title: Early rise of anti-pseudomonas antibodies and a mucoid phenotype of pseudomonas aeruginosa are risk factors for development of chronic lung infection--a case control study.
abstract: P. aeruginosa is the most significant pathogen in CF lung disease. Chronic infection is preceded by a period of intermittent colonization. Early aggressive antimicrobial treatment at initial detection of P. aeruginosa in lower respiratory tract (LRT) secretions can prevent transition to chronic infection in approximately 80% of the patients, while the rest progress to chronic infection in spite of treatment. To analyze risk factors for development of chronic infection, a cohort of 89 CF patients free of chronic infection at the study period start was followed for 10 years. 28 of the patients (study group) developed chronic infection in spite of early treatment and 28 age-matched patients who did not (controls) were included in the analysis. During the 3 years period prior to onset of chronic infection, P. aeruginosa-positive cultures were more frequent in the study group than in the controls (2.2 vs. 0.5 per year, p<0.0001). Growth of mucoid strains of P. aeruginosa was more frequent in study group than in controls (11.5% vs. 0%, p<0.0001). Most important, specific anti-pseudomonal IgG serum antibodies were significantly higher in the study group than in controls (0.98 Elisa Units vs. 0.53, p=0.04) already 3 years prior to onset of chronic infection and increased 0.44 EU pr year in the study group but remained at the initial level in the control group (p<0.005). Occurrence of Aspergillus-positive cultures were significantly more frequent in the study group than in controls (p=0.01). The strongest risk factor for development of chronic P. aeruginosa infection was increasing levels of specific anti-pseudomonal antibodies, specifically of IgG1 and IgG4 subclass and total anti-Pseudomonas IgG, 3 years prior to onset of chronic infection, with odds ratio (OR) 8.9, 7.7 and 7.4, respectively (p<0.005), and growth of mucoid P. aeruginosa strains with OR of 7.4, p=0.006). Occurrence of Aspergillus was also a risk factor for developing chronic P. aeruginosa infection with the OR of 4.7 (p=0.008).
authors.affiliation: Copenhagen Cystic Fibrosis Center, Department of Paediatrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen [corrected] Denmark. tania@rh.dk
authors.forename: Tacjana
authors.initials: T
authors.lastname: Pressler
authors.forename: Birgitte
authors.initials: B
authors.lastname: Frederiksen
authors.forename: Marianne
authors.initials: M
authors.lastname: Skov
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.forename: Christian
authors.initials: C
authors.lastname: Koch
authors.forename: Niels
authors.initials: N
authors.lastname: Høiby
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006025:Glycosaminoglycans / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D010641:Phenotype; D011552:Pseudomonas Infections / Q000150:complications* / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D013183:Sputum / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; D006025:Glycosaminoglycans; C046129:mucoid exopolysaccharide (P aeruginosa)