Chronic Pseudomonas aeruginosa lung infections are found in patients suffering from bronchiectasis, cystic fibrosis (CF) and chronic obstructive pulmonary disorder (COPD) and once colonisation is established, it is difficult to remove by current methods. Recently, we identified a subset of patients with bronchiectasis and chronic P. aeruginosa infection had excess IgG2 specific to their cognate bacterial O-antigen. In contrast to the serum bactericidal effect normally associated with antibody, this IgG2 inhibited complement-mediated killing of the infecting strain. Crucially, patients with impaired serum killing had worse lung function than patients with normal serum killing. Two critically ill patients with this IgG2 were treated with plasmapheresis in an attempt to remove the inhibitory antibody. Both patients had immediate benefit from this treatment with a significant drop in hospitalisations, antibiotic use and markers of inflammation. Both patients lost culturable P. aeruginosa in their sputum for up to four months after treatment. Return of the inhibitory antibody in patients coincided with bacteria in their sputum and degrading health. Finally, we investigated the prevalence of this inhibitory antibody in bronchiectasis associated with P. aeruginosa infection via an ELISA-based screen using a panel of P. aeruginosa O-antigen serotypes removing the need for patient isolates. 14% of over 200 patients with bronchiectasis had high titres of IgG2 to at least one O-antigen serotype. Screening of a further cohort of patients with rheumatoid arthritis, which has a significant overlap with bronchiectasis, revealed similar high prevalence of inhibitory antibody. These findings indicate that inhibitory anti-O-antigen IgG2 may be a significant problem in bronchiectasis, and that finding ways to remove or counteract this antibody could lead to improvement in health.