Diagnosis and treatment of cystic fibrosis in India: What is at stake for developing countries?

Cystic fibrosis (CF) is a life-threatening monogenic disease affecting thousands of people worldwide. Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that facilitates transportation of water and salts across epithelial cell membranes through the conductance of Cl- and other anions. A dysfunctional CFTR due to abnormalities in the cftr gene causes CF, which is believed to be a rare disease in India mainly due to mis/underdiagnosis. Although numerous diagnostic methods and treatment options are available for CF globally, most of these are unaffordable for developing countries like India. Currently, CF symptoms are managed with mucolytics, antibiotics, anti-inflammatory drugs, and various CFTR modulators based on the type of defect. While a definitive cure for CF remains elusive, advancements in stem cell and gene therapies hold promise for permanent cure in the near future. In this review, we discuss the prevalence of CF cases in India, affordable diagnostic methods, and treatment options amenable for developing countries. We further emphasize the scope for the universal newborn screening programme.

Role of innate immunity and systemic inflammation in cystic fibrosis disease progression.

Pathophysiological manifestations of cystic fibrosis (CF) result from a functional defect in the cystic fibrosis transmembrane conductance regulator (CFTR) paving way for mucus obstruction and pathogen colonization. The role of CFTR in modulating immune cell function and vascular integrity, irrespective of mucus thickening, in determining the host cell response to pathogens/allergens and causing systemic inflammation is least appreciated. Since CFTR plays a key role in the conductance of anions like Cl-, loss of CFTR function could affect various basic cellular processes, such as cellular homeostasis, lysosome acidification, and redox balance. CFTR aids in endotoxin tolerance by regulating Toll-like receptor-mediated signaling resulting in uncontrolled activation of innate immune cells. Although leukocytes of CF patients are hyperactivated, they exhibit compromised phagosome activity thus favouring the orchestration of sepsis from defective pathogen clearance. This review will emphasize the importance of innate immunity and systemic inflammatory response in the development of CF and other CFTR-associated pathologies.