Gastroesophageal Reflux-related Chronic Cough GERD is a very common problem.

Surveys of the general population have led to estimates that 10% of the adult population of the United States have daily heartburn and a third have intermittent symptoms; moreover, GERD has been shown to cause 10% to 40% of cases of chronic cough. Cough in GERD is triggered by reflux of acid into the distal esophagus and stimulation of an esophageal-tracheobronchial reflex. Cough is not dependent on aspiration into the larynx or tracheobronchial tree. Proving the relationship of chronic cough to GERD can be difficult. The lack of typical symptoms of reflux and negative endoscopic and radiographic studies do not rule it out. The 24-hour esophageal pH monitoring test has become the gold standard for diagnosis and has both a sensitivity and specificity approaching 90%. Correlation of the results of pH monitoring with response to therapy adds to the reliability of the test. If GERD is the sole cause of chronic cough, aggressive anti-reflux therapy should eliminate the cough in nearly all cases. One study reported 100% success. Treatment involves the use of dietary, mechanical and drug therapy. Drug therapy should be initiated with proton pump inhibitors and prokinetic agents. H2antagonist can be substituted for the proton pump inhibitor after 3 months.

Mechanism of Cough Cough is a protective reflex serving a normal physiologic function of clearing excessive secretions and debris from the pulmonary tract. The cough reflex has 3 components: an afferent sensory limb, a central processing center, and an efferent limb.2 The trigeminal, glossopharyngeal, and vagus nerves supply the afferent pathways for cough receptors; the vagus, through its pharyngeal, superior laryngeal, and pulmonary branches, supplies the large majority of these receptors. Receptors are located throughout the airway from the pharynx to the terminal bronchioles, with the greatest concentration located in the larynx, carina, and the bifurcation of larger bronchi.6 Three types of receptors are predominant:7,8,9

Terdapat afferent limb receptors reflex batuk pada gaster dan esofagus bag bawah, maka GERD batuk kronik Penderita GERD termasuk dalam 3 penyebab utama batuk kronik, dengan mekanisme : 1. Iritasi esophagus dengan stimulasi esophagealtracheobronchial reflex 2. Nocturnal aspiration cairan asam lambung

Rapidly adapting receptors (RARs) that respond to mechanical stimuli, cigarette smoke, ammonia, acidic and alkaline solutions, hypotonic and hypertonic saline, pulmonary congestion, pulmonary congestion, atelectasis, and bronchoconstriction Slowly adapting receptors (SARs) Nociceptors on C-fibers that respond to chemical stimuli as well as inflammatory and immunological mediators such as histamine, bradykinin, prostaglandins, substance P, capsaicin, and acidic pH

Afferent impulses are transmitted to the cough center of the brain, located in the nucleus tractus solitarius of the medulla of the brainstem, which is connected to the central respiratory generator.

To complete the reflex arc, efferent impulses leave the medulla and travel to the larynx and tracheobronchial tree via the vagus while the phrenic and spinal motor nerves of C3 to S2 supply the intercostals muscles, abdominal wall, diaphragm, and pelvic floor.6 This cough reflex has been shown to have neuroplasticity such that a hypersensitive response is elicited over time due to the cough itself inducing chronic irritation and inflammation and tissue remodeling.8 Both peripheral (increase in sensitivity of cough receptors) and central (changes in central processing in the brainstem) sensitization can account for an exaggerated cough response that is common in patients and further contributes to the maintenance of chronic cough.9 Causes of Chronic Cough The etiologies of chronic cough are numerous and may include pathology from the nose and nasopharynx to the distal bronchial tree. Obvious causes such as smoking and angiotensin-converting enzyme (ACE) inhibitor use can be easily ascertained from the history. After this, the challenge for the clinician lies in how to efficiently and systematically evaluate the patient without an overly exhaustive workup. Further compounding this is the fact that oftentimes more than one condition is simultaneously present. Prospective studies have shown that 3 conditions account for the etiologic cause of chronic cough in 92-100% of immunocompetent, nonsmoking patients with normal chest radiograph findings.10 In order of frequency, they are as follows: 1. Upper airway cough syndrome (UACS), previously referred to as postnasal drip syndrome (PNDS) 2. Asthma

3. Gastroesophageal reflux disease (GERD)

These 3 conditions make up what is called the pathogenic triad of chronic cough. A fourth etiology that deserves mention is nonasthmatic eosinophilic bronchitis (NAEB), which is relatively common, easy to diagnose and treat, and should be considered early on in the diagnostic evaluation. Another way to categorize the etiologies is to draw a distinction between cough due to eosinophilic airway diseases (asthma and NAEB) and noneosinophilic chronic cough.11 Eosinophilic airway diseases have airway inflammation due to eosinophils, which can be diagnosed by raised induced sputum eosinophil counts and increased exhaled nitric oxide levels. They are also associated with good steroid responsiveness.11 The physician who focuses on diagnosing and treating these conditions will be extremely successful at treating chronic cough. Gastroesophageal reflux disease The following 2 mechanisms have been postulated for GERDassociated cough:13

Distal esophageal acid exposure that stimulates an esophageal-tracheobronchial cough reflex via the vagus nerve Microaspiration of esophageal contents into the laryngopharynx and tracheobronchial tree

The second entity refers to laryngopharyngeal reflux (LPR) or extraesophageal GERD, and it differs from traditional GERD in that it does not manifest as heartburn and tends to occur when the patient is upright as opposed to lying flat. This silent GERD can be present in as many as 75% of patients with chronic cough.14 Symptoms of LPR include throat clearing, hoarseness, and globus sensation. Empiric treatment includes acid suppression and lifestyle and dietary modifications.