Potential of anti-inflammatory treatment for cystic fibrosis lung disease

Figures & data

Figure 1 Complex interactions contributing to CF airway inflammation. Several proinflammatory mechanisms have been identified in research of cystic fibrosis (CF) airway disease. Heightened proinflammatory signaling pathways, impaired redox-regulation and anti-inflammatory signaling pathways, and perpetual proteolytic and oxidative stress are some of the most well-described mechanisms driving the neutrophil-dominated host response. This neutrophilic inflammation, along with ineffective airway clearance and chronic airway infection, lead to progressive bronchiectasis and impaired lung function.

Abbreviations: PMN, polymorphonuclear cell, ie, neutrophil; ROS, reactive oxygen species; NO, nitric oxide.

Table 1 Current and potential outcome measures for use in clinical trials of new anti-inflammatory therapies in CF

Outcome measure	Examples	Reference(s)
Clinical efficacy	FEV 1, rate of decline of FEV 1, rate of exacerbations	^Citation10, ^Citation11, ^Citation13, ^Citation14, ^Citation97, ^Citation98
Patient reported outcome	CF-HQR	^Citation102
BAL markers	Neutrophils, bacterial count, elastase IL-8, TNF-α, soluable ICAM-1, LB4	^Citation122^–^Citation131
EBC markers	NO, pH, MMP-9	^Citation132^–^Citation139
Sputum markers	White cell count, bacterial count, elastase IL-6, IL-8, IL-10, TNF-α	^Citation140^–^Citation143
Systemic markers	CRP, NE-APC, TNF-α, IL-1, IL-2, IL-8, EGF	^Citation104^–^Citation119
CT scan	CT score, airway trapping, airway wall thickening	^Citation145^–^Citation152
MRI	Structural changes, lung perfusion/pulmonary blood flow, ventilation defects	^Citation154^–^Citation158

Note: Table does not include exhaustive list of examples for each outcome measure. For comprehensive review of outcome measures in clinical trials for CF patients/ candidate biomarkers for CF airway inflammation. See references ⁷⁴ and ¹²¹.

Abbreviations: FEV ₁, forced expiratory volume in 1 second; IL, interleukin; TNF, tumor necrosis factor; L, leukotriene; NO, nitric oxide; MMP, matrix metalloprotein; CRP, C-reactive protein; NE-APC, neutrophil antiproteinase complex; EGF, endothelial growth factor; CT, computed tomography; MRI, magnetic resonance imaging; CF, cystic fibrosis.

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