Volume 5, Issue 1, Pages 77-84 (March 2004)

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Measurements of airway mechanics in spontaneously breathing young children

Abstract

This paper gives an overview of the general principles of airway mechanics and methods to measure lung fuction in non-sedated, spontaneously breathing young children. Although lower airway obstruction is probably best evaluated using FEV1, other techniques can be applied when such measurement is impossible, as in young children. These techniques include measurement of resistance using the interrupter or impulse oscillation techniques.

Keywords: pulmonary function, airway mechanics, young children

Article Outline

• Abstract

• INTRODUCTION

• GENERAL PRINCIPLES OF RESPIRATORY MECHANICS

• Modelling of the respiratory system

• The time constant

• Elastance and compliance

• Resistance

• THE INFLUENCE OF ANATOMY ON AIRWAY MECHANICS

• The upper airway

• The lower airway

• Small airways

• THE INFLUENCE OF GROWTH AND DEVELOPMENT ON AIRWAY MECHANICS

• Developmental anatomy and physiology of the respiratory system

• TECHNIQUES FOR MEASURING RESISTANCE IN SPONTANEOUSLY BREATHING YOUNG CHILDREN

• Respiratory system resistance (R)

• Active breathing against occlusion

• Passive measurements: airway occlusion, oscillation and interrupter techniques

• The airway occlusion technique

• Oscillation techniques

• The interrupter technique (R)

• Airway resistance (R)

• COMPARISON OF DIFFERENT TECHNIQUES

• FINAL CONSIDERATIONS

• PRACTICE POINTS

• RESEARCH DIRECTIONS

• References

• Copyright

INTRODUCTION

In preschool children, respiratory function measurements are rarely available.

The most frequently used measurement in older children is the forced expiratory volume in 1second (FEV1) obtained from a maximal expiratory flow volume curve (MEFV). This technique is not usable in infants and most preschool children.1., 2., 3. The aim of this article is to describe the airway mechanics of young children and techniques to measure pulmonary function in them.

GENERAL PRINCIPLES OF RESPIRATORY MECHANICS

Modelling of the respiratory system

The respiratory system can be considered a collection of physical components interacting with one another and with the environment. Although in-vivo measurements show that the lungs do not function as a single compartment, the simplification of the respiratory system into a linear model enables easier analysis.

The most simple model is that of a single balloon on a pipe. The relationship at any moment (t) between the pressure applied at the opening of the model (P(t)) and the volume in the model (V(t)) during emptying of this balloon can be described as a first order model:

(E=elastance of the balloon; R=resistance of the pipe; and V′=flow through the opening). Using regression analysis, one can calculate E and R from P(t), V(t) and V′(t).

The values of R and E, as applied to the respiratory system, reflect the resistance of the airways and the elastance of the respiratory system, whereas V(t) is the volume increase from functional residual capacity (FRC) when the mouth pressure is zero.

The three important components of this linear model are the time constant (τ), compliance (C) or elastance (E) and resistance R. The relationship of these is given by the equations:

The time constant

The time constant (τ) describes the expiratory airflow generated by the elastic properties of the respiratory system.4 During passive emptying, the time to reduce by 63% is known as the time constant of the respiratory system. This allows the lung to empty at the end of each breath to FRC. In healthy infants with normal lungs, the time constant (τ) is 0.3s and, in infants with stiff lungs, it is decreased.5

Elastance and compliance

When mechanical forces are applied to elastic structures, they will resist deformation by producing an opposing force. This opposing force is called elastic recoil. The pressure needed to overcome elastic recoil, the elastic recoil pressure (Pel), depends on the lung volume above or below the equilibrium volume. The Pel divided by the lung volume gives a measure of the elastic properties of the lung tissue and is called elastance (E). The slope of the volume (V) vs pressure (Pel) gives the reciprocal of elastance i.e. compliance (C):

Resistance

Resistance is expressed as changes in pressure divided by changes in flow:

In other words, the flow (V′) measured at the mouth depends on the driving pressure (i.e. the pressure difference between alveoli [Palv] and mouth [Pmo]) and the airway resistance (Raw):

If the mouth pressure is 0 (i.e. atmospheric pressure), the driving pressure is the alveolar pressure.

Airways resistance (Raw) is the sum of the peripheral airways resistance (peripheral intrathoracic airways <2mm diameter; Rawp), the central airways resistance (large intrathoracic airways >2mm diameter; Rawc) and the extrathoracic airways resistance (especially glottis; Rext). In healthy people Rext accounts for 50% of the total Raw and Rawp for about 15%. Rawp and Rawc are influenced by lung volume. Higher lung volumes give higher Pel and therefore increase airway diameter. With increasing volumes during inspiration, the increased Pel is counteracted by Ppl, resulting in increased radial distending force. This distending force is the transmural pressure and is the difference between pressure in (Pin) and pressure outside (Pout) the airway.

At zero airflow the pressure inside the airways (Pin) equals atmospheric pressure and transmural pressure (Ptm) equals the elastic recoil pressure (Pel):

Airway diameter approximates to a sigmoidal relationship with Ptm of the intrathoracic airways. This results in volume dependency of Raw. At higher lung volumes Rawp decreases. The specific relation between Rawp (or its reciprocal conductance Gaw [=1/Raw]) and volume is mirrored by the specific Raw (sRaw) and specific Gaw (sGaw):

Values of sRaw and sGaw are remarkably constant regardless of age or height.

THE INFLUENCE OF ANATOMY ON AIRWAY MECHANICS

The total respiratory resistance (Rrs) consists of the resistance of the airways (Raw), the resistance of the lung (RL) and the resistance of the chest wall (Rcw):

In older children, Rcw and RL represent only 10–20% of Rrs,6 but, in newborns, RL could be higher.7

The upper airway

The upper airway starts at the mouth (or nose) and ends at the larynx. Breathing through the nose causes greater resistance, the nose accounting for 50% of the total respiratory resistance in adults; it is less in children. During mouth breathing, 15–50% of the airway resistance is caused by the oral cavity, pharynx and larynx,8., 9., 10. the larynx causing up to 25%.11., 12. The vocal cords produce an important resistance to air flow.9., 13., 14. They move apart during inspiration and narrow during expiration.15 Infants are considered obligatory nose breathers but, at all ages, mouth breathing is possible.16., 17.

The pharynx is the most compliant region of the upper airways, and negative pressures may cause collapse. This is prevented by airway muscle tone, but can cause very high resistance measurements in children with anatomic abnormalities or muscle dysfunction.

The lower airway

The diameter of the lower airways is maintained by a balance of forces.

Sympathetic impulses relax and parasympathetic impulses constrict the muscles. Airways dilatation may occur as a result of sympathomimetic agents (e.g. epinephrine or adrenaline). Narrowing forces are bronchial smooth-muscle contraction, mediated by efferent autonomic nerve control. Constriction can also occur as a result of irritants (e.g. dust, smoke or cold), hyperventilation and because of vaso-active agents (e.g. acetylcholine, histamine or bradykinin).

Additional narrowing occurs during forced expiration, when there is dynamic airway compression caused by pleural and peribronchial pressures. This is counteracted by the intraluminal pressure and the tethering action of the surrounding lung (Fig. 1).

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Figure 1. The relation of pressures in- and expanding the airway lumen. EPP=equal pressure point; Pex=dynamic compression by pleural and peribronchial pressure; Pin=pressure inside airways.

Small airways

The contribution of the small airways (<2mm diameter) to total resistance in adults is only 20%, owing to the vast number of small peripheral airways, providing a large cross-sectional area for airflow. That is why small airway disease may severely impair ventilation of distal air spaces but go undetected by total airway resistance measurements. However, in children, small peripheral airways may contribute up to 50% of the total airway resistance. This proportion does not decrease until about 5 years of age. This increases the usefulness of resistance measurements in small children affected by small airway diseases.

THE INFLUENCE OF GROWTH AND DEVELOPMENT ON AIRWAY MECHANICS

Developmental anatomy and physiology of the respiratory system

Normal values of pulmonary function are usually referenced by standing height and sex. However age, arm-span,18 sitting height19 and ethnicity20 also influence them.

Lung volume and volume-pressure relationships (e.g. compliance) reflect parenchymal (air space) development, whereas airflow and pressure-flow relationships (resistance and conductance) predominantly reflect airway development.

Pulmonary compliance depends on the number of expanded air spaces, the size and geometry of the air spaces, the characteristics of the surface lining layer and the properties of the lung parenchyme, which change with growth and maturation. This is represented by changes in the shape of the volume-pressure curve. When corrected by expressing the volumes as a percentage of the maximal observed lung volume, these are more curved in infants than in older children (Fig. 2).

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Figure 2. Deflation volume-pressure curves of the lung at different ages (obtained from studies on excised lungs).21 With increasing age up to young adulthood, the curves become straighter and, at a given lung volume, elastic recoil pressure is greater. The curve from elderly individulas resembles that from a 7-year-old respiratory system.

This probably reflects the immature rather than the mature alveoli and hence the differences in the elastin-collagen ratio with age.21 The lung volume at which airway closure occurs is higher in children under 7 years of age.22 Pressure-volume relationships are also more curvilinear in infants.23 Chest-wall compliance is 50% greater in infants.

Hogg et al.24 divided airways resistance measurements into central and peripheral components, and found that, in preschool children, the contribution of the peripheral airways was greater than in adults.24 This increases the usefulness of resistance measurements in children, especially those with small airway disease. It also shows that the infant bronchial tree is not simply a miniature of the adult.25

Some studies suggest variability in the interaction between parenchyma and airway growth,26., 27. which may be genetically determined. There is increasing evidence that diseases in early childhood are linked to physiological indicators of lung and airway size, already present in early infancy.28., 29., 30. Growth and development of the respiratory system require the use of age-specific lung function values. Some have been developed for preschool children.31., 32., 33., 34., 35.

TECHNIQUES FOR MEASURING RESISTANCE IN SPONTANEOUSLY BREATHING YOUNG CHILDREN

Techniques for measuring resistance in spontaneously breathing young children have been developed for the measurement of airway resistance Raw, total pulmonary resistance (Rtot=RL+Raw) and active or passive respiratory system resistance (Rrs=Raw+RL+Rcw) (Table 1).

Table 1.

Measurement of resistance in humans

Respiratory system resistance	Total pulmonary resistance	Airway resistance
(Rrs=RL+Raw+Rcw)	(Rtot=RL+Raw)	(Raw)
Active breathing against occlusiona	Intra-oesophageal balloon	Body plethysmographya
Airway occlusion techniquea
Force oscillation technique (FOT)b
Impulse oscillation technique (IOS)b
Interrupter technique (RINT)b

Techniques that are possible in infants and in spontaneously breathing pre-school children are indicated.

Infants.

Children.

During the measurement of resistance, pressure is measured at the mouth and at the alveoli The corresponding flow of air is also recorded. Measurement of the alveolar pressure is difficult. With most techniques, pressure and flow are measured at the mouth, and alveolar pressure can be measured at the mouth after airway occlusion when alveolar and mouth pressures will be the same.

Respiratory system resistance (Rrs)

This can be measured, using active and passive techniques.

Active breathing against occlusion

Measurements of active Rrs can be performed in infants during quiet breathing under sedation or spontaneous sleep. Simultaneously, pressure, volume and air flow are measured. After a normal breath, the airway is occluded at end of expiration. During the following occluded inspiratory effort, repetitive measurements of pressure can be related to flow, and volume measured during the preceding breath. From these, elastance E, compliance C and resistance Rrs can be calculated. Inspiratory resistance measured in this way represents about 70% of expiratory resistance during infancy.36

Passive measurements: airway occlusion, oscillation and interrupter techniques

The airway occlusion technique

After airway occlusion at end of inspiration, the Hering Breuer reflex causes apnoea, the inspiratory and expiratory respiratory muscles relax and a passive expiratory flow-volume curve can be analysed after release of the occlusion.37 Without sedation, it is only possible in infants.

During expiration, the recoil pressure is approximately proportional to lung volume added to FRC. Flow will only be restricted by frictional resistance, lung-tissue resistance and the pressure required to overcome inertia. Flow decreases with time during expiration. Inertia is negligible.4 A passive expiratory flow volume curve can be constructed. The slope of the linear part of the curve is equal to the reciprocal of the time constant of the respiratory system (τrs) during expiration. Respiratory system resistance (Rrs) can be calculated by dividing τrs by Crs.

Both single breath- and multiple-breath occlusion techniques are used. With the latter technique, brief airway occlusions are performed on multiple breaths and at different volumes above FRC; the individual measurements are plotted as volume vs pressure. The slope of the line of ‘best fit’ derives the compliance of the respiratory system It is important to note that compliance is lung-volume related, and that one single number is at best only an approximation to physiological reality in a complex system.

Oscillation techniques

Total pulmonary resistance can be measured in infants and children using the forced oscillation technique. A sinusoidal pressure applied at the individual’s mouth (or mouth and nose) alters the airflow allowing the resistance to be calculated. When the forced oscillations are applied at the so-called resonance frequency of the lung (5–7Hz in children38), it is assumed that the forces, required to overcome elastic resistance and inertia, are equal and opposite and therefore cancel each other out.

The forced oscillation technique (FOT) was introduced by Dubois et al.,39 to characterise respiratory impedance (Zrs) and its two components reactance (Xrs) and resistance (Rrs) over a wide range of frequencies.40

The oscillation system is shown in Fig. 3. Flow oscillations, generated by a loud speaker, are applied and superimposed on normal breathing. A large bore impedance tube directs the oscillations to the patient without offering any resistance to spontaneous breathing. Bias flow prevents rebreathing of the expired gases.

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Figure 3. General set up of oscillation system.

The driving pressure, either sinusoidal (single frequency) or composite (multiple frequencies), results in flow oscillations, the magnitude and phase of which are determined by the resistive, elastic and inertial properties of the respiratory system (Fig. 4). The resulting pressure and flow signals are recorded at the mouth using a pressure transducer and a pneumotachograph. These signals contain waveforms of several frequencies. For each frequency, the ratio of pressure to flow can be calculated (i.e. the impedance).41., 42., 43., 44.

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Figure 4. A sinusoidal pressure wave causes a flow wave that is analysed using Fourier analysis. From the relationship of pressure and flow changes, resistance (R) and reactance (X) can be calculated. The absolute values of pressure and flow make up the value of the resistance, and the time it takes pressure changes to change the flow makes up reactance. The combination of both parameters makes up impedance.

With the random noise or pseudo random noise method, oscillations of different frequencies are analysed and the frequency dependency of resistance and reactance can be found.41., 45. Microprocessor techniques allow analysis of the complex signals by Fourier transform.45., 46., 47.

In children and obstructive patients, the resistance is frequency dependent, with higher Rrs at lower frequencies. During inspiration, the vocal cords are more open than during expiration,48 making measurements obtained during inspiration more appropriate. From clinical studies, it appears that Rrs at low frequencies allows the best discrimination between healthy individuals and various obstructive disorders.49 Xrs is mainly determined by the elastic and mass-inertial properties of the airways, lung tissue and chest wall. At low frequencies the elastic properties dominate (negative Xrs), at higher frequencies the mass-inertial forces take over (positive Xrs). The frequency at which Xrs crosses zero is called the resonant frequency (RF). In obstructive airway disease, Xrs deviates to more negative values,49., 50. and therefore the RF will be reached at higher frequencies. Both the Xrs and RF are useful indices in establishing positive reactions to provocation tests.

An alternative method for forced oscillation uses an impulse oscillation system (IOS, 5–35Hz).3., 51. In this technique, an impulse (a rectangular wave form), rather than a pseudorandom noise signal (a mixture of several sinusoidal wave forms) is applied by a loud speaker. There are recommendations for measurement of respiratory input impedance by means of forced oscillations, but the IOS technique has not been standardised.52

The interrupter technique (Rint)

The interrupter technique (Rint) is a non-invasive method of measuring airflow resistance.53 During transient interruption of the tidal airflow, alveolar pressure and mouth pressure equilibrate within a few milliseconds. The alveolar pressure can therefore be derived from the pressure measurement at the mouth immediately after interruption (Fig. 5). If the flow is measured immediately before interruption, the ratio of flow to pressure changes gives the interrupter resistance (Rint). A revival of the interrupter method technique has recently occurred.54

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Figure 5. Interrupter resistance. During tidal breathing, a short interruption of airflow (V′) causes changes in respiratory system pressure that can be measured at the mouth (Pmo). Pint is computed by back extrapolation of a line through two points, centred at 30 and 70Msec (which are blocked averages of pressure during 10Msec) to the point at 15Msec from the start of occlusion (t=0).54

The time course of the post-occlusion pressure tracing is influenced by the compliance of the upper airways (especially cheeks), air in the lungs, airways resistance and the inertia of the system.55., 56., 57.

Increased airway resistance and upper airway compliance prolong the equilibration time from 40Msec in healthy children to above100Msec. Most devices use interruption times of 100Msec. Back-extrapolation of the post-occlusion pressure tracing to the time of valve closure is considered the best method to approximate the resistive pressure drop across the airways at the time of interruption. For this, the pressure trace between 40 and 80Msec or 30 and 70Msec are recommended.53., 54. This is late enough to allow equilibration of mouth and alveolar pressure in most patients, and early enough to prevent active breathing against the valve.

Airway resistance (Raw)

Airways resistance (Raw) in adults and older children is most commonly measured using body plethysmography. The method is based on the assumption that when a shutter occludes the tube, airflow ceases and the mouth pressure equals alveolar pressure. At BTPS conditions, Raw can be determined from the difference between alveolar pressure (Palv) and airway opening pressure (Pao), divided by airflow (V′).

COMPARISON OF DIFFERENT TECHNIQUES

When measuring resistance, changes in flow are measured at the mouth but the pressure changes relate to differences between mouth and alveolar pressure (bodyplethysmography, Raw), mouth and pleural pressure (oesophageal balloon, total lung resistance [Rtot]) or mouth and thoracic wall pressure (oscillation and interrupter techniques, total respiratory system resistance [Rrs]). FOT and IOS measurements are, in principle, comparable.46

In animal studies Rint levels are higher than those measured with bodyplethysmography, probably due to a contribution of chest wall rigidity and the glottis.58

Both interrupter and oscillation techniques measure total respiratory resistance, but the oscillation method can show frequency dependency. In healthy people, the most representative resistance values are found with frequencies around 10Hz. These values correlate well with those using the interrupter method.59 Reproducibility of the oscillation technique has shown to be dependent on the support of cheeks and the patience of the investigator. They can vary from 5–20%.38., 42., 60., 61.

In children with asthma and cystic fibrosis (CF) Rint underestimated Raw, especially in children with severe airway obstruction.62 In these patients, equilibration times are probably longer than 70–80Msec, and the extrapolation method underestimates true resistive pressure drop across the airways.53

IOS has been well validated against FOT63 and against body plethysmography51 in children.

Most reproducibility studies of techniques applicable to young children show the intrasubject coefficient of variation (CV) of Rint, Rrs and sRaw are comparable (9–13%), but higher than FEV1 (5%) and PEF (5%).3., 51., 64., 65.

Klug et al.66 showed that, in 2–6-year old children, the within-subject standard deviation (SD) was not significantly different in observers, but the between-observer variability was greater for Rint than for Rrs5, Xrs5 and sRaw.66

Bridge and McKenzie evaluated Rint in preschool children and found that expiratory Rint was significantly higher (4%) than inspiratory Rint but with no significant differences in bronchodilator response.67

Several confounders may be responsible for the relative lack of reproducibility of resistance measurements, such as a switch from nasal to oral breathing in young children using a face mask, changes in breathing patterns, respiratory muscle activity, tongue movements and glottic size.68

The use of a face mask with inner mouthpiece vs mouth piece with nose clip in 4–7 year old children resulted in comparable repeatability but in higher Rint values (P=0.0002).69

Bisgaard and Klug3 found that the order of sensitivity of different techniques to assess airway obstruction was Zios>sRaw>FEV1>Rint. Reasons for the relative lack of sensitivity of Rint measurements are retarded pressure equilibration in the presence of airway obstruction (underestimation), inhomogeneity of airway patency and extrathoracic airway compliance (underestimation).70

Rint has been used to try to distinguish preschool children with recurrent wheeze from those with recurrent cough and from healthy children. Rint was higher in wheezers but coughers did not differ significantly from normal children. The bronchodilator response (defined as the ratio between pre and post bronchodilator Rint) differed between the three groups. A bronchodilator response of >1.22 had a specificity and sensitivity for wheeze of 80% and 76%, respectively.32

Rint and Rrs5 are less useful for determining of reversible airway obstruction than Xrs5 and sRaw.3., 49., 51., 71.

FINAL CONSIDERATIONS

Although the assessment of patients with lower airway obstruction is probably best performed using FEV1, resistance measurement can be applied when MEFV measurements are impossible. The development of simple techniques to measure airway and respiratory system resistance might open new doors for diagnosis and follow-up.41., 45.

Interrupter and oscillation techniques are not difficult to undertake. They are simple, do not require sedation, are non-invasive and require only passive patient co-operation. These techniques are suitable in daily practice, in a laboratory setting or for research purposes.

However, the paediatric lung is not a miniature adult lung, and developmental changes influence lung function results. Especially in infants with airways obstruction, airway occlusion does not lead to even distribution of airway pressure between the mouth and the alveoli. This might lead to inaccurate airway resistance values. Because specific techniques are only possible at specific ages (e.g. baby body box, squeeze jacket technique, airway occlusion technique), follow-up studies using the same technique throughout life are nearly impossible. Until now, no single pulmonary function test is applicable in spontaneously breathing infants, children and adults. However, resistance parameters are measured during spontaneous quiet breathing. They may therefore be more representative of normal breathing in daily life situations rather than forced expiratory manoeuvres. Resistance measurements require only passive co-operation, only take a short time and are non-invasive, apart from a closely fitting mask. Their general acceptance is good in young children.

Finally, during childhood, most important pulmonary diseases show an obstructive airways picture, and peripheral airways resistance is better mirrored by resistance measurements. Changes in the lungs after treatment, or with disease progression, are measured as well with these techniques as with ‘gold standard’ measurements.

PRACTICE POINTS

•Interrupter and oscillation techniques are suitable in daily practice and in research.

•During childhood, the most important chest diseases have an obstructive picture.

•Changes in peripheral airways resistance are better mirrored by resistance measurements in children.

•Changes in airway mechanics are as well measured by resistance parameters as using ‘gold standards’.

•International standardisation is required before we can recommend the widescale use of these resistance measurements.

RESEARCH DIRECTIONS

•International standardisation of new devices to measure pulmonary function.

•Reference equations of pulmonary function parameters.

•The significance of pulmonary function test results in the individual vs results in population studies.

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Department of Paediatric Pulmonology, KH 01.419.0, University Medical Centre Utrecht, PO BOX 85090, 3508 AB Utrecht, The Netherlands

Correspondence to: H. G. M. Arets. Tel.: +31 302 504 690; Fax: +31 302 250 4747

PII: S1526-0542(03)00101-5

doi:10.1016/j.prrv.2003.09.004

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