Identifying biomarkers in pediatric rare lung disease: Child grows up

Children’s interstitial and diffuse lung disease (chILD) has been recognized as distinct from adult interstitial lung diseases for nearly 2 decades after the first descriptions of disorders of surfactant metabolism and neuroendocrine cell hyperplasia of infancy (NEHI) (1, 2). In that interval, advances in clinical phenotyping, histopathology, genetic testing, and imaging have improved diagnostic capabilities and led to the discovery of novel chILD disorders (3). However, although blood or airway-derived biomarkers can be informative in adult ILD (4, 5), similar biomarkers do not exist in chILD, and lung biopsy is often still required to make a definitive diagnosis. In recognition of these limitations, a recent National Heart, Lung, and Blood Institute workshop to advance chILD identified a “lack of validated biomarkers or outcome measures suitable for use in infants and young children” as a key gap (6). In this issue of the Journal, Deterding and colleagues (pp.1496–1504) help to address this gap through the use of aptamer-based proteomics to identify proteins and related pathways in BAL fluid that distinguish two of the most common chILD disorders (NEHI and disorders of surfactant metabolism) from each other and from control individuals without chILD (7). Although this was a single-center study on a relatively small population, these findings represent a significant step forward in the study of these rare lung diseases

Cytoplasmic “ciliary inclusions” in isolation are not sufficient for the diagnosis of primary ciliary dyskinesia

Background: The diagnosis of primary ciliary dyskinesia (PCD) is difficult and requires a combination of clinical features, nasal nitric oxide testing, cilia ultrastructural analysis by electron microscopy (EM), and genetics. A recently described cytoplasmic ultrastructural change termed “ciliary inclusions” was reported to be diagnostic of PCD; however, no supporting evidence of PCD was provided. In this study, we sought to confirm, or refute, the diagnosis of PCD in subjects with “ciliary inclusions” on EM. Methods: Six subjects from five families with previous lab reports of “ciliary inclusions” on EMs of ciliated cells were identified and evaluated at a Genetic Disorders of Mucociliary Clearance Consortium site. We performed a detailed clinical history, nasal nitric oxide measurement, genetic testing including whole-exome sequencing (WES), and when possible, repeat ciliary EM study. Results: Only one of six subjects had multiple and persistent clinical features congruent with PCD. No subject had situs inversus. Only one of six subjects had a very low nasal nitric oxide level. No “ciliary inclusions” were found in three subjects who had a repeat ciliary EM, and ciliary axonemal ultrastructures were normal. Genetic testing, including WES, was negative for PCD-causing genes, and for pathogenic variants in gene pathways that might cause “ciliary inclusions,” such as ciliary biogenesis. Conclusion: “Ciliary Inclusions”, in isolation, are not sufficient to diagnosis PCD. If seen, additional studies should be done to pursue an accurate diagnosis

Optical properties of MgH2 measured in situ in a novel gas cell for ellipsometry/spectrophotometry

The dielectric properties of alpha-MgH2 are investigated in the photon energy range between 1 and 6.5 eV. For this purpose, a novel sample configuration and experimental setup are developed that allow both optical transmission and ellipsometric measurements of a transparent thin film in equilibrium with hydrogen. We show that alpha-MgH2 is a transparent, colour neutral insulator with a band gap of 5.6 +/- 0.1 eV. It has an intrinsic transparency of about 80% over the whole visible spectrum. The dielectric function found in this work confirms very recent band structure calculations using the GW approximation by Alford and Chou [J.A. Alford and M.Y. Chou (unpublished)]. As Pd is used as a cap layer we report also the optical properties of PdHx thin films.Comment: REVTeX4, 15 pages, 12 figures, 5 table