Provocative Dose of Methacholine Causing a 20% Drop in FEV<sub>1</sub> Should Be Used to Interpret Methacholine Challenge Tests with Modern Nebulizers

Dell, Sharon D.; Bola, Sundeep S.; Foty, Richard; Marshall, Laura; Nelligan, Kathleen; Coates, Allan L.

doi:10.1513/annalsats.201409-433oc

Cited by 42 publications

(31 citation statements)

References 25 publications

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“…The FEV 1 was measured 3 minutes after each dose of methacholine and the challenge test was terminated when the subject had completed all inhalations, or when FEV 1 had fallen by 20% or more from the baseline value. The dose of methacholine that caused 20% reduction of FEV 1 (PD 20 ) was calculated and expressed in µmol, 17 and twice the highest dose was arbitrarily used as the PD 20 for subjects who completed all steps in the protocol without a 20% reduction in FEV 1 18 …”

Section: Methodsmentioning

confidence: 99%

Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents

Kalm-Stephens

Malinovschi

Janson

et al. 2020

Pediatric Pulmonology

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Objectives The aim of this study was to investigate airway responsiveness and eosinophil and neutrophil inflammatory markers in clinically confirmed nonasthmatic adolescents with elevated fractional exhaled nitric oxide (FeNO), a marker of type‐2 inflammation in the airways. Methodology A total of 959 subjects from a general population, aged 12 to 15 years, answered a standardised questionnaire and underwent FeNO measurements at a screening visit at school. Adolescents without asthma, who had elevated FeNO (FeNO100 > 15 ppb) (n = 19), and control subjects, with low FeNO (FeNO100 < 5 ppb) and without reported symptoms of asthma or allergy (n = 28), participated in a follow‐up study where FeNO50, airway responsiveness to methacholine (PD20), blood eosinophil counts, and serum neutrophil lipocalin (HNL) and myeloperoxidase (MPO) levels were measured. Questionnaire follow‐ups were performed 4 and 16 years later. Results Airway responsiveness (PD20: 6.94 [1.87, 11.39] vs 11.42 [6.33, 59.4] µmol; P < .05) and blood eosinophil counts (0.31 [0.20, 0.44] vs 0.13 [0.1, 0.22] 109/L; P < .001) (geometric mean [95% CI]) were higher among cases than controls. A significant correlation between blood eosinophils and FeNO was found (rho = 0.41; P = .005). In contrast, serum HNL and MPO were lower in cases than controls (P < .05 both), and there was a negative correlation between HNL and FeNO (r = −0.31; P = .04). At both follow‐ups, a higher proportion of subjects reported allergic symptoms compared with baseline (P = .02, P = .01). Conclusions Elevated FeNO in nonasthmatic adolescents was associated with airway hyperresponsiveness, elevated blood eosinophil counts, and lower systemic activation of neutrophils.

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Section: Methodsmentioning

confidence: 99%

Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents

Kalm-Stephens

Malinovschi

Janson

et al. 2020

Pediatric Pulmonology

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“…The provocative concentration (or dose) causing a 20% fall in FEV 1 (PC 20 FEV 1 ) is calculated by interpolation from the dose causing ≥20% fall in FEV 1 and the penultimate dose on a semi-log scale. It is maybe not surprising that determining the actual dose delivered (PD 20 ) appears to be a more robust measure than simply using the concentration of agonist (PC 20 ) (25). The dose response slope (or DRS), also referred to as the response dose ratio (RDR), is calculated as the slope of the dose response curve plotted with a linear dose axis.…”

Section: Measurement Of Ahr: To What Do We Respond and How Do We Mmentioning

confidence: 99%

Mechanisms of airway hyper‐responsiveness in asthma: the past, present and yet to come

Chapman

Irvin

2015

Clin Experimental Allergy

124

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Airway hyperresponsiveness (AHR) has long been considered a cardinal feature of asthma. The development of the measurement of AHR forty years ago initiated many important contributions to our understanding of asthma and other airway diseases. However, our understanding of AHR in asthma remains complicated by the multitude of potential underlying mechanisms which in reality are likely to have different contributions amongst individual patients. Therefore the present review will discuss the current state of understanding of the major mechanisms proposed to contribute to AHR and highlight the way in which AHR testing is beginning to highlight distinct abnormalities associated with clinically relevant patient populations. In doing so we aim to provide a foundation by which future research can begin to ascribe certain mechanisms to specific patterns of bronchoconstriction and subsequently match phenotypes of bronchoconstriction with clinical phenotypes. We believe that this approach is not only within our grasp but will lead to improved mechanistic understanding of asthma phenotypes and hopefully better inform the development of phenotype-targeted therapy.

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“…There is emerging evidence that to better compare MCT methods, PD 20 , which is the dose of methacholine that causes 20% fall in FEV 1 , would be a better measure to interpret MCT. Dell et al and Coates et al, found that in children and adults PD 20 had better correlation, compared to PC 20 , using different nebulizers (English‐Wright and AeroEclipse II BAN) and should be used to determine bronchial responsiveness . The most recently ERS task force report endorsed the use of PD 20 when resulting methacholine challenge test .…”

Section: Discussionmentioning

confidence: 99%

Methacholine challenge test: Comparison of tidal breathing and dosimeter methods in children

Mazi

Lands

Zielinski

2017

Pediatric Pulmonology

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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

Abstract: 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).

Cited by 42 publications

References 25 publications

Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents

Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents

Mechanisms of airway hyper‐responsiveness in asthma: the past, present and yet to come

Methacholine challenge test: Comparison of tidal breathing and dosimeter methods in children

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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

Abstract: 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).

Cited by 42 publications

References 25 publications

Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents

Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents

Mechanisms of airway hyper‐responsiveness in asthma: the past, present and yet to come

Methacholine challenge test: Comparison of tidal breathing and dosimeter methods in children

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Product

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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