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.