Clinical lung and heart/lung transplantation
Airway Colonization and Gastric Aspiration After Lung Transplantation: Do Birds of a Feather Flock Together?

https://doi.org/10.1016/j.healun.2008.05.022Get rights and content

Background

Both gastroesophageal reflux and airway colonization with Pseudomonas aeruginosa (P aeruginosa) are common in lung transplantation (LTx) recipients. There is mounting evidence that, due to their interaction with the epithelium, both may be involved in chronic allograft dysfunction/bronchiolitis obliterans syndrome (BOS) after LTx. We investigated whether gastric aspiration and airway colonization with P aeruginosa after LTx are associated.

Methods

In this retrospective, cross-sectional, case–control study, 24 stable double (SS) LTx recipients were included. Markers of gastroesophageal reflux (pepsin, bile acids) and airway inflammation (neutrophilia and interleukin-8 (IL-8)) were evaluated in bronchoalveolar lavage (BAL) samples of post-operatively colonized (n = 12) and non-colonized matched-control LTx recipients (n = 12).

Results

BAL bile acid levels, but not pepsin levels, as well as neutrophilia and IL-8 protein levels were significantly elevated in colonized compared with non-colonized patients. Furthermore, bile acid levels, but not pepsin levels, correlated positively with BAL neutrophilia and IL-8 protein levels.

Conclusions

Bile acid aspiration and airway colonization by P aeruginosa after LTx seem to be associated. This relationship between reflux and airway colonization and their role in the development of chronic allograft dysfunction/BOS after LTx should be further elucidated; nevertheless, induction of IL-8–mediated neutrophilic airway inflammation may be a putative mechanism.

Section snippets

Study Population

In this retrospective cross-sectional case–control study, approved by the ethics review board of the University Hospital Gasthuisberg, inflammatory markers (IL-8 protein levels and cell differentials), as well as markers of gastroesophageal reflux (pepsin, bile acids) were evaluated in bronchoalveolar lavage (BAL) fluid of stable double lung transplant (SSLTx) recipients. Patients were selected from a group of 92 out of 125 patients transplanted between January 2000 and December 2005 at our

Study Population

Based on the aforementioned inclusion and exclusion criteria, 24 SSLTx recipients were included in the current study. Patients' characteristics are given in Table 1. Recipients' age, gender, FEV1 at time of BAL sampling after LTx, and therapeutic regimen were comparable between colonized and non-colonized patients (p = not significant [NS]). At the moment of BAL sampling, none of the included patients received azithromycin treatment, as outlined in the inclusion criteria. In this small cohort,

Discussion

In this study we sought to determine whether airway colonization by P aeruginosa and aspiration of gastroduodenal refluxate after LTx are associated. We could confirm that LTx recipients colonized by P aeruginosa had elevated BAL bile acid, but not pepsin, levels compared with non-colonized patients, possibly suggesting that specifically non-acid (bile) reflux may predispose to airway colonization after LTx. Furthermore, bile acid levels, but not pepsin levels, positively correlated with BAL

References (36)

  • E. Cantu et al.

    J. Maxwell Chamberlain Memorial PaperEarly fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease

    Ann Thorac Surg

    (2004)
  • B.M. Button et al.

    Gastroesophageal reflux (symptomatic and silent): a potentially significant problem in patients with cystic fibrosis before and after lung transplantation

    J Heart Lung Transplant

    (2005)
  • L. Law et al.

    Early changes in basement membrane thickness in airway walls post-lung transplantation

    J Heart Lung Transplant

    (2005)
  • E. Yabuuchi et al.

    Proposal of Burkholderia gen. nov. and transfer of seven species of the genus Pseudomonas homology group II to the new genus, with the type species Burkholderia cepacia (Palleroni and Holmes 1981) comb. nov

    Microbiol Immunol

    (1992)
  • S. Sethi et al.

    Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review

    Clin Microbiol Rev

    (2001)
  • M. Proesmans et al.

    Evaluating the “Leeds criteria” for Pseudomonas aeruginosa infection in a cystic fibrosis centre

    Eur Respir J

    (2006)
  • C.M. Greene et al.

    TLR-induced inflammation in cystic fibrosis and non-cystic fibrosis airway epithelial cells

    J Immunol

    (2005)
  • J. Tseng et al.

    Innate immune responses of human tracheal epithelium to Pseudomonas aeruginosa flagellin, TNF-alpha, and IL-1beta

    Am J Physiol Cell Physiol

    (2006)
  • Cited by (61)

    • The effect of gastric juice on interleukin-8 production by cystic fibrosis primary bronchial epithelial cells

      2013, Journal of Cystic Fibrosis
      Citation Excerpt :

      Since aspiration of duodeno-gastric contents was linked to the development of bronchiolitis obliterans syndrome after lung transplantation, several studies have been performed to determine their exact relationship. A clear correlation was found between bile acid levels and IL-8 concentrations and the number of neutrophils in bronchoalveolar lavage fluid of lung transplant patients, suggesting that bile acids are capable of inducing IL-8 expression [9,10]. Our group previously demonstrated that concentrations of bile acids in sputum of CF patients correlate with levels of neutrophil elastase, an inflammatory marker in the lungs [6].

    View all citing articles on Scopus

    Supported by the Research Foundation of Flanders (FWO; Grants G.0493.04, G.0518.06 and G.0643.08), a research grant from Sandhill Scientific (Denver, CO) and an educational grant from AstraZeneca (Belgium) (to D.S.).

    R.V. and K.B. contributed equally contributed to this study.

    View full text