PRINCIPLES OF THE INTERRUPTER TECHNIQUE

The interrupter technique is not new; it was first described by Neergard and Wirz⁷ in 1927 and was used widely in the 1940s and 1950s^8–10 before being largely discarded because it was not clear exactly what it was measuring. The advent of modern computers has allowed a thorough examination of the interrupter technique and an understanding of the physiology underlying the measurements.^11–16 The basic assumption underlying the interrupter technique is that, following an instantaneous interruption of airflow at the airway opening (by closing a valve or shutter), there is an instantaneous equilibration of pressure between the alveoli and the airway opening (behind the occlusion). The technique further assumes that there is a single value of alveolar pressure. Following the occlusion, a rapid change in pressure is seen which is equal to the Newtonian (that is, frictional) fall in pressure between the alveoli and the airway opening. Dividing this pressure change by the flow occurring immediately before the occlusion allows the calculation of resistance (R)—that is, R = pressure/flow. The initial rapid pressure change is followed by a second slower change in pressure which is related to the viscoelastic properties of the respiratory tissues, together with any gas redistribution that occurs between lung units following the occlusion. The direction of these pressure changes depends on the phase of respiration, with occlusions made during inspiration (or at end inspiration) being followed by falls in airway opening pressure, and occlusions made during expiration being followed by increases in airway opening pressure.

LIMITATIONS OF THE INTERRUPTER TECHNIQUE

There are, however, several problems with the assumptions underlying the interrupter technique that have practical consequences for its use in humans.

(1) An instantaneous occlusion is physically unrealisable and any valve or shutter takes a finite time to close. During this time some gas will continue to pass through the valve and the lung volume (and thus alveolar pressure) will continue to change. These effects have been examined in detail^15,16 and were found to be of little clinical importance provided the valve closes within 10–20 ms.

(2) There is not instantaneous equilibration of alveolar and airway opening pressure following occlusion. The equilibration time is affected by the resistance of the airways and the time constant of pressure transmission. These effects are small in normal lungs, but become increasingly important in the presence of increased resistance and ventilation inhomogeneity. This effect can systematically bias against the use of the interrupter technique for challenge tests such as methacholine challenge.

(3) The presence of a compliant compartment between the resistive airways and the airway opening may buffer the initial rapid “resistive” pressure change, making the calculation of resistance less accurate. These effects are real and potentially clinically important in patients with markedly increased airway resistance or during challenge tests where the airway resistance is deliberately increased. The major compliant pathway in preschool children is the cheeks and upper (extrathoracic) airway, and measurements are routinely made with the subject’s cheeks supported in an attempt to minimise this problem.

(4) There is not a single value of alveolar pressure and thus not a single value of airway resistance. While this may seem like a fatal flaw, careful animal studies in which alveolar pressure was measured directly using alveolar capsules^12,13 showed that the value of resistance calculated from the airway opening pressure represented an “average” resistance and was thus of potential clinical value.

(5) The interrupter resistance has been shown to measure more than the fall in resistive pressure across the airways, and includes all Newtonian resistance from the respiratory system including components from the pulmonary tissues and chest wall, both of which are expected to change under various circumstances likely to be encountered during clinical measurements. Pulmonary tissue resistance increases with increasing lung volume—the opposite to the changes seen in airway resistance with changes in lung volume¹⁷—and also increases with methacholine challenge.^18–20 Both pulmonary tissue and chest wall resistance show changes with age.^21,22

CLINICAL USE OF THE INTERRUPTER TECHNIQUE

Despite these reservations, measurement of Rint by the interrupter technique, if used carefully, does have a place in the measurement of lung function clinically in young children.

Commercially available equipment allows the measurement of Rint at peak tidal flow or at set flows during either inspiration or expiration. This equipment includes a rapidly closing valve that occludes the airway for 100 ms before allowing normal respiration to resume. There is no simple answer to the most correct or reliable protocol. Airway resistance is dependent on the lung volume at which it is measured, increasing with decreasing lung volume. Rint is also flow dependent, increasing with increasing flow. There are expected physiological variations between inspiration and expiration, with airway resistance being lower during inspiration due to the airway being “pulled open” by the forces of interdependence. In practice, neither flow nor volume dependence of resistance have been found to be important effects during the tidal volume range.^23–25 What is more important is to ensure an adequate signal to noise ratio and reproducible data. For practical purposes, most investigators appear to be adopting the practice of measuring Rint during the expiratory phase of respiration at peak tidal flow, which hopefully coincides with the mid tidal volume range.^5,6,23

Both of the recent papers published in Thorax^5,6 deal with the repeatability of Rint measurements. Repeatability is a crucial issue for the use of a lung function test. The interrupter technique has been shown to have a good short term repeatability (over a time span of minutes) in preschool children.^23,26,27 Rint repeatability has also been shown to be age dependent, with younger children having higher variability between measurements.^27,28 Both Chan et al⁵ and Beelen et al⁶ reported good short term repeatability. They also evaluated long term repeatability (over a time span of weeks) and found good long term repeatability, which was similar in the two papers, in children with no history of respiratory symptoms⁵ and in a sample of the general population,⁶ confirming the findings previously reported in clinically stable preschool children with a history of either cough or wheeze.²³ However, greater long term variability between measurements was found in children with persistent cough or previous wheeze,⁵ which suggests that the lower long term repeatability in symptomatic children might be due to the variability of the disease rather than the variability of the technique.

Many other technical issues also need to be considered, including (1) what constitutes an acceptable measurement; (2) how should the post-occlusion mouth pressure be calculated; and (3) whether the mean or median of a series of measurements should be reported. Each single interruption should be considered acceptable when the trace of mouth pressure versus time has the correct shape. A trace from an occlusion made during expiration in which mouth pressure decreases or stays flat after the initial rapid change suggests air leakage around the mouthpiece or an altered ventilatory pattern^27,29 and should be discarded. Pressure-time traces obtained when the child was breathing irregularly, had the neck hyperextended or flexed, or was speaking or moving his/her tongue should also be discarded. Several algorithms for calculating mouth pressure during airflow interruption have been proposed. Four main models have so far been used: curvilinear back extrapolation (Rint_C), two-point linear back extrapolation (Rint_L, usually from 70 and 30 ms to 15 or 0 ms after interruption), end oscillatory pressure (Rint_EO), and end interruption pressure (Rint_EI). The Rint values obtained with these algorithms have been compared with airway resistance obtained with body plethysmography (Raw) in a study by Phagoo et al in healthy adults.³⁰ Rint_C values were similar to Raw, while Rint values calculated with the other three algorithms were significantly higher. Another study in healthy adults showed that Rint_EI and Rint_L were more sensitive than Rint_C in detecting airway calibre change during methacholine challenge testing.³¹ Until more studies show which algorithm is most sensitive in detecting bronchial obstruction in clinical practice, it has been proposed that the linear back extrapolation should be used for Rint calculation.³² A recent paper has shown that mean and median Rint values are not significantly different.³³ However, since the Rint values obtained during a measurement session are not normally distributed, it was also suggested that median values should be used as they are theoretically more correct.²⁹ What is critical is for investigators to report accurately their measurement conditions—including the triggering conditions for Rint measurements—to ensure that readers are able to compare “like with like”.

CONCLUSIONS

Measurement of Rint is a technique that shows considerable promise for assessing lung function in children of preschool age. However, proper attention must be paid to the assumptions that underlie the technique, and appropriate consideration of the effect of the measurement conditions on these assumptions is important for producing reliable data. From the studies reported to date, one has confidence that Rint can be used clinically to follow changes in lung function with growth and development, be used to manage lung disease in young children, and to measure acute response to bronchodilators. The use of Rint as the primary outcome for challenge tests such as methacholine requires further study, and whether Rint proves to be more or less useful than other measurements of lung function currently being investigated in preschool children, such as the forced oscillation technique and spirometry, remains to be seen. However, for Rint to be a useful measurement, standard procedures must be developed for performing the measurement and for reporting the results, and these standards must be adhered to.