asthma-chronic obstructive pulmonary disease overlap syndrome

8/10/2019 Asthma-chronic obstructive pulmonary disease overlap syndrome

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R E V I E W A R T I C L E

Denitions

Ashma is recognised as an allergic disease, usually saring in

childhood, characerized by reversible airflow obsrucion wih

episodic course and avourable prognosis in general, due o

good response o ani-inflammaory reamen. On he conrary,

chronic obsrucive pulmonary disease (COPD) is ypically

caused by obacco smoking, develops aer he ourh decade

o lie and displays incompleely airlow obsrucion, resuling

in progressive decline in lung uncion and premaure deah.

American Toracic Sociey (AS), in heir guidelines o 1995 (1)

defined ashma, chronic bronchiis, emphysema, COPD, airflow

obsrucion and idenified 11 disinc syndromes. Tere was an

overlap a 6 o hese 11 syndromes.

Overlap syndrome percenages are increased rom mid olaer lie progressively (2).

he Spanish COPD guidelines propose our COPD

phenoypes ha deermine differenial reamen: nonexacerbaor

wih emphysema or chronic bronchiis, mixed COPDashma,

exacerbaor wih emphysema and exacerbaor wih chronic

bronchii s (3). he mixed COPDashma pheno ype was

defined as an airflow obsrucion ha is no compleely reversible

accompanied by sympoms or signs o an increased reversibiliy

Asthma-chronic obstructive pulmonary disease overlap syndrome

(ACOS): current literature review

Antonis Papaiwannou

1

, Paul Zarogoulidis

1

, Konstantinos Porpodis

1

, Dionysios Spyratos

1

, Ioannis Kioumis

1

, GeorgiaPitsiou1, Athanasia Pataka1, Kosmas Tsakiridis2, Stamatis Arikas2, Andreas Mpakas2, Theodora Tsiouda3, Nikolaos

Katsikogiannis4, Ioanna Kougioumtzi

4, Nikolaos Machairiotis

4, Stavros Siminelakis

5, Alexander Kolettas

6, George

Kessis7, Thomas Beleveslis

8, Konstantinos Zarogoulidis

1

1Pulmonary Department-Oncology Unit, G. Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece;2Cardiology Department, Saint Luke Private Clinic, Thessaloniki, Panorama, Greece; 3Surgery Department (NHS), University General

Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece; 4Internal Medicine Department, Theageneio

Cancer Hospital, Thessaloniki, Greece; 5Department of Cardiac Surgery, University of Ioannina, School of Medicine, Greece; 6Anesthisiology

Department, 7Oncology Department, 8Cardiology Department, Saint Luke Private Clinic, Thessaloniki, Panorama, Greece

ABSTRACT Ashma and chronic obsrucive pulmonary disease (COPD) are chronic diseases, very common in general populaion.

hese obsrucive airway illnesses are maniesed wih chronic inlammaion aecing he whole respiraory rac.

Obsrucion is usually inermien and reversible in ashma, bu is progressive and irreversible in COPD. Ashma and

COPD may overlap and converge, especially in older people [overlap syndromeashma-chronic obsrucive pulmonary

disease overlap syndrome (ACOS)]. Alhough ACOS accouns approximaely 15-25% o he obsrucive airway diseases,

is no well recognised because o he srucure o clinical rials. COPD sudies exclude ashma paiens and ashma sudies

exclude COPD paiens, respecively. I is crucial o deine ashma, COPD and overlap syndrome (ACOS), as noable

clinical eniies, which hey share common pahologic and uncional eaures, bu hey are characerized rom differences in

lung uncion, acue exacerbaions, qualiy o lie, hospial impac and moraliy.

KEYWORDS Chronic obsrucive pulmonary disease (COPD); ashma; overlap

J Thorac Dis 2014;6(S1):S146-S151. doi: 10.3978/j.issn.2072-1439.2014.03.04

Correspondence to: Paul Zarogoulidis. Pulmonary Department, G. Papanikolaou

General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. Email:

[email protected].

Submitted Mar 02, 2014. Accepted for publication Mar 04, 2014.

Available at www.jthoracdis.com

ISSN: 2072-1439

Pioneer Bioscience Publishing Company. All rights reserved.


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Journal of Thoracic Disease, Vol 6, Suppl 1 March 2014 S147

o he obsrucion (3).

In anoher recen sudy rom Spain, as well, Soler-Caalua et al.

deined he clinical phenoype known as overlap phenoype

COPD-ashma (4). For his diagnosis were esablished wo

major and wo minor crieria. Major crieria include very posiive

bronchodilaor es (increase in FEV115% and 400 mL),

eosinophilia in spuum and personal hisory o ashma. Minor

crieria include high oal IgE, personal hisory o aopy and

posiive bronchodilaor es (increase in FEV112% and 200 mL)

on 2 or more occasions (4). However; hese crieria are neiher

speciic nor sensiive. Airway eosinophilia is no exclusive o

ashma and is presen in COPD paiens (5). Furhermore, a

clinically signiican bronchodilaor response (15%) can be

elicied in he majoriy o COPD paiens (6).

Zeki et al., (7) deined he ACOS as one o wo clinical

phenoypes: (I) ashma wih parially reversible airlow

obsrucion, wih or wihou emphysema or reduced carbonmonoxide diffusing capaciy (DLco) o 10 pack-years,

posbronchodilaor FEV1


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Papaiwannou et al. Overlap syndrome: current reviewS148

o spuum eosinophil coun or deecing COPD wih ashma,

using 2.5% as he cuoff value.

Remodeling

In obsrucive pulmonary diseases and in overlap syndrome,

we can no i ce h e remo deling ph enom enon . e mo deli ng

consiss o: mucosal edema, inflammaion, mucus hypersecreion,

ormaion o mucus plugs, hyperrophy and hyperplasia o he

airway smooh muscle. Te increased wall hickness, as i can be

seen on high resoluion C o paiens wih overlap (27), resuls

in airway obsrucion in mos airway diseases (28,29), and i is

more prominen in ashma, in comparison wih COPD (30).

Furhermore, increased airway wall ibrosis is repored in

boh ashma and COPD (31- 33). Air way remod eling occurs

hroughou he whole respiraory rac, bu remodeling o

he small airways is largely responsible or he decline in lunguncion in COPD and long-sanding ashma (34). I will

hereore be undersandable ha pharmacokineic sraegy

should ocus in small airways. In long-sanding ashma ha

previously menioned, we can noice incompleely reversible

airflow obsrucion, as i happens in COPD (35,36).Concerns

mainly ashmaics, older, male wih increased risk o deah

(27,37) I is impressive he ac ha 16% o ashmaics had

developed incomplee airlow reversibiliy aer 21-33 years o

ollow-up, as a longiudinal sudy showed (38).

Bronchial hyperresponsiveness (BHR)

BH is he exaggeraed response o a variey o simuli which can

cause bronchospasm and can be presen in inflammaory airway

diseases. Such simuli are: pes, pollen, bugs in home, ungus,

dus, srong odors, cold air, polluion, smoke, chemical umes,

exercise, anger, sress, ec. I is believed ha he person ha

develops BH o various simuli, will develop bronchodilaor

response afer proper reamen, as well. Tis happens due o he

ac ha boh bronchoconsricor and bronchodilaor response

relecs he same underlying disease, and we can observe i

in ashma and COPD (39,40). In ac, in severe obsrucion,

bro nch ospas m provoca ion es s are con ra ind icaed (41),and have been replaced wih reversibiliy ess, or securiy

reasons. BH can be noiced in almos all paiens wih ashma,

especially in hose wih sympoms and in up o wo hird o

COPD paiens (42). In order o recognise overlap syndrome in

COPD paiens wih airflow obsrucion we can use provocaion

ess wih proper agens ha do no cause direc airway smooh

muscle conracion, such as hisamine, manniol, adenosine,

hyperonic saline. BH raises is prevalence wih he age and

smoking and is presen in up o 10-20% o general populaion,

ofen being asympomaic (43,44). SAPALDIA sudy (Sudy on

Air Polluion and Lung Diseases in Aduls) proved ha 17% o

general populaion had BH o mehacholine and 50% o hem

were asympomaic, hence a 9% had asympomaic BH (45).

Furhermore, asympomaic BH is a r isk acor or developing

ashma and COPD and is associaed wih new sympoms o

wh eez ing , chronic cough, annual dec lin e in FEV1 and new

diagnosis o COPD afer 11 years o ollow-up (46). Smoking

in urn leads o increased risk o esablishing BH (47,48),

wh ile he sev eriy o BH is hig hly corre laed wih sev ere

sympoms and grea decline in FEV1, in ashmaics and COPD

paiens (42,49).

Exacerbations

Ashma and COPD are puncuaed by exacerbaions, bu overlapsyndrome may be associaed wih hree imes he requency

and severiy o exacerbaions (50,51). Exacerbaions increase

morbidiy, moraliy and he economic burden o disease, as 50-

75% o COPD healhcare cos in he USA is due o he reamen

o acue exacerbaions (1). Severe o very severe COPD

paiens experience 2 or more exacerbaions annually, as much

as ashmaics experience (52), while overlap paiens suer

rom signiicanly more exacerbaions, up o 2 or 2.5 imes as

many as hose wih lone COPD (50). Furher up, Menezes et al.

evaluaing he PLAINO sudy populaion showed, among

oher, ha subjecs wih ashma-COPD overlap had higher riskor exacerbaions [P 2.11; 95% confidence inerval (CI): 1.08-

4.12], compared o hose wih COPD (53). Exacerbaions are

riggered by viral, mainly, or bacerial rac inecion and can lead

o acceleraed loss o lung uncion (54). Tus, he phenoype o

requen exacerbaor mus be sudied urher.

Why does overlap happen?

Having already analyzed all he poenially imporan common

risk acors or overlapping ashma and COPD, such as

increasing age, smoking, BH, inlammaion, remodeling and

exacerbaions, he big quesion is why does overlap happen.Duch hypohesis ries o answer he quesion, saing ha

ashma and BH predispose o COPD laer in lie and ha

ashma, COPD, chronic bronchiis, and emphysema are differen

expressions o a single airway disease. Furhermore, he presence

o hese expressions is inluenced by hos and environmenal

acors (55). Epidemiological sudies, on he oher hand, proved

a correlaion beween respiraory illnesses during childhood and

impaired adul lung uncion (56). Knowing ha airway growh


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sars in uero, eal or childhood exposures may conribue o

adul ashma or COPD (57).

Plasma and sputum biomarkers

he ongoing eors in dierenial diagnosis o ashma-COPD

overlap syndrome (ACOS) could no ignore plasma and

spuum biomarkers. Iwamoo et al. (58) invesigaed our

poenial biomarkers o COPD: suracan proein a (SP-A),

soluble recepor or advanced glycaion end-producs (sRGE),

myeloperoxidase (MPO) and neurophil gelainase-associaedlipocalin (NGAL). SP-A and sAGE are pneumocye-derived

markers. MPO and NGAL are neurophil-derived molecules,

bu NGAL can be also expressed by respiraory epihelial cells.

Tere were five differen subjec groups: non-smokers, smokers,

ashma paiens, COPD paiens, ashma-COPD overlap

paiens. In order o ideniy overlap syndrome, he researchers

discovered ha only spuum NGAL was significanly increased

in overlap group, compared wih COPD group (P=0.00016) and

could diereniae paiens wih overlap rom COPD paiens.

Tis means ha elevaed induced spuum levels o NGAL should

poin he overlap diagnosis, suggesing enhanced neurophilic

airway inlammaion or airway epihelial injury in overlap, asIwamoo and his colleagues have proven.

Quality of life and hospital burden

Qualiy o lie maybe is no considered a very imporan

parameer or docors and researchers, bu i is crucial or

paiens. Kauppi et al. (59), based on paien-repored oucomes

and rerospecive medical record daa, divided a paien

populaion o 1,546 subjecs ino hree groups: (I) ashma only;

(II) COPD only; (III) ashma-COPD overlap and hey ocused

in healh-relaed qualiy o lie (HQoL). In he overlap group

HQoL was he poores o all. In he logisic regression model,

wih he ashma group as he reerence, boh he overlap and

he COPD group showed higher risk or low HQoL [odd

raio (O): 1.9; 95% CI: 1.2-3.2; and O: 1.8; 95% CI: 1.0-

3.2; respecively]. I is clear ha overlap was associaed wih

low HQoL, when compared wih ashma or COPD only.

Miravilles et al. (60), analysed daa rom he EPI-SCAN sudy,

an epidemiological sudy in Spain ha included 3,885 subjecs

previously diagnosed wih ashma. 17.4% o hem were classified

wih he ashma-COPD overlap phenoype and i was ound

ha hey had more dyspnea, wheezing, exacerbaions, reduced

levels o physical aciviy and worse respiraory-specific qualiy

o lie (11.1 unis on he S. Georges espiraory Quesionnaire-

SGQ, 95% CI: 4.88-17.36). Discussing abou hospial impacwe have already men ioned Menezes et al. (53) beore, who

evaluaed PLAINO sudy populaion and ound ha paiens

wih overlap were a higher risk no only or exacerbaions,

bu or hospializaion as well (P 4.11; 95% CI: 1.45-11.67),

compared o COPD paiens. Furhermore, Andersn et al.

analysed daa rom hospialisaions o Finnish people in a period

beween 1972 and 2009, covering in number he enire Finnish

populaion (5.35 million in 2009). hey ocused on paiens

wih primar y or secondar y diagnosis o ashma or COPD and

hey ound ha average number o reamen periods during

2000-2009 was 2.1 in ashma, 3.4 in COPD and 6.0 in overlapsyndrome (61).

Conclusions

In summary, i has been already undersood he speciiciy o

a separae clinical eniy called ACOS. Even hough ACOS

develops indisinc clinical and pahophysiological eaures

ha oen are complicaed wih hose o ashma or COPD, we

mus emphasize he imporance o he syndrome. Sudying

urher he syndrome may we discover mechanisic pahways

leading o he developmen o COPD. And his is imporan

because i is widely known ha paiens wih COPD oen areunderdiagnosed, possibly or decades. By recognizing common

risk acors i will, maybe, become possible o undersand and

modiy he progressive deerioraion o lung uncion, which

leads o COPD (Figure 1).

Acknowledgements

Disclosure: Te auhors declare no conflic o ineres.

Figure 1.Ashma and COPD connecion.

Asthma

Excerbation

COPD

Disease

progression


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Cite this article as:Papaiwannou A, Zarogoulidis

P, Porpodis K, Spyraos D, Kioumis I, Pisiou G,Paaka A, sakiridis K, Arikas S, Mpakas A, siouda

, Kasikogiannis N, Kougioumzi I, Machairiois

N, Siminelakis S, Koleas A, Kessis G, Beleveslis ,

Zarogoulidis K . Ashma-chronic obsrucive pulmonary

disease overlap syndrome (ACOS): curren lieraure

review. J horac Dis 2014;6(S1):S146-S151. doi:

10.3978/j.issn.2072-1439.2014.03.04

asthma-chronic obstructive pulmonary disease overlap syndrome

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