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.