General principles of measurement

Lung function measurements are made to describe the lung for diagnostic purposes and subsequently in monitoring change. Accuracy and consistency are therefore very important and conventions exist for the procedures of measurement and expression of results. In general, a measurement will only be accepted after multiple attempts have been scrutinized and expressed under standard conditions. These are usually body temperature and atmospheric pressure (BTPS). To guarantee accuracy, laboratory practice should include regular physical and biological calibration of the equipment. Standards for good laboratory conduct have been described (British Thoracic Society/Association of Respiratory Technologists and Physiologists 1994). In health there are several factors that influence the magnitude of lung function. These include height, sex and age and to a lesser degree weight and ethnic origin (Anthonisen 1986, Cotes 1993). As a result, assessment of normality can only be made by comparison with reference values. The latter are obtained from the study of large numbers of normal people from the relevant population (European Community for Coal and Steel 1983). Once obtained, results can be expressed as percentage predicted or, more correctly, by comparison with the 95% confidence interval for that value.

Airway function

For the purposes of measurement the lung has only one portal of entry and exit, i.e. through the mouth, and airway function is assessed by quantification of gas flow or volume. The calibre of the airways reduces through their generations and the major resistance to gas flow is normally in the upper airway. The larger airways are supported by cartilage, while the smaller airways are held patent by the radial traction of the surrounding lung so that their calibre increases with the volume of the lung. The diameter of these airways is also controlled by neural tone, which is predominantly parasympathetic.

The disruption of airway function can occur through physical or rigid obstruction to a large airway by, for example, a tracheal tumour. It may also occur because of more widespread disease in asthma, when large numbers of smaller airways are affected by episodic alteration of their calibre by smooth muscle contraction, mucosal oedema and intraluminal secretions. In chronic bronchitis, obstruction occurs by mucosal thickening and mucus secretion but in emphysema the mechanism is different. Though seldom occurring in isolation from other forms of airway obstruction, the result of parenchymal emphysema is to weaken the elastic structure which maintains radial traction on the airways and allows them to close too early in expiration.

Tests of airway function measure airway calibre and are now well established in clinical practice. Most tests of airway patency examine expiratory function. There are three common methods:

spirometry (FEV₁ and FVC)

flow–volume curves

peak expiratory flow (PEF).

Production of the spirogram from a maximal forced expiration following a full inspiration is reliable and provides the forced expiratory volume in 1 second (FEV₁) and the forced vital capacity (FVC) (Fig. 3.1). The measurement is usually made using a spirometer, which measures volume, or is derived from a flow signal obtained from a pneumotachograph or turbine. Most commonly, the FEV₁ and FVC are measured during the same manoeuvre, but a greater vital capacity may be obtained in patients with airway disease if it is performed slowly. Reduction in FEV₁ with relative preservation of FVC or vital capacity (VC) is known as an ‘obstructive’ pattern, which indicates and grades airway obstruction: FEV₁/FVC <75% is graded as mild, <60% as moderate and <40% as severe impairment (American Thoracic Society 1986). Simultaneous reduction in both FEV₁ and FVC with an increase in the FEV₁/FVC ratio is called a ‘restrictive’ defect and is usually associated with a reduction in lung volume. Abnormal values are defined as those recognized to be outside the normal range of two standard deviations for sex, height and age. This usually requires a reduction of about 15% from predicted values. Thus simple spirometry can detect and quantify airway obstruction, but gives no indication of the cause.

Figure 3.1 (A) In the normal spirogram the major part of the vital capacity (FVC) is expelled in 1 s (FEV₁). (B) In patients with airway obstruction the FEV₁ is reduced to a greater degree than the FVC. This pattern is known as ‘obstructive’. (C) When the lungs are small and empty quickly the pattern is known as ‘restrictive’.

Measurement of the flow–volume curve is now commonplace and can provide information about the nature of airway obstruction. In this test, the gas flow from a full maximum expiration is plotted against the expired volume as the lung empties (Fig. 3.2). The flow of gas from the lung reaches a peak expiratory flow (PEF) after about 100 milliseconds and then declines linearly as the lung empties. If the measurement is continued into the subsequent full inspiration, a flow–volume ‘loop’ is produced and inspiratory flow rates can be measured. The shape of the expiratory and inspiratory portions are different, since in expiration the active expulsion is assisted by the elastic recoil of the lung while inspiratory flow rates are a reflection of airway calibre and inspiratory muscle strength only. Something of the nature of the airway obstruction can be learnt from consideration of the actual and relative values of PEF, peak inspiratory flow (PIF) and the values of expiratory flow at 50% and 75% vital capacity (MEF₅₀ and MEF₇₅). Simple inspection of the loop is often sufficient to distinguish between rigid upper airway obstruction, intraluminal obstruction in chronic bronchitis and asthma, and the ‘pressure-dependent’ collapse seen in pure emphysema with relative preservation of inspiratory flow rates.

Figure 3.2 (A) The normal flow–volume loop has a characteristic shape. (B) Airway obstruction from asthma or chronic bronchitis appears as a concave expiratory limb and reduced inspiratory flows. (C) In emphysema the expiratory flows are suddenly attenuated but the inspiratory flows are relatively well preserved. (D) A rigid obstruction to a major airway can produce an oval loop. (E) Inspiratory flows are reduced in diaphragm weakness or extrathoracic tracheal obstruction.

The PEF is one component of the flow–volume manoeuvre that is widely used owing to the availability of simple devices for its measurement. Provided that the patient does not have weak respiratory muscles and has made a maximum effort, the PEF will reflect airway calibre. The absolute values obtained are not particularly helpful unless they are extremely low but the easily repeated measurements can be used to obtain valuable insight into the mechanisms of variable airway obstruction in asthma. There is a normal diurnal variation in airway calibre of about 50 ml/min, which is exaggerated in patients with poorly controlled asthma (Benson 1983). Wider variation will be seen approaching or recovering from an attack and following exposure to trigger factors.

The real value of the PEF lies in its repeatability and its portability. The issue of meters to patients with asthma allows domiciliary and occupational investigation of asthma. PEF also provides an objective measurement for patients to use to monitor their asthma as part of a self-management plan and it can be used during hospital admissions to record the progress and predict the discharge of patients with airway disease. Although this is valuable in asthma where the airway obstruction is variable, it can show no change at all in patients with chronic airflow limitation in spite of a clinical improve ment. In this case the twice-weekly measurement of FEV₁ and FVC is more likely to mirror progress than will the slavish recording of the PEF chart (Gibson 1995).

Changes in spirometry are poorly related to clinical improvements after bronchodilator therapy in chronic obstructive pulmonary disease (COPD). O’Donnell et al (1999) have suggested that an increase in inspiratory capacity (a reflection of resting lung hyperinflation) may reflect improvements in exercise endurance capacity and dyspnoea more accurately than FEV₁ or FVC measures. Airway responsiveness is a measure of the degree of airway narrowing to specific and non-specific stimuli. Histamine and methacholine are the most widely used non-specific stimuli in challenge tests. Using the tidal breathing method (Juniper et al 1994), doubling concentrations of methacholine (0.03 to 16 mg/ml) are nebulized via a Wright nebulizer. Airway hyperresponsiveness is defined as a >20% fall in FEV₁ with a concentration of <8 mg/ml (PC₂₀FEV₁ <8 mg/ml).

Most asthmatics have a combination of eosinophilic airway, airway responsiveness and variable airflow obstruction to the extent that many definitions of asthma now include these three features. There is evidence that directing treatment at improving airway responsiveness reduces mild exacerbations of asthma. Elevated exhaled nitric oxide concentration due to increased inducible nitric oxide synthetase (INOS) expression and activity in the bronchial epithelium is a feature of untreated asthma (Kharitonov et al 1994). The relationship between nitric oxide (NO) and asthma severity or response to treatment is unclear (Sont et al 1999).

The physical properties of the lung

The two lungs contain millions of alveoli within a fibroelastic matrix. They do not have a very rigid structure and are held in contact with the rib cage by surface tension forces at the apposition of the two pleural surfaces. The resting volume of the lung (the functional residual capacity (FRC)) is thus determined by the outward spring of the rib cage and the inward elastic recoil of the lung matrix. Expansion and contraction of the lung therefore involves the controlled stretching or relaxation of the lung by the respiratory muscles away from FRC. The position of FRC can be influenced if the lung is stiffer than usual (as in interstitial disease) or if it is more compliant (as when damaged by emphysema). The measurement of the lung’s volume can therefore give some insight into these conditions.

For obvious reasons direct measures of lung volume cannot be made. The most familiar method is helium dilution, which involves rebreathing through a closed circuit a mixture of gases containing a known concentration of helium, which is not absorbed into the circula tion. The measurement of the final concentration of helium is used to calculate the gas dilution, or the ‘accessible’ volume, of the lung. An alternative method uses the Boyle’s law principle: gas in the chest is compressed and the change in pressure is used to calculate the volume of gas within the chest. This method requires a large airtight box or plethysmograph. In both the actual volume that is estimated is the FRC, and total lung capacity (TLC) and residual volume (RV) are obtained from an additional spirometric trace. A further method involves the calculation of the total volume of the lung from the dimensions of a chest radiograph. This volume includes the total volume of gas, tissue and blood. Since the techniques do measure different aspects of volume, consistency in sequential measurements is important. In normal lungs the results are very similar, but where there is airway obstruction the values may be disparate. Such disparity can be used to advantage, e.g. in calculating the degree of trapped gas as the difference between the plethysmographic and helium dilution lung volumes.

The chest wall and the respiratory muscles

To maintain their shape the lungs depend on the support of the rib cage and the patency of the airways and alveoli. The expansion of the rib cage by the respiratory muscles is responsible for the tidal flow of gas into and out of the lungs. Over the past few years there has been increasing awareness of the importance of dysfunction of the respiratory muscles and the bony rib cage in contributing to respiratory failure. Such conditions include myopathies and polio as well as skeletal mal-formations such as scoliosis, which decrease rib cage compliance and reduce the effectiveness of the musculature.

The respiratory muscles include the diaphragm as the major muscle of inspiration and the intercostal muscles and scalenes. The latter, together with the sternomastoids, are known as the ‘accessory muscles’, but actually have a stabilizing role in tidal breathing. The combination of the respiratory muscles and the bony rib cage is called the ‘chest wall’ and conceptually is considered as the organ which inflates the lungs. Weakness of the respiratory muscles will eventually lead to ventilatory failure which may first become apparent during the night as an exaggeration of the normal nocturnal hypoventilation (Shneerson 1988).

The function of the respiratory muscles is difficult to study directly since the muscles have complex origins and insertions. Furthermore, their product, which is the pressure generated within the thoracic cavity, depends on the coordinated action of many muscles, the individual functions of which may be difficult to distinguish in life. It is possible to make some assessment of both the strength and endurance of the muscles and also to separate the diaphragm from the other muscles. The simple strength that the inspiratory and expiratory muscles can generate as pressure is easy to measure. The maximum inspiratory pressure (P_imax) and expiratory pressure (P_emax) are easy to measure with a manometer or electronic gauge. The normal values of approximately −100 cmH₂O and +120 cmH₂O (Black & Hyatt 1971) are well in excess of that needed to inflate the lungs (5–10 cmH₂O) and therefore provide a sensitive measure of developing muscle weakness. These measurements do have a learning requirement and are not suitable for monitoring of patients with rapidly developing muscle weakness, such as in Guillain–Barré syndrome. Under these circumstances the sequential measurement of the vital capacity is much more reliable, since a failure to maintain it will predict ventilatory failure.

The strength of the diaphragm can be separated from the other muscles by measuring the pressure gradient across it. This is achieved by using balloons attached to pressure transducers to estimate the pressure in the oesophagus and the stomach. The gradient across the diaphragm during a maximum inspiration or sniff is an indirect measure of the strength of the diaphragm. Normal values for sniff pressures have now been published (Uldry & Fitting 1995). If required, a value free of volition can be obtained by electrical stimulation of the phrenic nerve in the neck or even by magnetic stimulation of the cerebral cortex.

Fortunately, measurements of separate diaphragm strength are seldom required in clinical practice. A simple guide to diaphragm function can be obtained by observation of the change in vital capacity with posture. When supine, the vital capacity normally falls by 8–10%, but when diaphragm weakness is present it may fall by more than 30%. The measurement of the supine vital capacity is therefore a good screening test of diaphragm function (Green & Laroche 1990) and the measurement of sniff pressures at the mouth or nose is a reflection of pure diaphragmatic activity.