Role of gastroesophageal reflux disease in lung transplantation

Table 1 Papers summarizing effects of gastroesophageal reflux disease on transplant outcomes

Ref.	Population	Definition GERD and/or aspiration	Outcomes evaluated	Adjunctive therapy
King et al[29], 2009	59 pts. Post-LTx	Abnormal acid and non-acid reflux on esophageal impedance monitoring	Effect of reflux on time to development of BOS via hazard ratio
Hadjiliadis et al[33], 2003	43 pts. Post-LTx, survived > 6 mo, and underwent pH and manometry testing	Abnormal acid exposure time on 24-h pH testing	Effect of reflux on FEV1 (via Pearson correlation coefficient for time of study, via multivariable linear regression to assess overall effect)	PPI d/c’ed > 5 d prior to testing, H2 blockers and pro-motility agents > 1 d prior to testing
Stovold et al[35], 2007	36 asymptomatic pts. Post-LTx vs 4 healthy volunteers vs 17 patients with chronic cough	Increased levels of pepsin in BALF	Presence of pepsin, association between level of pepsin and acute rejection	30 LTx patients on antireflux therapy
Blondeau et al[36], 2009	24 pts. Post-LTx	Abnormal reflux on 24-h impedance-pH testing, bile acids in BALF	Relationship between acid exposure, volume exposure, or reflux events and bile acids in BALF	PPI d/c’ed 1 wk prior to testing
D’Ovidio et al[37], 2005	120 pts. Post-LTx	Increased levels of bile acids in BALF	Relationship between increased levels of bile acids, IL-8, neutrophils on development of BOS
Benden et al[41], 2005	10 pts. Post-LTx	Abnormal reflux on 24-h pH testing	Prevalence of GERD in population
Fisichella et al[42], 2013	105 pts. Post-LTx with 257 BALF samples	24-h pH testing and DeMeester score calculation, Increased levels of pepsin in BALF	Association between aspiration and patterns of dysregulation of immune mediator concentrations and BOS	PPI d/c’ed 2 wk prior to testing, H2 blocker d/c’ed 3 d prior to testing
Young et al[56], 2003	23 pts. evaluated pre- and post-LTx	Total, upright, and supine acid exposure time on 24-h pH testing, esophageal manometry, gastric-emptying study	Paired comparison between pre-transplant and post-transplant results (paired t test)	Acid suppression and gastric motility meds discontinued before testing
D’Ovidio et al[57], 2006	70 pts. Post-LTx	Esophageal manometry, 24-h pH-testing (DeMeester score calculation, Castell’s method) and gastric emptying study; BALF analysis	Actuarial freedom from BOS, impact of aspiration on pulmonary surfactant collectin proteins	PPI d/c’ed 7 d prior, H2-blockers d/c’ed 2 d prior
Fisichella et al[58], 2012	61 pts. Post-LTx	Esophageal impedance-manometry, 24-h pH testing (DeMeester score calculation), EGD, barium swallow, gastric emptying study	Relationship between prevalence and extent of GERD and type of transplant (unilateral vs bilateral vs retransplant)	PPI d/c’ed 14 d prior to pH testing, H2 blockers stopped 3 d prior to pH testing
Fisichella et al[74], 2012	8 pts. Post-LARS and LTx in whom BALF had been collected	Esophageal 24-h impedance-pH testing (DeMeester score calculation), gastric emptying study	Comparison of BALF concentrations of leukocytes, immune mediators, and pepsin pre- and post-LARS and post-LTx	PPI d/c’ed 14 d prior to pH testing, H2 blockers stopped 3 d prior to pH testing
Blondeau et al[78], 2008	45 pts. Post-LTx off PPI, 18 pts. Post-LTx on PPI	Esophageal 24-h impedance-pH catheter, BALF analysis for pepsin and bile acids	Association between the prevalence and type of reflux and gastric aspiration in pts. with and without BOS	Antacids and promotility agents d/c’ed > 14 d prior to testing vs remained on for testing
Griffin et al[45], 2013	18 pts. Post-LTx	RSI, esophageal manometry and 24-h impedance-pH monitoring, BALF analysis	Quantification of reflux, aspiration, and allograft injury immediately post-operatively	Testing performed on PPI
Davis et al[84], 2013	100 pts Post-LTx with 252 BALF samples	BALF pepsin concentration, esophageal manometry, esophageal 24-h pH catheter (DeMeester score calculation), gastric emptying study	Association between concentration of pepsin in BALF and results of esophageal function testing, barium swallow and gastric emptying to identify risk factors for GERD	PPI d/c’ed 14 d prior to pH testing, H2 blockers d/c’ed 3 d prior to pH testing
Hartwig et al[71], 2006	7 models of rat lung transplantation	Weekly injection of gastric contents for 4-8 wk	Degree of pulmonary allograft dysfunction reflective of chronic aspiration	N/A
Li et al[72], 2008	9 models of rat lung transplantation	Weekly injection of gastric contents for 8 wk	Association between chronic aspiration and development of OB	N/A
Meltzer et al[73], 2008	3 models of swine lung transplantation	Daily injection of gastric contents for 50 d	Effect on chronic aspiration on the direct and indirect pathways of allorecognition	N/A

BALF: Bronchoalveolar lavage fluid; BOS: Bronchiolitis obliterans syndrome; OB: Obliterative bronchiolitis; RSI: Reflux severity index; GERD: Gastroesophageal reflux disease; N/A: Not available.