Marked deterioration in the quality of life of patients with idiopathic pulmonary fibrosis during the last two years of life

RESEARCH ARTICLE Open Access Ma ked de e io a ion in he quali y o li e o pa ien s wi h idiopa hic pulmona y ib osis du ing he las wo yea s o li e K. Rajala 1,2* , J. T. Leh o 3 , E. Su inen 4 , H. Kau iainen 5 , M. Myllä niemi 6 and T. Saa o 7 Abs ac Backg ound: Idiopa hic pulmona y ib osis (IPF) is a ch onic disease wi h a high symp om bu den and poo su i al ha in luences pa ien s’heal h- ela ed quali y o li e (HRQOL). We aimed o e alua e IPF pa ien s’symp oms and HRQOL in a well-documen ed clinical coho du ing hei las wo yea s o li e. Me hods: In Ap il 2015, we sen he Modi ied Medical Resea ch Council Dyspnea Scale (MMRC), he modi ied Edmon on Symp om Assessmen Scale (ESAS) and a sel - a ing HRQOL ques ionnai e (RAND-36) o 300 IPF pa ien s, o which 247 (82%) esponded. The ea e , ollow-up ques ionnai es we e sen e e y six mon hs o wo yea s. Resul s: Nine y- wo pa ien s died by Augus 2017. Among hese pa ien s, HRQOL was ound o be conside ably low al eady wo yea s be o e dea h. The mos p ominen declines in HRQOL occu ed in physical unc ion, i ali y, emo ional ole and social unc ioning (p< 0.001). The p opo ion o pa ien s wi h MMRC sco es ≥3 inc eased nea dea h. B ea hlessness and a igue we e he mos se e e symp oms. Symp om se e i y o he ollowing symp oms inc eased signi ican ly and eached he highes mean sco es du ing he las six mon hs o li e (nume ic a ing scale/ s anda d de ia ion): b ea hlessness (7.1/2.8), i edness (7.0/2.3), d y mou h (6.0/3.0), cough (5.8/2.9), and pain wi h mo emen (5.0/3.5). Conclusions: To ou knowledge his is he i s s udy demons a ing, ha IPF pa ien s expe ience ema kably low HRQOL al eady wo yea s be o e dea h, especially ega ding physical ole. In addi ion, hey su e om se e e b ea hlessness and a igue. Fu he mo e, physical, social and emo ional wellbeing de e io a e, and symp om bu den inc eases nea dea h. Regula symp om and HRQOL measu emen s a e essen ial o assess pallia i e ca e needs in pa ien s wi h IPF. Keywo ds: Idiopa hic pulmona y ib osis, Pallia i e ca e, Heal h ela ed quali y o li e, Symp oms Backg ound Idiopa hic pulmona y ib osis (IPF) is a ch onic disease wi h high mo bidi y and poo su i al [1–4]. I occu s mainly in olde adul s, bu he e iology o his p og essi e disease is s ill unknown [1]. Al hough he disease ajec- o y o IPF is a iable, o many pa ien s wi h IPF, su i al is wo se han many common malignancies. This necessi- a es ea ly in eg a ion o pallia i e ca e o imp o e pa- ien s’quali y o li e (QOL) and o elie e symp oms in addi ion o disease-speci ic pha macological ea men and lung ansplan assessmen [5–9]. Exis ing s udies ha e shown low heal h- ela ed quali y o li e (HRQOL) in IPF pa ien s. Howe e , only ew o hem we e p ospec i e longi udinal s udies, and mos we e ela i ely small in e ms o sample size o we e concen a ed on pha macological ea men [10–12]. IPF pa ien s ha e been shown o su e om lowe HRQOL in eal-li e s udies han in clinical s udies [12,13]. IPF pa ien s su e om many di icul symp oms, o which b ea hlessness and cough a e he mos common ones [8,10,14–20]. In addi ion, a subs an ial p opo ion o pa ien s epo anxie y, dep ession and pain [10,21–26]. Dyspnea is a majo con ibu o o HRQOL, and de- c eased HRQOL is associa ed wi h highe mo ali y [27, 28]. In a p ospec i e Aus alian longi udinal egis y s udy, impai ed HRQOL was ela ed o equen espi a o y * Co espondence: [email p o ec ed] 1 Depa men o Pallia i e Ca e, Comp ehensi e Cance Cen e ,, Helsinki Uni e si y Hospi al, Paciuksenka u 21, Po BOX 180, FI-00290 Helsinki, Finland 2 Facul y o Medicine, Uni e si y o Helsinki, Helsinki, Finland Full lis o au ho in o ma ion is a ailable a he end o he a icle © The Au ho (s). 2018 Open Access This a icle is dis ibu ed unde he e ms o he C ea i e Commons A ibu ion 4.0 In e na ional License (h p://c ea i ecommons.o g/licenses/by/4.0/), which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided you gi e app op ia e c edi o he o iginal au ho (s) and he sou ce, p o ide a link o he C ea i e Commons license, and indica e i changes we e made. The C ea i e Commons Public Domain Dedica ion wai e (h p://c ea i ecommons.o g/publicdomain/ze o/1.0/) applies o he da a made a ailable in his a icle, unless o he wise s a ed. Rajala e al. BMC Pulmona y Medicine (2018) 18:172 h ps://doi.o g/10.1186/s12890-018-0738-x hospi aliza ions and highe mo ali y [27]. Howe e , o ou knowledge, no p e ious s udies ha e epo ed changes in HRQOL and symp om bu den in connec ion wi h o hcoming dea h. This s udy aimed o in es iga e IPF pa ien s’HRQOL and symp om bu den du ing he las wo yea s o li e in a p ospec i e longi udinal ollow-up s udy o ecognise needs o pallia i e ca e and end-o -li e ca e planning and o cha ac e ise hei symp om bu den in a unique ollow-up se ing. Ma e ials and me hods S udy popula ion The FinnishIPF s udy is a na ional p ospec i e clinical egis y o IPF pa ien s ha was es ablished in 2012. IPF diagnosis is based on he ATS/ERS 2011/2015 c i e ia [1, 6]. Nea ly all Finnish IPF pa ien s a e ini ially e alua ed a public uni e si y and cen al hospi als. Pa ien s om hese specialis cen es wi h in o med consen a e included in he FinnishIPF egis y, which consis s o app oxima ely 76% o all Finnish IPF pa ien s [2]. Cu en ly, he egis y con ains da a om o e 700 IPF pa ien s. All 300 pa ien s egis e ed in he FinnishIPF s udy in Ap il 2015 we e asked o pa icipa e in his subs udy by sending an in o med consen o m oge he wi h he ques ionnai es. Those who did no espond wi hin wo weeks we e called and eminded. O he 300 egis e ed pa ien s, 247 (82%) p o ided in o med consen o his subs udy, answe ed he i s ques ionnai e and we e in- cluded in his s udy. Subsequen ly, he same ques ion- nai e was sen o he pa ien s i e imes a six mon hs in e als un il Augus 2017. Da a collec ion and ques ionnai es Disease and sociodemog aphic cha ac e is ics we e col- lec ed om pa ien eco ds and wi h a sepa a e ques- ionnai e (Addi ional ile 1). These included he da e o bi h, sex, age, ma i al s a us, educa ion, li ing condi- ions, physical ac i i y le el, he need o assis ance in daily ac i i ies, he da e o IPF diagnosis, smoking s a us, and como bidi ies. Pa ien s we e asked he equency o leisu e ime physical exe cise ha causes b ea hlessness and swea ing o a minimum 30 min du ing he p eced- ing six mon hs. Dea h ce i ica es we e acqui ed om he “Na ional Au ho i y o Collec ing and Compiling S a is ics on Va ious Fields o Socie y and Economy”. The ques ionnai es ega ding HRQOL and symp oms we e he RAND 36-I em Heal h Su ey (RAND-36), he Modi ied Medical Resea ch Council Dyspnea Scale (MMRC), and he modi ied Edmon on Symp om Assess- men Scale (ESAS). RAND-36 [29] is a gene al QOL measu emen ool wi h exis ing Finnish gene al popula ion e e ence alues [30]. RAND-36 is simila o he p e iously IPF- alida ed sho -Fo m-36 [30–32]. RAND-36 is di ided in o eigh heal h concep s [29,30]. Concep s a e sco ed on a scale om 1 o 100, whe e a lowe sco e indica es a wo se HRQOL du ing he pas ou weeks [29,30]. The concep s a e as ollows: “gene al heal h”( i e ques ions), “ i ali y” ( ou ques ions ega ding ene gy le el and i edness), “bodily pain”( wo ques ions), “physical unc ioning”( en ques ions ega ding he abili y o ake ca e o pe sonal hy- giene and he abili y o mo e and exe cise), “physical ole” ( ou ques ions ega ding ole limi a ions due o physical heal h), “men al heal h”( i e ques ions ega ding mood, dep ession and anxie y), “emo ional ole”( h ee ques ions ega ding ole limi a ions due o emo ional p oblems), and “social unc ioning”( wo ques ions) [29,30]. The sel - a ed MMRC measu es he deg ee o disabili y ha b ea hlessness causes du ing day- o-day ac i i ies on a scale om 0 o 4, in which 0 indica es no b ea hlessness excep du ing s enuous exe cise, 1 indica es sho ness o b ea h when walking up a sligh hill o hu ying on a le el, 2 indica es walking slowe han people o same age on a le el because o b ea hlessness o needing o s op o o b ea h when walking a one’s own pace on a le el, 3 indi- ca es needing o s op o b ea h a e a ew minu es when walking on a le el o a e walking app oxima ely 100 m, and 4 indica es ha he pa ien is oo b ea hless o lea e he house o is b ea hless when d essing o und essing [33,34]. The ESAS is a nume ic sel - a ing symp om-based scale ha was o iginally de eloped o assess he symp oms o cance pa ien s [35,36]. Di e en symp oms a e measu ed on Nume ic Ra ing Scale (NRS) om 0 (no symp oms) o 10 ( he wo s possible symp oms) [36–38]. In his s udy, we used a e sion including 12 symp oms (pain a es , pain wi h mo emen , i edness, nausea, dep ession, anx- ie y, insomnia, loss o appe i e, sho ness o b ea h, cough, cons ipa ion, d y mou h, and o e all wellbeing). The e is a lack o e idence o ecommend cu -o poin s o he ESAS. Howe e , an NRS sco e ≥4iscommonlyusedasa igge o mo e comp ehensi e symp om assessmen in clinical p ac ice [39]. S a is ics and e hical aspec s The s udy popula ion cha ac e is ics a e p esen ed as he means wi h s anda d de ia ions (SD) o as coun s wi h pe cen ages. Pa ien s’answe s we e g ouped, acco ding he ime hey answe ed om he aspec o dea h. The Kaplan-Meie me hod was used o es ima e he cumula- i e mo ali y a e he diagnosis. We used es ic ed cubic splines o de ec a possible non-linea dependency. A non- linea ela ionship be ween he RAND-36 domains, symp- om se e i y, he MMRC and ime be o e dea h we e assessed by using 5-kno - es ic ed cubic spline Rajala e al. BMC Pulmona y Medicine (2018) 18:172 Page 2 o 9 andom-e ec s eg ession models wi h app op ia e dis i- bu ion and link unc ions. Models included age and gen- de (only main e ec s) as co a ia es. A es o in e ac ion be ween independen a iables was pe o med h ough he MFPIgen command. The leng h o he dis ibu ion (mon hs be o e dea h) o kno s was loca ed a he 5 h, 27.5, 50 h, 72.5, and 95 h pe cen iles, which co espond o ime be o e dea h o −22, −15, −9, −5and−1. The loca- ions o he kno s we e de e mined by he pe cen iles ec- ommended in Ha ell’s publica ion [40].The no mali y o he a iables was es ed by using he Shapi o-Wilk es . The Finnish gene al popula ion alues o he eigh Rand-36 domains we e weigh ed o ma ch he gende and age dis ibu ion o he s udy popula ion, s a is ical analysis be ween ou popula ion and gene al popula ion was no pe o med [30]. The S a a 15.0 [41] s a is ical package was used o he analysis. The e hics commi ee o Helsinki Uni e si y Cen al Hospi al app o ed his s udy (381/13/03/01/2014). The Finnish Na ional Ins i u e o Heal h and Wel a e (Dn o THL/1161/5.05.01/2012) app o ed he sc eening o hos- pi al egis ies o pa ien s wi h IPF. All pa icipa ing pa- ien s p o ided w i en in o med consen o pa icipa e o his speci ic s udy. Resul s O he 247 pa ien s included in he s udy 92 (37%) died by Augus 2017 and we e included in ou ollow-up co- ho (Fig. 1). The cumula i e mo ali y o he pa ien coho (n=92) is p esen ed in Fig. 2. The median o e all su i al was 4.4 yea s (IQR 3.1–5.7). Pa ien cha ac e is ics a e shown in Table 1. A majo i y o he pa ien s had como bidi ies, o which ca dio ascula diseases we e he mos common ones. None o he pa ien s had lung cance when en e ing he s udy, bu wo pa ien s we e diagnosed wi h lung cance du ing he ollow-up. Lung unc ion measu emen s wi hin he las six mon hs o li e we e a ailable in only 28 (30%) o he pa ien s (mean FVC 2.2 l (SD 0.6), 57%). An i ib o ic medica ion was used by 33 (35%) o he pa ien s. The p opo ion o he pa ien s who could no pe o m con inuous mode a e in ensi y physical exe cise o a leas 30 min du ing he p e ious six mon hs inc eased om 34% 18–24 mon hs be o e dea h o 62% du ing he las six mon hs o li e. Six mon hs be o e dea h, 67% o he pa ien s epo ed needing assis ance wi h hei daily ac i i ies, while 18–24 mon hs be o e dea h his p opo - ion was 56%. Heal h- ela ed quali y o li e Figu e 3shows he changes in he di e en dimensions o HRQOL measu ed wi h RAND-36 du ing wo yea s Fig. 1 Flowcha o pa ien ec ui men and esponse a e Fig. 2 Cumula i e mo ali y a e he diagnosis o IPF. Time-poin o he diagnosis is ma ked wi h 0 and 95% con idence in e als wi h he g ey a ea. Kaplan-Meie me hod was used o es ima e he cumula i e mo ali y Rajala e al. BMC Pulmona y Medicine (2018) 18:172 Page 3 o 9 be o e dea h. The decline in HRQOL was highly signi i- can in all dimensions excep in physical ole, which showed e y low sco es by 24 mon hs be o e dea h. Symp oms The in ensi y change o he symp oms measu ed by he ESAS du ing he las wo yea s o li e is p esen ed in Fig. 4. The in ensi y o all symp oms excep pain a es and insomnia inc eased signi ican ly nea dea h. Du ing he las six mon hs o li e, he mean NRS sco es we e as ollows: 7.1 (SD 2.8) o b ea hlessness, 7.0 (SD 2.3) o i edness, 6.0 (SD 2.5) o wellbeing, 6.0 (SD 3.0) o d y mou h, 5.8 (SD 2.9) o cough, 5.0 (SD 3.5) o pain wi h mo emen , 3.9 (SD 3.1) o insomnia, 3.9 (SD 2.9) o anxie y, 3.8 (SD 2.9) o dep ession, 3.6 (SD 3.1) o con- s ipa ion, 3.4 (SD 3.3) o loss o appe i e, 3.1 (SD 2.8) o pain a es and 1.8 (SD 2.5) o nausea. The s eep change in he p opo ion o pa ien s wi h MMRC sco es ≥3 (needing o s op walking a e app oxi- ma ely 100 m o a ew minu es because o b ea hlessness) du ing he las wo yea s o li e is shown in Fig. 5. Discussion In his s udy, we demons a e a apidly inc easing impai - men in HRQOL and escala ing symp om bu den in IPF pa ien s app oaching dea h. Low HRQOL oge he wi h se e e b ea hlessness and a igue we e de ec ed as ea ly as wo yea s be o e dea h. In addi ion, se e al dimensions o HRQOL declined u he and he se e i y o many symp- oms o he han dyspnea inc eased du ing he las wo yea s o li e. In he p esen s udy, HRQOL was conside ably im- pai ed wo yea s p io o dea h in IPF pa ien s. Physical ole, i.e., ole limi a ions due o physical heal h, was excep- ionally low, bu physical unc ioning, i ali y and gene al heal h appea ed o be below he gene al popula ion le el as well. Simila o ou indings, an Aus alian egis y s udy o 516 IPF pa ien s epo ed HRQOL impai men s in all domains, wi h he lowes sco e in ac i i y, i.e., ac i - i ies ha cause o a e limi ed by b ea hlessness [27]. The impo ance o dec eased HRQOL was u he highligh ed in a ecen s udy by Fu ukawa e al. ha demons a ed ha low HRQOL was ac ually an independen p ognos ic ac o [28]. Al hough p e ious s udies ha e demons a ed low HRQOL in IPF pa ien s [10–12], none o hem ocused on he HRQOL om he aspec o app oaching dea h in a ollow-up se ing. The uniqueness o his s udy s ems om he con inuing ollow-up un il dea h, and he sub- sequen inding o a salien decline in HRQOL du ing he las wo yea s o li e ha was in ensi ied nea dea h. De e io a ion was iden i ied in all domains excep phys- ical ole, which was al eady ema kably low wo yea s be o e dea h. The mos in eg al impai men was in phys- ical, social and emo ional unc ioning and i ali y. In he Aus alian egis y s udy, app oxima ely one- hi d (38%) o he IPF pa ien s expe ienced clinically impo an di - e ences in he decline o HRQOL du ing 12 mon hs [27]. Howe e , in ha s udy, no HRQOL da a was a ail- able om he pe iod p eceding dea h [27]. In lung cance , unc ional conce ns ela ing o physical mo emen o unc ioning p edomina e pa ien s’symp- om bu den h oughou he disease cou se and ha e a nega i e impac on HRQOL [42]. In addi ion, he se e - i y o symp oms escala es, and he numbe o se e e symp oms inc eases du ing he las h ee mon hs o li e [42–44]. A s eep decline in HRQOL a he end-o -li e is Table 1 Pa ien cha ac e is ics To al numbe o pa ien s 92 Age, mean ( ange) 75 (57–92) Males n (%) 67 (73) Du a ion o IPF in yea s, mean (SD) 3.6 (2.3) Educa ion in yea s, mean (SD) 10 (3) Li ing alone, n (%) 31 (34) Wo king, n (%) 4 (4) Smoking s a us, n (%) a Smoke 6 (7) Ex-smoke 50 (54) Ne e -smoke 36 (39) FVC (li es), mean (SD) b 2.9 (0.8) FVC (% o p edic ed), mean (SD) b 78 (16) Di usion capaci y, mean(SD) c 54 (13) Co-mo bidi ies e , n (%) Hype ension 41 (45) Co ona y hea disease 35 (38) Diabe es 24 (26) Hea ailu e 23 (25) COPD 20 (22) Cance 16 (17) As hma 8 (9) No co-mo bidi ies 13 (14) Numbe o co-mo bidi ies, median ( ange) 2 (0–7) Place o dea h, n (%) b Hospi al d 62 (67) Home 19 (22) Nu sing home 4 (5) Hospice 3 (3) a smoking s a us, o ced olume i al capaci y (FVC) and di usion capaci y a e eco ded a he ime o diagnosis and o he ac o s a he ime o he i s ques ionnai e b Da a missing om 4 pa ien s; c da a missing om 12 pa ien s; d 10 in in ensi e ca e uni ; e pa ien - epo ed co-mo bidi ies Rajala e al. BMC Pulmona y Medicine (2018) 18:172 Page 4 o 9 ypical in pa ien s dying o cance compa ed wi h o he e minally ill pa ien s [45,46]. In COPD pa ien s, HRQOL g adually declines o e ime wi hou a s eepe decline a he end-o -li e [47]. Ou da a imply ha pa- ien s wi h IPF expe ience g adual impai men s in HRQOL compa able o COPD pa ien s bu su e om a p onounced, apid de e io a ion in HRQOL du ing he las yea o li e, mo e closely esembling he disease a- jec o y o cance . Ou esul s co obo a e ea lie indings on dyspnea and cough as he mos se e e symp oms in IPF pa ien s ega dless o he disease phase [10,21,27,48]. The in- ensi y o dyspnea inc eased du ing he ollow-up, being one o he mos se e e symp oms be o e dea h. In a p e ious IPF egis y s udy, dyspnea yielded he s on- ges associa ion wi h impai ed HRQOL accoun ing o 71% o he a ia ion in HRQOL [27]. In addi ion, exe ion dyspnoea measu ed by he MMRC has been shown o co ela e o HRQOL and symp om bu den [21,49]. In addi ion o dyspnea, o he ac i i y-limi ing symp oms such as a igue and pain in mo emen we e among he mos se e e symp oms in ou s udy. These ac i i y-limi - ing symp oms can lead o physical inac i i y and unc- ional impai men , igge ing a icious ci cle wi h wo se HRQOL. The in ensi y o dep ession and anxie y we e, howe e , ela i ely mild wo yea s be o e dea h, al hough hese symp oms inc eased he ea e . In a ecen s udy, dep ession was an independen p edic o o HRQOL im- pai men , al hough i only accoun ed o 3.5% o he a i- a ion, whe eas dyspnea accoun ed o 71% [27]. Ou esul s sugges ha he elie o ac i i y-limi ing symp oms oge he wi h psychosocial suppo may imp o e HRQOL in ad anced IPF. Fig. 3 Rela ionships be ween Heal h- ela ed quali y o li e domains (RAND-36) wo yea s be o e dea h. The cu es we e de i ed om a 5-kno es ic ed cubic splines eg ession models. The models we e adjus ed o age and gende . The g ey a ea ep esen s 95% con idence in e als. Dashed lines ma k Finnish gene al popula ion le els Rajala e al. BMC Pulmona y Medicine (2018) 18:172 Page 5 o 9 As discussed abo e, pa ien s wi h ad anced IPF, COPD and lung cance su e om a hea y symp om bu den and de e io a ing HRQOL. This calls o comp ehensi e symp om managemen and in eg a ed pallia i e ca e concomi an wi h disease-modi ying he apies [21,27, 47,50–52]. Ea ly in eg a ed pallia i e ca e o pa ien s wi h lung cance has shown subs an ial bene i s, such as lowe dep ession sco es, highe HRQOL, be e commu- nica ion o end-o -li e ca e p e e ences, less agg essi e ca e a he end-o -li e, and longe o e all su i al [51, 53]. Simila ly, a andomised ial demons a ed be e con ol o dyspnea and a su i al bene i wi h in eg a ed pallia i e ca e in pa ien s wi h COPD and in e s i ial lung disease [54]. In addi ion o cance pa ien s, ea ly in- eg a ed pallia i e ca e may educe end-o -li e acu e ca e u ilisa ion, and allow pa ien s wi h IPF o die in hei p e e ed loca ions [55–58]. In eg a ed pallia i e ca e in IPF pa ien s seems o lowe espi a o y- ela ed eme - gency oom isi s and hospi alisa ions and may allow mo e pa ien s o die a home [55]. In his s udy, 67% o pa ien s died in hospi al and 11% in in ensi e ca e, which is in line wi h ea lie indings, implying he necessi y o imp o emen s in ad anced ca e planning and pallia i e ca e o pa ien s wi h IPF [55,59]. Ou e- sul s p o ide insigh in o he mos impo an needs o end-s age IPF pa ien s and suppo he use o ea ly-in eg a ed pallia i e ca e, which should include symp om con ol beyond ea men o dyspnea and psy- chosocial suppo . The ela i ely small s udy popula ion limi s ou s udy, as did no ha ing sys ema ic ollow-up da a on lung unc ion, which is a leas pa ially due o he poo con- di ions o many o ou pa ien s. Ou s udy is o ou knowledge i s o p esen ollow-up da a o HRQOL and symp oms o o e wo yea s be o e dea h. The s eng h is i s eal-li e longi udinal design, wi h a unique coho o IPF pa ien s app oaching dea h wi h an ou - s anding esponse a e, pa icula ly conside ing he ac ha some o he pa ien s we e p obably oo weak o e- spond du ing hei inal days o weeks o li e. To ou knowledge, his is he i s s udy desc ibing comp ehen- si e pa ien - epo ed da a on he HRQOL and symp om bu den o IPF pa ien s om he pe spec i e o ap- p oaching dea h. Fig. 4 Rela ionships o symp om se e i y measu ed by ESAS wo yea s be o e dea h. The cu es we e de i ed om a 5-kno es ic ed cubic splines eg ession models. The models we e adjus ed o age and gende . G ey a ea ep esen s 95% con idence in e als. ESAS, Edmon on symp om assessmen scale Rajala e al. BMC Pulmona y Medicine (2018) 18:172 Page 6 o 9 Conclusion Pa ien s wi h IPF su e om excep ionally low HRQOL oge he wi h se e e b ea hlessness and a igue al eady wo yea s be o e dea h. In addi ion, physical and emo ional wellbeing u he de e io a es nea dea h con- cu en ly wi h escala ing o e all symp om bu den. In clinical p ac ice, s uc u ed measu emen s o HRQOL and symp oms a e necessa y o guide high-quali y ea ly-in eg a ed pallia i e ca e and end-o -li e planning in IPF pa ien s. Addi ional ile Addi ional ile 1: Disease and sociodemog aphic cha ac e is ics. The ques ionnai e used o collec disease and sociodemog aphic cha ac e is ics. (DOCX 35 kb) Abb e ia ions COPD: Ch onic obs uc i e pulmona y disease; EOL: End-o -li e; ESAS: Modi ied Edmon on Symp om Assessmen Scale; FVC: Fo ced i al capaci y; HRQOL: Heal h- ela ed quali y o li e; IPF: Idiopa hic pulmona y ib osis; IQR: In e qua ile ange; MMRC: Modi ied Medical Resea ch Council Dyspnea Scale; NRS: Nume ic a ing scale; RAND-36: RAND 36-I em Heal h Su ey; SD: S anda d de ia ion; SGRQ: S Geo ges Respi a o y Ques ionnai e Acknowledgemen s We a e g a e ul o he pa ien s ha consen ed in pa icipa ing his s udy. The au ho s exp ess g a i ude o he pa icipan s o he FinnishIPF conso ium: Kaa eenaho R, Saa elainen S, Kankaan an a H, Böök A, Salomaa ER, Kaunis o J, Hodgson U and Pu oki i M. The au ho s a e also immensely g a e ul o he nume ous pulmona y physicians, who ha e con ibu ed o he s udy by including pa ien s and asking o in o med consen s: Vaden J, Pekonen M, Tapanainen H, Lajunen H, Saa inen A, Suu onen U, Lammi L, Leh onen K, Männis ö J, Salmi I, To kko M, To kko P, E kkilä M, Ande sen H, Jaakkola J, Rinne H, Alho M-L, Pie iläinen M, Toljamo T, Palomäki M, Nylund E, Ahonen E, Impola P, Sa ia o S, Pusa L, Vilkman S, Ek oos H, Vuo i P Hedman J, Lah i M and Mu su A. Funding The Academy o Finland, Sig id Jusélius Founda ion, Founda ion o he Finnish An i-Tube culosis Associa ion, Go e nmen al subsidy o heal h sciences esea ch ha e suppo ed Lung Fac o esea ch g oup. Kaisa Rajala has ecei ed g an s men ioned on con lic s o in e es . A ailabili y o da a and ma e ials Ou da ase se is no publicly a ailable due o he ela i ely small Finnish IPF popula ion we could no gua an ee indi iduals anonymi y. Au ho s’con ibu ions S udy design: KR, JL, ES, TS, MM. Da a Collec ion: KR, ES, MM. Da a analysis: KR, JL, ES, TS, MM, HK. W i en epo : KR, JL, ES, TS, MM, HK. All au ho s ead and app o ed he inal manusc ip . KR akes esponsibili y o he whole wo k. E hics app o al and consen o pa icipa e The Finnish Na ional Ins i u e o Heal h and Wel a e (Dn o THL/1161/5.05.01/ 2012) app o ed he sc eening o hospi al egis ies o pa ien s wi h IPF. Helsinki Uni e si y Cen al Hospi al e hics commi ee app o ed his s udy (381/13/03/ 01/2014). All pa icipa ing pa ien s ga e hei w i en in o med consen o pa icipa e o his speci ic s udy. Consen o publica ion No applicable. Compe ing in e es s Kaisa Rajala has ecei ed g an s om Founda ion o he Finnish An i- Tube culosis Associa ion, Helsinki Uni e si y Hospi al Comp ehensi e Cance Fig. 5 Change in he p opo ion o pa ien s wi h MMRC sco e ≥3 du ing he las wo yea s o li e. The cu es we e de i ed om a 5- kno es ic ed cubic splines logis ic eg ession models. The models we e adjus ed o age and gende . The g ey a ea ep esen s 95% con idence in e als Rajala e al. BMC Pulmona y Medicine (2018) 18:172 Page 7 o 9 Cen e and Väinö and Laina Ki i ounda ion. O he au ho s ha e no con lic s o in e es a ec ing his wo k. Publishe ’sNo e Sp inge Na u e emains neu al wi h ega d o ju isdic ional claims in published maps and ins i u ional a ilia ions. Au ho de ails 1 Depa men o Pallia i e Ca e, Comp ehensi e Cance Cen e ,, Helsinki Uni e si y Hospi al, Paciuksenka u 21, Po BOX 180, FI-00290 Helsinki, Finland. 2 Facul y o Medicine, Uni e si y o Helsinki, Helsinki, Finland. 3 Depa men o Oncology, Pallia i e Ca e Uni , Tampe e Uni e si y Hospi al and Facul y o Medicine and Li e Sciences, Uni e si y o Tampe e, Tampe e, Finland. 4 Facul y o Medicine, Uni e si y o Helsinki, Helsinki, Finland. 5 P ima y Heal h Ca e Uni , Kuopio Uni e si y Hospi al, Finland and Folkhälsan Resea ch Cen e , Helsinki, Finland. 6 Uni e si y o Helsinki and Helsinki Uni e si y Hospi al, Hea and Lung Cen e , Depa men o Pulmona y Medicine, Helsinki, Finland. 7 Helsinki Uni e si y Hospi al, Comp ehensi e Cance Cen e , Depa men o Pallia i e Ca e and Facul y o Medicine, Uni e si y o Helsinki, Helsinki, Finland. Recei ed: 10 July 2018 Accep ed: 8 No embe 2018 Re e ences 1. Raghu G, Colla d HR, Egan JJ, Ma inez FJ, Beh J, B own KK, e al. 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