Dysfunctional inflammation drives Cystic Fibrosis lung damage, highlighting novel anti-inflammatory agents and CFTR modulators.

Cystic Fibrosis (CF) is a genetic disorder caused by mutations in the CFTR protein, an ATP-gated chloride channel crucial for airway epithelial function. Its dysfunction leads to defective ion transport and airway surface liquid dehydration, trapping pathogens in thick mucus. This creates a highly inflammatory microenvironment, severely compromising lung function and leading to progressive damage. Current standard-of-care often falls short in effectively managing this chronic, dysfunctional inflammation, necessitating the exploration of novel therapeutic strategies.

This comprehensive review synthesized existing literature on the mechanisms of dysfunctional inflammation in Cystic Fibrosis airways and evaluated current and emerging therapeutic strategies. The authors critically assessed the limitations of traditional anti-inflammatory approaches and explored the potential of novel anti-inflammatory agents. Furthermore, the review examined the anti-inflammatory properties of CFTR modulators, a class of drugs directly addressing the underlying genetic defect, and considered the implications of SARS-CoV-2 infection for CF patients.

The review established that chronic, dysfunctional inflammation is a central driver of lung damage in Cystic Fibrosis, exacerbating epithelial dysfunction and infection susceptibility. It highlighted that traditional anti-inflammatory therapies often provide limited clinical benefits due to their broad action or side effects. Significant efforts have identified new molecules with potential anti-inflammatory effects, offering promising alternative treatments for CF patients. The authors also critically reviewed evidence suggesting that CFTR modulators, beyond correcting the primary ion transport defect, may possess intrinsic anti-inflammatory properties, potentially offering a dual benefit. The synthesis emphasized the need for targeted anti-inflammatory strategies to mitigate CF pathophysiology more effectively.