Risk of Lung Allograft Dysfunction Associated With Aspergillus Infection

Abstract

Background. We sought to determine whether invasive aspergillosis (IA) during the first year after lung transplantation increased the risk of chronic lung allograft dysfunction (CLAD). Methods. We retrospectively reviewed the records of 191 patients who underwent lung transplantation at our institution between January 2013 and December 2017. Screening for Aspergillus was with bronchial aspirates, bronchoalveolar lavage if indicated or during surveillance bronchoscopy, radiography, and computed tomography. We used Fine and Gray multivariable regression to identify potential risk factors for CLAD. Results. During the first posttransplant year, 72 patients had at least 1 deep-airway sample positive for Aspergillus ; 63 were classified as having IA and were included in the study. Median number of endoscopies per patient during the first year was 9 (range, 1–44). Median time from transplantation to first Aspergillus -positive sample was 121 d. Bronchial aspirate samples and bronchoalveolar lavage fluid were positive in 71 and 44 patients, respectively. Aspergillus fumigatus (n = 36, 50%) predominated; bacterial samples were also positive in 22 (31%) patients. IA within 4 mo after transplantation was independently associated with CLAD development (subdistribution hazard ratio, 3.75; 95% confidence interval [CI], 1.61-8.73; P < 0.01) by regression analysis. Survival at 3 and 5 y conditional on 1-y CLAD-free survival was 37% (95% CI, 24%-58%), and 24% (95% CI, 11%-52%) in the IA <4 mo group compared to 65% (95% CI, 57%-73%) and 54% (95% CI, 43%-66%) in the non-IA group and to 69% (95% CI, 58%-83%) and 54% (95% CI, 35%-82%) in the IA ≥4 mo group, respectively ( P < 0.01, logrank test). Conclusions. Our evaluation of de novo IA showed that this infection was most strongly associated with CLAD when found within 4 mo after transplantation.

Aspergillus-Specific IgG Antibodies are Associated With Fungal-Related Complications and Chronic Lung Allograft Dysfunction After Lung Transplantation

“…This retrospective study of prospectively collected data in a large cohort of LTx recipients demonstrated for the first time that Aspergillus species specific IgG was associated with later fungal isolation and fungal-related complications (IFD,CLAD). This study also confirmed previously published findings that mold isolation, especially Aspergillus species, was associated with CLAD development and impaired survival ( 3 – 5 ).…”

“…Invasive fungal infections are a known risk factor for CLAD, and even without signs of infection Aspergillus species isolation from airway sampling is considered a risk factor for CLAD. In our study, Aspergillus species were cultured in 74.3% of the respiratory samples demonstrating molds, and Aspergillus species isolation was significantly associated with CLAD and impaired survival, confirming findings from earlier studies ( 2 – 5 ). There was no significant difference in CLAD occurrence in patients with Aspergillus IFD vs. non-IFD Aspergillus isolation.…”

“…CLAD is the leading cause of death beyond the first post-transplant year. Respiratory infections are among the many elements reported to contribute to CLAD ( 4 , 5 , 17 – 19 ). Indeed, presence of molds within the airways after transplantation may result in local innate inflammation and epithelial injury followed by dysregulation of repair mechanisms, ultimately responsible for chronic fibroproliferation and progressive graft dysfunction ( 4 , 5 , 20 – 22 ).…”

“…These numbers are notably higher than after other solid-organ transplantations ( 1 ). Aspergillus fumigatus is a known risk factor for chronic lung allograft dysfunction (CLAD), the leading cause of death beyond the first year after LTx, even in patients that are only colonized without signs of infection ( 2 – 5 ). However, respiratory samples are not always readily available, as not all patients produce sputum.…”

“…Subclinical presence of Aspergillus fumigatus could thus remain undetected. The role of other Aspergillus species or non- Aspergillus molds in the pathogenesis of CLAD is currently unclear ( 2 , 3 , 5 ).…”