Christopher S. Robinson, Jennifer A. Wyderko, Yeng Vang, Galen T Martin, R. T. Youker
{"title":"Differential Effects of Oleuropein and Hydroxytyrosol on Aggregation and Stability of CFTR NBD1-ΔF508 Domain","authors":"Christopher S. Robinson, Jennifer A. Wyderko, Yeng Vang, Galen T Martin, R. T. Youker","doi":"10.3390/jor1030019","DOIUrl":"https://doi.org/10.3390/jor1030019","url":null,"abstract":"Cystic Fibrosis (CF) is caused by loss of function mutations in the Cystic Fibrosis transmembrane conductance regulator (CFTR). The folding and assembly of CFTR is inefficient. Deletion of F508 in the first nucleotide binding domain (NBD1-ΔF508) further disrupts protein stability leading to endoplasmic reticulum retention and proteasomal degradation. Stabilization and prevention of NBD1-ΔF508 aggregation is critical to rescuing the folding and function of the entire CFTR channel. We report that the phenolic compounds Oleuropein and Hydroxytryosol reduce aggregation of NBD1-ΔF508. The NBD1-ΔF508 aggregate size was smaller in the presence of Hydroxytryosol as determined by dynamic light scattering. Neither phenolic compound increased the thermal stability of NBD1-ΔF508 as measured by differential scanning fluorimetry. Interestingly, Hydroxytyrosol inhibited the stabilizing effect of the indole compound BIA, a known stabilizer, on NBD1-ΔF508. Molecular docking studies predicted that Oleuropein preferred to bind in the F1-type core ATP-binding subdomain in NBD1. In contrast, Hydroxytyrosol preferred to bind in the α4/α5/α6 helical bundle of the ABCα subdomain of NBD1 next to the putative binding site for BIA. This result suggests that Hydroxytyrosol interferes with BIA binding, thus providing an explanation for the antagonistic effect on NBD1 stability upon incubation with both compounds. To our knowledge, these studies are the first to explore the effects of these two phenolic compounds on the aggregation and stability of NBD1-ΔF508 domain of CFTR.","PeriodicalId":284235,"journal":{"name":"Journal of Respiration","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127526516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Effect of High Flow Nasal Cannula Therapy in Exercised-Induced Asthma of Children","authors":"René D. ter Wee, B. Thio","doi":"10.3390/JOR1030018","DOIUrl":"https://doi.org/10.3390/JOR1030018","url":null,"abstract":"High flow nasal cannula (HFNC) therapy is a non-invasive oxygen delivery mode which is safe and well tolerated by adults and children with respiratory distress. HFNC is increasingly used in children with respiratory distress due to mucus retention, such as bronchiolitis and acute asthma. However, he effectiveness of this therapy in acute asthma has not been well researched. To evaluate HFNC for acute childhood asthma, we designed a randomized prospective crossover trial. In the trial, children aged 6–18 years, with a forced expiratory volume in one second (FEV1) lability of ≥30% during an exercise challenge test (ECT) are included. The time of fully recovered lung function within 10% of the baseline after peak fall of FEV1 is compared with and without HFNC therapy. A 50% reduction of recovery time during HFNC therapy compared to recovery time without HFNC is considered clinically relevant, with a power of 80% and a significance level of 5%. Secondly, the pressure used by the HFNC device to deliver the constant present flow is evaluated. A relationship between the measured pressure and the degree of recovery may reveal a working mechanism behind HFNC.","PeriodicalId":284235,"journal":{"name":"Journal of Respiration","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123170825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between Obstructive Lung Disease and Cardiovascular Disease: Results from the Vermont Diabetes Information System","authors":"M. Ramos-Nino, Charles D MacLean, B. Littenberg","doi":"10.3390/jor1030016","DOIUrl":"https://doi.org/10.3390/jor1030016","url":null,"abstract":"The association between obstructive lung disease and cardiovascular disease (CVD) has been suggested previously, but few studies have looked at this association in a diabetic cohort, a population highly susceptible to both comorbidities. A total of 1003 subjects in community practice settings were interviewed at home at the time of enrolment into the Vermont Diabetes Information System, a clinical decision support program. Patients self-reported their personal and clinical characteristics, including any obstructive lung disease. Laboratory data were obtained directly from the clinical laboratory. We performed a cross-sectional analysis of the interviewed subjects to assess a possible association between obstructive lung disease and CVD. In a multivariate logistic regression model, obstructive lung disease was significantly associated with CVD, even after correcting for potential confounders, including gender, obesity, low income, cigarette smoking, alcohol problems, and high comorbidity (odds ratio = 1.96; 95% confidence interval 1.37–2.81; p < 0.01). All components of CVD, including coronary artery disease (CAD), congestive heart failure (CHF), peripheral vascular disease (PVD), and cerebrovascular accidents (CVA), were also significantly associated with obstructive lung disease. These data suggest an association between obstructive lung disease and CVD in patients with diabetes. Future studies are needed to identify the mechanism supporting this association","PeriodicalId":284235,"journal":{"name":"Journal of Respiration","volume":"66 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131317624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Gopalaswamy, V. N. A. Dusthackeer, Silambuchelvi Kannayan, S. Subbian
{"title":"Extrapulmonary Tuberculosis—An Update on the Diagnosis, Treatment and Drug Resistance","authors":"R. Gopalaswamy, V. N. A. Dusthackeer, Silambuchelvi Kannayan, S. Subbian","doi":"10.3390/JOR1020015","DOIUrl":"https://doi.org/10.3390/JOR1020015","url":null,"abstract":"Pathogenic Mycobacterium tuberculosis complex organisms (MTBC) primarily cause pulmonary tuberculosis (PTB); however, MTBC are also capable of causing disease in extrapulmonary (EP) organs, which pose a significant threat to human health worldwide. Extrapulmonary tuberculosis (EPTB) accounts for about 20–30% of all active TB cases and affects mainly children and adults with compromised immune systems. EPTB can occur through hematogenous, lymphatic, or localized bacillary dissemination from a primary source, such as PTB, and affects the brain, eye, mouth, tongue, lymph nodes of neck, spine, bones, muscles, skin, pleura, pericardium, gastrointestinal, peritoneum, and the genitourinary system as primary and/or disseminated disease. EPTB diagnosis involves clinical, radiological, microbiological, histopathological, biochemical/immunological, and molecular methods. However, only culture and molecular techniques are considered confirmatory to differentiate MTBC from any non-tuberculous mycobacteria (NTM) species. While EPTB due to MTBC responds to first-line anti-TB drugs (ATD), drug susceptibility profiling is an essential criterion for addressing drug-resistant EPTB cases (DR-EPTB). Besides antibiotics, adjuvant therapy with corticosteroids has also been used to treat specific EPTB cases. Occasionally, surgical intervention is recommended, mainly when organ damage is debilitating to the patient. Recent epidemiological studies show a striking increase in DR-EPTB cases ranging from 10–15% across various reports. As a neglected disease, significant developments in rapid and accurate diagnosis and better therapeutic interventions are urgently needed to control the emerging EPTB situation globally. In this review, we discuss the recent advances in the clinical diagnosis, treatment, and drug resistance of EPTB.","PeriodicalId":284235,"journal":{"name":"Journal of Respiration","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126190927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Jackson, Opeyemi Kafi, D. Bhullar, Jordan Scott, C. Storey, Saara Hyatali, Hannah Carlin, Andrew Brown, E. Grimshaw, Joseph Miller, H. Rank, S. Porritt, M. Carling, A. Aujayeb
{"title":"Complications after Thoracocentesis and Chest Drain Insertion: A Single Centre Study from the North East of England","authors":"K. Jackson, Opeyemi Kafi, D. Bhullar, Jordan Scott, C. Storey, Saara Hyatali, Hannah Carlin, Andrew Brown, E. Grimshaw, Joseph Miller, H. Rank, S. Porritt, M. Carling, A. Aujayeb","doi":"10.3390/JOR1020014","DOIUrl":"https://doi.org/10.3390/JOR1020014","url":null,"abstract":"Introduction: There are no prospective studies looking at complications of pleural procedures. Previous British Thoracic Society Pleural audits and retrospective case series inform current practice. Incidence of any complication is between 1–15%. We sought to add to the existing literature and inform local practice with regards to intercostal drains and thoracocenteses. Methods: Local Caldicott approval was sought for a review of all inpatient adult pleural procedures coded as ‘T122 drainage of pleural cavity’ and ‘T124 insertion of tube drain into pleural cavity’. Those undergoing thoracocentesis (all with a Rocket 6 Fg catheter) and intercostal drain insertion (ICD, all with Rocket 12 Fg drain) were identified. Continuous variables are presented as mean (±range) and categorical variables as percentages where appropriate. Results: 1159 procedures were identified. A total of 199 and 960 were done for pneumothorax and effusions respectively. Mean age was 68.1 years (18–97). There were 280 thoracocenteses and 879 ICDs. Bleeding occurred in 6 (0.5%), all ICDs (clotting and platelets were within normal range; one patient was on aspirin and one on aspirin and clopidogrel). All settled except for one who had intercostal artery rupture needing cardiothoracic intervention (no anti-coagulation). Nine pneumothoraces occurred (0.78%) in seven ICDs and two aspirations). There were three definite pleural space infections (0.3%) with three ICDs. Fall out rates for ICDs were 35 (3%). Nine were not sutured, and out of those, seven inserted in the Accident and Emergency department, out of hours. All others ‘came out’ due to patient factors (previous quoted rates up to 14%). Surgical emphysema occurred in 43 (41 ICDs), 3.7%. Eight were due to fall outs and three required surgical intervention. There was no re-expansion pulmonary oedema nor direct deaths. Conclusions: Complication rates of ICD and thoracocenteses are low. Checklists might help to remind operators of the need for suturing. Limitations of this study are its retrospective nature and reliance on correct hospital coding. We are currently contributing to a prospective observational study on pleural complications.","PeriodicalId":284235,"journal":{"name":"Journal of Respiration","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129015428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Drug Regimen for Patients after a Pneumonectomy","authors":"N. Kim, R. Priefer","doi":"10.3390/JOR1020013","DOIUrl":"https://doi.org/10.3390/JOR1020013","url":null,"abstract":"Pneumonectomy is an entire lung removal and is indicated for both malignant and benign diseases. Due to its invasiveness and postoperative complications, pneumonectomy is still associated with high mortality and morbidity. Appropriate postoperative management is crucial in pneumonectomy patients to improve quality of life and overall survival rates. Diverse drug regimens are under development to be used in adjuvant chemotherapy or to improve respiratory health after a pneumonectomy. The most common causes for a pneumonectomy are non-small cell lung cancer, malignant pleural mesothelioma, and tuberculosis; thus, an appropriate drug regimen is necessary. The uncommon incidence of pneumonectomy cases remains the major obstacle in studies of postoperative drug regimens. As the majority of current studies include post-lobectomy and post-segmentectomy patients, it is highly recommended that further research of postoperative drug regimens be focused on post-pneumonectomy patients.","PeriodicalId":284235,"journal":{"name":"Journal of Respiration","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133060047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Fajardo-Rivero, M. Mogollón, Diego F García-Bohórquez, A. Villabona-Rueda, Tania Mendoza-Herrera, A. Ramírez-Sarmiento, Fabio Bolívar-Grimaldos, M. Orozco-Levi
{"title":"Characterization of a Cohort of Patients with Chronic Thromboembolic Pulmonary Hypertension from Northeastern Colombia (REHINO Study)","authors":"J. Fajardo-Rivero, M. Mogollón, Diego F García-Bohórquez, A. Villabona-Rueda, Tania Mendoza-Herrera, A. Ramírez-Sarmiento, Fabio Bolívar-Grimaldos, M. Orozco-Levi","doi":"10.3390/JOR1020012","DOIUrl":"https://doi.org/10.3390/JOR1020012","url":null,"abstract":"Chronic thromboembolic disease (CTEPH) is one of the causes for developing pulmonary hypertension (PH). PH is characterized by an increase in pulmonary vascular pressure and resistance, ultimately leading to chronic overload. This study describes the clinical, functional, and hemodynamic characteristics as well as the established treatment strategy for a cohort of patients diagnosed with CTEPH in Bucaramanga, Colombia. In Colombia, PH is considered as an orphan disease with limited epidemiological data. We aim to provide useful information in order to help guide future clinical decisions for PH treatment and prevention. We conducted a cross-sectional study, obtaining clinical data from patients under follow-up, over 18 years of age, with hemodynamic confirmation of CTEPH in two pulmonary outpatient centers in Bucaramanga, Colombia between 2012 and 2018. 35 patients with diagnosis of CTEPH were included. Mean age was 52.3 ± 17.9 years. The mean time between the onset of symptoms to diagnosis was 14 months. 71% had a previous thrombotic event and 69% had functional class III and IV according to the world health organization (WHO) criteria. Most of the patients were classified as at high risk of mortality according to the European Society of Cardiology (ESC) and the European Respiratory Society (ERS/ESC) criteria and 60% were referred to undergo thromboendarterectomy. Most of the patients were under monotherapy treatment with Bosentan, the most prescribed medication in both monotherapy and dual therapy. This study identified a high number of patients in advanced stages of CETPH due to late diagnosis, related to health care limitations. This resulted in worse prognosis and quality of life. In addition, low adherence to non-pharmacological interventions was evidenced in patients who were not candidates for thromboendarterectomy despite the onset of pharmacological therapy.","PeriodicalId":284235,"journal":{"name":"Journal of Respiration","volume":"558 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125931490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Malignant Pleural Effusions Impact on Fatigue (IMPE-F): A Prospective Observational Cohort Pilot Study","authors":"A. Aujayeb, D. Wakefield","doi":"10.3390/JOR1020011","DOIUrl":"https://doi.org/10.3390/JOR1020011","url":null,"abstract":"Introduction: Cancer-related fatigue is well described. Fatigue in patients with a malignant pleural effusion (MPE) has not been directly studied. Methods: A prospective observational cohort pilot study ‘Do Interventions for Malignant Pleural Effusions (MPE) impact on patient reported fatigue levels (IMPE-F study)’ is planned to determine whether pleural interventions reduce fatigue in MPE. Fatigue will be assessed with a validated patient reported outcome measure, FACIT-F. Discussion: MPE-F has funding from Rocket Medical Plc, and is part of a Masters in Clinical Research at Newcastle University. Respondent fatigue will be addressed by the investigators going through the questionnaire with the participants. Inclusion criteria are all patients above 18 years of age with a presumed MPE undergoing a procedure and able to consent. The expected number of participants is 50. Trial registration: The IMPE-F study has Research Ethics Committee (REC) [20/YH/0224] and Health Research Authority (HRA) and Health and Care Research Wales (HCRW) approvals [IRAS project ID: 276451]. The study has been adopted on National Institute for Health Research portfolio [CPMS ID 46430].","PeriodicalId":284235,"journal":{"name":"Journal of Respiration","volume":"99 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130670057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spontaneous Pneumothorax: New Horizons","authors":"A. Aujayeb","doi":"10.3390/JOR1010008","DOIUrl":"https://doi.org/10.3390/JOR1010008","url":null,"abstract":"Spontaneous pneumothorax can be divided into two categories: primary and secondary. The management of each one depends on resource availability, physician preference, and procedural capability, and is broadly based on guidelines that are over a decade old. Emerging evidence from three recent randomized controlled trials on ambulatory pneumothorax pathways are exciting and herald a new era for management of spontaneous pneumothorax. These three trials and their implications are discussed.","PeriodicalId":284235,"journal":{"name":"Journal of Respiration","volume":"198 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134515814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Leifer, M. Kleinman, D. Blake, D. Tratt, C. Marston
{"title":"Wildfire Smoke Exposure: Covid19 Comorbidity?","authors":"I. Leifer, M. Kleinman, D. Blake, D. Tratt, C. Marston","doi":"10.3390/JOR1010007","DOIUrl":"https://doi.org/10.3390/JOR1010007","url":null,"abstract":"Air pollution, particularly fine and ultrafine particulate matter aerosols, underlies a wide range of communicable and non-communicable disease affecting many systems including the cardiopulmonary and immune systems, and arises primarily from transportation and industry. A number of air pollution driven diseases also are Covid19 comorbidities. Thus, a number of studies on air pollution exposure, particularly particulate matter, strongly indicate air pollution is an important underlying factor in Covid19 transmission, severity, and mortality. This suggests that air pollution from natural sources, particularly wildfires, could play a role in the Covid19 pandemic. We tested this hypothesis on three wildfire smoke events in Orange County, CA, each of which was followed by Covid19 case increases after an approximately one-week lag. This lag was consistent with combined incubation time and testing/reporting times. Moreover, the three events suggest a dose dependency. The wildfire comorbidity hypothesis implies that at-risk-populations should reduce smoke exposure from wildfires, as well as indoors from biomass burning for heating, cooking, and aesthetic purposes.","PeriodicalId":284235,"journal":{"name":"Journal of Respiration","volume":"111 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133814894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}