Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans

Ding, Defang; Martin, James G.; Macklem, Peter T.

doi:10.1152/jappl.1987.62.3.1324

Cited by 301 publications

(235 citation statements)

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“…Our finding that low operating lung volumes, due to obesity, had no effect on the maximal response to methacholine differs from the findings of previous studies in lean, non-asthmatic subjects in whom an acute reduction in lung volumes was associated with increased maximal response. 13,14 The reason for the difference is unclear, but we speculate that differences in lung elastic recoil between obese and non-obese subjects may be a contributing factor. The mechanism of the increased maximal response with reduced lung volume has been attributed to a reduction in lung elastic recoil, which unloads the airway smooth muscle allowing it to shorten excessively when activated.…”

Section: Discussionmentioning

confidence: 92%

“…[3][4][5][6][7] However, obesity is more likely to affect the maximal response, because obesity reduces operating lung volume 12 and breathing at low operating lung volumes is known to induce increased maximal airway narrowing in non-asthmatic subjects. 13,14 The effect of low lung volume on maximal airway narrowing in obese, non-asthmatic subjects has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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Effect of obesity on breathlessness and airway responsiveness to methacholine in non-asthmatic subjects

et al. 2007

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Background: Obesity is associated with increased prevalence and incidence of asthma, but the mechanism is unknown. Obesity reduces lung volumes, which can increase airway responsiveness, and increases resistive and elastic work of breathing, which can increase dyspnea. Objective: To determine if the intensity of dyspnea due to airway narrowing or if airway responsiveness is increased in obese, non-asthmatic subjects. Subjects: Twenty-three obese (BMI (body mass index) X30 kg m À2 ) and 26 non-obese (BMI o30 kg m À2 ) non-asthmatic subjects, aged between 18 and 70 years. Methods: High-dose methacholine challenge was used to determine the sensitivity and the maximal response to methacholine. Respiratory system resistance (Rrs) and reactance were measured, using the forced oscillation technique, as indicators of resistive and elastic loads during challenge. Perception of dyspnea was measured by the Borg score during challenge. Static lung volumes were measured by body plethysmography. Results: Static lung volumes were reduced in the obese subjects. There were no significant differences in the sensitivity or maximal response to methacholine between obese and non-obese subjects. The magnitude of change in Rrs was similar in both groups, but obese subjects had more negative reactance after challenge (P ¼ 0.002) indicating a greater elastic load. The intensity of dyspnea was greater in obese subjects (P ¼ 0.03). Conclusions: Obesity reduces lung volumes, but does not alter the sensitivity or maximal response to methacholine. However, obese subjects have enhanced perception of dyspnea, associated with greater apparent stiffness of the respiratory system, and may therefore be at greater risk of symptoms.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Effect of obesity on breathlessness and airway responsiveness to methacholine in non-asthmatic subjects

et al. 2007

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“…43 For example, increased abdominal and chest wall mass in obese individuals causes reduced functional residual capacity, 48 a major determinant of airway diameter. 52 Consequently, it is likely that obesity-related changes in forced reserve capacity unload the airway smooth muscle cells, thereby allowing them to shorten excessively when activated. Further evidence of a direct association between obesity and airway hyperreactivity has been shown in an experimental study in which ozone-induced airway hyperreactivity and bronchial inflammation in obese mice were more pronounced than that observed in lean wild-type mice.…”

Section: Potential Mechanisms Of Obesity-asthma Relationshipmentioning

confidence: 99%

Obesity induced bronchopulmonary hyperresponsiveness in Tunisian women

et al. 2010

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Objective: The specific objective of this investigation was to determine whether bronchopulmonary responsiveness (BPR) to methacholine (MCH) was associated with the body mass index (BMI) of Tunisian women. Subjects: In all, 160 healthy nonsmoker women (52 lean, 45 overweight and 63 obese) were recruited and examined in the Clinical Laboratory of Physiology located in the Medical School of Sousse. The average ages ( ± s.e.) of the three categories of lean, overweight and obese subjects were 27.7±1.1, 33.2±1.7 and 37.5±1.3 years, respectively. Their corresponding mean BMIs ( ± s.e.) were 21.9 ± 0.3, 27.7 ± 0.2 and 36.5 ± 0.8 kg m À2 , respectively. Measurements: Before their inclusion into the study, subjects were screened for their lung status by measuring their pulmonary function testing parameters using a whole body plethysmograph. BPR was assessed, using a cumulative concentration response curve technique, by measuring with a spirometer the decrease in forced expiratory volume in 1 s (FEV 1 ) in response to a cumulative dose of MCH. Results: After adjusting for age, significant differences in both FEV 1 and forced vital capacity (VC) were found between the obese and lean groups (Po0.01), as well as between the obese and overweight groups (Po0.01). In addition, forced expiratory flow between 25 and 75% of VC was significantly different between the obese and lean groups (Po0.001), as well as between the lean and overweight groups (P ¼ 0.015). The mean maximum fall of FEV 1 in response to MCH challenge was significantly higher for the obese group (12.0%) than for the overweight (9.8%) or the lean (6.6%) group (Po0.01). Furthermore, the efficacy of the MCH agonist promoting the maximal response (E max ) and its potency or effective dose producing 50% of the maximal response (ED 50 ) were both associated with BMI (the higher the BMI, the higher the E max and the lower the ED 50 ). Conclusion: Our data clearly show that obesity affects pulmonary function performance in Tunisian women by potentially promoting their bronchial hyperreactivity as suggested by the significant correlation between their BMI and the efficacy of the MCH, as well as its potency.

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“…Rrs also changes with flow associated with turbulence and other effects and in anaesthetised children can change two-fold with a three-fold change in flow under isovolumetric conditions [38]. Agonists can modulate the volume dependence of Rrs [39,40], which may have contributed to the changes in Rrs and Rrs SD in asthma and with BD. However, the effects of a BD on median Rrs were similar in both groups and no changes were observed in tidal volume with BD or between asthma and controls.…”

Section: Variation In Rrsmentioning

confidence: 99%

“…However, the effects of a BD on median Rrs were similar in both groups and no changes were observed in tidal volume with BD or between asthma and controls. Differences in Rrs could also be attributed to changes in functional residual capacity, which was not measured [9,39].…”

Section: Variation In Rrsmentioning

confidence: 99%

Airway resistance variability and response to bronchodilator in children with asthma

Lall¹,

Cheng²,

Hernández³

et al. 2007

European Respiratory Journal

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Variability of airway function is a feature of asthma, spanning timescales from months to seconds. Short-term variation in airway resistance (Rrs) is elevated in asthma and is thought to be due to increased variation in the contractile activation of airway smooth muscle. If true, then variation in Rrs should decrease in response to bronchodilators, but this has not been investigated.Using the forced oscillation technique, Rrs and the variation in Rrs from 4-34 Hz were measured in 39 children with well-controlled mild-to-moderate asthma and 31 healthy controls (7-13 yrs) before and after an inhaled bronchodilator (200 mg salbutamol) or placebo.In agreement with other findings, baseline Rrs at all frequencies and the SD of Rrs (Rrs SD) below 14 Hz were found to be elevated in asthma while neither forced expiratory volume in one second nor the mean forced expiratory flow between 25 and 75% of forced vital capacity were different compared with controls. The present authors found that Rrs SD changed the most of any measurement in asthma, and this was the only measurement that changed significantly more in children with asthma following bronchodilator administration.The present results show that like airway narrowing, short-term airway variability of resistance may be a characteristic feature of asthma that may be useful for monitoring response to therapy.

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Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans

Cited by 301 publications

References 0 publications

Effect of obesity on breathlessness and airway responsiveness to methacholine in non-asthmatic subjects

Effect of obesity on breathlessness and airway responsiveness to methacholine in non-asthmatic subjects

Obesity induced bronchopulmonary hyperresponsiveness in Tunisian women

Airway resistance variability and response to bronchodilator in children with asthma

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