Marcia Soares

Lung clearance index in adults with non-cystic fibrosis bronchiectasis

BackgroundLung clearance index (LCI) is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout (MBW) technique. We aimed to determine the clinical utility of LCI in non-CF bronchiectasis, and to assess two novel MBW parameters that distinguish between increases in LCI due to specific ventilation inequality (LCIvent) and increased respiratory dead space (LCIds).MethodsForty-three patients with non-CF bronchiectasis and 18 healthy control subjects underwent MBW using the sulphur hexafluoride wash-in technique, and data from 40 adults with CF were re-analysed. LCIvent and LCIds were calculated using a theoretical two-compartment lung model, and represent the proportional increase in LCI above its ideal value due to specific ventilation inequality and increased respiratory dead space, respectively.ResultsLCI was significantly raised in patients with non-CF bronchiectasis compared to healthy controls (9.99 versus 7.28, p < 0.01), and discriminated well between these two groups (area under receiver operating curve = 0.90, versus 0.83 for forced expiratory volume in one second [% predicted]). LCI, LCIvent and LCIds were repeatable (intraclass correlation coefficient > 0.75), and correlated significantly with measures of spirometric airflow obstruction.ConclusionLCI is repeatable, discriminatory, and is associated with spirometric airflow obstruction in patients with non-CF bronchiectasis. LCIvent and LCIds are a practical and repeatable alternative to phase III slope analysis and may allow a further level of mechanistic information to be extracted from the MBW test in patients with severe ventilation heterogeneity.

Domiciliary exhaled nitric oxide and eosinophilic airway inflammation in adults with asthma.

Sputum eosinophils are the gold standard measure of eosinophilic airway inflammation and there is strong evidence that titrating corticosteroid therapy to sputum eosinophils reduces the rate of asthma exacerbations [1]. However, this measurement is time consuming and requires specific technical expertise. Exhaled nitric oxide (FeNO) is a noninvasive surrogate marker of eosinophilic airway inflammation that may be measured using small portable devices. Studies of using FeNO to titrate therapy have yielded mixed results [2, 3]. However, it is possible that one-off clinic readings may not be the best method of utilising FeNO, and the home monitoring potential of FeNO has not yet been fully explored. Exhaled nitric oxide home monitoring is a promising surrogate marker of eosinophilic airway inflammation in asthma http://ow.ly/108ak4

Particles in exhaled air (PExA): non-invasive phenotyping of small airways disease in adult asthma

RATIONALE Asthma is often characterised by inflammation, damage and dysfunction of the small airways, but no standardised biomarkers are available. OBJECTIVES Using a novel approach-particles in exhaled air (PExA)-we sought to (a) sample and analyse abundant protein biomarkers: surfactant protein A (SPA) and albumin in adult asthmatic and healthy patients and (b) relate protein concentrations with physiological markers using phenotyping. METHODS 83 adult asthmatics and 21 healthy volunteers were recruited from a discovery cohort in Leicester, UK, and 32 adult asthmatics as replication cohort from Sweden. Markers of airways closure/small airways dysfunction were evaluated using forced vital capacity, impulse oscillometry and multiple breath washout. SPA/albumin from PEx (PExA sample) were analysed using ELISA and corrected for acquired particle mass. Topological data analysis (TDA) was applied to small airway physiology and PExA protein data to identify phenotypes. RESULTS PExA manoeuvres were feasible, including severe asthmatic subjects. TDA identified a clinically important phenotype of asthmatic patients with multiple physiological markers of peripheral airway dysfunction, and significantly lower levels of both SPA and albumin. CONCLUSION We report that the PExA method is feasible across the spectrum of asthma severity and could be used to identify small airway disease phenotypes.

P69 An exploratory study to investigate the relationship between fraction of exhaled nitric oxide (FeNO) home monitoring and eosinophilic airway inflammation in adults with severe asthma

Introduction FeNO is a non-invasive surrogate marker of corticosteroid-responsive airway inflammation that may be measured using small portable devices. We aimed to determine (i) the reliability and feasibility of twice-daily FeNO home monitoring in adults with severe asthma, as well as (ii) to explore the relationship between serial FeNO measurements and gold standard markers of eosinophilic airway inflammation. Methods Ten patients with severe asthma (BTS treatment steps 4/5) were recruited from the Difficult Asthma Clinic at Glenfield Hospital. Patients were provided with portable FeNO monitors (NOBreath, Bedfont Scientific Ltd., Maidstone, UK) for a period of eight weeks, and asked to record twice-daily FeNO (at a flow rate of 50 ml/s) and PEF readings, as well as daily visual analogue scores for cough, breathlessness and wheeze, using paper diaries. They attended fortnightly visits during the study period, at which they underwent sputum induction and full blood count. Results Nine patients completed the study. The median (range) intraclass correlation coefficient of triplicate FeNO measurements was 0.83 (0.78 – 0.92) for morning measurements and 0.82 (0.71 – 0.97) for evening measurements. There was a median of 7.1% missing data (range 2.7 – 14.3%). FeNO measurements correlated strongly with sputum and blood eosinophil counts, with the strongest correlations observed with a 9-day FeNO moving average, and a lag time of -1 day for sputum eosinophils (r = 0.571, p < 0.001) and -2 days for blood eosinophil counts (r = 0.691, p < 0.0001), suggesting that changes in sputum and blood eosinophil counts tended to precede changes in FeNO by 1 and 2 days respectively. In contrast there were no consistent relationships seen between FeNO and either PEF or visual analogue scores. Conclusion Home monitoring of FeNO is feasible and the measurements are repeatable. Daily FeNO measurements correlate strongly with sputum and blood eosinophil counts, and are most useful when a moving average is taken over approximately 9 days. Further studies are required to determine if daily FeNO measurements may have a role in predicting loss of asthma control or exacerbations.

S120 Hyperpolarised 3HE diffusion MRI and multiple breath inert gas washout in patients with asthma

Background Multiple breath inert gas washout (MBW) is a technique for detecting abnormal ventilation distribution in patients with asthma and other airway diseases. Scond and Sacin are measures of convective-dependent inhomogeneity (CDI) and diffusion-convection-dependent inhomogeneity (DCDI) respectively. Hyperpolarised 3He diffusion magnetic resonance imaging (3He-MRI) may be used to probe lung microstructure at a variety of length scales, with short timescale (14 ms) apparent diffusion coefficient (ADC) corresponding to diffusion within an alveolus or a single acinar airway, and long timescale (1.5s–6s) ADC corresponding to diffusion path lengths of up to 8mm. We aimed to determine the microstructural correlates of Scond and Sacin in patients with asthma, using 3He-MRI. Methods Twenty-nine patients with asthma underwent MBW using sulphur hexafluoride as the inert tracer gas, and the parameters Scond and Sacin were calculated. 3He-MRI was performed and the ADC was calculated at both short (14ms) and long (1.5s, 3s and 6s) timescales. 3He-MRI data was also fitted to a previously reported geometrical model of the acinus (Yablonskiy DA et al , J Appl Physiol. 2009;107(4):1258–65), and estimates of the alveolar duct outer radius (R) and alveolar sleeve width (h) were derived. Results Correlations between MBW and 3He-MRI parameters are shown in Table 1. The approximate length scales probed by short and long timescale ADC are also indicated for reference. Significant positive correlations were observed between Sacin and ADC at 14ms, 1.5s and 3s, but not 6s. In a stepwise linear regression model, ADC at 1.5s was the only significant determinant of Sacin, with a model R2 of 0.334. Scond did not correlate significantly with any of the MRI parameters. Yablonskiy model estimates of alveolar sleeve width and alveolar duct outer radius did not correlate significantly with either Scond or Sacin. Abstract S120 Table 1. Correlations between multiple breath washout and 3He-MRI parameters Scond Sacin ADC 14 ms (0.5mm) .264 .470* ADC 1.5s (4mm) -.080 .578** ADC 3s (5.5mm) -.050 .471* ADC 6s (8mm) -.058 .214 Alveolar duct outer radius (R) .113 .273 Alveolar sleeve width (h) .239 -.002 ADC = apparent diffusion coefficient. Significant correlations are indicated * (p < 0.05) or ** (p < 0.01). Conclusion Sacin in patients with asthma is associated with an elevated ADC at 1.5s, corresponding to length scales of the order of 4mm. This suggests that DCDI in asthma is associated with structural asymmetries at the level of the distal acinar airways and/or collateral ventilation between parallel intra-acinar airways.