Discussion
This investigation followed the PFT changes over time in pediatric
patients with PIBO, diagnosed on the basis of previously mentioned
characteristic clinical and HRCT findings with a PIBO
score>7. In our study, patients always showed impaired
pulmonary function with an obstructive pattern, but improvement in
pulmonary function were observed. We found that our sample of twelve
children diagnosed with PIBO, on average, has an FVC and
FEV1 that has much increased; however,
FEV1/FVC declined significantly over time.
Most of our studied subjects developed PIBO before 3 years of age
(66.7%), there were also two children at pre-school and two at school
age diagnosed with PIBO in the study, and they were all Han race.
Adenovirus and mycoplasma were the predominant microorganism involved in
the PIBO pathology, occurring in 75% of the patients together (nine out
of twelve patients), which is similar to the results reported in
previous studies[3,14,15]. In addition, measles
virus was also a common cause. We also found that six individuals
required mechanical ventilation, which may be an independent risk factor
for developing PIBO[16].
In this group of patients, typical findings on HRCT chest scan were
defined as a mosaic perfusion pattern, because of patchy areas of
hyperinflation and vascular attenuation, whereas air trapping was more
apparent in expiration. We also identified bronchial wall thickening and
bronchial dilation. These HRCT findings were consistent with previous
studies in patients with PIBO[2,3].
PFTs are important ancillary studies, whether for diagnosis or follow-up
of patients with PIBO. There were pronounced decrease in
FEV1, FEV1/FVC and
MMEF25%-75% in the study, which are characteristic of
obstructive airway disease, especially small airway. Our findings
corroborate the conclusion that pediatric patients with PIBO have a
common pattern of severe pulmonary function impairment, characterized by
marked airway obstruction[17-19]. Meanwhile, the
decrease of FVC seemed to be combined with restrictive dysfunction, but
it does not really restrict when lung volumes measured by
plethysmography are available.
In our patients, we observed that FVC, FEV1, and
MMEF25-75% were much improved over time. FVC increased
more than FEV1, so the FEV1/ FVC
significantly decreased. Although spirometry parameters increased,
pulmonary function remained moderately impaired in childhood, especially
small airways. The pulmonary function improved indicates that airway
damaged with conserved normal lung growth. That is, the concept of the
neoalveolisation throughout childhood and adolescence postulated by
Narayanan et al[20]. The fact that
FEV1/ FVC ratio decreased is probably because of the
unequal growth of the lung parenchyma and airways, indicative of a
‘dysynaptic growth’ of the lung. However, this catch-up growth after the
lung injury could be possible in terms of alveolar number, but may be
not as much for airway size[20,21]. Such as those
with PIBO, are more likely to be volume responders than flow
responders[22]. This has been demonstrated by some
other studies [7,10] and confirmed by the present
case series. Some else research draw different conclusions just like
longitudinal data from 6 children showed unchanged abnormal lung
function many years after
treatment[8], and a study
including 11 patients with PIBO, reported that pulmonary function
declined with growth[9]. It is possibly because we
included a homogeneous group of younger children who have more
opportunities for alveolar development, and relatively not severe forms
of the symptom.
At the initial PFTs, 10 (83.3%) pediatric PIBO patients demonstrated a
significant bronchodilator response according to the ATS/ERS
recommendations, that is, FEV1 was significantly
improved after inhalation of bronchodilators (on average 23.01%), but
the children with positive results decreased during the follow-up, it
was 7 (58.3%) at the final PFTs. And longitudinal assessment of the
bronchodilator response over the follow-up period demonstrated that
positive response for FEV1 remained in over half PFT
sessions (Figure 2). In children with PIBO, the most severe obstruction
is at the small airway, so we observed the higher β2agonist responses in terms of the MMEF25%-75%.
However, MMEF25%-75% is usually highly variable in
control groups and lacks the consistent standard, therefore the
variation is not easily interpreted[23]. Although,
theoretically, a bronchodilator response should be absent in children
with fixed airway obstruction such as in PIBO, there is controversy
regarding reversibility of airway obstruction in PIBO. Mattiello R et
al. reported 72 children with PIBO that the bronchodilator response was
significant in 42 patients (58.3%),and they considered that age at
viral aggression, a family history of asthma, and allergy had no
significant effects on bronchodilator
responses[10]. HL Chung et al. observed bronchial
hyper responsiveness was in more than 40% of PIBO patients and it was
not related with the atopic status of the
patients[24]. We also found that neither age at
diagnosis, nor allergy factors had any significant effect on the
magnitude of the bronchodilator response. And some patients with PIBO
show hyperresponsiveness to methacholine[25].
Castro-Rodriguez et al. using impulse oscillometry also observed a
significant bronchodilator response in children with PIBO in
Chile[14].
The concept of PIBO as irreversible, fixed obstruction does not seem to
apply to all pediatric patients with PIBO. The mechanisms underlying
bronchial hyper responsiveness in such patients remain unclear. It could
be explained either by an innate predisposition to PIBO in children who
have previously (prior to the diagnosis) had a phenotype of airway hyper
reactivity[14], while the small caliber of the
airways in young children makes it difficult to assess bronchodilation
in PFTs, or by acquired airway hyperreactivity later in the disease.
There may be persistent airway hyperresponsiveness secondary to complex
damage of bronchiolar functioning which includes chronic inflammatory
process, scarring, narrowing and air trapping. But it seemed that poor
response to bronchodilators increased as fibrosis progresses. Although
the PFT parameters didn’t achieve normality after the use of
bronchodilators, it can help improve lung function in these patients.
Further investigations are needed in order to research the mechanisms of
airway hyper responsiveness and assess benefits of the use of
bronchodilators in PIBO patients with a significant bronchodilator
response.
In conclusion, the present case series study results demonstrated that
pediatric patients with PIBO have an obstructive pattern of pulmonary
function impairment. The FVC, FEV1 and
MMEF25%-75% all improved as they grew old, while
FEV1/FVC ratio decreased. This improvement may be mainly
due to the development of lung parenchyma more than airway growth. And
airway obstruction of some pediatric patients with PIBO can improve with
the use of β2 agonists. In future, larger populations
and long term follow-ups are needed to validate these observations.