Mucoid Pseudomonas aeruginosa is isolated from most patients with cystic fibrosis, in whom it causes a chronic, incurable lung infection. Bronchopulmonary disease is the cause of death in 95% of patients with cystic fibrosis,'2 and mucoid P aeruginosa was cultured from 94% of Danish patients with cystic fibrosis at death.3 Typically the airways are colonised initially with non-mucoid strains of P aeruginosa" and after a variable period of colonisation, usually one to two years, mucoid strains emerge that produce large amounts of the extracellular polysaccharide alginate. Compared with non-mucoid strains, infection with mucoid P aeruginosa is associated with a poorer clinical state,6 lower pulmonary function,78 and greater risk of death.7Infection with mucoid strains was also associated with an increased humoral immune response to P aeruginosa.`0 An increased antibody response is associated with poorer pulmonary function7"' and the lung damage in cystic fibrosis is mediated by immune complexes.'213 This suggests that alginate is a virulence factor in chronic P aeruginosa pulmonary infection in cystic fibrosis.'4Our objective was to test the hypothesis that alginate producing, mucoid P aeruginosa is more virulent than non-mucoid strains. We studied 73 patients with cystic fibrosis classified according to their sputum bacteriology longitudinally and determined their antibody responses to P aeruginosa alginate and somatic antigens, lung function, and nutritional state for three years before and for up to 10 years after the onset of chronic P aeruginosa lung infection. Patients and methodsThe diagnosis of cystic fibrosis was based on repeatedly raised electrolyte concentrations in sweat and characteristic clinical features. The criteria for entry into the study were that the onset of chronic P aeruginosa infection was after 1975, that the patient had been followed up monthly at the Danish Cystic Fibrosis Centre at Rigshospitalet before the onset of infection, and that sputum bacteriology had been recorded for at least eight months of each year. Data were recorded prospectively and included forced vital capacity (FVC), height, weight, and sputum bacteriology. Since 1976 all patients with chronic P aeruginosa infection have been admitted to the centre every three months for intravenous courses of antipseudonomas chemotherapy.'5 BACTERIOLOGY The onset ofchronic P aeruginosa infection was defined as the time when P aeruginosa had been grown in consecutive monthly sputum cultures over six months.

Mannose-binding lectin (MBL) is a key factor in innate immunity, and lung infections are the leading cause of morbidity and mortality in cystic fibrosis (CF). Accordingly, we investigated whether MBL variant alleles, which are associated with recurrent infections, might be risk factors for CF patients. In 149 CF patients, different MBL genotypes were compared with respect to lung function, microbiology, and survival to end-stage CF (death or lung transplantation). The lung function was significantly reduced in carriers of MBL variant alleles when compared with normal homozygotes. The negative impact of variant alleles on lung function was especially confined to patients with chronic Pseudomonas aeruginosa infection. Burkholderia cepacia infection was significantly more frequent in carriers of variant alleles than in homozygotes. The risk of end-stage CF among carriers of variant alleles increased 3-fold, and the survival time decreased over a 10-year follow-up period. Moreover, by using a modified life table analysis, we estimated that the predicted age of survival was reduced by 8 years in variant allele carriers when compared with normal homozygotes. Presence of MBL variant alleles is therefore associated with poor prognosis and early death in patients with CF.

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