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Eu opean Clinical Respi a o y Jou nal
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Daily physical ac i i y and lung unc ion decline in
adul -onse as hma: a 12-yea ollow-up s udy
Juho Loponen, Pinja Ilma inen, Leena E. Tuomis o, Onni Niemelä, Minna
Tommola, Pen i Nieminen, Lau i Leh imäki & Hannu Kankaan an a
To ci e his a icle: Juho Loponen, Pinja Ilma inen, Leena E. Tuomis o, Onni Niemelä, Minna
Tommola, Pen i Nieminen, Lau i Leh imäki & Hannu Kankaan an a (2018) Daily physical ac i i y
and lung unc ion decline in adul -onse as hma: a 12-yea ollow-up s udy, Eu opean Clinical
Respi a o y Jou nal, 5:1, 1533753, DOI: 10.1080/20018525.2018.1533753
To link o his a icle: h ps://doi.o g/10.1080/20018525.2018.1533753
© 2018 The Au ho (s). Published by In o ma
UK Limi ed, ading as Taylo & F ancis
G oup.
View supplemen a y ma e ial
Published online: 24 Oc 2018.
Submi you a icle o his jou nal
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View C ossma k da a
Daily physical ac i i y and lung unc ion decline in adul -onse as hma: a
12-yea ollow-up s udy
Juho Loponen
a,b
, Pinja Ilma inen
a
, Leena E. Tuomis o
a
, Onni Niemelä
c
, Minna Tommola
a
,
Pen i Nieminen
d
, Lau i Leh imäki
b,e
and Hannu Kankaan an a
a,b
a
Depa men o Respi a o y Medicine, Seinäjoki Cen al Hospi al, Seinäjoki, Finland;
b
Facul y o Medicine and Li e Sciences, Uni e si y o
Tampe e, Tampe e, Finland;
c
Depa men o Labo a o y Medicine and Medical Resea ch Uni , Seinäjoki Cen al Hospi al and Uni e si y o
Tampe e, Seinäjoki, Finland;
d
Medical In o ma ics and S a is ics Resea ch G oup, Uni e si y o Oulu, Oulu, Finland;
e
Alle gy Cen e, Tampe e
Uni e si y Hospi al, Tampe e, Finland
ABSTRACT
Backg ound: The e is a lack o knowledge on he associa ion be ween daily physical ac i i y and
lung unc ion in pa ien s wi h as hma.
Objec i e: This s udy aims o examine he associa ion be ween daily physical ac i i y and as hma
con ol, lung unc ion, and lung unc ion decline in pa ien s wi h adul -onse as hma.
Design: This s udy is pa o Seinäjoki Adul As hma S udy (SAAS), whe e 201 pa ien s we e
ollowed o 12 yea s a e as hma diagnosis. Daily physical ac i i y was assessed a ollow-up by a
s uc u ed ques ionnai e and used o classi y he popula ion in o subg oups o low (≤240 min) o
high (>240 min) physical ac i i y. Th ee spi ome y e alua ion poin s we e used: 1. diagnosis, 2.
he maximum lung unc ion du ing he i s 2.5 yea s a e diagnosis (Max
0-2.5
), 3. ollow-up a
12 yea s.
Resul s: High physical ac i i y g oup had slowe annual FEV
1
(p<0.001) and FVC
(p<0.018) decline. Addi ionally, he high physical ac i i y g oup had highe FEV
1
alues a
ollow-up, and highe FEV
1
/FVC a ios a ollow-up and diagnosis. The e was no di e ence in
BMI, smoking, medica ion, o equency o physical exe cise be ween high and low physical
ac i i y g oups. Di e ences emained signi ican a e adjus men s o possible con ounding
ac o s.
Conclusion: This is he i s demons a ion o an associa ion be ween long- e m FEV
1
decline and
daily physical ac i i y in clinical as hma. Low physical ac i i y is independen ly associa ed wi h
as e decline in lung unc ion. Daily physical ac i i y should be ecommended in ea men
guidelines in as hma.
ARTICLE HISTORY
Recei ed 12 Janua y 2018
Re ised 26 Sep embe 2018
Accep ed 26 Sep embe 2018
KEYWORDS
As hma; adul ; adul -onse ;
FEV
1
decline; lung unc ion
decline; physical ac i i y;
sys emic in lamma ion
In oduc ion
Physical ac i i y has been shown o ha e se e al heal h
bene i s such as educing he isk o ischemic hea dis-
ease, diabe es and colon cance [1]. Mos o he p e ious
esea ch on physical ac i i y has ocused on mode a e o
igo ous in ensi y ac i i ies such as unning whe eas less
is known on he low in ensi y e e yday mo emen which
cons i u es he majo i y o he physical ac i i y accumu-
la ed h oughou he day. A s uc u ed exe cise p og am
is o en used as an in e en ion in s udies, bu he es o
he daily physical ac i i y is equen ly o e looked.
Caspe sen e al. [2] de ined physical ac i i y as ‘any bodily
mo emen p oduced by skele al muscles ha equi es
ene gy expendi u e’and physical exe cise as ‘a subse o
physical ac i i y ha is planned, s uc u ed, and epe i i e
and has as a inal o an in e media e objec i e he
imp o emen o main enance o physical i ness’. These
de ini ions a e cu en ly used by he Wo ld Heal h
O ganiza ion (WHO) [3]. Physical ac i i y hus includes
all human mo emen whe eas physical exe cise is high o
mode a e in ensi y mo emen conduc ed wi h a pu pose
o sho e pe iods o ime. I is impo an o di e en ia e
be ween hese wo e ms since di e en in ensi ies o
physical ac i i y ha e di e en e ec s on he body [4].
Thus, i is c ucial o s udy physical ac i i y as a whole
ins ead o ocusing solely on he mode a e o igo ous
in ensi y ac i i ies. In he con ex o his s udy he e m
physical ac i i y includes all physical ac i i ies om loun-
ging a ound he shopping mall o going o a jog and he
e m exe cise only means mode a e o high in ensi y
ac i i ies.
CONTACT Juho Loponen [email p o ec ed] Depa men o Respi a o y Medicine, Seinäjoki Cen al Hospi al, FIN-60220 Seinäjoki, Finland
This s udy is egis e ed a www.ClinicalT ials.go wi h iden i ie numbe NCT02733016.
Supplemen a y da a o his a icle can be accessed he e.
EUROPEAN CLINICAL RESPIRATORY JOURNAL
2018, VOL. 5, 1533753
h ps://doi.o g/10.1080/20018525.2018.1533753
© 2018 The Au ho (s). Published by In o ma UK Limi ed, ading as Taylo & F ancis G oup.
This is an Open Access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion-NonComme cial License (h p://c ea i ecommons.o g/licenses/by-nc/4.0/), which
pe mi s un es ic ed non-comme cial use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly ci ed.
As hma is a ch onic in lamma o y disease o he
ai ways. O e he pas yea s esea che s ha e iden i ied
se e al pheno ypes o as hma e ealing he he e ogene-
i y o he disease [5,6]. Age o onse o as hma has been
ound as a key di e en ia ing ac o be ween he phe-
no ypes. I has been shown ecen ly ha he adul -
onse pheno ypes di e as ly om childhood-onse
as hma [5,6]. Childhood as hma is o en an a opic
disease cha ac e ized by high numbe s o b onchial
eosinophils and high se um le els o IgE wi h a good
esponse o glucoco icoid ea men . In con as ,
pa ien s wi h disease onse a adul hood ha e o en
mo e se e e as hma ha a ely emi s [7]. Recen ly,
as hma diagnosed a adul -age has been shown o con-
s i u e a majo i y among all new cases o as hma [8],
and i seems ha se e al li es yle ac o s such as ciga -
e e smoking and obesi y a e majo ac o s in adul -
onse as hma [6,9]. Since he concep o adul -onse
pheno ypes is a he new, only ew s udies exis on i
and he e is no clea consensus on he bes he apy o
hese pa ien s. Occasionally, adul -onse as hma may
also be di icul o dis inguish om ch onic obs uc i e
pulmona y disease (COPD) due o he o e lap o
symp oms and isk ac o s [10].
Physical exe cise has been shown o be a bene icial
ac o in he con ol o as hma [11]. Physical exe cise
educes sys emic and b onchial in lamma ion, and
inc eases maximal oxygen up ake [12,13]. Mos
esea ch on daily physical ac i i y in as hma ocuses
ei he on he isk o de eloping as hma o exe cise-
induced b onchocons ic ion. The e a e no published
long- e m s udies on daily physical ac i i y in pa ien s
wi h clinical as hma. Daily physical ac i i y has been
s udied ex ensi ely in COPD whe e highe le els o
physical ac i i y decele a e lung unc ion decline and
imp o e he quali y o li e [14,15]. P e ious epo s
ha e shown ha high physical ac i i y is associa ed
wi h be e lung unc ion, slowe lung unc ion decline,
and lowe mo ali y also in he gene al popula ion
[16,17]. Howe e , so a he e a e no p e ious s udies
on he associa ion be ween physical ac i i y and lung
unc ion change o e se e al yea s in pa ien s wi h
clinical as hma.
The aim o his s udy was o examine he associa ion
be ween daily physical ac i i y and as hma con ol,
lung unc ion, o lung unc ion decline in pa ien s
wi h adul -onse as hma.
Ma e ials and me hods
S udy popula ion and design
Seinäjoki Adul As hma S udy (SAAS) is a single-cen e
(Depa men o Respi a o y Medicine, Seinäjoki Cen al
Hospi al, Seinäjoki, Finland) 12-yea ollow-up s udy. The
s udy p o ocol and he inclusion and exclusion c i e ia
ha e been p e iously published [18]. S udy popula ion
consis s o 260 consecu i e pa ien s who we e diagnosed
wi h adul -onse as hma in 1999–2002 by a espi a o y
physician (Figu e 1). Pa ien s we e ec ui ed om he
diagnos ic isi . Diagnosis was based on ypical symp oms,
and i was con i med by objec i e lung unc ion measu e-
men s [18]. Smoke s (cu en o ex-) and pa ien s wi h co-
mo bidi ies we e included in he s udy. The pa ien s we e
ea ed and moni o ed acco ding o Finnish As hma
P og am guidelines [19] ei he in he specialized ca e o
in p ima y ca e. The collec ion o esea ch da a has been
p e iously epo ed [7,9,10,20]. A diagnosis, da a was
collec ed on lung unc ion, blood eosinophils, he ini ial
pha maco he apy, and as hma symp oms by Ai ways
Ques ionnai e 20 (AQ20) [21]. A opy was de ined as a
leas one posi i e esponse (≥3 mm) in skin p ick owa d
common ae oalle gens. A e 12 yea s pa ien s we e
in i ed o a e-e alua ion (2012–2013), and 201 (77%)
Figu e 1. Flow cha o he s udy.
2J. LOPONEN ET AL.
pa ien s a i ed o he ollow-up isi . A ollow-up in o -
ma ion was collec ed on as hma s a us, medica ion, and
co-mo bidi ies by s uc u ed ques ionnai e. Lung unc ion,
blood eosinophils and neu ophils, IgE le els, ac ion o
exhaled ni ic oxide (FeNO), in e leukin-6 (IL-6), and high
sensi i i y C- eac i e p o ein (hsCRP) we e measu ed.
Pa ien s also illed As hma Con ol Tes (ACT) [22],
AQ20, and a s uc u ed li es yle ques ionnai e.
Speci ically ained esea ch nu se e iewed all ques ion-
nai es wi h he pa ien s o limi misunde s andings. A
w i en in o med consen was ob ained o a s udy p o ocol
app o ed by he E hics commi ee o Tampe e Uni e si y
Hospi al, Tampe e, Finland (R12122).
De e mina ion o physical ac i i y
The le el o physical ac i i y was assessed a ollow-up by a
s uc u ed ques ionnai e. O e all daily physical ac i i y
was assessed by an open ques ion: ‘How many minu es
in a day do you spend mo ing?’A e p e-e alua ion,
pa ien s we e di ided in o high and low daily physical
ac i i y g oups. Cu o -poin was es ablished a 240 min
o daily physical ac i i y pe day. The equency o physical
exe cise was es ima ed by he ollowing ques ion: ‘How
o en do you ake pa in leisu e ime ac i i ies o a leas
hal an hou so ha you a e a leas somewha b ea hless
and swea y?’This ques ion had eigh choices anging om
ne e o e e yday. In his s udy, physical ac i i y ime and
physical exe cise equency a e assessed as hei own a i-
ables and a e no o be con used wi h each o he .
De e mina ion o lung unc ion
Lung unc ion was assessed using a spi ome e (Vmax
Enco e 22, Viasys Heal hca e, Palm Sp ings, CA, USA)
acco ding o in e na ional ecommenda ions [23]and
Finnish e e ence alues [24]. Pos -b onchodila o mea-
su emen s we e aken 15 min a e inhala ion o salbu a-
mol (400 µg). A e he ini ia ion o as hma he apy, only
p e-b onchodila o spi ome y was measu ed on mos o
he pa ien s, and he e o e we e alua ed he changes in
p e-b onchodila o spi ome y alues h oughou he
s udy. Lung unc ion measu emen poin s we e: (1) base-
line (i.e. ime o as hma diagnosis), (2) he maximum
lung unc ion (Max
0-2.5
) du ing he i s 2.5 yea s a e
diagnosis (i.e. a e s a o an i-in lamma o y he apy)
based on he highes p e-b onchodila o FEV
1
% p e-
dic ed, and (3) a e 12 yea s o ollow-up (Figu e 2)[9].
S a is ical analyses
Con inuous da a is exp essed as mean (SD) o a iables
wi h no mal dis ibu ion and as median and in e qua -
ile ange o a iables wi h skewed dis ibu ion. To
assess di e ences be ween high and low physical ac i i y
g oups, we used Mann-Whi ney es o con inuous
a iables wi h skewed dis ibu ions, independen sam-
ples - es o con inuous a iables wi h no mal dis i-
bu ion, and Chi-Squa e es o ca ego ized a iables.
Mul iple linea eg ession analysis was pe o med o
analyze ac o s associa ed wi h FEV
1
decline om poin
o Max
0-2.5
o he ollow-up isi . To a oid mul icollinea -
i y, explana o y a iables we e checked o s ong (>0.7)
mu ual co ela ion. Pa ien s whose BMI di e ed o e 3 SD
(n=4)o whoseFEV
1
decline di e ed o e 3.3 SD (n=3)
om mean we e emo ed om he linea eg ession ana-
lysis as ou lie s o ensu e homoscedas ici y. Fo wa d, back-
wa d and en e me hods we e used o imp o e model i .
S a is ical analyses we e pe o med using SPSS so wa e,
e sion 23 (IBM SPSS, Chicago, IL, USA). A p- alue <0.05
was ega ded as s a is ically signi ican .
Resul s
Pa ien cha ac e is ics
Cha ac e is ics o he pa ien s who a ended he ollow-
up isi a e shown a eTable 1. The median age o he
s udy popula ion was 45 (SD 14) yea s a diagnosis and
58% we e emales. O he pa ien s, 53% had smoking
his o y. The p opo ion o daily inhaled glucoco icoid
use s was 8% a diagnosis, 96% a Max
0-2.5
, and 76% a
Figu e 2. Rep esen a ion o he h ee lung unc ion measu emen poin s.
EUROPEAN CLINICAL RESPIRATORY JOURNAL 3
ollow-up. Pa ien s epo ed a median o 360 (in e -
qua ile ange 180–540) min o daily physical ac i i y.
When pa ien s we e di ided in o wo g oups based
on he le el o daily physical ac i i y (≤240 min s.
>240 min) he g oup wi h he highe amoun o phy-
sical ac i i y was younge and hey had ea lie as hma-
onse (Table 1). The high physical ac i i y g oup
included a highe pe cen age o emales han he low
physical ac i i y g oup. The high physical ac i i y
g oup also included less pa ien s wi h pos -b onchodi-
la o FEV
1
/FVC<0.7 and a his o y o smoking o a
leas 10 pack yea s (Table 1), cha ac e is ics which may
indica e an as hma-COPD o e lap synd ome (ACOS)
[25]. No ably, he e we e no di e ences in BMI, smok-
ing s a us, medica ion o as hma, o equency o
physical exe cise be ween he wo g oups (Table 1).
Associa ion be ween physical ac i i y and lung
unc ion
Lung unc ion was signi ican ly di e en be ween he high
and low physical ac i i y g oups. The high physical ac i i y
g oup had highe p e- and pos -b onchodila o FEV
1
-
alues a ollow-up (Table 2) bu only p e-b onchodila o
FEV
1
- alue was highe a diagnosis (eTable 2). FEV
1
/FVC-
a ios (p e- and pos -BD) we e signi ican ly di e en a
diagnosis and a ollow-up be ween he g oups (Table 2,
eTable 2). A e emo al o pa ien s wi h pos -b onchodi-
la o FEV
1
/FVC<0.7 and a smoking his o y o a leas 10
pack yea s (eTable 3), which may indica e he p esence o
ACOS [25], pos -b onchodila o FEV
1
/FVC- a io a ol-
low-up emained signi ican ly lowe in he low ac i i y
g oup (p= 0.032). This indica es ha possible ACOS is
no explaining he esul s.
Associa ion be ween physical ac i i y and lung
unc ion decline
When e alua ing lung unc ion decline om Max
0-2.5
o ollow-up isi in he high and low physical ac i -
i yg oups,amo e apiddeclineinFEV
1
(ml and %
o e e ence) and FVC (ml) in he g oup wi h less
daily physical ac i i y was obse ed (Table 3,
Figu e 3). The measu emen poin o Max
0-2.5
was
chosen because he pa ien s had un ea ed as hma a
diagnosis, and hei lung unc ion imp o ed signi i-
can ly du ing he ollowing mon hs due o s a o
as hma he apy. The e o e, compa isons be ween
diagnos ic and ollow-up alues would be compa i-
sons be ween un ea ed and ea ed as hma. The
di e ences be ween he g oups emained signi ican
when pa ien s wi h pos -b onchodila o FEV
1
/
FVC<0.7 and a smoking his o y o a leas 10 pack
yea s we e emo ed om he coho (eTable 4). The
equency o physical exe cise had no e ec on lung
unc ion decline (da a no shown).
Associa ion be ween daily physical ac i i y, as hma
con ol, and symp oms o as hma
The high and low physical ac i i y g oups had no
signi ican di e ence in as hma con ol o symp oms
when measu ed by using AQ20 o e all sco es
(eTable 5) o ACT (Table 4). Howe e , when analyz-
ing he sepa a e ques ions in ACT and AQ20 ques-
ionnai es, di e ences we e ound. The low physical
ac i i y g oup had mo e sho ness o b ea h and a
wo se sel -pe cei ed as hma con ol (ACT ques ions
2and5;Table 4). In AQ20 ques ionnai e he low
physical ac i i y g oup epo ed mo e b ea hlessness
in ques ions 3 (b ea hlessness du ing ga dening)
(p= 0.002), 13 (b ea hlessness du ing housewo k)
(p= 0.020) and 10 (di icul ies in ge ing a ound
hehousedue oches p oblems)(p= 0.028)
(eTable 5).
Table 1. Basic subjec cha ac e is ics by physical ac i i y g oups.
≤240 min o
physical
ac i i y/day
>240 min o
physical
ac i i y/day p- alue*
Numbe o pa ien s 74 127
Age (yea s) 61 (13) 57 (14) 0.036
Age o onse (yea s) 49 (13) 44 (14) 0.029
Males 39 (53%) 45 (35%) 0.018
Du a ion o daily physical
ac i i y (min)
135 (90–180) 480 (360–600) <0.001
Pa ien s exe cising a leas
3 imes pe week
43 (58%) 69 (54%) 0.660
BMI (kg/m
2
) 28.7 (5.2) 28.4 (5.8) 0.807
Ex o cu en smoke 38 (51%) 68 (54%) 0.772
Pack yea s (o ex- and
cu en smoke s)
20 (10–32) 15 (4–27) 0.067
Pos -b ochodila o FEV
1
/
FVC <0.7 and a leas
10 pack yea s
17 (24%) 16 (13%) 0.050
Pa ien s wi h a leas one
co-mo bidi y
51 (70%) 76 (60%) 0.172
Numbe o co-mo bidi ies,
COPD included
1(0–3) 1 (0–2) 0.091
Daily ICS use s 60 (81%) 93 (73%) 0.233
ICS dose (μg budesonide
equi alen )
800 (400–
1000)
800 (280–
1000)
0.393
Pa ien s who ecei ed o al
co icos e oids
30 (41%) 35 (28%) 0.062
Daily add-on medica ion
(includes LABA)
39 (53%) 62 (49%) 0.661
A opy 18 (27%) 49 (42%) 0.055
*S a is ical signi icances we e e alua ed using Mann-Whi ney es , inde-
penden samples - es o Chi-squa e es , espec i ely. Resul s a e dis-
played as median (in e qua ile ange), mean (SD), o n(%). BMI: body
mass index; FEV
1
: o ced expi a o y olume in 1 s; FVC: o ced i al
capaci y; COPD: ch onic obs uc i e pulmona y disease; ICS: inhaled
co icos e oid; LABA: long ac ing be a-ad enocep o agonis .
4J. LOPONEN ET AL.

Associa ion o daily physical ac i i y, sys emic and
ai way in lamma o y pa ame e s
Blood neu ophils, eosinophils, FeNO, IL-6, and
hsCRP we e measu ed. No di e ences we e
obse ed in any o hese bioma ke s o in lamma-
ion be ween he high and low ac i i y g oups
(eTable 6).
Fac o s associa ed wi h lung unc ion decline
To assess whe he lowe physical ac i i y emains
s a is ically signi ican ac o associa ed wi h mo e
apid lung unc ion decline in pa ien s wi h adul -
Figu e 3. Changes in mean P e-BD FEV
1
(mL) du ing 12 yea s o ollow-up in he g oups o <240 o ≥240 min o daily physical
ac i i y.
Table 2. Lung unc ion a ollow-up by physical ac i i y g oups.
≤240 min o physical ac i i y/day >240 min o physical ac i i y/day p- alue*
FVC (% e ) p e-BD 95 (16) 98 (15) 0,222
FVC (% e ) pos -BD 97 (16) 99 (14) 0,269
FEV1 (% e ) p e-BD 81 (19) 88 (16) 0,004
FEV1 (% e ) pos -BD 84 (18) 91 (16) 0,004
FEV1/FVC p e-BD 0.71 (0.63–0.78) 0.75 (0.69–0.79) 0,002
FEV1/FVC pos -BD 0.72 (0.65–0.79) 0.77 (0.71–0.81) 0,001
*S a is ical signi icances we e e alua ed using Mann-Whi ney es o independen samples - es . Resul s a e displayed as median (in e qua ile ange) o
mean (SD).FVC: o ced i al capaci y; BD: b onchodila o ; FEV1: o ced expi a o y olume in 1 s.
Table 3. Annual p e-BD lung unc ion decline om Max
0-2.5
o ollow-up by physical ac i i y g oup.
≤240 min o physical ac i i y/day >240 min o physical ac i i y/day p- alue*
ΔFVC/yea , p e-BD (ml) −43.6 (42.1) −29.3 (39.7) 0.018
ΔFVC/yea , p e-BD (%) −0.12 (1.14) 0.03 (0.95) 0.325
ΔFEV1/yea , p e-BD (ml) −58.8 (37.3) −41.4 (34.2) 0.001
ΔFEV1/yea , p e-BD (%) −0.83 (1.13) −0.39 (0.97) 0.005
ΔFEV1/ΔFVC - a io/yea , p e-BD −0.0052 (−0.0101 o −0.0019) −0.0041 (−0.0075 o −0.0016) 0.062
*S a is ical signi icances we e e alua ed using Mann-Whi ney es o independen samples - es . Resul s a e displayed as median (in e qua ile ange) o
mean (SD). FVC: o ced i al capaci y, BD: b onchodila o , FEV1: o ced expi a o y olume in 1 s.
Table 4. As hma con ol and symp oms a ollow-up.
≤240 min o
physical
ac i i y/day
>240 min o
physical
ac i i y/day p- alue*
Uncon olled as hma** 27 (36.5) 32 (25.2) 0.234
ACT sco e a ollow-up 22 (17–24) 22 (20–24) 0.159
ACT Q2 sho ness o b ea h
a leas 3–6 imes/week
22 (29.7) 16 (12.6) 0.005
ACT Q5 as hma somewha
con olled, poo ly
con olled, no a all
con olled
25 (33.8) 25 (19.7) 0.029
*S a is ical signi icances we e e alua ed using Chi-squa e es o Mann-
Whi ney es . Resul s a e displayed as n(%) o median (in e qua ile
ange). ACT: as hma con ol es .
**As assessed acco ding o GINA 2010 as p e iously desc ibed [18].
EUROPEAN CLINICAL RESPIRATORY JOURNAL 5
onse as hma a e adjus ing o age, sex, smoking,
BMI, a opy, and use o inhaled glucoco icoid, we
ca ied ou mul iple linea eg ession analysis. Daily
physical ac i i y ≤240 min emained s a is ically sig-
ni ican ly associa ed wi h mo e apid decline in FEV
1
in adjus ed analysis. O he explana o y ac o s o
as e lung unc ion decline we e sex (male), a opy,
and a highe BMI. (Table 5)Du ing hebuildingo
his linea eg ession model o he a iables we e
ied bu inclusion o hese a iables ga e he bes
model.
Discussion
The aim o his s udy was o examine he signi icance o
daily physical ac i i y in adul -onse as hma. Ou da a
indica es ha highe daily physical ac i i y is associa ed
wi h slowe decline in lung unc ion e en when adjus -
ing o sex, age, BMI, a opy, medica ion, and smoking.
High and low physical ac i i y g oups in his s udy had
no di e ence in BMI, smoking, medica ion, in e leukin-
6, hs-CRP, IgE, blood neu ophil o eosinophil coun s,
FeNO le els, o he equency o exe cise. The ac ha
he e was no di e ence in BMI was su p ising since high
BMI has been linked o low physical ac i i y [26]. The
low cu -o poin o 240 min could explain he absence
o di e ences in in lamma o y ma ke s. Also, di e -
ences in die a y habi s and ene gy expendi u e can
explain he absence o BMI di e ence. High physical
ac i i y g oup had a highe pe cen age o emales,
which sugges s ha emales do mo e low in ensi y phy-
sical ac i i ies in his se up. The e was no di e ence in
bioma ke s o sys emic in lamma ion be ween he
g oups wi h lowe and highe daily physical ac i i y
e en hough i has been shown ha egula physical
exe cise can educe sys emic in lamma ion [27]. The
equency o exe cise was no associa ed wi h lung unc-
ion decline in his s udy, which was expec ed since
he e we e no signi ican di e ences in he equency
o exe cise be ween he wo g oups o high and low
le els o daily physical ac i i y.
To ou knowledge his s udy is he i s o examine
he associa ion be ween daily physical ac i i y and
FEV
1
decline in clinical as hma. Ou inding is sup-
po ed by a simila associa ion ecen ly epo ed
be ween leisu e ime ac i i y and lung unc ion change
in pe sons ha ing sel - epo ed as hma in a popula ion
based coho o he No d-T øndelag Heal h S udy [28].
Ou s udy has se e al s eng hs. All as hma ics we e
ca e ully diagnosed by a espi a o y physician, and he
diagnosis was e i ied wi h spi ome y, se ial peak low
measu es, o measu es o b onchial hype eac i i y.
Mos pa ien s we e ea ed wi h a leas inhaled gluco-
co icoids be ween Max
0-2.5
and ollow-up. Smoke s
and pa ien s wi h co-mo bidi ies we e no excluded
making his a eal li e s udy. Du ing 1999–2002 a
conside able p opo ion o no el as hma diagnoses in
he egion we e made a Seinäjoki Cen al Hospi al and
>94% o he pa ien s ob aining diagnosis o as hma in
his hospi al a he s udy pe iod ook pa in he s udy
[18]. The e o e, his s udy popula ion well ep esen s a
p ima y ca e popula ion wi h as hma. Howe e ,
pa ien s wi h e y mild o seasonal as hma may ha e
been excluded since pa ien s had o ill he s ic lung
unc ion c i e ia [18].
The cu -o poin o high and low le els o daily
physical ac i i y in his s udy was chosen a 240 min o
physical ac i i y pe day. The cu -o poin di ided he
coho in o he lowes one hi d agains he wo highes
hi ds. The pa ien s we e made well awa e o wha he
ques ion mean so ha all misunde s andings could be
minimized. Pa ien s in his s udy had a median o
360 min o daily physical ac i i y, which is simila o
le els measu ed by accele ome e s in pa ien s wi h
ch onic diseases ( ange 308–395 min) [29–31]. The
cu -o poin o 240 min o physical ac i i y is a ela-
i ely low le el conside ing ha e en olde ca e home
esiden s in he UK [32] and aged (73–98 yea -olds)
Icelandic people [33] accumula ed 122–190 min o
daily physical ac i i y. The cu -o poin was in en ion-
ally se a his ela i ely low le el o allow examina ions
o he e ec s o e y low amoun s o physical ac i i y.
The mos signi ican limi a ion o his s udy is he
absence o spi ome ic pos -b onchodila o alues a
Max
0-2.5
. This is due o he ac ha he pa ien s we e
ea ed acco ding o he Finnish as hma guidelines
whe e sys ema ic eco ding o pos -b onchodila o y
alues was no ecommended a ha ime. E en hough
he pa ien s’es ima es on hei physical ac i i y a e close
o measu ed alues on simila coho s, i would ha e
been op imal o eco d daily physical ac i i y using
accele ome e s. In addi ion, physical ac i i y was
Table 5. Associa ion o explana o y ac o s wi h lung unc ion
decline om Max
0-2.5
o ollow-up in mul iple linea eg ession.
Va iable
Es ima e
(Δml)
95% Con idence
In e al p- alue
(Cons an ) −22.39 −69.16 o 24.39 0.346
Physical ac i i y o e
240 min/day
17.90 8.00 o 27.80 <0.001
Sex ( emale) 13.12 3.08 o 23.16 0.011
Age a ollow-up −0.23 −0.59 o 0.13 0.209
BMI a ollow-up −1.01 −2.02 o −0.01 0.048
No a daily ICS use a
ollow-up
1.40 −10.15 o 12.95 0.811
A opy −11.38 −21.72 o −1.04 0.031
E e smoke a ollow-up −1.97 −11.70 o 7.76 0.690
n = 173 (ou lie s: n = 7, missing da a: n = 21), BMI: body mass index, ICS:
inhaled co icos e oid.
6J. LOPONEN ET AL.
assessed only a ollow-up isi . Howe e , i has been
shown ha mos o ou heal h ela ed habi s a e o med
du ing childhood o ea ly adul hood and decline slowly
o emain cons an du ing adul hood. Signi ican
changes in heal h ela ed habi s a e unlikely o happen
wi hou a comp ehensi e li es yle in e en ion [34,35].
The e o e, i can be assumed ha he high physical
ac i i y g oup had highe ac i i y le els also a diagnosis.
Simila indings o ou s udy ha e been p e iously
ob ained in pa ien s wi h COPD and in gene al popu-
la ion [14,16]. Du ing an 11-yea ollow-up in pa ien s
wi h COPD, low physical ac i i y g oup had a as e
decline in lung unc ion (−4.8 ml/yea as e d op o
FEV
1
,−7.7 ml/yea as e d op o FVC) when com-
pa ed o high physical ac i i y g oup [14]. Slowe FEV
1
decline wi h highe physical ac i i y has been de ec ed
on gene al popula ion also [16]. In ou s udy FEV
1
declined 17.4 ml/yea as e , and FVC declined
14.3 ml/yea as e in he low ac i i y g oup. Sex
(male), high equency o disease exace ba ions, old
age, absence o glucoco icoid ea men , and smoking
ha e been ound o accele a e FEV
1
decline in as h-
ma ics [9,36,37]. A e adjus ing o hese ac o s wi h
mul iple linea eg ession analysis, he associa ion o
physical ac i i y wi h FEV
1
decline emained signi i-
can . Exace ba ions we e no included in he linea
eg ession, bu he e was no di e ence in he p opo -
ion o hose pa ien s ecei ing o al co icos e oid
ea men du ing he ollow-up pe iod be ween he
physical ac i i y g oups sugges ing ha he e was no
di e ence in exace ba ions.
The indings a e clinically signi ican , since emis-
sion a e in adul onse as hma is low [7] and mos
pa ien s su e om as hma o decades. The linea i y
o he e ec o physical ac i i y on lung unc ion
emains unclea . We ound one daily physical ac i i y
in e en ion s udy in pedia ic pa ien s wi h as hma
[38], and no change in FEV
1
was egis e ed du ing a
one-week ollow-up. Also, in a ecen c oss-sec ional
s udy [39] daily physical ac i i y had no e ec on
spi ome ic alues o heal hy adolescen s. In pa ien s
wi h childhood-onse as hma he e is a posi i e asso-
cia ion be ween physical ac i i y and lung unc ion
du ing a 3 week pe iod [40], bu his could be due o
se e al acu e b onchodila ions o pa ien s uncon-
sciously adjus ing hei daily ac i i y acco ding o
hei lung unc ion ea lie ha day. In ligh o his
e idence i seems likely ha daily physical ac i i y
does no cause long e m imp o emen s in FEV
1
, bu
ha i slows down FEV
1
decline. Howe e , as he da a
on physical ac i i y was collec ed a ollow-up isi , he
ela ion be ween lung unc ion decline and physical
ac i i y le el may also e lec ha hose wi h mo e
apid lung unc ion decline a e p one o dec ease
hei le el o physical ac i i y.
Conclusion
This s udy highligh s he impo ance o ac i e li es yle
and he pe ils o seden a y habi s. Mode n physical
ac i i y guidelines ocus on highe in ensi y ac i i ies,
bu i would be impo an o include low in ensi y
ac i i ies o hese guidelines o mo e holis ic app oach.
Mo e s udies wi h a p ecise analysis o he ac i i y
in ensi y a e needed o u he explo e he e ec o
physical ac i i y on pa ien s wi h as hma.
Acknowledgmen s
Aino Sepponen (Dep o Respi a o y Medicine, Seinäjoki
Cen al Hospi al, Seinäjoki, Finland) is g a e ully acknowl-
edged o he help h ough all he s ages o his wo k.
Funding
This s udy was sponso ed by Tampe e Tube culosis
Founda ion (Tampe e, Finland), he Finnish An i-
Tube culosis Associa ion Founda ion (Helsinki, Finland),
Jalma i and Rauha Ahokas Founda ion (Helsinki, Finland),
he Compe i i e S a e Resea ch Financing o he Expe
Responsibili y A ea o Tampe e Uni e si y Hospi al
(VTR,Tampe e,Finland),and heMedicalResea ch
Fund o Seinäjoki Cen al Hospi al (Seinäjoki, Finland)
[G an numbe 1717/6044]. None o he sponso s pa ici-
pa ed in he planning, execu ion, d a ing, o w i ing o
his s udy.
Con ibu o s
JL analyzed and in e p e ed he da a, and w o e he
manusc ip .HK,LL,ONandLET designed he s udy.
PI con ibu ed o he s udy design, in e p e a ion o he
da a, and w i ing o he manusc ip . MT con ibu ed o
he planning o lung unc ion decline analyses. PN p o-
ided s a is ical ad ice and commen ed on d a s o he
manusc ip .HK,PI,LL,ON,LETandMTcommen ed
on d a s o he manusc ip . All au ho s accep ull
esponsibili y o he conduc o he s udy, had access
o he da a, and con olled he decision o publish. JL is
he gua an o .
Compe ing in e es s
Weha e eadandunde s oodEu opeanClinical
Respi a o y Jou nal policy on decla a ion o in e es s and
decla e he ollowing. JL, ON and PN ha e no hing o
disclose. PI epo s pe sonal ees om Mundipha ma, pe -
sonal ees om O ion, pe sonal ees om As aZeneca,
ou side he submi ed wo k. LT epo s o he om
Takeda, Chiesi and O ion, o he om TEVA, o he om
EUROPEAN CLINICAL RESPIRATORY JOURNAL 7
Filha y, ou side he submi ed wo k. MT epo s pe sonal
ees om As a Zeneca, pe sonal ees om Boeh inge
Ingelheim, pe sonal ees om Filha y, pe sonal ees
om GlaxoSmi hKline, ou side he submi ed wo k. LL
epo s pe sonal ees om Boeh inge -Ingelheim Finland,
pe sonal ees om O ion Pha ma, pe sonal ees om GSK,
pe sonal ees om Chiesi, pe sonal ees om
Mundipha ma, pe sonal ees om As a Zeneca, pe sonal
ees and non- inancial suppo om No a is, pe sonal
ees and non- inancial suppo om Te a, pe sonal ees
om ALK, ou side he submi ed wo k. HK epo s pe so-
nal ees and non- inancial suppo om Almi all, g an s,
pe sonal ees and non- inancial suppo om As aZeneca,
pe sonal ees om Chiesi Pha ma AB, pe sonal ees om
GlaxoSmi hKline, pe sonal ees and non- inancial suppo
om Boeh inge -Ingelheim, pe sonal ees om Lei as-
Takeda, pe sonal ees om MSD, pe sonal ees om
No a is, pe sonal ees om Mundipha ma, pe sonal ees
om Medi h, pe sonal ees om Resmed Finland, non-
inancial suppo om In e mune, pe sonal ees om
Roche, pe sonal ees om O ion Pha ma, ou side he
submi ed wo k.
No es on con ibu o s
Juho Loponen, BM. Cu en ly a medical s uden a
Uni e si y o Tampe e. Academic in e es s include physical
ac i i y, in lamma ion and as hma.
Pinja Ilma inen, PhD. Resea che a Seinäjoki Cen al
Hospi al, Finland. He esea ch ocuses on in lamma o y
lung diseases and especially pheno ypes and media o s o
adul -onse as hma.
Leena E Tuomis o, MD, PhD. Senio espi a o y specialis a
Seinäjoki Cen al Hospi al. He esea ch in e es s include
adul -onse as hma om diagnosis o p ognosis.
Onni Niemelä, MD, Ph.D. P o esso o Labo a o y Medicine
a Seinäjoki Cen al Hospi al and Uni e si y o Tampe e.
Resea ch in e es s include li e diseases, as hma, exe cise
physiology and in lamma ion.
Minna Tommola, MD. Consul an in espi a o y medicine
in Cen al Finland Cen al Hospi al, Jy äskylä, Finland.
Resea ch in e es s include smoking and as hma.
Pen i Nieminen, PhD. Cu en ly an associa e p o esso in
medical in o ma ics and da a-analysis a he Uni e si y o
Oulu. Resea ch in e es s include scien i ic communica ion,
bios a is ics and medical educa ion.
Lau i Leh imäki, MD, PhD. Consul an in espi a o y med-
icine a Alle gy Cen e, Tampe e Uni e si y Hospi al,
Finland. He also wo ks as associa e p o esso a Facul y o
Medicine and Li e Sciences a Uni e si y o Tampe e. His
main clinical in e es is se e e as hma and his esea ch
ocuses on in lamma o y lung diseases.
Hannu Kankaan an a, MD, PhD. Head o Respi a o y
Medicine a Seinäjoki Cen al Hospi al, Seinäjoki, Finland.
He also wo ks as a p o esso o espi a o y medicine a he
Facul y o Medicine and Li e Sciences a Uni e si y o
Tampe e. His main esea ch in e es is adul -onse as hma.
ORCID
Juho Loponen h p://o cid.o g/0000-0003-3129-2221
Pinja Ilma inen h p://o cid.o g/0000-0002-8758-2431
Minna Tommola h p://o cid.o g/0000-0003-4201-389X
Hannu Kankaan an a h p://o cid.o g/0000-0001-5258-
0906
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