As pancreatic fibrosis eventually can lead to CF-related diabetes (CFRD), it is recommended to annually screen with an oral glucose tolerance test from the age of ten. Pancreatic exocrine insufficiency is found in 60–80% of pwCF at birth leading to malabsorption and malnutrition when untreated. In the pancreas, the pancreatic fluid’s viscosity is causing obstruction and secondary tissue destruction, resulting in the formation of cysts and fibrosis. ![]() The manifestation of impaired CFTR function in the gastrointestinal tract already starts in utero. This technique is less dependent on patient effort, making it very suitable for the pediatric population. ![]() ![]() Recently, multiple breath washout testing has become important in clinical research and care with the lung clearance index (LCI) as a primary outcome. A disadvantage of this method is that the technique is too difficult for children below the age of 6. Lung function is crucial in monitoring disease progression and is universally measured through spirometry. The upper airways are also frequently affected and often require sinus surgery due to nasal polyposis, mucocele, and sinusitis. This allergic bronchopulmonary aspergillosis contributes to chronic pulmonary function decline. An increased rate of allergic reactions to Aspergillus is seen in pwCF. The last group of pathogens found in the lungs are fungi, particularly Aspergillus species. Along with bacterial infections, pwCF are also more prone to viral infections, which are linked to exacerbations. However, when the disease progresses, more unusual pathogens like Achromobacter xylosoxidans, Burkholderia cepacia, Strenotrophomonas malthophilia, and mycobacteria can be cultured of which the latter is more challenging to treat. The pathogens Staphylococcus aureus and Pseudomonas aeruginosa are most prevalent. Besides dense mucous, CFTR dysfunction in bronchial epithelia also leads to increased inflammatory response and impaired immune response making it prone to acute infections and chronic bacterial colonization of the lung. Structural lung damage can already be visible on computed tomography images in asymptomatic infants. The respiratory manifestations are caused by chronic pulmonary infections, which eventually lead to progressive lung function decline and respiratory failure, which is the leading cause of death for pwCF. Disease severity and the number of organ systems involved vary from patient to patient. ĬF is often seen as a pulmonary disease however, the lack of CFTR function affects multiple organ systems. This disease variation is most clearly related to the type of CFTR mutation, but is also influenced by additional non-CFTR genetic and environmental factors. However, there is a wide range of disease severity with a median age of survival approaching 50 years. Classes IV to VII have residual CFTR function and tend to be less severe (Fig. Classes I to III are associated with little to no CFTR function and therefore associated with a more severe phenotype. Mutations are classified into seven different classes based on functional impairments. All these mutations result, to some extent, in abnormal chloride and bicarbonate transportation across epithelial cells. This abnormal fluid consistency leads to infections, inflammation, malnutrition, and finally, progressive multi-organ dysfunction.Īt this point, over 2000 CFTR mutations have been reported causing a variety of different disease phenotypes ( ). When CFTR is absent or does not function properly, accumulation of viscous mucus in the pulmonary and gastrointestinal tract will occur. The CFTR protein is an essential regulator of many mucosal surfaces’ fluid and electrolyte homeostasis. Cystic fibrosis (CF, OMIM #219,700) is a rare, autosomal recessive, monogenetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
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