Tidal volume single breath washout of two tracer gases--a practical and promising lung function test

Background Small 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). Methods The 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. Results USFM 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%. Conclusion The 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.

Fluctuation phenotyping based on daily fraction of exhaled nitric oxide values in asthmatic children

Fraction of exhaled nitric oxide (Feno), a marker of airway inflammation, has been proposed to be useful for asthma management, but conclusions are inconsistent. This might be due to the failure of mean statistics to characterize individual variability in Feno values, which is possibly a better indicator of asthma control than single measurements.

End-tidal CO(2). An important parameter for a correct interpretation in functional brain studies using speech tasks

The aim was to investigate the effect of different speech tasks, i.e. recitation of prose (PR), alliteration (AR) and hexameter (HR) verses and a control task (mental arithmetic (MA) with voicing of the result on end-tidal CO2 (PETCO2), cerebral hemodynamics and oxygenation. CO2 levels in the blood are known to strongly affect cerebral blood flow. Speech changes breathing pattern and may affect CO2 levels. Measurements were performed on 24 healthy adult volunteers during the performance of the 4 tasks. Tissue oxygen saturation (StO2) and absolute concentrations of oxyhemoglobin ([O2Hb]), deoxyhemoglobin ([HHb]) and total hemoglobin ([tHb]) were measured by functional near-infrared spectroscopy (fNIRS) and PETCO2 by a gas analyzer. Statistical analysis was applied to the difference between baseline before the task, 2 recitation and 5 baseline periods after the task. The 2 brain hemispheres and 4 tasks were tested separately. A significant decrease in PETCO2 was found during all 4 tasks with the smallest decrease during the MA task. During the recitation tasks (PR, AR and HR) a statistically significant (p < 0.05) decrease occurred for StO2 during PR and AR in the right prefrontal cortex (PFC) and during AR and HR in the left PFC. [O2Hb] decreased significantly during PR, AR and HR in both hemispheres. [HHb] increased significantly during the AR task in the right PFC. [tHb] decreased significantly during HR in the right PFC and during PR, AR and HR in the left PFC. During the MA task, StO2 increased and [HHb] decreased significantly during the MA task. We conclude that changes in breathing (hyperventilation) during the tasks led to lower CO2 pressure in the blood (hypocapnia), predominantly responsible for the measured changes in cerebral hemodynamics and oxygenation. In conclusion, our findings demonstrate that PETCO2 should be monitored during functional brain studies investigating speech using neuroimaging modalities, such as fNIRS, fMRI to ensure a correct interpretation of changes in hemodynamics and oxygenation.

Influence of end-expiratory level and tidal volume on gravitational ventilation distribution during tidal breathing in healthy adults

Our understanding of regional filling of the lung and regional ventilation distribution is based on studies using stepwise inhalation of radiolabelled tracer gases, magnetic resonance imaging and positron emission tomography. We aimed to investigate whether these differences in ventilation distribution at different end-expiratory levels (EELs) and tidal volumes (V (T)s) held also true during tidal breathing. Electrical impedance tomography (EIT) measurements were performed in ten healthy adults in the right lateral position. Five different EELs with four different V (T)s at each EEL were tested in random order, resulting in 19 combinations. There were no measurements for the combination of the highest EEL/highest V (T). EEL and V (T) were controlled by visual feedback based on airflow. The fraction of ventilation directed to different slices of the lung (VENT(RL1)-VENT(RL8)) and the rate of the regional filling of each slice versus the total lung were analysed. With increasing EEL but normal tidal volume, ventilation was preferentially distributed to the dependent lung and the filling of the right and left lung was more homogeneous. With increasing V (T) and maintained normal EEL (FRC), ventilation was preferentially distributed to the dependent lung and regional filling became more inhomogeneous (p < 0.05). We could demonstrate that regional and temporal ventilation distribution during tidal breathing was highly influenced by EEL and V (T).

Lung-function tests in neonates and infants with chronic lung disease: tidal breathing and respiratory control

This paper is the fourth in a series of reviews that will summarize available data and critically discuss the potential role of lung-function testing in infants with acute neonatal respiratory disorders and chronic lung disease of infancy. The current paper addresses information derived from tidal breathing measurements within the framework outlined in the introductory paper of this series, with particular reference to how these measurements inform on control of breathing. Infants with acute and chronic respiratory illness demonstrate differences in tidal breathing and its control that are of clinical consequence and can be measured objectively. The increased incidence of significant apnea in preterm infants and infants with chronic lung disease, together with the reportedly increased risk of sudden unexplained death within the latter group, suggests that control of breathing is affected by both maturation and disease. Clinical observations are supported by formal comparison of tidal breathing parameters and control of breathing indices in the research setting.

Fluctuation analysis of lung function as a predictor of long-term response to beta2-agonists

The response to beta(2)-agonists differs between asthmatics and has been linked to subsequent adverse events, even death. Possible determinants include beta(2)-adrenoceptor genotype at position 16, lung function and airway hyperresponsiveness. Fluctuation analysis provides a simple parameter alpha measuring the complex correlation properties of day-to-day peak expiratory flow. The present study investigated whether alpha predicts clinical response to beta(2)-agonist treatment, taking into account other conventional predictors. Analysis was performed on previously published twice-daily peak expiratory flow measurements in 66 asthmatic adults over three 6-month randomised order treatment periods: placebo, salbutamol and salmeterol. Multiple linear regression was used to determine the association between alpha during the placebo period and response to treatment (change in the number of days with symptoms), taking into account other predictors namely beta(2)-adrenoceptor genotype, lung function and its variability, and airway hyperresponsiveness. The current authors found that alpha measured during the placebo period considerably improved the prediction of response to salmeterol treatment, taking into account genotype, lung function or its variability, or airway hyperresponsiveness. The present study provides further evidence that response to beta(2)-agonists is related to the time correlation properties of lung function in asthma. The current authors conclude that fluctuation analysis of lung function offers a novel predictor to identify patients who may respond well or poorly to treatment.

Relative impact of respiratory muscle activity on tidal flow and end expiratory volume in healthy neonates

INTRODUCTION: It has been suggested that infants dynamically regulate their tidal flow and end-expiratory volume level. The interaction between muscle activity, flow and lung volume in spontaneously sleeping neonates is poorly studied, since it requires the assessment of transcutaneous electromyography of respiratory muscles (rEMG) in matched comparison to lung function measurements. METHODS: After determining feasibility and repeatability of rEMG in 20 spontaneously sleeping healthy neonates, we measured the relative impact of intercostal and diaphragmatic EMG activity in direct comparison to the resulting tidal flow and FRC. RESULTS: We found good feasibility, repeatability and correlation of timing indices between rEMG activity and flow. The rEMG amplitude was significantly dependent on the resistive load of the face mask. Diaphragm and intercostal muscle activity commenced prior to the onset of flow and remained active during the expiratory cycle. The relative contribution of intercostal and diaphragmatic activity to flow was variable and changed dynamically. CONCLUSION: Using matched rEMG, air flow and lung volume measurements, we have found good feasibility and repeatability of intercostal and diaphragm rEMG measurements and provide the first quantitative measures of the temporal relationship between muscle activity and flow in spontaneously sleeping healthy neonates. Lung mechanical function is dynamically regulated and adapts on a breath to breath basis. So, non-invasive rEMG measurements alone or in combination with lung function might provide a more comprehensive picture of pulmonary mechanics in future studies. The data describing the timing of EMG and flow may be important for future studies of EMG triggered mechanical ventilation.

Risk of severe asthma episodes predicted from fluctuation analysis of airway function

Asthma is an increasing health problem worldwide, but the long-term temporal pattern of clinical symptoms is not understood and predicting asthma episodes is not generally possible. We analyse the time series of peak expiratory flows, a standard measurement of airway function that has been assessed twice daily in a large asthmatic population during a long-term crossover clinical trial. Here we introduce an approach to predict the risk of worsening airflow obstruction by calculating the conditional probability that, given the current airway condition, a severe obstruction will occur within 30 days. We find that, compared with a placebo, a regular long-acting bronchodilator (salmeterol) that is widely used to improve asthma control decreases the risk of airway obstruction. Unexpectedly, however, a regular short-acting beta2-agonist bronchodilator (albuterol) increases this risk. Furthermore, we find that the time series of peak expiratory flows show long-range correlations that change significantly with disease severity, approaching a random process with increased variability in the most severe cases. Using a nonlinear stochastic model, we show that both the increased variability and the loss of correlations augment the risk of unstable airway function. The characterization of fluctuations in airway function provides a quantitative basis for objective risk prediction of asthma episodes and for evaluating the effectiveness of therapy.

Pelagic molybdenum concentration anomalies and the impact of sediment resuspension on the molybdenum budget in two tidal systems of the North Sea

The seasonal dynamics of molybdenum (Mo) were studied in the water column of two tidal basins of the German Wadden Sea (Sylt-Rømø and Spiekeroog) between 2007 and 2011. In contrast to its conservative behaviour in the open ocean, both, losses of more than 50% of the usual concentration level of Mo in seawater and enrichments up to 20% were observed repeatedly in the water column of the study areas. During early summer, Mo removal by adsorption on algae-derived organic matter (e.g. after Phaeocystis blooms) is postulated to be a possible mechanism. Mo bound to organic aggregates is likely transferred to the surface sediment where microbial decomposition enriches Mo in the pore water. First δ98/95Mo data of the study area disclose residual Mo in the open water column being isotopically heavier than MOMo (Mean Ocean Molybdenum) during a negative Mo concentration anomaly, whereas suspended particulate matter shows distinctly lighter values. Based on field observations a Mo isotope enrichment factor of ε = −0.3‰ has been determined which was used to argue against sorption on metal oxide surfaces. It is suggested here that isotope fractionation is caused by biological activity and association to organic matter. Pelagic Mo concentration anomalies exceeding the theoretical salinity-based concentration level, on the other hand, cannot be explained by replenishment via North Sea waters alone and require a supply of excess Mo. Laboratory experiments with natural anoxic tidal flat sediments and modelled sediment displacement during storm events suggest fast and effective Mo release during the resuspension of anoxic sediments in oxic seawater as an important process for a recycling of sedimentary sulphide bound Mo into the water column.

End-tidal CO2 pressure: an important parameter for a correct interpretation of changes in cerebral hemodynamics and oxygenation measured with functional near infrared spectrophotometry (fNIRS)

The aim of the present study was to investigate the effects of different speech tasks (recitation of prose (PR), alliteration (AR) and hexameter (HR) verses) and a control task (mental arithmetic (MA) with voicing of the result) on endtidal CO2 (ET-CO2), cerebral hemodynamics; i.e. total hemoglobin (tHb) and tissue oxygen saturation (StO2). tHb and StO2 were measured with a frequency domain near infrared spectrophotometer (ISS Inc., USA) and ET-CO2 with a gas analyzer (Nellcor N1000). Measurements were performed in 24 adult volunteers (11 female, 13 male; age range 22 to 64 years) during task performance in a randomized order on 4 different days to avoid potential carry over effects. Statistical analysis was applied to test differences between baseline, 2 recitation and 5 recovery periods. The two brain hemispheres and 4 tasks were tested separately. Data analysis revealed that during the recitation tasks (PR, AR and HR) StO2 decreased statistically significant (p < 0.05) during PR and AR in the right prefrontal cortex (PFC) and during AR and HR in the left PFC. tHb showed a significant decrease during HR in the right PFC and during PR, AR and HR in the left PFC. During the MA task, StO2 increased significantly. A significant decrease in ET-CO2 was found during all 4 tasks with the smallest decrease during the MA task. In conclusion, we hypothesize that the observed changes in tHb and StO2 are mainly caused by an altered breathing during the tasks that led a lowering of the CO2 content in the blood provoked a cerebral CO2 reaction, i.e. a vasoconstriction of blood vessels due to decreased CO2 pressure and thereby decrease in cerebral blood volume. Therefore, breathing changes should be monitored during brain studies involving speech when using functional near infrared spectroscopy (fNIRS) to ensure a correct interpretation of changes in hemodynamics and oxygenation.

The dementia cognitive fluctuation scale, a new psychometric test for clinicians to identify cognitive fluctuations in people with dementia.

OBJECTIVES Cognitive fluctuation (CF) is a common feature of dementia and a core diagnostic symptom for dementia with Lewy bodies (DLB). CF remains difficult to accurately and reliably detect clinically. This study aimed to develop a psychometric test that could be used by clinicians to facilitate the identification of CF and improve the recognition and diagnosis of DLB and Parkinson disease, and to improve differential diagnosis of other dementias. METHODS We compiled a 17-item psychometric test for identifying CF and applied this measure in a cross-sectional design. Participants were recruited from the North East of England, and assessments were made in individuals' homes. We recruited people with four subtypes of dementia and a healthy comparison group, and all subjects were administered this pilot scale together with other standard ratings. The psychometric properties of the scale were examined with exploratory factor analysis. We also examined the ability of individual items to identify CF to discriminate between dementia subtypes. The sensitivity and specificity of discriminating items were explored along with validity and reliability analyses. RESULTS Participants comprised 32 comparison subjects, 30 people with Alzheimer disease, 30 with vascular dementia, 29 with DLB, and 32 with dementia associated with Parkinson disease. Four items significantly discriminated between dementia groups and showed good levels of sensitivity (range: 78.6%-80.3%) and specificity (range: 73.9%-79.3%). The scale had very good levels of test-retest (Cronbach's alpha: 0.82) and interrater (0.81) reliabilities. The four items loaded onto three different factors. These items were: 1) marked differences in functioning during the daytime; 2) daytime somnolence; 3) daytime drowsiness; and 4) altered levels of consciousness during the day. CONCLUSIONS We identified four items that provide valid, sensitive, and specific questions for reliably identifying CF and distinguishing the Lewy body dementias from other major causes of dementia (Alzheimer disease and vascular dementia).