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We report 3 cystic fibrosis newborn screen-positive infants with the DeltaF508/R117H-7T genotype who had Pseudomonas aeruginosa detected in oropharyngeal cultures early in life and a fourth who had pulmonary symptoms and Gram-negative growth on multiple oropharyngeal cultures. All 4 patients were followed prospectively from the time of genetic diagnosis. As many regions implement newborn screening for cystic fibrosis, there is concern regarding which mutations should be included in genetic panels used to make the cystic fibrosis diagnosis. Some have recommended that mutations not specifically associated with classic cystic fibrosis be excluded. Our cases highlight the importance of considering keeping so-called mild mutations on cystic fibrosis newborn screening panels and the need to follow children with these mutations closely. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic accuracy of thermal imaging (TI) in the setting of focal consolidative pneumonia with chest X-ray (CXR) as the gold standard., Setting: A large, 973-bed teaching hospital in Boston, Massachusetts., Participants: 47 patients enrolled, 15 in a training set, 32 in a test set. Age range 10 months to 82 years (median=50 years)., Materials and Methods: Subjects received CXR with subsequent TI within 4 hours of each other. CXR and TI were assessed in blinded random order. Presence of focal opacity (pneumonia) on CXR, the outcome parameter, was recorded. For TI, presence of area(s) of increased heat (pneumonia) was recorded. Fisher's exact test was used to assess the significance of the correlations of positive findings in the same anatomical region., Results: With TI compared with the CXR (the outcome parameter), sensitivity was 80.0% (95% CIs 29.9% to 98.9%), specificity was 57.7% (95% CI 37.2% to 76.0%). Positive predictive value of TI was 26.7% (95% CI 8.9% to55.2%) and its negative predictive value was 93.8% (95% CI 67.7% to 99.7%)., Conclusions: This feasibility study confirms proof of concept that chest TI is consistent with CXR in suggesting similarly localised focal pneumonia with high sensitivity and negative predictive value. Further investigation of TI as a point-of-care imaging modality is warranted., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Cystic fibrosis was previously thought to be a disease of childhood. With a better understanding of this condition along with improvements in therapy, patients with cystic fibrosis are now living well into adulthood. The aim of this article is to familiarize the intensive care unit physician with cystic fibrosis care, to discuss complications associated with cystic fibrosis specifically related to the intensive care unit, and to detail the current recommendations for the clinical management of the patient with cystic fibrosis. With advancing disease, the most severely affected organs are the lungs. Obstruction, infection, and inflammation contribute to the decline of pulmonary function, ultimately leading to death. Some patients may be eligible for lung transplantation, but choosing wisely will affect posttransplant survival. Because other organs are affected by the genetic defect and associated treatments, serious complications related to the liver, pancreas, intestines, and kidneys must be considered by the intensivist faced with a patient with cystic fibrosis. As practitioners, the fact that not all patients will survive and help our patients and families gracefully through the end-of-life process should be accepted.

Objectives: Newborn screening for cystic fibrosis (CF) provides a model to investigate the implications of applying multiple-mutation DNA testing in screening for any disorder in a pediatric population-based setting, where detection of affected infants is desired and identification of unaffected carriers is not. Widely applied 2-tiered CF newborn screening strategies first test for elevated immunoreactive trypsinogen (IRT) with subsequent analysis for a single CFTR mutation (DeltaF508), systematically missing CF-affected infants with any of the >1000 less common or population-specific mutations. Comparison of CF newborn screening algorithms that incorporate single- and multiple-mutation testing may offer insights into strategies that maximize the public health value of screening for CF and other genetic disorders. The objective of this study was to evaluate technical feasibility and practical implications of 2-tiered CF newborn screening that uses testing for multiple mutations (multiple-CFTR-mutation testing)., Methods: We implemented statewide CF newborn screening using a 2-tiered algorithm: all specimens were assayed for IRT; those with elevated IRT then had multiple-CFTR-mutation testing. Infants who screened positive by detection of 1 or 2 mutations or extremely elevated IRT (>99.8%; failsafe protocol) were then referred for definitive diagnosis by sweat testing. We compared the number of sweat-test referrals using single- with multiple-CFTR-mutation testing. Initial physician assessments and diagnostic outcomes of these screened-positive infants and any affected infants missed by the screen were analyzed. We evaluated compliance with our screening and follow-up protocols. All Massachusetts delivery units, the Newborn Screening Program, pediatric health care providers who evaluate and refer screened-positive infants, and the 5 Massachusetts CF Centers and their affiliated genetic services participated. A 4-year cohort of 323 506 infants who were born in Massachusetts between February 1, 1999, and February 1, 2003, and screened for CF at approximately 2 days of age was studied., Results: A total of 110 of 112 CF-affected infants screened (negative predictive value: 99.99%) were detected with IRT/multiple-CFTR-mutation screening; 2 false-negative screens did not show elevated IRT. A total of 107 (97%) of the 110 had 1 or 2 mutations detected by the multiple- CFTR-mutation screen, and 3 had positive screens on the basis of the failsafe protocol. In contrast, had we used single-mutation testing, only 96 (87%) of the 110 would have had 1 or 2 mutations detectable by single-mutation screen, 8 would have had positive screens on the basis of the failsafe protocol, and an additional 6 infants would have had false-negative screens. Among 110 CF-affected screened-positive infants, a likely "genetic diagnosis" was made by the multiple-CFTR-mutation screen in 82 (75%) versus 55 (50%) with DeltaF508 alone. Increased sensitivity from multiple-CFTR-mutation testing yielded 274 (26%) more referrals for sweat testing and carrier identifications than testing with DeltaF508 alone., Conclusions: Use of multiple-CFTR-mutation testing improved sensitivity and postscreening prediction of CF at the cost of increased referrals and carrier identification.

Study Objective: To evaluate the practice of using nasopharyngoscopy without routine fiberoptic bronchoscopy for children presenting to a pediatric pulmonary practice with nonspecific noisy breathing., Design: Retrospective chart review. Records of patients who underwent nasopharyngoscopy between January 1, 1990, and December 31, 1999, were reviewed. Follow-up was obtained by office records and direct contact with the patient's family and/or primary care physician., Setting: Academic, tertiary care facility., Results: Eighty-one children who underwent upper airway endoscopy to evaluate noisy breathing consistent with extrathoracic lesions were identified. One child had two evaluations separated by years for differing complaints, making a total of 82 procedures. Stridor was the chief complaint in three fourths of the children. Half of the children with stridor were found to have laryngomalacia. Long-term follow-up was available for 75 of 81 children, with median follow-up of 6 years (range, 1 to 13 years). No medical problems related to missed airway lesions developed in any infants initially evaluated using nasopharyngoscopy., Conclusions: Nasopharyngoscopy without lower airway endoscopy can be used safely for the initial evaluation of noisy breathing in infants and children provided excellent follow-up is available.

Localized pneumothorax adjacent to a collapsed lobe has been reported in children with bronchial obstruction. We present our findings in seven children with a similar phenomenon occurring in association with diffuse obstructive airway disease. The children, aged from 3 weeks to 17 years, were admitted for diffuse obstructive airway disease and, subsequently, developed lobar collapse with adjacent localized pneumothorax. In five of the seven patients there was a paradoxical shift of the mediastinum toward the side of the pneumothorax. In six cases, the pneumothorax resolved spontaneously with lobar reexpansion. A conservative treatment approach to patients with this constellation of radiographic findings appears justified.

Five patients in a pediatric population were identified with idiopathic follicular bronchitis (IFB) by open lung biopsy and their case records were reviewed. All were tachypneic and had a chronic cough by 6 weeks of age. The physical examination was characterized by diffuse fine crackles in four patients and by coarse rhonchi in one. The chest radiographs in all demonstrated a diffuse interstitial pattern. None had a collagen vascular or an autoimmune disease demonstrable. Response to corticosteroid therapy was minimal. Associated or coincidental esophageal reflux was treated surgically in two. No viral or bacterial agents were isolated in the sputum or the biopsy specimens. Patients have been followed up for 2 to 15 years; the conditions of all patients improved at about 2 to 4 years of age. The older patients have residual mild obstructive lung disease. To our knowledge, this is the first reported series of IFB in the pediatric population.

Pulse oximetry provides a noninvasive, painless, accurate, and rapid method for measuring arterial oxygen saturation (SaO2). It has been shown to be valuable in anesthesia and critical care and recently has been used extensively in the outpatient setting. As is often the case with new technologies, little has been published on the basic issues of reliability, reproducibility, and effect on patient care. This prospective clinical study evaluated the basic principles of pulse oximetry in the pediatric emergency department setting and tested the hypotheses that pulse oximetry SaO2 measurements are reliable and provide valuable information, in addition to clinical and laboratory data which affect patient assessment and management. One hundred twenty patients were enrolled in phase 1 and 437 in phase 2 of the study. Pulse oximetry readings were reproducible with an intraclass correlation of 0.87. SaO2 measurements changed the assessed degree of illness in 188 (53%) patients; 47 (13%) were felt to be more ill and 130 (37%) to be less ill than at initial assessment. Sixty-nine (17%) patients were identified in whom SaO2 readings changed management plans; 27 (8%) were managed more aggressively (intubation, surgery, or admission), while 40 (11%) were managed less aggressively (discharged). In three cases, pulse oximetry was instrumental in the diagnosis of a serious illness. The results from this study indicate that pulse oximetry SaO2 readings are stable and reproducible and provide information which impacts significantly on patient assessment and management.

To characterize the outcome of lobectomy in infancy and the low expiratory flows which persist after lobectomy for congenital lobar emphysema, 15 subjects with this history were studied at age 8-30 yr. Total lung capacity was normal in all, but higher values (P < 0.05) were observed in nine subjects with upper lobectomy than in five subjects with right middle lobectomy. Ratio of residual volume to total lung capacity was correlated (P < 0.05) with the amount of lung missing as estimated from normal relative weights of the respective lobes. Xe(133) radiospirometry in eight subjects showed that the operated and unoperated sides had nearly equal volumes at total lung capacity, but that the operated side was larger than the unoperated side at residual volume. Perfusion was equally distributed between the two sides. Similar findings were detected radiographically in four other subjects. Forced expiratory volume in 1 s and maximal midexpiratory flow rate averaged 72 and 45% of predicted, respectively. Low values of specific airway conductance and normal density dependence of maximal flows in 12 subjects suggested that obstruction was not limited to peripheral airways. Pathologic observations at the time of surgery and morphometry of the resected lobes were not correlated with any test of pulmonary function. These data show that lung volume can be completely recovered after lobectomy for congenital lobar emphysema in infancy. The volume increase occurs on the operated side, and probably represents tissue growth rather than simple distension. The response to resection is influenced by the particular lobe resected and may be associated with decreased lung recoil near residual volume. Low expiratory flows in these subjects could be explained by several mechanisms, among which a disproportion between airway and parenchymal growth in infancy (dysanaptic growth) is most compatible with our data.

To determine the effects of the pulmonary hypoplasia present at birth in infants with congenital diaphragmatic hernia upon subsequent development of the lung, 19 patients who had undergone surgical repair before the age of one year were studied at ages 6 to 18 years. Total lung capacity and vital capacity averaged 99% of predicted value. Diffusing capacity for carbon monoxide was normal. Forced expiratory volume in one second averaged 89% of predicted value and 80% of vital capacity. Total respiratory system conductance and maximum expiratory flow volume curves obtained during air and helium-oxygen breathing were normal. Xenon 133 radiospirometry performed in nine patients revealed equal distribution of lung volumes on the two sides. Ventilation to the hernia side was reduced in only two patients. Blood flow to the hernia side was reduced in all nine patients. Chest radiographs supported the physiologic observations. These findings are consistent with the persistence of a reduction in the number of branches or generations of pulmonary arteries and bronchi on the side of the hernia. Since a substantial part of the vascular resistance resides in peripheral vessels, this developmental abnormality influences the distribution of pulmonary blood flow, although it has little effect on tests reflecting airway resistance or the distribution of ventilation.

A boy with glutaric acidemia had psychomotor retardation first noted at age 6 months, recurrent metabolic acidosis, and a progressive quadriparesis with choreoathetosis. He died at age 3 1/2 years. Cultured skin fibroblasts lacked glutaryl-CoA dehydrogenase activity. There was a biochemical, but not a clinical, response to dietary restriction of lysine and tryptophan. The caudate and putamen of the brain showed severe loss of nerve cells and fibers with proliferation of astrocytes, as well as markedly reduced gamma-aminobutyric acid and glutamate decarboxylase activity.