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.