Single-breath Washout Test Research Articles

LAMA improves tissue oxygenation more than LABA in patients with COPD.

The effect of bronchodilators is mainly assessed with forced expiratory volume in 1 s (FEV1) in chronic obstructive pulmonary disease (COPD). Their impact on oxygenation and lung periphery is less known. Our objective was to compare the action of long-acting β2-agonists (LABA-olodaterol) and muscarinic antagonists (LAMA-tiotropium) on tissue oxygenation in COPD, considering their impact on proximal and peripheral ventilation as well as lung perfusion. FEV1, Helium slope (SHe) from a single-breath washout test (SHe decreases reflecting a peripheral ventilation improvement), frequency dependence of resistance (R5-R19), area under reactance (AX), lung capillary blood volume (Vc) from double diffusion (DLNO/DLCO), and transcutaneous oxygenation (TcO2) were measured before and 2 h post-LABA (day 1) and LAMA (day 3) in 30 patients with COPD (FEV1 54 ± 18% pred; GOLD A 31%/B 48%/E 21%) after 5-7 days of washout, respectively. We found that TcO2 increased more (P = 0.03) after LAMA (11 ± 12% from baseline, P < 001) compared with LABA (4 ± 11%, P = 0.06) despite a lower FEV1 increase (P = 0.03) and similar SHe (P = 0.98), AX (P = 0.63), and R5-R19 decreases (P = 0.37). TcO2 and SHe changes were negatively correlated (r = -0.47, P = 0.01) after LABA, not after LAMA (r = 0.10, P = 0.65). DLNO/DLCO decreased and Vc increased after LAMA (P = 0.04; P = 0.01, respectively) but not after LABA (P = 0.53; P = 0.24). In conclusion, LAMA significantly improved tissue oxygenation in patients with COPD, while only a trend was observed with LABA. The mechanisms involved may differ between both drugs: LABA increased peripheral ventilation, whereas LAMA increased lung capillary blood volume. Should oxygenation differences persist over time, LAMA could arguably become the first therapeutic choice in COPD.NEW & NOTEWORTHY Long-acting muscarinic antagonists (LAMAs) significantly improved tissue oxygenation in patients with COPD, while only a trend was observed with β2-agonists (LABAs). The mechanisms involved may differ between drugs: increased peripheral ventilation for LABA and likely lung capillary blood volume for LAMA. This could argue for LAMA as the first therapeutic choice in COPD.

COPD patients with peripheral airway obstruction reversibility identified by exhaled nitric oxide

Rationale: Besides its role as an inflammatory marker in asthma, fractional exhaled nitric oxide (FENO) provides information on the extent of the airway obstruction process through evaluating its change after bronchodilation. Objective: To investigate whether FENO change after bronchodilation can identify different sites of airway obstruction in COPD patients. Methods: FENO, FEV1 and the slopes (S) of the alveolar plateau of the single breath washout test (SBWT) were measured in 61 stable COPD patients (FEV1 34.5% predicted) before and after the inhalation of 400 μg salbutamol. SBWT used Helium (He), and sulfur-hexafluoride (SF6). Obstruction relief occurring in pre-acinar and intra-acinar small airways is expected to decrease SHe and SSF6, respectively. Indices changes (Δ) after bronchodilation were expressed as a percentage of pre-bronchodilation values. Results: FENO stability (∣ΔFENO∣ ≤ 11%) was observed in 19 patients [−2.7(6.7)%] [mean (SD)] (NO = group); ΔFENO > 11% [+37.4(27.7)%] in 20 patients (NO+ group) and ΔFENO < −11% in 22 patients [−31.2(9.8)%] (NO− group). A similar ΔFEV1 (p = 0.583; [+9.4(9.6)%]) was found in the three groups. In NO = and NO+ groups, neither SHe nor SSF6 changed; in NO− both SHe [−12.4(27.5)%, p = 0.007] and SSF6 [−20.2(20.4)%, p < 0.001] significantly decreased. Conclusion: Different patterns of FENO response to β2-agonists were observed in COPD most likely depending on the extent of the dilation process. A profile of airway obstruction with an extensive β2-agonist response down to lung periphery is identified by FENO reduction after acute bronchodilation in 30% of COPD patients. The clinical relevance of this profile requires further investigation.

Small airways dysfunction: the link between allergic rhinitis and allergic asthma.

Abnormal airway reactivity and overproduction of nitric oxide (NO) occurring in small airways have been found in asthma. If the "one airway, one disease" concept is consistent, such dysfunctions should also be detected in the peripheral airways of patients suffering from allergic rhinitis.We investigated whether peripheral airway reactivity and NO overproduction could be documented in distal airways in patients with allergic rhinitis. Exhaled NO fraction (FeNO) and the slope (S) of phase III of the single-breath washout test (SBWT) of helium (He) and sulfur hexafluoride (SF6) were measured in 31 patients with allergic asthma, 23 allergic rhinitis patients and 24 controls, before and after sputum induction. SBWT is sensitive to airway calibre change occurring in the lung periphery.The FeNO decrease was more significant in asthma and rhinitis than in controls (-55.1% and -50.0%, respectively, versus -40.8%) (p=0.007 and p=0.029, respectively). SSF6 and SHe increased in all groups. Change in SHe (ΔSHe) > ΔSSF6 was observed in rhinitis (p=0.004) and asthma (p<0.001), whereas ΔSSF6 = ΔSHe in controls (p=0.431).This study provides evidence of peripheral airway dysfunction in patients with allergic rhinitis quite similar to that described in asthma. Furthermore, a large proportion of the increased NO production reported in allergic rhinitis appears to originate in the peripheral airways.

Nitrogen single-breath washout test for evaluating exercise tolerance and quality of life in patients with chronic obstructive pulmonary disease

Pulmonary function tests (PFTs) traditionally used in clinical practice do not accurately predict exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to assess whether the nitrogen single-breath washout (N2SBW) test explains exercise intolerance and poor quality of life in stable COPD patients. This cross-sectional study included 31 patients with COPD subjected to PFTs (including the N2SBW test) and a cardiopulmonary exercise test (CPET). Patients were also evaluated using the following questionnaires: the COPD assessment test (CAT), the 36-Item Short Form Health Survey (SF36) and St. George's Respiratory Questionnaire (SGRQ). Peak oxygen uptake (peak VO2) was negatively correlated with the phase III slope of the N2SBW (SIIIN2) (r=-0.681, P<0.0001) and positively correlated with forced expiratory volume in one second (FEV1; r=0.441, P=0.013). Breathing reserve was negatively correlated with SIIIN2, closing volume/vital capacity, and residual volume (RV) (r=-0.799, P<0.0001; r=-0.471, P=0.007; r=-0.401, P=0.025, respectively) and positively correlated with FEV1, forced vital capacity (FVC) and FEV1/FVC (r=0.721; P<0.0001; r=0.592, P=0.0004; r=0.670, P<0.0001, respectively). SIIIN2 and CAT were independently predictive of VO2 and breathing reserve at peak exercise. RV, FVC, and FEV1 were independently predictive of the SF36-physical component summary, SF36-mental component summary, and breathing reserve, respectively. The SGRQ did not present any independent variables that could explain the model. In stable COPD patients, inhomogeneity of ventilation explains a large degree of exercise intolerance assessed by CPETs and, to a lesser extent, poor quality of life.

Cardiopulmonary exercise testing and second-line pulmonary function tests to detect obstructive pattern in symptomatic smokers with borderline spirometry

BackgroundThe need for additional research on symptomatic smokers with normal spirometry has been recently emphasized. Albeit not meeting criteria for Chronic obstructive pulmonary disease (COPD) diagnosis, symptomatic smokers may experience activity limitation, evidence of airway disease, and exacerbations. We, therefore, evaluated whether symptomatic smokers with borderline spirometry (post-bronchodilator FEV1/FVC ratio between 5th to 20th percentile of predicted values) have pulmonary function abnormalities at rest and ventilatory constraints during exercise. Methods48 subjects (aged 60 ± 8 years, mean ± SD, 73% males, 16 healthy, and 17 symptomatic smokers) underwent cardiopulmonary exercise testing (CPET), body plethysmography, nitrogen single-breath washout test (N2SBW), lung diffusion for carbon monoxide (DLCO), and forced oscillation technique (FOT). ResultsCompared to healthy subjects, symptomatic smokers showed: 1) reduced breathing reserve (36 ± 17 vs. 49 ± 12%, P = 0.050); 2) exercise induced dynamic hyperinflation (−0.20 ± 0.17 vs. −0.03 ± 0.21 L, P = 0.043); 3) higher residual volume (158 ± 22 vs. 112 ± 22%, P < 0.001); 4) phase 3 slope at N2SBW (4.7 ± 2.1 vs. 1.4 ± 0.6%, P < 0.001); 5) no significant differences in DLCO and FOT results. ConclusionsIn smokers with borderline spirometry, CPET and second-line pulmonary function tests may detect obstructive pattern. These subjects should be referred for second line testing, to obtain a diagnosis, or at least to clarify the mechanisms underlying symptoms. Whether the natural history of these patients is similar to COPD, and they deserve a similar therapeutic approach is worth investigating.

Alternative inert gas washout outcomes in patients with primary ciliary dyskinesia.

The lung clearance index (LCI) derived from a nitrogen multiple breath washout test (N2-MBW) is a promising tool to assess small airways disease in primary ciliary dyskinesia, but it is difficult to apply in routine clinical settings because of its long measuring time. In this study, we aimed to assess alternative indices derived from shorter washout protocols.49 patients with primary ciliary dyskinesia (mean age 14.7±6.6 years) and 37 controls (mean age 14.3±1.4 years) performed N2-MBW and double-tracer gas (DTG) single-breath washout tests. Global (LCI and moment ratio (M2/M0)), conductive (Scond) and acinar ventilation inhomogeneity (DTG Slope III (SIII-DTG)) were determined for each individual. The main outcomes were 1) the ability to detect abnormal lung function from washout indices (>1.64 z-scores) and 2) measurement duration.The prevalence of abnormal values for LCI2.5% was 37 out of 47 (79%), for LCI5% was 34 out of 47 (72%), for M2/M0 was 34 out of 47 (72%), for Scond was 36 out of 46 (78%) and for SIII-DTG was 12 out of 35 (34%). Mean±sd duration of measurement was 19.8±11.2 min for LCI2.5%, 10.8±4.6 min for LCI5% and 8.6±2.3 min for ScondCompared to standard LCI2.5%, ventilation inhomogeneity was detected by LCI5%, moment ratio and Scond with comparable sensitivity while measurement duration was significantly shorter. Longitudinal studies will show which outcome is most suitable and practical in terms of sensitivity, duration and variability within the course of primary ciliary dyskinesia lung disease.

Single-Breath Washout Tests to Assess Small Airway Disease in COPD

Current functional assessments do not allow a reliable assessment of small airways, which are a major site of disease in COPD. Single-breath washout (SBW) tests are feasible and reproducible methods for evaluating small airway disease. Their relevance in COPD remains unknown. We performed a cross-sectional study in 65 patients with moderate to severe COPD. Phase III slope of nitrogen (SIIIN2) and double tracer gas (SIIIDTG) SBW tests were used as a measure of ventilation inhomogeneity. The association of both markers with established physiological and clinical features of COPD was assessed. Ventilation inhomogeneity as measured by SIIIN2 and SIIIDTG was increased in patients with COPD compared with healthy subjects (P< .001 and P< .001, respectively). SIIIN2 was associated with FEV1 predicted, residual volume (RV)/total lung capacity (TLC) and diffusing capacity of the lung for carbon monoxide (Dlco) (all P< .001). Furthermore, SIIIN2 was related to dyspnea, exercise-induced desaturation, and exercise capacity (P= .001, P< .001, and P= .047, respectively). SIIIDTG was associated with TLC, Dlco, and cough (P< .001, P= .001, and P= .009, respectively). In multivariate regression models, we demonstrated that these associations are largely independent of FEV1 and mostly stronger than associations with FEV1. In contrast, FEV1 was superior in predicting emphysema severity. SIIIN2 and SIIIDTG, two fast and clinically applicable measures of small airway disease, reflect different physiological and clinical aspects of COPD, largely independent of spirometry. ISRCTN99586989, Ethics committee Beider Basel (approval number 295/07).

Different patterns of exhaled nitric oxide response to β2-agonists in asthmatic patients according to the site of bronchodilation

In asthmatic patients undergoing airway challenge, fraction of exhaled nitric oxide (FENO) levels decrease after bronchoconstriction. In contrast, model simulations have predicted both decreased and increased FENO levels after bronchodilation, depending on the site of airway obstruction relief. We sought to investigate whether β2-agonists might induce divergent effects on FENO values in asthmatic patients as a result of airway obstruction relief occurring at different lung depths. FENO, FEV1, and the slope of phase III of the single-breath washout test (S) of He (S(He)) and sulfur hexafluoride (S(SF6)) were measured in 68 asthmatic patients before and after salbutamol inhalation. S(He) and S(SF6) decreases reflected preacinar and intra-acinar obstruction relief, respectively. Changes (Δ) were expressed as a percentage from the baseline. No FENO change (|ΔFENO| ≤ 10%) was found in 16 patients (mean [SD]: 2.5% [5.2%]; ie, FENO= group); a ΔFENO value of greater than 10% was found in 23 patients (31.7% [20.3%]; ie, the FENO+ group); and a ΔFENO value of less than -10% was found in 29 patients (-31.5% [17.3%]; ie, the FENO- group). All groups had similar ΔFEV1 values. In the FENO= group neither S(He) nor S(SF6) changed, in the FENO+ group only S(He) decreased significantly (-21.8% [SD 28.5%], P = .03), and in the FENO- group both S(He) (-29.8% [24.0%], P < .001) and S(SF6) (-27.2% [23.3%], P < .001) decreased. Three FENO behaviors were observed in response to β2-agonists: a decrease likely caused by relief of an intra-acinar airway obstruction that we propose reflects amplification of nitric oxide back-diffusion, an increase likely associated with a predominant dilation up to the preacinar airways, and FENO stability when obstruction relief involved predominantly the central airways. In combination, these results suggest a new role for FENO in identifying the site of airway obstruction in asthmatic patients.

Actualités ≪ environnement et pollution ≫

Current functional assessments do not allow a reliable assessment of small airways, which are a major site of disease in COPD. Single-breath washout (SBW) tests are feasible and reproducible methods for evaluating small airway disease. Their relevance in COPD remains unknown.We performed a cross-sectional study in 65 patients with moderate to severe COPD. Phase III slope of nitrogen (SIIIN2) and double tracer gas (SIIIDTG) SBW tests were used as a measure of ventilation inhomogeneity. The association of both markers with established physiological and clinical features of COPD was assessed.Ventilation inhomogeneity as measured by SIIIN2 and SIIIDTG was increased in patients with COPD compared with healthy subjects (P < .001 and P < .001, respectively). SIIIN2 was associated with FEV1 predicted, residual volume (RV)/total lung capacity (TLC) and diffusing capacity of the lung for carbon monoxide (Dlco) (all P < .001). Furthermore, SIIIN2 was related to dyspnea, exercise-induced desaturation, and exercise capacity (P = .001, P < .001, and P = .047, respectively). SIIIDTG was associated with TLC, Dlco, and cough (P < .001, P = .001, and P = .009, respectively). In multivariate regression models, we demonstrated that these associations are largely independent of FEV1 and mostly stronger than associations with FEV1. In contrast, FEV1 was superior in predicting emphysema severity.SIIIN2 and SIIIDTG, two fast and clinically applicable measures of small airway disease, reflect different physiological and clinical aspects of COPD, largely independent of spirometry.ISRCTN99586989, Ethics committee Beider Basel (approval number 295/07)

Abnormal Small Airways Function in Children With Mild Asthma

Small airways disease is a hallmark in adults with persistent asthma, but little is known about small airways function in children with mild asthma and normal spirometry. We assessed ventilation heterogeneity, a marker of small airways function, with an easy tidal breath single-breath washout (SBW) technique in school-aged children with mild asthma and normal FEV1 and healthy age-matched control subjects. The primary outcome was the double-tracer gas phase III slope (SDTG), an index of ventilation heterogeneity in acinar airways derived from the tidal double-tracer gas SBW test. The second outcome was the nitrogen phase III slope (SN2), an index of global ventilation heterogeneity derived from the tidal nitrogen SBW test using pure oxygen. Triplicate SBW and spirometry tests were performed in healthy children (n=35) and children with asthma (n=31) at baseline and in children with asthma after bronchodilation. Acinar (SDTG) but not global (SN2) ventilation heterogeneity was significantly increased in asthma despite normal FEV1. Of the 31 children with asthma, abnormal results were found for SDTG (≤-2 z scores) in 11; forced expiratory flow, midexpiratory phase (FEF25%-75%) in three; and FEV1 in zero. After bronchodilation, SDTG, SN2, FEF25%-75%, and FEV1 significantly changed (mean [95% CI] change from baseline, 36% [15%-56%], 38% [18%-58%], 17% [9-25%], and 6% [3%-9%], respectively). Abnormal acinar ventilation heterogeneity in one-third of the children suggests that small airways disease may be present despite rare and mild asthma symptoms and normal spirometry. The easy tidal SBW technique has considerable potential as a clinical and research outcome in children with asthma.

Exhaled nitric oxide: A biomarker integrating both lung function and airway inflammation changes

The increased fraction of exhaled nitric oxide (Feno) values observed in asthmatic patients are thought to reflect increased airway inflammation. However, Feno values can be affected by airway caliber reduction, representing a bias when using Feno values to assess asthma control. We sought to determine the effect of changes in both airway caliber and inflammation on Feno values using the allergen challenge model. FEV1 and Feno values were measured during early airway responses (EARs) and late airway responses after challenge with house dust mite allergens in 15 patients with mild allergic asthma. Helium and sulfur hexafluoride (SF6) phase III expired concentration slopes (SHe and SSF6, respectively) from single-breath washout tests were measured to identify sites of airway constriction. In EARs, FEV1 and Feno value decreases reached 36.8% and 22%, respectively (P < .001). ΔSHe was greater than ΔSSF6 (+189.4% vs +82.2%, P = .001). In late airway responses FEV1 and Feno value decreases reached 31.7% and 28.7%, respectively (P < .001), with the same ΔSHe and ΔSSF6 pattern (+155.8% vs +76%, P = .001). Eight hours after the EAR, FEV1 was still decreased (P < .001), whereas Feno values had returned to baseline. At 24 hours, FEV1 had returned to baseline, with Feno values increased by 38.7% (P = .04). In patients with mild allergic asthma, airway caliber changes modulate changes in Feno values resulting from airway inflammation. Therefore Feno should no longer be considered solely an inflammation biomarker but rather a biomarker that integrates both airway inflammation and lung function changes. Furthermore, early and late phases resulting from allergen exposure were shown to involve similar lung regions.

Predictors of phase III slope of nitrogen single-breath washout in COPD

The nitrogen (N2) single-breath washout (SBW) test is a measure of ventilation distribution inhomogeneity and also a small airway function that offers complementary information to spirometry; however, the relevance to the forced oscillation technique (FOT) and pulmonary emphysema in COPD is not fully understood. We hypothesized that pulmonary functions, forced oscillatory parameters, and emphysema extent would contribute independently to the results of the SBW test. In this cross-sectional study we assessed the relationship between the phase III slope (delta N2) derived from N2 SBW and these parameters. Spirometry, lung volumes, N2 SBW, and the broadband frequency FOT were performed in 56 patients with COPD. Emphysema extent was measured by high-resolution computed tomography and scored. In multiple regression analyses, the delta N2 was independently predicted by forced vital capacity, resonant frequency, and emphysema score (R2=0.57, p<0.0001). The degree of ventilation inhomogeneity derived from N2 SBW is independently predicted by spirometry, lung mechanics, and the degree of emphysema.

Ventilation heterogeneity in the acinar and conductive zones of the normal ageing lung

RationaleSmall airways function studies in lung disease have used three promising multiple breath washout (MBW) derived indices: indices of ventilation heterogeneity in the acinar (Sacin) and conductive (Scond) lung zones,...

Effects on small airway obstruction of long-term treatments with beclomethasone/formoterol hydrofluoroalkane (metered-dose inhaler) versus fluticasone/salmeterol (dry-powder inhaler) in asthma: A preliminary study

New formulations of extrafine particles of long-acting beta-2 agonists plus inhaled corticosteroids (LABA + ICS) have been shown to reach peripheral regions of the lung. The aim of the study was to assess the effect on small airway obstruction of long-term treatments with two different LABA + ICS formulations in asthma. Ten subjects with moderate persistent asthma were enrolled. After a 4-week washout period they were treated in a randomized crossover design for 24 weeks with formoterol, 12 micrograms, and beclomethasone, 200 micrograms, hydrofluoroalkane (HFA; by metered-dose inhaler) b.i.d. (FB) or salmeterol, 50 micrograms, and fluticasone, 250 micrograms (by dry-powder inhaler), b.i.d. (SF). At baseline and at the end of each period subjects underwent an Asthma Control Test (ACT) and Pulmonary Function Testing. The N(2) phase III slope and closing volume (CV) during single-breath washout test and difference between the maximal expiratory flow rates with air and heliox at isovolume corresponding to 50% [Delta(heliox-air)MEF(50%)] were measured to assess changes on peripheral airways function. Two subjects dropped out and eight completed the study. After SF and FB, forced expiratory volume at 1 second (FEV(1); p < 0.01) and FEV(1)/forced vital capacity (FVC; p < 0.01 for SF and p < 0.05 for FB) increased when compared with baseline. Although both FB and SF treatments slightly increased delta(heliox-air)MEF(50% isovolume) versus baseline, only after FB the N(2) phase III slope and CV decreased from 1.61 ± 0.61%/L to 1.35 ± 0.49 N(2)%/L (p = 0.054) and from 0.98 ± 0.56 L to 0.88 ± 0.58 L (p < 0.05), respectively. ACT score raised from 19 ± 5 (baseline) to 23 ± 1 after FB (p < 0.02) and 23 ± 2 after SF (p < 0.05). When compared with baseline and in contrast to SF (50/250 micrograms b.i.d.), FB HFA (12/200 micrograms b.i.d.) significantly improved functional parameters reflecting small airway obstruction in asthmatic patients. Registered in the public trial registry at www.ClinicalTrials.gov identifier: NCT01255579.

Tidal Volume Single Breath Washout of Two Tracer Gases - A Practical and Promising Lung Function Test

BackgroundSmall airway disease frequently occurs in chronic lung diseases and may cause ventilation inhomogeneity (VI), which can be assessed by washout tests of inert tracer gas. Using two tracer gases with unequal molar mass (MM) and diffusivity increases specificity for VI in different lung zones. Currently washout tests are underutilised due to the time and effort required for measurements. The aim of this study was to develop and validate a simple technique for a new tidal single breath washout test (SBW) of sulfur hexafluoride (SF6) and helium (He) using an ultrasonic flowmeter (USFM).MethodsThe tracer gas mixture contained 5% SF6 and 26.3% He, had similar total MM as air, and was applied for a single tidal breath in 13 healthy adults. The USFM measured MM, which was then plotted against expired volume. USFM and mass spectrometer signals were compared in six subjects performing three SBW. Repeatability and reproducibility of SBW, i.e., area under the MM curve (AUC), were determined in seven subjects performing three SBW 24 hours apart.ResultsUSFM reliably measured MM during all SBW tests (n = 60). MM from USFM reflected SF6 and He washout patterns measured by mass spectrometer. USFM signals were highly associated with mass spectrometer signals, e.g., for MM, linear regression r-squared was 0.98. Intra-subject coefficient of variation of AUC was 6.8%, and coefficient of repeatability was 11.8%.ConclusionThe USFM accurately measured relative changes in SF6 and He washout. SBW tests were repeatable and reproducible in healthy adults. We have developed a fast, reliable, and straightforward USFM based SBW method, which provides valid information on SF6 and He washout patterns during tidal breathing.

Multimodality measurements of small airways disease

Small airways disease has long been recognised as being physiologically important in obstructive lung diseases, particularly in chronic obstructive pulmonary disease (COPD) 1. The study of Cosio et al. 2, in which the severity of small airway inflammation and remodelling in smokers correlated with airway closure and ventilation maldistribution, as measured by single breath washout tests, is a landmark one because it linked small airways tests with pathology. Furthermore, these parameters of small airway function were more sensitive than spirometry for the presence of small airways disease. Results of more recent studies, in which small airway function was measured by the newer multiple breath nitrogen washout, showed that small airway function becomes abnormal after only 10 pack-yrs smoking, whereas spirometry becomes abnormal after 20 pack-yrs 3. In asthma, however, the function of the small airways has been studied much less, perhaps due to the paucity of resected lung specimens on which correlations can be made between measurements of small airway function and pathology. The disease-related changes to the structural components of the airways in asthma involve both small and large airways 4. These pathological changes, often referred to as remodelling, lead to thickening of the walls of the small airways. This is a feature that seems particularly characteristic of asthma as opposed to COPD 5. There is now an increasing body of evidence suggesting that small airways disease in asthma has important clinical consequences, to which the study by Zeidler et al. 6, in this issue of the European Respiratory Journal , makes an important contribution. In the study by Zeidler et al. 6, high-resolution computed tomography (HRCT) …

113: Comparison of exhaled nitric oxyde (eNO) and Helium slope (SHe) for the early detection of graft dysfunction after heart-lung (HLT) and bilateral lung (BLT) transplantation

The slope of the alveolar plateau for Helium (SHe) measured during a single-breath washout test allows early detection of bronchiolitis obliterans syndrome (BOS) stage 1 after lung transplantation. The aim of this study was to examine the relationship over time between the development of BOS stage 0-p and changes in both eNO and SHe. 59 patients (14 HLT and 45 BLT), of whom 17 developed BOS 0-p, were studied. There were 34 patients who had been transplanted before 09/2000 and were in BOS 0, and 25 patients who were transplanted after 09/2000. Standard pulmonary function tests, eNO (measured at 200ml/s following ERS guidelines), and single-breath washouts were measured on 765 occasions from 09/2000 to 12/2004 (median follow-up 1179 days); only data obtained while patients were free of acute infection and rejection were included in the analysis. The lowest values of eNO and SHe obtained in each of the 17 patients during the BOS 0 period (T1) were compared to values obtained at the end of the BOS 0 period immediately before the change to BOS 0-p (T2), and to values obtained during the BOS 0-p period (T3). Average (SD) values for eNO at T1, T2, and T3 were 4.0 (2.4), 4.5 (1.6), and 8.0 (6.0) ppb; corresponding values for SHe were 1.6 (1.0), 4.0 (3.3), and 5.9 (4.2) %/l. For eNO, the only significant difference was found between T3 and T1 (p <0.001); for SHe, both T2 and T3 were significantly greater than T1 (p <0.001). eNo increased above the 95% confidence interval computed from all values recorded in BOS 0 in 0/17 patients at T2, and 7/17 patients at T3; corresponding values for SHe were 10/17 at T2 and 13/17 at T3. The 7 patients who had an increase in eNO at T3 also had an increase in SHe. We conclude that 1) SHe has a better sensitivity than eNO for the early detection of graft dysfunction; 2) SHe and BOS stage 0-p have complementary roles as early markers of graft dysfunction, and adding eNO does not improve the detection.

Airway closure in microgravity

Recent single breath washout (SBW) studies in microgravity and on the ground have suggested an important effect of airway closure on gas mixing in the human lung, reflected particularly in the phase III slope of vital capacity SBW and bolus tests. In order to explore this effect, we designed a SBW in which subjects inspired 2-l from residual volume (RV) starting with a 150 ml bolus of He and SF6. In an attempt to vary the pattern of airways closure configuration before the test, the experiments were conducted in 1G and in microgravity during parabolic flight allowing the pre-test expiration to RV to be either in microgravity or at 1.8 G, with the actual test gas inhalation performed entirely in microgravity. Contrary to our expectations, the measured phase III slope and phase IV height and volume obtained from seven subjects in microgravity were essentially identical irrespective of the gravity level during the pre-test expiration to RV. The results suggest that airway closure configuration at RV before the test inspiration has no apparent impact on phases III and IV generation.

Peripheral airway function in childhood asthma, assessed by single-breath He and SF6 washout.

To assess whether the peripheral airways are involved in pediatric asthma, 10 asthmatic children (aged 8-15 years), hyperresponsive to dry-air hyperventilation challenge (DACh), performed spirometry and a vital capacity He/SF(6) single-breath washout test at rest, after DACh, and after beta(2)-therapy. The normalized phase III slopes (Sn(III)) of the expired He and SF(6) concentrations served as measures of overall ventilation inhomogeneity, and the (SF(6) - He) Sn(III) difference served to indicate where along the peripheral airways obstruction occurs. While a greater increase in the He vs. SF(6) slope indicates that obstruction has occurred in the vicinity of the acinar entrance, the reverse suggests obstruction deeper in the intraacinar airways. The mean (SD) fall in FEV(1) after DACh was 35 (14)%. Both He and SF(6) Sn(III) increased significantly (P < 0.05) after the challenge, and were restituted after beta(2)-therapy (P < 0.05). After DACh, Sn(III) increased more for He than for SF(6), resulting in a negative (SF(6) - He) Sn(III) difference (P < 0.01), which was restituted after beta(2)-therapy (P < 0.05). Even though there was no correlation between baseline FEV(1) and the magnitude of the subsequent fall in this parameter after DACh (r(2) = 0.04; n.s.), a strong correlation was found between the (SF(6) - He) Sn(III) difference at rest and its change after DACh (r(2) = 0.81; P < 0.001). We conclude that airways close to the acinar entrance participate in the airway response to DACh in asthmatic children. The magnitude of this peripheral airway response is related to the severity of resting peripheral airway dysfunction.

Gravitational independence of single-breath washout tests in recumbent dogs.

To examine the mechanisms of lung filling and emptying, Ar-bolus and N2 single-breath washout tests were conducted in 10 anesthetized dogs (prone and supine) and in three of those dogs with body rotation. Transpulmonary pressure was measured simultaneously, allowing identification of the lung volume above residual volume at which there was an inflection point in the pressure-volume curve (VIP). Although phase IV for Ar was upward, phase IV for N2 was small and variable, especially in the prone position. No significant prone to supine differences in closing capacity for Ar were seen, indicating that airway closure was generated at the same lung volumes. The maximum deflections of phase IV for Ar and N2 from extrapolated phase III slopes were smaller in the prone position, suggesting more uniform tracer gas concentrations across the lungs. VIP was smaller than the closing volume for Ar, which is consistent with the effects of well-developed collateral ventilation in dogs. Body rotation tests in three dogs did not generally cause an inversion of phase III or IV. We conclude that in recumbent dogs regional distribution of ventilation is not primarily determined by the effect of gravity, but by lung, thorax, and mediastinum interactions and/or differences in regional mechanical properties of the lungs.