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Clinical value of bronchial provocation testing in childhood asthma.

Previous studies have shown a positive relationship between the results of skin tests, radioallergosorbent tests, and bronchial provocation testing. The purpose of this study was to compare the results of skin and bronchial provocation testing to determine the extent to which the results of provocation testing could be predicted from puncture and intracutaneous skin tests. In the 1,596 provocation tests performed in 276 patients, more than 90% of patients with a wheal greater than or equal to 5 mm in diameter on skin testing by puncture technique using 1:20 w/v allergen extract experienced positive reactions on provocation testing for most antigens. If the wheal produced by puncture testing was less than 5 mm in diameter, a large wheal on intracutaneous testing only slightly increased the likelihood of a positive challenge, but if the wheal on intracutaneous testing was less than 5 mm, a positive challenge did not occur. It is concluded that the results of provocation tests may often be predicted from simple skin testing, and that in clinical use, provocation testing is likely to be useful primarily in patients for whom skin testing indicates moderate sensitization to allergens.

Adolescent↗

Metered-dose inhaler to deliver methacholine in bronchial provocation testing: a pilot study.

BACKGROUND: Nonspecific bronchial provocation tests may be simplified by the use of hand-held devices to deliver methacholine. OBJECTIVE: To study the feasibility of using a metered-dose inhaler (MDI) to administer methacholine in bronchial provocation tests, and the ability of such a device to diagnose bronchial hyperresponsiveness (BHR) accurately. METHODS: In an open randomized crossover pilot study, we compared the provocative dose that induces a 20% fall in FEV1 (PD20 FEV1) obtained with the methacholine MDI with that obtained using a conventional nebulizer in 20 hyperresponsive and 20 nonhyperresponsive subjects. The MDI delivers 400 doses of 100 microg of methacholine, and was used via a spacer. Bronchial hyperresponsiveness (BHR) was defined as a PD20 FEV1 <2,000 microg with the conventional test using the nebulizer. The tests were performed in each subject in a randomized order, 1 to 7 days apart. RESULTS: Of the subjects who had a nebulizer PD20 FEV1 <2,000 microg, all but one had an MDI PD20 FEV1 <800 microg. When 800 microg was taken as the threshold for the diagnosis of BHR with the MDI test, the accuracy of this test to diagnose BHR was 97.5%, and the two tests were highly concordant for the diagnosis of BHR (Pearson chi2, 36.19; p<0.0001). CONCLUSION: A hand-held device may be suitable for delivery of methacholine during bronchial provocation tests, if these results are confirmed in large samples.

Adult↗

[Factors modifying late bronchial response in the bronchial provocation test in asthmatic children].

When the test of bronchial provocation with inhalant allergens is performed in atopic asthmatics, we may find an immediate response (IR), a late response (LR) or a dual response (IR-LR). The immediate response occurs between 10 to 30 minutes after the allergenic exposition and it is resolved spontaneously in about one to two hours. A proportion of these patients, estimated around 47-73% presented a LR. The LR is manifested 3 or 5 hours after the inhalation test, maximum at 6-12 hours and may persist until 24 hours. The late response serves as a clinical model of asthma because the bronchial response is more prolonged and severe than the immediate response. This is best controlled with corticosteroids while bronchial reversibility is difficult with sympathomimetics only, a fact commonly observed in the natural course of asthma. The early response was observed to be in relation with multiple factors more predictable than the late response. The object of this work was to evaluate if the LR was related with factors such as the degree of obstruction previous to the test, the intensity of immediate bronchial response and the maximum dose of inhaled allergen. The present study was performed in 34 children of both sexes with ages ranging between 6 and 14 years, diagnosed with bronchial asthma caused by Dermatophagoides (26 patients), and Alternaria (8 patients) through the score of Foucard with positive bronchial provocation test with the allergen. The BPT was performed according to the method described for Cockcroft, utilizing a continuous pressured nebulizer, inhaling for two minutes at current volume. We employed the De Villbis 646 model nebulizer with flow of air at 6 l/min and output at 0.13-0.16 ml/min. The inhaled concentrations of allergen progressively increased by ten fold, in Dermatophagoides 0.01; 0.1; 1 and 10 BU/ml, and for Alternaria 1/1,000,000, 1/100,000 and 1/10,000 P/V. Ten minutes after each dose a spirometric function with pneumoscreen Jaeger was performed. If the FEV1 was decreased by 20% from the control value, we considered the IR positive. The late response was evaluated through an hourly control of the peak respiratory flow rate (PEFR) with a Mini Wright within a 24 hours period after the test, respecting nocturnal sleep. We considered positive (LR) if PEFR fall was equal or superior to 40% of the basal value and the presence of bronchial symptoms.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Intradermal skin tests with Dermatophagoides pteronyssinus in asthmatic children: correlation with specific IgE and bronchial provocation tests.

The purpose of the present study was to compare the results of the skin tests, the specific IgE levels and bronchial provocation tests in a group of sensitive asthmatic children with a Dermatophagoides pteronyssinus extract standardized by the RAST inhibition method. Skin tests showed a positive 'end point' in twelve children of 0.5 U/ml antigen; in eleven 5 U/ml; seven of 50 U/ml; six of 500 U/ml. Specific IgE was present in thirty-three children (92%). A close relationship between positive skin tests and serum IgE levels was found. Bronchial provocation tests were positive in twenty-eight children (78%): eight children with both positive RAST and positive skin tests had negative bronchial provocation tests.

Adolescent↗

[The pertinence of bronchial provocation tests to allergens].

The contribution and the relevance of bronchial provocation tests to allergens have been evaluated in the realm of clinical research and in the diagnosis of the aetiology of asthma. These tests enable the recognition or to confirm the role of certain allergens in asthma, as well as to study the delayed reaction which occurs in some cases after the inhalation of an allergen as well as the relations existing between HRBNS and bronchial provocation tests to allergens. They also can show the preventative action of certain drugs on the immediate and/or delayed reaction induced by allergens. The methodology of bronchial provocation tests to allergens, notably their variability and their reproductibility, as well as the initial and maximal inhaled doses that can be realistically used, are discussed. The final point touched upon concerns the justification of bronchial provocation tests to allergens in the aetiological diagnosis of asthma. The indications of these tests have been restricted, they seen nonetheless always to be of interest in cases of discordance with the clinical history, cutaneous tests and/or measures of specific serum IgE.

Allergens↗

[Bronchial provocation tests using methacholine, cycle ergometer exercise and free running in children with intermittent asthma].

OBJECTIVE: To compare airway responsiveness to methacholine, cycle ergometer exercise and free running in children with intermittent asthma. METHODS: A randomized study was conducted with 30 children of both genders with intermittent asthma. Each child was submitted to challenge testing on three separate days, in random order: a) Methacholine challenge using a dosimeter; b) Exercise challenge testing -- free running along a 50-meter-long corridor; c) Dry-air exercise challenge on a cycle ergometer. Target heart rate during exercise was 80 to 90% of the maximum predicted value. Spirometry was performed 3, 6,10,15,20 and 30 minutes after exercise. Exercise-induced bronchospasm was defined as a decrease in FEV1 of > or = 10% in comparison to pretest values. RESULTS: Mean age was 11+/-3 years. FEV1 and FEV1/FVC ratios were normal and similar before all provocation tests. The maximum heart rate was 178+/-7 bpm during cycling and 181+/-6 bpm during the free running test (p > 0.05). Significant bronchospasm was observed with methacholine in 23 cases, after free running in 19 and after cycling in 14 children (p < 0.05, methacholine vs exercise tests). Taking all FEV1 measurements after exercise into account, the free running test resulted in greater exercise-induced bronchospasm in comparison with exercise made on a cycle ergometer (p = 0.003, chi2 = 8.948). There was a significant, but poor, correlation between the maximum percentage decrease in FEV1 after free running and cycling (r = 0.46, p < 0.01). CONCLUSIONS: Methacholine challenge identifies a greater number of asthmatics in comparison to exercise tests. When bronchial provocation test with methacholine is not available, free running should be the test of choice due to its simplicity and greater ability to induce bronchospasm.

Adolescent↗

[Validity of a specific bronchial provocation test with proteolytic enzymes in occupational bronchial asthma caused by enzymatic detergents].

Six asthmatic subjects exposed to enzymatic detergents derived from B. Licheniformis were examined by means of a specific Bronchial Provocative Test (sBPT) with solutions of the enzyme. All subjects, except for one, were positive to prick tests with solutions of the "crude" enzyme and with Alcalase, and showed high levels of specific IgE by RAST. The sBPT with solutions of the enzyme, administered by means of a Bird Mark 7 nebulyzer in IPPB with measurement of the delivered dose, showed a positive response in all 6 subjects. No positive result was obtained in 5 normal subjects and in 5 non exposed asthmatic patients, even at much higher doses of the delivered enzyme. The occupational-type sBPT showed only two positive results out of the 6 examined. A good relationship was observed between bronchial hyperresponsiveness and provocative dose of the enzyme. Therefore, the sBPT with solutions of the enzyme is proved to be highly sensitive and specific in confirming the diagnosis of occupational asthma due to proteolytic enzymes.

Adult↗

Decrease of complement hemolytic activity after an allergen-house dust-bronchial provocation test.

Twenty-two children with bronchial asthma and positive skin tests to house-dust allergen were subjected to a bronchial provocation test with the allergen, and both bronchial reactions and serum complement hemolytic activity were measured at different intervals after the challenge. Changes in complement hemolytic activity did not correspond either with early or late bronchial reaction to the allergen. A reproducible drop in complement hemolytic activity after allergen challenge was observed in eight patients and could be prevented in four out of seven patients by sodium cromoglycate. The duration of early bronchial obstructive reaction was longer in tests where parallel complement changes were observed.

Adolescent↗

Allergy to Olea europaea pollen: relationship between skin prick tests, RAST, ELISA and bronchial provocations tests.

Olea Europaea is the most important allergenic tree in Southern Italy and in the Naples area. Its pollination period lasts from the middle of April to the end of June. In our pollinosis patients we observed frequency of sensitization of 13.05% to Olea pollen. That means that this pollen follows Parietaria (47.80%) and Gramineae (34.70%) regarding the frequency of allergic sensitization. In an attempt to evaluate the degree of allergic sensitization to Olea pollen and the concordance of various tests, we studied 24 asthmatic patients with skin positivity to only this pollen using commercially available allergen extracts and reagents. The patients were examined by SPT, RAST, ELISA and BPT with allergen. Our study has shown that there is no relationship between the results of SPT and Phadebas RAST; a slight relationship between SPT and Phadezym RAST, and a very good relationship between Phadebas and Phadezym RAST. Bronchial challenge with Olea extract was positive in all patients. These results may be interpreted considering the low degree of purification of Olea pollen extracts available commercially.

Adolescent↗

[Choice of positive criteria in specific bronchial provocation tests with a purified acarian extract (Pharmalgen)].

Bronchial provocation tests (PT) were performed with a purified and standardized extract of the house dust mite Dermatophagoides pteronyssinus (D. ptero.) in an attempt to determine the most sensitive criteria of bronchospasm. Nineteen asthmatic patients with skin test and RAST positive for D. ptero. had a positive bronchial PT. More than 40% increase of Raw insp. simultaneously with dyspnea or wheezing was found in each patient, whereas only 6/19 had a 20% increase of FEV1. 47% of the patients had a slight to moderate late phase of bronchial obstruction. None of the 9 asthmatic patients with skin test and RAST negative for mites had bronchospasm. It is concluded that a 40% in Raw insp., combined with clinical signs of bronchospasm, is a sensitive, specific and safe method of determining the threshold of bronchial sensitivity to a standardized allergen.

Allergens↗

Cardiac arrhythmia monitoring during bronchial provocation test with methacholine.

STUDY OBJECTIVES: During a bronchial provocation test (BPT), the performance of maximal inspiratory-expiratory maneuvers, causing abrupt and marked shifts in intrathoracic pressure, may increase the risk of cardiac arrhythmias. Moreover, the inhalation of methacholine (MCh), a cholinergic agonist agent, could favor the development of unwelcome cardiovascular events, namely, cardiac arrhythmias. SUBJECTS AND METHODS: We studied the number and severity of cardiac arrhythmias by ECG-Holter monitoring before, during, and after BPTs with MCh challenge in a group of 46 consecutive nonselected subjects (28 men and 18 women) with clinical indications for BPT, without preexisting cardiovascular diseases, and not receiving arrhythmogenic drugs. The subjects performed a routine pulmonary function test (PFT), followed by BPT, during ECG-Holter monitoring. Determination of the serum potassium concentration, a baseline arterial blood gas analysis, and monitoring of oxyhemoglobin saturation also were performed. RESULTS: We found no significant increase in the number of supraventricular and ventricular arrhythmias during the performance of PFTs and of BPTs with MCh in the subjects, either with or without bronchial hyperresponsiveness (BHR). However, during the performance of BPTs, we observed a significant reduction in mean heart rate. CONCLUSIONS: Our results indicate that the performance of PFTs and BPTs with MCh does not increase the cardiac arrhythmogenic risk in subjects without cardiovascular diseases, as well as in those with BHR, suggesting that these tests are safe to perform in most subjects.

Adult↗

[Is the bronchial provocation test justified in occupational respiratory disease?].

Specific bronchial provocation tests can confirm the diagnosis of occupational respiratory disease and also identify the causal agent of occupational asthma. The changes in French regulations established in 1993 which allow other agents to be recognized as causal in compensation for occupational diseases has increased interest in these tests. The different diagnostic methods used for occupational asthma are discussed here with special emphasis on limitations in each case: history taking, immunological investigations, respiratory function tests, measurement of peak flow during occupational activity and holidays, sequential measurements of non-specific bronchial hyperreactivity. The difficulty in standardizing specific provocation tests used for occupational asthma is related to the wide variety of causal agents which can be inhaled as gas, aerosols or powders. Because of the required precautions, these tests must be performed by specialized personnel in hospital units. There are also limitations to specific provocation tests. False positives require placebo tests and false negatives may result from insufficient identification of the causal agent. Exposure time may be too short or concentrations too low, and may depend on how long the causal agent has been evicted. Specific provocation tests may be avoided when the clinical history reveals a typical situation due to an agent known to cause occupational asthma and repeated peak flow measurements at the working site and/or immunological sensitisation tests provide objective evidence. But in a certain number of cases, specific investigations are required to obtain the precise etiological diagnosis required to evict the allergen rapidly and avoid chronic asthma.

Asthma↗

Potential for lung sound monitoring during bronchial provocation testing.

BACKGROUND: The use of lung sound monitoring during bronchial provocation testing has not been clearly demonstrated. The appearance of wheeze and changes in inspiratory breath sound intensity have been analysed and related to changes in spirometric parameters and to airways hyperresponsiveness. METHODS: Lung sounds were recorded in 38 patients undergoing a routine carbachol airway challenge (CAC) test. Spirometric testing was performed before and after the inhalation of each of five cumulative doses of 320 micrograms carbachol; a fall in forced expiratory volume in one second (FEV1) by 20% or more was considered as significant. Lung sound analysis was carried out using a computerised system. RESULTS: The CAC test was positive (CAC+) in 21 patients and negative (CAC-) in 17. At the final stage of the challenge, wheeze was identified in 10 positive patients (48%) and in one negative patient (6%); in non-wheezers the inspiratory breath sound intensity decreased significantly from baseline in 11 CAC+ patients (mean (SD) change -35 (24%)) but not in 16 CAC- patients (mean (SD) change 5 (24%)). In all non-wheezers a linear relationship was found between breath sound intensity and the squared inspiratory airflow (r = 0.53-0.92) which became looser after the inhalation of carbachol. CONCLUSION: When unertaking bronchial provocation testing the accurate identification of wheeze may prove useful in avoiding or shortening the test because of the presumed relationship between wheeze and airways hyperresponsiveness. Changes in breath sound intensity may also be useful, but further studies are required to define the threshold for significant changes in this index.

Adult↗

Clinical experiences with bronchial provocation test using oscillation technique in Chinese patients.

Bronchial provocation tests using the forced oscillation method were conducted on 115 Chinese. Each subject continuously inhaled stepwise increased concentrations of methacholine and respiratory resistance (Rrs) was measured. The test results were regarded as responsive if Rrs increased by twice the baseline values. It was found that all normal subjects and patients with restrictive lung diseases were nonresponders. One hundred percent of the asthmatic patients and 61% of the patients with chronic obstructive pulmonary disease (COPD) were responders. However, only 29% of the 28 patients with acute bronchitis showed bronchial hyperreactivity. Baseline Rrs values for the various groups are as follows: normal subjects, 3.2 +/- 0.7 cmH2O/L/sec; patients with restrictive lung diseases, 4.2 +/- 0.6 cmH2O/L/sec; asthmatic patients, 5.6 +/- 0.9 cmH2O/L/sec; COPD patients, 7.5 +/- 0.7 cmH2O/L/sec; and those with acute bronchitis, 4.3 +/- 0.8 cmH2O/L/sec. Baseline Rrs was significantly higher in patients with airway obstruction than in normal subjects. The cumulative dose (DA, the bronchial sensitivity) of methacholine to induce a positive reaction in responders was not correlated with either respiratory conductance (Grs) or the bronchial reactivity (SGrs, the slope of Grs during a positive reaction). The dose-response curves can be classified into 6 types according to their appearances: flat form (type I), isolated spike form (type II), terminal spike form (type III), triangular form (type IV), step form (type V) and mixed form (type VI). Normal subjects and patients with restrictive lung diseases usually manifested with type I or II curves. Most asthmatic patients had type IV curves, but occasionally types V and VI were also encountered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Is it possible to predict the result of the bronchial provocation test in children with asthma?].

Bronchial hyperreactivity (BHR) to different allergic and non-allergic stimuli is characteristic feature of asthma. Sometimes however it is not possible to perform bronchial provocation test (BPT) assessing reactivity. It was interesting for us if the result of BPT can be predicted on the base of routine lung tests. The aim of the study is evaluation of the relationship between BPT results and baseline lung function tests assessing small bronchi obstruction in children suffering from asthma. Investigated group comprised 139 children aged 7 to 17 years, with episodic, mild or moderate asthma. During bronchial challenge lung function was assessed on the base of spirography and maximal flows at 50% and 25% of forced vital capacity (MEF50 and MEF25) and other indices as surface under end-half of flow-volume curve and mean flow times T50 and T25. The study results confirmed good correlation between BPT result and baseline lung function. Those children which had worse initial lung tests had more pronounced bronchial hyperreactivity. This relationship was the closest in the group of children with small bronchi obstruction. Analysis of correlation showed highly significant relationship between baseline lung function tests and degree of bronchial reactivity. The highest significance was observed for MEF50 and MEF25. We conclude that small bronchi test disturbances in children with asthma could predict with high probability results of bronchial challenge.

Adolescent↗

[Aerosol deposit sample in aspecific bronchial provocation test: a nuclear medicine study for quantification].

A method of standardization of inhalation bronchial provocation tests is induced. The distribution of radioactivity of in- and exhaled 99mTc human albumin (Venticoll) enables an exact calculation of intrabronchial aerosol deposition. The investigations were carried out at twelve normal test persons by using the device of bronchial provocation tests of PARI. Linearity exists between nebulized aerosol quantity in the bag and bronchial aerosol deposition. The intrabronchial aerosol deposition is calculated about 100 mg after emptying the ten liter-bag. Slowly inspiratory maneuvers of vital capacity produce a precision of the inhaled aerosol of about 15 percent.

Aerosols↗

Responsiveness to three bronchial provocation tests in patients with asthma.

STUDY OBJECTIVES: To compare a new bronchial provocation test, the mannitol challenge, with cold air and histamine challenges to demonstrate airway hyperresponsiveness (AHR) in patients with difficult-to-diagnose asthma. DESIGN: A prospective study. PARTICIPANTS: Thirty-seven consecutive patients with recently diagnosed, steroid-naive, mild, or atypical asthma fulfilling the diagnostic criteria of Finnish Social Insurance Institution, and 10 healthy control subjects. INTERVENTIONS: Each subject completed a symptom questionnaire and underwent spirometry, diffusion capacity measurement, skin-prick tests, and bronchial provocations with mannitol, histamine, and cold air. The severity of asthma was classified according to the Global Initiative for Asthma (GINA). RESULTS: Fifty-one percent of the asthmatic patients responded to mannitol (> or =15% fall in FEV(1)), 24% to cold air (> or =9% fall in FEV(1)), and 81% or 49% to histamine (provocative dose causing a 15% fall in FEV(1) [PD(15)] < 1.0 mg or < 0.4 mg, respectively). None of the healthy control subjects responded. The GINA classification was not associated with responsiveness to any of the challenges. CONCLUSIONS: Mannitol is more sensitive than cold air in demonstrating AHR in patients with mild or atypical asthma. Histamine was more sensitive than both mannitol and cold air if 1.0 mg was used as a cut-off value for histamine PD(15). However, if the cut-off value for histamine PD(15) is lowered to 0.4 mg, which represents a specific diagnosis of asthma according to previous studies, the sensitivity values of mannitol and histamine challenges are comparable.

Adult↗