Pediatric Year in Review

PEDIATRIC YEAR IN REVIEW 12 in adolescence versus childhood, though 45% report missing school for respiratory illness in the past year, and the median of 32 lifetime episodes LRTI treatment remains quite elevated. Overall, the incidence of bronchiectasis is decreasing in AN children, from 18 cases per 1000 births in the 1980’s to 6.7 cases per 1000 births in the 2000’s. Comments 1. While the severity and frequency of lower respiratory tract exacer- bations improve during a “honeymoon period” in AN adolescents with CSLD and bronchiectasis, significant disease burdens persist at baseline with abnormal lung function, abnormal physical exam findings, and school absenteeism for respiratory reasons. 2. Despite this persistence of lung disease in AN adolescents with CSLD and bronchiectasis, the number of prescribed antibiotic courses remains low, possibly reflecting the difficulties in regular medical follow up for this fragile and maturing population. 3. Despite a honeymoon period in adolescent CSLD and bronchi- ectasis, regular clinical follow up is essential to monitor for lower respiratory disease progression, which may have profound long- term effects if ignored. 4. Access to medical care, vaccines, and clean drinking water seem to have improved the bronchiectasis incidence in AN children of the Yukon Kuskokwim Delta region. DIAGNOSIS OF PRIMARY CILIARY DYSKINESIA Shapiro AJ, Davis SD, Polineni D, Manion M, Rosenfeld M, Dell SD, Chilvers MA, Ferkol TW, Zariwala MA, Sagel SD, Josephson M, Morgan L, Yilmaz O, Olivier KN, Milla C, Pittman JE, Daniels MLA, Jones MH, Janahi IA, Ware SM, Daniel SJ, Cooper ML, Nogee LM, Anton B, Eastvold T, Ehrne L, Guadagno E, Knowles MR, Leigh MW, Lavergne V. Diagnosis of Primary Ciliary Dyskinesia. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med . 2018 Jun 15;197(12):e24-e39. doi: 10.1164/rccm.201805-0819ST. Summary Primary Ciliary Dyskinesia (PCD) is difficult to diagnose as no single test detects all forms of this disease, and certain diagnostic tests (ciliary transmission electron microscopy (TEM) and high speed videomicroscopy (HSVM)) require expertise to correctly perform and interpret test results. Four PICO questions on nasal nitric oxide (nNO), extended panel genetic testing of >12 PCD genes, HSVM, and ciliary beat frequency (CBF) are researched, and diagnostic accuracy for each test is compared against a reference standard of classic TEM ultrastructural defect and/or 2 genetic mutations in a known PCD gene. In order to maximize diagnostic accuracy, only patients with appropriate PCD clinical phenotypes (often including year-round wet cough since infancy, year-round nasal congestion since infancy, neonatal respiratory distress, or an organ laterality defect) are included. In patients with strong PCD phenotypes, both nasal nitric oxide measurement and extended genetic panel testing of >12 PCD genes are the most standardized, feasible, and accurate PCD diagnostic tests that are currently available (nNO testing sensitivity 96%, specificity 96%; extended panel genetic testing sensitivity 80%, specificity 99.5%). HSVM testing is not recommended as sample preparation procedures and interpretation of test results are non-standardized and too subjective to provide reliable diagnostic accuracy at present. CBF analysis should also be avoided due to poor diagnostic accuracy compared against the reference standard. Comments 1. The North American PCD clinical diagnostic tests of choice are now nNO measurement and extended genetic panel testing, while ciliary motility assessments should remain in research settings until standardized methodology and interpretation techniques are available across clinical centers. 2. Nasal nitric oxide testing has limitations, as it can be artificially decreased by other issues (like acute viral respiratory infection or cystic fibrosis), and repeat nNO values on separate occasions, with cystic fibrosis ruled out, are required to make a PCD diagno- sis. 3. Nasal nitric oxide values can rarely be normal with certain PCD genotypes, so negative nNO results do not “rule out” PCD in cases where the PCD phenotype is very strong. 4. Widespread use of nNO testing in populations without strong PCD phenotypes will result in much worse diagnostic accuracy than reported here. 5. As more genes causing PCD are discovered, the diagnostic accuracies of all other tests will likely worsen as genetic testing accuracy improves. CILIARY MOTILITY ANALYSIS IN PCD Rubbo B, Shoemark A, Jackson CL, Hirst RA, Thompson J, Hayes J, Frost E, Copeland F, Hogg C, O’Callaghan C, Reading I, Lucas JS. Accuracy of high-speed video analysis to diagnose primary ciliary dyskinesia. Chest. 2019 Feb 28. pii: S0012-3692(19)30205-3. doi: 10.1016/j. chest.2019.01.036. [Epub ahead of print] Summary High-speed videomicroscopy analysis (HSVM) of ciliary motility is recommended for PCD diagnosis in European Respiratory Society (ERS) guidelines. However, this technique requires ultra-specialized testing methods at UPDATE ON PCD AND NON-CF BRONCHIECTASIS