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Increased bronchial responsiveness in primary Sjögren's syndrome. A sign of tracheobronchial involvement.

Thirty-six patients with primary Sjögren's syndrome (pSS) and 60 healthy volunteers underwent provocative bronchial testing with aerosolized dosed methacholine. On the average, pulmonary functions tests performed before bronchial testing were normal. However, 18/36 patients (50%) had bronchial hyper-responsiveness (BH), an incidence higher that that found in our control population (6.6%). No difference between BH and normally responsive patients was found in the duration of disease, immunological abnormalities or symptoms, and only the FEF50 was significantly lower in the BH group. It is therefore hypothesized that in pSS bronchial hyper-responsiveness may be due to lymphocytic inflammation and an alteration in secretion secondary to gland damage.

Adult↗

Five-year follow-up on the PAT study: specific immunotherapy and long-term prevention of asthma in children.

BACKGROUND: A 3-year course of specific immunotherapy (SIT) in children with hay fever to grass and/or birch pollen significantly reduced the risk of developing asthma. To investigate the long-term preventive effect, we performed a follow up--2 years after termination of immunotherapy. METHODS: A total of 183 children, aged 6-14 years with grass and/or birch pollen allergy could be investigated 2 years after discontinuation of SIT or no treatment. Conjunctival provocation tests (CPTs) and methacholine bronchial provocation tests were carried out during the season and winter after 5 years. The development of asthma was assessed by clinical evaluation. RESULTS: The significant improvement in hay fever and CPT results observed after 3 years of SIT persisted at the 5-year follow-up. No difference in bronchial responsiveness to methacholine was found after 5 years because of spontaneous improvement during the follow-up period in the control patients. The immunotherapy-treated children had significantly less asthma after 5 years as evaluated by clinical symptoms [odds ratio 2.68 (1.3-5.7)] in favor of SIT for prevention of development of asthma and significantly less patients reported an increase in asthma scores (P < 0.01). CONCLUSION: Immunotherapy for 3 years with standardized allergen extracts of grass and/or birch shows long-term clinical effect and preventive effect on development of asthma in children with seasonal rhinoconjunctivitis.

Adolescent↗

Diagnostic tests in allergy to green coffee.

Twenty-two coffee roastery workers with work-related symptoms of various degree from the eyes, nose or bronchi were tested with partly purified water-soluble extract from dust of green coffee beans (GCB). Eighteen persons had a positive prick test, eight a positive bronchial provocation test and seven a positive nasal provocation test. Fourteen had a positive methacholine test, indicating unspecific bronchial hyperreactivity. Specific IgE antibodies to GCB extract were found in sera of 11 workers and to castor bean (CB) extract in 16. The workers measured their lung function with an air flow meter, three times a day for 1 week, and the values were lower in the second half of the week for the workers with IgE antibodies to GCB, but not for the others. It is concluded that the case history, prick test, RAST, and simple lung function tests for one or a few weeks are the best tools when investigating occupational allergy. When the allergen is unknown, but the occurrence of an IgE-mediated allergy is suspected, serial lung function measurements and determinations of total serum IgE, in addition to taking a careful case history, are valuable methods with which to start the investigation.

Adult↗

A new risk of occupational disease: allergic asthma and rhinoconjunctivitis in persons working with beneficial arthropods.

Allergic asthma and rhinoconjunctivitis have been reported in workers who are constantly in close contact with arthropods during the course of breeding and research. We investigated a group of ten people working with beneficial arthropods in a "bio-factory." The following tests were carried out: skin prick test with allergens present in the workplace, baseline pulmonary function test, aspecific bronchial provocation test with ultrasonically nebulized distilled water, and pulmonary function test after workplace exposure in two subjects. The results demonstrated a good correlation between skin prick test, previous RAST positive reactions, clinical symptoms, and exposure. Pulmonary function test after workplace exposure proved positive in one asthmatic subject and in one subject with rhinoconjunctivitis. It is concluded that the evidence supports the occupational nature of these allergic diseases and that there is a need for careful surveillance and environmental monitoring within the workplace.

Adult↗

Induction of IgE antibodies with predefined specificity in rhesus monkeys with recombinant birch pollen allergens, Bet v 1 and Bet v 2.

BACKGROUND: Recombinant birch pollen allergens Bet v 1 and Bet v 2 (birch profilin) have been characterized in vitro previously. OBJECTIVE: To establish a close-to-man model of type I allergy, recombinant birch pollen allergens were injected into rhesus monkeys. METHODS: The allergens were expressed in Escherichia coli, purified to homogeneity and injected into rhesus monkeys with aluminium hydroxide as adjuvans. The development of type I allergy was monitored by measurement of specific IgE, in vitro histamine release tests, cellular proliferation assays, skin testing, and bronchial provocation tests. RESULTS: Immunized rhesus monkeys displayed symptoms of type I allergy comparable to those of allergic patients, and cross-reactivity of IgE antibodies with Bet v 1 and Bet v 2 homologous allergens was observed. Systemic application of corticosteroids during secondary immunizations suppressed specific antibody responses. CONCLUSION: Recombinant birch pollen allergens (Bet v 1 and Bet v 2) were effective to establish a close-to-man model of natural type I allergy in rhesus monkeys, allowing study of specific IgE regulation in vivo.

Allergens↗

IgE-mediated inhalant allergy against human corticotropin-releasing hormone.

A 25-year-old female developed IgE-mediated sensitization against human recombinant corticotropin-releasing hormone (CRH) with symptoms of allergic rhinoconjunctivitis and bronchial asthma. The occupational allergy was proved by positive skin prick test, bronchial provocation, dose-dependent histamine release, RAST measurements with CRH allergen (RAST class 3) and RAST inhibition. Using the immunoblot technique, a single allergen band with a molecular weight of less than 14.4 kD in the range between the isoelectric point 5.2 and 5.7 was detected for the CRH extract. Since no endocrinological and behavioral disorders were found, increased CRH-specific IgE was not able to influence the regulatory control of this neuropeptide. After 18 months of avoiding the occupational CRH exposure allergen-specific histamine release and RAST were negative.

Adult↗

Occupational asthma caused by Papaver somniferum.

Twenty eight workers of a pharmaceutical factory were studied. The company produced morphine and other alkaloids extracting the active principles from shells of Papaver somniferum. Six of the exposed subjects had clinical symptoms of sensitization to this allergen and positive skin tests. A bronchial provocation test was found to be positive on 4 workers and specific IgE could be found on the 6 sensitized patients by an ELISA and a RAST test using an aqueous extract of P. somniferum. A histamine release using the same antigen was also positive in the 4 samples from sensitized patients available. An SDS-PAGE of the extract revealed a major protein band with an estimated mol wt of 52,000 d. This band had the highest IgE-binding capacity as shown by immunoblotting. All these facts suggest that P. somniferum allergy is mediated by an IgE mediated mechanism and not by a pharmacological or toxic effect of the alkaloids or polyphenols.

Allergens↗

Diagnostic value of a glass fibre-based histamine analysis for allergy testing in children.

The aim of this study was to compare the diagnostic value of common allergy tests with basophil histamine release in 124 children with symptoms of asthma. The patients were evaluated by case history, skin prick test, RAST-analysis, and basophil histamine release using a glass fibre-based histamine assay to 10 common inhalant allergens. The bronchial provocation test was used as a reference of "true" IgE-mediated asthma. To compare the various diagnostic parameters each absolute test value was classified into a scoring system. The concordance between the tests varied between 85-97%. In general, the best concordance was found between basophil histamine release and RAST. Sensitivity, specificity and predictive values were calculated on the basis of 104 bronchial provocation tests. It was found that histamine release was the best single analysis, followed by RAST and prick testing. The sensitivity of RAST and histamine release was very high (1.00) for pollen and house dust mites. Histamine release showed a predictive value between 0.91 and 1.00 for pollen and house dust mites, thus indicating the possibility of omitting the bronchial provocation test. In the dander group histamine release gave the best sensitivity (0.91), however at the expense of specificity (0.64), whereas RAST and skin prick test gave a specificity of 1.00. In the mould group histamine release also showed the best diagnostic value. The combination of skin testing with histamine release or RAST was of no additional diagnostic help. It is concluded that the glass fibre-based histamine analysis, which makes routine histamine release testing possible, is a reliable diagnostic test in children.

Asthma↗

[Non-allergenic bronchial hyperreactivity. Measurement methods and reproducibility].

Different methods are available to measure non-allergic airway responsiveness. In the last years, efforts have been made to improve standardization of these methods, in order to allow comparison of data from different sources. The most currently used bronchial provocation tests are those with nebulisation of histamine or methacholine either a tidal volume or from a dosimeter, a dose-response curve being obtained in measuring expiratory flows or airway resistance. Inhalation of non-iso-osmolar solutions, cold air hyperventilation, exercise or other agents and stimuli may be used to estimate airway response, but they are more useful as a research tool than for clinical purposes. The reproducibility of bronchial provocation tests is dependent of different factors such as those related to the subject (asthma stability, performance of tests, medications, circadian variations), technical factors (type and calibration of the apparatus, nebulizer output, measurements, solutions) and to the methods of calculation of the bronchial response. Short-term reproducibility of the different types of bronchial provocation tests is usually good although long-term stability needs to be further assessed. A correlation has been reported between the response to most of the different bronchoconstrictor agents, although variable.

Administration, Inhalation↗

Occupational asthma induced by chromium salts.

Five patients with asthma related to exposure to chromium salts, in their work area, are presented. All of them were non atopics and presented a history of contact dermatitis, with positive patch tests to potassium dichromate, previous to the onset of bronchial asthma. Solutions of K2Cr2O5 were prepared in normal saline at 0.01, 0.1 and 1 mg/ml for skin prick tests (SPT) and bronchial provocation tests (BPT). Immediate cutaneous reaction by SPT was negative for controls and patients. BPT were performed by the tidal breathing method, with positive results in all subjects. A negative response was recorded in 4 control unexposed asthmatics. An attempt to inhibit BPT with sodium cromoglycate was unsuccessful. The diversity of reactions (immediate, dual and late) registered in BPT, support that bronchial reactivity can be induced specifically by inhalation of chromium salts. The data of follow-up indicates a good prognosis, provided that patients remain out of exposure. The lack of facts suggesting an IgE-mediated reaction puts forward for consideration other pathophysiologic mechanisms.

Adult↗

Parental smoking enhances bronchial responsiveness in nine-year-old children.

We studied the relationship between parental smoking habits and atopy and bronchial responsiveness (BR) in 9-year-old, non-selected schoolchildren. A questionnaire on respiratory disease and maternal and paternal smoking habits was administered to one parent. Skin prick tests using the most common allergens present in central Italy, a flow-volume spirometric test, and a bronchial provocation test using carbachol in increasing doses were performed. Male children with smoking parents had significantly increased BR when compared to those whose parents did not smoke (Odds Ratio (OR) = 4.3, p = 0.009). No such significant increase in BR was found in female children of smoking parents (OR = 1.5, p = 0.4). The relationship between BR in children and smoking in parents was stronger in asthmatics (p = 0.02), but was still significant after controlling for asthma and atopy. Bronchial responsiveness was significantly correlated with atopy (p = 0.001). This was also true for nonasthmatic children and for both males and females separately. Male children of smoking parents had increased reactivity to allergens as assessed by the skin prick test index (p = 0.001). It is hypothesized that passive smoking, by increasing the frequency of BR and of atopy, may increase the risk of asthma in childhood and particularly in boys.

Adult↗

A study on bronchial responsiveness to methacholine in subjects with untreated autoimmune hyperthyroidism.

Because hyperthyroidism can mimic respiratory disorders with dyspnoea, this study was carried out in order to determine whether bronchial hyperresponsiveness is more frequent in hyperthyroid patients versus controls. Eighteen nonatopic subjects with newly-diagnosed untreated Graves' disease and 18 control subjects entered the study. All subjects underwent an aspecific bronchial provocation test with methacholine. Bronchial hyperresponsiveness was diagnosed in seven patients with hyperthyroidism and in two controls, with no statistically significant difference between the groups (Fisher's exact test; p = 0.1212). In conclusion, these results suggest that hyperthyroidism is not associated with a higher frequency of bronchial hyper-responsiveness to methacholine with respect to euthyroid subjects.

Adolescent↗

Glutathione S-transferase genotypes and allergic responses to diisocyanate exposure.

Diisocyanates are the most common low molecular weight chemicals to cause occupational asthma. However, only some 5-10% of exposed workers develop asthma, which suggests an underlying genetic susceptibility. Diisocyanates and their metabolites may be conjugated with glutathione by glutathione S-transferases (GSTs). We examined whether polymorphisms in the GSTM1, GSTM3, GSTP1 and GSTT1 genes modify allergic responses to diisocyanate exposure. The study population consisted of 182 diisocyanate exposed workers, 109 diagnosed with diisocyanate-induced asthma and 73 without asthma. Lack of the GSTM1 gene (null genotype) was associated with a 1.89-fold risk of diisocyanate-induced asthma [95% confidence interval (CI) 1.01-3.52]. Moreover, among the asthma patients, the GSTM1 null genotype was associated with lack of diisocyanate-specific immunoglobulin (Ig)E antibodies [odds ratio (OR) 0.18, 95% CI 0.05-0.61] and with late reaction in the specific bronchial provocation test (OR 2.82, 95% CI 1.15-6.88). Similarly, GSTM3 AA genotype was related to late reaction in the specific bronchial provocation test (OR 3.75, 95% CI 1.26-11.2). The GSTP1 Val/Val genotype, on the other hand, was related to high total IgE levels (OR 5.46, 95% CI 1.15-26.0). The most remarkable effect was seen for the combination of GSTM1 null and the GSTM3 AA genotype which was strongly associated with lack of diisocyanate-specific IgE antibodies (OR 0.09, 95% CI 0.01-0.73) and with late reaction in the bronchial provocation test (OR 11.0, 95% CI 2.19-55.3). The results suggest, for the first time, that the polymorphic GSTs, especially the mu class GSTs, play an important role in inception of ill effects related to occupational exposure to diisocyanates.

Adult↗

Anacardium occidentale (cashew) pollen allergy in patients with allergic bronchial asthma.

BACKGROUND: The cashew tree grows in abundance in the hills and plains of Goa, India. Because of the financial yield, more and more trees are being planted each year. The cashew tree flowers once a year between January and March, but pollination is mostly entomophilous. OBJECTIVE: For the first time, a study was conducted to establish the possible role of the cashew pollen in triggering allergic asthma. METHODS: A stock solution of pollen extract was prepared with the standard weight/volume method for intradermal skin tests and a bronchial provocation tests (BPTs). The protein content of the antigen, estimated with the use of Folin phenol reagent and a spectrophotometer, was 28.72 mg/ml. Ten healthy volunteers and 65 subjects with allergic asthma, as documented by previous positive skin test reactions to various pollens, were studied. RESULTS: Of the 65 patients, 26 (40%) had positive skin test reactions in various grades. BPTs were performed in 22 of the 26 patients after their baseline peak expiratory flow volume was assessed. Twenty (90.9%) patients had a positive BPT result, and the majority of patients had grade III and grade IV reactions. None of the control subjects (n = 10) had positive responses to either intradermal tests or the BPT. Serum IgE levels, estimated by ELISA, were high in patients with positive skin test responses and showed a linear correlation with cutaneous sensitivity. Control subjects showed normal levels of IgE (39.0 +/- 7.87 IU/ml). CONCLUSIONS: This study provided us with knowledge of an additional pollen, Anacardium occidentale, which could trigger an asthmatic response in allergic individuals.

Adolescent↗

Specific bronchial reactivity to toluene diisocyanate: dose-response relationship.

20 patients with toluene diisocyanate (TDI)-induced asthma were examined in order to assess their threshold of response to TDI during specific bronchial provocative tests (BPT). Specific bronchial hyperresponsiveness was evaluated by performing, on different days, specific BPT with increasing concentrations of TDI until a positive response was obtained; the threshold of response to TDI (low: 0.02-0.05 ppm; moderate: 0.1 ppm; high: 0.2-0.25 ppm) and the pattern of positive response were evaluated in comparison with some clinical features of the disease. The threshold of airway response to TDI was low in 9, moderate in 7 and high in 4 patients. No evident relationship was observed between the threshold of response to TDI and the pattern of positive response to the lower TDI concentration (immediate in 5, late in 8 and dual in 7 subjects) or other clinical features (duration of asthmatic symptoms, smoking habits, cessation of work, nonspecific bronchial hyperresponsiveness to methacholine); however, 6 out of 9 patients with low threshold had nonspecific bronchial hyperreactivity in comparison with 6 out of 11 patients with moderate or high threshold. In 10 out of 13 patients who performed two positive BPT with different TDI concentrations, the pattern of response was the same either at lower and at higher TDI concentrations; 3 subjects who had a late reaction at the lower concentration showed a dual reaction to the higher TDI concentration. A relationship between the degree of the specific bronchial reaction (% fall in FEV1 from baseline value) and TDI concentration during BPT was observed for the immediate reaction but not for the late reaction.

Asthma↗

[Bronchial response to a provocation test in children allergic to Dermatophagoides pteronyssinus].

Bronchial provocation tests with allergens are becoming recognized as one of the most important diagnostic parameters for the detection and confirmation of the role of the allergic component directly on the reaction site. Twenty-seven children with positive skin tests and RAST for Dermatophagoides Pteronyssinus were challenged with solutions of the same antigen. Twenty-one (77%) had positive responses expressed by different patterns: Six (28.5%) showed isolated early reaction, seven (33.3%) had biphasic responses. Six (28.5%) showed dual response with prolonged (1-2 hours) late reaction. One child had dual late reaction after 35 hours (ultra-late reaction). Six (28.5%) patients had negative reactions. The results suggest that bronchial provocation tests with antigens performed as outlined in this study can also be applied in the diagnosis of pediatric allergy.

Adolescent↗

Formaldehyde asthma--rare or overlooked?

A total of 230 persons who had been exposed to formaldehyde and suffered from asthma-like respiratory symptoms were examined between January 1, 1977, and May 31, 1983. All the subjects had a bronchial provocation test with formaldehyde. On the basis of the medical and occupational history of the patients, the specific bronchial provocation test, and other test results, 12 cases were considered to be caused by specific sensitization to formaldehyde. All subjects had been exposed occupationally. An exposure period of between 1 mo and 19 yr preceded the onset of symptoms. Three persons displayed no bronchial hyperreactivity as assessed with a histamine or metacholine provocation test. Eleven of the 12 reactions were triggered by about 2.5 mg/m3 and one reaction by about 1.2 mg/m3 of formaldehyde. The late reaction in 1 patient was completely blocked by the inhalation of 100 micrograms of beclomethasone di-isoproprionate before the challenge with formaldehyde. Seventy-one of the 218 subjects who did not react when they were challenged with formaldehyde demonstrated bronchial hyperreactivity. We conclude that formaldehyde asthma, although apparently a rare disease, is under reported. Removal from exposure has a favorable effect on the symptoms. Low domestic exposures, however, may maintain the symptoms in individuals already sensitized.

Adult↗