunity becomes obsolete. It may be even more difficult to control such illnesses as the common cold because of the...

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 .

Questions For Chapter

Of Spitzbergen Island off the coast of Norway (see Fig. 3.2). Suppose that a team of scientists plans to visit this island by special boat during the Christmas holiday season. How might this visit change the pattern of respiratory infections you have been observing What criteria must exist for this visit to have an effect on the pattern of viral respiratory illness on the island

Regulating the Public Sector

Even though algorithms may be closely followed, what is uncertain is how much diagnosis creep occurs (Hsia et al., 1988 Carter et al., 1990). For instance, in response to patient pressure, or their own inclinations, is clinic staff more likely to diagnose a lower respiratory tract infection requiring antimicrobial therapy, rather than upper respiratory tract infection, which algor-ithmically does not require antimicrobials, even though the signs and symptoms might be characteristic of the latter Or diagnose dysentery (also requiring antimicrobial therapy) rather than watery diarrhea, which does not require antimicrobial therapy

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...

The Cultural Perspective

Cultural views of infectious conditions that require antibiotic treatment differ between countries.15 Deschepper and co-investigators have contrasted labeling of disease and patients' attitude toward upper respiratory tract infections (URTI) in a Dutch and a Belgian city.16 The Dutch participants labeled most URTI episodes as common cold or flu. The Flemish participants labeled most of their URTI episodes as bronchitis and used more antibiotics. In general, participants with a Protestant background were more skeptical about antibiotics than those with a Catholic background. Likewise, antibiotic consumption in countries with predominantly Protestant populations is generally lower than those with predominantly Catholic populations.2 However, this is not always true notably Austria has an antibiotic consumption comparable to that of Germany.5 This suggests that, although the main religious background is part of a country's culture, other factors may be better suited to describe the...

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,...

Symptoms And Signs

After an incubation period of 2-4 days, the illness starts with symptoms of nasal congestion blockage and irritation, sneezing and a sore throat. Excess nasal secretion follows which is serous at first and later becomes purulent if secondary bacterial infection ensues. Cough is a frequent symptom, as is headache during the first days of illness. Fever occurs seldom, and if so, it is moderate. Rhinovirus infection causes the same symptoms in all age groups. The infection is limited to the respiratory tract. It has been suggested that rhinoviruses may cause a more serious infection of the lower respiratory tract in small children. Rhinovirus infection has also been shown to precipitate attacks of asthma in children and aggravate chronic bronchitis in adults. Asymptomatic infections are reported to occur in about 25 of individuals infected with rhinovirus. Differential diagnosis. Symptoms of common cold, particularly in children, may be due to other virus infections, e.g. influenzavirus,...

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...

Therapy And Prophylaxis

In addition to inhalation of droplets, spread of infection by contact is considered to play a significant role. Measures should be taken to avoid infection from virus-contaminated hands. Persons suffering from asthma and from chronic bronchitis should avoid close contact with common cold patients.

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& shy matory test to Stepwise Approach to the Treatment of Seasonal Allergic Rhinitis Perennial allergic rhinitis in adults Intermittent disease ''Sedating, traditional (first-generation) antihistamine therapy is a consideration because of cost of second-generation antihistamines. However, functional impairment occurs with...

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.

Sexually Transmitted Diseases

After colds and the flu, STDs are the most common infectious diseases in the United States, with more than 15 million new cases each year, 3 million of them among teenagers. By age 21, nearly one in five Americans requires treatment for a disease acquired through sexual contact.

Respiratory Syncytial Virus

RSV is the most important pathogen encountered in lower respiratory tract infections (bronchiolitis and pneumonia) in infants and small children. Among older children and adults reinfections are common. Clinically, these reinfections are usually manifested as upper respiratory tract infection (URTI). Epidemics of RSV occur regularly during the colder months in temperate climates and during the rainy season in tropical areas.

Pulmonary Pathophysiology

Bronchitis is an inflammation of the airways resulting in excessive mucus production in the bronchial tree. Bronchitis occurs when the inner walls of the bronchi become inflamed. It often follows a cold or other respiratory infection and happens in virtually all people, just as the common cold. When the bronchitis does not go away quickly but persists, then it is termed chronic bronchitis.

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)....

Equilibrium density gradient centrifugation See isopycnic gradient centrifugation

Equine arteritis virus (EAV) The type species in the genus Arterivirus. Horses are the only susceptible species. Causes epizootics and is highly contagious, infecting mainly young animals via the respiratory tract. Causes fever, conjunctivitis, rhinitis, edema of the legs and trunk, enteritis and colitis. In pregnant mares the fetus may become infected and abortion occurs. Bronchopneumonia and pleural effusions occur in fatal cases. There is medial necrosis of small arteries and when the intima is involved, thrombosis. The virion is 50-70nm in diameter with a core 20-30nm in diameter, enveloped, inactivated by lipid solvents and low pH. Replicates in horse kidney cell cultures with CPE. Virus becomes attenuated on passage in tissue culture and can be used as a vaccine. Synonyms epizootic cellulitis virus equine infectious arteritis virus equine influenza virus fievre typhoide du cheval virus infectious arteritis of horses virus pferdestaupe virus pink eye virus.

Equine morbillivirus EMV See Hendra virus

Equine rhinitis A virus (ERAV) A species in the genus Aphthovirus. Causes upper respiratory tract infections of horses whereas all other members of the genus cause foot-and-mouth disease. Included in the genus because of similarities in genome organization and structure to Foot-and-mouth disease virus. Synonym equine rhinovirus 1. Equine rhinitis B virus (ERBV) An unas-signed species in the family Picornaviridae. Causes upper respiratory tract infections of horses. equine rhinovirus 1 Former name for Equine rhinitis A virus. equine rhinovirus 2 Former name for Equine rhinitis B virus. equine rhinovirus 3 (ERV3) An unassigned virus in the family Picornaviridae. Replicates with CPE in cell cultures of horse, monkey, humans and rabbit tissue. Does not require low temperature or low bicarbonate. Worldwide infection causing rhinitis and pharyngitis, often with fever. Incubation period 3-7 days. Rabbits, guinea pigs, monkeys and humans can be infected. Spreads readily in stables virus may...

Far East Russian encephalitis virus

Feline calicivirus (FCV) A species in the genus Vesivirus. Several serotypes are described. Most strains have been isolated from the respiratory tract but some may be associated with the gastrointestinal tract. Experimental exposure to aerosol of virus caused rhinitis, conjunctivitis, oral ulceration and pneumonia. Infection most often seen in catteries, may be mild or severe, even fatal. Replicates in cultures of feline cells more readily than rhi-novirus. An attenuated strain is used as a vaccine, given intranasally or i.m. Synonyms cat flu virus.

Clinical Signs and Diagnosis

Acute adenoiditis may occur alone or in association with rhinitis or tonsillitis. It produces pain behind the nose and postnasal catarrh, lack of resonance of the voice, nasal obstruction, and feeding difficulties in infants, and it is often accompanied by cervical adenitis. Chronic adenoiditis may result from repeated acute attacks or from infection in small adenoid remnants. The main symptom is postnasal drip. This secretion is seen to hang down behind the soft palate as tenacious mucopus. Mouth breathing and persistent rhinitis are characteristic symptoms. With severe adenoid hypertrophy, the mouth is kept open during the day as well as during sleep, and the mucous membranes of the mouth and lips are dry. Chronic nasopharyngitis may be constantly present or recur frequently. The voice is altered, with a nasal, muffled quality. The breath is foul smelling and frequently offensive, and taste and smell are impaired. A harassing cough may be present, especially at night, resulting from...

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.

Infections And Their Management

Innocuous viruses increasingly recognised. For example, rhinoviruses, a cause of the common cold, are now known to be associated with severe lower respiratory disease in the immunocompromised and exacerbations of asthma (Gern and Busse, 1999 Greenberg, 2003). Similarly, though it is true that many viral infections remain untreatable, effective treatment is now available for several serious conditions, such as aciclovir in herpes simplex virus (HSV) encephalitis, ribavirin for Lassa fever, and combination antiretroviral therapy for human immunodeficiency virus (HIV).

Limit antiviral use where possible

In the majority of patients most viral infections do not require treatment. This will limit adverse effects and selection of resistant virus. For example, although aciclovir is an effective treatment for primary varicella zoster infection (chickenpox), there is little benefit in treating children with uncomplicated infection, as the illness is generally self-limiting with serious complications being rare (Tarlow and Walters, 1998). Similarly, although the drug pleconaril has recently been shown to reduce the severity of rhinovirus infections (Hayden et al., 2003), its use is not currently indicated in upper respiratory tract infections in otherwise healthy patients. It is also important not to use antivirals in situations where they have been shown not to be of benefit. Thus, although aciclovir can inhibit Epstein-Barr virus replication in vitro, it has not been shown to be effective in cases of glandular fever, probably due to the immune-mediated nature of the illness (van der Horst...

Human astrovirus 18 HAstV1 to

Human coronaviruses 229E and OC43 (HCV-229E and HCV-OC43) Species in the genus Coronavirus. Cause acute respiratory disease (common colds) in humans mainly from January to March. 229E virus was isolated in 1966 in human embryonic kidney cells from a medical student with a cold. OC43 virus was isolated in 1967 in organ culture from a patient with respiratory infection. Not always easy to isolate human tracheal organ cultures are probably the best method for primary isolations. The corona-like virus particles seen in feces and associated with diarrhea are difficult to isolate even in organ cultures. Strains have a common CF antigen but differences in antigenic structure can be demonstrated by neutralization tests and they belong to different coronavirus anti-genic groups. OC43 is antigenically related to mouse hepatitis virus and 229E is related to coronaviruses of pigs (TGEV) and cats (FECV). Some strains of OC43 virus agglutinate human and monkey erythrocytes at 4 C, and chicken, rat...

Human parvovirus See B19 virus

May occur repeatedly, although serious disease is associated with the first or second infection. Causes 'colds' in captive chimpanzees. Causes no symptoms in ferrets and can be serially passaged in them. Freezing of specimens for virus isolation reduces the chance of success. Diagnosis is by immunofluorescence using exfoliated cells, or by ELISA test of respiratory secretions. Replicates in human cell lines such as HeLa and Hep-2 and less readily in monkey kidney cell cultures. Small syncytia appear and within 1-4 days the whole cell sheet is involved. No demonstrable hemadsorp-tion. No replication in eggs. Virion 90-120nm in diameter and variable in size. Matures at the cell surface by budding in polarized epithelial cells budding is from the apical surface. There is a helical nucleocapsid 12-15nm in diameter containing negative-sense single-stranded RNA, 15222 nucleotides in length, encoding 10 genes. The virion RNA gene order is 3'-NS1-NS2-N-P-M-SH-G-F-M2-L-5'. The 3' end has a...

Human respiratory syncytial virus S2 A

Human rhinovirus A (HRV-A) A species in the genus Rhinovirus containing 18 serotypes that all use ICAM-1 as a receptor. The cause of most human 'colds' and some other respiratory tract infections. Do not hemagglutinate. Strains which replicate in rhesus monkey kidney cell cultures are called M strains the majority, which multiply only in human cells, are called H strains. Some strains can only be isolated in organ cultures of respiratory epithelium. Optimal conditions for propagation are sodium bicarbonate concentration of not more than 0.35g l, temperature 33 C, slow rotation of culture, islands of cells rather than confluent sheet and minimal concentration of serum compatible with maintenance of cells. Best cells for isolation are primary human kidney or lung or diploid human cell lines. CPE may not be seen for 10 days or only on passage. No vaccine available but experiments suggest immunity to an individual strain can be produced. A drug (Pleconaril) is under development....

Spectrum of Disease

Based on the host's response, the spectrum of disease caused by M. leprae ranges from subclinical infection to intermediate stages of disease to full-blown and serious clinical manifestations involving the skin, upper respiratory system, testes, and peripheral nerves. The two major forms of the disease are a localized form called tuberculoid leprosy and a more disseminated form called lepromatous leprosy. Patients with lepromatous leprosy are anergic to M. leprae because of a defect in their cell-

Inhibitors Of Respiratory Viruses

Overview - The three major respiratory viruses, human rhinovirus (HRV), respiratory syncytial virus (RSV) and influenza, continue to be significant sources of epidemic infection (120). The prevalence of RSV remains underestimated since this virus is frequently mistaken for influenza, a situation complicated further with the identification of a new pneumovirus that causes symptoms similar to RSV (121-123). This virus, designated human metapneumovirus (hMPV), has been circulating for at least 50 years in Europe and may be a significant cause of respiratory infections (123). The influenza inhibitor market is dominated by the orally active neuraminidase (NA) inhibitor oseltamivir, prescribed preferentially over the topical NA inhibitor zanamivir, whilst a third NA inhibitor, peramivir, is undergoing pivotal P3 trials (124,125). An NDA for the HRV capsid inhibitor pleconaril (picovir) was filed in July 2001, seeking approval to market this agent as the first antiviral treatment for the...

Japanese hemagglutinating virus

JC Polyomavirus (JCPyV) A species in the genus Polyomavirus. Antigenically distinguishable from BK virus and SV40 virus. Agglutinates human group O erythro-cytes. Originally isolated from the brain of a patient with progressive multifocal leukoencephalopathy (PML) by inoculation of homogenized brain tissue into primary human fetal glial cell cultures. Has been clearly identified as the cause of PML, as well as renal disease and upper respiratory tract infections. Can be

Define reactive airway disease in particular asthma

The term reactive airway disease (RAD) is used to describe a family of diseases that shares an airway sensitivity to physical, chemical, or pharmacologic stimuli. This sensitivity results in a bronchoconstrictor response and is seen in patients with asthma, chronic obstructive pulmonary disease (COPD), emphysema, viral upper respiratory illness, and other disorders.

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. Isolated reactions to the skin (e.g., urticaria with and without angioedema) Systemic reactions (laryngeal edema, rhinitis conjunctivitis, Heiner's syndrome Rhinitis and asthma

Pulmonary Reactions Involving Food

Rhinitis and or asthma-like symptoms (wheezing, respiratory distress) occur as part of systemic anaphylaxis to foods. It has been shown in studies of children with atopic dermatitis who are allergic to foods that after specific food avoidance, followed by DBPCFC 2 wk later, one-third are likely, upon challenge, to develop respiratory symptoms, such as rhinitis or asthma, along with exacerbation of their skin rash. Other than these two situations, isolated rhinitis after food ingestion as a result of allergy is rare. From studies in the United Kingdom, there appears to be an increase risk (5- to 10-fold) of future respiratory allergy (rhinitis or asthma or both) in infants who have an allergy to eggs or egg and milk, especially if they have eczema.

Mammalian orthoreovirus 1Lang MRV

1) A serotype of Mammalian orthoreovirus in the genus Orthoreovirus. The type strain is Lang. Recovered from a number of mammalian species including humans, dogs, cattle, macaque monkeys and cercop-ithecine monkeys. Antibodies have been detected in sera from a wide range of mammalian species. Experimental infection of mice, hamsters, ferrets and rats causes obstructive hydrocephalus, and in pregnant mice fetal resorption, intra-uterine death, malformation or neonatal death occurs. In humans infection is usually symptomless, or associated with mild upper respiratory disease (common cold). Rarely, reovirus type 1 has been isolated from fatal encephalitis cases in children.

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.

Limiting Human Consumption of Antibiotics

One way to lower consumption is to increase restrictions on use, particularly when the type of use is inappropriate. Almost half of antibacterial consumption in hospitals is considered by some researchers to be inappropriate.192 In the community, treatment of the common cold serves as a good example of inappropriate use. Antibacterial agents fail to cure this illness because it is caused by a virus. Nevertheless, patients often insist that physicians prescribe antibacterials for colds. Patients feel that they should get something tangible when they visit their physician, and no effective antiviral agent is available for colds. Moreover, patients and many physicians believe that taking antibiotics is generally innocuous. The pressure is so intense that some physicians admit that they would rather write prescriptions than argue with patients. In many cases, the patient will simply go elsewhere to get a prescription if the physician does not comply. The situation is worse when these...

Box 102 Antibiotic Use in France and Germany

A comparison of two adjacent countries with similar levels of healthcare reveals striking differences, some of which may account for France having a prevalence of antibiotic-resistant pneumococci three times that of Germany.193 From 1985 to 1997, France had almost three times more antibiotic sales, and during that time Germany tended to use narrowspectrum agents more than France. For common colds, 50 of consultations with physicians resulted in antibiotic prescriptions in France, whereas the number was only 8 in Germany. German physicians tended to take a wait-and-see attitude. For respiratory tract infections, German doctors ordered diagnostic tests 40 of the time compared with 20 in France. Germans also received higher doses of penicillin than the French, especially with children.

What are the implications of occupational latex exposure

Currently about 70 of all allergic reactions are reported in health care workers, and it is estimated that 3 to 12 of this group have developed some degree of latex sensitivity. The majority of allergic reactions are probably caused by inhalational exposure from latex particles adhering to the powder of powdered gloves. Since signs and symptoms may be very nonspecific (puffy eyes, nasal congestion, sneezing, wheezing, coughing, hoarseness), the connection may not be made to an occupational exposure. Workers who develop hand dermatitis or have an atopic history may be at increased risk. It is important to note that, although sensitization may occur at work, severe allergic manifestations may occur while these workers are receiving medical care. The key to the protection of health care workers is to reduce work-related exposure (Stop the Sensitization ). The use of nonpowdered latex or latex-free gloves is probably the most important intervention. Maintaining good skin care is also...

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...

Secondgeneration Antihistamines

Another difference between first- and second-generation antihistamines is that some of the latter bind to the H2, as well as the H1, receptor. This appears to be especially important for azelastine and epinastine. This property could at least be theoretically important in that the capacitance vessels in the nasal turbinates and the conjunctiva respond to the H2 stimulation by dilating, thus causing nasal congestion and conjunctival erythema. This may explain the observation that azelastine reduces nasal airway resistance, an effect not associated with the administration of an H1 antagonist.

Antiviral RNAiBased Strategies

Another respiratory virus for which RNAi therapeutics are being developed is respiratory syncytial virus (RSV). In fact, RSV was the first virus for which RNAi-mediated inhibition was demonstrated (Bitko and Barik 2001) and synthetic siRNAs are currently entering phase II clinical trials. RSV belongs to the paramyxoviridae and is an enveloped, nonsegmented, negative-strand RNA virus. RSV is a major cause of respiratory illness in both the upper and lower respiratory tract, typically leading to common cold-like symptoms that in some cases - especially in young children - lead to more serious illness such as bronchiolitis and pneumonia. In mice, replication of RSV and also human parainfluenza virus could be blocked by synthetic siRNAs (Bitko et al. 2005). Synthetic siRNAs and intranasal administration of plasmids expressing shRNAs resulted in a significant decrease of the RSV load (Zhang et al. 2005). Similar to siRNA-induced inhibition of influenza virus, the siRNAs against RSV were...

Suggested Reading

Casale TB, et al Safety and efficacy of once daily fexofenadine, HCL hydrochloride ACL, in the treatment of autumn seasonal allergic rhinitis. Allergy Asthma Proc 1999 20 193-198. Dykewicz MS, Fineman S. Diagnosis and management of rhinitis parameter documents of the joint task force on practice parameters in allergy, asthma, and immunology. Ann Allergy Asthma Immunol 1998 81 501-505.

Evaluation of Ad Replication in Hamster Lungs

The natural site of Ad5 replication in humans is the lung, where it causes a mild respiratory illness in young children. In order to evaluate the replication of an oncolytic Ad vector in the lungs and thus the cancer-specificity of your vector, inoculate the hamster by endotracheal instillation of the vector, harvest the lungs, and determine the total virus yield from the lungs.

Discussion Of Results And Implications For Practice

In the studies of the use of delayed antibiotic prescriptions for URIs and otitis media, significant patient morbidity was not observed (Arroll et al., 2002 Dowell et al., 2001 Little et al., 2001). As the outcome of viral respiratory tract infections is not altered by antibiotics, these are not unexpected results for the studies of URIs. It is important, however, to have data that demonstrates this lack of morbidity for illnesses such as acute bronchitis and purulent rhinitis where the etiologic agent, while usually viral, is often thought to be bacterial by many practitioners. The demonstration that there is no benefit to immediate use of antibiotics may serve to convince many physicians and patients that antibiotics are not needed for these conditions. Delayed prescriptions for acute otitis media in children are frequently used in many European countries but have not gained popularity in North America. This pragmatic study (Little et al., 2001) demonstrates that waiting a few days...

Methods of public education

Health professionals should also use leaflets as part of the consultation (see later) in place of the prescription, perhaps augmented by further detailed, personalised printed materials. Leaflets should be eye catching and give a clear message with possibly more detailed information in smaller font. They should explain their purpose (Why), what behaviour is expected (What), how to get further help (How), who to consult (Who), and what to do (Actions to take). Figure 1 illustrates the range of leaflets recently produced in Grampian for flu, coughs, colds, and cystitis (reproduced with the permission of NHSGrampian). Figure 2 illustrates some of the text for the flu leaflet emphasising why antibiotics use should be restricted.

Biosynthesis And Potency Of Leukotrienes

Various clinical models have been utilized to establish the role of antileukotriene agents in asthma management. Antileukotrienes have been shown to reduce bronchosonstriction produced by a variety of stimuli, including LTD4, exercise, cold air, sulfur dioxide, and aspirin. These agents also block both the early- and late-phase response to allergen challenge and the subsequent influx of inflammatory cells in BAL fluid. Montelukast and pranlukast have also been shown to reduce sputum, BAL, and peripheral blood eosino-phils in clinical trials of patients with asthma. In patients who are aspirin sensitive, antileukotrienes prevent the aspirin challenge-induced production of asthma and rhinitis symptoms, which is consistent with the hypothesis that aspirin sensitivity is medicated in some fashion by CysLTs. Zafirlukast has also been given to patients who were undergoing a desensitization procedure with much difficulty, and it allowed for safe desensi-tization to occur in such individuals.

Reticuloendotheliosis virus strain TA

Some 40 of cases have an association with various drugs or chemicals, especially aspirin and related salicylates. There are often symptoms and signs of upper respiratory tract infection, and an association with various viruses has been suggested, but the evidence is not very strong and environmental or constitutional factors may be important. The addition of warning notices on aspirin bottles in the USA has helped to reduce the number of cases. Synonym Reye-Johnson syndrome.

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 .

Irreversible Inhibitors

B-Unsaturated Esters - The a, p-unsaturated ester moiety was first reported as an irreversible inhibitor for papain in 1982 (42). Subsequent publications have highlighted utility of this approach for the irreversible inhibition of cysteine proteases (43-45). Recently, the development of a series of potent irreversible a, p-unsaturated ester inhibitors of the rhinovirus 3C protease (HRV-14 3CP) have been disclosed. Initial studies based upon the known pentapeptide substrate H2N-Thr-Leu-Phe-Gln-Gly-Pro-CO2H showed that the scissile amide bond between Gin and Gly could be replaced by an a, P-unsaturated ester group and that the P1-P3 amino acids Leu-Phe-GIn could serve as an appropriate minimal HRV-14 3CP specificity determinant. These design considerations have led to the tripeptide a, p-unsaturated ethyl ester 41 which is an irreversible inhibitor of HCV-14 3CP with a kobs l 25,000 M1s1 (46). Compound 41 inhibits several rhinovirus serotypes when tested in cell cultures with an EC50...

Miscellaneous Infections Caused by Other Agents

Rhinoscleroma is a rare form of chronic, granulomatous infection of the nasal passages, including the sinuses and occasionally the pharynx and larynx. Associated with Klebsiella rhinoscleromatis, the disease is characterized by nasal obstruction appearing over a long period, caused by tumorlike growth with local extension. Another species, Klebsiella ozaenae, can also be recovered from upper respiratory tract infections. This organism may contribute to another infrequent condition called ozena, characterized by a chronic, mucopurulent nasal discharge that is often foul-smelling. It is caused by secondary, low-grade anaerobic infection.

Anticholinergic Drugs In Respiratory Diseases

Secretions of the upper airways and to reduce laryngospasm. It is still found in some oral preparations used in the treatment of rhinitis. Ipratropium bromide (Atrovent), a quaternary ammonium derivative of atropine, is the anticholinergic currently indicated for use in the treatment of COPD, allergic and nonallergic rhinitis, and the rhinorrea of the common cold. It is also utilized in the treatment of asthma because of its bronchodilatory properties. Table 2 compares ipratropium bromide and atropine characteristics. It is available in an aqueous nasal spray for rhinitis, in an aqueous nebulizer solution for use in COPD, and in a metered-dose inhaler either alone or in combination with albuterol (Combivent). Its inhibition of rhinorrea makes it a useful medication for the symptomatic relief of allergic and nonallergic rhinitis, gustatory rhinitis (onset of rhinorrea induced by eating hot and spicy foods), and the common cold, conditions for which it is also indicated. It is available...

Anticholinergic Drugs In Asthma And Copd

Ipratropium Bromide in Chronic Rhinitis Ipratropium Bromide in Chronic Rhinitis and nonallergic perennial rhinitis Available as a 0.03 solution for perennial rhinitis Available as a 0.06 solution for the common cold The recommended dose for rhinitis is two sprays in each nostril For the common cold the recommended dose is two sprays in each Useful in gustatory rhinitis

Antibiotic Use And Cost Trends

Most information available comes from industrialised countries with minimal data from the developing world. In the United States, antimicrobial prescription rates by office-based physicians remained unchanged from 1980 through 1992 however, prescriptions for children increased by 48 (McCaig and Hughes, 1995). A large portion of these prescriptions was for the treatment of colds, upper respiratory tract infections, and bronchitis conditions where there is no proven benefit of antibiotic therapy. Trends in antimicrobial prescribing at visits to office-based physicians, hospital outpatient departments, and hospital emergency departments from 1992 to 2000 in the United States declined by 25 (McCaig et al., 2003). Amoxicillin and the cephalosporins were most prescribed (annual drug prescription rate per 1,000 population) in outpatient settings between 1980 and 1992 (McCaig and Hughes, 1995 Steinman et al., 2003). Even though antibiotic use in ambulatory patients is decreasing, use of...

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.

Communication Between the Industry and Physicians Is Required but is Becoming More and More Restricted

I have had a couple of personal examples of trying to deal with these questions that I would like to share with you. The first came when my team at Wyeth was trying to develop a drug for Respiratory-Syncytial Virus (RSV). RSV causes severe respiratory disease and death in infants and young children and causes everything from colds to pneumonia in older children and adults. RSV is deadly to immuno-compromised patients like those who are recovering from bone marrow transplants. For the population as a whole, it is just as deadly as influenza for which we now have both vaccines and antiviral drugs. For RSV, there is only one product marketed. It is an antibody used to prevent disease in premature infants with severe underlying cardiac or lung disease. That's it. One problem is, because there is no treatment, physicians don't try and diagnose the disease. That would mean that if there were a new treatment, no one would know when to use it since they wouldn't know if their patient had RSV,...

Medical Students and Residents

That overuse of antibiotics has a major role in increasing antimicrobial resistance, 20 answered that antibiotics are useful in the treatment of common cold, more than 30 would prescribe antibiotics when the diagnostic is not certain, and only 21 knew that there is no resistance to penicillin for Streptococcus pyogenes. Ibia et al. (2005) surveyed senior medical students in 21 medical schools in New England and the Mid-Atlantic States to evaluate their knowledge of and compliance with principles of judicious antimicrobial use, as defined by the Centers for Disease Control and others. Ninety-nine percent of the students were aware of the increase in antimicrobial resistance, but almost 50 had read none of the principles, and only 2.9 had read all six. Thirty percent answered that they would treat a 4-year-old child with pharyngitis (with no positive culture) with antibiotics, and 60 thought that an 18-month-old toddler with purulent rhinitis and wheezing should be treated with...

Community Interventions

Conducted a multifaceted intervention to improve antimicrobial prescribing for upper respiratory tract infections (URTIs) in a small rural community in Utah. The intervention involved patient education materials, a media campaign to increase public awareness, small group sessions involving physicians, and physician use of URTI algorithms. After 6 months, the percentage of patients in the community who received antibiotics for URTIs during the intervention period was 15.6 less than that for the baseline period. There was a decrease of 56 on antibiotic prescriptions for acute bronchitis and a 13.4 decrease on macro-lides prescriptions. Among hospitalized patients, there was no significant decrease in the number of patients with URTI who were prescribed an antibiotic, although there was also a decrease in macrolide use (11.2 ). In Australia, Dollman et al. (2005) conducted a community-based intervention to reduce antibiotic use for upper respiratory tract infections. These investigators...

APCs In Initiation Of Mucosal Immune Responses

Antigens can be taken up across the epithelial linings of various mucosal tissues, and many of these tissues then generate robust sIgA responses. Most of our knowledge about this response has been gained from studies of gut-associated lymphoid tissue in rodents and of human tonsils. The major inductive sites of the mucosal immune system are follicles and organized aggregates of follicles, exemplified by Peyer's patches in the intestine and referred to generically as mucosa-associated lymphoid tissue (MALT). Antigens are often efficiently absorbed by specialized cells in the epithelium overlaying the MALT, the morphologically distinct M cells (37,38). In some cases dendritic cells extend processes between neighboring epithelial cells to sample antigens in the external milieu (39). Despite the well-developed conjunctival lymphoid follicles, however, most of the IgA+ plasma cells that populate the lacrimal glands appear to be generated in the gut or upper respiratory system, rather than...

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.

Rupatadine Fumarate Antiallergic [9193

Rupatadine fumarate, a novel antiallergic drug with a dual mechanism of action, was introduced last year in Spain as an oral treatment for perennial and seasonal rhinitis. Rupatadine acts as non-sedating histamine H1 receptor antagonist and platelet-activating factor (PAF) antagonist. Its Kav values against 3H WEB-2086 binding to rabbit platelet membrane PAF receptors and 3H pyralimine binding to guinea pig cerebellum membrane H1 histamine receptors are 0.55 and 0.10 mM, respectively. It has a rapid onset of action, with patients experiencing relief of symptoms within 2 h, and its long duration of action (> 24 h) permits once-daily dosing. Rupatidine is prepared in a 6-step convergent synthesis, with the key steps involving the Grignard reaction of a N-alkyl-4-chloropiperdine with a benzocycloheptapyridinone intermediate, followed by dehydration. Rupatadine is rapidly absorbed after oral administration. The time to reach maximum plasma concentration is 0.75-1 h and the mean...

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. Controlled clinical studies demonstrate that allergen immunotherapy is effective for patients with respiratory allergies (Table 1). Immunotherapy...

Scope Of Inappropriate Antibiotic

Many descriptive studies show that, while recent efforts to curtail unnecessary antibiotic use have met with some success, there is evidence that there is still a long-standing and continuing problem with unnecessary antibiotic use in the United States for both adults and children, and that use of broad-spectrum antibiotics has been increasing. During the 1990s, adult antibiotic use fell by 23 for upper respiratory infections, and by 22 for bronchitis, but broad-spectrum antibiotic use doubled. By 2001-2002, 49 of adult outpatient visits for respiratory tract infections (acute bronchitis, cough, upper respiratory tract infection, and laryngitis, all conditions for which an antibiotic is rarely indicated) still received an antibiotic prescription, and 77 of these were for a broad-spectrum antibiotic, an increase of 87 over 6 years (22). Among children during the 1990s, antibiotic use decreased by 49 for upper respiratory tract infections, and by 13 for bronchitis, but broad-spectrum...

The Epidemiology of MRSA

Epidemiologic data have shown for more than a century and a half that HCWs spread microbes from patients to patient via transiently contaminated hands. Sometimes HCWs are colonized in the nose. Most likely, staphylococcal nasal carriers contaminate their fingers and hands by direct contact with the anterior nares, as suggested by Hare and Thomas (1956). A controlled trial published in 1966 showed that refraining from hand hygiene was associated with significantly greater spread of S. aureus (Mortimer et al. 1966). The extent to which contaminated environmental surfaces contribute to transmission of MRSA to patients has not been established. The main reason for this is that whenever there is a possibility for transfer via contaminated surfaces, there is always the possibility of transfer by other routes. However, the environment can become heavily colonized with MRSA and may serve as the reservoir for continued spread of the organism (Crossley et al. 1979). In one report, 35 of...

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...

Medical Provider Interventions

Centers for Disease Control and Prevention (CDC) has recently completed a series of practice guidelines regarding appropriate antibiotic use for adult acute respiratory infection, including bronchitis (71), exacerbations of chronic obstructive pulmonary disease (72), pharyngitis (73), sinusitis (74), and nonspecific upper respiratory tract infections (75), and publishes regular guideline updates for influenza (76). The Infectious Diseases Society of America (3) and the American Thoracic Society (77) published recommendations for the management of adult community-acquired pneumonia. The American Academy of Pediatrics published guidelines for the diagnosis and antibiotic treatment of pediatric acute otitis media, the most common outpatient diagnosis for which an antibiotic is prescribed for children (78,79), and pediatric sinusitis (79).

Examples Of Successful Interventions To Reduce Inappropriate Antibiotic

The full intervention site received household- and office-based patient educational materials. Household materials were mailed to families and included magnets outlining preventive and self-care issues, what to expect for a visit for respiratory illness, a CDC pamphlet entitled Your Child and Antibiotics, an industry-sponsored pamphlet regarding handwashing, and a letter from their practice's medical director about the importance of reducing unnecessary antibiotic use. Office-based materials, directed at patients and family medicine and internal medicine clinicians, included posters regarding (i) the lack of effect of antibiotic treatment on duration of illness for bronchitis or chest colds, (ii) a graphic showing the increased prevalence of invasive antibiotic-resistant S. pneumoniae in Colorado, and (iii) a graph showing risk of carriage of PRSP stratified by prior antibiotic use. The clinician intervention consisted of a 30-min education session about how to reduce unnecessary...

Synergistic Antimicrobial Combinations

Some of the combinations that showed synergy are used routinely for the therapy of mixed aerobic-anaerobic infections. These include the combination of clindamycin or metro-nidazole plus an aminoglycoside used for the therapy of intra-abdominal and pelvic infections, and the combination of metronidazole and a macrolide for the therapy of upper respiratory tract infections. The synergistic effect against some anaerobic strains noticed by the above studies (Table 8) is a valuable additional asset.

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...

Guidol Ma English 1st Sem Result 2015

Arroll, B., Kenealy, T., and Kerse, N., 2002, Do delayed prescriptions reduce the use of antibiotics for the common cold J. Fam. Pract., 51, 324-328. Dowell, S. F., Marcy, S. M., Phillips, W. R., Gerber, M. A., and Schwartz, B., 1998, Principles of judicious use of antimicrobial agents for pediatric upper respiratory tract infections. Pediatrics, 101, 163-184. Gonzales, R., Steiner, J. F., and Sande, M., 1997, Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. JAMA, 278, 901-904. Gordon, M., Lovell, S., and Dugdale, A. E., 1974, The value of antibiotics in minor respiratory illness in children. A controlled trial. Med. J. Aust., 1, 304-306. Kaiser, L., Lew, D., and Stalder, H., 1996, Effects of antibiotic treatment in the subset of common-cold patients who have bacteria in nasopharyngeal secretions. Lancet, 347, 1507-1510. Mainous, A. G. I., Hueston, W. J., and Clark, J. R., 1996, Antibiotics and upper...

Biochemistry of HIV1 Protease and Development of Inhibitors

Rhinoviruses cause a significant fraction of the common colds suffered by the human population. However, members of the Rhinovirus genus (Picornaviridae family) include 100 different serotypes that infect humans, making a vaccine strategy impractical. Thus, alternative strategies are needed to intervene in these non-life-threatening but inconvenient infections.

ARCAs for Prostate Cancer CV706 and CV787

Members of the human Adenoviridae family were first cultured from the tonsils and adenoids of children in 1953 29 . They represent 51 different serotypes which are distinguishable by antibody reactivity to epitopes on the virion surface. Each serotype is assigned to one of five subgroups (A-E). Adenovirus type 5 (Ad5), a member of Subgroup C, is associated with a self-limiting, febrile respiratory illness and ocular disease in humans infectious virus can be recovered from the throat, sputum, urine, and rectum. Ad5 is also associated with renal impairment, hepatic necrosis, and gastric erosions in immunosuppressed individuals 30, 31 . Ad5 and the other Subgroup C viruses have little or no oncogenic potential in mammals 32 .

A 3yearold child presents for an elective tonsillectomy His mother reports that for the past 3 days he has had a runny

Young children can average five to eight URIs per year, mostly from fall through spring. If a 4- to 7-week delay for elective surgery were rigorously followed, then elective surgery might be postponed indefinitely. Therefore most anesthesiologists distinguish uncomplicated URI with chronic nasal discharge from nasal discharge associated with more severe URI with or without lower respiratory infection (LRI). Chronic nasal discharge is usually noninfectious in origin and caused by allergy or vasomotor rhinitis. An uncomplicated URI is characterized by sore or scratchy throat, laryngitis, sneezing, rhinorrhea, congestion, malaise, nonproductive cough, and temperature < 38 C. More severe URI or LRI may include severe nasopharyngitis, purulent sputum, high fever, deep cough, and associated auscultatory findings of wheezes or rales.

Other Therapeutic Uses for Cromolyn or Nedocromil

Other reports have proposed that intranasal cromolyn or nedocromil (not commercially available in the United States as an intranasal preparation) may benefit the common cold. The causative viruses or atypical bacteria may produce a variety of inflammatory mediators, including histamine, cytokines, leukotrienes, and nitric oxide. Compared to placebo, both cromolyn and nedocromil provide a swifter resolution and reduced severity of symptoms in nonallergic subjects. Both drugs also reduce symptoms of virus-induced asthma exacerbations.

Early DP antagonists and their related analogs

BW A868C (2) is one of the early DP antagonists reported in the literature. It binds the DP receptor with a Kd value of 1.45 nM (Kd was determined using human platelets) 28 . S-5751 (3) was the first DP antagonist reported to be under evaluation in clinical trials for rhinitis and asthma 29 . S-5751 demonstrated binding IC50 value of 1.9 nM in 3H -PGD2 binding assays using human platelet membranes. It also inhibited PGD2-induced cAMP formation in human platelets with an IC50 of 0.9 nM 30 . Several other DP antagonists, structurally similar to 3, were described in the literature. Compound 4 had a binding IC50 value of 130 nM and an IC50 value of 70 nM in a functional assay 31 .

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,...

Antibacterial Treatment of Community Acquired Respiratory Tract Infections

Introduction - Community-acquired respiratory tract infections (CARTIs) represent one of the most globally prevalent classes of infection. Acute RTIs account for approximately 75 of all antibiotic prescriptions and 20 of all medical consultations (1). Community-acquired upper respiratory tract infections (CAURTI) (pharyngitis tonsillitis, laryngitis, otitis media and sinusitis) and viral RTIs (rhinorrhea the common cold, influenza A B, adenovirus, parainfluenza and syncytial virus) are typically not life-threatening unless complicated by a coinfection or an immunocompromised host (e.g. meningitis, HIV, etc.). Generally, CAURTIs respond well to front-line antibiotics such as penicillins, erythromycin, azithromycin, amoxicillin clavulanate or cefpodoxime. Viral RTIs are usually self-limiting and only require symptomatic support (2,3). Of greater concern are lower respiratory tract infections (LRTI) which include community-acquired pneumonia (CAP) and acute exacerbations of chronic...

Subacute myeloopticoneuropathy virus

Suid herpesvirus 2 (SuHV-2) An unas-signed species in the family Herpesviridae. Causes rhinitis and destruction of the turbinates, with distortion of the snout, epistaxis and sneezing, notably in 2-week-old piglets, when death is common. Transmission is possible in piglets but not in adult pigs. Disease occurs in outbreaks and inclusions are present in the cells of many organs. Can be cultivated in primary pig cell cultures, replicating better in epithelial than in fibroblastic cells. Synonyms inclusion-body rhinitis virus swine cytomegalovirus.

Pathophysiology of

Upper respiratory tract infection Urinary tract infections Amyloidosis Tubular disease Glomerulonephritis a Increased in bacterial infections such as pneumonia, upper respiratory tract infection, bacterial meningitis, tonsillitis, gastroenteritis, enterocolitis, streptococcal infection, mononucleosis, lymphadenitis, conjunctivitis, and whooping cough. bIncreased in severe viral infections such as mumps, varicella (chicken pox), influenza A and B, common cold, viral meningitis, infectious mononucleosis, measles (rubeola), or rotavirus-V enteritis. Severe viral infections are defined by increased lymphocyte count.