Double-tracer Gas Single-breath Washout Research Articles

Evaluation of the Double-Tracer Gas Single-Breath Washout Test in a Pediatric Field Study

The early life origins of chronic pulmonary diseases are thought to arise in peripheral small airways. Predictors of ventilation inhomogeneity, a proxy of peripheral airway function, are understudied in schoolchildren. Is the double-tracer gas single-breath washout (DTG-SBW) measurement feasible in a pediatric field study setting? What are the predictors of the DTG-SBW-derived ventilation inhomogeneity estimate in unselected schoolchildren? In this prospective cross-sectional field study, a mobile lung function testing unit visited participating schools in Switzerland. We applied DTG-SBW, fraction of exhaled nitric oxide (Feno), and spirometry measurements. The DTG-SBW is based on tidal inhalation of helium and sulfur-hexafluoride, and the phase III slope (SIIIHe-SF6) is derived. We assessed feasibility, repeatability, and associations of SIIIHe-SF6 with the potential predictors of anthropometrics, presence of wheeze (ie, parental report of one or more episode of wheeze in the prior year), Feno, FEV1, and FEV1/FVC. In 1,782 children, 5,223 DTG-SBW trials were obtained. The DTG-SBW was acceptable in 1,449 children (81.3%); the coefficient of variation was 39.8%. SIIIHe-SF6 was independently but weakly positively associated with age and BMI. In 276 children (21.2%), wheeze was reported. SIIIHe-SF6 was higher by 0.049 g.mol.L-1 in children with wheeze compared with those without and remained associated with wheeze after adjusting for age and BMI in a multivariable linear regression model. SIIIHe-SF6 was not associated with Feno, FEV1, and FEV1/FVC. The DTG-SBW is feasible in a pediatric field study setting. On the population level, age, body composition, and wheeze are independent predictors of peripheral airway function in unselected schoolchildren. The variation of the DTG-SBW possibly constrains its current applicability on the individual level. ClinicalTrials.gov; No.: NCT03659838; URL: www. gov.

LuftiBus in the school (LUIS): a population-based study on respiratory health in schoolchildren.

Respiratory disease is common in children and strongly associated with lifestyle and environmental exposures. Thus, it is important to study the epidemiology locally. The LuftiBus in the School (LUIS) study was set up to assess the respiratory health of schoolchildren in the canton of Zurich, Switzerland. LUIS is a cross-sectional population-based study that was carried out 2013 to 2016. Children aged 6–17 years living in the canton of Zurich were eligible to participate. All schools in the canton were approached and the school head decided whether the school would participate and with which classes. Consenting parents answered a standardised questionnaire at home and assenting children completed a shorter questionnaire by interview at school. Trained technicians measured children’s lung function, including spirometry, double tracer gas single-breath washout (DTG-SBW) and fractional exhaled nitric oxide (FeNO). Address histories of participants were geocoded to be linked with area-based socioeconomic measures and environmental exposures such as spatiotemporal air pollution estimates for specific time periods and locations. A subgroup was seen again 12 months later using the same procedures to collect longitudinal data. The study included 3870 children at baseline and 655 at the 1-year follow-up. Median age was 12.7 years; 281 (8%) had wheezed in the past year. At baseline we collected 3457 (89%) parental and 3546 (92%) child questionnaires, and 3393 (88%) FeNO, 3446 (89%) spirometry, and 1795 (46%) DTG-SBW measurements. LUIS is a rich resource of health-related data, with information on lung function, environmental exposures and respiratory health on Swiss schoolchildren.

A simple method to reconstruct the molar mass signal of respiratory gas to assess small airways with a double-tracer gas single-breath washout

For the assessment of small airway diseases, a noninvasive double-tracer gas single-breath washout (DTG-SBW) with sulfur hexafluoride (SF6) and helium (He) as tracer components has been proposed. It is assumed that small airway diseases may produce typical ventilation inhomogeneities which can be detected within one single tidal breath, when using two tracer components. Characteristic parameters calculated from a relative molar mass (MM) signal of the airflow during the washout expiration phase are analyzed. The DTG-SBW signal is acquired by subtracting a reconstructed MM signal without tracer gas from the signal measured with an ultrasonic sensor during in- and exhalation of the double-tracer gas for one tidal breath. In this paper, a simple method to determine the reconstructed MM signal is presented. Measurements on subjects with and without obstructive lung diseases including the small airways have shown high reliability and reproducibility of this method.

Function and Ventilation of Large and Small Airways in Children and Adolescents with Inflammatory Bowel Disease.

Extraintestinal manifestations are common among patients with inflammatory bowel disease (IBD), whereas pulmonary involvement is considered rare. However, chronic lung diseases begin with subclinical changes of the small airways and often originate in childhood. Pulmonary involvement, particularly of the small airways, can be assessed using novel inert gas washout tests. In this prospective, single-center study, 30 children and adolescents (mean age, 14 years; SD, ±2.6; 13 boys) with IBD (mean disease duration, 3.2 years; SD, ±2.8), and 32 healthy age-matched controls, performed nitrogen multiple-breath washout, double-tracer gas single-breath washout, and diffusion capacity for carbon monoxide. Patients with IBD additionally performed spirometry, plethysmography, and measurement of exhaled nitric oxide. Patients with IBD demonstrated no abnormalities in classical lung function tests. There was no difference between active disease and remission. The lung clearance index, a very sensitive indicator for small airway function, did not differ between patients with IBD and healthy controls (mean difference [95% confidence interval] -0.01 [-0.28 to 0.25]). Specific markers for peripheral lung ventilation (Sacin and Scond) were also within the normal range (0.002 [-0.003 to 0.008] and -0.002 [-0.020 to 0.015], respectively). No association was found between measures of lung function and IBD subtype, clinical disease activity scores, laboratory values, treatment modalities, or disease duration. In our cohort of pediatric and adolescent patients with IBD without respiratory symptoms, there was no evidence of significant lung disease on extensive screening testing. General screening of asymptomatic patients therefore appears unnecessary and is not recommended in this population.

Double tracer gas single-breath washout: reproducibility in healthy subjects and COPD.

The applicability and interpretation of inert tracer gas washout tests is hampered by the lack of feasible protocols and reproducibility data. We assessed feasibility, variability and reproducibility of a new easy to perform double tracer gas (DTG) single-breath washout (SBW) test and compared this with conventional nitrogen washouts. In 40 healthy nonsmokers and 20 patients with stable chronic obstructive pulmonary disease (COPD), we performed three N2 vital capacity SBWs, three N2 multiple-breath washouts and three tidal DTG-SBW tests. Follow-up was after 1 week, 1 month and 6 months. Main outcomes were the lung clearance index (LCI) (N2 multiple-breath washout), slope of phase III (dN2) (N2 vital capacity SBW) and slope of phase III (SIIIDTG) (DTG-SBW). In healthy subjects, mean±sd LCI at baseline was 6.94±0.61, dN2 0.99±0.42% N2 per litre and SIIIDTG -0.206±0.108 g·mol(-1)·L(-1). In COPD, LCI and dN2 were significantly higher (LCI 12.23±2.67, dN2 7.43±5.38% N2 per litre; p<0.001) and SIIIDTG significantly steeper (-0.653±0.428 g·mol(-1)·L(-1), p<0.001). Reproducibility was high for main outcome parameters: the intraclass correlation coefficient over 6 months was 0.77 (0.86 in COPD) for LCI, 0.82 (0.89) for dN2 and 0.83 (0.93) for SIIIDTG. The tidal DTG-SBW is a reproducible test in healthy and COPD subjects that seems attractive for use in routine clinical settings.

A new double-tracer gas single-breath washout to assess early cystic fibrosis lung disease

In cystic fibrosis (CF), tests for ventilation inhomogeneity are sensitive but not established for clinical routine. We assessed feasibility of a new double-tracer gas single-breath washout (SBW) in school-aged children with CF and control subjects, and compared SBW between groups and with multiple-breath nitrogen washout (MBNW). Three SBW and MBNW were performed in 118 children (66 with CF) using a side-stream ultrasonic flowmeter setup. The double-tracer gas containing 5% sulfur hexafluoride and 26.3% helium was applied during one tidal breath. Outcomes were SBW phase III slope (SIII(DTG)), MBNW-derived lung clearance index (LCI), and indices of acinar (S(acin)) and conductive (S(cond)) ventilation inhomogeneity. SBW took significantly less time to perform than MBNW. SBW and MBNW were feasible in 109 (92.4%) and 98 (83.0%) children, respectively. SIII(DTG) differed between children with CF and controls, mean±sd was -456.7±492.8 and -88.4±129.1 mg·mol·L(-1), respectively. Abnormal SIII(DTG) was present in 36 (59%) children with CF. SIII(DTG) was associated with LCI (r= -0.58) and S(acin) (r= -0.58), but not with S(cond). In CF, steeply sloping SIII(DTG) potentially reflects ventilation inhomogeneity near the acinus entrance. This tidal SBW is a promising test to assess ventilation inhomogeneity in an easy and fast way.