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Health effects of organic dust exposure in dairy farmers.

Exposure to farm dust may cause asthma, rhinitis, allergic alveolitis, organic dust toxic syndrome, and chronic bronchitis. Febrile reactions to inhaled dusts are common and are usually of a toxic rather than an allergic type. Some evidence indicates that dairy farmers may have an increased prevalence of chronic bronchitis, allergic asthma, rhinitis, and chronic airflow limitation, but this has not been conclusively shown. Storage mites and cow dander are important allergens in dairy farming. Inflammation of airways may in part be caused by immediate or delayed hypersensitivity. Other mechanisms, such as activation of inflammatory cells from toxic agents or high exposure levels, may be of considerable importance in causing airway and lung disease.

Agricultural Workers' Diseases↗

The effects of airway hyperresponsiveness, wheezing, and atopy on longitudinal pulmonary function in children: a 6-year follow-up study.

We examined growth of spirometric lung function in 696 children of European ancestry who were followed from ages 9 to 15 years and stratified according to their degree of responsiveness to methacholine inhalation challenge, atopic status, and respiratory symptoms. Subjects were participants in the longitudinal Multidisciplinary Health and Development Study in Dunedin, New Zealand. Forced expired volume in 1 second (FEV1), and vital capacity (VC) were measured at 9, 11, 13, and 15 years of age, concurrently with assessment of airway responsiveness determined by the concentration of methacholine causing a 20% fall in FEV1 (PC20 FEV1). Atopic status was assessed at age 13 by skin-prick testing to 11 allergens. In children demonstrating airway hyperresponsiveness, FEV1 increased with age at a slower rate, and the FEV1/VC ratio had a faster rate of decline through childhood, compared to non-responsive children. Subjects with positive skin tests to house dust mite and cat dander also had lower mean FEV1/VC ratios than the control group. Any reported wheezing was associated with slower growth of FEV1 and VC in males. We conclude that in New Zealand children with airway responsiveness and/or atopy to house dust mite or cat growth of spirometric lung function is impaired.

Adolescent↗

Relationship between atopy and frequent bronchial response to exercise in school children.

The natural history of a bronchial response to exercise (BRE) was studied in a cohort of primary-school children, who were followed over a 2-year period. In 1,094 children, three free-running tests were performed in 1-year intervals. Children who responded in one of the tests were designated as "infrequent" responders (20.5%), whereas those responding at two or all three occasions were designated as "frequent" responders (7.4%). A frequent positive BRE was closely associated with atopy (defined as skin test positivity to 1 of 7 common aeroallergens) and respiratory symptom status. Compared to atopics without respiratory symptoms, an increased risk for a frequent positive BRE was seen for atopic children who were symptomatic during the whole study period [odds ratio (OR) 25.4; confidence interval (CI) 6.9-94.0], who had gained symptoms (OR, 11.0; CI, 2.8-43.2) or who had symptoms at the beginning of the study but had lost them during follow-up (OR, 4.6; CI, 1.0-20.6). A sensitization to dust mites (OR, 8.0; CI, 4.3-15.0) but not to animal dander (OR, 2.3; CI, 1.0-5.2) or pollen (OR, 0.7; CI, 0.3-1.6) was significantly related to a frequent positive BRE. Our findings support the notion that while "children grow out of asthma," they might maintain their bronchial hyperresponsiveness. Regarding specific sensitization, mite allergy seems to play the predominant role.

Allergens↗

Evaluation of the potency of allergenic extracts by inhibition of IgG-antibody binding.

A method is described for the in vitro potency evaluation of allergenic extracts by using their capacity of binding to specific human IgG antibodies. The results obtained with this inhibition-type enzyme immunoassay are compared with the analyses by the customary method of IgE antibody binding. A large series of allergenic protein fractions from the pollen of the Gramineae, Olea europea, Parietaria judaica, and from the dust mite Dermatophagoides pteronyssinus as well as from cat dander and peanuts were examined for inhibition of specific antibodies of both IgG and IgE isotypes. Potency evaluation by inhibition assays for IgE- and IgG-binding showed a significant correlation for the points of 50% inhibition (r = 0.92, p = 0.0001), but not for the slopes of the inhibition curves, i.e. the respective antibody avidities. Evidence is provided that the strict relationship between IgE- and IgG-inhibition by allergens could not be explained by possible cross-contaminations of the anti IgE- or anti IgG-reagents employed in the immunoassays. It is concluded that the inhibition of IgG-antibody binding presents a fast, reliable and low-cost alternative for the potency control of allergens used in clinical practice.

Allergens↗

Allergen source materials and quality control of allergenic extracts.

Allergen extracts are prepared from a wide variety of source materials including pollens, fungi, arthropods, animal danders, foods, and dusts. The composition of allergen extracts can vary depending on the allergen source, manufacturing process, and storage conditions. Allergen-specific immunoglobulin E (IgE) assays and skin tests employ a variety of allergen-containing reagents that confer specificity on the test. Given that the allergen source materials are heterogenous mixtures of proteins, glycoproteins, carbohydrates, and other substances that are not allergenic, it is not unexpected that variability exists between test results obtained with different allergen-containing reagents. Variability within a single manufacturer's allergen product can be controlled by using reproducible extraction and processing procedures, single large lots of allergen source materials, and solid-phase supports. These controls do not, however, ensure the consistency of products between manufacturers or laboratories because allergen source materials, manufacturing procedures, and acceptance criteria for allergen reagents may vary.

Allergens↗

Bacteria and their products peptidoglycan and teichoic acid potentiate antigen-induced histamine release in allergic patients.

Histamine release was examined in leukocyte suspensions from patients allergic to grass pollen, mite or cat dander or to bacteria (antigen). When the cells were challenged with specific antigen plus bacteria to which the person was not sensitized, these bacteria were found to potentiate the allergic histamine release. The potentiating effect by bacteria might be due to the bacterial cell wall components, peptidoglycan and teichoic acid, which mimic the effect of bacteria.

Antigens, Bacterial↗

Hypersensitivity pneumonitis: correlation of cellular and immunologic changes with clinical phases of disease.

Many airborne organic antigens in the form of fungal spores and thermophilic bacteria or dander and aerosolized proteins can cause hypersensitivity pneumonitis after repeated inhalational exposure. Although a syndrome of acute illness often occurs, many people who are exposed and become sensitized can remain asymptomatic. However, immunologic evidence from an analysis of cells and antibodies obtained by bronchoalveolar lavage from asymptomatic subjects may indicate an ongoing alveolitis. With chronic illness, which has many characteristics of an interstitial fibrotic pneumonitis, a lymphocytic alveolitis and granulomatous reaction develop in the lungs. This review emphasizes the immunological changes in the lungs that occur at different phases of hypersensitivity pneumonitis and contribute to current concepts about pathogenetic mechanisms.

Adult↗

Immunotherapy in allergic respiratory diseases.

Much more work is needed to specify the correct indications for immunotherapy in respiratory allergic diseases. Immunotherapy with pollen and mite extracts has shown some clinical efficacy versus placebo in controlled studies in allergic rhinitis and/or asthma. However, controlled studies comparing the cost, the risk factors and the efficacy of immunotherapy versus treatment with antihistaminic drugs, bronchodilators and topical steroids are needed. Additional studies are needed to established the place of immunotherapy in animal danders and mould allergy. In any case, before initiating immunotherapy in respiratory allergy the following questions must be answered: is there sufficient evidence of a close relationship between symptoms and allergen exposure? is it possible to achieve efficient allergen avoidance? is simple drug treatment no sufficient? is there evidence in the literature of effectiveness of IT for this allergen? is the patient able to comply with a long and constraining treatment?

Allergens↗

Diagnosis of sulfite and aspirin sensitivity.

In addition to the well-recognized allergic responses of individuals to high mol wt substances, such as pollens, molds, and animal dander, susceptible asthmatics may also experience adverse reactions to low mol wt substances such as sulfites, ASA, and NSAIDs. The diagnosis of sulfite and aspirin sensitivity can only be made by appropriately conducted provocative challenge. Every precaution should be taken to assure the safety of the patients, since life-threatening reactions can occur. A better understanding of the mechanism or mechanisms involved in the adverse reactions to these substances will not only provide information to better diagnose the reaction, but also improve our understanding of the treatment of asthma.

Anti-Inflammatory Agents, Non-Steroidal↗

The dilemma of occupational rhinitis: management options.

Occupational rhinitis is a common heterogeneous group of inflammatory conditions in the nose, caused by exposure to airborne irritants and sensitizers in the occupational environment. The mechanism can be allergic, neurogenic or toxic. Data from several epidemiologic studies indicate that animal dander, organic dusts, latex and chemicals can cause occupational rhinitis, but because of methodological problems as well as weaknesses in the definition of occupational rhinitis, occupational exposure is probably an underestimated cause of rhinitis. The effect of rhinitis on the mental aspects of quality of life and substantial costs due to loss of productivity make it important to diagnose and treat occupational rhinitis. Diagnosis relies on a history of exposure, skin prick testing and, if possible, nasal provoacation. Avoidance of exposure, protective measures at the workplace and medical treatment, with agents such as second generation antihistamines and nasal corticosteroids, can make it possible to avoid progress of the disease from rhinitis to asthma. The efficacies of montelukast, a leukotrienne receptor antagonist, and omalizumab, an anti-immunoglobulin E monoclonal antibody in the treatment of occupational rhinitis are yet to be evaluated

Allergens↗

Haemolytic complement consumption by Parietaria pollen extracts in relation to peptide-bound flavonoids.

Inhaled allergens from house dust, mites or animal danders activate human complement in vitro by engaging the C1-component through a non-antibody-dependent mechanism. These earlier findings are extended by showing that the allergenic components in extracts of Parietaria pollen are almost equally potent complement activators as those from house dust or mites. Spectroscopic evidence indicates that haemolytic complement consumption by the Parietaria allergens and their enzymic fragments is most likely related to post-translational side-chains comprising flavonoid derivatives. These adsorbed and/or peptide-bound tannin-like structures may also explain the exceptional stability of the high- and low-molecular mass allergenic components in Parietaria pollen extracts.

Complement Activation↗

[Atopic patch test. Atopic eczema and allergy].

The role of IgE-mediated allergic reactions in atopic eczema remains controversial. Using the atopy patch test, aeroallergens such as house dust mites, animal dander or pollen can be identified as relevant trigger factors in a subgroup of patients with atopic eczema. The atopy patch test is an epicutaneous patch test employing allergens known to elicit IgE-mediated reactions and used to evaluate eczematous skin reactions. In a series of single- and multicenter studies, a method was developed, standardized and compared to other diagnostic techniques (specific serum-IgE, skin prick test) in atopic eczema patients. With regard to clinical history, the most specific results were obtained with the atopy patch test (allergen-dependent 69-92%), while sensitivity was higher for skin prick test (69-82%) and specific IgE (65-94%). The characterization of a patient subgroup with relevant IgE-mediated allergy may lead to more efficient avoidance and perhaps even specific immunotherapy strategies in the management of atopic eczema.

Adolescent↗

Modulation of the immediate allergic wheal reaction in the skin by drugs inhibiting the effects of leukotriene C4 and prostaglandin D2.

OBJECTIVE: To study the effect of nordihydroguaiaretic acid (NDGA), zafirlukast and indomethacin on the size of the size of the allergic prick-test wheal. METHOD: In the first part of the study, NDGA and indomethacin, as well as the mepyramine control (10 micrograms/ml and 100 micrograms/ml), were injected intracutaneously 10 min before prick-testing with the cow dander allergen in 51 sensitised atopic subjects. In the second part, five other subjects were prick-tested with several allergens followed by administration of 40 mg zafirlukast or 100 mg indomethacin and re-prick-testing 2 h or 4 h later. RESULTS: The intracutaneous indomethacin at both concentrations enlarged the wheal by 27 +/- 50% and 29 +/- 51% (P < 0.02, n = 51), respectively. Likewise, the peroral indomethacin significantly increased the wheal area by 17 +/- 30% (P = 0.035, n = 5). Neither intracutaneous NDGA in 51 subjects nor peroral zafirlukast in 5 subjects had marked effects on the size of the prick-test wheal. As expected, mepyramine (10 micrograms/ml) decreased the wheal area by 33 +/- 32% (P < 0.001, n = 51), but 14 subjects did not show any decrease after administration of this H1-antihistamine. CONCLUSION: The prostaglandin synthesis inhibitor (indomethacin) augments the prick-test wheal, but the leukotriene synthesis inhibitor (NDGA) and leukotriene C4 antagonist (zafirlukast) have no marked effects on the size of the prick-test wheal.

Administration, Cutaneous↗

Release of histamine and leukotriene C4 in immediate allergic wheal reaction as measured with the microdialysis technique.

Other mediators as well as histamine can contribute to the allergic wheal reaction. In this study, the microdialysis technique was used to monitor the release of histamine, leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) in prick-test wheal reactions induced by cow dander allergen. Of 31 atopic subjects, 25 showed detectable histamine release that correlated significantly with the number of tryptase-positive mast cells and serum cow-specific IgE but not with the wheal size. Detectable LTC4 release was shown by 16 of 18 subjects, but PGD2 release was shown by only 7 of 17 subjects, and neither mediator was associated with tryptase-positive mast cells, IgE levels or wheal size. An inverse association between histamine release and LTC4 release in these 18 subjects was found rather than a direct correlation. With advancing age of the subject histamine release (n = 31) tended to decrease, although insignificantly, but LTC4 release (n = 18) and sensitivity to histamine prick increased significantly, which seemed to parallel the changes in the wheal size induced by cow allergen. In conclusion, the results showed that the release of histamine, LTC4 or PGD2 alone cannot explain the extent of the wheal reaction. In addition, the amount of histamine released was not related to the amount of LTC4 released, but rather an inverse association existed between these mediators.

Adult↗

The risk of occupational rhinitis.

OBJECTIVE: Reports on the aetiology and risk of occupational rhinitis in different occupations are scarce. METHOD: The purpose of this study was to find the occupations with an increased risk of occupational rhinitis. Age and gender differences in occupational rhinitis and occupational asthma were also compared, and the most common causes of occupational rhinitis were analysed. DESIGN: This study covered the cases of occupational rhinitis and asthma reported to the Finnish Register of Occupational Diseases during the years 1986-1991. The cases on the Register were linked to the longitudinal census data file from the Finnish censuses. RESULTS: During 1986-1991, 1244 new cases of occupational rhinitis (474 women and 497 men) and 1867 new cases of occupational asthma (916 women and 951 men) were reported to the Register. Animal dander, flours, wood dusts, textiles, phthalic acid anhydrides and storage mites were important causes of occupational rhinitis. The highest relative risk of occupational rhinitis was among furriers, the age-standardized rate ratio (SRR) was 30.0. Bakers and livestock breeders had also a markedly elevated relative risk (SRR = 22.0). Men had the highest incidence of occupational rhinitis at the age of 25-29 years and among women the incidence gradually increased and reached the peak in the group 40-44 years of age. CONCLUSION: Furriers, bakers, and livestock breeders had the most elevated relative risk of occupational rhinitis. Occupational rhinitis cases reported at a younger age than asthma, suggesting that rhinitis often precedes asthma.

Adolescent↗

Lessons from atopy patch testing in atopic dermatitis.

The exposure of atopic eczema (AE) patients to their relevant protein allergens (eg, from house dust mite, cat dander, grass pollen, or food allergens) can trigger an exacerbation or maintain the disease. Diagnostic procedures are needed to specify allergen avoidance recommendations for the individual patient. Skin prick tests and specific serum IgE tests might be helpful in pointing out potential trigger factors, but relevance needs to be confirmed (eg, with food provocation tests). The atopy patch test (APT) involves the epicutaneous application of intact protein allergens in a diagnostic patch test setting with an evaluation of the induced eczematous skin lesions after 24 to 72 hours. The APT targets the cellular component of AE and helps round out the AE test spectrum. As a number of apparently minor test modifications greatly influence the sensitivity, specificity, and reproducibility of the APT, the European Task Force on Atopic Dermatitis (ETFAD) has developed a standardized APT technique. It consists of purified allergen preparations in petrolatum, applied in 12-mm diameter Finn chambers mounted on Scanpor tape to non-irritated, non-abraded, or tape-stripped skin of the upper back. The APT is read at 48 and 72 hours according to the test criteria and reading key of the ETFAD for appearance of erythema, and number and distribution pattern of the papules. In contrast with skin prick tests, the APT might even detect a relevant sensitization in the absence of specific IgE. Many studies have been undertaken to objectify the sensitivity and specificity of the APT to show its diagnostic use in clinical practice.

Advisory Committees↗

Prevention of antigen-induced bronchoconstriction by lodoxamide ethyl, a new orally active antiallergic drug.

Lodoxamide ethyl, an orally active drug with pharmacologic activity similar to that of cromolyn sodium, blocks passive cutaneous anaphylaxis (PCA) in rats and antigen-induced bronchoconstriction in guinea pigs and monkeys. Its effectiveness in preventing antigen-induced airway obstruction was studied in 12 asymptomatic asthmatic adults with immediate skin test sensitivity to ragweed, Alternaria, or animal dander. The dose required to reduce the forced expiratory volume in 1 sec (FEV1) by 20% (PD20) was determined by dosimeter bronchoprovocation challenge with the appropriate antigen. At 1-wk intervals each subject received either placebo of 1, 3, or 10 mg drug in a randomized, double-blind fashion 30 min prior to starting bronchoprovocation challenge. On average, 1 mg increased the PD20 fivefold, 3 mg about sixfold, and 10 mg about 27-fold. Dose-related side effects began 10 min after drug and lasted up to 40 min. Thus the oral administration of lodoxamide ethyl was effective in preventing antigen-induced bronchoconstriction, and both the beneficial effects and side effects are dose related.

Adult↗

Antibodies to purified bee venom proteins and peptides. II. A detailed study of changes in IgE and IgG antibodies to individual bee venom antigens.

Antibodies to individual bee venom antigens were studied in detail in nine bee sting-allergic patients who received venom immunotherapy without side effects, in two patients who failed to reach maintenance, and in two whose sensitivity returned. The study was confined to patients who had IgE antibodies to at least one of four purified bee venom antigens at the start of treatment. IgE and IgG antibodies to phospholipase A2 (PLA2), hyaluronidase (HYAL), and acid phosphatase (ACID P) and IgE antibodies to melittin (MEL) were measured, and changes in the antibody levels were followed during bee venom immunotherapy. Two contrasting patterns of antibody response were seen in the nine successfully treated patients. In five patients there was a rise in serum IgG antibodies to the same antigens as the IgE antibodies. In two patients' serum IgE antibody to HYAL or ACID P fell without a marked IgG antibody response to these antigens, although high levels of IgG antibody to PLA2 were present in both. Although the first pattern is consistent with a "blocking" role for IgG antibody, clearly the second is not. Not all patients can be conveniently divided into these two categories, and two patients did not show any significant change in either IgG or IgE antibody but were nevertheless able to tolerate the maintenance dose of 100 micrograms of venom. Two patients who failed to reach the maintenance dose of 100 micrograms because of their allergic reactions to the injections of venom were distinguished by (1) very high serum IgE antibody and (2) a low ratio of IgG/IgE antibody. Passive immunization with IgG antibody from a hyperimmune beekeeper was, however, protective in these patients, although it did not raise their overall serum IgG antibody level very much. We are unable to explain either the failure of conventional therapy or the beneficial effect of passive immunization in these two patients. Two bee sting--allergic beekeepers lost their sensitivity to stings, but later, when their sera contained IgE antibody to another bee venom antigen, they reacted to stings and inhalation of beehive dander. These data suggest that either falling IgE antibody or IgG- "blocking" antibody could be responsible for providing clinical protection to bee venom--allergic subjects. Renewed clinical sensitivity was observed when the IgE response was modulated, with patients making IgE antibody first to one antigen and then to another.

Acid Phosphatase↗