significant differences

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Thorax 1995;50:1285-1291 Significant differences in flow standardised breath sound spectra in patients with chronic obstructive pulmonary disease, stable asthma, and healthy lungs L Pekka Malmberg, Leena Pesu, Anssi R A Sovijarvi Abstract Background - Spectral characteristics of breath sounds in asthma and chronic ob- structive pulmonary disease (COPD) have not previously been compared, although the structural differences in these dis- orders might be reflected in breath sounds. Methods - Flow standardised inspiratory breath sounds in patients with COPD (n = 17) and stable asthma (n= 10) with sig- nificant airways obstruction and in control patients without any respiratory disorders (n =11) were compared in terms of es- timates of the power spectrum. Breath sounds were recorded simultaneously at the chest and at the trachea. Results - The median frequency (F50) of the mean (SD) breath sound spectra re- corded at the chest was higher in asth- matics (239 (19) Hz) than in both the control patients (206 (14) Hz) and the patients with COPD (201 (21) Hz). The total spectral power of breath sounds re- corded at the chest in terms of root mean square (RMS) was higher in asthmatics than in patients with COPD. In patients with COPD the spectral parameters were not statistically different from those of control patients. The Fso recorded at the trachea in the asthmatics was significantly related to forced expiratory volume in one second (FEVy) (r= -0.77), but this was not seen in the other groups. Conclusions - The observed differences in frequency content of breath sounds in patients with asthma and COPD may re- flect altered sound generation or trans- mission due to structural changes of the bronchi and the surrounding lung tissue in these diseases. Spectral analysis of breath sounds may provide a new non-invasive method for differential diagnosis of ob- structive pulmonary diseases. (Thorax 1995;50:1285-1291) Keywords: respiratory sounds, asthma, chronic ob- structive pulmonary disease. Computer assisted techniques for lung sound analysis1`6 have provided new data on the re- lationship between respiratory sounds and different pathophysiological conditions of the lung. By using these methods, changes in pul- monary and tracheal breath sounds as well as adventitious breath sounds - for example, wheezes and crackles - can be objectively and accurately recorded. In early studies Forgacs7 showed that breath sound intensity at the mouth was associated with forced expiratory volume in one second (FEVI) in patients with asthma and chronic obstructive bronchitis, but not in those with emphysema. Later it was shown that lung sound intensity is related to regional distribution of ventilation8 and is re- duced primarily by airflow limitation in patients with emphysema.9 Spectral changes dis- tinguishing the asthma patients from healthy subjects have been described.3`510 In addition, the frequency content of breath sounds was found to be dependent on the degree of bron- chial obstruction during challenge tests, even in the absence of wheezing sounds."'-" Standards for the diagnosis of obstructive pulmonary diseases are available.'4 In clinical and functional patterns there is a considerable overlap between asthma and chronic ob- structive pulmonary disease (COPD), although the morphological and structural changes in the bronchi and lung parenchyma, as well as the site of these changes in the bronchial tree, are partly different. 516 The different structural and morphological changes in COPD and asthma might be reflected in breath sounds. At present there are few data available on the spectral characteristics of breath sounds in COPD, and no comparative data on the breath sounds of patients with asthma and COPD. The aim of the present study was to investigate the spectral characteristics of patients with COPD and stable asthma with significant air- ways obstruction under standardised con- ditions, and to compare them with those of sex and age matched control patients with healthy lungs. Methods PATIENTS Thirty eight male outpatients referred to the Lung Function Laboratory at Helsinki Uni- versity Central Hospital were selected for the study. Their anthropometric and lung function data are presented in table 1. Seventeen patients had stable chronic ob- structive pulmonary disease diagnosed pre- viously according to ATS criteria'4; all were heavy current or ex-smokers. The degree of obstruction assessed by spirometric tests ranged from mild to very severe. None of the Department of Medicine, Division of Pulmonary Diseases and Clinical Physiology, Helsinki University Central Hospital, 00290 Helsinki, Finland L P Malmberg A R A Sovijarvi Laboratory of Biomedical Engineering, Helsinki University of Technology, Helsinki, Finland L Pesu Reprint requests to: Professor A R A Sovijarvi. Received 12 January 1995 Returned to authors 23 March 1995 Revised version received 12 June 1995 Accepted for publication 30 August 1995 1285

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  • Thorax 1995;50:1285-1291

    Significant differences in flow standardisedbreath sound spectra in patients with chronicobstructive pulmonary disease, stable asthma,and healthy lungs

    L Pekka Malmberg, Leena Pesu, Anssi R A Sovijarvi

    AbstractBackground - Spectral characteristics ofbreath sounds in asthma and chronic ob-structive pulmonary disease (COPD) havenot previously been compared, althoughthe structural differences in these dis-orders mightbe reflected in breath sounds.Methods - Flow standardised inspiratorybreath sounds in patients with COPD (n =17) and stable asthma (n= 10) with sig-nificant airways obstruction and in controlpatients without any respiratory disorders(n =11) were compared in terms of es-timates of the power spectrum. Breathsounds were recorded simultaneously atthe chest and at the trachea.Results - The median frequency (F50) ofthe mean (SD) breath sound spectra re-corded at the chest was higher in asth-matics (239 (19) Hz) than in both thecontrol patients (206 (14) Hz) and thepatients with COPD (201 (21) Hz). Thetotal spectral power of breath sounds re-corded at the chest in terms of root meansquare (RMS) was higher in asthmaticsthan in patients with COPD. In patientswith COPD the spectral parameters werenot statistically different from those ofcontrol patients. The Fso recorded at thetrachea in the asthmatics was significantlyrelated to forced expiratory volume in onesecond (FEVy) (r= -0.77), but this was notseen in the other groups.Conclusions - The observed differencesin frequency content of breath sounds inpatients with asthma and COPD may re-flect altered sound generation or trans-mission due to structural changes of thebronchi and the surrounding lung tissue inthese diseases. Spectral analysis ofbreathsounds may provide a new non-invasivemethod for differential diagnosis of ob-structive pulmonary diseases.(Thorax 1995;50:1285-1291)

    Keywords: respiratory sounds, asthma, chronic ob-structive pulmonary disease.

    Computer assisted techniques for lung soundanalysis1`6 have provided new data on the re-lationship between respiratory sounds anddifferent pathophysiological conditions of thelung. By using these methods, changes in pul-monary and tracheal breath sounds as well

    as adventitious breath sounds - for example,wheezes and crackles - can be objectively andaccurately recorded. In early studies Forgacs7showed that breath sound intensity at themouth was associated with forced expiratoryvolume in one second (FEVI) in patients withasthma and chronic obstructive bronchitis, butnot in those with emphysema. Later it wasshown that lung sound intensity is related toregional distribution of ventilation8 and is re-duced primarily by airflow limitation in patientswith emphysema.9 Spectral changes dis-tinguishing the asthma patients from healthysubjects have been described.3`510 In addition,the frequency content of breath sounds wasfound to be dependent on the degree of bron-chial obstruction during challenge tests, evenin the absence of wheezing sounds."'-"

    Standards for the diagnosis of obstructivepulmonary diseases are available.'4 In clinicaland functional patterns there is a considerableoverlap between asthma and chronic ob-structive pulmonary disease (COPD), althoughthe morphological and structural changes inthe bronchi and lung parenchyma, as well asthe site of these changes in the bronchial tree,are partly different.516 The different structuraland morphological changes in COPD andasthma might be reflected in breath sounds.At present there are few data available on

    the spectral characteristics of breath sounds inCOPD, and no comparative data on the breathsounds of patients with asthma and COPD.The aim of the present study was to investigatethe spectral characteristics of patients withCOPD and stable asthma with significant air-ways obstruction under standardised con-ditions, and to compare them with those of sexand age matched control patients with healthylungs.

    MethodsPATIENTSThirty eight male outpatients referred to theLung Function Laboratory at Helsinki Uni-versity Central Hospital were selected for thestudy. Their anthropometric and lung functiondata are presented in table 1.

    Seventeen patients had stable chronic ob-structive pulmonary disease diagnosed pre-viously according to ATS criteria'4; all wereheavy current or ex-smokers. The degree ofobstruction assessed by spirometric testsranged from mild to very severe. None of the

    Department ofMedicine,Division of PulmonaryDiseases andClinical Physiology,Helsinki UniversityCentral Hospital,00290 Helsinki,FinlandL P MalmbergA R A Sovijarvi

    Laboratory ofBiomedicalEngineering,HelsinkiUniversity ofTechnology,Helsinki, FinlandL Pesu

    Reprint requests to:Professor A R A Sovijarvi.Received 12 January 1995Returned to authors23 March 1995Revised version received12 June 1995Accepted for publication30 August 1995

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  • Malmberg, Pesu, Sovijarvi

    Table 1 Median (range) anthropometric and lung function data of the patients with asthma, chronic obstructivepulmonary disease (COPD) and controls

    Asthma COPD Controls(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 transfercoefficient.* p

  • Flow standardised breath sound spectra

    of the recorder was digitised in a data ac-quisition and control unit (HP 3852A) with13-bit analogue-to-digital conversion; the sam-pling rate was 12 kHz for sound and 100 Hzfor the airflow. A Bessel type low pass filterwith a cut off frequency of 4 kHz (24 dB/oct)was used to prevent aliasing. The data fromthe flow and sound signals were stored on amagneto-optical disk of a Unix work station(HP 9000/330C). The sound signal was di-gitally high pass filtered (Kaiser-FIR) with acut off frequency of 100 Hz (24 dB/oct).The flow and sound signals were sub-

    sequently analysed on a computer by usingcustom made software based on Labview toolpackage. For the spectral analysis of soundsignals 2048-point fast Fourier transforms wereperformed with 50% overlapping of adjacentHanning data windows; the spectra were av-eraged over 8-10 consecutive breathing cyclesby the method of Welch.'9 The effective fre-quency resolution of the spectral estimates wasapproximately 5 Hz. Only sound samples ofinspiratory sounds that occurred at flows from1-0/s to target flow (1 -25 /s) were used forcalculation of averaged spectra. The averagepower spectra of background noise were sim-ilarly estimated from sound samples within aflow gate of 0 + 0-1/s. These spectra wereused to evaluate the signal-to-noise ratio ofthe recordings. Expiratory sounds were notanalysed because the breathing pattern couldnot be standardised among the patient groupsdue to expiratory flow limitation in somepatients with asthma or COPD.The upper frequency limits for the second

    quartile (F50, the median frequency) and thethird (F75) quartile of the spectral power werecalculated within a measuring band of100-2000 Hz on the linear amplitude scale.The frequency of maximum intensity (Fmax)and the lung sound amplitude in terms of theroot mean square (RMS) value of the totalspectral power were also determined within thesame measuring band.The presence or absence of wheezes in the

    sound samples was evaluated by visual ex-amination ofthe sound signal in time-expandedwaveform analysis (1000 mm/s) and in fre-

    quency domain (FFT). The criteria for awheeze were the presence of a sinusoidal wave-form with a duration of more than 200 ms oran intensity peak distinctly separated from itssurrounding intensity in the FFT spectrum.Within the inspiratory flow gate chosen foranalysis (1-0-1-25 l/s) none of the patients wasfound to wheeze.

    DATA ANALYSISThe breath sound variables between the studygroups were compared by the non-paired t testwith the p values being adjusted for multiplecomparison according to the Bonferroni equa-tion (p*=pK; K=k(k-1)/2 where p* is theadjusted value of p and k is the number ofgroups).20 For correlative analysis within thegroups, Pearson's correlation coefficient wascalculated. A p value of less than 0-05 wasconsidered significant.

    ResultsExamples ofphonopneumograms and averagedinspiratory spectra recorded at the chest inpatients with asthma, COPD, and normal lungsare illustrated in fig 1. The spectra are cal-culated from sound samples at an airflow gateof 1 -0-1-25 1/s. In each spectrum plotted ona log-log scale the F50 is indicated and thebackground spectra (sound at 0 +0-1 /s flow)presented. The expiratory flow profiles differedbetween the patients with different diagnosesas shown in fig 1, but inspiratory flow profilesappeared quite similar. The spectra in fig 1 aresmooth in shape without irregularities or peaksthat could indicate wheezing sounds. The spec-trum of the asthma patient is broader in shape,indicating increased sound energy at a fre-quency range of 200-1000 Hz; consequently,the F50 is increased compared with that of thecontrol patient. In the patient with COPD theattenuation of the sound power is more gradualover the whole frequency range, but the globalfrequency distribution in terms of F50 is notsignificantly different from that of the controlpatient. In the whole group of patients withCOPD we did not find any characteristic spec-

    Control patienti1s .0

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    Figure 1 Examples ofphonopneumograms and flow standardised inspiratory spectra recorded at the chest in a control patient and patients with asthmaand 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 averagedspectra. In each spectrum the median frequency (solid vertical line) is indicated and the background (sound at 0+ 0-1 lls flow) spectra presented (dottedline).

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  • Flow standardised breath sound spectra

    not explained by differences in the severity ofairways obstruction.High quality equipment was used for re-

    cording of breath sounds.6 Different micro-phones were used at the trachea and at thechest for anatomical reasons so the sound spec-tra cannot be critically compared between thetwo locations. It should be noted that the fre-quency characteristics of the microphones,27and specifically the dimensions of the air coup-ling cavity," have been shown to modify theshape of lung sound spectra. With the presentcondenser microphone of 5 mm cavity depthsome high frequency components may there-fore have been attenuated in the chest wallrecordings. However, the same microphoneswere used for all patients and their char-acteristics cannot therefore explain the differ-ences among the patient groups.The frequency spectra were averaged to

    minimise the effect of random noise. A cutofffrequency level of 100 Hz was chosen to elim-inate the muscular29 and cardiovascular30sounds from the respiratory sound analysis.Calculation of background noise enabled us toevaluate the signal-to-noise ratio of the sound.The background spectra were not subtractedfrom the analysed breath sound spectra becauserelevant information may have been lost fortwo reasons. Firstly, the background spectrawere derived under dynamic conditions (duringbreathing with flows up to + 0.01 l/s) and in-evitably contained a small contribution of lungsounds. Secondly, in some individuals therewere insufficient data points to create an ac-curate estimate from the background spectrum(even if the level of signal-to-noise ratio couldbe estimated). We believe that, if subtractionofbackground noise is preferred, sound duringbreath holding should be used.3' Our pref-erence to use background noise at zero flow asquality control is the same as that ofPasterkampet al.27 The same recording room and conditionswere used for every patient so the ambientnoise during recordings did not vary sig-nificantly from patient to patient.The flow at the mouth was carefully con-

    trolled during lung sound recordings so thatinspiratory tidal peak flow and pattern weresimilar in the patient groups. The spectral shapehas been shown to be quite stable at high flowrates above 1'0 I/s,3233 but to be dependent onflow at low flow rates.310 Flow gated samplingof respiratory sounds was originally describedby O'Donnel and Kraman.34 In this study weused only sound samples of a defined in-spiratory flow gate (1I0-1 -25 U/s) for the spectralanalysis, ensuring that breath sound spectraamong the patient groups were derived fromexactly the same flows. Differences in airflowor breathing pattern cannot therefore explainthe differences in frequency distribution oflungsounds among the patient groups. Since onlyinspiratory breath sounds were analysed, ex-piratory flow limitation occurring in somepatients with COPD did not influence the res-ults. In contrast, clear differences in expiratoryflow patterns did not allow valid comparisonof expiratory breath sounds so the latter werenot included in the study.

    Compared with control and COPD patients,the different frequency content of breathsounds in the asthmatics was reflected inchanges in F50, F75, and the total spectral power.The presence of adventitious lung sounds suchas wheezes and crackles could change thesespectral indices, but there were no wheezingsounds during the inspiratory sound samplesselected for analysis. Crackling sounds were notcounted, but on visual examination appeared tobe rare in our patients with COPD. Fur-thermore, the averaging method used is rel-atively insensitive to non-stationary changes ofbreath sounds such as crackles. It is thereforeunlikely that adventitious breath sounds wouldhave markedly contributed to the changes ob-served in averaged frequency spectra.

    It may be argued that the present parameterschosen to characterise the breath sound spectra(RMS, Fmax, and the quartiles) are not suffi-cient as they do not provide specific informationabout the pattern of the spectral curve. How-ever, they have been widely used in clinicalstudies of breath sounds in asthma'0 11 13 and,in particular, the quartiles give an estimateof the global frequency distribution of breathsounds, the primary interest of our study.Normal tracheal sounds are characterised by

    a broad spectrum of frequencies with a sharpdecrease ofpower above 800-1600 Hz. Normalvesicular lung sounds in the chest contain aspectrum of frequencies up to approximately500 Hz; the frequency components of lungsounds above this are effectively filtered by thelung tissue and the chest wall.35 In normalmen inspiratory sounds containing substantialpower relative to background noise up to2000 Hz have been reported when high airflowrates are used (up to 2-5 l/s).27 In the presentstudy the usual frequency range at which thebackground noise was reached in chest re-cordings was 1 0-1 2 kHz. However, the targetflow was set at a relatively low level (1I 25 l/s) dueto the reduced ventilatory function in patientswith asthma and COPD.

    In previous studies the frequency spectra ofasthmatics were found to differ from those ofhealthy controls during episodes ofwheezing.3In patients with acute asthma the proportionof the respiratory cycle occupied by wheezingwas found to correlate with FEVI.36 In previousstudies on asthmatics during challenge tests thefrequency distribution of breath sounds wasshown to be related to the degree of bronchialobstruction, with higher F50 values being foundduring bronchial obstruction11-3 and also inthe absence ofwheezing sounds. Schreur et all'recently found similar changes in frequencydistribution of lung sounds in asthma patientseven with normal lung function. The presentfinding that sound energy is shifted towardshigher frequencies in asthmatics compared withcontrols is in accordance with previously re-ported studies.

    In the previous literature there are only fewdata available about the spectral characteristicsof breath sounds in COPD. Gavriely et al37used lung sound analysis for respiratory healthscreening and found that 30 out of 62 subjectswith clinical COPD had abnormal breath

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  • Malmberg, Pesu, Sovijarvi

    sound spectra. They used regression analysisof the spectral curve to define abnormality,which is a particularly useful method to detectcurve irregularities caused by wheezing sounds.The quartile frequencies were not used in thisstudy, and the patterns of abnormalities inCOPD were not compared with those inasthma. In our study flow standardised in-spiratory breath sounds that did not containwheezes did not differ between COPD andcontrol patients, but in asthmatic patients sig-nificantly higher RMS, F50 and F75 values werefound than in patients with COPD. The spec-tral shapes did not differ visually betweenpatients with COPD and control patients, andthe frequency range that contained breathsounds with substantial power relative to back-ground spectra was about the same in thetwo groups. However, the frequency contentof inspiratory vesicular lung sounds in patientswith COPD seemed to be affected by the pres-ence ofemphysema, patients with reduced Kcohaving lower F50 values.

    It has been shown that the auscultatory find-ing of damped breath sounds in patients withemphysema is predominantly due to airflowlimitation, and that at standardised airflows thebreath sound intensity is similar in patientswith emphysema and healthy controls.9 TheRMS values in the present study were cal-culated from the power spectrum and are nottherefore equivalent to breath sound intensity.However, our finding that the total spectralpower did not differ between the COPDpatients and controls was consistent with theprevious literature. During episodes of normallung function in asthmatic patients Schreur etallo found that, at a given airflow, expiratorysounds were lower in intensity than those ofthe healthy controls. In contrast, they did notfind any difference in inspiratory sound in-tensity between their study groups as we didbetween the control patients and asthmaticpatients with airways obstruction.The generally accepted view is that vesicular

    lung sounds are generated predominantly byturbulence in the larger airways (main, lobar,and segmental bronchi) and transmitted fromthese locations to the chest wall.2" The cal-culations from gas density, viscosity, andvelocity predict laminar and, presumably,soundless flow in more peripheral airways.However, there is experimental evidence toshow that at least the inspiratory portion ofvesicular lung sounds is produced locally insmall airways by non-turbulent mechanisms.38In asthmatic patients the increase in frequencycontent of breath sounds during broncho-constriction can be explained by the local in-crease of flow velocity through the narrowedbronchi which results in increased kinetic en-ergy and turbulence, characterised by a higherpitch sound.39 According to the model of un-stable vortices by Hardin and Patterson40 thesound frequency produced is inversely relatedto the diameter of the airways at a given massflow; higher sound frequencies are thus ex-pected to be found in asthmatics with narrowedairways. The present finding that the F5,, issignificantly correlated with FEV, in asthmatic

    patients also indicates the close relationshipbetween frequency distribution of breathsounds and narrowing of the airways.The present results indicate that, in patients

    with COPD, the vesicular lung sounds areeither unchanged in spite of airway narrowingor some other mechanisms are involved thatcounteract the effect of increased turbulencein the bronchi. The sound generation in asthmaand COPD may be different since the structuralchanges in the bronchi in patients with COPDare situated more peripherally in small airwayswhere turbulence does not occur in normalconditions. The trend between Kco and F50 ofinspiratory lung sounds in COPD suggests thatthe sound is affected by the degree of em-physema. The lung parenchyma and the chestwall act like a band pass filter. The averagedensity of lung tissue is reduced in emphysemadue to tissue destruction; this should affect thetransmission of lung sounds from their sourceto the chest wall22 and accentuate the low passfiltration effect of the thorax. Consequently,lower frequency lung sounds would be detectedat the chest, a possible explanation for thedifference between asthma and COPD.

    Breath sounds heard at the trachea are pre-sumably generated in the very central airwaysby turbulent mechanisms, and the larynx mayalso contribute to the sound production byacting as a nozzle, creating a jet of air.2' Thecorrelation between FEV, and F50 in asthmaticpatients may relate to increased turbulencein central airways, probably caused by airwaynarrowing. The frequency distribution oftrach-eal sounds has high intersubject variation whichrelates to individual resonant frequencies withaccentuated intensities. Thus, significantdifferences between the patient groups couldnot be found for tracheal sounds.The finding that breath sound spectral pat-

    terns in patients with COPD and asthma differsignificantly may have also clinical implications,since it provides new tools for differential diag-nosis of obstructive lung disorders. In the pres-ent study, however, the F50 values in asthmaand in COPD partly overlapped, and the speci-ficity of a given F50 value is probably not veryhigh. Further studies may reveal other spectralestimators that could be used to separate thegroups more effectively.

    In conclusion, the present findings indicatethat the frequency spectra of breath sounds inpatients with stable asthma, but not in patientswith COPD, differ significantly from those inpatients with healthy lungs. It is postulated thatthe structural changes in the bronchi and in thesurrounding lung tissue in COPD and asthmaresult in different breath sound generation ortransmission. Breath sound spectral analysismay provide a new non-invasive method fordifferential diagnosis of bronchial obstruction.

    This study was supported by the Ida Montin Foundation,Finland. The authors are grateful to Erkki Paajanen and KariKallio for their technical collaboration.

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