Background With newborn screening (NBS) for cystic fibrosis (CF) eradication of

Background With newborn screening (NBS) for cystic fibrosis (CF) eradication of (PA) is possible if PA detection occurs early. with Rabbit Polyclonal to HLA-DOB. weighted receiver operating characteristic (ROC) curves was used to determine best antibody titer cutoff values to predict subsequent PA positive cultures. Results Using weighted ROC curves cell lysate was more sensitive than exotoxin A which was more sensitive than elastase but all age-specific cutoffs were better than fixed cutoffs previously used. Age-specific serological cutoffs both predict and detect PA respiratory infections with a higher sensitivity and specificity. Serological responses to the PA antigens decided that a response to cell lysate occurs significantly earlier than culture positivity. Conclusions Age-specific serological cutoffs rather than fixed values against common PA antigens improve early PA identification in infants and young children diagnosed with NBS. Regular serological assessment with age-specific cutoffs in these children appears to be a worthy diagnostic tool. (PA) it has become clear that better methods of detecting PA-associated respiratory infections are sorely needed. Typically infants diagnosed with CF by NBS are free of PA whereas about 30% of those diagnosed by traditional methods following signs/symptoms of CF have already acquired the pathogen.1 “The potential to eradicate nonmucoid PA and even to delay transformation to mucoid species makes ascertainment of the initial PA infection one of the highest priorities in current clinical management ” as stated by Farrell and Govan.2 The controversy that currently exists is usually which PA identification method is usually most favorable in this patient population. Oropharyngeal (OP) swab culture in young CF children is the most widely-used test for PA detection but studies have shown a variable and limited sensitivity for this screening.3-8 In 2001 Burns et al demonstrated that this identification of PA improved from 72.5% using cultures obtained by bronchoalveolar lavage (BAL) and OP swab sampling to 97.5% when combined with serological testing during the first three years of life in a cohort of 40 CF patients.9 The serological analysis performed was an immunoblot that detected antibodies against whole-cell proteins from PA.9 Previous studies have suggested that rising antibody titers to several PA antigens may occur before detection of the organism by culture of respiratory secretions.11-15 In a recent study da Silva Filho et al10 performed a cross-sectional analysis in 87 CF patients (mean age 9.7 years) comparing three different methods of PA identification: microbiological culture; polymerase chain reaction (PCR) Protopine targeting the algD GDP mannose dehydrogenase gene of PA obtained from sputum or OP swab samples; and serum antibodies against three PA antigens elastase alkaline protease and exotoxin A. Microbiological cultures were positive in samples from 42 patients (48.2%) PCR was positive in 53 (60.9%) patients and serological testing was positive in 38 patients (43.6%).10 The difference among the three methods was not statistically significant but the combination of PCR and PA serology was Protopine significantly superior to single methods to PCR and microbiological cultures and to PA serology and microbiological cultures.10 However the sensitivity and specificity of PA serology and the optimal discriminating or cutoff values for serological values have not been adequately studied especially in infants and young children with CF. Thus we designed this analysis to address that gap in knowledge with a working hypothesis that serological cutoffs based on age are more useful in assessing PA infection as compared to a standard cutoff for all those ages. Our goal is to identify PA respiratory infections in young children with CF as early as possible using serological values for diagnostic and prognostic purposes. Methods Characteristics of study patients A total of 69 patients that were all diagnosed through NBS at the Madison and Milwaukee CF Centers were followed with characteristics of the study population summarized in Table 1. We included CF patients of the screened group who were assessed Protopine successfully with serial serology and had concurrent respiratory secretions cultures. Patients enrolled in this prospective study are described in detail Protopine elsewhere.14-15 Our screening project and the PA antibody titer evaluation study were approved by the institutional review boards (IRB’s) of the.