Abstract
Objective:  We aimed to further assess the evolution of pulmonary function and bronchodilator response in the Chinese case series with post-infectious bronchiolitis obliterans (PIBO).
Methods:  Twelve children with PIBO, aged 59-110 months, were retrospectively studied between 2011 and 2019. According to the ATS/ERS recommendations, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC and maximal midexpiratory flow velocity 25%-75% (MMEF25%-75%)were collected at each pulmonary function tests (PFTs), as well as bronchodilator responses were evaluated. Spirometric parameters were monitored over time, and generalized linear mixed models were used to analyze longitudinal panel data.
Results:  The median baseline PFT values for FVC, FEV1, FEV1/FVC ratio and MMEF25% -75% were 41.6%, 39.75%, 90.7% and 22.2% respectively. At the initial PFTs, 10 (83.3%) patients demonstrated a significant bronchodilator response. FVC and FEV1 increased by a mean of 8.212%/year and 5.007%/year, and FEV1/FVC ratio with an average decrease of 3.537%/year. MMEF25-75% showed an average increase of 1.583% per year. Over all, FEV1 and MMEF25%-75% showed different degrees of improvement after inhaled bronchodilators at each PFT sessions for ten patients, and FEV1 was with significant (>12%) β2-bronchodilation in 53% of PFT sessions.
Conclusions:  Pediatric patients with PIBO showed an obstructive defect of pulmonary function. The FVC, FEV1 and MMEF25%-75% improved as they grew old, while FEV1/FVC ratio decreased. It may be due to the development of lung parenchyma more than airway growth. Airway obstruction of some patients improved with the use of β2agonists.
Short title: Longitudinal Assessment of Pulmonary Function of PIBO children
Keywords: post-infectious bronchiolitis obliterans, children, pulmonary function, bronchodilator responses, longitudinal assessment
Introduction
Bronchiolitis obliterans (BO) is a rare small airway injury-related chronic inflammation airflow obstruction syndrome. Many conditions may trigger BO, such as infection, lung transplantation, bone marrow transplantation, toxic gases, chronic aspiration, connective tissue diseases, and certain drugs[1]. In which, post infectious BO (PIBO) is especially common in children. There are reports of PIBO secondary to infection with adenovirus, influenza, parainfluenza, respiratory syncytial virus, measles virus, and mycoplasma pneumonia and so on[2-4]. Histopathological features of PIBO include the concentric narrowing and obliteration of small airways due to an inflammatory process surrounding the bronchiolar lumen[5]. Its primary clinical manifestations are usually repeated cough, wheezing and shortness of breath, accompanied by varying degrees of dyspnea and decreased activity tolerance. In addition to clinical characteristics, pulmonary function shows a severe airway obstruction, and high resolution computed tomography (HRCT) shows characteristic mosaic patterns and bronchiectasis[2,3]. Some scholars have suggested a PIBO score to diagnose the disease. In which, the typical clinical history represents four points, adenovirus infection three points, and chest HRCT with mosaic perfusion pattern four points. A score above 7 predicted the diagnosis[6].
In PIBO, as in other chronic lung diseases, determining pulmonary function is important for the diagnosis, classifying the severity of the condition and monitoring its progression. PIBO usually occurs in infants[4], which cannot perform the spirometry maneuver, and some patients were lost during the follow-up periods, so there has been only a few study that followed its evolution on the basis of the pulmonary function tests (PFTs)[7-10]. On the other hand, PIBO is a rare disease, although it was first described in 1901 by German pathologist Lange, we does not recognize and diagnose the disease for a long time. Our current knowledge about the evolution of pulmonary function in children with PIBO is limited and controversial. It usually considered PIBO as a disorder involving fixed obstruction with no significant bronchodilator response. Some authors observed pulmonary function in PIBO patients was unchanged even declined with growth[8,9]. However, other previous study demonstrated lung function slowly improved[7,10], and it was reported that some patients with PIBO showed positive β2 agonist responses[8,11,12].The objective of this study was to further assess the evolution of pulmonary function and bronchodilator response in the Chinese case series with PIBO. Profiling the longitudinal pulmonary function of children with PIBO could be beneficial to study and treat the disease.