As previously reported where Pseudomonas is frequently isolated in patients with bronchiectasis and LTX recipients, our study demonstrated that LTX recipients with bronchiectasis other than CF experienced high rate of pre- and post-transplant Pseudomonas colonization with statistical significance. Nevertheless, long-term survival in the bronchiectasis group was as great as the non-bronchiectasis group or other disease categories, and bronchiectasis was not an independent risk for CLAD development. Our results were consistent with other analyses that survival rate was similar between bronchiectasis (n = 42) vs other disease requiring bilateral LTX in UK and between bronchiectasis with CF (n = 42) and non-CF (= 33) in Israel although isolation of Pseudomonas aeruginosa was common in those population. In view of these considerations, it is conceivable that bronchiectasis, despite high prevalence of pre- and post-transplant Pseudomonas colonization, is not a prominent risk factor for the post-transplant mortality and the development of CLAD. However, as numerous confounding factors affect the outcomes after transplantation, multivariate analysis would be helpful for further understanding of the risks in those population. To this end, the study including a large number of patients should be planned to see which variables among the individuals with bronchiectasis would have an impact on the post-transplant outcomes.
Given their ubiquitous presence in many environments, both NTM and Aspergillus are also frequently identified from LTX recipients but considered more unfavorably due to their pathogenic roles, and currently regarded as probable risk factors for the poor outcomes among LTX recipients. A higher cumulative incidence of post-transplant NTM colonization was found in bronchiectasis compared to other diseases (Log-rank 0.042), whereas the post-transplant prevalence of Aspergillus was high in the suppurative disease rather than the other categories (Log-rank p = 0.022). In view of the graft and native lungs that accompany anatomic abnormalities and are constantly exposed to ubiquitous environmental micro-organisms, superinfection or double- or triple-isolation of Pseudomonas, NTM and Aspergillus is of expected consequence after LTX. However, pathogenic roles of those organisms are not clearly defined because of complicated pathogen-host interactions especially under immune-suppressants and the heterogeneous pathogenesis of bronchiectasis. Furthermore, microbiological assessment of the pathogenic aspect of those organisms is challenging as there are no validated biomarkers to distinguish infection from colonization and also the majority of LTX recipients is routinely or repeatedly on anti-microbial agents for prophylaxis or treatment. With our analysis, the post-transplant prevalence of Pseudomonas, NTM and Aspergillus was high in LTX recipients with bronchiectasis. Nevertheless, an extended study to see how those micro-organisms influence the graft function and how anti-microbial agents, together with immunosuppression, play roles in such population are needed.
A prominent feature of bronchiectasis other than CF is an involvement of chronic sinusitis with little known etiology. Sinusitis is considered a reservoir for allograft colonization of micro-organisms after LTX. In our assessment, chronic sinusitis was an independent risk factor for CLAD (HR 2.56, 95% CI 1.10–5.99) and post-transplant Pseudomonas colonization (HR 2.75, 95% CI 1.21–6.28). In previous studies, sinus surgery led to an improvement in pulmonary function in LTX recipients with sinusitis and reduced Pseudomonas colonization in CF-LTX recipients. Importantly, there was a high correlation between pre-transplant sinus and post-transplant BAL cultures for Pseudomonas and the same isolates was found in between nasal lavage and BAL performed on the same visit in CF patients. With those features in mind, it should be reasonable to consider the early intervention of sinus surgery prior to LTX or in the early phase after LTX, which may be capable of preventing from the development of CLAD in the specific population with chronic sinusitis. Thus, our next challenge is to consider the clinical trial to prospectively intervene whether sinus surgery affect the transplant outcome in patients with sinusitis.
Nonetheless, our study must be interpreted with caution and a number of limitations should be considered. First, we have insufficient sample size for further analysis. In order to seek the risk factors for outcomes, there were variables that needed to be included for the analysis, such as bronchiectasis, pre-transplant Pseudomonas colonization and chronic sinusitis, with which multivariate analysis should be performed. Due to shortage of the bronchiectasis patients (n = 13), the multivariate cox hazard model showed a wide confidence interval (supplemental data) and was not worth documenting. Despite the univariate analysis that lacks adjustments for comparisons or power for multivariate analysis, comparable survival rates and a high rate of pre- and post-transplant Pseudomonas colonization in bronchiectasis were evident from our study. A multicenter study including a large number of patients with bronchiectasis for analysis would be beneficial in seeing the outcome calculated on the basis of a multivariate analysis. Second, we were unable to analyze whether the post-transplant Pseudomonas led to the CLAD onset, or vice versa. An etiology between post-transplant Pseudomonas colonization and CLAD development is a chicken-or-egg problem and remains unexplored, yet colonized Pseudomonas was partially or somewhat considerably associated with developing or worsening CLAD. To understand whether the duration of one variable is a risk factor for another variable is complicated when it may occur at some time after LTX. Apart from causality that has never been proven through observational studies, the recent study from clinical practice demonstrated Pseudomonas eradication after LTx improved CLAD-free and graft survival and maintained pulmonary function. This kind of intervention is a means to prove its complicated relationship and a feasible approach to seek how best we could provide better outcome among individuals with bronchiectasis after LTX.