Optimizing Care for Atypical Manifestations of Upper GI Disease

At an industry-sponsored symposium held in conjunction with the American College of Gastroenterology’s 2002 Annual Scientific Meeting, a panel of experts reviewed the evidence linking gastrointestinal (GI) disease with sleep disturbance, noncardiac chest pain, and cough. The panel discussed approaches for rapid and accurate assessment and management of such patients who are referred by primary care physicians and other specialists.

This program was sponsored by The University of Arizona College of Medicine at the Arizona Health Sciences Center. This program was supported by an unrestricted educational grant from
Wyeth Pharmaceuticals.

This material represents a compilation from a series of industry-sponsored educational symposia presented October 18–23, 2002 in conjunction with the Annual Meeting of the American College of Gastroenterology. This compilation is provided for information and critical scrutiny by physician readers, and is not intended to replace clinical judgment by the physician as to a specific patient.

The proceedings arise from industry-sponsored sessions, not from the official ACG program, and this synopsis/compilation of these sessions does not represent the official viewpoint of the American College of Gastroenterology.

Case #1: The Patient With Disturbed Sleep

• 58-yr-old male with obstructive sleep apnea (loud persistent snoring, daytime sleepiness)
• heartburn nearly every day
• awakens at least 5x/wk with acid taste in mouth
• hypertension, type 2 diabetes
• heartburn score 4 (scale 1-5)
• sleepiness level 5 (very sleepy most of day)
• Epworth sleepiness score 11
• short sleep onset latency (11 min)
• moderate obstructive apnea
• no significant O2 desaturation
• arousal index 25x/hr
• total% acid contact time (ACT) = 7·3
• upright %ACT = 10
• supine %ACT = 4
• after 1 wk CPAP, total %ACT = 6
• upright %ACT = 12
• supine %ACT = 2

Why Should We Be Concerned About Nocturnal Reflux?
The patterns of daytime and nocturnal reflux are completely different, according to William C. Orr, PhD, President and CEO, Lynn Health Science Institute, and Clinical Professor of Medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. In the daytime, episodes of reflux (pH<4) are numerous, primarily postprandial, and of short duration (Figure 1A). At night, the acid dwells longer in the esophagus (Figure 1B), increasing the likelihood that proximal migration of acid will spill over into the aerodigestive tract and the pharyngeal area. Thus, even a single episode of nocturnal reflux results in significant esophageal acid exposure, and cumulative exposures may lead to esophageal and extra-esophageal manifestations and complications.

What Are the Diagnostic and Treatment Options for Patients With Suspected Nocturnal Reflux and Disturbed Sleep?
Ideally, patients should undergo 24-hour pH testing and a sleep laboratory evaluation to distinguish between symptoms of obstructive and reflux-related sleep apnea. Continued sleep apnea even after treatment with continuous positive airway pressure (CPAP) indicates significant reflux disease, which requires acid suppression (eg, therapy with proton pump inhibitors [PPIs]). If the patient shows substantial improvement, the PPI dosing may be tapered, with continued CPAP.

Appropriate Indications for the Use of Proton Pump Inhibitors and H2 Antagonists
PPIs and H2 antagonists appear to be efficacious in resolving reflux symptoms. With both types of drugs, treating nocturnal reflux is important, eg, with BID dosing. More severe symptoms would require PPI treatment for optimal clinical response. Patients with reflux-related sleep apnea need long-term treatment, as do all patients with gastroesophageal reflux disease (GERD).

How Are GERD and Sleep Apnea Related?
Intra-thoracic negative pressure created by upper airway occlusion may induce reflux. Although studies to date have not found a specific relationship between such an obstructive event and an episode of gastroesophageal reflux, they have shown that the patients had excessive acid contact time (Ing AJ, et al. Am J Med. 2000;108(suppl 4A):120S). Physicians must be aware of the complexities of treating co-existing sleep apnea and GERD. Patients in whom the obstructive sleep apnea has been treated may still be experiencing significant acid reflux, and this condition also requires treatment.

Case #2: The Noncardiac Chest Pain Patient

• 45-yr-old male with intermittent epigastric and midsternal pain (described as pressure) radiating into lower/mid-chest region
• occurred 2x at night, 1x at daytime
• minimal relief with Maalox
• risk factors: tobacco (1 ppd for 10 yr); elevated cholesterol, now treated with atorvastatin; most recent LDL 86 mg/dL
• no stress-induced ECG changes
• normal peak stress perfusion
• mild gastritis on endoscopy
• standard PPI therapy 1x/day

In Patients Presenting With Indigestion or Heartburn, How Do We Determine that They Have Cardiac Rather than Reflux Disease?
Considerable overlap exists between the symptoms of reflux disease and cardiac disease, reported Michael C. Kontos, MD, Assistant Professor in the Department of Internal Medicine (Cardiology) and Emergency Medicine at the Medical College of Virginia School of Medicine in Richmond, Virginia. The patient’s chest pain characteristics (frequency, duration, association with exertion), history of coronary disease, gender, and age, and the number of risk factors are the most important considerations for predicting the nature of the disease.

Chest pain that lasts for a few seconds or for days, or pain that occurs at rest and is not associated with exertion, is unlikely to be caused by myocardial ischemia. Nocturnal (nonexertional) chest pain is not common in patients with cardiac disease, but in cases of coronary vasospasm or Prinzmetal angina, symptoms often occur at night and can clearly mimic reflux esophagitis.

How Do You Determine that the Pain Is Noncardiac in Nature and How Do You Treat the Patient?
A coronary angiogram usually is used to rule out significant cardiac disease in patients suspected of having cardiovascular symptoms. Patients with a lower pre-test likelihood (few risk factors, atypical chest pain) undergo pre-testing (eg, stress test) before being referred for coronary angiography. Patients with noncardiac chest pain often will be treated with anti-reflux therapy, such as a proton pump inhibitor (PPI), and are referred to a gastroenterologist for further evaluation.

What Is the Importance of Linked Angina?
Initial research has demonstrated that exposure of the distal esophagus to acid results in decreased blood flow within the coronary arteries (Chauhan A, et al. Eur Heart J. 1996;17:407). The complexity and overlapping nature of the vasculature of the chest organs might explain why patients with no abnormalities on angiography subsequently experience chest pain.

Patients with syndrome X or microvascular angina have abnormalities in their microvasculature, which can result in chest pain and abnormal coronary flow reserve. However, they do not have obstructive disease and the reason for their chest discomfort remains to be determined.

Case #3: The Patient With Chronic Cough

• 47-yr-old male smoker with chronic night cough
• mild nighttime heartburn
• history of hiatus hernia
• family history of pulmonary fibrosis
• “dirty” lungs on chest X-ray
• mild interstitial prominence
• CO diffusion capacity mildly abnormal
• lung volumes and spirometry normal
• DeMeester scores 50.5, 44.0 for distal, proximal esophagus
• double-dose PPI for 6 wk, lifestyle modifications, bed elevation
• 1-yr follow-up: stable, asymptomatic (cough and heartburn relieved)

How Often Is Chronic Cough Related to Gastroesophageal Reflux Disease (GERD)?
When evaluating patients with unexplained chronic cough, conditions associated with smoking, such as respiratory bronchiolitis, associated interstitial disease, and chronic bronchitis, usually are considered first. Patients with intractable cough that does not respond to bronchodilator therapy should be evaluated for gastroesophageal reflux, advises Ganesh Raghu, MD, FACP, FCCP, Professor of Medicine and Laboratory Medicine, Chief of the Chest Clinic, and Director of the Lung Transplant Program at the University of Washington, in Seattle, Washington.

What Are the Possible Mechanisms Involved in Nocturnal Chronic Cough Associated With GERD?
Acid in the distal esophagus can cause bronchoconstriction and airflow obstruction, manifesting as a cough due to neural mechanisms. Additionally, acid that is proximally propagated to and pools in the cricopharyngeal area may reach the pharynx, causing pharyngospasm and laryngospasm. If the acid reaches the trachea, it may induce chronic cough.

How Is the Finding of “Dirty Lungs” Related to GERD in This Patient?
The finding of interstitial lung disease in this patient is provocative, because his mother has idiopathic pulmonary fibrosis. The cause of this disease is unknown but gastroesophageal reflux may be a risk factor. Micro-droplets of aerosolized acid have been hypothesized to reach the terminal bronchioles, leading to recurrent inflammatory/mesenchymal fibrosis. Patients with interstitial lung disease and unexplained cough often have proximal esophageal reflux.

What Therapies are Available for Such Patients, and Is Surgery an Option?
If the reflux is clearly associated with the lung disease, proton pump inhibitors (BID dosing) should be used, with 24-hour pH monitoring at 6 weeks. Only 45%-48% of patients with physiologically detectable acid reflux are symptomatic, thus 24-hour pH monitoring, which is the most sensitive method for detecting acid reflux, is essential to ascertain the effectiveness of the PPI therapy. For patients who do not respond to maximal PPI or prokinetic therapies, fundoplication may be considered.

Is There a Relationship Between Pulmonary Fibrosis and GERD?
A prospective study has shown that 90% of patients with idiopathic pulmonary fibrosis have significant gastroesophageal acid reflux, as determined by 24-hour pH monitoring (Tobin RW, et al. Am J Respir Crit Care Med. 1998;158:1804). Genetic predisposition may be an important risk factor in idiopathic pulmonary disease, but other extrinsic factors, such as acid regurgitation, also can play a role. The family history of this patient, whose mother had idiopathic pulmonary disease, suggest that if the acid reflux, which may instigate epithelial mesenchymal reactions in the lungs, is not treated early, it could contribute to idiopathic pulmonary disease later in life. However, currently no evidence exists to support the use of PPIs to stabilize pulmonary fibrosis.

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