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.