Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that primarily affects the respiratory and gastrointestinal systems. It results from variants in the CFTR gene, leading to dysfunctional chloride channels, thickened mucus secretion, and subsequent multisystem complications. Significant advances have been made in CF treatment, particularly with the development of CFTR modulators, which are unique to genotypes and have improved clinical outcomes in many people with CF. However, the benefits of these therapies are not universal, with a considerable portion of the CF population—especially those with rare mutations—still without access to effective treatment options. This review provides a comprehensive overview of the pathophysiology and genetic basis of CF, explores current and emerging treatments, and discusses the ongoing challenges in the field. Cite this article as: Yıldız CA, Gökdemir Y, Eralp EE, Ergenekon P, Karakoç F, Karadağ B. Cystic fibrosis treatment landscape: Progress, challenges, and future directions. Turk Arch Pediatr. 2025;60(2):117-125.

Background: We hypothesise that the lung clearance index (LCI) would be superior to spirometry in diagnosing early-stage respiratory diseases earlier and, more precisely, in patients who received medical or surgical treatment for empyema. Methods: Children over 5 years old diagnosed with empyema at least 6 months ago were recruited. In addition, a control group was created from healthy individuals between the ages of 5–18 years. Spirometry and LCI were performed in both groups. Results: The spirometric values of the patients were compared with the spirometric values of the controls; there was no significant difference between the patient and control groups' forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and FEV₁/FVC z scores results when compared (p=0.610, p=0.342 and p=0.298, respectively). In addition, when the LCI 2.5% values of the patients were compared with the LCI 2.5% values of the controls and reference values, the LCI 2.5% was found to be significantly abnormal (p=0.003 and p=0.005, respectively). Conclusion: In the long-term follow-up of patients who received inpatient treatment for empyema, airway disease that could not be detected by spirometry was obtained using the LCI method.

Sleep apnea,central apnea,children