Tobacco Documents Online

"Papers Age specific trends in asthma mortality in England and Wales, 1983-95: results of an observational study MJ Campbell, G R Cogman, S T Hoigate, S L Johnston Abstract Objective: To determine trends in asthma mortality by age group in England and Wales during'1983-95. Design: Observational study. Setting: England and Walex Subjects: All deaths classified as having an underlying cause of asthma registered from 1January 1983 to 31 December 1995. Main outcome measure: Tame trends for age specific asthma deaths. Restdts: Deaths in the age group 5.14 years showed an irregular downward trend during 1983-95; deaths in the age groups 15-44, 45-64, and 65-74 years peaked l~fore 1989 and then showed a downward trend; and deaths in the age group 75-84 years peaked between 1988 and 1993 and subsequently dropped. Trends were: age group 5.14 years, 6% (95% confidence interval 3% to 9%); 15-44 years, 6% (5% to 7%); 45-64 years, 5% (4% to 6%); 65-74 years, 2% (1% to 3%o). Deaths in the 75-84 and 85 and over categories plateaued. Conclusions: There are downward trends in asthma mortality in Britain, which may be due to increased use of prophylactic treaanent. Ina-oduction It is now over 10 years since trends and seasonality in asthma mortality were investigated in England and Wales,~'s and the long term trends over the period 1974-84 were found to be increasing. We aimed at updating these ~dings in the light of changing views on the appropriateness of n-eatment for asthma, increasing concerns in relation to environmental effects on asthma, and also concerns on admission rotes for asthma.4 Method The data were obtained from the Office of Population Cereuses and Surveys (now the Office for National Stadstics). They consisted of all deaths classified as hav- ing an underlying cause of asthma (International Classification of Diseases, ninth revision (ICD-9), codes 493.0 to 493.9 indnsive) registered in England and Wales from 1 January 1983 to 31 December 1995. Some coding procedures were changed in 1983, so the data were analysed including and excluding that year to see if the changd affected condusions. Data included the date of death, cause of death, sex of subject, and age at death. Annual age specific population sizes and death rates for all respiratory deaths (ICD-9 codes 460-519) were obtained from Office of Population Censuses and Surveys publications. For analysis the data were split into seven age groups, coinciding with the Office of Population Censuses and Surveys age classifications 04, 5-14, 15-44, 45-64, 65-74, 75-84, and 85 years and over. The number of people alive during each year in these age groups was obtained fi~om census projections. Deaths ~-~re aggregated into years. The appendix describes the method of analysis. Results In total, 23 311 asthma deaths were registered between 1 January 1983 and 31 December 1995. The proportions of these deaths in each age group 0-4, 5-14, 15-44, 45.64, 65-74, 75-84, and 85 and over were 0.5% 1%, 12%, 27%, 26°/o, 24%, and 10% respectively. 1983 N ~ ~ 87 ~ 89 ~ 91 92 ~ N 95 Year Rg 1 Dea~ rotes from ~thma per million popula~on by 3ge group from 1983 to 1~5 Southampton University Deparmaent of Medical Statistics and Computing, Southampton General Hospital, Southampton S016 6YD MJ Campbell, G R Cogman~ M..~ student Southampton UniversRy Department of Medicine, Southampton General Hospital S T Holgate, S LJohmton, Correspondem:e m: Dr Campbell BM] 1997;314:1439-41 o 0 BMJ VOLUME316 I'/MAY 19~Y

Papers Table 1 Trends in asthma mortality 1983-95 A~e ~ I~ ~ qvadmt~ (yea~)de|tha c~eff]cl|n~ E~tlmatet $| P 5-14 277' Time -,~.0593 0.0164 Time~ O.OQ06 0.0049 0.914 16-44 2874 Time -0.0598 0.0064 <0.001 Time~ -0.0091 0.0015 <0.001 45*64 5185 Time -0.0489 0,0(~6 <0.001 Tim~ -0.0071 0.0011 <0.001 65-74 6005 Time -O.01gO 0.0038 <0.001 Tim~ -0.0(]62 0.0011 <0.001 75-84 5717 Time 0.003~ 0.0037 0.31 Timez -O.O(OG 0.0011 <0.001 ~85 2253 Time 0.0311 0.0062 <0.001 Tim~ -0.0076 0.0018 <0.001 tCoeffldent from Poisson regression for annual asthma deaths. Figure.1 shows the yearly asthma death rates plot- ted on a log scale for each age groulx Table I gives the results of the Poisson analysis. Little could be made of the data for the under 58 because the numbers were too small. For all age groups except 5-14 there was a signlticant quadratic term. For each age group between 15 and 74 both linear and quadratic terms were nega- tive, implying an accelerating decline which started before 1989. For subjects aged 75-84 the linear term was positive, suggesting that mortality initially rose and then either peaked or phteaued after 1989. Visual inspection of the data suggests that for those aged 75-84 there was a drop in 1994 and 1995, but for those aged 85 and over no decline was evident. Excluding 1983 made little difference to the results. As the model was on a log scale, disregarding the quadratic term we can interpret the linear coefficients as a proportionate drop. Hence for deaths between 5 and 14 years of age the drop was about 6% a year (95% conlidence interval 3% to 9% ), for deaths at? ages 15-44 years it was also 6% (5% to 7%), for deaths at ages 45-64 years itwas 5% (4% to 6%), and for deaths at ages 65-74 years it was 2% (1% to 3%). For deaths in subjects aged 75 and over the rate was flat. Total respiratory deaths also decreased after about 1991 in subjects aged 5-14 and 15-44. In 1991 as a proportion of all respiratory deaths asthma deaths accounted for 44% among subjects aged 5-14 years, 31% among those aged 15-44, 11% among those aged 45-64, and 2% among those over 65. Discussion In contrast with studies up to the mid-1980s~', which showed increasing mortality, we have shown that since the late 1980~ asthma mortality in England and Wales seems to have dropped except among people aged over 85. Other countries have had different experi- ences. In Scotland mortality was stable between 1975 and 1989 for 5-44 year olds? In France a peak in mortality for both the under 358 and over 358 was observed from 1985 to 1987; this was atm"outed to influenza epidemics, and though death rates were lower subsequently there was no evidence of a trencL6 • Asthma mortality in England and Wales is dropping by about 6% a year in people aged 5,.64 years • It is changing only slowly in those aged 65 and over In contrast, deaths in New Zealand at ages 5-54 years showed a downward t~end from 1986 to 19927 Trends in asthma mortality among children are reflected in the u~ends in asthma .admissions to hospitaL Routine data for asthma admissions are not available for England after1985, but for Wales admis- sions showed a steady rise from 1983 to 1988 and then a drop in 19~9 and 19907 Age standardised death rates seem to reflect this trencL .T~ere has been considerable concern in tl~e medical community and in the public domain over repom of increasing asthma prevalence.' It is encouraging to note that even with a background of increasing prevalence there were downward trends in mortality in the under 758 in the five to seven years before 1995. It is possible that these trends were a result of increased awareness among physicians and patients of the inflammatory basis of asthma and the need for prophylactic treatment, particularly in view of the increased prescn%ing of corti- costeroids as a proportion of all prescriptions for asthma.' Diagnostic transfer is a possibility, but it is reas- suring that respiratory deaths are also dropping in younger people. The accuracy of death certification in asthma was not good in 1979 but has been shown to be more accurate for younger people)6 In old people asthma deaths form only a small proportion of all respi- ratory deaths and it would be impossible to quantify the extent of diagnostic uamfer. The trends in asthma mortality may be related to the increased use of prophylactic treatment, the use of which should continue to be encouraged. We thank the Offace for National Statistics (formerly the Ol~ce of Population Censuses and Su~eys) for the data and Mr S A Julious for additional referea~ces. Funding: Non~ Appendix Ana~ was by Poir~on regre~ion in STATAJt The midyear population was included as an ~offset," which ensured the analysis was based on a rate and allowed for changes in the age structure of the population. Checks for overdispersion and serial correlation of the residuais were carried out but it was not fohnd necessary to make allowances for them. Trend terms were centred on the midyear 1989. When the linear and quadratic terms were negative dais implied that the fitted model peaked before 1989. When the linear term was positive and the quadratic term was negative this implied that the model had peaked or phteaued or was expected to peak or plateau after 1989. When both coefficients were positive an increasing and accelerating rate was implied. 1 Khot A, Burn R. Seasonal vat'ion and time trends of dea~s from a,~hma in Engiand and Wales 1960-82. BMJ 1984;289".233-4. 2 Burney PGJ. Asthma mortality in Engiand and Wales: evidence for a fia-- th~ increa~, 197484./_zmcet 1986;ii'.323-6. 0", 0~

Papers Rates of admission to hospital fo¢ as~ma. BM] 1994"308:1596600. 5 Mack, ay TW, Wathen CG, Stal~ow M~, Elton RA, Cau/ton E. Factors atfect- ing asthma mor~ity in Scod~d. &oa Ma/J 1992;37'.5-7. 6 Cadet B, RobineJM, Leibovici D. Dynamic of asthma mor~ity in France: seasonal variation and peaking of mortality in 19~5-87. R~ Ep/de~/d 8aat, Pu~/qu* 1994;49:103-18. 7 GarrettJ, KolleJ, Richarch G, Whitdock T, Rae FL Major reductionjn What lessortt have bee~ learned? T/um~ 1995;50".303-I 1. 8 Phelan PD. Asthma in childhood: epidemiolog]~ BMJ 1994.308:1584.5. 9 Baldwin DR. Ommrod LP, Mackay AD, Stableforth DE. Change in hos- pital management of acute severe asthma by. genend and ~oracic physi- cians in Birmingham and Mancheste~ during 1978 and 1985. 1990;45:130-5. 10 BTA Research Committee~ Accuracy of death certifumes in bronchial asthma. T&nax 11 StatCorlx S~ua sta~/st/ca~ soflwa~: nlm~ 5.0. College Station, Texas: Stata Corporation. 1997. (Aca,pt~d 6 Mar~ 1997) Effect of long term treatment with salmeterol on asthma control: a double blind, randomised crossover study Paul Wilding, Miranda Clark, Joanna Thompson Coon, Sarah Lewis, Lesley Rushton, Jon Bennett, Janet Obome, Susan Cooper, Anne E Tattersfield Abstract Objectives: To determine the effect of adding salmetem150 ~tg twice daily for six months to current treatrnent in subjects with asthma who control their inhaled corticosteroid dose according to a management plan. Design: A double blind, randomised crossover stud~ Setting: Nottingham. Subjects: 101 subjects with mild or moderate asthma taking at least 200 ttg twice daily ofbedomethasone dipmpionate or budesonide. Interventions: Salmetem150 ~tg twice daily and placebo for six months each, with a one month washout. Subjects adjusted inhaled steroid dose according to guidelines. Main outcome measure: Reduction in inhaled steroid use, exacerbations of asthma, and use of oral steroids. Results: Data were available for 87 subjects. When compared with placebo salmeterol treatment was associated with a 17% reduction in inhaled steroid use (95% confidence interval 12% to 22%) with no significant difference in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%) or use of oral steroid~ For secondary end points salmeterol treatment was associated with higher morning and evening peak expiratory flow and forced expiratory volume in one second; a reduction in symptoms, bronchodilator use, and a/rway responsiveness to methacholine; and no effect on serum potassium concentration, 24 hour heart rate, or the final forced expiratory volume in one second achieved during a salbutamol dose-respome study. Condnsions: In subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmetero150 ~tg twice daily was assodated with a reduction in inhaled steroid use and improved lung function and symptom control Introduction Salmeterol, a long acting ~, agonist, when inhaled twice daffy, causes bronchodilatation that is maintained over 24 hours2 ~ The findings by Sears et al that asthma control was worse when subjects took the short acting ~h agonist fenoterol regularly rather than a p~ agonist as required' led to concerns that regular treatment with long adting ~, agonists might have similar adverse effects. Subsequent studies comparing salmetero150 gg twice daily with placebo have shown that salmeterol causes bronchodilatation that is maintained for at least three months45 and an improvement in quality of lif@ and symptom controL~ When compared with placebo or salbutamol, however, saimeterol has usually not reduced exacedoatious,45 ~" nor does it reduce inflam- mation in asthmatic airway~'~ ~s Current recommendations suggest that treatment for asthma should be modified according to symptoms and peak expiratory flow measurementsJ4 ~ The intro- duction of a long acting ~ agonist may therefore lead to a reduction in inhaled corticosteroid us~ Previous studies have looked at the effect of adding saimeterol when inhaled steroid dose is kept constant. We determined the effect of adding salmeterol to other treatment on the basis of current practice, with subjects changing their inhaled steroid dose according to predetermined criteria based on symptoms and peak exphatory flow. We studied the long term efficacy and safety of salmeterol in subjects with mild or moderate asthma who took salmeterol and placebo for six months each. Methods s~ts We recruited 101 subjects (50 female) aged 19-60 years from our register of asthma volunteers and fro~ outpatient clinics in Nottingham and Mansfield. The subjects had to have a forced expiratory volume in one second of at least 500/0 predicted and either (a) a 15°/0 increase in forced expiratory volume in one second after inhaling salbutamol 400 gg at entry or within a year or (b) 15% diurnal variability in peak expiratory flow recordings. All were receiving an inhaled short acting ~3~ agonist as needed and at least 400 gg/day bedomethasone dipropionate or budesonide. Two subjects were taking ipmtropium bromide and two theophylline, both in constant dose throughout the study..~11 had stable asthma at entry, with no exacerba- tious or respiratory tract infection in the previous six Div/sion of Respiratory Medicine, City Hospital, Nottingham NG5 IPB Paul W'dding, Miranda Joanna Thompson Coon, research a~sistanz Sarah Lew~ statistician .[on Bermeth research fellow Janet Obom~ Susan Cooper, research asmtant Ann~ E Tatt~field, D~art~ent of PubSc Health Medidn~ University Hospital, Nottingham NG7 2UH Lesley Rushton, Correspondence to: Professor Tatterstidd. BM] 1997"~14:1441-6