Discussion
The absence of clear national or international guidelines for the eradication and suppression of Pa in children with non-CF chronic endobronchial infection resulted in a non-unanimous approach from the doctors serving in our department, with treatment decisions being based on the subjective clinical judgment of each physician. Nevertheless, the different therapeutic attitudes were an advantage for this retrospective study which aimed to explore the efficacy of different treatment modalities. The study showed that treatment with inhaled colistin increased whereas the presence of radiologically confirmed bronchiectasis reduced the rate of remission. Our data were unable to show any significant correlation between remission and the two other treatment modalities namely, azithromycin and inhaled hypertonic saline.
The presence of Pa in the airways of patients with non-CF bronchiectasis has been associated with accelerated lung function decline and increased morbidity and mortality7,13,14. However, despite the advantages in our knowledge of Pa bronchial infections, much of our understanding is still extrapolated from CF15. Furthermore, it is difficult to estimate the true impact of primary Pa infection in pediatric patients. Indeed, specific data on children are lacking and most of the available studies in adults have concentrated on chronic – and not primary - infection.
There is no universally accepted definition of chronic Pa infection with most of the currently used definitions being based on microbiological results from sputum cultures in CF patients16. However, young children rarely expectorate sputum and this fact dictates the use of alternative methods for microbiological sample collection. BAL is taken through an interventional procedure and cannot be used in the usual follow-up. Practically, cough and throat swabs are the only possible alternatives to sputum. These latter methods, however, despite being very convenient, place considerable uncertainty on the results as they lack the sensitivity of sputum or BAL cultures17. Furthermore, in cases of biofilm formation, it can be difficult to recover all the clinically significant bacteria through conventional cultures 18. For the above reasons, the isolation of Pa for the first time cannot exclude the existence of a chronic Pa infection, especially if the symptoms persist for a long period and/or the child has repeatedly not responded in conventional antibiotics. The difficulty and ambiguity in characterizing a first-time Pa isolation as new onset or chronic infection can justify the use of inhaled antibiotics for prolonged periods.
Inhaled antibiotics deliver very high drug concentrations at the airways without the adverse effects that are observed when they are administered through systemic routes19,20. Although many inhaled antibiotics have been developed and are currently in use, only colistin was available for our patients since it is the only inhaled antibiotic that is compensated by the national health insurance system for non-CF patients. Long-term treatment with inhaled antibiotics reduces the number of exacerbations, decreases bacterial load, and improves pulmonary function in several chronic endobronchial infections19,21-23. Our data are in general agreement with the above results as they demonstrated that the prolonged use of inhaled colistin increased the rate of remission.
Bronchiectasis is the end stage of chronic endobronchial infections2 and its presence is correlated with the severity of clinical symptoms and the intensity of neutrophilic inflammation in the airways3. As such it is inherently hard – though not impossible - to remit10,24. Given so, our finding that the presence of bronchiectasis reduces the rate of remission was somehow expected as bronchiectasis denotes the most severely affected patients.
The present study suffers from some limitations. First of all, it was a single-centre observational study that reflected the population served by our department, and the results cannot be generalized. The number of patients was relatively small and so type 2 errors (false-negative results) concerning treatment with azithromycin and nebulized hypertonic saline, may have occurred. Finally, we used a functional definition of remission which may not be equivalent to true remission.
In conclusion, inhaled colistin is a useful therapeutic modality in children with CSLD and non-CF bronchiectasis. Children with CSLD have a more favourable prognosis compared to children with established bronchiectasis.
Figure 1 : Persistence of the disease in patients with and without treatment with nebulized antibiotics (A), and presence or absence of bronchiectasis (B)
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Authors’ Contributions : K.D. conceived and designed the study and analyzed the data; I.L. and K.P. co-designed the study. K.D. and E.K. wrote the first draft of the manuscript; S.H. performed the microbiological analysis; O.S., D.M. and A.G. collected the data; S.P., A.M. and E.A. reviewed and summarized the radiological data. All authors have read and agreed to the published version of the manuscript.
Funding : This research received no external funding.
Conflicts of Interest : The authors declare no conflict of interest.