Effects of Asymptomatic Proximal and Distal Gastroesophageal Reflux on Asthma Severity

DiMango, Emily; Holbrook, Janet T.; Simpson, Erin M.; Reibman, Joan; Richter, Joel E.; Narula, Surinder; Prusakowski, Nancy; Mastronarde, John G.; Wise, Robert A.

doi:10.1164/rccm.200904-0625oc

Cited by 59 publications

(39 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While the possibility that the participants' nocturnal cough may have been related to uncontrolled asthma was not specifically addressed by the authors, the study still raises the important issue that symptoms from proximal GERD such as cough may mimic asthma and may confound measurements of asthma control in the clinical and research setting. A subgroup (n ¼ 242) of participants in the American Lung Association's Study of Acid Reflux and Asthma [Mastronarde et al 2009] underwent dual-probe pH esophageal monitoring [DiMango et al 2009]. Thirty-eight percent of participants demonstrated proximal GERD, but concordance between proximal and distal GERD on pH probe was poor.…”

Section: Pathogenesismentioning

confidence: 99%

The relationship between gastroesophageal reflux and asthma: an update

McCallister

Parsons

Mastronarde

2010

Ther Adv Respir Dis

Self Cite

View full text Add to dashboard Cite

Asthma and gastroesophageal reflux disease (GERD) are both common conditions and, hence, they often coexist. However, asthmatics have been found to have a much greater prevalence of GERD symptoms than the general population. There remains debate regarding the underlying physiologic mechanism(s) of this relationship and whether treatment of GERD actually translates into improved asthma outcomes. Based on smaller trials with somewhat conflicting results regarding improved asthma control with treatment of GERD, current guidelines recommend a trial of GERD treatment for symptomatic asthmatics even without symptoms of GERD. However, recently a large multicenter trial demonstrated that the treatment of asymptomatic GERD with proton-pump inhibitors did not improve asthma control in terms of pulmonary function, rate of asthma exacerbations, asthma-related quality of life, or asthma symptom frequency. These data suggest empiric treatment of asymptomatic GERD in asthmatics is not a useful practice. This review article provides an overview of the epidemiology and pathophysiologic relationships between asthma and GERD as well as a summary of current data regarding links between treatment of GERD with asthma outcomes.

show abstract

Section: Pathogenesismentioning

confidence: 99%

The relationship between gastroesophageal reflux and asthma: an update

McCallister

Parsons

Mastronarde

2010

Ther Adv Respir Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…The high doses of tiotropium, atropine and dexamethasone fully prevented this moderate increase in epithelial thickening. Acetylcholine stimulates the proliferation of rat airway epithelial cells through the activation of M1 muscarinic receptors and nicotinic receptors [4], an observation that may help explain the inhibitory effects of atropine and tiotropium on the epithelium thickening. A nonsignificant increase in the smooth muscle thickness was observed in mice treated with anticholinergics or dexamethasone but the weak increase in untreated mice precludes any firm conclusion on the preventive effect of these drugs.…”

Section: Discussionmentioning

confidence: 98%

“…In children with GORD and asthma-like symptoms, neutrophilia have previously been shown to positively correlate with IL-8 levels in BALF [26], and both neutrophilia and IL-8 levels were demonstrated to correlate with the number of proximal reflux events [16]. In vitro studies have revealed that muscarinic receptor stimulation, particularly the M3 receptor subtype, triggers the release of proinflammatory mediators involved in neutrophil recruitment, such as IL-8 and leukotriene (LT)B 4 , from airway smooth muscle, epithelial cells and alveolar macrophages [27][28][29]. IL-8 and LTB 4 are also involved in monocyte chemoattraction [24,30].…”

Section: Discussionmentioning

confidence: 99%

“…KEYWORDS: Airway inflammation, airway smooth muscle, anticholinergics, gastro-oesophageal reflux, glucocorticosteroids, mouse P atients with severe chronic obstructive pulmonary disease (COPD) or asthma have a high prevalence of gastro-oesophageal reflux disease (GORD), which is considered a potential trigger for airway symptoms and exacerbations [1][2][3][4]. Medical and surgical treatments for reflux improve wheezing and coughing in ,66% of asthmatic patients, reduce the use of on-demand inhalers in more than half, and improve lung function in nearly 25% of them [1].…”

mentioning

confidence: 99%

“…Medical and surgical treatments for reflux improve wheezing and coughing in ,66% of asthmatic patients, reduce the use of on-demand inhalers in more than half, and improve lung function in nearly 25% of them [1]. Recent studies, however, have challenged the role of GORD as a cause of poorly controlled asthma, at least in patients with asymptomatic GORD [3,4].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Tiotropium reduction of lung inflammation in a model of chronic gastro-oesophageal reflux

Cui

Devillier²,

Kuang³

et al. 2009

Eur Respir J

View full text Add to dashboard Cite

Gastro-oesophageal reflux is frequent in chronic airway diseases and is considered a trigger for symptoms. In animal models, bilateral vagotomy or muscarinic antagonists prevent the increase in airway resistance and the microvascular leakage induced by acute oesophageal acid instillation.The present study investigates lung inflammation and remodelling in an animal model of chronic gastro-oesophageal reflux disease (GORD), and the effectiveness of pretreatments with tiotropium, atropine and dexamethasone.Mice were exposed to twice-daily intra-oesophageal HCl instillations for 21 days. Exposure to HCl causes: marked infiltration by inflammatory cells of the airways and of peribronchial areas; an increase in epithelial thickness; histological features of interstitial pneumonitis; an increase in cell numbers and in the levels of interleukin-8; and soluble intercellular adhesion molecule in bronchoalveolar lavage fluids, as well as of in vitro tracheal contractility. The administration of nebulised tiotropium or intraperitoneal atropine prior to each instillation of HCl, considerably inhibited all these changes.These results indicate a major role of acetylcholine in airway inflammation and remodelling in a GORD model, and demonstrate that tiotropium and atropine can prevent lung inflammation with an effectiveness similar to intraperitoneal dexamethasone, providing additional evidence that anticholinergics might contribute to the control of inflammatory processes in airway diseases.

show abstract

Lansoprazole for Children With Poorly Controlled Asthma: A Randomized Controlled Trial

Holbrook¹,

Wise²,

Gold³

et al. 2012

JAMA: The Journal of the American Medical Association

204

102

View full text Add to dashboard Cite

Context Asymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. It is not known whether treatment of GER with a proton-pump inhibitor (PPI) improves asthma control. Objective To determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER. Design, Setting, and Patients A multicenter, randomized, masked, placebo controlled, parallel clinical trial comparing lansoprazole to placebo in children with poor asthma control on inhaled corticosteroid treatment conducted at 18 academic clinical centers. Participants were followed for 24 weeks. A subgroup had an esophageal pH study before randomization. Intervention Children received either lansoprazole (15 mg daily < 30 kg; 30 mg ≥ 30 kg) or placebo, 1:1 allocation ratio. Main outcome The primary outcome was the change in Asthma Control score (ACQ, range from 0 to 6). Secondary outcomes included lung function measures, asthma-related quality of life and acute episodes of poor asthma control. Results 306 children were enrolled from April 2011 to August 2010, the median age was 11. The mean change (95% confidence interval (CI)) in the ACQ score was −0.1 (−0.2, 0.1) and −0.2 (−0.4, −0.1) units for the lansoprazole and placebo groups, respectively (P=0.12). There were no detectable treatment differences in secondary outcomes (mean (95% CI) for FEV1(0.00 (−0.08, 0.08)), asthma quality of life (−0.1 (−0.4, 0.1) or episodes of poor asthma control, hazard ratio of 1.18 (95% CI 0.91, 1.53). Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no treatment effect for lansoprazole versus placebo was observed for any asthma outcome. Children treated with lansoprazole reported more upper respiratory infections (63% vs 49%, P=0.02), sore throats (52% vs 39%, P=0.02), and bronchitis (7% vs 2%, P=0.05). Conclusion Among children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, as compared to placebo, did not improve symptoms nor lung function but was associated with increased adverse events.

show abstract

Effects of Asymptomatic Proximal and Distal Gastroesophageal Reflux on Asthma Severity

Cited by 59 publications

References 33 publications

The relationship between gastroesophageal reflux and asthma: an update

The relationship between gastroesophageal reflux and asthma: an update

Tiotropium reduction of lung inflammation in a model of chronic gastro-oesophageal reflux

Lansoprazole for Children With Poorly Controlled Asthma: A Randomized Controlled Trial

Contact Info

Product

Resources

About