Novel gas mixture combined with an auto-transfusion tourniquet enhances cerebral O2 transport and hemodynamic indices in CPR swine. Part B - A pilot experimental study.

Objectives: The cognitive outcome of CPR is poor. This study aims to evaluate if enhancing blood flow to the brain and oxygen dissociation from the hemoglobin improve cerebral O2 transport during CPR in cardiac arrest swine. Methods: Standard swine-CPR model of induced VF and recovery was treated with an auto-transfusion tourniquet (A-TT®; HemaShock® (HS) Oneg HaKarmel Ltd. Israel) and ventilation with a novel mixture of 30% Oxygen, 5% CO2, and 65% Argon (COXAR™). Five swine received the study treatment and 5 controls standard therapy. Animals were anesthetized, ventilated, and instrumented for blood draws and pressure measurements. Five minutes of no-CPR arrest were followed by 10 min of mechanical CPR with and without COXAR-HS™ enhancement followed by defibrillation and 45 min post ROSC follow-up. Results: All 5 COXAR-HS™ animals were resuscitated successfully as opposed to 3 of the control animals. Systolic (p < 0.05), and diastolic (p < 0.01) blood pressures, and coronary (p < 0.001) and cerebral (p < 0.05) perfusion pressures were higher in the COXAR-HS™ group after ROSC, as well as cerebral flow and O2 provided to the brain (p < 0.05). Blood pressure maintenance after ROSC required much higher doses of norepinephrine in the 3 resuscitated control animals vs. the 5 COXAR-HS™ animals (p < 0.05). jugular vein PO2 and SO2 exceeded 50 mmHg and 50%, respectively with COXAR-HS™. Conclusions: In this pilot experimental study, COXAR-HS™ was associated with higher diastolic blood pressure and coronary perfusion pressure with lower need of vasopressors after ROSC without significant differences prior to ROSC. The higher PjvO2 and SjvO2 suggest enhanced O2 provision to the brain mitochondria, while limb compression by the HS counteracts the vasodilatory effect of the CO2. Further studies are needed to explore and validate the COXAR-HS™ effects on actual post-ROSC brain functionality.

Pressure pulsations enhance penetration index in COPD.

This study was done in order to evaluate the effect of a novel pressure pulsation device (Pulsehaler™, Respinova Ltd., Israel) on the deposition pattern of inhaled aerosol in the lungs of COPD patients. Fifteen COPD patients were recruited to undergo spirometry and SPECT-CT lung scan following nebulization of radioactively labeled albuterol in saline solution with a jet nebulizer ("NEB") and with a combined Pulsehaler™/jet nebulizer ("PH + NEB") treatment. Central and peripheral segments of the coronal and transverse SPECT scans were evaluated for total counts and for the ratios between peripheral counts and central counts (penetration Index, "PI"). There was a significant improvement in FEV1 from before to after albuterol treatment in the PH + NEB group (151 ml ± 187, p < 0.008), but not in the NEB only group (66 ml ± 125, p = 0.06). FVC, FEF25-75, FEV1%, FVC%, FEF25, FEF50, and FEF75 also improved significantly in the PH + NEB group but not the NEB group. There were significant improvements seen between treatments for FEF25-75 (PH + NEB > NEB, p = 0.0176), FEF75 (PH + NEB > NEB, p = 0.0028), but not for the other spirometry measures. Borg scores also were improved significantly improved in PH + NEB vs NEB (p = 0.0006). Total lung deposition and total body deposition were lower in the PH + NEB treatments vs the NEB treatments. However, PI values were 3.08 ± 0.67 times greater on average with the PH + NEB (p = 0.026) as compared to NEB only. The magnitude of the increased penetration index observed in this study indicates that pressure pulsations should be further explored as means to improve drug delivery into the distal small airways of the bronchial tree. Effects of the pressure pulsations on small airway patency could be the mechanism by which the effect was achieved.

Effect of positive end-expiratory pressure on acoustic wave propagation in experimental porcine lung injury.

To evaluate the effect of positive end-expiratory pressure (PEEP) on sound propagation through injured lungs, we injected a multifrequency broad-band sound signal into the airway of eight anesthetized, intubated and mechanically ventilated pigs, while recording transmitted sound at three locations bilaterally on the chest wall. Oleic acid injections effected a severe pulmonary oedema predominately in the dependent lung regions, with an average increase in venous admixture from 19 ± 15 to 59 ± 14% (P < 0.001), and a reduction in dynamic respiratory system compliance from 34 ± 7 to 14 ± 4 ml cmH2 O(-1) (P < 0.001). A concomitant decrease in sound transit time was seen in the dependent lung regions (P < 0.05); no statistically significant change occurred in the lateral or non-dependent areas. The application of PEEP resulted in a decrease in venous admixture, increase in respiratory system compliance and return of the sound transit time to pre-injury levels in the dependent lung regions. Our results indicate that sound transmission velocity increases in lung tissue affected by permeability-type pulmonary oedema in a manner reversible during alveolar recruitment with PEEP.

Effect of PEEP on breath sound power spectra in experimental lung injury.

BACKGROUND: Acute lung injury (ALI) is known to be associated with the emergence of inspiratory crackles and enhanced transmission of artificial sounds from the airway opening to the chest wall. Recently, we described the effect of ALI on the basic flow-induced breath sounds, separated from the crackles. In this study, we investigated the effects of positive end-expiratory pressure (PEEP) on these noncrackling basic lung sounds augmented during ALI. METHODS: Lung sounds were recorded in six anesthetized, intubated, and mechanically ventilated pigs at three locations bilaterally on the chest wall. Recordings were obtained before and after induction of lung injury with oleic acid and during application of incremental positive end-expiratory pressure. RESULTS: Oleic acid injections caused severe pulmonary edema predominately in the dependent-lung regions. Inspiratory spectral power of breath sounds increased in all lung regions over a frequency band from 150 to 1,200 Hz, with further power augmentation in dependent-lung areas at higher frequencies. Incremental positive end-expiratory pressure reversed the spectral power augmentation seen with ALI, reducing it to pre-injury levels with PEEP of 10 and 15 cmH2O in all lung regions at all frequencies. The application of positive end-expiratory pressure to normal lungs attenuated spectral power slightly and only over a band from 150 to 1,200 Hz. CONCLUSIONS: We confirm a gravity-related spectral amplitude increase of basic flow-induced breath sounds recorded over lung regions affected by permeability-type pulmonary edema and show that such changes are reversible by alveolar recruitment with PEEP.

Changes in breath sound power spectra during experimental oleic acid-induced lung injury in pigs.

To evaluate the effect of acute lung injury on the frequency spectra of breath sounds, we made serial acoustic recordings from nondependent, midlung and dependent regions of both lungs in ten 35- to 45-kg anesthetized, intubated, and mechanically ventilated pigs during development of acute lung injury induced with intravenous oleic acid in prone or supine position. Oleic acid injections rapidly produced severe derangements in the gas exchange and mechanical properties of the lung, with an average increase in venous admixture from 16 ± 12 to 62 ± 16% (P < 0.01), and a reduction in dynamic respiratory system compliance from 25 ± 4 to 14 ± 4 ml/cmH2O (P < 0.01). A concomitant increase in sound power was seen in all lung regions (P < 0.05), predominantly in frequencies 150-800 Hz. The deterioration in gas exchange and lung mechanics correlated best with concurrent spectral changes in the nondependent lung regions. Acute lung injury increases the power of breath sounds likely secondary to redistribution of ventilation from collapsed to aerated parts of the lung and improved sound transmission in dependent, consolidated areas.

Childhood Pneumonia Screener: a concept.

Childhood pneumonia continues to be the number one cause of death in children under five years of age in developing countries. In addition to mortality, pneumonia constitutes an enormous economic and social burden because late diagnosis is associated with high cost of treatment and often leads to chronic health problems. There are several bottlenecks in developing countries in the case flow of a child with lung infection: 1) recognising the symptoms as a reason to seek care, 2) getting the patient to a first-tier health facility, 3) scarcity of trained healthcare personnel who can diagnose the condition and its severity, 4) access to a second-tier facility in severe cases. These factors are commonly present in rural areas but even in more urban settings, access to a physician is often delayed. The Childhood Pneumonia Screener project aims at bridging the diagnostic gap using emerging technology. Mobile "smart" phone communication with several inexpensive dedicated sensors is proposed as a rapid data-collection and transmission unit that is connected to a central location where trained personnel assisted by sophisticated signal processing algorithms, evaluate the data and determine if the child is likely to have pneumonia and what the level and urgency of care should be.

Validation of an ambulatory cough detection and counting application using voluntary cough under different conditions.

BACKGROUND: While cough is an important defence mechanism of the respiratory system, its chronic presence is bothersome and may indicate the presence of a serious disease. We hereby describe the validation process of a novel cough detection and counting technology (PulmoTrack-CC, KarmelSonix, Haifa, Israel). METHODS: Tracheal and chest wall sounds, ambient sounds and chest motion were digitally recorded, using the PulmoTrack(R) hardware, from healthy volunteers coughing voluntarily while (a) laying supine, (b) sitting, (c) sitting with strong ambient noise, (d) walking, and (e) climbing stairs, a total of 25 minutes per subject. The cough monitoring algorithm was applied to the recorded data to detect and count coughs.The detection algorithm first searches for cough 'candidates' by identifying loud sounds with a cough pattern, followed by a secondary verification process based on detection of specific characteristics of cough. The recorded data were independently and blindly evaluated by trained experts who listened to the sounds and visually reviewed them on a sonogram display.The validation process was based on two methods: (i) Referring to an expert consensus as gold standard, and comparing each cough detected by the algorithm to the expert marking, we marked True and False, positive and negative detections.These values were used to evaluate the specificity and sensitivity of the cough monitoring system. (ii) Counting the number of coughs in longer segments (t = 60 sec, n = 300) and plotting the cough count vs. the corresponding experts' count whereby the linear regression equation, the regression coefficient (R2) and the joint-distribution density Bland-Altman plots could be determined. RESULTS: Data were recorded from 12 volunteers undergoing the complete protocol. The overall Specificity for cough events was 94% and the Sensitivity was 96%, with similar values found for all conditions, except for the stair climbing stage where the Specificity was 87% with Sensitivity of 97%. The regression equation between the PulmoTrack-CC cough event counts and the Experts' determination was with R2 of 0.94. DISCUSSION: This validation scheme provides an objective and quantitative assessment method of a cough counting algorithm in a range of realistic situations that simulate ambulatory monitoring of cough. The ability to detect voluntary coughs under acoustically challenging ambient conditions may represent a useful step towards a clinically applicable automatic cough detector.

Children with nocturnal asthma wheeze intermittently during sleep.

Nocturnal asthma indicates poor overall control of asthma and adversely affects the quality of life of the patient. The purpose of the present study was to compare the objective measurement of nocturnal wheeze with clinical state, recall of symptoms, and changes in lung function. Nine asthmatic children aged 9 to 16 years were followed with an asthma diary and diurnal measurement of peak flow for a week before the nocturnal study; all but two were apparently well controlled. Breath sounds were recorded and analyzed continuously overnight to quantify wheeze using a phonopneumography sensor attached over the trachea. The analytical system (PulmoTrack) utilized an algorithm to detect wheeze and reject interference. The wheeze rate (Tw/Ttot = duration of wheeze/duration of recording) was calculated minute by minute throughout the night. Recordings lasted over 8 hours and all but two children had wheeze lasting for a total time of between 11 and 87 minutes. The pattern of wheezing was very variable during sleep, with episodes of wheeze separated by periods of quiet breathing. There was no relationship between subjective perception of nocturnal asthma, forced expiratory volume in 1 s (FEV(1)) next morning, and the objective measurement of wheeze. Total overnight wheeze was significantly related to the total diary symptom score and to the (small) diurnal variability of peak expiratory flow (PEF). Four of the seven children with asthma who were apparently well controlled had considerable amounts of wheeze during the night that was episodic in nature and unrelated to conventional measures of lung function or nocturnal symptoms.

Respiratory modulation of heart sound morphology.

Heart sounds, the acoustic vibrations produced by the mechanical processes of the cardiac cycle, are modulated by respiratory activity. We have used computational techniques of cluster analysis and classification to study the effects of the respiratory phase and the respiratory resistive load on the temporal and morphological properties of the first (S1) and second heart sounds (S2), acquired from 12 healthy volunteers. Heart sounds exhibited strong morphological variability during normal respiration and nearly no variability during apnea. The variability was shown to be periodic, with its estimated period in good agreement with the measured duration of the respiratory cycle. Significant differences were observed between properties of S1 and S2 occurring during inspiration and expiration. S1 was commonly attenuated and slightly delayed during inspiration, whereas S2 was accentuated and its aortic component occurred earlier at late inspiration and early expiration. Typical split morphology was observed for S1 and S2 during inspiration. At high-breathing load, these changes became more prominent and occurred earlier in the respiratory cycle. Unsupervised cluster analysis was able to automatically identify the distinct morphologies associated with different respiratory phases and load. Classification of the respiration phase (inspiration or expiration) from the morphology of S1 achieved an average accuracy of 87 +/- 7%, and classification of the breathing load was accurate in 82 +/- 7%. These results suggest that quantitative heart sound analysis can shed light on the relation between respiration and cardiovascular mechanics and may be applied to continuous cardiopulmonary monitoring.

Effects of diameter, length, and circuit pressure on sound conductance through endotracheal tubes.

We evaluated the acoustic frequency response of endotracheal tubes (ETs) to assess their effect on respiratory system sound transmission studies. White noise 150-3300 Hz was introduced into 4.0-, 6.0-, and 8.0-mm ETs and recorded at their proximal and distal ends. Four tubes of each size were studied at their original and normalized lengths, in straight and bent configurations, and at circuit pressures from 0 to 20 cmH2O. The characteristics of the sound transmission were compared using an analysis of variance for repeated measures. The average transmission amplitude varied directly with tube diameter. The position of peaks and troughs on the amplitude frequency distribution depended on tube length but not on tube diameter. The angle of the phase-frequency plot correlated well with the length of the tube and was independent of its diameter. A 90 degrees bend in the tube had no effect on its sound transmission. Increasing the circuit pressure above ambient modified the frequency response only if volume changes occurred in the test lung. When used to conduct sound into the respiratory system an ET affects the incident signal predictably depending on its length and diameter but not on its curvature or circuit pressure.

Measurements and theory of normal tracheal breath sounds.

We studied the mechanisms by which turbulent flow induces tracheal wall vibrations detected as tracheal breath sounds (TRBSs). The effects of flow rate at transitional Reynold's numbers (1300-10,000) and gas density on spectral patterns of TRBSs in eight normal subjects were measured. TRBSs were recorded with a contact sensor during air and heliox breathing at four flow rates (1.0, 1.5, 2.0, and 2.5 l/s). We found that normalized TRBSs were proportional to flow to the 1.89 power during inspiration and to the 1.59 power during expiration irrespective of gas density. The amplitude of TRBSs with heliox was lower than with air by a factor of 0.33 +/- 0.12 and 0.44 +/- 0.16 during inspiration and expiration, respectively. The spectral resonance frequencies were higher during heliox than air breathing by a factor of 1.75 +/- 0.2-approximately the square root of the reciprocal of the air/heliox wave propagation speed ratio. In conclusion, the flow-induced pressure fluctuations inside the trachea, which cause tracheal wall vibrations, were detected as TRBSs consist of two components: (1) a dominant local turbulent eddy component whose amplitude is proportional to the gas density and nonlinearly related to the flow; and (2) a propagating acoustic component with resonances whose frequencies correspond to the length of the upper airway and to the free-field sound speed. Therefore, TRBSs consist primarily of direct turbulent eddy pressure fluctuations that are perceived as sound during auscultation.

Response of acoustic transmission to positive airway pressure therapy in experimental lung injury.

OBJECTIVE: To evaluate the effect of positive end-expiratory pressure on the sound filtering characteristics of injured lungs. DESIGN AND SETTING: Prospective experimental study in the animal laboratory in an academic medical center. PATIENTS AND PARTICIPANTS: Six 35- to 45-kg anesthetized, intubated pigs. INTERVENTIONS: Acute lung injury with intravenous oleic acid. MEASUREMENTS AND RESULTS: We injected a multifrequency broad-band sound signal into the airway while recording transmitted sound at three locations bilaterally on the chest wall. Oleic acid injections effected a severe pulmonary edema predominantly in the dependent lung regions, with an average increase in venous admixture from 16+/-14% to 57+/-13% and a reduction in static respiratory system compliance from 31+/-6 to 16+/-3 ml/cm H(2)O. A significant concomitant increase in sound transfer function amplitude was seen in the dependent and lateral lung regions; little change occurred in the nondependent areas. The application of PEEP resulted in a decrease in venous admixture, increase in respiratory system compliance, and return of the sound transmission to preinjury levels. CONCLUSIONS: Acute lung injury causes regional acoustic transmission abnormalities that are reversed during alveolar recruitment with PEEP.

Adenosine bronchial provocation with computerized wheeze detection in young infants with prolonged cough: correlation with long-term follow-up.

BACKGROUND: Chronic cough in babies is often associated with bronchial hyperreactivity (BHR). The objective documentation of BHR in babies is difficult, and acoustic methods have been described (provocative concentration of a substance causing wheeze) for conducting bronchial provocation tests (BPTs). We conducted a study to evaluate automatic computerized wheeze detection (CWD) in determining BHR in young infants with prolonged cough, and its correlation with the subsequent development of wheezing. METHODS: Infants aged < 24 months with prolonged cough (ie, > 2 months) underwent acoustic BPTs with the response determined by CWD and auscultation by a physician. Telephone interviews with parents were conducted after 1 month and yearly for the next 3 years. RESULTS: A total of 28 infants who were 4 to 24 months old with prolonged cough were included in the study. Twenty of these infants (71.4%) had BHR as determined by a positive acoustic BPT result. In 11 of these 20 tests, the CWD occurred earlier, and in 9 tests it occurred at the same step as auscultation by a physician. Rhonchi or whistles often preceded wheezes. Seventeen of the 20 patients with BHR completed 3 years of follow-up. Of these, 14 had recurrent episodes of wheezing and shortness of breath, and 3 were well. Six of the eight adenosine-negative patients completed 3 years of follow-up and had no symptoms of BHR. CONCLUSIONS: Acoustic BPT is a technically feasible test for the detection of BHR in young infants. CWD provides an earlier detection of wheeze than stethoscope auscultation. In our group of infants, a positive acoustic BPT result had high correlation with symptoms compatible with BHR over the next 3 years.

Detection of porcine oleic acid-induced acute lung injury using pulmonary acoustics.

To evaluate the utility of monitoring the sound-filtering characteristics of the respiratory system in the assessment of acute lung injury (ALI), we injected a multifrequency broadband sound signal into the airway of five anesthetized, intubated pigs, while recording transmitted sound over the trachea and on the chest wall. Oleic acid injections effected a severe lung injury predominantly in the dependent lung regions, increasing venous admixture from 6 +/- 1 to 54 +/- 8% (P < 0.05) and reducing dynamic respiratory system compliance from 19 +/- 0 to 12 +/- 2 ml/cmH(2)O (P < 0.05). A two- to fivefold increase in sound transfer function amplitude was seen in the dependent (P < 0.05) and lateral (P < 0.05) lung regions; no change occurred in the nondependent areas. High within-subject correlations were found between the changes in dependent lung sound transmission and venous admixture (r = 0.82 +/- 0.07; range 0.74-0.90) and dynamic compliance (r = -0.87 +/- 0.05; -0.80 to -0.93). Our results indicate that the acoustic changes associated with oleic acid-induced lung injury allow monitoring of its severity and distribution.