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Home , Airway resistance

Bill Brashier, Chest Research Foundation, Sundeep Salvi, Chest Research [email protected] Marigold Complex, Kalyaninagar, Foundation, Marigold Complex, Sundeep Salvi Pune, India Kalyaninagar, Pune 411014, India

Measuring function using sound waves: role of the forced oscillation technique and impulse oscillometry system

Introduction was a ­measure of respiratory impedance Measuring lung function is an important (Zrs), which included the respiratory resis- Conflict of interest component in the decision making process tance (Rrs) and respiratory reactance (Xrs) None declared for patients with obstructive airways disease measured over a range of frequencies (usually (OAD). Not only does it help in arriving at a from 3 to 35 Hz). These parameters provided specific diagnosis, but it also helps in evalu- valuable information about the mechanical ating severity so that appropriate pharmaco- properties of the airways and lung paren- therapy can be instituted, it helps determine chyma. The main advantage of this device was prognosis and it helps evaluate response that the procedure was easy to perform and to therapy. is currently the most provided information about the lung which commonly performed lung function test in was different from that given by the spirome- clinical practice and is considered to be the ter. The earlier FOT instruments allowed only gold standard diagnostic test for and one sound frequency to be passed at a time. COPD. However, spirometry is not an easy To measure Zrs over a range of sound frequen- test to perform because the forceful expi- cies therefore took a long time. Some of the ratory and inspiratory manoeuvres require more recent FOTs now use sound waves of good patient co-operation. Children aged two or three different frequencies at one time. <5 years, elderly people and those with phys- The main advantage of FOT is that it provides ical and cognitive limitations cannot perform very good time resolution with measures of spirometry easily. respiratory resistance. In 1956, DuBois et al. [1] described the In 1975, Michaelson et al. [2] developed a ERS 2015 forced oscillation technique (FOT) as a tool computer-driven loudspeaker output to apply to measure lung function using sinusoidal bursts of square wave oscillatory sound waves of single frequencies gener- (5 times⋅s−1) of multiple sound frequencies and HERMES syllabus link: ated by a loud speaker and passed into the analysed the –flow relationship using module D.1 during tidal . The output spectral analysis. This improvised ­technique

DOI: 10.1183/20734735.020514 Breathe | March 2015 | Volume 11 | No 1 57 Measuring lung function using sound waves

of FOT that could use multiple sound fre- flow sensor-based spirometer does. Both the quencies at one time was called the impulse FOT and IOS devices measure Rrs and Xrs at oscillometry system (IOS). The temporal res- multiple frequencies, but they do not neces- olution of IOS is slightly inferior to FOT and sarily show similar values. it sends pulses of pressure waves inside the lungs that can be a bit uncomfortable. How- ever, the IOS provides extensive description What are the parameters of oscillatory pressure–flow relationships over that FOT/IOS measure? a range of frequencies between 4 and 32 Hz and gives better mathematical analyses of The impulses generated by the loudspeaker resistance and reactance using the fast fou- travel superimposed upon the normal tidal rier transform (FFT) technique [3]. Moreover, breathing through the large and small airways. the mixed multi-frequency waveform provides Higher frequencies (>20 Hz) travel shorter improved signal-to-noise characteristics [4]. distances (generally up to the large airways), This new technique was subsequently refined while lower frequencies (<15 Hz) travel deeper over the years by Jaeger and became commer- into the lung and reach the small airways and cially available in 1998 [5]. Both FOT and IOS lung parenchyma (fig. 1). A useful analogy here are widely used in paediatric clinics across the is radio waves: radio waves of high frequency, world as well as in several lung physiology lab- such as FM radio travel shorter distances, oratories as a valuable clinical research tool. while radio waves of lower frequency, such as The main advantage of FOT/IOS is that AM radio travel long distances. A pressure– the patient needs to perform simple tidal flow transducer measures inspiratory and breathing manoeuvres that require less effort expiratory flow and pressure, which are then and co-operation than spirometry, meaning separated from the breathing pattern by “sig- that children and the elderly can therefore nal filtering”. Measured Zrs is the sum of all perform this test easily. Moreover, it can be the forces (Rrs and Xrs) opposing the pres- performed in patients on ventilators and also sure impulses (oscillations) and is calculated during sleep. One of the most remarkable fea- from the ratio of pressure and flow at each fre- tures of FOT/IOS in relation to spirometry is quency [6]. The FOT/IOS is therefore an accu- that it has much greater sensitivity to detect rate and powerful method that measures Rrs peripheral airways obstruction. In most cases, and Xrs from input Zrs measurements made spirometry does not provide a clear indication over a range of frequencies. of peripheral airway obstruction regardless of the information contained in the flow–vol- Respiratory resistance ume curve and the forced expiratory flow at 25–75% of forced (FEF25–75%). Rrs measured by FOT and IOS includes the FOT/IOS are therefore more sensitive instru- resistance of the oropharynx, larynx, trachea, ments to detect small airways obstruction in large and small airways, lung and chest wall patients with asthma and chronic obstructive tissue. However, the use of multiple oscilla- pulmonary disease (COPD). More recently, the tion frequencies permits a dissection of large within-breath analysis of Rrs and Xrs has been airway behaviour from that of peripheral small shown to help differentiate between asthma airways. Sound waves at frequency <15 Hz and COPD and also offer more useful infor- travel more distally and those >20 Hz are mation about the pathophysiology of asthma damped out in the intermediate sized airways. and COPD, which the spirometer does not. The resistance at 5 Hz (R5) represents the The differences between spirometry and FOT/ total airway resistance, and the resistance at IOS are described in table 1. 20 Hz (R20) represents the resistance of the Choosing between FOT and IOS to mea- large airways. Subtracting R20 from R5 (R5−R20) sure respiratory resistance and reactance is reflects resistance in the small airways. like choosing between a volume–­displacement In healthy adult subjects, R is nearly inde- spirometer and a flow sensor-based spirometer pendent of oscillation frequency (i.e. resis- respectively. Although the volume–displacement tance is more or less the same at frequencies spirometers offer more accurate measures of between 5 and 20 Hz). When airway obstruction­ than the flowsensor-based ­ spi- occurs, either central or peripheral, R5 is rometers, they are bulky, ­difficult to maintain increased above normal values. Central ­airway and do not offer important readouts that a ­obstruction elevates R evenly independent

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Table 1 Differences between spirometry and FOT/IOS

Parameter Spirometry FOT/IOS

Main principle Flow sensor/volume displacement helps Forced oscillations of single frequency measure flow rates and lung volumes sound waves (FOT) or impulses of multiple frequency sound waves (IOS) are pushed into the lungs as pressure waves to measure respiratory resistance and reactance

Main parameters Volumes: FEV1, FVC Zrs, Rrs, Xrs, Fres, Ax

Flows: PEFR, FEF25–75%

Patient co-operation required +++ +

Type of breathing manoeuvre Forced Tidal breathing

Variability (intra-subject) 3–5% 5–15%

Sensitivity to airway location

Central + +++

Peripheral ++ +++

Cut off for response 12–15% for FEV1 40% for R5 or X5

Cut off for bronchoconstrictor response 20% for FEV1 50% for R5

Insight into lung mechanics + +++

Standardised methodology +++ ++

Availability of robust reference values +++ +

FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; PEFR: rate; FEF25–75%: forced expiratory flow at 25–75% of FVC; Zrs: respiratory impedance; Rrs: respiratory resistance; Xrs: respiratory reactance; Fres: resonant frequency; Ax: reactance area; R5: respiratory resistance at 5 Hz; X5: respiratory reactance at 5 Hz. of oscillation frequency, whereas peripheral the to store energy and is ­airways obstruction increases R at low frequen- primarily located in the lung periphery. cies, an effect that diminishes with increasing C and I are in opposite phase with each frequency (fig. 2). Therefore, in small airways other, and unlike resistive properties of the obstruction, R becomes frequency depen- normal respiratory system, they are depen- dent and is considered to be a characteristic dent on oscillation frequency. At low fre- feature. Small children normally present fre- quencies, the magnitude of the oscillatory quency dependence of resistance, and this capacitative pressure loss is relatively large may be greater than in adults in the presence and that of inertive pressure loss is relatively of peripheral airflow obstruction. Resistance is small. Therefore, at low frequencies, the −1 −1 −1 −1 measured in cmH2O⋅L ⋅s or kPa⋅L ⋅s . capacitative properties of the small peripheral airways dominate. As oscillation frequency increases, the magnitude of the capacitative Respiratory reactance pressure dissipation decreases, while that Xrs is the imaginary part of Zrs and includes of inertive pressure increases. Therefore, at the mass-inertive forces of the moving air col- high frequencies, the inertive properties of umn expressed in terms of inertance (I) and the large airways dominate. By convention, the elastic properties or compliance of lung capacitative pressure losses are designated periphery expressed as capacitance (C). Reac- negative, and inertive pressure losses, posi- tance can be viewed as the rebound resistance,­ tive [3]. Accordingly, the balance between the or an echo, giving information about the two is negative at low frequencies and ­positive ­distensible airways. C represents the ability of at high frequencies (fig. ).3 Like resistance

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Sinusoidal wave Square wave Frequency dependence of Xrs

oscillation of FOT oscillation of IOS –1 Reactance area (AX) ·s –1 O·L

2 Resonant frequency (Fres)

0

Mouth, cheeks, "C portion" "I portion" throat Reactance cmH

5 10 15 20 25 R20 R5 Frequency Hz Figure 3 Reactance values in a healthy subject showing the “C” (compliance) and “I” (inertance) portions of reactance, area of reactance (AX) and resonant frequency (Fres).

capacitative energy is primarily manifest in the small airways, X5 can provide important infor- mation about the distal/small airways. States that reduce the elasticity of the lung, such as fibrosis and hyperinflation make the capaci- tance increasingly negative, i.e. more negative or higher X5 values.

Resonant frequency

Alveoli At one intermediate frequency, the magni- tudes of capacitative and inertive pressure Figure 1 components are equal. Since they are opposite Type of sound waves in FOT and IOS and distances in sign, the total reactance at this frequency is travelled by sound waves of different frequencies. zero. This frequency is called the resonant fre- quency (Fres). Fres marks the transition from Small airways obstruction capacitative dominance at low frequencies to –1 Large airways obstruction ·s inertive dominance at high frequencies. This –1 also helps conveniently categorise frequencies O·L 2 below Fres as low and above Fres as high, and

indicates a frequency at which the total imped- ance to airflow is totally flow resistive. Normal Normal resistance Fres is approximately 6–11 Hz. Fres tends to be higher in children, decreases with age and

Resistance cmH increases in both obstructive and restrictive 5 10 15 20 25 diseases. Frequency Hz Figure 2 Reactance area Respiratory resistance versus frequency. Reactance area (AX), also called the “Gold- values, reactance ­values are also measured in man Triangle” (named after Michael Goldman −1 −1 −1 −1 cmH2O⋅L ⋅s or kPa⋅L ⋅s . who described it for the first time) is the inte- The reactance at 5 Hz (X5) reflects the com- grated low frequency respiratory reactance bined effect of tissue elastance and inertance, magnitude between 5 Hz and Fres (fig. )3 and although at this lower frequency, the effect of is measured in cmH2O⋅L−1 or kPa⋅L−1. AX is a tissue elastance would dominate. X5 therefore useful index related to respiratory compliance reflects of the peripheral airways and therefore of small airways patency. AX is [7]. Because the ability of the lungs to store a single quantity that reflects changes in the

60 Breathe | March 2015 | Volume 11 | No 1 Measuring lung function using sound waves degree of peripheral airway obstruction and the forced manoeuvres of spirometry have an closely correlates with R5−R20. The normal AX impact on resistance and reactance values. is generally <0.33 kPa⋅L−1. Some common artefacts include:

●● Poor cheek support. Because pressure How to perform the test oscillations are applied at the mouth, the impedance of extra-thoracic airway walls, The IOS instrument should be calibration including cheek, tongue, mouthpiece and checked every day for volume using a 3-L upper airway affects the results of measure- syringe and for resistance using a reference ments. If the cheeks are not held firmly, R20 −1 −1 resistance of 0.2 kPa⋅L ⋅s to ensure that the values reduce significantly and are therefore sensors are working accurately. underestimated. Absence of cheek support The procedure should be explained to the affects the values of R5 and X5 significantly patient and the sitting position is preferred. in patients with obstructive airways dis- Legs must be kept uncrossed in order to ease as well as interstitial lung disease, and reduce extra-thoracic pressure and a nose clip has relatively little impact on healthy sub- should be worn. The mouthpiece of the FOT/ jects [8]. Although the cheek support can IOS should be at a comfortable height so that be given by the patient or an assistant, it the neck is slightly extended. Ensure that there has been shown that cheeks supported by is a tight seal between the mouthpiece and lips as assistant show slightly reduced R5 and to prevent air leak. The cheeks should be held increased X5 [8]. This is probably because firmly either by the patient with his/her hands of the position of arms and chest wall while or by an assistant who presses the cheeks holding the cheeks. firmly from behind fig.( ).4 ●● Use of bacterial filters. The use of a bacterial Ask the patient to perform normal tidal filter adds a volume of around breathing in a relaxed state during the FOT/ 60 mL and increases FOT/IOS resistance IOS procedure. The recording should be per- values by around 0.04 kPa⋅L−1⋅s−1. Resis- formed for at least 30–45 s. During this period, tance values measured with a bacterial filter around 120–150 sound impulses are pushed will therefore be slightly greater than those into the lungs from which the mean reactance without a filter. and resistance values are determined at fre- ●● Tongue position. If the tongue position quencies from 5 to 20 Hz. A minimum of three interferes with free airflow through the such tests should be performed. Care should mouthpiece, a uniform increase in resis- be taken to ensure reproducible results with- tance is seen at all frequencies. This can- out any artefacts as mentioned below. If there not be identified by a single FOT/IOS are breathing segments which contain arte- test. Therefore, multiple tests need to be facts, they should be discarded. performed and looked for repeatable mea- If spirometry and FOT/IOS are going to sures. The tongue position has little effect be performed at the same visit, spirometry on the reactance values at all frequencies. should be performed after FOT/IOS because ●● In addition to the above, air leaks, swallow- ing, breath holding and vocalisation are the other common artefacts that should be avoided.

For bronchodilator reversibility assessment, a short-acting bronchodilator is administered

Cheek support and an equal number of measurements are performed in the same fashion. Neck in neutral position In IOS, the quality assurance is measured by “coherence”, which is an index that recog- nises the validity of the results. It is a value between 0 and 1 that reflects the reproducibil- ity of impedance measurements. Coherence at

Figure 4 5 Hz should ideally be >0.8 cmH2O and coher- Position of the patient while performing IOS. Note ence at 20 Hz between 0.9 and 1.0. These how the cheeks are held firmly. values are for adults and, so far, there are no

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validated values for children. Coherence is predicted values for different parts of the decreased by improper technique, swallowing,­ world. glottis closure, obstruction of airflow by the tongue or irregular breathing. The day-to-day variability for IOS parame- Adults ters has been shown to be 5–15% in adults and Compared with children, there have been 16–17% in children. This degree of variability fewer attempts to develop normal predicted indicates that obtaining similar repeated mea- FOT/IOS values for adults. So far, there have sures is not difficult, and that IOS is a fairly been four published studies that have derived reproducible test although not as much as the predicted values. Like in children, height has spirometric indices of forced expiratory volume been shown to be the most influential pre- in 1 s (FEV1) and forced vital capacity (FVC). dictor of FOT/IOS values. The KORA (Coop- erative Health Research in the Augsburg Region) study cohort population from Ger- Predicted values many among 154 and 243 nonsmoking men and women, respectively, was used to study It must be emphasised that FOT and IOS do the predicted values for IOS among Caucasian not produce equal measurements of resis- adults aged ≥ 45 years [10]. They showed that tance and reactance, therefore predicted 1) females had higher resistance and lower values derived by an FOT machine may not reactance values than men, 2) R5-R20, AX and necessarily be applicable for IOS machines. Fres showed age-related changes, 3) X5 values Tanimura et al. [9] compared the resistance and showed age-related changes only in females, reactance values between MostGraph (FOT) 4) body weight was a significant predictor and Jaeger (IOS) using phantom models. The for most IOS parameters in females, but not resistance values varied by up to 10% from males, and 5) obesity was shown to cause an estimated values in both devices. Additionally, elevation in X5 and AX values. Unfortunately, there was a difference in frequency depen- the predicted values in this study were quite dence for the resistance between devices. The different from those reported in earlier studies reactance values were higher with the FOT although they were from the same Caucasian than IOS. Clearly, more studies are required population. There is an urgent need to develop to establish reliable device-specific predicted robust predictive equations for the adult pop- values. ulation for both FOT and IOS from different parts of the world. Children In children, age and height have been shown FOT/IOS in respiratory to have a significant impact on resistance and reactance values. As the lung grows, the air- disorders way calibre increases as well as the number FOT/IOS in asthma and size of alveoli. Therefore, on one hand, respiratory resistance values at all frequen- Childhood asthma is often a clinical diagno- cies decrease with growing age and increasing sis because of the lack of a reliable and prac- height. On the other hand, as age and height tical objective diagnostic tool. Ortiz et al. [11] increase, X5 values become less negative with were among the first to show that children little change in X20. Height has been shown aged 2–5 years with a suspected diagnosis to be the strongest covariate, contributing to of asthma in whom spirometry could not be around 56–60% variance for impedance, resis- performed, showed significant improvements tance, reactance, Fres and AX values. Studies in in IOS parameters after giving bronchodilator Caucasian and Oriental children have shown treatment. more or less similar predicted values, sug- Although it is possible to perform spi- gesting that predicted values generated at one rometry in older children, often children pre- place can be used globally. There are at least senting with asthma symptoms have normal seven studies that have reported predicted val- spirometry, yet show abnormal changes in IOS ues for FOT/IOS values for children, although parameters such as X5 and AX. Giving these most of them have been for IOS. However, children inhaled corticosteroids has produced more studies are required to generate­ robust marked improvements in their ­symptoms [12].

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Abnormal IOS parameters therefore help FOT/IOS in COPD improve confidence when making a diagnosis Pulmonary mechanics caused by airflow of asthma in children, even when spirometry obstruction in COPD are better seen in reports are normal. ­reactance values than resistance values, unlike Many children with asthma have difficulty in asthma where resistance values are more verbalising symptoms and some find it difficult impaired. Patients with self-reported symp- to perceive changes in their respiratory status. toms suggestive of COPD have been shown to Objective parameters, such as spirometry, have reduced X5, irrespective of whether they peak flow measurement or even exhaled breath have normal or abnormal spirometry [19]. X5 nitric oxide do not accurately reflect a decline in is the only parameter that has been shown to asthma control. Recent studies have suggested ­correlate significantly with decrements in FEV1 that those children who have currently con- in patients with COPD over time [20]. trolled asthma but have increased peripheral In 1993, Peslin et al. [21] reported that some airway IOS indices, often show a greater risk of patients with COPD on losing asthma control over the next 2–3 months developed large negative swings in Xrs during [13]. Children with an increased R5−R20 of exhalation when measured by FOT. This was >1.5 kPa⋅L−1⋅s−1 and AX values of ≥7.0 kPa⋅L−1 explained on the basis that low-frequency more often showed an increased risk of losing oscillatory signals cannot pass the choke point asthma control. These observations suggest (caused by small airways collapse) and reach that monitoring small airway function by IOS the alveoli during expiration. This leads to a can be useful in identifying children who are at marked reduction in respiratory compliance, i.e. risk for losing asthma control. a fall in Xrs. In 2004, Dellacà et al. [22] reported More recently, three-dimensional analysis that the differences between inspiratory and of resistance and reactance using FOT has expiratory phases of respiratory reactance shown unique patterns for controlled versus ( Xrs) measured by the FOT were due to expira- uncontrolled asthma in children [14]. Δ tory flow limitation (EFL), which is a character- In adult asthmatics, small airway dysfunc- istic feature of patients with moderate-to-severe tion as evaluated by IOS has been shown to be COPD that manifests clinically as dynamic associated with excessive hyperinflation. This within-breath difference and poor asthma control [15]. The IOS param- between inspiratory and expiratory reactance at eter R5−R20 has been shown to be a useful low frequencies, called X5 was therefore found marker of fluctuation of the heterogeneity of air- Δ to provide valuable information regarding EFL way constriction over time and has been shown in patients with COPD. The normal Xrs values to predict future asthma exacerbations [16]. Δ are ≤0.07 kPa⋅L−1⋅s−1. In patients with asthma, Mori et al. [17] have reported that coloured this increases to around 0.10 kPa L−1 s−1, while three-dimensional analyses of respiratory ⋅ ⋅ in patients with COPD it increases to more than resistance and reactance, especially ΔX5 (i.e. 0.21 kPa L−1 s−1 [23]. These cut off values are the difference between inspiratory and expi- ⋅ ⋅ based on only one study, and more work needs ratory X5), can help differentiate asthma from to be done to identify robust cut-off values. COPD with confidence. More recently, Mikamo et al. [24] reported Furthermore, Shirai et al. [18] have recently that high EFL index ( 0.55 kPa L−1 s−1) mea- reported that coloured three-dimensional > ⋅ ⋅ sured by FOT was independently predicted by images of respiratory impedance obtained emphysema extent measured by high-resolu- using FOT show unique phenotypes of tion computed tomography (HRCT), periph- asthma. The typical asthma–asthma pheno- eral airway obstruction expressed by FEF25–75%, type presents with moderately high Rrs over all hyperinflation as expressed by functional resid- frequencies with slight changes in Xrs, espe- ual capacity, and airway calibre as expressed by cially X5, while the asthma–COPD phenotype whole breath R5. The ΔXrs also correlated well presents with much higher Rrs and Xrs with a with the modified Medical Research Council marked respiratory cycle and frequency depen- scale for breathlessness. These results suggest dence, while the asthma–normal phenotype that EFL or ΔX5 measured by FOT is a good presents with low Rrs and Xrs and few within-­ global measure of COPD. It is hoped that, in breath changes. Although very exciting and the future, Xrs will help evaluate the severity promising, more work is required to under- Δ of COPD as well as response to treatment in stand the true value of these observations in patients of COPD. clinical practice.

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IOS and interstitial lung disease (mean −0.08 kPa⋅L−1⋅s−1) and positive in ILD (+0.05 kPa⋅L−1⋅s−1). Mirror changes were seen Patients with interstitial lung disease (ILD) in ΔAX values (fig. ).5 show reduced FVC with a normal FEV1/FVC More recently, Fuji et al. [29] reported that ratio on spirometry, which is however not diag- inspiratory Fres values measured on FOT nostic of ILD. Total lung capacity measured ­correlated independently with the fibrosis by body plethysmography and lung diffusion extent on HRCT as well as with the compos- measured by single-breath ite pulmonary index (FEV1, FVC and DLCO). of the lung for CO (DLCO) with a 10-s breath The authors suggested that inspiratory Fres hold provide the most useful physiological is a measure of increased lung elastic recoil measure of ILD. However, these tests are not resulting from fibrosis in ILD and may have easily available in most clinics and, quite often, prognostic value. The ability for FOT parame- patients with ILD find it difficult to perform a ters to predict the composite pulmonary index good-quality test. and HRCT, if confirmed in multicentre studies, In 1968, Fisher et al. [25] showed evidence would be of immense clinical benefit because of increased respiratory resistance on FOT in many patients with ILD are not able to per- patients with ILD, but the sample size was form good quality spirometry or even the sin- small and the FOT analysis was only very gle breath DLCO tests. However, prospective basic. In 2009, van Noord et al. [26] reported clinical trials are needed to evaluate the true increased Rrs and reduced Xrs in patients with benefit of FOT/IOS in these settings. advanced ILD, but these values were similar to those observed in patients with moderate-­ to-severe COPD. The authors therefore com- The future mented that the results of FOT cannot help differentiate between obstructive and restric- Despite the advantages of FOT/IOS in terms tive disorders. of its noninvasiveness and lack of dependency In 2013, Mori et al. [27] reported that on patient cooperation, the FOT has not yet although the total X5 values were lower in become a standard methodology for the ILD and comparable to patients with COPD, routine assessment of lung function in clini- the X5 values were smaller in the expiratory cal practice. Although obtaining respiratory phases compared with the inspiratory phases impedance values is easy, the interpretation in ILD, which is the reverse of what is found in of resistance and reactance curves and the patients with COPD. Sugiyama et al. [28] also derived parameters requires training and expe- reported that inspiratory X5 values were more rience, and it is a difficult task for an untrained negative than expiratory X5 values in patients pulmonologist. This may be one of the main with ILD and was exactly the opposite of what reasons why FOT/IOS has not progressed as was found in patients with COPD (in which much as it should have. expiratory X5 values were more negative). The More recently, attempts have been made to ΔX5 values were therefore negative in COPD develop machine learning algorithms that help

a) 1.0 b) 0.06

0.8 0.04 0.02 –1 –1 0.6 ·s

–1 0.00 0.4 –0.02 kPa·L X kPa·L 5 –0.04 ∆ A 0.2 ∆ X –0.06 0 –0.08 –0.2 –0.1 Healthy Asthma COPD ILD Healthy Asthma COPD ILD subjects subjects Figure 5 Mean a) ΔAX and b) ΔX5 values in healthy subjects, and patients with asthma, COPD and ILD. Adapted from [28] with permission from the publisher.

64 Breathe | March 2015 | Volume 11 | No 1 Measuring lung function using sound waves make diagnosis easy and automated. ­Amaral progression, evaluating risk of future disease et al. [30] have recently reported that using exacerbations and guiding therapy. These are k-nearest neighbour and random forest clas- still early days, but in the future we are likely sifiers, which are different types of machine to see diagnostic algorithms being developed learning algorithms, it was possible to diag- for asthma, COPD and other lung diseases nose and categorise COPD airway obstruction for FOT and IOS which will help clinicians and also assist clinicians in tracking disease ­tremendously.

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Breathe | March 2015 | Volume 11 | No 1 65