The protective effect of a beta 2 agonist against excessive airway narrowing in response to bronchoconstrictor stimuli in asthma and chronic obstructive lung disease.

Bel, EH; Zwinderman, Aeilko H.; Timmers, Mieke; Dijkman, J. H.; Sterk, Peter J.

doi:10.1136/thx.46.1.9

Cited by 80 publications

(38 citation statements)

References 31 publications

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“…These results differ from the previous report by BEL et al [3] when the protective effect of salbutamol was followed by a sudden fall in FEV1. It is speculated that this may have been a consequence of the short duration of action of salbutamol and not to a true increased reactivity of the airways.…”

Section: Discussioncontrasting

confidence: 57%

“…It may be possible this is partly a result of a change in perception of dyspnoea due to the b 2 -agonist. Furthermore, the suggestion has been made that after prior administration of a bronchodilator, there may be an exaggerated fall in forced expiratory volume in one second (FEV1) when the bronchial provocation test is continued [3]. Therefore, this study investigated whether poor perception of dyspnoea may be caused by long-acting b 2 -agonist treatment, by assessing dyspnoea scores during a provocation test performed after maximal bronchodilation from inhaled long-acting b 2 -agonists.…”

mentioning

confidence: 99%

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Unaltered perception of dyspnoea during treatment with long-acting β₂-agonists

Woude

Aalbers²

2001

Eur Respir J

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Unaltered perception of dyspnoea during treatment with long-acting b 2 -agonists. H.J.van der Woude, R. Aalbers. #ERS Journals Ltd 2001. ABSTRACT: There is the possibility that during treatment with inhaled long-acting b 2 -agonists that a loss of perception of dyspnoea might occur and that the forced expiratory volume in one second (FEV1) might fall precipitously during bronchial provocation. This study investigated these possibilities during methacholine provocation, continued until there was ¢30% fall in FEV1, mimicking a moderate asthma attack.Nineteen asthmatic patients were asked to score their dyspnoea as a Borg score during provocation with methacholine. One hour prior to this provocation, the patients used the last morning dose of 14 days treatment with either formoterol (twice daily 24 mg by Turbuhaler1), salmeterol (twice daily 100 mg by Diskhaler TM ) and placebo in a double-blind, randomized, double-dummy, cross-over design.The perception of dyspnoea, expressed as the Borg score divided by the change in FEV1 at ¢30% fall in FEV1, was similar on the three test days at 0.067, 0.076 and 0.074% -1 after formoterol, salmeterol and placebo treatment, respectively (p=0.16). The slope of the methacholine dose response curve did not differ (p=0.52).In conclusion, no suggestion was found for an abnormal perception of dyspnoea or an exaggerated fall in forced expiratory volume in one second during provocation with methacholine under long-acting b 2 -agonist treatment. In the treatment of asthma, the inhaled long-acting b 2 -agonists formoterol and salmeterol have obtained an important role due to their excellent bronchodilating and bronchoprotective effects [1]. This excellent bronchodilating effect could have a negative influence; patients may be unable to perceive a deterioration of the effects of airway inflammation [2]. It may be possible this is partly a result of a change in perception of dyspnoea due to the b 2 -agonist. Furthermore, the suggestion has been made that after prior administration of a bronchodilator, there may be an exaggerated fall in forced expiratory volume in one second (FEV1) when the bronchial provocation test is continued [3]. Therefore, this study investigated whether poor perception of dyspnoea may be caused by long-acting b 2 -agonist treatment, by assessing dyspnoea scores during a provocation test performed after maximal bronchodilation from inhaled long-acting b 2 -agonists. In addition the slope of the methacholine dose response curve was measured to see if it was increased. Materials and methods PatientsNineteen nonsmoking patients aged 18-50 yrs with a diagnosis of asthma according to the American Thoracic Society Guidelines [4] were invited to participate in the study (table 1). Eligible patients had an FEV1w1.5 L andw60% of predicted [5], a 20% fall in FEV1 after provocation with methacholine ¡4 mg?mL -1 and a fall of ¢30% in FEV1 on continuing the test. Exclusion criteria were: concomitant diseases that might interfere with the study; use of long-acting b 2 -agonists, or...

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Section: Discussioncontrasting

confidence: 57%

mentioning

confidence: 99%

Unaltered perception of dyspnoea during treatment with long-acting β₂-agonists

Woude

Aalbers²

2001

Eur Respir J

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“…AHR in patients with asthma is characterised by the loss of the maximal or plateau response that is observed in normal subjects [182,183]. One study has shown that plateau responses occur in patients with COPD [184] and another has not [185]. In addition, while patients with asthma respond to both direct smooth muscle/ nerve stimulation and to indirect stimuli, patients with COPD generally respond only to direct smooth muscle stimulation with histamine or methacholine [9,184].…”

Section: Ahr: Asthma Versus Copdmentioning

confidence: 99%

Clinical relevance of airway remodelling in airway diseases

James¹,

Wenzel²

2007

European Respiratory Journal

301

214

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Asthma and chronic obstructive pulmonary disease (COPD) are characterised by airflow obstruction, airway remodelling (measurable structural change) and inflammation. The present review will examine the relationship between airway remodelling in these two conditions with respect to symptoms, abnormal lung function, airway hyperresponsiveness and decline in lung function. The potential for remodelling to be a protective response will also be discussed.Asthma is associated with variable symptoms and changes in lung function and also fixed abnormalities of lung function and an increased rate of decline in lung function with age. There is a relative preservation of the relaxed airway lumen dimensions, prominent thickening of the smooth muscle layer and reduced airway distensibility. The severity of asthma is related to the degree of airway remodelling, which is most marked in cases of fatal asthma.In COPD, symptoms are persistent and predictable but also progressive and are related to fixed abnormalities of lung function. Remodelling is associated with narrowing of the airway lumen and an increased thickness of the airway wall, although not usually to the extent seen in asthma. COPD is most often due to smoking where there is also remodelling of the parenchyma that may contribute to symptoms.

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“…A maximal response that is increased to a severe or even unmeasurable degree of airway narrowing is potentially dangerous. The major reason why asthmatics get into trouble is not primarily the increased sensitivity of their airways to bronchoconstrictor stimuli, but the excessive degree of airway narrowing [23,24]. Successful treatment of their asthma, therefore, should be directed towards preventing or at least diminishing this excessive response.…”

Section: Discussionmentioning

confidence: 99%

Effects of fluticasone propionate on methacholine dose-response curves in nonsmoking atopic asthmatics

Overbeek¹,

Vons²,

Mulder³

et al. 1996

Eur Respir J

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E Ef ff fe ec ct ts s o of f f fl lu ut ti ic ca as so on ne e p pr ro op pi io on na at te e o on n m me et th ha ac ch ho ol li in ne e d do os se e--r re es sp po on ns se e c cu ur rv ve es s i in n n no on ns sm mo ok ki in ng g a at to op pi ic c a as st th hm ma at ti ic cs s ABSTRACT: Methacholine is frequently used to determine bronchial hyperresponsiveness (BHR) and to generate dose-response curves. These curves are characterized by a threshold (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) =sensitivity), slope (reactivity) and maximal response (plateau). We investigated the efficacy of 12 weeks of treatment with 1,000 µg fluticasone propionate in a double-blind, placebo-controlled study in 33 atopic asthmatics. The outcome measures used were the influence on BHR and the different indices of the methacholine dose-response (MDR) curve. After 2 weeks run-in, baseline lung function data were obtained and a MDR curve was measured with doubling concentrations of the methacholine from 0.03 to 256 mg·mL -1 . MDR curves were repeated after 6 and 12 weeks. A recently developed, sigmoid cumulative Gaussian distribution function was fitted to the data. Although sensitivity was obtained by linear interpolation of two successive log 2 concentrations, reactivity, plateau and the effective concentration at 50% of the plateau value (EC50) were obtained as best fit parameters.In the fluticasone group, significant changes occurred after 6 weeks with respect to means of PC20 (an increase of 3.4 doubling doses), plateau value fall in forced expiratory volume in one second (FEV1) (from 58% at randomization to 41% at 6 weeks) and baseline FEV1 (from 3.46 to 3.75 L) in contrast to the placebo group. Stabilization occurred after 12 weeks. Changes for reactivity were less marked, whereas changes in log 2 EC50 were not significantly different between the groups.We conclude that fluticasone is very effective in decreasing the maximal airway narrowing response and in increasing PC20. However, it is likely that part of this increase is related to the decrease of the plateau of maximal response.

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The protective effect of a beta 2 agonist against excessive airway narrowing in response to bronchoconstrictor stimuli in asthma and chronic obstructive lung disease.

Cited by 80 publications

References 31 publications

Unaltered perception of dyspnoea during treatment with long-acting β₂-agonists

Unaltered perception of dyspnoea during treatment with long-acting β₂-agonists

Clinical relevance of airway remodelling in airway diseases

Effects of fluticasone propionate on methacholine dose-response curves in nonsmoking atopic asthmatics

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The protective effect of a beta 2 agonist against excessive airway narrowing in response to bronchoconstrictor stimuli in asthma and chronic obstructive lung disease.

Cited by 80 publications

References 31 publications

Unaltered perception of dyspnoea during treatment with long-acting β2-agonists

Unaltered perception of dyspnoea during treatment with long-acting β2-agonists

Clinical relevance of airway remodelling in airway diseases

Effects of fluticasone propionate on methacholine dose-response curves in nonsmoking atopic asthmatics

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Product

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Unaltered perception of dyspnoea during treatment with long-acting β₂-agonists

Unaltered perception of dyspnoea during treatment with long-acting β₂-agonists