BRONCHIAL ASTHMA IN ADULTS—Causes and Treatment

Food and inhalant allergens were of about equal importance in producing bronchial asthma in 907 adults between the ages of 15 and 55 years.Drug and especially bacterial allergens were infrequent causes.Psychogenic factors may activate or exaggerate causes mentioned but were not the sole cause of any case in this series.Food allergens are best studied and controlled by the standardized cereal-free elimination diet and at times other elimination diets. Test-negative diets usually fail because of the fallibility of both negative and positive skin tests.Inhalant allergy is controlled by the elimination of causative allergens by varying degrees of environmental control and often by pollen and dust filters in the window. Desensitization is necessary against those allergens that cannot be removed from the environment. Dilutions in the millions and billions may be required.Morphine and other opiates, Demerol, chloral, paraldehyde and large or moderate doses of barbiturates are contraindicated in bronchial asthma, as emphasized by deaths resulting from the use of them.Bronchoscopy is indicated for bronchial obstruction due to inspissated mucous plugs, but the danger of the procedure, especially with much sedation, must be recognized.When secondary infection is probable, the use of sulfadiazine, penicillin, aureomycin and chloramphenicol must be considered.     

ASTHMA IN CHILDREN—PROBLEMS IN DIAGNOSIS

Bronchial asthma in children may be difficult to diagnose. Education of the parents regarding allergic conditions, specifically bronchial asthma, is exceedingly important in order to assure satisfactory treatment and clinical results.Chest symptoms of unexplained origin in early life should immediately arouse suspicion of allergic disease. Other causes of asthmatic symptoms must be borne in mind and excluded before a positive diagnosis of bronchial asthma is established.Of the many factors to be considered in investigating a child with asthma, a comprehensive history is most essential. The climate to which the patient is exposed and the psychic influences must be taken into account. Physical examination, x-ray films and laboratory procedures should be carefully executed. Skin testing, especially with food allergens, should not be relied upon to give all the information in allergic disease. Some form of diet trial, such as elimination diets, should be used if sensitivity to food is suspected.     

Asthma in children--problems in diagnosis

Bronchial asthma in children may be difficult to diagnose. Education of the parents regarding allergic conditions, specifically bronchial asthma, is exceedingly important in order to assure satisfactory treatment and clinical results. Chest symptoms of unexplained origin in early life should immediately arouse suspicion of allergic disease. Other causes of asthmatic symptoms must be borne in mind and excluded before a positive diagnosis of bronchial asthma is established. Of the many factors to be considered in investigating a child with asthma, a comprehensive history is most essential. The climate to which the patient is exposed and the psychic influences must be taken into account. Physical examination, x-ray films and laboratory procedures should be carefully executed. Skin testing, especially with food allergens, should not be relied upon to give all the information in allergic disease. Some form of diet trial, such as elimination diets, should be used if sensitivity to food is suspected.     

Allergic bronchial asthma and rhinitis; the importance of studies for sensitivity to foods

The authors consider sensitivity to foods and sensitivity to inhalants about equal in importance in bronchial asthma, allergic rhinitis and allergic bronchitis. Food allergens are the sole cause of bronchial and nasal allergic disease in 20 to 40 per cent of cases throughout life, including old age; inhalants are the sole cause in approximately an equal number; and sensitivity to foods and to inhalants are often associated. THEIR FREQUENT RECOGNITION OF SENSITIVITY TO FOODS AS A CAUSE OF DISEASE, THE AUTHORS BELIEVE, DEPENDS ON: (1) The recognition of the fallibility of skin testing and the usual negative skin reactions to allergenic foods in chronic and recurrent bronchial asthma and allergic rhinitis. (2) The adequate use of trial diets, especially cereal-free elimination diet. (3) The realization that ingested foods remain in the body usually for two to four weeks and that the diet must be continued until symptoms have been relieved for two to three times as long as preceding relief between attacks.     

ALLERGIC BRONCHIAL ASTHMA AND RHINITIS—The Importance of Studies for Sensitivity to Foods

The authors consider sensitivity to foods and sensitivity to inhalants about equal in importance in bronchial asthma, allergic rhinitis and allergic bronchitis. Food allergens are the sole cause of bronchial and nasal allergic disease in 20 to 40 per cent of cases throughout life, including old age; inhalants are the sole cause in approximately an equal number; and sensitivity to foods and to inhalants are often associated.Their frequent recognition of sensitivity to foods as a cause of disease, the authors believe, depends on: (1) The recognition of the fallibility of skin testing and the usual negative skin reactions to allergenic foods in chronic and recurrent bronchial asthma and allergic rhinitis. (2) The adequate use of trial diets, especially cereal-free elimination diet. (3) The realization that ingested foods remain in the body usually for two to four weeks and that the diet must be continued until symptoms have been relieved for two to three times as long as preceding relief between attacks.     

西安地区儿童支气管哮喘吸入性过敏原的调查分析

目的:探讨西安地区儿童支气管哮喘吸入性过敏原的分布情况。方法:选择950例来自西安地区的支气管哮喘患儿为研究对象,采用过敏原皮肤点刺试验检测,以组胺作为阳性对照,生理盐水为阴性对照,分析不同年龄和性别的患儿过敏原的分布情况。结果:950例支气管哮喘患儿中,384例皮肤点刺过敏原检测呈阳性,占40.4%,男女患儿过敏原检测阳性分布无明显差异(P0.05);尘螨为主要的过敏原,其次为艾蒿和霉菌类;随着患儿年龄的增加,其过敏原检测的阳性率明显升高(P0.05),且大多数过敏原检测阳性患儿至少合并2-3种过敏原阳性。结论:西安地区支气管哮喘患儿吸入性过敏原阳性率与其性别无关,但与其年龄有关,过敏原以尘螨类为主,大多数检测阳性的患儿对至少一种以上的过敏原阳性。     

Pathophysiological mechanisms of asthma. Application of cell and molecular biology techniques

Asthma is a common increasing and relapsing disease that is associated with genetic and environmental factors such as respiratory viruses and allergens. It causes significant morbidity and mortality. The changes occurring in the airways consist of a chronic eosinophilic and lymphocytic inflammation, together with epithelial and structural remodeling and proliferation, and altered matrix proteins, which underlie airway wall narrowing and bronchial hyperresponsiveness (BHR). Several inflammatory mediators released from inflammatory cells such as histamine and cysteinyl-leukotrienes induce bronchoconstriction, mucus production, plasma exudation, and BHR. Increased expression of T-helper 2 (Th2)-derived cytokines such as interleukin-4 and 5 (IL-4,5) have been observed in the airway mucosa, and these may cause IgE production and terminal differentiation of eosinophils. Chemoattractant cytokines (chemokines) such as eotaxin may be responsible for the chemoattraction of eosinophils to the airways. The initiating events are unclear but may be genetically determined and may be linked to the development of a Th2-skewed allergen-specific immunological memory. The use of molecular biology techniques on tissues obtained from asthmatics is increasing our understanding of the pathophysiology of asthma. With the application of functional genomics and the ability to transfer or delete genes, important pathyways underlying the cause if asthma will be unraveled. The important outcome of this is that new preventive and curative treatments may ensue.     

The effect of sodium nucleinate on allergic and immunological reactions

Experiments on immunized rabbits and guinea pigs indicated that sodium nucleinate (SN) was capable of weakening or entirely eliminating anaphylactic and skin reactions of delayed type hypersensitivity to repeated administration of staphyloanatoxin, APDT vaccine. The findings on patients with the infectious form of bronchial asthma and chronic rheumatism showed that sodium nucleinate attenuated reactions to the subcutaneous administration of staphylococcal and streptococcal allergens. The treatment of patients suffering from infectious-allergic bronchial asthma and rheumatism with SN resulted in the recovery of deficient T cells, T-suppressors, normalization of immunoglobulin concentrations. In children with acute glomerulonephritis sodium nucleinate normalized decreased T-suppressor cells and increased IgG and circulating immune complexes (CIC), resulting in a pronounced remission of disease. The mechanism of desensitization and elimination of CIC by SN has not been explored, however, the parameters of SN-induced immunomodulation are known rather completely. It is suggested that SN brings about accumulation in the cell of cyclic AMP which diminished membrane permeability, activates monoaminooxidase resulting in the degradation of histamine and other biogenic amines, enhances the synthesis of endogenous corticosteroids with their desensitizing properties. All these effects contribute to the elimination of delayed type hypersensitivity. The role of SN in the inhibition of delayed type hypersensitivity remains obscure.     

The gene coding for the major birch pollen allergen Betv1, is highly homologous to a pea disease resistance response gene.

Pollen of the white birch (Betula verrucosa) is one of the main causes of Type I allergic reactions (allergic rhinoconjunctivitis, allergic bronchial asthma) in Middle and Northern Europe, North America and the USSR. Type I allergies are a major threat to public health in these countries, since 10-15% of the population suffer from these diseases. BetvI, an allergenic protein with an Mr of 17 kd is a constituent of the pollen of white birch and is responsible for IgE binding in more than 95% of birch pollen allergic patients. Here, we report the complete nucleotide sequence and deduced amino acid sequence of a cDNA clone coding for the major pollen allergen (BetvI) of white birch. It is similar to the N-terminal peptide sequences of the allergens of hazel, alder and hornbeam (close relatives) but it has no significant sequence homology to any other known allergens. However, it shows 55% sequence identity with a pea disease resistance response gene, indicating that BetvI may be involved in pathogen resistance of pollen.     

Prevalence of asthma in adults in Busselton,Western Australia.

OBJECTIVE--To estimate whether the prevalence of asthma in adults increased over a nine year interval. DESIGN--Serial cross sectional studies of the population with a protocol that included both subjective and objective measurements. SETTING--Busselton, Western Australia. SUBJECTS--A random sample of 553 subjects aged 18-55 years in 1981, and of 1028 subjects aged 18-55 years in 1990. MAIN OUTCOME MEASURES--Respiratory symptoms measured by self administered questionnaire, bronchial responsiveness measured by bronchial challenge with histamine, and allergy measured by skin prick tests. RESULTS--Symptoms with increased prevalence were those with significant association with allergy in this population. Recent wheeze increased from 17.5% to 28.8% (p < 0.001) and diagnosed asthma increased from 9.0% to 16.3% (p < 0.001). The increase was greatest in subjects less than 30 years old. The prevalence of shortness of breath coming on at rest and of hay fever also increased significantly, but the prevalence of shortness of breath on exertion, chronic cough, bronchial hyperresponsiveness, current asthma (defined as recent wheeze plus bronchial hyperresponsiveness), and allergy did not increase. The severity of bronchial responsiveness did not change significantly in any symptom group. CONCLUSIONS--Young adults showed a significant increase in reporting of symptoms related to allergy but not in the prevalence of current asthma. The increase in symptoms may be due to increased awareness of asthma in this community, to changed treatment patterns, or to increased exposures to allergens.     

NONALLERGIC ASTHMA—Differential Diagnosis and Treatment

A classification of asthma into allergic and nonallergic has gained support from the more recent studies on the underlying causes of the disease.The majority of instances of nonallergic asthma occur after middle life and result from recurrent infections of the upper and lower respiratory tract. Status asthmaticus is a frequent complication of infectious asthma.Chronic and intractable asthma may be present also in a patient with allergic asthma complicated by a superimposed infection of the sinuses, bronchi and lungs.There are many secondary or precipitating causes that may bring on asthmatic paroxysms. The most important of these are acute respiratory infections, mechanical and chemical irritants, autonomic imbalance, hormonal deficiencies and psychogenic influences. These secondary causes play a more important role in nonallergic asthma because of the greater tendency to chronicity in this form of the disease.The effective treatment of chronic asthma depends largely on the successful control of the secondary or precipitating causes of the asthmatic attacks.The introduction of the antibiotics and corticosteroids in the treatment of infectious asthma has supplied potent weapons to combat the disease. The use of these therapeutic agents makes possible the control of two of the important pathologic lesions of asthma—bronchial infection and bronchial inflammation.At present combined antibiotic and cortisone or hydrocortisone therapy of asthma seems to be the most rational method of preventing the disease from becoming chronic and intractable. Their value in infectious asthma is due to their anti-infective and antiflammatory action.When prolonged treatment is essential, combined therapy also lessens the dangers arising from the presence of masked infections.     

ATOPIC DERMATITIS—ETIOLOGY AND CLINICAL MANAGEMENT

Atopic dermatitis is primarily an allergic problem, similar in most of its aspects to that of allergic bronchial asthma. It should be studied and treated like asthma, with especial emphasis on the significance of inhalant allergens. It is doubtful that psychic factors are of importance in primary genesis of the disease although they may be involved in exacerbation of it.     

Atopic dermatitis-etiology and clinical management

Atopic dermatitis is primarily an allergic problem, similar in most of its aspects to that of allergic bronchial asthma. It should be studied and treated like asthma, with especial emphasis on the significance of inhalant allergens. It is doubtful that psychic factors are of importance in primary genesis of the disease although they may be involved in exacerbation of it.     

Cytokines, from atopy to asthma: the Th2 dogma revisited.

Asthma is a spreading condition in Western countries, in most cases in relationship with atopy. Atopy is defined by an individual predisposition to develop allergic diseases in response to environmental allergens. The atopic immune system is characterized by a Th2 deviation determined by genetic and environmental factors. Among these factors, the role of allergen exposure, dietary behavior, air pollution and early exposure to microbes is discussed. In asthma, a Th2 cell activation is evident, but is accompanied by a Tc1 cell activation. These Tc1 cells probably down-regulate Th2 cells, but are also relevant to the bronchial hyperresponsiveness characterizing asthma. We propose that Tc1 activation in asthma could be the link between allergy and bronchial hyperresponsiveness.     

Respiratory and psychiatric abnormalities in chronic symptomatic hyperventilation.

Many physicians believe that the hyperventilation syndrome is invariably associated with anxiety or undiagnosed organic disease such as asthma and pulmonary embolus, or both. Twenty one patients referred by specialist physicians with unexplained somatic symptoms and unequivocal chronic hypocapnia (resting end tidal Pco2 less than or equal to 4 kPa (30 mm Hg) on repeated occasions during prolonged measurement) were investigated. All but one complained of inability to take a satisfying breath. Standard lung function test results and chest radiographs were normal in all patients, but histamine challenge showed bronchial hyper-reactivity in two of 20 patients tested, and skin tests to common allergens were positive in three of 18. Ventilation-perfusion scanning was abnormal in a further three of 15 patients studied, with unmatched perfusion defects in two and isolated ventilation defects in one. None of the 21 had thyrotoxicosis, severe coronary heart disease, or other relevant cardiovascular abnormalities. Ten of the 21 patients were neurotic and suffered from chronic psychiatric disturbance characterised by anxiety, panic, and phobic symptoms. The remainder had no detectable psychiatric disorders but reported proportionately more somatic than anxiety symptoms. Severe hyperventilation can occur in the absence of formal psychiatric or detectable respiratory or other organic abnormalities. Asthma and pulmonary embolus must be specifically excluded.     

MEDICAL PROGRESS: Histamine and the Antihistaminic Drugs

The tissues affected by histamine and anaphylactic reactions are identical. Epinephrine antagonizes the action of histamine by acting on effector cells in a direction opposite to that of histamine. The so-called antihistaminic drugs block rather than antagonize the action of histamine. The injection into the human body of epinephrine or certain antihistaminic substances provokes the release of histamine and thereby produces a rise in the histamine blood level.There is a remarkable conformity of potency of antihistaminics as determined by Dale experiments and by histamine intoxication experiments in the intact guinea pig. Neoantergan, Pyribenzamine and Histadyl are usually superior to other compounds when potency is assayed by these methods.All antihistaminics provide similar protection again animal anaphylaxis. Larger doses are necessary to protect against anaphylaxis than against histamine intoxication.The differences in potency as determined by Dale experiments and histamine experiments in animals are not found in clinical use. One compound is not generally superior to all others in the treatment of any one or several allergic disorders.The antihistaminic drugs are beneficial in the symptomatic treatment of allergic rhinitis, acute urticaria and angioneurotic edema, and mild non-infective bronchial asthma. Their effectiveness in the management of moderately severe and severe non-infective bronchial bronchial asthma; infective bronchial asthma; migraine; atopic dermatitis (disseminated neurodermatitis), and pruritus of skin disorders other than acute urticaria and angioneurotic edema, is not worthy of particular commendation.The size of the dose of any antihistaminic substance influences the incidence of but not the type of side-effect that may accompany its usage. The quality of side effects varies according to the drug, although there is an individuality of response for each patient which must be reckoned with. In selecting an antihistaminic compound it is necessary to consider the percentage of cases in which side effects occur, as well as the percentage of good results. Optimal results are obtained by employing combinations of compounds and changing from one to the other as the case demands.     

Histamine and the antihistaminic drugs

The tissues affected by histamine and anaphylactic reactions are identical. Epinephrine antagonizes the action of histamine by acting on effector cells in a direction opposite to that of histamine. The so-called antihistaminic drugs block rather than antagonize the action of histamine. The injection into the human body of epinephrine or certain antihistaminic substances provokes the release of histamine and thereby produces a rise in the histamine blood level. There is a remarkable conformity of potency of antihistaminics as determined by Dale experiments and by histamine intoxication experiments in the intact guinea pig. Neoantergan, Pyribenzamine and Histadyl are usually superior to other compounds when potency is assayed by these methods. All antihistaminics provide similar protection again animal anaphylaxis. Larger doses are necessary to protect against anaphylaxis than against histamine intoxication. The differences in potency as determined by Dale experiments and histamine experiments in animals are not found in clinical use. One compound is not generally superior to all others in the treatment of any one or several allergic disorders. The antihistaminic drugs are beneficial in the symptomatic treatment of allergic rhinitis, acute urticaria and angioneurotic edema, and mild non-infective bronchial asthma. Their effectiveness in the management of moderately severe and severe non-infective bronchial bronchial asthma; infective bronchial asthma; migraine; atopic dermatitis (disseminated neurodermatitis), and pruritus of skin disorders other than acute urticaria and angioneurotic edema, is not worthy of particular commendation. The size of the dose of any antihistaminic substance influences the incidence of but not the type of side-effect that may accompany its usage. The quality of side effects varies according to the drug, although there is an individuality of response for each patient which must be reckoned with. In selecting an antihistaminic compound it is necessary to consider the percentage of cases in which side effects occur, as well as the percentage of good results. Optimal results are obtained by employing combinations of compounds and changing from one to the other as the case demands.     

The epithelial anion transporter pendrin is induced by allergy and rhinovirus infection, regulates airway surface liquid, and increases airway reactivity and inflammation in an asthma model

Asthma exacerbations can be triggered by viral infections or allergens. The Th2 cytokines IL-13 and IL-4 are produced during allergic responses and cause increases in airway epithelial cell mucus and electrolyte and water secretion into the airway surface liquid (ASL). Since ASL dehydration can cause airway inflammation and obstruction, ion transporters could play a role in pathogenesis of asthma exacerbations. We previously reported that expression of the epithelial cell anion transporter pendrin is markedly increased in response to IL-13. Herein we show that pendrin plays a role in allergic airway disease and in regulation of ASL thickness. Pendrin-deficient mice had less allergen-induced airway hyperreactivity and inflammation than did control mice, although other aspects of the Th2 response were preserved. In cultures of IL-13-stimulated mouse tracheal epithelial cells, pendrin deficiency caused an increase in ASL thickness, suggesting that reductions in allergen-induced hyperreactivity and inflammation in pendrin-deficient mice result from improved ASL hydration. To determine whether pendrin might also play a role in virus-induced exacerbations of asthma, we measured pendrin mRNA expression in human subjects with naturally occurring common colds caused by rhinovirus and found a 4.9-fold increase in mean expression during colds. Studies of cultured human bronchial epithelial cells indicated that this increase could be explained by the combined effects of rhinovirus and IFN-gamma, a Th1 cytokine induced during virus infection. We conclude that pendrin regulates ASL thickness and may be an important contributor to asthma exacerbations induced by viral infections or allergens.     

Molecular and immunological characterization of a wheat serine proteinase inhibitor as a novel allergen in baker's asthma

IgE-mediated sensitization to wheat flour belongs to the most frequent causes of occupational asthma. A cDNA library from wheat seeds was constructed and screened with serum IgE from baker's asthma patients. One IgE-reactive phage clone contained a full-length cDNA coding for an allergen with a molecular mass of 9.9 kDa and an isoelectric point of 6. According to sequence analysis it represents a member of the potato inhibitor I family, a group of serine proteinase inhibitors, and thus is the first allergen belonging to the group 6 pathogenesis-related proteins. The recombinant wheat seed proteinase inhibitor was expressed in Escherichia coli and purified to homogeneity. According to circular dichroism analysis, it represented a soluble and folded protein with high thermal stability containing mainly beta-sheets, random coils, and an alpha-helical element. The recombinant allergen showed allergenic activity in basophil histamine release assays and reacted specifically with IgE from 3 of 22 baker's asthma patients, but not with IgE from grass pollen allergic patients or patients suffering from food allergy to wheat. Allergen-specific Abs were raised to localize the allergen by immunogold electron microscopy in the starchy endosperm and the aleuron layer. The allergen is mainly expressed in mature wheat seeds and, despite an approximately 50% sequence identity, showed no relevant cross-reactivity with allergens from other plant-derived food sources such as maize, rice, beans, or potatoes. Recombinant wheat serine proteinase inhibitor, when used in combination with other specific allergens, may be useful for the diagnosis and therapy of IgE-mediated baker's asthma.     

Proteome mining for novel IgE-binding proteins from the German cockroach (Blattella germanica) and allergen profiling of patients

Although cockroaches are known to produce allergens that can cause IgE-mediated hypersensitivity reactions, including perennial rhinitis and asthma, the various cockroach allergens have not yet been fully studied. Many proteins from the German cockroach show high IgE reactivity, but have never been comprehensively characterized. To identify these potential allergens, proteins were separated by 2-DE and IgE-binding proteins were analyzed by nanoLC-MS/MS or N-terminal sequencing analysis. Using a combination of proteomic techniques and bioinformatic allergen database analysis, we identified a total of ten new B. germanica IgE-binding proteins. Of these, aldolase, arginine kinase, enolase, Hsp70, triosephosphate isomerase, and vitellogenin have been reported as allergens in species other than B. germanica. Analysis of the Food Allergy Research and Resource Program allergen database indicated that arginine kinase, enolase, and triosephosphate isomerase showed significant potential cross-reactivity with other related allergens. This study revealed that vitellogenin is an important novel B. germanica allergen. Personalized profiling and reactivity of IgE Abs against the panel of IgE-binding proteins varied between cockroach-allergic individuals. These findings make it possible to monitor the individual IgE reactivity profile of each patient and facilitate personalized immunotherapies for German cockroach allergy disorders.