Sympathoadrenal Reactivity in Exercise-induced Asthma

It is well known that 3-adrenoceptor blockade may cause bronchoconstriction and that -adrenoceptor stimulation induces bronchodilation in patients with bronchial asthma. There is also evidence (or the existence of a-adrenoceptors in human airways, the stimulation of which may induce contraction of human bronchial smooth muscle. Conversely, a-adrenoceptor blockade may counteract or reduce bronchoconstriction provoked by allergen, exercise, or histamine. Hence, adrenergic mechanisms seem to be important for the regulation of bronchial tone in patients with bronchial asthma. This raises two questions. First, is the liberation of endogenous adrenergic agonists altered, ie, is sympathoadrenal reactivity altered in asthmatic patients? Second, is there an altered adrenergic receptor sensitivity in asthma, as suggested by Szentivanyi.

Sympathoadrenal reactivity in asthma has not been the subject of intense investigation. However, some studies have shown that patients with exercise-induced asthma (EIA) obtain higher plasma levels of noradrenaline during work than healthy control subjects. The conclusion of these studies has been that postexercise bronchoconstriction is the result of a-adrenoceptor stimulation caused by an excessive production of endogenous noradrenaline.

Since there are limitations with regard to patient selection, standardization of antiasthmatic treatment, and standardization of the experimental procedures in the above-mentioned studies, we attempted to study these problems further. The present report concerns sympathoadrenal reactivity in asthmatic patients with a history of EIA and in patients with nonexercise-induced asthma (NEIA).

Exercise-induced asthma

Material and Methostrong

Sixteen asthmatic patients and eight healthy control subjects participated in the study. The patients were divided into two groups, one with a history of EIA and one with a history of NEIA. The healthy control subjects (group C) had no history of asthma or any other allergic manifestation. All subjects were nonsmokers, and the three groups were matched with regard to sex and age (Table 1). Articles about bronchical asthma treatment see in category

Each subject was studied on two occasions, separated by less than two months. On the first occasion a pretrial exercise test was performed on a treadmill to define the maximal work capacity of each individual. During this exercise test, the maximal ventilation (Ve) and the maximal oxygen
uptake (Vo2) were measured. The exercise was submaximal during the first five minutes, after which die work was increased stepwise until exhaustion. Before, immediately after, and 5, 10, and 20 minutes after this exercise test, FEVj and VC were measured with a Vitalo-graph. Subsequendy, 160 tig of isoproterenol (Isoprenaline, ACO, Sweden) was inhaled from a pressurized aerosol, and five minutes later a final spirometric measurement was performed. This pretrial exercise test was used to confirm the existence of exercise-induced bronchoconstriction and to predict the work level at which the experimental exercise test should be performed. Exercise-induced asthma was defined as a decrease in FEVj of more than 15 percent when compared with basal preexercise values. Also read the article: “ATS Publishes Clinical Practice Guidelines on Exercise-Induced Bronchoconstriction“.

On the second occasion all subjects had been without any kind of medication for at least seven days. Thoracic gas volume (TGV), airways resistance (Raw), and, from this, specific airways conductance (Sgaw) were measured in a volume-constant body plethysmograph. The mean values of ten initial measurements at the subject’s functional residual capacity (FRC) were calculated. The subjects then received a venous cannula, after which they rested in the supine position for 25 minutes. After this rest, two venous blood samples (10 ml) were collected at five-minute intervals, and heart rate, blood pressure, and lung function were measured. Blood pressure was measured with a conventional arm cuff; the diastolic pressure was defined as the point where the Korotkoff sounds were muffled. This procedure was repeated after another five minutes of rest, after which an orthostatic test was performed. Heart rate and blood pressure were measured in the recumbent position, immediately after standing, and after four and eight minutes in the upright position. At the end of the orthostatic test, a venous blood sample was collected, and measurements in the body plethysmograph and the Vitalograph were repeated. Thereafter, an exercise test was performed on the treadmill at a submaximal work level (90 percent of maximal Vo2) during eight minutes. The breathing frequency was registered during the last minute of exercise and heart rate was continuously monitored by ECG. Following this exercise test, venous blood samples were collected at 0, 5, and 25 minutes. Plethysmographic measurements were made at 6, 11, and 26 minutes after exercise and FEV1 and VC were measured immediately thereafter. Outcomes of airway remodeling see here.

Venous blood was collected in ice-cooled centrifuge tubes containing EDTA (10 mM final concentration). The samples were centrifuged in the cold, and plasma was subsequently stored at — 80 °C. Plasma samples were later analyzed for contents of adrenaline, noradrenaline, and dopamine (by HPLC with electrochemical detection according to Hjemdahl et al), glycerol, and cAMP. The catecholamine assay sensitivity was better than 0.05 nM for all three catecholamines using 2 ml of plasma. The inter- and intra-assay coefficients of variation in the assay were 2 to 3 percent for noradrenaline (at basal levels of 1 to 2 nM) and 9 to 12 percent for adrenaline and dopamine (at basal levels of 0.1 to 0.2 nM, less at higher levels).

On the days of the exercise tests the patients were supposed to be in a free interval of their disease. Therefore, the basal FEVj was not allowed to differ more than 10 percent between the two occasions. Statistical evaluation was performed by three-way analysis of variance. Results are presented as mean values ± SEM.

This study was approved by the Ethical Committee of Karolinska Institutet, Stockholm.

Table 1—Clinical Data

Group Subject/Age, yr/Sex EIA 1/61/M Height,cm164 Weight,kg67 VerifiedAllergy Duration Asthma, ]4 offt Medication (when required: w.r.) Fenoterol (aerosol) w.r.
2/21/M 187 75 11 Fenoterol (aerosol) w.r.
3/23/F 172 65 2 Terbutaline 2.5 mg (tab) w.r.
4/30/F 159 53 4 Terbutaline (aerosol) w.r.
5/48/M 175 63 8 Disodium cromoglycate (Spinhaler) w.r. Fenoterol (aerosol) w.r.
6/25/M 179 67 8 Salbutamol (aerosol) w.r.
7/21/M 180 63 1 Disodium cromoglycate (Spinhaler) q.i.d.
8/23/M 185 82 1 Terbutaline (aerosol) w.r.
NEIA 1/53/M 184 80 51 Terbutaline 2.5 mg (tab) w.r.Disodium cromoglycate (Spinhaler) w.r.
2/22/M 189 74 20 Disodium cromoglycate (Spinhaler) t.i.d.
3/27/F 168 73 1 Choline theophyllinate 135 mg (tab) w.r.
4/35/F 170 69 32 Salbutamol (aerosol) w.r.
5/52/M 180 85 10
6/28/M 185 99 10
7/15/M 177 65 1 Terbutaline 5 mg (tab) w.r.
8/21/М 169 68 1 Fenoterol (aerosol) w.r.
С 1/60/M 182 83
2/25/M 172 57
3/24/F 163 55
4/28/F 168 68
5/54/M 192 103
6/25/M 180 78
7/20/M 183 61
8/21/М 181 74