Interactive Cohort Identification of Sleep Disorder Patients Using Natural Language Processing and i2b2.

UNLABELLED: Nationwide Children's Hospital established an i2b2 (Informatics for Integrating Biology & the Bedside) application for sleep disorder cohort identification. Discrete data were gleaned from semistructured sleep study reports. The system showed to work more efficiently than the traditional manual chart review method, and it also enabled searching capabilities that were previously not possible. OBJECTIVE: We report on the development and implementation of the sleep disorder i2b2 cohort identification system using natural language processing of semi-structured documents. METHODS: We developed a natural language processing approach to automatically parse concepts and their values from semi-structured sleep study documents. Two parsers were developed: a regular expression parser for extracting numeric concepts and a NLP based tree parser for extracting textual concepts. Concepts were further organized into i2b2 ontologies based on document structures and in-domain knowledge. RESULTS: 26,550 concepts were extracted with 99% being textual concepts. 1.01 million facts were extracted from sleep study documents such as demographic information, sleep study lab results, medications, procedures, diagnoses, among others. The average accuracy of terminology parsing was over 83% when comparing against those by experts. The system is capable of capturing both standard and non-standard terminologies. The time for cohort identification has been reduced significantly from a few weeks to a few seconds. CONCLUSION: Natural language processing was shown to be powerful for quickly converting large amount of semi-structured or unstructured clinical data into discrete concepts, which in combination of intuitive domain specific ontologies, allows fast and effective interactive cohort identification through the i2b2 platform for research and clinical use.

Early immune response to the components of the type III system of Pseudomonas aeruginosa in children with cystic fibrosis.

The lungs of patients with cystic fibrosis (CF) are colonized initially by Pseudomonas aeruginosa, which is associated with progressive lung destruction and increased mortality. The pathogenicity of P. aeruginosa is caused by a number of virulence factors, including exotoxin A (ETA) and the type III cytotoxins (ExoS, ExoT, ExoU, and ExoY). P. aeruginosa contacts the plasma membrane to deliver type III cytotoxins through a channel formed by PopB, PopD, and PcrV; ETA enters mammalian cells via receptor-mediated endocytosis. The Wisconsin CF Neonatal Screening Project is a longitudinal investigation to assess the potential benefits and risks of newborn screening for CF; the project was the source of serum samples used in this study. Past studies evaluated the longitudinal appearance of antibodies to ETA and elastase and P. aeruginosa infections in patients with CF. The current study characterized the longitudinal appearance of antibodies to components of the type III system in children with CF. Western blot analyses showed that serum antibodies to PopB, PcrV, and ExoS were common. Longitudinal enzyme-linked immunosorbent assays determined that the first detection of antibodies to pooled ExoS/PopB occurred at a time similar to those of detection of antibodies to a P. aeruginosa cell lysate and the identification of oropharyngeal cultures positive for P. aeruginosa. This indicates that children with CF are colonized early with P. aeruginosa expressing the type III system, implicating it in early pathogenesis, and implies that surveillance of clinical symptoms, oropharyngeal cultures, and seroconversion to type III antigens may facilitate early detection of P. aeruginosa infections.

Detection of Pseudomonas aeruginosa type III antibodies in children with tracheostomies.

Pseudomonas aeruginosa is often cultured from the airways of children with tracheostomies. P. aeruginosa produces exotoxin A (ETA) and type III cytotoxins. This study tested the hypothesis that children with tracheostomies are colonized by P. aeruginosa that express these virulence factors and will have antibodies directed against these virulence factors, indicating infection rather than only colonization. A convenience sample of 30 patients, ranging in age from 2 months-22 years, was recruited. Serum was tested for the presence of antibodies to ETA and components of the type III system by Western blot analysis. Twenty-one of 39 patients (70%) had antibodies to components of the type III system. Fifteen of 30 (50%) were seropositive for ETA. Sera from patients who were antibody-positive for ETA were also seropositive for either ExoS or ExoU. Nine of 30 patients (30%) did not possess antibodies to ETA or components of the type III system. In conclusion, these data identified a seropositive reaction to P. aeruginosa cytotoxins in some patients with tracheostomies, suggestive of infection by cytotoxic strains of P. aeruginosa. Future studies will determine the utility of measuring seroconversion to these cytotoxins as an early indication of infection in children with tracheostomies.

Acceleration of lung disease in children with cystic fibrosis after Pseudomonas aeruginosa acquisition.

As part of the ongoing Wisconsin Cystic Fibrosis (CF) Neonatal Screening Project, we had the unique opportunity to study the longitudinal relationship between Pseudomonas aeruginosa (Pa) acquisition and infection and developing lung disease in children with CF. The primary objective was to determine whether acquisition of Pa was associated with a measurable change in the progression of lung disease. Two outcome measures were used to study 56 patients who were diagnosed through newborn screening: 1) Wisconsin additive chest radiograph score (WCXR), based on the average of scores from a pulmonologist and a radiologist, and 2) the highest forced expired volume in 1 sec (FEV(1))/forced vital capacity (FVC) ratio. We used two measures of Pa acquisition: 1) time of first positive protocol-determined oropharyngeal (with cough) culture, and 2) the magnitude of antibody titer detected by ELISA assays, using as antigen a crude cell lysate, purified exotoxin A, or an elastase toxoid prepared from three Pa strains. Other predictor variables included age, pancreatic status, height-for age, and weight-for-age-percentiles. The best regression model for predicting changes in the WCXR included time to first positive culture and antibody titer for Pa elastase. Prior to Pa acquisition, WCXR worsened by 0.45 points/year (P > 0.25); after Pa acquisition, the rate of worsening increased significantly (P < 0.001) to 1.40 points/year. Each antibody titer level (log base 2) increased the score by 0.48 points (P < 0.001). The best regression model for predicting change in the FEV(1)/FVC included only time to first positive culture. Prior to Pa acquisition, the FEV(1)/FVC ratio declined by 1.29%/year; after Pa infection, the rate of decrease significantly accelerated to 1.81%/year (P = 0.001). Our data show that Pa acquisition is associated with declining pulmonary status in children with CF, and that this effect is probably gradual rather than precipitous. Because these patients were diagnosed and treated aggressively, our estimates of the effects of Pa acquisition may be conservative. We also conclude that the WCXR appears to be more sensitive than FEV(1)/FVC in detecting early changes in lung disease associated with CF.

Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. Wisconsin Cystic Fibrosis Neonatal Screening Study Group.

OBJECTIVE: Despite its relative frequency among autosomal recessive diseases and the availability of the sweat test, cystic fibrosis (CF) has been difficult to diagnose in early childhood, and delays can lead to severe malnutrition, lung disease, or even death. The Wisconsin CF Neonatal Screening Project was designed as a randomized clinical trial to assess the benefits and risks of early diagnosis through screening. In addition, the incidence of CF was determined, and the validity of our randomization method assessed by comparing 16 demographic variables. METHODOLOGY: Immunoreactive trypsinogen analysis was applied to dried newborn blood specimens for recognition of CF risk from 1985 to 1991 and was coupled to DNA-based detection of the DeltaF508 mutation from 1991 to 1994. Randomization of 650 341 newborns occurred when their blood specimens reached the Wisconsin screening laboratory. This created 2 groups-an early diagnosis, screened cohort and a standard diagnosis or control group. To avoid selection bias, we devised a unique unblinding method with a surveillance program to completely identify the control subjects. Because sequential analysis of nutritional outcome measures revealed significantly better growth in screened patients during 1996, we accelerated the unblinding and completely identified the control group by April 1998. Having each member of this cohort enrolled and evaluated for at least 1 year and having completed a comprehensive surveillance program, we performed another statistical analysis of anthropometric evaluated indices that includes all CF patients without meconium ileus. RESULTS: The incidence of classical CF, ie, patients diagnosed in this trial with a sweat chloride of 60 mEq/L greater, was 1:4189. By incorporating other CF patients born during the randomization period, including 2 autopsy diagnosed patients and 8 probable patients, we calculate a maximum incidence of 1:3938 (95% confidence interval: 3402-4611). Although there were group differences in the proportion of patients with DeltaF508 genotypes and with pancreatic insufficiency, validity of the randomization plan was demonstrated by analyzing 16 demographic variables and finding no significant difference after adjustment for multiple comparisons. Focusing on patients without meconium ileus, we found a marked difference in the mean +/- standard deviation age of diagnosis for screened patients (13 +/- 37 weeks), compared with the standard diagnosis group (100 +/- 117). Anthropometric indices of nutritional status were significantly higher at diagnosis in the screened group, including length/height, weight, and head circumference. During 13 years of study, despite similar nutritional therapy and the inherently better pancreatic status of the control group, analysis of nutritional outcomes revealed significantly greater growth associated with early diagnosis. Most impressively, the screened group had a much lower proportion of patients with weight and height data below the 10th percentile throughout childhood. CONCLUSIONS: Although the screened group had a higher proportion of patients with pancreatic insufficiency, their growth indices were significantly better than those of the control group during the 13-year follow-up evaluation and, therefore, this randomized clinical trial of early CF diagnosis must be interpreted as unequivocally positive. Our conclusions did not change when the height and weight data before 4 years of age for the controls detected by unblinding were included in the analysis. Also, comparison of growth outcomes after 4 years of age in all subjects showed persistence of the significant differences. Therefore, selection bias has been eliminated as a potential explanation. In addition, the results show that severe malnutrition persists after delayed diagnosis of CF and that catch-up may not be possible. We conclude that early diagnosis of CF through neonatal screening combined with aggressive nutritional therapy can result

Comprehensive analysis of risk factors for acquisition of Pseudomonas aeruginosa in young children with cystic fibrosis.

The objective of this study was to identify risk factors of significance for acquisition of Pseudomonas aeruginosa by children with cystic fibrosis (CF). Our working hypothesis is that exposure of infants and young children with CF to older, infected patients increases their risk for acquiring this organism. A special opportunity arose to study this question in detail, as we have been performing a randomized clinical trial of neonatal screening for CF throughout the state of Wisconsin during the period of 1985-1994. Patients were selected for this study based on either early identification through screening or diagnosis by standard methods. A longitudinal protocol employed at Wisconsin's two CF Centers includes routine cultures of respiratory secretions and collection of clinical, demographic, and activity information on patients and their families. Previous observations in our trial revealed that one center at an old hospital in an urban location showed a significantly shorter time to acquisition of P. aeruginosa for CF patients followed there. To study the center effect further, we performed statistical analyses using survival curves and stepwise regression analysis of all life history covariates available. The results of these analyses showed that the statistically significant correlations involve the following risk factors: 1) center and old hospital (r=0.42); 2) center and original physician (r=0.61); 3) center and exposure to pseudomonas-positive patients (r=0.29); and 4) population density and urban location (r=0.49). The final statistical model demonstrated that increased risk due to aerosol use (odds ratio=3.45, P=0.014) and a protective effect associated with education of the mother (odds ratio=0.81, P=0.024) were the most significant factors for acquisition of P. aeruginosa. The previously observed center effect was confined to the 1985-1990 interval at the old hospital (odds ratio=4.43, P < 0.001). We conclude that multiple factors are involved in increasing the risk of young children with CF to acquire P. aeruginosa, and that the observed center effect can best be explained by a combination of factors. These results suggest that facilities and methods used to care for young children with CF can significantly influence their likelihood of acquiring pseudomonas in the respiratory tract.

Survival and functional outcome of children requiring endotracheal intubation during therapy for severe traumatic brain injury.

OBJECTIVE: To determine the predictors of survival and functional outcome of pediatric patients with traumatic brain injury severe enough to require endotracheal intubation and mechanical ventilation. DESIGN: Retrospective, observational cohort study. SETTING: Pediatric intensive care unit (ICU) at a tertiary care children's hospital. PATIENTS: All children (n = 105) admitted over a 5-yr period with traumatic brain injury severe enough to require endotracheal intubation and mechanical ventilation. The median age was 43 months (range 1 month to 14 yrs). Of these children, 74% were male and 70% were white. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Variables studied included vital signs during the first 24 hrs of admission, Pediatric Risk of Mortality (PRISM) score, Glasgow Coma Score, duration of mechanical ventilation, and number of pediatric ICU and hospital days. Functional status was graded as normal, independent, partially dependent, or dependent in the areas of locomotion, self-care, and communication. This status was assessed at hospital discharge by chart review and at follow-up by telephone interview. The median Glasgow Coma Score was 6 (range 3 to 14) and the median PRISM score was 13 (range 1 to 51). There were 19 (18.1%) deaths, 17 in the pediatric ICU and two after hospital discharge. Of the patients who survived to hospital discharge, 39 (37.1%) patients were completely normal or independent, 42 (40%) patients were partially dependent, and seven (6.7%) patients were dependent in all three areas of function. Follow-up evaluations were available for 80 patients, with a median follow-up time of 24.5 months (range 8 to 70). Of the 78 patients who survived and were available for follow-up, the number who were functionally normal or independent increased to 69 (65.7%). At follow-up, there were eight (7.6%) patients remaining with partial dependency in at least one area of function while one (0.9%) patient continued to be dependent in all three areas of function. Mortality and dependent functional outcome were more likely in patients with younger age, lower Glasgow Coma Score, and higher PRISM score at hospital admission. Of the 27 patients with a Glasgow Coma Score of < or = 5, 11 (40.7%) survived with normal or independent functional status at follow-up. Of the 24 patients with PRISM scores of > 20, only five (20.8%) were functionally normal or independent at follow-up. The relative risk of a bad outcome for patients with a Glasgow Coma Score of < or = 5 and a PRISM score of > or = 20 was ten times higher than the group of patients with a Glasgow Coma Score of < or = 5 but a PRISM score of < 20. CONCLUSIONS: Children with severe traumatic brain injury who survive to hospital discharge will continue to improve in their functional status over the next few years. Although low Glasgow Coma Score is strongly associated with death or poor functional outcome after therapy for traumatic brain injury, many patients with Glasgow Coma Score of < or = 5 can survive with good function. PRISM scores add to the power of Glasgow Coma Score to predict survival and functional outcome in tracheally intubated pediatric patients with Glasgow Coma Score of < or = 5.

Newborn screening for cystic fibrosis in Wisconsin: comparison of biochemical and molecular methods.

OBJECTIVES: To evaluate neonatal screening for cystic fibrosis (CF), including study of the screening procedures and characteristics of false-positive infants, over the past 10 years in Wisconsin. An important objective evolving from the original design has been to compare use of a single-tier immunoreactive trypsinogen (IRT) screening method with that of a two-tier method using IRT and analyses of samples for the most common cystic fibrosis transmembrane regulator (CFTR) (DeltaF508) mutation. We also examined the benefit of including up to 10 additional CFTR mutations in the screening protocol. METHODS: From 1985 to 1994, using either the IRT or IRT/DNA protocol, 220 862 and 104 308 neonates, respectively, were screened for CF. For the IRT protocol, neonates with an IRT >/=180 ng/mL were considered positive, and the standard sweat chloride test was administered to determine CF status. For the IRT/DNA protocol, samples from the original dried-blood specimen on the Guthrie card of neonates with an IRT >/=110 ng/mL were tested for the presence of the DeltaF508 CFTR allele, and if the DNA test revealed one or two DeltaF508 alleles, a sweat test was obtained. RESULTS: Both screening procedures had very high specificity. The sensitivity tended to be higher with the IRT/DNA protocol, but the differences were not statistically significant. The positive predictive value of the IRT/DNA screening protocol was 15.2% compared with 6.4% if the same samples had been screened by the IRT method. Assessment of the false-positive IRT/DNA population revealed that the two-tier method eliminates the disproportionate number of infants with low Apgar scores and also the high prevalence of African-Americans identified previously in our study of newborns with high IRT levels. We found that 55% of DNA-positive CF infants were homozygous for DeltaF508 and 40% had one DeltaF508 allele. Adding analyses for 10 more CFTR mutations has only a small effect on the sensitivity but is likely to add significantly to the cost of screening. CONCLUSIONS: Advantages of the IRT/DNA protocol over IRT analysis include improved positive predictive value, reduction of false-positive infants, and more rapid diagnosis with elimination of recall specimens.

Failure of aggressive therapy to alter outcome in pediatric near-drowning.

OBJECTIVES: To identify predictors of outcome in pediatric near-drowning victims, and to measure the effectiveness of therapy in pediatric near-drowning victims by assessing clinical outcome as a function of injury severity at presentation and therapeutic interventions during hospitalization. DESIGN: Retrospective chart review at a tertiary care university associated Children's Hospital from January 1976 to July 1992. MEASUREMENTS AND MAIN RESULTS: Initial intensive care unit (ICU) assessment included a Glasgow Coma Score (GCS) and a Pediatric Risk of Mortality (PRISM) Score. Outcome was assessed using a standard scoring system classifying functional abilities at hospital discharge as no functional disability, independent, partially independent, or total dependence on caregivers for function. Forty (49%) of 81 died. Of the survivors, 26 (63%) had no functional disability or were partially dependent at hospital discharge. Of the 47 (64%) patients with a GCS < or = 4 on presentation to the ICU, 37 (79%) died and 10 (21%) were dependent in all areas of function at discharge. Of the 40 (60%) patients who had a PRISM score < 20, 98% either died or were completely dependent at discharge. Of the 49 patients who were asystolic upon arrival to the emergency department (ED), 76% died, and the rest were completely dependent. Logistic regression showed that therapy had no independent effect on outcome when disease severity was accounted for. CONCLUSIONS: Severity of illness measured by GCS and PRISM score in the ICU can be useful in predicting outcome. For patients cared for in a Pediatric Intensive Care Unit, those with asystole on arrival at the ED had uniformly poor outcome. Currently available therapies do not alter outcome.

Acquisition of Pseudomonas aeruginosa in children with cystic fibrosis.

OBJECTIVE: This study was pursued as an extension of a randomized clinical investigation of neonatal screening for cystic fibrosis (CF). The project included assessment of respiratory secretion cultures for pathogens associated with CF. The objective was to determine whether patients diagnosed through neonatal screening and treated in early infancy were more likely to become colonized with Pseudomonas aeruginosa compared with those identified by standard diagnostic methods. METHODOLOGY: The design involved prospective cultures of respiratory secretions obtained generally by oropharyngeal swabs at least every 6 months and more often if clinically indicated. Patients were managed with a standardized evaluation and treatment protocol at the two Wisconsin certified CF centers; however, there were community and environmental variations associated with the follow-up period as described below. RESULTS: Overall, there were no differences in acquisition of respiratory pathogens between the screened and the control (standard diagnosis) groups. Evaluation of the data between and within the two centers, however, revealed significant differences with earlier acquisition of P aeruginosa in the center with the following distinguishing characteristics: urban location; following patients with the standard US approach in which newly diagnosed, young children were interspersed with older CF patients; and where there were more opportunities for social interactions with other CF patients. The differences were confined to the screened group followed in the urban center in which the median pseudomonas-free survival period was 52 weeks contrasted with 289 weeks in the other center. In addition, assessment of data for the entire CF populations followed at the two centers revealed that the urban center showed a significantly higher prevalence of P aeruginosa colonization in patients between the ages of 3 and 9 years. CONCLUSIONS: These results present questions and generate hypotheses on risk factors for acquisition of P aeruginosa in CF and suggest that clinic exposures and/or social interactions may predispose such patients to pseudomonas infections.

Nutritional benefits of neonatal screening for cystic fibrosis. Wisconsin Cystic Fibrosis Neonatal Screening Study Group.

BACKGROUND: Many patients with cystic fibrosis are malnourished at the time of diagnosis. Whether newborn screening and early treatment may prevent the development of a nutritional deficiency is not known. METHODS: We compared the nutritional status of patients with cystic fibrosis identified by neonatal screening or by standard diagnostic methods. A total of 650,341 newborn infants were screened by measuring immunoreactive trypsinogen on dried blood spots (from April 1985 through June 1991) or by combining the trypsinogen test with DNA analysis (from July 1991 through June 1994). Of 325,171 infants assigned to an early-diagnosis group, cystic fibrosis was diagnosed in 74 infants, including 5 with negative screening tests. Excluding infants with meconium ileus, we evaluated nutritional status for up to 10 years by anthropometric and biochemical methods in 56 of the infants who received an early diagnosis and in 40 of the infants in whom the diagnosis was made by standard methods (the control group). Pancreatic insufficiency was managed with nutritional interventions that included high-calorie diets, pancreatic-enzyme therapy, and fat-soluble vitamin supplements. RESULTS: The diagnosis of cystic fibrosis was confirmed by a positive sweat test at a younger age in the early-diagnosis group than in the control group (mean age, 12 vs. 72 weeks). At the time of diagnosis, the early-diagnosis group had significantly higher height and weight percentiles and a higher head-circumference percentile (52nd, vs. 32nd in the control group; P=0.003). The early-diagnosis group also had significantly higher anthropometric indexes during the follow-up period, especially the children with pancreatic insufficiency and those who were homozygous for the deltaF508 mutation. CONCLUSIONS: Neonatal screening provides the opportunity to prevent malnutrition in infants with cystic fibrosis.

Wire stent for tracheomalacia in a five-year-old girl.

A wire stent was used successfully to treat life-threatening tracheomalacia in a 5-year-old girl. Wire stents placed bronchoscopically are nonobstructing and have the potential for balloon expansion to accommodate growth.

Survival and functional outcome of children requiring mechanical ventilation during therapy for acute bacterial meningitis.

OBJECTIVE: To determine predictors of survival and functional outcome of pediatric patients requiring mechanical ventilation during therapy for acute bacterial meningitis. DESIGN: Retrospective case series. SETTING: Pediatric intensive care unit (ICU) at a midwestern tertiary care children's hospital. PATIENTS: Consecutive sample of 32 patients (median age 9.8 months; range 9 days to 12 yrs) from 1985 to 1990 with acute bacterial meningitis severe enough to require mechanical ventilation during therapy. Of these patients, 59% were female and 59% were white. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were analyzed to identify predictors of survival and functional status after hospital discharge. Variables included were vital signs, Pediatric Risk of Mortality (PRISM) score within the first 24 hrs of hospitalization, Glasgow Coma Score, and course of illness. Functional status was assessed at hospital discharge and at follow-up (median follow-up: 41.5 months, range 7 to 77) in the areas of locomotion, self-care, and communication. There were ten inhospital deaths. The 22 survivors formed three groups. At hospital discharge, seven children showed no functional disability. Seven patients were dependent in all three areas of function at discharge, with six still dependent at follow-up evaluation. Eight patients showed mild to moderate impairment in at least one area of function at hospital discharge. At follow-up, four of these eight patients demonstrated no functional disability, one had improved status, two were unchanged, and one was lost to follow-up. The best predictor of death and functional status at follow-up was the admission PRISM score. Hypotension and tachycardia within the first 24 hrs after pediatric ICU admission were strongly associated with poor outcome. CONCLUSIONS: After bacterial meningitis in children whose care included mechanical ventilation, half of the patients died or survived with severe functional deficits. Patients with mild or moderate functional deficits at hospital discharge improved with time.

Pancreatitis associated with remote traumatic brain injury in children.

Vomiting, abdominal distension, and feeding intolerance are common findings following brain injury in children, and are usually attributed to the brain injury or to delayed gastric emptying: a specific cause is usually not sought. We report six children who developed mild to moderate pancreatitis at least 7 days following apparently isolated brain injury, a previously unreported association. Five of the six patients received drugs that are known or suspected pancreatotoxins; all recovered without changes in the medications. When children develop feeding intolerance or upper gastrointestinal symptoms following traumatic brain injury pancreatitis should be suspected.

Immune responses to Aspergillus fumigatus and Pseudomonas aeruginosa antigens in cystic fibrosis and allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) in Cystic Fibrosis (CF) is well documented. Aspergillus fumigatus is the causative agent of ABPA, and Pseudomonas aeruginosa particularly the mucoid variety has been frequently isolated from the sputum of patients with CF. This study investigates the cellular and humoral immune response to both A fumigatus and P aeruginosa antigens in patients with CF and ABPA (CF/ABPA), CF only, and healthy controls. The A fumigatus and P aeruginosa antigen specific IgE and IgG in sera and peripheral blood mononuclear cell culture supernatants (PBMC sups), lymphoproliferation to antigens, and leukotriene B4 (LTB4) were measured. Results indicate significant elevated levels of A fumigatus specific IgG (A fumigatus-IgG) and Paeruginosa-IgE in serum. Significant Paeruginosa-IgG was measured in PBMC sups. The concanavalin A nonbinding A fumigatus antigen, previously shown to induce specific T-cell responses in vitro in patients with ABPA, elicited significant lymphoproliferative response in a greater proportion of patients with CF/ABPA and not in CF or controls, underlining the importance of this antigen in the diagnosis of ABPA. In contrast, a greater proportion of the CF group responded to P aeruginosa antigens compared with the controls and CF/ABPA. Hence, the CF and CF/ABPA groups respond to both P aeruginosa and A fumigatus antigens with the former group responding strongly to P aeruginosa and the latter to A fumigatus antigens.

Brain abscess caused by Blastomyces dermatitidis in a child with cystic fibrosis.

An 8-year-old girl with moderately severe cystic fibrosis and right upper lobe bronchiectasis developed a cerebellar abscess caused by Blastomyces dermatitidis. To our knowledge, this is the youngest child with cystic fibrosis and a brain abscess, and the first documented case caused by a fungus.