Bronchiolitis obliterans: A new disease? Robert Gie, Pierre Goussard, Sharon Kling Department Paediatrics and Child Health Faculty of Health Sciences Stellenbosch University

9 Month old girl referred pneumonia not responding to treatment Normal antenatal and neonatal history No previous lower respiratory infections or wheezing episodes Child needed intubation and ventilation Bilateral hyperinflation with wheezing Crepitations bilaterally

Course Ventilated for 17 days Adenovirus cultured from tracheal aspirate All other cultures was negative HIV negative

Follow - up Repeated episodes of lower respiratory tract infections with wheezing No response on inhalation steroids Chronic hyperinflation Harrison sulci Persistent crepitations bilaterally

Bronchioloitis obliterans Associated with airway epithelial injury: –Developed countries with transplant programs Allograft recipients Collagen vascular disorders Toxic fume inhalation Chronic hypersensitivity pneumonitis Drugs (penicilalamine, cocaine) Steven Johnson syndrome –Post infectious BO Adenovirus Influenza virus Respiratory syncitial virus Mycoplasma pneumoniae

Post infectious Bronchiolitis obliterans Commonest cause world wide World wide distribution unusual: –Southern Hemisphere New Zealand Argentina Chile Australia South Africa –Genetic predisposition

Clinical picture

Pathogenesis

Other studies demonstrated increased serum concentrations of interlukin-6 (IL- 6), IL-8, and tumor necrosis factor-alpha (TNF-a), as well as decreased numbers of T-lymphocytes, natural killer (NK), CD4þ T, and B1 B-cells in children severely affected by adenoviral pneumonia.

Diagnosis Clinical clues Chest radiography Radio-isotope studies Chest computer tomography Lung function tests Lung biopsy

Swyer James /Macleod Syndrome

Lung perfusion scans. Lung perfusion scan of a 1.5-year-old boy 5 months after initial episode of AVB shows segmental defects in the right upper lobe, middle lobe, and left lower lobe.

Lung biopsy Non-homogenous distribution of disease Sampling error Not the gold standard

Criteria for suspecting Bronchiolitis Obliterans 1.Absence of respiratory illness during the perinatal period and up to the onset of viral illness 2.Severe Bronchiolitis in a previously healthy infant requiring hospital admission, needing additional oxygen and demonstrating low oxygen saturation levels for more than a month 3.Following the acute phase of the ilness, persistence for more than 3 months of respiratory distress, signs of bronchial obstruction and airtrapping, with arterial oxygen saturations < 95%

Clinical criteria: Chronic persistent cough Co-existent chronic pansinusitis Course crackles Bilateral small nodular disease on CXR/CT FEV1/FVC < 70% Cold agglutinins > 1:64

Treatment of Bronchiolitis obliterans Fixed airway obstruction and poor response to long-term steroid treatment. Supplemental oxygen to keep hemoglobin saturation at or above 94%. Nutrition status. Chest physiotherapy: bronchiectasis.

Exacerbations, usually due to viral infections, demand a more aggressive approach with liberal use of antibiotics, oral steroids and bronchodilators. As an alternative to continuous oral steroids required in patients with severe PBO, pulse therapy with methylprednisolone (30 mg/kg/day) for three days monthly, has been proposed.

Prognosis The overall prognosis for patients with PBO is good. Some children, especially those who present initially with respiratory failure, may develop severe obstruction,hyperinflation and CO2 retention and may progress to cor pulmonale

With growth of the lungs, peripheral airway conductance increases. Clinical improvement observed in patients with postinfectious BO may be due to normal lung growth and not regression of the pathology in the small airways.

Unanswered questions: Which children are predisposed to developing BO? Can BO be prevented during adenovirus pneumonia? What are the surrogate markers of disease progression? What are the exact criteria for making the diagnosis? What is the best treatment of BO? Should long-term immune modulation be used? What are the factors that determine prognosis? Should re-ventilation be considered? Why are we not reporting from SA? Does HIV infection influence BO?