Thorax 1989;44:660-667 Disturbance in respiratory mechanics in infants with bronchiolitis J SEIDENBERG, I B MASTERS, I HUDSON, A OLINSKY, P D PHELAN From the Professorial Department of Thoracic Medicine, Royal Children's Hospital, and University Department of Paediatrics, Melbourne, Australia ABSTRACT The passive flow-volume and partial forced expiratory flow-volume techniques were used to assess pulmonary function in 14 spontaneously breathing infants with acute respiratory syncytial virus bronchiolitis. Two additional infants were studied while paralysed and ventilated. During the acute stage of the illness there was a significant reduction in forced expiratory flow rates and an increase in respiratory resistance. Although the mean thoracic gas volume for the group was increased, five infants did not compensate for their airways obstruction by hyperinflation. Curvilinear passive flow-volume curves were seen in three of the 14 non-ventilated infants and in both ventilated infants. At follow up three to four months later all passive flow-volume curves were linear. There was a significant reduction in hyperinflation and an increase in forced expiratory flow rates, but values still differed significantly from those in normal infants. Introduction Acute viral bronchiolitis is the most common serious lower respiratory infection in the first six months of life. The clinical picture is one of small airway obstruction and pulmonary hyperinflation. Pulmon- ary function tests in the acute phase of the illness confirm the clinical and radiological evidence of airflow obstruction and gas trapping.'2 Criticism has, however, been levelled at the tests used to assess lung function, suggesting that they may not reflect changes in airway function accurately.34 New methods of evaluating lung function in young infants have been developed recently. Total res- piratory system compliance and resistance have been measured by the occlusion and passive flow-volume techniques in newborn and older infants"6 and maxi- mum expiratory flow rates by the partial forced expiratory flow-volume technique."8 The two tech- niques allow measurements to be made without oeso- phageal balloons, which have major methodological problems in infancy,3 and without the complex equip- ment needed for the rebreathing method for measur- ing airways resistance,9 which is not particularly suitable for ill infants. The passive technique makes Address for reprint requests: Dr A Olinsky, Professorial Department of Thoracic Medicine, Royal Children's Hospital, Parkville 3052, Victoria, Australia. Accepted 24 April 1989 use of the observation that infants have a Hering- Breuer reflex.'0 After transient occlusion at end ins- piration the infant expires passively; the normal plot of expiratory flow against lung volume is a straight line. This allows calculation of the resistance and com- pliance of the respiratory system without use of invasive techniques.5 In the present study we combined the two tech- niques to study infants with acute bronchiolitis due to respiratory syncytial virus during the acute and recovery phases of the illness. In addition, passive expiration was studied in two paralysed and ventilated infants with bronchiolitis. The aim was to document abnormalities in respiratory mechanics and to obtain insights into mechanisms used by the infants to compensate for the pathological changes. Methods PATIENTS We studied 16 previously healthy infants admitted to hospital with acute bronchiolitis. The project was approved by the hospital ethics committee and infor- med consent obtained from the parents. In most cases one parent was present during the examination. The mean age of the 14 infants studied at about the eighth day of the illness was 20 (range 4-41) weeks. They were studied again three to four months later. Two infants aged 6 and 8 weeks were studied while paralysed and ventilated. The diagnosis of bron- chiolitis was based on the presence of tachypnoea, 660 on April 19, 2021 by guest. Protected by copyright. http://thorax.bmj.com/ Thorax: first published as 10.1136/thx.44.8.660 on 1 August 1989. Downloaded from
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Thorax 1989;44:660-667
Disturbance in respiratory mechanics in infants withbronchiolitisJ SEIDENBERG, I B MASTERS, I HUDSON, A OLINSKY, P D PHELANFrom the Professorial Department of Thoracic Medicine, Royal Children's Hospital, and University DepartmentofPaediatrics, Melbourne, Australia
ABSTRACT The passive flow-volume and partial forced expiratory flow-volume techniques wereused to assess pulmonary function in 14 spontaneously breathing infants with acute respiratorysyncytial virus bronchiolitis. Two additional infants were studied while paralysed and ventilated.During the acute stage of the illness there was a significant reduction in forced expiratory flow ratesand an increase in respiratory resistance. Although the mean thoracic gas volume for the group wasincreased, five infants did not compensate for their airways obstruction by hyperinflation.Curvilinear passive flow-volume curves were seen in three ofthe 14 non-ventilated infants and in bothventilated infants. At follow up three to four months later all passive flow-volume curves were linear.There was a significant reduction in hyperinflation and an increase in forced expiratory flow rates, butvalues still differed significantly from those in normal infants.
Introduction
Acute viral bronchiolitis is the most common seriouslower respiratory infection in the first six months oflife. The clinical picture is one of small airwayobstruction and pulmonary hyperinflation. Pulmon-ary function tests in the acute phase of the illnessconfirm the clinical and radiological evidence ofairflow obstruction and gas trapping.'2 Criticism has,however, been levelled at the tests used to assess lungfunction, suggesting that they may not reflect changesin airway function accurately.34New methods of evaluating lung function in young
infants have been developed recently. Total res-piratory system compliance and resistance have beenmeasured by the occlusion and passive flow-volumetechniques in newborn and older infants"6 and maxi-mum expiratory flow rates by the partial forcedexpiratory flow-volume technique."8 The two tech-niques allow measurements to be made without oeso-phageal balloons, which have major methodologicalproblems in infancy,3 and without the complex equip-ment needed for the rebreathing method for measur-ing airways resistance,9 which is not particularlysuitable for ill infants. The passive technique makes
Address for reprint requests: Dr A Olinsky, Professorial Departmentof Thoracic Medicine, Royal Children's Hospital, Parkville 3052,Victoria, Australia.
Accepted 24 April 1989
use of the observation that infants have a Hering-Breuer reflex.'0 After transient occlusion at end ins-piration the infant expires passively; the normal plot ofexpiratory flow against lung volume is a straight line.This allows calculation of the resistance and com-pliance of the respiratory system without use ofinvasive techniques.5
In the present study we combined the two tech-niques to study infants with acute bronchiolitis due torespiratory syncytial virus during the acute andrecovery phases of the illness. In addition, passiveexpiration was studied in two paralysed and ventilatedinfants with bronchiolitis. The aim was to documentabnormalities in respiratory mechanics and to obtaininsights into mechanisms used by the infants tocompensate for the pathological changes.
Methods
PATIENTSWe studied 16 previously healthy infants admitted tohospital with acute bronchiolitis. The project wasapproved by the hospital ethics committee and infor-med consent obtained from the parents. In most casesone parent was present during the examination.The mean age of the 14 infants studied at about the
eighth day of the illness was 20 (range 4-41) weeks.They were studied again three to four months later.Two infants aged 6 and 8 weeks were studied whileparalysed and ventilated. The diagnosis of bron-chiolitis was based on the presence of tachypnoea,
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Disturbance in respiratory mechanics in infants with bronchiolitis
hyperinflation, wheezing, and widespread crepita-tions. These were present at the time of the first study,though the spontaneously breathing infants no longerrequired nursing in a high oxygen environment. Allpatients had a positive result in the immunofluores-cence test for respiratory syncytial virus antigen in thenasopharyngeal secretions. In the follow up studyeight babies still had intermittent wheeze but wereotherwise well.
INVESTIGATIONSThe spontaneously breathing infants were studiedlying supine with the neck slightly extended in a 40 litrebody plethysmograph, after receiving 80 mg/kgchloral hydrate. A three position slide valve, modifiedfrom that originally described by Le Souef et al,5 wasfixed to the face with silicone putty. Flow wasmeasured with a Fleisch No 1 pneumotachograph anda Validyne DP 45 pressure transducer. Volume wasdetermined by electronic integration of the flow signaland drift was carefully adjusted. Flow and volumewere displayed on a Tektronix 5223 digitising oscillo-scope and recorded on tape with a Racal thermionicstore 4D recorder. These signals and pressure werealso displayed on a chart recorder (HP 7754A). Mouthpressure was measured via a port between the facemask and slide valve by means of a Hewlett Packard128 OC pressure transducer. The pressure in theplethysmograph and cuff used for compression weremeasured with similar transducers.
Respiratory timingDuring spontaneous tidal ventilation the duration ofa respiratory cycle (Ttot) and inspiratory time (Ti)were measured from the flow tracings and expressed asTi/Ttot.
Passive expiratoryflow manoeuvreThe passive compliance (Crs), resistance (Rrs), andtime constant (Trs) ofthe total respiratory system wereobtained by the airway occlusion technique.5 Briefocclusion at end inspiration was performed with theslide valve between mask and pneumotachograph.The occlusion was released as soon as a plateau ofmouth pressure was reached and, in the absence offlow, equalisation of pressure within the respiratorysystem was assumed. The linear part of the passiveexpiratory flow-volume (PEFV) curve was extra-polated to the flow and volume axes to calculate Crs,Rrs, and Trs (fig 1). (Compliance (Crs) =extrapolated expired volume (VE)/occlusion mouthpressure (Pao), and resistance (Rrs) = occlusionmouth pressure (Pao)/extrapolated expiratory flow(Vo) at end inspired volume.)
In the two paralysed and ventilated infants the slidevalve was attached to the endotracheal tube and
Crs = VE/PaoRrs = Pao/VoTrs = Crs. Rrs = VE/VO
VEFig 1 Passive expiratoryflow-volume curvefrom one infant.The slope is extrapolated to theflow (Vo) and volume ( VE)axes. Calculations are described in the text.
ventilating bag, which bypassed the pneumo-tachograph. Constant pressure tracings during iso-volume ventilation and pressure plateau duringocclusion excluded any appreciable leak around theendotracheal tube or in the measuring device. Becauseof the prolonged expiration to zero flow in theseinfants with severe airways obstruction, oxygen en-riched air was supplied before each measurement andskin colour and heart rate were constantly monitored.Occlusion was performed at several different lungvolumes, but before each occlusion the lungs wereinflated to total lung capacity to standardise precedingpressure-volume relationships." PEFV curves wererecorded after removal of the occlusion and theexpiration was allowed to continue until there hadbeen no expiratory flow for 3 to 4 seconds. The PEFVcurves obtained in an individual patient initiated fromdifferent lung volumes were compared by assumingthat after each passive expiration the same absoluteend expiratory volume was achieved. We found thatthe PEFV curves of an individual infant were super-imposed, except for the transient rise in flowimmediately after occlusion. The transient flow recor-ded immediately after removal of the occlusion wasignored and Trs, Rrs, and Crs were calculated for eachlung volume at which the occlusion was performed.
Forced expiratoryflow manoeuvrePartial forced expiratory flow-volume (FEFV) curvesand maximum flow at functional residual capacity(VmaxFRC) were obtained by a modified version ofthe rapid compression technique.8 The chest andabdomen were compressed by rapid inflation of aplastic cuffenclosed in a nylon mesh jacket (fig 2). Thecuff covered the chest and abdomen and its positiondid not change throughout the examination. The outernylon jacket minimised pressure dissipation awayfrom the chest. With this device about 70% of the cuffpressure was transmitted to the alveoli and airways as
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measured by the increase in mouth pressure duringocclusion.'2 Virtually instantaneous inflation of thecuff was achieved by decompressing a gas storagedrum through a wide bore connecting tube.'2 Pressurewithin the drum was carefully regulated by a waterfilled manometer and a safety blow off valve. FEFVcurves were obtained by progressively and carefullyincreasing chest compression until the shape of theFEFV curve and VmaxFRC were constant and didnot increase with further increases in chest compres-sion pressure. Care was taken to avoid a negative"effort" effect when increasing pressure resulted insubmaximum flow. With this occurred the cuff pres-sure was reduced until true maximum flow was againachieved. Final selection of curves with maximumflow for analysis was made when the raw signals wereplayed back from the tape on to an oscilloscope.
Thoracic gas volwneThoracic gas volume (TGV) was measured at endexpiration in the constant volume body plethysmo-graph by the classic method of DuBois. As the infantattempted three or four spontaneous breaths afterairways occlusion mouth pressure and box pressurewere plotted on the x and y axes of a storageoscilloscope and TGV was calculated by applyingBoyle's law.2 Calculations were corrected for deadspace and adjusted for the difference between themeasured and previously stable FRC. TGV at end
inspiration was also measured in 10 babies during thefirst study, though unless otherwise stated TGV refersto end expiratory TGV.
DATA ANALYSISCalculations were made after slowly playing back thetaped records on to the oscilloscope and XY plotter(National VP 6123A). Each final measurement was a
mean of at least five individual measurements madefrom technically satisfactory curves except in the caseof VmaxFRC, where the highest value achieved wastaken. The results were compared with normal dataobtained by the same investigators from six healthyinfants studied longitudinally on four occasions whenaged 4-55 weeks. Prediction values based on heightwere.derived from that study.8The Wilcoxon signed rank and Mann-Whitney tests
were used to compare the data from the infants withbronchiolitis and to compare these with the data fromthe normal infants. The 0-05 level of probability wasassumed to be significant.
Results
ACUTE STUDIESMean end expiratory TGV for the 14 infants wasincreased (table 1), though five infants had an endexpiratory TGV within the normal range (less than 30ml/kg). Mean (SEM) end inspiratory TGV minus tidal
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volume in the 10 babies in whom this measurementwas performed was 42 (3 5) ml/kg, significantly higherthan end expiratory TGV (37 (3 5) ml/kg; p < 0-05).End inspiratory TGV less tidal volume was higherthan end expiratory TGV in infants both with andwithout hyperinflation, though more strikingly in theformer.The passive expiratory flow-volume (PEFV) curve
was a straight line in 11 of the 14 spontaneouslybreathing patients. In the remaining three patients itbecame curvilinear towards end expiration. Super-imposing the forced, passive, and tidal volume curvesproduced similar lines for the three curves in thesepatients (fig 3).Mean Rrs for the 14 infants was significantly
increased, whereas mean specific compliance (sCrs)
(that is, compliance divided by the lung volume atwhich it was measured) and mean specific conduc-tance (sGrs) were significantly less than in the normalinfants (table 1).The FEFV curve was convex towards the x axis in
13 of the 14 patients. There was a significant decreasein the mean VmaxFRC and mean VmaxFRC/TGV(table 1). Twelve of the 14 infants had VmaxFRC/TGV below the 95% prediction interval (fig 4). Themean compression pressure needed to achieve Vmaxin the patients was 35 cm H20 compared with 34 cmH20 in normal infants.The five infants without hyperinflation had changes
in VmaxFRC/TGV, mean sCrs, and mean sGrssimilar to those of the infants with hyperinflation,though mean (SEM) Ti/Ttot was significantly shorter(0-382 (0 04) v 0-426 (0'03); p < 0'05).
In the two paralysed infants with severe bronchio-litis the PEFV curves were also curvilinear. Occlusionat different lung volumes allowed measurement of Rrsand Crs at varying lung volumes and showed increas-ing Rrs towards end expiration, followed by decreas-ing Crs at slightly lower lung volumes (fig 5).
FOLLOW UPLung function in most infants had improved whenretested three to four months later. No PEFV curveremained curvilinear. TGV/kg was significantly lessthan during the acute phase of the illness (p < 0 05)and VmaxFRC/TGV was increased (p < 0-002). Trsand sGrs had not changed significantly, whereas sCrshad increased (p < 0'05). By comparison with a groupof healthy infants (table 2), however, significant gastrapping and decreased volume corrected flow rateswere still evident.
E
Fig 3 Tidal, passive, andpartialforced expiratoryflow-volume curvesfrom one infant. Thepassive curve was superinposed by extrapolating all curves to zeroflow on the asswnption thatthis occurs at the same absolute lung volume. Note the expiratoryflow limitation in tidal andpassive expiratory curves.
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Fig 4 Relation between lmaxFRC/TGVand height' during the acute phase (blacksquares) and recovery phase (white squares). The solid and dashed lines represent themean and 95% predicted intervalsfor normal infants.
Discusion
This study has shown a pronounced reduction inforced expiratory flow and an increase in respiratoryresistance in infants with viral bronchiolitis. Thoracicgas volume at functional residual capacity was sub-stantially increased. Total respiratory compliance didnot differ significantly from that of normal babies,though specific compliance was reduced, a reflectionof the increase in TGV. The time constant of therespiratory system did not differ from that of normal
Table 2 Pulmonaryfunction measurements (mean (SEM))in 14 infants who had recoveredfrom acute viral bronchiolitiscompared with measurements in six healthy infants
SignificanceBronchiolitis Normal ofdifferencerecovery phase infants between(n= 14) (n= 6) groups (p)
babies. These findings are similar to those reported instudies using oesophageal balloons to measure intra-thoracic pressure2 and the forced oscillation tech-nique.' 13 The scientific validity of both these tech-niques has been questioned.34The techniques used in this study have been
developed over recent years. The forced expiratorytechnique was first applied to newborn infants andpapers are now appearing on its use in older in-fants.6141 One potential problem with this method isthat the infant may start inspiration before reachingVmaxFRC. The consistency in the forced expiratoryflow-volume curves in this study suggests that expira-tion concluded at a similar point with successivecompressions. To obtain reproducible forced expira-tory curves, it is important that the compressionpressure is gradually increased until maximum flow isobtained, as was done in this study. The compressionpressure needed to achieve maximum flow in thebabies with bronchiolitis was similar to that in normalinfants.The original studies of the passive technique were
also undertaken in newborn infants but there are nowreports of its use in healthy older infants8 and in theevaluation ofthe efficacy of salbutamol in infants withacute viral bronchiolitis.'6 It relies on the presence ofthe.Hering-Breuer reflex and the assumption that aftera period of short occlusion the infant passively expiresto FRC. To exclude active respiratory muscle activityrequires direct measurement of muscle activity, whichis difficult in infants." There may be an initial flow
Disturbance in respiratory mechanics in infants with bronchiolitis
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-4
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Fig 5 Passive expiration in one of the paralysed and ventilated infants: (a)curvilinear passive expiration (the bar below indicates the volumes ofrespirator tidalventilation); (b) calculated Crs and Rrs at the different lung volumes during thepassive expiration shown in (a).
transient at the start of passive expiration, reflectingpressurisation of the pneumotachograph.5
Thoracic gas volume was measured in the standardway used in this laboratory for 20 years.2"' One grouphas recently reported low values ofTGV in babies withclinically obvious hyperinflation and offered severalpossible explanations.'9 Other laboratories, however,have confirmed hyperinflation in infants with airwaysobstruction.22" The suggestion that differences incalibration may explain the different findings is un-
likely as similar methods have been used by theworkers who found hyperinflation clinically andphysiologically and by those who did not.2 18 Furtherwork is necessary to account for these differentfindings. Interestingly, end inspiratory TGV minustidal volume was slightly greater than end expiratoryTGV, which is the opposite of previous findings ininfants with airways obstruction.2' 22
The most interesting findings in this study were thecurvilinearity ofthe PEFV curves in three patients, theabsence of hyperinflation in five, and the measure-
ments made in the two ventilated paralysed infants. Innormal infants the PEFV curve is a straight line.823Linearity implies that the product of Crs and Rrsremains constant during passive expiration.'25 Thecurvilinearity found in the patients with bronchiolitisindicates a changing time constant during expiration,probably due to varying speeds ofemptying ofareas oflung with different degrees of obstruction. In theparalysed infants there was a rapid rise in resistancewith a fall in compliance towards smaller lungvolumes, suggesting progressive narrowing and finallyclosure of small airways with air trapping. Glotticnarrowing is suggested as another possible explana-tion but was excluded in our intubated, paralysedinfants; so airways closure is the most likely explana-tion. Further, with glottic narrowing the initialexpiratory resistance usually exceeds end expiratoryresistance.6 Flattening of the PEFV curve thereforeoccurs at the beginning rather than towards endexpiration. Another possible explanation for thecurvilinearity is expiratory muscular activity during
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expiration.24 If this occurred early in expiration, anadditional increase in mouth pressure should havebeen observed.
Eleven infants had linear PEFV curves in thepresence of increased resistance and hyperinflation.The likely explanation is that tidal breathing wasoccurring at higher lung volumes where Rrs and Crsdid not change during expiration. Possibly, however,increasing resistance was balanced by decreasingcompliance during expiration so that their productremained constant.The bar below the curvilinear PEFV curve for the
paralysed and ventilated patient shown in figure 5indicates the volume of ventilator tidal ventilation. Itshows that an increase in end expiratory volumeallowed breathing at a lower time constant. This leadsto increased ventilation without any change in res-piratory frequency. This compensation for airwaysclosure may explain why no difference was found intime constants from the passive curve between infantswith bronchiolitis and the normal controls. The forcedexpiratory flow-volume curve showed increased con-cavity with decreased VmaxFRC in the infants withbronchiolitis. This apparent discrepancy may havearisen because during passive expiration the increasein Rrs is balanced by a decrease in Crs, so that the timeconstant is unchanged. During the forced manoeuvre,however, the driving pressure for expiration is sig-nificantly decreased by the pressure transmitted fromthe cuffto the pleural space. In the presence ofairwaysdisease this pressure leads to narrowing or closure ofairways (or both) with a resultant reduction inexpiratory flow rates.The reduction in VmaxFRC is most likely to be due
to disease of intrapulmonary airways. It has beensuggested that expiratory narrowing of the glottis,"laryngeal braking," may be important in maintaininghyperinflation in asthma," but if this was a factor inthese babies some flattening of the initial portion ofthe PEFV curve and a much greater rise in Rrs wouldhave been expected.
Five patients with flow limitation, two ofwhom hadcurvilinear PEFV curves, did not compensate byhyperinflation. This group appeared to maintainadequate ventilation by spending relatively more timeon expiration. The reason for this mode ofcompensa-tion was not clear. A similar pattern was seen in somepatients recovering from acute asthma many yearsago.'To analyse the Crs and Rrs when PEFV curves are
curvilinear requires interruption during expiration, asin our paralysed infants. This analysis should also bepossible in spontaneously breathing infants with theinterruptor technique described for animals.28 Withcurvilinear PEFV curves calculation of Crs and Rrsfrom the initial part of passive expiration, which
Seidenberg, Masters, Hudson, Olinsky, Phelanapproximates to a straight line, may be misleading.Extrapolation of the straight part to the volume axiswill underestimate the passive expired volume and afalsely low Crs will be calculated. Similarly, thecalculated Rrs will underestimate the change in Rrsduring expiration and so is valid only for the lungvolume at end inspiration.Thus our studies using recently developed tech-
tiques showed substantial reduction in forcedexpiratory flow in infants with acute viral bronchiolitisand suggest that this is due to changes in intrapulmon-ary airways. There was a much smaller change in Rrs,which is probably more influenced by disease in largerairways. Some infants did not compensate for airwaysnarrowing with hyperinflation and they had severeexpiratory flow limitation. Further investigation ofwhy they failed to adopt this defence mechanism maygive a better understanding of its origin. Althoughfunctional impairment was less at follow up three tofour months after the acute bronchiolitis lung functionwas still significantly different from that of normalinfants.
JS was supported by the Deutsche Forschunggemein-schaft, Federal Republic of Germany.
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