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Published on: March 9, 2018
Non-Aspergillus fumigatus mould infections in lung transplant recipients: an international, multicentre, case-control
Benoît Henry1, Laura N Walti2, Sagar Kothari3
1Transplant Infectious Diseases Program, Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada; Service des Maladies Infectieuses et Tropicales, Hôpital Universitaire Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin-Bicêtre, France.
Background:
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.
Methods:
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.
Findings:
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.
Interpretation:
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.
Funding:
None.
Insights
Non-Aspergillus fumigatus mould infections (NAFMIs) in lung transplant recipients often present similarly to Aspergillus fumigatus infections. Pre-transplant immunosuppression is a key risk factor for NAFMIs, necessitating thorough investigation of airway mould findings.
Area of Science:
- Pulmonology
- Infectious Diseases
- Transplantation Medicine
Background:
- Invasive fungal infections (IFIs) pose a significant threat to lung transplant recipients.
- While Aspergillus fumigatus is common, non-A. fumigatus mould infections (NAFMIs) represent a substantial portion of IFIs.
Purpose of the Study:
- To investigate the epidemiology, clinical characteristics, risk factors, and outcomes of NAFMIs post-lung transplantation.
- To compare NAFMIs with Aspergillus fumigatus infections and IFI-free controls.
Main Methods:
- Retrospective, international, multicentre case-control study involving 120 NAFMI cases and 240 controls (120 A. fumigatus IFI, 120 IFI-free).
- Data collected on clinical presentation, outcomes (12-week response, 12-month survival, CLAD), and risk factors using logistic regression.
Main Results:
- Aspergillus flavus and Aspergillus niger were the most frequent NAFMI pathogens.
- Clinical presentations and 12-month mortality/CLAD rates were similar between NAFMI and A. fumigatus groups.
- Pre-transplant immunosuppression and ICU stay were independently associated with NAFMI development.
Conclusions:
- NAFMIs are primarily caused by non-fumigatus Aspergillus species.
- Diagnostic features of NAFMIs resemble those of A. fumigatus infections.
- Pre-transplant immunosuppression increases NAFMI risk, underscoring the need for diligent airway mould investigation post-transplant.
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