The effects of hypercapnia and hypocapnia on respiratory resistance were studied in 15 healthy subjects and 30 asthmatic subjects. Respiratory resistance (impedance) was measured with the pseudo-random noise forced oscillation technique while the subjects rebreathed from a wet spirometer in a closed respiratory circuit in which end tidal carbon dioxide tension (Pco2) could be controlled. Hypercapnia was induced by partially short circuiting the carbon dioxide absorber, and hypocapnia by voluntary hyperventilation. The circulating air was saturated with water vapour and kept at body temperature and ambient pressure. A rise of end tidal Pco2 of 1 kPa caused a significant fall in respiratory resistance in both normal and asthmatic subjects (15% and 9% respectively). A fall of Pco2 of 1 kPa did not cause any significant change in impedance in the control group. In the asthmatic patients resistance increased by 13%, reactance fell by 45%, and the frequency dependence of resistance rose 240%. These findings confirm that hypocapnia may contribute to airway obstruction in asthmatic patients, even when water and heat loss are prevented.

SUMMARY A double blind cross-over trial of the non-selective beta-blocker propranolol and the betalselective blocker metoprolol was carried out in 8 hypertensive patients. At the end of each 4-week period of treatment haemodynamic and respiratory indices and perceived exertion were studied during moderate exercise. Both beta-blockers resulted in reduced heart rate, cardiac output, and blood pressure, whereas the stroke volume increased. Total peripheral resistance did not change. During exercise the expiratory peak flow rate equally increased in every period. However, the peak flow rate at rest, as well as during exercise, was reduced by propranolol, while metoprolol had no such influence. Neither of the beta-blockers changed 02 consumption, CO2 production, tidal volume, or respiratory rate. Moreover, they did not influence perceived exertion. These results suggest that the arteriolar and bronchiolar beta2-receptors do not play a major role in the alteration of circulation and ventilation during exercise. As far as their practical use as antihypertensive agents is concerned, this study shows no advantage in the use of either of these beta-blockers.

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In patients with emphysema the integrity of the extracellular matrix (connective tissue skeleton) is compromised. In this study we analyzed glycosaminoglycans, which are main constituents of this matrix, in urines from patients with chronic obstructive pulmonary disease (COPD)/emphysema. Glycosaminoglycans (GAGs) were purified by anion exchange chromatography and quantified using the 1,9-dimethylmethylene blue assay. Heparan sulfate (HS) was assayed using three different chemical methods: digestion with heparitinase or with nitrous acid and by use of an adapted 1,9-dimethylmethylene blue assay. A specific epitope on the HS molecule, defined by the monoclonal antibody JM403, was determined using an inhibition enzyme immunoassay. In patients with COPD total urinary glycosaminoglycan and HS content were not altered. The JM403 epitope of HS, however, was greatly decreased in patients (0.6 versus 4.1 units/mg creatinine for control subjects, p < 0.0001). A similar pattern was observed when patients with bronchial carcinoma with and without emphysema were compared (0.4 versus 2.4 units/mg creatinine respectively, p < 0.0005). Patients with sarcoidosis did not show a decreased epitope content. These results indicate a structural change or an altered processing of the HS molecule in patients with emphysema. Taking into consideration the importance of HS for the stability of the alveolar extracellular matrix, this change may be associated with the pathogenesis of emphysema.

Beta adrenoceptor function in central airway smooth muscle of patients with chronic airflow obstruction was investigated by radioligand binding studies and isoprenaline relaxation experiments. Receptor characteristics were determined in tracheal smooth muscle preparations obtained at necropsy from 12 patients and in bronchial tissue obtained at thoracotomy from 21 patients with chronic airflow obstruction. Receptor characteristics were compared with those obtained in airway tissue preparations from 65 control subjects without chronic airflow obstruction. The number ofbeta adrenoceptors, their binding affinity for the radioligand ['25I]-(-)-cyanopindolol, and the tissue binding characteristics of isoprenaline were similar in tissue from patients with chronic airflow obstruction and from control subjects. Isoprenaline induced relaxation of tracheal smooth muscle without precontraction by methacholine showed slightly (though not significantly) less sensitivity to isoprenaline in patients with chronic airflow obstruction than in control subjects (mean (SEM) pD2-the negative logarithm of the concentration producing 50% relaxation--632 (0'16) v 6-62 (0 15)). The same pattern of pD2 values was found in segmental bronchial strips without precontraction by methacholine (chronic airflow obstruction 655 (0'27), control 7 14 (0'12)). Isoprenaline relaxation in segmental bronchial strips when contracted maximally was significantly less in the patients with airflow obstruction than in the control subjects (pD2 value 5'99 (0-18) v 6'45 (0'07)). These results suggest that beta adrenoceptors in airway smooth muscle of patients with chronic airflow obstruction are not abnormal in number or in binding affinity but that there is less effective coupling between components of the relaxant system distal to the beta adrenoceptor. The possibility that the reduced isoprenaline sensitivity is a consequence of previous bronchodilator treatment cannot be excluded.