CASE PRESENTATION
A former full-term female presented with failure to thrive, cough, and hypoxemia (Sp02 70-80%) that progressed to acute respiratory failure requiring endotracheal intubation and mechanical ventilation. Repeat chest radiographs were notable for right upper lobe, lingular, and left lower lobe opacities that did not respond to multiple antibiotic courses. Initial flexible bronchoscopy was notable for significant tracheobronchomalacia with at least 50% collapse of distal trachea and proximal right mainstem bronchus. Additional work up included a normal brain MRI and initial echocardiogram. Chest CT was notable for multiple ground glass opacities suggestive of ILD or chronic aspiration (Figure 1). Given concern for aspiration she was advanced to post pyloric feeding. Lung biopsy was done and notable for bronchiolar lymphoid hyperplasia, chronic bronchiolitis, mild alveolar simplification, lymphocytic infiltration and interspersed plasma cells, architectural remodeling, and distortion of small airways (Figure 2). Electron microscopy noted normal lamellar body ultrastructure. Due to concern for ILD and lack of clinical improvement with post pyloric feeds, she was started on methylprednisolone pulses (10 mg/kg for 3 days, monthly) for 6 months. Absolute CD3, CD3/CD4, CD3/CD8, and NK cells were low. She remained admitted until 9 months of age and was discharged with gastrojejunal feeds, tracheostomy, oxygen supplementation, and ventilator support. Her hospital course was complicated by secondary hypertension and left ventricular hypertrophy that resolved with steroid wean. Genetic studies sent prior to discharge resulted in heterozygous pathogenic variant in COPA gene (E241K5(NM_001098398: exon 9: c.G721A)) reported to be extremely rare and not present in 60,000 unrelated individuals in the ExAC database (http://exac.broadinstitute.org/). Follow up chest CT at 15 months of age demonstrated progression of findings with patchy areas of consolidation and air bronchograms. Traction bronchiectasis were also seen peripherally in the lower lobes (Figure 1). Repeat bronchoscopy noted improvement of bronchomalacia. Around 22 months of age, she was noted to be ANA positive (1:320) and p-ANCA positive (1:160). Rheumatoid factor negative. No evidence of vasculitis or arthritis at time of evaluation. She was started on rituximab and azathioprine as early treatment to prevent progression of pulmonary hemorrhage, as well as renal and joint disease6. Due to adverse effects, immunosuppressive therapy was changed to methotrexate weekly. At 3 years of age, chest CT exhibited scattered nodules, diffuse bronchial thickening, and air trapping. Repeat bronchoscopy and BAL showed blood tinged secretions with >100 hemosiderin laden macrophages. Routine surveillance labs indicated increased ANA to 1:1280 and ANCA >1:640. Given these findings, the methotrexate dose was increased. Additional immunosuppressive therapy is currently being considered. Meanwhile, she has clinically improved and has weaned off oxygen and no longer required ventilator support. She has digital clubbing on exam but has excellent growth and development.