Hartjes, F.J. (2016) Effects of inhaled corticosteroids on eosinophils and neutrophils in blood, sputum, airway wall biopsies and BAL and their association with clinical characteristics in COPD patients. thesis, Medicine.
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Abstract
Introduction: Chronic Obstructive Pulmonary Disease (COPD) is defined as an incompletely reversible and mainly progressive airflow limitation. Neutrophilic airway inflammation is considered a distinctive feature of COPD, while an increase in eosinophils is observed in 15-40% of stable COPD patients and has been associated with a better inhaled corticosteroid (ICS) response with respect to preventing exacerbations. Notwithstanding this, the value of neutrophils and eosinophils as biomarkers of ICS response in blood, sputum, airway wall biopsies or bronchoalveolar lavage (BAL) has not been extensively studied, and even less is known about the association of these cells between these four different bodily compartments. Materials & methods: This study is a prospective, two-centre, double blind, longitudinal, randomized trial on the effects of ICS on pulmonary outcomes in COPD. From 2000 till 2007, 114 steroid-naïve current or former smokers with COPD were included with an intended follow-up period of 30 months receiving ICS treatment (with or without a Long-acting β2-agonist) or placebo. At baseline, 6 months and 30 months of follow-up, cell counts (primary outcome) in blood, sputum, airway wall biopsies and BAL were obtained, as well as the Clinical COPD Questionnaire (CCQ) and lung function measurements. This lung function consists of the forced expiratory volume in one second (FEV1) and, as marker of hyperinflation, residual volume (RV) as percentage of total lung capacity (TLC). We investigated cross-sectional and longitudinal associations between eosinophils and neutrophils in the four compartments, and their predictive value for changes in respiratory symptoms and lung function with ICS treatment. Results: At baseline, higher blood eosinophil levels were positively significantly correlated with higher eosinophil levels in sputum, biopsies and BAL. The positive correlation of eosinophils between blood and sputum as found at baseline, remained significant during 6- and 30-month ICS treatment. Importantly, baseline eosinophils and neutrophils did not predict longitudinal changes in FEV1 in whichever compartment measured. Finally, higher eosinophils in biopsies at baseline were associated with fewer symptoms and with deterioration of symptoms during 6- and 30-month ICS treatment. Conclusion: Measuring blood eosinophils gives a good reflection of their presence in sputum, biopsies and BAL, a finding that, when measuring blood and sputum associations, is independent of ICS treatment. This may open avenues for monitoring instable COPD patients despite ICS treatment and for investigation of novel treatments able to reduce eosinophils with clinical benefit to patients. Eosinophils and neutrophils are, however, both not good predictors of ICS response in the short- and long-term with respect to the lung function. An interesting finding that needs further study is the observation that eosinophils in biopsies predict less respiratory symptoms at baseline, but predict deterioration after short- and long-term ICS treatment.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Faculty supervisor: and Postma, Prof. dr. D.S. and Vonk, Dr. J.M. and Berge, Dr. M. van den and Groningen Research Institute for Asthma and COPD (GRIAC) and Department of Pulmonary Medicine and Tuberculosis and University Medical Center Groningen |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:06 |
| Last Modified: | 25 Jun 2020 11:06 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2610 |
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