Extraesophageal reflux has been implicated in many disorders affecting the upper airway. This article reviews the recent literature regarding the relationship of refractory chronic rhinosinusitis with extraesophageal reflux. Recent studies have shown that patients with refractory chronic rhinosinusitis have an increased prevalence of extraesophageal reflux. An association may exist between gastroesophageal reflux and rhinosinusitis, especially in individuals with medically and surgically refractory disease. These studies have a poor level of evidence and data supporting causation are lacking. However, evaluation and treatment should be considered in patients with chronic rhinosinusitis, especially in those with refractory disease.
The gastrointestinal tract was implicated in the pathogenesis of chronic sinusitis more than 50 years ago when Holmes and colleagues proposed a connection between sinonasal disease and gastric hypersecretion. However, it has only been in the last few years that clinicians’ awareness of gastroesophageal reflux (GER) as a potential exacerbating factor of upper airway inflammatory disease has increased. Thus far, most studies evaluating the association have been retrospective and a scientifically valid relationship remains elusive.
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Relationship between reflux and rhinosinusitis still poorly defined.
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Reflux may be the cause of some symptoms attributed to rhinosinusitis (eg, postnasal drip).
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Consider reflux as a factor in patients with refractory sinonasal inflammatory disease.
To solidify the association between GER and chronic rhinosinusitis (CRS), 3 criteria should be met:
- 1.
Patients with CRS should have a higher prevalence of GER than patients without CRS.
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The pathophysiologic mechanisms between GER and CRS should help explain how the disease processes interact.
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If GER is a contributing factor to CRS, then GER treatment should improve or resolve CRS in most patients.
This article reviews the literature regarding these criteria.
Prevalence of GER in patients with CRS
DiBaise and colleagues showed a high prevalence of GER in patients with CRS. They found that 78% of patients with CRS had GER based on 24-hour esophageal pH monitoring (pH<4.0 more than 9.2% of total time at the distal site or more than 3.3% of total time at the proximal site). Furthermore, results from a large case-control epidemiologic study showed that adults with complicated GER were more likely to have sinusitis (odds ratio, 1.60; 95% confidence interval [CI], 1.51–1.70) than were controls. Pincus and colleagues also found reflux in 25 of 30 patients with CRS. These 25 patients were placed on proton pump inhibitor therapy and were reevaluated 1 month later, at which point 14 of 15 evaluable patients reported improvement in their symptoms, including 7 who had almost/complete resolution. However, several methodological problems limit interpretation of the study including, but not limited to, the short follow-up, lack of a control group, the potential for recall bias, as well as limited documentation of CRS disease severity. Furthermore, Onerci and colleagues, using a nasal lavage pepsin assay and 24-hour dual-probe monitoring, found that 88% of patients with CRS had pharyngeal acid reflux compared with 55% of controls. The investigators acknowledged the higher incidence (55%) of reflux in the control group than previously reported. The investigators attributed this finding to the nutritional habits of the Turkish population, although they did not elaborate on the nature of the potential causative nutritional habits.
Studies on GER and Refractory CRS
A few studies have specifically investigated medically and surgically refractory CRS.
Ulualp and colleagues also showed a significantly higher prevalence of GER in patients with CRS unresponsive to conventional therapy compared with normal controls ( P <.05), and postulated that GER may contribute to the pathogenesis of CRS in some adult patients.
Chambers and colleagues found that the presence of GER was a predictor of poor symptomatic outcome after sinus surgery in adults.
Similarly, Delgaudio, using a specially designed pH probe, showed increased reflux at the nasopharynx, upper esophageal sphincter, and distal esophagus in patients with medically and surgically refractory rhinosinusitis compared with controls. He concluded that it is likely that reflux is an important causative factor of refractory CRS in adults. Although his study does show an association, causation is far from clear given from the information provided. In an unpublished study, our group studied 22 patients with medically and surgically refractory rhinosinusitis. All subjects underwent comprehensive testing for extra-esophageal reflux (EER) including 24-hour pharyngeal pH probe, aerosolized nasopharyngeal pH testing, and nasopharyngeal tissue biopsy for pepsin analysis. In addition, the last 5 subjects underwent nasal secretion analysis for pepsin. A control group of healthy subjects underwent the same nasal secretion pepsin analysis. The pharyngeal pH probe results were positive in 19 of 20 (95%), whereas the DeMeester score was positive in 9 of 19 (47%). The nasopharyngeal pH probe data were available in 17 of 20 patients and correlated poorly with the pharyngeal pH probe testing. In all 20 subjects, nasopharyngeal tissue biopsies were negative for pepsin. However, the 5 subjects who underwent nasal pepsin analysis were all pepsin positive, whereas 5 healthy controls nasal lavages were negative for pepsin. Thus this study supports an association of EER with medically and surgically refractory CRS.
The finding of pepsin in nasal aspirates suggests that direct contact of the refluxate with the paranasal sinus mucosa may play a role in the pathophysiology of CRS in this patient population. In addition, evaluation for pepsin in nasal fluid is a viable method for determining the presence of refluxate in the nose and paranasal sinuses (Loehrl TA and colleagues Triological Thesis Reflux and Refractory Chronic Rhinosinusitis . September, 2010).
In children, several investigators have suggested a relationship between GER and CRS. Contencin and Narcy initially showed a possible relationship between GER and chronic upper airway inflammation in the pediatric population. Subsequent studies, both retrospective and prospective, have shown a high prevalence of GER (especially pharyngeal reflux) in children with CRS, providing further evidence in support of the relationship. These studies are all retrospective and lack control groups.
Possible pathophysiologic mechanisms between reflux and CRS
The mechanism(s) by which reflux affects the sinonasal cavity remains unclear, but 3 mechanisms have been proposed:
- 1.
Refluxate effect on the mucosa
- 2.
Vagally mediated neurogenic mechanism(s)
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Helicobacter pylori.
Refluxate Effect on Mucosa
The first proposed mechanism is that the refluxate has a direct effect on the mucosa, resulting in an inflammatory response with edema and impaired mucociliary clearance. These events result in sinus ostial obstruction and infection. In children, reflux to the nasopharynx has been shown using 24-hour pH probe studies. In infants and children with previously documented reflux, Contencin and Narcy showed that, when a 2-site pH probe was placed with one site in the esophagus and the other in the hypopharynx, refluxate frequently extended above the cricopharyngeus. Phipps and colleagues showed that 63% of patients with CRS showed GER, which is considerably more than the prevalence in a normal healthy population. Furthermore, 32% of these patients showed nasopharyngeal reflux. In addition, as noted earlier, in an unpublished study, our group showed pepsin in nasal secretions in all 5 patients with medically/surgically refractory rhinosinusitis, whereas none of the healthy controls had evidence of pepsin in their nasal secretions.
Neurogenic Mechanism
The second theory revolves around a vagally mediated neurogenic mechanism. This mechanism may involve dysfunction of the autonomic nervous system, resulting in sinonasal edema and secondary ostial obstruction. This disorder has been shown in the lower airway by Lodi and colleagues and Harding and colleagues. They found that patients with asthma and GER disease have exaggerated vagal responsiveness, compared with age-matched controls. Dysfunction of the autonomic nervous system was shown by Loehrl and colleagues in patients with chronic upper airway inflammation. They found that these patients, compared with a group of age-matched and sex-matched controls, have significant ( P = .02) autonomic nervous system dysfunction characterized by adrenergic hypofunction. In addition, it was noted that patients with documented extraesophageal reflux and vasomotor rhinitis had statistically significant evidence of more adrenergic hypofunction than those with vasomotor rhinitis alone.
H pylori
The third possible mechanism involves the potential role of H pylori in CRS. H pylori is a microaerophilic gram-negative spiral organism that has been shown to play a large role in stomach ulcers and gastritis. It has also been shown in human dental plaque, oral lesions and saliva. Ozdek and colleagues used polymerase chain reaction to detect H pylori in 4 of 12 patients with CRS, whereas it was not detected in any patient without CRS. In 3 of the 4 patients in whom H pylori was detected, the patients had GER-related complaints. However, it remains unknown whether H pylori is a causative agent for CRS or whether it results from CRS.
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