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SUMMARY AND CONCLUSIONSOtitis media with effusion continues to be one of the most prevalent childhood diseases besides being the commonest cause of deafness in children, but much controversy remains regarding its pathogenesis. OME is primarily a chronic inflammatory condition and the causes of inflammation are multifactorial.An increasing weight of clinical evidence suggests that the refluxed gastric contents may reach to the hypopharynx and nasopharynx (laryngopharyngeal reflux). Reflux of acid and pepsin into the middle ear from the nasopharynx is possible due to the angle of immature Eustachian tube in children. This would cause inflammation of the nasopharynx and Eustachian tube leading to Eustachian tube dysfunction. Gastric reflux may therefore be the primary factor in the initiation of OME, instigating a cascade of inflammatory events leading to the conditions seen in the disease.This prospective case series study is designed in an attempt to identify any possible etiological relationship between GERD and OME in children. This is verified by detecting the presence or absence of gastric juice in the middle ear in cases of OME. If gastric contents had refluxed into the middle ear, pepsin will be present in active or inactive form, depending on the pH of the effusion. Middle ear effusion partly consists of a plasma transudate and we therefore need to differentiate between pepsin from gastric juice and that derived from plasma pepsinogen. Also, this work studied the value of dual-probe 24-hour pH monitoring and the characteristics of its parameters for the detection of extra-esophageal reflux in children with OME.This is a prospective study that had been carried out on 64 children with OME, 50 of these children were refractory to the usual conservative lines of treatment for more than 3 months and planed to be managed surgically for their OME, while the other 14 children responded to the conservative lines of treatment within a period of 3 months. Thirty-one children out of the 64 children were subjected to dual-probe pH monitoring, 17 of them were taken form the 50 children who undergone surgical interference for their persistent OME and the remaining 14 children were these children who responded to the conservative medical lines of treatment. In addition, another 10 children were randomly selected from the 31 patients; who underwent pH monitoring; to continue for bilirubin monitoring in another sitting.In this work, the pH of the effusion samples was measured using pocket pH meter and was found to be alkaline. All effusions collected from the 50 children with OME contained pepsin/pepsinogen protein. The concentrations of pepsin/pepsinogen protein measured in the effusions were found to be up to 540 times higher than the levels found in the serum of the same patients as detected in each case separately. At the same time, fibrinogen (one of serum proteins) was detected in all effusion samples in concentration levels which were more or less of the same order as those found in serum. Immunohistochemical analysis of middle ear biopsy samples demonstrated that the middle ear is not capable of secreting pepsin/pepsinogen.These data show that serum factors are not being concentrated in the effusion; therefore the pepsin detected in the middle ear effusions unlikely to have originated from a transudate of plasma. The only other source is reflux of gastric contents.The present study indicates that LPR may play an important etiologic role in the pathogenesis of OME, on the basis of the statistically significant number of pharyngeal reflux episodes occurred in all 31 patients. Twenty-two children (71%) of those patients had pathologic LPR on considering that even a single extraesophageal reflux with pH<4 is significant. Although more severe pathologic forms of acid reflux occurred in groupI we couldn’t distinguish a significant difference between the 2 groups of children (GPI “surgical group” and GPII “medical group”) as regard the presence or absence of LPR (GP I=70.6% and GP II=71.4%). This result may suggest the underlying role of LPR as a major predisposing factor for OME and consequently other tubo-tympanal disorders whether treated medically or surgically.On the other hand, GERD was successfully diagnosed in only 6/31 children (19.4%) on the basis of reflux index > 4.2% with pH<4; including 3/17 cases (17.6%) in group I and another 3/14 cases (21.4%) in group II. All these 6 children with GERD had LPR, whereas 51.6% of LPR patients had normal distal (esophageal) acid exposure time. Again, these data delineate the potential role of LPR and not GERD in the development of OME in those children.In the present study, other ORL symptoms that can be related to reflux were reviewed and the following results were obtained: recurrent otitis media (93.5%), rhinorrhea (77.4%), otalgia (16.1%), stertor (9.7%), and laryngeal spasm (16.5%), and they were grouped as upper respiratory disorders. 41.9% of children suffered from recurrent bronchitis and 6.5% had bronchial asthma and they were grouped as lower respiratory disorders. Only 5 cases (16.1%) reported significant GER symptoms in the form of vomiting and regurgitation, while 4 cases of them (12.9%) presented with failure to thrive. All GER symptoms were present in group II “medical group”, while group I “surgical group” had no GIT symptoms at all (silent GERD).On considering the surgical procedures to which children of this study were exposed to in a trial to relieve their presenting disorders; the surgical interference was significantly greater in group I than group II, where about 50 surgical procedures were done in this group as a trial for relieving their ORL disorders.This study supports raising the pH threshold in proximal pH monitoring up to 5 instead of 4 to ensure more valid diagnosis and avoiding missing cases with extraesophageal reflux. When we applied this parameter to the patients in our project; only as regard to the proximal probe; more proximal measures were significantly recorded. Also, the diagnosis of LPR increased to 87.1% (27/31) instead of 71% (22/31), where 3 cases in group I and 2 cases in group II were additionally diagnosed as having abnormal proximal acid exposure.This study identified factors in the intraesophageal acid exposure (predictors) that may have their impact on the incidence of extraesophageal reflux events. As a result, acid proximal total reflux episodes can be predicted in about 77% of cases of OME (in children of the same age group) using the intra-esophageal pH measures.The present study revealed a significant positive correlation between the pepsin levels detected in the effusion samples of 17 children (in group I) who underwent surgical interference for their OME and the LPR episodes detected in the dual-probe 24-hour pH monitoring test. So, the levels of pepsin in the effusion of these children had a significant correlation with the number of episodes detected in the pharynx whether using the threshold of pH<4 or pH<5.As a preliminary study, we tried to cast shadow on the involvement of bile reflux in the development of OME in the children of our study. Ten children underwent bilirubin monitoring; 6 of them had pathologic bile reflux either those from groupI or II. All the selected 10 children had pathologic LPR and 3 of them had pathologic GERD as recorded by pH monitoring. So, bile reflux detected in the 6 children could be one of the constituents of their refluxate.CONCLUSIONSlaryngopharyngeal reflux; another manifestation of extraesophageal reflux disease; should be thought of by ENT specialists in case of gastroesophageal reflux disease. LPR may cause nasopharyngitis leading to Eustachian tube pathological changes and consequently OME or even many other middle ear disorders.The incidence LPR is greatly underestimated by a single-probe intraesophageal pH monitoring. Ambulatory 24-hour dual–probe pH monitoring (with pH electrodes in the distal esophagus and the hypopharynx) is considered the most sensitive and the most specific diagnostic test available for the evaluation of LPR in children.The antibody used for pepsin assay is commercially available and stable to storage, and the assay itself can be performed on multiple stored specimens and requires little more than a microfuge and a microplate autoreader as equipments. So, the used technique of enzyme-linked immunosorbent assay (ELISA) for detection of pepsin in the effusion of children with OME; using monospecific antipepsin antibodies; can be considered a reliable marker for assessment of reflux in similar children specially those patients suspected of having other LPR- related otolaryngologic disorders.Given the results of the present study, it’s thought that tests for evaluation of GER or LPR as well as implementation of antireflux therapy should be used when other usual methods yield no improvements of the middle ear condition or in those patients showing frequent recurrences of middle ear problems e.g. recurrent otitis media. Also, the main goal of reflux control in these children is to achieve a stable middle ear status with no complain and prevent the progression to the status of persistent middle ear effusion resistant to treatment as antireflux therapy may not have a role at this time. However, those patients who had to undergone a surgical intervention to control their OME may get benefit from controlling their reflux by preventing the recurrence of otitis media or other reflux-related disorders e.g. persistent rhinorrhea, otalgia….etc.Middle ear disease caused by LPR reacts favorably to antireflux treatment combining PPIs and conservative antireflux measures. Also, the antireflux therapy needed for middle ear disease patients requires a long duration to become free of symptoms, and a high maintenance dose is required for them to remain symptom-free (Poelmans et al., 2001; and Poelmans et al., 2002).Further research is still needed to delineate the role of bile in cases of OME using the same principle of antibodies against bile components.Control of LPR may be an essential component in the successful diagnosis and management of OME in pediatric patients. Better understanding, identification, and control of reflux certainly lead to improved outcome of medical and surgical interventions, as well as decreased morbidity, in children with LPR-related- OME or other tubo – tympanic disorders.
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