346 Thorax 1995;50:346-352 Analysis of tidal expiratory flow pattern in the assessment of histamine-induced Thorax: first published as 10.1136/thx.50.4.346 on 1 April 1995. Downloaded from bronchoconstriction M J Morris, R G Madgwick, D J Lane Abstract tidal breathing would be useful in cir- Background - There are times in clinical cumstances where forced expiratory man- practice when it would be useful to be able oeuvres are unreliable or inapplicable. to assess the severity of airways ob- (Thorax 1995;50:346-352) struction from tidal breathing. Three in- dices of airways obstruction derived from Keywords: tidal expiratory flow, histamine-induced analysis of resting tidal expiratory flow bronchoconstriction. have previously been described: (1) Tme/ TE =time to reach maximum expiratory flow/expiratory time; (2) Krs = decay con- Expiratory tidal flow has a different pattern in stant of exponential fitted to tidal ex- patients with significant airways obstruction piratory flow versus time curve; and (3) than in normal subjects.'`7 Buohuys4 stated in EV = extrapolated volume - that is, area 1957 that "in most cases the difference between under the curve when the fitted ex- normal and abnormal records can be seen at a ponential is extrapolated to zero flow. In glance: the abnormal records show a constant this paper a further index - dt,/TE, time pattern in all cycles, the maximum expiratory from the beginning of expiration till the flow rate is reached early in expiration and the rapid decay offlow beginslexpiratory time record is smooth without the normal small - is evaluated. The aim of this study was variations in flow rate". In his study, although to assess the ability of these indices to he found the time to reach maximal tidal ex- detect mild airways obstruction. piratory flow considerably shortened in patients http://thorax.bmj.com/ Methods - A histamine bronchial pro- with significant airways obstruction, he felt the vocation test was performed in 20 adult degree of overlapping ofnormal with abnormal patients with a diagnosis of asthma or subjects for this finding was such that it could symptoms of cough and/or shortness of not be used to distinguish normal from ab- breath. Baseline forced expiratory volume normal records. in one second (FEV,), functional residual The most commonly employed tests of air- capacity (FRC), and specific inspiratory ways obstruction are those in which maximally conductance were (sGaw) measured and forced flow rates are measured. Such tests are on September 27, 2021 by guest. Protected copyright. the measurements repeated after the final not applicable in uncooperative or unconscious inhalation of histamine. Expiratory flow adult patients, or in infants or young children. patterns during quiet breathing over five In such circumstances, and in large epi- consecutive representative breaths were demiological studies, a portable test of airways analysed before and after histamine. The obstruction requiring only a short run of tidal test was concluded in 12 subjects when breathing would be useful. With the recent FEV, had decreased by 20% of the post emphasis on the benefits of non-invasive tech- saline value, and in the remaining eight nology and the advent ofcomputerisation there after inhalation of 16 or 32 mg/ml his- has been a resurgence of interest in the analysis tamine. oftidal flow patterns as a tool in the assessment Results - FEV1, sGaw, FRC, Krs, EV, and of airways obstruction. This has resulted in a dt,JTE were all different after histamine growing core of published work, mainly by (paired t test). For Tme/TE no difference paediatricians, to validate these measure- was shown. Change in EV detected change ments.8-14 in end tidal volume but underestimated it We have described three indices Osler Chest Clinic, previously Churchill Hospital, compared with the change measured by of airways obstruction derived from analysis of Oxford OX3 7LJ, UK body plethysmography. Percentage fall in resting tidal expiratory flow67 (fig 1) and have M J Morris Krs after histamine correlated with per- postulated the following interpretations ofthese R G Madgwick D J Lane centage fall in FEV, (r=0.527, Pearson indices: correlation coefficient). This was ofa sim- (1) Tme/TE = time to reach maximum ex- Reprint requests to: Dr M J Morris. ilar order to the correlation between the piratory flow/expiratory time (this index was Received percentage fall in sGaw and in FEV, (r= originally described as dt/t by us6 and is now 30 September 1993 0-543). called Tme/TE by other workers"'1 12). As nor- Returned to authors 16 December 1993 Conclusions - Analysis of expiratory tidal mal post inspiratory muscle braking is lost in Revised version received flow-time patterns predicted a decrease in airways obstruction, Tme/TE decreases. 22 March 1994 Accepted for publication FEV, following histamine challenge as did (2) Krs =decay constant of exponential fitted 19 December 1994 measurement of sGaw. This analysis of to tidal expiratory flow versus time curve during Analysis of tidal expiratory flow pattern 347 A chial challenge in our laboratory for clinical Flow indications were studied. These patients were Expiration known to suffer from asthma or had presented with episodic cough and/or shortness of breath Thorax: first published as 10.1136/thx.50.4.346 on 1 April 1995. Downloaded from for which a diagnosis was being sought. Forced 0 expired volume in one second (FEVI) was Time measured with a Vitalograph spirometer and dtr specific inspiratory conductance (sGaw) and B functional residual capacity (FRC) were meas- Flowyaek ured and spirometry repeated in a Jaeger Mas- Expiration Y =ae terlab constant volume plethysmograph before AL A(" Krs the histamine challenge test. Histamine was inhaled in increasing concentrations via a Wright's nebuliser according to the protocol of Cockcroft."5 A run of at least 10 breaths of Tme TE~~E tidal breathing (flow versus time) was recorded Tie TE at the completion of the above tests using a Fleisch no. 3 pneumotachograph and Gould Figure 1 Schematic representation of tidal expiratory flow showing the appearance in (A) a normal subject and Brush recorder 260 in 18 patients and RASP (B) a patient with airways obstruction, and the derived computer program" in the last two patients. indices Tme/TE, Krs, EV and dt,ITE. In some normal The analogue flow signal was taken into an subjects dtITE is greater than TmelTE. When airways obstruction is induced Elonex PC-433 via Analogue Devices 12 bit dtr/TE approaches TmelTE. AID interface card, sampling rate 80/second. The Fleisch pneumotachograph, tubing, pre- the second half of tidal expiration. In Otis' amplifier and recorder system were tested over simple model of the respiratory system,8 con- the range of 0-21/s and found to have a linear sisting of a single compartment of constant response over this range. The Gould recorder elastance served by a pathway of constant re- had a frequency response flat up to 60 Hz. sistance, the decay of flow or volume against Flow was calibrated with a flow signal of 1 1/s time should be a single exponential. Applied via a rotameter and the flow signal was in- to spontaneous breathing this model assumes tegrated to give volume. Tidal flow over five no respiratory muscle activity or laryngeal brak- consecutive representative breaths was ana- ing over the range that the exponential is fitted. lysed to give mean Tme/TE. An exponential Then compliance x resistance = 1 /Krs where was fitted to the flow versus time decay during 1/Krs = time constant ofthe respiratory system. the period between 50% and 90% tidal volume http://thorax.bmj.com/ In asthma, assuming compliance is unchanged, expired beginning where, by eye, the rapid Krs decreases as resistance increases. decay of flow was deemed to begin (starting (3) EV = extrapolated volume - that is, area point 50-70% of tidal volume expired) (figs 1 under the curve when the fitted exponential is and 3). Mean Krs and EV for the same five extrapolated to zero flow. EV is the volume of breaths were calculated. When the RASP com- the end expiratory tidal volume (FRC) above puter program was used (in the last two the relaxation equilibrium volume of the re- patients) a straight line was fitted to the flow- spiratory system.7 volume curve from the onset of rapid decay of on September 27, 2021 by guest. Protected copyright. In this study we have added a fourth index, flow to determine Krs, the slope of this line dtr/TE (fig 1), which is a revised version of (fig 2). A revised index dt`TE was calculated the original Tme/TE (see Methods section for as the time from the beginning of expiration description). until the exponential decay began (rather than The main aim of this study was to see the peak) divided by expiratory time (fig 1). whether, in the most difficult cases when within Within observer variation of dtr/TE expressed subject variability is maximum4 - that is, sub- as coefficient ofvariation was 1 1 % baseline and jects with normal lung function who develop 8% after histamine. Between observer co- very mild airways obstruction - this analysis, efficient of variation was 7% baseline and 7% using all the indices that we have described, after histamine. Because in some normal sub- could detect change. We studied adult patients jects there was a plateau of flow after the peak in whom airways obstruction was induced by was reached before the exponential decay be- inhalation of histamine to determine whether gan, this index was larger than Tme/TE (paired (1) acute overinflation (acute change in FRC) t test, t=3.62, p=0 0005 baseline, and t= could be detected and quantified by analysis 1 65, p=0 05 after histamine) (fig 1).