Performance Characteristics of Spirometry With Negative Bronchodilator Response and Methacholine Challenge Testing and Implications for Asthma Diagnosis

Canadian Respiratory Research Network

doi:10.1016/j.chest.2020.03.052

Performance Characteristics of Spirometry With Negative Bronchodilator Response and Methacholine Challenge Testing and Implications for Asthma Diagnosis

Canadian Respiratory Research Network

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

Abstract

Background: In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT). Research Question: We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis. Study Design and Methods: Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6 weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20% drop in FEV₁ [PC₂₀] > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months. Results: Of 500 subjects (50.5 ± 16.6 years old, 68.0% female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95% CI, 1.17-3.04). MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist. Interpretation: In subjects with a self-reported physician diagnosis of asthma, absence of bronchodilator reversibility had a negative predictive value of only 57% to exclude asthma. A finding of spirometric airflow limitation significantly increased chances of asthma. MCT results varied with medication taper and over time, and pulmonologists were sometimes prepared to give a clinical diagnosis of asthma despite negative MCT. Correspondingly, in patients for whom a high clinical suspicion of asthma exists, repeat testing appears to be warranted.

Original language	English
Pages (from-to)	479-490
Number of pages	12
Journal	Chest
Volume	158
Issue number	2
DOIs	https://doi.org/10.1016/j.chest.2020.03.052
Publication status	Published - Aug 2020
Externally published	Yes

Bibliographical note

Funding Information:
FUNDING/SUPPORT: This work was supported by grant MOP-115073 from the Canadian Institutes of Health Research received by Drs Aaron, FitzGerald, Gupta, Pakhale, Vandemheen, Lemière, Boulet, and Hernandez. Methapharm Inc supplied provocholine; Trudell Medical International supplied peak flow meters; and ASDE Survey Sampler organized the random digit dialing.

Funding Information:
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: M. A. reported receiving speaking honoraria from Boehringer Ingelheim Canada. C. L. reported serving on advisory boards for GlaxoSmithKline, Teva, AstraZeneca, and Methapharm Inc; and serving as a member of the Asthma Clinical Assembly of the Canadian Thoracic Society. S. K. F. reported receiving grants from Boehringer Ingelheim, Novartis, AstraZeneca, GlaxoSmithKline, and Synertec; receiving speaking honoraria from Boehringer Ingelheim, Novartis, and Grifols; and serving on advisory boards for Teva and Roche. P. H. reported serving on advisory boards for Actelion, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Sanofi, and Teva; receiving fees for delivering accredited medical education from AstraZeneca, Boehringer Ingelheim; and his institution receiving grants for conduct of research/clinical trials from Boehringer Ingelheim, Cyclomedica, Grifols, Prometric, and Respivant Sciences. L.-P. B. reported receiving research grants for participation to multicenter studies from AstraZeneca, Boston Scientific, GlaxoSmithKline, Hoffman La Roche, Novartis, Ono Pharmaceutical Co, Ltd, Sanofi, and Takeda Pharmaceutical Company, Ltd; receiving support for investigator-generated research projects from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, and Takeda Pharmaceutical Company, Ltd; receiving fees for consulting and advisory boards from Astra Zeneca, GlaxoSmithKline, Novartis, Merck, and Sanofi-Regeneron; receiving nonprofit grants for production of educational materials from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Novartis, and Teva; and receiving conference fees from AstraZeneca, GlaxoSmithKline, Merck, Novartis, and Teva. None declared (J. S., S. D. A., J. R. S., K. L. V., J. M. F., R. A. M., I. M., S. M., G. G. A., S. P., R. M., S. G.).

Publisher Copyright:
© 2020 The Authors

ASJC Scopus Subject Areas

Pulmonary and Respiratory Medicine
Critical Care and Intensive Care Medicine
Cardiology and Cardiovascular Medicine

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10.1016/j.chest.2020.03.052

Cite this

@article{a286824b3c1943aaa7d4114a02fbb66d,

title = "Performance Characteristics of Spirometry With Negative Bronchodilator Response and Methacholine Challenge Testing and Implications for Asthma Diagnosis",

abstract = "Background: In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT). Research Question: We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis. Study Design and Methods: Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6 weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20% drop in FEV1 [PC20] > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months. Results: Of 500 subjects (50.5 ± 16.6 years old, 68.0% female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95% CI, 1.17-3.04). MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist. Interpretation: In subjects with a self-reported physician diagnosis of asthma, absence of bronchodilator reversibility had a negative predictive value of only 57% to exclude asthma. A finding of spirometric airflow limitation significantly increased chances of asthma. MCT results varied with medication taper and over time, and pulmonologists were sometimes prepared to give a clinical diagnosis of asthma despite negative MCT. Correspondingly, in patients for whom a high clinical suspicion of asthma exists, repeat testing appears to be warranted.",

author = "{Canadian Respiratory Research Network} and Janannii Selvanathan and Aaron, {Shawn D.} and Sykes, {Jenna R.} and Vandemheen, {Katherine L.} and FitzGerald, {J. Mark} and Martha Ainslie and Catherine Lemi{\`e}re and Field, {Stephen K.} and McIvor, {R. Andrew} and Paul Hernandez and Irvin Mayers and Sunita Mulpuru and Alvarez, {Gonzalo G.} and Smita Pakhale and Ranjeeta Mallick and Boulet, {Louis Philippe} and Samir Gupta and Shawn Aaron and James Martin and Peter Par{\'e} and James Hogg and Christopher Carlsten and Jonathon Leipsic and Don Sin and Wan Tan and Jordan Guenette and Mark FitzGerald and Harvey Coxson and Mohsen Sadatsafavi and Carlo Marra and John Mayo and David Proud and Richard Leigh and Anita Kozyrskyj and Jacqueline Quail and Andrew Halayko and Marni Brownell and Grace Parraga and Parameswaran Nair and Martin Stampfli and Paul O'Byrne and Noe Zamel and Felix Ratjen and Dina Brooks and Andrea Gershon and Teresa To and Wendy Ungar and Diane Lougheed and Denis O'Donnell and Bernard Thebaud",

note = "Funding Information: FUNDING/SUPPORT: This work was supported by grant MOP-115073 from the Canadian Institutes of Health Research received by Drs Aaron, FitzGerald, Gupta, Pakhale, Vandemheen, Lemi{\`e}re, Boulet, and Hernandez. Methapharm Inc supplied provocholine; Trudell Medical International supplied peak flow meters; and ASDE Survey Sampler organized the random digit dialing. Funding Information: Financial/nonfinancial disclosures: The authors have reported to CHEST the following: M. A. reported receiving speaking honoraria from Boehringer Ingelheim Canada. C. L. reported serving on advisory boards for GlaxoSmithKline, Teva, AstraZeneca, and Methapharm Inc; and serving as a member of the Asthma Clinical Assembly of the Canadian Thoracic Society. S. K. F. reported receiving grants from Boehringer Ingelheim, Novartis, AstraZeneca, GlaxoSmithKline, and Synertec; receiving speaking honoraria from Boehringer Ingelheim, Novartis, and Grifols; and serving on advisory boards for Teva and Roche. P. H. reported serving on advisory boards for Actelion, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Sanofi, and Teva; receiving fees for delivering accredited medical education from AstraZeneca, Boehringer Ingelheim; and his institution receiving grants for conduct of research/clinical trials from Boehringer Ingelheim, Cyclomedica, Grifols, Prometric, and Respivant Sciences. L.-P. B. reported receiving research grants for participation to multicenter studies from AstraZeneca, Boston Scientific, GlaxoSmithKline, Hoffman La Roche, Novartis, Ono Pharmaceutical Co, Ltd, Sanofi, and Takeda Pharmaceutical Company, Ltd; receiving support for investigator-generated research projects from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, and Takeda Pharmaceutical Company, Ltd; receiving fees for consulting and advisory boards from Astra Zeneca, GlaxoSmithKline, Novartis, Merck, and Sanofi-Regeneron; receiving nonprofit grants for production of educational materials from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Novartis, and Teva; and receiving conference fees from AstraZeneca, GlaxoSmithKline, Merck, Novartis, and Teva. None declared (J. S., S. D. A., J. R. S., K. L. V., J. M. F., R. A. M., I. M., S. M., G. G. A., S. P., R. M., S. G.). Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

month = aug,

doi = "10.1016/j.chest.2020.03.052",

language = "English",

volume = "158",

pages = "479--490",

journal = "Chest",

issn = "0012-3692",

publisher = "American College of Chest Physicians",

number = "2",

}

TY - JOUR

T1 - Performance Characteristics of Spirometry With Negative Bronchodilator Response and Methacholine Challenge Testing and Implications for Asthma Diagnosis

AU - Canadian Respiratory Research Network

AU - Selvanathan, Janannii

AU - Aaron, Shawn D.

AU - Sykes, Jenna R.

AU - Vandemheen, Katherine L.

AU - FitzGerald, J. Mark

AU - Ainslie, Martha

AU - Lemière, Catherine

AU - Field, Stephen K.

AU - McIvor, R. Andrew

AU - Hernandez, Paul

AU - Mayers, Irvin

AU - Mulpuru, Sunita

AU - Alvarez, Gonzalo G.

AU - Pakhale, Smita

AU - Mallick, Ranjeeta

AU - Boulet, Louis Philippe

AU - Gupta, Samir

AU - Aaron, Shawn

AU - Martin, James

AU - Paré, Peter

AU - Hogg, James

AU - Carlsten, Christopher

AU - Leipsic, Jonathon

AU - Sin, Don

AU - Tan, Wan

AU - Guenette, Jordan

AU - FitzGerald, Mark

AU - Coxson, Harvey

AU - Sadatsafavi, Mohsen

AU - Marra, Carlo

AU - Mayo, John

AU - Proud, David

AU - Leigh, Richard

AU - Kozyrskyj, Anita

AU - Quail, Jacqueline

AU - Halayko, Andrew

AU - Brownell, Marni

AU - Parraga, Grace

AU - Nair, Parameswaran

AU - Stampfli, Martin

AU - O'Byrne, Paul

AU - Zamel, Noe

AU - Ratjen, Felix

AU - Brooks, Dina

AU - Gershon, Andrea

AU - To, Teresa

AU - Ungar, Wendy

AU - Lougheed, Diane

AU - O'Donnell, Denis

AU - Thebaud, Bernard

N1 - Funding Information: FUNDING/SUPPORT: This work was supported by grant MOP-115073 from the Canadian Institutes of Health Research received by Drs Aaron, FitzGerald, Gupta, Pakhale, Vandemheen, Lemière, Boulet, and Hernandez. Methapharm Inc supplied provocholine; Trudell Medical International supplied peak flow meters; and ASDE Survey Sampler organized the random digit dialing. Funding Information: Financial/nonfinancial disclosures: The authors have reported to CHEST the following: M. A. reported receiving speaking honoraria from Boehringer Ingelheim Canada. C. L. reported serving on advisory boards for GlaxoSmithKline, Teva, AstraZeneca, and Methapharm Inc; and serving as a member of the Asthma Clinical Assembly of the Canadian Thoracic Society. S. K. F. reported receiving grants from Boehringer Ingelheim, Novartis, AstraZeneca, GlaxoSmithKline, and Synertec; receiving speaking honoraria from Boehringer Ingelheim, Novartis, and Grifols; and serving on advisory boards for Teva and Roche. P. H. reported serving on advisory boards for Actelion, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Sanofi, and Teva; receiving fees for delivering accredited medical education from AstraZeneca, Boehringer Ingelheim; and his institution receiving grants for conduct of research/clinical trials from Boehringer Ingelheim, Cyclomedica, Grifols, Prometric, and Respivant Sciences. L.-P. B. reported receiving research grants for participation to multicenter studies from AstraZeneca, Boston Scientific, GlaxoSmithKline, Hoffman La Roche, Novartis, Ono Pharmaceutical Co, Ltd, Sanofi, and Takeda Pharmaceutical Company, Ltd; receiving support for investigator-generated research projects from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, and Takeda Pharmaceutical Company, Ltd; receiving fees for consulting and advisory boards from Astra Zeneca, GlaxoSmithKline, Novartis, Merck, and Sanofi-Regeneron; receiving nonprofit grants for production of educational materials from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Novartis, and Teva; and receiving conference fees from AstraZeneca, GlaxoSmithKline, Merck, Novartis, and Teva. None declared (J. S., S. D. A., J. R. S., K. L. V., J. M. F., R. A. M., I. M., S. M., G. G. A., S. P., R. M., S. G.). Publisher Copyright: © 2020 The Authors

PY - 2020/8

Y1 - 2020/8

N2 - Background: In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT). Research Question: We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis. Study Design and Methods: Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6 weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20% drop in FEV1 [PC20] > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months. Results: Of 500 subjects (50.5 ± 16.6 years old, 68.0% female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95% CI, 1.17-3.04). MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist. Interpretation: In subjects with a self-reported physician diagnosis of asthma, absence of bronchodilator reversibility had a negative predictive value of only 57% to exclude asthma. A finding of spirometric airflow limitation significantly increased chances of asthma. MCT results varied with medication taper and over time, and pulmonologists were sometimes prepared to give a clinical diagnosis of asthma despite negative MCT. Correspondingly, in patients for whom a high clinical suspicion of asthma exists, repeat testing appears to be warranted.

AB - Background: In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT). Research Question: We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis. Study Design and Methods: Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6 weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20% drop in FEV1 [PC20] > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months. Results: Of 500 subjects (50.5 ± 16.6 years old, 68.0% female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95% CI, 1.17-3.04). MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist. Interpretation: In subjects with a self-reported physician diagnosis of asthma, absence of bronchodilator reversibility had a negative predictive value of only 57% to exclude asthma. A finding of spirometric airflow limitation significantly increased chances of asthma. MCT results varied with medication taper and over time, and pulmonologists were sometimes prepared to give a clinical diagnosis of asthma despite negative MCT. Correspondingly, in patients for whom a high clinical suspicion of asthma exists, repeat testing appears to be warranted.

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JF - Chest

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Performance Characteristics of Spirometry With Negative Bronchodilator Response and Methacholine Challenge Testing and Implications for Asthma Diagnosis

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