Cystic fibrosis: current survival and population estimates to the year 2000

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1 Thorx 1991;46: Respirtory Medicine Unit, City Hospitl, Nottinghm NGS IPB J S Elbom D J Shle J R Britton Reprint requests to: Dr Elborn, Deprtment of Tuberculosis nd Chest Diseses, Llndough Hospitl, Penrth, South Glmorgn CF6 IXX Accepted 19 September 1991 Cystic fibrosis: current survivl nd popultion estimtes to the yer 2 J S Elborn, D J Shle, J R Britton Abstrct Bckground Survivl from cystic fibrosis is incresing rpidly. Estimtes of the extent of this improvement should llow helth cre fcilities to be plnned to del with the expnding popultion of ptients with cystic fibrosis. Estimtes of life expectncy re lso essentil if ccurte informtion on current prognosis is to be given to prents of n ffected child, or to prospective prents deciding whether to proceed with pregnncy where the fetus my be ffected. Methods Survivl trends in the ntionl dt on cystic fibrosis hve been nlysed to produce estimtes of the likely size of the cystic fibrosis popultion over the next decde nd to predict the life expectncy of children born with cystic fibrosis in the yers up to 199. Results In Englnd nd Wles the estimted number of ptients with cystic fibrosis is t present bout 52, of whom 33 (63%) re ged under 16 yers. By the yer 2 the totl popultion will increse to 6, with 34 (57%) ged under 16. Thus the number of children with cystic fibrosis will remin firly constnt over the next 1 yers, wheres dult numbers will increse by bout 36% (from 191 to 2577). The medin life expectncy ofchildren with cystic fibrosis born in 199 is estimted to be 4 yers, double tht of 2 yers go. Conclusion This study suggests tht helth service provision for children will not need to chnge substntilly over the next 1 yers wheres services for dults will need to increse by bout third. Prents cn be counselled tht the medin life expectncy of newborn child with cystic fibrosis is currently likely to be of the order of 4 yers. The prognosis for ptients with cystic fibrosis hs improved substntilly over the pst four decdes.'2 The improved survivl hs been ttributed to severl fctors, including erlier dignosis,2 improved mngement of meconium ileus,' better dietry mngement nd pncretic enzyme supplementtion,2 4 routine physiotherpy,5 the development of potent ntipseudomonl ntibiotics,6 nd the emergence of specilist tretment centres.27 The reltive importnce ofthese tretments remins uncertin,2 though most ptients with cystic fibrosis now receive extensive medicl nd 881 prmedicl support, often with repeted dmissions to hospitl.238 As the cystic fibrosis popultion expnds medicl fcilities will hve to increse to cope with their requirements. To provide estimtes of the likely extent of the increse in numbers of ptients with cystic fibrosis we hve used mortlity dt for Englnd nd Wles to predict the likely trend in survivl over the next decde, nd to produce estimtes of the size nd ge distribution of the cystic fibrosis popultion. Another importnt spect of the mngement of cystic fibrosis is the counselling of prents of ffected children t the time of dignosis.9 The recent development of ccurte prentl dignostic methods for cystic fibrosis""'2 is lso likely to led to rpid increse in the numbers of prents seeking dvice on whether to bort n ffected fetus." 13 In both of these circumstnces ccurte dt on survivl prospects re required, nd re currently not vilble. We hve therefore used our dt predictions to estimte the likely life expectncy of children born with cystic fibrosis in Englnd nd Wles up to the present dy. Methods Mortlity dt for cystic fibrosis in Englnd nd Wles from 1959 to 1986 were obtined from the Office of Popultion, Censuses, nd Surveys.'4 The number of children born with cystic fibrosis ech yer ws estimted from the totl recorded live births,'5 16 on the ssumption tht one infnt in 25 is homozygous for cystic fibrosis.'7 We combined these estimtes to produce life tbles nd nnul mortlity rtes for cystic fibrosis for ech yer of birth cohort from 1959 to 1986, using the Sttisticl Pckge for the Socil Sciences (SPSS-X).'8 Predictions of survivl up to the yer 2 were derived by logistic nd lest squres regression, the generlised liner interctive modelling pckge (GLIM) being used.'9 In ll birth cohorts mortlity ws much higher in the first yer of life thn in subsequent yers, though first yer mortlity improved substntilly during the study period (fig 1A). Mortlity fter the first yer ws reltively constnt within birth cohorts. First yer mortlity ws therefore nlysed nd predicted seprtely from subsequent mortlity. A logistic regression eqution,y = x + b, ws fitted to the proportion of ffected children dying from cystic fibrosis in the first yer of life for ech birth cohort from 1959 to 1986, where y represents the logit of the proportion of deths in ny yer, x the yer, the logistic grdient Thorx: first published s /thx on 1 December Downloded from on 17 October 218 by guest. Protected by copyright.

2 882 Elborn, Shle, Britton ). - ) 1) c 6) A U B U... C U, U -ạ. _ U U * _ * Yer of birth Figure I A-Proportion of live births with cystic fibrosis dying in the} B-logistic intercepts; C-logistic grdientsfor the modelfitted to survivl fter thefirst yer o, of birth cohorts bornfrom 1959 to * 8199 )8 \ 398 -, 6 - \ ~ u i I. I I. I. I Age (yers) Figure 2 Survivl curves for cohorts born t the beginning of ech decde,extrpolted to the yer 2., (the increse in the logit for ech yer), nd b the logistic intercept (the proportion dying in 1959). This eqution ws then used to estimte the proportion ofchildren dying in the first yer of life for birth cohorts from 1987 to 2. As figures for live births were vilble only up to (personl communiction for 1988), we estimted tht the number of nnul live births for Englnd nd Wles from 1989 to 2 would be pproximtely equl to the verge 8 ~'* v for ( births yer). From these 198 estimtes we clculted the number of children with cystic fibrosis born ech yer up to 2 who would be expected to survive to their first birthdy. Mortlity ws then nlysed for those surviving to their first birthdy in ech yer ofbirth cohort by fitting different logistic model, this time to the proportion dying ech yer within ech cohort. In this model of y = x + b, y represents the logit of the proportion dying t ge x, the increse in the logit for ech yer of ge, nd b the logit of the proportion dying in,,., the second yer of life. We could not fit relible 198 model to cohorts born fter 1981 becuse there were few deths nd insufficient yers of dt, so mortlity fter the first yer ws predicted for ech yer of birth cohort, model bsed on the trends for being used. The intercept of the logistic model for ech cohort showed progressive liner fll over the yers (fig 1B) so we extrpolted this trend by lest squres regression to provide intercepts for subsequent yers. The grdient of the logistic eqution did not show pronounced trend with time from 1959 to 1981, however (fig 1C), so we used the men vlue for the grdient in the lst five yers of dequte dt ( ) for sub-.,-,-,--,--, sequent cohorts. 198 The logistic model defined by this grdient nd the extrpolted intercept for ech yer ws then pplied to the projected first yer survivors irst yer oflife; f life within yer from 1982 to 2 nd used to estimte the number of deths for individuls bom with cystic fibrosis until 2. These predictions were used to produce life tbles for ll nnul cohorts from 1959 to 2 nd hence to estimte the size ofthe cystic fibrosis popultion for ech yer until the yer 2. Results The proportion of ptients dying in the first yer of life declined substntilly over the study period (fig la). A logistic model fitted this trend well, with scled residul devince of 26-4 on 25 degrees of freedom. The lest squres regression ofthe logistic intercept with time (fig I B) ws lso good description ofthe dt, with n r2 vlue of 68. Log trnsformtion did not improve this fit. We elected to use the men logistic grdient for future predictions becuse the lest squres regrssion of this 196 grdient ginst time did not differ significntly from zero (fig 1C) nd becuse extrpoltion of the logistic grdient long the wekly positive I I, regression prediction produced implusible 4 survivl curves in which medin survivl fell fter 199. One finl predictive model produced series of survivl curves, of which intervl exmples re shown in figure 2. Popultion Thorx: first published s /thx on 1 December Downloded from on 17 October 218 by guest. Protected by copyright.

3 Cysticfibrosis: current survivl nd popultion estimtes to the yer Tble 1 Number of live births nd number of deths during thefirstyer of life nd subsequentfiveyer ge bnds by yer of birth (ctul births nd deths bove the line, estimtes from this study below the line; incomplete five yer cohorts in prentheses) No of children No of deths by yer born with cystic fibrosis < > (6) (4) (2) (3) (9) (7) (9) (11) (26) (14) (11) (5) (24) (19) ( 7) (16) (18) (13) (7) (3) (8) (6) (3) (1) (4) (2) (1) (1) (1) (1) (1) figures derived from these curves, mlgmted up to the present dy re shown in figure 4. into five yer ge groups, re summrised in Children born in 199 hve predicted medin tble 1. survivl of 4 yers. From these dt numbers of cystic fibrosis ptients were estimted by yer from 198 to 2 s the number of dults (ged 16 or over) Discussion nd children (under 16 yers, tble 2, fig 3). A This study ws conducted primrily to modest increse of only 133 children with estimte the numbers of ptients with cystic cystic fibrosis (4%) is predicted for Englnd fibrosis by the end of the next decde, nd to nd Wles from 199 to 2, wheres the provide estimtes of life expectncy for chilincrese in the dult popultion will be of the dren with cystic fibrosis born now. We hve order of 36% (676 individuls). The gretest used deth certificte dt from the Office of increse in the dult popultion will occur in Popultion Censuses nd Surveys s this is the those over 25 yers (from 517 to 128). most complete source of ntionl mortlity dt Estimted medin survivl for cohorts born vilble. Coding for cystic fibrosis deths hs chnged on two occsions since For the Tble 2 Estimted numbers of ptients with cysticfibrosis in ge bnds offiveyers from yers the Interntionl Clssifiction 198 to 2 in Englnd nd Wles of Diseses (ICD) Code ws nd included other diseses of the pncres. For Age (yers) Totls these yers the mortlity from cystic fibrosis ws djusted by excluding deths over the ge wdutdbexlindhso > 25 Children Adults All rteg of 5 yers; we hve previously rgued tht the djustment is unlikely to hve introduced ny serious distortion into the estimtes of number of deths.'4 From 1968 onwrds n exclusive c ctegory for cystic fibrosis hs been vilble so tht little misclssifiction of reported deths Thorx: first published s /thx on 1 December Downloded from on 17 October 218 by guest. Protected by copyright.

4 884 Elborn, Shle, Britton 1) - E z O Yer Figure 3 Estimted numbers ofptients with cysticfibrosis by yerfrom 198 to In, vn_, * Yer of birth Figure 4 Medin survivl byyer ofbirthfrom 1959 to 199. Tble 3 Estimted numbers ofptients with cystic fibrosis by region in 199 nd 2 Age (yers) <16 >16 Region NW Thmes NE Thmes SE Thmes SW Thmes Northern Yorkshire Trent Est Angli Wessex Oxford South West West Midlnds Mersey North West Wles from cystic fibrosis is likely to hve occurred cumultive effect of misclssifiction of deths since then. from cystic fibrosis is unlikely to be substntil. We recognise tht n unknown proportion of The nture of the model used to predict deths of ptients with cystic fibrosis will tbe numbers will obviously ffect the survivl clssified under other cuses nd thus excluded estimtes. We produced our model so fr s from the survivl clcultions. Recent ll cu= se possible from logicl first principles nd mortlity dt show tht the proportion ( of experimented in the process of the clcultions deths from cystic fibrosis clssified under oth( with vrious predictive models. In the event er cuses is currently very smll (4% of detd the predictions for totl numbers of dults nd due to cystic fibrosis in 1985 nd 1986; personl children were reltively robust to differences in communiction, Office of Popultion Census( es the method of prediction, but medin survivl es nd Surveys), but it is likely tht some deti estimtes were less stble. The model we from cystic fibrosis re unrecognised, tht sortie dopted fitted the dt well nd produced live hve been recognised s being from cystic popultion estimtes similr to those of n fibrosis but this dignosis is excluded from tiie independent survey of prevlence by the Britd ish Peditric Assocition Working Prty on certificte, nd tht some ptients hve die from genuinely unconnected cuses. The regi, s- Cystic Fibrosis. For 198 the British Peditric tered mortlity by 27 yers of ge in the erliler Assocition's estimte of the totl United cohorts, however, ccounts for well-over 7,O Kingdom cystic fibrosis popultion ws 4326, of the expected number in ech cohort,'4 su; g which compres fvourbly with our estimte gesting tht the dt re in fct resonb] ly of 3747 for Englnd nd Wles lone. The complete even in the erlier yers; with - ccurcy of our estimte lso depends on n lownce for improvements in dignosis nd ssumption tht there will be no mjor chnge cse scertinment since the erly 196s tiie in the live birth rte in the next decde. In fct, the number of live births hs incresed stedily over the pst six yers,'6 nd if this trend continues the number of young children with / cystic fibrosis will exceed our estimtes slightly. A striking feture of our estimtes is the 36% increse in dults with cystic fibrosis from 199 to 2. As the mgnitude of this increse ws reltively robust to different prediction models we believe it to be relible. This expnsion in numbers will hve implictions for the provision of services for dult ptients, which will hve to grow to cope with this increse over the next 1 yers. In contrst, the number of children with cystic fibrosis remins reltively constnt, so current service provision my be sufficient. As deths from cystic fibrosis will occur incresingly mong dults morbidity is lso likely to be greter in older ptients. This will move the need for intensive inptient cre from the peditic to the dult services, nd 9 mke it likely tht by the yer 2 the cre of dults will require t lest the sme resources I s those currently vilble for the cre of children. To give n indiction of the likely Thorx: first published s /thx on 1 December Downloded from on 17 October 218 by guest. Protected by copyright.

5 Cysticfibrosis: current survivl nd popultion estimtes to the yer 2 brekdown of popultion chnges by regionl helth uthority pproximte numbers of ptients were clculted by region on the bsis of the proportionl verge live birth rte from 1978 to 1988; these re shown in tble 3. The increse in the cystic fibrosis popultion my be ffected in future by the consequences of the recent discovery of the cystic fribrosis gene,2 21 which my led to popultion screening" 12 nd reduction in the number of children born with cystic fibrosis. Widespred screening is unlikely before 1995, however, nd even if optimum uptke occurs reduction in ffected live births by only 4% hs been suggested.'2 This might hve smll effect on the numbers of children born by 2, but will not effect the size of the dult popultion until well into the next century. The prognosis for ptients with cystic fibrosis hs shown progressive improvement over the pst 3 yers, nd survivl curves for Englnd nd Wles re similr to others bsed on popultions in Europe7 2 nd North Americ. ' 5 The improvement in survivl is likely to continue over the next decde with improved medicl cre nd incresed vilbility ofhertlung trnsplnttion. Our predictions of medin survivl for future cohorts were very sensitive to the model used, so we hve reported our estimtes only up to the present birth cohort. As these predictions re bsed on cumultive estimtes from multiple birth cohort survivl predictions they contin n element of error tht is difficult to estimte. As there is so fr no evidence tht survivl is plteuing, our current estimtes re likely to be resonbly ccurte. The reltively fvourble outlook (compred with tht of 3 yers go) for child born in 199 with cystic fibrosis should llow resonbly optimistic dvice to be given to prents. The current medin ge of deth in Englnd nd Wles is of the order of 2 yers,'4 nd dvice bsed on these figures will be unduly pessimistic. The continuing improvement in prognosis lso rises questions bout the cceptbility of popultion nd prentl screening,23 s mny couples re likely to question the morlity of n bortion when child born with cystic fibrosis my hve medin survivl of the order of 4 yers." It my lso be difficult to justify expensive popultion screening for disese with such prognosis,11 given tht mny dults with cystic 885 fibrosis enjoy good qulity of life nd contribute to society economiclly nd socilly.24 We believe tht our figures provide grounds for some optimism for those concerned with the cre of ptients with cystic fibrosis nd with counselling prents of children born recently with cystic fibrosis, prents of fetus likely to be ffected by cystic fibrosis, nd young ptients with the disese. J S E is supported by the Cystic Fibrosis Reserch Trust. We lso thnk Richrd Somerville nd Niruph Lkhni from the Office of Popultion Censuses nd Surveys for supplying the rw dt nd Jim Person for dditionl sttisticl dvice. 1 Wrwick WJ, Pogue RE, Gerber HU, Nesbitt CJ. Survivl ptterns in cystic fibrosis. J Chron Dis 1975;28: Anonymous. Survivl in cystic fibrosis [editoril]. Lncet 1984;ii: Dvid TJ. Cystic fibrosis. Arch Dis Child 19;65: Corey M, McLughlin FJ, Willims M, Levison H. A comprison of survivl, growth nd pulmonry function in ptients with cystic fibrosis in Boston nd Toronto. J Clin Epidemiol 1988;41: Hung NN, Mcri CN, Girone J, Sproul A. Survivl of ptients with cystic fibrosis. Med JAust 197;i2: Pheln PD, Alln JL, Lndu LI, Bmes GL. Improved survivl of ptients with cystic fibrosis. Med J Aust 1979;i: Nielsen OH, Schoitz PO. Cystic fibrosis in Denmrk in the period Evlution of centrlised tretment. Act Peditr Scnd 1982;supple 31: British Thorcic Society. Report on the orgnistion of cre for dult ptients with cystic fibrosis. British Thorcic Society News 1989;4: Dodge JA. Implictions of the new genetics for screening for cystic fibrosis. Lncet ii: Lemn WK, Feldmn GL, Krem BS, et l. Muttion nlysis for heterozygote detection in the prentl dignosis of cystic fibrosis. N Engl J Med 199;322: Colten HR. Screening for cystic fibrosis. N Engl J Med 199;322: Anonymous. Cystic fibrosis: prospects for screening nd therpy. Lncet 199;i: Ten-Kte LP, Tijmstr TJ. Crrier screening for cystic fibrosis. Lncet 1989;ii: Britton JR. Effects of socil clss, sex nd region of residence on ge t deth from cystic fibrosis. BMJ 1989;298: Office of Popultion Censuses nd Surveys. Birth sttistics London: HMSO, (Series FMI No 2.) 16 Office of Popultion Censuses nd Surveys. Birth sttistics London: HMSO, (Series FMI No 2.) 17 Dodge JA. Cystic Fibrosis in the United Kingdom : n improving picture. BMJ 1988;297: SPSS-X. SPSS-X users guide. 2nd ed. New York: McGrw Hill, Numericl Algorithms Group. The generlised liner interctive modelling system. Relese Oxford: Royl Sttisticl Society, Rommens JM, Inuzzi MC, Krem B-S, et l. Identifiction of the cystic fibrosis gene: chromosome wlking nd jumping. Science 1989;245: Riordn JR, Rommens JM, Krem B-S, et l. Identifiction of the cystic fibrosis gene: cloning nd chrcteristion of complementry DNA. Science 1989;245: Kollberg H. Incidence nd survivl curves for cystic fibrosis. Act Peditr Scnd 1982;71: Knight RA, Hodson ME. Identifiction of the cystic fibrosis gene. BMJ 199;3: Btten JC. The dolescent nd dult. In: Hodson ME, Btten JC, eds. Cystic fibrosis. Oxford: Blliere Tindll, Thorx: first published s /thx on 1 December Downloded from on 17 October 218 by guest. Protected by copyright.