Bronchiectasis and deteriorating lung function in agammaglobulinaemia despite immunoglobulin replacement therapy

Abstract

Immunoglobulin replacement therapy enhances survival and reduces infection risk in patients with agammaglobulinemia. We hypothesized that despite regular immunoglobulin therapy some patients will experience ongoing respiratory infections and develop progressive bronchiectasis with deteriorating lung function. 139 (70%) of 199 patients aged 1 to 80 years from nine cities in the UK with agammaglobulinemia currently listed on the UKPID registry were recruited to this retrospective case study and their clinical and laboratory features analyzed. 94% were male of whom 78% had BTK gene mutations. All patients were on immunoglobulin replacement therapy and 52% had commenced therapy by the time they were two years old. 60% were also taking prophylactic oral antibiotics. 56% of patients had radiological evidence of bronchiectasis, which developed between the ages of 7 to 45 years. Multi-variate analysis showed that three factors were significantly associated with bronchiectasis: reaching 18 years old (relative risk (95% CI) 14.2 (2.7 – 74.6)), history of pneumonia (3.9 (1.1 – 13.8)) and IVIG rather than SCIG (3.5 (1.2 – 10.1)), while starting immunoglobulin replacement after reaching two years old, gender and recent serum IgG concentration were not significantly associated. Independent of age, patients with bronchiectasis had significantly poorer lung function (predicted FEV₁ 74% (50 – 91)) than those without this complication (92% (84 – 101)) (p < 0.001). We conclude that despite immunoglobulin replacement therapy, many patients with agammaglobulinemia can develop chronic lung disease and progressive impairment of lung function.