Novel Indices to Improve the Diagnostic Ability of Nocturnal Oximetry in Children with OSAS.

Nocturnal pulse oximetry (NOx) is an alternative diagnostic test for obstructive sleep apnea syndrome (OSAS) in childhood yet with variable diagnostic performance. Our aim was to apply advanced signal analysis to develop novel and more accurate NOx indices. We studied 45 children aged 3-10 years who underwent adenotonsillectomy for adenotonsillar hypertrophy and OSAS symptoms. Participants performed NOx before and three months after surgery, and the changes in McGill oximetry score (MOS), oxygen desaturation ≥3% index (ODI3), and the novel parameters-cumulative saturation area (CSA) and oxygen saturation sample entropy (SSE)-were assessed. There was a significant improvement (p < 0.001) in all NOx indices. When pre- and post-adenotonsillectomy NOx recordings were compared, the MOS had an area under the curve (AUC) of 0.811 with 63.2% sensitivity and 100% specificity at a cutoff >1. The AUC of ODI3 was 0.994, with 97.8% sensitivity and 91.1% specificity at a cutoff of >3.6 events per hour. The CSA and SSE had an AUC of 1.00, with 100% sensitivity and specificity at a cutoff of >293 and >0.99, respectively. We conclude that the herein-introduced indices-CSA and SSE-hold promise in improving the diagnostic ability of NOx in children suspected of OSAS.

Novel volumetric capnography indices measure ventilation inhomogeneity in cystic fibrosis.

Background: Volumetric capnography (VCap) is a simpler alternative to multiple-breath washout (MBW) to detect ventilation inhomogeneity in patients with cystic fibrosis (CF). However, its diagnostic performance is influenced by breathing dynamics. We introduce two novel VCap indices, the capnographic inhomogeneity indices (CIIs), that may overcome this limitation and explore their diagnostic characteristics in a cohort of CF patients. Methods: We analysed 320 N2-MBW trials from 50 CF patients and 65 controls (age 4-18 years) and calculated classical VCap indices, such as slope III (SIII) and the capnographic index (KPIv). We introduced novel CIIs based on a theoretical lung model and assessed their diagnostic performance compared to classical VCap indices and the lung clearance index (LCI). Results: Both CIIs were significantly higher in CF patients compared with controls (mean±sd CII1 5.9±1.4% versus 5.1±1.0%, p=0.002; CII2 7.7±1.8% versus 6.8±1.4%, p=0.002) and presented strong correlation with LCI (CII1 r2=0.47 and CII2 r2=0.44 in CF patients). Classical VCap indices showed inferior discriminative ability (SIII 2.3±1.0%/L versus 1.9±0.7%/L, p=0.013; KPIv 3.9±1.3% versus 3.5±1.2%, p=0.071), while the correlation with LCI was weak (SIII r2=0.03; KPIv r2=0.08 in CF patients). CIIs showed lower intra-subject inter-trial variability, calculated as coefficient of variation for three and relative difference for two trials, than classical VCap indices, but higher than LCI (CII1 11.1±8.2% and CII2 11.0±8.0% versus SIII 16.3±13.5%; KPIv 15.9±12.8%; LCI 5.9%±4.2%). Conclusion: CIIs detect ventilation inhomogeneity better than classical VCap indices and correlate well with LCI. However, further studies on their diagnostic performance and clinical utility are required.

Lung Function Variability in Children and Adolescents With and Without Asthma (LUV Study): Protocol for a Prospective, Nonrandomized, Clinical Trial.

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.

Breath-to-breath variability of exhaled CO2 as a marker of lung dysmaturity in infancy.

The concept of diffusional screening implies that breath-to-breath variations in CO2 clearance, when related to the variability of breathing, may contain information on the quality and utilization of the available alveolar surface. We explored the validity of the above hypothesis in a cohort of young infants of comparable postmenstrual age but born at different stages of lung maturity, namely, in term-born infants ( n = 128), preterm-born infants without chronic lung disease of infancy (CLDI; n = 53), and preterm infants with moderate/severe CLDI ( n = 87). Exhaled CO2 volume (VE,CO2) and concentration (FE,CO2) were determined by volumetric capnography, whereas their variance was assessed by linear and nonlinear variability metrics. The relationship between relative breath-to-breath change of VE,CO2 (ΔVE,CO2) and the corresponding change of tidal volume (ΔVT) was also analyzed. Nonlinear FE,CO2 variability was lower in CLDI compared with term and non-CLDI preterm group ( P < 0.001 for both comparisons). In CLDI infants, most of the VE,CO2 variability was attributed to the variability of VT ( r2 = 0.749), whereas in term and healthy preterm infants this relationship was weaker ( r2 = 0.507 and 0.630, respectively). The ΔVE,CO2 - ΔVT slope was less steep in the CLDI group (1.06 ± 0.07) compared with non-CLDI preterm (1.16 ± 0.07; P < 0.001) and term infants (1.20 ± 0.10; P < 0.001), suggesting that the more dysmature the infant lung, the less efficiently it eliminates CO2 under tidal breathing conditions. We conclude that the temporal variation of CO2 clearance may be related to the degree of lung dysmaturity in early infancy. NEW & NOTEWORTHY Young infants exhibit appreciable breath-to-breath CO2 variability that can be quantified by nonlinear variability metrics and may reflect the degree of lung dysmaturity. In infants with moderate/severe chronic lung disease of infancy (CLDI), the variability of the exhaled CO2 is mainly driven by the variability of breathing, whereas in term-born and healthy preterm infants this relationship is less strong. The slope of the relative CO2-to-volume change is less steep in CLDI infants, suggesting that dysmature lungs are less efficient in eliminating CO2 under tidal breathing conditions.