Eur Respir J 1989, 2, 34o-343

Effects of maximal breath holding on maximal expiratory flow

P. Mialon, L. Barthelemy, P. Sebert

Effects of maximal breath lwlding on maximal expiraJory flows. P. Mialon, L. Barthelemy, P. Sebert.

Service de Physiologie, Faculte de 22, Avenue Camille Desmoulins BR EST ·Cedex, France. ' ABSTRACT: Effects of breath holdings (OH) on bronchomotor tone,

maintained until their breaking points, bave been studied using maximal expiratory flow volume curves (MEFVC). BHs have been performed either at high lung volume (total lung capacity, EIBH) or at low lung volume (residual volume +250 ml, EEBH), an Inspiratory manoeuvre Im­mediately preceding the MEFVC. The results show that: (1) EIBH induces a significant Increase of expiratory flow at 25% of FVC; (2) EEBH Induces a significant and constant decrease of expiratory flows at SO% and 25% ot FVC. The same modlncatlons were recorded after inhalation of 400 J.Lg of Fenoterol or 80 llC of Ipratropium bromide. The observed results are suggestive of mechanical effects of BH on expira­tory flows. After EIBH airway hysteresis dominates over lung hysteresis, wltb opposite effects after EEDH.

Corr~sponden~c: Or P. Mialon, Setvj01

Phystologte, l'acuM de Medecine 22 A~ Camille Desmoolins, 29 285 RREST .QiWJ France. ~--;tf,

Eur Respir J., 1989, 2, 340-343.

The relationships between lung volumes and expira­tory flows are well known [1): Short breath holds (BH) have been performed between partial expiratory flow/volume curves (PEFVC) as a tool for investigat­ing effects of different volume histories on subsequent expiratory flows [2), but the possibility that maximal BH could affect subsequent expiratory flows had not been considered. Since breaking point of BH is depend­ent on various stimuli [3-6) which could modulate bronchomotor tone, we have examined the possible effects of maximal BH on expiratory flows using maxi­mal expiratory flow/volume curves (MEFVC) that arc generally considered to be quite insensitive to lung vol­ume history [2).

Subjects and methods

Twenty healthy subjects (8 men, 12 women; 39±1.9 years, body weight, 63±2.8kg, height 1.68±0.02 m). without any history of smoking, lung disease or allergy, voluntarily perfonned MEFVC in a sitting position. All studies were performed between 10 and 11 am on a Transferscreen 11 (Jaeger) set with a PT36 Lilly transducer. On the first day, the. subject performed two MEFVC separated by 10 min of quiet breathing (VT level); on the second day at the same hour, the subject performed in a randomized order and in duplicate a MEFVC at the end (breaking point) of inspiratory (fLC level) BH (EIBH, about 60s) and at the end (breaking point) of expiratory ("'250 ml above RV, residual vol­ume, level) BH (EEBH, about 30s). An inspiratory manoeuvre thus preceded the expiratory manoeuvre.

Each manoeuvre was separated from the previo3 by 10 min of quiet breathing. Partial end Cltpi pressures of 0~ and C01 were also measured (Po Pco1, Jaeger analysers) at the brealcing point of sf.L

Two additional series of experiments were co~>J .... ::d in a subgroup of 5 subjects with the same protocol be" fore and after inhalation of two drugs: (I) selective 1%. agonist (Fenoterol, 400 Jl&, given 20 mln before); (2J anticholinergic agent (lpratropium bromide, 80 ~.1 given 30 rnin before). These drugs were administcrocl-; using a metered dose inhaler activated at the onset rl inspiration from RV, with a BH of lOs at TLC. Onl1 one drug was given on a given day.

FVC PEF PIF MEF;. MEF;: FEV,

fig. 1. - Variations of maximal inspiratory and expiratory naw• B tcr end-inspiratory BH (ElBH, shaded columns) or end-c~pu·atOIY (EEBII. clear columns). Abbreviations with asterisks: the C(lllll

nows are significantly different between EIBH and EilBH: ~ with asterisks: the considered flows (EIBH or EEBH) are J'~" lC

different from basal values (mean of 2 MEPVC after quiet l>~t: ing). Results are expressed as mean±sEM. •p<0.05, .. p<O.OI

I!FFECTS OP MAXIMAL BREATH IIOLD1NG ON MAXIMAL EXPIRATORY FLOWS

Table 1. - Mean values ±SEM of the 20 subjects, without any drugs, on day 1 "Basal values", after breath holding at high lung volume "EIBH", and after breath holding at low lung volumes "EEBH".

Basal va!U<.'S EIBH EEBH

FVC BTPS 4.5±0.23 4.4±0.21 4.5±0.22 FEV

1 BTPS 3.55±0.15 3.60±0.17 3.54±0.16 PEF BTPS·min·' 502.0±26.8 495.6±38.1 508.8±29.3 MEF50 BTPS·min·' 247.0±16.1 251.8±15.7 224.8±16.6"' MEF2S BTPS·min· ' 93.0±7.6 105.9±9.6* 81.6±7.6*

*p<0.05

MEF 110 (/ BTPS·mJn·')

400 • 200 IIH BH

•

200

RE REF 0"------L--------'

0 . 200 400 0"------L-----~

0 100 200

341

2. - Individual variations of maximal expiratory flows at 50% and 25% of FVC wilhout (REF) and after end inspiratory BH (EffiH: circles) or end expiratory BH (EEBH: open circles). Each data point is a mean of 2 mea1un:ments.

Table 2. - Results of pharmacological challenge in the subgroup of 5 subjects (mean values ±seM)

FVC FEY, PEF MEFSO MEFlS (I BTPS) (I BTPS) (I BTPS·min·1) (IH·rPs·min· 1) (I BTPS·min·')

Without ~2 agonists Reference 5.54±0.55 4.49±0.39 728.4±87.0 275.4±26.4 120.2±21.0 EIBH 5.46±0.59 4.37±0.38 662.4±88.2 265.8±24.6 132.6±28.8 EEBH 5.70±0.60 4.34±0.44 672.2±66.0 253.8±36.8 103.8±31.2

After ~2 agonists Reference 5.65±0.56 4.53±0.42 699.0±63.6 283.8±46.8 125.4±30.0 EIBH 5.57±0.57 4.44±0.39 655.8±62.4 274.8±23.4 137.4±32.0 EEBH 5.68±0.57 4.46±0.46 705.0±70.8 267.0±51.0 99.0±28.8

Without anticholinergic Reference 5.64±0.58 4.37±0.39 663.6±99.6 274.8±36.0 115.2±22.8 EIBH 5.51±0.53 4.21±0.42 643.8±73.8 262.8±29.4 123.0±21.6 EEBH 5.70±0.60 4.40±0.45 690.0±78.0 240.6±36.0 100.8±27.0

After anticholinergic Reference 5.70±0.57 4.50±0.42 630.0±57.6 297.0±40.2 127.2±27.2 EIBH 5.53±0.58 4.36±0.37 666.0±66.6 306.0±24.0 136.8±25.8 EEBH 5.64±0.61 4.50±0.47 656.4±64.8 273.0±40.8 114.6±35.4

342 MIA!.ON I!T AL.

The values which have been considered arc: peak inspiratory (PIF) and expiratory (PEF) flows; forced expiratory volume in the 1st second (FEV

1); forced vi­

tal capacity (FVC); maximal expiratory flows at 50% (MEF~ and 25% (MEFz.s) of PVC. Each data point represents the mean of 2 measurements. Each subject being his own control, flow variations after BH have been compared to a basal value equal to the mean of the data from the 2 MEFVC performed on day 1 after quiet breathing (table 1).

The statistical significance of the results has been estimated at the 5% level by ANOV A.

Results

FVC, FEYt and peak flows (PEF and PIF) were not modified by the condition. There were, however, sig­nificant modifications of maximal expiratOry flows (figure I and table 1): MEP~ after EEB H only (-8%, p<0.05) and MEF25 arter both condi tions (- 12% artcr EEBH, p<0.05; +16% after EffiH, p<0.05). Conse­quently, when EEBH is compared to EIBH, MEF~0 and MEF~ are lower (-12%, p<O.OS and -28%, p<O.OI, re­spectively). Figure 2 shows individual variations of MEF50 and MEF25; variations of MEF15 are rather con­stant in our subjects. Po2 and PC92 values at the break­ing point of BH are not very different between EIBH (Po1: 89±2.9 torr; Pco1 : 40±1.6 torr) and EEBH (Po1:

87±4·.1 torr; Pco1: 43±1.3 to11'). Modifications of maximal expiratory flows by BH

were not significantly different aiter either drug (lhe ~1 agonist Fenoterol, or the anticholinergic agent Ipratro­pium bromide} in our subgroup (n=5) (table 2).

Discussion

Though maximal BH do not modify FVC, statistically significant changes of expiratory flows are recorded. These changes are greater than the coefficient of vari­ation of these parameters in our laboratory (MEF~cf:5%, MEF~9% on 3 manoeuvres in 10 healthy subjects at the 95% confidence interval). They could be the result of bronchomotor tone modulation and/or mechanical processes.

The events taking place in the course of BH and leading to stop the BH may modulate bronchomotor tone. The involved factors may be chemical (Pao

2,

Paco2), acting on peripheral and central chemoreceptors

[4, 6], or mechanical (lung volume, VL), acting on pulmonary and probably thoracic and diaphragmatic rcceptors (3. 5]. It is unlikely that the very small dif­ferences in Po2 and Pco2 could explain the modifica­tions of expiratory flows between EIBH and EEBH; these values of 0 2 and CO., arc in keeping with previ­ous data (7] . Evidence that"diaphragmatic activity may modulate bronchomotor tone is Jacking.

Lung receptors are mainly of three types: slowly adapting stretch receptors (SAR), rapidly adapting re­ceptors (RAR) and bronchial and pulmonary C fibres receptors. All are sensitive, although at various degrees,

to transpulmonary pressure (TPP) changes and lh fected by bronchomotor tone. Bronchial c fibr liS ~ also stimulated by hypercapnia, and pulmonary c en -by pulmonary congestion [8]. lo EffiH (•60 s) aJJ rcccptors are stimulated, but only SARs arc stead spondees; the effects of their activation should lh~ prcd?minant, resulting in bronch~lation (such a cho~ gerg1c reflex has been reported m the cat (91 and ~ [10, 11]. On the other hand, in EEBH (,..30 s) only ""'Y• tmlhoracic SARs (and they are few [8)), RARs maybe C fibre.s (only via possible lung congesllon cause C fibres do not respond below FRC level (8)) stimulated, and the expected result is bronchoco~ Lion (8]. So it could be possible to explain the Ob·.1Cnllft•• variations in expiratory flow by bronchomotor modulation. However, after cholinergic blockade or~ adrenergic stimulation, the modifications of expi~, flows remained unchanged. It could seem possible that cholinergic blockade, or ~1 adrenergic stimulation too weak with the inhaled drugs, but SANTAMAR!A ~~al. [12] used the same pharrilacologic challenge {but ill diff~rent mechanical conditions; no BH betw~n MEFVC) and found equivalent bronchodilation (MBP and MEF15,..+15%) for both drugs. The present resul; of drug challenge deny that the cholinergic system plays a great role, if any, in BH modulation of maximal cut .. piratory flows. There is still a possibility for a nervoua path via non-adrenergic non-cholinergic mechanismS> (ill· hibitory for EIBH, excitatory for EEBH), but as ~ knowledge on these two systems in man is limited (13} it is very difficult to investigate their roles.

A more interesting hypothesis seems to be that BH modulates expiratory flows by mechanical processea related to previous volume history, although each MEFVC was started after a 1LC manoeuvre: in healthY subjects, short inhalation to 1LC usually (though in~ sistenlly) leads to bronchodilation and higher maximal expiratory flows than during a partial flow/volume turve (PEFVC) [2, 14, 15) and exhalation from mid vital capacity after a RV history leads also to higher mPi• mal expiratory flows (PEFVC) [16]. One can consider that the intensity of variations of expiratory flows af· ter maximal respiratory manoeuvres depends on the relative hysteresis of lung (static pressure/volume curve) and airways (transmural pressure/bronchial calibre curve), as suggested by FROEB and MEAD [17]: a greater degree of airway hysteresis compared to lung hyst~ sis (greater bronchial calibre for the same transm..!!'~ pressure) resulting from the long stay (""60 s) at lLA­

Ievcl (EffiH) would lead to higher expiratory flows. Is it possible to explain the results after EEBH in the 511~ manner? After a long BH near RV level and a bn TLC volume history, 16 out of 20 subjects tiCC-~ their maximal expiratory flows. However, after a ,btl RV volume history, WEU.MAN et at [14] recorded h1~h~ expiratory flows on a PEFVC: the proposed me<ha.niStll was an increase of lung clastic recoil surp3SSJOS :::: increase of R (resistance from the alveolus to . tiC Equal Pressur~s Point) []]. Increase of lu~g cll,lS U recoil after a long RV volume history ts a we established fact (18] . ted

Thus the present data after EEBH may be interpre

d

EFFECTS OF MAXIMAL BREATH HOLDING ON MAXIMAL EXPIRATORY FLOWS 343

result of higher increase of R compared to the of lung clastic recoil in theSe dynamic condi­

BBBI I leads to sustained extreme TPP changes ,.na11 airway closure so !hat the recovery of air­rn~le wne [19] could be incomplete. This would

10 lower airways hysteresis with respectS to pul­hyst.cresis whatever !he action of drugs on bron­

This is a rnther unusual fact for healthy during normal ventilation, but it has been in some asthmatics [20, 21) in relation with inflammation.

, !his study shows that in normal subjects expiratory flows are increased after EIBH and

after EEBH. These modifications are slight JJliY be mostly, if not exclusively, explained by

degrees of mechanical changes at the level of and of the airways.

Acknowkdg~m~nu: The authors !hank lhe techni­cal staff or the pulmonary function test unit "Lavoisier" for !heir participation and S. Madec for typing !his manuscript.

References

Hyatt RE. - Expiratory flow-limitation. J Appl Physiol: Environ Exercise Physiol, 1983, 55 (1), 1-8.

M, Mead I. - Time dependence of flow volume I Appl Physiol, 1974, 37 (6) 793-797.

BA, Guz A, Jain SK, Archer S, Stevens I, F. - The effect of anaesthesia of the airway in dog a study of respiratory reflexes, sensations and lung

Clin Sci Mol Med, 1976, 50, 439-454. l!.Ja,v1dSon IT, Whipp B, Wasserman K. Koyal SN,

. - Role of the carotid bodies in breath holding. Med, 1974, 290, 819- 822.

J, Trenchard D. Burki N, Guz A. - The effect of W~l block on respiratory sensations and control in man

Set, 1968, 35, 23-33. Otls AB, Rahn M, Ferm WO. - Alvrolar gas changes

breath holding. Am J Physiol, 1948, 152, 674-686. SV, Lin YC, Lally DA, Yin JB, Kominami N,

, Moore TO. - Alvrolar gas exchanges and cardia-functions during breath holding with air. 1 Appl

1971, 30 (4), 540-547. Ambrogio G. - Nervous receptors of the trachco­

lree. Ann Rev Physiol, 1981, 49, 6!1- 627. Widdicombe JG, Nadel JA. - Reflex effects of lung in-

on lracheal volume. 1 Appl Physiol, 1963, 18, 681-686. Bowes G, Shakin EJ, Phillipson EA, Zamel N. - An

pathway mediating reflex tracheal dilation in awake J Appl Pllysiol: RespiraJ Environ Exercise Physio/, 57 (2) 4 \3-418.

JE, Sellick H, Widdicombe JG. - The role of lung receptors in respiratory responses to multiple pulmo­

embolisms, anaphylaxis and histamine bronchocon­J Physiol, (Lond.), 1969, 203, 337- 357.

12. Santamaria S, Guillemi S, Osbome S, Coppin C, Dahlby R, Pare PD. - Site of bronchodilation with inhaled ipratro­pium bromide and Fenoterol in normal subjects. Chest, 1987, 91 (1). 86-90. 13. Lundberg IM, Saria A. - Polypeptide-containing neurons in airway smooth muscle. Ann Rev Physiol, 1981, 49, 551-512. 14. Orehek J, Gayrard P, Grimaud C, Charpin I. - Effect of maximal respiratory manoeuvres on bronchial sensitivity of asthmatic patients as compared to normal people. Br Med J, 1975, 1, 123-126. 15. Vincent NI, Knudson R, Leith DE, Macklem PT, Mead I. - Factors influencing pulmonary resistance. J Appl Phys­iol, 1970, 29 (2), 236-243. 16. Wellman JJ, Brown R, Ingram RH Jr, Mead I, McFaddcn ER Jr. - Effect of volume history on successive partial expiratory flow-volume manoeuvres. J Appl Physiol, 1976, 41 (2), 153- 168. 17. Proeb HP, Mead I. - Relative hysteresis of the dead space and lung in vivo. J Appl Physiol, 1968, 25 (3), 244-248. 18. Butler J, Caro CO, Alcala R, Dubois AB. - Physiologi­cal factors affecting airway resistance in normal subjects and in patients with obstructive respiratory disease. J Clin Invest, 1960, 39, 584-591. 19. Gunst SI. - Contractile force of canine airway smooth muscle during cyclical length changes. J Appl Physiol: Respi­rat Environ, Exercise Physiol, 1983, 55 (3), 759-769. 20. Gayrard P, Orehelc J, Grimaud C, Charpin J. - Bron­choconstrictor effects of a deep inspiration in patients with asthma. Am Rev Respir Dis, 1975, 111, 433-439. 21. Pichurko BM, Ingram RH Jr. - Effects of airway tone and volume history on maximal expiratory flow in asthma. J Appl Physiol, 1987, 62 (3), 1133- 1140.

EffeJs des apnees volontaires maximales sur les debits expi­raJoires maximaux. P. Mialon, L. Barthi/emy, P. Sebert. RESUME: Les effets des apnees volontaires poursuivies jusqu'a leur point de rupture, sur le tonus broncho-moteur, ont ete ctudies en utilisant les courbes volume-debits expiratoires mnximnux. L'npnu volontaire a ete r4nllsee, soit 11 un vol ­ume pulmonaire elev6 (cap.u:ite pulmonnire totale, EIBH) ou /) un petit volume pulmonaire (volume residucl+250 ml, EEBH). une manoeuvre inspiratoire pr~anl imm&liatemcnt hl mesurc de In courbo volume-debit expiratoin: m~tJtimum. Nos resultats montrent que 1) EIBH entraine une augmenta­tion significative du debit expiratoire a 25% de la capacite vitalc forcee, 2) EEBH entraine une diminution significative Cl constantc des debits expiratoirc.s a 50 et a 25% de Ja CB·

pncitc vitale for<:U. Les mernc modi fiC3tions ont Cte cnregis­trecs npres inhalation de 400 ).lg de fenoteml ou de 80 ).lg de bromide d'iprntropiunl. Les rerult:us observes suggercnt des cffcts m&nniques de l'opnee volontuirc $111 Jcs debits e.11pira-1oires; apres une upnee inspintoirc, c'cst !'hysteresis des voies ol!ricnncs qui domine sur l' hyst~esis pulmonnirc. et npres une :~rnce expiratoin: c'cst J'cffet oppose qui se produit. Eur Respir 1 .. 1989. 2, 340-343.