Cystic Fibrosis: Pathophysiology of Lung Disease

Abstract

Cystic fibrosis (CF) is a common, life-threatening, multisystemic, autosomal recessive disorder. In the last few years, giant steps have been made with regard to the understanding of CF pathophysiology, allowing the scientific community to propose mechanisms that cause the myriad of CF clinical manifestations. Following the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989, the structure and function of the CFTR protein were described. Since then, more than 2,000 variants of the CFTR gene and their impact on the amount and function of the CFTR protein have been reported. The role of the CFTR protein as an ion channel transporting chloride and bicarbonate and its repercussions on different epithelial cell-lined organs and mucus are now better understood. Mechanisms behind susceptibility to infection in CF have also been proposed and include abnormalities in the composition, volume and acidity of the airway surface liquid, changes in the submucosal gland's anatomy and function, and deficiencies in the mucociliary clearance system. Numerous hypotheses explaining the excessive inflammatory response in CF are also debated and involve impaired mucociliary clearance, persistent hypoxia, lipid abnormalities, protease and antiprotease disproportion, and oxidant and antioxidant imbalance. The purpose of this review is to summarize our current knowledge of CF pathophysiology, including significant historic discoveries and most recent breakthroughs, and to improve understanding and awareness of this fatal disease.

COVID-19 and Cystic Fibrosis: Diagnostic Difficulties or Incorrect Methods?

“…When comparing the tomography of September 2019 with the tomography of April 2020 (Fig. 2), we found that both present chronic lesions typical of cystic fibrosis and patches of ground glass patches of subpleural distribution in the basal lobes, which corresponds to the process chronic inflammatory 2,9,15 .…”

Dysfunctional Inflammation in Cystic Fibrosis Airways: From Mechanisms to Novel Therapeutic Approaches

“…Moreover, this abnormally thick and sticky mucus layer entraps noxious agents and pathogens that initiate a persistent and self-perpetuating inflammatory response. This latter is recognized as a major driver of the progressive structural damage of the airways and lung parenchyma in CF patients, ultimately leading to bronchiectasis and respiratory failure [1].…”

The c.3274T> C mutation in the CFTR gene results in bronchiectasis and loss of lung function in a 44-year-old Peruvian woman: A very rare condition

“…The latter is very frequent in countries such as Peru where the prevalence of tuberculosis is high. Adults with CF may have a residual function of the gene involved in CF, and thus, the sweat chloride test with pilocarpine (gold standard test) is usually not positive, leading to indeterminate results (3,4), making molecular biology studies necessary to achieve a definitive diagnosis (1,5).…”

“…More than 2,000 mutations have been described in this gene, but only 412 mutations have been fully characterized (6). The different variations in mutations can be classified as: a) CF-causing variants, b) pathogenic variants of variable clinical significance, c) non-disease-causing variants, and d) variants of uncertain significance (3,4). The most frequent mutation worldwide is delta F508, although its presence varies considerably between races and regions.…”