eComment. Benefits of macrolide usage and bacteriological profile in patients with diffuse panbronchiolitis

We read with great interest the article by Sugimoto et al. [1] where they described their experience with lung transplantation for diffuse panbronchiolitis (DPB), a chronic, idiopathic airways disease primarily affecting the East Asian population. Our aim is to appraise certain authors' statements by using the current evidence on the benefits of macrolide usage in patients with DPB, as well as to assess the bacteriological profile in those with this long-term condition.

Despite the need for lung transplantation in certain progressive DPB patients (as described in this paper), it is well-known that the advent of macrolide therapy has substantially changed the disease prognosis due to its anti-inflammatory and immunoregulatory effects. Hence the statement by the authors that the long-term macrolide therapy has been shown to significantly improve the survival in patients with DPB can be considered legitimate.

Still, a Cochrane review on this topic has emphasized the absence of high-quality evidence to support the usage of macrolides in the treatment of DPB, as the use of macrolides for this indication is based on retrospective and non-randomized controlled studies [2]. Even so, the Cochrane review states that, for the time-being, the use low-dose macrolides soon after establishing a diagnosis is a reasonable approach, extending their use for at least six months (in accordance to current guidelines) [2].

The Cochrane review also cautions that additional insights are definitely required on the subset of patients more likely to benefit from this treatment approach, as well as more information on the most suitable dose, type and duration of administration [2]. Since some patients in this study by Sugimoto et al. received macrolide therapy for up to 20 years and still deteriorated [1], proper assessment of the treatment efficacy and rationale for continuing macrolide therapy over protracted time periods in non-responsive individuals should be addressed earlier in the course of disease.

The authors further state that Pseudomonas aeruginosa (P. aeruginosa) was preoperatively isolated in the sputa of all five patients, which is an expected finding in the later course of the disease, as detection rates of P. aeruginosa rise to 60% or more after four years of treatment [3]. Nonetheless, no information was given as to whether the samples were tested for some other pathogens, which could also have be found in the sputa of patients with DPB, such as Haemophilus influenzae [3,4]. More importantly, defects of mucociliary clearance found in DPB may predispose individuals to infection with non-tuberculous mycobacteria (NTM) [5].

In a recent retrospective study from Japan, Tsuji et al. found that the overall prevalence of NTM in DBP was 21.2%, which was higher than the previous surveillance of NTM in the general Japanese population [5]. The most common isolate was Mycobacterium avium complex followed by Mycobacterium kansasii and Mycobacterium chelonae [5]. Such high prevalence of NTM associated with DPB raises concerns of generating macrolide-resistant NTM infections due to the use of clarithromycin in monotherapy of patients with DPB. Therefore, the presence of these mycobacteria should be confirmed or excluded by appropriate microbiological analysis.

Conflict of interest: none declared.