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Sensitivity and specificity of bronchial provocation testing. An evaluation of four techniques in exercise-induced bronchospasm.

The thresholds used to define a positive result for bronchial provocation challenges (BPC) are arbitrary. Requiring smaller decrements in expired flow to define a positive study would capture more cases of reactive airways (increased sensitivity) but would include some "normal" responses (decreased specificity). To examine the relationship between threshold definition and the ability to correctly classify subjects as either normal or as having airways hyperresponsiveness (AHR), four different BPC tests were administered on different days to 20 patients with a clinical diagnosis of exercise-induced bronchospasm (EIB) and 20 control subjects. The four BPC tests were indoor exercise on a cycle ergometer, methacholine inhalation challenge (MIC), eucapnic voluntary hyperventilation (EVH) with dry gas, and EVH with cold gas. Our results indicate that the thresholds which best separate the two groups are different for each of the four BPC techniques. For methacholine inhalation (MIC), a fall in FEV1 (d%FEV1) of 15 percent or greater at 188 cumulative breath units was 100 percent specific for AHR but had a sensitivity of only 55 percent. Eucapnic voluntary hyperventilation (EVH) with room temperature dry gas was 100 percent specific at a d%FEV1 of 11 percent, but, at that threshold, sensitivity was only 50 percent. EVH with cold air was 100 percent specific at a d%FEV1 of 12 percent but sensitivity was only 35 percent. The bicycle ergometer challenge was far too insensitive to be of value in evaluating AHR. Based on their respective receiver operating characteristic curves, the best separation of the two subject groups occurred at a d%FEV1 of 5 percent and 12 percent for the two EVH techniques and MIC, respectively. An individual's response to one test was highly correlated with the response to either of the other two (r = 0.66, p less than 0.001 for dry vs cold gas EVH; r = 0.56, p less than 0.001 for dry gas EVH vs methacholine; and r = 0.69, p less than 0.001 for cold gas EVH vs methacholine). Thus, MIC and EVH techniques are equally useful in defining AHR and each has its optimal threshold for a positive test result.

Adult↗

[Validity of nonspecific bronchial provocation tests for the diagnosis of airway hyperresponsiveness--a comparison of different methods].

OBJECTIVE: To compare the validity of different methods for the assessment of bronchial hyperresponsiveness used by different centers. METHODS: Case series of 648 subjects referred to six pulmonary centers, all with a history of shortness of breath without airway obstruction, without use of medication that might influence the tests and without viral infections during the previous two weeks. All subjects answered a questionnaire of recent symptoms and underwent bronchial challenge with a chemical stimulus according to each center's protocol. Analysis was performed by receiver operating characteristic (ROC) plots using the questionnaire's answers as the gold standard. Diagnostic test sensitivities at the cut-offs for bronchial hyperresponsiveness indicated by each center were compared. RESULTS: ROC plots showed poor validity of all tests, i.e. both acceptable sensitivity and specificity were not observed with any test. There was no obvious difference of the slope of the ROC plots between the different centers. However, maximal sensitivity differed considerably: for "wheeze during the previous 12 months", sensitivity at each center's cut-off for the definition of bronchial hyperresponsiveness varied between 0.35 and 0.73. The choice of the question used as the standard had little influence on test validity. CONCLUSION: Although some of the differences between centers may be explained by subject characteristics, the large differences of the test sensitivities are unacceptable and underscore the need for standardization of these tests, primarily with respect to sufficient sensitivity.

Adolescent↗

[Recommendations for the standardization of bronchial provocation tests using bronchoconstriction agents].

The author is resuming part of the reports and discussions from the 26th Golnik symposium with the main topic "The measurement of nonspecific bronchial responsiveness." The indications for nonspecific bronhcoprovocation tests, different methods for production of aerosol and ways of inhalation of bronchoconstrictory agent are discussed. Further on the procedures for measurement of bronchial response, shorter one by inhalation of one dose and longer one by increased quantities of metacholine or histamine together with the interpretation of the results have been introduced as well.

Bronchial Provocation Tests↗

Oral and bronchial provocation tests with aspirin for diagnosis of aspirin-induced asthma.

In 35 asthmatic patients with acetylsalicylic acid (aspirin; ASA) intolerance (AIA) and 15 asthmatics tolerating ASA well, the authors compared the diagnostic value of the placebo-controlled oral ASA versus inhaled L-lysine (L) ASA challenges. All AIA subjects gave a history of asthmatic attacks following ingestion of ASA and in all of them the intolerance was confirmed by oral challenge test over the past 10 yrs. Doses of ASA increasing in geometric progression were used in oral tests 10-312 mg (cumulative dose 500 mg); in bronchial tests 0.18-115 mg (cumulative dose 182 mg). Either challenge was considered as positive, if forced expiratory volume in one second (FEV1) dropped at least 20% from the baseline value and/or strong extrabronchial symptoms of intolerance occurred. Urinary leukotriene E4 excretion was determined at baseline and following the challenges. In 24 out of 35 patients the oral test was positive, based on a 20% decrease in FEV1. When including extrabronchial symptoms this was positive in 31 cases. Bronchial L-ASA challenge led to > or =20% fall FEV1 in 21 out of 35 cases, and in 27 cases when including extrabronchial symptoms. No correlation was observed between ASA provocative dose causing a 20% fall in FEV1, determined by the oral route compared to the inhalation route. Urinary LTE4 increased after both challenges the rise being higher following oral as compared to inhalation provocation (p=0.0001). It is concluded that both tests had similar specificity whilst the oral test showed a tendency to higher sensitivity for the clinical diagnosis of acetylsalicylic acid intolerance. The inclusion of extrabronchial symptoms into the criteria of test positivity enhanced the diagnostic value of both procedures. In both tests the highest leukotriene E4 increases were found in the presence of extrabronchial symptoms, suggesting the participation of tissues other than the lung in aspirin induced leukotriene E4 release to urine.

Adult↗

Effect of a bronchial provocation test with house-dust mite on blood eosinophilia, eosinophil cationic protein, soluble interleukin-2 receptor, and interleukin-6 in asthmatic children.

Eighteen children with perennial asthma and allergy to house-dust mite (HDM) underwent a bronchial challenge with HDM. Before and 24 h after the test, a venous blood sample was taken to determine levels of eosinophils, eosinophil cationic protein (ECP), soluble interleukin-2 receptor (IL-2R), and interleukin-6 (IL-6). A histamine challenge was performed before and 24 h after the HDM challenge. All subjects showed an immediate asthmatic reaction (IAR). A definite late asthmatic reaction (LAR) was observed in 15 children, a probable LAR in two, and no LAR in one. Because of persistent bronchial obstruction (FEV1 < 70%), eight children were unable to perform a histamine challenge 24 h after the allergen challenge. These were the children with the lowest prechallenge provocation dose (PD20) of histamine. In the other 10 children, the mean PD20 histamine decreased after the HDM challenge (mean PD20 before was 0.56 mg/ml; after challenge it was 0.14 mg/ml; P = 0.007). After the HDM challenge, an increase was detected in the mean values of blood eosinophils (mean before was 446/mm3; mean after was 733/mm3; P = 0.002), ECP (mean before was 26.3 micrograms/l; mean after was 34.3 micrograms/l; P < 0.040), and IL-2R (mean before was 116.35 U/ml; mean after was 128.52 U/ml; P < 0.040). On the other hand, IL-6 remained unchanged after the HDM challenge (mean before was 9.47 pg/l; mean after was 9.70 pg/l; P = 0.360).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Simultaneous recording of spirometric parameters and total respiratory resistance on the Astograph in nonspecific bronchial provocation tests using methacholine].

Parallel study results of spirometric parameters (S.P.) FEV1, FEF50, FEF25 and total respiratory resistance (Rrs) measured by Astograph in nonspecific metacholine bronchoprovocation test were analyzed in 378 patients suspected of bronchial asthma. The patients were divided into 7 groups based on Astograph and S.P. instances criteria. Of 92 patients with positive test results, 91% met the set Astograph criterium; 72% met all three S.P. criteria, 1% one criterium and 12% failed to meet any of the S.P. criteria. It was noted that the patients met more the FEF50 and FEF25 criteria (87%) than FEV1 (73%). Also, there was no significant increase in respiratory resistance for those with a predominant reaction in small airways (9%). This fact points to the need of introducing appropriate complementary Astograph methods.

Adult↗

Peak expiratory flow monitoring and airway response to specific bronchial provocation tests in asthmatics.

To assess the validity of peak expiratory flow (PEF), measured by means of a peak flow meter, in comparison to forced expiratory volume in one second (FEV1) for measuring the airway response during specific bronchial challenges, we registered PEF and FEV1 in a random sequence during 75 positive (decrease in FEV1 of > or = 15% from baseline) and 75 negative (decrease in FEV1 < 15% from baseline) challenges with chemicals or allergens. The correlation between PEF and FEV1 in terms of absolute values and of percentage of change from baseline was statistically highly significant (p < 0.001) in all challenges and in the different pattern of response, immediate, dual and late. Relative operating characteristic analysis showed that an absolute decrease in PEF of > or = 70 l.min-1 in the immediate and of > or = 80 l.min-1 in the late phase of the response (cut-off points) gave optimal discrimination between challenges with a bronchoconstrictive response (defined as a FEV1 decrease > or = 15% from baseline), and challenges without. These cut-off points, however, were highly specific (92 and 93.3%, respectively), but not as sensitive (70.6 and 61.1%, respectively), and smaller absolute changes in PEF from baseline do not exclude a bronchoconstrictive response. Our data suggest that PEF readings are a useful diagnostic tool in assessing the airway response during a specific bronchial challenge in asthmatics, although with some limitations. PEF readings can be used to monitor the late response to a challenge during the evening and the night if PEF readings are carefully considered in relation to clinical symptoms.

Adolescent↗