Long-term follow-up of cystic fibrosis newborn screening: psychosocial functioning of adolescents and young adults.

BACKGROUND: Long-term psychosocial outcomes of cystic fibrosis (CF) patients diagnosed through newborn screening remain unknown. METHODS: This cross-sectional study compared three groups of youths (16 to 22 years): CF patients diagnosed through NBS (CF-NBS, n = 13), CF patients diagnosed through standard practice (CF-SP, n = 26) and healthy peers (H, n = 42), plus 72 of their parents. We hypothesized that adolescent psychological functioning would be mediated by parent depression and quality of parent-child communication and cohesiveness. RESULTS: A path analysis showed significantly more depression among CF-NBS group parents (p = .006-.008). Parent-child cohesiveness was related to communication (p < .001). Cohesiveness and communication were associated with youth Internalizing Problems (p = .037, p = .009), Emotional Symptoms (p = 0.018, p = 0.022), and Personal Adjustment (communication only, p = 0.009). Parent depression was related to youth Personal Adjustment (p = 0.022). CONCLUSIONS: CF patients report psychosocial function similar to healthy peers. Parents of children diagnosed with CF through NBS may be at risk for depressive symptoms when their children reach adolescence.

Health-related quality of life in children and adolescents with cystic fibrosis: convergent validity with parent-reports and objective measures of pulmonary health.

OBJECTIVE: This study examined the convergent validity of health-related quality of life (HRQOL) reported by patients with cystic fibrosis compared with their parents' reports and objective pulmonary measures across 3 time points. METHODS: Ninety-two children (8-13 years) and adolescents (14-18 years) with cystic fibrosis and their parents completed Cystic Fibrosis Questionnaires to examine concordance with Wisconsin chest x-ray (WCXR) scores and pulmonary function tests, for example, forced expiratory volume at 1 second (FEV1), and parent-child/adolescent concordance across multiple HRQOL domains. Concordance was analyzed relative to patient age and gender. RESULTS: Parent-reports were closely aligned with WCXR scores, whereas patient reports were more closely aligned with FEV1. Adolescents and parents of both age groups had more HRQOL domains concordant with pulmonary health measures than did child self-reports. Parent-child concordance was inversely related to child age, particularly with male adolescents. Children generally reported better HRQOL than parents. Male adolescents and their parents were more likely to have significantly discordant HRQOL scores than female adolescents and their parents. Male and female adolescents reported higher HRQOL than their parents reported for all but vitality and health perception domains. Younger male children showed concordance with their parents on 5 of 7 domains. CONCLUSIONS: Parent-child/adolescent discordance on HRQOL was consistent with normative child development expectations. Findings underscore the value of enlisting perspectives from parents as well as children regarding HRQOL.

Relationships among health-related quality of life, pulmonary health, and newborn screening for cystic fibrosis.

BACKGROUND: The objective of this study was to examine relationships between pulmonary health and health-related quality of life (HRQOL) in patients with cystic fibrosis (CF) evaluated longitudinally in the Wisconsin Newborn Screening Project. METHODS: Patients aged 8 to 18 years (mean ± SD, 13.5 ± 2.8) in early diagnosis (n = 45) and control (n = 50) groups completed Cystic Fibrosis Questionnaires (CFQs) to measure HRQOL at three data points over a 2-year period. Pulmonary health was evaluated concurrently by the Wisconsin chest x-ray scoring system (WCXR) and pulmonary function tests (PFTs). RESULTS: WCXR showed significant group differences (P ≤ .023), with the early diagnosis group showing more-severe lung disease. When adjusted for group differences in mucoid Pseudomonas aeruginosa status and pancreatic status, however, WCXR differences and PFT data were not significant. Most patients (74%) had FEV(1) values ≥ 80% predicted (within normal range). For patients aged < 14 years, as WCXR scores worsened CFQ respiratory and physical domain scores decreased (both P ≤ .007). FEV(1)/FVC showed a positive relationship with the respiratory and physical domains (both P ≤ .006). WCXR scores for patients aged ≥ 14 years were associated with CFQ weight, respiratory, and health domains (all P ≤ .011). FEV(1) was associated with CFQ weight, respiratory, health, and physical domains (all P ≤ .003). Changes in pulmonary health were not associated with changes in CFQ over time. Significant group differences on the CFQ-Child social functioning domain favored the control group. CONCLUSIONS: To our knowledge, this study is the first to compare pulmonary outcomes with HRQOL indicators assessed by serial, standardized, patient-reported outcome measures for patients with CF identified either through newborn screening or diagnosed by use of traditional methods. This study found no benefits of newborn screening for pulmonary health or HRQOL after controlling for risk factors. Using WCXR and PFT data collectively helped to identify associations between pulmonary health and HRQOL.

Association between mucoid Pseudomonas infection and bronchiectasis in children with cystic fibrosis.

PURPOSE: To correlate the severity of bronchiectasis in children with cystic fibrosis with clinical and microbiologic variables in order to clarify risk factors for the development of irreversible lung disease. MATERIALS AND METHODS: After institutional review board approval and parental informed consents were obtained, a HIPAA-compliant longitudinal epidemiologic evaluation was performed in patients with cystic fibrosis who were enrolled in the Wisconsin trial of newborn screening from 1985 to 2009. Thin-section chest computed tomography (CT) was used in a prospective cross-sectional design to study patients ranging in age from 6.6 to 17.6 years (mean, 11.5 years). Thin-section CT scores were determined objectively on coded images by multiple raters in a standardized fashion. Microbiologic data were obtained by means of culture of respiratory secretions by using methods for differentiation of Pseudomonas aeruginosa (PA) as either nonmucoid or mucoid. RESULTS: Eighty-three percent of patients (68 of 82) showed bronchiectasis of varying severity. Of 12 potential risk factors, only respiratory infection with mucoid PA correlated significantly with bronchiectasis (P = .041). CONCLUSION: The severity of bronchiectasis in children with cystic fibrosis is significantly related to respiratory infection with mucoid PA; attempts to prevent bronchiectasis should include reducing exposure to and early eradication of PA.

Clues that aid in the diagnosis of nonaccidental trauma presenting as an apparent life-threatening event.

BACKGROUND: Apparent life-threatening events (ALTEs) can encompass many different diagnoses. Nonaccidental trauma (NAT) is one potential serious diagnosis. OBJECTIVE: (1) To identify key elements in the history and physical exam in infants presenting with an ALTE that aid in the subsequent diagnosis of NAT; and (2) to evaluate the role of diagnostic studies in these infants in confirming the diagnosis of NAT. DESIGN/METHODS: A retrospective chart review analysis, over a 2-year period, of infants with an ALTE was performed. From this group, all children with a discharge diagnosis of child physical abuse, shaken infant syndrome, or NAT were included in the study. RESULTS: 4 patients were found to be victims of NAT based on their clinical histories and physical examinations. Although confirmatory, ophthalmologic exams, skeletal surveys, and head CT scans had a lower sensitivity for NAT. CONCLUSIONS: NAT should be considered when an infant is admitted for evaluation of an ALTE.

Ibuprofen therapy and nasal polyposis in cystic fibrosis patients.

OBJECTIVE: To assess the effects on nasal polyposis from high-dose ibuprofen therapy used in children with cystic fibrosis (CF) pulmonary disease. DESIGN: Retrospective case series. MAIN OUTCOME MEASURE: Presence or absence of nasal polyps. RESULTS: Twenty-two patients treated with high-dose ibuprofen therapy to benefit pulmonary function were identified from 235 patients with CF. Sinonasal disease was present in 19 patients, of whom 12 had nasal polyposis. All 12 patients had observed absence of nasal polyps at some point during their ibuprofen course. Nasal polyps were present in five patients during ibuprofen therapy, and all resolved with increased ibuprofen doses. Polyps occurred in six of eight patients after ibuprofen therapy ceased. Five of the 12 patients required endoscopic sinus surgery for polyposis. CONCLUSION: High-dose ibuprofen therapy chronically administered at appropriate weight-based dosing is a possible treatment option for children and young adults with CF polyposis. More testing is indicated.

Facial nerve palsy associated with a low serum vitamin A level in an infant with cystic fibrosis.

A previously healthy 10-week-old infant presented with isolated unilateral facial nerve paralysis which progressed to bilateral paralysis over a 2-week period. Evaluation including MRI and CT of the brain and facial nerve, CSF evaluation and EMG yielded no diagnosis. A single F508 gene mutation on the newborn screen prompted sweat chloride testing which confirmed a diagnosis of cystic fibrosis. On measurement of fat-soluble vitamins, levels of vitamin A were approximately 10% of the lower normal range, in the absence of objective evidence of pseudotumor cerebri. This case emphasizes an important association between hypovitaminosis A, cystic fibrosis and facial nerve palsy.

A teenage girl with extreme tachypnea.

Dyspnea and tachypnea are common presenting complaints in an emergency department. Respiratory and cardiac causes are the most common etiology. Functional respiratory disorders should be considered in patients with atypical presentation to avoid extensive investigations. We describe an adolescent who presented to our emergency department with extreme tachypnea.

Cystic fibrosis mutations and genotype-pulmonary phenotype analysis.

BACKGROUND: Although there are more than 1000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, most of them are uncommon and only limited information exists regarding genotype-pulmonary phenotype relationships. METHODS: We determined and classified the CFTR mutations using denaturing high-performance liquid chromatography and developed new, quantitative methods to categorize pulmonary phenotypes. RESULTS: Two novel alleles were discovered, namely G1047R and 1525-2A-->G, which were accompanied by F508del and G551D mutations, respectively. Assessment of numerous options revealed that CF pulmonary phenotype categorization in children cannot be accomplished with clinical or pulmonary function data but is facilitated by longitudinal quantitative chest radiology. It was most useful to categorize pulmonary disease status by evaluating the typical pattern of abnormalities in patients homozygous for the F508del mutation, and then compare patients with minor mutations to this typical CF pulmonary phenotype. By this method, both patients with novel mutations have pulmonary phenotypes typical of F508del homozygotes. However, patients with class IV mutations (e.g., R347P) or with pancreatic sufficiency showed serial chest radiographs that were atypically mild. CONCLUSIONS: Longitudinal quantitative chest radiography provides a new strategy for CF pulmonary phenotype categorization that should be useful for genotype-phenotype delineation in individual patients and in both epidemiologic studies and clinical trials involving groups of children with CF.

Resident interest and factors involved in entering a pediatric pulmonary fellowship.

BACKGROUND: Relatively little is known about interest in pediatric pulmonology among pediatric residents. The purpose of this study, therefore, was to determine at this institution: 1) the level of pediatric resident interest in pursuing a pulmonary fellowship, 2) potential factors involved in development of such interest, 3) whether the presence of a pulmonary fellowship program affects such interest. METHODS: A questionnaire was distributed to all 52 pediatric residents at this institution in 1992 and to all 59 pediatric residents and 14 combined internal medicine/pediatrics residents in 2002, following development of a pulmonary fellowship program. RESULTS: Response rates were 79% in 1992 and 86% in 2002. Eight of the 43 responders in 1992 (19%) had considered doing a pulmonary fellowship compared to 7 of 63 (11%) in 2002. The highest ranked factors given by the residents who had considered a fellowship included wanting to continue one's education after residency, enjoying caring for pulmonary patients, and liking pulmonary physiology and the pulmonary faculty. Major factors listed by residents who had not considered a pulmonary fellowship included not enjoying the tracheostomy/ventilator population and chronic pulmonary patients in general, and a desire to enter general pediatrics or another fellowship. Most residents during both survey periods believed that they would be in non-academic or academic general pediatrics in 5 years. Only 1 of the 106 responding residents (~1%) anticipated becoming a pediatric pulmonologist. CONCLUSIONS: Although many pediatric residents consider enrolling in a pulmonary fellowship (~10-20% here), few (~1% here) will actually pursue a career in pediatric pulmonology. The presence of a pulmonary fellowship program did not significantly alter resident interest, though other confounding factors may be involved.

Apnea and bradycardia due to anaphylaxis to tobacco glycoprotein in the infant rabbit.

Prenatal and postnatal exposure to cigarette smoke is associated with an increased incidence of the sudden infant death syndrome, although the cause(s) for this is unknown. Tobacco glycoprotein (TGP), a group of proteins purified from cured tobacco leaves and present in cigarette smoke, have been shown to cause anaphylaxis in excised hearts and lungs of adult rabbits that were neonatally sensitized to TGP and later rechallenged. We sought to determine whether anaphylaxis occurred in live infant rabbits who were neonatally sensitized to TGP. At the age of 1 day, 12 animals were sensitized to TGP (0.1mg in 0.25 cc alum) via intraperitoneal injection (i.p.i.) followed by a booster ipi at the age of 30 days (TGP-S). Seven animals received i.p.i. of antigen-free alum only (controls). All animals underwent an intravenous TGP challenge at age 42+/-2 days. Heart rate (HR) and respiratory rate (RR) were recorded for 2 min prior to and 5 min after the challenge. Baseline HR (approximately 260) and RR (approximately 120) were similar in all animals. Seven TGP-S animals developed apnea (1.9-4.7s) within 60s of the challenge while none of the controls did. The TGP-S also became bradycardic (the lowest HR over 50 consecutive beats), with the HR decreasing from 260 to 220 vs the controls, whose HR remained constant (approximately 250). We conclude that some rabbits neonatally sensitized to TGP develop apnea and bradycardia upon further intravenous TGP challenge. These studies suggest that cigarette smoke exposure may be associated with a higher rate of SIDS via an anaphylactic mechanism.

A comparison of apparent life-threatening events before and after the back to sleep campaign.

OBJECTIVES: The incidence of the Sudden Infant Death Syndrome (SIDS) has decreased significantly in the United States since the 1992 recommendation that healthy term infants be placed on their backs or sides during sleep. However, little is known regarding the effect that this recommendation has had on the incidence and epidemiology of apparent life-threatening events (ALTEs) in this country. METHODS: To examine this, we completed a retrospective chart review study of all infants admitted to the Children's Hospital of Wisconsin with the diagnosis of an ALTE during two study periods before and after the back to sleep initiative: January 1, 1991 to December 31, 1992 and January 1, 1996 to December 31, 1997. RESULTS: There were 81 ALTEs in 1991-1992 vs. 102 in 1996-1997. Infants in both groups were similar with respect to gender, race, and age, with approximately 80% in each group < 4 months of age. ALTEs occurred equally throughout the year during both time periods. The majority of episodes occurred during sleep; 74% of the 1991-1992 cohort and 59% of the 1996-1997 infants did not have information in the medical record describing their position during the ALTE. Three infants (2 during 1991-1992) died during the hospitalization and were subsequently diagnosed with SIDS or probable SIDS.