Respiratory infections with Pseudomonas aeruginosa in children with cystic fibrosis: early detection by serology and assessment of risk factors.
BACKGROUND
Patients with cystic fibrosis (CF) are susceptible to lower respiratory tract infections with Pseudomonas aeruginosa and typically acquire this organism in early childhood. Once P aeruginosa infection is established, eradication may be impossible, and progressive lung disease often aggravates morbidity and mortality risks. The ability to diagnose CF by genetic testing at birth makes it possible to determine the temporal sequence of events that result in P aeruginosa-associated pulmonary infections.


OBJECTIVE
To evaluate the longitudinal relationship between the production of an antibody response against P aeruginosa and clinical factors associated with P aeruginosa pulmonary infections in patients with CF diagnosed in early life.


METHODS
Serum samples and oropharyngeal cultures (protocol cultures) were obtained at 6-month intervals from April 15, 1985, to April 15, 2000 (or for up to 180 months depending on their enrollment date) from 68 patients at 2 centers in Madison and Milwaukee, Wis, diagnosed through the Wisconsin CF Neonatal Screening Project, a longitudinal cohort study. Additional cultures were obtained at examining physicians' discretion (all cultures).


METHODS
Time to serum IgG, IgA, and IgM antibody titer of at least 1:256 against P aeruginosa, assessed by enzyme-linked immunosorbent assay using cell lysate, exotoxin A, and elastase as antigens; time to organism isolation from respiratory samples; time to Wisconsin Cystic Fibrosis Radiograph (WCXR) score of 5 or more.


RESULTS
The median time to an antibody titer of at least 1:256 was 17.8, 24.2, and 70.9 months for cell lysate, exotoxin A, and elastase, respectively. The rise of anti-cell lysate and anti-exotoxin A titers to 1:256 or more occurred a mean of 11.9 (P<.001) and 5.6 (P =.04) months, respectively, before the isolation of P aeruginosa for all cultures and 18.2 (P<.001) and 11.9 (P =.006) months, respectively, before protocol cultures. There was no significant difference between the rise of anti-cell lysate and anti-exotoxin A titer and a WCXR score of 5 or more (P =.24 and.32, respectively). Treatment with long-term, non-Pseudomonas oral antibiotics and integration of CF infants with older, chronically infected patients were associated with a significantly increased risk of P aeruginosa pulmonary infection.


CONCLUSIONS
In CF patients diagnosed through neonatal screening, P aeruginosa pulmonary infections occurred 6 to 12 months before the organism was isolated from respiratory secretions. The longitudinal monitoring of P aeruginosa antibody titers, in concert with WCXR score, should facilitate diagnosis and treatment of P aeruginosa pulmonary infections in young children with CF.
West
Susan E H
SE
Department of Pathobiological Sciences and School of Veterinary Medicine, University of Wisconsin, 1300 University Ave, Madison, WI 53706, USA.
Zeng
Lan
L
Lee
Bee Leng
BL
Kosorok
Michael R
MR
Laxova
Anita
A
Rock
Michael J
MJ
Splaingard
Mark J
MJ
Farrell
Philip M
PM
D036002:ADP Ribose Transferases / Q000276:immunology; D000907:Antibodies, Bacterial / Q000097:blood*; D001427:Bacterial Toxins; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications*; D004797:Enzyme-Linked Immunosorbent Assay; D005098:Exotoxins / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015233:Models, Statistical; D009960:Oropharynx / Q000382:microbiology; D010196:Pancreatic Elastase / Q000276:immunology; D011552:Pseudomonas Infections / Q000097:blood / Q000175:diagnosis* / Q000209:etiology*; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000302:isolation & purification; D012044:Regression Analysis; D012141:Respiratory Tract Infections / Q000097:blood / Q000175:diagnosis* / Q000209:etiology*; D012307:Risk Factors; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D005098:Exotoxins; D010196:Pancreatic Elastase; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A