Gastroesophageal reflux disease (GERD) in patients who undergo lung transplantation increases the risk of post-transplant aspiration. That can result in acute rejection by inducing an inflammatory cascade in the allograft, and recurrent episodes of acute rejection can culminate in graft failure.

Researchers at Brigham and Women’s Hospital drew two conclusions from a recent retrospective study: routine pre-transplant esophageal motility and reflux evaluation identifies patients at increased risk of GERD-related allograft injury, and timely testing should result in optimal medical or surgical anti-reflux intervention after transplant within six months.

Wai-Kit Lo, MD, MPH, assistant professor in the Division of Gastroenterology, Hepatology and Endoscopy, Walter W. Chan, MD, MPH, director of the Center for Gastrointestinal Motility in the Division, and colleagues propose a standardized approach to reflux evaluation and management in lung transplant recipients in Clinical and Translational Gastroenterology.

Methods

The team analyzed data on 175 adults who underwent a lung transplant at the Brigham between 2007 and 2016. All had pretransplant reflux testing with 24-hour pH monitoring with or without multichannel intraluminal impedance. The average follow-up time was 2.7 years.

Proton pump inhibitors (PPIs) were not prescribed routinely after transplantation. They were given for any reflux-associated symptoms or if the patient had evidence of objective reflux on pretransplant testing.

In some cases, a clinical decline in pulmonary function prompted more aggressive anti-reflux management, including medical acid suppression. Anti-reflux surgery (ARS) was offered only if reflux had been diagnosed on objective testing before transplantation.

Rejection Outcomes

Patients were classified into three groups for comparison of rejection outcomes:

• No GERD—No objective reflux on pretransplant monitoring (n=101)

• Timely treatment—Objective reflux pretransplant; PPI only (n=34), or ARS pretransplant or within six months post-transplant (n=22)

• Delayed treatment—Objective reflux pretransplant; no PPI or ARS within six months post-transplant (n=18)

On multivariable analyses, compared with patients who received timely treatment, patients who received delayed treatment had significantly increased risk of:

• Acute rejection (AR)—HR, 3.81
• Bronchiolitis obliterans syndrome (BOS)—HR, 2.22
• Chronic lung allograft dysfunction (CLAD)—HR, 2.97

Likewise, compared with patients who had no GERD, patients who received delayed treatment had a significantly increased risk of:

• AR—HR, 2.26
• BOS—HR, 2.40
• CLAD—HR, 3.21

Both PPI and ARS were well tolerated overall.

Subgroup Analyses

On subgroup analyses, the timely treatment group was separated into patients who received PPI only and those who underwent early ARS. The risks of AR, BOS, and CLAD were:

• Similar between those two groups
• Significantly better than in the delayed treatment group
• Similar to the risks in the no GERD group

Suggested Reflux Evaluation and Management

All transplant candidates should undergo the following:

• Pretransplant high-resolution esophageal manometry—Findings will contribute to risk assessment and planning of perioperative care, including consideration of referral to centers highly specialized in high-risk populations

• Pretransplant ambulatory reflux monitoring—Patients with positive results should start PPI therapy and be considered for ARS, to be performed within six months after the transplant

Having a standard protocol is more important than whether the reflux monitoring is completed before or soon after the transplant. The distinction may depend on local volume, expertise, testing capacity, and, if needed, surgical wait time.

ARS should remain the mainstay of reflux therapy in lung transplantation, with PPI serving mainly as adjunctive treatment or a bridge to ARS after transplant.