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1.
Curr Opin Infect Dis ; 35(4): 346-352, 2022 08 01.
Article in English | MEDLINE | ID: covidwho-1948615

ABSTRACT

PURPOSE OF REVIEW: We describe recent changes in care for people with cystic fibrosis (PwCF) that could impact infection prevention and control (IP&C) practices. RECENT FINDINGS: Current IP&C guidelines primarily aim to prevent acquisition and transmission of pathogens in PwCF utilizing evidence-based recommendations for healthcare settings. Currently, highly effective modulator therapy (HEMT) is dramatically improving the clinical manifestations of cystic fibrosis and reducing pulmonary exacerbations and hospitalizations. Thus, it is feasible that long-term, sustained improvements in pulmonary manifestations of cystic fibrosis could favorably alter cystic fibrosis microbiology. The COVID-19 pandemic increased the use of virtual care, enabling PwCF to spend less time in healthcare settings and potentially reduce the risk of acquiring cystic fibrosis pathogens. The increasing use of whole genome sequencing (WGS) shows great promise in elucidating sources of cystic fibrosis pathogens, shared strains, and epidemic strains and ultimately could allow the cystic fibrosis community to monitor the safety of changed IP&C practices, if deemed appropriate. Finally, given the nonhealthcare environmental reservoirs for cystic fibrosis pathogens, practical guidance can inform PwCF and their families about potential risks and mitigation strategies. SUMMARY: New developments in the treatment of PwCF, a shift toward virtual care delivery of care, and use of WGS could change future IP&C practices.


Subject(s)
COVID-19 , Cystic Fibrosis , COVID-19/prevention & control , Cystic Fibrosis/drug therapy , Humans , Pandemics
2.
Pediatr Pulmonol ; 57(7): 1814-1817, 2022 07.
Article in English | MEDLINE | ID: covidwho-1913872

ABSTRACT

This pilot study successfully implemented a standardized protocol for tablet-based ototoxicity screening in pediatric cystic fibrosis (CF) patients exposed to aminoglycosides. Further studies are needed to assess the impact of implementation in a larger number of patients, as well as to determine barriers that may exist at centers with variation in available resources. This method of ototoxicity screening represents an accessible alternative to traditional audiology testing, and given the continued improvements in expected life span for people with CF, it is imperative that patients have regular access to this type of screening to allow for early identification of medication-related toxicities.


Subject(s)
Audiology , Cystic Fibrosis , Ototoxicity , Aminoglycosides/adverse effects , Anti-Bacterial Agents/adverse effects , Child , Cystic Fibrosis/drug therapy , Humans , Pharmacists , Pilot Projects
3.
J Clin Lab Anal ; 36(6): e24427, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1877605

ABSTRACT

BACKGROUND: Azithromycin (AZM), sold under the name Zithromax, is classified as a macrolide. It has many benefits due to its immunomodulatory, anti-inflammatory, and antibacterial effects. This review aims to study different clinical and biochemisterial aspects and properties of this drug which has a priority based on literature published worldwide. METHODS: Several databases including Web of Science, Google Scholar, PubMed, and Scopus were searched to obtain the relevant studies. RESULTS: AZM mechanism of action including the inhibition of bacterial protein synthesis, inhibition of proinflammatory cytokine production, inhibition of neutrophil infestation, and macrophage polarization alteration, gives it the ability to act against a wide range of microorganisms. Resistant organisms are spreading and being developed because of the irrational use of the drug in the case of dose and duration. AZM shows synergistic effects with other drugs against a variety of organisms. This macrolide is considered a valuable antimicrobial agent because of its use as a treatment for a vast range of diseases such as asthma, bronchiolitis, COPD, cystic fibrosis, enteric infections, STIs, and periodontal infections. CONCLUSIONS: Our study shows an increasing global prevalence of AZM resistance. Thus, synergistic combinations are recommended to treat different pathogens. Moreover, continuous monitoring of AZM resistance by registry centers and the development of more rapid diagnostic assays are urgently needed.


Subject(s)
Azithromycin , Cystic Fibrosis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Azithromycin/pharmacology , Azithromycin/therapeutic use , Bacterial Proteins , Cystic Fibrosis/drug therapy , Cystic Fibrosis/microbiology , Humans
4.
Clin Pharmacol Ther ; 111(6): 1324-1333, 2022 06.
Article in English | MEDLINE | ID: covidwho-1802136

ABSTRACT

Cystic fibrosis transmembrane conductance regulator (CFTR) modulating therapies, including elexacaftor-tezacaftor-ivacaftor, are primarily eliminated through cytochrome P450 (CYP) 3A-mediated metabolism. This creates a therapeutic challenge to the treatment of coronavirus disease 2019 (COVID-19) with nirmatrelvir-ritonavir in people with cystic fibrosis (CF) due to the potential for significant drug-drug interactions (DDIs). However, the population with CF is more at risk of serious illness following COVID-19 infection and hence it is important to manage the DDI risk and provide treatment options. CYP3A-mediated DDI of elexacaftor-tezacaftor-ivacaftor was evaluated using a physiologically-based pharmacokinetic modeling approach. Modeling was performed incorporating physiological information and drug-dependent parameters of elexacaftor-tezacaftor-ivacaftor to predict the effect of ritonavir (the CYP3A inhibiting component of the combination) on the pharmacokinetics of elexacaftor-tezacaftor-ivacaftor. The elexacaftor-tezacaftor-ivacaftor models were verified using independent clinical pharmacokinetic and DDI data of elexacaftor-tezacaftor-ivacaftor with a range of CYP3A modulators. When ritonavir was administered on Days 1 through 5, the predicted area under the curve (AUC) ratio of ivacaftor (the most sensitive CYP3A substrate) on Day 6 was 9.31, indicating that its metabolism was strongly inhibited. Based on the predicted DDI, the dose of elexacaftor-tezacaftor-ivacaftor should be reduced when coadministered with nirmatrelvir-ritonavir to elexacaftor 200 mg-tezacaftor 100 mg-ivacaftor 150 mg on Days 1 and 5, with delayed resumption of full-dose elexacaftor-tezacaftor-ivacaftor on Day 9, considering the residual inhibitory effect of ritonavir as a mechanism-based inhibitor. The simulation predicts a regimen of elexacaftor-tezacaftor-ivacaftor administered concomitantly with nirmatrelvir-ritonavir in people with CF that will likely decrease the impact of the drug interaction.


Subject(s)
COVID-19 , Cystic Fibrosis , Aminophenols/pharmacology , Benzodioxoles/pharmacology , COVID-19/drug therapy , Chloride Channel Agonists/therapeutic use , Cystic Fibrosis/drug therapy , Cystic Fibrosis Transmembrane Conductance Regulator , Cytochrome P-450 CYP3A/metabolism , Drug Combinations , Drug Interactions , Humans , Indoles/pharmacology , Lactams/pharmacokinetics , Leucine/pharmacokinetics , Mutation , Nitriles/pharmacokinetics , Proline/pharmacokinetics , Pyrazoles/pharmacology , Pyridines/pharmacology , Pyrrolidines , Quinolines/pharmacology , Quinolones , Ritonavir/pharmacokinetics
5.
Chest ; 161(5): 1167-1179, 2022 05.
Article in English | MEDLINE | ID: covidwho-1559566

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, the University of Virginia adult cystic fibrosis (CF) center transitioned from in-person clinical encounters to a model that included interdisciplinary telemedicine. The pandemic presented an unprecedented opportunity to assess the impact of the interdisciplinary telemedicine model on clinical CF outcomes. RESEARCH QUESTION: What are the clinical outcomes of a care model that includes interdisciplinary telemedicine (IDC-TM) compared with in-person clinical care for patients with CF during the COVID-19 pandemic? STUDY DESIGN AND METHODS: Adults with CF were included. The prepandemic year was defined as March 17, 2019, through March 16, 2020, and the pandemic year (PY) was defined as March 17, 2020, through March 16, 2021. Patients were enrolled starting in the PY. Prepandemic data were gathered retrospectively. Telemedicine visits were defined as clinical encounters via secured video communication. Hybrid visits were in-person evaluations by physician, with in-clinic video communication by other team members. In-person visits were encounters with in-person providers only. All encounters included previsit screening. Outcomes were lung function, BMI, exacerbations, and antibiotic use. FEV1 percent predicted, exacerbations, and antibiotic use were adjusted for the effect of elexacaftor/tezacaftor/ivacaftor treatment. RESULTS: One hundred twenty-four patients participated. One hundred ten patients were analyzed (mean age, 35 years; range, 18-69 years). Ninety-five percent had access to telemedicine (n = 105). Telemedicine visits accounted for 64% of encounters (n = 260), hybrid visits with telemedicine support accounted for 28% of encounters (n = 114), and in-person visits accounted for 7% of encounters (n = 30). No difference in lung function or exacerbation rate during the PY was found. BMI increased from 25 to 26 kg/m2 (t100 = -4.72; P < .001). Antibiotic use decreased from 316 to 124 episodes (z = 8.81; P < .0001). INTERPRETATION: This CF care model, which includes IDC-TM, successfully monitored lung function and BMI, identified exacerbations, and followed guidelines-based care during the pandemic. A significant decrease in antibiotic use suggests that social mitigation strategies were protective. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04402801; URL: www. CLINICALTRIALS: gov.


Subject(s)
COVID-19 , Cystic Fibrosis , Telemedicine , Adult , Anti-Bacterial Agents/therapeutic use , COVID-19/epidemiology , Cystic Fibrosis/drug therapy , Cystic Fibrosis/therapy , Humans , Pandemics , Retrospective Studies
6.
Pulm Pharmacol Ther ; 71: 102095, 2021 12.
Article in English | MEDLINE | ID: covidwho-1504574

ABSTRACT

Macrolide antibiotics are well known for their antibacterial properties, but extensive research in the context of inflammatory lung disease has revealed that they also have powerful immunomodulatory properties. It has been demonstrated that these drugs are therapeutically beneficial in various lung diseases, with evidence they significantly reduce exacerbations in patients with COPD, asthma, bronchiectasis and cystic fibrosis. The efficacy demonstrated in patients infected with macrolide tolerant organisms such as Pseudomonas aeruginosa supports the concept that their efficacy is at least partly related to immunomodulatory rather than antibacterial effects. Inconsistent data and an incomplete understanding of their mechanisms of action hampers the use of macrolide antibiotics as immunomodulatory therapies. Macrolides recently demonstrated no clinically relevant immunomodulatory effects in the context of COVID-19 infection. This review provides an overview of macrolide antibiotics and discusses their immunomodulatory effects and mechanisms of action in the context of inflammatory lung disease.


Subject(s)
COVID-19 , Cystic Fibrosis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cystic Fibrosis/drug therapy , Humans , Immunomodulation , Macrolides/pharmacology , SARS-CoV-2
7.
N Engl J Med ; 385(9): 815-825, 2021 08 26.
Article in English | MEDLINE | ID: covidwho-1373470

ABSTRACT

BACKGROUND: Elexacaftor-tezacaftor-ivacaftor is a small-molecule cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be efficacious in patients with at least one Phe508del allele, which indicates that this combination can modulate a single Phe508del allele. In patients whose other CFTR allele contains a gating or residual function mutation that is already effectively treated with previous CFTR modulators (ivacaftor or tezacaftor-ivacaftor), the potential for additional benefit from restoring Phe508del CFTR protein function is unclear. METHODS: We conducted a phase 3, double-blind, randomized, active-controlled trial involving patients 12 years of age or older with cystic fibrosis and Phe508del-gating or Phe508del-residual function genotypes. After a 4-week run-in period with ivacaftor or tezacaftor-ivacaftor, patients were randomly assigned to receive elexacaftor-tezacaftor-ivacaftor or active control for 8 weeks. The primary end point was the absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline through week 8 in the elexacaftor-tezacaftor-ivacaftor group. RESULTS: After the run-in period, 132 patients received elexacaftor-tezacaftor-ivacaftor and 126 received active control. Elexacaftor-tezacaftor-ivacaftor resulted in a percentage of predicted FEV1 that was higher by 3.7 percentage points (95% confidence interval [CI], 2.8 to 4.6) relative to baseline and higher by 3.5 percentage points (95% CI, 2.2 to 4.7) relative to active control and a sweat chloride concentration that was lower by 22.3 mmol per liter (95% CI, 20.2 to 24.5) relative to baseline and lower by 23.1 mmol per liter (95% CI, 20.1 to 26.1) relative to active control (P<0.001 for all comparisons). The change from baseline in the Cystic Fibrosis Questionnaire-Revised respiratory domain score (range, 0 to 100, with higher scores indicating better quality of life) with elexacaftor-tezacaftor-ivacaftor was 10.3 points (95% CI, 8.0 to 12.7) and with active control was 1.6 points (95% CI, -0.8 to 4.1). The incidence of adverse events was similar in the two groups; adverse events led to treatment discontinuation in one patient (elevated aminotransferase level) in the elexacaftor-tezacaftor-ivacaftor group and in two patients (anxiety or depression and pulmonary exacerbation) in the active control group. CONCLUSIONS: Elexacaftor-tezacaftor-ivacaftor was efficacious and safe in patients with Phe508del-gating or Phe508del-residual function genotypes and conferred additional benefit relative to previous CFTR modulators. (Funded by Vertex Pharmaceuticals; VX18-445-104 ClinicalTrials.gov number, NCT04058353.).


Subject(s)
Aminophenols/therapeutic use , Benzodioxoles/therapeutic use , Chloride Channel Agonists/therapeutic use , Cystic Fibrosis/drug therapy , Indoles/therapeutic use , Pyrazoles/therapeutic use , Pyridines/therapeutic use , Quinolines/therapeutic use , Adolescent , Adult , Aminophenols/adverse effects , Benzodioxoles/adverse effects , Child , Chloride Channel Agonists/adverse effects , Chlorides/analysis , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Double-Blind Method , Drug Combinations , Female , Genotype , Humans , Indoles/adverse effects , Male , Pyrazoles/adverse effects , Pyridines/adverse effects , Quinolines/adverse effects , Sweat/chemistry
8.
Signal Transduct Target Ther ; 6(1): 183, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1230872

ABSTRACT

CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (either viral and host proteins). CK2 is also considered an emerging target for neurological diseases, inflammation and autoimmune disorders, diverse ophthalmic pathologies, diabetes, and obesity. In addition, CK2 activity has been associated with cardiovascular diseases, as cardiac ischemia-reperfusion injury, atherosclerosis, and cardiac hypertrophy. The hypothesis of considering CK2 inhibition for cystic fibrosis therapies has been also entertained for many years. Moreover, psychiatric disorders and syndromes due to CK2 mutations have been recently identified. On these bases, CK2 is emerging as an increasingly attractive target in various fields of human medicine, with the advantage that several very specific and effective inhibitors are already available. Here, we review the literature on CK2 implication in different human pathologies and evaluate its potential as a pharmacological target in the light of the most recent findings.


Subject(s)
COVID-19 , Cardiovascular Diseases , Casein Kinase II , Cystic Fibrosis , Eye Diseases , Mental Disorders , Protein Kinase Inhibitors/therapeutic use , SARS-CoV-2 , COVID-19/drug therapy , COVID-19/enzymology , COVID-19/genetics , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/enzymology , Cardiovascular Diseases/genetics , Casein Kinase II/antagonists & inhibitors , Casein Kinase II/genetics , Casein Kinase II/metabolism , Cystic Fibrosis/drug therapy , Cystic Fibrosis/enzymology , Cystic Fibrosis/genetics , Eye Diseases/drug therapy , Eye Diseases/enzymology , Eye Diseases/genetics , Humans , Mental Disorders/drug therapy , Mental Disorders/enzymology , Mental Disorders/genetics , Mutation , Phosphorylation , Signal Transduction/drug effects , Signal Transduction/genetics
9.
Cochrane Database Syst Rev ; 4: CD003424, 2021 04 27.
Article in English | MEDLINE | ID: covidwho-1202661

ABSTRACT

BACKGROUND: Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. This is an update of a previously published review. OBJECTIVES: To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic and non-electronic database searches, handsearches of relevant journals,  abstract books and conference proceedings. Both authors double checked the reference lists of the searches Most recent search of the Group's Trials Register: 26 April 2021. On the 26 April 2021 further searches were conducted on the clinicaltrials.gov register to identify any ongoing trials that may be of relevance. The WHO ICTRP database was last searched in 2020 and is not currently available for searching due to the Covid-19 pandemic. SELECTION CRITERIA: All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, assessed trial quality and extracted data. MAIN RESULTS: The searches identified 40 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. All the trials were run in single centres and duration ranged from five days to six months. The included trials were generally not reported adequately enough to allow judgements on risk of bias. However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival. AUTHORS' CONCLUSIONS: Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.


Subject(s)
Cystic Fibrosis/complications , Gastric Acid/metabolism , Histamine H2 Antagonists/therapeutic use , Proton Pump Inhibitors/therapeutic use , Abdominal Pain/drug therapy , Adult , Child , Cystic Fibrosis/drug therapy , Dietary Fats/pharmacokinetics , Gastrointestinal Agents/therapeutic use , Humans , Intestinal Absorption/drug effects , Pancreas/enzymology , Randomized Controlled Trials as Topic
10.
J Am Pharm Assoc (2003) ; 61(5): e119-e125, 2021.
Article in English | MEDLINE | ID: covidwho-1193366

ABSTRACT

BACKGROUND: As a result of the coronavirus disease 2019 (COVID-19) pandemic, institutions needed innovative solutions to provide care. With implementation of telehealth, a cystic fibrosis (CF) pharmacist was able to incorporate a virtual medication tour during appointments. OBJECTIVE: The purpose of our study was to describe the uptake and impact of pharmacist-led virtual medication tours during telehealth visits in the CF clinic setting. PRACTICE DESCRIPTION: Before the COVID-19 pandemic, a CF pharmacist participated in in-person multidisciplinary team visits to complete medication history reconciliation, assess adherence, assess efficacy and address possible adverse effects of medications, and work collaboratively with the CF care team and patient to create therapeutic plans. The virtual medication tour described in this study was completed in addition or as a complement to these pre-existing pharmacist roles and responsibilities. PRACTICE INNOVATION: Patients seen via telehealth visit were asked to provide a virtual tour of their medications. A pharmacist completed medication history and evaluated whether storage conditions were appropriate in regard to temperature, humidity, light exposure, and accessibility to children. EVALUATION METHODS: A pharmacist recorded findings from the virtual medication tours and made interventions when appropriate. Descriptive statistics were used for analysis. RESULTS: Of 20 patients seen via telehealth for a quarterly visit during the first 3 months after implementation, 13 were willing to participate in a virtual medication tour. Before the visit, 25% had information missing from their medication list. Virtual medication tour allowed for resolution of this information 80% of the time. Three of the 4 participating patients with a child under 12 years old had medications stored in a location accessible to children. CONCLUSION: A virtual medication tour led by a pharmacist can be successfully incorporated into telehealth visits and was accepted by a majority of patients. Most patients stored medications appropriately but might benefit from education on poison prevention practices.


Subject(s)
COVID-19 , Cystic Fibrosis , Telemedicine , Child , Cystic Fibrosis/drug therapy , Humans , Pandemics , Pharmacists , SARS-CoV-2
11.
Int J Mol Sci ; 22(4)2021 Feb 16.
Article in English | MEDLINE | ID: covidwho-1106098

ABSTRACT

Cystic fibrosis (CF) is an inherited disorder caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an ATP-gated chloride channel expressed on the apical surface of airway epithelial cells. CFTR absence/dysfunction results in defective ion transport and subsequent airway surface liquid dehydration that severely compromise the airway microenvironment. Noxious agents and pathogens are entrapped inside the abnormally thick mucus layer and establish a highly inflammatory environment, ultimately leading to lung damage. Since chronic airway inflammation plays a crucial role in CF pathophysiology, several studies have investigated the mechanisms responsible for the altered inflammatory/immune response that, in turn, exacerbates the epithelial dysfunction and infection susceptibility in CF patients. In this review, we address the evidence for a critical role of dysfunctional inflammation in lung damage in CF and discuss current therapeutic approaches targeting this condition, as well as potential new treatments that have been developed recently. Traditional therapeutic strategies have shown several limitations and limited clinical benefits. Therefore, many efforts have been made to develop alternative treatments and novel therapeutic approaches, and recent findings have identified new molecules as potential anti-inflammatory agents that may exert beneficial effects in CF patients. Furthermore, the potential anti-inflammatory properties of CFTR modulators, a class of drugs that directly target the molecular defect of CF, also will be critically reviewed. Finally, we also will discuss the possible impact of SARS-CoV-2 infection on CF patients, with a major focus on the consequences that the viral infection could have on the persistent inflammation in these patients.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Cystic Fibrosis/drug therapy , Inflammation/drug therapy , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Azithromycin/pharmacology , Azithromycin/therapeutic use , COVID-19/complications , COVID-19/drug therapy , COVID-19/metabolism , Cannabinoids/pharmacology , Cannabinoids/therapeutic use , Cystic Fibrosis/complications , Cystic Fibrosis/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Eicosanoids/metabolism , Humans , Inflammation/complications , Inflammation/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Roscovitine/pharmacology , Roscovitine/therapeutic use , Signal Transduction/drug effects , Thymalfasin/pharmacology , Thymalfasin/therapeutic use
12.
J Cyst Fibros ; 20(1): 31-35, 2021 01.
Article in English | MEDLINE | ID: covidwho-1065291

ABSTRACT

BACKGROUND: The clinical course of severe COVID-19 in cystic fibrosis (CF) is incompletely understood. We describe the use of alpha-1 antitrypsin (AAT) as a salvage therapy in a critically unwell patient with CF (PWCF) who developed COVID-19 while awaiting lung transplantation. METHODS: IV AAT was administered at 120 mg/kg/week for 4 consecutive weeks. Levels of interleukin (IL)-1ß, IL-6, IL-8, and soluble TNF receptor 1 (sTNFR1) were assessed at regular intervals in plasma, with IL-1ß, IL-6, IL-8 and neutrophil elastase (NE) activity measured in airway secretions. Levels were compared to baseline and historic severe exacerbation measurements. RESULTS: Systemic and airway inflammatory markers were increased compared to both prior exacerbation and baseline levels, in particular IL-6, IL-1ß and NE activity. Following each AAT dose, rapid decreases in each inflammatory parameter were observed. These were matched by marked clinical and radiographic improvement. CONCLUSIONS: The results support further investigation of AAT as a COVID-19 therapeutic, and re-exploration of its use in CF.


Subject(s)
COVID-19/complications , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , alpha 1-Antitrypsin/therapeutic use , Adult , Biomarkers/blood , COVID-19/diagnostic imaging , Cystic Fibrosis/diagnostic imaging , Female , Humans , Ireland , Respiratory Function Tests , SARS-CoV-2
13.
Med Hypotheses ; 147: 110481, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1009754

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused more than 52.775.271 million confirmed cases, 1.293.106 deaths, globally, and afflicted 208 countries, areas, or territories; and almost three months have passed since the World Health Organisation (WHO) declared COVID-19 as a pandemic. Despite the dramatic and global impact of the Coronavirus, the knowledge about the SARS-CoV-2 infection has been improved remarkably. Herein, we provided the rationale for SARS-CoV-2 infection as endothelial dysfunction rather than respiratory disease. Accordingly, we strongly invited the researchers to look beyond pulmonary injury and shift their attention from respiratory disease to endothelial disorder. This strategy could be particularly relevant to identifying therapeutic weapons stabilizing the endothelium rather than the lungs.


Subject(s)
COVID-19/complications , COVID-19/drug therapy , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , Lung Diseases/complications , Lung Diseases/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , Critical Illness , Endothelium, Vascular/metabolism , Humans , Inflammation , Lung , Pandemics
14.
Curr Opin Pulm Med ; 26(6): 696-701, 2020 11.
Article in English | MEDLINE | ID: covidwho-780547

ABSTRACT

PURPOSE OF REVIEW: The current review provides an overview of key psychological issues and challenges for the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator era of care. It discusses research from diagnosis and beyond, to patient-team communication with a particular focus on medical trials, adherence and living with CFTR modulators. RECENT FINDINGS: The impact of the diagnosis on parents is immense and the complexity of treatment now and in the future, are a challenge for both parents and teams. Communicating digitally is starting to become daily practice for many in CF care, with coronavirus disease 2019 accelerating this process. Participating in trials has a psychological impact, but most of all the (delayed) access and timing of accessing CFTR modulators is an important theme. Adherence remains of significance, both to 'old' and 'new' treatments. Living with CF in the era of CFTR modulators is beginning to impact on patients' quality of life, including new possibilities, opportunities and challenges. SUMMARY: Psychological care needs to engage and keep pace with the rapid medical changes. Some care priorities remain the same, including psychological screening and assessment, as well as psychoeducation, communication training and psychotherapy. The presence of CF psychologist in the CF clinic remains as important as ever.


Subject(s)
Communication , Coronavirus Infections , Cystic Fibrosis/drug therapy , Cystic Fibrosis/psychology , Medication Adherence , Pandemics , Pneumonia, Viral , Betacoronavirus , COVID-19 , Clinical Trials as Topic/psychology , Cystic Fibrosis/diagnosis , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Humans , Quality of Life , SARS-CoV-2
15.
Genes Immun ; 21(4): 260-262, 2020 08.
Article in English | MEDLINE | ID: covidwho-623318

ABSTRACT

Cystic fibrosis (CF) is one of the most common autosomal recessive life-limiting conditions affecting Caucasians. The resulting defect in the cystic fibrosis transmembrane conductance regulator protein (CFTR) results in defective chloride and bicarbonate secretion, as well as dysregulation of epithelial sodium channels (ENaC). These changes bring about defective mucociliary clearance, reduced airway surface liquid and an exaggerated proinflammatory response driven, in part, by infection. In this short article we explore the overlap in the pathophysiology of CF and COVID-19 infection and discuss how understanding the interaction between both diseases may shed light on future treatments.


Subject(s)
Coronavirus Infections/metabolism , Cystic Fibrosis/metabolism , Pneumonia, Viral/metabolism , Angiotensin-Converting Enzyme 2 , Animals , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Cytokines/metabolism , Humans , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology
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