Chronic bronchitis and chronic obstructive pulmonary disease. The Finnish Action Programme, interim report

ARTICLE IN PRESS Respiratory Medicine (2007) 101, 1419–1425

Chronic bronchitis and chronic obstructive pulmonary disease. The Finnish Action Programme, interim report A. Pietinalhoa,, V.L. Kinnulab, A.R.A. Sovija ¨rvic, S. Vilkmand, O. Sa ¨yna ¨ja ¨kangase, K. Liippof, E. Kontulaa, L.A. Laitineng a

Filha (Finnish Lung Health Association), Sibeliuksenkatu 11 A 1, FI-00250 Helsinki, Finland Department of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Box 34, FI-00029 HUS, Finland c Department of Clinical Physiology, University of Helsinki and Helsinki University Hospital, Box 34, FI-00029 HUS, Finland d Department of Pulmonary Medicine, Porvoo Hospital, Sairaalatie 1, FI-06200 Porvoo, Finland e Department of Pulmonary Medicine, Lapland Central Hospital, Box 8041, FI-96101 Rovaniemi, Finland f Department of Pulmonary Medicine, Turku University Hospital, Alvar Aallon tie 275, FI-21540 Preitila ¨, Finland g University of Helsinki, Box 63, FI-00014 Helsinki, Finland b

Received 8 August 2006; accepted 29 January 2007 Available online 13 March 2007

KEYWORDS Chronic bronchitis; Obstructive pulmonary disease; COPD; Treatment programme; Guidelines; Smoking cessation

Summary The Finnish National Prevention and Treatment Programme for Chronic Bronchitis and COPD, launched in 1998, has, to date, been running for 6 years (2003). The goals of this action programme were to reduce the incidence of COPD and the number of moderate and severe cases of the disease, and to reduce both the number of days of hospitalisation and treatment costs. A prevalent implementation of over 250 information and training events started. Health centres and pharmacies appointed a person in charge of COPD patients. In order to improve the cooperation between primary and specialised care, two thirds of hospital districts created local COPD treatment chains. The early diagnosis of COPD by spirometric examination was activated during the programme. Number of health centres with available spirometric services increased to 95%. Before the start of the programme, approximately 5–9% of the adult population had COPD. During the whole programme, the proportion of male and female smokers decreased from 30% to 26% and from 20% to 19%, respectively. The total number of hospitalisation periods and days due to COPD decreased by 15% and 18%, respectively. Both the number of pensioners and daily sickness days due to COPD also decreased by 18%. Registered COPD induced deaths remained at their previous levels during the monitoring period, i.e. around

Corresponding author. Tel.: +358 9 4542120; fax: +358 9 45421210.

E-mail address: [email protected] (A. Pietinalho). 0954-6111/$ - see front matter & 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmed.2007.01.022

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A. Pietinalho et al. 1000 deaths out of 5.2 millions annually. The measures recommended by the programme have been widely introduced but they need to be still more effective. & 2007 Elsevier Ltd. All rights reserved.

Introduction Chronic obstructive pulmonary disease (COPD) is marked public health problem. In 1998, approximately 400,000 Finns out of a total population of 5.2 million had chronic bronchitis, and half of them symptomatic pulmonary obstruction.1 The total annual treatment costs for COPD are around 0.8 billion EUR. The national programme of Chronic Bronchitis and Chronic Obstructive Pulmonary Disease was designed by The Finnish Lung Health Association (Filha) between 1996 and 1997 in cooperation with the Ministry of Social Affairs and Health and with the help of a working group of experts. It was subsequently published on behalf of the Ministry of Social Affairs and Health in 1998.2–4 This action programme aims to reduce the incidence of COPD and the number of moderate and severe cases of the disease as well as to reduce the number of days of hospitalisation and the treatment costs (Table 1). Before or outside the COPD Programme, the Finnish Tobacco Act first prohibited advertising as early as 1976 and in 1994 smoking in public places and at the workplace as well as the sale of tobacco products to minors. Filha has been the main organisation coordinating the programme. For that purpose, Filha set up a working group of experts to gather and assess data on the work carried out in Finland in connection with the implementation of the COPD Programme, on the resources available and on the treatment given during the course of the programme in Finland.

Actions taken Filha has been providing on-going support for the training and implementation of the programme jointly with Uni-

Table 1

versity Hospitals and Health Care Centres (Table 2). Initially, information on the programme was widely distributed to health care professionals in all hospital districts between 1997 and 1999. Nationwide training of occupational health care workers followed this, organised in cooperation with regional occupational health care institutions in 2000. Seminar topics included COPD as a disease, its diagnosis and treatment, smoking cessation, and regional treatment chains. Between 2001 and 2003 a multidisciplinary, interactive training project for all health centres (156 of 271) was carried out. Also, representatives of local pharmacies were invited. Training material was based on the COPD Programme and on the evidence-based medicine (EBM) guidelines of the Finnish Medical Society Duodecim.2,5 Events for education and practical training for spirometry were arranged in the whole country. Also the hospital districts organised local training for their primary health care workers. At the order of the Ministry of Social Affairs and Health and with its support, Filha, in 2002 and 2003, carried out measures in connection with the implementation of the EBM Guideline on Smoking, Nicotine Dependency and Smoking Cessation.6 Also, Pulmonary Association Heli trained counsellors for smoking cessation groups and has been running of a national free-of-charge ‘‘quit line’’, called Stumppi since 2003. In addition, around 10 hospitals had by 2003 signed up to Finland’s Smoke-free Hospital Network, based on the EU network project titled Health Promoting Hospitals. Published national guidelines for measurement and assessment of spirometry and PEF (peak expiratory flow)7 were effectively distributed to laboratories and units performing these examinations thus improving the quality of spirometry especially for early detection of bronchial obstruction.

Goals and measures for the COPD Programme.2–4

Goals for prevention and treatment of chronic bronchitis and COPD (1) Decrease in occurrence of chronic bronchitis (2) Recovery of as many patients suffering from chronic bronchitis as possible (3) Maintenance of capacity for work and functional capacity of patients with COPD (4) Reduction in percentage of patients with moderate to severe COPD (5) Twenty-five per cent decrease in number of days spent by COPD patients in hospital (6) Decrease in annual costs per patient Measures for achievement of goals of programme for prevention of chronic bronchitis and COPD (1) Reduction in smoking (2) Reduction in work related and outdoor air pollutants and improvement of quality of air indoors (3) Increase in knowledge about risk factors and treatment of the disease in key groups (4) Promotion of early diagnosis and active treatment, among smokers in particular (5) Improvement in guided self-care (6) Early commencement of rehabilitation, planned individually and mainly implemented as an element in treatment (7) Encouragement of scientific research

ARTICLE IN PRESS Chronic bronchitis and chronic obstructive pulmonary disease

Table 2 Heli.

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COPD-related training for health care professionals in 1997–2003, organised by Filha and Pulmonary Association

Project/event

Training organised by Filha First National COPD Day Seminars for individual hospital districts Seminars organised with regional occupational health institutions Training at individual health centres COPD Programme presented at the physicians’ event ‘‘Doctors Days’’ Project to improve the quality of spirometric examinations Other training Training organised by Pulmonary Association Heli Information meetings for health care professionals Total

During the implementation of the programme, hospitals and health care centres were encouraged to build up treatment chains and to improve resources, particularly in primary health care. The overall aim of the COPD Programme was broadly to encourage a healthy lifestyle among COPD patients. Given the high number of COPD patients and long distances in the north of Finland, Ranua health centre in Lapland put special emphasis to COPD patients in 1998 and 1999, to diagnose and treat COPD and particularly to treat exacerbations and manage oxygen therapy at home. The Pulmonary Association Heli is the most important patient organisation supporting COPD patients. During the first 6 years of the COPD Programme, Heli ran three projects supported by the Finnish Slot Machine Association that have been useful for the treatment of COPD patients: (1) the ‘‘Oxygen Network’’ project, (2) a family-centred rehabilitation project for respiratory patients, and (3) a compact guide, ‘‘’Good Practice in the Rehabilitation of Respiratory Patients’’, especially for occupational health services and health centres. The number of rehabilitation courses organised by Association Heli for COPD patients as well as the number of participants increased seven times between 1997 and 2003. Outpatient rehabilitation courses were organised on three occasions from 1997 to 1999.

Outcomes Improvements in passive exposure to tobacco smoke, smoking habits and treatment of smoking As a result of the Tobacco Act, involuntary exposure to tobacco smoke at the workplace has been declining. The proportion of non-smokers who are not exposed to tobacco smoke during their working day increased from 21% to 71%

Time (year(s))

Number of events

Number of health care professionals participating

1997 1997–1999 2000

1 27 7

300 2000 600

2001–2003 1998–1999

156 3

3500 200

2001–2003 1997–2003

25 20

800 1400

1998–2003

21

1400

260

10,200

between 1994 and 1998.8 The amendments of the Act in 1999 resulted in a gradual ban of smoking in restaurants. The implementation of the COPD Programme and EBM Guideline on Smoking Cessation2,6 improved considerably the attitude of health personal to smoking cessation and it was accepted as a part of the treatment of COPD. At first time, tobacco contact nurses were established in primary health care and hospitals. Smoking among Finns slightly decreased during the programme. Thirty per cent of adult men and 20% of women were smokers in 1997. In 2003, the proportion of male and female smokers had fallen to 26% and 19%, respectively.9 In the late 1980s, almost 40% of 16-year-old boys smoked, but according to the recent Study on Adolescent Health 2003, conducted by STAKES (the National Research and Development Centre for Welfare and Health), 23% of boys aged between 14 and 18 smoked; among girls, the proportion of smokers was 26%. Studies conducted in 1987 and again 1997 found that the proportion of smokers among pregnant mothers had remained the same, 15%.10

Still high prevalence of COPD in Finland Before the COPD Programme, approximately 400,000 people (10% of adults) in Finland were calculated to have chronic bronchitis, with 200,000 of them (5% of adults) having symptomatic COPD.1 In 1995, the FinEsS project, an extensive on-going epidemiological study on asthma, COPD and pulmonary symptoms, was launched in three countries: Finland, Estonia and Sweden. Based on those studies,11 5.4% of Finns aged between 21 and 70 had COPD (British Thoracic Society (BTS) criteria). When the GOLD criteria (Global Initiative for Chronic Obstructive Lung Disease) were applied, the percentage was 9.4%. So, the real number of COPD patients is at least as high as the old estimations showed.

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A. Pietinalho et al.

Lesser need of hospitalisation and lover mortality Hospitalisation due to COPD was decreased: 18% fewer hospitalisation days and 15% fewer hospitalisation periods occurred in 2003 compared to that in 1997,12 (www.stakes.fi). The biggest change was observed among the elderly. These decreases from 1997 to 2003 were highly significant in all age groups for men ðpo0:001Þ, but for women only in the age group 65–74. According to the statistics of the Finnish Population Register in 1998, 1147 COPD-related deaths were recorded and in 2003 the number was 1041. Since 1998, mortality has decreased annually by 2.8%, at best.

Improvement of treatment chains and resources Filha conducted two surveys among the chief physicians of 30 pulmonary units, one in 2000 and the other in 2003 (Pietinalho A, personal communication). The response rate to both surveys was 97%. In 2000, half of chief physicians in pulmonary units and three years later, 70% reported the existence of a regional programme. Twelve of the regional treatment chain programmes are published on the Internet: www.Terveysportti.fi. Health centre resources for the treatment and diagnosis of COPD patients were assessed during the three-year training project for individual health centres ðn ¼ 156Þ carried out by Filha (2001–2003) (Kontula E, personal communication). Ninety-two health centres (59%) replied (Table 3). Correspondingly, the resources of the Asthma Programme13 and for the treatment of asthma were assessed in a study using structured telephone interviews with 271 health centres14 (Table 3). In addition to primary and specialist health care, there were around 600 pharmacies in Finland where asthma counsellors were appointed. Now, they work also as counsellors for COPD patients and for supporting smoking cessation. A follow-up quality assessment on spirometric examinations was conducted by a postal survey in 1999. The opportunities for diagnosing COPD, i.e. for performing spirometric examinations, were relative good in health centres. During nine years, the quality of spirometric examinations was clearly improved, although some problems still existed. The frequency of spirometer calibration and the use of recommended Finnish reference values

Table 3

(1982)15 had markedly increased but questions regarding the quality of a single graph and the repeatability of graphs were problematic (Table 4).16

Treatments of exacerbations in primary health care as well In 2003, as the result of the training project centre the treatment of COPD exacerbations had become more effective in Ranua health centre and the use of specialist health care for COPD patients had decreased significantly. As one of the treatment options for COPD patients, home nursing units have been set up in different parts of Finland in recent years. According to an experiment at the hospital of Porvoo, one half of the COPD exacerbations requiring hospital care could be managed at home.17

Activated use of respiratory devices The supply and use of respiratory devices is regulated by the Act on Health Care Devices and Equipment.18 One evaluation of the use of the respiratory devices was made just before the programme in 199719 and four were made during the period 1998–2003. These showed that the number of patients using respiratory devices increased constantly and was statistically significant increased until the year 2003: users of oxygen therapy from 1810 to 2198 ðpo0:001Þ and CPAP devices from 3741 to 10,510 ðpo0:001Þ.

Rehabilitation more ordinary The statistics of the Finnish Social Insurance Institution (SII) and the employment pension system show that the number of COPD-related sickness pensions granted decreased between 1996 and 2002 by 14% (from 2252 to 1944) and the number of COPD-related daily sickness allowance periods paid by the SII decreased by 18% (from 1509 to 1235).

Increased research activity One of the measures of the COPD Programme was to encourage scientific research. A number of studies have been made. The previously mentioned FinEsS project is expected to bring further long-awaited clarification to the epidemiology of COPD.11,20–24 In addition to this, ongoing

Health centre resources for the treatment of asthma and COPD.

Question/information sought

Is familiar with the programme/the EBM guideline There is a physician in charge There is a nurse in charge The health centre has a spirometry device The health centre gives advice on smoking cessation EBM ¼ evidence based medicine.

Treatment resources in Treatment resources in accordance with the Asthma accordance with the COPD Programme Programme14 (%) (Kontula E, personal communication) (%)

83 94 95 53

78/85 30 34 82 63

ARTICLE IN PRESS Chronic bronchitis and chronic obstructive pulmonary disease

Table 4

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Quality index for spirometric examinations16 (www.filha.fi).

Criterion number

Criterion (main points)

Maximum score

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Time reserved for the examination Calibration frequency Written instructions for calibration Use of a nose clip Asking about medication and drawing conclusions from the response Criteria for approving an exhalation Criteria for the repeatability of graphs Reference value praxis Following recommendations on spirometric examinations Printing each graphs Giving an end result graph of the result Parameters printed Giving a report on the spirometry Participating in training or in courses on spirometry (in relation to the number of staff) Total

6 6 2 4 10 8 12 8 4 6 4 15 5 10 100

COPD-related research is being carried out in Finland in cooperation with the Department of Respiratory Diseases at HUCH, the Skin and Allergy Hospital and Oulu University Hospital. There is also collaboration with the University of Southampton and the Denver Jewish Medical Research Center. The purpose of the above studies is to develop new non-invasive examination methods to assess the inflammation and tissue damage observed in connection with smoking and COPD focusing on sputum and exhaled air.25–27 The studies also assess the lung’s defence mechanisms by examining biopsy samples taken from smokers and COPD patients, and look for factors that might indicate the development or progress of the disease.28–30 The National Public Health Institute annually monitors the health habits of adults (aged 16–64) on the basis of 10,000-person population samples. Smoking habits of the population were assessed as part of this.9,10 Separate studies have been carried out to investigate smoking and exposure to tobacco smoke among employees8 and smoking habits among health care professionals. At the same time, attempts have been made to assess the attitudes of health care staff to smoking cessation. Smoking among health care professionals has clearly reduced. The significance of passive exposure to tobacco smoke has also been studied in Finland, and it has proved for the first time that passive exposure to tobacco smoke increases the lifetime risk of asthma.31

Discussion The single most important factor causing COPD is smoking and the main goal of the programme is to stop people smoking. A study published by Lundba ¨ck’s Swedish research group indicates that up to half of smokers may develop COPD, whereas the previous estimates were 15–20%.32 The state and municipalities play an important role in preventing young people from starting smoking. The Finnish Tobacco Act aims to reduce passive exposure to tobacco

smoke in particular. The Act and the resulting discussion have been exceptionally effective in reducing smoking among adults but less so among adolescents. The information given during the implementation of the COPD Programme may also have influenced smoking habits among adults. At the start of the programme, attitude surveys conducted during training events for health care professionals still showed that smoking cessation was not considered the task of health care professionals but was thought to be the responsibility of NGOs. This situation has already changed (Table 3). In addition, the practical implementation of the EBM Guideline for Smoking Cessation5 began at the end of 2002. Information campaigns and increased access to smoking cessation services may also have helped to reduce smoking among adults. COPD is often diagnosed in older patients who have a long history of smoking. The Finnish population is ageing, which further increases the incidence of COPD. Even if we were able to influence the extent of smoking immediately, the associated decrease in COPD would be slow. The monitoring period for the programme is still too short to observe any convincing changes in the COPD prevalence. In the mid-1990s, it was expected that the number of COPD-related days of hospitalisation and days of hospital treatment would double by 2020.33 One of the aims of the COPD action programme is to achieve an overall 25% reduction in hospitalisation (Table 1). The programme can explain the reduced number of hospitalisation days partly. Already before the programme the structure of the hospital networks changed. For example reduced number of hospital beds and increased emphasis on outpatient care were having an influence on the figures. On the other hand, the decreasing needs for hospital care,12 as well as the reduction in the number of sickness leave periods and retirements may indicate that patients are coping better despite the disease. The long-acting bronchodilators and a new long-acting anticholinergic medication33 that have become available to COPD patients during the programme may improve the

ARTICLE IN PRESS 1424 patients’ ability to cope. Also, the stuff of primary health care is now more aware of COPD and its treatment. During the programme, the number of patients with severe COPD and those who use oxygen therapy has continued to rise. This is mainly due to the fact that the criteria for treatment have been clarified and that the availability of treatment has improved. One of the aims of the action programme is to reduce severe disease and the number of COPD-related deaths. However, since 1998, mortality has been decreasing annually by 2.8% at best. On the other hand, the mortality figures are evidently underestimations despite the 6-years’ period of the COPD Programme: a cardiac event, for instance, is often registered as the cause of death of a COPD patient. Diagnostic resources and quality of the COPD seems to be improved during the programme;14,16 the patients’ access to spirometry has enhanced and the technical quality and interpretation abilities have improved, partly by the aid of effectively launched Finnish Guidelines for recording and assessment of spirometry.7 More frequent detection of irreversible small airways obstruction in asymptomatic smokers may have improved the motivation to stop smoking. The systematic practical implementation of the COPD Programme2 and the Asthma Programme13 preceding it seems to have created opportunities for effective COPD diagnosis and treatment in all health care sectors. It is crucially important that education about COPD and the development of health care structures are continued in order to ensure early diagnosis, early treatment, smoking cessation, appropriate patient monitoring and early rehabilitation. Since the COPD Programme started in 1998, a few criticisms have been directed at it. In the literature,34 national COPD treatment guidelines including the Finnish treatment programme2 have been criticised for not being based on scientific evidence. However, the National COPD Programme2 was based on the available literature and the experiences and knowledge of a wide group of experts. The programme also gave recommendations for the organisation of the COPD work. Further more, the Finnish EBM guideline for COPD5,35 was published only a year after the publication of the COPD Programme. The content of the guideline could therefore be quickly added to the tools for the practical implementation of the programme. There was, consequently, confirmed scientific evidence for the message. To date, the COPD Programme has been successful in reaching its targets partly. Nevertheless, some changes in the development recommended by the programme may be due to changes in health care resources and organisations and developments in medication.

Acknowledgements The Ministry of Social Affairs and Health supported the making of the COPD Programme and Finland’s Slot Machine Association together with Filha supported the implementation of the programme during the two first years. Also pharmaceutical industry has partly supported the implementation. Filha has supported this follow-up report of the Finnish COPD Programme. We thank Pentti Tukiainen for his

A. Pietinalho et al. contribution to the report, and Timo Klaukka for his assistance, as well.

References 1. Aromaa A, Helio ¨vaara M, Impivaara O. Terveys, toimintakyky ja hoidontarve Suomessa. Kansanela ¨kelaitoksen julkaisuja, vol. AL: 32. Helsinki ja Turku, 1989 [in Finnish]. 2. Krooninen keuhkoputkitulehdus ja keuhkoahtaumatauti. Valtakunnallinen ehka ¨isy- ja hoitoohjelma 1998–2007. Sosiaali- ja terveysministerio ¨. Julkaisuja 1998; 4 [in Finnish]. 3. Chronic bronchitis and chronic obstructive pulmonary disease. National Guidelines for prevention and treatment 1998–2007. Ministry of Social Affairs and Health. Publications, 1998:16. 4. Laitinen L, Koskela K and the expert advisory group listed in the foreword. Chronic bronchitis and chronic obstructive pulmonary disease: Finnish National Guidelines for Prevention and Treatment 1998–2007. Respir Med 1999;93:297–332. 5. The Finnish Respiratory Society. COPD treatment guideline. Duodecim 1999;115:496–505 [in Finnish]. 6. Working Group appointed by the Finnish Association for General Practice. Smoking, nicotine dependency and smoking cessation. Evidence Based Medicine guideline. Duodecim 2002. hhttp:// www.kaypahoito.fi/i [in English]. 7. Sovija ¨rvi ARA, Piirila ¨ P, Korhonen O, Louhiluoto E, Pekkanen L, Forstedt M. Performance and evaluation of spirometric and PEF measurements, offprint 3. KP-paino, Kokkola: Kliinisten Laboratoriotutkimusten Laaduntarkkailu Oy; Moodi 1995 [in Finnish]. 8. Heloma A, Jaakkola MS, Ka ¨hko ¨nen E, Reijula K. The short-term impact of national smoke-free workplace legislation on passive smoking and tobacco use. Am J Public Health 2001;91(9): 1416–8. 9. Helakorpi S, Patja K, Pra ¨tta ¨la ¨ R, Aro AR, Uutela A. The health behavior of Finnish adults. The National Health Institute B17/ 2003, spring 2003. hwww.ktl.fi.i [in Finnish]. 10. Jaakkola N, Jaakkola MS, Gissler M, Jaakkola JJK. Smoking during pregnancy in Finland: determinants and trends, 1987–1997. Am J Public Health 2001;91:284–6. 11. Kotaniemi JT, Sovija ¨rvi A, Lundba ¨ck B. Chronic obstructive pulmonary disease in Finland: prevalence and risk factors. COPD: J Chronic Obstructive Pulm Dis 2005;3:331–9. 12. Sa ¨yna ¨ja ¨kangas O, Lampela P, Pietinalho A, Kontula E, Tuuponen T, Keistinen T. Keuhkoahtaumataudin valtakunnallinen ehka ¨isyja hoito-ohjelma puoliva ¨lissa ¨—miten sairaalahoidon tarve on muuttunut? Finnish Med J 2003;58:4729–32 [in Finnish]. 13. Ministry of Social Affairs and Health. Asthma Programme in Finland 1994–2004, with introduction by T. Haahtela, L.A. Laitinen. Report of a Working Group. Clin Exp Allergy 1996; 26 (Suppl.1): 1–24. 14. Erhola M, Ma ¨kinen R, Koskela K, et al. The asthma programme of Finland: an evaluation survey in primary health care. Int J Tuberc Lung Dis 2003;7(6):592–8. 15. Viljanen AA, editor. Reference values for spirometric, pulmonary diffusing capacity and body plethysmographic studies. Scand J Clin Invest 1982;42 (Suppl. 159):1–50. 16. Piirila ¨ P, Pietinalho A, Loponen M, Naumanen H, Nurminen M, Salo S-P, et al. The quality of spirometric examinations in Finland; results from a national questionnaire survey. Clin Physiol Funct Imaging 2002;22:233–9. 17. Vilkman S, Nyberg A, Poussa T, Ranta P. Keuhkoahtaumataudin (COPD) akuutin pahenemisvaiheen hoito kotisairaalassa. Finnish Med J 2001;56(43):4387–91 [In Finnish]. 18. Act on health care devices and equipment. Finnish Law So 511.29.12.1994/1505. 19. Ha ¨ma ¨la ¨inen P. Home respiratory care. PhD Thesis, monography, Acta Universitatis Tamperensis 673, University of Tampere, 1999.

ARTICLE IN PRESS Chronic bronchitis and chronic obstructive pulmonary disease 20. Hassi J, Remes J, Kotaniemi J-T, Kettunen P, Na ¨yha ¨ S. Dependence of cold-related coronary and respiratory symptoms on age and exposure to cold. Int J Circumpolar Health 2000; 59:210–5. 21. Kotaniemi J-T, Hassi J, Kataja M, et al. Does non-responder bias have a significant effect on the results in a postal questonaire study? Eur J Epidemiol 2002;17:809–17. 22. Kotaniemi J-T, Pallasaho P, Sovija ¨rvi ARA, Laitinen LA, Lundba ¨ck B. Respiratory symptoms and asthma in relation to cold climate, inhaled allergens and irritants: a comparison between Northern and Southern Finland. J Asthma 2002;39(7):649–58. 23. Lindstro ¨m M, Kotaniemi J-T, Jo ¨nsson E, Lundba ¨ck B. Smoking, respiratory symptoms and disease. Chest 2003;119:853–61. 24. Kotaniemi J-T, Latvala J, Lundba ¨ck B, Sovija ¨rvi ARA, Hassi J, Larsson K. Does living in a cold climate or recreational skiing increase the risk for obstructive respiratory diseases or symptoms? Int J Circumpolar Health 2003;62:142–57. 25. Metso T, Rytila ¨ P, Peterson C, Haahtela T. Granulocyte markers in induced sputum in patients with respiratory diseases and healthy persons obtained by two sputum processing methods. Respir Med 2001;1:48–55. 26. Rytila ¨ P, Lindqvist A, Laitinen LA. Safety of sputum induction in chronic obstructive pulmonary disease of various degrees of severity. Eur Respir J 2000;15:1116–9. 27. Peleman RA, Rytila ¨ PH, Kips JC, Joos GF, Pauwels RA. Cellular characteristics of induced sputum in COPD. Eur Respir J 1999;13:839–43.

1425 28. Harju T, Kaarteenaho-Wiik R, Soini Y, Sormunen R, Kinnula VL. Diminished immunoreactivity of g-glutamylcysteine synthetase in the airways of smoker’s lung. Am J Respir Crit Care Med 2002;166:754–9. 29. Kinnula VL, Crapo JD. Superoxide dismutase in lung and lung diseases. Review. Am J Respir Crit Care Med 2003;167: 1600–19. 30. Kinnula VL. Focus on antioxidant enzymes and antioxidant strategies in smoking related airway diseases. Thorax 2005; 60:693–700. 31. Jaakkola MS, Piipari R, Jaakkola N, Jaakkola JJK. Environmental tobacco smoke and adult-onset asthma: a population-based incident case–control study. Am J Public Health 2003;93(12): 2055–60. 32. Lundba ¨ck B, Lindberg A, Lindstro ¨m M, et al. Not 15 but 50% of smokers develop COPD?—report from the obstructive lung disease in Northern Sweden Studies. Respir Med 2003;97: 115–22. 33. Keistinen T, Tuuponen T, Vilkman V, Kivela ¨ S-L. Kun suuret ika ¨luokat sairastuvat. Kroonista ahtauttavaa keuhkosairautta sairastavien potilaiden sairaalapalvelujen tarpeesta 2000-luvun alkupuolella. Finnish Med J 1996;51:2395–9 [in Finnish]. 34. Lacasse Y, Ferreira I, Brooks D, Newman T, Goldstein RS. Critical appraisal of clinical guide lines targeting chronic obstructive pulmonary disease. Arch Acta Intern Med 2001;16(1):69–74. 35. The Finnish Respiratory Society. Updated current care guideline for COPD. Duodecim 2003;119:2523–4.