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MMP 62 is mainly secreted by neutrophils and macrophages, and relies on cofactors such as zinc and calcium to actively degrade the extracellular matrix causing airway destruction and remodeling in COPD patients, 63 and activates the nuclear factor-B signaling pathway, Toll-like receptors and Wnt signaling pathway through a series of reactions, thereby increasing the secretion of MMP and the expression of intercellular adhesion molecules, promoting inflammatory cell aggregation and exacerbating COPD progression

doi: 10.1126/scisignal.2001173 43 DokumcuKFarahaniRM

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It usually happens when the dose is increased or when the medication is first started