Claire Shackleton

Respiratory impedance and bronchodilator responsiveness in healthy children aged 2-13 years

The forced oscillation technique (FOT) can be used in children as young as 2 years of age and in those unable to perform routine spirometry. There is limited information on changes in FOT outcomes in healthy children beyond the preschool years and the level of bronchodilator responsiveness (BDR) in healthy children. We aimed to create reference ranges for respiratory impedance outcomes collated from multiple centers. Outcomes included respiratory system resistance (Rrs) and reactance (Xrs), resonant frequency (Fres), frequency dependence of Rrs (Fdep), and the area under the reactance curve (AX). We also aimed to define the physiological effects of bronchodilators in a large population of healthy children using the FOT.

Tidal changes in respiratory resistance are sensitive indicators of airway obstruction in children

Rationale Individual assessment of airway obstruction in preschool-age children requires sensitive and specific lung function methods with low demand of cooperation. Although the forced oscillation technique (FOT) is feasible in young children, conventional measurements of respiratory impedance (Zrs) have limited diagnostic power in individuals. Objective To find descriptors of within-breath Zrs that are sensitive indicators of airway obstruction during tidal breathing in children. Methods Zrs was measured with (i) a standard multifrequency FOT (4–26 Hz) to assess the mean values of resistance and reactance for whole breaths and (ii) a 10 Hz signal to track the within-breath changes. Various Zrs measures obtained in healthy children (n=75) and those with acute wheeze (n=31) were investigated with receiver operator characteristic (ROC) analysis. The cut-off values obtained for airway obstruction were then tested in children with recurrent wheeze (n=20) before and after administration of salbutamol. Results The largest area under the ROC curve (0.95) was observed for the tidal changes of resistance between the zero-flow values (ΔR). The ΔR cut-off value of 1.42 hPa s/L detected airway obstruction with sensitivity of 92% and specificity of 89% in children with acute wheeze and distinguished children with recurrent wheeze (16/20 above the cut-off value) from healthy children (22/23 below the cut-off value). Furthermore, ΔR significantly decreased after salbutamol in wheezy children but remained unchanged in healthy children. Conclusions New lung function measure ΔR is able to detect airway obstruction with high sensitivity and specificity and is suitable for use in lung function testing in young children.

Rangos de referencia en niños preescolares mexicanos con el empleo de la técnica de oscilación forzada

INTRODUCTION Recently, multi-ethnic reference ranges for spirometry have been created for use worldwide. In comparison, forced oscillation technique (FOT) reference values are limited to specific equipment and study populations, with current FOT reference ranges created in a Caucasian population. We aimed to develop FOT reference ranges for preschool-aged Mexican children and to compare these with current FOT reference ranges. PATIENTS AND METHODS Respiratory resistance (Rrs) and reactance (Xrs) was measured in healthy Mexican children three to five years of age using commercial FOT equipment. The relationship between height and Rrs and Xrs was determined using regression analyses, taking into account age, weight, sex, and exposure to tobacco smoke. Reference equations were calculated for the Mexican children and Z-scores determined for Rrs and Xrs at 6 and 8Hz. A paired t-test assessed the difference in Z-scores between the Australian reference values and those created for the Mexican cohort. RESULTS FOT was successfully measured in 584 children. Height was a significant predictor of Rrs and Xrs at 6 and 8Hz (P<.05). Z-scores calculated using the Australian reference equations overestimated lung function in Mexican children for both Rrs and Xrs at 6 and 8Hz (P<.001). CONCLUSION The development of FOT reference ranges specific to Mexican preschool-aged children will allow for the correct interpretation of FOT measurements. This study also showed that current FOT reference ranges overestimate lung function in Mexican children. Highlighting, the importance of using ethnic appropriate reference ranges for interpreting lung function.

Feasibility of parental collected nasal swabs for virus detection in young children with cystic fibrosis

Abstract Background The detrimental role of viruses has been well described in CF, although the pattern of virus infections has not been investigated in a longitudinal study. The primary aim was to determine the feasibility of fortnightly parent collected swabs in young children with CF. Methods Children under three years with CF were recruited. Nasal swabs were collected by parents every fortnight and during periods of symptoms over 12months. Nasal swabs were posted and virus detected using real-time PCR. Results Only 27% of the patients completed the study to 10months, although 98% of the swabs returned were adequate for analysis. Mould was observed growing on 23% of the returned swabs. There was no evidence to demonstrate relationships with symptoms and viruses, prolonged symptoms, prolonged shedding or patterns of virus infections. Conclusions This study highlights the need to further investigate the role of viruses in children with CF using a robust method of frequent collection in children for a longitudinal study, with appropriate storage and shipping techniques to avoid mould growth or other potential contaminants.

Forced oscillation technique in spinal muscular atrophy

BACKGROUND Spinal muscular atrophy (SMA) causes respiratory compromise that is difficult to assess in young children. The forced oscillation technique (FOT) is commercially available for children as young as 2 years of age and is nonvolitional. The aim of this study was to assess the usefulness of FOT in young children with SMA. METHODS Children with SMA aged < 10 years were recruited. FOT was performed every 3 months for 12 months (five visits). Spirometry and assisted and unassisted peak cough flow (PCF) were performed where possible. Polysomnography was performed on children with type 2 SMA. Clinical information included SMA type, chest infections, Cobb angle, medications, and mobility. Regression analysis assessed relationships between FOT and FVC, PCF, and apnea/hypopnea index (AHI). Analysis of variance sought relationships to clinical characteristics. RESULTS Twelve children (seven male) were recruited; mean age was 6.26 (± 2.59) years. Respiratory reactance at 8 Hz (Xrs8) (mean z score, +1.41; SD, 1.90; P < .03) and respiratory resistance at 8 Hz (Rrs8) (mean z score, +0.66; SD, 1.34; P = .12) were abnormal. Four children performed spirometry. Linear relationships to Xrs8 exist: FVC (R2, 0.54), unassisted PCF (R2, 0.33), assisted PCF (R2, 0.43), and AHI (R2, 0.32). Over 12 months, Xrs8z score worsened (rate of change of +1.08, P < .001) and Rrs8z score worsened (rate of change +0.51, P < .001). No relationship (P > .05) was found between clinical characteristics and FOT values. CONCLUSIONS FOT is feasible in young children with SMA, with abnormal values of reactance and resistance on grouped data, worsening over 12 months. Xrs8 is related to respiratory tests used to monitor progress in SMA (FVC, PCF, AHI). Further research on the value of FOT in managing individuals is warranted.

Evaluating hypoxia during air travel in healthy infants

Up to a third of ex-preterm infants flying near term exhibit pulse oxygen saturation (SpO2) of less than 85% during air travel. A hypoxia challenge test (HCT) is recommended to evaluate the requirement for in-flight supplemental O2. The validity of the HCT in healthy, term infants has not been reported. This study aimed to characterise the in-flight hypoxia response and the accuracy of the HCT to predict this response in healthy, term infants in the first year of life. Infants (n=24: (15 male)) underwent a HCT prior to commercial air travel during which parents monitored SpO2. Thirty-two flights were undertaken with six infants completing multiple flights. The median in-flight SpO2 nadir was 87% and significantly lower than the HCT SpO2 nadir (92%: p<0.001). Infants on seven flights recorded SpO2<85% with one infant recording a HCT with a SpO2 less than 85%. There was marked variability in the in-flight SpO2 in the six infants who undertook multiple flights, and for three of these infants, the SpO2 nadir was both above and below 85%. We report that in healthy term infants an in-flight SpO2 below 85% is common and can vary considerably between flights and that the HCT poorly predicts the risk of in-flight hypoxia (SpO2<85%). As it is common for healthy term infants to have SpO2 less than 85% during air travel further research is needed to clarify whether this is an appropriate cut-off in this age group.

Defining ‘healthy’ in preschool‐aged children for forced oscillation technique reference equations

Selecting ‘healthy’ preschool‐aged children for reference ranges may not be straightforward. Relaxing inclusion criteria for normative data does not affect spirometry z‐scores. We therefore investigated the effect of similarly relaxing inclusion criteria in preschoolers on reference ranges for respiratory impedance (Zrs) using a modified forced oscillation technique (FOT).

Effect of omega-3 fatty acids supplementation during pregnancy on lung function in preschoolers: a clinical trial

ABSTRACT Rationale: Prenatal omega-3 fatty acids improve alveolarization, diminish inflammation, and improve pulmonary growth, but it is unclear whether these outcomes translate into improved postnatal lung function. Objective: We assessed the effect of prenatal supplementation with docosahexaenoic acid (DHA) on offspring lung function through 60 months of age. Methods: We included a cohort of 772 Mexican preschoolers whose mothers participated in a clinical trial (NCT00646360) of supplementation with DHA or a placebo from week 18–22 of gestation through delivery. Measurements: The children were followed after birth and anthropometric measurements and forced oscillation tests were performed at 36, 48, and 60 months of age. The effect of DHA was tested using a longitudinal mixed effect models. Results: Overall, mean (Standard Deviation) of the measurements of respiratory system resistance and respiratory system reactance at 6, 8, and 10 Hz during follow up period were 11.3 (2.4), 11.1 (2.4), 10.3 (2.2) and –5.2 (1.6), –4.8 (1.7), –4.6 (1.6), respectively. There were no significant differences in pulmonary function by treatment group. DHA did not affect the average lung function or the trajectories through 60 months. Conclusions: Prenatal DHA supplementation did not influence pulmonary function in this cohort of Mexican preschoolers.

Investigating the relationship between environmental factors and respiratory health outcomes in school children using the forced oscillation technique

The environmental factors which may affect childrens respiratory health are complex, and the influence and significance of factors such as traffic, industry and presence of vegetation is still being determined. We undertook a cross-sectional study of 360 school children aged 5-12 years who lived on the outskirts of a heavy industrial area in Western Australia to investigate the effect of a range of environmental factors on respiratory health using the forced oscillation technique (FOT), a non-invasive method that allows for the assessment of the resistive and reactive properties of the respiratory system. Based on home address, proximity calculations were used to estimate childrens exposure to air pollution from traffic and industry and to characterise surrounding green space. Indoor factors were determined using a housing questionnaire. Of the outdoor measures, the length of major roads within a 50m buffer was associated with increased airway resistance (Rrs8). There were no associations between distance to industry and FOT measures. For the indoor environment the presence of wood heating and gas heating in the first year of life was associated with better lung function. The significance of both indoor and outdoor sources of air pollution and effect modifiers such as green space and heating require further investigation.

P-344: Volatile Organic Compounds Exposure and Respiratory Function in Preschoolers from Mothers whose Participated in a Randomized Clinical Trial during Pregnancy

Background . Early exposure to air pollution is crucial in the development of the immune response and monitoring of respiratory function is important in the diagnostic and management of respiratory diseases. Objective: To determine the impact of air pollution on respiratory function in preschool-aged Mexican children and evaluate the interaction between supplementation with omega-3 fatty acids and air pollution exposure in this population. Methods. The forced oscillation technique (Respiratory resistance (Rrs6, 8Hz) and reactance (Xrs6, 8Hz ) using Cosmed Quark i2m, Italy) were used to measure respiratory function in 585 children (292 males) 3-5 years old once as part of the Omega-3 Supplementation Study in Mexico. Measurements were performed according to ATS/ERS standards. For environmental exposure, we conducted local monitoring of Volatile Organic Compounds air concentrations (Benzene, toluene, xilene, heptanes and hexane)) in diferent parts of the city and the association between respiratory function and air pollution exposure were analyzed using lineal regression models. Results . The lung function did not differ significantly between groups of supplementation. The volatile organic compounds (BTX, heptanes, hexane) air concentrations were significantly inverse related to respiratory function (Rrs6, 8Hz and Xrs6, 8Hz (p<0.05). We did not observe a potential interaction between treatment groups and air pollution exposure. Conclusions. Exposure to volatile organic compounds air concentrations in the general environment decrease the respiratory function in Mexican Preschoolers.