Sulfur Hexafluoride Multiple Breath Washout Research Articles

Limitations of regional ventilation inhomogeneity indices in children with cystic fibrosis.

Scond is a multiple breath washout (MBW) index that measures convection-dependent ventilation inhomogeneity (CDI) arising within conductive airways, but the calculation method is unreliable in subjects with advanced cystic fibrosis (CF) lung disease. A new CDI index, Scond *, has been proposed for use in adults with CF and moderate to severe ventilation inhomogeneity. We aimed to evaluate the most appropriate CDI index in children and adolescents with CF and various degrees of inhomogeneity, and from that the most appropriate diffusion-convection-interaction index (Sacin or Sacin *). Scond , Sacin and the alternative indices, Scond *, and Sacin * were retrospectively calculated in subjects with CF aged 3 to 18 years and age-matched controls, who underwent sulfur hexafluoride MBW between 2003 and2015. The upper limit of normalwas based on 95th percentile of the control population. One hundred and twenty-sevensubjects with CF (44% male;mean age ± SD: 7.5 years ± 4.9) and 94 controls (53% male;7.9 years ± 5.1) were included in the final analysis. All measures of ventilation inhomogeneity were significantly higher in children with CF. As predicted, Scond reached a maximum value at lung clearance index (LCI) values of approximately 9. In subjects with LCI ≥ 9 Scond * showed good correlation with LCI, whilst Scond had no relationship with LCI (Spearman rank correlation Scond */LCI, 0.49;P < .01; Scond /LCI, -0.068;P = .46). In subjects with mild disease (LCI < 9) Scond was more frequently abnormal than Scond * (37% vs 16%;P = .01). Scond and Sacin are sensitive indices of early regional inhomogeneity, but are of no value when LCI ≥ 9. In these subjects, Scond * & Sacin * are potential alternatives.

Lung clearance index in detection of post-transplant bronchiolitis obliterans syndrome.

BackgroundLong-term outcomes after lung transplantation are often limited by the development of obliterative bronchiolitis (OB), which is clinically defined using spirometry as bronchiolitis obliterans syndrome (BOS). Lung clearance index (LCI), derived from multiple breath washout (MBW) testing, is a global measure of ventilation heterogeneity that has previously been shown to be a more sensitive measure of obstructive small airway diseases than spirometry. We aimed to assess the feasibility of LCI in adult lung transplant patients and to compare LCI to BOS grade.Methods51 stable adult double-lung transplant recipients performed sulfur hexafluoride MBW in triplicate on a single occasion, using a closed-circuit Innocor device. BOS grades were derived from serial spirometry according to International Society for Heart and Lung Transplantation criteria and, where available, high-resolution computed tomography (HRCT) evidence of OB was recorded.ResultsLCI was successfully performed in 98% of patients. The within-visit coefficient of variation for repeat LCI measurements was 3.1%. Mean LCI increased significantly with BOS grades: no BOS (n=15), LCI 7.6; BOS-0p (n=16), LCI 8.3; BOS-1 (n=11), LCI 9.3; BOS-2–3 (n=9), LCI 13.2 (p<0.001). 27 patients had HRCT within 12 months. LCI in those with HRCT evidence of OB was higher than those without OB (11.1 versus 8.2, p=0.006). 47% patients displayed abnormal LCI (>7) despite a normal forced expiratory volume in 1 s (FEV1) (>80% of baseline).ConclusionsLCI measurement in lung transplant recipients is feasible and reproducible. LCI increased with increasing BOS grade. A significant proportion of this cohort had abnormal LCI with preserved FEV1, suggesting early subclinical small airway dysfunction, and supporting a role for MBW in the early identification of BOS.

Lung clearance index for early detection of pulmonary complications after allo-HSCT in children.

Pulmonary chronic graft-vs-host disease (cGvHD) after hematopoietic stem cell transplantation (HSCT) is characterized by impairment of the small airways. Assessment of lung clearance index (LCI) gained from multiple breath washout (MBW) is more sensitive than spirometry in detection of small airways disease. The aim of this study was to describe the development of LCI during the first year after pediatric HSCT and how LCI relates to other pulmonary function parameters and cGvHD. This prospective, longitudinal study included 28 pediatric HSCT-recipients. Spirometry, Sulfur hexafluoride MBW and diffusion capacity of the lungs were performed before and at 3, 6, 9, and 12 months after HSCT. Respiratory symptoms and signs of cGvHD were recorded at each visit. Before HSCT, 47.8% had abnormal LCI and 12.5% had abnormal forced expiratory volume in 1 second (FEV1 ). Patients with persisting respiratory symptoms 12 months post-HSCT had higher median LCI (factor 5.7, P = 0.0018) and lower FEV1 z-scores (-1.5, P = 0.033) post-HSCT compared to patients free of respiratory symptoms. Overall, post-HSCT LCI values were 3.49 times higher and FEV1 was 2.31 z-scores lower in eight patients with cGvHD in any organ system compared with patients without cGvHD (P = 0.0089 and P < 0.0001). LCI values during the first 3 months were not predictive of pulmonary cGvHD. LCI is a sensitive marker for cGvHD and high LCI values were associated with persisting respiratory symptoms after 1 year. Further evaluation of MBW in early detection of HSCT-related pulmonary complications require larger patient cohorts and closer follow-up during the first months after HSCT.

Impact of leaks in sulfur hexafluoride and nitrogen multiple-breath washout systems.

Sulfur hexafluoride multiple-breath washout is insensitive to inspiratory leaks http://ow.ly/Y3o830lKOpY

Difference between SF6 and N2 multiple breath washout kinetics is due to N2 back diffusion and error in N2 offset.

Measurement of lung clearance index (LCI) by multiple breath washout (MBW) is a sensitive method for monitoring lung disease in patients with cystic fibrosis (CF). To compare nitrogen MBW (N2-MBW) and sulfur hexafluoride MBW (SF6-MBW), we connected these two gas analysis systems in series to obtain truly simultaneous measurements, with no differences other than the gas used. Nonsmoking healthy controls (HC) and subjects with CF were recruited at two institutions. The Exhalyzer-D (for N2-MBW measurement) was connected in series with the Innocor (for SF6-MBW measurement). Subjects washed in SF6 from a Douglas bag with tidal breathing and washed out SF6 and nitrogen with 100% oxygen provided as bias flow. Washout of both gases was continued past the LCI point (1/40th of equilibration concentration) in triplicate. N2-MBW resulted in higher cumulative exhaled volume, functional residual capacity (FRC), and LCI when compared with SF6-derived parameters in HC subjects (P < 0.0001 for all comparisons). All N2-MBW parameters were also significantly higher than SF6-MBW parameters in subjects with CF (P < 0.01 for all comparisons). After recalculation with a common FRC, N2-MBW LCI was higher than SF6-MBW LCI in subjects with CF (19.73 vs. 11.39; P < 0.0001) and in HC (8.12 vs. 6.78; P < 0.0001). Adjusting for N2 back diffusion and an offset error in the nitrogen measurement resulted in near complete agreement between the two methodologies. We found significant differences in LCI and FRC measurements using two different gases for MBW. This may have significant implications for the future use and interpretation of LCI data in clinical trials and routine clinical care.NEW & NOTEWORTHY This study provides important insights into the differences between the two techniques used for measuring lung clearance index (LCI): N2 and SF6 multiple breath washout. Differences between measurements made by these two methods in subjects with cystic fibrosis and healthy controls could be explained by nitrogen back diffusion and N2 offset error. This is important for use and interpretation of LCI data as an outcome measure for clinical trials and in routine clinical care.

Determinants of early-life lung function in African infants.

BackgroundLow lung function in early life is associated with later respiratory illness. There is limited data on lung function in African infants despite a high prevalence of respiratory disease.AimTo assess the determinants of early lung function in African infants.MethodInfants enrolled in a South African birth cohort, the Drakenstein child health study, had lung function measured at 6–10 weeks of age. Measurements, made with the infant breathing via a facemask during natural sleep, included tidal breathing, sulfur hexafluoride multiple breath washout and the forced oscillation technique. Information on antenatal and early postnatal exposures was collected using questionnaires and urine cotinine. Household benzene exposure was measured antenatally.ResultsSuccessful tests were obtained in 645/675 (95%) infants, median (IQR) age of 51 (46–58) days. Infant size, age and male gender were associated with larger tidal volume. Infants whose mothers smoked had lower tidal volumes (−1.6 mL (95% CI −3.0 to −0.1), p=0.04) and higher lung clearance index (0.1 turnovers (95% CI 0.01 to 0.3), p=0.03) compared with infants unexposed to tobacco smoke. Infants exposed to alcohol in utero or household benzene had lower time to peak tidal expiratory flow over total expiratory time ratios, 10% (95% CI −15.4% to −3.7%), p=0.002) and 3.0% (95% CI −5.2% to −0.7%, p=0.01) lower respectively compared with unexposed infants. HIV-exposed infants had higher tidal volumes (1.7 mL (95% CI 0.06 to 3.3) p=0.04) compared with infants whose mothers were HIV negative.ConclusionWe identified several factors including infant size, sex, maternal smoking, maternal alcohol, maternal HIV and household benzene associated with altered early lung function, many of which are factors amenable to public health interventions. Long-term study of lung function and respiratory disease in these children is a priority to develop strategies to strengthen child health.

Lung clearance index and moment ratios at different cut-off values in infant multiple-breath washout measurements.

Multiple-breath washout (MBW) is increasingly used for infant lung function testing. Current guidelines recommend calculating lung clearance index (LCI) and functional residual capacity (FRC) at 2.5% of normalized tracer gas concentration, without clear recommendation for moment ratios (MR). Whether the 2.5% cut-off has the highest discriminative power to detect ventilation inhomogeneity in infants with lung diseases is unknown. We used sulfur-hexafluoride MBW measurements from 32 infants with cystic fibrosis, 32 preterm infants, and 32 healthy controls at postmenstrual age of 41-54 weeks. We compared the discriminative power to detect pathological values above the upper limit of normal for 12 different cut-offs between 20% and 1.5% for first and second MR (MR1, MR2), LCI, and FRC. MR and LCI results changed significantly at different cut-offs. Mean MR2 in infants with cystic fibrosis increased from 2.4 to 7.2 units between 20% and 1.5% SF6 . The ability of MR and LCI to discriminate between health and disease increased significantly with lower cut-offs. The 1.5% cut-off showed highest discriminative power: in infants with cystic fibrosis pathological MR2 values were found in 27 out of 89 (30%) and for LCI in 28/89 (32%). In preterm infants, pathological MR2 values were detected in 39 out of 73 (53%), and for LCI in 35/73 (48%). FRC remained stable throughout the washout. In infants, the diagnostic performance of MBW strongly depends on the point of analysis. The cut-off with the highest discriminative power to detect ventilation inhomogeneity in infants with cystic fibrosis and after preterm birth was at 1.5% tracer gas concentration. Pediatr Pulmonol. 2016;51:1373-1381. © 2016 Wiley Periodicals, Inc.