Inhaled corticosteroids do not reduce initial high activity of matrix metalloproteinase (MMP)-9 in exhaled breath condensates of children with asthma exacerbation: a proof of concept study

Abstract

Inhaled corticosteroids (ICS) are the key component of asthma treatment. However, it is unclear whether they could control the activity and level of matrix metalloproteinase (MMP)-9, which is an important factor in asthma-associated inflammation and airway remodeling. Therefore, the aim of this proof of concept study was to analyze the influence of increased doses of ICS on MMP-9 in exhaled breath condensates (EBC) of patients with allergic asthma exacerbation. Apart from MMP-9, the assessment concerned selected inflammation markers – exhaled nitric oxide (eNO) and cytokines (IL-8 and TNF).The study involved a small group (n = 4) of individuals with asthma exacerbation. The intervention concerned increased doses of ICS with β-mimetics for 4 weeks. In addition to clinical evaluation, eNO measurements and EBC collections were done before and after 4 weeks of intense ICS treatment. The biochemical assessment of EBC concerned MMP-9, IL-8 and TNF. The data were compared to results of healthy controls (n = 6).The initial levels of eNO, MMP-9 and TNF in EBC were higher in the asthma group than in controls. In all subjects IL-8 levels were below the detection limit. After 4 weeks of ICS treatment in all patients we observed improvement of clinical and laboratory parameters. Interestingly, despite reduction of eNO and TNF, the activity of MMP-9/EBC remained on the initial level.Practical relevance of our results is limited by a small group. Nevertheless, our data suggest that ICS, although sufficient to control symptoms and inflammatory markers, may be ineffective to reduce MMP-9/EBC activity in asthma exacerbation and, possibly, airway remodeling.

Increased angiogenic factors in exhaled breath condensate of children with severe asthma – New markers of disease progression?

“…We have used 23 randomly selected samples of already deposited breath condensates, excessively collected during our recent projects, focused on children with severe (n ¼ 6) and mild asthma (n ¼ 8), respectively [5,6]. The control group comprised samples of breath condensates (n ¼ 9) from age-matched healthy individuals.…”

Exhaled matrix metalloproteinase 9 in patients with stable COPD - an observational study

“…In an older study, Russell et al 11 reported that dexamethasone decreased the production of MMP -9 by BALF-derived alveolar macrophages from COPD patients. On the other hand, Grzela et al 21,41 found that ICSs do not decrease MMP -9 activity in EBC in asthma, either during prolonged treatment in patients with stable disease or during disease exacerbation. Nevertheless, these findings cannot be directly compared with our results, as they were observed in a different study population, that is, children with asthma.…”

Exhaled Breath Condensate in Childhood Asthma: A Review and Current Perspective

“…After treatment of the exacerbation (defined according to GINA guidelines), no differences were found between asthmatic and healthy children (29). The third study assessed the cytokines tumor necrosis factor (TNF) and IL-8, and a marker of airway remodeling [matrix metalloproteinase (MMP)-9] in EBC in a very small group ( n = 4) of children with an asthma exacerbation (30). After 4 weeks of increasing the ICS dose, the concentration of TNF in EBC significantly decreased (30).…”

“…The third study assessed the cytokines tumor necrosis factor (TNF) and IL-8, and a marker of airway remodeling [matrix metalloproteinase (MMP)-9] in EBC in a very small group ( n = 4) of children with an asthma exacerbation (30). After 4 weeks of increasing the ICS dose, the concentration of TNF in EBC significantly decreased (30). However, the concentration of MMP-9 did not change, and more importantly, IL-8 was below the detection limit in all children (30).…”

“…After 4 weeks of increasing the ICS dose, the concentration of TNF in EBC significantly decreased (30). However, the concentration of MMP-9 did not change, and more importantly, IL-8 was below the detection limit in all children (30).…”