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Decreased prevalence of moderate to severe COPD over 15 years in northern Sweden

Open ArchivePublished:March 21, 2016DOI:https://doi.org/10.1016/j.rmed.2016.03.013

      Highlights

      • The prevalence of moderate to severe COPD has decreased in northern Sweden from 1994 to 2009.
      • The decrease appears after more than three decades of decreasing smoking prevalence in the area.
      • The risk factor pattern for COPD was altered in 2009, probably at least partly due to the decreased smoking habits.

      Abstract

      Background

      The burden of COPD in terms of mortality, morbidity, costs and prevalence has increased worldwide. Recent results on prevalence in Western Europe are conflicting. In Sweden smoking prevalence has steadily decreased over the past 30 years.

      Aim

      The aim was to study changes in prevalence and risk factor patterns of COPD in the same area and within the same age-span 15 years apart.

      Material and methods

      Two population-based cross-sectional samples in ages 23–72 years participating at examinations in 1994 and 2009, respectively, were compared in terms of COPD prevalence, severity and risk factor patterns. Two different definitions of COPD were used; FEV1/FVC < LLN and FEV1/FVC < 0.7. The severity of COPD was assessed by FEV1, both as % of predicted and in relation to the LLN.

      Results

      The prevalence of COPD decreased significantly from 9.5% to 6.3% (p = 0.030) according to the FEV1/FVC < LLN criterion, while the decrease based on the FEV1/FVC < 0.7 criterion from 10.5% to 8.5% was non-significant. The prevalence of moderate to severe COPD decreased substantially and significantly, and the risk factor pattern was altered in 2009 when, beside age and smoking, also socio-economic status based on occupation was significantly associated with COPD.

      Conclusions

      Changes in both prevalence and risk factor patterns of COPD were observed between surveys. Following a continuing decrease in smoking habits over several decades, a decrease in the prevalence of moderate to severe COPD was observed from 1994 to 2009 in northern Sweden.

      Keywords

      1. Introduction

      The prevalence of COPD has increased in most parts of the world during the last decades, and today COPD is recognized as the third leading cause of death worldwide [
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      ]. COPD imposes a high burden also in terms of morbidity, disability with impaired quality of life and high costs [
      Global Burden of Disease Study 2013 Collaborators
      Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.
      ,
      • Vestbo J.
      • Hurd S.S.
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      • Jones P.W.
      • Vogelmeier C.
      • Anzueto A.
      • et al.
      Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.
      ,
      • Annesi-Maesano I.
      • Lundbäck B.
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      Chapter on chronic obstructive pulmonary disease.
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      Epidemiology and costs of chronic obstructive pulmonary disease.
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      • Jansson S.A.
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      • Stenling A.
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      ]. Tobacco use became common world-wide during the past century and smoking is by far the most important risk factor for COPD in westernized countries, and epidemiological data indicate that up to a half of smokers develop COPD sooner or later if they continue to smoke [
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      • Lydick E.
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      • Villasante C.
      • Masa J.F.
      • et al.
      Geographic variations in prevalence and underdiagnosis of COPD: results of the IBERPOC multicentre epidemiological study.
      ,
      • Lundback B.
      • Lindberg A.
      • Lindstrom M.
      • Ronmark E.
      • Jonsson A.C.
      • Jonsson E.
      • et al.
      Not 15 but 50% of smokers develop COPD?–report from the obstructive lung disease in Northern Sweden studies.
      ,
      • Jyrki-Tapani K.
      • Sovijarvi A.
      • Lundback B.
      Chronic obstructive pulmonary disease in Finland: prevalence and risk factors.
      ]. The prevalence of COPD may continue to increase in several areas of the world as the number of smokers rises and the populations are ageing [
      • Ng M.
      • Freeman M.K.
      • Fleming T.D.
      • Robinson M.
      • Dwyer-Lindgren L.
      • Thomson B.
      • et al.
      Smoking prevalence and cigarette consumption in 187 countries, 1980-2012.
      ,
      • Lopez-Campos J.L.
      • Tan W.
      • Soriano J.B.
      Global burden of COPD.
      ]. Despite the substantial burden of COPD, the recognition in health care is still insufficient with a huge under-diagnosis [
      • Lopez-Campos J.L.
      • Tan W.
      • Soriano J.B.
      Global burden of COPD.
      ,
      • Lindberg A.
      • Bjerg A.
      • Ronmark E.
      • Larsson L.G.
      • Lundback B.
      Prevalence and underdiagnosis of COPD by disease severity and the attributable fraction of smoking report from the obstructive lung disease in Northern Sweden Studies.
      ,
      • Lamprecht B.
      • Soriano J.B.
      • Studnicka M.
      • Kaiser B.
      • Vanfleteren L.E.
      • Gnatiuc L.
      • et al.
      Determinants of underdiagnosis of COPD in national and international surveys.
      ,
      • Halbert R.J.
      • Natoli J.L.
      • Gano A.
      • Badamgarav E.
      • Buist A.S.
      • Mannino D.M.
      Global burden of COPD: systematic review and meta-analysis.
      ], and it is important to study trends in COPD prevalence [
      • Lopez-Campos J.L.
      • Tan W.
      • Soriano J.B.
      Global burden of COPD.
      ,
      • Halbert R.J.
      • Natoli J.L.
      • Gano A.
      • Badamgarav E.
      • Buist A.S.
      • Mannino D.M.
      Global burden of COPD: systematic review and meta-analysis.
      ]. The recommended approach to evaluate changes in COPD prevalence over time is to repeatedly examine representative population samples in the same areas within the same age-range with spirometry [
      • Annesi-Maesano I.
      • Lundbäck B.
      • Viegi G.
      Chapter on chronic obstructive pulmonary disease.
      ,
      • Bakke P.S.
      • Ronmark E.
      • Eagan T.
      • Pistelli F.
      • Annesi-Maesano I.
      • Maly M.
      • et al.
      Recommendations for epidemiological studies on COPD.
      ]. Today, there are few such studies available [
      • Ford E.S.
      • Mannino D.M.
      • Wheaton A.G.
      • Giles W.H.
      • Presley-Cantrell L.
      • Croft J.B.
      Trends in the prevalence of obstructive and restrictive lung function among adults in the United States: findings from the National Health and Nutrition Examination surveys from 1988-1994 to 2007-2010.
      ,
      • Soriano J.B.
      • Ancochea J.
      • Miravitlles M.
      • Garcia-Rio F.
      • Duran-Tauleria E.
      • Munoz L.
      • et al.
      Recent trends in COPD prevalence in Spain: a repeated cross-sectional survey 1997-2007.
      ,
      • Vasankari T.M.
      • Impivaara O.
      • Heliovaara M.
      • Heistaro S.
      • Liippo K.
      • Puukka P.
      • et al.
      No increase in the prevalence of COPD in two decades.
      ].
      Over the past two decades varying estimates of COPD prevalence have been presented [
      • Pena V.S.
      • Miravitlles M.
      • Gabriel R.
      • Jimenez-Ruiz C.A.
      • Villasante C.
      • Masa J.F.
      • et al.
      Geographic variations in prevalence and underdiagnosis of COPD: results of the IBERPOC multicentre epidemiological study.
      ,
      • Lundback B.
      • Lindberg A.
      • Lindstrom M.
      • Ronmark E.
      • Jonsson A.C.
      • Jonsson E.
      • et al.
      Not 15 but 50% of smokers develop COPD?–report from the obstructive lung disease in Northern Sweden studies.
      ,
      • Jyrki-Tapani K.
      • Sovijarvi A.
      • Lundback B.
      Chronic obstructive pulmonary disease in Finland: prevalence and risk factors.
      ,
      • Lopez-Campos J.L.
      • Tan W.
      • Soriano J.B.
      Global burden of COPD.
      ,
      • Lindberg A.
      • Bjerg A.
      • Ronmark E.
      • Larsson L.G.
      • Lundback B.
      Prevalence and underdiagnosis of COPD by disease severity and the attributable fraction of smoking report from the obstructive lung disease in Northern Sweden Studies.
      ,
      • Lamprecht B.
      • Soriano J.B.
      • Studnicka M.
      • Kaiser B.
      • Vanfleteren L.E.
      • Gnatiuc L.
      • et al.
      Determinants of underdiagnosis of COPD in national and international surveys.
      ,
      • Halbert R.J.
      • Natoli J.L.
      • Gano A.
      • Badamgarav E.
      • Buist A.S.
      • Mannino D.M.
      Global burden of COPD: systematic review and meta-analysis.
      ,
      • Soriano J.B.
      • Ancochea J.
      • Miravitlles M.
      • Garcia-Rio F.
      • Duran-Tauleria E.
      • Munoz L.
      • et al.
      Recent trends in COPD prevalence in Spain: a repeated cross-sectional survey 1997-2007.
      ,
      • Vasankari T.M.
      • Impivaara O.
      • Heliovaara M.
      • Heistaro S.
      • Liippo K.
      • Puukka P.
      • et al.
      No increase in the prevalence of COPD in two decades.
      ]. In ages >40 years the prevalence of COPD ranged from 10% to more than 25% between the Burden of Obstructive Lung Disease (BOLD) study centers [
      • Buist A.S.
      • McBurnie M.A.
      • Vollmer W.M.
      • Gillespie S.
      • Burney P.
      • Mannino D.M.
      • et al.
      International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study.
      ] using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) [
      • Vestbo J.
      • Hurd S.S.
      • Agusti A.G.
      • Jones P.W.
      • Vogelmeier C.
      • Anzueto A.
      • et al.
      Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.
      ] criterion FEV1/FVC < 0.7 of COPD. In the same study the prevalence was reduced by 30%–50% when based on the lower limit of normal (LLN) criterion [
      • Vollmer W.M.
      • Gislason T.
      • Burney P.
      • Enright P.L.
      • Gulsvik A.
      • Kocabas A.
      • et al.
      Comparison of spirometry criteria for the diagnosis of COPD: results from the BOLD study.
      ]. The term “clinically relevant COPD” has been discussed for a reduced ratio in combination with a reduced FEV1, either FEV1 < LLN [
      • Hnizdo E.
      • Glindmeyer H.W.
      • Petsonk E.L.
      • Enright P.
      • Buist A.S.
      Case definitions for chronic obstructive pulmonary disease.
      ] or FEV1 < 80% of predicted (GOLD severity grade ≥2) [
      • Annesi-Maesano I.
      • Lundbäck B.
      • Viegi G.
      Chapter on chronic obstructive pulmonary disease.
      ,
      • Bakke P.S.
      • Ronmark E.
      • Eagan T.
      • Pistelli F.
      • Annesi-Maesano I.
      • Maly M.
      • et al.
      Recommendations for epidemiological studies on COPD.
      ,
      • Celli B.R.
      • Halbert R.J.
      • Isonaka S.
      • Schau B.
      Population impact of different definitions of airway obstruction.
      ], the latter yielding a prevalence of 6–18% in the BOLD study [
      • Annesi-Maesano I.
      • Lundbäck B.
      • Viegi G.
      Chapter on chronic obstructive pulmonary disease.
      ,
      • Buist A.S.
      • McBurnie M.A.
      • Vollmer W.M.
      • Gillespie S.
      • Burney P.
      • Mannino D.M.
      • et al.
      International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study.
      ]. Also the ERS Monograph about Respiratory Epidemiology presents COPD prevalence based on GOLD severity grade ≥2 [
      • Annesi-Maesano I.
      • Lundbäck B.
      • Viegi G.
      Chapter on chronic obstructive pulmonary disease.
      ].
      One recent study in Europe suggests the prevalence of COPD to be levelling [
      • Vasankari T.M.
      • Impivaara O.
      • Heliovaara M.
      • Heistaro S.
      • Liippo K.
      • Puukka P.
      • et al.
      No increase in the prevalence of COPD in two decades.
      ], while another reveal a decrease [
      • Soriano J.B.
      • Ancochea J.
      • Miravitlles M.
      • Garcia-Rio F.
      • Duran-Tauleria E.
      • Munoz L.
      • et al.
      Recent trends in COPD prevalence in Spain: a repeated cross-sectional survey 1997-2007.
      ]. Studies performed in Sweden around the millennium shift found the prevalence of GOLD severity grade ≥2 in ages >40 years to be 7–8% [
      • Lundback B.
      • Lindberg A.
      • Lindstrom M.
      • Ronmark E.
      • Jonsson A.C.
      • Jonsson E.
      • et al.
      Not 15 but 50% of smokers develop COPD?–report from the obstructive lung disease in Northern Sweden studies.
      ,
      • Lindberg A.
      • Jonsson A.C.
      • Ronmark E.
      • Lundgren R.
      • Larsson L.G.
      • Lundback B.
      Prevalence of chronic obstructive pulmonary disease according to BTS, ERS, GOLD and ATS criteria in relation to doctor's diagnosis, symptoms, age, gender, and smoking habits.
      ,
      • Danielsson P.
      • Olafsdottir I.S.
      • Benediktsdottir B.
      • Gislason T.
      • Janson C.
      The prevalence of chronic obstructive pulmonary disease in Uppsala, Sweden–the Burden of Obstructive Lung Disease (BOLD) study: cross-sectional population-based study.
      ]. Other major risk factors than personal smoking have been identified [
      • Vestbo J.
      • Hurd S.S.
      • Agusti A.G.
      • Jones P.W.
      • Vogelmeier C.
      • Anzueto A.
      • et al.
      Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.
      ,
      • Annesi-Maesano I.
      • Lundbäck B.
      • Viegi G.
      Chapter on chronic obstructive pulmonary disease.
      ,
      • Chapman K.R.
      • Mannino D.M.
      • Soriano J.B.
      • Vermeire P.A.
      • Buist A.S.
      • Thun M.J.
      • et al.
      Epidemiology and costs of chronic obstructive pulmonary disease.
      ,
      • Lopez-Campos J.L.
      • Tan W.
      • Soriano J.B.
      Global burden of COPD.
      ], and their relative importance may increase parallel to decreasing smoking prevalence. Only few studies have aimed to compare COPD prevalence trends and risk factor patterns in the same population within the same age range based on both the GOLD and the LLN-criterion.
      We aimed to study changes in prevalence and risk factor patterns of COPD in the same area and within the same age-span 15 years apart, in 1994 and in 2009. We hypothesize that the prevalence has decreased due to decreased smoking habits over 30 years in the area [
      • Backman H.
      • Hedman L.
      • Jansson S.A.
      • Lindberg A.
      • Lundback B.
      • Ronmark E.
      Prevalence trends in respiratory symptoms and asthma in relation to smoking - two cross-sectional studies ten years apart among adults in northern Sweden.
      ,
      • Lundback B.
      • Nystrom L.
      • Rosenhall L.
      • Stjernberg N.
      Obstructive lung disease in northern Sweden: respiratory symptoms assessed in a postal survey.
      ]. A further aim was to compare outcomes of two different COPD-criteria in terms of prevalence, disease severity and risk factors.

      2. Material and methods

      2.1 Study area

      The study was performed in Norrbotten, the northernmost county of Sweden, with a subarctic climate with long winters and short but warm summers. The county comprises 25% of the area of Sweden but is sparsely inhabited with a population of about 250,000 the decades before and after the millennium shift. The study was performed within the research programs of the Obstructive Lung Disease in Northern Sweden (OLIN) Studies, in progress since 1985. The study was approved by the Regional Ethical Review Board at Umeå University.

      2.2 Study population

      In 1992, a postal questionnaire survey on respiratory symptoms and diseases was performed among a random sample of 4851 (85% of invited) adults [
      • Larsson L.G.
      • Lindberg A.
      • Franklin K.A.
      • Lundback B.
      Symptoms related to obstructive sleep apnoea are common in subjects with asthma, chronic bronchitis and rhinitis in a general population.
      ]. Of the responders, 660 subjects (68.0% of invited, 23–72 years) participated in structured interviews and spirometry with adequate technique in 1994 [
      • Warm K.
      • Lindberg A.
      • Lundback B.
      • Ronmark E.
      Increase in sensitization to common airborne allergens among adults - two population-based studies 15 years apart.
      ]. In 2006, a new random sample in ages 20–69 years, n = 7997, was invited to participate in a postal questionnaire survey [
      • Backman H.
      • Hedman L.
      • Jansson S.A.
      • Lindberg A.
      • Lundback B.
      • Ronmark E.
      Prevalence trends in respiratory symptoms and asthma in relation to smoking - two cross-sectional studies ten years apart among adults in northern Sweden.
      ]. In addition, another randomly selected population sample in ages 30–84 years, which had participated in a similar questionnaire survey in 1996 [
      • Lindstrom M.
      • Kotaniemi J.
      • Jonsson E.
      • Lundback B.
      Smoking, respiratory symptoms, and diseases: a comparative study between northern Sweden and northern Finland: report from the FinEsS study.
      ], was also invited, n = 7004 [
      • Backman H.
      • Hedman L.
      • Jansson S.A.
      • Lindberg A.
      • Lundback B.
      • Ronmark E.
      Prevalence trends in respiratory symptoms and asthma in relation to smoking - two cross-sectional studies ten years apart among adults in northern Sweden.
      ]. Overall 12,055 subjects (80% of the invited) participated in the 2006 postal survey [
      • Warm K.
      • Lindberg A.
      • Lundback B.
      • Ronmark E.
      Increase in sensitization to common airborne allergens among adults - two population-based studies 15 years apart.
      ]. After stratification by the age and sex distribution of the population of the county, a randomly selected sample of the questionnaire responders, n = 1016, was invited to clinical examinations including pre- and post-bronchodilator spirometry and a structured interview in 2009 [
      • Warm K.
      • Lindberg A.
      • Lundback B.
      • Ronmark E.
      Increase in sensitization to common airborne allergens among adults - two population-based studies 15 years apart.
      ]. Of the invited, 726 (71.5%) subjects performed spirometry with adequate technique and completed the interview. 660 participants in 1994 and 623 participants in 2009 within the overlapping 23–72 years age-range were included in the current study. On-line Fig. 1 illustrates a study flow chart.

      2.3 Questionnaire

      The same method and questionnaire, the OLIN-questionnaire, was used in both studies. It has recently been externally validated against the Swedish version of the Global Allergy and Asthma European Network (GA2LEN) questionnaire [
      • Ekerljung L.
      • Ronmark E.
      • Lotvall J.
      • Wennergren G.
      • Toren K.
      • Lundback B.
      Questionnaire layout and wording influence prevalence and risk estimates of respiratory symptoms in a population cohort.
      ] and previously described in detail [
      • Pallasaho P.
      • Lundback B.
      • Laspa S.L.
      • Jonsson E.
      • Kotaniemi J.
      • Sovijarvi A.R.
      • et al.
      Increasing prevalence of asthma but not of chronic bronchitis in Finland? report from the FinEsS-Helsinki study.
      ]. The questionnaire consists of a self-administrated short version with core questions and an extended version for interviews. The questions are focused on respiratory and allergic symptoms and diseases, their comorbidities, medication, family history of obstructive airway diseases and allergy, smoking habits, occupation, socio-economic status and a screening for other potential risk factors for respiratory diseases. The questionnaire has been used in several national and international epidemiological studies [
      • Lundback B.
      • Lindberg A.
      • Lindstrom M.
      • Ronmark E.
      • Jonsson A.C.
      • Jonsson E.
      • et al.
      Not 15 but 50% of smokers develop COPD?–report from the obstructive lung disease in Northern Sweden studies.
      ,
      • Jyrki-Tapani K.
      • Sovijarvi A.
      • Lundback B.
      Chronic obstructive pulmonary disease in Finland: prevalence and risk factors.
      ,
      • Backman H.
      • Hedman L.
      • Jansson S.A.
      • Lindberg A.
      • Lundback B.
      • Ronmark E.
      Prevalence trends in respiratory symptoms and asthma in relation to smoking - two cross-sectional studies ten years apart among adults in northern Sweden.
      ,
      • Lindstrom M.
      • Kotaniemi J.
      • Jonsson E.
      • Lundback B.
      Smoking, respiratory symptoms, and diseases: a comparative study between northern Sweden and northern Finland: report from the FinEsS study.
      ,
      • Pallasaho P.
      • Lundback B.
      • Laspa S.L.
      • Jonsson E.
      • Kotaniemi J.
      • Sovijarvi A.R.
      • et al.
      Increasing prevalence of asthma but not of chronic bronchitis in Finland? report from the FinEsS-Helsinki study.
      ].

      2.4 Spirometry

      Both in 1994 and 2009 at least three forced vital capacity (FVC) maneuvers were performed, and forced expiratory volume during the first second (FEV1) was assessed. The procedures followed the ERS/ATS guidelines [
      • Miller M.R.
      • Hankinson J.
      • Brusasco V.
      • Burgos F.
      • Casaburi R.
      • Coates A.
      • et al.
      Standardisation of spirometry.
      ], but with a repeatability criterion of <5%, or <100 ml in case the values were <2.0 L, difference between the two best FVC and the two best FEV1 values, respectively. In the 1994 survey a dry volume spirometer, Minjhardt Vicatest 5, and in the 2009 survey two Masterscope (Jaeger) spirometers were used. Daily check-ups of the calibration were performed in both studies. Reversibility testing was performed using 0.4 mg salbutamol via discus in all subjects in the 2009 survey, and in all subjects with FEV1 <90% of predicted values and/or a ratio of FEV1/VC < 0.7 in 1994. Post-bronchodilator spirometric values were defined as the highest values before or after reversibility testing in both surveys. Additional sensitivity analyses were performed based on pre-bronchodilator spirometry. Height and weight was measured at the examination, and age was calculated as the difference between date of birth and date of examination. The internally and externally validated OLIN reference values for spirometry were used [
      • Backman H.
      • Lindberg A.
      • Oden A.
      • Ekerljung L.
      • Hedman L.
      • Kainu A.
      • et al.
      Reference values for spirometry – report from the obstructive lung disease in Northern Sweden studies.
      ].

      2.5 Definitions

      COPD was defined based on post-bronchodilator spirometry according to two different definitions: 1. The GOLD-criterion: FEV1/FVC < 0.70 [
      ] and 2. The LLN-criterion: FEV1/FVC < LLN, as recommended by the European Respiratory Society/American Thoracic Society (ERS/ATS) [
      • Bakke P.S.
      • Ronmark E.
      • Eagan T.
      • Pistelli F.
      • Annesi-Maesano I.
      • Maly M.
      • et al.
      Recommendations for epidemiological studies on COPD.
      ,
      • Pellegrino R.
      • Viegi G.
      • Brusasco V.
      • Crapo R.O.
      • Burgos F.
      • Casaburi R.
      • et al.
      Interpretative strategies for lung function tests.
      ].
      Moderate to severe COPD was defined accordingly for the GOLD-criterion: FEV1/FVC < 0.70 in combination with FEV1 < 80% of predicted (GOLD ≥ 2) [
      ], and for the LLN-criterion: FEV1/FVC < LLN in combination with FEV1 < LLN, as in the NHANES III [
      • Hnizdo E.
      • Glindmeyer H.W.
      • Petsonk E.L.
      • Enright P.
      • Buist A.S.
      Case definitions for chronic obstructive pulmonary disease.
      ]. All subjects with COPD were also stratified into severity grades of airflow limitation based on FEV1 as percent of predicted with cut-offs according to GOLD grades 1–4 [
      ]. When based on the GOLD-criterion, the severity grades are explicitly labelled GOLD grades.
      Ischemic heart disease (IHD) was defined as a history of myocardial infarction, coronary surgery or angina pectoris. Asthma was defined as a report of ever having had asthma. Smoking habits were categorized as current smokers, ex-smokers or never-smokers. Ex-smokers were defined as those who had quit smoking at least 12 months prior to the interview. Socioeconomic status was based on occupation according to classifications by Statistics Sweden.

      2.6 Analyses

      The prevalence of COPD was calculated both unadjusted and adjusted to the contemporary sex- and age-distributions of the county. In bivariate analyses, the Fisher exact test was used to test for differences in proportions and the student's t-test for differences in means. For comparisons of proportions across more than two groups, the Mantel-Haenszel test for trend was used. A p-value<0.05 was considered statistically significant. Multiple logistic regression analysis was used to test independent determinants of COPD and moderate to severe COPD, respectively, with non-COPD as reference. Factors with significant associations in unadjusted analyses (on-line Table 1) were included as covariates in the models. Adjusted results are presented as odds ratios (OR) with 95% confidence intervals (CI).

      3. Results

      3.1 Basic characteristics

      The mean age of the participants in the 1994 and 2009 surveys was 49.1 and 50.2 years, and 50.3% and 49.6% were women. Current smoking was significantly more common among women at both surveys, and decreased between surveys among women from 30.5% to 20.5% (p = 0.004) and among men from 22.6% to 11.8% (p < 0.001) (Table 1, on-line Fig. 2). The decrease in current smoking appeared in young (p = 0.014) and middle aged (p < 0.001) subjects, while never-smoking decreased in age >60 years (p = 0.014) (Table 1). The distribution of socio-economic status did not change between the surveys (on-line Fig. 3).
      Table 1Smoking habits, family history of obstructive airway disease and comorbidities by age group, sex and study year. Difference (p-value) by age, sex and study year.
      CharacteristicYear≤40 y41–60 y>60 yWomenMenAllDifference (p-value) by
      Age
      Test for linear trends in characteristics by age groups.
      Sex
      Fisher's exact test comparing characteristics between men and women.
      Year
      Fisher's exact test comparing characteristics between study years.
      N = 660 in 1994, N = 623 in 2009
      Never-smoker199453.4%38.3%50.0%49.5%40.2%44.9%0.3860.019
      200970.3%45.7%35.5%44.8%54.0%49.4%<0.0010.0250.117
      Ex-smoker199421.9%27.9%38.2%19.9%37.2%28.5%0.001<0.001
      200915.8%37.9%46.7%34.7%34.2%34.5%<0.0010.9330.026
      Current smoker199424.7%33.8%11.8%30.5%22.6%26.6%0.0230.022
      200913.9%16.4%17.8%20.5%11.8%16.1%0.3570.004<0.001
      Family history of OAD199426.3%31.2%22.2%31.9%23.8%27.9%0.5140.024
      200931.6%27.2%20.3%25.2%28.0%26.6%0.0240.4690.661
      Ischemic heart disease19940.0%5.6%14.6%5.7%6.4%6.1%<0.0010.746
      20090.0%1.9%15.0%2.3%7.0%4.7%<0.0010.0070.322
      Hypertension19945.0%19.3%32.6%19.0%17.7%18.3%<0.0010.688
      20097.6%23.1%46.4%27.8%22.0%24.9%<0.0010.0960.005
      Asthma ever199412.3%8.9%13.9%10.5%11.3%10.9%0.7450.803
      200916.5%16.0%11.1%13.9%15.9%14.9%0.1890.5020.037
      OAD=Obstructive airway disease (asthma, chronic bronchitis, COPD or emphyzema).
      a Test for linear trends in characteristics by age groups.
      b Fisher's exact test comparing characteristics between men and women.
      c Fisher's exact test comparing characteristics between study years.

      3.2 Prevalence and severity of COPD

      The sex- and age-adjusted over-all prevalence of COPD over the 15 year-period decreased significantly from 9.5% to 6.3% (p = 0.030) according to the LLN-criterion, while the decrease from 10.5% to 8.5% based on the GOLD-criterion was non-significant (Table 2). The corresponding prevalence estimates in ages >40 years were 10.7% and 7.4% (p = 0.088) based on the LLN-criterion and 13.2% and 11.2% (p = 0.324) based on the GOLD-criterion. The prevalence tended to decrease among men in all age groups and among women up to age 60, while it tended to increase among women aged >60 years.
      Table 2Prevalence of COPD according to different criteria by age group, sex and study year. Difference (p-value) by age, sex and study year.
      ≤40 y41–60 y>60 yAllAll$Difference (p-value) by
      WomenMenAllWomenMenAllWomenMenAllWomenMenAllAge
      Test for linear trends in COPD prevalence by age groups.
      Sex
      Fisher's exact test comparing COPD prevalence between men and women.
      Year
      Fisher's exact test comparing COPD prevalence (All$) between study years based on post-BD spirometry.
      Year 1994
      N98811791681693376678144332328660
      FEV1/FVC < 0.76.1%6.2%6.1%9.5%10.7%10.1%15.2%25.6%20.8%9.6%13.1%11.4%10.5%<0.0010.178
      FEV1/FVC < LLN9.2%6.2%7.8%8.3%11.2%9.8%7.6%17.9%13.2%8.4%11.6%10.0%9.5%0.1140.195
      Year 2009
      N82761581571553127083153309314623
      FEV1/FVC < 0.71.2%3.9%2.5%5.7%6.5%6.1%22.9%18.1%20.3%8.4%8.9%8.7%8.5%<0.0010.8870.254
      FEV1/FVC < LLN2.4%5.3%3.8%3.8%7.1%5.4%8.6%13.3%11.1%4.5%8.3%6.4%6.3%0.0090.0710.030
      All$ = Adjusted to the sex- and age-distribution of the area.
      a Test for linear trends in COPD prevalence by age groups.
      b Fisher's exact test comparing COPD prevalence between men and women.
      c Fisher's exact test comparing COPD prevalence (All$) between study years based on post-BD spirometry.
      The sex- and age-adjusted prevalence of moderate to severe COPD decreased from 8.5% to 3.9% (p < 0.001) based on the GOLD-criterion and from 8.1% to 3.2% (p < 0.001) based on the LLN-criterion. The corresponding prevalence estimates in ages >40 years were 11.6% and 5.6% (p = 0.001) based on the GOLD-criterion and 9.7% and 4.6% (p = 0.002) based on the LLN-criterion. The prevalence of moderate to severe COPD decreased significantly by at least half between surveys among men according to both criteria, while the decrease only reached statistical significance for the LLN-criterion among women (Fig. 1). Fig. 2a–d displays the prevalence of COPD and moderate to severe COPD, respectively, in 1994 and 2009, by criteria, age and smoking.
      Figure thumbnail gr1
      Fig. 1Prevalence of moderate to severe COPD in 1994 and 2009, by criteria and sex. Difference (p-value) in prevalence between years for women and men, respectively.
      Figure thumbnail gr2
      Fig. 2a–d. Prevalence of COPD and moderate to severe COPD, respectively, in 1994 and 2009, by criteria, age and smoking. Difference (p-value, test-for-trend) in prevalence within combined age-smoking categories between years.
      The mean FEV1 as percent of predicted among subjects with COPD increased between surveys from 67.0% to 83.4% (p < 0.001) based on the GOLD-criterion and from 67.1% to 79.6% based on the LLN-criterion (p < 0.001). The prevalence of both COPD with FEV1 50–80% of predicted and COPD with FEV1 < 50% of predicted decreased markedly and significantly according to both criteria (Table 3). On-line Table 2 illustrates the overlap between the GOLD-criterion and the LLN-criterion by level of airflow limitation severity.
      Table 3Prevalence (%) of COPD stratified by level of airflow limitation based on FEV1 as percent of predicted with cut-offs according to GOLD. Difference (p-value) by study year.
      Definition of COPDYearFEV1 > 80% of predFEV1 80–50% of predFEV1 < 50% of pred
      WomenMenAllP-value
      Fisher's exact test comparing prevalence among all between study years based on post-BD spirometry.
      WomenMenAllP-value
      Fisher's exact test comparing prevalence among all between study years based on post-BD spirometry.
      WomenMenAllP-value
      Fisher's exact test comparing prevalence among all between study years based on post-BD spirometry.
      GOLD-criterion FEV1/FVC < 0.719943.0%0.9%2.0%5.1%10.4%7.7%1.5%1.8%1.7%
      20094.9%4.5%4.7%0.0073.6%4.1%3.9%0.0040.0%0.3%0.2%0.006
      LLN-criterion FEV1/FVC < LLN19943.3%0.6%2.0%3.6%9.1%6.4%1.5%1.8%1.7%
      20092.3%3.5%2.9%0.3632.3%4.5%3.4%0.0140.0%0.3%0.2%0.006
      N = 660 in 1994, N = 623 in 2009.
      a Fisher's exact test comparing prevalence among all between study years based on post-BD spirometry.
      The sensitivity analyses of prevalence based on pre-bronchodilator spirometry revealed that moderate to severe COPD decreased from 9.2% to 5.1% (p = 0.005) based on the GOLD-criterion and from 8.5% to 4.7% (p = 0.007) based on the LLN-criterion. The over-all COPD prevalence based on GOLD was unchanged on 11.2% while the prevalence based on the LLN-criterion decreased from 10.0% to 8.7% (p = 0.443). Further, the mean pre-bronchodilator FEV1% of predicted among subjects with COPD increased between surveys from 65.1% to 82.6% (p < 0.001) based on the GOLD-criterion and from 65.5% to 81.2% based on the LLN-criterion (p < 0.001).

      3.3 Symptoms, co-morbid conditions and smoking in COPD

      Most respiratory symptoms were more common in GOLD ≥ 2 with decreased prevalence in 2009 compared to 1994, while the symptoms were not significantly different between subjects with GOLD1 and non-COPD subjects. Ischemic heart disease was more common in GOLD ≥ 2 than in non-COPD in both 1994 and 2009 (p = 0.260; p = 0.004), and so was hypertension (p = 0.038; p = 0.003). The prevalence of physician-diagnosed COPD, chronic bronchitis or emphysema increased substantially in GOLD ≥ 2, from 12.9% in 1994 to 40.0% in 2009 (p = 0.008) (on-line Table 3).
      In 1994 and 2009 respectively, any respiratory symptom were reported by 90.3% and 84% (p = 0.464) among the subjects with moderate to severe COPD according to the GOLD-criterion (GOLD ≥ 2), whereas the corresponding figures for the LLN-criterion were 91.2% and 95.2%, respectively (p = 1.000). Current smoking was reported by approximately half of these subjects at both surveys for both criteria (on-line Fig. 4), while there was a decrease between surveys among non-COPD subjects (from 24% to 15%, p < 0.001). Based on the GOLD-criterion, all subjects with moderate to severe COPD in 1994 and all but one subject in 2009 reported any respiratory symptom and/or a history of smoking. The corresponding figures for the LLN-criterion were all but two subjects in 1994 and all subjects in 2009. The proportion who had any of physician-diagnosed COPD, chronic bronchitis or emphysema, or asthma or used medicines for airways last 12 months among subjects with moderate to severe COPD based on the GOLD-criterion (GOLD ≥ 2) increased from 30.6% in 1994 to 56.0% in 2009 (p = 0.049). The corresponding increase for the LLN-criterion was from 38.6% to 52.4% (p = 0.310).

      3.4 Factors independently associated with COPD

      COPD based on the GOLD-criterion was strongly associated with current smoking and age > 60 years at the two surveys, and in the 1994 survey also with ex-smoking and family history of OAD. For COPD GOLD ≥ 2 the association with current smoking was even stronger at both surveys, (OR 8.84; OR 9.97) but the association with age > 60 was similar. In the 2009 survey, in contrast to 1994, the risk factor pattern for COPD GOLD ≥ 2 included the socio-economic groups manual workers in industry and self-employed (Table 4).
      Table 4Risk factors for COPD and moderate to severe COPD according to different criteria by multiple logistic regression, by year.
      YearFEV1/FVC < 0.7FEV1/FVC < 0.7 & FEV1 < 80% of predFEV1/FVC < LLNFEV1/FVC < LLN & FEV1 < LLN
      OR(95% CI)OR(95% CI)OR(95% CI)OR(95% CI)
      Risk factors (covariates)
      Male sex19941.35(0.74–2.46)1.69(0.86–3.35)1.51(0.81–2.81)1.78(0.90–3.54)
      20091.06(0.56–2.01)1.20(0.46–3.13)2.12(1.014.45)2.33(0.80–6.75)
      Ages >60 y19944.14(2.317.43)5.27(2.7510.11)2.15(1.134.08)2.79(1.425.49)
      20094.56(2.488.39)4.49(1.8211.06)1.94(0.96–3.94)2.62(0.98–6.97)
      Family history of OAD19942.10(1.223.60)2.23(1.234.07)2.17(1.243.79)2.48(1.364.53)
      20090.96(0.48–1.92)1.27(0.49–3.25)1.63(0.80–3.29)1.71(0.64–4.53)
      Ex-smoker19942.90(1.435.90)3.60(1.568.32)2.98(1.386.46)3.43(1.438.21)
      20091.71(0.81–3.62)2.07(0.59–7.27)1.91(0.82–4.44)2.69(0.66–10.96)
      Current smoker19945.69(2.8011.57)8.84(3.8020.54)5.98(2.8312.61)7.62(3.2517.84)
      20095.46(2.5111.89)9.97(2.9533.67)5.18(2.1512.51)11.90(3.0246.95)
      Socioeconomic status*
      Non-manual employees19940.93(0.39–2.22)0.79(0.29–2.16)0.82(0.32–2.05)0.68(0.24–1.91)
      20091.96(0.76–5.06)4.95(0.89–27.51)3.27(1.099.80)8.57(0.90–81.31)
      Manual work in service19940.89(0.43–1.84)0.71(0.31–1.65)0.86(0.41–1.83)0.76(0.33–1.74)
      20091.65(0.70–3.91)3.27(0.62–17.37)2.12(0.74–6.08)6.91(0.78–61.07)
      Manual work in industry19940.92(0.43–1.98)1.04(0.46–2.33)0.93(0.42–2.03)0.99(0.44–2.25)
      20092.10(0.85–5.14)5.55(1.0629.06)2.21(0.75–6.48)7.95(0.90–70.14)
      Self-employed19941.16(0.37–3.63)1.30(0.40–4.24)0.74(0.19–2.81)0.77(0.20–3.02)
      20093.08(0.86–11.08)15.11(2.4194.68)3.79(0.90–15.89)21.38(2.05222.66)
      Othersˆ19940.82(0.17–4.03)1.10(0.21–5.63)1.49(0.37–6.01)1.16(0.22–6.06)
      2009N/AN/AN/AN/A
      Othersˆ = Housewifes, unemployed and students, OAD=Obstructive airway disease, *Academics as reference category, N/A = Not available.
      Bold values indicate statistical significance based on the 95% CI.
      When COPD was defined by the LLN-criterion, the risk factor pattern was similar. However, the association with age >60 years was of lower magnitude in both surveys. In 2009, the association with non-manual employees reached statistical significance. Moderate to severe COPD defined by the LLN-criterion was significantly associated with current smoking at both surveys (OR 7.62; OR 11.90) and with self-employed in 2009 (Table 4).
      These risk factor patterns remained also when hypertension, asthma and ischemic heart disease were added one by one to the model (data not shown). Male sex yielded odds ratios higher than one, but these were non-significant in all but one analysis.

      4. Discussion

      The main result of this study was that the prevalence of moderate and severe COPD decreased substantially from 8.5% to 3.9% based on the GOLD-criterion and from 8.1% to 3.2% based on the LLN-criterion over the 15-year period. This decrease was of greater magnitude among men, and reached statistical significance only for the LLN-criterion among women. Overall, the prevalence of COPD decreased from 10.5 to 8.5% based on GOLD-criterion and from 9.5 to 6.3% based on the LLN-criterion. Also, compared to previous studies in Sweden [
      • Lundback B.
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      • Lindberg A.
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      ,
      • Danielsson P.
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      ] our results indicate a decreased prevalence of particularly moderate to severe COPD in subjects older than 40 years. To the best of our knowledge, this is the first study beside the Spanish study [
      • Soriano J.B.
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      • Duran-Tauleria E.
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      ] that shows a decreasing tendency in COPD prevalence in Europe. In the US, the Nhanes have shown minor changes in the over-all COPD prevalence while the prevalence of severe COPD has decreased [
      • Ford E.S.
      • Mannino D.M.
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      ].
      Historically, men have smoked more than women in most countries, but in 1985, when one third of the adult population in the studied area was current smokers, smoking had become equally common in women and men [
      • Siafakas N.M.
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      ]. Thereafter the prevalence of smoking has decreased in both sexes, and much more pronounced among men compared to among women. The decrease between 1994 and 2009 was seen in younger and middle-aged subjects, while there was an increase among the elderly. From a public health perspective, reduced smoking prevalence among younger subjects is very important, while the somewhat increasing smoking prevalence trend among the elderly probably is a cohort effect. In the current study women smoked more than men at both surveys, but COPD still tended to be more common among men. The lag between exposure and outcome typical for COPD may contribute, as long-term exposure rather than short-term is the cause of chronic airway obstruction.
      The cross-sectional questionnaire surveys performed in the same area in 1996 and 2006 [
      • Backman H.
      • Hedman L.
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      ] presented evidence of not only a decreased smoking prevalence in the county but also that those who smoked in 2006 smoked fewer cigarettes per day. In parallel to the decrease in smoking, the prevalence of bronchitic symptoms decreased [
      • Backman H.
      • Hedman L.
      • Jansson S.A.
      • Lindberg A.
      • Lundback B.
      • Ronmark E.
      Prevalence trends in respiratory symptoms and asthma in relation to smoking - two cross-sectional studies ten years apart among adults in northern Sweden.
      ].
      The reduction in smoking prevalence is most likely a contributor to the altered risk factor pattern for COPD observed in 2009. Although smoking and age remained as important risk factors, the socioeconomic groups manual workers in industry, non-manual employees and self-employed other than academics, with academics as reference, emerged as more strongly associated with COPD in 2009, while ex-smoking and a family history of obstructive airway diseases lost its significance. Associations with other factors may be more obvious and easier to identify when smoking prevalence decreases, even if they are of less importance for the public health compared to smoking.
      The underdiagnosis of COPD is well known, and it has been estimated that merely 20–30% of all subjects with COPD are identified by health care [
      • Lindberg A.
      • Bjerg A.
      • Ronmark E.
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      ,
      • Lindberg A.
      • Jonsson A.C.
      • Ronmark E.
      • Lundgren R.
      • Larsson L.G.
      • Lundback B.
      Prevalence of chronic obstructive pulmonary disease according to BTS, ERS, GOLD and ATS criteria in relation to doctor's diagnosis, symptoms, age, gender, and smoking habits.
      ,
      • Danielsson P.
      • Olafsdottir I.S.
      • Benediktsdottir B.
      • Gislason T.
      • Janson C.
      The prevalence of chronic obstructive pulmonary disease in Uppsala, Sweden–the Burden of Obstructive Lung Disease (BOLD) study: cross-sectional population-based study.
      ]. Even though the underdiagnosis of COPD decreased from 1994 to 2009, it was still large; three out of five subjects with moderate to severe COPD were un-diagnosed. Cost-effective public health planning is dependent on accurate knowledge on how common a disease is and on awareness of the current prevalence trend and the impact of different risk factors. The best way to achieve this is to repeatedly estimate the prevalence and risk factor pattern in the population under study, with identical methods in the same area and within the same age-span [
      • Annesi-Maesano I.
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      ,
      • Bakke P.S.
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      ]. A Spanish survey [
      • Soriano J.B.
      • Ancochea J.
      • Miravitlles M.
      • Garcia-Rio F.
      • Duran-Tauleria E.
      • Munoz L.
      • et al.
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      ] used a repeated cross-sectional study design within the 40–69 year age-range with surveys performed mainly in the same areas in the two study years. In line with our study, this Spanish study found decreasing prevalence trends of both COPD (from 9.1% to 4.5%) and the level of airflow limitation in COPD between 1997 and 2007, despite only limited parallel reduction in smoking prevalence [
      • Soriano J.B.
      • Ancochea J.
      • Miravitlles M.
      • Garcia-Rio F.
      • Duran-Tauleria E.
      • Munoz L.
      • et al.
      Recent trends in COPD prevalence in Spain: a repeated cross-sectional survey 1997-2007.
      ]. A repeated cross-sectional study in Finland found no change in COPD prevalence or in the severity levels of airflow limitation between 1978–81 and 2000–01 [
      • Vasankari T.M.
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      ]. However, among women an increase in prevalence of current smokers and a tendency of an increase in prevalence of COPD was observed, while among men no such changes were found.
      Several review studies have presented pooled prevalence estimates of spirometrically defined COPD since the millennium shift, i.e. 9–10% based on mainly European studies from the 1990's or later [
      • Halbert R.J.
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      ] and on studies world-wide from 2003 to 2012 [
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      ], and an all-ages world-wide number of 328 million people (of which 51% men) in 2013 as estimated by the Global Burden of Disease Study [
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      ]. It is however recognized that it is difficult to compare prevalence estimates between studies, and over time, due to the heterogeneity of the sample compositions and the COPD definitions used [
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      ,
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      ].
      The definition of COPD has changed over time, and the definition of a decreased post-bronchodilator FEV1/FVC ratio is under debate [
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      • et al.
      An Official American Thoracic Society/European Respiratory Society Statement: research questions in chronic obstructive pulmonary disease.
      ], where the most commonly used definitions today are the GOLD [
      • Vestbo J.
      • Hurd S.S.
      • Agusti A.G.
      • Jones P.W.
      • Vogelmeier C.
      • Anzueto A.
      • et al.
      Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.
      ,
      ] and ERS/ATS [
      • Pellegrino R.
      • Viegi G.
      • Brusasco V.
      • Crapo R.O.
      • Burgos F.
      • Casaburi R.
      • et al.
      Interpretative strategies for lung function tests.
      ,
      • Quanjer P.H.
      • Ruppel G.
      • Brusasco V.
      • Perez-Padilla R.
      • Fragoso C.A.
      • Culver B.H.
      • et al.
      COPD (confusion over proper diagnosis) in the zone of maximum uncertainty.
      ] definitions of a post-bronchodilator FEV1/FVC < 0.7 and FEV1/FVC < LLN, respectively. The simplicity is the main argument for the fixed ratio criterion advocated by GOLD, while the ERS/ATS points out under-diagnosis among younger subjects and over-diagnosis among elderly associated with the fixed ratio criterion. The GOLD-criterion has been most frequently used, while in more recent epidemiological studies on COPD the LLN-criterion is markedly gaining ground.
      The most commonly used measure of COPD severity has been to analyze FEV1 as percent of predicted as an indicator for the level of airflow limitation, which in turn is associated with mortality [
      • Stavem K.
      • Aaser E.
      • Sandvik L.
      • Bjornholt J.V.
      • Erikssen G.
      • Thaulow E.
      • et al.
      Lung function, smoking and mortality in a 26-year follow-up of healthy middle-aged males.
      ]. Recently, the GOLD consortium has presented ABCD groups for guiding of treatment based also on symptoms and exacerbations, beside the GOLD grades 1–4 of airflow limitation [
      ]. Recent publications provide evidence that the spirometric GOLD grades 1–4 predicts mortality at least as good [
      • Leivseth L.
      • Brumpton B.M.
      • Nilsen T.I.
      • Mai X.M.
      • Johnsen R.
      • Langhammer A.
      GOLD classifications and mortality in chronic obstructive pulmonary disease: the HUNT study, Norway.
      ,
      • Johannessen A.
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      • Storebo M.
      • Gulsvik A.
      • Eagan T.
      • Bakke P.
      Comparison of 2011 and 2007 global initiative for chronic obstructive lung disease guidelines for predicting mortality and hospitalization.
      ], and they are still widely used in epidemiological studies despite the arbitrary cut-offs.
      Without underestimating the quality of our study, some weaknesses should be mentioned. For one, the brand of the spirometers and the criterion for reversibility testing differed between the two surveys. To our knowledge, there is no study comparing the Minjhardt Vicatest with the Jaeger Masterscope, but we are confident that there would be little changes to the results if the same type of spirometer had been used, especially since the spirometers were checked-up on a daily basis and no obvious deviations were observed. The repeatability criterion was identical in the two surveys but is not quite in accordance with the <150 ml difference criterion recommended by the ERS/ATS [
      • Miller M.R.
      • Hankinson J.
      • Brusasco V.
      • Burgos F.
      • Casaburi R.
      • Coates A.
      • et al.
      Standardisation of spirometry.
      ]. This choice of repeatability criterion enabled less biased comparison between the 2009 and the 1994 surveys, why it was preferred over the ERS/ATS criterion. The differences in criteria for performing reversibility testing between surveys may have affected the results. However, the sensitivity analyses based on pre-bronchodilator values confirmed the main results of decreased prevalence of moderate to severe COPD and decreased level of airflow limitation in COPD. Furthermore, if the exact criteria for reversibility testing from 1994 had been applied in 2009, only one subject with COPD would have been missed based on the GOLD-criterion and also one based on the LLN-criterion, both of which had normal FEV1 pre as well as post bronchodilation. The lack of comparable data on pack-years of smoking is another weakness. Valid data on exacerbations, and pack-years as well, was available in 2009 but not in 1994, and could thus not be included in this comparison over time, and why the ABCD-classification cannot be used.
      Some of the strengths of the study include that the studies were repeated in the same geographical area, with the same interview core questions, within the same age range and using the same definition of COPD based on spirometric data of high quality. The data collection was performed by a well-experienced research staff and the participation rates were high at both surveys. The estimates can thus be expected to be comparable with limited bias [
      • Bakke P.S.
      • Ronmark E.
      • Eagan T.
      • Pistelli F.
      • Annesi-Maesano I.
      • Maly M.
      • et al.
      Recommendations for epidemiological studies on COPD.
      ]. Further, at least 40 years of age has previously been a common inclusion criterion when basing the spirometric criteria on the GOLD-fixed ratio criterion since few are identified in younger ages than 40. Thus, many studies have only included subjects aged 40 years or older [
      • Pena V.S.
      • Miravitlles M.
      • Gabriel R.
      • Jimenez-Ruiz C.A.
      • Villasante C.
      • Masa J.F.
      • et al.
      Geographic variations in prevalence and underdiagnosis of COPD: results of the IBERPOC multicentre epidemiological study.
      ,
      • Lamprecht B.
      • Soriano J.B.
      • Studnicka M.
      • Kaiser B.
      • Vanfleteren L.E.
      • Gnatiuc L.
      • et al.
      Determinants of underdiagnosis of COPD in national and international surveys.
      ,
      • Buist A.S.
      • McBurnie M.A.
      • Vollmer W.M.
      • Gillespie S.
      • Burney P.
      • Mannino D.M.
      • et al.
      International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study.
      ,
      • Danielsson P.
      • Olafsdottir I.S.
      • Benediktsdottir B.
      • Gislason T.
      • Janson C.
      The prevalence of chronic obstructive pulmonary disease in Uppsala, Sweden–the Burden of Obstructive Lung Disease (BOLD) study: cross-sectional population-based study.
      ], disregarding the importance of identifying younger subjects early in the disease progress. This is important since we know today that COPD is initiated earlier in life than previously thought, e.g. due to prenatal or childhood exposures to harmful agents [
      • Annesi-Maesano I.
      • Lundbäck B.
      • Viegi G.
      Chapter on chronic obstructive pulmonary disease.
      ,
      • Chapman K.R.
      • Mannino D.M.
      • Soriano J.B.
      • Vermeire P.A.
      • Buist A.S.
      • Thun M.J.
      • et al.
      Epidemiology and costs of chronic obstructive pulmonary disease.
      ,
      • Lopez-Campos J.L.
      • Tan W.
      • Soriano J.B.
      Global burden of COPD.
      ]. Now, however, the LLN can identify not-fully reversible airway obstruction in subjects younger than 40 in a more sensitive way, and younger ages are important to include for achieving a full picture of the prevalence and burden of COPD. The age-range of 23–72 years in our study is thus of clinical importance.
      In conclusion, changes in both prevalence and risk factor patterns of COPD were observed from 1994 to 2009. The prevalence of moderate to severe COPD decreased and the severity of airflow limitation among subjects with COPD according to both the GOLD and the LLN criteria decreased substantially. Apart from the known risk factors smoking and older ages, the risk factor pattern was altered in 2009, when the socio-economic group academics had a lower risk for COPD as compared to other groups, while ex-smoking and a family history of obstructive airway disease no longer were significant.

      Acknowledgements

      We would like to acknowledge the OLIN staff for collecting the data. Financial support was received mainly from The Swedish Heart & Lung Foundation ( 20050428 , 20090244 and 20150488 ), The Swedish Research Council ( 80586701 ), ALF ( 216371 )–a regional agreement between Umeå university and Norrbotten County Council ( NLL-574941 ), Norrbotten County Council , the Swedish Asthma-Allergy Foundation and Visare Norr .

      Appendix A. Supplementary data

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