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. 2023 Apr 6:18:483-492.
doi: 10.2147/COPD.S392070. eCollection 2023.

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

Dennis Bouhuis  1 , Maaike Giezeman  1   2 , Mikael Hasselgren  1   2 , Christer Janson  3 , Marta A Kisiel  4 , Karin Lisspers  5 , Scott Montgomery  6   7   8 , Anna Nager  9 , Hanna Sandelowsky  7   9   10 , Björn Ställberg  5 , Josefin Sundh  11
Affiliations

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

Dennis Bouhuis et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

Background: 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: CAT; COPD; body mass index; chronic bronchitis; exacerbations; heart failure; lung function; sex.

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Conflict of interest statement

Professor Christer Janson reports personal fees from AstraZeneca, Novartis, Boehringer Ingelheim, GlaxoSmithKline, Chiesi, Orion and Sanofi, outside the submitted work. Dr Karin Lisspers reports personal fees from Novartis, AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline, outside the submitted work. Dr Hanna Sandelowsky reports personal fees from Boehringer Ingelheim, Chiesi, Novartis, AstraZeneca, GlaxoSmithKline, and TEVA, outside the submitted work. Dr Björn Ställberg reports personal fees from AstraZeneca, Novartis, Boehringer Ingelheim, GlaxoSmithKleine, Meda/Mylan, Chiesi, and Teva, outside the submitted work. Dr Josefin Sundh reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi and Novartis, outside the submitted work. The authors report no other conflicts of interest related to this study.

Figures

Figure 1
Figure 1
Flow chart describing the selection and data collection within the study.
Figure 2
Figure 2
The non-exacerbator phenotype by severity of COPD proportions of patients with no exacerbations in every COPD stage.
Figure 3
Figure 3
Factors associated with having no exacerbations in COPD results from multivariable analysis, adjusted for sex, age, smoking, level of education, BMI, COPD stage, CAT, chronic bronchitis, heart failure, ischemic heart disease, atrial fibrillation and depression/anxiety.
See this image and copyright information in PMC

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