DISCUSSION
In this retrospective study we have shown that a significant
inflammatory reaction at airway level is present in children with airway
malacia due to mediastinal vascular anomalies and recurrent respiratory
symptoms. A significant neutrophilic alveolitis was detectable by
bronchoalveolar lavage thought the procedure was performed when children
were in well-being conditions, at least four months after the last
respiratory infection. Additionally, microbiological analysis of BAL
fluid demonstrated bacterial growth in more than one third of them, but
with a pathogen load > 105 CFU/mL
only in a small proportion. Haemophilus influenzae was the
pathogen most frequently isolated. In a total of 512 bronchoscopies,
airway malacia was diagnosed in 160 children (94 males) at a median age
of 4.0 years (range, 0 to 17 years). Airway malacia is not a rare
condition in the general paediatric population, as reported by Boogaard
and co-workers [12]. Out of total of 512 bronchoscopies performed in
children with a median age of 4.0 years, 160 cases of airway malacia
were detected and classified as primary in 136 cases and secondary in 24
cases [12]. Airway malacia, inducing a dynamic collapse of the
airway lumen, reduces cough effectiveness and interferes with
mucociliary clearance, favoring airway plugging by bronchial secretions
and possibly bronchiectasis formation [13]. Moreover, in a study in
which bronchoscopy was performed to exclude other wheezing diseases in
children with “severe chronic asthma” (likely including a group with
airway malacia), Fayon M and co-workers, showed lower airway
neutrophilia and infection (>104 CFU/mL)
with Haemophilus influenzae detectable in 39.5% of BAL cultures
[14]. Chronic wet cough, evidence of bronchitis at bronchoscopy and
airway neutrophilic inflammation are the hallmark of protracted
bacterial bronchitis (PBB) [15]. In the first study defining this
disorder, Chang AB and co-workers reported that trachea-bronchomalacia
was found in 33% of children with chronic cough and BAL cultures in PBB
group were positive in 47% of samples for Haemophilus
influenzae , in 35% for Streptococcus pneumoniae and in 26% forMoraxella catarrhalis [16]. More than one organism grew in a
significant number of PBB patients and 48% of the children had a
positive clinical response to 14 days of amoxicillin clavulanate (22.5
mg/kg/dose, b.i.d.) [16,17]. In a follow-up study, Chang AB group
evaluated the 2-year outcomes of 161 PBB children [18]. They found
that a great proportion of them (43.5%) had more than three episodes of
bacterial bronchitis per year, and 8.1% were diagnosed with
bronchiectasis (vs the 13% of our patient group) [18].Haemophilus influenzae infection was demonstrated in BAL fluid of
85% of children with bronchiectasis and of 49% of children without
bronchiectasis. Recurrent PBB episodes and high Haemophilus
influenzae titers in BAL fluid were major risk factors for
bronchiectasis at 2 years follow-up, suggesting a role of this specific
infection in bronchiectasis pathogenesis [18]. In our patient group,
72.7% of the isolates were Haemophilus influenzae positive but
only one child with bronchiectasis had a positive culture forHaemophilus influenzae. Through its ability to form biofilms,Haemophilus influenzae is a chief bacterial pathogen associated
with chronic respiratory disorders [19] and subinhibitory
concentrations of beta-lactam antibiotics may promote its transformation
into the biofilm phenotype, favoring antibiotic resistance and increased
susceptibility to reinfection [20]. In randomised controlled trial
in children with chronic wet cough it was reported that many of the
children whose symptom was not cured by 2 weeks of amoxicillin
clavulanate had underlying tracheo-bronchomalacia and needed a longer
treatment duration before their cough disappeared [15,21].
Therefore, in view of high frequency of positive isolates forHaemophilus influenzae but also of the general low bacterial load
and the significat coesistence of bronchiectasis, caution should be used
in inappropriate antibiotic prescription in patients with secondary
airway malacia and recurrent respiratory infections. This approach may
be chiefly important in children with bronchiectasis, in which chest
physiotherapy can be of great benefit [22]. When possible,
antibiotics should be chosen on the basis of sputum or cough-swab
culture and sensitivity, adherence to treatment should be monitored and
the opportunity to switch from twice to thrice daily administration or
to increase the dosage should be taken in consideration in specific
cases to lengthen the time at higher minimum inhibitory concentration
levels [15].