Non-Aspergillus fumigatus mould infections in lung transplant recipients: an international, multicentre, case-control study.

Abstract

Invasive fungal infections (IFIs) are of major concern in lung transplant recipients. Although Aspergillus fumigatus is the predominant pathogen, non-A fumigatus mould infections (NAFMIs) also account for a substantial proportion of IFIs. We aimed to describe the epidemiology, clinical spectrum, risk factors, and outcomes of NAFMIs after lung transplantation. We performed a retrospective, international, multicentre, case-control study across nine tertiary care centres in Canada and Europe. We included adult (aged ≥18 years) lung transplant recipients. Cases were defined as individuals with proven or probable IFIs caused by a mould other than A fumigatus (NAFMI group). Exclusion criteria were a concomitant infection with A fumigatus and a non-A-fumigatus mould and isolated positivity of galactomannan in serum or bronchoalveolar lavage. Two controls per case were included: one with IFI due to A fumigatus (A fumigatus control group) and one free of any IFI (IFI-free control group). 1:1:1 matching was done according to centre and time after transplantation (for IFI-free controls). We reviewed medical records to assess the clinical and radiological presentation and clinical outcomes (including 12-week therapeutic response, 12-month survival, development of chronic lung allograft dysfunction [CLAD] and post-transplant lymphoroliferative disorder) and used logistic regression models to assess risk factors for IFIs. The primary outcomes were the description of the microbial aetiologies of NAFMI, survival and CLAD 12-month post-IFI, and identification of factors associated with NAFMI. Between Jan 1, 2010, and Jan 1, 2020, we included 120 individuals in the NAFMI group and 240 individuals in the control groups (n=120 in each control group). Median age at transplantation was 56 years (IQR 44-63); 170 (47%) of 360 participants were female and 190 (53%) were male. Only eight (7%) of 120 individuals in the NAFMI group had a polyfungal or mixed infection. Aspergillus flavus (26 [22%] of 120) and Aspergillus niger (24 [20%]) were the most common pathogens in the NAFMI group, followed by Scedosporium apiospermum (9[8%]). Respiratory symptoms predominated in individuals with IFI, and clinical presentations were similar in individuals with NAFMI and A fumigatus IFI. 12-month mortality was comparable across groups (NAFMI: 37/118 [31%], A fumigatus: 36/117 [31%], p=1; IFI-free controls: 25/120 [21%], p=0·11 compared with NAFMI). CLAD at 12-month post-IFI occurred at similar frequencies in cases and controls (NAFMI: 13/108 [12%], A fumigatus 17/111 [15%], p=0·69; IFI-free controls: 8/110 [7%], p=0·36 compared with NAFMI). Pre-transplant immunosuppression (adjusted odds ratio 3·82, 95% CI 1·55-9·38; p=0·0039) and pre-transplant intensive care unit stay (3·07, 1·01-9·34; p=0·048) were independently associated with NAFMI occurrence, when compared with IFI-free controls. NAFMIs mostly involve non-fumigatus Aspergillus spp. Diagnostic features of NAFMIs are similar to those of A fumigatus infections; pre-transplant immunosuppression can increase the risk of NAFMI onset. These findings reinforce the importance of a thorough investigation when a mould is isolated from the airways after lung transplantation. None.