Non-invasive biomarkers of oxidative stress and cell defence in COPD and asthma : specific emphasis on smoking cessation
Year: 2012
Type: dissertation
Abstract: Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction that is mostly irreversible. The typical features of COPD are chronic inflammation in the small airways, with varying degrees of chronic bronchitis and/or emphysema. Long-term smoking is the major risk factor for COPD. Oxidative stress and protease/antiprotease imbalance play major roles in the pathogenesis of smoking related airway disease such as COPD. The diagnosis of COPD is based on spirometry. Diagnosis is however often delayed since during its early stages, clear symptoms are lacking, even though the lung damage is already extensive. The differential diagnosis of COPD from asthma is especially difficult in smokers. There is a clear need to develop reliable biomarkers that would detect early COPD, differentiate the sub-phenotypes of COPD as well as COPD from asthma and finally be useful in developing treatment strategies for different phenotypes and used in monitoring disease activity and progression. The first goal of this study was to compare different potential markers in various sample types that reflect oxidative stress in the lung, how they are related to each other, and to find the most specific markers for the early detection and monitoring of COPD and asthma and differentiation of these diseases as well as the disease from the condition of healthy smoker . Another goal was to examine the effects of smoking cessation on the best potential markers of oxidative and protease burden. Recent lung proteomic studies have indicated that SP-A could be potential marker for COPD; sputum proteomics was used to find other biomarkers for early COPD. FeNO levels were elevated in mild asthma and eosinophils were elevated in asthmatic adults and patients with COPD exacerbation when compared to healthy controls. No significant differences were detected in sputum 8-isoprostane levels between subjects with mild asthma and healthy controls, but in patients with COPD exacerbation, the 8-isoprostane levels were greatly increased when compared to healthy subjects. In the smoking cessation studies, smokers had elevated levels of all of the investigated markers at the baseline compared to non-smokers. Neutrophil counts increased after 3 months of quitting of smoking in the group of chronic bronchitis/COPD but at 6 months neutrophils had returned to the levels of non-smokers. 8-Isoprostane declined significantly but the levels of FeNO, nitrotyrosine and MMP-8 did not change significantly during 3 months after smoking cessation, although after 6 months, the levels of MMP-7, -8 and TIMP-1 decreased to the levels of non-smokers and only MMP-9 remained elevated at 6 months of smoking cessation. However, the symptoms declined significantly already after 3 months of smoking cessation. The plasma levels of SP-A, SP-D, MMP-9, TIMP-1 and the ratio of MMP-9/TIMP-1 were increased by long-term smoking and COPD, and SP-A correlated with the extent of airway limitation. In proteomic screening of sputum, PIGR was found to be elevated in smokers and in mild to moderate COPD, and this was confirmed in lung tissue and plasma specimens. To conclude, it seems that sputum 8-isoprostane is not sensitive enough in detecting oxidative stress in mild recent asthma while in COPD it may be useful. After smoking cessation, the symptoms decline significantly already after a few months but the oxidant and protease burdens seem to persist in the airways for months. SP-A and PIGR can be proposed as representing new promising markers in smoking related chronic airway inflammation and COPD.
Source: Työväentutkimus Vuosikirja
Author: Noora Louhelainen
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1489532520