Postinfectious bronchiolitis obliterans (PIBO) is a rare, chronic obstructive lung disease in infants and in children, usually following a severe respiratory infection. Characterized by inflammation and fibrosis in the terminal bronchioles, it leads to airway blockage. The condition typically affects infants under 12 months, and while the exact prevalence is unknown, PIBO is underreported among pediatric respiratory diseases [1]. Frequence of PIBO is probably underestimated, but the disease belongs to the group of rare diseases [2]. Viruses, particularly adenovirus, are the primary triggers for PIBO, although bacteria like Mycoplasma pneumoniae have also been implicated [3-6]. Diagnosis is generally based on typical clinical history, respiratory symptoms (tachypnea, cough, wheeze) and computed tomography (CT) imaging (mosaic perfusion), as lung biopsy is often too invasive for routine pediatric practice [4,7]. Treatment lacks standardized guidelines, but intravenous corticosteroid pulses are commonly used, with some studies showing the effectiveness of combined treatments with inhaled corticosteroids (ICS), montelukast, and low-dose azithromycin [8,9]. PIBO’s prognosis remains unclear, as existing studies are limited and sample sizes are small [10]. Bronchopulmonary dysplasia (BPD) is a frequent complication of prematurity, increasing in frequency and severity with the degree of prematurity. Immature lungs are highly susceptible to be attacked, particularly by respiratory viruses, and few articles in the literature study the link between BPD and the development of PIBO. The pathophysiology remains unexplained.

This study examines a larger cohort of infants with PIBO, primarily evaluating the effectiveness of intravenous corticosteroids, and secondarily exploring the impact of BPD as a comorbidity.

Our study described the clinical and functional characteristics of a cohort of 57 children with PIBO treated with methylprednisolone pulses. Our main objective was to determine the evolution in the first 2 years of life. We compared the clinical course of these children in the 24 months following diagnosis of PIBO, and highlighted a subgroup of patients with a history of BPD. To our knowledge, we report here one of the few European cohorts, most articles being of South American and Asian origin [11,12]. The diagnosis of PIBO was made according to currently accepted criteria, and 85% of our patients had a CT scan with the presence of abnormalities indicative of bronchiolar involvement [1]. The demographic characteristics of our patients were comparable to those described in the literature. Indeed, the mean age at diagnosis of PIBO was less than 12 months [3]. Although male gender has not been identified as a risk factor for the development of PIBO, more than two-thirds of the cohort were boys, as observed in other series [3,5]. This rate is much higher than that observed in other infant respiratory diseases [13,14]. We have shown that the presence of pulmonary comorbidities is not negligible in this cohort, particularly the presence of BPD. Indeed, half of our cohort was premature, and 20% of them had presented with BPD. Tomikawa et al. [15] reported 12.5% prematurity in their cohort of 40 children. Moreover, in the BPD subgroup, the onset of chronic respiratory symptoms was later. This is explained by the fact that these premature infants were discharged from hospital later, and had a delayed exposure to respiratory viruses.

We found about 30% of malacia in our cohort. Malacie is common in the first years of life, and almost always has a favorable outcome. It may be responsible for an increased cough, with a characteristic noise, but it is not responsible for bronchial obstruction and mosaic scan abnormalities. It was not therefore possible to be responsible for the clinical presentation of our patients.

We report that the first viral etiology identified is RSV, followed by rhino-enteroviruses, with adenovirus only in third place. This frequency is in line with the epidemiological descriptions we reported in a large study of acute bronchiolitis [16]. All viruses are known to be associated with bronchiolitis obliterans, but the predominance of RSV has not been reported [12]. In the German study by Jerkic et al. [11], RSV accounted for only 2 of 21 cases. Also, the frequency of coinfections, found in more than one in 4 cases, is less frequent in the BPD group. The rate of viral codetection in our study is high, particularly for rhinoviruses and bocavirus, and especially in the “PIBO with BPD” group. Several studies show that the presence of viral codetection does not increase the severity of infection [17]. Indeed, studies using the PCR technique have shown that viruses can be excreted for prolonged periods without associated clinical symptoms [18,19]. Consequently, codetection is not systematically synonymous with coinfection. Other studies showed that the prognosis of respiratory infections can be altered, positively or negatively, by specific viral interactions [20,21]. In a third of cases, no virus was detected, as described in other cohorts [11].

We report on a cohort treated with methylprednisolone pulses, with an early start to treatment, lasting an average of 6 months. We observed a 58% reduction in the number of exacerbations from the first 6 months, which was maintained during the 2-year follow-up. Concomitantly, we also showed that at 6 and 12 months of evaluation, the number of children presenting no exacerbation during the follow-up period increases from 39% to 61%, and stabilizes for 50% of the population at 18 and 24 months. Very few studies have reported the efficacy of methylprednisolone pulses. Only Tomikawa et al. [15] describes the number of exacerbations: they showed a reduction during the first 6 months, which is maintained up to 18 months. In this series, only 33% of patients were exacerbation-free at 24 months. This may be explained by different populations: in Tomikawa's study, patients were more heterogeneous in age, and the diagnostic delay was much longer (up to 32 months). In our study, this rapid reduction in exacerbations is important, as exacerbations have been shown to be a major factor in lasting impairment of respiratory function. At the same time, we observed a reduction in the dose of ICS administered to children over the follow-up period. This decrease became significant from 12 months onwards, reflecting a consolidation of the therapeutic effect of pulses at 6 months.

In conclusion, this study demonstrates the effectiveness of intravenous corticosteroid pulses in treating PIBO, with sustained improvements in respiratory health over 24 months. Our findings support the role of BPD as a comorbidity in PIBO, with corticosteroid therapy beneficial for children with and without BPD.