Background: The long term clinical significance of respiratory infections after lung transplantation remains uncertain.
Methods: In this retrospective single-center cohort study of 441 lung transplant recipients, we formally evaluate the association between respiratory infection and chronic lung allograft dysfunction (CLAD). We furthermore hypothesized that bronchoalveolar lavage fluid (BALF) CXCL9 concentrations are augmented during respiratory infections, and that episodes of infection with elevated BALF CXCL9 are associated with greater CLAD risk.
Results: In univariable and multivariable models adjusted for other histopathologic injury patterns, respiratory infection, regardless of the causative organism, was a strong predictor of CLAD development (adjusted HR 1.8 95% CI 1.3-2.6). Elevated BALF CXCL9 concentrations during respiratory infections markedly increased CLAD risk in a dose-response manner. An episode of respiratory infection with CXCL9 concentrations greater than the 25th, 50th, and 75th percentile had adjusted HRs for CLAD of 1.8 (95% CI 1.1-2.8), 2.4 (95% CI 1.4-4.0) and 4.4 (95% CI 2.4-8.0), respectively.
Conclusions: Thus, we demonstrate that respiratory infections, regardless of the causative organism, are strong predictors of CLAD development. We furthermore demonstrate for the first time, the prognostic importance of BALF CXCL9 concentrations during respiratory infections on the risk of subsequent CLAD development.
Keywords: CXCL9; CXCR3; Lung transplantation; chronic lung allograft dysfunction; infection.
Conflict of interest statement
Competing Interests The authors have declared that no competing interests exist.
The prognostic importance of CXCR3 chemokine during organizing pneumonia on the risk of chronic lung allograft dysfunction after lung transplantation.PLoS One. 2017 Jul 7;12(7):e0180281. doi: 10.1371/journal.pone.0180281. eCollection 2017. PLoS One. 2017. PMID: 28686641 Free PMC article.
The Prognostic Importance of Bronchoalveolar Lavage Fluid CXCL9 During Minimal Acute Rejection on the Risk of Chronic Lung Allograft Dysfunction.Am J Transplant. 2018 Jan;18(1):136-144. doi: 10.1111/ajt.14397. Epub 2017 Aug 2. Am J Transplant. 2018. PMID: 28637080 Free PMC article.
Impact of Allograft Injury Time of Onset on the Development of Chronic Lung Allograft Dysfunction After Lung Transplantation.Am J Transplant. 2017 May;17(5):1294-1303. doi: 10.1111/ajt.14066. Epub 2016 Oct 31. Am J Transplant. 2017. PMID: 27676455 Free PMC article. Clinical Trial.
Infectious Triggers of Chronic Lung Allograft Dysfunction.Curr Infect Dis Rep. 2016 Jul;18(7):21. doi: 10.1007/s11908-016-0529-6. Curr Infect Dis Rep. 2016. PMID: 27221821 Free PMC article. Review.
Early Identification of Chronic Lung Allograft Dysfunction: The Need of Biomarkers.Front Immunol. 2019 Jul 17;10:1681. doi: 10.3389/fimmu.2019.01681. eCollection 2019. Front Immunol. 2019. PMID: 31379869 Free PMC article. Review.
- Christie JD, Edwards LB, Kucheryavaya AY, Benden C, Dobbels F, Kirk R, et al. The registry of the international society for heart and lung transplantation: Twenty-eighth adult lung and heart-lung transplant report−−2011. J Heart Lung Transplant. 2011; 30: 1104–1122. - PubMed
- Billings JL, Hertz MI, Savik K, Wendt CH. Respiratory viruses and chronic rejection in lung transplant recipients. J Heart Lung Transplant. 2002; 21: 559–566. - PubMed
- Fisher CE, Mohanakumar T, Limaye AP. Respiratory virus infections and chronic lung allograft dysfunction: Assessment of virology determinants. J Heart Lung Transplant. 2016; 35: 946–947. - PubMed
- Khalifah AP, Hachem RR, Chakinala MM, Schechtman KB, Patterson GA, Schuster DP, et al. Respiratory viral infections are a distinct risk for bronchiolitis obliterans syndrome and death. Am J Respir Crit Care Med. 2004; 170: 181–187. - PubMed