1. Method for differential diagnosis of centrally and peripherally generated wheezes Raymond Murphy and Andrey Vyshedskiy, Brigham and Women’s / Faulkner Hospitals, Boston MA The concept of “acoustic symmetry”IntroductionResults As part of an effort to understand the nature and clinical significance of lung sounds we became interested in the site of origin of wheezing. One of the potential clinical applications of knowing the site of origin of wheezing is to help distinguish Vocal Cord Dysfunction (VCD) from asthma. Patients with VCD present with wheezing and shortness of breath and are commonly misdiagnosed as having bronchial asthma and are often mistreated. Under the assumption that centrally generated wheezes such as those of VCD are more symmetrically distributed over the chest than peripherally distributed wheezes such as those of asthma or chronic obstructive lung disease (COPD) patients, we developed a computer program to assess the symmetry of wheezes. As voice sounds are generated centrally, i.e. in the vocal cords, we tested this algorithm on voice sounds as compared to wheezes. The goal of this study was to determine whether voice sounds were more symmetrical than wheezes as detected by this algorithm. Materials and Methods Patients were selected for this study from a pool of patients who had undergone lung sound analysis as a part of a broader study of the correlation of disease processes with lung sounds patterns. Patients with a wheeze rate of 12% per breath or more were chosen for the study from a pool of over 1,000 patients. These included 32 patients with Asthma, 45 with COPD, and three with VCD. In addition, we analyzed spoken voice sounds from 53 patients with asthma, 64 patients with COPD, and 145 subjects with no diagnosed lung disease. A 16-channel lung sound analyzer (shown below) was used to collect 20 second samples of sound during deeper than normal breathing. The STG software automatically identified wheezes in all full breaths. Inspiratory and expiratory wheezes were analyzed separately.. Wheeze rate (percent of breath cycle occupied by wheezing) and wheeze pitch in patients selected for the study were not statistically significantly different. Acoustic Symmetry Coefficient (ASC) Frequency distribution of the acoustic symmetry coefficient of wheezes and voice sounds Average acoustic symmetry coefficient of wheezes and voice soundsLimitations This study was limited to only three confirmed VCD patients. More studies are needed to find out if ASC is useful in differential diagnosis of asthma and VCD patients. Discussion The computerized analytic technique of calculating an acoustic symmetry coefficient (ASC) showed higher values for voice sound than for wheezes. As voice sounds are generated centrally in the vocal cords and wheezes of asthma and COPD are generated peripherally in the lung this provides evidence that the ASC is useful in determining that a sound is generated centrally rather than peripherally. The ASC was greater than 50% in all voice sounds and was less than 50% in all wheezes. In two patients with VCD the ASC was 55 and 68 consistent with central generation of this sound. One VCD patient had an ASC of 40%. This is relatively high but indicates that more VCD patients needs to be studied to determine the sensitivity and specificity of this method. High Left to Right Symmetry (ASC=55%) The frequency distribution of the acoustic symmetry coefficient in wheezing patients with asthma and COPD was compared to the ASC in the same patients saying “eee”. Note that the transmission of centrally-generated vocal sounds is significantly more symmetrical (greater ASC) than the transmission of peripherally-generated wheezing All wheezes had an ASC less than 50. All vocal sounds had ASC greater than 50. The three patients with confirmed VCD had ASC's of 40, 55 and 68. This figure shows time-expanded sound waveforms of wheezes recorded from a patient with asthma. The waveforms are superimposed on a body plot. Each waveform is positioned on the part of the body plot where the sound was recorded. A prominent wheeze is seen on the tracing from channel 14. The amplitude of the wheeze decays at a distance away from the microphone 14. The site responsible for generation of this wheeze is likely located closer to microphone 14 than to the other microphones. Conclusions This study provides evidence that acoustic symmetry calculations have the promise of being useful in the differential diagnosis of asthma and VCD patients. Currently the gold standard for VCD diagnosis is video laryngoscopy. This test is both expensive and inconvenient. It has to be conducted when the patient is wheezing. The assessment of ASC is non-invasive and can be performed at the bedside within minutes. AsthmaCOPDVCD Inspiratory wheeze rate (%)27±18 (n=20) 22±18 (n=20) N/A Expiratory wheeze rate (%)48±25 (n=29) 46±24 (n=30) 54±14 (n=3) Inspiratory wheeze pitch (Hz) 256±100191±77N/A Expiratory wheeze pitch (Hz) 248±80215±94 Hz387±162 Wheeze Rate and Pitch Low Left to Right Symmetry (ASC=18%) This figure shows sound waveforms recorded from a patient with VCD. Notice that in this patient it is much harder to pinpoint the microphone closest to the wheeze generating part of the bronchial tree. The sinusoidal wheeze pattern is prominent at most channels including the tracheal channel. The distribution of the sound amplitude looks more symmetrical than in the patient with asthma. An acoustic symmetry coefficient (ASC) was calculated using a technique that crosscorrelated the signal between all symmetrical channels. ASC=100% when sounds in the left and right lungs are identical. ASC=0% when sounds are completely different between left and right lungs. Inspiratory wheezes and voiceExpiratory wheezes and voice Acoustic symmetry coefficient (%) Number of Patients AsthmaCOPDVCDNormals Inspiratory wheeze ASC (%) 27±11 (n=20) 29±9 (n=20) N/A Expiratory wheeze ASC (%) 31±8 (n=29)31±8 (n=30) 54±14 (n=3) N/A Voice ASC (%) 74±970±12N/A74±10 Wheezing in patients with asthma and COPD was asymmetrical with ASC in the range between 20 and 50%. The ASC’s in patients with asthma, COPD, and persons with no significant lung disease saying “eee” were in the range of 50 to 90%. The ASC’s of wheezes were similar in patients with asthma and COPD. The ASC’s of voice sounds were also similar in patients with asthma, COPD, and in subjects with no recognized lung disease. The ASC’s of voice sounds were statistically different from ASC’s of wheezes (p<0.0001).