rsibility of induced bronchoconstriction by deep inspiration in asthmatic and normal subjects J.R. Wheatley, P.D. Pare, LA. Enget of induced bronchoconstriction by deep inspiration in asthmatic Thoracic Medicine Unit, Westmead Hospital, ., ...,~"~''" · J.R. Wheatley, P.D. Pare, L.A. Engel. Wes!mead NSW 2145, Australia . normal and flve asthmatic subjects underwent a Correspoodence: Dr I.R. Wheatley, Tho111cic Medi· methacholine provocation study. Af each concentration In· cine Unit. Dept of Medicine. We..trnead Hospital. pulmonary resistance (RL) was measured, as well as lsovolumlc We..tmead NSW 2145, Australia. now and residual volume from both partial and complete Keywords: Airway closure; airway obstruction; lrallons. Results were compared over the RL range of '-11 aitway mislllnce; panial flow-volume curve•. 1• The reversibility of bronchoconstrlctlon by deep Inspiration as the ratio or the flow Increase to potential maximal In· Received: February, 1988; accepted after revision: the reverslblUty or gas trapping was the ratio or decrease In November 21, 1988. volume to potential maximal decrease. The reverslblllty or bron- Supported by NSW Department of Health and NH lon did not differ between the groups. In contrast, the revers!· and-MRC of Australia. tra,~nlru• was smaller In asthmatic subjects (21±17%) than ). As gas trapping renects airway closure, our find­ that during Induced bronchoconstrlctlon airway closure ls ~11sta 1nt to the effects or deep Inspiration In asthmutk: than In subjects but the reversibility or bronchoconstrlctlon by deep ls not different. J .. 1989, 2, 331-339. c0onnal subjects with pharmacologically-induced reference lung volume and decreases in residual volume, a deep inspiration transiently re­ following a deep inspiration, we derived indices of airway resistance [1). However, in asthmatic sub­ reversibility that differed conceptually from those pre­ the effect of a deep inspiration is variable. With viously used and allowed quantitative comparisons be­ IIJtalllCO I~s asthma, deep inspiration usually results in tween the two groups of subjects. ncru:JCOJutrJctil)n [2-7] whereas during pharmacologi­ airway narrowing transient bronchodilata- is the usual response [3, 6, 8, 9-12). In fact, it has Methods suggested that the ability of a deep inspiration tO induced bronchoconstriction may be less in asth­ We studied five nonnal (4 men and 1 woman) labo­ than in nonnal subjects. FisH et al. [ 13) showed ratory personnel and five asthmatic (4 men and I when airway responsiveness to inhaled meth­ woman) volunteers (table 1), none of whom had ever is used to distinguish normal and asthmatic smoked cigarettes on a regular basis. The nonnal sub­ a clear separation between the two groups can jects gave no history to suggest that they were atopic CJCJnn,,<lr"''"'rl by using tests which involve a deep and had no history of respiratory symptoms. Asthmatic such as the forced expired volume in one subjects gave histories of regular episodic attacks of 1) or maximal expiratory flow.s. In contrast. wheezing since childhood requiring bronchodilator treat­ as airway resistance, or maximal flow rrom ment. All had refrained from use of inhaled broncho­ flow-volume curve do not demonstrate a de­ dilators for six hours prior to the study and none separation. The authors suggested that a major complained of dyspnoea Or wheezing on the day. Theo­ between asthmatic and nonnal subjects might phylline was also withheld for 48 h. No subject gave impaired bronchodilating capacity of a deep a history of respiratory· uact infection during the ...,,. ,_,,,ft rather than enhanced end-organ responsive- preceding month. Informed consent was obtained and [4]. the protocol was approved by the Medical Ethics further investigate these differences, we have Committee of the Institution. the bronchodilating effect of a deep inspi­ Each subject was studied in the prechallenge baseline an a group of highly hyperresponsive asthmatics state and !hen inhaled doubling concentrntions of nebu­ a &roup of non-atopic normal subjects during a lized methacholine (0.03~ 128 mg·ml·1) according to the 'llllllli!Pr,..... inhaled melhacholine provocation study. protocol of CocKCROFT et al. [14). We used a Becton­ increases in maximal expiratory flow at a fixed Dickinson nebulizer which delivered 0.26-0.30 ml of 332 1.R. WHEATLEY P.D. PARE, L.A. ENGEL Table 1. - Baseline anthropometric data and lung function Age Sex FEV1 FVC TLC FRC RV RL Vmax,0, Vmax,o. FE VI cmHzO FVC yrs %pred %prod %pred %pn:d %prcd P·s·• l·s·• l·s·• % mg·mt-1 NolTilal 1 35 M 108 102 96 108 78 1.4 3.8 3.3 87 >128 2 45 F 116 113 104 88 82 2.8 2.4 2.4 86 >64 3 26 M 107 106 112 102 114 2.7 2.7 3.0 83 >128 4 40 M 103 111 119 132 128 2.1 1.9 1.9 76 >64 5 31 M 100 102 112 142 143 2.6 2.5 2.5 82 >128 Mean ±SBM 35 107 107 109 114 109 2.3 2.7 2.6 83 ±3 ±3 i2 :l4 ±10 ±13 ±0.3 ±0.3 ±0.2 ±2 Asthmatic 1 25 M 69 106 119 146 150 8.9 0.6 0.7 57 0.02 2 35 F 102 118 121 123 134 3.0 1.4 1.3 72 0.03 3 28 M 88 112 117 151 140 3.2 0.9 1.8 66 0.4 4 26 M 88 105 108 121 108 4.0 0.8 1.0 69 0.4 5 25 M 89 104 96 87 63 3.3 1.5 1.5 70 0.9 Mean ±sBM 28 87 109 112 126 119 4.5 1.0 1.2 67 ±2 ±5 ±'3 :15 ±ll ±16 ±1.1 ±0.2 ±0.2 ±3 FEV1: forced expiratory volume in one second; PVC: ron:cd vilal capacil}': TLC: total lung capacily; FRC: ftmctional Mf capacity; RV: residual volume; R1..: pulmonary resist.mcc: 'Vm31CJF\! Vmax,o.: muimal expiratory flow at 30% or viull to on a pattial and complete forced c.~tpi rati on, respectively; FBV 1 C: ratio of FBV PVC on a c:omple1c forced exp PC10: provocalion c:oncentralion of methacholine needed to produce n 20% foil in FEV1; lrcatment regimens: I: salbutomol P" 2: regular salbutamol daily; 3: rcgulor salbutamol and tJ~eophyllin e SR dai ly. methacholine solution over 2 min at an air flow rate TLC of 6 l·min·•. After each dose of methacholine, subjects were instructed to avoid deep inspirations or sighing for 2 min. following which the measurements were made. Asthmatic subjects commenced with 0.03 mg·ml·1 meth­ acholine and doubling concentrations were inhaled until FEV1 decreased by at least 50%. In contrast, normal subjects started with 0.5 mg·ml·1 methacholine and were given doubling concentrations until 64-128 mg-mt·• was reached. After a stable end-expiratory lung volume had been AV, established, pulmonary resistance (RL) was measured Time while subjects breathed ~t a spontaneous frequency. Tidal volume was fixed at 750 ml by having the sub­ ject breathe between predetermined limits displayed t9 Fig. 1. - Scllemalic represenlation of the Jequence of forced ~ them on an oscilloseope. A partial forced expiration ra1ion1 for eaeth set of measun:men1.1. RV and RV, _•rc: the rcJ volumes after the p:anial and complete loreed a ptrallonJ, re~ from tidal end-inspiratory volume to residual volume lively. VtN.\'"" and \)mu, •re the maximal cxpiraWI)' no~:. (RV,> was then performed, followed by a rapid inspi­ 30% of basehne vital <:apac11'y on pantal and complete "'llll(J(U ration to total lung capacity ('ILC) and an immediate resp«li vely. TLC is tolnl lung c:apacily. complete forced expiration to residual volume (RV,) (fig. 1). This sequence of measurements was obtained During measurements of RI., flow was recorded u~= under baseline conditions and after each dose of meth­ a Flcisch No. 2 pneumotachograph coupled to a . ,. idyne MP 45 (±5 cmH 0) differential preSS11 acholine. 2 10 Transpulmonacy pressure was measured by com­ transducer and the signal was elecrrically integrn te!es. paring mouth and oesophageal pressure using a Val­ give volume. During forced expiratory m n!l oe~ flow and volume were measured with an idyne MP 45 (±100 cmH 10) differential pressure c l~ the transducer. Oesophageal pressure was measured with a autospirometer (Minato AS-800) and recorded wllh ncl balloon using the technique of Miuc-EMJU et al. {15). pressure signals on a Hewlett-Packard 8-c ban REVERS!Dll.ITY 01' INDUCED BRONCHOCONSTRICTION 333 recorder (7758B) and magnetic tape recorder (Vmax3o) manoeuvres (fig. 1). The isovolumic points The transpulmonary pressure-flow relationship are more accurately determined by subtracting a fixed subsequently measured by the method of MEAD volume from TLC (which does not change) than by \VI{Trll!NBEROI!R [16] and RL was obtained from adding a fixed volume to RV (which increases with Jnsplrotory limb of the pressure-flow curve at bronchoconstriction). 1 rate of 0.5 l·s- • On a separate occasion, abso­ To compare the effectiveness of a deep inspiration in volumcs were measured in a volume displace- reversing bronchoconslriction and gas trapping in nor­ plethysmograph using the Boyle's Law method mal and asthmatic subjects, we measured the responses to a deep inspiration at similar levels of RL (as a meas­ ure of induced bronchoconstriction). Mean values of Vmax~, VmaxlOc' RV and RV. were compared in the range 6-11 cmHP·i·•.$-•. This resistance range was cho­ lung capacity was assumed not to change sen as there was a reasonable overlap of values between the study. including the period of induced the two groups (fig.