['Exaggerated pressure fluctuation between the thorax and abdomen during exercise or with pulmonary disease may challenge the gastroesophageal barrier and allow reflux of gastric juice into the esophagus. The aim of this study was to investigate the pressure differentials in the region of the gastroesophageal junction to better understand the relationship between the thoraco-abdominal pressure gradient and the lower esophageal sphincter (LES) barrier function.', 'We reviewed the esophageal motility and 24-h pH studies in 151 patients with a manometrically normal lower esophageal sphincter who did not have pulmonary disease, history of anti-reflux surgery, hiatal hernia, or ineffective esophageal motility (IEM). Intra-abdominal gastric and intra-thoracic esophageal pressure fluctuations with respiration were measured and the thoraco-abdominal pressure gradients were calculated during both inspiratory and expiratory phases of the respiratory cycle. Predictive factors for an abnormal composite pH score were identified by multivariable analysis.', 'An inspiratory thoraco-abdominal pressure gradient that was higher than the resting LES pressure was found in 27 patients. In 23 of these patients (85.2%) there was increased esophageal acid exposure (OR 13.5, 95% CI 4.4-41.8). An abnormal composite pH score was predicted by a high inspiratory thoraco-abdominal pressure gradient (P < 0.001), greater fluctuation between inspiratory and expiratory thoracic pressure (P = 0.023), lower LES resting pressure (P = 0.049) and a decreased residual pressure after a swallow induced relaxation (P = 0.002).'] Do thoraco-abdominal pressure gradients during the phases of respiration contribute to gastroesophageal reflux disease?