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). Indices of tidal expiratory flow pattern, and (2) the ofrespiratory pattern, frequency f, tidal volume indices Tme/TE, dt,ITE, and Krs could detect VT, mean inspiratory flow rate VT/Ti, and in- an increase in airways obstruction and whether spiratory duty cycle Ti/TTOT, were calculated changes in these indices correlated with from the same five breaths. These tests were changes in other recognised indices of airways repeated after the final inhalation ofhistamine. obstruction. The histamine challenge test was concluded in 12 patients when FEV, had decreased by 20% of the post saline value, and in the remaining Methods eight patients after inhalation of histamine at Twenty consecutive patients, 10 men, of mean a concentration of 16 or 32 mg/ml (range of age 45-3 (range 29-71) years, two current and final histamine concentration 0-125-32 mg/ six ex-smokers, undergoing histamine bron- ml). 348 Morris, Madgwick, Lane Baseline After histamine
.0 Thorax: first published as 10.1136/thx.50.4.346 on 1 April 1995. Downloaded from 0.5] .a_ x llJ
0 0 Volume
0-5 - I\ FEV1~~~~~~-=-4 I\ I\ FEV1 = 2.41
c \ ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~I0 0.5- .C_ = x tl tan 0 Krs wJ
0 A E I 1 %fl I --' LL. Volume
-0-5-
FEV, = 2-6 FEV1 = 2.2 1
Figure 2 Tidal flow-volume tracings (RASP computer program) in two patients showing linear decay offlow against volume before and after histamine. The straight line was fitted between the dotted lines. The upper two graphs show no change in slope (Krs) or in EV in a normal subject whose FEV, did not change after histamine. The lower two graphs show a decrease in slope and increase in EV in a mild asthmatic whose FEV, decreased.
DATA ANALYSIS was taken as a positive challenge response to http://thorax.bmj.com/ Regression analysis was carried out to describe histamine. Sensitivity of a new method of the relationships between the various indices detecting a positive histamine challenge was in the cross sectional group after histamine defined as the percentage of true positives inhalation, and between the percentage change found to be positive by the new technique of the various indices resulting from the in- and specificity as the percentage of true halation of histamine. The paired t test was negatives found to be negative. A 35% fall used to test whether significant change had in Krs was taken as the cut off between a occurred in the individual indices with the positive and histamine as negative challenge, on September 27, 2021 by guest. Protected copyright. inhalation of histamine. The square of Pear- ROC curve analysis showed this to be the son's correlation coefficient (r) for the linear cut off that correctly assessed most subjects regression between log flow measured at 0-2 (17 of 20) and maximised the sum of sensi- second intervals and time was taken as a meas- tivity and specificity. ure of goodness of fit of the exponential and for the linear regression between flow and vol- ume in the two subjects in whom the RASP Results computer program was used to analyse the Results of lung function measurements made tracings. On each subject, for each index, stan- before any inhalations and after the final in- dard deviation (SD) was measured for the five halation of histamine are shown in table 1. All breaths analysed before and after the inhalation subjects had FEV1 greater than 70% predicted of histamine. The paired t test was used to at the beginning ofthe study and the maximum test if there was any change in within subject fall in FEV, in any subject was 40% of baseline variability as indicated by SD of any of the value after the final inhalation of histamine. indices after histamine. A fall of 20% in FEV1 There was a consistent smoothing of the flow
Table 1 Mean (SD) lungfunction data in 20 patients before and after inhalation of histamine FEV, FRC sGaw TmelTE dtr/TE Krs EV litres % pred litres % pred (kPa - ' s- ') (G/) (Go/) (s ') (ml) Baseline 3-4 (1-0) 102 (16) 3-4 (0 8) 110 (21) 2-6 (0-9) 27 (8) 40 (14) 1-73 (0 52) 23 (4) After histamine 2-7 (0 9) 80 (19) 3-9 (0-9) 126 (26) 1.1 (1-4) 26 (12) 33 (15) 1-08 (0 62) 146 (14) p <0-001 <0-01 <0 001 NS <0 005 <0 001 <0 01 FEV, = forced expiratory volume in one second; FRC= functional residual capacity; sGaw = specific inspiratory conductance; Tme/TE, dt0/TE, Krs, EV= indices derived from expiratory tidal flow (five breaths in each subject before and after histamine). p values indicate significance of difference between baseline values and those after histamine. Analysis of tidal expiratory flow pattern 349 Baseline After histtamine (0 03) (after histamine). There was no differ- cn ence between these two values (paired t test .0 zf ~ t=0-82, p=NS). .f I ) 20 .lj :-) Linear regression analysis in this group of Thorax: first published as 10.1136/thx.50.4.346 on 1 April 1995. Downloaded from v V i subjects after histamine showed that Tme/TE x w correlated with FEV1 (slope=0-31, r=0-49, p<0 05) and with sGaw (slope=7-1, r=0-82, = 1- p<0 001), Krs with sGaw (slope=0-28, r= II P# ~ 0-62, p<0 01) but not with FEV1, and the 0 - - /\- f\,- r--\ J: !V v .j \ -..NV A-) u correlation of sGaw with FEV1 just missed ._- QC -1 - statistical significance (slope = 0004, r= 042, x W Time Time 1 s p 6- 7- 6- V 5 - A 5- - - = - g- http://thorax.bmj.com/ , i 5 - 5- 4- cn 4- In a) In .) L- 0- 4 _i 3- 3 - 2- 2- 3- on September 27, 2021 by guest. Protected copyright. 1- 1- 0 - 2- FEV, sGaw FRC 60 4- 500- I I 50 ,,%%to 3- ...... tt 400- 10 .*, '*I,. 40 300- 1* A -R In 2- 41 30 200- I7 ... 0.... 1- 20 100 - -.. 10 0-1 0- V o Tme/TE Krs -AEV ~~~-a Figure 4 Graphical representation ofpaired data before and after histamine inhalation for three recognised measures of airways obstruction (FEV,, sGaw and FRC), andfor three indices derived from expiratory tidalflow pattern. All group means before and after histamine are statistically different except TmelTE (see text). - =group mean. 350 Morris, Madgwick, Lane 70 - A 100 y = 1 *280x + 9.976, r = 0.526 60 - 75 * Thorax: first published as 10.1136/thx.50.4.346 on 1 April 1995. Downloaded from H UE0 . 0) 50K . 50 - -c 0 U - -< mm 4 %%. % cn . 4 '% 4. 25 [- I- 40 -- . V- 4. 0- . . 0 30 - . * -25_X 0 10 20 30 40 50 FEV1 (% change) 20 - B y = 1 *674x + 25-978, r = 0.543 100 n m - m 10 0 10 s Baseline Histamine 0 m m m Figure 5 Changes in the index dtgTE after histamine 50 _ challenge, p<0005. -=group mean. 0) C.) 0 SD of dt,/TE from 8-9% to 5-7% (t=2-46, p<0 03). There was no change in within subject o variation of SD of the other indices, Tme/TE Cl, and EV. With linear regression analysis the percentage . fall in Krs after the inhalation of histamine http://thorax.bmj.com/ was shown to be significantly related to the I~~~~~~~~~~~~~~~~~~~~~~~~~-50 L I percentage fall in FEV, (fig 6, table 2). This 0 10 20 30 40 50 was ofan order similar to that ofthe relationship FEV1 (% change) between the percentage fall in sGaw and the percentage fall in FEVI. The sensitivity of a Figure 6 Graphs showing (A) % change in Krs and (B) 35% fall in Krs of predicting a 20% fall in sGaw versus % change in FEV, after histamine challenge. FEV, was 92%, specificity 75%. The sensitivity of a 35% (or 40%) fall in sGaw (the usual index of a positive histamine challenge test) on September 27, 2021 by guest. Protected copyright. of predicting a 20% fall in FEV, was 92%, In 17 other normal subjects repeated meas- specificity 25%. Table 2 shows regression re- urements (n = 101) were made of these new lationships of the percentage change in the indices from tidal breathing on the same and indices derived from expiratory flow against different days. Mean within subject standard the percentage change in FEV1 % predicted and deviations were Krs 0 58 s -, Tme/TE 7%, dt,l in sGaw. TE 7%, EV 0-02 litres, coefficients of variation Frequency (f), tidal volume (VT), inspiratory Krs 21%, Tme/TE 21%, and dtr/TE 10%. In duty cycle (Ti/TToT) and mean inspiratory flow 11 patients with airways obstruction (FEVy 47 rate (VT/Ti) did not change after histamine, (21)% predicted) mean within subject standard nor did the within subject SD of any of these deviations (33 measurements) were Krs indices. 0-06 s-1, Tme/TE 1-5%, dtfTE 3-8%, EV 0-05 litres, coefficients of variation Krs 7%, Tme/ TE 6%, dtr/TE 10%, and EV 16%. Table 2 Summary of regression analyses ofpercentage change in expiratory flow indices against percentage change in FEV, (% predicted) and sGaw after histamine Discussion inhalation This study shows that analysis oftidal breathing y axis x axis Slope Intercept r p gives indices that can detect both increase in airways obstruction and increase in end tidal Krs FEV, 1-28 10 1 0-52 <0 05 Kr sGaw 0-31 18-7 0-39 NS volume after histamine inhalation. Tme/TE FEV, 0-83 -10-5 0-38 NS Histamine-induced bronchoconstriction was Tme/TE sGaw 0-38 -16-4 0 54 <0 05 used as a model of asthma so that acute changes dt,ITE FEV, 0 5 6-3 0-22 NS dt,,TE sGaw 0-34 -3 9 0-46 NS in FRC could be studied. The size of the (<0-1) significant change in EV which occurred after sGaw FEV, 1-67 26-0 0-54 <0 05 the inhalation of histamine did not correlate For definition of abbreviations see footnote to table 1. with the change in the plethysmographically Analysis of tidal expiratory flow pattern 351 measured FRC. Where the plethysmograph subjects after histamine inhalation, as did the measured large changes in FRC, changes of new index, dtr/TE. similar magnitude were not detected by the We did not find change in Tme/TE as useful extrapolated volume method. Plethys- an index of airways obstruction induced by mography has been shown to overestimate lung histamine in adults as the related volume index Thorax: first published as 10.1136/thx.50.4.346 on 1 April 1995. Downloaded from volume in patients with airways obstruct- has been found by Cutrera et al in children." ion,'718 and it may be that FRC measured in This difference may be attributable to the smal- this way is overestimated after histamine when ler number of subjects in our study and to the bronchoconstriction has been induced.'8 In wider range of bronchoconstriction in their some of these subjects such big changes in study, 15 of their 41 subjects having a fall in FRC seem surprising in the face of such mild FEVy of 40-70% of baseline after histamine. airways obstruction. The usual precautions of In our study no patient had a fall in FEVy keeping the cheeks flat when the shutter came greater than 40% of the baseline value. across and panting at low frequency were taken, The regression coefficients between per- but the compliant upper airways were not centage change of the new indices and per- otherwise controlled. The other alternative is centage change in FEV, and sGaw after that the large plethysmographically measured histamine were all positive (table 2), but the volume changes are true and that the ex- relationship was only significant between Krs trapolated volume method underestimates the and FEV, and between Tme/TE and sGaw. volume change. One explanation ofthis second Although the correlation between change in possibility is that the expiratory tidal flow curve, Krs and change in FEV, was weak, change in with its fitted exponential and extrapolated Krs detected histamine-induced broncho- volume, refers only to that part of the lung constriction, measured by change in FEVy, as subtended by open airways during tidal breath- well as did sGaw, being equally sensitive and ing. In this case the change in EV is the increase more specific. Krs, which is the reciprocal of in lung volume of this section of the lung and the time constant of the respiratory system, does not include the increase in lung volume depends on compliance as well as on airways due to an increase in trapped gas in parts of resistance. Other accepted measurements of the lung beyond the closed airways. This latter airways obstruction - for example, peak ex- increase in lung volume will be included in the piratory flow and FEV, - are also non-specific, body plethysmographic measurement of lung being affected by muscle strength, chest wall volume. Ifthis hypothesis is correct, the change and lung recoil, lung and airways compliance, in EV should correlate better with the change as well as by the calibre of the airways. Despite in lung volume when the latter is measured by this, these measurements are extremely useful helium dilution. in the practical assessment of airways ob- Assumptions made using the extrapolated struction. The lack of specificity of the indices http://thorax.bmj.com/ volume method include (1) that there is no of tidal expiration, Krs, Tme/TE, and dtr/TE, respiratory muscle activity or laryngeal braking does not therefore rule them out as potentially during the time over which the exponential is useful in the assessment of airways obstruction. fitted,7 22 (2) that a single exponential de- The model of asthma that we chose caused scribes the decay of flow towards the end of only mild bronchoconstriction rather than sig- resting tidal expiration,8 23-25 and (3) that the nificant clinical asthma. The visual impression relaxation equilibrium volume of the re- of less variability in the tidal expiratory flow spiratory system does not change with the in- pattern in airways obstruction than in normal on September 27, 2021 by guest. Protected copyright. duction of bronchoconstriction. There are subjects, that we in this study and others4 have theoretical objections to each of these commented on, is documented in this study as assumptions22 2&29 which, because oflimitations a decrease within subjects of SD of Krs and of of space, cannot be discussed in this paper. dtfTE after histamine compared with baseline However, our findings that (1) the fit of a SDs. It is our beliefthat change from normality single exponential to the flow versus time curve to very mild airways obstruction is a "worst towards the end oftidal expiration is good both case") scenario for this analysis because of the before and after histamine, and (2) that the variability of these indices in normal subjects baseline time constant (1/Krs) for the group as described by Buohuys.4 We are encouraged (0-58 seconds) calculated from this exponential by the modest success of this analysis in de- approaches the previously determined time tecting these small changes after histamine, and constant of free collapse from TLC in con- a study is underway to test the usefulness of sciously breathing and paralysed normal sub- this analysis in acute severe asthma where the jects,'9232528 lead us to conclude that this practical benefits of a test not requiring re- analysis should give an approximate estimate spiratory gymnastics will be more evident. In of acute dynamic hyperinflation not including the computer analysis a straight line is fitted to trapped gas. Our data show that a change the expiratory flow-volume decay rather than, in the tidal expiratory flow pattern sensitively as in the first part of this study, an exponential detects the occurrence of acute hyperinflation, to the flow-time decay. This is an improvement but underestimates the plethysmographically to the method because immediate assessment measured change in volume. by eye of the goodness of fit of the imposed We have confirmed previous cross sectional line and thus of the validity of the derived findings"8'0 in that the indices of airways ob- results is possible. struction, Krs and Tme/TE, derived from the There is no doubt that a reliable method of tidal flow pattern, correlated with other re- quantifying the degree of airways obstruction, cognised indices of airways obstruction in these requiring from the patient only a run of tidal 352 Morris, Madgwick, Lane for the measurement of tidal breathing parameters in breathing through a pneumotachometer, would newborns. PediatrPulmonol 1992;14:187-92. be useful in situations where maximum forced 15 Cockcroft DW, Killian DN, Mellon JJA, Hargreave FE. Bronchial reactivity to inhaled histamine: a method and manoeuvres are unreliable or inapplicable. clinical survey. Clin Allergy 1977;7:235-43. 16 RASP Respiratory Analysis Program users' guide. Newbury, Thorax: first published as 10.1136/thx.50.4.346 on 1 April 1995. Downloaded from The authors are grateful to Allen & Hanburys for their support UK: Physiologic Ltd. of the Osler Chest Clinic Lung Function Laboratory. RG 17 Shore S, Milic-Emili J, Martin JG. Assessment of body Madgwick is the Allen & Hanburys Respiratory Technician. We plethysmographic technique for the measurement of thor- also thank P McShane for his help with the statistical analysis. acic gas volume in asthmatics. Am Rev Respir Dis 1982; 126:515-20. 18 Stanescu DC, Rodenstein D, Cauberghs M, Van de Woe- 1 Have J Th ten. Over adensnelherd, adengrootte en ad- stijne KP. Failure of body plethysmography in bronchial emarbeid. Thesis, University ofUtrecht, The Netherlands, asthma. JAppl Physiol: Respirat Environ Exerc Physiol 1982; 1905. 52:939-48. 2 Englmann K. Arch Klin Med 1927;157:280. 19 Shee CD, Ploy-Sang-sang Y, Milic-Emili J. Decay of in- 3 Kaye R, Whittenberger JL, Silverman L. Respiratory airflow spiratory muscle pressure during expiration in conscious patterns in children. Am _7 Dis Child 1949;77:625-41. humans. J Appl Physiol 1985;58:1859-65. 4 Bouhuys A. The clinical use of pneumotachography. Acta 20 Agostoni E. Dynamics. In: Campbell EGM, Agostoni E, Med Scand 1957;159:91-103. Newsome Davis J, eds. The respiratory muscles mechanics 5 Phelan PD, Williams HE, Freeman M. The disturbance of and neural control. London: Lloyd-Luke (Medical Books) ventilation in acute viral bronchiolitis. Aust Paediatr _7 Ltd, 1970:96. 1968;4:96-104. 21 Mortola JPO, Milic-Emili J, Noworaj A, Smith B, Fox G, 6 Morris MJ, Lane DJ. Tidal expiratory flow patterns in Weeks S. Muscle pressure and flow during expiration in airflow obstruction. Thorax 1981;36: 135-42. infants. Am Rev Respir Dis 1984;129:49-53. 7 Morris MJ, Madgwick RG, Frew AJ, Lane DJ. Breathing 22 Citterio G, Agostoni E, del Santo A, Marazzini L. Decay of muscle activity during expiration in patients with chronic inspiratory muscle activity in chronic airflow obstruction. airflow obstruction. Eur RespirJ7 1990;3:901-9. J Appl Physiol: Respirat Environ Exerc Physiol 1981 ;51: 8 Otis AB, Fenn WO, Rahn H. Mechanics of breathing in 1388-97. man. Appl Physiol 1950;2:592-607. 23 Pierce JA. Studies of free collapse in the intact human lung. 9 Martinez FD, Morgan WJ, Wright AL, Holberg CJ, Taussig J Lab Clin Med 1959;54:96-106. LM. Diminished lung function as a predisposing factor 24 Brody AF. Mechanical compliance and resistance of the for wheezing respiratory illness in infants. N Engl I Med lung thorax calculated from the flow recorded during 1988;319:1112-7. passive expiration. Am J Physiol 1954;178:189-96. 10 Morgan WJ, Tepper RS, Wilcox E, Taussig LM, CHMA 25 Mcllroy MB, Tierney DF, Nadel JA. A new method for Pediatricians. Shape and moment analysis of tidal ex- measurement of compliance and resistance of lungs and piration in normal and bronchopulmonary dysplasia in- thorax. J Appl Physiol 1963;18:424-7. fants. Am Rev Respir Dis 1984;129(Suppl 2):A215. 26 Muller N, Bryan AC, Zamel N. Tonic inspiratory muscle 11 Cutrera R, Filtchev SI, Merolla R, Willim G, Haluska J, activity as a cause of hyperinflation in histamine-induced Ronchetti R. Analysis of expiratory pattern for monitoring asthma. JAppl Physiol: Respirat Environ Exerc Physiol 1980; bronchial obstruction in school-age children. Pediatr Pul- 49:869-74. monol 1991;10:6-10. 27 Martin J, Powell E, Shore S, Emrich J, Engel LA. The role 12 Carlsen KH, Lodrup KC. Tidal flow volume loops in the of respiratory muscles in the hyperinflation of bronchial assessment of reversibility to salbutamol in pre-school asthma. Am Rev Respir Dis 1980;121:441-7. children with and without asthma. Eur Respir 1992; 28 Chelucci GL, Brunet F, Dall' Ava-Santucci J, Dhainaut JF, 5(Suppl 15):276s. Paccaly D, Armaganidio A, et al. A single compartment 13 Stocks J, Jackson E, Gappa M, Mukhtar Z, Costeloe K, model cannot describe passive expiration in intubated, Dezateux C. Analysis of tidal expiration - how stable is paralysed humans. Eur Respirj7 1991;4:458-64. Tme/TE? Eur Respir 1992;5(Suppl 15):38s. 29 Freedman S, Tattersfield AE, Pride NB. Changes in lung 14 Stich SM, Ellis E, LeSouef PN, Sly PD. Validation of mechanics during asthma induced by exercise. J Appl respiratory inductance plethysmography ("Respitrace") Physiol 1975;38:974-82. http://thorax.bmj.com/ on September 27, 2021 by guest. Protected copyright.