Thorax: first published as 10.1136/thx.35.4.298 on 1 April 1980. Downloaded from

Tl.orax, 1980, 35, 298-302 elastic recoil and reduced airflow in clinically stable asthma D S McCARTHY AND M SIGURDSON From the Department ofMedicine, University ofManitoba, Respiratory Division, Clinical Investigation Unit, Winnipeg, Manitoba, Canada

ABSTRACT , maximum expiratory flow rates, and static volume-pressure curves were measured in 16 patients with clinically stable asthma. It was found that flow rates were reduced in such patients because of the combined effects of reduced elastic recoil (transpulmonary pressure) and intrinsic diseases of the airways. In nine patients treated with an aerosol of isoprenaline, flow rates improved as a result of reduction in airways resistance as the static recoil pressure of the fell further in those patients. The possibility is suggested that muscle tone in peripheral airways or alveolar ducts contributed to the elastic recoil measurements.

Table 1 Age, sex, and diagnostic criteria used to A number of studies have demonstrated that select 16 patients with asthma acute exacerbations of asthma may be ac- companied by shifts in the pressure-volume Criteria Total group Isoprenaline group curve of the lungs indicating reduction of elastic (n = 16) (n =9) recoil. For example, Gold et all found that lung Male 11 6 Female 5 3 http://thorax.bmj.com/ elastic recoil was decreased in 12 asthmatic Age (yr) (mean and range) 46 (25-65) 46 (20-70) patients before treatment. Later, Finucane et Positive skin tests (type 1) 11 (69%) 6 (67%) Eosinophil counts > 400/ml 11 (69%) 5 (56 Y.) at2 reported that elastic retraction was decreased 16 9 in 10 asthmatic subjects with reduced forced Paroxysmal episodes expired volume in the first second (FEVy). In response both series, the lung recoil usually returned to (mean Y. predicted and range) baseline values when the airflow obstruction was FEVI before (5% predicted) 62 (49-77) 59 (44-77) relieved. Similar findings were reported by FEV, after (% predicted) 92 (84-108) 89 (69-107)

Mansell et al3 after antigen-induced asthma. on September 28, 2021 by guest. Protected copyright. However, Woolcock et al4 found that reduced five women, who were studied are shown in lung elastic recoil persisted in five of 10 asth- table 1; nine patients who were not dissimilar matic subjects even when had to the entire group received aerosol isoprenaline. returned to normal. Since many patients with No effort was made to allocate patients asthma satisfactorily controlled from a clinical selectively to this group. All patients were adult standpoint (stable) have persistent airflow non-smokers and the age distribution was similar obstruction, we wished to determine whether in both groups. The following features supported there was persistent loss of lung elastic recoil in the diagnosis of bronchial asthma. Reaginic such patients which would tend to decrease ex- mediated, wheal and flare reactions (type 1) piratory flow. We also wished to examine the were obtained in the majority of patients (69% immediate effects of bronchodilator therapy on and 62 %) on skin testing with a range of elastic recoil in clinically stable asthmatics. common allergens. Peripheral blood eosinophilia, as indicated by eosinophil counts in excess of Methods 400/ml, was present in most patients (69% and 56%). The five patients with normal counts were The characteristics of 16 patients, 11 men and taking corticosteroid medication. All patients had a history of paroxysmal episodes of wheeze and dyspnoea developing over an hour or less Address for reprint requests: Dr DS McCarthy, Department of Medicine, University of Manitoba, Respiratory Division, Clinica without symptoms of respiratory infection. All Investigation Unit, Winnipeg, Manitoba, Canada. 298 Thorax: first published as 10.1136/thx.35.4.298 on 1 April 1980. Downloaded from

Lung elastic recoil and reduced airflow in clinically stable_asthma 299 had shown reversibility of airway obstruction in increased their pulse rates by 20% or they that they had demonstrated at some time in the developed palpitations or became "shaky". All past an increase of at least 20% in FEV1 im- measurements were repeated within 45 minutes. mediately after of bronchodilator. Six subjects had radiological evidence of hyper- Results inflation while the remainder had normal chest radiographs. All subjects were outpatients at the Though our asthmatic subjects were in clinical time of the study and were deemed by their remission at the time of this study, airflow physician to be in a "stable" state. This was obstruction was present in all patients (table 2). indicated by a satisfactory clinical state and by The maximum expiratory flow rate of 50% VC spirometric values which were within 10% of was less than 80% predicted in all patients and the patients' best efforts over the previous six residual volume (RV) was increased in 15 months, during which three or more interval patients. Static pressure-volume curves of the measurements were made. All patients were lung are shown in fig 1, volume being expressed taking oral aminophylline 325 mg four times as per cent predicted TLC. It can be appreciated per day and aerosol isoprenaline more than twice that especially at high lung volume the pressure- per day. Five patients were taking prednisone, volume relationships were in general displaced, 5-15 mg daily at the time of the study and had indicating loss of recoil pressure. The pressure- been doing so for between two and four years. volume curve for the nine patients before Two further patients had been treated with isoprenaline approximates more closely to the systemic corticosteroids in the past and three normal predicted values than those of the entire patients were taking inhaled beclomethasone. group because a number of subjects with (VC), FEVY, and maximal relatively normal curves are included in the expiratory flow-volume curves were measured with former group. an automated wedge spirometer.5 Using these The relationship between maximum expiratory curves, flow rates at 90, 75, 50, and 25 % VC airflow and static transpulmonary pressure were measured. Functional residual capacity defines the resistance upstream from the equal a and (FRC) was measured using body plethysmo- pressure point.8 This relationship at 90, 70, http://thorax.bmj.com/ graph.6 The elastic recoil of the lungs was 50 per cent of TLC predicted is shown in fig 2. determined with the subject seated. The static Because of gas trapping, data were not always transpulmonary pressure-volume curve of the available at 50% and 70% predicted TLC. In lungs was measured during interrupted vital these patients only data acquired at higher lung capacity expirations; the interruptions were ac- volumes is shown. Maximum flow rates were complished by occluding the mouthpiece. reduced in our patients; only two achieved flows Transpulmonary pressure was measured as the exceeding 5 I/s at 90% predicted TLC. Some difference between pressures measured at the patients showed low flow rates despite relatively mouth and in the oesophagus. Oesophageal normal static recoil pressures, their curves were on September 28, 2021 by guest. Protected copyright. pressure was recorded from a 10 cm latex displaced down and to the right. In these in- balloon containing 0 5 ml air at the end of a dividuals, flow rates were low primarily because small polyethylene catheter which was connected upstream resistance was increased. This is well to a differential strain gauge and positioned in the mid-oesophagus according to the method of Table 2 Lung volume and flow rates in the 16 Milic-Emili et al.7 The other side of the differ- asthmatic subjects at the time of the study ential strain gauge was connected to a lateral pressure tap in the mouthpiece. Lung volumes Y. VC Flow (I/s) Mean ±SD % predicted were determined by integration of airflow 90 6 84+2 01 84 measured at the mouth by means of a Fleisch 75 413±207 57 50 2-02±108 40 pneumotachograph (no 3) connected to a 25 0-72±0-41 30 Statham strain gauge (no 5). Normal values for FEVi (1) 2-42+0-91 72 lung elastic recoil and upstream resistance were FEV1/VC(%) 57 +14 those measured in the same way in 30 age- TLC (1) 7-30+1-4 121 in our own FRC (1) 4-10+1-0 122 matched normal non-smokers RV 3-04+1-0 152 laboratory. (1) After the above measurements, nine subjects Mean values ± 1 SD; per cent predicted (Y. PR); airflow at 90, 75, a hand 50, and 25 per cent vital capacity (Y. VC); total lung capacity inhaled 0'5% isoprenaline delivered by (TLC); functional residual capacity (FRC); and residual volume nebuliser (DeVilbiss no 42 nebuliser) until they (RV). Thorax: first published as 10.1136/thx.35.4.298 on 1 April 1980. Downloaded from

300 D S McCarthy and M Sigurdson 10- 140 - i 8- 20- 6-

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0 60 10 20 Pst (cmH20) Fig 2 Relationship between maximal expiratory 40 --i flow (Vmax) and static recoil pressure of the lungs in 16 patients with chronic asthma. Transpulmonary pressure on the abscissa is plotted against expiratory .A-I flow rate in litres per second on the ordinate at 90, .-- 70, and 50% TLC predicted. Normal values from 30 matched subjects for pressure and flow ± ISD C. 20..C indicated by the bars at 90 (A), 70 (0), and http://thorax.bmj.com/ I:: 50% (A) TLC (predicted). Fig. 1 Static expiratory lung pressure-volume curves from 16 patients with chronic asthma. Transpulmonary pressure on the abscissa is plotted against lung volume as per cent total lung capacity predicted. Stippled area represents five values ±'I SD from 30 normal matched subjects. The 19n2 observed value for TLC in each normal subject was

la on September 28, 2021 by guest. Protected copyright. designated 100% and the transpulmonary pressure ._ 0o calculated in decrements of 10%. ,0100- seen in four of the patients. However, in more g 80- /X / than half the patients the data fell within the *," / predicted pressure-flow relationships, indicating in these in was that subjects reduction flow rate 04 caused predominantly by loss of lung elastic oF. 60 recoil. */ After use of the bronchodilator aerosol there a was an increase in maximum expiratory flow (table 3) which was significant at all lung 5 10 15 20 volumes except 25% VC. Figure 3 demonstrates that the lung elastic recoil was reduced after Pst (cmH20) isoprenaline. There was no significant change Fig 3 Static expiratory pressure-volume curves in lung volumes. Three patients had similar before (-) and after (O) isoprenaline. studies before and after inhalation of 6 mls Transpulmonary pressure on the abscissa is plotted of aerosolised normal saline. No change in lung against lung volume per cent predicted on the function was observed. ordinate; *=statistically significant change (<0,05). Thorax: first published as 10.1136/thx.35.4.298 on 1 April 1980. Downloaded from

Lung elastic recoil and reduced airflow in clinically stable asthma 301 Table 3 Maximum expiratory flow-volume before not thought justifiable to treat our patients who and af er isoprenaline were satisfactorily controlled on a clinical level with further medication in order to achieve Per cent Patients Flow rate Flow rate p capacity before (l/s) after (I/s) normal airflow measurements and possible reversal of the lung elastic recoil change. From 90 9 6-35+2 16 7-05±2-00 < 0-01 75 9 3-43±1-95 4-16±2 36 < 0 025 the data quoted above and reported here, it 50 9 1-67±1-08 1-99+1-25 < 0.025 would seem that many asthmatic patients with 25 9 0-64+0-42 0 90±0 65 NS residual or no airflow obstruction and in clinical FEVI (1) 9 1-97+0-82 2-40+-0-91 < 0-001 remission have reduced lung elastic recoil. FEV1/VC (Y) 9 52+10 60±12 < 0 001 The mechanism responsible for loss of lung p =statistical significance of the changes. elastic recoil in asthma is not known. Published reports of the morbid anatomy of asthma do not contain descriptions of pathological emphysema. Discussion Because lung recoil has been shown to decrease rapidly with the onset of an attack, changes in Our results suggest that many patients with the amount or type of surfactant are unlikely, asthma have diminished pulmonary elastic recoil but it is possible that the distribution of even when they are in a satisfactory clinical surfactant is altered with asthma. It was state (fig 1). The relevance of decreased lung suggested by Woolcock et a!4 that prolonged elastic recoil is illustrated in fig 2 which indicates steroid therapy many have contributed to that in some patients reduced airflow ra-tes ap- reduced elastic recoil. This is an unlikely ex- peared largely because of decreased lung elastic planation as six of our patients who had never recoil. However, increased airflow resistance is been treated with corticosteroids demonstrated also important as flow rates after use of the decreased elastic recoil. It is also unlikely that aerosol increased despite lung tobacco smoking influenced the measurements elastic recoil decreasing or remaining unchanged as only two of our patients had ever smoked. (table 3, fig 3). Our finding of reduced lung The rapidity of the changes of lungs and chest elastic recoil in stable asthma is in agreement wall recoil in the course of an asthmatic attack http://thorax.bmj.com/ with that of Woolcock et a!4 who found that loss are compatible with a neurogenic mechanism of elastic recoil persisted in five of 10 asthmatics and such a mechanism has been postulated.9 when the acute attack subsided. Finucane et a!2 Persistence of loss of recoil in some asthmatics also found that in four of 10 patients decreased in complete remission reported by Woolcock elastic recoil persisted for more than six weeks et a!4 and by Finucane et a!2 is further evidence of remission after successful treatment of acute that the mechanism of loss of lung elastic recoil attacks. The latter authors suggested on the is complex and not well related to airway basis of their observations that some asthmatics obstruction as measured by tests such as FEV1, may have permanent reduction of elastic recoil. airway resistance, or MMF. on September 28, 2021 by guest. Protected copyright. Conversely, Gold et all found decreased elastic We found that in our stable asthmatic patients recoil in seven young (<28 yr) patients with inhalation of isoprenaline was associated with chronic asthma but recoil reverted to normal a further decrease in elastic recoil (fig 3). after intensive therapy and return of airway McFadden et al'0 noted that elastic recoil in the resistance to normal. Our study population mid and upper lung volumes decreased after differed from Gold et al! in that our group of normal subjects inhaled isoprenaline but the chronic stable asthmatics was older, in clinical change;s they observed were smaller than the remission, and already receiving what was con- ones we noted. Our results were similar to obser- sidered adequate bronchodilator therapy though vations made by Colebatch" who found that evidence of residual airflow obstruction peristed. isoprenaline decreased recoil in cat lungs. He The difference in age between the patients in postulated that this was because it reduced our study and those studied by Gold et all is smooth muscle tone in peripheral airways which unlikely to be the total explanation as three of contribute to lung elastic recoil. This hypothesis the five patients with persistent loss of lung would explain our findings. A recent publication elastic recoil reported by Woolcock et a!4 were by Laitinen et al,12 describing an increase in lung young (<30yr). Neither is the duration of the recoil in normal subjects after intravenous disease likely to be important as the mean histamine, gives support to the suggestion that duration in our study was 7-6 years while that peripheral airways may contribute to lung recoil in the study of Gold et all was 11 5 yrs. It was measurements in humans. Thorax: first published as 10.1136/thx.35.4.298 on 1 April 1980. Downloaded from

302 D S McCarthy and M Sigurdson In conclusion, we wish to point out that in 6 DuBois AB, Botelho SY, Bedell GN, Marshall R, many asthmatic patients in clinical remission Comroe JH Jr. A rapid plethysmographic there is evidence of reduced lung elastic recoil method for measuring thoracic gas volume: a which contributes to reduced airflow measure- comparison with a method for ments in such patients. It is possible that muscle measuring functional residual capacity in normal tone in the peripheral airways underlies the subjects. J Clin Invest 1956; 35:322-6. 7 Milic-Emili J, Mead J, Turner JM, Glauser EM. changes observed. Improved technique for estimating pleural We thank Dr N R Anthonisen for his con- pressure from esophageal balloons. J Appl structive criticism in the preparation of this Physiol 1964; 19:207-11. paper. 8 Mead J, Turner JM, Macklem PT, Little JB. Significance of the relationship between lung References recoil and maximum expiratory flow. J Appl 1 Gold WM, Kaufman HS, Nadel JA. Elastic Physiol 1967; 22:95-108. recoil of the lungs in chronic asthmatic patients 9 Peress L, Sybrecht G, Macklem PT. The before and after therapy. J Appl Physiol 1967; mechanism of increase in total lung capacity 23:433-8. during acute asthma. Am J Med 1976; 61:165-9. 2 Finucane KD, Colebatch HJH. Elastic behavior 10 McFadden ER, Newton-Howes J, Pride NB. of the lungs in patients with airway obstruction. Acute effects of inhaled isoproterenol on the J Appl Physiol 1969; 26:330-8. mechanical characteristics of the lungs in normal 3 Manswell A, Dubrawsky C, Levison H et al. man. J Clin Invest 1970; 49:779-90. Lung mechanics in antigen-induced asthma. J 11 Colebatch HJH. The humoral regulation of Appl Physiol 1974; 37:297-301. alveolar ducts. In: Bouhouys A (ed). Airway 4 Woolcock AJ, Read J. The static elastic proper- Dynamics. Springfield, Illinois: Charles C ties in the lungs in asthma. Am Rev Respir Dis Thomas, 1970; 169-89. 1968; 98:788-94. 12 Laitinen LA, Empey DW, Poppius H, Lemen 5 Cherniack RM, Raber MB. Normal standards RJ, Gold WM, Nadel JA. Effects of intravenous for ventilatory function using an automated histamine on static and airway wedge spirometer. Am Rev Respir Dis 1972; 106: resistance in normal man. Am Rev Respir Dis 38-46. 1976; 114:291-5. http://thorax.bmj.com/ on September 28, 2021 by guest. Protected copyright.