The Effects of an Inhaled β2-Adrenergic Agonist on Lower Esophageal Function: A Dose-Response Study

doi:10.1378/chest.120.4.1184

Chest

Volume 120, Issue 4, October 2001, Pages 1184-1189

https://doi.org/10.1378/chest.120.4.1184 Get rights and content

Study objectives

Albuterol, aβ ₂-adrenergic agonist that is commonly used to treat asthma, reduces bronchial smooth muscle tone. The pharmacodynamics of inhaled albuterol on esophageal function were studied in healthy volunteers.

Design

A prospective, randomized, placebo-controlled, double-blind crossover design.

Setting

An academic medical center.

Patients

Nine healthy volunteers (five men, four women; age, 22 to 30 years).

Interventions

Albuterol (2.5 to 10 mg) or placebo was given via nebulizer. Volunteers were studied at two sessions, 1 week apart, using a 6-cm manometry assembly and a low-compliance pneumohydraulic pump. The percentage of lower esophageal sphincter (LES) relaxation, the frequency of transient LES relaxations (TLESRs), and the amplitude, duration, and propagation velocity of esophageal contractions were measured at 5 and 10 cm above the LES. Dependent measures were evaluated using two-way, repeated-measures analysis of variance.

Measurements and results

Albuterol therapy reduced LES basal tone in a dose-dependent manner (baseline, 17.0 ± 2.6 mm Hg; at 10 mg, 8.9 ± 2.1 mm Hg; p = 0.01). The frequency of TLESRs was not different from placebo (not significant). Albuterol reduced the amplitude of esophageal contractions at 5 cm above the LES (baseline, 72.5 ± 18.6 mm Hg; at 10 mg, 48.8 ± 10.0 mm Hg; p < 0.05). A significant reduction in esophageal body contractile amplitudes was noted at 10 cm (F[1,6] = 7.05; p < 0.05).

Conclusions

Inhaled albuterol reduced LES basal tone and contractile amplitudes in the smooth muscle esophageal body in a dose-dependent manner. Inhaled β₂-agonists may increase the likelihood of acid reflux in a subset of patients who receive cumulative dosing.

Section snippets

Materials and Methods

A prospective, randomized, double-blind, placebo-controlled crossover design was used to evaluate the effects of increasing doses of inhaled albuterol (Glaxo-Wellcome; Research Triangle Park, NC), 2.5 to 10 mg, or placebo on LES tone, the percentage of LES relaxation, and the frequency of transient LES relaxations (TLESRs). The amplitude, duration, and propagation velocity of esophageal contractions at 5 and 10 cm above the LES also were measured. Esophageal manometry was completed in nine

Results

As illustrated in Figure 1, albuterol inhalation produced a dose-dependent reduction in LES basal tone from 17.0 ± 2.6 mm Hg at baseline to 8.9 ± 2.1 mm Hg at the maximum cumulative dose of 10 mg (F[4,32] = 3.91; p = 0.01) compared to placebo. Reductions in LESP were noted beginning at the cumulative dose of 7.5 mg total (p = 0.02) and were maintained through the 10-mg cumulative dose (p = 0.02). The frequency of TLESRs decreased from 2.2 ± 1.1 to 1.6 ± 1.8/h but did not reach statistical

Discussion

Asthma is a common problem in the United States. It affects approximately 4 to 5% of the US population.¹ Standard outpatient therapy involves the use of inhaledβ ₂-agonists, inhaled steroids, cromolyn sodium, theophylline, and oral steroids. GER is known to play a significant role in the development and persistence of asthma and is a critical factor in patients with difficult-to-control asthma.⁸

The primary pathophysiologic mechanisms proposed to account for GER are reduced tonic pressures in

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Inhaled short-acting β₂-adrenergic agonists can rarely elicit paradoxical bronchospasm (PB), which may be fatal. The purpose to this study was to determine whether post-bronchodilator PB is reported in spirometry test results of veterans with Chronic Obstructive Pulmonary Disease (COPD) or asthma followed at the Jesse Brown Veterans Affairs (VA) Medical Center in Chicago between 2017-2020. Eighteen of 1,150 test reports reviewed were identified with post-bronchodilator PB (1.5%).12 out of the 18 identified patients with PB had COPD, 4 hadasthma and 2 had asthma/COPD. No report alluded to post-bronchodilator PB. Among the identified PB patients, there were 17 males and one female, 14 African Americans, 3 Caucasian and one Latinx, aged 67±8 years (mean±SD) with BMI 28±5 kg/m². Thirteen were ex-tobacco smokers, 4 current smokers and one never smoked. Most recent chest CT revealed emphysema in 8 veterans with COPD and bronchial wall thickening in 3. Chest radiographs of 4 veterans with asthma were unremarkable. All veterans were treated with inhaled β₂-adrenergic agonists. Five were treated with cardio selective beta₁ blockers and 10 for gastroesophageal reflux disease. Eleven veterans were diagnosed with obstructive sleep apnea. In 12 veterans, inhaled albuterol (4 actuations)-induced decrease in FEV₁ was 22±8% and 367±167 mL from baseline. In 6 veterans, only FVC decreased significantly from baseline (14±3% and 448±179 mL). No veteran reported respiratory symptoms during or after spirometry testing. Two veterans died during follow-up. Based on spirometry test reports, inhaled β₂-adrenergic agonists were discontinued in 2 veterans with COPD and asthma. We propose that post-bronchodilator PB observed during spirometry testing of veterans should be recognized and reported, and its possible clinical implications addressed accordingly.
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Patients should be carefully followed up in order to recognize timely any relapse of digestive or reflux related respiratory symptoms and, in this event, the deescalating strategy should be rediscussed. LABA might worsen the reflux by decreasing the tone of the lower esophageal sphincter [79]. Sleep troubles are highly prevalent among COPD patients and are mainly related to respiratory symptoms.
Chronic obstructive pulmonary disease (COPD) is commonly associated with other chronic diseases, which poses several diagnostic and therapeutic problems. Indeed, important comorbidities frequently remain unrecognized and, then, untreated, whereas respiratory drugs may have non respiratory side effects, and selected non respiratory drugs may variably affect the respiratory function.
to describe: how COPD affects the presentation and contributes to the diagnostic challenges of its most common comorbidities; how coexisting COPD impacts the therapeutic approach to selected comorbidities and viceversa.
we distinguish comorbidities of COPD depending upon whether they are complications of COPD or share risk factors, mainly smoke, with it or, finally, aggravate COPD. We describe atypical presentations of and diagnostic clues to comorbidities and suggest screening procedures. Finally, the main therapeutic problems, as resulting from the risk of untoward effects of therapies of COPD and its comorbidity, with special attention to drug-drug interactions and possible overdosages, are described.
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a truly comprehensive view of the complex COPD patient, hopefully capitalizing on multidimensional geriatric assessment, is needed to dissect the many components of health status impairment and to provide the optimal care. Selected screening procedures are highly desirable to identify frequently missed comorbidities. Pharmacosurveillance is an essential part of the approach to COPD and its comorbidities.

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: A portion of this study was originally presented at the annual American Gastroenterology Association meeting in Orlando, FL, May 1999.

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Chest

Clinical InvestigationsEsophagusThe Effects of an Inhaled β2-Adrenergic Agonist on Lower Esophageal Function: A Dose-Response Study

Study objectives

Design

Setting

Patients

Interventions

Measurements and results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

Gastroenterology

Gastroenterology

Chest

Chest

J Allergy Clin Immunol

Gastroenterology

Chest

Gastroenterology

Chest

Chest

Chest

Am J Med

Chest

Am J Gastroenterol

Asthma

N Engl J Med

Clinical Investigations
Esophagus
The Effects of an Inhaled β₂-Adrenergic Agonist on Lower Esophageal Function: A Dose-Response Study