1 Cardiovascular and airways response to two non‐cardioselective beta‐ adrenoceptor blocking drugs, propranolol and pindolol (with partial agonist activity) and two cardioselective beta‐adrenoceptor blocking drugs, acebutolol (with partial agonist activity) and atenolol, were compared in twelve patients with asthma. 2 All four drugs produced a significant reduction in resting pulse rate and prevented the increase in heart rate following inhaled isoprenaline (1,500 microgram). 3 Seven patients in clinical remission showed no significant bronchoconstrictor response to any of the drugs. In the remaining five patients, bronchoconstriction was greatest following propranolol (mean reduction in FEV1 26.6%) and least following atenolol (mean reduction in FEV1 6.5%). 4 The bronchodilator response to inhaled isoprenaline was blocked by propranolol and pindolol but not by acebutolol and atenolol. 5 Partial agonist activity did not appear to be clinically useful.

To understand more fully the nature of events leading to asthmatic death, we conducted a confidential enquiry prospectively throughout 1994-96 among the surviving relatives and respective general practitioners of subjects whose deaths could be attributed to asthma, whether wholly or partly. We also reviewed relevant hospital records and autopsy reports, and we submitted all the gathered information to an enquiry panel for evaluation. The subjects were identified from death certificates issued in five districts of the Northern Health Region of England (population 1 million) on which asthma was recorded as the primary cause of death. The enquiry panel agreed that asthma had been a critical factor in causing death in only 33 of the 79 certified cases for which there were sufficient data. The level of concordance was substantially greater for subjects aged < 65 years (76%) than for those who were older (17%). In 16 of the 33 cases asthma alone appeared to be responsible for death, but in 17 cases a wide variety of additional, co-morbid, disorders appeared to have contributed. They included, during the 24 h preceding death, gastric aspiration, septicaemia, a single dose of a beta-blocker, the abuse of organic solvents or illicit drugs and possibly, an inadvertent exposure to horse allergen. More chronic causes of co-morbidity included ischaemic heart disease, chronic obstructive pulmonary disease (COPD), thoracic cage deformity and alcohol abuse. There were possible errors of judgement in two cases by the supervising physician (6%) and in three cases by the patient (9%). Poor compliance and psychosocial disruption probably exerted an additional adverse influence in nine cases (27%). We conclude: (1) that asthma death certification in subjects aged 65 years or more is very unreliable, (2) that for approximately half of the deaths in which asthma exerted a critical role there were critical co-morbid disorders and (3) that errors of judgement, poor compliance, or psychosocial disruption are likely to have exerted an additional adverse influence in an important minority of cases.

Asthma morbidity in England and Wales appears to have increased in recent decades, despite advances in therapy, and this is widely attributed to increasing asthma prevalence. This increase has not, however, been fully reflected by mortality trends, and in children and young adults, there have been no clear changes. In adults aged Š45 yrs (in whom >85% of current asthma deaths are recorded), mean annual mortality doubled between the mid1970s and the early 1990s in both sexes [1,2]. The rate of change and the degree of annual fluctuation increased with age, and the apparent increase was most evident in those aged Š65 yrs.The cause of the marked increase in recorded asthma deaths in this age group is uncertain. If correct, it could reflect improved diagnostic recognition, an increase in asthma prevalence, an increase in disease severity or an adverse effect of medication. The 1979 and 1984 changes in international coding practice (International Classification of Diseases (ICD) 9, implementation of rule 3) artificially increased the mortality rate in those aged <45 yrs and >75 yrs, respectively, but this provides insufficient explanation for the observed trends [2][3][4].Alternatively, the increase may be largely artefactual. The accuracy of death certification is known to decline with advancing age, and there is concern that recent trends, especially in the elderly, may be attributable to diagnostic transfer [5,6]. An audit investigation in the period 1980-1989 in one district of the Northern Health Region of England suggested that the majority of certified "asthma deaths" had occurred in elderly smokers who had neither died from asthma nor suffered from it [7]. Other studies have suggested that asthma death certification for the whole population may overestimate the number of true asthma deaths by 13-47%, with the degree of inaccuracy in certification rising in the elderly to 39-80% [8][9][10].The recorded asthma mortality rates of 3.94 and 3.64 per 100,000 for the Northern Health Region (population 3.07 million) for the years 1991 and 1992, respectively, closely reflect the national figures for England and Wales of 3.67 and 3.48 (total population 51 million). Therefore, experience within the northern region as a whole is likely to be representative of the national picture. The aim of this study was, consequently, to estimate the magnitude of any inaccuracy in death certification for asthma within this region, and hence, to assess whether the apparent increase in asthma mortality in the elderly could have occurred, at least partly, as a result of diagnostic transfer. Methods SubjectsPermission was obtained from 13 of the 16 local Health Authorities for a review of death certificates for the years , 1991. D.W.E.C. Reid, V.J. Hendrick, T.C. Aitken, W.T. Berrill, S.C. Stenton, D.J. Hendrick. ©ERS Journals Ltd 1998. ABSTRACT: Asthma mortality appeared to increase two-fold in the UK from the mid-1970s to the early 1990s, but there is evidence of inaccuracy in asthma death certification and so a region-wide investigat...

Age 5-14 Age 45-64 Age 15-44 Age 65-74 Death rates (per million population per year) by month of death and age group

Summary A case of acute renal failure is reported in a patient with severe lithium intoxication. Renal biopsy showed damage in the proximal tubules with less marked changes in the glomeruli and interlobular arteries. Lithium was withdrawn, and after treatment with peritoneal dialysis the patient regained normal renal function. The accumulation of lithium is known to lead to acute renal failure in the rat and the dog, and this report provides further evidence that it may do so in man.