Methods
The present study was conducted in the Pediatric Pulmonology Unit of the
Attikon University Hospital in Athens, which is one of the main tertiary
referral centres for pediatric pulmonary disorders in Greece.
We retrospectively analysed data
of 54 children with
CSLD/bronchiectasis, without an
identifiable cause, who had been diagnosed and followed in our
department. Investigations in all patients included sweat test and/or CF
gene mutation analysis and measurement of serum immunoglobulins. Nasal
nitric oxide test and high-speed video microscopy analysis were
performed only in patients who fit the clinical phenotype of primary
ciliary dyskinesia. All had Pa isolated at least once in their sputum,
or cough/throat swabs, or bronchoalveolar lavage (BAL) cultures.
Data regarding the time of chronic wet cough commencement, the time of
referral to our department (which coincided with the time of diagnosis
of CSLD/bronchiectasis), and the duration of follow up were retrieved
from the medical records. Microbiological data and the percent-predicted
FEV1 (ppFEV1) values (calculated with the NHANES III reference
equations) of all patients with valid spirometries were also retrieved.
For the purposes of this study,
disease remission was defined as the absence of daily wet cough for four
months along with three negative cultures taken during the last three
consecutive follow-up visits. All patients received ciprofloxacin per os
for at least 3 weeks after the isolation of Pa, and started (if they had
not already been on) daily chest physiotherapy. Some of them also
received long term treatment with twice-daily inhaled colistin and/or
thrice-weekly azithromycin and/or nebulized hypertonic saline.
Three-monthly follow-up visits were arranged for all children. In all
visits, sputum or cough/throat swabs cultures were obtained and
spirometry was performed on all patients ≥5 years old who were able to
cooperate.
Radiological records were retrospectively reviewed for the presence of
bronchiectasis in chest high-resolution computed tomography (HRCT) scans
which were obtained before or at about the same time with the isolation
of Pa. The evaluation of the HRCT scans was performed by the pediatric
radiologists of our hospital (E.A., S.P., and A.M.) who were aware of
the patients’ clinical history. The criteria for the diagnosis of
bronchiectasis on HRCT were dilatation of bronchi with a
broncho-arterial ratio > 0.8010,11;
parallel bronchial walls in a longitudinal section (tram sign);
visualization of bronchi within 1 cm of pleura. The modified Bhalla score
was used to quantify the severity of bronchiectasis12.
Statistical analysis : Variables are described as medians with
interquartile range (IQR). Univariate comparisons were performed with
Fisher’s exact test and Wilcoxon rank-sum test. Graphical presentation
of the data was performed with Kaplan–Meier survival curves.
Multivariate analysis was
performed with a Cox proportional hazard model, with age, presence of
bronchiectasis, use of inhaled colistin, azithromycin, and inhaled
hypertonic saline, as the covariates. The proportionality assumption was
checked with the Schoenfeld test.