REVIEW ARTICLE 41 Abdominophrenic Dyssynergia: A Narrative Review REVIEW ARTICLE John A. Damianos, MD1, Sanjeevani K. Tomar, MD2, Fernando Azpiroz, MD, PhD3 and Elizabeth Barba, MD, PhD4 Chronic bloating and abdominal distension are common and highly bothersome gastrointestinal symptoms. Although the differential diagnoses for bloating and distension are broad, these symptoms are frequently associated with disorders of the gut-brain interaction. Functional abdominal bloating may be a result of visceral hypersensitivity, whereas abdominal distension seems to be a somatic behavioral response associated with abdominophrenic dyssynergia, featuring diaphragmatic contraction and abdominal wall relaxation. We review the available literature regarding abdominophrenic dyssynergia and comment on its epidemiology, diagnosis, treatment, and avenues to address in the near future. Am J Gastroenterol 2023;118:41–45. https://doi.org/10.14309/ajg.0000000000002044 INTRODUCTION (APD) without substantial increments in intra-abdominal con- Chronic bloating and abdominal distension are common in the tents (1–7). In APD, an abnormal somatic response causes par- general population and particularly common in disorders of the adoxical movement of the chest and abdominal wall that results in gut-brain interaction (DGBIs). Although there are many causes abdominal distension (Figure 1). This response is often triggered of bloating in DGBIs, a series of studies by Azpiroz et al. indicated by the sensation of bloating. In this review, we summarize the that abdominal distension in patients with functional gut disor- current understanding of APD and what is needed to better serve ders is by and large mediated by abdominophrenic dyssynergia patients with this disorder. 1 Department of Internal Medicine, Yale New Haven Health System, Yale School of Medicine, New Haven, Connecticut, USA; 2Department of Internal Medicine, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Erie County Medical Center, David K. Miller Building, Buffalo, New York, USA; 3Digestive System Research, University Hospital Vall’Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Universitat Autónoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain; 4Gastroenterology and Motility Department, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain. Correspondence: Elizabeth Barba. E-mail: barba@clinic.cat. Received June 19, 2022; accepted August 16, 2022; published online September 30, 2022 Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology The American Journal of GASTROENTEROLOGY 42 Damianos et al. (FD). Indeed, up to 90% of patients with IBS and 85% of patients with DGBIs regularly experience these symptoms (8,10). Multiple mechanisms may contribute to bloating and distension in DGBIs, including dysbiosis, small intestine bacterial overgrowth, dys- REVIEW ARTICLE motility, pelvic floor dysfunction, aerophagia, abnormal gas handling, carbohydrate intolerance or malabsorption, visceral hypersensitivity, central sensitization, and abnormal viscer- osomatic responses (11,12). Abnormal viscerosomatic responses seem to be a key con- tributor to bloating and distension in DGBIs. This phenomenon was first identified by the Barcelona group when a small cohort of patients with either IBS or functional bloating developed ab- dominal pain and distension associated with dystonia of the ab- dominal wall when they were challenged with rectal gas infusion (1). Specifically, the abdominal wall failed to contract and there was paradoxical relaxation of the internal oblique muscle. This Figure 1. Schematic representation of abdominophrenic interactions. (a) abnormal response (which was not seen in healthy controls) In normal conditions, the abdominal walls actively adapt to its content: A explained the exaggerated abdominal distension in response to volume increase elicits a coordinated relaxation of the diaphragm and intestinal gas infusion (1). A subsequent study used computed contraction of the anterior wall to expand the abdominal cavity without tomography (CT) to compare intestinal gas volumes in healthy anterior protrusion. (b) In patients, abdominal distension is produced by a paradoxical contraction of the diaphragm and anterior wall relaxation. controls, in those with DGBIs, and in patients with small bowel dysmotility (chronic intestinal pseudo-obstruction) (2). During reported periods of bloating, patients with dysmotility had in- BACKGROUND creased intestinal gas volumes and anterior protrusion of the Bloating refers to the subjective sensation of abdominal fullness, abdominal wall, which is consistent with the impaired intestinal pressure, or gas and has been recently defined as the sensation of motor function. Patients with IBS and FD, however, had no in- increased abdominal pressure/tension, whereas distension de- crease in gas volume but did show a diaphragmatic descent and scribes the objective (visible) increase in abdominal girth. These 2 caudoventral redistribution of the abdominal wall and intestinal phenomena are often associated (and frequently conflated), but contents (2) (Figure 2). The role of the diaphragm in bloating and up to 50% of the time, bloating occurs without distension (8). distension was also demonstrated in a cohort of patients with Occasional bloating and distension are common in the general either functional bloating or IBS with constipation (3). Electro- population, with a prevalence of approximately 40% (9). Al- myography (EMG) identified that abdominal distension in these though bloating and distension are associated with a wide range patients was driven by paradoxical contraction of the diaphragm of pathologies (both gastrointestinal and nongastrointestinal) and relaxation of the internal oblique muscle, and the term (Table 1), these symptoms are particularly common in DGBIs abdominophrenic dyssynergia was coined for this condition (3). such as irritable bowel syndrome (IBS) and functional dyspepsia The same pathophysiology was subsequently demonstrated in Table 1. Differential diagnosis for bloating and distension Nongastrointestinal Gastrointestinal DGBIs • Food (flatulogenic diet, FODMAPs • Small intestinal bacterial overgrowth • IBS [fermentable oligosaccharides, • Lactose, fructose, or other carbohydrate • Chronic idiopathic constipation disaccharides, monosaccharides, and malabsorption/intolerances • Opioid-induced constipation polyols], insoluble fibers, osmotic solutes • Celiac disease • Dyssynergic defecation/pelvic floor [xylitol], and salt) • Pancreatic insufficiency dysfunction • Medications (lactulose, opioids, and • Prior gastrointestinal surgery (fundoplication • FD nonsteroidal anti-inflammatory drugs) and bariatric surgery) • Aerophagia • Obesity • Gastric outlet obstruction • Functional bloating and distension • Gynecologic malignancy • Gastroparesis • Hypothyroidism • Ascites • Premenstrual syndrome • Gastrointestinal malignancy • Endometriosis • Small bowel dysmotility • Connective tissue disorders (Ehlers-Danlos) • Small intestine diverticulosis • Postural orthostatic tachycardia syndrome • Mechanical obstruction • Scoliosis • Chronic intestinal pseudo-obstruction • Helicobacter pylori and chronic enteric infections (e.g., giardiasis) DGBI, disorders of the gut-brain interaction; FD, functional dyspepsia; FODMAP, low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet; IBS, irritable bowel syndrome. The American Journal of GASTROENTEROLOGY VOLUME 118 | JANUARY 2023 www.amjgastro.com Abdominophrenic Dyssynergia 43 episodes of distension or induced distension, consistently dem- onstrates increased activity of the diaphragm (causing di- aphragmatic descent) coupled with decreased postural tone of the anterior abdominal wall, as compared with basal conditions REVIEW ARTICLE (3,4,6,7). Under normal conditions, the activity of the diaphragm is counterbalanced by the costal wall to preserve pulmonary function (i.e., diaphragmatic descent is compensated by the de- scent of the costal wall) (19). By contrast, diaphragmatic descent during conditions of abdominal distension is associated with paradoxical elevation of the costal wall, driven by intercostal contraction, and resulting in hyperinflation of the chest. This condition functionally mimics status asthmaticus, explaining the shortness of breath characteristic of episodes of severe abdominal distension (6). Presumably, there is dysregulation along the gut- brain axis, which executes this abnormal response. Although the Figure 2. Example of abdominal distension. Three-dimensional recon- exact neurologic mechanism is not known, it has been hypothe- structions of CTscans obtained in the same patient during basal conditions sized that APD develops as a maladaptive response to gastroin- and during an episode of abdominal distension. Note diaphragmatic de- testinal pain or discomfort (13). Mechanosensors in the lumen of scent and abnormal redistribution of abdominal content associated with the gastrointestinal tract feed information about luminal contents distension. CT, computed tomography. and distension to the brain, which processes the information and in turn influences viscerosomatic physiology, such as by regu- patients with FD complaining of distension: In patients, ab- lating neural and muscular activity and coordinating chest and dominal distension in response to a test meal was related to APD; abdominal wall musculature (20). DGBIs commonly feature by contrast, the test meal in healthy subjects induced a co- central sensitization and visceral hypersensitivity, and so it is ordinated relaxation of the diaphragm and anterior wall con- possible that APD arises as a reaction to pain derived from the traction (4). Furthermore, ingestion of lettuce (which is a low gas- gastrointestinal tract (21). Dysautonomia or abnormal auto- releasing substrate for microbial fermentation) led to abdominal nomic responses have also been documented in DGBIs and as- distension, produced by uncoordinated activity of the abdominal sociated with psychopathology and trauma and additionally wall, in patients who believed that eating lettuce would cause supported by the fact that diaphragmatic breathing can improve them gas and bloating (5), suggesting that distension is a be- symptoms (22). havioral response. More recently, a study in healthy volunteers demonstrated that voluntary contraction of the diaphragm is DIAGNOSIS associated with abdominal distension and symptoms of bloating There are no current diagnostic criteria for APD (although as and abdominal discomfort (13). aforementioned, functional bloating and distension can be di- APD seems to be an important mediator of bloating and agnosed by symptoms alone by the Rome IV criteria). The liter- distension in IBS and FD, although other mechanisms also con- ature documenting APD has used various methods to detect its tribute. Certain patients, however, have isolated bloating and/or presence. Barba et al. (6) found that the morphological and vol- distension. APD has also been documented in pediatric patients, umetric differences observed in abdominothoracic CT scans usually in association with aerophagia (14,15).These patients obtained during periods of severe distension and periods with have functional bloating and distension as defined by the Rome minimal or no distension are related to the functional differences IV criteria (Table 2) (16). in EMG activity in the abdominal walls. However, CT and EMG should be reserved for use in patients with suspected intestinal dysmotility and luminal pooling (6). Other studies have used EPIDEMIOLOGY abdominal inductance plethysmography to measure changes in Because of the paucity of studies on APD, its prevalence is largely abdominal girth, ultrasound to assess the movement of the di- unknown. Presumably, given the high global prevalence of DGBIs aphragm, and manometry to monitor esophageal and gastric (approximately 40%) and the association between DGBIs and pressures (1,13,19,23). Because the abnormal contraction of the APD, APD is likely a common and under-recognized phenom- enon (17). APD may be more likely in women than in men, paralleling other DGBIs. Indeed, in the studies on APD to date, 93% of participants are women. As described above, APD is Table 2. Rome IV criteria for functional bloating and distension commonly associated with DGBIs, including IBS, FD, aerophagia Recurrent bloating and/or distension occurring at least 1 d per wk on average (4,13,14), and functional bloating and distension, andis, thus, likely also associated with pathologies commonly comorbid in Bloating and distension should be the predominant gastrointestinal DGBIs, including anxiety, depression, trauma, and chronic pain symptom. syndromes (18). Patients should not meet criteria for IBS, functional constipation, functional diarrhea, or postprandial distress syndrome. PATHOPHYSIOLOGY Symptom onset should have occurred at least 6 mo before diagnosis. Central to the pathophysiology of APD is the abnormal co- Symptoms should be active within the preceding 3 mo. ordination of the diaphragm and abdominal wall musculature. IBS, irritable bowel syndrome. EMG obtained during abdominal distension, either spontaneous Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology The American Journal of GASTROENTEROLOGY 44 Damianos et al. diaphragm seems to be an important driver of APD, perhaps pregabalin 225 mg twice daily significantly improved abdominal ultrasound could provide a simple, inexpensive, noninvasive, and bloating (36). However, the role of neuromodulators in visible reliable way to help identify paradoxical diaphragmatic move- abdominal distension and APD remains to be established (32). ment reflective of APD (6,19). CBT seems promising because it targets maladaptive behaviors and REVIEW ARTICLE helps regulate psychological and physiologic responses to emo- TREATMENT tional and physical stimuli. At present, there are no standardized treatments of APD specif- Finally, associated comorbidities and symptoms, including ically; however, multiple treatments of functional abdominal IBS, FD, pelvic floor dysfunction, endometriosis, anxiety, de- bloating and distension have been studied and discussed else- pression, and PTSD, should be appropriately treated. CBT may be where (6,24). In this study, we focus on treatments that specifi- particularly useful in patients with significant psychological cally target the physiology that underlies APD. comorbidities. EMG biofeedback CONCLUSION AND FUTURE DIRECTIONS Patients in the study by Barba et al. (6) used EMG activity as a APD is characterized by the pathologic contraction and descent of visual signal for biofeedback. Using the real-time EMG signal, the diaphragm and relaxation and protrusion of the abdominal they were able to decrease EMG activity for the diaphragm and wall. A series of studies indicate that this abnormal response con- intercostal muscles, and this response was associated with the tributes to distension in DGBIs, including IBS, FD, and functional ascension of the diaphragm, reduction in abdominal girth, and bloating and distension. There are currently no diagnostic criteria improvement in the subjective sensation of abdominal distension for APD. Dynamic cross-sectional imaging can identify APD, but (6). Similarly, in a subsequent placebo-controlled trial, Barba et al. less expensive and easily accessible technologies, such as ultra- (7) found that the biofeedback technique enabled patients with sound, may be more useful in identifying and even treating APD. various DGBIs and symptoms of postprandial bloating to reduce There are promising data to support the use of biofeedback to treat intercostal muscle activity and increase anterior wall muscle ac- APD, but there are currently no standardized treatment protocols, tivity, thereby reducing the sensation of abdominal distension and access to biofeedback is limited. Adjunctive treatments tar- and perceived girth. These data indicate that patients can be geting central sensitization and visceral hypersensitivity may also trained to control abdominophrenic postural tone, release the be helpful. With the growing appreciation of APD and its contri- diaphragmatic blockade, and correct abdominal distension. bution to DGBIs, future efforts should increase the understanding Hence, biofeedback may be useful to correct APD and abdominal of APD, develop standardized diagnostic criteria, and propose distension; however, the EMG technique used is complex and evidence-based treatment recommendations. expensive, and there is currently extremely limited access and no standardized protocols. CONFLICTS OF INTEREST Diaphragmatic breathing Guarantor of the article: Fernando Azpiroz, MD, PhD. Diaphragmatic breathing is effective for treating aerophagia, Specific author contributions: J.D., S.T., and E.B.: study design, belching, and rumination syndrome (25–28). This technique may conduction of review, data analysis. F.A.: data interpretation. also be effective for the management of bloating, because it targets Financial support: None to report. the maladaptive somatic response. 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