A study of the link between gastric reflux and chronic sinusitis in adults.
Much discussion is taking place regarding the role of gastric reflux disease in the development and maintenance of chronic sinus disease. We studied 31 patients in a large urban private practice who had recalcitrant chronic sinusitis despite aggressive medical and surgical therapy. After we obtained information on the severity of each patient's sinus disease, we performed either double- or triple-catheter probe pH testing to assess the presence of reflux disease. Of the 30 patients who were successfully tested (1 patient did not tolerate probe testing), 25 demonstrated reflux disease, including 2 whose reflux reached the level of the nasopharynx. These 25 patients were placed on a proton-pump inhibitor (PP1) regimen and reassessed at least 1 month later. At follow-up, 14 of 15 evaluable patients demonstrated at least some improvement in their sinus symptoms, including 7 who experienced either a complete or almost-complete resolution of symptoms. The improvements in sinus symptoms corresponded with improvements in reflux symptoms. These findings suggest that antireflux therapy might play a role in the treatment of recalcitrant chronic sinus disease.
Sinusitis affects almost 30 million people in the United States, and it accounts for 14.1 million office visits annually. (1) The pathophysiologic mechanism of sinusitis, as proposed by Messerklinger, is thought to begin with mild edema that leads to obstruction at the draining sinus ostia. (2) The obstruction is believed to initiate a cycle of reactive mucosal edema that results in further occlusion of the ostia. Mucus stasis and respiratory ciliary dysfunction occur, leading to bacterial overgrowth.
Many possible triggers of the initial obstruction at the sinus ostia have been proposed, with allergy and viral upper respiratory infection being the most widely considered. A new mechanism has recently been proposed as an inciting factor for sinusitis: nasal or nasopharyngeal irritation from gastric acid reflux. In 1999, Bouchard et al demonstrated that children with otolaryngologic disorders, including sinusitis, were more likely to have gastric reflux than were controls without ENT disorders. (3) The same year, Ulualp et al reported a higher incidence of gastric reflux in adults with sinusitis than in those without. (4) Five years earlier, Beste et al had reported that gastric refluxate reached as far as the choanae in 4 children with bilateral choanal atresia. (5) Again in 1999, Bothwell et al demonstrated the importance of gastric reflux in the pathogenesis of chronic sinusitis in children. (6) They also reported that gastric reflux therapy was effective in the treatment of childhood chronic sinusitis.
We studied an adult population with recalcitrant chronic sinusitis that persisted despite aggressive medical and surgical therapy. Our aim was to help determine the incidence of gastric reflux in patients with sinus infections and to assess the efficacy, if any, of proton-pump inhibitor (PPI) therapy in alleviating any symptoms associated with sinusitis. In some reports of recent studies, investigators have continued to postulate a relationship between reflux and sinusitis. (7-9)
Patients and methods
Our study population was made up of 31 adults--24 women and 7 men, aged 26 to 68 years (mean: 43.97 [+ or -] 11.77)--who were patients in a private otolaryngology practice in a large urban area. All 31 patients had been diagnosed with chronic sinusitis based on history, physical examination, at least one postantibiotic computed tomography scan of the sinuses, and intraoperative findings in those who had undergone sinus surgery. Each patient had complained of recurrent sinus infections and/or chronic symptoms of sinusitis despite multiple courses of antibiotics and oral steroids.
All 31 patients were questioned about any symptoms of gastric reflux that they might have experienced, including heartburn, regurgitation, sour taste, hoarseness, globus sensation, and throat soreness. They were also asked about the presence and severity of symptoms associated with chronic sinusitis--specifically, nasal congestion, rhinorrhea/postnasal drip, headache and/or facial pain--and they were asked to rate their smelling ability. Symptom severity was rated as absent (0), intermittent (1), or constant (2), and sense of smell was rated as excellent (0), impaired (1), or anosmic (2). The pretreatment (pre-Tx) sinus score was determined by obtaining the sum of the individual symptom scores. Finally, patients were questioned about any related concomitant conditions, including environmental allergies, asthma, ciliary disorders, immune disorders, or gastrointestinal disorders.
Each patient underwent a thorough otolaryngologic examination, which included nasal endoscopy and laryngoscopy. The presence of nasal mucosal edema, purulent discharge, and polyps was noted, as were any findings consistent with laryngeal reflux. Subsequently, all patients underwent a 24-hour ambulatory pH test, regardless of whether they had symptoms consistent with reflux. Prior to each test, each patient was asked to abstain from taking any antacid medication for at least 72 hours. A Synectics Digitrapper Mark III device equipped with a monocrystal antimony pH catheter was used. The catheter was calibrated with solutions of pH 1 and 7 prior to use. Both double-and triple-catheter devices were used. The catheters were placed transnasally under fiberoptic guidance. The final positions of the catheters were (1) 5 cm above the lower esophageal sphincter, (2) above the cricopharyngeus, and (3) in the nasopharynx for patients in whom triple catheters were used.
Each patient was given a diary to note meals, belches, and sleep periods. They were also asked to record any reflux symptoms they experienced during the study. Physiologic reflux was defined as having occurred when the recorded pH was below 4 during periods of noted belching and during and immediately after meals. (10) Pathologic gastric reflux was deemed to have occurred when the recorded pH was below 4 outside mealtimes and periods of belching. (10)
After pH testing, patients were placed on one of three PPIs: omeprazole 40 mg/day, lansoprazole 30 mg/day, or rabeprazole 20 mg/day. After a treatment period of at least 1 month, patients were contacted by telephone and asked to rate their reflux symptoms and sinusitis symptoms according to the scoring system previously described.
We used the chi-square test to compare the frequency of gastric reflux in our patients with that of historical controls who did not have chronic sinusitis.
Prior to treatment, 28 of the 31 patients reported intermittent or constant nasal congestion, 27 had nasal discharge, 26 had headaches and/or facial pain, and 16 had a diminished sense of smell (table 1). Twenty-eight patients had a pre-Tx sinus score of 3 or higher (figure 1). Thirteen patients denied any symptoms consistent with gastric reflux (table 1). Nine patients had environmental allergies, and the most common related diagnosis was asthma, which affected 7 patients. Other related diagnoses included IgG deficiency, hiatal hernia, and common variable immunodeficiency.
[FIGURE 1 OMITTED]
One patient was unable to tolerate the insertion of the pH catheters, and therefore testing was not performed on her. Of the remaining 30 patients, 23 underwent triple-catheter probe pH testing and 7 underwent double-catheter testing. Of the 23 patients who underwent triple-catheter testing, reflux was detected in 20; 16 had laryngopharyngeal reflux (LPR), 2 had nasopharyngeal reflux (NPR), and 2 had gastroesophageal reflux disease (GERD) (table 1). Of the 7 patients who underwent double-catheter testing, 2 had LPR, 3 had GERD, and 2 had no reflux (table 1). In all, some type of reflux was found in 25 of the 30 patients (83.3%) who underwent probe testing. Statistically, this rate is significantly higher than the rate of reflux in healthy controls reported by Ulualp et al (18%; p < 0.001). (4)
The 25 patients who were found to have some type of reflux were scheduled to undergo PPI therapy for at least 1 month. However, during the treatment period, 4 patients stopped taking their medication prematurely and 2 others underwent sinus surgery (table 2). Data on these 6 patients were therefore excluded from the final analysis. In addition, data on another 4 patients were excluded because we were unable to obtain follow-up information from them (table 2). In sum, data on PPI efficacy for the treatment of sinus complaints were available for 15 patients.
A comparison of the pre- and post-Tx sinus scores among the 15 evaluable patients confirms that PPI therapy did indeed alleviate sinus symptoms (figure 2). Fourteen of 15 patients experienced a reduction in their pre-Tx sinus score; 6 patients had a 1-point improvement and 8 had an improvement of 2 or more points. Five patients who had a pre-Tx sinus score of 4 or 5 improved to the point where their post-Tx score was only 1. Of 11 patients who had a pre-Tx sinus score of 4, 5, or 6, only 1 remained in that range following PPI therapy. A post-Tx sinus score of 0 or 1 was reported by 7 patients.
[FIGURE 2 OMITTED]
Patients who experienced the greatest improvement in their post-Tx sinus score also reported either a complete or nearly complete resolution of their reflux symptoms. Conversely, of 7 patients who experienced either no improvement or only a 1-point improvement in their post-Tx sinus score, only 3 reported symptomatic improvement of their reflux symptoms.
The importance of gastric reflux to the otolaryngologist has been well documented. With double-catheter pH testing, Koufman has demonstrated that gastric reflux often reaches the level of the larynx and that most of these patients are asymptomatic. (10,11) When symptoms do occur, they may not be the classic symptoms associated with GERD (e.g., heartburn, belching, and regurgitation). Instead, patients with LPR may display hoarseness, globus, chronic throat clearing, and chronic cough. In our study, 6 of 18 patients with probe-documented LPR exhibited none of the typical symptoms of reflux.
Mucosal disease resulting from exposure to gastric acid in the aerodigestive tract is associated with disorders of the larynx, subglottis, and pulmonary system. (3,10,11) The possible role of gastric reflux in initiating and maintaining chronic sinus disease has been suggested in studies of children. The capability of gastric acid to reach as far cephalad as the nasopharynx was demonstrated in the study of bilateral choanal atresia repair by Beste et al. (5) Despite the successful creation of "neochoanae," these children required repeated dilation and stenting because of choanal restenosis. The role of gastric acid in restenosis was documented by probe pH testing in 3 of these infants and by radionuclide testing in 1. In our study, 2 patients demonstrated significant reflux to the level of the nasopharynx on triple-catheter probe pH testing. This finding confirmed that gastric refluxate can reach as far cephalad as the nasopharynx in adults.
In the previously mentioned study by Bouchard et al, double-catheter probe pH testing showed that 40% of children with recurrent sinusitis tested positive for reflux. (3) In the study by Bothwell et al, 25 of 28 children with chronic sinusitis who had been scheduled for invasive treatment were able to avoid surgery after a course of aggressive PPI therapy. (6)
The role of reflux in initiating and maintaining sinusitis in adults is not as clear-cut as it is in children. Chambers et al suggested that the presence of reflux portends a poor symptomatic outcome after surgery for chronic sinusitis in adults, but they did not elaborate on the possible reasons why. (12) Although Ulualp et al (4) found a higher incidence of reflux in patients with sinusitis, as did we, no study has been conducted on the clinical course of patients with reflux and sinusitis who were treated with antacid therapy. We found that most adults with recalcitrant sinusitis despite conventional medical and surgical therapy responded favorably to PPI therapy, including some whose improvement was dramatic. Those patients who derived the most benefit from PPI therapy in terms of their sinus symptoms also experienced the most improvement in terms of their reflux symptoms. Even the 9 patients with environmental allergies in our study experienced significant alleviation of their sinus symptoms with control of their reflux symptoms.
Our study had several limitations. Measurements of our patients' pretreatment sense of well-being and their sinus symptoms were subjective. Furthermore, our study might have suffered from recall bias.
There is a clear need for further research into the relationship between sinusitis and reflux disease. Long-term double-blind prospective studies based on objective and validated symptom-based outcomes criteria are needed to further evaluate the efficacy of PPIs in treating recalcitrant sinusitis. Also, the presence of bilious reflux at the level of the larynx has been suggested by Malthaner et al (13) and by Marshall at al, (14) so the role of nonacidic gastric reflux on upper esophageal pathology should be explored, as well. In the interim, our findings suggest that reflux disease may play a role in the failure of aggressive medical therapy to resolve chronic sinusitis. Certain patients with recalcitrant sinusitis may benefit from the addition of reflux therapy to the treatment of their sinus disease.
(1.) Centers for Disease Control. National Center for Health Statistics. Fastats A to Z. www.cdc.gov/nchs/fastats/sinuses.htm (accessed Jan. 26, 2006).
(2.) Messerklinger W. Endoscopy of the Nose. Baltimore: Urban & Schwarzenberg, 1978.
(3.) Bouchard S, Lallier M, Yazbeck S, Bensoussan A. The otolaryngologic manifestations of gastroesophageal reflux: When is a pH study indicated? J Pediatr Surg 1999;34:1053-6.
(4.) Ulualp SO, Toohill RJ, Hoffmann R, Shaker R. Possible relationship of gastroesophagopharyngeal acid reflux with pathogenesis of chronic sinusitis. Am J Rhinol 1999;13:197-202.
(5.) Beste DJ, Conley SF, Brown CW. Gastroesophageal reflux complicating choanal atresia repair. Int J Pediatr Otorhinolaryngol 1994;29:51-8.
(6.) Bothwell MR, Parsons DS, Talbot A, et al. Outcome of reflux therapy on pediatric chronic sinusitis. Otolaryngol Head Neck Surg 1999; 121:255-62.
(7.) DiBaise JK, Olusola BF, Huerter JV, Quigley EM. Role of GERD in chronic resistant sinusitis: A prospective, open label, pilot trial. Am J Gastroenterol 2002;97:843-50.
(8.) Loehrl TA, Smith TL. Chronic sinusitis and gastroesophageal reflux: Are they related? Curr Opin Otolaryngol Head Neck Surg 2004; 12:18-20.
(9.) Weber RK, Jaspersen D, Keerl R, et al. [Gastroesophageal reflux disease and chronic sinusitis]. Laryngorhinootologie 2004;83: 189-95.
(10.) Koufman JA. Theotolarygologic manifestations of gastroesophageal reflux disease (GERD): A clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope 1991; 101 (4 pt 2 suppl 53): 1-78.
(11.) Koufman JA. Laryngopharyngeal reflux is different from classic gastroesophageal reflux disease. Ear Nose Throat J 2002;81 (suppl 2):7-9.
(12.) Chambers DW, Davis WE, Cook PR, et al. Long-term outcome analysis of functional endoscopic sinus surgery: Correlation of symptoms with endoscopic examination findings and potential prognostic variables. Laryngoscope 1997; 107:504-10.
(13.) Malthaner RA, Newman KD, Parry R, et al. Alkaline gastroesophageal reflux in infants and children. J Pediatr Surg 1991;26: 986-90.
(14.)Marshall RE, Anggiansah A, Owen WA, Owen WJ. The relationship between acid and bile reflux and symptoms in gastro-esophageal reflux disease. Gut 1997;40:182-7.
Robert L. Pincus, MD; Harold H. Kim, MD; Stacy Silvers, MD; Scott Gold, MD
From the New York Otolaryngology Group, New York City.
Reprint requests: Robert L. Pincus, MD, New York Otolaryngology Group, 36AE. 36th St., Suite 200, New York, NY 10016. Phone: (212) 889-8575, ext. 312; fax: (212) 686-3292; e-mail: robert. firstname.lastname@example.org
Table 1. Pretreatment profile of the study population Reflux Reflux Type Pt. Age/sex symptoms of reflux * 1 52/M No GERD/2 2 32/F No GERD/3 3 37/F No GERD/2 4 55/F Yes GERD/3 5 51/F Yes GERD/2 6 29/M Yes None/2 7 43/F No None/3 8 29/F No LPR/3 9 45/F No LPR/3 10 52/M No LPR/3 11 26/F No LPR/3 12 50/F Yes LPR/3 13 40/F Yes LPR/3 14 66/M Yes NPR/3 15 54/F Yes LPR/3 16 39/M Yes LPR/3 17 46/F Yes LPR/3 18 42/F Yes LPR/3 19 34/M Yes LPR/2 20 34/F No LPR/3 21 37/M Yes NPR/3 22 62/F No None/3 23 68/F Yes LPR/2 24 64/F Yes LPR/3 25 37/F Yes LPR/3 26 44/F Yes N/A 27 52/F No None/3 28 34/F No None/2 29 30/F No LPR/3 30 29/F Yes LPR/3 31 50/F Yes LPR/3 Sinusitis Nasal Nasal Headache/ Pt. congestion discharge facial pain 1 1 1 0 2 1 1 1 3 1 1 1 4 2 2 1 5 2 2 0 6 1 1 1 7 1 1 1 8 2 2 2 9 1 1 1 10 2 2 1 11 2 1 1 12 0 0 0 13 0 1 1 14 1 1 0 15 1 1 1 16 0 0 2 17 1 1 1 18 1 1 1 19 1 1 2 20 2 1 1 21 2 0 1 22 1 0 1 23 1 1 1 24 2 1 0 25 2 2 1 26 2 2 1 27 2 2 1 28 1 1 1 29 1 1 1 30 1 1 1 31 2 2 1 Sinusitis Sense Pre-Tx Pt. of smell sinus score 1 2 4 2 2 5 3 1 4 4 0 5 5 0 4 6 0 3 7 1 4 8 0 6 9 2 5 10 0 5 11 2 6 12 1 1 13 0 2 14 2 4 15 0 3 16 2 4 17 0 3 18 2 5 19 1 5 20 0 4 21 2 5 22 0 2 23 0 3 24 0 3 25 0 5 26 2 7 27 0 5 28 1 4 29 2 5 30 1 4 31 0 5 * The numeral in the "Type of reflux" column indicates whether a double (2) or triple (3) pH probe was used. The diagnoses of gastroesophageal reflux disease (GERD), laryngopharyngeal reflux (LPR), and nasopharyngeal reflux (NPR) are based on the most cephalad level that reflux was noted. "None" indicates than no reflux was noted. Patient 26 did not tolerate probe pH testing, and therefore it was not completed. Table 2. Posttreatment profile of the study population Reflux Nasal Nasal Headache/ Pt. symptoms congestion discharge facial pain 1 Never 1 0 0 2 Never 1 1 1 3 N/A N/A N/A N/A 4 Improved 1 0 0 5 Resolved 1 0 0 6 No change N/A N/A N/A 7 Never N/A N/A N/A 8 Never 2 2 1 9 Never 0 0 0 10 Never 2 2 0 11 Never 2 1 0 12 Resolved 0 0 0 13 No change 0 0 1 14 No change 1 1 0 15 Resolved 1 1 0 16 Improved 0 0 2 17 Resolved 1 1 0 18 Resolved 1 0 1 19 Resolved 0 0 1 20 Never 1 0 0 21 Improved 1 0 0 22 Never N/A N/A N/A 23 N/A N/A N/A N/A 24 No change 1 1 0 25 No change 2 2 0 26 N/A N/A N/A N/A 27 N/A N/A N/A N/A 28 N/A N/A N/A N/A 29 N/A N/A N/A N/A 30 N/A N/A N/A N/A 31 N/A N/A N/A N/A Sense Post-Tx Pre-Tx Completed Pt. of smell sinus score sinus score study? 1 1 2 4 Yes 2 2 5 5 Yes 3 N/A N/A 4 No, stopped taking meds 4 0 1 5 Yes 5 0 1 4 Yes 6 N/A N/A 3 No, no reflux 7 N/A N/A 4 No, no reflux 8 0 5 6 No, underwent surgery 9 1 1 5 No, stopped taking meds 10 0 4 5 No, stopped taking meds 11 0 3 6 Yes 12 0 0 1 Yes 13 0 1 2 Yes 14 1 3 4 Yes 15 0 2 3 Yes 16 1 3 4 Yes 17 0 2 3 Yes 18 1 3 5 Yes 19 0 1 5 Yes 20 0 1 4 Yes 21 0 1 5 Yes 22 N/A N/A 2 No, no reflux 23 N/A N/A 3 No, unavailable for follow-up 24 0 2 3 No, underwent surgery 25 0 4 5 No, stopped taking meds 26 N/A N/A 7 No, did not tolerate testing 27 N/A N/A 5 No, no reflux 28 N/A N/A 4 No, no reflux 29 N/A N/A 5 No, unavailable for follow-up 30 N/A N/A 4 No, unavailable for follow-up 31 N/A N/A 5 No, unavailable for follow-up