Insult of gastroesophageal reflux on airway: clinical significance of pharyngeal nozzle

Abstract

At the very time of global paying the highest attention to the worst insults of smoking as well as haze on the airway, everybody knows both are exogenous and noticeable. However, people mostly, including many medical personnel, do not know how badly the gastroesophageal reflux (GER) insults on our own airway. Symptoms of GER are commonly seen as heartburn and regurgitation, which can be mostly tolerated. However, when the up going gastric content reversely passes the esophagus and then the distal pharynx, where it appears a beak like stricture, serving as a nozzle, so as to produce numerous micro-particles and reach the oro-nasal cavity and also the airway causing allergic rhinitis and asthmatic attacks, even pulmonary parenchyma lesions. It will reduce life quality or even jeopardize life. The point that the endogenous insult appears in the respiratory system, but originates from the digestive tract is not well known and often undiagnosed and not correctly treated. The GER induced airway challenge is a treatable and preventive entity, as soon as a diagnosis is made, a good relief could be expected by means of life style adjustment, medicine, or fixation of the patulous cardia through radiofrequency or fundoplication. The author Dr. Zhonggao Wang had suffered it for long and symptoms disappeared for 8 years after anti-reflux surgery. Here is a presentation of Dr. Zhonggao Wang and his team’s work and would call attention to the public so as to recognize this relatively unknown entity — a treatable condition occurring from human itself, but not from outside surroundings as smoking or haze does.

Keywords

gastroesophageal reflux / airway / pharyngeal nozzle / micro-aspiration / asthma

Introduction

Before March 2003, the author Dr. Zhonggao Wang had lived a miserable life with the diagnoses of first “allergenic rhinitis” and then “bronchial asthma.” His life is under threatening by the exacerbations of severe crisis: episodic nocturnal neck tightening, breathlessness, with difficulty in inspiration and the more in expiration, accompanying intensive productive cough, sputum, nasal discharge, notably declined exercise tolerance which required 4 times of emergency ICU care with respirator at that time, he was suffocated, and once with comatose. He himself insistently denied the diagnoses of “bronchial asthma,” although no proper cause he could figure out. On his insistence, a 24-h pH monitoring found out that he had gastroesophageal reflux (GER). At that time, he convicted himself that “It is gastroesophageal reflux disease, but not asthma.” Consequently, a laparoscopic Nissen fundoplication was performed in March 2006 at his strong request. Since then he had a normal respiration without any attacks of asthma. He presented himself as a case report to remind related doctors who are not familiar to this disease [ 1] and established a Center for GER to treat patients with similar suffering a month after his surgery.

A glance of pharyngeal nozzle

An esophageal barium study was performed for him the next day after fundoplication, the barium could not swollen freely (he had dysphagia at that time), but as soon as the barium cumulated in the esophagus and furthermore reached to the distal end of pharynx, he found a pharyngeal beak or a nozzle, which can be vividly seen (Fig. 1) [ 1]. And he envisioned immediately that this nozzle exists in all living being, since any pharynx should have its nature tension established by upper esophageal sphincter (UES) and is thus closed normally. This nozzle may serve as a key anatomical structure to produce vast amount of micro-particles through a trans-nozzle spray, surely beyond the pharynx. And this spraying formed micro-particles pushing into the oro-nasal cavities including larynx, and through larynx, the micro-particles may directly invade into or passively aspirate into the airway by aspiration function. This may call as a micro-aspiration [ 2]. However, no mention about how the microparticles is formed. In any rate, both direct invasion or passive inspiration of the microparticles into the airway may insult the entire airway by refluxate in the esophagus due to GER.

Animal study

A series of experiments were conducted on rats and rabbits as well (Fig. 2) and this hypothesis was confirmed [ 3, 4]. So long as there is an energy sufficient gastroesophageal reflux in the esophagus, this reflux push through the nozzle, i.e., to overcome the pressure of the UES and create phenomenon of spray or burst out a vast amount of microparticles, in addition to spill and spurt causing under different pressure [ 3]. As a matter of fact, definition of spray is: “A jet of liquid in fine drops, coarser than a vapor, is produced by forcing the liquid from the minute opening of an atomizer mixed with air.” In this clinical setting, the elastically constricting pharynx functions as an atomizer while strong reflux action occurs in the esophagus [ 4].

Clinical significance of pharyngeal nozzle

The trans-pharyngeal spray causes instant irritation first directly onto the upper airway, including a rather wide naso-pharynx cavity with nasal cannels, auditory tube, frontal, maxillary, and sphenoidal sinuses, naso-lacrimal duct, etc., causing sneeze, running or stuff nose, post-nasal drip, tearing, tingling, even hearing disturbance, like symptoms in allergic rhinitis; at the same time or then, the invading reflux micro-particles go into the larynx, trachea, bronchus, and beyond leading to sour throat, especially choking, which means the irritation enters the trachea, causing a series of crisis to the patients: asthmatic attack, severe breathlessness, neck tightening, even suffocation. As time goes, this irritation process reaches the lower airways and pulmonary parenchyma causing pulmonary fibrosis and many related lesions [ 7– 9] (Fig. 3).

The trans-pharyngeal spray causes microaspiration, which mainly reaches the central airway. It is a different form of attack distinguishing from massive and deep aspiration in trauma, drunk, drug poisoning, stroke, coma, epilepsy, tracheoesophageal fistula and other similar conditions threatening patients, which usually results in acute or repeat aspiration pneumonia [ 10] rather than paroxysmal asthmatic symptoms. The respiratory and laryngopharynx presentation caused by GER are not only common and risky, but also with low awareness rate in the public. Dr. Zhonggao Wang thus raised a concept of gastroesophago-laryngotracheal syndrome (GELTS) in 2007, or one cavity two tract syndrome, which is characteristics of phasing the gastroesophageal junction as the generator, the pharynx the reactor, the nose-oral cavity the effector, the larynx and respiratory tract the asthmatic producer [ 7, 11]. GER is now considered a common cause or aggravating factors of chronic esophageal or extraesophageal symptoms, a disease comprising symptoms, end-organ effects and related to the reflux of gastric contents into the esophagus, oral cavity, larynx, trachea, branchus even lungs. The definition for gastroesophageal reflux disease (GERD) has been improved by consensus in 2013: symptoms or complications resulting from the reflux of gastric contents into the esophagus or beyond, into the oral cavity (including larynx) or lung [ 12].

UES, the pharyngeal nozzle, is a high-pressure zone comprising functional activity of three adjacent muscles together with cartilage and connective tissue. In humans, this high-pressure zone is between 2 and 4 cm in length and extends rostrally from the laryngeal distal opening [ 13]. Acting as a barrier between the pharynx and esophagus, the UES prevents entry of air into the digestive tract, prevents the reflux of material from the esophagus into the pharynx when swallowing, and yet still allows the release of intra-esophageal material when belching or vomiting, that is a process of the aforementioned spill or spurt in addition to spray, the key mechanism [ 13]. Resting pressures of UES in normal subjects have been reported at between 35 and 200 mmHg [ 14, 15]. Although UES has been intensely studied, however, none has considered it as a nature giving nozzle and its trans-nozzle spray phenomenon.

UES pressure increases in acute stress, esophageal distension and existence of intra-esophageal acid [ 16– 18]. On the contrary, UES pressure almost entirely eliminated and esophago-UES contractile reflex (EUCR), a protective reflex, could not be triggered during slow wave sleep [ 19, 20] and has been shown to be low in infants and the elderly [ 21, 22]. Moreover, laryngo-UES contractile reflex, another protective reflex, in humans deteriorates with age [ 23]. In addition to the degradation of the gastroesophageal junction and impaired esophageal clearance with age, which result in the increase of esophageal acid exposure in despite of the diminished perception of reflux symptoms in old patients [ 23]. The increased GER and decreased UES protective function may contribute to more trans-pharyngeal spray and microaspiration leading to a high prevalence of related respiratory symptoms and disease in the affected individuals [ 24].

Clinical practice and study of team work

The armament for reflux control including life modulation, medication (mainly acid inhibitor), and anti-reflux procedures to restore the anatomy of the gastroesophageal conjunction.

Proton pump inhibitor (PPI) had no effect for children with poorly controlled asthma, but produced side effects in asymptomatic gastroesophageal reflux children reported by Holbrook et al. [ 25], and for adult, the conclusion from a review by McCallister et al. [ 26] was similar: current available data has shown to date PPI trails showed limited benefits of treatment of symptomatic GER on asthma outcomes and no clear benefit of asthma control and the clinicians should focus on other factors which can affect asthma control.

In three centers, one in Beijing and two others in Zhengzhou, we performed Stretta or indigenous radiofrequency in more than 1600 cases and laparoscopic fundoplication in over 1800 GERD patients in 8 years [ 27]. Our study of laparoscopic fundoplication on GER-related respiratory symptoms showed that the outcome of respiratory symptoms after surgery was excellent in 35.9% cases, good in 43.8%, fair in 7.8% and poor in 12.5% ; accordingly the mean respiratory symptom score decreased from 6.3±2.65 to 2.33±2.37 at a mean follow-up of 12 months [ 28]. Our surgical outcome was similar with that of others [ 29]. Another study of Stretta radiofrequency for 505 patients with mainly wheezing and chronic cough enrolled from April 2006 to October 2008 resulted in a wheezing score decreased from 7.83 to 3.07, cough from 6.77 to 2.85, heartburn from 5.31 to 1.79 (P<0.01) at a mean follow-up of 12 months [ 30].

Long-term follow-up of 138 similar patients found that Stretta radiofrequency was effective for 110 eases (79.71%) during 5 years. About discontinuing status of drug, there were 28 patients (30.77%) gradually discontinued PPI in 2 to 12 months, 63 patients (69.23%) had medication dose decreased. The lower esophageal sphincter pressure was significantly increased and esophageal acid exposure reduced [ 31].

Our recent study of 83 patients with GERD-related cough underwent laparoscopic fundoplication (n = 35) and Stretta radiofrequency (n = 48), and was followed up 36.78±16.12 months (range 13–55 months). During the follow-up, the post-treatment scores were statistically lower as compared with the pre-treatment scores in both groups, 64 (65.1%) patients achieved complete PPI therapy independence after anti-reflux therapy [ 32]. Moreover, anti-reflux therapies were also found effective for GERD induced cough syncope [ 33]. We also found that the radiofrequency and fundoplication were both effective for GER childhood-to-adult persistent asthmatic patients who had inadequate response to medical treatment for asthma [ 34], and that two children who had difficult-to-treat asthma were cured by anti-reflux interventions [ 35], and that active anti-reflux treatments can be beneficial to patients with bronchiectasis for reducing their disabling respiratory symptoms [ 24]. In the near future, more of our findings will be presented.

Some patients had severe asthma with multiple rescues, bronchiectasis, post-tracheotomy, post-pneumolobectomy, severe pulmonary damage, even as candidate for lung transplantation. After diagnosis was confirmed and radiofrequency applied, all had dyspnea relief although without distinctive improving parenchymal damage [ 7, 36]. More effective anti-reflux procedure, such as the ones we advocated, the laparoscopic fundoplication plus highly selective vagotomy [ 37] and laparoscopic Roux-en-Y jejunum diversion [ 38] has also been applied in our practice with encouraging outcome.

As a matter of fact, we feel that all means in benefit to reduce reflux regarding in either volume or duration or frequency or height or acid generation would thus all offset the insult of trans-nozzle spray, which would all be effective to treat respiratory puzzles induced by GER. Acid inhibition dose not solve the patulous cardia, but radiofrequency and laparoscopic fundoplication do.

Debate

Recently, a guideline issued by the American Journal of Gastroenterology [ 12] suggested that surgery should generally not be performed to treat extraesphageal symptoms of GERD in patients who do not respond to acid suppression with a PPI. However, it seems as a paradox to us and as we described aforementioned that PPI and surgery for anti-reflux have substantially two different mechanisms. A failure of PPI may only means acid inhibition for reflux cannot eliminate the airway insult to result in a therapeutic effect, indeed, you may very easily think about if what the patient has is a neutral or even alkaline reflex, what will PPIs do for that. However, the surgical intervention restores the anti-reflux barrier to prevent GER from its generating, which is to benefit from its origin to offset the gastroesophageal-airway insult. Thus we suggest that the patient who has extraesophageal symptoms and does not respond to acid suppression with PPIs is still suitable for radiofrequency or surgery, if no other contraindications.

Summary

Some of the mainstream clinical and research body still consider asthma is a no cure disorder, although the diagnostic test, medical therapy and basic research had made real progress in the past 200 years [ 39]. However, we suggest there is a kind of patients who suffer from a pure GER induced severe asthma. That is to say, this is a kind of different asthma caused by trans-nozzle spray from GER. This could be effectively treated by means of treating GER by fixation of the patulous cardia through radiofrequency or fundoplication. After all, the GER induced airway problems is a different treatable entity [ 40]. As soon as a purely GER induced severe asthma is diagnosed, a good outcome is almost obtained with proper regime; though some patients may suffer from GER insult and allergic bronchial asthma as well, how to treat that combination is a topic for further study.

Compliance with ethics guidelines

Zhonggao Wang, Zhiwei Hu, Jimin Wu, Feng Ji, Hongtao Wang, Yungang Lai, Xiang Gao, Yachan Ning, Chengchao Zhang, Zhitong Li, Weitao Liang, and Jianjun Liu declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author(s) received no financial support for the research, authorship, and/or publication of this article. This manuscript does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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