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Provocative dose of methacholine causing a 20% drop in FEV1 should be used to interpret methacholine challenge tests with modern nebulizers.
Ann Am Thorac Soc. 2015 Mar; 12(3):357-63.AA

Abstract

RATIONALE

The American Thoracic Society guidelines (1999) for methacholine challenge tests (MCTs) using the 2-minute tidal breathing protocol were developed for the now-obsolete English-Wright (EW) nebulizer. In addition, the guideline recommendation to use the provocative concentration of methacholine causing a 20% drop in FEV1 (PC20) rather than the provocative dose of methacholine causing a 20% drop in FEV1 (PD20) for determining the level of bronchial hyperresponsiveness has been challenged.

OBJECTIVES

To determine if cumulative dose or concentration of methacholine delivered to the airways is the determinant for airway responsiveness and to validate use of the AeroEclipse* II BAN (Aero; Trudell Medical International, London, ON, Canada) nebulizer compared with use of the reference standard EW nebulizer.

METHODS

Subjects with asthma (10-18 yr old) participated in randomized, controlled cross-over experiments comparing four MCT protocols using standard methacholine concentrations, but varying: (1) methacholine starting concentration (testing for cumulative effect); (2) nebulizer (EW versus Aero); and (3) inhalation time. PD20 was calculated using nebulizer output rate, inhalation time, and preceding doses delivered. ANOVA analyses were used to compare geometric means of PC20 and PD20 between protocols.

RESULTS

A total of 32 subjects (17 male) participated. PC20 differed when starting concentration varied (0.46 vs. 0.80 mg/ml; P<0.0001), whereas PD20 did not (0.06 vs. 0.08 mg). PC20 differed with the EW versus the Aero nebulzer with 30-second inhalation (1.19 vs. 0.43 mg/ml; P=0.0006) and the EW versus the Aero nebulizer with 20-second inhalation (1.91 vs. 0.89 mg/ml; P=0.0027), whereas PD20 did not (0.07 vs. 0.06 mg and 0.11 vs. 0.09 mg, respectively).

CONCLUSIONS

In MCTs, the cumulative dose (PD20), not the PC20, determines bronchial responsiveness. Modern nebulizers may be used for the test if clinical interpretation is based on PD20. Clinical trial registered with www.clinicaltrials.gov (NCT01288482).

Authors+Show Affiliations

1 Division of Respiratory Medicine, and.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25575246

Citation

Dell, Sharon D., et al. "Provocative Dose of Methacholine Causing a 20% Drop in FEV1 Should Be Used to Interpret Methacholine Challenge Tests With Modern Nebulizers." Annals of the American Thoracic Society, vol. 12, no. 3, 2015, pp. 357-63.
Dell SD, Bola SS, Foty RG, et al. Provocative dose of methacholine causing a 20% drop in FEV1 should be used to interpret methacholine challenge tests with modern nebulizers. Ann Am Thorac Soc. 2015;12(3):357-63.
Dell, S. D., Bola, S. S., Foty, R. G., Marshall, L. C., Nelligan, K. A., & Coates, A. L. (2015). Provocative dose of methacholine causing a 20% drop in FEV1 should be used to interpret methacholine challenge tests with modern nebulizers. Annals of the American Thoracic Society, 12(3), 357-63. https://doi.org/10.1513/AnnalsATS.201409-433OC
Dell SD, et al. Provocative Dose of Methacholine Causing a 20% Drop in FEV1 Should Be Used to Interpret Methacholine Challenge Tests With Modern Nebulizers. Ann Am Thorac Soc. 2015;12(3):357-63. PubMed PMID: 25575246.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Provocative dose of methacholine causing a 20% drop in FEV1 should be used to interpret methacholine challenge tests with modern nebulizers. AU - Dell,Sharon D, AU - Bola,Sundeep S, AU - Foty,Richard G, AU - Marshall,Laura C, AU - Nelligan,Kathleen A, AU - Coates,Allan L, PY - 2015/1/10/entrez PY - 2015/1/13/pubmed PY - 2015/12/15/medline KW - asthma KW - bronchial hyperreactivity KW - diagnosis KW - methacholine KW - nebulizers SP - 357 EP - 63 JF - Annals of the American Thoracic Society JO - Ann Am Thorac Soc VL - 12 IS - 3 N2 - RATIONALE: The American Thoracic Society guidelines (1999) for methacholine challenge tests (MCTs) using the 2-minute tidal breathing protocol were developed for the now-obsolete English-Wright (EW) nebulizer. In addition, the guideline recommendation to use the provocative concentration of methacholine causing a 20% drop in FEV1 (PC20) rather than the provocative dose of methacholine causing a 20% drop in FEV1 (PD20) for determining the level of bronchial hyperresponsiveness has been challenged. OBJECTIVES: To determine if cumulative dose or concentration of methacholine delivered to the airways is the determinant for airway responsiveness and to validate use of the AeroEclipse* II BAN (Aero; Trudell Medical International, London, ON, Canada) nebulizer compared with use of the reference standard EW nebulizer. METHODS: Subjects with asthma (10-18 yr old) participated in randomized, controlled cross-over experiments comparing four MCT protocols using standard methacholine concentrations, but varying: (1) methacholine starting concentration (testing for cumulative effect); (2) nebulizer (EW versus Aero); and (3) inhalation time. PD20 was calculated using nebulizer output rate, inhalation time, and preceding doses delivered. ANOVA analyses were used to compare geometric means of PC20 and PD20 between protocols. RESULTS: A total of 32 subjects (17 male) participated. PC20 differed when starting concentration varied (0.46 vs. 0.80 mg/ml; P<0.0001), whereas PD20 did not (0.06 vs. 0.08 mg). PC20 differed with the EW versus the Aero nebulzer with 30-second inhalation (1.19 vs. 0.43 mg/ml; P=0.0006) and the EW versus the Aero nebulizer with 20-second inhalation (1.91 vs. 0.89 mg/ml; P=0.0027), whereas PD20 did not (0.07 vs. 0.06 mg and 0.11 vs. 0.09 mg, respectively). CONCLUSIONS: In MCTs, the cumulative dose (PD20), not the PC20, determines bronchial responsiveness. Modern nebulizers may be used for the test if clinical interpretation is based on PD20. Clinical trial registered with www.clinicaltrials.gov (NCT01288482). SN - 2325-6621 UR - https://www.unboundmedicine.com/medline/citation/25575246/Provocative_dose_of_methacholine_causing_a_20_drop_in_FEV1_should_be_used_to_interpret_methacholine_challenge_tests_with_modern_nebulizers_ L2 - http://www.atsjournals.org/doi/full/10.1513/AnnalsATS.201409-433OC?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -