Lung Transplant Outcomes in Systemic Sclerosis with Significant Esophageal Dysfunction. A Comprehensive Single-Center Experience

Abstract

Rationale: Consideration of lung transplantation in patients with systemic sclerosis (SSc) remains guarded, often due to the concern for esophageal dysfunction and the associated potential for allograft injury and suboptimal post-lung transplantation outcomes.

Objectives: The purpose of this study was to systematically report our single-center experience regarding lung transplantation in the setting of SSc, with a particular focus on esophageal dysfunction.

Methods: We retrospectively reviewed all lung transplants at our center from January 1, 2000 through August 31, 2012 (n = 562), comparing the SSc group (n = 35) to the following lung transplant diagnostic subsets: all non-SSc (n = 527), non-SSc diffuse fibrotic lung disease (n = 264), and a non-SSc matched group (n = 109). We evaluated post-lung transplant outcomes, including survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates. In addition, we defined severe esophageal dysfunction using esophageal manometry and esophageal morphometry criteria on the basis of chest computed tomography images. For patients with SSc referred for lung transplant but subsequently denied (n = 36), we queried the reason(s) for denial with respect to the concern for esophageal dysfunction.

Measurements and main results: The 1-, 3-, and 5-year post-lung transplant survival for SSc was 94, 77, and 70%, respectively, and similar to the other groups. The remaining post-lung transplant outcomes evaluated were also similar between SSc and the other groups. Approximately 60% of the SSc group had severe esophageal dysfunction. Pre-lung transplant chest computed tomography imaging demonstrated significantly abnormal esophageal morphometry for SSc when compared with the matched group. Importantly, esophageal dysfunction was the sole reason for lung transplant denial in a single case.

Conclusions: Relative to other lung transplant indications, our SSc group experienced comparable survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates, despite the high prevalence of severe esophageal dysfunction. Esophageal dysfunction rarely precluded active listing for lung transplantation.

Keywords: acute rejection; esophageal dysfunction; gastroesophageal reflux; lung transplantation; scleroderma.

Figure 1.

Product-limit survival estimates, with number of subjects at risk. Kaplan-Meier curves for post–lung transplant survival for all cohorts. Log-rank test systemic sclerosis (SSc) versus the following: non-SSc (P = 0.31), diffuse fibrotic lung disease (DLFD) (P = 0.20), and matched groups (MG) (P = 0.95).

Figure 2.

Product-limit survival estimates, with number of subjects at risk. Kaplan-Meier curves for post–lung transplantation bronchiolitis obliterans syndrome–free survival for all cohorts. Log-rank test systemic sclerosis (SSc) versus the following: non-SSc (P = 0.57), diffuse fibrotic lung disease (DFLD) (P = 0.62), and matched groups (MG) (P = 0.55).

Figure 3.

Comprehensive results of available gastrointestinal testing and computed tomography (CT) chest imaging for the systemic sclerosis (SSc) cohort (n = 35) before lung transplantation (n = 35); each row represents an individual lung transplant recipient with SSc. (−) implies the study was not performed before lung transplantation Shaded boxes imply the study was abnormal; open boxes imply the study was normal (if the study was performed). pH probe: abnormal is DeMeester score > 14.7; *off acid suppression; the absence of * implies the study was done on acid suppression. Peristalsis (as assessed by esophageal manometry): *severe esophageal dysmotility; **esophageal aperistalsis. Esophagitis: abnormal implies upper endoscopy findings consistent with reflux esophagitis. Air fluid level (AFL): abnormal is the presence of AFL by CT chest imaging. Patulous esophagus (PE): abnormal is presence of a patulous esophagus by CT chest imaging. Maximum esophageal diameter (MED): abnormal is MED ≥ 15 mm by CT chest imaging.

Figure 4.

The reasons for lung transplantation (LT) denial for the 36 patients with systemic sclerosis (SSc) referred to the University of California Los Angeles Lung Transplant Program over the 12-year study period. ¹Multifactorial includes one or more of the following: age, prior pectus deformity surgery, moderate to severe aortic stenosis, renal insufficiency, body mass index ≥ 40, restrictive cardiomyopathy, history of papillary thyroid cancer, abnormal neuropsychiatric testing, multiple prior transient ischemic attacks, recurrent lower extremity ischemic ulceration. ²Gastrointestinal concerns included one or more of the following: clinically uncontrolled gastroesophageal reflux despite optimal medical therapy and lifestyle modifications, recurrent esophageal dilation due to achalasia, severe gastric dysmotility. ³This patient had recurrent episodes of clinically overt aspiration pneumonia requiring hospitalization despite optimal medical therapy for gastroesophageal reflux.