Manifestaciones hepáticas en niños con fibrosis quística y uso de moduladores CFTR. ¿Qué debemos monitorizar? / Hepatic manifestations in children with cystic fibrosis and use of CFTR modulators. What should we monitor?

La enfermedad hepática relacionada con fibrosis quística se observa en el 10% de las personas portadoras de la enfermedad. La terapia con moduladores ha mejorado la morbimortalidad, pero teniendo en cuenta que presentan efectos secundarios infrecuentes es necesario monitorizar. Se analiza el algoritmo propuesto por Eldredge et al, que sugiere las decisiones a tomar basado en el resultado de perfil hepático y su aplicación en la práctica clínica.

Cystic fibrosis-related liver disease is seen in 10% of people with the disease. Therapy with modulators has improved morbidity and mortality, but taking into account that they present infrequent side effects, monitoring is necessary. The algorithm proposed by Eldredge et al is analyzed, which suggests the decisions to be made based on the liver profile result and its application in clinical practice.

Multi-disciplinary team of the treatment of bilateral lung transplantation for pediatric cystic fibrosis / 器官移植

Objective To improve the surgical efficacy of bilateral lung transplantation for pediatric cystic fibrosis through multi-disciplinary team (MDT). Methods Preoperative MDT consultation was delivered for a 10-year-old child with rare end-stage cystic fibrosis to establish the corresponding treatment protocol. Results The child was diagnosed with cystic fibrosis for 5 years, and the indication of lung transplantation were confirmed. After preoperative MDT consultation, bilateral lung transplantation via a Clam-shell incision was determined. The vital signs were maintained stable during operation. Postoperatively, ventilator-assisted ventilation, anti-infection, immunosuppression, acid suppression, prevention of stress ulceration and other treatments were delivered. Individualized treatment was given according to the characteristics of the child, and the child was well recovered. Conclusions Through preoperative MDT consultation, lung transplantation yields satisfactory surgical efficacy in treating pediatric cystic fibrosis and lowers the risk of postoperative complications, which deserves application in clinical practice.

Efficacy of Qingfei Huatantang in Treatment of COPD by Up-regulating Expression of CFTR Through JAK2/STAT3 Pathway / 中国实验方剂学杂志

Objective:To explore the efficacy and mechanism of Qingfei Huatan Tang on chronic obstructive pulmonary disease (COPD). Method:The rat model of COPD was established through smoke inhalation combined with lipopolysaccharide (LPS) and pulmonary compound injection. After successful modeling, the rats were randomly divided into 6 groups, namely the control group, the COPD model group, low, medium and high-dose Qingfei Huatan Tang groups and the ambroxol group. After 28 days of modeling, the drug was administered. Low, medium and high-dose Qingfei Huatan Tang (7.5, 15, 30 g·kg-1) and ambroxol (35 mg·kg-1) were administered continuously for 14 days. Immunohistochemistry and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect protein expression and mRNA expression of cystic fibrosis transmembrane conductance regulator (CFTR) in pulmonary fibrosis. NCI-H292 cells were induced by LPS to establish a mucus hypersecretion model. The experiment was divided into 8 groups, namely the blank control group, LPS group, LPS+10% fetal bovine serum group, LPS+ physiological serum group, LPS+5% drug serum group, LPS+10% drug serum group, LPS+20% drug serum group and LPS+AG490 group. Immunofluorescence, Western blot and Real-time PCR were used to observe the protein and mRNA expressions of CFTR in NCI-H292 cells after LPS stimulation, and western blot was used to detect the expression of tyrosine kinase 2/transcription factor 3 (JAK2/STAT3) signaling pathway in NCI-H292 cells after LPS stimulation. Result:There were a large number of brown particles around the lumen of lung tissues in the normal group, with increased COPD expression. There were a few brown particles around the lumen of lung tissues in the model group compared with the normal group, with decreased COPD expression. Compared with the normal group, mRNA and protein expressions of CFTR in the lung tissues of the COPD model group were significantly decreased (P<0.05). Compared with the model group, mRNA and protein expressions of CFTR in the lung tissues of low, medium and high-dose Qingfei Huatan Tang groups (P<0.05). Compared with the blank control group, mRNA and protein expressions of CFTR in NCI-H292 cells of the LPS group (P<0.05), with significant increases in protein expressions of p-JAK2 and p-STAT3 (P<0.05). Compared with the model group, 5%, 10%, 20% Qingfei Huatan Tang-containing serum groups showed significant increases in mRNA and protein expressions of CFTR, but with significant decreases in p-JAK2, p-STAT3 protein expressions (P<0.05, P<0.01). Conclusion:Qingfei Huatan Tang up-regulated CFTR in the treatment of COPD by inhibiting JAK2/STAT3 pathway.

Ivacaftor in cystic fibrosis: the first disease modifying agent.

The exact magnitude of cystic fibrosis (CF) in India is not known, as it is often misrepresented and underdiagnosed. CF is caused by a mutation in the gene that encodes for the CF transmembrane conductance regulator (CFTR) protein whose dysfunction leads to multiorgan manifestations. Most CF mutations either reduce the number of CFTR channels at the cell surface or impair the channel function. Current treatments (mucolytics, antibiotics and anti-inflammatory agents) target the secondary effects of CFTR dysfunction and help to ameliorate the symptoms but do not address the basic defect of the disease. Ivacaftor is a first-in-class oral CFTR potentiator that increases the CFTR channel opening. In clinical trials, ivacaftor has shown improved pulmonary function, normalization of sweat chloride concentration, substantial weight gain as well as acceptable safety profile. The most frequent adverse effects associated with ivacaftor include headache, oropharyngeal pain, upper respiratory tract infection, nasal congestion, abdominal pain and nasopharyngitis. FDA has approved this agent for the treatment of CF in patients aged 6 years or older with at least one copy of the G551D mutation in the CFTR gene. Searches of medline, cochrane database, medscape, SCOPUS and clinicaltrials.org were made for terms like CFTR potentiator, cystic fibrosis, and ivacaftor. Relevant journal articles from last 5 years were chosen.

Report of a Korean Patient with Cystic Fibrosis, Carrying Q98R and Q220X Mutations in the CFTR Gene

Although cystic fibrosis (CF) is one of the most frequently seen autosomal-recessive disorders in Caucasians, it is extremely rare in the Korean population. Recently, a 15-yr-old Korean boy was admitted to our hospital complaining of coughing, sputum, and exertional dyspnea. Chest radiographs and computed tomographic chest and paranasal sinus scans revealed diffuse bronchiectasis and pansinusitis. Pulmonary function tests revealed severe obstructive impairment. The average sweat chloride concentrations on both of the patients' forearms were 63.0 mM/L (reference limit: < 40 mM/L). Upon mutation analysis, two different mutations (Q98R and Q220X) were identified in the cystic fibrosis transmembrane conductance regulator gene, both of which had been previously detected in CF patients, one from France and the other from England. As CF is quite rare in Korea, the diagnosis of CF in this patient might be delayed. Therefore, we recommend that a diagnosis of CF should be suspected in patients exhibiting unexplained chronic respiratory symptoms.