Download Advancements in Lung Sound Analysis: Linking Acoustics and Lung Mechanics and more Summaries Medicine in PDF only on Docsity!
Am J Respir Crit Care Med Vol. 156. pp. 974–987, 1997
State of the Art
Respiratory Sounds
Advances Beyond the Stethoscope
HANS PASTERKAMP, STEVE S. KRAMAN, and GEORGE R. WODICKA
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba; VA Medical Center, Lexington, Kentucky; School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana
CONTENTS
Introduction Sound at the Body Surface Stethoscopes Sensors for Lung Sound Recording Sound Transmission Models and Predictions Sound Transmission Measurements Effects of Pulmonary Pathology Respiratory Sounds Classification and Nomenclature Normal Lung Sounds Normal Tracheal Sounds Adventitious Sounds Summary and Future Directions
INTRODUCTION
In many ways, the sounds of respiration have remained time- less since Laënnec (1) improved their audibility with the stethoscope. Indeed, 30 yr ago, Forgacs (2) characterized the field by stating that “the sound repertoire of a wet sponge such as the lung is limited.” Why then is there a growing inter- est in the acoustics of respiration, as evidenced by recent edi- torial comments in leading pulmonary and physiology journals (3–5)? Also, why is there a multinational effort, funded by the European Commission, 1 to standardize computerized respira- tory sound analysis? It is precisely the application of computer technology that has provided new insights into acoustic mechanisms and new measurements of clinical relevance since the last State of the Art review on lung sounds in this Journal was published 13 yr ago (6). A closer bridging of pulmonary acoustics with tradi- tionally measured lung mechanics, e.g., air flow and volume, and the use of digital techniques to extract information on average sounds under standardized conditions were major steps that have advanced the utility of lung sounds beyond the stethoscope. Lung sound analysis to detect flow obstruction during bronchial provocation testing, for example, has drawn
much attention (3) because it does not require maximal breath- ing effort and can therefore be used with young patients. Re- spiratory acoustic measurements have also shown promise in the investigation of upper airway pathology, e.g., in patients with obstructive sleep apnea or with tracheal narrowing. This review begins with the current understanding of the thorax and upper airways as an acoustic system. Some details about the methods for lung sound measurement are provided, but interested readers will find more comprehensive informa- tion in a recent monograph (7). The following sections focus on the present state of knowledge about normal and adventi- tious lung sounds, their origin, and their clinical relevance. Fi- nally, a view on the likely areas of practical application for res- piratory sound analysis is presented.
SOUND AT THE BODY SURFACE
Stethoscopes Despite the high cost of many modern stethoscopes, these in- struments remain simply conduits for sound conduction be- tween the body surface and the ears. Stethoscopes are rarely tested, rated, or compared and are often chosen for their ap- pearance, reputation, and inadequately supported claims of performance. They are less than ideal acoustic instruments be- cause they do not provide a frequency-independent, uncol- ored transmission of sounds. Rather, they can selectively am- plify or attenuate sounds within the spectrum of clinical interest. Amplification tends to occur below 112 Hz and attenuation at higher frequencies (8). This feature is inherent in the design of the stethoscope that often places convenience and clinical util- ity ahead of acoustic fidelity. Amplification at low frequencies is appreciated by cardiologists since heart sounds are in this frequency range, which is poorly perceived by the human ear. Auscultation of the lung, however, could benefit from a more faithful representation of sounds than present stethoscopes provide.
Sensors for Lung Sound Recording Two types of transducers are in common use for lung sound recording and research: the electret microphone with coupling chamber and the accelerometer (9). Small electret microphones are widely available for speech and music recording. When coupled to the skin by a sealed chamber, similar to a stetho- scope bell, this type of microphone is a sensitive lung sound transducer. Different sizes and shapes of coupling chambers have been found to affect the overall frequency response of this coupling. Those arrangements with smaller, conically shaped chambers are more sensitive to higher lung sound frequencies (10, 11), but also highly susceptible to ambient noise. Contact accelerometers are also popular in lung sound research and can be calibrated on a vibration table so their output is quanti-
( Received in original form January 30, 1997 and in revised form June 4, 1997 ) Supported by the Children’s Hospital of Winnipeg Research Foundation. Dr. Wodicka is the recipient of Young Investigator Award BES-9257488 from the National Science Foundation of Canada. Correspondence and requests for reprints should be addressed to Dr. Hans Pas- terkamp, CS531A–840 Sherbrook St., Children’s Hospital, Winnipeg, MB, R3A 1S1 Canada. (^1) CORSA project, Contract No. BMH1-CT94-0928/DG12SSMA.
State of the Art 975
fied. However, they are typically more expensive than electret microphones, are often fragile, and may exhibit internal reso- nances near the lung sound frequencies of interest.
SOUND TRANSMISSION
Models and Predictions
Many factors that influence auscultation, including the re- sponse of the stethoscope and psychoacoustic phenomena, have contributed to concepts that are now widely taught to students in the health care professions. These concepts include: that there is relatively little bilateral asymmetry of sound ampli- tude and that asymmetry indicates disease, that sounds on the chest surface are primarily filtered versions of those detected over the trachea or neck, and that flow effects are of little di- agnostic importance as long as near- or above-normal rates are attained. Although these and other concepts have proven useful in many clinical circumstances, recent acoustic investi- gations with high-fidelity measurements indicate that consid- erably more information of clinical utility can be gathered from respiratory sounds. This information often cannot be ob- tained by auscultation, and some of the new findings can only be interpreted by taking an acoustical perspective and extend- ing or even breaking down a few traditional concepts. For ex- ample, it has become clear that inspiratory sounds measured simultaneously over the extrathoracic trachea and at the chest surface contain highly unique regional information that can only be reproducibly extracted with a knowledge of the breath- ing flow rate. Such realizations are stimulating the investi- gation of the acoustic properties of the respiratory system to improve their use for diagnostic, screening, and monitoring purposes. The respiratory tract consists of the vocal tract, which has been studied extensively, and the subglottal airways, which are now the topic of more detailed acoustic investigations. It is the combined effect of these two components that gives rise to the highly unique properties of the overall tract. The branch- ing airways in the thorax have been modeled by a number of investigators to assess the structural determinants of sound re- flection and transmission measurements (12–18). Although the exact branching structure is important at high audible fre- quencies (14), at the relatively low frequencies and long wave- lengths associated with lung sounds the system possesses pri- marily two distinct features: the large airway walls vibrate in response to intraluminal sound (16, 18), allowing significant sound energy to be coupled directly into the surrounding pa- renchyma; and the entire branching network behaves to a first approximation as a single nonrigid tube that is open at its dis- tal end to the relatively large air volume in the numerous smaller airways and alveoli (18, 19). This tubelike behavior in concert with wall vibration yields airway resonances with a fundamental frequency near 650 Hz for the subglottal system, as measured in tracheostomized patients (13), and at a lower frequency when the entire respiratory tract is patent. At higher audible frequencies, the airway walls become effec- tively rigid because of their inherent mass (20), allowing more sound energy to remain within the airway lumen and poten- tially travel farther into the branching structure. The lung parenchyma consists primarily of alveoli and small airways, capillaries, and supporting tissues. At frequen- cies in the audible range below about 10,000 Hz where the sound wavelengths significantly exceed alveolar size, the pa- renchyma has been modeled as a foamlike substance that is a homogeneous mixture of air and waterlike tissue, assuming that no gas exchange occurs because of the sound wave propa- gation (21). Here the composite density is dominated by the
tissue component and the composite stiffness by the air, re- sulting in a mixture with a relatively low sound speed (on the order of 50 m/s) and therefore short wavelength at a given fre- quency as compared with propagation in air or tissue alone (with respective sound speeds of roughly 350 and 1,500 m/s). These relatively shorter sound wavelengths suggest that more regional information concerning lung structure can be ob- tained from low-frequency acoustic measurements than had first been hypothesized. In addition, the effect of changing the amount or type of gas in the mixture on parameters such as sound speed is significantly less than if propagation were through the gas alone. To estimate the losses associated with sound propagation through the parenchyma, the parenchymal mixture has been represented as air bubbles (alveoli) in water (lung tissue) at both low (18) and high (22) audible frequen- cies. These models suggest that the absorption of sound en- ergy is highly frequency-dependent even for this simple geom- etry, with very large losses at higher frequencies where the wavelength approaches alveolar size. More complicated theo- retical approaches that include the effects of small airways (23) have also been used to predict the frequency dependence of sound speed and other properties over a wide frequency range. The encasement of the lung parenchyma by the chest wall is an important factor that affects sound propagation to the chest surface. The chest wall, although relatively thin com- pared with the extent of the parenchyma, is significantly more massive and stiff. In addition, the heterogeneous composition of bone, muscle, skin, and other tissues makes it a complex surface upon which to make acoustic measurements, with a potential for surface waves to travel between transducers on the skin and poor transmission to areas overlying bones such as the scapulae (24, 25). It has been estimated that the me- chanical/acoustic impedance mismatch between the paren- chyma and the chest wall can account for as much as an order of magnitude decrease in the amplitude of sound propagation (25) and significant alterations in the timing and waveform shape of adventitious lung sounds such as crackles (24). How the airways, parenchyma, and chest wall interact to produce the measurable acoustic properties of the thorax is the topic of considerable interest, debate, and investigation. With the knowledge of relatively short sound wavelengths in the pa- renchyma, earlier models (26) served as the precursors to more recent approaches that treat the thorax from an acousti- cal perspective like a large cylindrical drum (18, 27). Wodicka and coworkers (18) represented the respiratory tract at low frequencies as a single nonrigid tube that was at the center of the drum, was open on its distal end, and was assumed to be the source of an outgoing cylindrical sound wave into a sur- rounding parenchymal mixture that included losses. The pre- dicted amplitude on the surface of the drum (the chest wall) of sound originating from the tube (the central airways) com- pared well as a function of frequency with transmission mea- surements performed on healthy human subjects (28). The model highlighted the importance of tubelike resonances of the respiratory tract and of propagation losses in the lung pa- renchyma and chest wall. A model by Vovk and coworkers (27) also predicts a preferential transmission to the chest sur- face at low frequencies not unlike that of lung sounds, al- though it does not allow for regional sound generation in the branching airways.
Sound Transmission Measurements To measure the response of the thorax to sonic perturbations of known quality, a number of investigations have focused on the transmission of sound from introduction at the mouth to
State of the Art 977
(42, 44, 45), indicating a primarily parenchymal propagation. At higher frequencies, phase delays are significantly affected by low (43) and high density gas mixtures (45), which confirms that gas density does affect the acoustic transmission over the frequency range of lung sounds and highlights the strong fre- quency dependence of the acoustical properties of the thorax ( see Figure 1).
Effects of Pulmonary Pathology
The changes in lung structure that occur in disease affect the amplitude and timing of sound transmission from the airways to the chest surface. In patients with emphysema, a decrease (47) and larger variability (48) of transmitted amplitude at low frequencies was observed, which is qualitatively consistent with the common auscultatory finding of decreased lung sound in- tensity. In contrast, cardiogenic pulmonary edema was found to increase the amplitude of sound transmitted to the chest wall in dogs in a linear fashion over a wide frequency band- width relative to postmortem wet to dry weight ratios (49), a finding consistent with that of bronchial breathing heard over consolidated lung. Other mechanisms of sound introduction into the thorax such as percussion of the sternum and mea- surement of the transmission to the posterior chest surface, have also been investigated (50, 51). Through analysis of the transmitted amplitude, large pleural effusions could be de- tected, but deeper intrapulmonary masses could not, presum- ably because the majority of the transmission was through the bony chest wall rather than through lung tissue.
RESPIRATORY SOUNDS
Classification and Nomenclature
Lung-sound nomenclature has long suffered from imprecision and ambiguity. Until the last few decades, the names of lung sounds were derived from the originals given by Laënnec (1) and translated into English by Forbes (52). These names carried the implication of the pathologic mechanism of their produc- tion, e.g., humid or dry rales, or the character of the sound, e.g., hissing rale. The need for a more objective naming sys- tem has long been recognized (2, 53). In 1985, at the 10th meet-
ing of the International Lung Sounds Association, an ad hoc committee agreed on a schema that included fine and coarse crackles, wheezes, and rhonchi (54). Each of these terms can be described acoustically and does not assume a generating mechanism or location. These terms are now widely accepted, although the term “rale,” generally meaning “crackle,” is still frequently used (55). Further classification of lung sounds is still vague. No single characteristic distinguishes perfectly between the fine and coarse crackles although combinations of features provide ad- equate discrimination (56). The fact that fine and coarse crackles tend to appear at different times within the inspira- tory cycle assists in their differentiation (57). Wheezes occur within a broad frequency range. Rather than separating low pitched wheezes as “rhonchi” it may be more useful to apply the term “rhonchus” to repetitions of complex sound struc- tures that have a tonal, snorelike characteristic and are likely related to airway secretions and collapse. The nomenclature of the normal lung sound, also called the breath sound ( see also Other Respiratory Sounds in R ESPIRATORY SOUNDS sec- tion) or vesicular sound, has not attracted much attention. These terms are usually synonymous and we will refer to the normal lung sound in this review, recognizing that “normal” in this context refers to the basic breath sound without implica- tion on the normality of the lung ( see Table 1).
Normal Lung Sounds The breathing-associated sound heard on the chest of a healthy person is called the normal lung sound. It is a noise that peaks in frequency below 100 Hz (58), where it is mixed with and not easily distinguished from muscle and cardiovas- cular sounds. The lung sound energy drops off sharply be- tween 100 and 200 Hz (59), but it can still be detected at or above 1,000 Hz with sensitive microphones in a quiet room (60). The normal lung sound spectrum is devoid of discrete peaks and is not musical. It appears well established that its in- spiratory component is generated primarily within the lobar and segmental airways, whereas the expiratory component comes from more proximal locations (61–66). Air turbulence is presumed to generate the normal lung sound. However, tur-
TABLE 1 CATEGORIES OF RESPIRATORY SOUNDS* Respiratory Sound Mechanisms Origin Acoustics Relevance Basic sounds Normal lung sound
Turbulent flow vortices, unknown mechanisms
Central airways (expiration), lobar to segmental airway (inspiration)
Low-pass filtered noise (range , 100 to. 1,000 Hz)
Regional ventil- ation, airway caliber
Normal tracheal sound
Turbulent flow, flow impinging on airway walls
Pharynx, larynx, trachea, large airways
Noise with resonances (range , 100 to. 3,000 Hz)
Upper airway configuration
Adventitious sounds Wheeze Airway wall flutter, vortex shedding
Central and lower airways
Sinusoid (range z 100 to
. 1,000 HZ; duration, typically. 80 ms)
Airway obstruc- tion, flow limitation Rhonchus Rupture of fluid films, airway wall vibrations
Larger airways Series of rapidly dampened sinusoids (typically , 300 Hz and duration. 100 ms)
Secretions, ab- normal airway collapsiblility Crackle Airway wall stress-relaxation
Central and lower airways
Rapidly dampened wave deflection (duration typically , 20 ms)
Airway closure, secretions
- This table lists only the major categories of respiratory sounds and does not include other sound such as squawks, friction rubs, grunt- ing, snoring, or cough. Current concepts on sound mechanisms and origin are listed but these concepts may be incomplete and uncon- firmed.
978 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL. 156 1997
bulence is a density-dependent phenomenon, and the behav- ior of lung sounds in response to low-density gas breathing is peculiar. Austrheim and Kraman (67) found that breathing He-O 2 diminished the tracheal sound amplitude by 45% while the simultaneously recorded sound over several locations on the chest decreased by only 13 to 16%. Pasterkamp and Sanchez (68) found a 17% decrease in lung sound amplitudes on He- O 2 below 300 Hz, where most of the acoustic energy resides, but 40% attenuation above 300 Hz. They concluded that flow turbulence produced the sound in the higher frequency range ( see Figure 2). Although vorticeal airflow is well known to ex- ist in airways, and this has been postulated as a cause of nor- mal lung sounds (69), the mechanisms that produce the nor- mal lung sound, at least at frequencies to 300 Hz, are not understood. Lung sound amplitude differs between persons and differ- ent locations on the chest surface, but primarily varies with the square of the air flow (59, 65, 70). The effect of lung volume on lung-sound amplitude has been studied relatively less. Kra- man (71) found minor effects of volume changes on lung sounds and only over the upper lobes, although this study was limited by musculoskeletal noise at the extremes of the vital capacity. Investigations by Vanderschoot and Schreur (72) have suggested that lung volume effects on normal lung sounds can be separated from the more prominent effects of airflow. Normal lung sounds exhibit noticeable amplitude variation across the chest. The extent of this variation and its cause have been investigated during the past three decades. Nairn and Turner-Warwick (73), using radioactive xenon lung scanning, found a strong positive relationship between ventilation and lung sound amplitude, and they concluded that diminished lung sound intensity correlated with poor ventilation. Leblanc and coworkers (64) and Ploysongsang and colleagues (36, 74) also found a relationship between lung sound amplitude and regional ventilation as assessed by radionuclide lung scanning. They concluded that the sounds were loudest over the best ventilated lung units, after correction for sound transmission
through the lung. These studies, however, included few loca- tions on the chest and were limited to sounds below 300 Hz. The extent of the spatial inhomogeneity of the inspiratory sound was not defined until the early 1980s when researchers began to use chest surface mapping. O’Donnell and Kraman (75) produced linear maps of inspiratory lung sounds in 2 cm increments and found the amplitude to increase toward the base posteriorly, decrease toward the base anteriorly and to remain approximately stable in the horizontal plane. They also found significant right-to-left differences and small scale variations in amplitude, and marked subject-to-subject varia- tion. Dosani and Kraman (76) mapped inspiratory and expira- tory lung sounds across 20-cm-square grids over the right and left posterolateral chest wall. This study revealed a heteroge- neous distribution of lung sound over the chest and different patterns for expiratory and inspiratory sounds. Although dem- onstrating these amplitude variations in detail, neither this study nor any other explained the causes for these phenomena. Body size affects respiratory sounds. Children have a dis- tinct quality of lung sounds, which is generally attributed to acoustic transmission through smaller lungs and thinner chest walls. Laënnec introduced the term of “puerile respiration,” which referred primarily to increased sound intensity (77). Acoustic measurements have shown higher median frequen- cies of normal lung sounds in infants than in older children and adults (78, 79). Pasterkamp and coworkers (60) compared normal lung sounds at flows normalized by body weight in 29 infants, children, and adults. They found that higher median frequencies in infants were explained by less power at low fre- quencies, whereas the decrease in power toward higher fre- quencies was similar at all ages. They suggested that the differ- ent resonance behavior of a small thorax or less contribution of low frequency muscle noise may explain the difference of normal lung sounds in young children. The changes in lung sounds imposed by obstructive pulmo- nary disease are interesting and clinically helpful. Pardee and coworkers (80) used the subjective assessment of four trained examiners to estimate the loudness of lung sounds in 183 pa- tients undergoing pulmonary function testing. They found a strong correlation between the perceived lung sound intensity and the percent-predicted FEV 1. Although lung sounds were insensitive to mild degrees of ventilatory impairment in this study, definitely reduced intensity was a strong indicator of obstructive pulmonary disease, and normal lung sounds virtu- ally excluded the possibility of severe reductions in FEV 1. Re- cent observations on changes of normal lung sounds during in- duced airway narrowing ( see Wheezes in R ESPIRATORY S OUNDS section) illustrate that milder degrees of flow obstruction may be detectable by objective acoustic measurements. It is uncertain what causes the apparent decrease of in- spiratory lung sound amplitude in obstructive airway disease. In emphysema, parenchymal destruction could decrease the lung’s ability to transmit sound, and diminished airflows could produce less sound than expected. It would seem that the lat- ter explanation is less likely because airflow limitation in em- physema is an expiratory phenomenon. However, in a study to address this question, Schreur and coworkers (81) measured lung sound intensity at equal airflow rates in eight healthy men and in nine men with severe emphysema. They found no significant differences between the lung sound intensity of the two groups and concluded that the perceived decreased lung sound intensity on auscultation of emphysematous patients is due to airflow limitation. This appears to contradict the com- mon finding of a “silent” chest in patients with emphysema who presumably have little inspiratory airflow obstruction. The use of a relatively shallow filter by these investigators may
Figure 2. Power spectra of normal lung sounds in a healthy adult male subject, recorded with a contact sensor over the superior right lower lobe. Inspiratory sounds at flows of 1.5 to 2.0 L/s were averaged. Background noise spectra were obtained during breath- hold at end-expiration. The subject breathed air and then Heliox (80% helium/20% O 2 ). Lung sounds are measurably above back- ground noise at frequencies as high as 1,000 Hz. The most promi- nent effect of lower gas density and presumably lesser flow turbu- lence is seen at frequencies above 500 Hz.
980 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL. 156 1997
plied in adults (93–95) and in children (96). Tracheal sound microphones have become part of commercial apnea monitor- ing devices. In most of these applications, however, the focus is on the detection and monitoring of snoring. Pasterkamp and coworkers (90) measured normal tracheal sounds at standard- ized airflow in awake patients with obstructive sleep apnea (OSA) and in snorers without OSA. Pharyngeal dynamics ap- peared to be different in the patients with OSA who showed a significantly greater increase of tracheal sound intensity in the supine position. Presumably, this finding is related to struc- tural and functional abnormalities in OSA. Narrowing below the glottis can also be studied by the analysis of tracheal sounds. Pasterkamp and Sanchez (97) ob- served that tracheal sound levels reflected the degree of in- spiratory flow obstruction in a child with infectious laryngo- tracheitis. Yonemaru and coworkers (92) found a rise in power at high frequencies in 13 patients with significant tracheal stenosis compared with five control subjects. Greater power at high frequencies was also observed in sounds of airflow through partially obstructed tracheostomy tubes (98).
Adventitious Sounds
Wheezing. Wheezing is probably the most widely used acousti- cal term in respiratory medicine. Hundreds of publications ev- ery year refer to wheeze as an indicator of airway obstruction in infants, as a parameter to gauge the severity of asthma, or as a classifier in epidemiologic surveys, to name just a few ex- amples. Considering the clinical importance of this acoustical sign, there have been few objective studies of wheezing. Wheezes are musical adventitious lung sounds, also called “continuous” since their duration is much longer than that of “discontinuous” crackles. They may not necessarily extend more than 250 ms, as suggested in an ATS proposal for lung sound nomenclature (99), but they will typically be longer than 80 to 100 ms. Their frequency range extends from less than 100 Hz to more than 1 kHz, and higher frequencies may be measured inside the airways (100). The pathophysiologic mechanisms that generate wheezing are still not entirely clear. Movement of airway secretions may play a role, but the flutter of airway walls is probably more sig- nificant. Grotberg and Davis (101) presented a theoretical model that predicts oscillating wall motion in collapsible tubes at critical airway diameters and at gas velocities greater than those of flow limitation. Their model infers that flow is always limited when wheezing is present but also that flow may be limited without wheeze. In a series of investigations, Gavriely and colleagues tested the occurrence of wheezelike sound pressure oscillations in an isovolume, constant-flow model of animal lung (102), in a physical model of collapsible tubes (103), and in healthy adults during forced expiration (104). They found that flow limitation was necessary for wheezing and that critical transpulmonary pressures were required in normal subjects, presumably to flatten intrathoracic airways downstream from the choke point. The theoretical model of flutter in flow-limited collapsible tubes predicts that factors such as airway wall thickness, bend- ing stiffness, and longitudinal tension will affect the sound fre- quency of wheezing (101). Because the airway wall mass is much greater than that of the airway gas, effects of gas density on wheezing are predicted to be minor (101). Clinical observa- tions in support of this prediction were described by Forgacs (61). More recently, the lack of gas density effects on forced expiratory wheezes was confirmed in normal subjects who were breathing at comparable pressures and flows (105). Although the sound frequencies of wheezing do not appear to change, lower gas density has been found to increase the critical pres-
sure and lower the lung volume at which wheeze occurs during forced expiration in normal adults (106). Forced expiratory wheezes are reproducible in most nor- mal subjects (107), and they have therefore been used to in- vestigate physiologic mechanisms. The limited number of dis- crete frequency components in forced expiratory wheezes of normal adults, for example, suggests that the source of these wheezes is in the larger airways (108). Considering the appear- ance of wheeze during forced exhalations in healthy subjects, however, it is not surprising that forced expiratory wheezing lacks specificity and is not useful for the clinical diagnosis of asthma (109–111). The generation of wheeze during spontaneous or induced airway narrowing in patients with obstructive lung diseases may be different from that during forced expiration. Objective data on the characteristics of natural occurring wheeze, e.g., in acute asthma or bronchiolitis, are sparse. A wide range of sound patterns has been described in children who develop wheezing during bronchial provocation testing (112). Infants in particular may present with a different type of wheezing that is acoustically characterized by complex repetitive sound waves, more similar to rhonchi or snoring than to the typical wheeze of older patients with asthma (113). It is possible that this type of wheezing reflects a different sound source, e.g., secretions in large airways. Acoustic measurements are needed to define a prognostic significance of different wheeze patterns, i.e., to determine if wheezy infants with complex repetitive sounds rather than typical wheezes may be at a lower risk for future manifestations of asthma. Spontaneous wheeze is often present during inspiration in adults (114) and children (115) with asthma, a situation that healthy subjects cannot reproduce even during forced maneu- vers. Regional flow limitation during inspiration is a possibil- ity but has not been proven. Spontaneous wheeze may also oc- cur during tidal breathing, with low transpulmonary pressures and at very low airflows (61, 116). This may suggest a genera- tion mechanism of spontaneous wheeze by vortex-induced vi- brations, which requires much lower flow velocities and does not depend on flow limitation (117). The musical sound of wheezing is easily recognized by ear since it stands out from the noise of normal lung sounds. Wheeze of medium to loud intensity is also easy to notice as sharp peaks in the power spectrum of respiratory sounds. Computer-based detection of wheeze is possible with algo- rithms that relate the amplitude of these spectral peaks to the average lung sound amplitude (105, 118, 119). When wheezing is faint but still audible, the automated recognition by com- puter becomes more difficult. Digital sonography ( see Figure
- translates the acoustic information into graphic images (120), which allows the visual identification of wheezes even at low intensities. Quantification of wheeze over time has been used to ex- press wheeze severity relative to flow obstruction. The pro- portion of the breath cycle occupied by wheezing (Tw/Ttot) was inversely related to the FEV 1 in adult asthmatics with moderate to severe flow obstruction (118) and to FEV 1 , maxi- mal midexpiratory flow, and specific conductance in adoles- cents with exercise-induced bronchospasm (121). Wheeze quantification offers a possibility for noninvasive monitoring in nocturnal asthma. The first promising applications were re- ported more than 10 yr ago (122, 123). Advances in computer technology and improved methods for acoustical pattern rec- ognition are likely to give us lung sound analyzers for ex- tended observations in clinical respiratory medicine. As can be expected, the computer analysis of lung sounds allows a reproducible quantification of wheezing in contrast to
State of the Art 981
subjective auscultation (124). However, the simple detection of wheeze is just as easily achieved by stethoscope. Ausculta- tory detection of wheeze as an indicator of significant flow ob- struction was first advocated in 1988 (125, 126) for bronchial provocation testing of young children. Subsequent reports have also found subjective tracheal auscultation to be useful under these circumstances (127, 128), and a recent editorial in this Journal has emphasized the potential value of lung sound anal- ysis in bronchial provocation testing (3). Beck and coworkers (129) described the use of computerized lung sounds analysis during histamine challenge in 12 children. They found that wheeze appeared in most of these patients before FEV 1 had decreased by 20% or more. Other computer-based studies of lung sounds during bronchial provocation in children with asthma (115) or with cystic fibrosis (130), and in adults ex- posed to occupational hazards (131) also found wheezing in most subjects who responded positively to the challenge. How- ever, these studies revealed that the sensitivity of wheezing to detect bronchial hyperactivity was only 50 to 75%. Using methacholine inhalation in a recent study of adults with asthma, Spence and coworkers (132) did not find wheeze in three of eight patients, even when the FEV 1 had decreased as low as 44% of the baseline value. Lung sound analysis confirms the well-recognized finding on subjective auscultation (133, 134) that wheezing is absent in many patients with significant airway obstruction. However, other changes in lung sounds during flow obstruction can be recognized on auscultation, most noticeably a decrease in breath sound intensity. Bohadana and coworkers (135) de-
scribed the close correlation between a breath sound intensity score and objective indices of flow obstruction, e.g., FEV 1 maximal midexpiratory flow, and specific conductance, in hos- pitalized patients with obstructive airway disease. More re- cently, Bohadana and colleagues (136, 137) confirmed these observations by objective measurements of inspiratory breath sound intensity during bronchial provocation. They also showed that a decrease of inspiratory breath sound intensity without wheeze was as common as the appearance of wheeze in patients with a positive response to methacholine, that in most subjects the acoustic findings appeared one or more con- centrations before FEV 1 had decreased 20% or more from baseline, and that these observations could be reliably made on subjective auscultation (138). A decrease in breath sound intensity as the maximal bron- chial constriction was also apparent in patients with asthma during histamine challenge who were studied by Anderson and coworkers (139). Lung sound spectra during bronchial ob- struction were characterized by a redistribution of power to- ward higher frequencies and a corresponding upward shift of median frequencies. Similar findings were reported by Pas- terkamp and coworkers (140) who recorded breath sounds si- multaneously at eight sites on the chest and over the trachea of children during methacholine challenge. Airway narrowing in their subjects was accompanied by changes in lung sounds, with a decrease in power at low frequencies during inspiration ( see Figure 5) and an increase of power at high frequencies during expiration. These changes already occurred at a de- crease in FEV 1 of less than 10% from baseline and were fully
Figure 4. Digital respirosonogram of sounds over the right anterior upper lobe during three complete respiratory cycles in a boy with asthma. Time is on the horizontal and frequency on the vertical axis. Sound intensity (in decibels) is shown on a gray scale. Airflow is plot- ted above the sonogram. The vertical bar at 1.6 s highlights a segment of expiratory sound that contains wheeze. This segment is shown in detail on the right , revealing a sinusoidal wave in the time-amplitude display ( top ) and two harmonically related peaks in the Fourier power spectrum ( bottom ).
State of the Art 983
tion, which is widely used to study the noiselike lung sounds, is poorly suited to short bursts of sound. Thus, the most com- monly used indices are the time duration of the initial deflec- tion and the first two cycles of the waveform, introduced by Holford (156). These parameters appear to do reasonably well in distinguishing fine from coarse crackles even in the absence of knowledge of timing or effect of gravity or cough. Other ef- forts at refining the discriminatory powers of crackle measure- ments (56, 157) have not proven superior. It is important to note that sound filters, typically used to suppress low-fre- quency rumble from muscle noise, can have a major effect on the appearance of crackle waveforms (158). A number of investigators have examined the usefulness of detecting and classifying crackles to help identify pathologic processes. Although fine crackles have generally been as- sumed to reflect lung dysfunction, Thacker and Kraman (159) and Workum and coworkers (160) found that about half of the healthy young adults could generate crackles over the anterior lung bases by inhaling slowly from residual volume. Ploysong- sang and Schonfeld (161) achieved similar results in subjects breathing air or oxygen at low lung volumes. It is reasonable to conclude that the closure of small airways is the condition that results in crackles. Explosive airway reopening is proba- bly normal once the airway has been closed. Although many investigators have explored the potential specificity of crackle features and characteristics to certain dis- eases (151, 162–166), those with established clinical utility ap- pear to be: the presence or absence of crackles to distinguish pulmonary fibrosis (crackles usually prominent) from sarcoid- osis (crackles usually scant or absent) (167); fine, late inspira- tory crackles indicating fibrotic lung disease and early, coarse crackles indicating obstructive lung disease (162, 168); crack- les as an early (perhaps first) sign of asbestosis (169–171), and crackles indicating heart failure (163, 166, 172, 173). Despite the ease with which an experienced examiner can distinguish fine from coarse crackles by ear, much effort has been expended on developing and validating devices to do this chore automatically (174–180). These schemes have been mostly successful, but none has yet enjoyed wide use, perhaps because they are esoteric, inconvenient, of unproved utility, and not reimbursable, or perhaps clinicians are already satis- fied with their ability to classify lung sounds without computer assistance. Nevertheless, there could be a place for such de- vices in industrial screening, especially in workers at risk for asbestos exposure. Other respiratory sounds. The terms “lung sound” and “breath sound” are usually used synonymously. However, Forgacs reserved the term breath sound to refer to the sound of breathing heard at the mouth. He and his colleagues (181,
- described a direct relationship between the loudness of the breath sound and the degree of airway obstruction. They attributed this to the extra turbulence within abnormally nar- rowed airways of patients with obstructive airway disease. However, breath sounds at the mouth have attracted virtually no further investigational attention since the early 1970s. The squawk is a short, inspiratory wheeze that occurs pri- marily in restrictive lung diseases such as idiopathic interstitial fibrosis and allergic alveolitis (183, 184). They have not been well-studied, but squawks appear to always occur along with crackles and are often noted to begin with a crackle, suggest- ing that they are caused by oscillatory motion in a newly opened airway. Cough and snoring are not usually considered lung sounds, but they have been studied as such. Cough has been analyzed by many researchers (185–191). These studies defined the components of the normal cough, the effect of asthma or
chronic bronchitis on the sound of a cough, and differences in cough sounds in asthma, chronic bronchitis, and acute bron- chitis. However, there has been little confirmation of these studies. One could question the usefulness of cough analysis, except that the expanding use of remote telemedicine puts greater emphasis on audio and video for diagnosis. This could prove to be the venue of clinical utility. Snoring sounds have recently become important as indica- tors of sleep apnea. In the sleep laboratory, a record of snor- ing activity can, along with other standard measurements, help distinguish central from obstructive sleep apnea or simple snoring (95, 192, 193). Sound level meters are already part of some in-home sleep apnea monitors (194). More sophisticated devices may be developed to acoustically distinguish between the very common “benign” forms of snoring and those that in- dicate significant airway compromise.
SUMMARY AND FUTURE DIRECTIONS
Lung sounds have been valuable indicators of respiratory health and disease since ancient times. Laënnec’s stethoscope raised their diagnostic significance but other methods, more sensitive and specific for respiratory assessment, have largely replaced auscultation in clinical pulmonary diagnosis. We are now witnessing the next phase in the evolution of pulmonary assessment by acoustical means. Although the complexity of the respiratory system has slowed the formulation of a com- prehensive model of chest and lung acoustics, there have been major advances in understanding lung sounds during the last decade. More powerful yet smaller computers have made digi- tal respiratory sound analysis possible in ambulatory care and at the bedside. The next years will likely bring about an inte- gration of respiratory sound analyzers with more established computer-based spirometry. The most promising areas for respiratory acoustical mea- surements are in upper airway diagnosis and monitoring, e.g., in patients with obstructive sleep apnea, in the assessment of lower airway dynamics, e.g., in patients with asthma or bron- chiolitis, and in the assessment of regional ventilation. It may soon be possible to determine the site of upper airway ob- struction by the analysis of respiratory sounds and to follow the effect of therapy, e.g., the application of continuous posi- tive airway pressure, by acoustical means. Spirometry will re- main the standard for assessing lower airway flow obstruction, but lung-sound analysis can extend the assessment to younger patients. Objective characterization of wheezing should im- prove the epidemiologic understanding of acute and chronic lower airway obstruction, especially in children. Monitoring of regional ventilation by chest surface acoustical topography may now be possible with faster computers that allow the si- multaneous processing of sounds from multiple recording sites. The multisite recording of respiratory sounds and of pas- sively transmitted sounds could be particularly useful in criti- cal care, e.g., to monitor regional ventilation and lung water content in intubated patients. Certain technical challenges need to be resolved before lung sound analysis can enter into routine clinical practice. In particular, a robust and inexpensive sensor for lung sound re- cording that is relatively immune to ambient noise has yet to be developed. Furthermore, the automated recognition and rejection of artifacts as well as the separate processing of ad- ventitious and basic respiratory sounds need to be refined. However, advances in digital sound processing have already translated into enhancements of the traditional stethoscope, e.g., the use of active noise cancellation in high noise environ- ments (195, 196). Also, the teaching of chest auscultation to
984 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL. 156 1997
medical students has been enhanced by computer-aided in- struction (197–199). Lung sounds of high fidelity can be trans- ferred via telecommunication, as interested readers with ac- cess to the Internet can verify. 2 The sound repertoire of the lung may indeed be limited when heard through a stethoscope, but it clearly exhibits a much wider range of information content when digitally ana- lyzed. Computer analysis is now reaching beyond the capabili- ties of the human ear, e.g., to resolve changes in respiratory sounds during narrowing of the intrathoracic- or extrathoracic airways. With the disappearance of auscultation as the stan- dard to judge the clinical significance of acoustical findings, it becomes even more important to integrate lung sound analy- sis and traditional measurements of respiratory mechanics. One should keep in mind, however, that voice recognition of continuous speech, an easy task for the human listener, is still not possible on standard computers after decades of research and substantial investment from industry. Thus, one should not expect that computer-based lung sound analyzers will re- place the stethoscope-bearing clinician anytime soon, but they will expand the noninvasive diagnostic capabilities in respira- tory medicine.
References
- Laënnec, R. T. H. 1967. De l’auscultation médiate ou traité du diagnos- tic de maladies des poumons et du coeur, fondé principalement sur ce nouveau moyen d’exploration. Brosson et Chaudé, Paris. 1819.
- Forgacs, P. 1967. Crackles and wheezes. Lancet 2:203–205.
- Gavriely, N. 1996. Analysis of breath sounds in bronchial provocation tests (editorial). Am. J. Respir. Crit. Care Med. 153:1469–1471.
- Macklem, P. T. 1996. Airflow effects on amplitude and spectral content of normal breath sounds (editorial). J. Appl. Physiol. 80:3–4.
- Earis, J. 1992. Lung sounds (editorial). Thorax 47:671–672.
- Loudon, R. G., and R. L. Murphy. 1984. Lung sounds. Am. Rev. Respir. Dis. 130:663–673.
- Gavriely, N. 1995. Breath Sounds Methodology. CRC Press, Boca Ra- ton, FL.
- Abella, M., J. Formolo, and D. G. Penney. 1992. Comparison of the acoustic properties of six popular stethoscopes. J. Acoust. Soc. Am. 91:2224–2228.
- Pasterkamp, H., S. S. Kraman, P. D. DeFrain, and G. R. Wodicka.
- Measurement of respiratory acoustical signals: comparison of sensors. Chest 104:1518–1525.
- Wodicka, G. R., S. S. Kraman, G. M. Zenk, and H. Pasterkamp. 1994. Measurement of respiratory acoustic signals: effect of microphone air cavity depth. Chest 106:1140–1144.
- Kraman, S. S., G. R. Wodicka, Y. Oh, and H. Pasterkamp. 1995. Mea- surement of respiratory acoustic signals: effect of microphone air cavity width, shape and venting. Chest 108:1004–1008.
- Van Den Berg, J. W. 1960. An electrical analogue of the trachea, lungs and tissues. Acta Physiol. Pharmacol. Neerlandica 9:361–385.
- Ishizaka, K., M. Matsudaira, and T. Kaneko. 1976. Input acoustic- impedance measurement of the subglottal system. J. Acoust. Soc. Am. 60:190–197.
- Fredberg, J. J. 1978. A modal perspective of lung response. J. Acoust. Soc. Am. 63:962–966.
- Nemerovskii, L. I. 1980. Analysis of a pulmophonogram for assessing local pulmonary ventilation. Med. Tekh. 39–44.
- Jackson, A. C., C. A. Giudanella, and H. L. Dorkin. 1989. Density de- pendence of respiratory system impedances between 5 and 320 Hz in humans. J. Appl. Physiol. 67:2323–2330.
- Hudde, H., and H. Slatky. 1989. The acoustical input impedance of ex- cised human lungs: measurements and model matching. J. Acoust. Soc. Am. 86:475–492.
- Wodicka, G. R., K. N. Stevens, H. L. Golub, E. G. Cravalho, and D. C. Shannon. 1989. A model of acoustic transmission in the respiratory system. IEEE Trans. Biomed. Eng. 36:925–934.
- Mansfield, J. P., and G. R. Wodicka. 1995. Using acoustic reflectometry to guide breathing tubes. J. Sound Vibr. 188:167–188.
- Rice, D. A. 1980. Sound speed in the upper airways. J. Appl. Physiol. 40:326–336.
- Rice, D. A. 1983. Sound speed in pulmonary parenchyma. J. Appl. Physiol. 54:304–308.
- Goncharoff, V., J. E. Jacobs, and D. W. Cugell. 1989. Wideband acous- tic transmission of human lungs. Med. Biol. Eng. Comput. 27:513–519.
- D’yachenko, A. I., and G. A. Lyubimov. 1988. Propagation of sound in pulmonary parenchyma. Izv. Akad. Nauk SSSR 5:3–15.
- Kudoh, S. 1992. Wave form of intrabronchial spark sound on the chest wall and sound transmission in the lung-thoracic system. Nippon Ika Daigaku Zasshi 59:323–334.
- Vovk, I. V., V. T. Grinchenko, and V. N. Oleinik. 1995. Modeling the acoustic properties of the chest and measuring breath sounds. Acoust. Phys. 41:758–768.
- Böhme, H. R. 1974. Attempt at physical characterization of the passive sound behavior in the lung in a model. Z. Gesamte Inn. Med. 29: 401–406.
- Vovk, I., V. K. E. Zalutskii, and L. G. Krasnyi. 1994. Acoustic model of the human respiratory system. Acoust. Phys. 40:762–767.
- Wodicka, G. R., and D. C. Shannon. 1990. Transfer function of sound transmission in subglottal human respiratory system at low frequen- cies. J. Appl. Physiol. 69:2126–2130.
- Wodicka, G. R., A. Aguirre, P. D. DeFrain, and D. C. Shannon. 1992. Phase delay of pulmonary acoustic transmission from trachea to chest wall. IEEE Trans. Biomed. Eng. 39:1053–1059.
- Wodicka, G. R., K. N. Stevens, H. L. Golub, and D. C. Shannon. 1990. Spectral characteristics of sound transmission in the human respira- tory system. IEEE Trans. Biomed. Eng. 37:1130–1135.
- Böhme, H., and J. Löw. 1969. Behavior of the intrathoracic cavity in passage of low-frequency sound and its diagnostic importance. 1st communication: construction of apparatus. Z. Erkr. Atmungs. 130: 397–408.
- Böhme, H., and J. Löw. 1969. Behavior of the intrathoracic cavity in passage of low-frequency sound and its diagnostic importance. 2nd communication: basics of measurement and preliminary tests for in- terpretation of results. Z. Erkr. Atmungs. 131:55–58.
- Böhme, H. 1970. Behavior of the intrathoracic cavity in passage of low- frequency sound and its diagnostic importance. 3rd communication: comparative clinical-physiological examinations in changed respira- tory mechanics. Z. Erkr. Atmungs. 132:315–322.
- Böhme, H., and H. R. Böhme. 1971. Passive behavior of the lung fol- lowing low-frequency sound in healthy persons and in emphysema patients. Z. Gesamte Inn. Med. 26:582–588.
- Shioya, N., Y. Takezawa, R. Mikami, S. Kudoh, and A. Shibuya. 1984. Acoustic transmission of the respiratory system using orally intro- duced sinusoidal sound waves. Nippon Kyobu Shikkan Gakkai Zas- shi 22:125–130.
- Ploysongsang, Y., R. R. Martin, W. R. Ross, R. G. Loudon, and P. T. Macklem. 1977. Breath sounds and regional ventilation. Am. Rev. Respir. Dis. 116:187–199.
- Lu, S., P. C. Doerschuk, and G. R. Wodicka. 1995. Parametric phase- delay estimation of sound transmitted through intact human lung. Med. Biol. Eng. Comput. 33:293–298.
- Kraman, S. S., and O. Austrheim. 1983. Comparison of lung sound and transmitted sound amplitude in normal men. Am. Rev. Respir. Dis. 128:451–454.
- Kraman, S. S., and A. B. Bohadana. 1989. Transmission to the chest of sound introduced at the mouth. J. Appl. Physiol. 66:278–281.
- Wodicka, G. R., P. D. DeFrain, and S. S. Kraman. 1994. Bilateral asym- metry of respiratory acoustic transmission. Med. Biol. Eng. Comput. 32:489–494.
- Pasterkamp, H., S. Patel, and G. R. Wodicka. 1997. Asymmetry of res- piratory sounds and thoracic transmission. Med. Biol. Eng. Comput. 35:103–106.
- Mahagnah, M., and N. Gavriely. 1995. Gas density does not affect pul- monary acoustic transmission in normal men. J. Appl. Physiol. 78: 928–937.
- Jacobs, J. E. 1982. Wideband acoustic energy studies of pulmonary air- ways. Bioelectromagnetics 3:167–177.
- Kraman, S. S. 1983. Speed of low-frequency sound through lungs of normal men. J. Appl. Physiol. 55:1862–1867.
- Patel, S., S. Lu, P. C. Doerschuk, and G. R. Wodicka. 1995. Sonic phase delay from trachea to chest wall: spatial and inhaled gas dependency. Med. Biol. Eng. Comput. 33:571–574.
- Rice, D. A., and J. C. Rice. 1987. Central to peripheral sound propaga-
(^2) The R.A.L.E. Repository. (http://www.umanitoba.ca/faculties/medicine/ILSA/ sounds/ralrepos.html)
986 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL. 156 1997
possible association with lung compliance. Respiration 44:189–196.
- Marini, J. J., D. J. Pierson, L. D. Hudson, and S. Lakshiminarayan.
- The significance of wheezing in chronic airflow obstruction. Am. Rev. Respir. Dis. 120:1069–1072.
- King, D. K., B. T. Thompson, and D. C. Johnson. 1989. Wheezing on maximal forced exhalation in the diagnosis of atypical asthma: lack of sensitivity and specificity. Ann. Intern. Med. 110:451–455.
- Schreur, H. J., J. Vanderschoot, A. H. Zwinderman, J. H. Dijkman, and P. J. Sterk. 1994. Abnormal lung sounds in patients with asthma dur- ing episodes with normal lung function. Chest 106:91–99.
- Rietveld, S., E. H. Dooijes, L. H. Rijssenbeck-Nouwens, F. Smit, P. J. Prins, A. M. Kolk, and W. A. Everaerd. 1995. Characteristics of wheeze during histamine-induced airways obstruction in children with asthma. Thorax 50:143–148.
- Tal, A., I. Sanchez, and H. Pasterkamp. 1991. Respirosonography in in- fants with acute bronchiolitis. Am. J. Dis. Child 145:1405–1410.
- Shim, C. S., and M. H. Williams. 1983. Relationship of wheezing to the severity of obstruction in asthma. Arch. Intern. Med. 143:890–892.
- Sanchez, I., A. Avital, I. Wong, A. Tal, and H. Pasterkamp. 1993. Acoustic vs. spirometric assessment of bronchial responsiveness to methacholine in children. Pediatr. Pulmonol. 15:28–35.
- Pasterkamp, H. 1996. From auscultation to respiratory acoustical mea- surements: new aspects of lung sounds. Clin. Pulm. Med. 3:221–227.
- Gavriely, N., Y. Palti, G. Alroy, and J. B. Grotberg. 1984. Measurement and theory of wheezing breath sounds. J. Appl. Physiol. 57:481–492.
- Baughman, R. P., and R. G. Loudon. 1984. Quantitation of wheezing in acute asthma. Chest 86:718–722.
- Fenton, T. R., H. Pasterkamp, A. Tal, and V. Chernick. 1985. Auto- mated spectral characterization of wheezing in asthmatic children. IEEE Trans. Biomed. Eng. 32:50–55.
- Pasterkamp, H., C. Carson, D. Daien, and Y. Oh. 1989. Digital respiro- sonography: new images of lung sounds. Chest 96:1405–1412.
- Pasterkamp, H., A. Tal, F. Leahy, R. Fenton, and V. Chernick. 1985. The effect of anticholinergic treatment on postexertional wheezing in asthma studied by phonopneumography and spirometry. Am. Rev. Respir. Dis. 132:16–21.
- Baughman, R. P., and R. G. Loudon. 1985. Lung sound analysis for con- tinuous evaluation of airflow obstruction in asthma. Chest 88: 364–368.
- Lenclud, C., G. Cuttitta, A. Visconti, A. v. Muylem, V. Bellia, and J. C. Yernault. 1986. All night on line monitoring of wheezing: compari- son with monitoring of airway resistance in nocturnal asthma. Bull. Eur. Physiopathol. Respir. 22:191–199.
- Pasterkamp, H., W. Wiebicke, and R. Fenton. 1987. Subjective assess- ment vs computer analysis of wheezing in asthma. Chest 91:376–381.
- Adinoff, A. D., R. T. Schlosberg, and R. C. Strunk. 1988. Methacholine inhalation challenge in young children: results of testing and follow- up. Ann. Allergy 61:282–286.
- Avital, A., E. Bar-Yishay, C. Springer, and S. Godfrey. 1988. Bronchial provocation tests in young children using tracheal auscultation. J. Pe- diatr. 112:591–594.
- Noviski, N., L. Cohen, C. Springer, E. Bar-Yishay, and S. Godfrey.
- Bronchial provocation determined by breath sounds compared with lung function. Arch. Dis. Child 66:952–955.
- Sprikkelman, A. B., M. H. Grol, M. S. Lourens, J. Gerritsen, H. S. A. Heymans, and W. M. C. v. Aalderen. 1996. Use of tracheal ausculta- tion for the assessment of bronchial responsiveness in asthmatic chil- dren. Thorax 51:317–319.
- Beck, R., U. Dickson, M. D. Montgomery, and I. Mitchell. 1992. Hista- mine challenge in young children using computerized lung sounds analysis. Chest 102:759–763.
- Sanchez, I., R. E. Powell, and H. Pasterkamp. 1993. Wheezing and air- flow obstruction during methacholine challenge in children with cys- tic fibrosis and in normal children. Am. Rev. Respir. Dis. 147:705–709.
- Bohadana, A. B., N. Massin, D. Teculescu, and R. Peslin. 1994. Tra- cheal wheezes during methacholine airway challenge (MAC) in workers exposed to occupational hazards. Respir. Med. 88:581–587.
- Spence, D. P., D. R. Graham, G. Jamieson, B. M. Cheetham, P. M. Cal- verley, and J. E. Earis. 1996. The relationship between wheezing and lung mechanics during methacholine-induced bronchoconstriction in asthmatic subjects. Am. J. Respir. Crit. Care Med. 154:290–294.
- McFadden, E. R., R. Kiser, and W. J. deGroot. 1973. Acute bronchial asthma: relation between clinical and physiological manifestations. N. Engl. J. Med. 288:221–225.
- Baumann, U. A., E. Haerdi, and R. Keller. 1986. Relations between clinical signs and lung function in bronchial asthma: how is acute bronchial obstruction reflected in dyspnoea and wheezing? Respira- tion 50:294–300.
- Bohadana, A. B., R. Peslin, and H. Uffholtz. 1978. Breath sounds in the clinical assessment of airflow obstruction. Thorax 33:345–351.
- Bohadana, A. B., M. C. Kopferschmitt-Kubler, and G. Pauli. 1994. Breath sound intensity in patients with airway provocation challenge test positive by spirometry but negative for wheezing: a preliminary report. Respiration 61:274–279.
- Bohadana, A. B., R. Peslin, H. Uffholtz, and G. Pauli. 1995. Potential for lung sound monitoring during bronchial provocation testing. Thorax 50:955–961.
- Purohit, A., A. Bohadana, M. C. Kopferschmitt-Kubler, L. Mahr, J. Linder, and G. Pauli. 1997. Lung auscultation in airway challenge testing. Respir. Med. 91:151–157.
- Anderson, K., S. Aitken, R. Carter, J. E. MacLeod, and F. Moran. 1990. Variation of breath sound and airway caliber induced by histamine challenge. Am. Rev. Respir. Dis. 141:1147–1150.
- Pasterkamp, H., R. Consuniji-Araneta, Y. Oh, and J. Holbrow. 1997. Chest surface mapping of lung sounds during methacholine chal- lenge. Pediatr. Pulmonol. 2:21–30.
- Spence, D. P., S. Bentley, D. H. Evans, and M. D. Morgan. 1992. Effect of methacholine induced bronchoconstriction on the spectral charac- teristics of breath sounds in asthma. Thorax 47:680–683.
- Schreur, H. J., Z. Diamant, J. Vanderschoot, A. H. Zwinderman, J. H. Dijkman, and P. J. Sterk. 1996. Lung sounds during allergen-induced asthmatic responses in patients with asthma. Am. J. Respir. Crit. Care Med. 153:1474–1480.
- Malmberg, L. P., L. Pesu, and A. R. A. Sovijärvi. 1995. Significant dif- ferences in flow standardised breath sound spectra in patients with chronic obstructive pulmonary disease, stable asthma, and healthy lungs. Thorax 50:1285–1291.
- Malmberg, L. P., R. Sorva, and A. R. Sovijärvi. 1994. Frequency distri- bution of breath sounds as an indicator of bronchoconstriction dur- ing histamine challenge test in asthmatic children. Pediatr. Pulmonol. 18:170–177.
- Malmberg, L. P., A. R. Sovijärvi, E. Paajanen, P. Piirilä, T. Haahtela, and T. Katila. 1994. Changes in frequency spectra of breath sounds during histamine challenge test in adult asthmatics and healthy con- trol subjects. Chest 105:122–131.
- Tinkelman, D. G., C. Lutz, and B. Conner. 1991. Utilizing lung sounds analysis for the evaluation of acute asthma in small children. Ann. Allergy 67:339–344.
- Chadha, T. S., A. W. Schneider, S. Birch, G. Jenouri, and M. Sackner.
- Breathing pattern during induced bronchoconstriction. J. Appl. Physiol. 56:1053–1059.
- Nath, A. R., and L. H. Capel. 1980. Lung crackles in bronchiectasis. Thorax 35:694–699.
- Walshaw, M. J., M. Nisar, M. G. Pearson, P. M. Calverley, and J. E. Earis. 1990. Expiratory lung crackles in patients with fibrosing alveo- litis. Chest 97:407–409.
- Nath, A. R., and L. H. Capel. 1974. Inspiratory crackles and mechanical events of breathing. Thorax 29:695–698.
- Munakata, M., Y. Homma, M. Matsuzaki, H. Ogasawara, K. Tanimura, H. Kusaka, and Y. Kawakami. 1986. Production mechanism of crack- les in excised normal canine lungs. J. Appl. Physiol. 61:1120–1125.
- Mori, M., K. Kinoshita, H. Morinari, T. Shiraishi, S. Koike, and S. Mu- rao. 1980. Waveform and spectral analysis of crackles. Thorax 35: 843–850.
- Fredberg, J., and S. K. Holford. 1983. Discrete lung sounds: crackles (rales) as stress-relaxation quadrupoles. J. Acoust. Soc. Am. 73:1036–
- Benedetto, G., F. Dalmasso, and R. Spagnolo. 1988. Surface distribu- tion of crackling sounds. IEEE Trans. Biomed. Eng. 35:406–412.
- Murphy, R. L., S. K. Holford and W. C. Knowler. 1977. Visual lung- sound characterization by time-expanded wave-form analysis. N. Engl. J. Med. 296:968–971.
- Holford, S. K. 1982. Discontinuous adventitious lung sounds: measure- ment, classification and modeling (Sc.D.thesis). Massachusetts Insti- tute of Technology, Cambridge, MA.
- Maeda, Y., K. Nitta, Y. Yui, T. Shida, K. Wagatsuma, and T. Muraoka.
- A classification of crackles by the linear predictive coding method. Nippon. Kyobu Shikkan Gakkai Zasshi 26:587–593.
- Katila, R., P. Piirilä, K. Kallio, E. Paajanen, T. Rosqvist, and A. R. So- vijärvi. 1991. Original waveform of lung sound crackles: a case study of the effect of high-pass filtration. J. Appl. Physiol. 71:2173–2177.
- Thacker, R. E., and S. S. Kraman. 1982. The prevalence of auscultatory crackles in subjects without lung disease. Chest 81:672–674.
- Workum, P., S. K. Holford, E. A. Delbono, and R. L. Murphy. 1982. The prevalence and character of crackles (rales) in young women
State of the Art 987
without significant lung disease. Am. Rev. Respir. Dis. 126:921–923.
- Ploysongsang, Y., and S. A. Schonfeld. 1982. Mechanism of production of crackles after atelectasis during low-volume breathing. Am. Rev. Respir. Dis. 126:413–415.
- Epler, G. R., C. B. Carrington, and E. A. Gaensler. 1978. Crackles (rales) in the interstitial lung diseases. Chest 73:333–339.
- Piirilä, P., A. R. Sovijärvi, T. Kaisla, H. M. Rajala, and T. Katila. 1991. Crackles in patients with fibrosing alveolitis, bronchiectasis, COPD, and heart failure. Chest 99:1076–1083.
- Piirilä, P. 1992. Changes in crackle characteristics during the clinical course of pneumonia. Chest 102:176–183.
- al Jarad, N., B. Strickland, G. Bothamley, S. Lock, R. Logan-Sinclair, and R. M. Rudd. 1993. Diagnosis of asbestosis by a time expanded wave form analysis, auscultation and high resolution computed to- mography: a comparative study. Thorax 48:347–353.
- al Jarad, N., S. W. Davies, R. Logan-Sinclair, and R. M. Rudd. 1994. Lung crackle characteristics in patients with asbestosis, asbestos- related pleural disease and left ventricular failure using a time- expanded waveform analysis: a comparative study. Respir. Med. 88: 37–46.
- Baughman, R. P., R. T. Shipley, R. G. Loudon, and E. Lower. 1991. Crackles in interstitial lung disease: comparison of sarcoidosis and fi- brosing alveolitis. Chest 100:96–101.
- Sovijärvi, A. R. A., P. Piirilä, and R. Luukkonen. 1996. Separation of pulmonary disorders with two-dimensional discriminant analysis of crackles. Clin. Physiol. 16:172–181.
- Workum, P., E. A. DelBono, S. K. Holford, and R. L. H. Murphy. 1986. Observer agreement, chest auscultation and crackles in asbestos- exposed workers. Chest 89:27–29.
- Shirai, F., S. Kudoh, A. Shibuya, K. Sada, and R. Mikami, 1981. Crack- les in asbestos workers: auscultation and lung sound analysis. Br. J. Dis. Chest 75:386–396.
- Murphy, R. L., E. A. Gaensler, S. K. Holford, E. A. Del Bono, and G. Epler. 1984. Crackles in the early detection of asbestosis. Am. Rev. Respir. Dis. 129:375–379.
- Ploysongsang, Y., R. P. Michel, A. Rossi, L. Zocchi, J. Milic-Emili, and N. C. Staub. 1989. Early detection of pulmonary congestion and edema in dogs by using lung sounds. J. Appl. Physiol. 66:2061–2070.
- Deguchi, F., S. Hirakawa, K. Gotoh, Y. Yagi, and S. Ohshima. 1993. Prognostic significance of posturally induced crackles. Long-term follow-up of patients after recovery from acute myocardial infarc- tion. Chest 103:1457–1462.
- Benedetto, G., F. Dalmasso, M. Guarene, G. Righini and R. Spagnolo.
- A method for the acoustical analysis of respiratory crackles in cryptogenic fibrosing alveolitis. IEEE Trans. Biomed. Eng. 30:620–623.
- Dalmasso, F., M. Guarene, R. Spagnolo, G. Benedetto, and G. Righini.
- A computer system for timing and acoustical analysis of crack- les: a study in cryptogenic fibrosing alveolitis. Bull. Eur. Physio- pathol. Respir. 20:139–144.
- Ono, M., K. Arakawa, M. Mori, T. Sugimoto, and H. Harashima. 1989. Separation of fine crackles from vesicular sounds by a nonlinear dig- ital filter. IEEE Trans. Biomed. Eng. 36:286–295.
- Murphy, R. L., E. A. Del Bono, and F. Davidson. 1989. Validation of an automatic crackle (rale) counter. Am. Rev. Respir. Dis. 140:1017–
- Kaisla, T., A. R. Sovijärvi, P. Piirilä, H. M. Rajala, S. Haltsonen, and T. Rosqvist. 1991. Validated method for automatic detection of lung sound crackles. Med. Biol. Eng. Comput. 29:517–521.
- Pasika, H., and D. Pengelly. 1994. Lung sound crackle analysis using generalised time-frequency representations. Med. Biol. Eng. Com- put. 32:688–690.
- Sankur, B., E. C. Güler, and Y. P. Kahya. 1996. Multiresolution biolog- ical transient extraction applied to respiratory crackles. Comp. Biol. Med. 26:25–39.
- Forgacs, P., A. R. Nathoo, and H. D. Richardson. 1971. Breath sounds. Thorax 26:288–295.
- Forgacs, P. 1973. Noisy breathing. Chest 63(Suppl.):38S–41S.
- Earis, J. E., K. Marsh, M. G. Pearson, and C. M. Ogilvie. 1982. The in- spiratory “squawk” in extrinsic allergic alveolitis and other pulmo- nary fibroses. Thorax 37:923–926.
- Koyama, Y., N. Shioya, N. Narita, A. Shibuya, S. Kudoh and R. Mi- kami. 1987. Acoustic analysis of squawks. Nippon. Shikkan Gakkai Zasshi 25:880–887.
- Kelemen, S. A., T. Cseri, and I. Marozsan. 1987. Information obtained from tussigrams and the possibilities of their application in medical practice. Bull. Eur. Physiopathol. Respir. 13(Suppl. 10):51s–56s.
- Korpas, J., J. Sadlonova, D. Salat, and E. Masarova. 1987. The origin of cough sounds. Bull. Eur. Physiopathol. Respir. 23(Suppl. 10):47s–50s.
- Sadlonova, J., D. Salat, and V. Salatova. 1987. Tussiphonogram in pro- bands with chronic obstructive bronchitis. Acta Physiol. Hung. 70: 171–175.
- Salmi, T., A. R. A. Sovijärvi, P. Brander, and P. Piirilä. 1988. Long- term recording and automatic analysis of cough using filtered acous- tic signals and movements on static charge sensitive bed. Chest 94: 970–975.
- Piirilä, P., and A. R. Sovijärvi. 1989. Differences in acoustic and dy- namic characteristics of spontaneous cough in pulmonary diseases. Chest 96:46–53.
- Dawson, K. P., C. W. Thorpe, and L. J. Toop. 1991. The spectral analy- sis of cough sounds in childhood respiratory illness. J. Paediatr. Child Health 27:4–6.
- Thorpe, C. W., W. R. Fright, L. J. Toop, and K. P. Dawson. 1991. A mi- crocomputer-based interactive cough sound analysis system. Com- put. Methods Programs Biomed. 36:33–43.
- Perez-Padilla, J. R., E. Slawinski, L. M. Difrancesco, R. R. Feige, J. E. Remmers, and W. A. Whitelaw. 1993. Characteristics of the snoring noise in patients with and without occlusive sleep apnea. Am. Rev. Respir. Dis. 147:635–644.
- Issa, F. G., D. Morrison, E. Hadjuk, A. Iyer, T. Feroah, and J. E. Rem- mers. 1993. Digital monitoring of sleep-disordered breathing using snoring sound and arterial oxygen saturation. Am. Rev. Respir. Dis. 148:1023–1029.
- Stoohs, R., and C. Guilleminault. 1992. MESAM 4: an ambulatory de- vice for the detection of patients at risk for obstructive sleep apnea syndrome (OSAS). 101:1221–1227.
- Suzuki, A., C. Sumi, K. Nakayama, and M. Mori. 1995. Real-time adap- tive cancelling of ambient noise lung sound measurement. Med. Biol. Eng. Comput. 33:704–708.
- Patel, S., M. G. Callahan, and G. R. Wodicka. 1996. Active noise reduc- tion stethoscopy for lung sound measurement in loud environments (abstract). J. Acoust. Soc. Am. 99:2477.
- Pasterkamp, H. 1991. Computer assisted learning of chest auscultation: the Respiration Acoustics Laboratory Environment. In J. H. Van Bemmel and J. Zvarova, editors. Information and Medical Educa- tion. Elsevier North Holland, New York. 244–251.
- Mangione, S., L. Z. Nieman, and E. J. Gracely. 1992. Comparison of computer based-learning and seminar teaching of pulmonary auscul- tation to first-year medical students. Acad. Med. 67(Suppl.):S63–65.
- Sestini, P., E. Renzoni, M. Rossi, V. Beltrami, and M. Vagliasindi. 1995. Multimedia presentation of lung sounds as a learning aid for medical students. Eur. Respir. J. 8:783–788.
