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[Bronchial hyperreactivity--provocation tests and their standardization].

Asthma is characterized by attacks of bronchial obstruction due to bronchial hyperreactivity which are reversible spontaneously or as a result of therapy. Therefore, the demonstration of bronchial hyperreactivity is essential for diagnosing and grading of bronchial asthma. The different provocation tests with allergenes and spasmogenes which do not lead to delayed reaction are considered as well as medicaments which increase or decrease bronchial hyperreactivity. The chronic inflammation which is the underlying process of bronchial hyperreactivity in asthmatic patients can be assessed by mucociliary clearance measurements. The essentials of standardizations of bronchial provocation tests from the clinical point of view are mentioned.

Asthma↗

[Occupational asthma].

The diagnosis of occupational asthma requires the integration of a multiplicity of data; the history, cutaneous skin tests, biological tests, respiratory function tests and non-specific tests of bronchial hyperreactivity and specific bronchial provocation test. The history search for the presence of an atopic state, the occurrence of similar disorders in members of the same firm and also the timing of symptoms in relation to the occupational activities. Cutaneous tests are particularly helpful in IgE-mediated asthma in relation to the inhalation of animal or vegetable materials of glycoprotein origin. For haptens, the need for their prior coupling to a protein carrier causes problems which have not been entirely resolved. Laboratory tests run into the same snags. Respiratory function and non-specific bronchial provocation tests, confirm the diagnosis of asthma and enable the medium and long term prognostic to be assessed. Specific bronchial provocation tests are the most appropriate tests to establish an aetiological diagnosis in occupational asthma. Different technical methods are possible: quantitative administration of allergen aerosols, realistic tests, and tests using exposure chambers to achieve true test doses. The products responsible for occupational asthma are multiple. The different substances are characterised in a simplified manner: first animal matter (mammalian and arthropod allergens), secondly substances of vegetable origin (roots, leaves, flowers, grain and flour, wood and its derivates) and finally chemical products. The chemical products are primarily from the pharmaceutical and metal industries and above all from the plastics industry.

Allergens↗

Nasal provocation and passive anterior rhinomanometry (PAR).

A rapid and convenient method of nasal provocation (aerosol provocation combined with passive anterior rhinomanometry) is described. A comparative study between skin tests, bronchial provocations and nasal provocations highlights the usefulness of this method.

Adolescent↗

[Usefulness of Dermatophagoides pteronyssinus allergen extract from the Allergopharma J.G. Company for bronchial provocation in patients with bronchial asthma].

The value of Dpt allergen extract, produced by Allergopharma J.G., for performance of the bronchial provocation test in asthmatics was evaluated. The studies were carried out in 40 asthmatics with positive skin prick test with Dpt. Bronchial provocation test was performed according to Ryan's method. After an allergen inhalation, an early asthmatic reaction (EAR) and late asthmatic reaction (LAR) may appear. The following results were observed: a dual asthmatic reaction (EAR and LAR)--in 19 persons, the EAR--only in 9 patients, and the LAR--only in 1 patient. The negative result of the provocation were found in 11 patients. The frequency of particular patterns of the bronchial reactions was similar to those published before by us and other authors, with different allergen extracts. The allergen extract of Dpt from Allergopharma J.G. can be used to bronchial challenge.

Adolescent↗

[Longitudinal study of bronchial hyperreactivity using the carbachol test with school children].

STUDY DESIGN: Bronchial hyperresponsiveness of 476 schoolchildren (10.8 +/- 2.3 years) was studied three times at 12 months' intervals. The cumulative dose of 400 micrograms carbachol was applied in 50 + 50 + 100 + 200 micrograms steps. A fall of FEV1 of at least 15% was regarded as positive reaction. The test was save, as no severe obstruction was observed, only three children withdrew because of unpleasant cough. RESULTS: Reactivity was observed in 19.1, 10.0, and 5.2% of children at the occasion of the first, second and third test (sensitivity/specificity for prevalence of physician diagnosed asthma: 70/83, 35/91, and 24/96%, respectively). Reactivity was age dependent (7-11 years: 35%, 12-16 years: 18%), not influenced by sex, and the relative risk to be reactive was 1.9 in children 2-3 weeks after a respiratory tract infection. CONCLUSION: For epidemiological purposes carbachol provocation test--like other unspecific bronchial provocation tests--is inappropriate as a single test to classify individuals as asthmatics.

Adolescent↗

The FEF25-75% and the clinical diagnosis of asthma.

Nonspecific bronchial provocation testing is clinically useful in the evaluation of patients with symptoms suggestive of asthma. Testing is usually reserved for those with normal or near normal baseline spirometry. Although bronchial provocation testing is safe and widely available, the protocol is time consuming and not without expense. It has been reported that a reduced FEF25-75% in the context of an otherwise normal spirogram suggests that asthma should be considered. To evaluate this suggestion, we compared the baseline FEF25-75% (expressed as percent of predicted) with the results of the subsequent methacholine bronchial provocation test in 205 consecutive patients referred for testing. The mean baseline FEF25-75% in the 112 patients with normally responsive airways (ie, a negative bronchial provocation test) was 95.4 +/- 27.5%. In the 93 patients with a positive bronchial provocation test, the mean FEF25-75% was 77.6 +/- 27.2%. The mean FEF25-75% in those with hyperresponsive airways was significantly lower (t = 4.616, P < .0001). Of those patients with a positive bronchial provocation test, there was no significant correlation, however, between the baseline FEF25-75% and the degree of bronchial hyperresponsiveness as assessed by the PC20FEV1 (r = .154, P = .141). When a significant reduction in FEF25-75% was defined as less than 60% of predicted, the sensitivity of the prediction rule was 25.8%, the specificity was 92.0%, the positive predictive value was 72.7%, and the negative predictive value was 60.0%. From these results, we conclude that the FEF25-75% derived from simple spirometry may be useful in predicting the presence or absence, but not the degree, of bronchial hyperresponsiveness.

Adolescent↗

[Occupational asthma: methods of diagnosis and principle etiologies].

The diagnosis of occupational asthma requires the integration of a multiplicity of data; the history, cutaneous skin tests, respiratory function tests and non-specific tests of bronchial hyper-reactivity and specific bronchial provocation tests. The history remains fundamental in the investigation of occupational asthma. It should particularly search for the presence of an atopic trait, the occurrence of similar disorders in members of the same firm and also the timing of symptoms in relation to the occupational activities. Cutaneous tests are particularly helpful in IgE-mediated asthma in relation to the inhalation of animal or vegetable materials of glycoprotein origin. For haptens, the need for their prior coupling to a protein carrier causes problems which have not been entirely resolved. Laboratory tests (RAST, histamine liberation, TDBH...) run into the same snags. Respiratory function and non specific bronchial provocation tests confirm the diagnosis of asthma and enable the medium and long term progress to be assessed. Specific bronchial provocation tests are the most appropriate tests to establish an aetiological diagnosis in occupational asthma. Different technical methods are possible: quantitative administration of allergen, aerosols, and realistic tests using exposure chambers to achieve true test doses and to obtain dose dependent responses. The products responsible for occupational asthma are multiple and are gathered into two tables. The different substances are characterised in a simplified manner. First animal matter (mammalian and arthropod allergens), secondly substances of vegetable origin (roots, leaves, flowers, grain and flour, wood and its derivatives) and finally chemical products. The chemical products are primarily from the pharmaceutical and metal industries and above all from the plastics industry.

Allergens↗

[Bronchial asthmatic disease associated with tobacco dust--an occupational lung disease?].

Hypersensitivity to allergens in tobacco leaf as a cause of occupational asthma in workers of the tobacco manufacturing industry has been reported previously. We describe the case of a female employee working in a tobacco plant with asthmatic symptoms occurring at the working place. The symptoms described by the patient and the strong correlation to periods at work is highly suggestive for an occupational disease. The diagnosis of occupational bronchial asthma is supported by a positive skin test and bronchial provocation test with tobacco dust.

Air Pollutants, Occupational↗

Clinical prediction of airways hyperresponsiveness.

We tested the ability of chest physicians to detect increased airways responsiveness (IAR) in patients presenting with symptoms suggestive of asthma. Physicians ordering bronchial provocation tests for diagnostic purposes were asked to predict the clinical probability (based on the patient's history, examination, and spirometry) of IAR (defined by a PC20 for FEV1 less than or equal to 8 mg/ml of histamine). Presenting symptoms in the 38 subjects aged 16 to 78 years included cough, wheeze, dyspnea, chest tightness, and recurrent colds. There was no association between IAR and clinical probability dichotomized as less than or equal to 50 percent or greater than 50 percent (p = .16, Fisher test). The association was no stronger using only subjects in whom the clinical prediction was greater than 67 percent or less than 33 percent. If knowledge of the level of airway reactivity would influence subsequent patient management (eg, prescription of antiasthmatic therapy), then its clinical prediction should not be relied upon.

Adult↗

Three cases of childhood nocturnal asthma due to buckwheat allergy.

BACKGROUND: Buckwheat flour (BF) is known as a potent food allergen. Sensitization to it usually occurs by ingestion but also by inhalation in occupational or domestic exposure. Buckwheat chaff-stuffed pillows (BCP) can be contaminated with BF during the process of pilling, and many Korean children and adults use BCP for health reasons. METHODS AND RESULTS: We here present three cases of BF allergy in children using BCP, who had been treated as nonatopic asthmatics after undergoing the routine allergy skin tests and serologic tests. We took careful clinical histories, and performed skin prick tests (SPT), the radioimmunoassay (RIA) for specific IgE, the BCP-elimination test, the BF bronchial provocation test, and IgE Western blot. All three children showed positive skin reactions to BF, but none of them had positive reactions to house-dust mites. Nocturnal asthmatic symptoms were improved during 7 days of BCP elimination, and asthmatic responses were observed by bronchial provocation tests with homemade BF extract. Serum BF-specific IgE antibodies and several IgE-binding proteins were detected by RIA and Western blot analysis, respectively. CONCLUSIONS: Thus, a small amount of BF attached to BCP can induce BF sensitization, and BCP should be considered a main cause of childhood nocturnal asthma in those asthmatics exposed to these pillows.

Asthma↗

[Problems of the reproducibility of the inhaled dosage exemplified with the Pari provocation test I apparatus].

The unspecific bronchial provocation test--usually performed with histamine, metacholine or carbachol--is used to determine whether bronchial hyperreactivity is present, and to what degree. Epidemiological studies have shown, that an overlap exists between "healthy" and "sick". There are several reasons for this, the most important being the insufficient reproducibility of intrabronchial deposition and the fact that the total provocation dose is often unknown. The following factors must be taken into account to improve this situation: 1. Only those devices where the particle spectrum is not influenced by the inspiration flow (without additional airstream) should be used to produce aerosols. 2. The air current containing aerosols is vapour saturated when liquid aerosols are produced. As the vapour is derived from the nebulizing solution it forms part of the weight or volume loss, this can be up to 50% of the total weight/volume loss. The aerosol output is far more constant and practically independent of the vapour saturation and the temperature. The intrabronchial dose can therefore not be calculated according to the weight loss of the nebulizer, as this is incorrect. 3. The evaporation of the nebulizing solution leads to an increase in the concentration of the test substance, especially towards the end of the evaporation process. Thus, the volume of the nebulizing solution should always be as large as possible or renewed early. 4. The slower the inhalation maneuver, the less the reproducibility of the intrabronchial deposition is impaired. The intrabronchial deposition varies least, when a slow inspiratory vital capacity maneuver is carried out (inspiration time greater than 8 s). Exhalation should be normal or even rapid, as aerosol deposition is thus increased, due to airway collapse. Breath-holding at the end of inspiration, for about 3-4 seconds, is favourable. 5. The anatomy of the glottic region varies greatly interindividually, influencing intrabronchial deposition. To reduce this to a minimum, the average diameter of the particles should not exceed 2 microns. On the other hand, the diameter of particles should not be under 1 micron, as the inhaled amount of substance is then markedly reduced (volume approximately d3). 6. Reservoirs, storaging the aerosol before inhalation, increase reproducibility, since they stabilize the aerosol due to vapour saturation. Plastic reservoirs must either be of antistatic material, or made antistatic by being filled repeatedly. The reproducibility of intrabronchial deposition is in the range of +/- 15% for the PARI-Provokationstest device I, (determined by radioactive labelling).(ABSTRACT TRUNCATED AT 400 WORDS)

Aerosols↗

Bronchospasm and rhinitis induced in allergic patients by in vitro released mediators. I. Methodology.

This paper reports the development of an in vitro model of mediator production to be applied to patients with allergic asthma or rhinitis. All the selected patients were atopics and exhibited type I hypersensitivity to Candida alb., D. pter., or both. Heparinized blood was taken. The lymphomonocytes were separated and challenged in vitro with the specific antigen. After two hours of incubation and careful washing, the cells were further cultured for 24 hours and the supernatants removed. Skin tests and bronchial provocation tests were done with supernatants with known concentration of proteins. As a control for cell activation, two lymphokines, i.e. MIF and MF were determined in supernatants. The results demonstrated a dose-related bronchial and nasal response in allergic individuals with specific supernatants. On the other hand they failed to respond to supernatants recovered from non-sensitized cells, cells sensitized with unrelated antigens or sensitized cells obtained from non-allergic individuals. In almost 50% of the cases the immediate bronchial response, which was always present was sustained and persisted for several hours. Active supernatants always induced strong immediate skin responses. In conclusion, this in vitro model of mediator production seems to be valuable for the analysis of the physiopathological mechanism of these diseases.

Animals↗

Atopy may be related to exercise-induced bronchospasm in asthma.

BACKGROUND: Recent studies suggest that atopy may be associated with exercise-induced bronchospasm (EIB) in asthma. However, it is not clear whether atopy is related to EIB, regardless of airway hyper-responsiveness (AHR) to methacholine, because asthmatic subjects often show AHR to exercise and methacholine simultaneously. OBJECTIVE: To investigate whether atopy is related to EIB in asthmatic subjects, independently of AHR to methacholine. METHODS: Fifty-eight male asthmatic subjects were studied. Initial spirometry was performed. Skin prick test was carried out, using 53 common allergens including mites dust antigen. Atopy score was defined as a sum of mean weal diameters to all allergens tested. Methacholine bronchial provocation testing was performed. Twenty-four hours later, free running test was performed. Positive EIB was defined as a 15% reduction or more in FEV1 from baseline after exercise. RESULTS: All subjects had AHR to methacholine. The degree of AHR to methacholine in asthmatics with EIB was similar to that in asthmatics without EIB. However, atopy score and skin reaction to Dermatophagoides pteronyssinus significantly increased in asthmatics with EIB compared with those without EIB (P < 0.05, respectively). Furthermore, the degree of EIB significantly correlated with atopy score in all subjects (r = 0.35, P < 0.01). This relationship was maintained even after the exclusion of EIB-negative asthmatic subjects. CONCLUSION: Atopy defined as skin test reactivity may contribute to the development of EIB in asthma, independently of AHR to methacholine.

Adult↗

Occupational asthma in a coal miner.

Occupational asthma in coal miners is hardly recognised. A report is presented of a coal miner whose clinical picture suggested a respiratory allergy which occurred only in the mine where he worked. Serum specific IgE levels, skin tests, and bronchial provocation tests with different commercial extracts showed sensitisation to Rhizopus nigricans. Rhizopus spp were found inside the mine, as demonstrated by cultures on petri plates.

Adult↗

Objective assessment of lower airway involvement in chronic rhinosinusitis.

BACKGROUND: When associated with lower airway involvement, the morbidity and the cost of chronic rhinosinusitis (CRS) can increase. The aim of this prospective study was to assess the clinical and radiological characteristics of the upper airways in CRS patients scheduled for functional endoscopic sinus surgery and to correlate these findings with the functional changes of the lower airways. METHODS: Twenty-five adult patients with CRS were subjected to clinical and endoscopic assessments, computed tomography scan, and allergic assessments using validated scoring systems. Lower airways were assessed by clinical history, pulmonary function test, histamine bronchial provocation test, and chest x rays. RESULTS: Sixty percent of CRS patients were shown to have associated lower airway involvement, i.e., 24% had asthma and 36% had small airway disease (SAD). Nasal congestion and nasal polyps were the most common clinical findings in both of these subgroups of patients. In addition, there was a negative correlation between computed tomography scan findings of the sinuses and the obstructive parameters on pulmonary function test in SAD but not in the asthma subgroup. CONCLUSION: These results showed that different kinds of lower airway involvement frequently could be associated with CRS. Some are manifest such as asthma and some are hidden such as SAD and histamine bronchial hyperresponsiveness.

Adult↗

Clinical cross-reactivity between Artemisia vulgaris and Matricaria chamomilla (chamomile).

Artemisia vulgaris is a common weed and an important source of allergens on the subtropical island of Tenerife, Canary Islands, Spain. It pollinates mainly from July to September, although, due to some local climatic conditions, it may flower throughout the year. Cross-reactivity with hazelnut, kiwi, birch, several Compositae (Ambrosia, Chrysanthemum, Matricaria, Solidago) and grass allergens has been suggested. Few studies have addressed the issue of in vivo cross-reactivity between A. vulgaris and Matricaria chamomilla. The objective of this study was to perform conjunctival and bronchial challenges with A. vulgaris and M. chamomilla and oral challenge with chamomile in 24 patients with asthma and/or rhinitis sensitized primarily to A. vulgaris. Skin prick tests with M. chamomilla were positive in 21 patients. Eighteen patients had a positive conjunctival provocation test with a A. vulgaris pollen extract and 13 patients had a positive conjunctival provocation test with a M. chamomilla pollen extract. Bronchial provocation tests with A. vulgaris were positive in 15 patients and with M. chamomilla pollen in another 16 individuals. Oral provocation tests, conducted with a commercial chamomile infusion were positive in 13 patients. Nine of these individuals were skin test positive to food allergens and 17 to others pollens of the Compositae family. This study confirms a high degree of in vivo cross-reactivity between A. vulgaris and M. chamomilla. Sensitization to A. vulgaris seems to be a primary risk factor for experiencing symptoms after the ingestion of chamomile infusions. Based on the results of bronchial provocation tests, M. chamomilla pollen could be a relevant inhalant allergen.

Administration, Oral↗

Bronchial hyper-responsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever.

In children with mild asthma, symptoms are not always apparent. Therefore, results of tests play an important role for the diagnosis. First, to investigate whether children with bronchial hyper-responsiveness (BHR) but no symptoms of asthma in 1992 had developed clinical asthma at follow up in 1994. The second aim was to find out the diagnostic properties of tests for asthma/allergic inflammation, using either doctor diagnosed asthma (DDA), self-assessed symptoms of asthma or iso-capnic hyperventilation of cold air (IHCA), as the standard, to diagnose asthma in a group of children with hay fever. Twenty-eight children with pollinosis, 12 of them with a history of asthma for the first time during the season 1992, were studied during the birch pollen season and in the autumn of 1994. During both periods, the bronchial hyper-reactivity was estimated by methacholine bronchial provocation tests (MBPT), bronchial variability by peak expiratory flow rate variability, subjective symptoms of asthma by visual analogue scale (VAS) and bronchial inflammation by serum and urine levels of inflammatory mediators. In 1994 IHCA was added during both seasons. Eight of 16 children with BHR but without clinical asthma in 1992 had developed asthma in 1994, 14 of 16 reacted to IHCA and 13 to MBPT. All 12 children with DDA in 1992 had still asthma in 1994 and 14 children with BHR in 1992 had persistent BHR in 1994. Of 23 children with BHR in 1992, 17 had DDA in 1994 and all maintained their BHR. Furthermore, 20 of them reacted to IHCA in 1994. In 1994, 24 of 28 hay-fever children had a positive IHCA tests and 24 had positive MBPT. In relation to VAS, the sensitivity of IHCA and MBPT to predict present asthma was high, but the specificity low, whereas the specificity of most other tests was high, but based on few individuals. In relation to DDA both the IHCA test (65-80%) and the MBPT test (79-85%) had a high sensitivity and it was three to six times more likely to find a positive test among asthmatics than in non-asthmatics. Children with hay fever without clinical asthma have a high risk of developing asthma within 2 yr. In relation to DDA, inhalation of cold air and the MBPT showed a high sensitivity.

Adolescent↗

Allergy to cockroach antigens in asthmatic patients.

Cockroach allergy was investigated in a group of 56 patients with atopic bronchial asthma (37 men and 19 women with ages ranging from 16 to 65) all allergic to house dust antigen. In all patients, both intracutaneous tests and bronchial provocation tests were performed with cockroach antigen prepared from the species most common in Poland, Blattella germanica and Blatta orientalis. Positive skin reactions to cockroach antigen were found in 17 patients while an immediate bronchoconstrictive response was noted in 11. In the authors opinion, cockroach antigens may be partly responsible for the antigenic properties of house dust and may play a causative role in some cases of atopic asthma.

Adolescent↗