Pepsin concentrations are elevated in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis after lung transplantation.

BACKGROUND: Aspiration of gastroesophageal refluxate has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and the progression of bronchiolitis obliterans syndrome after lung transplantation. The goals of the present study were to identify lung transplant patients at the greatest risk of aspiration and to investigate the causative factors. MATERIALS AND METHODS: From September 2009 to November 2011, 252 bronchoalveolar lavage fluid (BALF) samples were collected from 100 lung transplant patients. The BALF pepsin concentrations and the results of transbronchial biopsy, esophageal function testing, barium swallow, and gastric emptying scan were compared among those with the most common end-stage lung diseases requiring lung transplantation: IPF, chronic obstructive pulmonary disease, cystic fibrosis, and α1-antitrypsin deficiency. RESULTS: Patients with IPF had higher BALF pepsin concentrations and a greater frequency of acute rejection than those with α1-antitrypsin deficiency, cystic fibrosis, or chronic obstructive pulmonary disease (P = 0.037). Moreover, the BALF pepsin concentrations correlated negatively with a lower esophageal sphincter pressure and distal esophageal amplitude; negatively with distal esophageal amplitude and positively with total esophageal acid time, longest reflux episode, and DeMeester score in those with chronic obstructive pulmonary disease; and negatively with the upright acid clearance time in those with IPF. CONCLUSIONS: Our results suggest that patients with IPF after lung transplantation are at increased risk of aspiration and a greater frequency of acute rejection episodes, and that the risk factors for aspiration might be different among those with the most common end-stage lung diseases who have undergone lung transplantation. These results support the role of evaluating the BALF for markers of aspiration in assessing lung transplant patients as candidates for antireflux surgery.

Survival and extrapulmonary course of connective tissue disease after lung transplantation.

BACKGROUND: Connective tissue disease (CTD)-related lung dysfunction is a common cause of morbidity and mortality; however, few lung transplantations (LTs) are performed in this population secondary to uncertainty regarding the posttransplant survival, outcome, and management. OBJECTIVES: The objectives were to evaluate the survival and the pulmonary and extrapulmonary courses of CTD after LT. METHODS: Survival outcomes of patients documented within the Organ Procurement and Transplantation Network who had undergone a LT for CTD were compared with those who underwent LT for chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In addition, the pulmonary and extrapulmonary courses of the CTD were evaluated after LT. RESULTS: From 1991 to 2009, there were 284 documented LT in patients with CTD. Post-LT cumulative survival of patients with CTD was less than that for COPD through 5 years, with a difference that peaked at 1 year (72.7% vs. 83.1%, P < 0.001). When patients with CTD were compared with those with IPF, a difference was only noted at 1 year (72.7% vs. 77.7%, P = 0.049). There were no documented post-LT pulmonary recurrences of the CTD, and extrapulmonary flares of the CTD were rare (1 possible flare per 20.3 patient-years and 1 probable flare per 81.0 patient-years). CONCLUSIONS: Cumulative survival of patients with CTD who underwent LT is similar to those with IPF and slightly less than those with COPD, with an increased risk of mortality that was most prominent at 6 months after transplant followed by subsequent narrowing of the survival differences over time. Lung transplantation may be a viable therapeutic option for patients with end-stage lung dysfunction resulting from a CTD.

Clinical pathway after lung transplantation shortens hospital length of stay without affecting outcome.

Transplant programs are under pressure to resolve multiple challenges related to quality, cost, and access in a resource-driven customer-focused health care environment. We reviewed outcomes of patients undergoing isolated lung transplantation using a single postoperative clinical pathway, developed between the specialties of Thoracic Surgery, Pulmonary and Critical Care Medicine, and Nursing. The data were retrospectively reviewed for mortality, length to extubation (LE), hospital length of stay (LOS), and readmissions of 183 consecutive patients. One hundred ten women and 73 men with a mean age of 48 +/- 12 years underwent 90 bilateral, 88 single, and 6 repeat lung transplantations. Median LE was 17 hours, and the LOS was 7 days. The operative mortality was 6.5%. One- and 3-year survivals were 82% and 73%, respectively. We conclude that a single multidisciplinary clinical pathway can facilitate early discharge from the hospital. Early hospital discharge after lung transplantation does not compromise early or late outcome.

The protective role of laparoscopic antireflux surgery against aspiration of pepsin after lung transplantation.

BACKGROUND: The goal of this study was to determine, in lung transplant patients, if laparoscopic antireflux surgery (LARS) is an effective means to prevent aspiration as defined by the presence of pepsin in the bronchoalveolar lavage fluid (BALF). METHODS: Between September 2009 and November 2010, we collected BALF from 64 lung transplant patients at multiple routine surveillance assessments for acute cellular rejection, or when clinically indicated for diagnostic purposes. The BALF was tested for pepsin by enzyme-linked immunosorbent assay (ELISA). We then compared pepsin concentrations in the BALF of healthy controls (n = 11) and lung transplant patients with and without gastroesophageal reflux disease (GERD) on pH-monitoring (n = 8 and n = 12, respectively), and after treatment of GERD by LARS (n = 19). Time to the development of bronchiolitis obliterans syndrome was contrasted between groups based on GERD status or the presence of pepsin in the BALF. RESULTS: We found that lung transplant patients with GERD had more pepsin in their BALF than lung transplant patients who underwent LARS (P = .029), and that pepsin was undetectable in the BALF of controls. Moreover, those with more pepsin had quicker progression to BOS and more acute rejection episodes. CONCLUSION: This study compared pepsin in the BALF from lung transplant patients with and without LARS. Our data show that: (1) the detection of pepsin in the BALF proves aspiration because it is not present in healthy volunteers, and (2) LARS appears effective as a measure to prevent the aspiration of gastroesophageal refluxate in the lung transplant population. We believe that these findings provide a mechanism for those studies suggesting that LARS may prevent nonallogenic injury to the transplanted lungs from aspiration of gastroesophageal contents.