Cardiovascular and Respiratory Interactions in Idiopathic Pulmonary Fibrosis by Extended Partial Directed Coherence: Short-term Effects of Supplemental Oxygen.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that can lead to chronic arterial hypoxemia, hypercapnia, and dyspnea. To improve clinical symptoms in IPF patients, supplemental oxygen (SupplO2) has been prescribed with the aim to maintain SpO2 level, and consequently to relieve dyspnea, increase physical activity and improve quality of life. In this study, we investigated the effect of disease and short-term SupplO2 on cardiovascular and respiratory autonomic regulation. Linear and nonlinear indices were extracted from the beat-to-beat variability of heart rate (HR), systolic (SYS) blood pressure and respiration (RESP) in IPF patients and healthy subjects spontaneously breathing ambient air (AA) and during SupplO2 at 3 L/min. It was found that the effects on autonomic nervous systems (ANS) regulation were better demonstrated by the Granger causality (GC) method. GC was significantly higher (p<0.01) in patients compared to controls for the interactions RESP→SYS and BBI→SYS.Clinical Relevance-Short-term SupplO2 in IPF could adversely affect systolic blood pressure variability in particular. This study may help in the management of SupplO2 administration.

Time-Frequency Analysis of Cardiovascular Variability during an Orthostatic Stress by Complete EMD.

Diverse analysis techniques have been used to comprehend the regulation by the autonomic nervous system (ANS) of the cardiovascular system when a human being faces a stressor. Recently, however, the complete ensemble empirical mode decomposition (EMD) with adaptive noise (CEEMDAN) allows analyzing nonstationary signals in a nonlinear and time- variant way. Consequently, CEEMDAN may provide a means to obtain clues about ANS regulation in health and disease. In this study, we analyze the average Hilbert-Huang spectrum (HHS) of cardiovascular variability signals by CEEMDAN during a head-up tilt test (HUTT) in 12 healthy female subjects and 18 orthostatic intolerance female patients. Beat-to-beat intervals (BBI) as well as systolic (SYS) blood pressure variability time series were analyzed. In addition, instantaneous amplitudes and frequencies of specific intrinsic mode functions (IMF) were investigated separately to define the influence of the disease on ANS regulation. Female groups demonstrated statistical differences in the high-frequency band of BBI but higher differences for the high and low-frequency bands of SYS from the mechanical transition of HUTT.Clinical Relevance- A relevant outcome of the study is the average HHS of healthy female subjects along HUTT. This HHS may be used as reference to help diagnose OI when HHS of the cardiovascular variability signals of any subject deviates from the normal course.

Characterization of EHG Contractions at Pregnancy and Term Labor by Multiscale Entropy Analysis.

Monitoring uterine activity by electrohysterogram (EHG), associated with contractions both in pregnancy and labor, may contribute to the knowledge for evaluating possible risks to the binomial mother-fetus. In this context, the aim of the present study was to explore the complexity of EHG generated by women during the third trimester of pregnancy (group P) and at term labor (group L). The EHG was obtained by band-pass filtering in the range from 0.1 to 3 Hz the monopolar raw signal of the electrode number 1, of a 4-by-4 sensor array, which was located near to the tocodynamometer transducer. Multiscale entropy (MSE) analysis measures the entropy over multiple time scales to provide the complexity of the EHG time series. The results pointed out that such nonlinear technique has the potential to discriminate contractions from both groups using the area under the MSE curve (AUC) as index. The highest complexity was obtained for group P (N= 8) as AUC was 13.9233 ± 0.2015 while the lowest complexity was for group L, with N=8 and AUC of 5.1675 ± 0.0783 (p<; 0.0001). Consequently, the complexity of EHG by MSE could provide an index to discriminate between the electrical uterine activity generated during pregnancy or at labor.

Temporal cardiovascular causality during orthostatic stress by extended partial directed coherence.

The aim of this study was to investigate the temporal dynamic behavior of cardiovascular interactions between heart period and systolic blood pressure during a 20-min head-up tilt test at 70° in young women with orthostatic intolerance compared to healthy women. Methods included the lagged and extended partial directed coherence applied to short-term windows shifted by 5 seconds, extracted from a multivariate set of cardiovascular and respiratory time series. Findings revealed significantly increased information flow (p <; 0.01) in patients from: a) heart period to blood pressure during supine position which subsequently decreased and b) blood pressure to heart period during the progression of orthostatic phase. Controls developed balanced cardiovascular interactions with smaller information flows than patients.

Study of impaired cardiovascular and respiratory coupling during orthostatic stress based on joint symbolic dynamics.

The present study investigates the instantaneous coupling among the cardiac, vascular, and respiratory systems, using the heart rate, respiration, and systolic and diastolic blood pressure variability in 12 healthy and 16 vasovagal syncope female subjects during a head-up tilt (HUT) testing protocol at 70° This study contributes to the coupling analysis by using a nonlinear joint symbolic dynamics (JSD) in a high-temporal resolution scheme, based on 5 min segments of the time series that are shifted every minute. For each segment, a bivariate JSD matrix was constructed to obtain global and local coupling indices in accordance to Shannon's entropy and the probability of occurrence of various bivariate words, respectively. The novel approach revealed important findings in the coupling dynamics of the systems, thus allowing the detection of group differences during the early orthostatic phase, and during the HUT test, before the occurrence of any pre-syncopal symptoms. In patients, the global indices indicated a significant decrease of cardiovascular coupling, starting at 10 min after the tilt-up, manifested by reduced baroreflex sensitivity and cardiorespiratory coupling that was initiated 8 min after the onset of the orthostatic phase (OP). A decreased autonomic control on cardiovascular-respiratory couplings was further evidenced by increased alterations of the JSD indices during the OP compared to the supine position in patients compared to controls. Furthermore, findings based on local indices demonstrated that female patients showed reductions and disengagements in cardiovascular (p < 0.001) and cardiorespiratory (p < 0.01) couplings, as early as the first 5 min and during the complete OP.

Multivariate symbolic dynamics for analysis of respiratory-cardiovascular interactions.

In this work, a nonlinear method to study multivariate interactions, called multivariate symbolic dynamics (MSD), was introduced. The usefulness of this technique was studied on respiratory-cardiovascular data from young women with vasovagal syncope (VVS) and from healthy subjects. The study included 16 female patients diagnosed with VVS and 24 age-matched healthy subjects (12 women). All subjects were enrolled in a head-up tilt (HUT) test, breathing normally, including 5 min of supine position and 18 to 28 min of 70° orthostatic phase. The MSD parameters were dynamically obtained for 5-min windows shifted by 1 min during HUT test. In supine position there were no considerable differences. During orthostatic phase, parameters from MSD showed a highly significantly (p=0.00005) increased occurrence of impaired respiratory-cardiovascular interactions in female patients susceptible to vasovagal syncope. This study provided promising results for a new multivariate method to investigate respiratory-cardiovascular interactions.

Men and women should be separately investigated in studies of orthostatic challenge due to different gender-related dynamics of autonomic response.

In studies of autonomic regulation during orthostatic challenges only a few nonlinear methods have been considered without investigating the effect of gender in young controls. Especially, the temporal development of the autonomic regulation has not yet been explicitly analyzed using short-term segments in supine position, transition and orthostatic phase (OP). In this study, nonlinear analysis of cardiovascular and respiratory time series was performed to investigate how nonlinear indices are dynamically changing with respect to gender during orthostatic challenges. The analysis was carried out using shifted short-term segments throughout a head-up tilt test in 24 healthy subjects, 12 men (26 ± 4 years) and 12 age-matched women (26 ± 5 years), at supine position and during OP at 70°. The nonlinear methods demonstrated statistical differences in the autonomic regulation between males and females. Orthostatic stress caused significantly decreased heart rate variability due to increased sympathetic activity mainly in men, already at the beginning and during the complete OP, revealed by (a) increased occurrence of specific word types with constant fluctuations as pW111 from symbolic dynamics, (b) augmented fractal correlation properties by the short-term index alpha1 from detrended fluctuation analysis, (c) increased slope indices (21ati and 31ati) from auto-transinformation and (d) augmented time irreversibility indices demonstrating more temporal asymmetries and nonlinear dynamics in men than in women. After tilt-up, both men and women increased their sympathetic activity but in a different way. Time-dependent gender differences during orthostatic challenge were shown directly between men and women or indirectly comparing baseline and different temporal stages of OP. The proposed dynamical study of autonomic regulation has the advantage of screening the fluctuations of the sympathetic and vagal activities that can be quantified by the temporal behavior of nonlinear indices. The findings in this paper strongly suggest the need for gender separation in studies of the dynamics of autonomic regulation during orthostatic challenge.

Orthostatic stress causes immediately increased blood pressure variability in women with vasovagal syncope.

The cardiovascular and respiratory autonomic nervous regulation has been studied mainly by hemodynamic responses during different physical stressors. In this study, dynamics of autonomic response to an orthostatic challenge was investigated by hemodynamic variables and by diverse linear and nonlinear indices calculated from time series of beat-to-beat intervals (BBI), respiratory cycle duration (RESP), systolic (SYS) and diastolic (DIA) blood pressure. This study included 16 young female patients (SYN) with vasovagal syncope and 12 age-matched female controls (CON). The subjects were enrolled in a head-up tilt (HUT) test, breathing normally, including 5min of baseline (BL, supine position) and 18min of 70° orthostatic phase (OP). To increase the time resolution of the analysis the time series were segmented in five-minute overlapping windows with a shift of 1min. Hemodynamic parameters did not show any statistical differences between SYN and CON. Time domain linear analysis revealed increased respiratory frequency and increased blood pressure variability (BPV) in patients during OP meaning increased sympathetic activity and vagal withdrawal. Frequency domain analysis confirmed a predominance of sympathetic tone by steadily increased values of low over high frequency power in BBI and of low frequency power in SYS and DIA in patients during OP. The nonlinear analysis by symbolic dynamics seemed to be highly suitable for differentiation of SYN and CON in the early beginning of OP, i.e., 5min after tilt-up. In particular the index SYS_plvar3 showed less patterns of low variability in patients reflecting a steadily increase in both BPV and sympathetic activity. The proposed dynamical analysis could lead to a better understanding of the temporal underlying mechanisms in healthy subjects and patients under orthostatic stress.

Delta space plot analysis of cardiovascular coupling in vasovagal syncope during orthostatic challenge.

In this work, a graphical method to study cardiovascular coupling, called delta space plot analysis (DSPA), was introduced. The graphical representation is susceptible to be parameterized in shape and orientation. The usefulness of this technique was studied on cardiovascular data from patients with vasovagal syncope (VVS) and from controls. The study included 15 female patients diagnosed with VVS and 11 age-matched healthy female subjects. All subjects were enrolled in a head-up tilt (HUT) test, breathing normally, including 5 minutes of supine position (baseline) and 18 minutes of 70° orthostatic phase. The DSPA parameters were obtained at different times during the HUT test, i.e., at baseline, early (first 5 min) and late (10-15 min) orthostatic phases. In baseline there were no considerable differences between female controls and female patients. During the late orthostatic phase, parameters from DSPA showed highly significantly (p=0.000003) reduced cardiovascular coupling in patients. Findings indicated a loss of control on cardiovascular coupling in female patients susceptible to vasovagal syncope during orthostatic challenge. In addition, this study provided promising results for a new graphical method to investigate cardiovascular coupling.

Temporal analysis of cardiac autonomic regulation during orthostatic challenge by short-term symbolic dynamics.

The gradual shift of cardiac autonomic regulation toward sympathetic predominance and vagal withdrawal during graded head-up tilt test in young controls has been demonstrated by parameters from symbolic dynamics obtained from short-term heart rate variability (HRV) analysis. In this study, the influence of gender and vasovagal syncope (VVS) on the autonomic response to an orthostatic challenge was investigated by HRV analysis using short-term symbolic dynamics (STSD). This study included 24 healthy young subjects (12 males; 12 age-matched females) and 16 female patients diagnosed with VVS. All subjects were enrolled in a head-up tilt (HUT) test, breathing normally, including 5 minutes of supine position (baseline) and 20-40 minutes of 70° orthostatic phase. The STSD parameters were obtained following their behavior at different times during the HUT test, i.e., at baseline, early and middle orthostatic phases. Gender differences including increased sympathetic activity in men were already present in baseline and in the middle tilt phase. In baseline there were no differences between female controls and female patients, but parameters from STSD showed highly significantly (p=0.0007) reduced heart rate variability due to increased sympathetic activity in female patients in the middle tilt phase. Furthermore a new nonlinear index for the estimation of sympatho-vagal balance was introduced.

Assessment of time-frequency representation techniques for thoracic sounds analysis.

A step forward in the knowledge about the underlying physiological phenomena of thoracic sounds requires a reliable estimate of their time-frequency behavior that overcomes the disadvantages of the conventional spectrogram. A more detailed time-frequency representation could lead to a better feature extraction for diseases classification and stratification purposes, among others. In this respect, the aim of this study was to look for an omnibus technique to obtain the time-frequency representation (TFR) of thoracic sounds by comparing generic goodness-of-fit criteria in different simulated thoracic sounds scenarios. The performance of ten TFRs for heart, normal tracheal and adventitious lung sounds was assessed using time-frequency patterns obtained by mathematical functions of the thoracic sounds. To find the best TFR performance measures, such as the 2D local (ρ(mean)) and global (ρ) central correlation, the normalized root-mean-square error (NRMSE), the cross-correlation coefficient (ρ(IF)) and the time-frequency resolution (res(TF)) were used. Simulation results pointed out that the Hilbert-Huang spectrum (HHS) had a superior performance as compared with other techniques and then, it can be considered as a reliable TFR for thoracic sounds. Furthermore, the goodness of HHS was assessed using noisy simulated signals. Additionally, HHS was applied to first and second heart sounds taken from a young healthy male subject, to tracheal sound from a middle-age healthy male subject, and to abnormal lung sounds acquired from a male patient with diffuse interstitial pneumonia. It is expected that the results of this research could be used to obtain a better signature of thoracic sounds for pattern recognition purpose, among other tasks.

Assessing the variability in respiratory acoustic thoracic imaging (RATHI).

Multichannel analysis of lung sounds (LSs) has enabled the generation of a functional image for the temporal and spatial study of LS intensities in healthy and diseased subjects; this method is known as respiratory acoustic thoracic imaging (RATHI). This acoustic imaging technique has been applied to diverse pulmonary conditions, but it is important to contribute to the understanding of RATHI characteristics, such as acoustic spatial distribution, dependence on airflow and variability. The purpose of the current study is to assess the intra-subject and inter-subject RATHI variabilities in a cohort of 12 healthy male subjects (24.3±1.5 years) using diverse quantitative indices. The indices were obtained directly from the acoustic image and did not require scores from human raters, which helps to prevent inter-observer variability. To generate the acoustic image, LSs were acquired at 25 positions on the posterior thoracic surface by means of airborne sound sensors with a wide frequency band from 75 up to 1000 Hz under controlled airflow conditions at 1.0, 1.5 and 2.0 L/s. To assess intra-subject variability, the degree of similitude between inspiratory acoustic images was evaluated through quadratic mutual information based on the Cauchy-Schwartz inequality (I(CS)). The inter-subject variability was assessed by an image registration procedure between RATHIs and X-ray images to allow the computation of average and variance acoustic image in the same coordinate space. The results indicated that intra-subject RATHI similitude, reflected by I(CS-global), averaged 0.960±0.008, 0.958±0.008 and 0.960±0.007 for airflows of 1.0, 1.5, and 2L/s, respectively. As for the inter-subject variability, the variance image values for three airflow conditions indicated low image variability as they ranged from 0.01 to 0.04. In conclusion, the assessment of intra-subject and inter-subject variability by similitude indices indicated that the acoustic image pattern is repeatable along different respiratory cycles and across different subjects. Therefore, RATHI could be used to explore different aspects of spatial distribution and its association with regional pulmonary ventilation.

Gender differences in cardiovascular and cardiorespiratory coupling in healthy subjects during head-up tilt test by Joint Symbolic Dynamics.

Gender related-differences in the autonomic regulation of the cardiovascular and cardiorespiratory systems have been studied mainly by hemodynamic responses during different physical stressors. In this study, the influence of gender on the autonomic response to an orthostatic challenge was investigated by obtaining the cardiovascular and cardiorespiratory coupling using the nonlinear technique known as joint symbolic dynamics (JSD) representation. This study includes 24 healthy young subjects. Males (N=12) and age-matched females (N=12) were enrolled in a head-up tilt (HUT) test, breathing normally, including 5 minutes of supine position (baseline) and 25-40 minutes of 70° orthostatic phase. The cardiovascular and cardiorespiratory couplings were obtained at baseline, early and middle orthostatic phases. Although in baseline there were some gender differences, parameters from JSD showed highly significant (p=0.0004) differences in specific cardiovascular coupling patterns in the early tilt phase. Furthermore, JSD analysis revealed that in males, due to increased sympathetic activity, exist a lower degree of cardiovascular coupling accompanied with an increased occurrence of tachycardic patterns. On the other hand, the cardiorespiratory coupling revealed only very few slightly significant differences in all three phases.

Adventitious lung sounds imaging by ICA-TVAR scheme.

Adventitious lung sounds (ALS) as crackles and wheezes are present in different lung alterations and their automated characterization and recognition have become relevant. In fact, recently their 2D spatial distribution (SD) imaging has been proposed to help diagnose of pulmonary diseases. In this work, independent component analysis (ICA) by infomax was used to find crackles sources and from them to apply a time variant autoregressive model (TVAR) to count and imaging the ALS. The proposed methodology was assessed on multichannel LS recordings by embedding simulated fine crackles with known SD in recorded normal breathing sounds. Afterwards, the adventitious image of two patients with fibrosis and emphysema were obtained and contrasted with the classical pulmonary auscultation provided by a pneumologist. The results showed that combining ICA and TVAR leads to a robust methodology to imaging ALS.

Characterization of EHG contractions at term labor by nonlinear analysis.

Uterine electromyogram on the abdomen of pregnant women (electrohysterogram, EHG) plays an interesting role to evaluate possible risks to the binomial mother-fetus. In this sense, the present study explored the characterization of contractions by EHG during active phase of labor at term in a population at low risk. The goal was to investigate the differences in the contractions generated by women that evolve labor to a vaginal delivery (group 1) to those associated with caesarean section (group 2). Abdominal signals were acquired using Ag-AgCl electrodes in a bipolar configuration and the EHG was obtained by band-pass filtering in the range of 0.3 to 4 Hz. Sample entropy (SampEn) was used to calculate the irregularity of manually selected contractions of the EHG time series. The results showed that it is plausible to discriminate contractions from both groups as the average SampEn was 2.1359 with a standard deviation of 0.0583 for group 1 (N=8), while for group 2 (N=8) was 2.0352 with standard deviation of 0.0946; it was found significant statistical difference between groups as p was 0.046. Consequently, the nonlinear analysis via SampEn of EHG could provide an index to evaluate the quality of the active phase labor at term.

Linear and nonlinear analysis of base lung sound in extrinsic allergic alveolitis patients in comparison to healthy subjects.

OBJECTIVE: Pulmonary disorders are frequently characterized by the presence of adventitious sounds added to the breathing or base lung sound (BLS). The aim of this work was to assess the features of BLS in extrinsic allergic alveolitis (EAA) patients in comparison to healthy subjects, applying linear and nonlinear analysis techniques. METHODS: We investigated the multichannel lung sounds on the posterior chest of 16 females, 8 healthy and 8 EAA patients, when breathing at 1.5 L/s. BLS linear features were obtained from the power spectral density (PSD) while nonlinear features were extracted by the concepts of irregularity and complexity, i.e., spectral, sample and multiscale entropy. RESULTS: The results demonstrated that spectral percentiles of BLS were lower in EAA patients than in healthy subjects but statistical significance (p<0.05) was obtained only for expiration at the left apical and both basal regions. Also, the maximum amplitude of the PSD in patients reached statistical significance ( p < 0.05) for the expiratory phase at basal regions. In the case of nonlinear techniques, significant lower values ( p < 0.05) were obtained for EAA patients during both respiratory phases at left apical and both basal regions. CONCLUSION: In conclusion, we found that BLS in chronic EAA patients is characterized by lower spectral percentiles, lower irregularity and lower complexity than in healthy subjects suggesting the feasibility of its clinical usefulness by screening its temporal alteration.

Assessment of ICA algorithms for the analysis of crackles sounds.

Blind source separation by independent component analysis has been applied extensively in the biomedical field for extracting different contributing sources in a signal. Regarding lung sounds analysis to isolate the adventitious sounds from normal breathing sound is relevant. In this work the performance of FastICA, Infomax, JADE and TDSEP algorithms was assessed using different scenarios including simulated fine and coarse crackles embedded in recorded normal breathing sounds. Our results pointed out that Infomax obtained the minimum Amari index (0.10037) and the maximum signal to interference ratio (1.4578e+009). Afterwards, Infomax was applied to 25 channels of recorded normal breathing sound where simulated fine and coarse crackles were added including acoustic propagation effects. A robust blind crackle separation could improve previous results in generating an adventitious acoustic thoracic imaging.

Assessment of multichannel lung sounds parameterization for two-class classification in interstitial lung disease patients.

This work deals with the assessment of different parameterization techniques for lung sounds (LS) acquired on the whole posterior thoracic surface for normal versus abnormal LS classification. Besides the conventional technique of power spectral density (PSD), the eigenvalues of the covariance matrix and both the univariate autoregressive (UAR) and the multivariate autoregressive models (MAR) were applied for constructing feature vectors as input to a supervised neural network (SNN). The results showed the effectiveness of the UAR modeling for multichannel LS parameterization, using new data, with classification accuracy of 75% and 93% for healthy subjects and patients, respectively.

Imaging the thoracic distribution of normal breath sounds.

OBJECTIVE: To assess the feasibility to generate a confident image of normal breath sounds (BS) based on the quantitative analysis of multichannel sensors and imaging them in three known clinical classes, i.e., tracheal, bronchial and vesicular, identifying their spatial distribution with high resolution on the posterior thoracic surface. METHODS: Three parametrization techniques, the percentile frequencies, the univariate AR modeling, and the eigenvalues of the covariance matrix were evaluated when applied to BS. These sounds were acquired in twelve healthy subjects by a 5x5 sensor array on the posterior thoracic surface plus the sound at the tracheal position, to obtain feature vectors that fed a supervised multilayer neural network. Based on BS classification rate, the spatial distribution of each BS class was obtained by constructing an image using deterministic interpolation. RESULTS: The univariate AR modeling was the best parametrization technique producing a classification performance of 96% during the validation phase and just 4% of not classified feature vectors. Corresponding values for the percentile frequencies were 92% and 7.7%, whereas for the eigenvalues were 91% and 9.0%. CONCLUSION: This work shows that it is possible to generate confident images associated with the distribution of normal BS classes. Therefore, a detailed image about the spatial distribution of BS in humans might be helpful for detecting lung diseases.

Respiratory acoustic thoracic imaging (RATHI): assessing intrasubject variability.

Respiratory acoustic thoracic imaging (RATHI) permits analysing lung sounds (LS) temporal and spatial distribution, however, a deep understanding of RATHI repeatability associated with the pulmonary function is necessary. As a consequence, in the current work intrasubject variability of RATHI is evaluated at different airflows. For generating RATHIs, LS were acquired at the posterior thoracic surface. The associated image was computed at the inspiratory phases by interpolation through a Hermite function. The acoustic information of eleven subjects was considered at airflows of 1.0, 1.5 and 2.0 L/s. Several RATHIs were generated for each subject according to the number of acquired inspiratory phases. Quadratic mutual information based on Cauchy-Schwartz inequality (I(CS)) was used to evaluate the degree of similitude between intrasubject RATHIs. The results indicated that, for the same subject, I(CS) averaged 0.893, 0.897, and 0.902, for airflows of 1.0, 1.5, and 2 L/s, respectively. In addition, when the airflow was increased, increments in intensity values and in the dispersion of the spatial distribution reflected in RATHI were observed. In conclusion, since the intrasubject variability of RATHI was low for airflows between 1.0 and 2.0 L/s, the pattern of sound distribution during airflow variations is repeatable but differences in sound intensity should be considered.