Thorax 1995;50:1285-1291 1285 Significant differences in flow standardised breath sound spectra in patients with chronic Thorax: first published as 10.1136/thx.50.12.1285 on 1 December 1995. Downloaded from obstructive pulmonary disease, stable , and healthy

L Pekka Malmberg, Leena Pesu, Anssi R A Sovijarvi

Abstract as adventitious breath sounds - for example, Background - Spectral characteristics of and - can be objectively and breath sounds in asthma and chronic ob- accurately recorded. In early studies Forgacs7 structive pulmonary disease (COPD) have showed that breath sound intensity at the not previously been compared, although mouth was associated with forced expiratory the structural differences in these dis- volume in one second (FEVI) in patients with orders mightbe reflected in breath sounds. asthma and chronic obstructive , but Methods - Flow standardised inspiratory not in those with emphysema. Later it was breath sounds in patients with COPD (n = shown that sound intensity is related to 17) and stable asthma (n= 10) with sig- regional distribution of ventilation8 and is re- nificant airways obstruction and in control duced primarily by airflow limitation in patients patients without any respiratory disorders with emphysema.9 Spectral changes dis- (n =11) were compared in terms of es- tinguishing the asthma patients from healthy timates of the power spectrum. Breath subjects have been described.3`510 In addition, sounds were recorded simultaneously at the frequency content of breath sounds was the chest and at the trachea. found to be dependent on the degree of bron- Results - The median frequency (F50) of chial obstruction during challenge tests, even the mean (SD) breath sound spectra re- in the absence of wheezing sounds."'-" corded at the chest was higher in asth- Standards for the diagnosis of obstructive matics (239 (19) Hz) than in both the pulmonary diseases are available.'4 In clinical control patients (206 (14) Hz) and the and functional patterns there is a considerable

patients with COPD (201 (21) Hz). The overlap between asthma and chronic ob- http://thorax.bmj.com/ total spectral power of breath sounds re- structive pulmonary disease (COPD), although corded at the chest in terms of root mean the morphological and structural changes in square (RMS) was higher in asthmatics the bronchi and lung parenchyma, as well as than in patients with COPD. In patients the site of these changes in the bronchial tree, with COPD the spectral parameters were are partly different.516 The different structural not statistically different from those of and morphological changes in COPD and control patients. The Fso recorded at the asthma might be reflected in breath sounds. trachea in the asthmatics was significantly At present there are few data available on related to forced expiratory volume in one the spectral characteristics of breath sounds in on September 29, 2021 by guest. Protected copyright. second (FEVy) (r= -0.77), but this was not COPD, and no comparative data on the breath seen in the other groups. sounds of patients with asthma and COPD. Department of Conclusions - The observed differences The aim of the present study was to investigate Medicine, Division of Pulmonary in frequency content of breath sounds in the spectral characteristics of patients with Diseases and patients with asthma and COPD may re- COPD and stable asthma with significant air- Clinical Physiology, flect altered sound generation or trans- ways obstruction under standardised con- Helsinki University Central Hospital, mission due to structural changes of the ditions, and to compare them with those of sex 00290 Helsinki, bronchi and the surrounding lung tissue in and age matched control patients with healthy Finland these diseases. Spectral analysis ofbreath lungs. L P Malmberg sounds may provide a new non-invasive A R A Sovijarvi method for of ob- Laboratory of structive pulmonary diseases. Methods Biomedical (Thorax 1995;50:1285-1291) Engineering, PATIENTS Helsinki Thirty eight male outpatients referred to the University of Keywords: , asthma, chronic ob- Technology, structive pulmonary disease. Lung Function Laboratory at Helsinki Uni- Helsinki, Finland versity Central Hospital were selected for the L Pesu study. Their anthropometric and lung function Reprint requests to: data are presented in table 1. Professor A R A Sovijarvi. Computer assisted techniques for lung sound Seventeen patients had stable chronic ob- Received 12 January 1995 analysis1`6 have provided new data on the re- structive pulmonary disease diagnosed pre- Returned to authors 23 March 1995 lationship between respiratory sounds and viously according to ATS criteria'4; all were Revised version received different pathophysiological conditions of the heavy current or ex-smokers. The degree of 12 June 1995 Accepted for publication lung. By using these methods, changes in pul- obstruction assessed by spirometric tests 30 August 1995 monary and tracheal breath sounds as well ranged from mild to very severe. None of the 1 286 Malmberg, Pesu, Sovijarvi

Table 1 Median (range) anthropometric and lungfunction data of the patients with asthma, chronic obstructive pulmonary disease (COPD) and controls

Asthma COPD Controls Thorax: first published as 10.1136/thx.50.12.1285 on 1 December 1995. Downloaded from (n= 10) (n = 17) (n = 11) Age (years) 50 (26-72) 58 (38-73) 50 (44-66) Height (cm) 176 (164-180) 172 (166-185) 174 (165-176) Weight (kg) 76 (58-99) 76 (57-97) 82 (67-87) FEV, (1) 2-59 (1-02-3-61)* 1-26 (0-59-3-20)* 3-55 (3-26-5.05) FEV, (% predicted'7) 67-5 (31-79)* 36 (16-79)* 95 (85-124) TLCO (% predicted'7) 57 (35-93) Kco (% predicted'7) 67 (40-105) FEV, forced expiratory volume in one second; TLco =carbon monoxide lung transfer factor; Kco =carbon monoxide transfer coefficient. * p<0-001 compared with control patients.

patients had oz,-antitrypsin deficiency. In 10 breath sounds. A rolling seal flow volume spir- patients with COPD the specific diffusing cap- ometer (CPI 220, Cardiopulmonary Instru- acity for carbon monoxide (Kco = diffusing ments, Houston, Texas, USA) connected to a capacity (TLCo) related to alveolar volume) was microcomputer system (Medikro 202, Medikro below that predicted, suggesting the presence Oy, Kuopio, Finland) was used to measure of emphysema; radiographically there were no FEV, and for assessment ofthe degree ofventil- signs of interstitial lung disorders such as pul- atory impairment; the highest value of at least monary fibrosis. Eleven of the patients with three successive determinations was recorded. COPD were on 2 sympathomimetics, nine The TLCo and Kco, corrected according to were on inhaled or oral corticosteroids, eight the actual blood haemoglobin concentration, were on theophylline, and five were taking were determined from the patients with COPD inhaled ipratropium bromide. In addition, two by the single breath method'8 (Masterlab, Erich patients with COPD were on long acting Jaeger GmbH, Wurzburg, Germany). The nitrates for mild coronary heart disease. mean value of two determinations was re- Ten patients had stable asthma diagnosed corded. previously according to the ATS criteria"4 but Breath sounds were recorded simultaneously had no other cardiorespiratory disease. None from the chest wall and the trachea. The of the asthmatics had smoked during the pre- method has been described earlier.6"' For re- vious 10 years. The degree of bronchial ob- cording of lung sounds an air-coupled con- struction ranged from mild to severe. All denser microphone (B&K 4134; sensitivity asthmatics were on regular 2 sympatho- 12-5 mV/Pa; free field frequency response mimetics; in addition, seven patients used in- 3-20 000 Hz (-3 dB)) was attached with a haled or oral corticosteroids, five theophylline, rubber belt to the patient's chest at the right http://thorax.bmj.com/ and two ipratropium bromide, but no other lower lobe area, approximately 10 cm below drugs. the margin ofthe scapula and 15 cm to the right Eleven patients with suspected coronary of the spine. The exact location was chosen by heart disease, referred to the laboratory for ordinary based on sufficient sound routine pulmonary function tests prior to cor- intensity. The microphone was encased in the onary angiography, were selected as controls, cup of a hearing shelter to reduce ambient matched according to age and sex. None had noise. The diameter and depth of the slightly symptoms or signs of any respiratory disease conical coupling cavity were 17 and 5 mm, on September 29, 2021 by guest. Protected copyright. or heart failure, and their spirometric values respectively. A small piezoelectric contact and chest radiographs were normal. None were sensor (PPG Sensor no. 102, Technion, Haifa, current or ex-smokers. They all had regular Israel; sensitivity 8 mV/Pa; free field frequency medication for coronary disease (eight were on response essentially flat (± 3 dB) within acetylsalicylic acid, nine were on long acting 100-1500 Hz) was hand held at the trachea on nitrates, seven I adrenergic blocking agents, the right side of the cricothyroid cartilage. The and three nifedipine), but not for any res- sound signals were prefiltered with a third order piratory disorder or for cardiac insufficiency; high pass filter with a cut off frequency of one control patient used digoxin for episodic 50 Hz (18 dB/oct) to prevent saturation of the supraventricular tachyarrhythmia. amplifier by low frequency noise. The amplifier No patient in any group had suffered from (B&K 2619) had a flat (±0-5 dB) frequency a respiratory infection during the two weeks response curve over 20-20 000 Hz. preceding the test, and the patients had used During breath sound recording the flow at their medication regularly when entering into the mouth was monitored with a pneumo- the study. tachograph (Medikro MF S202, Medikro Oy, Informed consent was obtained from every Kuopio, Finland) with a zero centre analogue patient and the study was approved by the monitor in front of the patient. Each patient ethics committee of the Department of Pul- wore a noseclip and was asked to keep his peak monary Diseases at Helsinki University Central inspiratory and expiratory flows at a target level Hospital. of 1 25 l/s; all patients were carefully trained in the technique before the recording. The sound and flow signals were recorded STUDY DESIGN with an eight channel DAT recorder (Teac Spirometric tests were performed on every RD-1 IT, frequency response DC patient 10-15 minutes before recording of -5 kHz + 0 5 dB). The analogue output signal Flow standardised breath sound spectra 1 287

of the recorder was digitised in a data ac- quency domain (FFT). The criteria for a quisition and control unit (HP 3852A) with were the presence of a sinusoidal wave- 13-bit analogue-to-digital conversion; the sam- form with a duration of more than 200 ms or Thorax: first published as 10.1136/thx.50.12.1285 on 1 December 1995. Downloaded from pling rate was 12 kHz for sound and 100 Hz an intensity peak distinctly separated from its for the airflow. A Bessel type low pass filter surrounding intensity in the FFT spectrum. with a cut off frequency of 4 kHz (24 dB/oct) Within the inspiratory flow gate chosen for was used to prevent aliasing. The data from analysis (1-0-1-25 l/s) none of the patients was the flow and sound signals were stored on a found to wheeze. magneto-optical disk of a Unix work station (HP 9000/330C). The sound signal was di- gitally high pass filtered (Kaiser-FIR) with a DATA ANALYSIS cut off frequency of 100 Hz (24 dB/oct). The breath sound variables between the study The flow and sound signals were sub- groups were compared by the non-paired t test sequently analysed on a computer by using with the p values being adjusted for multiple custom made software based on Labview tool comparison according to the Bonferroni equa- package. For the spectral analysis of sound tion (p*=pK; K=k(k-1)/2 where p* is the signals 2048-point fast Fourier transforms were adjusted value of p and k is the number of performed with 50% overlapping of adjacent groups).20 For correlative analysis within the Hanning data windows; the spectra were av- groups, Pearson's correlation coefficient was eraged over 8-10 consecutive cycles calculated. A p value of less than 0-05 was by the method of Welch.'9 The effective fre- considered significant. quency resolution of the spectral estimates was approximately 5 Hz. Only sound samples of inspiratory sounds that occurred at flows from Results 1-0/s to target flow (1-25 /s) were used for Examples ofphonopneumograms and averaged calculation of averaged spectra. The average inspiratory spectra recorded at the chest in power spectra of background noise were sim- patients with asthma, COPD, and normal lungs ilarly estimated from sound samples within a are illustrated in fig 1. The spectra are cal- flow gate of 0 + 0-1/s. These spectra were culated from sound samples at an airflow gate used to evaluate the signal-to-noise ratio of of 1 -0-1-25 1/s. In each spectrum plotted on the recordings. Expiratory sounds were not a log-log scale the F50 is indicated and the analysed because the breathing pattern could background spectra (sound at 0 +0-1 /s flow) not be standardised among the patient groups presented. The expiratory flow profiles differed due to expiratory flow limitation in some between the patients with different diagnoses patients with asthma or COPD. as shown in fig 1, but inspiratory flow profiles The upper frequency limits for the second appeared quite similar. The spectra in fig 1 are quartile (F50, the median frequency) and the smooth in shape without irregularities or peaks http://thorax.bmj.com/ third (F75) quartile of the spectral power were that could indicate wheezing sounds. The spec- calculated within a measuring band of trum of the asthma patient is broader in shape, 100-2000 Hz on the linear amplitude scale. indicating increased sound energy at a fre- The frequency of maximum intensity (Fmax) quency range of 200-1000 Hz; consequently, and the lung sound amplitude in terms of the the F50 is increased compared with that of the root mean square (RMS) value of the total control patient. In the patient with COPD the spectral power were also determined within the attenuation ofthe sound power is more gradual same measuring band. over the whole frequency range, but the global on September 29, 2021 by guest. Protected copyright. The presence or absence of wheezes in the frequency distribution in terms of F50 is not sound samples was evaluated by visual ex- significantly different from that of the control amination ofthe sound signal in time-expanded patient. In the whole group of patients with waveform analysis (1000 mm/s) and in fre- COPD we did not find any characteristic spec-

Control patient Patient with COPD i1s .0 Asthmatic patient 1 s s 1 s .b. [N. f N. &a .$ 1.001 iii flOa.04 1.00 a. .t1.00 - 00 0.00 0.00 ;Al & 1;Ibo -I- 0.00 0 ~ ~ ~ ~ VIFPY 0.00 rwqm i"-.AQib E -1.00 I -10 * 1 00 E ,, -1 0 C* Eu. ___ E -1.00 E 0 1 205 Hz 0- 267 Hz u - _1 190 Hz -5 - -10 -.__ ___ -10 -15 -15 .. lm m a 'a -20- -20' .. s 'a -25 -25 - L- -25 -310 a) -30 - 0) -10. 0 -35- -35 -35 a- 0 -40- 0- -40 - 0~ -40. -45- -45 .-. -45- 100 1000 2000 100 1000 2000 100 1000 2000 Frequency (Hz) Frequency (Hz) Frequency (Hz)

Figure 1 Examples ofphonopneumograms andflow standardised inspiratory spectra recorded at the chest in a control patient and patients with asthma and COPD. Only sound samples at a flow gate of 1 -0-1 -25 1/s (indicated as lines under the flow curve) were used for cakulation of the averaged spectra. In each spectrum the median frequency (solid vertical line) is indicated and the background (sound at 0+ 0-1 lls flow) spectra presented (dotted line). 1288 Malmberg, Pesu, Sovijarvi

275 n A RMS was not significantly different among the patient groups. The Fmax varied between in- 250 H dividuals, especially at the trachea, and no Thorax: first published as 10.1136/thx.50.12.1285 on 1 December 1995. Downloaded from A A significant differences between the study 225 [ A p<0.001 ------p<0OOO1l- A groups were found. Ir-4 0 LL 200 F A A NS -- Discussion 175 H The results of this study indicate that the fre- quency content of breath sounds in asthmatic 150 Controls Asthma COPD patients with airways obstruction differs mark- edly from that of patients with COPD and Figure 2 Distribution of inspiratory median ftrequency those with normal lungs. This observation may (F5) of breath sounds recorded at the chest in Ipatients with asthma, COPD, and healthy lungs (cont reflect different pathophysiological mech- COPD group open triangles refer to patients wiithreduced anisms of lung sound generation or trans- specific diffusing capacity. mission between asthma and COPD, and this may provide new tools for the differential diag- nosis ofobstructive pulmonary diseases. Breath sounds detected at the chest wall and at the tral pattern different from that obf control trachea are, to some extent, influenced by the patients. physical dimensions of the airways and struc- The values of the breath sound p:arameters ture of the surrounding lung tissue.2"22 In in the three patient groups are pre in COPD histological changes of peripheral air- table 2. The inspiratory F50 and sented F75hecor e ways disease and emphysema can be found at the chest wall were significantly hgher (P with both inflammation of the terminal and <0-001 and p <0-01, respectively) in the asth- respiratory bronchioles and fibrosis of the air- matic than in the control patients. TheSF50ofthe ways walls. In asthma the bronchial mucosa patients with COPD did not differ sig,nificantly is infiltrated with inflammatory cells, together from that of the control patients buit was sig- with shedding of the epithelium and smooth nificantly lower than that of the asthmatics (P muscle hypertrophy. The type of structural <0-0001). The distribution of F50 recorded at change and its site in the bronchi and lung the chest in each of the three patient groups is parenchyma differ between COPD and illustrated in fig 2. The spectral parameters asthma,51623 and this may account for the recorded at the trachea did not c er sig- differences in the frequency content of breath nificantly among the patient groups. sounds. In patients with asthma the F50 of breath The patients in this study were carefully http://thorax.bmj.com/ -a wabreah sound spectra recorded at the trachewa was.re- selected to meet the ATS criteria for asthma and lated to FEV, (r= -0 77, p <001) a*nd a sim- COPD,14 but had no other cardiorespiratory ilar but not statistically significant re]lationship disease; only non-smokers were included in the was recorded at the chest (r= -0 50, p <0.10); asthma group to ensure a diagnosis of pure patients with severe obstruction had t]he highest asthma. Since peripheral airways disease and F50 values. In patients with COPID and in emphysema often coexist in COPD and are controls the F50 was not significantly related to sometimes clinically difficult to distinguish, the FEV, either at the chest or at the tr In patients with COPD were treated as a single on September 29, 2021 by guest. Protected copyright. patients with COPD the inspiratory F acheae h group. It may be argued that the control to be weakly related to Kco so thattheemedthose patients did not represent a true healthy popu- patients with reduced Kco had lower]F50values; lation. However, they were non-smokers with however, the correlation was not st tatistically no respiratory disorders or heart failure which significant (r=0A43, p <0 10). alter the breath sounds. Most of these The total spectral power record( h might edhati control patients used adrenergic blocking chest in terms ofRMS was higher in a cs agents which are known to alter the bronchial than in patients with COPD. Othei tone in asthmatics; however, in patients with no history of asthma ,B adrenergic blockade should have no significant effects on the bron- Table 2 Mean (SD) total spectral power (RMS), frequency of maximum inttensity chi.24 In addition, the findings of flow-volume (Fmax), and upperfrequency limits for the second (F50) and the third (F75)

sound spectra. They used regression analysis patients also indicates the close relationship of the spectral curve to define abnormality, between frequency distribution of breath which is a particularly useful method to detect sounds and narrowing of the airways. Thorax: first published as 10.1136/thx.50.12.1285 on 1 December 1995. Downloaded from curve irregularities caused by wheezing sounds. The present results indicate that, in patients The quartile frequencies were not used in this with COPD, the vesicular lung sounds are study, and the patterns of abnormalities in either unchanged in spite of airway narrowing COPD were not compared with those in or some other mechanisms are involved that asthma. In our study flow standardised in- counteract the effect of increased turbulence spiratory breath sounds that did not contain in the bronchi. The sound generation in asthma wheezes did not differ between COPD and and COPD may be different since the structural control patients, but in asthmatic patients sig- changes in the bronchi in patients with COPD nificantly higher RMS, F50 and F75 values were are situated more peripherally in small airways found than in patients with COPD. The spec- where turbulence does not occur in normal tral shapes did not differ visually between conditions. The trend between Kco and F50 of patients with COPD and control patients, and inspiratory lung sounds in COPD suggests that the frequency range that contained breath the sound is affected by the degree of em- sounds with substantial power relative to back- physema. The lung parenchyma and the chest ground spectra was about the same in the wall act like a band pass filter. The average two groups. However, the frequency content density of lung tissue is reduced in emphysema of inspiratory vesicular lung sounds in patients due to tissue destruction; this should affect the with COPD seemed to be affected by the pres- transmission of lung sounds from their source ence ofemphysema, patients with reduced Kco to the chest wall22 and accentuate the low pass having lower F50 values. filtration effect of the thorax. Consequently, It has been shown that the auscultatory find- lower frequency lung sounds would be detected ing of damped breath sounds in patients with at the chest, a possible explanation for the emphysema is predominantly due to airflow difference between asthma and COPD. limitation, and that at standardised airflows the Breath sounds heard at the trachea are pre- breath sound intensity is similar in patients sumably generated in the very central airways with emphysema and healthy controls.9 The by turbulent mechanisms, and the larynx may RMS values in the present study were cal- also contribute to the sound production by culated from the power spectrum and are not acting as a nozzle, creating a jet of air.2' The therefore equivalent to breath sound intensity. correlation between FEV, and F50 in asthmatic However, our finding that the total spectral patients may relate to increased turbulence power did not differ between the COPD in central airways, probably caused by airway patients and controls was consistent with the narrowing. The frequency distribution oftrach- eal sounds has high intersubject variation which previous literature. During episodes of normal http://thorax.bmj.com/ lung function in asthmatic patients Schreur et relates to individual resonant frequencies with allo found that, at a given airflow, expiratory accentuated intensities. Thus, significant sounds were lower in intensity than those of differences between the patient groups could the healthy controls. In contrast, they did not not be found for tracheal sounds. find any difference in inspiratory sound in- The finding that breath sound spectral pat- tensity between their study groups as we did terns in patients with COPD and asthma differ between the control patients and asthmatic significantly may have also clinical implications, patients with airways obstruction. since it provides new tools for differential diag- The generally accepted view is that vesicular nosis of obstructive lung disorders. In the pres- on September 29, 2021 by guest. Protected copyright. lung sounds are generated predominantly by ent study, however, the F50 values in asthma turbulence in the larger airways (main, lobar, and in COPD partly overlapped, and the speci- and segmental bronchi) and transmitted from ficity of a given F50 value is probably not very these locations to the chest wall.2" The cal- high. Further studies may reveal other spectral culations from gas density, viscosity, and estimators that could be used to separate the velocity predict laminar and, presumably, groups more effectively. soundless flow in more peripheral airways. In conclusion, the present findings indicate However, there is experimental evidence to that the frequency spectra of breath sounds in show that at least the inspiratory portion of patients with stable asthma, but not in patients vesicular lung sounds is produced locally in with COPD, differ significantly from those in small airways by non-turbulent mechanisms.38 patients with healthy lungs. It is postulated that In asthmatic patients the increase in frequency the structural changes in the bronchi and in the content of breath sounds during broncho- surrounding lung tissue in COPD and asthma constriction can be explained by the local in- result in different breath sound generation or crease of flow velocity through the narrowed transmission. Breath sound spectral analysis bronchi which results in increased kinetic en- may provide a new non-invasive method for ergy and turbulence, characterised by a higher differential diagnosis of bronchial obstruction. pitch sound.39 According to the model of un- This study was supported by the Ida Montin Foundation, stable vortices by Hardin and Patterson40 the Finland. The authors are grateful to Erkki Paajanen and Kari sound frequency produced is inversely related Kallio for their technical collaboration. to the diameter of the airways at a given mass 1 Murphy RLH, Sorensen K. Chest auscultation in the flow; higher sound frequencies are thus ex- diagnosis of pulmonary asbestosis. Jf Occup Med 1973;15: pected to be found in asthmatics with narrowed 272-6. 2 Murphy RLH, Holford SK, Knowler WC. Visual lung- airways. The present finding that the F5,, is sound characterization by time-expanded wave-form ana- significantly correlated with FEV, in asthmatic lysis. N Engl_J Med 1977;296:968-71. Flow standardised breath sound spectra 1291

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