Pharmacological mechanism of roflumilast in the treatment of asthma–COPD overlap

Figures & data

Table 1 Role of roflumilast in asthma alone, COPD alone, and ACO

Asthma	COPD	ACO
1. Reduces airway inflammation	1. Reduces airway inflammation	1. Reduces airway inflammation
2. Reduces bronchoconstriction	2. Improves airway remodeling	2. Enhances mucociliary clearance
3. Enhances mucociliary clearance	3. Improves pulmonary ventilation function	3. Relieves airway hyperresponsiveness
4. Improves airway remodeling	4. Reduces oxygen free radical release	4. Improves airway remodeling
5. Relieves airway hyperresponsiveness	5. Inhibits pulmonary fibrosis	5. Improves pulmonary ventilation function
		6. Reduces bronchoconstriction
		7. Reduces oxygen free radical release
		8. Inhibits pulmonary fibrosis

Abbreviation: ACO, asthma–COPD overlap.

Figure 1 Pharmacological mechanism of roflumilast in ACO.

Abbreviations: ACO, asthma–COPD overlap; BEC, bronchial epithelial cells; cAMP, cyclic adenosine monophosphate; GM-CSF, granulocyte-macrophage colony stimulating factor; IL-X, interleukin-X; MUC5AC, mucin 5AC, oligomeric mucus/gel-forming; N-E, N-selectin; NF-κB, nuclear factor-kappa B; OFR, oxygen free radicals; PDE-4, phosphodiesterase-4 inhibitor; P-E, P-selectin; PM, pulmonary macrophage; R-N, roflumilast N-oxide; RORrt, retinoid-related orphan receptor-γt; SAG, sputum acid granulocytes; SMC, smooth muscle cells; STAAT6, signal transducer and activator of transcription 6; Th17, T helper 17 lymphocytes; TNF-α, tumor necrosis factor-alpha; VEC, vascular endothelial cells.

Figure 2 The signaling pathway of cAMP in the treatment of ACO.

Note: The dotted line represents suppression, and the solid line represents promotion.
Abbreviations: ACO, asthma–COPD overlap; APC, antigen-presenting cell; cAMP, cyclic adenosine monophosphate; CCL-X, chemokine C-C-motif ligand-X; CFTR, cystic fibrosis transmembrane conductance regulator; CK, cytokine; CXCL10, C-X-C motif chemokine 10; DC, dendritic cell; EMT, epithelial to mesenchymal transition; GM-CSF, granulocyte-macrophage colony stimulating factor; IFN-γ, interferon-γ; IL-X, interleukin-X; NF-κB, nuclear factor-kappa B; NO, nitric oxide; ROS, reactive oxygen species; SMC, smooth muscle cells; Th17, T-helper 17 lymphocytes; TNF-α, tumor necrosis factor-alpha.