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[The changes in plasma beta-thromboglobulin (beta-TG), platelet factor 4 (PF4) and thromboxane B2 (TXB2) after a bronchial provocation test (BPT) with house dust (HD) allergen].

In order to investigate the role of platelets in allergic asthma, the time related changes in plasma levels of beta-TG, PF4 and TXB2 were evaluated following BPT with HD in 19 patients with bronchial asthma who were positive in skin test and RAST to HD. The results obtained were as follows. 1) Plasma beta-TG and PF4 levels tended to increase following BPT with HD at the time of immediate asthmatic response (IAR) in patients showing IAR alone. 2) Plasma beta-TG and PF4 levels increased significantly (p less than 0.05) at IAR and tended to increase at the time of late asthmatic response (LAR) in patients showing a dual asthmatic response (DAR). 3) The levels of plasma TXB2 in patients showing IAR alone significantly increased at IAR (p less than 0.05) and gradually decreased and the levels of plasma TXB2 in patients showing a DAR increased in each period of IAR, 3 hr after BPT and LAR, and the peak of TXB2 was observed in 3 hours after BPT. 4) These results suggest that platelets are activated at IAR and there was also a possible activation in platelets at LAR.

Adult↗

Effect of BN 52063, a specific PAF-acether antagonist, on bronchial provocation test to allergens in asthmatic patients. A preliminary study.

Platelet Activating Factor, PAF-acether, elicits acute and more prolonged inflammatory responses in both experimental animals and man, and is recognised as a possible mediator of asthma. The effect of a specific PAF-acether antagonist, BN 52063, on the early asthmatic response to inhaled allergen was assessed in a randomised, double-blind, crossover study in eight atopic asthmatics, who received three days treatment with BN 52063 or placebo, separated by a one week washout. On the third day of treatment, subjects were challenged with nebulised house dust mite or pollen allergen. BN 52063 significantly antagonised early bronchoconstriction and showed a tendency to inhibit residual bronchial hyperreactivity, assessed six hours after allergen challenge by a provocation test to acetylcholine. No side effects were reported during active treatment. This is the first study in man demonstrating the efficacy of a specific PAF-acether antagonist on the immediate response to inhaled allergen challenge in asthmatics. The findings support the possible role of specific PAF-acether antagonists in the treatment of asthma.

Acetylcholine↗

Episodic asthma as a bronchial provocation test.

This study, originally designed to investigate the efficacy of a new inhaled steroid, flunisolide, in New Orleans, demonstrated that episodic asthma (known as "New Orleans Asthma") still occurs in that city. Although its outbreaks are less frequent and severe than reported in previous years, they are still intense enough to affect asthmatics who are on maximal drug therapy. We found in this study that patients who were taking a sympathomimetic, methyl xanthine, and steroids both by inhalation (flunisolide) and by mouth (prednisone) required more prednisone during outbreaks. During such outbreaks the use of flunisolide not only delayed the need for more prednisone but also reduced the dosage needed. Furthermore, flunisolide had over-all prednisone-sparing benefits during the course of the whole 18-week study. Finally, throughout the study, asthma was less frequent in patients on flunisolide therapy, their over-all therapeutic response being significantly better than that of a control group. The authors conclude that New Orleans Asthma provides a natural provocation for extrinsic asthmatics in their normal milieu and thus provides an ideal situation for testing new anti-asthmatic treatments, especially in individuals with severe asthma in whom deliberate challenge may be unethical.

Adult↗

[Bronchial provocation test with dermatophagoides in the diagnosis of infantile asthma: sensitivity, specificity and reproducibility].

The purpose of this study has been to prove if the lung is the target organ of an allergen against which a biological hypersensitivity, by means of skin test and RAST, has been found; comparing score Foucard diagnostic with inhalatory test result. At the same time, checking test specificity and reproductibility. Fourty children, both sexes aged between 6 and 14 years diagnosed of bronchial asthma divided in two groups were studied. First group included 31 children with hypersensitivity to dermatophagoides and second group was control group including 9 children. The test with dermatophagoides was performed in both groups according to Cockcroft method. The parameters which indicated test positivity were 20% fall in FEV1 for early response and 40% fall in PERF for late response. The results obtained show 83.9% positive tests with 80.6% early responses and 45.2% positive late response. The specificity and reproductibility were of 100%.

Adolescent↗

Sensitivity and validity of three bronchial provocation tests to demonstrate the effect of inhaled corticosteroids in asthma.

STUDY OBJECTIVES: To compare the sensitivity and validity of mannitol, histamine, and cold air challenges to demonstrate the effect of inhaled corticosteroids (ICS) in asthma. DESIGN: A prospective study. PARTICIPANTS: Seventeen patients with recently diagnosed, steroid-naive asthma who fulfilled the diagnostic criteria of Finnish Social Insurance Institution and were hyperresponsive to both mannitol and histamine. INTERVENTIONS: The following procedures were carried out at baseline and after 3 months and 6 months of treatment with inhaled budesonide, 800 microg/d: symptom assessment with a questionnaire, ambulatory peak expiratory flow (PEF) measurements twice daily for 2 weeks, and bronchial challenges with mannitol, histamine, and cold air. RESULTS: Budesonide decreased the sum symptom score, daily use of bronchodilating drugs, and diurnal PEF variation, but did not change FEV(1) percentage of predicted significantly. In addition, budesonide significantly decreased mannitol (p = 0.005) and histamine (p = 0.002) response dose ratios. The magnitude of the budesonide-induced change in responsiveness to these two challenges did not differ significantly. The effect of budesonide on cold air responsiveness did not reach statistical significance (p = 0.064). Change in mannitol responsiveness correlated significantly with the changes in sum symptom score and in FEV(1). Change in cold air responsiveness correlated with the changes in sum symptom score and in diurnal PEF variation. Change in histamine responsiveness correlated only with change in FEV(1). CONCLUSIONS: Mannitol challenge is both a sensitive and valid test to demonstrate the effects of ICS in asthma. Histamine challenge is equally sensitive for this purpose, but its validity may be lower than that of mannitol challenge. Cold air challenge seems to be a valid test to demonstrate the effects of ICS, but its sensitivity may be lower than that of mannitol and histamine challenges.

Administration, Inhalation↗

[Skin and bronchial provocation tests with inhalation allergens in asthmatics].

The examination was performed in 122 asthmatics with mean age of 32 years. Intracutaneous tests with inhalation allergens of 1200 PNU (protein nitrogen units) and bronchoprovocation tests with histamine and inhalation allergens of pollen and homedust. Effects of allergens of homedust and pollen obtained by intracutaneous and bronchoprovocation tests were compared. The Fischer exact test showed no statistically significant relationship between tests (intracutaneous and bronchoprovocation) for allergens of pollen and homedust (p = 0.081, p greater than 0.05, that is, p = 0.702, p greater than 0.05).

Adolescent↗

[Changes in lung function after a bronchial provocation test with cockroach antigens].

BACKGROUND: Cockroach allergens sensitized patients at a very young age and can predispose to severe asthma on atopic children. OBJECTIVE: To evaluate the FEV, changes induced after bronchoprovocation with Blatella germanica (Bg) or placebo on allergic respiratory children. MATERIAL AND METHODS: A prospective transversal study was performed in 25 children from 8 to 16 yr with allergic rhinitis and/or asthma diagnosis with sensibility only to Bg (Bayer Corp allergens) by Prick skin test, with a 1:20 weight/volume dilution. After previous training on spirometry, they assisted for a double blind bronchial challenge with 10, 25, 50, 75, 100, 150, 200, 300, 400, 500 until 750 proteic nitrogen units of Bg or 0.9% NaCl solution in a nebulized open circuit, with a 5 litter flow for 3 min. A week after, they returned for the crossover double blind bronchial challenge. At the beginning of the study a basal spirometry was performed and subsequent spirometrics at 1.5 and 3 min after each challenge with a 10 min rest between the challenges. The test was interrupted if cough, dyspnea, wheezing and/or a 15% or more FEV1 fall appeared. RESULTS: Twelve patients showed a FEV1 fall with the antigen challenge, all with specific lgE for Bg. All they had positive skin test to Bg, 9 had asthma and rhinitis and 3 only asthma. When placebo was used 6 patients showed a FEV1 fall. When comparing the average basal and final FEV1 values after the challenges, the fall was statistical significant in both groups with a p = 0.0015 when Bg was used, and p = 0.046 with placebo. CONCLUSION: These results show that two times fold number of patients challenged with Bg had a FEV1 fall than placebo, and the t Student test showed that antigen challenge was more significant than placebo. We demonstrated that respiratory allergic patients sensitised with Bg after a bronchial challenge with these allergens show a FEV1 fall. This suggests that cockroach allergen sensitisation can be on account of children's asthma.

Adolescent↗

Occupational type bronchial provocation tests: testing with soluble antigens by inhalation.

Thirty-seven patients with asthma or alveolitis thought to result from exposure to materials commonly encountered at their work were tested by inhalation of an aerosol of these materials. Twenty-four (65%) developed an immediate asthmatic reaction, which was followed by a non-immediate reaction in 10, of whom six developed the signs and symptoms of alveolitis. Eighteen (76%) patients with asthmatic reactions to test material were prick test positive to that material while only two our of 13 with a negative inhalation test were prick test positive (15%). Precipitating antibody to test material was measured in 23 and was present in nine (39%) of those with positive inhalation tests, and one (12%) of those with negative tests. It was present in five of the six with a reaction in the gas exchanging portions of the lung.

Adolescent↗

A new aerosol device for bronchial provocation tests.

A special new device for diagnostic (bronchoprovocation) and therapeutic aerosol application is described. It consists of a high quality nebulizer system combined with a 10-liter storage bag which serves as an aerosol 'conditioner' (saturated ambient temperature and pressure conditions) and as a holding chamber to increase the respirable aerosol fraction and hence pulmonary deposition (Pari Provocation Test I). It allows ten times better standardized pulmonary aerosol deposition compared with the generally used nebulizers for calculation of dose-response curves especially for asthma provocation and dilatation tests. If slow inspiratory vital capacity maneuvers are used, pulmonary deposition of about 100 mg aerosol is achieved in children and adults. This device is especially important when exact dosing (also for therapeutic reasons) is required in the expanding field of topical and systemic aerosol application to or via the lung.

Aerosols↗

[Evaluation of the bronchial provocation test with histamine in asthmatic children].

Histamine inhalation challenge was performed in 32 asthmatic children aged 6 through 13, 20 control children aged 8 through 14, and 16 control adults aged 24 through 37 years. Histamine concentration producing a 20% fall in baseline FEV1 (PC20FEV1) was obtained. No control adult had a value below 8 mg/ml unlike 7 (35%) control children, all of them with values between 4 and 8 mg/ml. Asthmatics only on intermittent bronchodilators had higher PC20FEV1 values than those requiring daily medications. A value of 2 mg/ml was roughly the limit between these two subpopulations of asthmatic children. Test showed a high reproducibility in a two hour interval. Histamine inhalation challenge is useful in diagnosis of asthma and in assessment of its, severity. A PC20FEV1 value of less than 8 mg/ml may not be always reliable in indicating bronchial hyperreactivity, depending on the method used and-or the population studied.

Adolescent↗

Increased lung deposition and biological effect of methacholine by use of a drying device for bronchial provocation tests.

A simple device aiming to increase deposition of nebulized methacholine in the lower airway was studied. The device controlled inspiratory flow and volume and dried the aerosol. The effect of drying on deposition in the throat and lower airways was studied in six subjects given an aerosol of 99mTechnetium-diethylenetriamine pentaacetate (DTPA) in saline with the device and with a reference device giving the same inspiratory flow and volume but no drying. Drying reduced throat deposition from 46 (range 26-61) to 13 (range 6-22)% (p less than 0.05) of the inhaled and retained dose. The effect of drying on the biological effect of nebulized methacholine was studied in 21 subjects who underwent three provocation tests on different days with doubling concentrations of methacholine from 0.5 to a maximum of 64 mg.ml-1, one with the reference device and two with the drying device. The percentage change in forced expiratory volume in one second (%FEV1) per cumulative dose of methacholine changed from -1.0 (2.6) %FEV1.mumol-1 (geom. mean and SD) with the reference device to -1.6 (3.6) with the drying device p less than 0.02. In an additional study 20 subjects underwent four provocation tests on different days, two with a different version of the drying device and two with the reference device. The slope changed from -1.1 (3.1) to -1.6 (3.3), p less than 0.02. The reproducibility of duplicate measurements did not improve with the drying device. Thus, the drying device decreased throat deposition and increased the biological effect of nebulized methacholine.

Administration, Inhalation↗

Comparison between incremental and single-dose allergen administration in bronchial provocation tests.

To study the effect of different schedules of allergen administration on the early (EAR) and late allergic reaction (LAR), 15 asthmatic patients with dual response after allergen challenge were submitted to two consecutive bronchoprovocation tests (BPT). BPT1 was carried out with semilogarithmic increases of allergen doses until a FEV1 drop of 20% was recorded. BPT2 was performed 2 weeks later using the highest allergen dose that had elicited the dual reaction in BPT1. Both EAR and LAR were very similar for a given patient. As the allergen dose used in BPT2 is smaller than the cumulative allergen dose administered in BPT1, this protocol takes into account a possible influence on BPT2 of bronchial hyperreactivity induced by BPT1 performed 2 weeks before.

Adult↗

A simple dosimeter for bronchial provocation testing using a solid-state electronic timing module.

In conducting inhalational challenge tests of airway responsiveness to methacholine, we prefer to deliver the challenge aerosol intermittently, using a dosimeter that turns the nebulizer on for about 0.5 to 0.6 second to deliver each "puff." To avoid the considerable expense of commercially available dosimeters, we constructed our own electronically controlled device, which, in conjunction with a DeVilbiss Model 646 nebulizer, is easily calibrated and permits reproducible and precise timing of challenge puffs. The device was constructed of readily available components and cost us only $100. An experienced technician can use it to trigger on the nebulizer within 0.5 second of the start of inspiration, and in more than one year's experience we have found the system to be completely satisfactory and reliable.

Bronchial Provocation Tests↗

Bronchial provocation testing of sodium iso-nonanoyl oxybenzene sulphonate.

1. Asthmatic symptoms have been reported in workers following occupational exposure to certain low molecular ratio chemicals. 2. A small number of workers involved in the initial manufacture of a new low temperature bleach activating chemical, sodium iso-nonanoyl oxybenzene sulphonate (SINOS) developed rashes, rhinitis and conjunctivitis following exposure to the compound. One worker also developed asthma. An investigative study was undertaken to examine the possible asthmatic effects of inhaling SINOS in naive non-asthmatic and asthmatic subjects handling the material in the laboratory setting. 3. Since SINOS has a similar chemical structure to aspirin, it was hypothesized that SINOS-associated asthma might be elicited by a mechanism similar to the mechanism associated with aspirin asthma. Therefore aspirin-sensitive asthmatics were also included in the study. 4. No adverse respiratory reactions were observed in the non-asthmatic subjects or in the aspirin and non-aspirin-sensitive patient volunteers following exposure to SINOS dust at atmospheric concentrations of up to 36.3 micrograms m-3. 5. Skin prick tests to increasing concentrations of SINOS were carried out in all subjects. No positive reactions were observed on any occasion. 6. This study indicates that SINOS does not elicit asthma via a mechanism similar to aspirin. Additionally, the study suggests that the addition of SINOS to washing powder will not cause significant respiratory reactions in consumers even if they are asthmatic or intolerant to aspirin.

Administration, Inhalation↗

Stability of methacholine chloride in bronchial provocation test solutions.

The stability of methacholine chloride (5 mg/ml) in 0.9% sodium chloride solution was measured. A reliable colorimetric assay (530 nm) based on the formation of a hydroxamic acid-iron complex was used. At appropriate time intervals, samples were removed from solutions stored at 4, 20, 37, 60, or 80 degrees C and assayed. The degradation of methacholine chloride followed apparent first-order kinetics of methacholine chloride followed apparent first-order kinetics at all temperatures, with observed half-lives ranging from 29.3 days at 80 degrees C to 693 days 4 degrees C. Methacholine chloride in 0.9% sodium chloride solution does not degrade as rapidly as previously suggested. According to an Arrhenius plot, storage of such solutions at 30 or 4 degrees C would result in not more than 10% degradation over a period of approximately two or five months, respectively. Thus, it should be possible to prepare stock solutions of this deliquescent drug.

Bronchial Provocation Tests↗

[The response to a specific bronchial provocation test and the evolution of occupational asthma. A longitudinal study in subjects with toluene diisocyanate-induced asthma].

The aim of this study was to investigate the progression and long-term consequences of occupational asthma and to evaluate the effect of the pattern of response to specific bronchoprovocation test (SBPT) in the prognosis of occupational asthma among 40 subjects with asthma due to toluene diisocyanate (TDI). Nine subjects had immediate asthma, 25 subjects had late asthma and 6 subjects had dual asthma. Respiratory symptoms, persistence of exposure to TDI and lung function have been investigated both at diagnosis and at follow-up examination. At follow-up examination, 70.0% of the subjects were not exposed to TDI, and only 14.3% of "non-exposed" subjects were completely asymptomatic. At follow-up examination, 71.4% of "exposed" subjects and 55.6% of "non-exposed" subjects were regularly treated with medications because of their asthma (no statistical difference). No significant differences have been found in symptoms prevalence or lung function between "exposed" and "non-exposed" subjects. After comparing the results obtained at diagnosis and at follow-up examination, a significant decrease in FVC both in "exposed" and "non-exposed" groups (p < 0.005 and p < 0.0005, respectively) and a significant decrement in FEV1 (p < 0.05) and FVC (p < 0.0005) among the subjects with late asthma, was found. We can conclude that, despite the removal from TDI exposure, occupational asthma can lead to permanent disability with important socio-economic consequences, and late response to SBPT may be a negative prognostic factor in TDI asthma.

Adult↗

Bronchial provocation tests before and after cessation of smoking.

We studied the effect of smoking cessation on airway reactivity. We recruited cigarette smokers who were attempting to stop smoking. Entry criteria required each subject to be smoking at least 10 cigarettes each day and report a chronic cough. Exclusion criteria included significant airflow obstruction or the presence of any medical condition contraindicating challenge testing. Carbachol challenge was performed to assess airway reactivity according to a standardized method. Baseline measurements of forced expiratory volume in 1 s (FEV1), specific airway conductance (SGaw) and the provocative dose of carbachol causing a 35% reduction in SGaw (PD35), and a 20% reduction in FEV1 (PD20) were established on entry while each subject was still smoking. Thereafter, repeat measurements were performed after 2 and 6 months of smoking cessation. Adherence to smoking cessation was checked by self-report and verified by measurement of alveolar carbon monoxide levels at each session. Of the 34 subjects who gave consent, 13 relapsed prior to the 2nd month and an additional 8 relapsed before the 6th month. Thirteen of the 34 remained abstinent throughout the 6-month study. All 13 subjects had complete resolution of their cough. The difference in reactivity on entry to that at the 2nd and 6th month was not significant. We conclude that (1) the symptom of chronic cough resolved completely after 2 months of smoking cessation, and (2) airway reactivity remained unchanged at 2 and 6 months of smoking cessation.

Adult↗

Reproducibility of standardized bronchial allergen provocation test.

Standardized bronchial allergen provocation was performed twice (with an interval of median 14 days (range 14-44)) in 19 extrinsic, well-defined asthmatic patients to study the reproducibility of the bronchial response. Smoking and medications were strictly withheld prior to the provocation. Ten-fold increasing concentrations of allergen solution 0.9 ml were inhaled by tidal volume breathing for 5 min at 10-min intervals. The actual dose given was expressed by the concentration of the solution used. Forced expiratory volume in the first second (FEV1) was used to determine responses, and the provocation continued until an allergen concentration (allergen PC20) was reached which caused at least 20% decrease of the post-saline FEV1. All provocations were followed by a bronchial reaction within clinically acceptable limits. The reproducibility was high, evaluated by the Spearman rank correlation coefficient Rho = 0.90 (P less than 0.01). It is concluded that bronchial provocation with allergens performed as outlined in this study represents a reproducible test which can be applied in routine allergy diagnostics, and in further investigations concerning specific bronchial reactivity.

Allergens↗