Increase In Asthma Mortality Research Articles

A Study of Self Poisoning with Oral Salbutamol - Laboratory and Clinical Features

1. The recent increase in asthma mortality coupled with reports of fatal asthma associated with beta-2-agonist therapy, has stimulated interest in the plasma concentrations of beta-2-agonists that produce systemic toxicity. 2. We prospectively studied 17 patients (9 male), mean age 23 years (range 2-72), who attended the emergency departments of hospitals throughout the United Kingdom having recently ingested an overdose of salbutamol. 3. Clinical, laboratory, ECG data, plasma and urine samples were obtained from each patient. Plasma was assayed for salbutamol concentration using a high performance TLC-photodensitometric method. 4. The mean (+/- s.d.) salbutamol dose reported to have been ingested was 89(+83)mg and the mean plasma salbutamol concentration was 166 (range 18-449) ng ml-1. The mean plasma potassium was 2.9 (s.d. +/- 0.6) mM (n = 16). None of the patients in this study developed serious cardiac dysrrhythmias. 5. There were significant correlations between the plasma salbutamol concentration and plasma potassium concentration (r = -0.85; P < 0.00005) and between plasma salbutamol concentration and pulse rate (r = 0.66; P < 0.005). 6. We conclude that in these patients, without respiratory decompensation, suprapharmacological plasma concentrations of salbutamol were tolerated without serious cardiac arrhythmias or any fatalities.

The clinical use of β-receptor agonists; for and against

Although β-receptor agonists are the most potent and fastest acting bronchodilators available at present, some studies have questioned their current use. Thus, the increase in asthma mortality in the U.K., New Zealand and Australia in the 1960s was linked to an increase in the use of inhaled β-agonists and has been attributed variously to the toxicity of β-agonists and especially isoprenaline or to the toxicity of propellant gases in aerosols. In addition, use of these products may cause the patient to delay seeking medical help. Due to the uncertainty concerning β-agonist use in asthmatic patients, the recomended approach to management of the disease is to use the least possible medication consistent with achieving therapeutic control. Within this framework, drug therapy may be started at a low level and be increased gradually, or maximum treatment may be given at the start, with later reduction. In this context, β-agonists play a major role and a therapeutic strategy with four steps in the management of asthma is presented, utilizing sodium cromoglycate, nedocromil sodium, inhaled corticosteroids, long-acting oral bronchodilators, anticholinergics, and oral corticosteroids for maintenance treatment and short-acting inhaled β 2-agonists when needed.

The Proper Role of β2-Adrenergic Agonists in the Treatment of Children with Asthma

β-Adrenergic agonist therapy was associated with increased asthma mortality when high-potency isoproterenol was used in the United Kingdom in the 1960s, and when the β-agonist fenoterol was used increasingly in New Zealand in the 1970s.1-3 Recently, a Canadian epidemiologic study reported an increased risk of death with regular use of β-agonists, particularly fenoterol.4 Fenoterol may be uniquely less safe than other β-agonists because of a greater cardiotoxic potential due to less β2 specificity (than terbutaline) and a greater relative dose per actuation.5 The concerns about the safety of β-agonists are linked intimately with the concerns about their effectiveness in asthma therapy.

Beta-agonists May Increase Asthma Morbidity and Mortality

Beta-agonists May Increase Asthma Morbidity and Mortality

Noncompliance could partly explain increased asthma mortality

Noncompliance could partly explain increased asthma mortality

Rising asthma mortality in young males in Hong Kong, 1976–85

The trend in asthma mortality in Hong Kong was estimated from published statistics for the years 1976-85. To avoid coding errors in death certifications, only asthma deaths in the age group 5-34 years were analysed. Mortality rose annually by an average of 10.5% in male (P less than 0.02), but not female asthmatics. Such an increase was not due to a change in coding as a result of the revision of the International Classification of Diseases in 1979, or an exchange of diagnostic labelling from other respiratory diseases. The exact causes for the increase in asthma mortality have yet to be determined.

Is current treatment increasing asthma mortality and morbidity?

Is current treatment increasing asthma mortality and morbidity?

Asthma deaths in England and Wales 1931-85: evidence for a true increase in asthma mortality.

A recent increase in asthma mortality has been reported in several countries. Such increases can be brought about by changes in factors acting close to the time of death, but they may also be caused by risk factors determined by the generation into which a person is born, as indicated by the year of birth. Asthma mortality rates since 1931 are independently associated with birthdate as well as date of death. In particular there has been an increase in asthma mortality in birth cohorts born since the 1940s. Such changes are unlikely to be due to a change in reporting of asthma deaths, and other evidence including the reported increase in the prevalence of eczema in succeeding National Birth cohorts supports the view that these changes may be due to an increased prevalence of atopy. In the absence of any further improvements in the management of asthma, such an increased prevalence of atopy implies that the mortality rate is unlikely to decline substantially for some years to come.

Morbidity and Mortality of Asthma

Morbidity and mortality of asthma has been on the upswing since the 1960s, as marked by increased hospitalizations with asthma since the early 1980s. This has not been explained adequately. The possibility of change in the natural history or increased exposure to environmental irritant chemicals or allergens has been suggested by some. There probably has been better recognition and diagnosis of asthma by distinguishing it from bronchitis, recurrent croup, and bronchiolitis in children. Despite evidence to suggest that this is the case, there are still some missing factors. The increase in asthma mortality is more understandable when one considers the fact the management of asthma has changed greatly in the past two decades. The use of corticosteroids orally, parenterally, and by inhalation has been a double-edged sword. There is no doubt that many asthmatics have a much improved sense of well-being and have lived more normal lives due to the use of corticosteroids. The inability of some patients, parents, or physicians to perceive impending respiratory difficulty, however, may result in underuse of drugs, including corticosteroids, leading to increased mortality. Other factors have led to increased mortality from asthma in recent years, and they include arrhythmias with combinations of theophylline, beta-agonists, and hypoxia. The psychological factors attendant to adolescence and psychological problems are probably quite important in the recent upsurge in asthma deaths in the 15- to 25-year age group. Many deaths are occurring outside of the hospital environment and may be largely preventable. There must be increased awareness by the patient, the family, and the physician. In view of the increased hospitalizations, the total number of deaths is not increasing at an alarming rate, yet it is necessary to make all of us who care for asthmatics aware and take corrective action as soon as we are aware of an asthmatic with respiratory problems.

Asthma mortality: England and Wales

1983. Approximately 25% of these discharges occurred among children less than 15 years of age. Among children, the discharge rate per 100,000 per year increased from 48 in 1965 to 263 in 1983. During the same period, the rate increased in adults (15 years and older) from 74 to 179 (112 if adjusted for the ICD change) per 100,000 per year. The data reflect that in the United States today there is a mild increase in the prevalence of asthma, a definite increase in mortality from asthma, and a very marked increase in hospitalization for asthma. The reasons for these events are far from being understood. 2. Evans R, Mullally DI, Wilson RW, Gergen PJ. Rosenberg HM, Grauman JS, Edmonds FC, Fbinleil M. National trends in the morbidity and mortality of asthma in the U.S.A. Chest (in press). 3. Markham D, Chang M, Evans R, MuIlally D. Epidemiologic study of deaths from asthma among children in U.S. 19651983 [Abstract]. J ALLERGY CLJN IMMIJNOL 1986;77:161. 4. Paulozzi W, Coleman JJ, Buist AS. A recent increase in asthma mortality in the Northwestern United States. Ann Allergy 1986;56:392. 5. Stableforth DE. Asthma deaths in the United Kingdom: international symposium on status asthmaticus and asthma deaths. Providence, R.I.: Brown University, 1985. 6. Mullally DI, Grauman JS, Evans R, Kaslow A. Hospitahzations of children for asthma in U.S.A. 19651982 [Abstract]. J ALLERGY CLIN IMMUNOL 1985;75:197.

Combination bronchodilator therapy.

Bronchodilators may be classified into 3 groups: anticholinergics, beta-adrenoceptor agonists and methylxanthines. These drugs act through related biochemical pathways and there are theoretical reasons for expecting beneficial additive or synergistic interactions between them. While there is in vitro evidence of synergistic interactions producing bronchodilatation, in vivo studies indicate that the interactions are additive rather than synergistic but still of therapeutic value. There have been no clinical studies on methylxanthines combined with anticholinergic drugs, but there is an extensive and growing literature on the other combinations. The majority show clear evidence of an additive bronchodilator effect when anticholinergics are combined with beta 2-adrenoceptor agonists, although atropine sulphate is less effective in this regard than atropine methylnitrate or ipratropium bromide. This type of combination has only been tested by inhalation and, because of the slower onset of action of the anticholinergic group, it is preferable that the beta 2-adrenoceptor agonist be inhaled first. There is no evidence for an additive interaction of the side effects of these drugs. In general, bronchitics respond better than asthmatics to anticholinergic drugs. Studies on methylxanthines (usually theophylline) and adrenoceptor agonists may be divided into 2 groups: those using ephedrine and those using more selective beta-adrenoceptor agonists. Ephedrine is a relatively ineffective bronchodilator and often fails to add any useful bronchodilatation to theophylline. Also, there does seem to be a synergistic increase in side effects of the two drugs and this combination is therefore undesirable. Ephedrine has now been superseded by the more selective beta 2-adrenoceptor agonist drugs all of which, whether given orally, intravenously or by inhalation, appear to have an additive effect with the methylxanthines. It is often possible to achieve the same therapeutic effect with half doses of drugs from 2 different groups as with a full dose of 1 drug. This may sometimes, but not always, reduce side effects. There is evidence that giving 2 drugs by different routes is a useful therapeutic procedure; for example, the addition of an inhaled beta 2-adrenoceptor agonist may improve upon the maximal bronchodilatation achieved with intravenous theophylline. When theophylline is administered plasma levels of the drug should be monitored and it is possible that, when used in combination with a beta 2-adrenoceptor agonist, a therapeutic range lower than that normally recommended may apply. There is no longer any place for fixed combination bronchodilators and, in spite of recent suggestions, there is no evidence that bronchodilator combinations are responsible for an increase in asthma mortality. Further studies to clarify some aspects of bronchodilator combinations are needed. The therapeutic use of various combinations is briefly discussed.

Letter: Increase in asthma mortality.

Letter: Increase in asthma mortality.

Asthma Mortality: A Possible Explanation of International Variations

A review of mortality statistics and medication usage indicates that marketing and consumption of a particular highly concentrated isoproterenol pressurized aerosol nebulizer appears to have contributed to the increased asthma mortality reported in certain countries. Those countries which had high sales volumes for the nebulizers but were spared the increased mortality apparently were protected by virtue of not having licensed this highly concentrated nebulizer.

2287. More results with aerosol propellants: Stopps, G. J. (1971). Sniffing syndrome. Br. med. J.2, 708 Jack, D. (1971). Sniffing syndrome. Br. med. J.2, 708 Clark, D. G. & Tinston, D. J. (1971). Sniffing syndrome. Br. med. J.3, 113 Harris, M. C. (1971). Are bronchodilator aerosol inhalations responsible for an increase in asthma mortality? Ann. Allergy29, 250

2287. More results with aerosol propellants: Stopps, G. J. (1971). Sniffing syndrome. Br. med. J.2, 708 Jack, D. (1971). Sniffing syndrome. Br. med. J.2, 708 Clark, D. G. & Tinston, D. J. (1971). Sniffing syndrome. Br. med. J.3, 113 Harris, M. C. (1971). Are bronchodilator aerosol inhalations responsible for an increase in asthma mortality? Ann. Allergy29, 250

ASTHMATIC DEATHS IN CHILDREN

Childhood deaths attributable to asthma may be more prevalent now than in previous years. A communication in a recent issue of the<i>American Journal Of Diseases of Children</i>¹reviews deaths from asthma at the Children's Hospital of Los Angeles between 1937 and 1963. Most of the patients were admitted in a moribund state. The investigators found a marked increase in asthma mortality as well as in the asthma death rate within the hospital in the last ten years of the study. Paradoxically, this is the period in which steroids and antibiotics became widely available and most of the patients in this study received them. It is not surprising that infection was the most important contributory factor in the deaths of these children. Why these deaths predominated since the advent and in spite of the administration of antibiotics is difficult to explain. Emergence of resistant organisms following the indiscriminate administration