Factors Associated with the Non-Exacerbator Phenotype of Chronic Obstructive Pulmonary Disease

Abstract

Dennis Bouhuis,1 Maaike Giezeman,1,2 Mikael Hasselgren,1,2 Christer Janson,3 Marta A Kisiel,4 Karin Lisspers,5 Scott Montgomery,6– 8 Anna Nager,9 Hanna Sandelowsky,7,9,10 Björn Ställberg,5 Josefin Sundh11 1School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 2Centre for Clinical Research and Education, Karlstad, Sweden; 3Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 4Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden; 5Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 6Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro, Sweden; 7Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; 8Department of Epidemiology and Public Health, University College, London, UK; 9Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden; 10Academic Primary Health Care Centre, Stockholm, Sweden; 11Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, SwedenCorrespondence: Josefin Sundh, Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden, Tel [phone], Email [email protected]: Patients with chronic obstructive pulmonary disease (COPD) and no exacerbations may need less maintenance treatment and follow-up. The aim was to identify factors associated with a non-exacerbator COPD phenotype.Methods: Cross-sectional analysis of 1354 patients from primary and secondary care, with a doctor’s diagnosis of COPD. In 2014, data on demographics, exacerbation frequency and symptoms using COPD Assessment Test (CAT) were collected using questionnaires and on spirometry and comorbid conditions by record review. The non-exacerbator phenotype was defined as having reported no exacerbations the previous six months. Multivariable logistic regression with the non-exacerbator phenotype as dependent variable was performed, including stratification and interaction analyses by sex.Results: The non-exacerbator phenotype was found in 891 (66%) patients and was independently associated with COPD stage 1 (OR [95% CI] 5.72 [3.30– 9.92]), stage 2 (3.42 [2.13– 5.51]) and stage 3 (2.38 [1.46– 3.88]) compared with stage 4, and with CAT score < 10 (3.35 [2.34– 4.80]). Chronic bronchitis and underweight were inversely associated with the non-exacerbator phenotype (0.47 [0.28– 0.79]) and (0.68 [0.48– 0.97]), respectively. The proportion of non-exacerbators was higher among patients with no maintenance treatment or a single bronchodilator. The association of COPD stage 1 compared with stage 4 with the non-exacerbator phenotype was stronger in men (p for interaction 0.048). In women, underweight and obesity were both inversely associated with the non-exacerbator phenotype (p for interaction 0.033 and 0.046 respectively), and in men heart failure was inversely associated with the non-exacerbator phenotype (p for interaction 0.030).Conclusion: The non-exacerbator phenotype is common, especially in patients with no maintenance treatment or a single bronchodilator, and is characterized by preserved lung function, low symptom burden, and by absence of chronic bronchitis, underweight and obesity and heart failure. We suggest these patients may need less treatment and follow-up, but that management of comorbid conditions is important to avoid exacerbations.Keywords: COPD, exacerbations, lung function, CAT, body mass index, chronic bronchitis, sex, heart failure

Keywords

• copd
• exacerbations
• lung function
• cat
• body mass index
• chronic bronchitis
• sex
• heart failure