gerd and respiratory system

Extraesophageal reflux disease (EERD) represents a wide spectrum of manifestations mainly related with the upper and the lower respiratory system such as laryngitis, asthma, chronic obstructive pulmonary disease, cough, hoarseness, postnasal drip disease-sinusitis, otitis media, recurrent pneumonia and laryngeal cancer. Non-cardiac chest pain is commonly grouped among the esophageal syndromes by the Montreal Classification. but is not one of the common symptoms of typical gastroesophageal reflux (GER) which are heartburn and regurgitation . The diagnosis and recommendations on initial empiric therapy for patients with suspected reflux related non-cardiac chest pain is similar to those of extraesophageal reflux which is why it is included in this chapter. GER contributes to extraesophageal syndromes by two mechanisms: direct (aspiration) or indirect (vagally-mediated) mechanisms .

Reflux of gastroduodenal contents into the esophagus and hypophayrnx may be classified as either “high” or “distal” . The pathogenesis of “high” esophageal reflux involves reflux that traverses the esophagus and induces cough either by direct pharyngeal or laryngeal stimulation or aspiration and causes a tracheal or bronchial cough response. In “distal” esophageal reflux, cough can be produced by a vagally-mediated trachealbronchial reflex . Embryologic studies show that esophagus and bronchial tree share a common embryologic origin and neural innervation via the vagus nerve. Pressure gradient changes between the abdominal and thoracic cavities during the act of coughing, may lead to a cycle of cough and reflux . A disturbance in any of the normal protective mechanisms such as disruption of the mechanical barrier for reflux (lower esophageal sphincter) or esophageal dysmotility may allow direct contact of noxious gastroduodenal contents with the larynx or the airway . In this article we will discuss the latest knowledge of the association between extraesophageal manifestations of GER such as chronic cough, laryngitis and asthma as well as non-cardiac chest pain of esophageal origin.We will discuss the current recommendations on diagnosis and treatment options for this difficult group of patients  (Burton DM,  et al ,2010)


Complicated GERD gastroesophageal acid reflux disease

Numerous complications have been associated with persistent GERD (gastroesophageal acid reflux disease), especially when it is nocturnal. In a study comparing daytime GERD(gastroesophageal acid reflux disease), nighttime GERD or a combination of both, the incidence of esophagitis was higher among individuals with nocturnal symptoms than those with daytime GERD(gastroesophageal acid reflux disease), although patients who had both experienced the highest rate of esophagitis . Poh et al.  recently demonstrated that the duration of nocturnal reflux events is longer and usually asymptomatic. The potential esophageal complications of persistent GERD(gastroesophageal acid reflux disease) include esophagitis, peptic strictures, esophageal ulcerations and bleeding, Barrett’s esophagus and esophageal adenocarcinoma. Management of complicated GERD(gastroesophageal acid reflux disease) includes dilation for benign peptic stricture in patients presenting with dysphagia. These patients should be supplemented with long-term PPI to reduce the need for repeated dilations (Poh CH, et al , 2010).

Patients presenting with bleeding esophageal ulcers can be treated endoscopically with adrenaline injections, hemoclips and heater probes. They should be on long-term PPI to ensure healing of the ulcer. The management of Barrett’s esophagus and esophageal adenocarcinoma is beyond the scope of this review. GERD(gastroesophageal acid reflux disease) in the elderly Gastrointestinal disorders are common in elderly patients. A population-based study from Finland showed that the prevalence of daily GERD(gastroesophageal acid reflux disease) symptoms in those aged 65 years and older was 8% in males and 15% in females . (Plant RL.1998)

Furthermore, Zhu et al. observed that abnormal  gastroesophageal reflux occurred more frequently in the elderly than in younger individuals. The mean time pH\4 was significantly higher in the elderly as compared to younger individuals, 32.5 versus 12.9%. In addition, more elderly patients (21%) have grade III–IV erosive esophagitis (based on Savary–Miller criteria) compared to younger patients (3.4%), p\0.002 . Aging may result in various physiological changes in the gastrointestinal tract . These changes may increase the risk of development of disorders such as GERD (gastroesophageal acid reflux disease). Co-morbidity and concomitant use of medications in the elderly can diminish esophageal sphincter tone, esophageal clearance mechanisms and saliva production. Some of the common medications that can predispose the elderly to reflux are calcium channel blockers, nitrates, narcotics, medications with anti-cholinergic effects and theophylline. The manifestation of GERD(gastroesophageal acid reflux disease) in the elderly differs from that in younger individuals. Heartburn occurs less frequently, and acid regurgitation is present in less than 25% of patients.( Mold JW, et al ,1991)

Mold et al.  reported that only 54% of elderly patients complained of heartburn. In contrast, atypical symptoms such as vomiting, anorexia, dysphagia, respiratory symptoms, belching, dyspepsia and postprandial fullness are common presentations in the elderly with GERD(gastroesophageal acid reflux disease) . The main clinical concern of atypical presentation of GERD in the elderly is the delay in diagnosis and hence the delay in giving the appropriate treatment. Diagnostic modalities for GERD (gastroesophageal acid reflux disease)that are available for elderly patients parallel those for younger patients. Upper endoscopy is usually advocated in the elderly because they present with atypical symptoms and are at increased risk for malignancy and peptic ulcer disease.   Treatment of GERD(gastroesophageal acid reflux disease) in the elderly is similar to the treatment in younger patients. However, a very aggressive therapeutic approach should be considered in elderly patients with GERD(gastroesophageal acid reflux disease) because they tend to present with more severe disease. When treating elderly patients with acid suppression therapy such as H2RAs and PPIs, caution needs to be exercised for potential drug interactions considering that polypharmacy in the elderly is not uncommon. Several recent studies suggested that elderly patients on long-term PPI treatment have an increased risk of bone fracture, community-acquired pneumonia and hospitalacquired Clostridium difficile diarrhea . While most of these studies were population based, not prospective studies, and remain to be proven, elderly patients should receive the lowest dose of PPI that controls their symptoms, and usage of PPI should be limited to peptic-related disorders. (Laheij RJF,, et al,2004)

Allergy Treatment for GERD

Allergy Treatment

Eosinophilic esophagitis is frequently misdiagnosed as GERD. Allergy treatment may be indicated in individuals who are not responsive to typical GERD therapies. Allergy testing to measure both IgE and IgG antibodies is indicated. In addition, dietary supplementation, using products to treat allergic reactions directly may also be necessary. Quercitin is a bioflavonoid often used in allergies because it has antihistamine, anti-inflammatory, and antioxidant effects. Vitamin C has been shown to be protective against GERD and to have antioxidant and some ( Mahmood A,,2007)

antihistamine properties.

Zinc Carnosine

Zinc carnosine has been shown to speed healing in many types of gastrointestinal lesions. Many studies refer to polaprezinc, a chelate compound consisting of zinc and L-carnosine. Studies show that polaprezinc has antioxidant activity and decreases the gastric inflammation caused by H. pylori infection. Polaprezinc has been shown to protect gastric mucosa from damaging free radicals as well as speed healing of gastric lesions in animal models.76 Additionally, studies show that zinc carnosine improves intestinal integrity and decreased labinduced gastric and small-intestine injury. ( Paraschos S,, , et al ,2007)


L-Glutamine is an amino acid utilized as an energy source by intestinal epithelium. Research has shown that supplementation with glutamine prevented the development in chemical- induced gastric lesions in stressed rats. Also, glutamine has been shown to decrease duration and severity of mucosal lesions induced by chemotherapy. Belladonna Atropa belladonna (belladonna) is a botanical often used for its anticholinergic activity. One of the constituents of belladonna is atropine. Although anticholinergics have been shown to aggravate GERD, atropine has been shown to be beneficial. It is possible that belladonna may be useful for treating GERD owing to the herb’s atropine component. ( Mahmood A,,2007)


Digestive Enzymes and acid reflux

Digestive Enzymes

Supplemental digestive enzymes may reduce GERD symptoms. Delayed gastric emptying and a large volume of food in the stomach are associated with GERD symptoms, and supplementation using digestive enzymes may reduce these factors. Digestive enzymes are commonly included in combination products, including lipase, amylase, protease, maltase, lactase, sucrase, phytase, and cellulase. Clinically, some patients actually benefit from hydrochloric acid and pepsin supplementation, including individuals who have low levels of stomach acid and delayed gastric emptying. ( Mahmood A,,2007)

Alternative Treatment for acid reflux

Alternative Treatment


Antioxidants have been shown to be protective in numerous diseases, such as GERD, gastric ulcers, and GI cancers. Oxidative stress of the esophageal mucosa is a contributing factor in the pathology of GERD. A study was performed with individuals with both erosive and nonerosive GERD pre- and post-antireflux surgery measuring oxidative stress. This study showed that individuals with GERD have lower glutathione levels in the distal esophagus compared with controls. In addition, myeloperoxidase activity in the distal esophagus decreased after antireflux surgery but never returned to levels found in the control group. Supplementation to increase glutathione levels with the precursors N-acetyl-cysteine and selenium may be beneficial. Additional studies have shown that oxygen-free radicals measured by arachidonic acid peroxidation metabolites are significantly higher in patients with GERD compared with controls.( Modzelewski B. et al , 2004)

Studies have also indicated that free-radical oxidative damage plays a role in gastric and duodenal ulcers as well in as gastric carcinoma. Although studies directly supporting antioxidant supplementation with GERD are lacking, ubstantial evidence supports using antioxidant therapy for patients with gastric ulcers and cancer, and shows that the therapy may also provide benefit for patients who have GERD. Research has shown that the hormone and potent antioxidant melatonin prevented gastric ulceration and reduced endogenous hydroxyl radicals by 88%. In fact, melatonin was shown to be more effective than ranitidine for preventing stress-related ulcers in animal models. Fish oil supplementation has also been shown to protect gastric mucosa and decrease the severity of gastric ulceration in animal studies. Fish oil increased antioxidant enzyme activity,decreased acid-pepsin secretion, increased mucin secretion, and decreased lipid peroxidation in the gastric mucosa.( Bhattacharya A, et al ,2006)

A study was performed with an antioxidant dietary supplement containing melatonin,  tryptophan, vitamin B6, folic acid, vitamin B12, methionine, and betaine. The supplement or omeprazole was given to individuals with GERD. In this study, 100% of individuals who took the supplement had complete regression of their GERD symptoms within 40 days compared with less than 66% of individuals who had regression of symptoms treated with omeprazole.( Pereira R de S., 2006)


D-limonene is a monoterpene in citrus oil. Numerous studies have shown that D-limonene exerts anti-cancer, antimicrobial, and anti-inflammatory effects. In particular, studies have shown that this constituent of citrus oil is protective against GI cancers, including cancers of the stomach and colon, decreasing both growth and metastasis.Although direct evidence of D-limonene’s effects on esophageal cancer is lacking, it is certainly possible that this monoterpene may be protective against Barrett’s esophagus and esophageal adenocarcinoma. Alternative practitioners often recommend D-limonene for treatment of GERD with generally good results, although studies are lacking.


Glycyrrhiza glabra (licorice) root has historically been used as a demulcent and anti-inflammatory botanical for treating conditions such as gastric and duodenal ulcers. Studies have shown that ingestion of deglycyrrhizinated licorice (DGL) may increase mucous production   and accelerate healing of duodenal and gastric ulcers. In addition, a small study showed that DGL also accelerates healing of aphthous ulcers. Although studies that correlate DGL with GERD directly are lacking, it is reasonable to assume that DGL may provide symptom relief in patients with GERD. Clinically, alternative health care providers often prescribe additional demulcent herbs for their healing and soothing properties, including such herbs as loe vera (aloe), Ulmus fulva (slippery elm), and Althaea officinalis  marshmallow).( Paraschos S,, , et al ,2007)


Pistacia lentiscus (mastic) resin is used medicinally for treating duodenal and gastric ulcers. Animal studies show that it decreased H. pylori colonies thirtyfold. Research has also indicated that mastic resin oral supplementation protects gastric mucosa from experimentally induced damage as well as decreasing free acidity.In addition, a small study showed that mastic supplementation provided symptomatic relief of duodenal ulcers in 80% of individuals who were treated with the supplement, and 70% experienced healing with endoscopy. The antisecretory and cytoprotective activity of mastic may provide benefit for individuals with GERD, although direct evidence is lacking. (Nishiwaki H,, et al , 1999)


Calcium carbonate, magnesium, aluminum, and phosphate salts are frequently used in overthe- counter antacids. Studies have indicated that antacids are effective for treating GERD symptoms, reducing acid regurgitation, and relieving both daytime and nighttime heartburn.74 Mineral supplementation, using calcium and magnesium, may reduce GERD symptoms, although direct evidence is lacking.( Mahmood A,,2007)