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European Review for Medical and Pharmacological Sciences 2016; 20: 4547-4552 Breathing training on lower esophageal sphincter as a complementary treatment of gastroesophageal reflux disease (GERD): a systematic review

M. CASALE1, L. SABATINO1, A. MOFFA1, F. CAPUANO1, V. LUCCARELLI2, M. VITALI3, M. RIBOLSI4, M. CICALA4, F. SALVINELLI1

1Unit of Otolaryngology, Campus Bio-Medico University, Rome, Italy 2Unit of Otolaryngology, Phoniatric Section, Campus Bio-Medico University, Rome, Italy 3Bio-Statistical Department, Campus Bio-Medico University, Rome, Italy 4Unit of Gastroenterology, Campus Bio-Medico University, Rome, Italy

Abstract. – OBJECTIVE: Gastroesophageal re- It accounts for one of the most common gas- flux disease (GERD) represents one of the most trointestinal disorder, though still representing a common gastrointestinal disorders, but is still a challenge to treat. A variable percentage ranging challenge to cure. Proton pump inhibitors (PPIs) are from 14 to 20% of adults in the USA have been currently the GERD’s standard treatment, although not successful in all patients; some concerns have reported to be affected, although those preva- been raised regarding their long term consump- lence data are based on self-reported chronic 2 tion. Recently, some studies showed the benefits heartburn symptoms . of inspiratory muscle training in increasing the low- GERD occurs along with an inappropriate re- er esophageal sphincter pressure in patients af- laxation of the lower esophageal sphincter (LES), fected by GERD, thereby reducing their symptoms. that causes the gastric acid to enter the distal MATERIALS AND METHODS: Relevant pub- esophagus, thereby stimulating the chemorecep- lished studies were searched in Pubmed, Google Scholar, Ovid or Medical Subject Headings using tors, causing irritation and leading to the onset the following keywords: “GERD” and physiothera- of symptoms. Both esophageal (heartburn) and py”, “GERD” and “exercise”, “GERD” and “breath- extraesophageal symptoms (including oral, pha- ing”, “GERD and “training”. ryngeal, laryngeal, and pulmonary disorders) of RESULTS: At the end of our selection process, GERD are triggered by mucosal injury and are four publications have been included for systemat- directly related to the frequency of reflux events, ic review. All of them were prospective controlled the duration of mucosal acidification, and the studies, mainly based on the training of the dia- 3,4 phragm muscle. GERD symptoms, pH-manometry caustic potency of the refluxate . values and PPIs usage were assessed. Frequently, GERD patients present to oto- CONCLUSIONS: Among the non-surgical, laryngologists with symptoms such as dry or non-pharmacological treatment modalities, the sore throat, globus sensation, hoarseness, chronic breathing training on diaphragm could play an cough, dysphagia, or buccal burning. However, important role in selected patients to manage the clinical examination cannot always reveal the symptoms of GERD. striking and/or suggestive pathological findings, Key Words and, as a direct consequence of this, the underly- Gastroesophageal reflux disease, Breathing training disease is not often primarily diagnosed. Fre- ing, Systematic review. quently, the misdiagnosed patients are commonly treated for (non-allergic) rhinitis with post-nasal drip, non-specific rhinopharyngitis, or recurrent Introduction sinusitis4. Reflux is physiologically prevented by specif- Gastroesophageal reflux disease (GERD) is ic esophageal anti-reflux barriers, including the “a condition which develops when the reflux of LES and the angle of His. stomach contents causes troublesome symptoms The LES is a bundle of tonically contracted (i.e., at least two heartburn episodes per week) circular smooth muscle fibers at the distal part and/or complications”1. of the esophagus. It is 2-4 cm in length and is

Corresponding Author: Lorenzo Sabatino, MD; e-mail: [email protected] 4547 M. Casale, L. Sabatino, A. Moffa, F. Capuano, V. Luccarelli, et al. surrounded by the diaphragm hiatus. In resting Nonetheless, there is an increasing interest on conditions, it generates a positive pressure higher how complementary therapy can increase GERD than the intra-abdominal pressure, preventing the patients’ quality of life13, and reduce the PPIs reflux of gastric contents into the esophagus and intake. Among the non-surgical and non-phar- consequently symptomatic heartburn. macological therapies7, physiotherapy of antire- The thoracic diaphragm consists of a costal flux-complex has been recently proposed as a and a crural part, inserted to the ribs and the ver- potential therapy for GERD. Similarly to any tebral column respectively. other striated muscle of the body, the crura of the The right and left crura tie the esophagus up diaphragm are prone to improve performance by creating a canal where the esophagus enters the physical exercise. abdomen. The outer fibers of the canal are ori- The aim of our work is to systematically re- ented in a cranial-to-caudal direction, whereas view the published literature regarding all the po- the inner fibers are oriented obliquely. The crural tential therapeutic effects of breathing exercises diaphragm exercises a pinchcock-like action on on GERD symptoms. the lower esophageal sphincter during contrac- tions, thus exerting an extrinsic sphincter effect. The phrenoesophageal ligament links anatomi- Materials and Methods cally the crural muscles and the LES supplying for an additional mechanism to prevent reflux of Search and study selection stomach contents into the esophagus. We performed a throughout search for ap- Both the lower esophageal sphincter and the propriate published studies in Pubmed, Google crural diaphragm contribute to the esophagogas- Scholar, Ovid, using either the following keywords tric junction (GEJ) pressure5. or, in case of Pubmed database, Medical Sub- The LES tone can be affected by drugs6 and ject Headings: (“Gastroesophageal reflux disease” different kind of food, through an effect on its AND physiotherapy”), (“Gastroesophageal reflux resting pressure eventually inducing reflux. Oth- disease” AND “exercise”), (“Gastroesophageal re- er contributing factors that increase intra-ab- flux disease” AND “breathing”), (“Gastroesopha- dominal pressure and overcome the antireflux geal reflux disease AND “training”) with no limit barrier include the Valsalva maneuver, weight for the year of publication (Figure 1). lifting, the Trendelenburg position, pregnancy Only studies in English, published in peer-re- or obesity7. viewed journals, reporting data about the use of When lifestyle modification fails to improve breathing exercises were included. No studies GERD symptoms, the next step for the treatment related to bariatric therapy, cystic fibrosis, COPD, of GERD is mainly medical and surgical in very exercise and physiotherapy considered as general selected cases8. physical activity have been considered. Proton pump inhibitors (PPIs) currently rep- Literature reviews, technical notes, case re- resent the pharmacological standard treatment of ports, letters to editors, and instructional courses GERD; however, some concerns have been raised were excluded. regarding the long-term intake of PPI. Specifical- Two authors (CM and SL) independently as- ly, chronic consumption of PPI have been linked sessed the full-text version of each publication, to an increased risk of hip fractures, community by selecting that on the basis of its content and acquired pneumonia, gastrinoma, diarrhea and excluding papers without the specific content. drug interactions, especially in patients treated Reference lists of each selected article were ana- with clopidogrel9. lyzed to find more relevant studies. Moreover, the withdrawal of PPIs is known to be difficult as showed by Jensen et 10 al . The surgical outcomes may be affected by consider- Results able side effects and endoscopic methods have largely failed to treat GERD11. Furthermore, PPI Four studies investigating the role of breathing treatment fails to normalize esophageal acid ex- exercises for the treatment of GERD has been re- posure in a considerable percentage of adults who ported in this review. The features of the studies experiences reflux, particularly those with severe are shown in Table I. or complicated GERD, who tend to continue ex- Nobre e Souza et al14 concentrated on motor periencing symptoms despite PPI treatment12. function, autonomic function and GERD symp-

4548 Breathing training on lower esophageal sphincter

Figure 1. Flow chart of the articles research for a systematic review.

toms improvement in patients undergoing inspi- was divided into 5 exercises: first and second ratory muscle training (IMT). Patients underwent focused on supine abdominal breathing, mov- an IMT program under progressive inspiratory ing the abdominal wall, eventually against re- resistance, managed by a physical therapist, for sistance, while relaxing thorax and lower inter- 5 days a week for 2 months. Each IMT session costal muscles, third, fourth and fifth focused consisted of 10 series of 15 inspirations (about 30 on seated and standing inspiratory training with minutes). This training resulted in a significantly slow expirations, eventually following abdominal decrease of heartburn and regurgitation symp- movements with arms elevations and vocalizing. toms after IMT, with a concomitant improved After a month, there was a statistically significant average EGJ pressure and reduced progression of decrease of acid exposure, an increase of Quality reflux in the upper part of the esophagus, evalu- of life (QoL) (measured by GERD Health-Re- ated by esophageal pH monitoring. lated Quality of Life Scale) in physiotherapy Carvalho de Miranda Chaves et al15 used a group, while the on-demand use of PPIs showed training program consisted of 40 maximum in- no statistical difference after 1 month. After an spirations form the residual volume, twice a day 8 months follow-up, there was a significant in- (morning and evening), 7 days a week over a pe- crease of QoL and a decrease of the need of on riod of eight weeks. They showed that constant or demand-PPI. progressive inspiratory muscle training in GERD Da Silva et al18 performed a randomized, patients causes a statistically significant increas- blind study, dividing the patients in two groups: ing of LES pressure in patients with hypotensive a group of 22 patients who really underwent LES, although they did not evaluate GERD cor- osteopathic treatment, and a second group of 16 related symptoms, as underlined by Iovino and patient who undergo to a placebo technique. The Ciacci16. treatment consisted of two steps: first step – four Eherer et al17 used a modified set of exercise deep respirations, in which the inspiration and typically used by professional singers, that aim expiration movements are exacerbated by the to involve diaphragm in respiration, changing investigator through manual contact on the lower the respiration from thoracic to abdominal. It rim of the last ribs; second step – four deep respi-

4549 M. Casale, L. Sabatino, A. Moffa, F. Capuano, V. Luccarelli, et al. decreased Result tLESR reduced, GERD syntoms reduced Increase LES pressure of by MRP patients, of in 75% increase EEP of in 60% patients. of Significant decrease in acid exposure in patients, QoL significantly improved scores months 9 After month. 1 after still on training usagePPI significantly increase significant Statistically ARPof in osteopatic technique group, no statistically significant difference in MEP Parameters EGJ manometry, assessment if tLESR, esophageal pH monitoring, pH heart rate variability Esophageal manometry, mid respiratory pressure, end expiratory pressure before and after therapy GERD Health-Related Quality Scale, Life of GIQLI

respiratoryAverage pressure (ARP), maximum expiratory pressure (MEP) after the treatment

Therapy Inspiratory muscle training

Inspiratory muscle training

Diaphragmatic contraction respiration

Modified osteopathic techniques for diaphragm stretching Patients 20 patients, 7 controls

20 patients, 9 controls

20 patients with GERD, randomized in training 10 group and 9 control group

38 patients38 with GERD randomly divided in 16 treated with sham tecnique and 22 treated with osteopatic thecnique Study design Prospective study Prospective study Prospective randomized controlled study

Prospective randomized study

Authors Nobre e Souza MÂ1, Lima MJ, Martins GB, Nobre RA, Souza MH, de Oliveira RB, dos Santos AA. de Miranda Chaves R, Suesada M, F, Polisel de Sá CC, Navarro- Rodriguez T. Eherer AJ, Netolitzky F, Högenauer C, F, Puschnig G, Hinterleitner TA, Scheidl S, Kraxner W, Krejs GJ, Hoffmann KM. da Silva RC, deda Sá CC, Silva RC, ÁO, Pascual-Vaca de Souza Fontes LH, Herbella Fernandes FA, Dib RA, Blanco CR, Queiroz RA, Navarro- Rodriguez T. Title Inspiratory muscle training improves antireflux barrier in GERD patients. physiotherapy can increase lower Respiratory esophageal sphincter patients. effectPositive of pressure in GERD abdominal breathing exercise on gastroesophageal reflux disease: a randomized, controlled study. Increase lower of esophageal sphincter pressure after osteopathic intervention on the diaphragm in patients with gastroesophageal reflux. Table I. Features of the selected studies.

4550 Breathing training on lower esophageal sphincter rations, in which, during the expiratory phase, the lack of consensus regarding which method could investigator will sustain the ribs grid using the be the best to objectivize those results. The ex- same contact to avoid the descent of the thoracic ercises themselves (physiotherapy, manipulative cage during the expiratory phase. The results osteopathy, inspiratory muscle training) are not were measured via manometry, choosing average standardized and not directly comparable due to respiratory pressure (ARP) and maximum expi- different muscle training protocols. ratory pressure (MEP) and highest point (HP), and the mean between all these parameters, all measured immediately after treatment. The re- Conclusions sults showed a statistically significant increase of average respiratory pressure in osteopathic Given its safety, cost effectiveness and lack technique group, but no statistically significant of collateral effects, the breathing training could difference in maximal expiratory pressure. play a crucial role in the management of mild GERD. Moreover, it may represent a promising option for the treatment of PPI-refractory GERD Discussion patients and could help in reducing the annual PPI needed intake in responder GERD patients, GERD represents an increasing burden on our as Erher suggested17. health-care system. Studies focused on GERD-re- A joint consensus regarding the breathing lated symptoms show a worldwide increase in training on LES would be desirable for encourag- prevalence, estimated approximately around 4% ing randomized, multicentric trials to confirm the per year. The possible contributing factors of this effectiveness of this non-pharmacological GERD trend include increased longevity and obesity treatment. rates, greater consumption of medications af- fecting the esophageal function, and potentially the changing prevalence rates of Helicobacter Conflict of Interests: pylori infection. GERD has a negative impact on All authors declare that they have no conflict of interest in patients‘ quality of life as well as on the economy connection with this paper. of the society19. PPIs currently represents the mainstay treatment of GERD, even though the long-term intake References of PPIs is not free of side effects10. Although lifestyle modifications lack suffi- 1) Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones cient data to show objective improvement of re- R. The Montreal definition and classification of flux 8,20[ ], patients usually experience a subjective gastroesophageal reflux disease: a global ev- advantage by changing their habits. idence-based consensus. Am J Gastroenterol 2006; 101: 1900-1920; quiz 1943. Among the non-surgical, non-pharmacolog- 2) Kahrilas PJ. Gastroesophageal reflux disease. N ical GERD treatments, the breathing exercises Engl J Med 2008; 359: 1700-1707. could represent a promising and rational treat- 3) Oleynikov D. Surgical Approaches to Esophageal ment. Disease, An Issue of Surgical Clinics: Elsevier It is known that the contraction of the crural Health Sciences, 2015. 4) Tauber S, Gross M, Issing WJ. Association of laryn- diaphragm has a pivotal role in the physiological gopharyngeal symptoms with gastroesophageal anti-GERD barrier; it has been reported to induce reflux disease. Laryngoscope 2002; 112: 879- a three-four fold increase of pressure within the 886. GEJ region. Being a striated muscle, the crural 5) Miller LS, Vegesna AK, Brasseur JG, Braverman AS, diaphragm has a dedicated innervation and ac- Ruggieri MR. The esophagogastric junction. Ann N Y Acad Sci 2011; 1232: 323-330. tively contracts during inspiration. The breathing 6) Lehmann A. Novel treatments of GERD: focus on training could train the crural diaphragm, there- the lower esophageal sphincter. Eur Rev Med fore positively influencing the anti-reflux barrier. Pharmacol Sci 2008; 12 Suppl 1: 103-110. Even though all the analyzed papers showed 7) Kahrilas PJ, Shaheen NJ, Vaezi MF, Hiltz SW, Black E, an overall positive effect of breathing training, Modlin IM, Johnson SP, Allen J, Brill JV. American Gastroenterological Association Medical Position the heterogeneity of methods and measured pa- Statement on the management of gastroesopha- rameters makes almost impossible to perform geal reflux disease. Gastroenterology 2008; 135: a metanalysis over those data. There is a clear 1383-1391, 1391.e1-5.

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