Alimentary TractLong-term clinical course of extra-oesophageal manifestations in patients with gastro-oesophageal reflux disease: A prospective follow-up analysis based on the ProGERD study☆
Introduction
Gastro-oesophageal reflux disease (GERD) represents a spectrum of symptoms and tissue damage of the oesophagus [1]. The relationship between GERD and extra-oesophageal complications has been recognised since the 1960s when Kennedy [2] observed pulmonary complications in patients with evidence of chronic reflux. Extra-oesophageal manifestations of GERD include pulmonary disorders (chronic cough, asthma) [3], [4], [5], upper respiratory manifestations (pharyngitis, laryngitis) [6], [7] and chest pain [8], [9], [10]. Up to 50% of patients with an endoscopically proven oesophagitis suffer from symptoms other than heartburn or acid regurgitation. The published estimates of extra-oesophageal disorders in patients with GERD vary widely, which may be a result of referral bias [11], [12], [13], [14], [15].
ProGERD is a prospective study in which patients with GERD are being followed up prospectively under routine clinical care by the discretion of their general practitioners [16]. The primary objective of this ongoing trial is to determine the endoscopic and symptomatic progressions of GERD. A secondary objective is to evaluate the prevalence of concomitant extra-oesophageal disorders and to compare their occurrence between patients with either symptomatic erosive reflux disease (ERD) or non-erosive reflux disease (NERD). The baseline data from this study have been published previously [12].
In contrast with data about GERD patients with classical heartburn, data on the long-term course of patients with extra-oesophageal reflux disease (EERD) are scanty. The aims of the analyses, therefore, were to follow up patients with chronic cough or laryngeal symptoms at baseline and to measure the incidence of these manifestations over the 2-year period.
Section snippets
Materials and methods
ProGERD is a prospective, multicentre, open cohort study currently being performed in Germany, Austria and Switzerland in which GERD patients are being followed for 5 years after healing treatment with esomeprazole [12]. The trial consists of a healing phase and a subsequent epidemiological follow-up phase. Recruitment took place from May 2000 to February 2001.
The study population presented with reflux symptoms and had been referred or came directly to hospital endoscopy clinics or specialised
Statistical methods
Bivariate comparisons were done with the χ2-test. A multivariate analysis was done using stepwise logistic regression analyses (according to the method of maximum likelihood) with disappearance of symptoms versus persistent symptoms for chronic cough and laryngeal disorders as dependent variables. The following independent variables were included in the regression model: gender, age, BMI, alcohol consumption (yes/no), cigarette smoking (yes/no/former smoker), GERD classification
Results
At baseline, 6215 patients were included (ERD: n = 2792, NERD: n = 2901 and Barrett's oesophagus: n = 522).
Of those, 810 patients (13%) had chronic cough and 645 patients (10%) had laryngeal symptoms [12]. Of the entire population, 4404 patients (71%) were available for analysis at 2 years, including 570 and 454 patients who had chronic cough and laryngeal disorders at baseline, respectively. In 63% (358/570) and 74% (336/454) of the patients, chronic cough and laryngeal disorders had resolved. Of
Discussion
GERD may lead to extra-oesophageal symptoms and complications. Recent data indicate that many patients with GERD also present with EERD [3], [4], [5], [6], [7], [8], [9], [10], [11]. However, the extra-oesophageal symptoms of GERD are difficult to study because of the different manifestations of these symptoms, which are largely non-specific in character [15], [19], [20], [21], [22]. Presently, apart from the favourable response of EERD to PPI therapy in some studies, there is no generally
Acknowledgement
The study was sponsored by a grant from AstraZeneca.
References (30)
Silent gastroesophageal reflux: an important but little known cause of pulmonary complications
Dis Chest
(1962)- et al.
The role of gastroesophageal reflux in chronic cough and asthma
Chest
(1997) - et al.
Reflux laryngitis: pathophysiology, diagnosis, and management
Am J Gastroenterol
(1999) - et al.
Frequency and site of gastroesophageal reflux in patients with chest symptoms
Chest
(1994) - et al.
A critical approach to non-cardiac chest pain: pathophysiology, diagnosis and treatment
Am J Gastroenterol
(2001) - et al.
Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in United States Military Veterans
Gastroenterology
(1997) - et al.
Risk factors of gastroesophageal reflux disease – methodology and first epidemiological results of the ProGERD study
J Clin Epidemiol
(2004) - et al.
Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease
Am J Gastroenterol
(2001) - et al.
Lansoprazole treatment of patients with chronic idiopathic laryngitis: a placebo-controlled trial
Am J Gastroenterol
(2001) Gastroesophageal reflux disease
Curr Treat Options Gastroenterol
(1998)
Chronic persistent cough and gastro-oesophageal reflux
Thorax
Chronic cough and hoarseness in patients with severe gastroesophageal reflux disease
Dig Dis Sci
Review-article: gastroesophageal reflux and laryngeal symptoms
Aliment Pharmacol Ther
Extraesophageal manifestations of gastroesophageal reflux: American Society for Gastrointestinal Endoscopy
Clin Update
Extra-esophageal disorders in gastroesophageal reflux disease
Dig Dis
Cited by (31)
pH/multichannel impedance monitoring in patients with laryngo-pharyngeal reflux symptoms – Prediction of therapy response in long-term follow-up
2016, Arab Journal of GastroenterologyCitation Excerpt :Whilst the American Gastroenterological Association does not recommend proton pump inhibitor (PPI) therapy in the absence of concomitant typical gastro-oesophageal reflux disease (GERD) symptoms, the American Academy of Otolaryngology-Head and Neck Surgery recommends in a position statement high dose acid suppression twice daily for prolonged periods of time [8]. Irrespective of the therapy concept, some symptom-based studies indicate a symptom relief during two year follow-up [9]; in other studies a substantial group of patients did not adequately respond to acid suppression [10]. Despite marginal therapeutic effects and potential side effects, long term PPI therapy is generally applied and generates a substantial economic burden [11,12].
Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease
2013, ChestCitation Excerpt :The systematic searches are summarized in Figure 1. Seven studies were excluded for the following reasons: Four were epidemiologic studies,17–20 one was not published in English,21 and two did not select patients based on the presence of chronic cough or LPR reflux.12,22 A citation list search of the remaining 24 studies identified four additional studies for potential inclusion (28 in total).
Relationship Between Gastro-Oesophageal Reflux and Airway Diseases: The Airway Reflux Paradigm
2011, Archivos de BronconeumologiaCheilitis: A new manifestation of gastro-oesophageal reflux?
2009, Annales de Dermatologie et de VenereologieGastroesophageal Reflux in Bronchiolitis Obliterans Syndrome: A New Perspective
2009, Journal of Heart and Lung TransplantationCitation Excerpt :The proposed mechanism for a link between GERD and BOS is one of silent aspiration of gastric contents causing direct damage to the airways and/or an immune response, resulting in OB. GERD has also been implicated in other respiratory diseases such as asthma, bronchiectasis, and pulmonary fibrosis as well as diseases of the dentition and middle ear.12,18–20 In LTx, GERD has also been associated with diffuse alveolar damage.21
Chronic cough and GORD in adult
2008, Revue Francaise d'Allergologie et d'Immunologie Clinique
- ☆
This work has been presented in part at the World Congress of Gastroenterology (WCOG) in Montreal, Canada in September 2005 and at the United European Gastroenterology Week (UEGW) in Copenhagen, Denmark in October 2005.