Identification and characterization of near-fatal asthma phenotypes by cluster analysis.

BACKGROUND: Near-fatal asthma (NFA) is a heterogeneous clinical entity and several profiles of patients have been described according to different clinical, pathophysiological and histological features. However, there are no previous studies that identify in a unbiased way--using statistical methods such as clusters analysis--different phenotypes of NFA. Therefore, the aim of the present study was to identify and to characterize phenotypes of near fatal asthma using a cluster analysis. METHODS: Over a period of 2 years, 33 Spanish hospitals enrolled 179 asthmatics admitted for an episode of NFA. A cluster analysis using two-steps algorithm was performed from data of 84 of these cases. RESULTS: The analysis defined three clusters of patients with NFA: cluster 1, the largest, including older patients with clinical and therapeutic criteria of severe asthma; cluster 2, with an high proportion of respiratory arrest (68%), impaired consciousness level (82%) and mechanical ventilation (93%); and cluster 3, which included younger patients, characterized by an insufficient anti-inflammatory treatment and frequent sensitization to Alternaria alternata and soybean. CONCLUSIONS: These results identify specific asthma phenotypes involved in NFA, confirming in part previous findings observed in studies with a clinical approach. The identification of patients with a specific NFA phenotype could suggest interventions to prevent future severe asthma exacerbations.

Cardiac interference reduction in diaphragmatic MMG signals during a Maintained Inspiratory Pressure Test.

A recursive least square (RLS) adaptive filtering algorithm for reduction of cardiac interference in diaphragmatic mecanomyographic (MMGdi) signals is addressed in this paper. MMGdi signals were acquired with a capacitive accelerometer placed between 7th and 8th intercostal spaces, on the right anterior axillary line, during a maintained inspiratory pressure test. Subjects were asked to maintain a constant inspiratory pressure with a mouthpiece connected to a closed tube (without breathing). This maneuver was repeated at five different contraction efforts: apnea (no effort), 20 cmH2O, 40 cmH2O, 60 cmH2O and maximum voluntary contraction. An adaptive noise canceller (ANC) using the RLS algorithm was applied on the MMGdi signals. To evaluate the behavior of the ANC, the MMGdi signals were analyzed in two segments: with and without cardiac interference (WCI and NCI, respectively). In both segments it was analyzed the power spectral density (PSD), and the ARV and RMS amplitude parameters for each contraction effort. With the proposed ANC algorithm the amplitude parameters of the WCI segments were reduced to a level similar to the one of the NCI segments. The obtained results showed that ANC using the RLS algorithm allows to significantly reduce the cardiac interference in MMGdi signals.

All night analysis of time interval between snores in subjects with sleep apnea hypopnea syndrome.

Sleep apnea-hypopnea syndrome (SAHS) is a serious sleep disorder, and snoring is one of its earliest and most consistent symptoms. We propose a new methodology for identifying two distinct types of snores: the so-called non-regular and regular snores. Respiratory sound signals from 34 subjects with different ranges of Apnea-Hypopnea Index (AHI = 3.7-109.9 h(-1)) were acquired. A total number of 74,439 snores were examined. The time interval between regular snores in short segments of the all night recordings was analyzed. Severe SAHS subjects show a shorter time interval between regular snores (p = 0.0036, AHI cp: 30 h(-1)) and less dispersion on the time interval features during all sleep. Conversely, lower intra-segment variability (p = 0.006, AHI cp: 30 h(-1)) is seen for less severe SAHS subjects. Features derived from the analysis of time interval between regular snores achieved classification accuracies of 88.2 % (with 90 % sensitivity, 75 % specificity) and 94.1 % (with 94.4 % sensitivity, 93.8 % specificity) for AHI cut-points of severity of 5 and 30 h(-1), respectively. The features proved to be reliable predictors of the subjects' SAHS severity. Our proposed method, the analysis of time interval between snores, provides promising results and puts forward a valuable aid for the early screening of subjects suspected of having SAHS.

Respiratory and spontaneous arousals in patients with Sleep Apnea Hypopnea Syndrome.

Sleep in patients with Sleep Apnea-Hypopnea Syndrome (SAHS) is frequently interrupted with arousals. Increased amounts of arousals result in shortening total sleep time and repeated sleep-arousal change can result in sleep fragmentation. According to the American Sleep Disorders Association (ASDA) an arousal is a marker of sleep disruption representing a detrimental and harmful feature for sleep. The nature of arousals and its role on the regulation of the sleep process raises controversy and has sparked the debate in the last years. In this work, we analyzed and compared the EEG spectral content of respiratory and spontaneous arousals on a database of 45 SAHS subjects. A total of 3980 arousals (1996 respiratory and 1984 spontaneous) were analyzed. The results showed no differences between the spectral content of the two kinds of arousals. Our findings raise doubt as to whether these two kinds of arousals are truly triggered by different organic mechanisms. Furthermore, they may also challenge the current beliefs regarding the underestimation of the importance of spontaneous arousals and their contribution to sleep fragmentation in patients suffering from SAHS.

Normal non-regular snores as a tool for screening SAHS severity.

Snoring is one of the earliest and most consistent sign of upper airway obstruction leading to Sleep Apnea-Hypopnea Syndrome (SAHS). Several studies on post-apneic snores, snores that are emitted immediately after an apnea, have already proven that this type of snoring is most distinct from that of normal snoring. However, post-apneic snores are more unlikely and sometimes even inexistent in simple snorers and mild SAHS subjects. In this work we address that issue by proposing the study of normal non-regular snores. They correspond to successive snores that are separated by normal breathing cycles. The results obtained establish the feasibility of acoustic parameters of normal non-regular snores as a promising tool for a prompt screening of SAHS severity.

Regular and non regular snore features as markers of SAHS.

Sleep Apnea-Hypopnea Syndrome (SAHS) diagnosis is still done with an overnight multi-channel polysomnography. Several efforts are being made to study profoundly the snore mechanism and discover how it can provide an opportunity to diagnose the disease. This work introduces the concept of regular snores, defined as the ones produced in consecutive respiratory cycles, since they are produced in a regular way, without interruptions. We applied 2 thresholds (TH(adaptive) and TH(median)) to the time interval between successive snores of 34 subjects in order to select regular snores from the whole all-night snore sequence. Afterwards, we studied the effectiveness that parameters, such as time interval between successive snores and the mean intensity of snores, have on distinguishing between different levels of SAHS severity (AHI (Apnea-Hypopnea Index) < 5h(-1), AHI <10 h(-1), AHI < 15 h(-1), AHI < 30 h(-1)). Results showed that TH(adaptive) outperformed TH(median) on selecting regular snores. Moreover, the outcome achieved with non-regular snores intensity features suggests that these carry key information on SAHS severity.

Analysis of forced wheezes in asthma patients.

BACKGROUND: Spirometric parameters can be normal in many stable asthma patients, making a diagnosis difficult at certain times in the course of disease. OBJECTIVES: The present study aims to find differences and similarities in the acoustic characteristics of forced wheezes among asthma patients with and without normal spirometric values. METHODS: Eleven chronic asthma patients (8 men/3 women) with moderate-to-severe airway obstruction (FEV1 48.4%), 9 stable asthma patients (6 males/3 females) with normal spirometry (FEV1 84.0%) and a positive methacholine test and 14 healthy subjects (8/6) were enrolled in the study. A contact sensor was placed on the trachea, and wheezes were detected by a modified Shabtai-Musih algorithm in a time-frequency representation. RESULTS: More wheezes were recorded in obstructive asthma patients than in stable asthma and control subjects: nonstable asthma 13.6 (13.3), stable asthma 3.5 (3.0) and control subjects 2.5 (2.1). The mean frequency of all wheezes detected was higher in control subjects than in either stable or non-stable asthma patients. The change in the total number of wheezes after terbutaline inhalation was more pronounced in nonstable asthma patients than in stable asthmatics and control subjects. CONCLUSIONS: This study confirms that wheeze recording during forced expiratory maneuvers can be a complementary measure to spirometry to identify asthma patients.

Monitoring of wheeze duration during spontaneous respiration in asthmatic patients.

Respiratory sound analysis can offer important information related to pulmonary diseases. Wheezes have been reported as adventitious respiratory sounds in asthmatic or obstructive patients, during forced exhalation maneuvers. In this work, we propose a method for monitoring and analysis of respiratory sounds in frequency domain, during spontaneous ventilation. The database analyzed was acquired during spontaneous ventilation for 120 seconds (DBsv), of 26 asthmatics patients. Using an autoregressive model (AR, order 16), the Power Spectral Density (PSD) was calculated for every phase of expiration and inspiration and the maximum frequency (fp) was estimated. From this parameter we study the time duration of the wheezes. The effect of bronchodilator inhalation in asthmatic patients was studied analyzing the duration of the wheezes in the bandwidth 600-2000 Hz (HFband). The wheeze duration is evaluated as the number of consecutive segments, with fp is inside of HFband, (for 3 or more segments in a cycle). The difference of the wheeze duration inside the respiratory cycles (Dwheez), before and after bronchodilator inhalation (POST) was evaluated. It was found a good correlation between Dwheez and FEV 1% improvement (FEV 1%_imp), for FEV1%_imp greater than 8%, whereas values FEV1%_imp less than 8% did not show any change of Dwheez. This last result suggests no difference in the wheeze duration between the baseline and POST records. This method could predict the FEV1%_imp by means of estimation of Dwheez during spontaneous ventilation.

Variability of snore parameters in time and frequency domains in snoring subjects with and without Obstructive Sleep Apnea.

Several studies have shown differences in spectral parameters between simple snorers and patients with Obstructive Sleep Apnea Syndrome (OSAS). Most of them analyzed a reduced number of snores and/or only post-apneic snores were selected in OSAS patients. Previous findings suggest that snore parameters have a greater variability as the severity of OSAS increases. In this work we propose to analyze the snoring variability through the magnitude of the first difference of snore parameters. The technique is applied to long time sound recordings from 9 simple snorers (15795 snores) and 15 OSAS patients (19263 snores). The snores are characterized by their sound intensity an by a set of spectral parameters The variability of snore parameters is well correlated to OSAS severity (r>0.7) and is significantly greater in OSAS patients than in simple snorers (p<0.005). The results are similar when post-apneic snores are excluded from the analysis. Snoring subjects are classified with a logistic regression model, which is validated with the live-one-out method. The model is adjusted to correctly classify 100% of OSAS patients for screening purposes previously to enroll for a whole polysomnographic study.

Analysis of wheezes in asthmatic patients during spontaneous respiration.

Respiratory sound analysis can offer important information related to pulmonary diseases. Wheezes have been reported as adventitious respiratory sounds in asthmatic or obstructive patients, during forced exhalation maneuvers. In this work, we propose a method for analysis of respiratory sounds in frequency domain, during spontaneous ventilation. Two databases were analyzed: signals acquired during spirometry (DBspir), composed by 23 subjects (N=15 asthmatics, N=8 control); and signals acquired during spontaneous ventilation for 120 seconds (DBsv), composed by 26 asthmatics. Using an autoregressive model (AR, order 16), it was calculated the Power Spectral Density (PSD) for each expiration and the peak frequency (fp) was estimated. Higher values of fp were found in asthmatic patients with severe obstruction in relation to light obstruction or control subjects. The effect of bronchodilator inhalation in asthmatic patients was studied in the database DBsv, analyzing contribution of wheezes in the bandwidth 600-2000 Hz (HFband)., Differences of number of respiratory cycles with wheezes (Dwheez index), before and after bronchodilator inhalation were evaluated. It was found a good correlation between Dwheez and FEV1% improvement (FEV1>%_imp), for FEV1%_imp > 10%. This method could predict the FEV1%_imp by means of estimation of Dwheez index during spontaneous ventilation.

Assessment of respiratory muscle effort studying diaphragm movement registered with surface sensors. Animal model (dogs).

The diaphragm movement (DM) signal during spontaneous ventilations is analyzed in this work. The DM signal is acquired by means two surface sensors (a piezoelectric contact sensor -PCS- and a piezoelectric accelerometer -ACP) applied on the costal wall. The main objective is to develop a new non invasive technique to assess respiratory muscle effort. Experiments were performed in an animal model: four pentobarbital-anesthetized and two awake mongrel dogs, carrying out spontaneous ventilations against an inspiratory load. DM signal has been decomposed in two components: a low frequency component (lower than 5 Hz) due to the overall lateral movement of the muscle (MOV component), and a high frequency component (higher than 5 Hz) due to the lateral vibration of active muscle fibers (VIB component). It has been seen that the PCS acquires only MOV components of MD signal, while ACP acquires both components. Positive high correlation coefficients have been found between amplitude parameters of VIB components of DM signal, acquired by means the ACP, and the respiratory muscle effort during ventilation, measured with inspiratory pressures.

Influence of estimators of spectral density on the analysis of electromyographic and vibromyographic signals.

Electromyographic (EMG) and vibromyographic (VMG) signals are related to electrical and mechanical muscle activity, respectively. It is known that variations in their frequency components are related to changes in muscle activity and fatigue. The aims of this study were: (1) to analyse the resolution, variance and bias of different estimations of power spectral density function (PSD); and (2) to evaluate the influence of the spectral estimation method on three indices calculated from the PSD of EMG and VMG signals: mean (f(m)) and median (f(c)) frequencies and the ratio of high and low frequency components (H/L ratio) to select the most suitable estimator. Myographic signals were recorded from the sternomastoid muscle, an accessory respiratory muscle, during breathing. For non-parametric methods, Welch periodograms and correlograms were analysed with different windows. Autoregressive (AR) moving average (MA) and ARMA models with different orders were evaluated in the parametric methods. The reproducibility of the results was also studied. Frequency indices, particularly the H/L ratio and f(c), changed considerably when varying the following parameters of the estimators: periodogram with segment durations longer than 150 ms in EMG and with any duration in VMG signals; correlogram with window length shorter than 10% of the total number of samples; and AR models with an order lower than 10, 20 and 40 in f(c), fm and H/L ratio, respectively, in both myographic signals.

Study of myographic signals from sternomastoid muscle in patients with chronic obstructive pulmonary disease.

Analysis of the respiratory muscle activity is a promising technique for diagnosis of respiratory diseases, such as chronic obstructive pulmonary disease (COPD). The sternomastoid muscle (SMM) was selected to study the activity of respiratory muscles due to its accessibility in order to define a noninvasive analysis. The aims of this work are two: analyze the relationship between the SMM function and pulmonary obstruction, and study the influence of spectral estimator on frequency parameters related with the muscle activity. For the first goal, we propose the analysis of vibromyographic and electromyographic signals from the SMM to study the muscle function during two ventilatory tests. Activity of SMM was found by means of several indexes: root-mean-square (rms) values, mean and median frequencies, and ratio between high and low-frequency components. For the second goal, spectral analysis was performed by means of nonparametric methods: Correlogram and Welch periodogram, and parametric methods: autoregressive (AR), moving average (MA), and ARMA models. It is deduced that these indexes show muscle activity and certain fatigue of the SMM, whose muscle function depends on the level of pulmonary obstruction, and they depend a lot of spectral estimator being the more suitable an AR model with high order.

Analysis of tracheal sounds during forced exhalation in asthma patients and normal subjects: bronchodilator response effect.

PURPOSE: During the past 10 years, the acoustic analysis of breath sounds has been used as a diagnostic tool in patients suffering from obstructive respiratory diseases. Acoustic analysis might be able to monitor the response to bronchodilator therapy in a clinical setting. So far, few studies have been carried out in asthmatic patients. To assess the responses of a sampling of asthma patients to an inhaled bronchodilator (terbutaline) by means of spectral analysis of the tracheal sound performed during forced expiratory maneuvers. MATERIAL AND METHODS: Seventeen nonsmoking asthma patients (9 were male, 8 were female) who had been suffering from the disease for > or = 15 years were included in the study, as were 15 normal subjects (7 were male, 8 were female). The average age (+/- SD) was 56.5 +/- 15.2 years (FVC, 2.7 +/- 0.9 L [63.4%]; FEV1, 1.5 +/- 0.6 L [53.0%]). The tracheal sounds were collected during three forced expiratory maneuvers with a sampling frequency of 5,000 Hz and were analyzed by applying a 16-parameter autoregressive model. RESULTS: The centroid frequency decreased after the bronchodilator was given at different flow segments between 1.2 and 0.4 L/s, with significant changes between 0.6 and 0.4 L/s. CONCLUSIONS: Patients with asthma showed changes in the spectral acoustic analysis frequencies after the administration of a bronchodilator drug (terbutaline) during forced expiratory maneuvers.

Indices of respiratory muscle endurance in healthy subjects.

BACKGROUND: The evaluation of respiratory muscle performance can be described in terms of strength and endurance, the latter usually being measured by means of resistive or threshold inspiratory loads, using devices that are also used for respiratory muscle training. Few authors, however, have published endurance reference values for healthy subjects. To that end, we studied two indices of respiratory muscle endurance in a population of 99 healthy volunteers (50 men, 49 women) divided into five age groups (20-70 years old) applying a modification of the methods of Martyn et al. and Nickerson and Keens. Inspiratory muscle endurance (Tlim) was defined as the time the subject was able to sustain breathing against an inspiratory pressure load equivalent to 80% of the maximum tolerated load (Cmax). Cmax was calculated using a 2-min incremental threshold load. RESULTS: We found that the heaviest inspiratory threshold load tolerated for 2 min and the time a load equivalent to 80% of Cmax (Tlim) could be sustained were not significantly different for male and female subjects. Tlim correlated with Cmax, age, height, and maximum respiratory pressures.

nCPAP treatment interruption in OSA patients.

This study has investigated the effect of interrupting nasal continuous positive airway pressure (nCPAP) therapy on 10 obstructive sleep apnoea (OSA) patients (nine male, one female) (53.6 +/- 7.3 years) treated over 2 years. The effect of nCPAP interruption was determined by variations in sleep counts and gasometric values during five consecutive nights. On the first night, the patient used his habitual nCPAP. On the remaining nights, nasal nCPAP was not applied. The apnoea-hypopnoea index (AHI) was found to increase significantly in the second night, attaining a similar level to that of the basal study (2 years ago). SaO2 minimum decreased and PaCO2 increased in the second night with respect to the first night. The interruption of nCPAP therapy in OSA patients treated over a long period of time increases the sleep counts and impairs the gasometric parameters. Consequently, any change in nCPAP time therapy must be checked to avoid negative effects.

Acoustic analysis of snoring sound in patients with simple snoring and obstructive sleep apnoea.

Snoring, a symptom which may indicate the presence of the obstructive sleep apnoea syndrome (OSA), is also common in the general population. Recent studies have suggested that the acoustic characteristics of snoring sound may differ between simple snorers and OSA patients. We have studied a small number of patients with simple snoring and OSA, analysing the acoustic characteristics of the snoring sound. Seventeen male patients, 10 with OSA (apnoea/hypopnoea index (AHI) 26.2 events x h(-1)) and seven simple snorers (AHI 3.8 events x h(-1)), were studied. Full night polysomnography was performed and the snoring sound power spectrum was analysed. Spectral analysis of snoring sound showed the existence of two different patterns. The first pattern was characterized by the presence of a fundamental frequency and several harmonics. The second pattern was characterized by a low frequency peak with the sound energy scattered on a narrower band of frequencies, but without clearly identified harmonics. The seven simple snorers and two of the 10 patients with OSA (AIH 13 and 14 events x h(-1), respectively) showed the first pattern. The rest of the OSA patients showed the second pattern. The peak frequency of snoring was significantly lower in OSA patients, with all but one OSA patient and only one simple snorer showing a peak frequency below 150 Hz. A significant negative correlation was found between AHI and peak and mean frequencies of the snoring power spectrum (p<0.0016 and p<0.0089, respectively). In conclusion, this study demonstrates significant differences in the sound power spectrum of snoring sound between subjects with simple snoring and obstructive sleep apnoea patients.

[Factors associated with pleural thickening in pleural tuberculosis. Review of 99 cases]. / Factores asociados al engrosamiento pleural en la pleuritis tuberculosa. Análisis de 99 casos.

OBJECTIVE: To analyze which factors were related to the development of pleural thickening in pleural tuberculosis (PT). METHODS: We reported 99 patients diagnosed as having PT separated into two different groups according to the presence of radiographic pleural thickening after completing the treatment: normal chest roentgenogram (group 1) or pleural thickening (group 2). We compared: clinical history, chest radiography, pleural fluid analysis, microbiological studies and effects of the treatment. RESULTS: 35 cases in group 1 (35.35%) and 64 in group 2 (64.45%). All the compared results did not differ between the two groups, excluding a higher incidence of febrile cases, increased white cell count and decreased relative percentage of pleural lymphocytes in group 1, and increased number of cases with hemoptysis, positive sputum cultures in patients with parenchymal infiltrates, relative percentage of pleural lymphocytes and decreased white cell count in group 2. CONCLUSIONS: We reported an elevated incidence of residual pleural thickening, but it is unlikely that all the cases could have any clinical significance. We didn't confirm a characteristic pattern. Our findings suggested that a different reaction related or not to the hypersensitivity, rather than the inflammatory response to infection was the responsible for the fibrosis.