The effect of aerosol distribution on airway responsiveness to inhaled methacholine in patients with asthma

Beth L. Laube; Philip S. Norman; G. K. Adams

doi:10.1016/0091-6749(92)90317-U

The effect of aerosol distribution on airway responsiveness to inhaled methacholine in patients with asthma

Beth L. Laube, Philip S. Norman, G. K. Adams

School of Medicine

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

47 Scopus citations

Abstract

It has been demonstrated that airway deposition of inhaled aerosols is more heterogeneous in patients with asthma than in normal subjects. Nevertheless, the influence of abnormal airway deposition on responses to bronchoactive aerosols is poorly understood. We altered bronchopulmonary deposition heterogeneity of methacholine aerosol in nine asymptomatic patients with asthma by controlling inspiratory flow at high (∼ 60 L/min) versus low (∼ 12 L/min) rates on 2 study days and determined the effect on the provocative dose of methacholine causing a 20% fall in FEV₁ (PD₂₀) (often used as a measure of airway responsiveness). Deposition uniformity was quantified from gamma-camera scans of the lungs in terms of the distribution of a technetium-labeled aerosol that was inhaled rapidly or slowly before the inhalation of methacholine. Increased deposition in an inner (large, central airways) versus an outer (peripheral airways and alveoli) zone of the right lung (inner/outer ratio, >1) and higher values of skew (an index of deposition asymmetry) and kurtosis (an index of deposition range) indicated enhanced heterogeneity of deposition. Mean (± SD) inner/outer ratio was significantly higher during rapid inspiration compared to slow inspiration with 2.91 ± 0.51 and 1.84 ± 0.30, respectively (p < 0.01). Mean skew and kurtosis were also significantly higher after rapid inspiration, with 1.12 ± 0.35 and 3.86 ± 1.25, respectively, compared to 0.74 ± 0.36 and 2.64 ± 0.77 after slow inhalation (p < 0.01). Geometric mean PD₂₀ methacholine was significantly reduced when the aerosol was inhaled rapidly, with 5.9 cumulative methacholine units compared to 15.7 units after slow inhalation (p < 0.02). A Spearman's rank-correlation test demonstrated that values of skew and kurtosis were inversely correlated with PD₂₀ methacholine (p < 0.02; r_s = -0.55 and -0.60, respectively). Results from these studies indicate that increased heterogeneity in aerosol deposition significantly decreases PD₂₀ methacholine in patients with asthma.

Original language	English (US)
Pages (from-to)	510-518
Number of pages	9
Journal	The Journal of allergy and clinical immunology
Volume	89
Issue number	2
DOIs	https://doi.org/10.1016/0091-6749(92)90317-U
State	Published - Feb 1992

Keywords

Aerosol distribution
airway reactivity
asthma
methacholine

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/0091-6749(92)90317-U

Cite this

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title = "The effect of aerosol distribution on airway responsiveness to inhaled methacholine in patients with asthma",

abstract = "It has been demonstrated that airway deposition of inhaled aerosols is more heterogeneous in patients with asthma than in normal subjects. Nevertheless, the influence of abnormal airway deposition on responses to bronchoactive aerosols is poorly understood. We altered bronchopulmonary deposition heterogeneity of methacholine aerosol in nine asymptomatic patients with asthma by controlling inspiratory flow at high (∼ 60 L/min) versus low (∼ 12 L/min) rates on 2 study days and determined the effect on the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) (often used as a measure of airway responsiveness). Deposition uniformity was quantified from gamma-camera scans of the lungs in terms of the distribution of a technetium-labeled aerosol that was inhaled rapidly or slowly before the inhalation of methacholine. Increased deposition in an inner (large, central airways) versus an outer (peripheral airways and alveoli) zone of the right lung (inner/outer ratio, >1) and higher values of skew (an index of deposition asymmetry) and kurtosis (an index of deposition range) indicated enhanced heterogeneity of deposition. Mean (± SD) inner/outer ratio was significantly higher during rapid inspiration compared to slow inspiration with 2.91 ± 0.51 and 1.84 ± 0.30, respectively (p < 0.01). Mean skew and kurtosis were also significantly higher after rapid inspiration, with 1.12 ± 0.35 and 3.86 ± 1.25, respectively, compared to 0.74 ± 0.36 and 2.64 ± 0.77 after slow inhalation (p < 0.01). Geometric mean PD20 methacholine was significantly reduced when the aerosol was inhaled rapidly, with 5.9 cumulative methacholine units compared to 15.7 units after slow inhalation (p < 0.02). A Spearman's rank-correlation test demonstrated that values of skew and kurtosis were inversely correlated with PD20 methacholine (p < 0.02; rs = -0.55 and -0.60, respectively). Results from these studies indicate that increased heterogeneity in aerosol deposition significantly decreases PD20 methacholine in patients with asthma.",

keywords = "Aerosol distribution, airway reactivity, asthma, methacholine",

author = "Laube, {Beth L.} and Norman, {Philip S.} and Adams, {G. K.}",

note = "Funding Information: From *The Johns Hopkins University School of Hygiene and Public Health, and **The Johns Hopkins University School of Medi-cine, Baltimore, Md. Supported in part by National Institutes of Health Grant No. A120136. Received for publication March 6, 1991. Revised Aug. 21, 1991. Accepted for publication Sept. 4, 1991. Reprint requests: Beth L. Laube, PhD, The Johns Hopkins Uni-versity School of Hygiene and Public Health, 615 North Wolfe St., Room 2001, Baltimore, MD 21205. l/1/33598",

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N1 - Funding Information: From *The Johns Hopkins University School of Hygiene and Public Health, and **The Johns Hopkins University School of Medi-cine, Baltimore, Md. Supported in part by National Institutes of Health Grant No. A120136. Received for publication March 6, 1991. Revised Aug. 21, 1991. Accepted for publication Sept. 4, 1991. Reprint requests: Beth L. Laube, PhD, The Johns Hopkins Uni-versity School of Hygiene and Public Health, 615 North Wolfe St., Room 2001, Baltimore, MD 21205. l/1/33598

PY - 1992/2

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N2 - It has been demonstrated that airway deposition of inhaled aerosols is more heterogeneous in patients with asthma than in normal subjects. Nevertheless, the influence of abnormal airway deposition on responses to bronchoactive aerosols is poorly understood. We altered bronchopulmonary deposition heterogeneity of methacholine aerosol in nine asymptomatic patients with asthma by controlling inspiratory flow at high (∼ 60 L/min) versus low (∼ 12 L/min) rates on 2 study days and determined the effect on the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) (often used as a measure of airway responsiveness). Deposition uniformity was quantified from gamma-camera scans of the lungs in terms of the distribution of a technetium-labeled aerosol that was inhaled rapidly or slowly before the inhalation of methacholine. Increased deposition in an inner (large, central airways) versus an outer (peripheral airways and alveoli) zone of the right lung (inner/outer ratio, >1) and higher values of skew (an index of deposition asymmetry) and kurtosis (an index of deposition range) indicated enhanced heterogeneity of deposition. Mean (± SD) inner/outer ratio was significantly higher during rapid inspiration compared to slow inspiration with 2.91 ± 0.51 and 1.84 ± 0.30, respectively (p < 0.01). Mean skew and kurtosis were also significantly higher after rapid inspiration, with 1.12 ± 0.35 and 3.86 ± 1.25, respectively, compared to 0.74 ± 0.36 and 2.64 ± 0.77 after slow inhalation (p < 0.01). Geometric mean PD20 methacholine was significantly reduced when the aerosol was inhaled rapidly, with 5.9 cumulative methacholine units compared to 15.7 units after slow inhalation (p < 0.02). A Spearman's rank-correlation test demonstrated that values of skew and kurtosis were inversely correlated with PD20 methacholine (p < 0.02; rs = -0.55 and -0.60, respectively). Results from these studies indicate that increased heterogeneity in aerosol deposition significantly decreases PD20 methacholine in patients with asthma.

AB - It has been demonstrated that airway deposition of inhaled aerosols is more heterogeneous in patients with asthma than in normal subjects. Nevertheless, the influence of abnormal airway deposition on responses to bronchoactive aerosols is poorly understood. We altered bronchopulmonary deposition heterogeneity of methacholine aerosol in nine asymptomatic patients with asthma by controlling inspiratory flow at high (∼ 60 L/min) versus low (∼ 12 L/min) rates on 2 study days and determined the effect on the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) (often used as a measure of airway responsiveness). Deposition uniformity was quantified from gamma-camera scans of the lungs in terms of the distribution of a technetium-labeled aerosol that was inhaled rapidly or slowly before the inhalation of methacholine. Increased deposition in an inner (large, central airways) versus an outer (peripheral airways and alveoli) zone of the right lung (inner/outer ratio, >1) and higher values of skew (an index of deposition asymmetry) and kurtosis (an index of deposition range) indicated enhanced heterogeneity of deposition. Mean (± SD) inner/outer ratio was significantly higher during rapid inspiration compared to slow inspiration with 2.91 ± 0.51 and 1.84 ± 0.30, respectively (p < 0.01). Mean skew and kurtosis were also significantly higher after rapid inspiration, with 1.12 ± 0.35 and 3.86 ± 1.25, respectively, compared to 0.74 ± 0.36 and 2.64 ± 0.77 after slow inhalation (p < 0.01). Geometric mean PD20 methacholine was significantly reduced when the aerosol was inhaled rapidly, with 5.9 cumulative methacholine units compared to 15.7 units after slow inhalation (p < 0.02). A Spearman's rank-correlation test demonstrated that values of skew and kurtosis were inversely correlated with PD20 methacholine (p < 0.02; rs = -0.55 and -0.60, respectively). Results from these studies indicate that increased heterogeneity in aerosol deposition significantly decreases PD20 methacholine in patients with asthma.

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The effect of aerosol distribution on airway responsiveness to inhaled methacholine in patients with asthma

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