ARTICLE IN PRESS

Respiratory Medicine (2007) 101, 13631367

SHORT COMMUNICATION

Factors affecting adherence to asthma treatment

in an international cohort of young and
middle-aged adults
Angelo G. Corsicoa,, Lucia Cazzolettib, Roberto de Marcob, Christer Jansonc,
Deborah Jarvisd, Maria C. Zoiaa, Massimiliano Bugianie, Simone Accordinib,
Simona Villanif, Alessandra Marinonif, David Gislasong, Amund Gulsvikh,
Isabelle Pini, Paul Vermeirej, Isa Cerveria
a

Division of Respiratory Diseases, Fondazione IRCCS Policlinico S. Matteo, University of Pavia,

via Taramelli 5, 27100 Pavia, Italy
b
Department of Medicine and Public Health, Unit of Epidemiology and Statistics, University of Verona, Italy
c
Department of Medical Sciences: Respiratory Medicine and Allergology, University of Uppsala, Sweden
d
Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College, London, UK
e
Unit of Respiratory Diseases, CPA-Asl4, Turin, Italy
f
Department of Applied Health Sciences, Section of Epidemiology and Medical Statistic, University of Pavia, Italy
g
Department of Allergy, Respiratory Medicine and Sleep, University Hospital, Reykjavik, Iceland
h
Department of Thoracic Medicine, Institute of Medicine, University of Bergen, Bergen, Norway
i
Departement de Pediatrie, CHU de Grenoble, France
j
University of Antwerp (Campus Drie Eiken), Antwerp, Belgium
Received 15 June 2006; accepted 15 November 2006
Available online 26 December 2006

KEYWORDS
Education;
Epidemiology;
Guideline;
Health beliefs

Summary
Background: A major reason of the poor control of asthma is that patients fail to adhere to
their treatment. The aim of the study was to identify factors affecting changes in asthma
treatment adherence in an international cohort.
Methods: A follow-up study was carried out by means of a structured clinical interview in
971 subjects with asthma from 12 countries who participated in both the European
Community Respiratory Health Survey: ECRHS-I (199094) and ECRHS-II (19982002).
Subjects were considered adherent if they reported they normally took all the prescribed
drugs. A logistic model was used to study the adjusted effect of the determinants.
Results: The net change in adherence to anti-asthmatic treatment per 10 years of followup was 2% (95% CI: 9.5, 5.5), 7.5% (2.6, 17.6), 15.0% (6.6, 23.5) and 19.8% (4.1, 35.5),

Corresponding author. Tel.: +39 0382 501029; fax: +39 0382 501359.

E-mail address: angelo.corsico@unipv.it (A.G. Corsico).

0954-6111/$ - see front matter & 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.rmed.2006.11.012

ARTICLE IN PRESS
1364

A.G. Corsico et al.

respectively, in Nordic, Mediterranean, Continental and extra-European areas. Among the
428 non-adherent subjects in ECRHS-I, having regular consultations with health care
professionals was the strongest predictor of increased adherence (OR 3.32; 95% CI:
1.0810.17). Among the 543 adherent subjects in ECRHS-I, using inhaled corticosteroids
significantly predicted a persistence of adherence (OR 2.04; 95% CI: 1.113.75). No effect
of gender, age, duration of the disease, smoking habit and educational level was observed.
Conclusions: Our findings highlight the key role of doctors and nurses in educating and
regularly reviewing the patients and support the efforts for an improvement of clinical
communication.
& 2006 Elsevier Ltd. All rights reserved.

Introduction
Medication regimens for asthma care are particularly vulnerable to adherence problems because of their duration, the use
of multiple medications mostly delivered as inhalation, and the
periods of symptom remission. Identifying the specific reasons
for non-adherence is essential in order to determine the best
way to intervene and to increase the control of asthma.17
In the frame of the European Community Respiratory
Health Survey I (ECRHS-I, 19901994) we documented that
self-reported adherence was poor worldwide.8 The followup study (ECRHS-II) carried out in 19982002 provided us
with the opportunity to study factors affecting changes in
asthma treatment adherence in population cohorts from a
large number of different countries.

Methods
The methods for the ECRHS-I and ECRHS-II have been
published in detail elsewhere9,10 and further information is
available at the studys website [www.ecrhs.org]. The flow

of subjects over time from ECRHS-I and II is shown in Fig. 1.

The study population were 971 subjects (398 men, 573
women; mean age at the first survey 34.077.2 years) who
had ever suffered from asthma confirmed by a doctor in
ECRHS-I or II, had been prescribed asthma treatment and
had answered questions on adherence in both ECRHS-I and II.
The patients adherence to anti-asthmatic treatment
during the stable condition was evaluated by the following
question: If you have been prescribed medicine for your
breathing, do you normally take all the medicine?.8
The following adherence-related variables were considered: Geographic macroareas (Mediterranean, Continental,
Nordic, Extra-European); smoking habit; educational level;
duration of asthma; having taken inhaled corticosteroids in
the previous 12 months or not; patients beliefs about their
therapy; having regular appointments for asthma with a
doctor or a nurse; having written instructions from a doctor;
having a personal peak expiratory flow (PEF) meter; having
had spirometry during the previous 12 months.
Ethics approval was obtained for each center from the
appropriate ethics committee, and written consent was
obtained from each participant.

Figure 1 Flow chart of the selection of the study population from 418,000 subjects participating to the clinical stage of ECRHS-I to
those participating to ECRHS-II.

ARTICLE IN PRESS
International changes in adherence

1365

Table 1 Mutually adjusted OR (95% CI) for the association between adherence-related variables and increased adherence or
persistent adherence, respectively, among the 428 non-adherent subjects and among the 543 adherent subjects in ECRHS I.
Increased adherence

Persistent adherence

Sex
Man
Woman

1.0
0.80 (0.39, 1.66)

1.0
1.29 (0.72, 2.32)

Age

1.00 (0.95, 1.05)

1.03 (0.99, 1.07)

Macroarea
Mediterranean
Continental
Nordic
Extra-European

1.0
0.96 (0.22, 4.11)
0.26 (0.06, 1.14)
0.24 (0.03, 2.00)

1.0
0.74 (0.26, 2.13)
0.22 (0.08, 0.59)
1.82 (0.28, 11.84)

Duration of asthma

1.00 (0.98, 1.04)

1.00 (0.97, 1.03)

Smoking habits in ECRHS I

Non-smokers
Past smokers
Current smokers

1.0
0.63 (0.23, 1.74)
0.42 (0.18, 1.01)

1.0
1.07 (0.52, 2.18)
0.71 (0.37, 1.38)

Full time education

Till 16-year old or less
More than 16-year old

1.0
1.01 (0.13, 1.92)

1.0
1.06 (0.52, 3.08)

Type of drug in ECRHS I

No ICS
ICS

1.0
1.15 (0.43, 3.06)

1.0
2.04 (1.11, 3.75)

Written instructions
No
Yes

1.0
1.33 (0.96, 4.38)

1.0
0.73 (0.35, 1.52)

PEF meter
No
Yes

1.0
1.78 (0.76, 4.17)

1.0
1.66 (0.86, 3.23)

Spirometry in the last 12 months

No
Yes

1.0
1.60 (0.39, 6.52)

1.0
1.78 (0.55, 5.75)

Regular appointments for asthma

No
Yes

1.0
3.32 (1.08, 10.17)

1.0
1.23 (0.55, 2.75)

Thinking it is bad to take medicines all the time to help breathing

No
Yes

1.0
0.13 (0.06, 0.31)

1.0
0.82 (0.46, 1.46)

Thinking they should take as much medicine needed to cure problems

No
Yes

1.0
2.05 (0.96, 4.38)

1.0
1.09 (0.60, 1.99)

ECRHS European Community Respiratory Health Survey; OR odds ratio; CI confidence interval; ICS inhaled corticosteroids;
PEF peak expiratory flow.
Mediterranean area Spain, France (except for Paris), Italy; Continental area Belgium, Germany, The Netherlands, UK,
Switzerland, Paris; Nordic area Iceland, Norway, Sweden, Estonia; extra-European area Portland, USA, Melbourne, Australia.

Statistics
Absolute net change in adherence status per year of followup was estimated using population averaged generalized
estimating equations, with participants identified as the
clustering factor and duration of follow-up as an indepen-

dent variable. Results are expressed as net change per 10

years of follow-up. Estimates from each area were examined
for heterogeneity using the test statistic Q.11 To study the
adjusted effect of the determinants of any change
in adherence during the follow-up and to allow for potential
sources of heterogeneity in the design of the study, a

ARTICLE IN PRESS
1366
two-level logistic random intercept model was used12 (Stata
software, release 8.0; Stata Corp, College Station, TX, USA).

Results
The mean length of follow-up was 8.171.4 years. There
were no significant differences in asthma treatment
adherence in ECRHS-I between those who participated in
the follow-up and those who did not.
The adherence to anti-asthmatic treatment in ECRHS-II
was 53.4%, 56.1%, 67.6%, 76.4% and the net change per 10
years of follow-up was 2% (95% CI: 9.5%, 5.5), 19.8% (4.1,
35.5), 7.5% (2.6, 17.6) and 15.0% (6.6, 23.5), respectively,
in Nordic, extra-European, Mediterranean and Continental
areas, with significant between-areas heterogeneity
p 0:009.
Among the 428 non-adherent subjects in ECRHS-I, the only
predictors of increased adherence among the variables
considered were having regular appointments for asthma or
not thinking that it is bad to take medicine all the time
(Table 1).
Among the 543 adherent subjects in ECRHS-I, subjects using
inhaled corticosteroids were significantly more likely to be
persistently compliant; in contrast, subjects living in Nordic
countries were less likely to be still compliant (Table 1).
Gender, age at baseline, duration of the disease, smoking
habit, educational level, having written instruction from a
doctor, having a personal PEF meter and having had
spirometry during the previous 12 months were not significant
determinants for the improvement or the persistence of
adherence to antiasthmatic treatment (Table 1).

Discussion
The main findings of our study are that during the follow-up
of this international cohort of young and middle-aged
adults: (1) adherence to asthma treatment remained low
worldwide although it significantly increased in Continental
and extra-European areas and (2) the major predictors of
increased or persistent adherence are having regular followup consultations with health care professionals, and having
positive beliefs about the medications.
Despite the significant improvement observed in Australia
and USA, the countries with the lowest adherence and the
highest morbidity from asthma in the early 1990s,8
adherence with asthma treatment remains far from optimal.
Our results substantiate that frequent contact with patients
is a key factor for adherence to asthma treatment,
highlighting the importance of a frequent reviewed and
reinforced partnership between patients and health care
professionals.1316 The significant negative association we
found between concerns about adverse effects of medications and adherence to therapy shows once again that real
fears exist, have a major influence on attitude and behavior
in asthma management and should receive particular
attention during asthma consultation. On the other hand,
to our knowledge, this is the first study to report a positive
association between using inhaled corticosteroids and
adherence to treatment showing that fears about corticosteroids side-effects may be overcome, likely by the

A.G. Corsico et al.

patients perceptions of the benefits of taking therapy and
by appropriate information.
The main strength of this investigation is the large sample
from many different countries, its prospective design and
the time period over which it has been conducted. In fact, to
our knowledge, this is the first prospective study on the
change in adherence to anti-asthmatic treatment in an
international cohort since international guidelines have
been introduced.17
Our study has some limitations. First, changes in social,
economic and geographical barriers that have taken place in
eastern part of Europe during the 1990s may have affected
our analysis,18,19 but only to a minor extent. In fact, when
excluding Germany and Estonia from the analysis the main
results did not change. Second, self-reports of adherence
are not the most accurate modality to estimate patient
adherence. Certainly, the most reliable methods that are
available in the clinical setting could not be used in large
epidemiological surveys.20 In our study the questions were
not asked by the doctor who prescribed the treatment and
self-reported overestimation due to the patients desire to
please should be limited. At variance, adherence may be
overestimated during a controlled trial with several visit to
the clinic than during long-term real life.
In conclusion, further improvement in asthma management through an improvement in the quality of clinical
communication is required because non-adherence still
remains a major health care problem across countries.

Acknowledgements
The coordination of ECRHS-II was supported by the European
Commission, as part of their Quality of Life program. The
Pavia center was supported by Ricerca Corrente 80149/RCR
1998 IRCCS Policlinico San Matteo. Funding for the other
individual centers is listed at: /www.ecrhs.orgS.
The Coordinating center was made up of the following
people. Project Leader: P. Burney; Statistician: S. Chinn;
Principal Investigator: D. Jarvis; Project Co-ordinator:
J. Knox; Principal Investigator: C. Luczynska; Assistant
Statistician: J. Potts; Data Manager: S. Arinze.
Members of the Steering Committee for the ECRHS-II were
as follows. U. Ackermann-Liebrich (University of Basel, Basel,
Switzerland), J.M. Anto
, (Institut Municipal dInvestigacio
Medica (IMIM-IMAS) and Universitat Pompeu Fabra (UPF),
Barcelona, Spain), P. Burney (Kings College London, London,
UK), I. Cerveri (University of Pavia, Pavia, Italy), S. Chinn
(Kings College London), R. de Marco (University of Verona,
Verona, Italy), T. Gislason (Iceland University Hospital,
Reykjavk, Iceland), J. Heinrich (GSFInstitute of Epidemiology, Munich, Germany), C. Janson (Uppsala University,
Uppsala, Sweden), D. Jarvis (Kings College London), J. Knox
(Kings College London), N. Kunzli (University of Southern
California, Los Angeles, USA), B. Leynaert (Institut National
de la Sante
et de la Recherche Me
dicale (INSERM), Paris,
France), C. Luczynska (Kings College London), F. Neukirch
(INSERM), J. Schouten (University of Groningen, Groningen,
The Netherlands), J. Sunyer (IMIM-IMAS and UPF), C. Svanes
(University of Bergen, Bergen, Norway), P. Vermeire
(University of Antwerp, Antwerp, Belgium), M. Wjst (GSF
Institute of Epidemiology).

ARTICLE IN PRESS
International changes in adherence
The principal investigators and senior scientific team
were as follows. South Antwerp and Antwerp City, Belgium:
P. Vermeire, J. Weyler, M. Van Sprundel, V. Nelen. Aarhus,
Denmark: E.J. Jensen. Tartu, Estonia: R. Jogi, A. Soon.
Paris, France: F. Neukirch, B. Leynaert, R. Liard, M. Zureik.
Grenoble, France: I. Pin, J. Ferran-Quentin. Erfurt,
Germany: J. Heinrich, M. Wjst, C. Frye, I. Meyer. Iceland,
Reykjavik: T. Gislason, E. Bjornsson, D. Gislason, T. Blondal,
A. Karlsdottir. Turin, Italy: M. Bugiani, P. Piccioni, E. Caria,
A. Carosso, E. Migliore, G. Castiglioni. Verona, Italy: R. de
Marco, G. Verlato, E. Zanolin, S. Accordini, A. Poli, V. Lo
Cascio, M. Ferrari. Pavia, Italy: A. Marinoni, S. Villani, M.
Ponzio, F. Frigerio, M. Comelli, M. Grassi, I. Cerveri,
A. Corsico. Groningen and Geleen, The Netherlands:
J. Schouten, M. Kerkhof. Bergen, Norway: A. Gulsvik,
E. Omenaas, C. Svanes, B. Laerum. Barcelona, Spain: J.M.
Anto
, J. Sunyer, M. Kogevinas, J.P. Zock, X. Basagana,
A. Jaen, F. Burgos. Huelva, Spain: J. Maldonado, A. Pereira,
J.L. Sanchez. Albacete, Spain: J. Martinez-Moratalla Rovira,
E. Almar. Galdakao, Spain: N. Muniozguren, I. Urritia.
Oviedo, Spain: F. Payo. Uppsala, Sweden: C. Janson,
G. Boman, D. Norback, M. Gunnbjornsdottir. Goteborg,
Sweden: K. Toren, L. Lillienberg, A.C. Olin, B. Balder,
A. Pfeifer-Nilsson, R. Sundberg. Umea, Sweden: E. Norrman,
M. Soderberg, K. Franklin, B. Lundback, B. Forsberg,
L. Nystrom. Basel, Switzerland: N. Kunzli, B. Dibbert,
M. Hazenkamp, M. Brutsche, U. Ackermann-Liebrich.
Norwich, UK: D. Jarvis, B. Harrison. Ipswich, UK: D. Jarvis,
R. Hall, D. Seaton.
Competing interest statement
No competing interests declared.

1367

5.
6.

7.

8.

9.

10.

11.
12.
13.

14.
15.

16.

References
17.
1. Garcia G, Adler M, Humbert M. Difficult asthma. Allergy
2003;58:11421.
2. de Marco R, Bugiani M, Cazzoletti L, et al. The control of asthma
in Italy. A multicentre descriptive study on young adults with
doctor diagnosed current asthma. Allergy 2003;58:2218.
3. Juniper EF. The impact of patient compliance on effective
asthma management. Curr Opin Pulm Med 2003;9(Suppl.
1):S8S10.
4. Apter AJ, Reisine ST, Affleck G, Barrows E, ZuWallack RL.
Adherence with twice-daily dosing of inhaled steroids. Socio-

18.
19.
20.

economic and health-belief differences. Am J Respir Crit Care

Med 1998;157(6 Part 1):18107.
Niggemann B. How can we improve compliance in pediatric
pneumology and allergology? Allergy 2005;60:7358.
Vermeire E, Hearnshaw H, Van Royen P, Denekens J. Patient
adherence to treatment: three decades of research. A
comprehensive review. J Clin Pharm Ther 2001;26:33142.
Janson C, de Marco R, Accordini S, et al. Changes in the use
anti-asthmatic medication in an international cohort. Eur
Respir J 2005;26:104755.
Cerveri I, Locatelli F, Zoia MC, Corsico A, Accordini S, de Marco
R. International variations in asthma treatment compliance: the
results of the European Community Respiratory Health Survey
(ECRHS). Eur Respir J 1999;14:28894.
Burney PG, Luczynska C, Chinn S, Jarvis D. The European
Community Respiratory Health Survey. Eur Respir J 1994;7:
95460.
The European Community Respiratory Health Survey Steering
Committee. The European Community Respiratory Health
Survey II. Eur Respir J 2002;20:10719.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control
Clin Trials 1986;7:17788.
Goldstein H. Multilevel statistical models. London: Edward
Arnold; 1995.
Caress AL, Beaver K, Luker K, Campbell M, Woodcock A.
Involvement in treatment decisions: what do adults with
asthma want and what do they get? Results of a cross sectional
survey. Thorax 2005;60:199205.
Partridge MR. The asthma consultation: what is important? Curr
Med Respir Opin 2005;21(Suppl. 4):S117.
Adams RJ, Smith BJ, Ruffin RE. Patient preferences for
autonomy in decision making in asthma management. Thorax
2001;56:12632.
Gibson PG, Powell H, Coughlan J, et al. Self-management
education and regular practitioner review for adults with
asthma (Cochrane review). In: The Cochrane Library, Issue 1.
Oxford: Update Software, 2003.
National Institute of Health, National Heart Lung and Blood
Institute (NHLBI). Global strategy for asthma management and
prevention. NIH publication no. 023659. Update from NHLBI of the
WHO workshop report, NHLBI, Bethesda, MD, 1995 [revised 2004].
European Observatory on Health Systems and Policies, vol. 6(9),
2004. p. 232. ISSN:1020-9077.
European Observatory on Health Systems and Policies, vol.
6(11), 2004. p. 140. ISSN:1020-9077.
Krishnan JA, Riekert KA, McCoy JV, et al. Corticosteroid use
after hospital discharge among high-risk adults with asthma. Am
J Respir Crit Care Med 2004;170:12815.