**Author details**

In contrast to ICS alone, the improved control of asthma severity, possibly due to better modulation of MMPs system, may be achieved by introducing a combination therapy, which comprises ICS and long acting β-agonists (LABA). Although both, *in vitro* and *in vivo* studies, confirmed superiority of combination therapy over ICS or LABA alone in this regard, they did not determine exactly, how this combination may affect MMP levels. [112–114] Possibly, the augmented effect of ICS-LABA combination can be, at least partially, explained by LABA ability to modulate NF-κB signaling pathway. Thus, inhibition of NF-κB will result in de‐ creased expression of MMP-9 gene, as has been recently shown for ultra-LABA – indacaterol. [115] Indeed, combination of ICS with LABA as both, maintenance and reliever therapy, significantly reduced MMP-9 levels in induced sputum of asthmatic patients. [116, 117] Remarkably, MMP-9 levels, observed in patients with asthma before and after combined treatment with ICS and LABA, seem to reflect the intensity of airways remodeling, as they revealed good correlation with bronchial wall thickening, visualized using high-resolution

Leukotriene-receptor antagonists (LTRA) may be considered as an alternative to ICS as "firstline asthma-controller therapy" or as "add-on therapy" in patients already receiving ICS. Montelukast, most commonly used LTRA, was found to decrease the expression of MMP-9 in activated eosinophils *in vitro*. [118] In children with asthma a treatment with LTRA resulted in clinical improvement –reduction of symptoms and increase of peak expiratory flow, which were associated with significant decrease of MMP-9 levels in plasma. [119] In experimental asthma model in mice LTRA treatment was shown to reverse airway remodeling and de‐ creased airway hyperresponsiveness after allergen challenge. Again, mentioned improvement

Despite extensive studies focused on role of MMPs in asthma and asthma-associated remod‐ eling, our knowledge regarding this issue is still far from a satisfactory level. Since there is no agreement among scientists regarding superiority of "destructive" or "protective" concept, the clarification of "Dr. Jekyll or Mr. Hyde ?" issue seems to have outstanding clinical rele‐ vance, especially when considering possible pharmacological interventions. Regrettably, the interpretation of results concerning exact place of MMPs in asthma pathogenesis may be impeded by different methodology and various populations analyzed in these studies. Such differences may certainly affect result of MMPs assessment across the studies. [57, 121] On the other hand, these discrepancies can be ascribed to real differences in MMPs amount and/or activity, depending on sample type and disease severity. Furthermore, local expression and activity of individual MMPs may vary in different airway compartments, thus adding complexity to the network of allergic inflammatory response. [61, 78, 122] Accordingly, the distribution of MMP-2, MMP-9 and MMP-12 in bronchial wall was shown to differ between

correlated with decrease of MMP-2 and -9 levels in BAL fluid. [120]

computed tomography. [116]

**3. Conclusions**

*2.7.6. Leukotriene-receptor antagonists*

58 Asthma - From Childhood Asthma to ACOS Phenotypes

Katarzyna Grzela, Agnieszka Strzelak, Wioletta Zagórska and Tomasz Grzela\*

\*Address all correspondence to: tomekgrzela@gmail.com

The Medical University of Warsaw, Department of Paediatrics, Pneumonology and Allergology (KG, AS, WZ), and Department of Histology and Embryology (TG), Poland
