Declaration
3. Equipment and methods
This section provides a theoretical background to infant respiratory function testing and a description of the equipment and the methods of measuring respiratory function used in this thesis. New respiratory function testing equipment assessed as part of the thesis and adaptations required for specific protocols are described in the relevant sections.
3.1 Pressure, airflow and volume m easurem ent
The majority of infant respiratory function tests involve the measurement of airflow and volume changes at the airway opening, and the measurement of pressure changes.
3.1.1 The theory of pressure, airflow and volume m easurem ents 3.1.1.1 P ressure transducers
Most pressure transducers consist of a chamber containing a diaphragm which is coupled to a sensing element. Movement of the diaphragm alters the electrical conductivity of the sensing element altering the electrical signal produced. The chamber of the pressure transducer is usually connected to the pressure source by tubing. Changes in pressure are transmitted to the transducer by displacement of small volumes of gas (or liquid) in the tubing, with the resulting change in chamber volume causing displacement of the diaphragm. Many transducers have connection ports on both sides of the diaphragm (differential pressure transducers) and hence their output is determined by the pressure difference across the diaphragm. Differential pressure transducers are used with most flow measuring devices as well as being used to measure pressures (e.g. at the airway opening) relative to atmospheric pressure.
The dynamic performance of pressure transducers depends on; • damping
• linear range
• coefficient of displacement • frequency response
3.1.1.1.1 Damping
Following a step change in input, a transducer responds with an output. The accuracy of the response depends on the physical characteristics of the transducer and its
connecting tubing. In the absence of any resistance in the tubing, the transducer output for a step change in input will overshoot and then oscillate around the new mean value. This is described as underdamped. As the amount of resistance in the system increases, the output for a step change in input will approach the new mean value without overshoot and without oscillation. This is described as critically damped. Further increases in resistance will result in overdamping with a delay in the output signal reaching the new steady state value. See Figure 3.1.
Figure 3.1: Critical damping of transducer signal
a) b)
7----
C) d)
Solid line: Input signal. Dashed line: Output signal.
a): undamped, b): underdamped, c): critically damped and d): overdamped.
3.1.1.1.2 Linear range
The linear range of a transducer describes the range of amplitudes over which the output from the transducer is able to accurately reproduce the input. Failure to keep within the linear range of a transducer results in inaccurate measurements.
3.1.1.1.3 Coefficient of displacement
The coefficient of displacement is defined as the change in volume of the transducer per unit change in pressure (AF7AP). The coefficient of displacement should be as small as possible, requiring minimal physical displacement of gas or liquid in the connecting tubing and transducer. This is particularly important when measuring oesophageal pressure as when the coefficient is large, relative to the inherent pressure-volume characteristics of the oesophagus, pressure will be lost within the oesophagus itself in order to displace the transducer diaphragm. This will result in an underestimate of pleural pressure.^^
3.1.1.1.4 Frequency response
Frequency response defines the ability of a device to reflect changing signals accurately. Frequency response has two components;
• magnitude, usually expressed as attenuation, the ratio between the output and input signals
• phase, the temporal relationship between the input and output signals, expressed either in degrees or as a time lag
The frequency response of equipment depends on; • dimensions
• compliance
• medium being measured
In general, the larger the diameter and shorter the length of the equipment, including connecting tubing, the better the frequency response. The less compressible the medium and the lower its inertia the better the frequency response. However, other factors including coefficient of displacement, damping and practicality also have to be considered.
A greater frequency response is required for infant measurements than measurements in older children and adults because of their higher respiratory rates. The need to minimise dead space makes achieving a good frequency response more difficult. The minimum requirement for frequency response for infant respiratory function testing has not been clearly defined.^^ A good frequency response to 10 Hz has been
suggested as adequate for spontaneously breathing infants/^ with values of between 20 and 100 Hz being suggested for ventilated infants/^
3.1.1.2 Flow and volume m easurem ent
The measurement of flow or volume changes is essential to most measurements of respiratory function. As flow is the rate of change of volume, it is usual to measure one and derive the other. In this thesis, flow has been measured and digitally integrated to give volume, the only exception being when respiratory inductance plethysmography has been used (see Section 3.5.2). Only flow measuring devices will be considered further.
For the measurement of air flow at the airway opening of infants, a flow measuring device must have the following characteristics;
• predictable steady state response • adequate working range
• adequate frequency response
• small or predictable dependence on gas temperature, humidity and composition • low dead space
• low resistance to airflow
In addition ideally it should be easy to use.
3.1.1.2.1 Steady state response
The steady state response is the relationship between constant applied flows and the output signal of the device. A linear relationship between the flow and the output of the flow meter simplifies calibration and calculation of tidal volumes and mechanics. However, this has become far less important with advances in computer technology that permit most non-linearities to be removed digitally, provided adequate calibration facilities exist.
3.1.1.2.2 Working range
The working range of a flow meter describes the range of steady state flows that the instrument can measure accurately. The working range must encompass the maximum flows achieved by the infant. This will depend on the size of the infant, whether the infant is breathing spontaneously, is mechanically ventilated or has
increased flows related to airway occlusions or forced expiratory manouvres. The maximum flow capability is usually limited by alinearities at high flows. Even if such alinearities are digitally corrected the resistance of the flow meter may become unacceptable. In general, the greater the maximum flow that can be measured the less sensitive the flow meter is at low flows. Sensitivity at low flows is usually limited by noise in the measurement system and limited resolution of the signal amplification and display system. Poor performance at low flows leads to inaccuracies in integrated values i.e. volume measurements.
3.1.1.2.3 Frequency response
Frequency response refers to the ability of a measuring device to reflect rapidly changing signals accurately as discussed previously in Section 3.1.1.1.4. For the most commonly used flow measuring devices (linear resistive pneumotachographs) frequency response is determined largely by the transducer and connecting tubing rather than the actual pneumotachograph.
3.1.1.2.4 R esponse to tem perature and gas composition
Expired gas differs from inspired gas in terms of temperature, humidity and the partial pressures of oxygen and carbon dioxide. Measurements are often made with infants breathing warmed, humidified and oxygen enriched air. If measurements are made during anaesthesia nitrous oxide may be used. Different gases will have different densities and viscosities. An ideal flow meter would have a response that is independent of the physical characteristics of the gases measured.
3.1.1.2.5 Dead space and resistance
An ideal flow meter has both a low dead space and a low resistance across the working range of flows. In general the smaller the device the higher the resistance and the less the working range. Smaller infants require lower dead space devices but can tolerate higher added resistance as their respiratory resistance is higher.
3.1.1.3 Types of flow measuring device
Several devices have been used to measure flow, the most popular being linear resistance pneumotachographs (PNTs). The linear resistance consists of either multiple parallel capillary tubes (Fleisch type) or a fine wire mesh screen. In both
types laminar flow is generated and a pressure drop develops that is dependent on the flow and the viscosity of the gas. The pressure gradient is measured using a differential pressure transducer and amplifier. The frequency response of the PNT- pressure transducer system is greatly influenced by the connections between the PNT and transducer. This is considered further in Section 3.1.1.4.1. Commercially available Fleisch and screen PNTs come in a range of sizes to suit preterm infants to adults. The minimum measured flow depends on the differential pressure transducer and amplifier used.
Many other types of flow meter have been described including; • ultrasonic flow meters (see Section 6.3.2)
• hot wire anemometers (see Section 6.3.2)
• nonlinear differential pressure based flow meters, e.g. variable orifice (see Section 5.3) and phot tubes (see Section 5.2)
3.1.1.4 Flow m easuring devices; practical considerations 3.1.1.4.1 Influence of connectors
Flow meters are sensitive to the distribution of flow which is influenced by the geometry of the connectors and tubing (including tracheal tubes) on either side of the flow meter. Both calibration and frequency response may be altered. Apparatus should therefore be both calibrated and assessed as used for measurements (see Section 5.3; The assessment of neonatal pulmonary monitors).
3.1.1.4.2 Gas composition, temperature and secretions
Most linear resistive PNTs are used with a heating shell to prevent condensation altering the resistance. Heating also prevents changes in gas viscosity between inspired and expired gas that otherwise occur due to temperature differences. Changes in gas composition e.g. the use of added oxygen or of anaesthetic gases will also alter viscosity. It is therefore important that PNTs are calibrated using an appropriate gas mixture. Secretions deposited within the PNT during prolonged measurements can affect calibration. This is a particular problem in intubated infants but can be minimised by the use of suction prior to measurements. Calibration checks at the end of a study are necessary to identify the problem.
3.1.1.4.3 Pressurisation of PNTs during IPPV
When a PNT is used within a ventilator circuit during intermittent positive pressure ventilation (IPPV) it is subjected to pressure swings as gas is driven into the patient’s lungs. The pressure changes are usually large relative to the changes due to flow across the PNT. There is no problem provided the airway pressure reaches both sides of the diaphragm of the differential pressure transducer simultaneously so that the differential pressure remains zero. However, any asymmetry in the construction of the transducer or the connecting tubing will result in a differential pressure giving an erroneous flow measurement.
3.1.1.5 Combining flow and pressure measuring equipment
When combining measuring devices to measure respiratory function, the frequency response of each transducer must be matched i.e. the equipment must not introduce an artefactual phase difference between pressure and flow changes. Combining equipment may degrade the frequency response of the components which should therefore be assessed for the fully assembled equipment. Care is necessary to ensure the airway opening pressure port is not placed in too narrow a part of the circuit or the pressure may be underestimated due to the Bernoulli effect.^^ When devices are combined it is important to consider the total dead space and resistance.
3.1.1.6 Signal processing
The output of most transducers is in the order of microvolts or millivolts. In order to display and process the signals they must be amplified. Amplifiers usually have adjustable sensitivity or gain and often incorporate filters. Filtering is the process whereby the relative amplitudes and phases of signals are changed in a systematic and frequency dependent way. The most commonly used filters during the measurement of respiratory mechanics are low-pass filters which attenuate or remove high frequency signals. Signals that are to be processed by computer must be low-passed filtered to prevent aliasing. Aliasing is the distortion that results when high frequency signals are sampled at lower frequency. Filters are also used to eliminate unwanted signals (noise). As filtering usually produces some phase change, it is important to filter all simultaneously collected signals in an identical manner.
Most measurements of respiratory mechanics are now made using computers. The voltage signal generated by the amplifiers must be digitised using an analog to digital converter. The analog signal is continuous but the computer stores a digital representation at defined intervals. The sampling frequency must be adequate to reproduce the analog signal faithfully. Respiratory signals can be described in terms of a fundamental frequency and a series of harmonics. The number of harmonics that need to be included depends on the complexity of the waveforms. The sampling frequency needs to be at least twice the highest harmonic frequency of interest. Recommended sampling frequencies and the measurement errors introduced by using lower sampling rates have been published.^^ It is usual for the computer to integrate the flow signal digitally to generate a volume signal. Digital filtering to correct for zero offset is often performed before further data analysis.
3.1.2 Equipment for pressure, flow and volume m easurem ents
This section provides details of the measuring equipment used for this thesis.
3.1.2.1 P ressure transducers
Unless otherwise stated, pressures were measured with Validyne (Northridge, CA) MP45 differential pressure transducers or Furness (Sussex, England) FC044 differential pressure transducers used with Validyne or Furness signal conditioning modules respectively. All simultaneously collected signals were collected with the same make of transducer. The low pass analog filters were set at 10 Hz unless otherwise stated. Transducers with linear ranges of ±0.2 kPa and ±5 kPa were used with PNTs and to measure pressure at the airway opening respectively. Low compliance, 3 mm internal diameter, translucent vinyl tubing (Portex, Hythe, England) was used to connect the transducers to the pressure ports on the PNTs or at the airway opening. The minimum practical lengths of tubing were used and identical lengths used with all simultaneously used transducers.
3.1.2.2 Pneum otachographs
Unless otherwise stated, flows were measured using Fleisch (Lausanne, Switzerland) size 0 or 1 PNTs or Hans Rudolph (Kansas City, MO) 0-10 or 0-35 L m m ' screen PNTs. The choice depended on the infant’s maximum flows and the ease with which
the different PNTs connected with other components of the measuring apparatus. All PNTs were heated with shell heaters. Where connectors were required they were constructed to avoid both excessive dead space and sudden changes in geometry that may have resulted in turbulence. The PNTs were all used within their linear ranges. The physical characteristics of the PNTs are given in Table 3.1.
Table 3.1; Characteristics of pneum otachographs
Pneumotachograph Dead space
mL Resistance! kPa L ' s Linear range* L min ' Fleisch 0 2.5 0.43 ±15 Fleisch 1 10 0.10 ±27
Fleisch 0 + cable release shutter 7.6 0.48 ±15
Fleisch 1 + cable release shutter 15 0.11 ±27
Fleisch 0 + plethysmograph shutter 7.6 0.78 ±15
Fleisch 1 + plethysmograph shutter 26 0.48 ±27
Hans Rudolph 0-10 L min ‘ 1.3 1.11 ±10
Hans Rudolph 0-35 L mm'
1 4 AA T - J ^ •
6.8 0.27 ±35
3.1.2.3 Data processing
All signals were processed using IBM compatible 386 or 486 personal computers. The analog outputs of the transducers were digitised using Analog Devices RTI 815 A-D converters. RASP (Respiratory Analysis Program, Physio Logic, Newbury, England) software was used to process, display and record the data. Signals were sampled at frequencies of between 50 and 200 Hz depending on the type of measurements being made and respiratory frequency. The flow signal was integrated digitally to yield volume. Data were collected in discrete epochs of 18-120 seconds depending on the sampling frequency, the number of simultaneous signals recorded and the version of the software used.
3.1.2.3.1 Calibration
Transducers for the measurement of pressure at the airway opening were calibrated by applying two known pressure signals: 0 and +20 cmHjO (1.964 kPa) using a water manometer.
The flow signal was calibrated by applying two known flows: 0 and 100 or 150 mL-s*‘ (depending on the size of the infant to be measured) using calibrated rotameters (KDG 1100, Sussex, England). The RASP software also allowed flow to be calibrated by applying known volume signals using a calibrated syringe (Hans Rudolph). This method was usually preferred when gas mixtures other than air were used. Flow calibration was performed with the equipment assembled ready for use and using gases of the same composition as those used for the measurements.
All calibrations were checked prior to and after completion of each measurement session using known signals.
3.1.2.3.2 Data analysis
Data analysis was performed using RASP software. The program permits the operator to control data selection and apply acceptance criteria while automating the repetitive mathematical processes involved in data analysis. All algorithms for derived parameters had been validated in the respiratory laboratory at the Institute of Child Health.
3.1.3 The m easurem ent of tidal breathing param eters
Tidal breathing parameters, in particular based on the measurement of airflow and volume are reported in Sections;
• 4.1: The reproducibility of ^ptef^^e infancy
• 4.2: The relationship between ^ptef*^e and specific airway conductance
• 4.3: Uncalibrated respiratory inductance plethysmography for the measurement of tidal breathing parameters
Data for the analysis of tidal breathing parameters were collected during sleep (natural or sedated depending on the protocol) using an appropriately sized Fleisch or Hans Rudolph PNT (see Section 3.1.2.2) attached to a Rendell-Baker Soucek face mask (Rusch UK Ltd, High Wycombe). Where passive mechanics or
plethysmographic measurements were also required, tidal breathing measurements were made using the passive mechanics or plethysmography equipment (see Sections 3.2.4 and 3.3.2).
Analysis of tidal breathing data was performed using RASP software. Mean values are based on the analysis of a minimum of 2 epochs of data with between 20 and 50 breaths. Figure 3.2 shows a time based trace of tidal flow and volume labelled to illustrate how the commonly used tidal breathing parameters are defined.
Figure 3.2: Tidal breathing param eters
I
0 E§
▲ inspiration 0 PEF expiration ▲ inspiration expiration timeTime based trace of tidal flow and volume, inspiratory time, expiratory time, PEF; peak expiratory flow and time to peak tidal expiratory flow.
3.2 Mechanics of breathing
The basic mechanics measurements are compliance and resistance. Compliance, a measure of elastic recoil, is defined as unit change in volume per unit change in pressure;
Resistance is defined as unit change in pressure per unit flow;
R = — A V
where R is resistance, P is pressure and V ’ is flow.
The terms respiratory compliance and respiratory resistance describe the combined properties of the lung and chest wall, whereas the terms pulmonary or lung compliance (Cl) and resistance (Ri) are used to describe the properties of the respiratory system less the chest wall (i.e. lungs and airways). Airway resistance (i?aw) is the resistance of the airways alone. The reciprocal of compliance is referred to as elastance and the reciprocal of resistance is conductance.
Determination of compliance and resistance therefore requires simultaneous measurements of airflow, volume and applied pressure. The measurement methods can be classified as;
• dynamic measurements which are made during either spontaneous or mechanical breaths
• passive measurements which are made during periods in which the respiratory muscles are relaxed either by reflex inhibition or pharmacologically