Thoracoabdominal pressure gradient and gastroesophageal reflux: insights from lung transplant candidates

Advanced lung disease is associated with gastroesophageal reflux disease (GERD). The thoracoabdominal pressure gradient (TAPG) facilitates gastroesophageal reflux, but the effects of TAPG on gastroesophageal reflux in patients with pulmonary disease have not been well defined. Patients diagnosed with end-stage lung disease are expected to have the most extreme derangement in respiratory mechanics. The aim of this study is to explore the relationship between TAPG and reflux in lung transplant (LTx) candidates. We reviewed LTx recipients who underwent pretransplant esophageal high-resolution manometry and a 24-hour pH study. Patients were excluded if they were undergoing redo LTx, had manometric hiatal hernia, or had previously undergone foregut surgery. TAPG was defined as the intra-abdominal pressure minus the intrathoracic pressure during inspiration. Adjusted TAPG was calculated by the TAPG minus the resting lower esophageal sphincter (LES) pressure (LESP). Twenty-two patients with normal esophageal function tests (i.e., normal esophageal motility with neither manometric hiatal hernia nor pathological reflux on 24-hour pH monitoring) were selected as the pulmonary disease-free control group. In total, 204 patients underwent LTx between January 2015 and December 2016. Of these, 77 patients met inclusion criteria. We compared patients with obstructive lung disease (OLD, n = 33; 42.9%) and those with restrictive lung disease (RLD, n = 42; 54.5%). 2/77 patients (2.6%) had pulmonary arterial hypertension. GERD was more common in the RLD group than in the OLD group (24.2% vs. 47.6%, P = 0.038). TAPG was similar between the OLD group and the controls (14.2 vs. 15.3 mmHg, P = 0.850); however, patients in the RLD group had significantly higher TAPG than the controls (24.4 vs. 15.3 mmHg, P = 0.002). Although TAPG was not correlated with GERD, the adjusted TAPG correlated with reflux in all 77 patients with end-stage lung disease (DeMeester score, r(s) = 0.256, P = 0.024; total reflux time, r(s) = 0.259, P = 0.023; total number of reflux episodes, r(s) = 0.268, P = 0.018). Additionally, pathological reflux was seen in 59.1% of lung transplant candidates with adjusted TAPG greater than 0 mmHg (i.e., TAPG exceeding LESP); GERD was seen in 30.9% of patients who had an adjusted TAPG <= 0 mmHg. In summary, TAPG varies based on the underlying cause of lung disease. Higher adjusted TAPG increases pathological reflux, even if patients have normal antireflux anatomy and physiology (i.e., no hiatal hernia and manometrically normal LES function). Adjusted TAPG may provide further insights into the pathophysiology of GERD.