Gastroesophageal Reflux in Patients with Subglottic Stenosis

ORIGINAL ARTICLE Gastroesophageal Reflux in Patients With Subglottic Stenosis

David L. Walner, MD; Yoram Stern, MD; Mark E. Gerber, MD; Colin Rudolph, MD; Constance Y. Baldwin, BS; Robin T. Cotton, MD

Objectives: To determine the incidence of gastroesopha- for reflux-associated symptoms have not been estab- geal reflux in patients with subglottic stenosis (SGS) and lished. Therefore, patients were grouped as having a pH to determine if upper esophageal reflux occurs in addi- of less than 4.0 in the upper esophagus for 0%, 0.1% to tion to lower esophageal reflux in these patients. 0.9%, 1.0% to 1.9%, 2.0% to 3.0%, or more than 3% of the study time. Design: Esophageal pH probe studies were reviewed in patients diagnosed as having SGS. Results: Thirty-seven of the 74 patients who underwent lower probe testing had a pH of less than 4.0 more Setting: A tertiary care pediatric medical center. than 5% of the study time, and 24 had a pH of less than 4.0 more than 10% of the study time. Twelve of the 55 Patients: All patients diagnosed as having SGS be- patients who underwent upper probe testing had no mea- tween January 1990 and July 1996 who had undergone surable reflux; 27 of the 55 had a pH of less than 4.0 more monitoring with an overnight esophageal pH probe. Sev- than 1% of the study time; 14 had a pH of less than 4.0 enty-four patients qualified for the study. All 74 pa- more than 2% of the study time, and 11 had a pH of less tients underwent lower probe testing, and 55 of the 74 than 4.0 more than 3% of the study time. underwent dual (upper and lower) probe testing. Conclusions: Gastroesophageal reflux is frequently Main Outcome Measures: The percent of time a pH present in patients with SGS. Gastric contents fre- measurement of less than 4.0 was recorded in the upper quently reach the upper and lower esophagus in these and lower esophagus. A lower probe pH measurement patients. In addition, the high incidence of gastroesopha- of less than 4.0 more than 10% of the study time was geal reflux in these patients suggests that it may play a considered high risk for developing reflux-associated role in the development of SGS. The possible effect of pathologic symptoms. A lower probe pH measurement gastroesophageal reflux on the surgical repair of SGS re- of less than 4.0 for 5% to 10% of the study time was quires further study. considered a marginal risk for developing reflux- associated pathologic symptoms. Upper probe criteria Arch Otolaryngol Head Neck Surg. 1998;124:551-555

HE INCIDENCE of subglottic rection into the esophagus. Brief epi- stenosis (SGS) in neonates sodes of GER occur in almost 50% of 4 From the Department of requiring endotracheal in- healthy infants less than 2 months of age. Pediatric Otolaryngology and tubation ranges from 1% to By the age of 12 months and thereafter, Maxillofacial Surgery 8%.1,2 The cause of acquired only 8% of children are thought to have (Drs Walner, Stern, Gerber, SGST is not well understood.3 Several syner- GER.5 In most infants and children, GER Baldwin, and Cotton, and gistic factors likely play a role in the devel- has no consequences, but airway symp- Ms Baldwin) and the Division opmentofthedisorder.Thesefactorsinclude toms have been shown to be related to GER of Pediatric Gastroenterology but are not limited to the size of the endo- in some patients. These symptoms in- and Nutrition (Dr Rudolph), tracheal tube, movement of the endotracheal clude aspiration pneumonia, exacerba- Children’s Hospital Medical tube, duration of intubation, traumatic in- tion of asthma, apnea, stridor, croup, and Center, Cincinnati, Ohio. tubation, presence of an infection while in- laryngitis or hoarseness.6-8 More specifi- Dr Walner is now with the 9 Department of Otolaryngology/ tubated, and possibly gastroesophageal re- cally, Jindal et al suggest that GER Bronchoesophagology, flux (GER) with or without intubation. may cause certain cases of SGS. Contencin Rush-Presbyterian-St Luke’s Gastroesophageal reflux occurs when et al6 comment on the close relationship Medical Center, Chicago, Ill. gastric contents move in a retrograde di- between SGS and GER. This relationship

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 PATIENTS AND METHODS from birth to 1 year of age, the proximal sensor of the probe was placed 5 cm above the distal sensor. For patients 1 to 3 years of age, the proximal sensor was A list was reviewed of all patients evaluated for SGS at placed 10 cm above the distal sensor. For patients 3 the Children’s Hospital Medical Center in Cincinnati, years and older, the proximal sensor was placed 15 cm Ohio, between January 1990 and July 1996. Of the more above the distal sensor. All patients underwent fluoros- than 300 patients evaluated, only those who had under- copy or chest radiography to confirm correct placement gone pH probe testing at our institution were included of the probe. A reference electrode was placed on the in the study. Many patients had undergone GER evalua- patient’s abdomen when required. Recordings were tion at other institutions, and as a result, details of their obtained for at least 18 hours. pH studies were unavailable, and they were not included All patients were instructed to pursue their normal in the study. Seventy-four patients qualified for the activities. Patients had no meal restrictions, but the study, and a retrospective chart review was performed beginning and ending of feeding times were recorded. If for each. patients were taking acid-inhibitory or prokinetic medi- The following information was recorded for each pa- cations, those regimens were discontinued at least 24 tient: sex, age at the time of testing, the presence of a tra- hours prior to the study (except in one patient who was cheotomy tube at the time of testing, associated medical taking ranitidine hydrochloride [Zantac] during our conditions and birth history, previous reflux surgery, grade study because pH probe testing at another institution of airway stenosis identified on endoscopy, and number of had indicated severe reflux). previous airway surgeries. Airway grading was recorded from The pH probe results were recorded and distin- the endoscopy performed closest to the date of pH probe guished based on upper and lower probe location and testing and was based on the Myer/Cotton grading system the percent of time with a pH measurement less than (Figure).10 4.0. This was calculated by adding the total time within All dual-probe monitoring was performed with a 60 minutes with a pH of less than 4.0 following a meal portable pH measuring unit (model Mk3 dual-channel to the total time for more than 60 minutes with a pH of Digitrapper, Synectics Medical). Single-probe studies less then 4.0 following a meal. This sum was then were performed with a Mark II single-channel unit (Syn- divided by the total time of the study and multiplied by ectics Medical. Most dual-probe studies were performed 100 to derive the percent of time with a pH less than 4.0. in the latter half of the study (1993-1996). All electrodes This calculation was performed separately for upper and were calibrated in buffer solutions with a pH of 7.0 and lower probe measurements. then in solutions with a pH of 1.0. The pH electrodes Lower pH probe measurements of less than 4.0 were were inserted through the patient’s nose into the esopha- recorded as occurring more than 10% of the study time, gus and placed such that the tip of the electrode was 2 to 5% to 10% of the study time, or less than 5% of the study 4 cm above the gastroesophageal junction. When pres- time. Upper pH probe results of less than 4.0 were re- ent, the upper probe was positioned within 1 to 2 cm of corded as occurring 0%, 0.1% to 0.9%, 1.0% to 1.9%, 2.0% the upper margin of the esophagus. Ideally, the probe to 3.0%, or more than 3% of the study time. was placed below the upper esophageal sphincter in the Kendall ␶ rank correlation analysis and nonparamet- esophageal inlet. One of 3 different-sized electrodes was ric analysis of variance were performed on all variables men- used, depending on the age of the child. For patients tioned.

could have implications for both the origin of SGS common were prematurity and bronchopulmonary and its treatment if GER is present. The prevalence dysplasia: of GER in patients with SGS has not been clearly estab- Medical Condition No. (%) of Patients lished. Prematurity 48 (64.9) The purpose of our study was to determine the preva- Bronchopulmonary dysplasia 23 (31.1) lence of GER in pediatric patients with SGS. Gastrostomy tube 13 (17.6) Tracheomalacia 11 (14.9) History of Nissen fundoplication 11 (14.9) RESULTS Reactive airway disease 10 (13.5) Patent ductus arteriosus ligation 10 (13.5) Of the 74 patients who qualified for the study, 43 Developmental delay 7 (9.5) (58%) were male and 31 (42%) were female. The aver- Congenital SGS 6 (8.1) age age of the patients at the time of pH probe testing Brain injury 6 (8.1) was 5 years (age range, 0.3-14.3 years). Fifty-five patients (74%) underwent dual (upper and lower) Eleven patients (14.9%) had undergone Nissen probe testing, and 19 (26%) underwent only lower fundoplication prior to our study, and 13 (17.6%) were probe testing. dependent on a gastrostomy tube. Of the patients who Sixty (81%) of the 74 patients were dependent on a had undergone endoscopy of the airway, 65 (88%) had tracheotomy tube at the time of pH probe evaluation. Of been diagnosed as having grade II or III stenosis (Fig- the 44 concomitant medical conditions identified, the most ure). Twenty-nine (39%) of the 74 patients had under-

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 gone previous airway reconstructive surgery, and 6 (21%) 50 of those 29 had undergone previous airway reconstruc- 44 tive surgeries. The high number of previous airway sur- 40 geries reflects the referral pattern of our institution. All 74 patients underwent lower pH probe testing. 30 21 The results were as follows: 20

% of Time pH Ͻ4.0 No. (%) of Patients No. of Patients 10 Ͻ5 37 (50.0) 6 5.0-10.0 13 (17.6) 3 0 Ͼ10.0 24 (32.4) llllll lV Fifty-five patients underwent dual probe testing and Grade of Stenosis thus had upper probe measurements. The results were Distribution of patients with subglottic stenosis in our study. as follows: % of Time pH Ͻ4.0 No. (%) of Patients 0 12 (21.8) 0.1-0.9 16 (29.1) he studied with laryngeal and tracheal stenosis. He de- 1.0-1.9 13 (23.6) fined an abnormal lower probe measurement as a pH of 2.0-3.0 3 (5.5) less than 4.0 more than 4.39% of the total study time Ͼ3.0 11 (20.0) (when the patient was either upright or supine). He found There was no correlation between grade of airway abnormal pharyngeal reflux, defined as any single epi- stenosis and the percent of time with a pH measure- sode of a pH less than 4.0, in 67% (10/15) of these pa- ment of less than 4.0. A correlation of 0.48 (P<.001) was tients. In another study, Koufman17 induced subglottic identified for percent of time with upper and lower pH mucosal injury in 20 dogs and painted the injured areas probe measurements less than 4.0. with saline solution, acid, or acid with pepsin. Findings Of the 11 patients who required fundoplication prior included nonhealing and inflammation in the acid with to our study, 4 now had lower pH probe measurements pepsin group. of less than 4.0 less than 5% of the time, 1 for 5% to 10% Based on the aforementioned information, many phy- of the time, and 6 for more than 10% of the time. The sicians consider SGS to be a complication of GER.18 With data indicate that 5 of these patients who required fun- respect to laryngotracheal reconstruction (LTR), Gray et doplication had significant reflux in the past. However, al19 report that patients with uncontrolled GER have a pH probe testing at our institution indicated no further higher rate of failure following surgical reconstruction reflux. than those without GER. Based on 20 years of experi- The presence of a tracheotomy tube did not in- ence, Cotton and O’Connor20 state that a “reflux workup” crease the risk of reflux in our study population. is now considered essential to the success of LTR. Em- pirical treatment of GER has been recommended for pa- 21 COMMENT tients undergoing LTR. The importance of GER in LTR has been refuted Gastroesophageal reflux is increasingly being recog- by Zalzal et al,22 who state that neither the presence of nized as a contributing factor in the pathogenesis of pe- GER nor its treatment are major factors in determin- diatric airway disorders. Such disorders include appar- ing the outcome of LTR. They studied 4 groups of ent life-threatening events, recurrent pneumonia, and patients who underwent LTR: those who had no pre- reactive airway disease.11-13 The percentage of children operative GER evaluation, those whose preoperative with respiratory problems thought to be induced by GER GER evaluation findings were normal, those whose is estimated at 30% in some reports.14 preoperative GER evaluation findings were abnormal The possibility that GER may cause SGS was first sug- who failed to receive appropriate treatment, and those gested in 1983 by Bain et al,15 who identified GER in 2 adult whose preoperative GER evaluation findings were ab- patients with SGS. This report by Bain et al and one clini- normal who received appropriate therapy consisting of 16 cal case of their own led Little et al to investigate the con- a prokinetic agent and/or a histamine2 blocker in most nection between GER and SGS using a canine model. They cases. Limitations of that study include the fact that it applied either water or gastric contents to experimentally was not double blind, a staging system for airway ste- induced mucosal lesions or cartilaginous lesions of the tra- nosis was not used, and the sample size of patients chea. Some animals were treated with histamine2 block- with GER was small; as a result, the conclusions of ers. The authors concluded that the application of acid to that study are questionable. Although not addressed in superficial lesions resulted in stenosis and delayed reepi- that article, 73% of the patients studied had evidence thelialization, which did not occur in the superficial le- of reflux. sions to which acid was not applied. Cartilaginous lesions Intraesophageal pH monitoring remains the crite- to which acid was applied showed slightly more stenosis rion standard for the diagnosis of GER.6,23,24 Gastro- than those to which acid was not applied. However, since esophageal reflux is best defined by distal esophageal acid only 1 animal was in each study group, no significant con- exposure, which is identified by a pH of less than 4.0. A clusions could be drawn. confounding factor in the diagnosis of GER is that cough- Koufman17 found abnormal lower pH probe results ing and wheezing can promote episodes of reflux, such in 23 (72%) of the 32 patients (11 pediatric and 21 adult) that a child with a tracheotomy tube may have more re-

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©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 flux than a child without a tracheotomy tube. However, membered that pH probe results do not identify basic and these episodes of esophageal acidification are usually brief neutral GER. If basic or neutral GER is suspected, a gastric- since acid clears rapidly. A pH of less than 4.0 more than emptying scan should be performed. It is generally ac- 10% of the time indicates pathologic reflux; a pH of less cepted that pH probe monitoring is more sensitive and than 4.0 more than 7% of the study time is associated specific in diagnosing GER than a gastric-emptying scan.29 with an increased risk of esophagitis and airway symp- It remains to be seen if laryngeal disorders or biopsy, which toms related to GER. A pH of less than 4.0 for 5% to 10% theoretically would indicate conclusively whether in- of the study time is considered a borderline risk for flammatory changes are present, will play a role in diag- esophagitis, while GER for less than 5% of the time is nosing GER in the future. We are currently investigat- considered normal.25 ing this question. Very few data are available on proximal pH probe A large number of patients in our study were born results. Ideally, the probe is placed below the upper esoph- prematurely and many had other notable associated ageal sphincter in the esophageal inlet. In a study by Dob- medical conditions. It is impossible to draw conclusions han and Castell,24 minimal acid exposure occurred in the about the relationship between GER and SGS from this proximal esophagus (Ͻ1% of the total time) in patients type of retrospective review. In addition, this study does with normal distal pH probe results. Shaker et al26 evalu- not examine what effect the presence of GER had on ated patients with reflux laryngitis using pH monitoring these patients after airway reconstruction. What can be at the distal esophagus, proximal esophagus, and phar- learned from these data is that the incidence of GER in ynx. Findings included a significantly higher percent- patients with SGS seen at our institution was at least 3 age of reflux episodes in the pharynges of patients with times greater than the incidence of GER reported in the laryngitis compared with control patients. The criteria general pediatric population. Well-controlled studies were the number of episodes with pH less than 4.0 in the are necessary to further our understanding of the role of specified anatomical location. Contencin and Narcy27 GER in the pathogenesis of SGS and to determine its monitored pharyngeal pH in infants and children with impact on the success of reconstructive surgery. and without laryngotracheitis. For the pharyngeal channel, acid reflux was defined as a decrease in pH below Accepted for publication February 4, 1998. 6.0. A pathologic condition was diagnosed if a pH of lower Presented at the 12th Annual Meeting of the Ameri- than 6.0 was recorded more than 1% of the total time. 28 can Society of Pediatric Otolaryngology, Scottsdale, Ariz, Another study found that patients without distal GER May 16, 1997. had a proximal esophageal pH of less than 4.0 for 0.76% Corresponding author: David L. Walner, MD, Depart- of the time, while patients with distal GER had a proxi- ment of Otolaryngology and Bronchoesophagology, Rush- mal esophageal pH of less than 4.0 for 6.5% of the time. Presbyterian-St Luke’s Medical Center, 1653 W Congress It is currently unclear what pH value should be used as Pkwy, Chicago, IL 60612. a cutoff to identify pathologic pharyngeal or upper esophageal reflux. 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