Pulmonary ionocytes are a newly discovered airway epithelial cell type proposed to be a major contributor to cystic fibrosis (CF) lung disease based on observations they express the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel at a higher level than any other cell type in the airway epithelia. Moreover, genetically manipulated experimental models that lack ionocytes develop NaCl transport abnormalities and airway surface liquid (ASL) dehydration consistent with CF. However, no direct evidence indicates ionocytes engage in NaCl transport or contribute to ASL formation, questioning the relevance of ionocytes to CF lung disease.
View Article and Find Full Text PDFPatients awaiting lung transplantation must learn new information to successfully navigate the transplant process. A supplemental video series was piloted to patients at home during the Covid-19 pandemic to improve pre-transplant education. A mixed methods study was undertaken to assess patient experiences with this method of education, confirm the ideal timing of the education, and identify gaps that require further attention.
View Article and Find Full Text PDFApixaban is frequently used off-label in transplant recipients. However, a potential drug interaction exists with the calcineurin inhibitors. We conducted an open-label drug-drug interaction study to determine the pharmacokinetics of apixaban in lung and kidney transplant recipients who were taking a calcineurin inhibitor.
View Article and Find Full Text PDFA controversial hypothesis pertaining to cystic fibrosis (CF) lung disease is that the CF transmembrane conductance regulator (CFTR) channel fails to inhibit the epithelial Na channel (ENaC), yielding increased Na reabsorption and airway dehydration. We use a non-invasive self-referencing Na-selective microelectrode technique to measure Na transport across individual folds of distal airway surface epithelium preparations from CFTR (CF) and wild-type (WT) swine. We show that, under unstimulated control conditions, WT and CF epithelia exhibit similar, low rates of Na transport that are unaffected by the ENaC blocker amiloride.
View Article and Find Full Text PDFThoracic dorsal root ganglia (tDRG) contribute to fluid secretion in the upper airways. Inflammation potentiates DRG responses, but the mechanisms remain under investigation. The receptor for advanced glycation end-products (RAGE) underlies potentiation of DRG responses in pain pathologies; however, its role in other sensory modalities is less understood.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2020
Sensing of pathogens by Toll-like receptor 4 (TLR4) induces an inflammatory response; controlled responses confer immunity but uncontrolled responses cause harm. Here we define how a multimodular scaffold, GIV (a.k.
View Article and Find Full Text PDFIntroduction: Providing support throughout the lung transplant process is an intensive task, which requires a dedicated caregiver. The needs of caregivers who must relocate with their loved one receiving the transplant are currently unknown. The objective of this study is to explore experiences and perceptions of lung transplant caregivers identified from a satellite clinic to inform the development of educational resources.
View Article and Find Full Text PDFThe human airway is protected by an efficient innate defense mechanism that requires healthy secretion of airway surface liquid (ASL) to clear pathogens from the lungs. Most of the ASL in the upper airway is secreted by submucosal glands. In cystic fibrosis (CF), the function of airway submucosal glands is abnormal, and these abnormalities are attributed to anomalies in ion transport across the epithelia lining the different sections of the glands that function coordinately to produce the ASL.
View Article and Find Full Text PDFInhaled hypertonic saline (HTS) treatment is used to improve lung health in patients with cystic fibrosis (CF). The current consensus is that the treatment generates an osmotic gradient that draws water into the airways and increases airway surface liquid (ASL) volume. However, there is evidence that HTS may also stimulate active secretion of ASL by airway epithelia through the activation of sensory neurons.
View Article and Find Full Text PDFCystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel, which can result in chronic lung disease. The sequence of events leading to lung disease is not fully understood but recent data show that the critical pathogenic event is the loss of the ability to clear bacteria due to abnormal airway surface liquid secretion (ASL). However, whether the inhalation of bacteria triggers ASL secretion and whether this is abnormal in cystic fibrosis has never been tested.
View Article and Find Full Text PDFCochrane Database Syst Rev
July 2013
Background: Cystic fibrosis is an inherited condition resulting in thickened, sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary infection and inflammation, is the most common cause of mortality. Muco-active therapies (e.
View Article and Find Full Text PDFMed Image Comput Comput Assist Interv
January 2008
A novel method is presented for creating a probability map from histologically defined cytoarchitectonic data, customised for the anatomy of individual fMRI volunteers. Postmortem structural and cytoarchitectonic information from a published dataset is combined with high resolution structural MR images using deformable registration of a region of interest. In this paper, we have targeted the three sub-areas of the primary auditory cortex (located on Heschl's gyrus); however, the method could be applied to any other cytoarchitectonic region.
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