Characteristics and Prognosis of Never-Smokers and Smokers with Asthma in the Copenhagen General Population Study. A Prospective Cohort Study.

RATIONALE Asthma is associated with complications, cardiovascular comorbidities, and higher mortality in some individuals. OBJECTIVES To test the hypothesis that, among individuals with asthma, never-smokers have different characteristics and a better prognosis than smokers. METHODS We recruited 94,079 individuals aged 20-100 years from the Copenhagen General Population Study, a prospective cohort study. Among these individuals, 5,691 (6%) had self-reported asthma (2,304 never-smokers, 2,467 former smokers, and 920 current smokers). We examined respiratory symptoms, lung function, and levels of inflammatory and allergic biomarkers in systemic circulation. Furthermore, we assessed prospectively the risk of asthma or chronic obstructive pulmonary disease (COPD) exacerbations, pneumonias, lung cancer, ischemic heart disease, ischemic stroke, and all-cause mortality during 4.5 years of follow-up. MEASUREMENTS AND MAIN RESULTS Compared with never-smokers without asthma, individuals with asthma had more respiratory symptoms and airflow limitation and higher levels of inflammatory and allergic biomarkers, which were most pronounced in smokers. Among individuals with asthma compared with never-smokers without asthma, multivariable adjusted hazard ratios for asthma exacerbations were 11 (95% confidence interval: 5.8-22) in never-smokers, 13 (6.2-29) in former smokers, and 18 (8.2-39) in current smokers. The corresponding values for other endpoints were, respectively, 8.9 (2.1-38), 23 (8.8-58), and 36 (12-105) for COPD exacerbations; 1.5 (0.9-2.2), 1.6 (1.0-2.4), and 2.4 (1.6-3.7) for pneumonias; 0.6 (0.1-5.1), 4.0 (1.3-12), and 13 (4.3-41) for lung cancer; 1.2 (0.9-1.6), 1.5 (1.2-2.0), and 2.0 (1.4-2.9) for ischemic heart disease; 1.4 (0.9-2.1), 1.2 (0.8-1.9), and 3.0 (1.7-5.3) for ischemic stroke; and 0.9 (0.6-1.3), 1.5 (1.1-2.0), and 2.7 (1.9-3.7) for all-cause mortality. CONCLUSIONS Never-smokers with asthma had an increased risk of asthma and COPD exacerbations, and possibly pneumonias. Importantly, the risks for lung cancer, cardiovascular comorbidities, and death were restricted to smokers with asthma. Thus, tobacco smoking was the main explanation for poor prognosis in asthma.

[1]  D. Jarvis,et al.  Interaction between asthma and smoking increases the risk of adult airway obstruction , 2014, European Respiratory Journal.

[2]  B. Nordestgaard,et al.  Characteristics and outcomes of chronic obstructive pulmonary disease in never smokers in Denmark: a prospective population study. , 2013, The Lancet. Respiratory medicine.

[3]  B. Nordestgaard,et al.  Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease. , 2013, JAMA.

[4]  R. de Marco,et al.  The Coexistence of Asthma and Chronic Obstructive Pulmonary Disease (COPD): Prevalence and Risk Factors in Young, Middle-aged and Elderly People from the General Population , 2013, PloS one.

[5]  C. Iribarren,et al.  Adult asthma and risk of coronary heart disease, cerebrovascular disease, and heart failure: a prospective study of 2 matched cohorts. , 2012, American journal of epidemiology.

[6]  N. Thomson,et al.  Smoking and asthma: dangerous liaisons , 2012, European Respiratory Journal.

[7]  Teresa To,et al.  Global asthma prevalence in adults: findings from the cross-sectional world health survey , 2012, BMC Public Health.

[8]  H. Morgenstern,et al.  Asthma and lung cancer risk: a systematic investigation by the International Lung Cancer Consortium. , 2012, Carcinogenesis.

[9]  C. Janson,et al.  The Impact of Cigarette Smoking on Asthma: A Population-Based International Cohort Study , 2012, International Archives of Allergy and Immunology.

[10]  S. Johnston,et al.  Asthma exacerbations: Origin, effect, and prevention , 2011, Journal of Allergy and Clinical Immunology.

[11]  P. Lange,et al.  Validity and underrecording of diagnosis of COPD in the Danish National Patient Registry. , 2011, Respiratory medicine.

[12]  M. Stanbrook,et al.  Smoking prevalence, behaviours, and cessation among individuals with COPD or asthma. , 2011, Respiratory medicine.

[13]  William W Busse,et al.  Severe exacerbations and decline in lung function in asthma. , 2009, American journal of respiratory and critical care medicine.

[14]  Fernando Holguin,et al.  Relation of adult-onset asthma to coronary heart disease and stroke. , 2008, The American journal of cardiology.

[15]  K. Rabe,et al.  Complex chronic comorbidities of COPD , 2008, European Respiratory Journal.

[16]  W. Poewe,et al.  Allergic rhinitis, asthma, and atherosclerosis in the Bruneck and ARMY studies. , 2005, Archives of internal medicine.

[17]  A. Folsom,et al.  Asthma and incident cardiovascular disease: the Atherosclerosis Risk in Communities Study , 2005, Thorax.

[18]  N. Thomson,et al.  Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma , 2005, Thorax.

[19]  Carlos Iribarren,et al.  Are patients with asthma at increased risk of coronary heart disease? , 2004, International journal of epidemiology.

[20]  Stefano Guerra,et al.  Asthma as a risk factor for COPD in a longitudinal study. , 2004, Chest.

[21]  Kevin B Weiss,et al.  Worldwide severity and control of asthma in children and adults: the global asthma insights and reality surveys. , 2004, The Journal of allergy and clinical immunology.

[22]  D. Postma,et al.  Risk factors associated with the presence of irreversible airflow limitation and reduced transfer coefficient in patients with asthma after 26 years of follow up. , 2003, Thorax.

[23]  L. Filleul,et al.  Long-term mortality among adults with or without asthma in the PAARC study , 2003, European Respiratory Journal.

[24]  K. J. Macleod,et al.  Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma , 2002, Thorax.

[25]  B. Toelle,et al.  Continuing the debate about measuring asthma in population studies , 2001, Thorax.

[26]  J Vestbo,et al.  A 15-year follow-up study of ventilatory function in adults with asthma. , 1998, The New England journal of medicine.

[27]  H. Storm,et al.  The Danish Cancer Registry--history, content, quality and use. , 1997, Danish medical bulletin.

[28]  J. Kaprio,et al.  Mortality of adults with asthma: a prospective cohort study. , 1997, Thorax.

[29]  V M Hawthorne,et al.  Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study , 1996, BMJ.

[30]  K. Torén,et al.  Do patients with severe asthma run an increased risk from ischaemic heart disease? , 1996, International journal of epidemiology.

[31]  P. Lange,et al.  Mortality in adults with self-reported asthma , 1996, The Lancet.

[32]  C. Ulrik,et al.  Mortality and markers of risk of asthma death among 1,075 outpatients with asthma. , 1995, Chest.

[33]  B Järvholm,et al.  Asthma and asthma-like symptoms in adults assessed by questionnaires. A literature review. , 1993, Chest.

[34]  P. Schnohr,et al.  Spirometric findings and mortality in never-smokers. , 1990, Journal of clinical epidemiology.

[35]  R. Gill,et al.  Cox's regression model for counting processes: a large sample study : (preprint) , 1982 .