Childhood Bronchiolitis Obliterans Research Articles

Postinfectious Bronchiolitis Obliterans

Childhood bronchiolitis obliterans (BO) is an uncommon complication that is characterized clinically by persistent and continuous obstructive respiratory symptoms, and has been described secondary to various etiologic factors, including drugs, exposure to toxic fumes, allergic reactions, collagen vascular disease or infections. BO occurs most commonly in children after an episode of acute bronchiolitis and is considered a long-term sequela of viral infection.Postinfectious Bronchiolitis Obliterans (PIBO) is characterized by persistent airway obstruction with functional and radiological evidence of small airway involvement that is in general unresponsive to bronchodilator treatment.Although the condition is relatively rare, and its exact incidence is unknown, it is important to keep it in mind. PIBO is complication of lower respiratory tract epithelial injury, and is often misdiagnosed, delaying recognition and potential treatment. A PIBO diagnosis is usually based on a few factors, including a good medical history, positive clinical findings, and lung function test and imaging results, although biopsy and histopathology remain as the optimum diagnostic approach. There have to date been few studies proposing treatments for the condition, and no accepted protocol exists in literature. There is usually a fixed airway obstruction in PIBO. Various treatment approaches have been extrapolated from studies of post bone marrow transplantations and lung transplant BO. The clinical course is variable, and good supportive therapy is essential, with anti-inflammatory therapy often being employed.

Childhood bronchiolitis obliterans in Hong Kong-case series over a 20-year period.

Bronchiolitis obliterans (BO) is a rare but serious condition. The natural history and outcomes remain poorly understood. In this clinical review, we aimed to describe the clinical characteristics and outcomes of children diagnosed with BO in Hong Kong (HK). This was a retrospective study of pediatric patients with BO under the care of six respiratory units in HK from January 1996 to December 2015. Information was retrieved from medical records. Fifty-six patients were included with a male predominance (67.9%). The median age at diagnosis was 1.98 years (interquartile range [IQR]: 0.84-4.99 years). Postinfectious BO (PIBO) was the commonest cause (64.3%) followed by posthematopoietic stem-cell transplant (21.4%). Adenovirus (63.2%) was the commonest causative pathogen among PIBO. The median follow-up duration was 9.7 years (IQR: 2.9-14.3 years). Twenty-five patients (44.6%) could achieve symptom-free recovery at the time of follow-up. Five (8.9%) and three (5.4%) were oxygen or ventilator dependent, respectively. There were two deaths, both had posttransplant BO. Patients who developed BO after transplant had significantly worse lung function than those with PIBO. There were no risk factors significantly associated with worse clinical outcomes (oxygen/ventilator dependence or death) by logistic regression. Among patients with PIBO, coinfection at presentation was significantly associated with persistent symptoms at follow-up (p = .028). The most common cause of childhood BO in HK is postinfectious and coinfection at presentation was associated with persistent symptoms at follow-up. Further studies are needed to better elucidate disease progression, treatment options and long term outcomes.

Diagnostic value of antineutrophil cytoplasmic antibodies in children with bronchiolitis obliterans.

Diagnosis of childhood bronchiolitis obliterans (BO) is difficult owing to non-specific clinical presentations and limited investigational options. There is a lack in established serum biomarkers for BO. While the diagnostic value of antineutrophil cytoplasmic antibodies (ANCAs) has been discussed, little is known about this in BO. We aimed to investigate the serological profiles of ANCAs against myeloperoxidase (MPO-ANCA) and proteinase-3 (PR3-ANCA) in BO and acute pneumonia. In this study, 42 BO children (BO group) and 43 with mild acute pneumonia (pneumonia group) were included, based on rigorous diagnostic criteria and additional constraints for minimizing selection bias. Serum MPO-ANCA and PR3-ANCA levels were measured on the first (baseline) and the last day of hospitalization (on discharge) by enzyme linked immunosorbent assay. Although the BO children had a longer hospital stay, the overall rate of positivity (≥180 AAU/mL) and median serum level of MPO-ANCA were higher in the BO group compared with the pneumonia group, either at baseline (69.1% vs. 9.3%, 292.00 vs. 104.75 AAU/mL, both P<0.001) or on discharge (61.9% vs. 9.3%, 310.50 vs. 95.42 AAU/mL). Similar was found for PR3-ANCA (38.1% vs. 4.7%, 106.66 vs. 54.56 AAU/mL at baseline; 35.7% vs. 2.3%, 97.98 vs. 57.23 AAU/mL on discharge, both P<0.001). There were a higher rate of dual-positivity and a lower rate of dual-negativity to both ANCAs in the BO group than those in the pneumonia group (all P<0.001). Detection of MPO- and PR3-ANCA can help diagnosis of childhood BO.

Diagnosis and treatment of childhood bronchiolitis obliterans

Clinical data of 28 cases of childhood bronchiolitis obliterans treated from September 2008 to November 2010 were retrospectively analysis.Pulmonary high-resolution CT (HRCT) showed that bronchial wall thicken was seen in all 28 patients,the mosaic pattern in 26 cases,patchy shadows in 18 cases,bronchiectasis with typical signet ring sign in 2 cases,atelectasis in 2 cases without pleural effusion.Pulmonary function tests and flexible bronchofiberscopy were performed in 6 cases,which showed the inflammation in bronchial tunica intima and obstruction of small airway.Blood routine,blood sedimentation,c-reaction protein,TORCH,hepatic function,renal function and immune function were normal.Patients received comprehensive treatment with methylprednisolone,clarithromycin and montelukast.The clinical conditions of 28 cases were improved with varying degrees after treatment and no significant side effects were observed. Key words: Bronchiolitis; obliterans ; Diagnosis; Therapy

Swyer-James-MacLeod syndrome; repeated chest drainages in a patient misdiagnosed with pneumothorax

Swyer-James-MacLeod Syndrome (SJMS) occurs as a result of childhood bronchiolitis obliterans. Typically, this disorder is diagnosed in childhood after evaluations for recurrent respiratory infections. One of the reasons to explain the difficulty in diagnosis is that when patients develop little bronchiectasis, and therefore, few symptoms, then this syndrome may not be recognized until adulthood. Here, we are presenting a 22-year-old female patient who was diagnosed with SJMS who was initially misdiagnosed with a pneumothorax and treated by multiple chest tube drainages. This case highlights the significance of taking a careful history, the application of computed tomography and scintigraphy in confirming the diagnosis of SJMS and in eliminating other diseases.

Nitric Acid-Induced Bronchiolitis in Rats Mimics Childhood Bronchiolitis obliterans

Background: Childhood bronchiolitis obliterans (CBO) is an infrequent but severe disease, characterized by persistent obstructive respiratory symptoms after an acute episode of bronchiolitis. Its etiology is mostly postviral, especially in developing countries. Pathologically, CBO is characterized as constrictive-type BO. The pathogenesis of this disease is poorly understood and there is no specific treatment. Animal models could help to better understand the sequence of events culminating in bronchiolar obliteration and serve as basis for experimental therapeutic research. Objectives: In this study, we adapted the nitric acid (NA) technique to develop a suitable model to study CBO in rats. Methods: We have intratracheally instilled 0.5% NA or saline and studied the histological lesions on days 2, 7, 14 and 30. NA-instilled animals developed a sequence of bronchiolar lesions that included necrotizing bronchiolitis, proliferative (PROL) bronchiolar lesions and constricitive (CONS) bronchiolar lesions with bronchiectasis, mucostasis and macrophagic accumulation. Results: The frequency of PROL lesions decreased and that of the CONS lesions increased, with a statistically significant difference at the sacrifice days, except for day 7 (PROL vs. CONS lesions day 2: p = 0.001; PROL vs. CONS lesions day 7: p = 0.38; PROL vs. CONS lesions day 14: p < 0.001; PROL vs. CONS lesions day 30: p < 0.001). Conclusions: We conclude that this model presents histological similarities with the histological picture of CBO, being suitable for further developmental and therapeutic experimental research in this field.

Pediatric Interstitial Lung Disease Masquerading as Difficult Asthma: Management Dilemmas for Rare Lung Disease in Children

Idiopathic nontransplant-related childhood bronchiolitis obliterans is an uncommon disease. Most patients present with chronic recurrent dyspnea, cough and wheezing, which are also features of asthma, by far a much more common condition. The present case study reports on a six-year-old girl who presented to a tertiary care centre with recurrent episodes of respiratory distress on a background of baseline tachypnea, chronic hypoxemia and exertional dyspnea. Her past medical history revealed significant lung disease in infancy, including respiratory syncytial virus bronchiolitis and repaired gastroesophageal reflux. She was treated for 'asthma exacerbations' throughout her early childhood years. Bronchiolitis obliterans was subsequently diagnosed with an open lung biopsy. She did not have sustained improvement with systemic corticosteroids, hydroxychloroquine or clarithromycin. Cardiac catheterization confirmed the presence of secondary pulmonary hypertension. Treatment options remain a dilemma for this patient because there is no known effective treatment for this condition, and the natural history is not well understood. The present case demonstrates the need for careful workup in 'atypical asthma', and the urgent need for further research into the rare lung diseases of childhood.

Lymphocytic inflammation in childhood bronchiolitis obliterans.

Childhood bronchiolitis obliterans (CBO) is an infrequent, severe disorder characterized by persistent obstructive respiratory symptoms after an acute episode of bronchiolitis. The viral etiology is most common, and adenovirus is the most frequently identified causative agent. Pathologically, the disease is characterized as constrictive type BO, with variable degrees of chronic inflammation and fibrosis in the bronchioles. The nature of the cellular infiltrate is largely unknown, and its characterization may provide better understanding of the disease and offer clues for therapy. Therefore, the aim of the present study was to characterize the inflammatory infiltrate in the bronchioles of 23 open lung biopsies of children with CBO and to compare this to the infiltrate in histologically normal airways. Our results show that CD3+ T cells were the most frequent cell type observed in CBO, with a predominance of the CD8+ T-cell subtype. When compared to the control group, there was a larger number of CD8+, CD4+, CD20+, granzyme B+, and perforin+ lymphocytes in the CBO group. Further studies are needed to address the role of different cell types in the development of CBO.

Histology of childhood bronchiolitis obliterans.

Childhood bronchiolitis obliterans (CBO) is an uncommon disease characterized by persistent signs and symptoms of obstructive respiratory disease after an acute bronchiolar injury. It is considered to be a complication of viral infection, most often of adenovirus, and is usually classified as a constrictive-type bronchiolitis obliterans (BO). Few reports have described its histology. We present the histopathological features of 34 pediatric patients with a diagnosis of BO, comprising 30 open lung biopsies (OLB), 2 lobectomies, and 2 autopsies. Quantitative analysis was performed on the OLB to better characterize the morphological changes observed in these lungs. Of 37 patients, 25 were male and 9 were female, ranging from 7 months to 15 years of age. Airway diameter in terminal bronchioles varied from 50-600 microm. Ninety-seven percent of the CBO were of constrictive type, with variable degrees of airway obstruction. Chronic inflammation in the bronchioles was mild in 63% of the patients. Aggregates of foamy macrophages, mucostasis, and bronchiectasis appeared in, respectively, 93%, 40%, and 30% of the biopsies. There was more hyperinflation than atelectasis (40.1% and 24.3%, respectively). Lobectomies and autopsies showed more severe bronchiolar obliteration, associated with bronchiectasis. The results show that CBO is characterized histologically mainly by a constrictive pattern, with variable degrees of inflammation and airway obliteration. Secondary signs of airway obstruction are invariably present. Mild histological changes may predominate and should be carefully evaluated by the pathologist.

An Unusual Presentation of a Rare Disorder: Swyer-James-Macleod???s Syndrome

Swyer-James-Macleod syndrome occurs as a result of childhood bronchiolitis obliterans. Typically this disorder is diagnosed in childhood during evaluation for recurrent respiratory infections. However, if the patient has little bronchiectasis and few symptoms, this syndrome may not be recognized until adulthood. We present a patient whose diagnosis of Swyer-James-Macleod syndrome was not established until he was 77 years of age. This case highlights the usefulness of computed tomography in confirming the diagnosis and in ruling out the variety of other disease processes that present with the radiographic appearance of a hyperlucent lung.