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Histologic versus pH probe results in pediatric laryngopharyngeal reflux
International Journal of Pediatric Otorhinolaryngology 77 (2013) 813–816
Contents lists available at SciVerse ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Histologic versus pH probe results in pediatric laryngopharyngeal reflux Thomas M. Andrews a,b,c,*, Nicklas Orobello d a
All Children’s Hospital/Johns Hopkins Medicine, St. Petersburg, FL, United States University of South Florida College of Medicine, Tampa, FL, United States c Pediatric Ear Nose and Throat Research Foundation, Inc., PO Box 76479, St. Petersburg, FL 33734-6479, United States d Davidson University, Davidson, NC 28036, United States b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 November 2012 Received in revised form 12 February 2013 Accepted 13 February 2013 Available online 13 March 2013
Objective: A comparison of histologic findings from the post-cricoid region versus nasopharyngeal pH probe results in the diagnosis of laryngopharyngeal reflux (LPR) in the pediatric patient. Study design: Retrospective review. Setting: Outpatient pediatric otolaryngology private practice. Subject and methods: 63 consecutive patients, age 6-months to 17-years between June 1, 2009 and October 6, 2010, tested by simultaneous post cricoid biopsy and nasopharyngeal pH probe monitoring using the Restech Dx-pH Measurement System (Respiratory Technology Corporation, San Diego, CA). Results: Of the 63 total patients (age 6-months to 17-years), 11 (17%) were excluded due to a pulled probe, one additional patient did not have a biopsy taken and one probe failed after insertion making a total of 50 patients with complete data sets. Thirty-six of those 50 patients had a positive probe with a negative biopsy (72%). Four (8%) had both a positive probe and biopsy and 10 (16%) had a negative probe and negative biopsy. No patients had a negative probe and positive biopsy. Symptoms used to identify patients suspected of reflux included: throat clearing, nasal congestion, cough, history of recurrent sinusitis with negative radiographic findings, halitosis, culture negative sore throat, post nasal drip, otalgia, poor appetite and stomach ache. Conclusion: Eighty percent of our patients (40) were either positive for reflux by pH probe or by pH probe and biopsy. The Restech Dx-pH Measurement System appeared to be well tolerated in all age groups. There were no complications. We found this a useful tool in confirming clinical suspicion of LPR. ß 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Reflux Laryngopharyngeal reflux Pharyngeal reflux pH probe GERD Nasal congestion Pediatric Children
1. Introduction Laryngopharyngeal reflux (LPR), has had many names in the past (extra esophageal reflux, pharyngeal reflux and supraesophageal reflux) and there is strong clinical evidence to suggest that LPR is an entity perhaps quite separate from gastroesophageal reflux (GERD) with its myriad of esophageal symptoms and wellestablished diagnostic criteria consisting of double-lumen esophageal pH probe and histology [1]. Controversy and confusion have arisen from the difficulty in making a firm diagnosis of LPR because the initial methods were an extension of the techniques used to diagnose gastroesophageal reflux. Hence, normative values and diagnostic thresholds did not seem to apply to reflux above the level of the upper esophageal sphincter. As Otolaryngologists, we
* Corresponding author at: Pediatric Ear Nose and Throat Research Foundation, Inc., PO Box 76479, St. Petersburg, FL 33734-6479, United States. Tel.: +1 727 329 5400; fax: +1 727 802 8962. E-mail address: [email protected] (T.M. Andrews). 0165-5876/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijporl.2013.02.017
are constantly faced with pediatric patients who may have reflux and present with a wide range of symptoms that defy conventional therapies. These symptoms may include: hoarseness, cough, throat clearing, otalgia, halitosis, chronic sore throat and radiographically negative sinus symptoms [2–5]. There appears to be a statistically significant association between reflux and laryngomalacia [6,7] and vocal cord nodules [2]. There has also been an association with poor wound healing in the treatment of laryngotracheal reconstruction that has led to the suspicion of reflux playing a significant role [8]. In working with the pediatric population, we found it difficult to obtain accurate data concerning LPR based on dual pH probe results and therefore turned to histologic examination of the post cricoid tissue as an indicator for LPR [7,9]. Based on previous work in patients with laryngotracheoplasty [8], we harvested post cricoid biopsies looking for histologic changes of basal cell hyperplasia, eosinophilic penetration, or elongation of rete pegs [9]. Clinically however, this method seemed somewhat unsatisfactory because several patients who had negative biopsies continued with symptoms leading to empiric reflux therapy that
814
T.M. Andrews, N. Orobello / International Journal of Pediatric Otorhinolaryngology 77 (2013) 813–816
anecdotally seemed to work. We therefore incorporated placement of the nasopharyngeal pH probe into our clinical evaluation process in 2009. In hopes of beginning a prospective study to determine the normative values for this probe, we retrospectively reviewed patients from the end of 2009 through October 2010 that had undergone posterior cricoid biopsy and nasopharyngeal pH probe placement simultaneously. Our hypothesis was that pH probe monitoring would allow the identification of a greater number of patients thought to have LPR than biopsy alone.
2. Methods Starting in October of 2010 we retrospectively reviewed all patients who underwent placement of the pH probe from the inception of that protocol in our practice (June 2009). Institutional IRB approval was obtained to collect the retrospective data. Our IRB strongly suggested that a prospective study to establish normative data in children would be difficult without at least a pilot study, such as this, to precede it. Patients were selected based on the following symptoms: chronic dry cough, throat clearing, chronic nasal congestion with negative allergy workup, history of recurrent sinusitis with negative radiographic findings, halitosis, culture negative sore throat, post nasal drip, otalgia, poor appetite and stomach ache (Table 1). Cases with an isolated complaint of hoarseness were not included since our practice policy is to evaluate those patients endoscopically, and, if vocal cord nodules or edema is present, start them on reflux therapy empirically. Many patients were having concomitant operative procedures, specifically: tympanostomy tube insertion, adenoidectomy and/or tonsillectomy, sinus culture and in one case endoscopic sinus surgery (Table 2). A few patients had previous surgery for recurrent sinusitis after which they continued to have symptoms of nasal obstruction, cough, and post nasal drip (Table 3). After pre-op teaching, the Dx-pH Measurement System (Respiratory Technology Corporation, San Diego, CA) a nasopharyngeal pH probe, was inserted under a general anesthetic. The probe was calibrated in pH 4 and 7 buffer solution per manufacturer’s protocol. The probe was inserted into the nasal cavity and the teardrop shaped probe with the blinking red LED could be easily visualized in the oral pharynx at the level of the soft palate/uvula. Once in place the probe was then taped to the
Table 3 Surgery prior to pH probe. Tonsil and/or adenoid None PET Sinus cultures FESS
24/50 22/50 21/50 12/50 3/50
ipsilateral cheek, around the ear and then taped to the neck. This 1.5 mm probe is connected to a wireless transmitter. The transmitting device was then clipped to the patient’s clothing and the wireless recording box was included with the patient to the recovery room where patient/parent education was undertaken for a second time. These data are recorded via a monitor (wireless) that must stay within approximately 20 ft of the patient. Patient data are collected on an SD memory card with corresponding input by parent or patient pressing a button on the monitor for meals, supine positioning and where applicable symptoms such as cough or throat clearing (Fig. 1). The patients were discharged from the outpatient recovery room to home with both written and verbal instructions as well as a patient diary to record events and meals. The patient returned the following day, approximately 24-h later, at which time the probe was removed in the office without difficulty. Most patients tolerated the probe well. Analysis was performed using proprietary software (Data View AEMC Instruments, Foxborough, MA) on a password protected computer used only for these patients. A written report and 24-h graph were generated of the patient’s results. Meals and acidic beverages were eliminated. Because no normal values exist for this age group, reflux was considered present if there was a rapid (0.5–2 s) vertical pH drop, signifying a >3 standard deviation from baseline [10]. The device records result every 0.5 s. Comparative graphs are shown in Fig. 2. Data gathered from the electronic medical record included patient’s initials, date of birth, age at the time of the procedure, sex, date of procedure, results of the pH probe, results of the post cricoid biopsy, any concomitant operative procedures performed, and, where applicable, follow up visits revealing the continuation or resolution of symptoms. Each patient was then assigned a research number. These files were kept in a separate secure location not associated with the patient’s electronic medical record.
[(Fig._1)TD$IG] Table 1 Symptoms of patients with complete data. Nasal congestion Cough PND Otalgia Halitosis Sore throat Poor appetite Recurrent sinusitis Stomach ache Burping
38/50 27/50 20/50 15/50 9/50 8/50 7/50 5/50 5/50 0/50
Table 2 Simultaneous surgeries. Sinus culture None PET Tonsillectomy Adenoidectomy alone Tonsil and adenoid FESS
23/50 11/50 10/50 5/50 4/50 4/50 1/50
Fig. 1. The Restech Dx-pH Measurement System with wireless receiver pictured with probe and attached transmitter.
[(Fig._2)TD$IG]
T.M. Andrews, N. Orobello / International Journal of Pediatric Otorhinolaryngology 77 (2013) 813–816
815
Fig. 2. A representative graph from a patient with positive findings for reflux (A) and a graph representing negative results (B).
3. Results Between June 2009 and October 2010 a total of 63 patients underwent placement of a nasopharyngeal pH probe. The age range was between 6-months and 17-years. Of the 63 patients, 10 probes were pulled resulting in no data. Three of these were pulled in the recovery room, 7 were pulled at home. Of the 3 pulled in the recovery room, the ages were 2, 5 and 8 years. Those pulled at home included 2 patients under 12-months, 2 patients who were 1-year of age, 1 who was 21-months and 2 who were 3 and 8 years old. One of the 63 probes failed after insertion and therefore no data was obtained. Three of the 63 (5%) did not have the post cricoid biopsy done and therefore were excluded. All eleven patients with a history of a pulled or failed pH probe were excluded (17%), two of these 11 did not have biopsies done, and one of the 11 patients had a probe that failed after insertion (1.5%). Of the 50 remaining patients, 36 (72%) had a positive pH probe with a negative histologic biopsy, 4 (8%) had a positive pH probe and a positive biopsy, 10 (16%) had a negative pH probe and a negative biopsy. No patients had a positive biopsy with a negative probe. Of the 50 patients with complete data sets, 35 were male and 15 were female. Of those 35 male patients, 28 or (80%) were positive for reflux by pH probe. Of the females, 12 of the 15 (80%) were positive for reflux by pH probe. Of the 50 patients with complete data sets, 40 were positive for reflux. Of those 40 patients with positive reflux by pH probe, only
four (three females and one male) also had a post cricoid biopsy with findings of reflux (Table 1). Thirty-eight were treated with a proton-pump inhibitor (PPI) and two were treated with a combination of PPI and H2 blocker. One of these on combination therapy was referred to GI for breakthrough symptoms. Seventeen of the 50 patients were lost to follow-up (34%). Follow-up for the remaining 23 (46%) ranged from 2 to 21 months with an average (median) of 15-months. 18 had resolved their symptoms (78%) and five did not (22%). 4. Discussion It is not surprising that a vast majority of our patients with complete data (40/50, 80%) were positive for reflux. These patients were originally selected based on a clinical suspicion of reflux having one or more of a spectrum of symptoms including but not limited to: dry cough, throat clearing, post-nasal drip, culture negative sore throat, history of recurrent sinusitis with negative radiographic studies, history of otalgia, halitosis, poor appetite or chronic nasal congestion. These symptoms have become well recognized as suggestive of LPR. Both the otolaryngology literature [1] and the gastroenterology literature [11–14] have noted the clinical and pH probe findings suggestive of reflux superior to the upper esophageal sphincter. Therefore, we propose that the disease process of LPR is no longer controversial, rather, the confusion lies in the accurate diagnosis of these patients. While recent studies [15,16] have
816
T.M. Andrews, N. Orobello / International Journal of Pediatric Otorhinolaryngology 77 (2013) 813–816
demonstrated normative data utilizing the Dx-pH Measurement System, there has been no normative data gathered for the pediatric population. This population is consistently problematic to establish normative data due to the difficulty in establishing minimally invasive protocols that meet IRB approval. Secondly, many of the symptoms of LPR which are subtle in the pediatric age group and mimic symptoms normally associated with common upper respiratory infections. LPR has been associated with Eustachian tube dysfunction [4], chronic sinus disease [3], otitis media [5], vocal cord nodules and hoarseness [1] and especially, laryngomalacia [6]. These associations illustrate the significant morbidity LPR can have for the pediatric patient. While it has been established that intraepithelial eosinophilia is pathognomonic for esophageal reflux [9], LPR can be associated with one or all of the following three histologic pictures: basal cell hyperplasia, chronic inflammation or elongation of the rete pegs [7,8] although none are pathognomonic for the disease. In some cases multiple biopsies have been shown to be illustrative of LPR even when histologic changes superior to the upper esophageal sphincter are negative [17]. Recent studies have demonstrated symptomatic reflux into the oropharynx in adults have a higher pH (median 5.6) as opposed to the more acidic pH (less than 4) associated with esophageal reflux [10]. Intuitively, this makes sense as the histologic make-up of the respiratory epithelium above the upper esophageal sphincter is less substantial and therefore more susceptible to a weakly acidic environment. This seems to be confirmed by normative data in adults for this same device which demonstrates a significantly lower percentage of time that the pH is less than 4 in the oral pharynx (0.02%) as compared with double lumen pH probes when the upper port is just superior to the upper esophageal sphincter [16]. Using a modified version of the mucousal biopsy grading scale previously discussed in comparing the post cricoid biopsy with pH probe results [8], we had been relying solely on histologic diagnosis for LPR for several years. In the last 2-years however, we began using the Dx-pH Measurement System in conjunction with post cricoid biopsies in the hopes of eliminating what were thought to be false negative biopsies. This study has several limitations, the first of which is its retrospective nature and high rate of patients lost to follow-up. The retrospective nature of the study precludes eliminating comorbidities and controlling for variables such as simultaneous routine surgeries. In addition, there has been no definitive evidence that histologic biopsy proves the presence (or absence) of LPR. Most notably, there is no normative data for the nasopharyngeal probe in the pediatric population to compare results. Because normative data have been established in adults with the same instrument, our goal is to provide the same normative data for the pediatric patient. In preparation for that prospective study, our review of these 50 patients undergoing simultaneous post cricoid biopsy and pH probe testing has allowed us to make several observations. First, it appears that the pH probe is much more frequently positive than the post cricoid histology. Within this group of positive responders, a high percentage (78%) resolved their symptoms with appropriate therapy. The follow-up, although short, should be long enough to allow adequate interpretation of response to therapy. Without normative data for this age group, we used diagnostic criteria established with the proprietary software that accompanied the Dx-pH probe Measurement System. We considered a positive event when there was a rapid pH drop of greater than 3 standard deviations from the running pH baseline as described in a previous study [10].
This device is uniquely suited for children due to its design with a 1.5 mm diameter and a 3.2 mm teardrop tip which is easy to insert. Because of its placement at the level of the soft palate, the patient does not complain of dysphagia, gagging or discomfort in the throat with swallowing. We place the probe while children are under general anesthesia for other procedures making the insertion painless. The only complaints about the probe were the removal of the adhesive on the cheek and neck after 24-h of use. The probe is well tolerated in children as young as 7-months, for a full 24-h. In this younger age group there is no doubt that the success of the probe is due in large part to the active participation of willing parent(s). Although there was a male predominance, the percentage of positive testing was identical in both groups (80%). Moving forward it is our hope to conduct a normative value study for this instrument in children that will further enhance both the appropriate use of the data obtained by this probe as well as a better understanding of the prevalence of LPR in children. Acknowledgements The authors gratefully acknowledges the hard work and assistance of Ms. Samantha Williams, Clinical Research Coordinator, Pediatric Ear, Nose, and Throat Research Foundation, Inc., for data management, patient education and editorial help with this manuscript. We would also like to thank Lesli Williams for manuscript preparation. References [1] J.A. Koufman, J.E. Aviv, R.R. Casiano, et al., Laryngopharyngeal reflux: position statement of the committee on speech, voice and swallowing disorders of the American academy of otolaryngology – head and neck surgery, Otolaryngol. Head Neck Surg. 127 (2002) 32–35. [2] J. Kuhn, R.J. Toohill, S.O. Ulualp, et al., Pharyngeal acid reflux events in patients with vocal cord nodules, Laryngoscope 108 (1998) 1146–1149. [3] C.D. Phipps, W.E. Wood, W.S. Gibson, et al., Gastroesophageal reflux contributing to chronic sinus disease in children, Arch. Otolaryngol. Head Neck Surg. 126 (2000) 831–836. [4] D.R. White, S.B. Heavner, S.M. Hardy, et al., Gastroesophageal reflux and Eustachian tube dysfunction in an animal model, Laryngoscope 112 (2002) 955–961. [5] A. Tasker, P.W. Dettmar, M. Panetti, et al., Is gastric reflux a cause of otitis media with effusion in children, Laryngoscope 112 (2002) 1930–1934. [6] B.L. Matthews, J.P. Little, W.E. McGuirt, et al., Reflux in infants with laryngomalacia: results of 24-hour double probe pH monitoring, Otolaryngol. Head Neck Surg. 120 (1999) 860–864. [7] V.K. Iyer, K. Pearman, F. Raafat, Laryngeal mucosal histology in laryngomalacia: the evidence for gastro-oesophageal reflux laryngitis, Int. J. Pediatr. Otorhinolaryngol. 49 (1999) 225–230. [8] J.S. McMurray, M. Gerber, Y. Stern, et al., Role of laryngoscopy, dual pH probe monitoring, and laryngeal mucosal biopsy in the diagnosis of pharyngoesophageal reflux, Ann. Otol. Rhinol. Laryngol. 110 (2001) 299–304. [9] H.S. Winter, J.L. Madara, R.J. Stafford, et al., Intraephithelial eosinophils: a new diagnostic criterion for reflux esophagitis, Gastroenterology 88 (1982) 818–823. [10] G.J. Wiener, R. Tsukashima, C. Kelly, et al., Oropharyngeal pH monitoring for the detection of liquid and aerosolized supraesophageal gastric reflux, J. Voice 23 (2009) 498–546. [11] P. Jacob, P.J. Kahrilas, G. Herzon, Proximal esophageal pH-metry in patients with reflux laryngitis, Gastroenterology 100 (1991) 305–310. [12] M.F. Vaezi, P.L. Schroeder, J.E. Richter, Reproducibility of proximal probe pH parameters in 24-hour ambulatory esophageal pH monitoring, Am. J. Gastroenterol. 92 (1997) 825–829. [13] M. Cool, J. Poelmans, L. Feenstra, et al., Characteristics and clinical relevance of proximal esophageal pH monitoring, Am. J. Gastroenterol. 99 (2004) 2317–2323. [14] H. Ikuo, J.E. Richter, ACG practice guidelines: esophageal reflux testing, Am. J. Gastroenterol. 702 (2002) 668–685. [15] N.N. Chheda, M.W. Seybt, R.R. Schade, et al., Normal values for pharyngeal pH monitoring, Ann. Otol. Rhinol. Laryngol. 118 (2009) 166–171. [16] G. Sun, S. Muddana, J.C. Slaughter, et al., A new pH catheter for laryngopharyngeal reflux: normal values, Laryngoscope 119 (2009) 1639–1643. [17] R. Mitzner, L. Brodsky, Multilevel esophageal biopsy in children with airway manifestations of extraesophageal reflux disease, Ann. Otol. Rhinol. Laryngol. 116 (2007) 571–575.
Contents lists available at SciVerse ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Histologic versus pH probe results in pediatric laryngopharyngeal reflux Thomas M. Andrews a,b,c,*, Nicklas Orobello d a
All Children’s Hospital/Johns Hopkins Medicine, St. Petersburg, FL, United States University of South Florida College of Medicine, Tampa, FL, United States c Pediatric Ear Nose and Throat Research Foundation, Inc., PO Box 76479, St. Petersburg, FL 33734-6479, United States d Davidson University, Davidson, NC 28036, United States b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 November 2012 Received in revised form 12 February 2013 Accepted 13 February 2013 Available online 13 March 2013
Objective: A comparison of histologic findings from the post-cricoid region versus nasopharyngeal pH probe results in the diagnosis of laryngopharyngeal reflux (LPR) in the pediatric patient. Study design: Retrospective review. Setting: Outpatient pediatric otolaryngology private practice. Subject and methods: 63 consecutive patients, age 6-months to 17-years between June 1, 2009 and October 6, 2010, tested by simultaneous post cricoid biopsy and nasopharyngeal pH probe monitoring using the Restech Dx-pH Measurement System (Respiratory Technology Corporation, San Diego, CA). Results: Of the 63 total patients (age 6-months to 17-years), 11 (17%) were excluded due to a pulled probe, one additional patient did not have a biopsy taken and one probe failed after insertion making a total of 50 patients with complete data sets. Thirty-six of those 50 patients had a positive probe with a negative biopsy (72%). Four (8%) had both a positive probe and biopsy and 10 (16%) had a negative probe and negative biopsy. No patients had a negative probe and positive biopsy. Symptoms used to identify patients suspected of reflux included: throat clearing, nasal congestion, cough, history of recurrent sinusitis with negative radiographic findings, halitosis, culture negative sore throat, post nasal drip, otalgia, poor appetite and stomach ache. Conclusion: Eighty percent of our patients (40) were either positive for reflux by pH probe or by pH probe and biopsy. The Restech Dx-pH Measurement System appeared to be well tolerated in all age groups. There were no complications. We found this a useful tool in confirming clinical suspicion of LPR. ß 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Reflux Laryngopharyngeal reflux Pharyngeal reflux pH probe GERD Nasal congestion Pediatric Children
1. Introduction Laryngopharyngeal reflux (LPR), has had many names in the past (extra esophageal reflux, pharyngeal reflux and supraesophageal reflux) and there is strong clinical evidence to suggest that LPR is an entity perhaps quite separate from gastroesophageal reflux (GERD) with its myriad of esophageal symptoms and wellestablished diagnostic criteria consisting of double-lumen esophageal pH probe and histology [1]. Controversy and confusion have arisen from the difficulty in making a firm diagnosis of LPR because the initial methods were an extension of the techniques used to diagnose gastroesophageal reflux. Hence, normative values and diagnostic thresholds did not seem to apply to reflux above the level of the upper esophageal sphincter. As Otolaryngologists, we
* Corresponding author at: Pediatric Ear Nose and Throat Research Foundation, Inc., PO Box 76479, St. Petersburg, FL 33734-6479, United States. Tel.: +1 727 329 5400; fax: +1 727 802 8962. E-mail address: [email protected] (T.M. Andrews). 0165-5876/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijporl.2013.02.017
are constantly faced with pediatric patients who may have reflux and present with a wide range of symptoms that defy conventional therapies. These symptoms may include: hoarseness, cough, throat clearing, otalgia, halitosis, chronic sore throat and radiographically negative sinus symptoms [2–5]. There appears to be a statistically significant association between reflux and laryngomalacia [6,7] and vocal cord nodules [2]. There has also been an association with poor wound healing in the treatment of laryngotracheal reconstruction that has led to the suspicion of reflux playing a significant role [8]. In working with the pediatric population, we found it difficult to obtain accurate data concerning LPR based on dual pH probe results and therefore turned to histologic examination of the post cricoid tissue as an indicator for LPR [7,9]. Based on previous work in patients with laryngotracheoplasty [8], we harvested post cricoid biopsies looking for histologic changes of basal cell hyperplasia, eosinophilic penetration, or elongation of rete pegs [9]. Clinically however, this method seemed somewhat unsatisfactory because several patients who had negative biopsies continued with symptoms leading to empiric reflux therapy that
814
T.M. Andrews, N. Orobello / International Journal of Pediatric Otorhinolaryngology 77 (2013) 813–816
anecdotally seemed to work. We therefore incorporated placement of the nasopharyngeal pH probe into our clinical evaluation process in 2009. In hopes of beginning a prospective study to determine the normative values for this probe, we retrospectively reviewed patients from the end of 2009 through October 2010 that had undergone posterior cricoid biopsy and nasopharyngeal pH probe placement simultaneously. Our hypothesis was that pH probe monitoring would allow the identification of a greater number of patients thought to have LPR than biopsy alone.
2. Methods Starting in October of 2010 we retrospectively reviewed all patients who underwent placement of the pH probe from the inception of that protocol in our practice (June 2009). Institutional IRB approval was obtained to collect the retrospective data. Our IRB strongly suggested that a prospective study to establish normative data in children would be difficult without at least a pilot study, such as this, to precede it. Patients were selected based on the following symptoms: chronic dry cough, throat clearing, chronic nasal congestion with negative allergy workup, history of recurrent sinusitis with negative radiographic findings, halitosis, culture negative sore throat, post nasal drip, otalgia, poor appetite and stomach ache (Table 1). Cases with an isolated complaint of hoarseness were not included since our practice policy is to evaluate those patients endoscopically, and, if vocal cord nodules or edema is present, start them on reflux therapy empirically. Many patients were having concomitant operative procedures, specifically: tympanostomy tube insertion, adenoidectomy and/or tonsillectomy, sinus culture and in one case endoscopic sinus surgery (Table 2). A few patients had previous surgery for recurrent sinusitis after which they continued to have symptoms of nasal obstruction, cough, and post nasal drip (Table 3). After pre-op teaching, the Dx-pH Measurement System (Respiratory Technology Corporation, San Diego, CA) a nasopharyngeal pH probe, was inserted under a general anesthetic. The probe was calibrated in pH 4 and 7 buffer solution per manufacturer’s protocol. The probe was inserted into the nasal cavity and the teardrop shaped probe with the blinking red LED could be easily visualized in the oral pharynx at the level of the soft palate/uvula. Once in place the probe was then taped to the
Table 3 Surgery prior to pH probe. Tonsil and/or adenoid None PET Sinus cultures FESS
24/50 22/50 21/50 12/50 3/50
ipsilateral cheek, around the ear and then taped to the neck. This 1.5 mm probe is connected to a wireless transmitter. The transmitting device was then clipped to the patient’s clothing and the wireless recording box was included with the patient to the recovery room where patient/parent education was undertaken for a second time. These data are recorded via a monitor (wireless) that must stay within approximately 20 ft of the patient. Patient data are collected on an SD memory card with corresponding input by parent or patient pressing a button on the monitor for meals, supine positioning and where applicable symptoms such as cough or throat clearing (Fig. 1). The patients were discharged from the outpatient recovery room to home with both written and verbal instructions as well as a patient diary to record events and meals. The patient returned the following day, approximately 24-h later, at which time the probe was removed in the office without difficulty. Most patients tolerated the probe well. Analysis was performed using proprietary software (Data View AEMC Instruments, Foxborough, MA) on a password protected computer used only for these patients. A written report and 24-h graph were generated of the patient’s results. Meals and acidic beverages were eliminated. Because no normal values exist for this age group, reflux was considered present if there was a rapid (0.5–2 s) vertical pH drop, signifying a >3 standard deviation from baseline [10]. The device records result every 0.5 s. Comparative graphs are shown in Fig. 2. Data gathered from the electronic medical record included patient’s initials, date of birth, age at the time of the procedure, sex, date of procedure, results of the pH probe, results of the post cricoid biopsy, any concomitant operative procedures performed, and, where applicable, follow up visits revealing the continuation or resolution of symptoms. Each patient was then assigned a research number. These files were kept in a separate secure location not associated with the patient’s electronic medical record.
[(Fig._1)TD$IG] Table 1 Symptoms of patients with complete data. Nasal congestion Cough PND Otalgia Halitosis Sore throat Poor appetite Recurrent sinusitis Stomach ache Burping
38/50 27/50 20/50 15/50 9/50 8/50 7/50 5/50 5/50 0/50
Table 2 Simultaneous surgeries. Sinus culture None PET Tonsillectomy Adenoidectomy alone Tonsil and adenoid FESS
23/50 11/50 10/50 5/50 4/50 4/50 1/50
Fig. 1. The Restech Dx-pH Measurement System with wireless receiver pictured with probe and attached transmitter.
[(Fig._2)TD$IG]
T.M. Andrews, N. Orobello / International Journal of Pediatric Otorhinolaryngology 77 (2013) 813–816
815
Fig. 2. A representative graph from a patient with positive findings for reflux (A) and a graph representing negative results (B).
3. Results Between June 2009 and October 2010 a total of 63 patients underwent placement of a nasopharyngeal pH probe. The age range was between 6-months and 17-years. Of the 63 patients, 10 probes were pulled resulting in no data. Three of these were pulled in the recovery room, 7 were pulled at home. Of the 3 pulled in the recovery room, the ages were 2, 5 and 8 years. Those pulled at home included 2 patients under 12-months, 2 patients who were 1-year of age, 1 who was 21-months and 2 who were 3 and 8 years old. One of the 63 probes failed after insertion and therefore no data was obtained. Three of the 63 (5%) did not have the post cricoid biopsy done and therefore were excluded. All eleven patients with a history of a pulled or failed pH probe were excluded (17%), two of these 11 did not have biopsies done, and one of the 11 patients had a probe that failed after insertion (1.5%). Of the 50 remaining patients, 36 (72%) had a positive pH probe with a negative histologic biopsy, 4 (8%) had a positive pH probe and a positive biopsy, 10 (16%) had a negative pH probe and a negative biopsy. No patients had a positive biopsy with a negative probe. Of the 50 patients with complete data sets, 35 were male and 15 were female. Of those 35 male patients, 28 or (80%) were positive for reflux by pH probe. Of the females, 12 of the 15 (80%) were positive for reflux by pH probe. Of the 50 patients with complete data sets, 40 were positive for reflux. Of those 40 patients with positive reflux by pH probe, only
four (three females and one male) also had a post cricoid biopsy with findings of reflux (Table 1). Thirty-eight were treated with a proton-pump inhibitor (PPI) and two were treated with a combination of PPI and H2 blocker. One of these on combination therapy was referred to GI for breakthrough symptoms. Seventeen of the 50 patients were lost to follow-up (34%). Follow-up for the remaining 23 (46%) ranged from 2 to 21 months with an average (median) of 15-months. 18 had resolved their symptoms (78%) and five did not (22%). 4. Discussion It is not surprising that a vast majority of our patients with complete data (40/50, 80%) were positive for reflux. These patients were originally selected based on a clinical suspicion of reflux having one or more of a spectrum of symptoms including but not limited to: dry cough, throat clearing, post-nasal drip, culture negative sore throat, history of recurrent sinusitis with negative radiographic studies, history of otalgia, halitosis, poor appetite or chronic nasal congestion. These symptoms have become well recognized as suggestive of LPR. Both the otolaryngology literature [1] and the gastroenterology literature [11–14] have noted the clinical and pH probe findings suggestive of reflux superior to the upper esophageal sphincter. Therefore, we propose that the disease process of LPR is no longer controversial, rather, the confusion lies in the accurate diagnosis of these patients. While recent studies [15,16] have
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T.M. Andrews, N. Orobello / International Journal of Pediatric Otorhinolaryngology 77 (2013) 813–816
demonstrated normative data utilizing the Dx-pH Measurement System, there has been no normative data gathered for the pediatric population. This population is consistently problematic to establish normative data due to the difficulty in establishing minimally invasive protocols that meet IRB approval. Secondly, many of the symptoms of LPR which are subtle in the pediatric age group and mimic symptoms normally associated with common upper respiratory infections. LPR has been associated with Eustachian tube dysfunction [4], chronic sinus disease [3], otitis media [5], vocal cord nodules and hoarseness [1] and especially, laryngomalacia [6]. These associations illustrate the significant morbidity LPR can have for the pediatric patient. While it has been established that intraepithelial eosinophilia is pathognomonic for esophageal reflux [9], LPR can be associated with one or all of the following three histologic pictures: basal cell hyperplasia, chronic inflammation or elongation of the rete pegs [7,8] although none are pathognomonic for the disease. In some cases multiple biopsies have been shown to be illustrative of LPR even when histologic changes superior to the upper esophageal sphincter are negative [17]. Recent studies have demonstrated symptomatic reflux into the oropharynx in adults have a higher pH (median 5.6) as opposed to the more acidic pH (less than 4) associated with esophageal reflux [10]. Intuitively, this makes sense as the histologic make-up of the respiratory epithelium above the upper esophageal sphincter is less substantial and therefore more susceptible to a weakly acidic environment. This seems to be confirmed by normative data in adults for this same device which demonstrates a significantly lower percentage of time that the pH is less than 4 in the oral pharynx (0.02%) as compared with double lumen pH probes when the upper port is just superior to the upper esophageal sphincter [16]. Using a modified version of the mucousal biopsy grading scale previously discussed in comparing the post cricoid biopsy with pH probe results [8], we had been relying solely on histologic diagnosis for LPR for several years. In the last 2-years however, we began using the Dx-pH Measurement System in conjunction with post cricoid biopsies in the hopes of eliminating what were thought to be false negative biopsies. This study has several limitations, the first of which is its retrospective nature and high rate of patients lost to follow-up. The retrospective nature of the study precludes eliminating comorbidities and controlling for variables such as simultaneous routine surgeries. In addition, there has been no definitive evidence that histologic biopsy proves the presence (or absence) of LPR. Most notably, there is no normative data for the nasopharyngeal probe in the pediatric population to compare results. Because normative data have been established in adults with the same instrument, our goal is to provide the same normative data for the pediatric patient. In preparation for that prospective study, our review of these 50 patients undergoing simultaneous post cricoid biopsy and pH probe testing has allowed us to make several observations. First, it appears that the pH probe is much more frequently positive than the post cricoid histology. Within this group of positive responders, a high percentage (78%) resolved their symptoms with appropriate therapy. The follow-up, although short, should be long enough to allow adequate interpretation of response to therapy. Without normative data for this age group, we used diagnostic criteria established with the proprietary software that accompanied the Dx-pH probe Measurement System. We considered a positive event when there was a rapid pH drop of greater than 3 standard deviations from the running pH baseline as described in a previous study [10].
This device is uniquely suited for children due to its design with a 1.5 mm diameter and a 3.2 mm teardrop tip which is easy to insert. Because of its placement at the level of the soft palate, the patient does not complain of dysphagia, gagging or discomfort in the throat with swallowing. We place the probe while children are under general anesthesia for other procedures making the insertion painless. The only complaints about the probe were the removal of the adhesive on the cheek and neck after 24-h of use. The probe is well tolerated in children as young as 7-months, for a full 24-h. In this younger age group there is no doubt that the success of the probe is due in large part to the active participation of willing parent(s). Although there was a male predominance, the percentage of positive testing was identical in both groups (80%). Moving forward it is our hope to conduct a normative value study for this instrument in children that will further enhance both the appropriate use of the data obtained by this probe as well as a better understanding of the prevalence of LPR in children. Acknowledgements The authors gratefully acknowledges the hard work and assistance of Ms. Samantha Williams, Clinical Research Coordinator, Pediatric Ear, Nose, and Throat Research Foundation, Inc., for data management, patient education and editorial help with this manuscript. We would also like to thank Lesli Williams for manuscript preparation. References [1] J.A. Koufman, J.E. Aviv, R.R. Casiano, et al., Laryngopharyngeal reflux: position statement of the committee on speech, voice and swallowing disorders of the American academy of otolaryngology – head and neck surgery, Otolaryngol. Head Neck Surg. 127 (2002) 32–35. [2] J. Kuhn, R.J. Toohill, S.O. Ulualp, et al., Pharyngeal acid reflux events in patients with vocal cord nodules, Laryngoscope 108 (1998) 1146–1149. [3] C.D. Phipps, W.E. Wood, W.S. Gibson, et al., Gastroesophageal reflux contributing to chronic sinus disease in children, Arch. Otolaryngol. Head Neck Surg. 126 (2000) 831–836. [4] D.R. White, S.B. Heavner, S.M. Hardy, et al., Gastroesophageal reflux and Eustachian tube dysfunction in an animal model, Laryngoscope 112 (2002) 955–961. [5] A. Tasker, P.W. Dettmar, M. Panetti, et al., Is gastric reflux a cause of otitis media with effusion in children, Laryngoscope 112 (2002) 1930–1934. [6] B.L. Matthews, J.P. Little, W.E. McGuirt, et al., Reflux in infants with laryngomalacia: results of 24-hour double probe pH monitoring, Otolaryngol. Head Neck Surg. 120 (1999) 860–864. [7] V.K. Iyer, K. Pearman, F. Raafat, Laryngeal mucosal histology in laryngomalacia: the evidence for gastro-oesophageal reflux laryngitis, Int. J. Pediatr. Otorhinolaryngol. 49 (1999) 225–230. [8] J.S. McMurray, M. Gerber, Y. Stern, et al., Role of laryngoscopy, dual pH probe monitoring, and laryngeal mucosal biopsy in the diagnosis of pharyngoesophageal reflux, Ann. Otol. Rhinol. Laryngol. 110 (2001) 299–304. [9] H.S. Winter, J.L. Madara, R.J. Stafford, et al., Intraephithelial eosinophils: a new diagnostic criterion for reflux esophagitis, Gastroenterology 88 (1982) 818–823. [10] G.J. Wiener, R. Tsukashima, C. Kelly, et al., Oropharyngeal pH monitoring for the detection of liquid and aerosolized supraesophageal gastric reflux, J. Voice 23 (2009) 498–546. [11] P. Jacob, P.J. Kahrilas, G. Herzon, Proximal esophageal pH-metry in patients with reflux laryngitis, Gastroenterology 100 (1991) 305–310. [12] M.F. Vaezi, P.L. Schroeder, J.E. Richter, Reproducibility of proximal probe pH parameters in 24-hour ambulatory esophageal pH monitoring, Am. J. Gastroenterol. 92 (1997) 825–829. [13] M. Cool, J. Poelmans, L. Feenstra, et al., Characteristics and clinical relevance of proximal esophageal pH monitoring, Am. J. Gastroenterol. 99 (2004) 2317–2323. [14] H. Ikuo, J.E. Richter, ACG practice guidelines: esophageal reflux testing, Am. J. Gastroenterol. 702 (2002) 668–685. [15] N.N. Chheda, M.W. Seybt, R.R. Schade, et al., Normal values for pharyngeal pH monitoring, Ann. Otol. Rhinol. Laryngol. 118 (2009) 166–171. [16] G. Sun, S. Muddana, J.C. Slaughter, et al., A new pH catheter for laryngopharyngeal reflux: normal values, Laryngoscope 119 (2009) 1639–1643. [17] R. Mitzner, L. Brodsky, Multilevel esophageal biopsy in children with airway manifestations of extraesophageal reflux disease, Ann. Otol. Rhinol. Laryngol. 116 (2007) 571–575.