Variability of peak flow measurements has been related to clinical outcomes in asthma. We hypothesised that the entropy, or information content, of airway impedance over short time scales may predict asthma exacerbation frequency.66 patients with severe asthma and 30 healthy control subjects underwent impulse oscillometry at baseline and following bronchodilator administration. On each occasion, airway impedance parameters were measured at 0.2-s intervals for 150 s, yielding a time series that was then subjected to sample entropy (SampEn) analysis.Airway impedance and SampEn of impedance were increased in asthmatic patients compared with healthy controls. In a logistic regression model, SampEn of the resistance at 5 Hz minus the resistance at 20 Hz, a marker of the fluctuation of the heterogeneity of airway constriction over time, was the variable most strongly associated with the frequent exacerbation phenotype (OR 3.23 for every 0.1 increase in SampEn).Increased airway impedance and SampEn of impedance are associated with the frequent exacerbation phenotype. Prospective studies are required to assess their predictive value.KEYWORDS: Airflow obstruction, asthma, entropy, oscillometry A cute exacerbations of asthma account for much of the morbidity and mortality associated with this condition [1]. However, there is no currently available biomarker that can accurately predict the risk of future exacerbations. Previous studies have suggested that a geometrically self-similar airway tree may confer increased risk of asthma exacerbations and that fatal asthma is associated with a reduction in the structural complexity of the airway tree [2]. Similarly, the ventilation heterogeneity observed in asthma follows power law behaviour, which predicts catastrophic closure of small airways [3]. Therefore, characterising structural complexity may have utility in predicting asthma exacerbations.It has been speculated that the temporal variability in lung function may also exhibit self-similarity at multiple time scales [4]. This would suggest that monitoring lung function over short time scales may provide insights into lung function variability over longer time scales of weeks to months, thus providing a more practical predictive tool for exacerbations. A number of tools have been utilised to characterise time series properties of physiological signals, including those that predict scaling and power law behaviour of information over multiple time scales and those that predict the probability of information repeating itself within a time series [5,6]. Fluctuations and power law behaviour observed in a time series of lung function measurements such as peak expiratory flow (PEF) may predict poor asthma control or exacerbations [7,8]. THAMRIN et al [9] found that the degree of long-range correlation (self-similarity at different temporal length scales) in PEF measurements appeared to provide additional predictive information with respect to exacerbations in mildto-moderate asthma, but less so in severe asthma.The force...

Previously reported markers of small airway obstruction do not appear to be independently associated with asthma disease expression. In contrast, the IOS parameter R20, a marker of mean airway resistance of both large and small airways, appears to have independent clinical significance. These observations require confirmation in prospective longitudinal studies.

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BACKGROUND: The respiratory mass spectrometer is the current gold-standard technique for performing multiple-breath inert gas washout (MBW), but is expensive and lacks portability. A number of alternative techniques have recently been described. OBJECTIVES: We aimed to validate, using an in vitro lung model, an open-circuit MBW system that utilises a portable photoacoustic gas analyser, with sulphur hexafluoride (SF6) as the inert tracer gas. METHODS: An acrylic glass lung model was utilised to assess the accuracy of functional residual capacity (FRC) measurements derived from MBW. Measurements were performed in triplicate at 20 combinations of simulated FRC, tidal volume and respiratory rate. FRC measured using MBW (FRCmbw) was compared to FRC calculated from the known dimensions of the model (FRCcalc). MBW was also performed in 10 healthy subjects and 14 patients with asthma. RESULTS: The MBW system measured FRC with high precision. The mean bias of FRCmbw with respect to FRCcalc was -0.4% (95% limits of agreement of -4.6 and 3.9%). The mean coefficient of variation of triplicate FRC measurements was 4.0% in vivo and 1.0% in vitro. MBW slightly underestimated low lung volumes and overestimated high lung volumes, but this did not cause a significant error in lung clearance index except at lung volumes below 1,500 ml. CONCLUSIONS: The open-circuit MBW system utilising SF6 as the inert tracer gas and a photoacoustic gas analyser is both accurate and repeatable within the adult range of lung volumes. Further modifications would be required before its use in young children or infants. The open-circuit MBW system utilising SF 6 as the inert tracer gas and a photoacoustic gas analyser is both accurate and repeatable within the adult range of lung volumes. Further modifications would be required before its use in young children or infants.

adherence and other aspects of basic management, as far as possible. We retrospectively evaluated 166 patients (median age at referral 11.7 years [4;17]; 61% males). SAFS (n¼76) was defined as specific IgE (spIgE) or skin prick test (SPT) positivity to any of Aspergillus fumigatus, Alternaria alternata or Cladosporium herbarum. Non-sensitised patients (n¼90) had negative spIgE and SPT to all fungal allergens tested. Age of onset, atopy, symptoms (asthma control test), medication usage, lung function and airway inflammation were assessed. Maintenance oral steroids were more frequently prescribed in SAFS (n¼18/76(24%) vs 8/88 (9%), p¼0.02). Symptoms and airway inflammation (assessed in sputum, bronchoalveolar lavage and endobronchial biopsy) were similar in children with and without fungal sensitisation. Conclusions Children with STRA and fungal sensitisation had lower lung function, earlier asthma onset, more atopy and more bronchodilator responsiveness. There is a need for a randomised controlled trial of antifungal therapy in paediatric SAFS.