China
Africa
Explore chapters and articles related to this topic
Organoid Technology for Basic Science and Biomedical Research
Published in Hyun Jung Kim, Biomimetic Microengineering, 2020
Szu-Hsien (Sam) Wu, Jihoon Kim, Bon-Kyoung Koo
Cystic fibrosis (CF) is caused by various mutations in the CFTR, with the most commonly occurring mutation worldwide being deletion of phenylalanine at position 508. In most cases, even with medical intervention, patients have a reduced quality of life and a short life expectancy of less than 40 years (Chin, Earlam, and Aaron 2015). Moreover, a significant portion of patients do not respond to the available drugs because of the variability in the mutations causing CF (Ratjen and Döring 2003). Dekkers et al. (2013) used human AdSC-derived intestinal organoids as a platform to develop functional assays for CFTR activity. In brief, treatment with forskolin induces swelling in normal organoids via water influx into the lumen; functional CFTR mediates the influx of water and therefore organoid swelling becomes a readout of CFTR functionality. For organoids with the common mutant version CFTRF508del, forskolin-mediated organoid swelling is compromised. The authors further demonstrated that the functionality of CFTRF508del could be restored through exposure to lower temperatures (27°C) as well as treatment with compounds such as VX-809 and VX-770 (Dekkers et al. 2013). This highlights the potential of organoid cultures to screen for therapeutic interventions that will be efficacious for individual patients.
Nanomedicines for the Treatment of Respiratory Diseases
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Brahmeshwar Mishra, Sundeep Chaurasia
Cystic fibrosis, a frequent inherited, autosomal recessive disorder. It is caused by a dysfunction of the epithelial chloride channel CFTR (cystic fibrosis transmembrane regulator) (Rosenstein and Zeitlin, 1998). So far, more than 500 mutations of the CFTR gene are known that are associated with cystic fibrosis (Stern, 1997). Apart from gastrointestinal manifestations such as pancreatic insufficiency, the major cause of morbidity results from airway disease (Rosenstein and Zeitlin, 1998). The hypersecretory-induced airway changes in cystic fibrosis are characterized by submucosal gland and goblet cell hyper- and metaplasia, leading to mucus over-production and distortion of the mucociliary clearance. As a result, airway plugging by mucus leads to chronic inflammatory changes and bacterial colonization (Groneberg et al., 2002; Ramsey, 1996).
Diffuse Lung Diseases (Emphysema, Airway and Interstitial Lung Diseases)
Published in de Azevedo-Marques Paulo Mazzoncini, Mencattini Arianna, Salmeri Marcello, Rangayyan Rangaraj M., Medical Image Analysis and Informatics: Computer-Aided Diagnosis and Therapy, 2018
Marcel Koenigkam Santos, Oliver Weinheimer
Cystic fibrosis is a genetic disorder that especially affects the lungs and pancreas in young Caucasian subjects. In these patients, chronic bacterial infection and inflammation lead to progressive bronchial dilatation, bronchiectasis and parenchymal destruction. There is no cure for CF, but in recent years, treatment has vastly evolved, leading to important increases in life expectancy. Several authors have used QCT to measure airway abnormalities on CF patients. In patients with CF, more bronchi are detected/analyzed when compared to normal subjects, and this parameter in even higher in patients with severe disease, reflecting a higher number of bronchiectasis (Wielpuetz et al. 2013a, Koenigkam-Santos et al. 2016). Airway diameter, wall area and wall thickness also correlate with clinical evaluation scores and function. QCT wall and luminal measures correlate with PFT and disease severity (de Jong et al. 2005, Montaudon et al. 2007). Wielpuetz et al. showed that patients with CF may also have emphysema, as assessed by QCT, even if they are never smokers, and that emphysema volume increases with age and contributes to airflow limitation (Wielpuetz et al. 2013b).
Compensatory changes in physical activity and sedentary time in children and adolescents with cystic fibrosis
Published in Journal of Sports Sciences, 2019
Kelly A. Mackintosh, Nicola D. Ridgers, Melitta A. McNarry
Cystic fibrosis (CF), currently affecting over 10,000 people in the UK (Cystic Fibrosis Trust, 2017), is the most prevalent inherited genetic disorder in the Caucasian population (Quinton, 1990). CF is a multi-system disease, which primarily affects the lungs and digestive system through mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene that lead to malfunctioning or absent CFTR proteins and impaired mucosal clearance mechanisms (Davies, Alton, & Bush, 2007; National Institute for Health and Care Excellence, 2017; Ratjen, 2009). Despite therapeutic advances and an increased life expectancy to 47 years for those born in 2017 (Cystic Fibrosis Trust, 2017), CF remains incurable, highlighting the need to enhance patient well-being.
Development of characteristic airway bifurcations in cystic fibrosis
Published in Aerosol Science and Technology, 2021
Karl Bass, Morgan L. Thomas, Mariette P. C. Kemner-van de Corput, Harm A. W. M. Tiddens, P. Worth Longest
With regard to diseased lung states, the complete-airway SIP models have only been applied to models of constricted airways in asthmatic adults (Walenga and Longest 2016). However, the bacterial infections that are associated with Cystic Fibrosis (CF) can cause various forms of damage to the respiratory airways, such as inflammation (narrowing of the airways), bronchiectasis (localized widening of the airways), and mucus plugging (obstructions and occlusion of the airways) (de Jong et al. 2004), which are not accounted for in current complete-airway models. Considering children, these forms of lung damage are observed in the computed tomography (CT) scans of patients that are diagnosed with CF at very early stages of their life (Tiddens et al. 2010, Sly et al. 2009, Sly et al. 2013). To date, few computational studies of aerosol transport through CF-diseased airways are available in the literature. Awadalla et al. (2014) presented a CFD study, which utilized a Large Eddy Simulation (LES) turbulence model, of a porcine airway anatomy that approximated CF in the human lung based on the same genetic defect. In human lungs, Bos et al. published two CFD studies (Bos et al. 2017, Bos et al. 2015) that evaluated the delivery of antibiotics to the airway surface liquid (ASL) in CF-diseased lungs. The lung anatomies in these two studies were developed by extracting the airways from CT scans of 40 children (from 5 to 17 years old). Due to the CT scan resolution, the most distal regions of the diseased lung that could be extracted and modeled in these studies was B6. However, in our experience, even at approximately B4, CT-extracted lung airways cease to resolve many of the expected physiological structures of lung bifurcations observed from casts. Considering these factors, significant work is needed to better resolve the intermediate TB airway anatomy in disease conditions such as CF. Accurate simulation of aerosol to and through the intermediate TB region is critical to determine drug delivery to the small TB airways and alveolar regions, which play prominent roles in lung inflammation, infection, and function.