Respiratory distress in a 2-month-old infant: Is the primary cause cardiac, pulmonary or both?

A 2-month-old female with worsening cough, respiratory distress and an abnormal chest X-ray was referred to our institution for further evaluation of suspected scimitar syndrome. She was found to have normal pulmonary venous drainage with a large patent ductus arteriosus and severe pulmonary arterial hypertension. Chest CT was suggestive of interstitial lung disease. Wedge lung biopsy revealed alveolar simplification and patchy pulmonary interstitial glycogenosis. A definitive diagnosis of Filamin A deficiency was made with genetic studies. The patient is currently showing clinical improvement on systemic glucocorticoid therapy.

Pulmonary Mycobacterium Avium-Intracellulare Complex Infection in an Infant: A Silent and Coincidental Finding.

An 11-month-old healthy infant girl was noted to have left lower lobe (LLL) opacities on chest X-ray (CXR) after developing desaturations during an elective cochlear implant surgery. Repeat CXR 10 days later revealed hyperexpansion of the left lung and persistent LLL opacity. Chest computerized tomography revealed enlarged mediastinal lymph nodes, left mainstem bronchial obstruction, and nodular opacities. Bronchoscopic biopsy of the endobronchial tissue revealed multiple necrotizing granulomas and grew Mycobacterium avium-intracellulare, Streptococcus viridans, and Actinomyces odontolyticus. This case illustrates the potential for significant mediastinal lymphadenopathy, and endobronchial and parenchymal lesions caused by nontuberculous mycobacteria, which can present insidiously and without respiratory symptoms in otherwise healthy infants, despite advanced pulmonary disease.

Bilateral diaphragmatic paresis following pediatric liver transplantation.

BACKGROUND: Although diaphragm paresis or paralysis is fairly common following cardiac procedures; it is a less common complication following liver transplantation. Unilateral diaphragm paresis, usually right sided, has been described following liver transplantation in adults and has been rarely described in children. PURPOSE: Diaphragmatic injury following LT is often unrecognized and is typically unilateral, involving the right hemidiaphragm. Bilateral diaphragm dysfunction following liver transplantation in children is a rare complication. METHODS: This is a case report of bilateral diaphragm paresis in a young child following a repeat liver transplantation. CONCLUSION: Bilateral diaphragm paresis following liver transplantation in children is rare and spontaneous resolution is possible. A conservative approach with noninvasive ventilation as a first line treatment to allow the diaphragm to regain function should be considered.

Emergency department use among children with tracheostomies: Avoidable visits.

PURPOSE: To characterize high emergency department (ED) use by children with tracheostomies and complex chronic conditions, to distinguish avoidable from unavoidable ED visits, and to describe the financial impact of avoidable visits. METHODS: Children with tracheostomies in a pediatric tertiary care center with the highest ED utilization were identified via analysis of administrative data. Six experts in interdisciplinary dyads reviewed the records from all ED visits for these children, and distinguished avoidable from unavoidable visits. Hospital cost data for avoidable visits is described. RESULTS: Among 75 children with tracheostomies and complex chronic conditions, 23 (31%) were high ED utilizers. These 23 children accounted for 74% of all ED discharges the total group of 75 children from 2008 to 2011. Four of these 23 children with high utilization were excluded, leaving 19 subjects for review. These 19 children had 312 ED visits, of which 103 (33%) were deemed avoidable. Leading reasons for avoidable visits were uncomplicated upper respiratory infections, gastrointestinal infections, and enteral feeding system problems. Avoidable visits cost the hospital {$}67,940. CONCLUSIONS: One-third of ED visits by children with tracheostomies and complex chronic conditions may be avoidable. Increased ambulatory access to interdisciplinary teams of providers familiar with these children's unique needs might reduce avoidable ED visits and improve health outcomes. Further studies on how this model of ambulatory care might affect ED utilization and total healthcare costs are needed.

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.

Noisy breathing and hemidiaphragm paralysis progressing to respiratory failure in an infant.

Spinal muscular atrophy with respiratory distress (SMARD1) is a rare autosomal recessive disease that is caused by mutations in the gene encoding for immunoglobulin µ-binding protein 2. Unlike the relatively more common spinal muscular atrophy, patients with SMARD1 have respiratory distress prior to manifestation of distal muscle weakness making the diagnosis a challenge. Because respiratory distress is a hallmark feature of this disease, pediatric pulmonologists should recognize its features, and consider it as a diagnostic entity.

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.

The FEF25-75 and its decline as a predictor of methacholine responsiveness in children.

BACKGROUND: Methacholine challenge (MCC) is an important diagnostic tool for asthma, especially in patients in whom routine pulmonary function testing (PFT) is normal or equivocal. The basis for a positive test per American Thoracic Society (ATS) guidelines is a methacholine concentration < or = 16 mg/mL that causes a 20% decrease in forced expiratory volume in 1 second (FEV(1)) (termed the PC20 for FEV(1)). There is little information in the medical literature that utilizes other flow rates during MCC, including small airway function parameters such as the forced expiratory flow rate 25-75% (FEF(25-75)). We question whether the FEF(25-75) may be a useful parameter to monitor during MCC and whether it may be predictive of a positive MCC. HYPOTHESIS: The baseline FEF(25-75) and its decline during a MCC are useful in the interpretation of a MCC. METHODS: We retrospectively analyzed all MCC performed at this institution between December 1998 and December 2006. Parameters reviewed included age, gender, race, weight, height, baseline PFT data including FVC, FEV(1), FEF(25-75), and forced expiratory time, methacholine PC20 for FEV(1), the relative changes from baseline for FEV(1) and FEF(25-75) during the MCC, and clinical symptoms during the MCC. RESULTS: A total of 532 MCC were completed during the 8-year study period in children 4 to 18 years of age. A total of 203 MCC (38%) were positive (defined by a PC20 < or = 16 mg/mL) and 329 studies were negative (62%). The baseline % predicted FEF(25-75) in positive MCC was 82.4 +/- 21.9 vs. 98.7 +/- 21.3 in the negative studies (p < 0.001). The FEF(25-75)/FVC ratio in positive MCC was 0.82 +/- 0.21 vs. 0.97 +/- 0.23 in negative studies (p < 0.001). In the positive MCC, the decrease in FEF(25-75) was much faster and of much greater degree than in the negative challenges. When a significant reduction in FEF(25-75) was defined as greater than 10% by the second concentration of methacholine (0.25 mg/mL), the sensitivity for a positive MCC was 63%, the specificity was 71%, the positive predictive value was 57%, and the negative predictive value was 76%. A comparison of the baseline FEF(25-75) to the PC20 for the positive MCCs revealed no statistical significance. CONCLUSIONS: The FEF(25-75) and its decline during a MCC appear to be useful information and potentially predictive of a positive MCC. We suggest that the forced expiratory flow rate 25-75% (FEF(25-75)) be considered as an adjunct to the FEV(1) to define a positive study.

Clarification of laboratory and clinical variables that influence cystic fibrosis newborn screening with initial analysis of immunoreactive trypsinogen.

OBJECTIVES: To ensure that each newborn receives an equitable test of the highest possible sensitivity, we recognized the necessity to reassess immunoreactive trypsinogen and DNA issues in cystic fibrosis newborn screening algorithms. Our objectives included clarification of various factors that influence immunoreactive trypsinogen concentrations and resolution of long-standing questions about variations in immunoreactive trypsinogen levels among newborns. METHODS: Immunoreactive trypsinogen data on 660443 newborns who were born between July 1, 1994, and June 30, 2004, were abstracted from the Wisconsin State Laboratory of Hygiene databases and deidentified for analysis. Using a compiled data set, we analyzed various demographic characteristics to determine their role, if any, in immunoreactive trypsinogen variation. Specifically, season of birth, reagent lot, and birth weight were examined. Sensitivities of the most common cystic fibrosis newborn screening protocols, namely immunoreactive trypsinogen/immunoreactive trypsinogen and immunoreactive trypsinogen/DNA, were also investigated. RESULTS: Mean and 95th percentile immunoreactive trypsinogen levels were shown to vary by both season and reagent lot number and affect sensitivity of the assay. Low birth weight infants had significantly higher immunoreactive trypsinogen values than normal birth weight infants. Sensitivities were also found to vary on the basis of the algorithm used, with the highest sensitivity of 96.2% calculated for an immunoreactive trypsinogen/DNA protocol with 23 cystic fibrosis transmembrane conductance regulator mutation analyses compared with 80.2% with the immunoreactive trypsinogen/immunoreactive trypsinogen method used in 9 states. CONCLUSIONS: Floating, rather than fixed, cutoff values for the initial immunoreactive trypsinogen portion of any cystic fibrosis newborn screening protocol are generally necessary on the basis of the seasonal and reagent lot variations observed. Because of its lower sensitivity, immunoreactive trypsinogen/immunoreactive trypsinogen does not optimize detection of patients with cystic fibrosis.

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.

Asthma and insulin resistance in morbidly obese children and adolescents.

BACKGROUND: Obesity is well recognized as a state of increased insulin resistance and has been implicated as a significant risk factor for both asthma prevalence and asthma severity in children and adolescents. However, little is known about the specific factors that relate asthma and obesity. Recently, the pro-inflammatory state in obesity and its association with insulin resistance have been recognized. We hypothesize that the effect of morbid obesity on asthma is related to insulin resistance. METHODS: The patient cohort in the obesity management program at the Children's Hospital of Wisconsin was retrospectively reviewed. Variables were collected from the program data base and chart review was done for missing variables. Patients were considered to have asthma if the evaluating physician confirmed the diagnosis through history and/or the patient had been on inhaled corticosteroids. Insulin resistance (IR) was calculated using a homeostasis model assessment (HOMA). Multivariate logistic regression was performed to identify variables that were significantly related to the odds of having asthma. RESULTS: Of the 415 patients included in the study, 146 (35%) were asthmatic and 269 (65%) were non-asthmatic. The asthma (AG) and non-asthma (NAG) groups were similar with respect to mean age (11.3 vs. 11.5 years), gender (45% vs. 43% males), mean body mass index (BMI) (36.4 vs. 34.9), and exposure to smoking (43% vs. 42%). Fhx of asthma was significantly higher in AG (71%) compared to NAG (40%). IR level+/-SD was 8.5+/-9.7 in AG compared to 5.3+/-6.7 in NAG (p<0.0001). Multivariate regression analysis found the following variables to be associated with having asthma: younger age (p<0.05), smoking exposure (p<0.05), positive Fhx of asthma (p<0.0001, odds ratio of 3.1), and IR (p<0.0001, odds ratio of 4.1). CONCLUSION: Morbidly obese asthma patients have a higher degree of insulin resistance compared to morbidly obese non-asthma patients. We speculate that the pro-inflammatory state of insulin resistance may contribute to the pathogenesis of asthma in obese patients. Future prospective studies should address insulin resistance as a possible risk factor for asthma in obese children and adolescents.

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.

Newborn screening for cystic fibrosis: parents' preferences regarding counseling at the time of infants' sweat test.

Newborn screening (NBS) protocols for cystic fibrosis (CF) are the first regional population-based programs to incorporate DNA analysis into their procedures. Research about these programs can inform policy and practice regarding how best to counsel families with abnormal NBS results. The grounded theory method guided interviews with 33 families whose infants had abnormal CF NBS results. A dimensional analysis of these interviews provided a theoretical framework describing parents' preferences regarding counseling during their infant's sweat test appointment. This framework describes the contexts and characteristics of the two main dimensions of parents' preferences: factual information and emotional support. Factual information included learning about the probability of a CF diagnosis, CF disease facts, sweat test procedure, and CF genetics. Social support consisted of offering parents a choice about the timing and amount of CF information, showing empathy for their distress, instilling hope, personalizing counseling, and providing hospitality. This framework also explains the consequences of counseling that matched versus mismatched parental preferences in these domains. Counseling that matched parents preferences reduced parents' distress while mismatched counseling tended to increase parents' worry about their infant.

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.