Prevalence of asthma-COPD overlap syndrome among primary care asthmatics with a smoking history: a cross-sectional study

ARTICLE OPEN P e alence o as hma–COPD o e lap synd ome among p ima y ca e as hma ics wi h a smoking his o y: a c oss-sec ional s udy Toni Kiljande 1 , Timo Helin 2 , Ka i Venho 3 , An e o Jaakkola 4 and Lau i Leh imäki 5 BACKGROUND: The o e lap be ween as hma and ch onic obs uc i e pulmona y disease (COPD) is an impo an clinical phenomenon. Howe e , he p e alence o as hma–COPD o e lap synd ome (ACOS) is no known. AIMS: To in es iga e he p e alence o ACOS among as hma ic pa ien s wi h a smoking his o y, and e alua e he ac o s p edic ing ACOS in his pa ien g oup. METHODS: We in es iga ed 190 p ima y ca e as hma pa ien s wi h no p e ious diagnosis o COPD, bu who we e ei he cu en o ex-smoke s, wi h a smoking his o y o a leas 10 pack-yea s. Spi ome y was pe o med on all he pa ien s while hey we e aking hei no mal as hma medica ion. Pa ien s we e conside ed o ha e ACOS i hei pos b onchodila o o ced expi a o y olume in 1 s/ o ced i al capaci y was o0.70. RESULTS: Fi y- wo (27.4%) o he pa ien s we e ound o ha e ACOS. Age ⩾60 yea s and smoking o ⩾20 pack-yea s we e he bes p edic o s o ACOS. I bo h o hese c i e ia we e me , he odds a io (95% confidence in e al) o ACOS was 6.08 (2.11–17.49), compa ed wi h he si ua ion whe e nei he o hese c i e ia we e ulfilled. CONCLUSIONS: The e is a high p e alence o ACOS among p ima y heal h ca e as hma ics wi h a posi i e smoking his o y bu no p e ious diagnosis o COPD. In his popula ion, age o e 60 yea s and a smoking his o y o mo e han 20 pack-yea s we e he bes p edic o s o ACOS. npj P ima y Ca e Respi a o y Medicine (2015) 25, 15047; doi:10.1038/npjpc m.2015.47; published online 16 July 2015 INTRODUCTION As hma and ch onic obs uc i e pulmona y disease (COPD) a e he wo mos common obs uc i e pulmona y diseases. Al hough as hma and COPD mos o en ep esen wo dis inc diseases, he e is also significan o e lap be ween hese wo diseases. 1,2 The defini ion o as hma–COPD o e lap synd ome (ACOS) is unde e mined. Mos commonly, i is defined as ei he he diagnosis o COPD in a pa ien wi h p e iously diagnosed as hma, o as incomple ely e e sible ai way obs uc ion accompanied by symp oms o signals o inc eased e e sibili y o he obs uc ion. 3 A ecen upda e o he GINA epo ecommended a s epwise app oach o he diagnosis o ACOS, and defined i as a synd ome cha ac e ized by pe sis en ai flow limi a ion wi h se e al ea u es usually associa ed wi h as hma and se e al ea u es usually associa ed wi h COPD. 1 Compa ed wi h as hma o COPD alone, ACOS is associa ed wi h wo se heal h- ela ed quali y o li e, 4,5 mo e equen exace ba ions, 5,6 inc eased hospi alisa ion 6,7 and highe heal h ca e cos s. 8 Al hough ACOS appea s o be clinically highly significan , li le is known abou he ea men o hese pa ien s, as hey a e ypically excluded om he apy ials o as hma o COPD. 9 The e is only some da a on he p e alence o ACOS. Ha din e al. 5 ound ha 13% o he COPD pa ien s in he COPDGene s udy epo ed a his o y o doc o -diagnosed as hma. Simila ly, Mi a i lles e al. 10 epo ed ha 17.4% o COPD pa ien s in he EPI-SCAN s udy epo ed ha hey had been p e iously diagnosed wi h as hma. The p e alence o o e lap synd ome has been shown o inc ease wi h age, 11 which may eflec he ac ha , o e he yea s, as hma ics may de elop fixed ai way obs uc ion, especially i hey do no use an i-inflamma o y medica ion 12 o i hey smoke. 13 So iano e al. 11 ound ha as many as hal o he pa ien s wi h obs uc i e pulmona y disease, aged 50 yea s o mo e, had simul aneously mo e han one obs uc i e condi ion. The aim o he p esen s udy was o in es iga e he p e alence o undiagnosed ACOS among p ima y heal h ca e as hma pa ien s who a e cu en o ex-smoke s, and he ac o s p edic ing ACOS in his pa ien g oup. MATERIALS AND METHODS This was a c oss-sec ional s udy. Pa ien s we e ec ui ed mos ly om he appoin men s o p ima y ca e physicians and h ough newspape ad e isemen s. In addi ion, a ew pa ien s we e also ec ui ed by p i a e pulmonologis s ea ing p ima y ca e-like as hma pa ien s. The s udy was app o ed by he E hics Commi ee o Pi kanmaa Heal h Ca e Dis ic , and e e y pa ien ga e w i en in o med consen be o e any s udy- ela ed p ocedu es we e pe o med. Pa ien s The inclusion c i e ia we e as ollows: age 18–70 yea s, cu en o ex-smoke wi h 10 o mo e pack-yea s, doc o -diagnosed as hma wi h special eimbu semen o as hma medica ion g an ed by he Na ional Heal h Insu ance. To quali y o his eimbu semen , pa ien s mus ha e ulfilled a leas one o he ollowing c i e ia: (1) ⩾12% (and 200 ml) 1 Depa men o Respi a o y Diseases, Te eys alo Hospi al, Tu ku, Finland; 2 Depa men o Alle gology, Helsinki Uni e si y Cen al Hospi al, Helsinki, Finland; 3 Depa men o Respi a o y Medicine, Cen al Hospi al o Cen al Finland, Jy äskylä, Finland; 4 Boeh inge Ingelheim Finland, Helsinki, Finland and 5 Depa men o Respi a o y Medicine, Uni e si y o Tampe e, Tampe e, Finland. Co espondence: D T Kiljande ( oni.kiljande @fimne .fi) Recei ed 13 Ap il 2015; accep ed 1 June 2015 www.na u e.com/npjpc m All igh s ese ed 2055-1010/15 © 2015 P ima y Ca e Respi a o y Socie y UK/Macmillan Publishe s Limi ed e e sibili y in o ced expi a o y olume in 1 s (FEV 1 ) o o ced i al capaci y (FVC) in a b onchodila ion es , (2) du ing a 2-week peak expi a o y flow moni o ing a leas h ee imes ei he a b onchodila o esponse o ⩾15% (and 60 l/min) o a diu nal a ia ion o ⩾20%, (3) mode a e- o-se e e b onchial hype esponsi eness in his amine o me hacholine inhala ion challenge o (4) FEV 1 had imp o ed mo e han 15% du ing a co icos e oid ea men es . The exclusion c i e ia we e as ollows: any se e e illness, any known pulmona y disease o he han as hma, use o inhaled an icholine gic o indaca e ol o o al oflumilas . Me hods A e in o med consen was ecei ed, he in es iga o and he pa ien comple ed a ques ionnai e including ques ions abou he inclusion and exclusion c i e ia, and he pa ien ’s as hma medica ion, symp oms and exace ba ions. The in es iga o s o ed he da a in a da abase. Body mass index and cu en smoking s a us we e eco ded as a s anda d p ocedu e when spi ome y was pe o med. Spi ome ies (Medik o Kuopio, Finland) we e pe o med acco ding o he guidelines 14 be o e and a e adminis a ion o 400 μg o inhaled salbu amol while he pa ien s we e aking hei usual as hma medica ion. The pa ien s we e conside ed o ha e ACOS i hei pos b onchodila o FEV 1 /FVC was less han 0.70. Pa ien s wi h ACOS we e di ided in o GOLD g ades o ai way obs uc ion acco ding o he GOLD epo . 2 Pa ien s we e conside ed o ha e had an exace ba ion du ing he p e ious yea i hey had been hospi alised, o had used a cou se o o al co icos e oids, o hei as hma du ing he p e ious yea . S a is ical analysis The p ima y ou come was he p e alence o ACOS, as defined abo e, among as hma ics wi h a smoking his o y o a leas 10 pack-yea s. The sample size calcula ion was based on he assump ion ha he p e alence o ACOS in as hma ics is app oxima ely 45%. 11 Using he la ge sample no mal app oxima ion, 265, 195, 149, 118 o 96 pa ien s would be equi ed o es ima e he p e alence o be 95% confiden ha he es ima e will no di e om he ue p e alence by mo e han 6, 7, 8, 9 o 10 pe cen , espec i ely. The final sample size o 219 ec ui ed pa ien s was assessed o be la ge enough o ob ain a su ficien p ecision. The 95% confidence in e al o p e alence was calcula ed using he la ge sample no mal app oxima ion. The dis ibu ion o he a iables was checked using he Kolmogo o –Smi no es and g aphical plo s. The dis ibu ions o demog aphic con inuous da a we e skewed and a e exp essed as medians (in e qua ile ange). The nonpa ame ic Mann–Whi ney U- es was used o compa e he g oups wi h and wi hou ACOS wi h espec o con inuous a iables. The Chi-squa e es and he exac Fishe 's es , when app op ia e, we e used o ca ego ical a iables. Spea man’s ank co ela ion (Rho) was used o s udy he associa ions be ween pos b onchodila o FEV 1 /FVC e sus age and pack-yea s. The ecei e ope a ing cu e analysis (ROC) was used o de e mine he bes cu -o alues o age and pack-yea s o di e en ia e be ween as hma pa ien s wi h and wi hou o e lap synd ome. Sensi i i y and specifici y we e assessed o be equally impo an when he bes cu -o alues we e chosen. In addi ion, posi i e p edic i e alues and nega i e p edic i e alues we e calcula ed. The po en ial p ognos ic ac o s o o e lap we e sex, age, body mass index, cu en smoking s a us and pack-yea s o smoking. Uni a iable logis ic eg ession analyses we e pe o med o s udy he associa ions. The esul s a e gi en as odds a ios wi h 95% confidence in e als. P alues less han 0.05 we e conside ed s a is ically significan . The analyses we e pe o med using IBM SPSS S a is ics o Windows ( e sion 22.0, A monk, NY, USA, IBM Co p.). RESULTS Two hund ed and nine een pa ien s we e ec ui ed and 190 o hem we e included in he analysis (Figu e 1). Thei median age ( ange) was 58 (23–70) yea s, hey had smoked o 20 (10–60) pack-yea s, and hei body mass index was 27.5 (16.1–50.3) kg/m 2 . Eigh y- h ee (44.1%) o he pa ien s we e cu en smoke s and 112 (58.9%) we e emale. Fi y- wo (27.4%, 95% confidence in e al 21–34%) pa ien s we e ound o ha e pos b onchodila o FEV 1 /FVC o0.70 and we e hus conside ed o ha e ACOS. Twel e (23.1%), 38 (73.1%) As hma pa ien s, n=219 Spi ome y measu emen s we e no a ailable, n=26 Spi ome y measu emen s we e a ailable, n=193 Spi ome y was no alid, n=3 Pa ien s included in analysis, n=190 Pos b onchodila o FEV1/FVC < 0.70, n= 52 (27.4%) Pos b onchodila o FEV1/FVC > 0.70, n= 138 (72.6%) Figu e 1. Flow o pa icipan s. FEV 1 , o ced expi a o y olume in 1 s; FVC, o ced i al capaci y. Table 1. Cha ac e is ics o 190 as hma ics wi h and wi hou o e lap synd ome Pa ien s wi h o e lap synd ome (N= 52) Pa ien s wi h as hma only (N= 138) P alue a Age (yea s) 63.0 (52.5–66.5) 57.0 (49.0–64.0) 0.008 Pack-yea s 24.5 (20.0–37.0) 20.0 (13.0–28.0) 0.003 BMI (kg/m 2 ) 26.2 (23.2–29.9) 27.8 (24.6–31.6) 0.09 Cu en smoke s 28 (54.9%) 55 (40.1%) 0.07 Females 31 (59.6%) 81 (58.7%) 0.91 Inhaled co icos e oid (ICS) 50 (96.2%) 129 (93.5%) 0.48 Inhaled co icos e oid+inhaled long-ac ing β 2 -agonis (ICS+LABA) 36 (69.2%) 86 (62.3%) 0.38 Sho -ac ing β-agonis (SABA) mo e o en han wice a week 19 (36.5%) 37 (26.8%) 0.19 Exace ba ion du ing p e ious yea 16 (30.8%) 35 (25.4%) 0.45 Significan e e sibili y 8 (15.4%) 9 (6.5%) 0.08 b All pa ien s we e cu en o ex-smoke s. Resul s a e gi en as median (in e qua ile ange) o numbe (%). Abb e ia ion: BMI, body mass index. a Mann–Whi ney U- es was used o con inuous a iables and Chi-squa ed es o ca ego ical a iables. b Fishe 's exac es . P e alence o as hma–COPD o e lap synd ome T Kiljande e al 2 npj P ima y Ca e Respi a o y Medicine (2015) 15047 © 2015 P ima y Ca e Respi a o y Socie y UK/Macmillan Publishe s Limi ed and 2 (3.8%) belonged o GOLD s ages 1, 2 and 3, espec i ely. None o he pa ien s belonged o GOLD s age 4. A compa ison o he pa ien s wi h ACOS and hose wi h as hma alone is shown in Table 1. Pa ien s wi h o e lap synd ome we e olde and had smoked mo e han pa ien s wi h as hma alone. O e lap pa ien s ended o be mo e o en cu en smoke s and o ha e mo e o en significan e e sibili y, bu hese di e ences we e no s a is ically significan . A nega i e co ela ion be ween pos b onchodila o FEV 1 /FVC and age (Spea man Rho = −0.28, Po0.001) and pack-yea s (Rho = −0.25, Po0.001) was ound (Figu e 2). ROC analysis o age and pack-yea s e ealed ha age ⩾60 yea s and smoking o ⩾20 pack-yea s we e he bes p edic o s o ACOS in he s udy popula ion (Figu e 3). The a ea unde he ROC cu e was 0.625 and 0.639 o age and pack-yea s, espec i ely. The cu -o poin o 60 yea s o age yielded 63.5% sensi i i y and 59.4% specifici y, and he cu -o poin o 20 pack-yea s 80.8% sensi i i y and 42.8% specifici y, o de ec o e lap synd ome (Table 2). Howe e , he combina ion o bo h age ⩾60 yea s and smoking o ⩾20 pack-yea s yielded he bes a ea unde he ROC cu e: 0.670, and 53.8% sensi i i y and 74.6% specifici y. The esul s o he logis ic eg ession analysis a e shown in Table 3. Using he cu -o poin s gi en by he ROC analysis, age and pack-yea s we e he only significan ac o s p edic ing o e lap synd ome. I he pa ien was a leas 60 yea s old and had simul aneously smoked o a leas 20 pack-yea s, he odds a io (95% confidence in e al) o o e lap synd ome was 6.08 (2.11–17.49), P= 0.001, compa ed wi h he si ua ion whe e nei he o hese c i e ia we e ulfilled. In pa ien s wi h one c i e ion ulfilled (age ⩾60 o smoking o ⩾20 pack-yea s), he isk o ACOS was abou wice as high as o pa ien s who we e younge han 60 yea s and had smoked less han 20 pack-yea s. In o he wo ds, i nei he o he c i e ia (age ⩾60 yea s and smoking ⩾20 pack-yea s) we e ulfilled, he p e alence o o e lap synd ome was 11.6% (5/43 pa ien s). I one o he c i e ia was me , hen o e lap synd ome was ound in 22.6% (19/84) o he pa ien s. I bo h c i e ia we e me he p e alence o o e lap synd ome was ound o be 44.4% (28/63 pa ien s). DISCUSSION Main findings We ound he p e alence o as hma–COPD o e lap synd ome o be 27.4% among p ima y heal h ca e as hma ics wi h no p e ious diagnosis o COPD, bu who we e ei he cu en o ex-smoke s wi h a smoking his o y o a leas 10 pack-yea s. The pa ien s wi h ACOS we e olde and had smoked mo e han pa ien s wi h as hma alone. S eng hs and limi a ions o his s udy The cu en s udy has i s weaknesses. Fi s , he numbe o pa icipan s was ela i ely small o in es iga e he di e ences be ween pa ien s wi h ACOS and as hma alone. Howe e , we we e able o find ha olde age and hea ie smoking his o y p edic ACOS, which a e he mos common a iables ound in o he s udies oo. Mo eo e , wi h 190 pa icipan s, we we e able o e alua e he p e alence o ACOS among as hma ics wi h a posi i e smoking his o y, which was he p ima y objec i e o he s udy. Second, as we did no in es iga e consecu i e pa ien s, he e migh ha e been selec ion bias. On he o he hand, as we excluded pa ien s wi h known COPD, and e en hose using he Age (yea s) FEV1(l)/FVC(l) 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Pack-yea s FEV1(l)/FVC(l) 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Rho= – 0.25 P< 0.001 Rho= –0.28 P< 0.001 6010 20 30 40 50 60 7020 30 40 50 Figu e 2. Sca e plo s and eg ession lines showing he associa ion be ween age and pack-yea s e sus pos b onchodila o FEV 1 /FVC in 190 as hma pa ien s wi h a posi i e smoking his o y. FEV 1 , o ced expi a o y olume in 1 s; FVC, o ced i al capaci y. 1-Speci ici y 0.5 Sensi i i y 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Age Pack-yea s Age.60 Pack-yea s.20 1.00 0.1 0.2 0.3 0.4 0.9 0.80.7 0.6 Figu e 3. Recei e ope a ing cu e (ROC) analysis o age and pack-yea s in 190 as hma ic pa ien s. The cu -o poin s o 60 yea s o age yielded 63.5% sensi i i y and 59.4% specifici y and he cu -o poin o 20 pack-yea s yielded 80.8% sensi i i y and 42.8% specifici y o de ec o e lap synd ome. Table 2. The bes cu -o alues o age and pack-yea s and hei combina ion o de ec as hma–COPD o e lap synd ome among 190 as hma ics wi h posi i e smoking his o y Sensi i i y (%) Specifici y (%) PPV (%) NPV (%) Age ⩾60 yea s 63.5 59.4 37.1 81.2 Pack-yea s ⩾20 80.8 42.8 34.7 85.5 Age ⩾60 yea s o pack-yea s ⩾20 90.4 27.5 32.0 88.4 Age ⩾60 yea s and pack-yea s ⩾20 53.8 74.6 44.4 81.1 Abb e ia ions: COPD, ch onic obs uc i e pulmona y disease; NPV, nega i e p edic i e alue; PPV, posi i e p edic i e alue. P e alence o as hma–COPD o e lap synd ome T Kiljande e al 3 © 2015 P ima y Ca e Respi a o y Socie y UK/Macmillan Publishe s Limi ed npj P ima y Ca e Respi a o y Medicine (2015) 15047 d ugs mos commonly p esc ibed o COPD, one could specula e ha he esul migh a he be biased he o he way. Thi d, as a ew pa ien s we e ec ui ed by p i a e pulmonologis s, one could a gue ha we did no in es iga e exclusi ely p ima y ca e pa ien s. Howe e , in Finland, ea men o he mos se e e as hma ics is concen a ed in cen al and uni e si y hospi als, and he ec ui ing p i a e pulmonologis s we e emphasised o ec ui only pa ien s who could also be ea ed by gene al p ac i ione s. Mo eo e , as ACOS pa ien s’COPD was mos ly mild, wi h 96% being classed as GOLD s ages 1 and 2, we s ongly belie e ha we in es iga ed p ima y heal h ca e ou pa ien s as was in ended. The s udy also has i s s eng hs. Fi s , as he c i e ia o special eimbu semen o as hma medica ion a e s ic , we a e posi i e ha all he pa ien s in es iga ed eally had as hma. Second, as a as we know his is he fi s s udy o in es iga e he p e alence o ACOS among p ima y heal h ca e as hma ics wi h a posi i e smoking his o y bu wi hou a p e ious diagnosis o COPD. In mos ea lie s udies, he p e alence o ACOS has been e alua ed among COPD pa ien s by asking hem i hey ha e doc o - diagnosed as hma. 5,10,15 In e p e a ion o findings in ela ion o p e iously published wo k Ha din e al. 5 ound he p e alence o as hma–COPD o e lap o be 13% among COPD pa ien s in he COPDGene popula ion. Mi a i lles e al. 10 ound ha 17.4% o COPD pa ien s in he EPI- SCAN popula ion epo ed hey had p e iously been diagnosed wi h as hma, and hus p esen ed wi h as hma–COPD o e lap. In he PLATINO s udy, 22.8% o pa ien s wi h FEV 1 /FVC o0.7 epo ed a p io diagnosis o as hma and can be conside ed as o e lap pa ien s. 15 The 27.4% p e alence o as hma–COPD o e lap synd ome ound in ou s udy is sligh ly highe han in p e ious s udies. We belie e ha he majo eason o his di e ence may be he ac ha we in es iga ed a di e en pa ien popula ion. We s udied as hma ic pa ien s and in es iga ed how o en hei pos b onchodila o FEV 1 /FVC is o0.7, whe eas o he s udies 5,10,15 ha e in es iga ed how o en pa ien s wi h pos - b onchodila o FEV 1 /FVC o0.7 epo ha hey ha e p e iously been diagnosed wi h as hma. On he o he hand, p e alences o o e lap e en highe han ou s ha e been sugges ed. Fo example, So iano e al. 11 ound ha as many as 50% o pa ien s wi h obs uc i e pulmona y disease, aged 50 yea s o mo e, may su e simul aneously om mo e han one obs uc i e condi ion. The high p e alence o ACOS may be explained by he ac ha as hma and ai way hype esponsi eness a e sugges ed o be isk ac o s o de eloping COPD. 2 Lange e al. 16 ha e shown ha decline in pulmona y unc ion is as e in as hma ics han among hose wi hou as hma, and ha he decline is as es among hose as hma ics who smoke. In he s udy by Vonk e al., 12 16% o pa ien s wi h as hma de eloped i e e sible ai way obs uc ion du ing a 26-yea ollow-up. I has been shown ha ai way hype esponsi eness, e en wi hou as hma, is an impo an isk ac o o de eloping COPD. 17 Smoking is he mos impo an isk ac o o COPD. 2 The e o e, i is no su p ising ha he ACOS pa ien s in ou s udy had smoked mo e han hose wi h as hma alone. Also in he s udy by Lee e al., 18 g ea e amoun o ciga e e smoking was ela ed o he de elopmen o fixed ai way obs uc ion among as hma ic pa ien s. We ound ACOS pa ien s o be olde han pa ien s wi h as hma alone. In he s udy by Menezes e al., 6 pa ien s wi h as hma–COPD o e lap we e also olde han pa ien s wi h as hma alone. In ha s udy, and in he COPDGene s udy, 5 pa ien s wi h COPD we e olde han he o e lap pa ien s. These findings migh sugges a con inuum om e e sible ai way obs uc ion, ia o e lap, o i e e sible obs uc ion in some pa ien s. The e is e idence ha some pa ien s wi h as hma de eloped i e e sible ai way obs uc- ion du ing long-enough ollow-up, 12 and ha longe du a ion o as hma may be associa ed wi h i e e sible ai way obs uc ion. 18 Un o una ely, in he cu en s udy, we we e unawa e o how long he pa ien s had had as hma. Howe e , we belie e ha he age o he pa ien s indi ec ly eflec s he du a ion o as hma, and he e o e, ou finding ha age is associa ed wi h low FEV 1 /FVC is in keeping wi h he esul s o he s udies sugges ing ha longe du a ion o as hma may be associa ed wi h i e e sible ai way obs uc ion. On he o he hand, aging pe se causes changes in lung elas ic ecoil and pulmona y mechanics ha causes FEV 1 /FVC o dec ease; hence, olde subjec s may be mo e p one o ulfil he diagnos ic c i e ia o ACOS ega dless o he du a ion o hei as hma. 19 Implica ions o u u e esea ch, policy and p ac ice In he cu en s udy, he bes p edic o s o ACOS we e smoking o ⩾20 pack-yea s and age ⩾60 yea s. I bo h o hese c i e ia we e me , hen ACOS was ound in almos hal o he pa ien s. Lee e al. 18 ound ha longe du a ion o as hma and g ea e amoun o ciga e e smoking we e associa ed wi h fixed ai way obs uc ion, ha is, ACOS, in pa ien s wi h se e e as hma. In e e yday li e, his could mean ha in he case o an elde ly as hma ic wi h a clea ly posi i e smoking his o y, whose as hma is di ficul o ea , a en ion should be gi en no jus o he known as hma, bu also one should ake he COPD componen o possible ACOS in o accoun as well. Table 3. As hma–COPD o e lap synd ome in associa ion o demog aphic cha ac e is ics in 190 as hma pa ien s wi h posi i e smoking his o y. Resul s a e gi en by uni a iable bina y logis ic eg ession analyses O e lap synd ome Unadjus ed P alue N a (%) OR 95% CI Sex Female 31/112 (27.7) 1.00 Male 21/78 (26.9) 0.96 0.50–1.84 0.91 Smoking Ex-smoke 23/105 (21.9) 1.00 Cu en smoke 28/83 (33.7) 1.82 0.95–3.47 0.07 BMI, kg/m 2 o25.0 18/56 (32.1) 1.00 25.0–29.9 21/72 (29.2) 0.87 0.41–1.85 0.72 ⩾30.0 12/60 (20.0) 0.53 0.23–1.23 0.14 Age, yea s 20–59 19/101 (18.8) 1.00 60–70 33/89 (37.1) 2.54 1.32–4.91 0.005 Pack-yea s 10–19 10/69 (14.5) 1.00 20–60 42/121 (34.7) 3.14 1.46–6.76 0.004 Age and pack-yea s Age o60 and pack-yea s o20 5/43 (11.6) 1.00 Age ⩾60 o pack-yea s ⩾20 19/84 (22.6) 2.22 0.77–6.43 0.14 Age ⩾60 and pack- yea s ⩾20 28/63 (44.4) 6.08 2.11–17.49 0.001 Abb e ia ions: CI, confidence in e al; COPD, ch onic obs uc i e pulmon- a y disease; OR, odds a io. a Numbe o pa ien s wi h o e lap synd ome/numbe o all pa ien s in he g oup. P e alence o as hma–COPD o e lap synd ome T Kiljande e al 4 npj P ima y Ca e Respi a o y Medicine (2015) 15047 © 2015 P ima y Ca e Respi a o y Socie y UK/Macmillan Publishe s Limi ed Conclusions The e is a high p e alence o ACOS among as hma ics wi h a posi i e smoking his o y bu no p e ious diagnosis o COPD. Age o e 60 yea s and smoking o mo e han 20 pack-yea s we e he bes p edic o s o ACOS in his popula ion. ACKNOWLEDGEMENTS Tuija Poussa is acknowledged o he help wi h he s a is ical analyses. CONTRIBUTIONS All he au ho s we e in ol ed in planning o he s udy and w i ing he manusc ip . TK was esponsible o w i ing he manusc ip . COMPETING INTERESTS TK ecei ed pe sonal ees om Boeh inge Ingelheim Finland, GSK, No a is and Mundipha ma. TH ecei ed pe sonal ees om Boeh inge Ingelheim Finland and Takeda. KV ecei ed pe sonal ees om Boeh inge Ingelheim Finland, Chiesi, GSK, No a is, Takeda, Te a, Mundipha ma and Almi all. AJ is an employee o Boeh inge Ingelheim Finland. LL ecei ed pe sonal ees om Almi all, As a-Zeneca, Boeh inge Ingelheim Finland, Chiesi, GSK, No a is, O ion Pha ma, Takeda and Mundipha ma. FUNDING The s udy was unded by Boeh inge -Ingelheim, Finland. REFERENCES 1 Global Ini ia i e o As hma (GINA). Global S a egy o As hma Managemen and P e en ion 2014. h p://www.ginas hma.o g/documen s/4, accessed Decembe 2014. 2 Global S a egy o Diagnosis, Managemen , and P e en ion o COPD (GOLD). Global Ini ia i e o Ch onic Obs uc i e Lung Disease (GOLD) 2014. h p://www.goldcopd.o g/guidelines-global-s a egy- o -diagnosis-managemen . h ml, accessed Decembe 2014. 3 Mi a i lles M, Sole -Ca aluna JJ, Calle M, So iano JB. T ea men o COPD by clinical pheno ypes: pu ing old e idence in o clinical p ac ice. Eu Respi J 2013; 41: 1252–1256. 4 Kauppi P, Kupiainen H, Lindq is A, Tammileh o L, Kilpeläinen M, Kinnula VL e al. O e lap synd ome o as hma and COPD p edic s low quali y o li e. 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The images o o he hi d pa y ma e ial in his a icle a e included in he a icle’s C ea i e Commons license, unless indica ed o he wise in he c edi line; i he ma e ial is no included unde he C ea i e Commons license, use s will need o ob ain pe mission om he license holde o ep oduce he ma e ial. To iew a copy o his license, isi h p://c ea i ecommons.o g/licenses/ by/4.0/ P e alence o as hma–COPD o e lap synd ome T Kiljande e al 5 © 2015 P ima y Ca e Respi a o y Socie y UK/Macmillan Publishe s Limi ed npj P ima y Ca e Respi a o y Medicine (2015) 15047