Difference between dosimeter and tidal breathing methacholine challenge - Contributions of dose and deep inspiration bronchoprotection

Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Chest (Impact Factor: 7.48). 01/2006; 128(6):4018-23. DOI: 10.1378/chest.128.6.4018
Source: PubMed


Two bronchoprovocation methods are widely used. Compared to the tidal breathing method, the dosimeter method delivers approximately half the dose and involves five deep inhalations. Both the lower dose and the bronchoprotective deep inhalations contribute to the lesser airway response of the dosimeter.
To determine the relative role of dose and deep inspiration in the difference between the two methods.
Subjects with asthma (n = 24) underwent three methacholine challenges: a dosimeter challenge, a 2-min tidal breathing challenge (twice the dose), and a modified 2-min tidal breathing challenge (twice the dose plus five deep inhalations).
The dosimeter method produced a nonsignificantly lower response than the modified tidal breathing method (p = 0.14). Both deep inhalation methods produced significantly less response than did the standard tidal breathing method (p = 0.011). In the 12 subjects with the most mild airway hyperresponsiveness (AHR), the differences between the deep inhalation method and the tidal breathing method were greater (p = 0.007). By contrast, deep inhalations produced no effect in the 12 subjects with greater AHR; the two tidal breathing methods produced identical results, while the dosimeter produced less response than either (p = 0.033). Six current asthmatics with mild airway responsiveness (tidal breathing method) had negative dosimeter methacholine challenge results.
In subjects with moderate airway responsiveness, the difference between the methods is due to the difference in dose, whereas in subjects with mild AHR, deep inhalations had a large effect overwhelming the dose effect and producing false-negative methacholine challenge results in 25% of the subjects.

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    • "It is possible that there could be important differences in the physiology of milder versus more severe asthma. Finally, the deep inhalations performed during the dosimeter protocol for methacholine challenge have been reported to result in bronchoprotection and falsely negative challenge results among mild asthmatics, compared to the tidal breathing protocol[17,18]. It would be of interest to have data on the relationship of Rmin to airway responsiveness assessed by both protocols. "
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    ABSTRACT: Asthmatics exhibit reduced airway dilation at maximal inspiration, likely due to structural differences in airway walls and/or functional differences in airway smooth muscle, factors that may also increase airway responsiveness to bronchoconstricting stimuli. The goal of this study was to test the hypothesis that the minimal airway resistance achievable during a maximal inspiration (R(min)) is abnormally elevated in subjects with airway hyperresponsiveness. The R(min) was measured in 34 nonasthmatic and 35 asthmatic subjects using forced oscillations at 8 Hz. R(min) and spirometric indices were measured before and after bronchodilation (albuterol) and bronchoconstriction (methacholine). A preliminary study of 84 healthy subjects first established height dependence of baseline R(min) values. Asthmatics had a higher baseline R(min) % predicted than nonasthmatic subjects (134 ± 33 vs. 109 ± 19 % predicted, p = 0.0004). Sensitivity-specificity analysis using receiver operating characteristic curves indicated that baseline R(min) was able to identify subjects with airway hyperresponsiveness (PC20 < 16 mg/mL) better than most spirometric indices (Area under curve = 0.85, 0.78, and 0.87 for R(min) % predicted, FEV1 % predicted, and FEF25-75 % predicted, respectively). Also, 80% of the subjects with baseline R(min) < 100% predicted did not have airway hyperresponsiveness while 100% of subjects with R(min) > 145% predicted had hyperresponsive airways, regardless of clinical classification as asthmatic or nonasthmatic. These findings suggest that baseline R(min), a measurement that is easier to perform than spirometry, performs as well as or better than standard spirometric indices in distinguishing subjects with airway hyperresponsiveness from those without hyperresponsive airways. The relationship of baseline R(min) to asthma and airway hyperresponsiveness likely reflects a causal relation between conditions that stiffen airway walls and hyperresponsiveness. In conjunction with symptom history, R(min) could provide a clinically useful tool for assessing asthma and monitoring response to treatment.
    Respiratory research 07/2011; 12(1):96. DOI:10.1186/1465-9921-12-96 · 3.09 Impact Factor
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    • "Recent studies performed in large numbers of individuals showed that approximately equivalent results for the two methods are seen in subjects with mild to moderate or greater airway hyperresponsivenss.8 However, the five-breath dosimeter method might protect from bronchoconstriction to methacholine in asthmatics with very mild airway hyperresponsiveness.9,10 These findings may result in the negative response regarding NSAH to methacholine seen in our patient. "
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    ABSTRACT: Hydroxyapatite is commonly used as a filler to replace amputated bone or as a coating to promote bone ingrowth into prosthetic implants. Many modern implants, such as hip replacements and dental implants, are coated with hydroxyapatite. We report a patient with occupational asthma due to hydroxyapatite, proven by a specific inhalation challenge, who experienced an early asthmatic reaction after exposure to hydroxyapatite, without increased airway responsiveness to methacholine despite an increased eosinophil count in the peripheral blood. A 38-year-old male dental implant worker visited our allergy department for the evaluation of occupational asthma. He had treated dental implant titanium surfaces with hydroxyapatite for 1.5 years. One year after starting his employment, he noticed symptoms of rhinorrhea, paroxysmal cough, and chest tightness. His symptoms were aggravated during and shortly after work and subsided several hours after work. When he stopped working for 2 months because of his chest symptoms, he became asymptomatic. After restarting his work, his symptoms reappeared and were aggravated. A methacholine bronchial challenge test had a negative response. The following day, a specific bronchial provocation test with wheat powder was negative. On the third day, a specific bronchial provocation test with hydroxyapatite powder produced an early asthmatic response. On the fourth day, a methacholine bronchial challenge test was negative. Further studies are needed to evaluate the exact pathogenetic mechanism of hydroxyapatite-induced occupational asthma.
    Allergy, asthma & immunology research 04/2011; 3(2):135-7. DOI:10.4168/aair.2011.3.2.135 · 2.43 Impact Factor
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    ABSTRACT: ABSTRACT Inpatients with mild COPD, the effect of deep inspirations (DI) to reverse methacholine-induced bronchoconstriction is largely attenuated. In this study, we tested the hypothesis that the effectiveness of DI is reduced with increasing disease severity and that this is associated with a reduction in the ability of DI to distend,the airways. F ifteen subjects (GOLD stage I-II: 7; GOLD stage III-IV: 8) underwent methacholine bronchoprovocation in the absence of DI, followed by DI. Theeffectiveness of DIwas,assessed by their ability to improve IVC and FEV1. To evaluate airway distensibility, two sets of HRCT scans (at RV and at TLC) were obtained prior to the challenge. In addition, mean parenchymal density was calculated on the HRCTs. We found a strong correlation between,the response,to DI and baseline FEV1% predicted (r 2
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