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For analysis, all RASP data were exported as ASCII (.DAT) files. Analog signals were digitised at 200 Hz and analysed using a software package developed in collaboration with Imperial College o f Science, Technology and Medicine.

Criteria for acceptability of forced expiratory flow volume curves were: regular tidal volume (Ft) and EEL for the tidal RTC or regular relaxed inflations for the raised volume RTC, jacket inflation initiated within 100 ms o f end inspiration with jacket inflation time less than 100 ms and peak expiratory flow being achieved before 30% o f inspired volume had been expired, expiration proceeding beyond the previous EEL, a smooth flow volume curve without significant glottic closure or flow transients, especially during the last half o f expiration, and no evidence o f leaks.

With respect to the raised volume RTC curves, the ‘best’ curve was defined as the technically acceptable curve with the highest sum o f FVC and FEV0.4 (Le Souëf et al. 1996). Criteria for acceptance o f the data included the fact that both FVC and FEV0.4 from the ‘best’ curve should be within 10% o f those from the next best manoeuvre, recorded under the same measurement conditions.

3.9.1 Parameters

Parameters analysed include forced vital capacity (FVC), duration o f forced expiration (fre), maximal expiratory flow at fixed proportions o f FVC (MEF%), and forced expiratory volume at specific time during expiration (FEVt).

3.9,1.1 Forced vital capacity (FVC)

FVC is the difference in the volume between the beginning o f the raised volume RTC manoeuvre and the ‘residual volume’ (RV) at the end o f the manoeuvre. The rate o f expiration can be measured at fixed proportions o f FVC e.g. maximal expiratory flow measured at 50%, 25% and 10% o f FVC. It is recognised that FVC will be dependent on the applied inflation pressure (which differs between centres) and that during the RVRTC in infants, there is no guarantee that either total lung

capacity (TLC) or residual volume (RV) will be reached. Consequently, during infant studies, the term FVCp is sometimes used with the p denoting inflation pressure e.g. FVC3.0 •

3,9,1,2 Forced expiratory volume (FEV)

Airway function can also be determined by examining the volume forcibly exhaled at timed intervals (FEVJ. In adults and older children, FEVi (i.e. the volume expired in one second) is the most useful respiratory function parameter. However, in infants, due to the rapid respiratory rate, FEV0.4, FEV0.5 and FEV0 75 are used instead (Figure 3.16). It is thought that the FEVt parameters may correlate better with the size of the infant and be more discriminatory in their ability to distinguish between normal and abnormal airways than FmaxPRC (Turner et al. 1995). However, much further work is required before the relative sensitivity and specificity of these various parameters can be determined.

Figure 3.16 Measurement of FEVt from full forced expiration

Jacket inflated Inflation o f breath i k FVC Passive expiration Tim e (sec) 100

Figure 3.17 Examples showing problems encountered with Raised Volume RTC curves 600 400 200 F=0 -200 60 40 20 0 -20 -40 1000 a) Late inflations, infant not relaxed

500 -500 f_=0 300 200 100 0 -100 b) Glottic closure 800 600 400 200 _F=0 -200

Too

Patho-physiology: evidence of tidal flow limitation

3.9.1.3 Maximal expiratory flow (ME F)

Maximal expiratory flow was measured at 25%, and 15% (i.e. MEF25 and MEF15) of forced vital capacity (Figure 3.18) with positive inflation pressure of 3.0 kPa (FVC3.0). In general, if flow limitation has been reached, MEF50 will reflect more central airway function, whereas MEF15/25 reflects more peripheral airway function. However, in practice, due to the difficulty in obtaining perfect manual timing during the manoeuvre, flow limitation is not always achieved at MEF5 0.

Figure 3.18 Maximal expiratory flow volume curve showing M EF measured at 50 and 25% O Ph 1000 M EF 50% 500 M EF 25% FVC 0 150 Volum e (m L)

3.9.2 Assessment of Raised Volume RTC param eters

Recent international collaboration has led to recommendations for standardisation of the most commonly used tests of infant lung function, including the RTC technique (Stocks et al. 1996; Frey et al. 2000; Sly et al. 2000). However, despite increasing interest in and use of the RVRTC technique, there is as yet no consensus regarding analysis when performing this technique (Gappa, 1999; Allen and Gappa, 2000). In addition, it is unclear as to what the parameters measured by the RVRTC technique actually represent in infancy, or which are the most appropriate parameters to report for specific research or clinical applications. Thus, a study looking at analytical issues such as assessing the feasibility of calculating a range of timed forced expiratory volumes (FEVt) and their relationships to FVC; examining the

relationship between MEF2 5, MEF 15 and F'maxFRc; and also assessing the within- subject variability o f F'maxFRC and that of various parameters derived from the RVRTC technique was performed.

3.9.2.1 Data analysis

Respiratory function data were analysed as described in Section 3.9. The variability for both volume (FVC and FEVt) and flow parameters (F'maxFRC and MEF%) was assessed from the within-subject coefficient o f variation [CV = (SD/Mean) x 100] (Hutchison et al. 1981). For FEVt, the number o f infants in whom each parameter could be obtained was calculated.

The relationship between the different FEVt and MEF% parameters was examined using least squares linear regression analysis and that between F'maxFRC and MEF 15 and MEF25 was assessed by Bland and Altman analysis (Bland and Altman, 1986).