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Objectives 3β-Hydroxysteroid dehydrogenase (3β-HSD) deficiency is a rare type of congenital adrenal hyperplasia caused by recessive loss-of-function mutations in HSD3B2 gene. Case presentation We report an 8.5-year-old, 46XY, Roma boy with advanced adrenarche signs born to consanguineous parents. He was born at term with ambiguous genitalia. At 15 days of age, he underwent replacement therapy with hydrocortisone and fludrocortisone due to a salt wasting (SW) crisis and adrenal insufficiency. At 3.5 years, he was admitted again with SW crisis attributed to the low – unadjusted to body surface area – hydrocortisone dose and presented with bilateral gynecomastia and adrenarche. At 8.5 years, his bone age was four years more advanced than his chronological age and he was prepubertal, with very high testosterone levels. Gas chromatography-mass spectrometry (GC-MS) urinary steroid metabolome analysis revealed the typical steroid metabolic fingerprint of 3β-HSD deficiency. Sequencing of the HSD3B2 gene identified in homozygosity the novel p.Lys36Ter nonsense mutation. Furthermore, this patient was found to be heterozygous for p.Val281Leu in the CYP21A2 gene. Both parents were identified as carriers of the p.Lys36Ter in HSD3B2. Conclusions A novel nonsense p.Lys36Ter mutation in HSD3B2 was identified in a male patient with hypospadias. 3β-HSD deficiency due to mutations in the HSD3B2 gene is extremely rare and the finding of a patient with this rare type of disorders of sex development (DSD) is one of the very few reported to date. The complexity of such diseases requires a multidisciplinary team approach regarding the diagnosis and follow-up.

As the COVID-19 pandemic is still evolving, guidelines on pulmonary function testing that may dynamically adapt to sudden epidemiologic changes are required. This paper presents the recommendations of the Hellenic Pediatric Respiratory Society (HPRS) on pulmonary function testing in children and adolescents during the COVID-19 era. Following an extensive review of the relevant literature, we recommend that pulmonary function tests should be carried out after careful evaluation of the epidemiologic load, structured clinical screening of all candidates, and application of special protective measures to minimize the risk of viral cross infection. These principles have been integrated into a dynamic action plan that may readily adapt to the phase of the pandemic.

Background: Correlated long-range fluctuations of lung function have been demonstrated in asthmatic adults. Objective: To determine the pattern of FEV1 fluctuation and its potential age dependence in healthy children and adolescents. Methods: The study of lung function variability in children and adolescents (NCT04163146) includes subjects aged 6-18 years who perform spirometry twice daily for 3 months (180 trials) using a portable device (Spirobank Smart). Here, we applied detrended fluctuation and sample entropy (SampEn) analysis to FEV1 data of healthy participants (no asthma, normal baseline spirometry). We evaluated the scaling exponent α (long-range correlations) and SampEn (regularity of data series) of consecutive FEV1 recordings in relation to age. Results: Our preliminary results (N=11; target >75) indicate the presence of correlated long-range (over weeks/months) fluctuations of FEV1. The scaling exponent α decreases with increasing age (r –0.738; P=0.0095) while SampEn increases (r 0.694; P=0.0178) (Figure). Conclusions: Healthy children and adolescents present correlated long-range fluctuations of FEV1, the pattern of which changes with age. Our findings suggest that developmental aspects may influence the complex temporal interaction between environmental stimuli and airway tone, hypothetically affecting the stability and adaptability of the respiratory system.

Background Variability analysis of peak expiratory flow (PEF) and forced expiratory volume at 1 second (FEV1) has been used in research to predict exacerbations in adults with asthma. However, there is a paucity of data regarding PEF and FEV1 variability in healthy children and adolescents and those with asthma. Objective The objective of this study is the assessment of PEF and FEV1 variability in (1) healthy children and adolescents, to define the normal daily fluctuation of PEF and FEV1 and the parameters that may influence it, and (2) children and adolescents with asthma, to explore the differences from healthy subjects and reveal any specific variability changes prior to exacerbation. Methods The study will include 100 healthy children and adolescents aged 6-18 years (assessment of normal PEF and FEV1 variability) and 100 children and adolescents of the same age with diagnosed asthma (assessment of PEF and FEV1 variability in subjects with asthma). PEF and FEV1 measurements will be performed using an ultraportable spirometer (Spirobank Smart; MIR Medical International Research) capable of smartphone connection. Measurements will be performed twice a day between 7 AM and 9 AM and between 7 PM and 9 PM and will be dispatched via email to a central database for a period of 3 months. PEF and FEV1 variability will be assessed by detrended fluctuation and sample entropy analysis, aiming to define the normal pattern (healthy controls) and to detect and quantify any deviations among individuals with asthma. The anticipated duration of the study is 24 months. Results The study is funded by the “C. Caratheodory” Programme of the University of Patras, Greece (PN 47014/24.9.2018). It was approved by the Ethics Committee (decision 218/19-03-2019) and the Scientific Board (decision 329/02-04-2019) of the University Hospital of Patras, Greece. Patient recruitment started in January 2020, and as of June 2020, 100 healthy children have been enrolled (74 of them have completed the measurements). The anticipated duration of the study is 24 months. The first part of the study (assessment of lung function variability in healthy children and adolescents) will be completed in August 2020, and the results will be available for publication by October 2020. Conclusions Healthy children and adolescents may present normal short- and long-term fluctuations in lung function; the pattern of this variability may be influenced by age, sex, and environmental conditions. Significant lung function variability may also be present in children and adolescents with asthma, but the patterns may differ from those observed in healthy children and adolescents. Such data would improve our understanding regarding the chronobiology of asthma and permit the development of integrated tools for assessing the level of control and risk of future exacerbations. Trial Registration ClinicalTrials.gov NCT04163146; https://clinicaltrials.gov/ct2/show/NCT04163146 International Registered Report Identifier (IRRID) DERR1-10.2196/20350