Chronic rhinosinusitis with nasal polyps in older adults : clinical presentation, pathophysiology, and comorbidity

Purpose of Review Chronic rhinosinusitis and nasal polyps (CRSwNP) is a common condition that significantly affects patients' life. This work aims to provide an up-to-date overview of CRSwNP in older adults, focusing on its aging-related clinical presentations, pathophysiology, and comorbidity associations including asthma. Recent Findings Recent large population-based studies using nasal endoscopy have shown that CRSwNP is a mostly late-onset disease. Age-related changes in physiologic functions, including nasal epithelial barrier dysfunction, may underlie the incidence and different clinical presentations of CRSwNP in older adults. However, there is still a paucity of evidence on the effect of aging on phenotypes and endotypes of CRSwNP. Meanwhile, late-onset asthma is a major comorbid condition in patients with CRSwNP; they frequently present with type 2 inflammatory signatures that are refractory to conventional treatments when they are comorbid. However, as they are more commonly non-atopic, causative factors other than classical atopic sensitization, such as Staphylococcus aureus specific IgE sensitization, are suggested to drive the type 2 inflammation. There are additional comorbidity associations in older patients with CRSwNP, including those with chronic otitis media and head and neck malignancy. Age is a major determinant for the incidence and clinical presentations of CRSwNP. Given the heterogeneity in phenotypes and endotypes, longitudinal investigations are warranted to elucidate the effects of aging on CRSwNP

Proximity-Directed Labeling Reveals a New Rapamycin-Induced Heterodimer of FKBP25 and FRB in Live Cells

Mammalian target of rapamycin (mTOR) signaling is a core pathway in cellular metabolism, and control of the mTOR pathway by rapamycin shows potential for the treatment of metabolic diseases. In this study, we employed a new proximity biotin-labeling method using promiscuous biotin ligase (pBirA) to identify unknown elements in the rapamycin-induced interactome on the FK506-rapamycin binding (FRB) domain in living cells. FKBP25 showed the strongest biotin labeling by FRB-pBirA in the presence of rapamycin. Immunoprecipitation and immunofluorescence experiments confirmed that endogenous FKBP25 has a rapamycin-induced physical interaction with the FRB domain. Furthermore, the crystal structure of the ternary complex of FRB-rapamycin-FKBP25 was determined at 1.67-angstrom resolution. In this crystal structure we found that the conformational changes of FRB generate a hole where there is a methionine-rich space, and covalent metalloid coordination was observed at C2085 of FRB located at the bottom of the hole. Our results imply that FKBP25 might have a unique physiological role related to metallomics in mTOR signaling.ope

Cough persistence in adults with chronic cough: a 4-year retrospective cohort study

BackgroundThere is very limited evidence regarding long-term prognosis of chronic cough. We examined longitudinal outcomes among patients with chronic cough, and explored predictors of cough persistence.MethodsA retrospective cohort was constructed of adults who had newly visited a specialist cough clinic in 2012–2013. All had undergone systematic investigation for chronic cough. The Hull Airway Reflux Questionnaire (HARQ) was administered to assess reflux cough symptoms. A follow-up survey was conducted in 2016–2017 to assess cough persistence.ResultsFrom 418 candidates, 323 participated in the follow-up study; main analyses focused on patients with chronic persistent cough (n=64; 19.8%) and remitted cough (n=193; 59.8%). Compared with remitted cough, chronic persistent cough group had more family history of chronic cough (17.2% vs. 4.7%, p=0.001) and cold air-sensitive cough (62.5% vs. 44.6%, p=0.013). The total HARQ score did not differ; however, two items (cough with eating and cough with certain foods) scored significantly higher in chronic persistent cough. In multivariate analyses, a family history of chronic cough (adjusted odds ratio 4.27 [95% confidence interval 1.35-9.89]), cold air-sensitive cough (2.01 [1.09-3.73]), and cough with eating (1.22 [1.02–1.45]) were associated with chronic persistent cough at 4 years.Conclusions Cough persists in about 20% of patients after 4 years following systematic assessment and treatments. Several cough characteristics, such as family history, cold air-sensitivity, or reflux cough, may be associated with cough persistence. Larger cohort studies are warranted to further understand long-term prognosis and confirm predictors of persistence in patients with chronic cough

Impact of Chronic Cough on Health-Related Quality of Life in the Korean Adult General Population: The Korean National Health and Nutrition Examination Survey 2010–2016

PurposeChronic cough is a prevalent condition in the community and may pose considerable impairment to quality of life (QoL). However, its disease burden remains largely undefined in the general population. The present study investigated the relationship between chronic cough and health-related QoL in a Korean nationwide population database, with an emphasis on clinical conditions which may confound the impact of cough.MethodsThis study analyzed cross-sectional datasets of adults (aged ≥ 40 years) in the Korean National Health and Nutrition Examination Survey 2010–2016. Health-related QoL was assessed using the 3-level EuroQoL 5-dimension component (EQ-5D-3L) index score. The presence of chronic cough and other conditions were defined using structured questionnaires.ResultsThe prevalence of chronic cough was 3.48% ± 0.17% among adults aged ≥ 40 years. The overall EQ-5D-3L index score was significantly lower in subjects with than without chronic cough (0.79 ± 0.01 vs. 0.86 ± 0.00, P < 0.001). In subgroup analyses by age and sex, chronic cough had a notably large impact on QoL in women aged ≥ 65 years (vs. those without chronic cough: 0.55 ± 0.04 vs. 0.70 ± 0.01, P < 0.001), although the mean difference in the scores exceeded the minimally important difference score of 0.05 in all subgroups. In multivariate analyses, chronic cough was significantly associated with QoL, independent of confounders including depression, arthritis, asthma, and chronic obstructive pulmonary disease. In dimension analyses, chronic cough was more associated with anxiety/depression, pain/discomfort, and usual activities than with self-care or mobility in the EQ-5D.ConclusionsThe present study demonstrated significant associations between chronic cough and health-related QoL in a nationwide large general adult population aged ≥ 40 years, which were independent of clinical confounders. The impact of chronic cough was greater in women aged ≥ 65 years. These findings indicate a considerable burden of chronic cough in the general population and warrant further investigations to assess the disease burden of chronic cough in a global scale

Could Fractional Exhaled Nitric Oxide Test be Useful in Predicting Inhaled Corticosteroid Responsiveness in Chronic Cough? A Systematic Review

© 2016 Background Fractional exhaled nitric oxide (FENO) is a safe and convenient test for assessing T H 2 airway inflammation, which is potentially useful in the management of patients with chronic cough. Objective To summarize the current evidence on the diagnostic usefulness of FENO for predicting inhaled corticosteroid (ICS) responsiveness in patients with chronic cough. Methods A systematic literature review was conducted to identify articles published in peer-reviewed journals up to February 2015, without language restriction. We included studies that reported the usefulness of FENO (index test) for predicting ICS responsiveness (reference standard) in patients with chronic cough (target condition). The data were extracted to construct a 2 × 2 accuracy table. Study quality was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Results We identified 5 original studies (2 prospective and 3 retrospective studies). We identified considerable heterogeneities in study design and outcome definitions, and thus were unable to perform a meta-analysis. The proportion of ICS responders ranged from 44% to 59%. Sensitivity and specificity ranged from 53% to 90%, and from 63% to 97%, respectively. The reported area under the curve ranged from abou t 0.60 to 0.87; however, studies with a prospective design and a lower prevalence of asthma had lower area under the curve values. None measured placebo effects or objective cough frequency. Conclusions We did not find strong evidence to support the use of FENO tests for predicting ICS responsiveness in chronic cough. Further studies need to have a randomized, placebo-controlled design, and should use validated measurement tools for cough. Standardization would facilitate the development of clinical evidence

Point prevalence and epidemiological characteristics of chronic cough in the general adult population: The Korean National Health and Nutrition Examination Survey 2010-2012

© 2017 the Author(s). Cough is frequently self-limiting, but may persist longer in certain individuals. Most of previous studies on the epidemiology of chronic cough have only measured period prevalence, and thus have afforded limited information on the burden and natural course. We aimed to investigate the epidemiology of chronic cough by using a point prevalence measure in a large-scale general population. We analyzed cross-sectional data collected from 18,071 adults who participated in the Korean National Health and Nutrition Examination Survey 2010-2012. Presence and duration of current cough was ascertained by structured questionnaires, and cough was classified into acute

Biochemical Markers as Predictors of In-Hospital Mortality in Patients with Severe Trauma: A Retrospective Cohort Study

Background Initial evaluation of injury severity in trauma patients is an important and challenging task. We aimed to assess whether easily measurable biochemical parameters (hemoglobin, pH, and prothrombin time/international normalized ratio [PT/INR]) can predict in-hospital mortality in patients with severe trauma. Methods This retrospective study involved review of the medical records of 315 patients with severe trauma and an injury severity score >15 who were managed at Gyeongsang National University Hospital between January 2005 and December 2015. We extracted the following data: in-hospital mortality, injury severity score, and initial hemoglobin level, pH, and PT/INR. The predictive values of these variables were compared using receiver operation characteristic curves. Results Of the 315 patients, 72 (22.9%) died. The in-hospital mortality rates of patients with hemoglobin levels <8.4 g/dl and ≥8.4 g/dl were 49.8% and 9.9%, respectively (P < 0.001). At a cutoff hemoglobin level of 8.4 g/dl, the sensitivity and specificity values for mortality were 81.9% and 86.4%, respectively. At a pH cutoff of 7.25, the sensitivity and specificity values for mortality were 66.7% and 77.8%, respectively; 66.7% of patients with a pH <7.25 died versus 22.2% with a pH ≥7.25 (P < 0.001). The in-hospital mortality rates for patients with PT/INR values ≥1.4 and <1.4 were 37.5% and 16%, respectively (P < 0.001; sensitivity, 37.5%; specificity, 84%). Conclusions Using the suggested cutoff values, hemoglobin level, pH, and PT/INR can simply and easily be used to predict in-hospital mortality in patients with severe trauma

Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein (RNP) electroporation

Background Genome editing has been considered as powerful tool in agricultural fields. However, genome editing progress in cattle has not been fast as in other mammal species, for some disadvantages including long gestational periods, single pregnancy, and high raising cost. Furthermore, technically demanding methods such as microinjection and somatic cell nuclear transfer (SCNT) are needed for gene editing in cattle. In this point of view, electroporation in embryos has been risen as an alternative. Results First, editing efficiency of our electroporation methods were tested for embryos. Presence of mutation on embryo was confirmed by T7E1 assay. With first combination, mutation rates for MSTN and PRNP were 57.6% ± 13.7% and 54.6% ± 13.5%, respectively. In case of MSTN/BLG, mutation rates were 83.9% ± 23.6% for MSTN, 84.5% ± 18.0% for BLG. Afterwards, the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep sequencing. Thirteen recipients were transferred for MSTN/PRNP, 4 calves were delivered, and one calf underwent an induction for double KO. Ten surrogates were given double-KO embryos for MSTN/BLG, and four of the six calves that were born had mutations in both genes. Conclusions These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively applied. Finally, MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.This study was financially supported by the National Research Foundation of Korea (NRF-2021R1A5A1033157 for SRC program: 382 Comparative medicine Disease Research Center; NRF-2021R1F1A105195313), the Research Institute of Veterinary Science, the BK21 Four for Future Veterinary Medicine Leading Education and Research Center, and a Seoul National University (SNU) grant (#550e2020005