20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/09/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/09/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Appearance of Pancreatic Sufficiency and Discontinuation of Pancreatic Enzyme Replacement Therapy (PERT) in Children with Cystic Fibrosis on Ivacaftor.

Ann Am Thorac Soc. 2020 Sep 15;:

Authors: Hutchinson I, McNally P

PMID: 32931706 [PubMed - as supplied by publisher]

Kwashiorkor-like dermatosis: a rare presentation of cystic fibrosis.

Clin Exp Dermatol. 2020 Sep 15;:

Authors: Shajil C, Sathishkumar D, Chiramel MJ, Kumar M, Varkki S, Rose W, Thomas M

PMID: 32931600 [PubMed - as supplied by publisher]

Sperm retrieval and intracytoplasmic sperm injection outcomes in men with cystic fibrosis disease versus congenital bilateral absence of the vas deferens.

Asian J Androl. 2020 Sep 11;:

Authors: McBride JA, Kohn TP, Mazur DJ, Lipshultz LI, Coward RM

Abstract
Recent data suggest that cystic fibrosis transmembrane conductance regulator (CFTR) gene alterations negatively impact male fertility beyond obstruction. We sought to compare gene alterations, sperm retrieval rates, and intracytoplasmic sperm injection (ICSI) outcomes among men with cystic fibrosis (CF) disease and congenital bilateral absence of the vas deferens (CBAVD) only. We retrospectively evaluated all men who underwent surgical sperm retrieval at two academic, high-volume andrology centers from 2010 to 2018. Only men with documented CFTR alterations and obstructive azoospermia from either CBAVD or CF were included. Differences between groups for CFTR abnormality, sperm retrieval, and ICSI outcomes were statistically analyzed. Overall, 39 patients were included with 10 in the CF and 29 in the CBAVD groups. Surgical sperm retrieval rates were significantly lower in the CF group for sperm concentration (14.8 × 10[6] ml-1 vs 61.4 × 10[6] ml-1, P = 0.02) and total motile sperm count (2.9 million vs 11.4 million, P = 0.01). This difference was only predicted by homozygous delta F508 CFTR mutations (P < 0.05). The CF group also demonstrated a significantly higher rate of rescue testicular sperm extraction (70.0% vs 27.6%, P < 0.03) and lower fertilization rate with ICSI (32.5% vs 68.9%, P < 0.01). In conclusion, those with CF demonstrated lower sperm quality, greater difficulty with sperm retrieval, and worse ICSI outcomes compared with CBAVD-only patients. Homozygous delta F508 CFTR mutations appear to significantly impair spermatogenesis and sperm function.

PMID: 32930103 [PubMed - as supplied by publisher]

Acute hyperosmolar hyperglycaemic state in cystic fibrosis-related diabetes caused by glucocorticoid and itraconazole interaction.

J Cyst Fibros. 2020 Sep 11;:

Authors: Bernhardt IT, Moore P, Currie S, Jefferies CA

Abstract
Hyperosmolar hyperglycaemic state (HHS) has not previously been reported in cystic fibrosis-related diabetes (CFRD). We report the case of a 15-year old boy with stable CFRD who developed acute HHS after treatment with glucocorticoids and itraconazole for presumed allergic broncho-pulmonary aspergillosis (ABPA). This case highlights the dangerous and preventable combination of high glucose intake, glucocorticoids and itraconazole inhibition of CYP3A4 (with resultant glucocorticoid accumulation) that can result in a state of life- threatening HHS in an adolescent with previously stable CFRD.

PMID: 32928702 [PubMed - as supplied by publisher]

Delayed glucose peak and elevated 1-hour glucose on the oral glucose tolerance test identify youth with cystic fibrosis with lower oral disposition index.

J Cyst Fibros. 2020 Sep 11;:2111

Authors: Tommerdahl KL, Brinton JT, Vigers T, Cree-Green M, Zeitler PS, Nadeau KJ, Chan CL

Abstract
BACKGROUND: Alternate methods for characterizing oral glucose tolerance tests (OGTT) have emerged as superior to the 2-hour glucose in identifying individuals at risk for type 2 diabetes. The significance of these methods in cystic fibrosis (CF) is unclear. We compared 3 OGTT classifications in youth with CF: 1. curve shape (biphasic vs. monophasic), 2. time to glucose peak (≤30minutes vs. >30minutes), 3. 1-hour glucose (1hG) <155 mg/dL vs. ≥155 mg/dL to traditional OGTT criteria to determine which best identifies lower oral disposition index (oDI), pulmonary function, and body mass index (BMI).
METHODS: Youth 10-18 years with CF, not on insulin, underwent 2-hour OGTT. Glucoses were classified by traditional criteria and 3 alternate methods as normal (biphasic curve, glucose peak ≤30minutes, and/or 1hG <155 mg/dL) or abnormal (monophasic curve, glucose peak >30minutes, and/or 1hG ≥155 mg/dL). oDI was calculated [1/fasting insulin*(ΔInsulin0-30 min/ΔGlucose0-30 min)]. Mean oDI, BMI, forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) were compared by OGTT classification.
RESULTS: Fifty-two youth with CF participated (mean±SD age 13±4years; 37% male; BMI z-score 0.0±0.8; FEV1 88±16.3%; FVC 97±14.8%). Late time to peak glucose and 1hG ≥155 mg/dL identified individuals with lower oDI (p=0.01); traditional OGTT criteria for prediabetes did not. No OGTT classification identified individuals with worse BMI nor pulmonary function. oDI was not associated with BMI, FEV1, or FVC.
CONCLUSIONS: Alternate OGTT measures including time to peak glucose and 1hG better identify oDI abnormalities than traditional criteria. Further studies are required to determine whether these alternate methods identify individuals with CF at risk for future clinical decline.

PMID: 32928701 [PubMed - as supplied by publisher]

The accuracy of four commercial broth microdilution tests in the determination of the minimum inhibitory concentration of colistin.

Ann Clin Microbiol Antimicrob. 2020 Sep 14;19(1):42

Authors: Yusuf E, van Westreenen M, Goessens W, Croughs P

Abstract
Colistin is considered as one of the last-resort antibiotics and reliable antimicrobial susceptibility testing is therefore crucial. The reference standard for AST according to EUCAST and CLSI is broth microdilution (BMD). However, BMD is labor intensive to perform. Commercial antimicrobial susceptibility tests derived from BMD method are available. We investigated the performance of four different commercial tests: Sensititre™, SensiTest™ Colistin, Micronaut MIC Strip Colistin and UMIC Colistin using 70 clinical isolates (half of them was deemed by VITEK2 as resistant), including isolates from cystic fibrosis patients and mcr-1 bearing isolates. We used two reference standards: BMD and composite MIC as determined by all four tests. Sensititre™ had essential agreement (EA, defined as minimum inhibitory concentration within ± 1 dilution) of 87% and 89% compared to BMD and composite reference standard, respectively. For SensiTest™, the EA's were 93% and 90%. For UMIC, 87% and 90%, and for Micronaut, 83% and 84%. All four tests demonstrated categorical agreement (CA) above 90%. CA for SensiTest™ and Micronaut was both 96%, UMIC 94%, and Sensititre™ 93%. All tests were reproducible as tested in two quality control isolates. In conclusion, in clinical isolates from a large referral center, the four commercial tests for determination of colistin minimum inhibitory concentrations showed acceptable performance.

PMID: 32928253 [PubMed - in process]

Roles of Specialized Pro-Resolving Lipid Mediators in Autophagy and Inflammation.

Int J Mol Sci. 2020 Sep 10;21(18):

Authors: Recchiuti A, Isopi E, Romano M, Mattoscio D

Abstract
Autophagy is a catabolic pathway that accounts for degradation and recycling of cellular components to extend cell survival under stress conditions. In addition to this prominent role, recent evidence indicates that autophagy is crucially involved in the regulation of the inflammatory response, a tightly controlled process aimed at clearing the inflammatory stimulus and restoring tissue homeostasis. To be efficient and beneficial to the host, inflammation should be controlled by a resolution program, since uncontrolled inflammation is the underlying cause of many pathologies. Resolution of inflammation is an active process mediated by a variety of mediators, including the so-called specialized pro-resolving lipid mediators (SPMs), a family of endogenous lipid autacoids known to regulate leukocyte infiltration and activities, and counterbalance cytokine production. Recently, regulation of autophagic mechanisms by these mediators has emerged, uncovering unappreciated connections between inflammation resolution and autophagy. Here, we summarize mechanisms of autophagy and resolution, focusing on the contribution of autophagy in sustaining paradigmatic examples of chronic inflammatory disorders. Then, we discuss the evidence that SPMs can restore dysregulated autophagy, hypothesizing that resolution of inflammation could represent an innovative approach to modulate autophagy and its impact on the inflammatory response.

PMID: 32927853 [PubMed - in process]

Urinary Exosomes of Patients with Cystic Fibrosis Unravel CFTR-Related Renal Disease.

Int J Mol Sci. 2020 Sep 10;21(18):

Authors: Gauthier S, Pranke I, Jung V, Martignetti L, Stoven V, Nguyen-Khoa T, Semeraro M, Hinzpeter A, Edelman A, Guerrera IC, Sermet-Gaudelus I

Abstract
Background: The prevalence of chronic kidney disease is increased in patients with cystic fibrosis (CF). The study of urinary exosomal proteins might provide insight into the pathophysiology of CF kidney disease. Methods: Urine samples were collected from 19 CF patients (among those 7 were treated by cystic fibrosis transmembrane conductance regulator (CFTR) modulators), and 8 healthy subjects. Urine exosomal protein content was determined by high resolution mass spectrometry. Results: A heatmap of the differentially expressed proteins in urinary exosomes showed a clear separation between control and CF patients. Seventeen proteins were upregulated in CF patients (including epidermal growth factor receptor (EGFR); proteasome subunit beta type-6, transglutaminases, caspase 14) and 118 were downregulated (including glutathione S-transferases, superoxide dismutase, klotho, endosomal sorting complex required for transport, and matrisome proteins). Gene set enrichment analysis revealed 20 gene sets upregulated and 74 downregulated. Treatment with CFTR modulators yielded no significant modification of the proteomic content. These results highlight that CF kidney cells adapt to the CFTR defect by upregulating proteasome activity and that autophagy and endosomal targeting are impaired. Increased expression of EGFR and decreased expression of klotho and matrisome might play a central role in this CF kidney signature by inducing oxidation, inflammation, accelerated senescence, and abnormal tissue repair. Conclusions: Our study unravels novel insights into consequences of CFTR dysfunction in the urinary tract, some of which may have clinical and therapeutic implications.

PMID: 32927759 [PubMed - in process]

Pursuit of Equity.

J Cyst Fibros. 2020 03;19(2):171

Authors: Flume P, Bell SC, Castellani C

PMID: 32527495 [PubMed - indexed for MEDLINE]

Lung immunoglobulin A immunity dysregulation in cystic fibrosis.

EBioMedicine. 2020 Sep 11;60:102974

Authors: Collin AM, Lecocq M, Noel S, Detry B, Carlier FM, Aboubakar Nana F, Bouzin C, Leal T, Vermeersch M, De Rose V, Regard L, Martin C, Burgel PR, Hoton D, Verleden S, Froidure A, Pilette C, Gohy S

Abstract
BACKGROUND: In cystic fibrosis (CF), recurrent infections suggest impaired mucosal immunity but whether production of secretory immunoglobulin A (S-IgA) is impaired remains elusive. S-IgA is generated following polymeric immunoglobulin receptor (pIgR)-mediated transepithelial transport of dimeric (d-)IgA and represents a major defence through neutralisation of inhaled pathogens like Pseudomonas aeruginosa (Pa).
METHODS: Human lung tissue (n = 74), human sputum (n = 118), primary human bronchial epithelial cells (HBEC) (cultured in air-liquid interface) (n = 19) and mouse lung tissue and bronchoalveolar lavage were studied for pIgR expression, IgA secretion and regulation.
FINDINGS: Increased epithelial pIgR immunostaining was observed in CF lung explants, associated with more IgA-producing plasma cells, sputum and serum IgA, especially Pa-specific IgA. In contrast, pIgR and IgA transport were downregulated in F508del mice, CFTR-inhibited HBEC, and CF HBEC. Moreover, the unfolded protein response (UPR) due to F508del mutation, inhibited IgA transport in Calu-3 cells. Conversely, pIgR expression and IgA secretion were strongly upregulated following Pa lung infection in control and F508del mice, through an inflammatory host response involving interleukin-17.
INTERPRETATION: A complex regulation of IgA secretion occurs in the CF lung, UPR induced by CFTR mutation/dysfunction inhibiting d-IgA transcytosis, and Pa infection unexpectedly unleashing this secretory defence mechanism.
FUNDING: This work was supported by the Forton's grant of the King Baudouin's Foundation, Belgium, the Fondazione Ricerca Fibrosi Cistica, Italy, and the Fonds National de la Recherche Scientifique, Belgium.

PMID: 32927272 [PubMed - as supplied by publisher]

A Survey of Pediatric Competencies in Entry-Level Physical Therapy Programs in Australia.

Pediatr Phys Ther. 2020 Sep 10;:

Authors: Baque E, Jones T, Bialocerkowski A

Abstract
PURPOSE: To describe perspectives of pediatric physical therapy clinical facilitators on contemporary curricula for Australian entry-level physical therapy programs.
METHODS: Physical therapy clinical facilitators completed an online survey based on the Academy of Pediatric Physical Therapy of the APTA essential competencies.
RESULTS: Conditions including cerebral palsy, cystic fibrosis, and prematurity were highly rated by most participants to include in an entry-level program. Exercise prescription, goal-directed training, and group-based physical therapy were the highest rated interventions. Outcome measures considered important to include were the Alberta Infant Motor Scale and Goal Attainment Scale. Students should demonstrate knowledge and skills using relevant frameworks and have practical opportunities to interact with children.
CONCLUSION: Pediatric clinical facilitators perceived that theoretical knowledge on frameworks, human development, movement skills, pediatric conditions, exercise prescription, and outcome measurement as well as face-to-face experiences with children are important to include in Australian entry-level physical therapy programs.

PMID: 32925813 [PubMed - as supplied by publisher]

Two-Step Testing for Clostridioides Difficile is Inadequate in Differentiating Infection From Colonization in Children.

J Pediatr Gastroenterol Nutr. 2020 Sep 09;:

Authors: Parnell JM, Fazili I, Bloch SC, Lacy DB, Garcia-Lopez VA, Bernard R, Skaar EP, Edwards KM, Nicholson MR

Abstract
OBJECTIVES: Recent Infectious Disease Society of America guidelines recommend multi-step testing algorithms to diagnose Clostridioides difficile infection (CDI), including a combination of nucleic acid amplification-based testing (NAAT) and toxin enzyme immunoassay (EIA). However, the use of these algorithms in children, including the ability to differentiate between C. difficile colonization and CDI, has not been evaluated.
METHODS: We prospectively enrolled asymptomatic pediatric patients with cancer, cystic fibrosis (CF), or inflammatory bowel disease (IBD) and obtained a stool sample for NAAT testing. If positive by NAAT (colonized), EIA was performed. In addition, children with symptomatic CDI who tested positive by NAAT via the clinical laboratory were enrolled, and EIA was performed on residual stool. A functional cell cytotoxicity neutralization assay (CCNA) was also applied to stool samples from both the colonized and symptomatic cohorts.
RESULTS: Of the 225 asymptomatic children enrolled in the study, 47 (21%) were colonized with C. difficile including 9/59 (15.5%) with cancer, 30/92 (32.6%) with CF and 8/74 (10.8%) with IBD. An additional 41 children with symptomatic CDI were enrolled. When symptomatic and colonized children were compared, neither EIA positivity (44% versus 26%, P = 0.07) nor CCNA positivity (49% versus 45%, P = 0.70) differed significantly or were able to predict disease severity in the symptomatic cohort.
CONCLUSIONS: Use of a multi-step testing algorithm with NAAT followed by EIA failed to differentiate symptomatic CDI from asymptomatic colonization in our pediatric cohort. As multi-step algorithms are moved into clinical care, the pediatric provider will need to be aware of their limitations.

PMID: 32925555 [PubMed - as supplied by publisher]

Monitoring early stage lung disease in cystic fibrosis.

Curr Opin Pulm Med. 2020 Sep 10;:

Authors: Nissenbaum C, Davies G, Horsley A, Davies JC

Abstract
PURPOSE OF REVIEW: Early stage lung disease has long been synonymous with infancy and childhood. As diagnosis happens earlier and conventional management improves, we are seeing larger proportions of people with cystic fibrosis (CF) in adolescence and even adulthood with well preserved lung health. The availability of highly effective cystic fibrosis transmembrane conductance regulator modulator drugs for a large proportion of the CF population will impact even further. Transitioning into adult care with 'normal' lung function will become more common. However, it is crucial that we are not blasé about this phase, which sets the scene for future lung health. It is well recognized that lung function assessed by spirometry is insensitive to 'early' changes occurring in the distal, small airways. Much of our learning has come from studies in infants and young children, which have allowed assessment and optimization of alternative forms of monitoring.
RECENT FINDINGS: Here, as a group of paediatric and adult CF specialists, we review the evidence base for sensitive physiological testing based on multibreath washout, lung imaging, exercise and activity monitoring, assessment of infection and quality of life measures.
SUMMARY: We seek to emphasise the importance of further work in these areas, as outcome measures become widely applicable to a growing CF population.

PMID: 32925367 [PubMed - as supplied by publisher]

Preserving Multidisciplinary Care Model and Patient Safety During Reopening of Ambulatory Cystic Fibrosis Clinic for Nonurgent Care: A Hybrid Telehealth Model.

Telemed J E Health. 2020 Sep 14;:

Authors: List R, Compton M, Soper M, Bruschwein H, Gettle L, Bailey M, Starheim E, Kalmanek J, Somerville L, Albon D

Abstract
Introduction: The University of Virginia's (UVA's) adult cystic fibrosis (CF) program implemented a rapid and successful transition to telemedicine care mid-March of 2020 in response to the coronavirus disease 2019 (COVID-19) pandemic. In May 2020, the adult UVA CF program redesigned the care model to adjust to the reopening of ambulatory operations and introduced hybrid clinics. The goal remained to minimize person-to-person contacts for patients and care team members (CTMs) while ensuring patient access to quarterly, coproduced, synchronous, multidisciplinary CF care, similar to pre-COVID-19 era regular CF care. Methods: Using quality improvement tools, the UVA adult CF program created a standardized hybrid model of care for in-clinic visits, which included combined components of in-person and synchronous virtual interactions with members of the multidisciplinary team. Results: A total of 16 hybrid visits occurred between May 14 and June 11, 2020. All hybrid visits were multidisciplinary and fulfilled patient requests to see CTMs. All patients seen by hybrid encounter participated in coproduced agenda setting, underwent spirometry, and obtained blood work; 75% provided sputum for surveillance culture. Each hybrid visit type was attended by an average of four CTMs and amounted to 63 separate interactions. Of these interactions, 28 were completed virtually, reducing in-person contacts and personal protection equipment utilization by 44% compared with a fully in-person model of care. Conclusions: Combining in-person and telehealth components in a multidisciplinary CF care model reduces patient and staff interactions and personal protective equipment utilization. The hybrid model of in-person/remote combined care enables reliable access to biological data to support medical decision making while mitigating the risks of person-to-person contact for patients and staff.

PMID: 32924854 [PubMed - as supplied by publisher]

Laying the Foundation for Cystic Fibrosis Therapy: An Interview with Michael Boyle.

Hum Gene Ther. 2020 Sep 11;:

Authors: Davies K

PMID: 32924627 [PubMed - as supplied by publisher]

Pendrin stimulates a chloride absorption pathway to increase CFTR-mediated chloride secretion from Cystic Fibrosis airway epithelia.

FASEB Bioadv. 2020 Sep;2(9):526-537

Authors: Bajko J, Duguid M, Altmann S, Hurlbut GD, Kaczmarek JS

Abstract
Cystic Fibrosis (CF), an inherited multi-system disease, is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) that disrupt its ability to secrete anions from epithelia. Recovery of functional anion secretion may be curative for CF, so different components of the ion transport machinery have become attractive therapeutic targets. Several members of the SLC26 ion transporter family have been linked to epithelial ion flux, some through putative functional interactions with CFTR. Using a small-scale qPCR screen, we confirmed that the anion transporter SLC26A4 (pendrin) is downregulated in CF. Upregulation of pendrin using interleukins IL-4 or IL-13 increased Cl- secretion through CFTR in human bronchial epithelial cell (HBEC) derived epithelia differentiated in vitro and measured in the Ussing Chamber. Inhibition or knockdown of pendrin prevented this increased secretion. Increased CFTR activity was not driven by increases in CFTR protein or upstream regulatory pathway components. When basolateral Cl- absorption through NKCC1 was inhibited, a pendrin-dependent Cl- absorption pathway allowing CFTR to continue secreting Cl- from the epithelium was revealed. Although CFTR is often considered the bottleneck in the transepithelial Cl- transport pathway, these studies indicate that basolateral Cl- permeability becomes limiting as CFTR activity increases. Therefore, an increase of epithelial Cl- absorption via pendrin might have additional therapeutic benefit in combination with CFTR modulators.

PMID: 32923987 [PubMed]

Preliminary report of In vitro and In vivo Effectiveness of Dornase alfa on SARS-CoV-2 infection.

New Microbes New Infect. 2020 Sep 07;:100756

Authors: Okur HK, Yalcin K, Tastan C, Demir S, Yurtsever B, Sir G, Kancagi DD, Abanuz S, Seyis U, Zengin R, Hemsinlioglu C, Kara M, Yildiz ME, Deliceo E, Birgen N, Pelit NB, Cuhadaroglu C, Kocagoz AS, Ovali E

Abstract
Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). It is well known that novel Coronavirus disease 2019 (COVID-19) pneumonia progresses to ARDS and even multiple organ failure. High blood neutrophil levels are an early indicator of COVID-19 and predict severe respiratory diseases. Also it is reported that mucus structure of COVID-19 is very similar to cystic fibrosis due to the accumulation of excessive NET in the lungs. In this study, we showed the recovery of three COVID-19 patients after including Dornase alfa in their treatment. We followed clinical improvement in the radiological analysis (2-of-3 cases), oxygen saturation (SpO2), respiratory rate, disappearing of dyspnea, coughing and a decrease in NET formation and SARS-CoV-2 viral load after the treatment. Also here, we share our preliminary results suggesting that Dornase alfa has an anti-viral effect against SARS-CoV-2 infection in a green monkey kidney cell line, Vero, and a bovine kidney cell line, MDBK without determined cytotoxicity on healthy peripheral blood mononuclear cells.

PMID: 32922804 [PubMed - as supplied by publisher]

Pathways in the Pathophysiology of Coronavirus 19 Lung Disease Accessible to Prevention and Treatment.

Front Physiol. 2020;11:872

Authors: Eisenhut M, Shin JI

Abstract
Background: In COVID 19 related lung disease, which is a leading cause of death from this disease, cytokines like tumor necrosis factor-alpha (TNF alpha) may be pivotal in the pathogenesis. TNF alpha reduces fluid absorption due to impairment of sodium and chloride transport required for building an osmotic gradient across epithelial cells, which in the airways maintains airway surface liquid helping to keep airways open and enabling bacterial clearance and aids water absorption from the alveolar spaces. TNF alpha can, through Rho-kinase, disintegrate the endothelial and epithelial cytoskeleton, and thus break up intercellular tight junctional proteins, breaching the intercellular barrier, which prevents flooding of the interstitial and alveolar spaces with fluid. Hypotheses: (1) Preservation and restoration of airway and alveolar epithelial sodium and chloride transport and the cytoskeleton dependent integrity of the cell barriers within the lung can prevent and treat COVID 19 lung disease. (2) TNF alpha is the key mediator of pulmonary edema in COVID 19 lung disease. Confirmation of hypothesis and implications: The role of a reduction in the function of epithelial sodium and chloride transport could with regards to chloride transport be tested by analysis of chloride levels in exhaled breath condensate and levels correlated with TNF alpha concentrations. Reduced levels would indicate a reduction of the function of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and a correlation with TNF alpha levels indicative of its involvement. Anti-TNF alpha treatment with antibodies is already available and needs to be tested in randomized controlled trials of COVID 19 lung disease. TNF alpha levels could also be reduced by statins, aspirin, and curcumin. Chloride transport could be facilitated by CFTR activators, including curcumin and phosphodiesterase-5 inhibitors. Sodium and chloride transport could be further regulated to prevent accumulation of alveolar fluid by use of Na(+)/K(+)/2Cl(-) cotransporter type 1 inhibitors, which have been associated with improved outcome in adults ventilated for acute respiratory distress syndrome (ARDS) in randomized controlled trials. Primary prevention of coronavirus infection and TNF alpha release in response to it could be improved by induction of antimicrobial peptides LL-37 and human beta defensin-2 and reduction of TNF alpha production by vitamin D prophylaxis for the population as a whole.

PMID: 32922301 [PubMed]