# ent

id: cord-286477-0euaaspo
type: PROTEIN
entity:
  procalcitonin globulin lactate 263 dehydrogenase LDH NT proB type natriuretic peptide NT proBNP d dimer alanine 264 aminotransferase aspartate aminotransferase total bilirubin conjugated bilirubin blood urea 265


id: cord-007866-2d6003r9
type: DISEASE
entity:
  human rhinovirus respiratory syncytial virus coronavirus adenovirus and influenza A virus through the role of autophagy in the defense against respiratory tract viruses


id: cord-314640-vik5rgnq
type: GGP
entity:
  lactoferrin r 0 58 P 01 IgG r 0 50 P 01 and total protein r 0 46 P 01 Fig 9 These experiments indicate that leu Ap


id: cord-258093-6fn8ei9f
type: ORG
entity:
  National Heart Lung and Blood Institute National Institute of Health National Asthma Education and Prevention Program Expert Panel Report


id: cord-259927-xh9cw9ao
type: GGP
entity:
  Peroxisome proliferator activated receptor g agonists eg rosiglitazone and pioglitazone are critical regulators of inflammation and have been promising in improving the clinical outcome of severe influenza infections 33 Their development slowed down from 2000 to 2005 because of possible cardiovascular side effects however in 2015 the US Food


id: cord-259927-xh9cw9ao
type: DISEASE
entity:
  influenza viruses respiratory syncytial virus and rhinoviruses being the most frequent and with the highest burden When considering prevention or treatment of viral respiratory tract infections


id: cord-259927-xh9cw9ao
type: CHEMICAL
entity:
  influenza A virus and the prediction of its efficacious clinical dose for the treatment of patients hospitalized with


id: cord-272214-rwkfev8j
type: GGP
entity:
  arg 9 lys bradykinin Fig 1 93 94 There are many observations and theories regarding a prominent role for bradykinin


id: cord-269776-hj1s3ipp
type: CL
entity:
  follicle stimulating hormone progesterone estradiol testosterone prolactin and sex hormone binding globulin SHBG


id: cord-269776-hj1s3ipp
type: CHEMICAL
entity:
  C1 inhibitor gene of a patient with type I hereditary angioneurotic edema Nonsense mutations affect C1 inhibitor


# bib

id: cord-007385-xcx4ic0s
title: The common cold: Current therapy and natural history()()()
author: Spector, Sheldon L.
date: 2005-11-30
txt: ./txt/cord-007385-xcx4ic0s.txt
cache: ./cache/cord-007385-xcx4ic0s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112258/
doi: 10.1016/s0091-6749(95)70218-0
summary:
  27 In a 1136 Spector J ALLERGY CLIN IMMUNOL MAY 1995 study by Sperber et al., 28 naproxen did not alter virus shedding or serum neutralizing antibody in experimental rhinovirus cold, but it had a beneficial effect on such symptoms as headache, malaise, myalgia, and cough. Although some time-honored treatments might have limited usefulness, novel attempts at ameliorating the symptoms of a common cold, such as the use of ipratropium bromide nasal spray or specific antiviral receptor therapy, might represent a significant advance. Potential role of hands in the spread of respiratory viral infections: studies with human parainfluenza virus 3 and rhinovirus 14 Development of common cold symptoms following experimental rhinovirus infection is related to prior stressful life events Analysis of nasal secretions during experimental rhinovirus upper respiratory infections Effect of experimental rhinovirus 39 infection on the nasal response to histamine and cold air challenges in allergic and nonallergic subjects

abstract:
  Despite its prevalence, the common cold is complicated and can be difficult to treat, even symptomatically. There is still no cure for the myriad of viruses that cause the common cold. Many of the most popular remedies are either ineffective or counterproductive. This paper reviews the causes and course of upper respiratory infections, and discusses treatment options, including a new anticholinergic aqueous formulation for controlling rhinorrhea. (J ALLERGY CLIN IMMUNOL 1995;95:1133-8.)


id: cord-007866-2d6003r9
title: Autophagy: Nobel Prize 2016 and allergy and asthma research
author: Renz, Harald
date: 2017-04-08
txt: ./txt/cord-007866-2d6003r9.txt
cache: ./cache/cord-007866-2d6003r9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125795/
doi: 10.1016/j.jaci.2017.03.021
abstract: nan
summary:
  The 2016 Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi, Professor at the Tokyo Institute of Technology, for ''''recycling.'''' Recycling on the cellular level is termed autophagy and is a fundamental process for degrading and recycling cellular components. A new type of vesicle was discovered and named autophagosomes, describing a process of ''''self-eating'''' to understand the mechanism of how such large cargos get into the lysosome. Although little work has been carried out in this regard thus far, there are convincing data available linking autophagy in airway epithelium, and autophagy might be essential for bronchial epithelial mucus secretion, as has been shown in an allergic asthma model. IL13 activates autophagy to regulate secretion in airway epithelial cells The complex roles of endoplasmic reticulum stress and autophagy in modulating Eotaxin-3 production and secretion from human airway epithelial cells


id: cord-010159-uo47oab1
title: Respiratory viruses and acute asthma in children
author: Jartti, Tuomas
date: 2007-04-02
txt: ./txt/cord-010159-uo47oab1.txt
cache: ./cache/cord-010159-uo47oab1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172149/
doi: 10.1016/j.jaci.2007.02.025
abstract: nan
summary:
  title: Respiratory viruses and acute asthma in children We read with great interest the article by Khetsuriani et al 1 on the prevalence of respiratory tract viruses in children with asthma. The results of PCR analysis of combined nasopharyngeal and throat swabs for 13 different viruses were positive in 63% of patients with asthma exacerbation in the 1-year study. We disagree with the low virus detection rate reported by Khetsuriani et al 1 because many studies in wheezing children have shown virus detection rates of close to 90%. 1 Interestingly, 2 or more viruses were detected in 43% of the children compared with 7% in the study by Khetsuriani et al. Our findings suggest that nearly all exacerbations of asthma in children necessitating hospitalization are associated with viral infection. Prevalence of viral respiratory tract infections in children with asthma Human bocavirus and acute wheezing in children


id: cord-025380-6bagohw8
title: Reply
author: Navel, Valentin
date: 2020-05-28
txt: ./txt/cord-025380-6bagohw8.txt
cache: ./cache/cord-025380-6bagohw8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253949/
doi: 10.1016/j.jaci.2020.05.010
abstract: nan
summary:
  Globally, emerging data may identify air pollution as a modulator to DNA methylation (DNAm) disturbing the inflammation process, allergic diseases development, and exacerbation risk. Considering that SARS-CoV-2 infection involves a proinflammatory cytokine storm as IL-6 and IL-1b, a putative hypothesis could explain that populations exposed to chronic air pollution are associated with a different COVID-19 incidence in line with chronic epigenetic deregulation. Affecting the immune system and the inflammatory pathways, DNAm related to air pollution could explain the disparities in COVID-19 in geographic zones in which genetically predisposed populations were living in climate favoring SARS-CoV-2 distribution.


id: cord-027511-j5ayp0tv
title: Reply
author: Navel, Valentin
date: 2020-06-22
txt: ./txt/cord-027511-j5ayp0tv.txt
cache: ./cache/cord-027511-j5ayp0tv.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306707/
doi: 10.1016/j.jaci.2020.06.003
abstract: nan
summary:
  2 Globally, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has upset the lifestyle of humans, increasing sedentary behaviors with quarantine (ie, staying at home, tele-working, screen activities), the fear of contagion (ie, social connections, mass transit, and compulsive disinfecting), and probably a city dweller migration to the periphery of crowed cities and surrounding countryside. Considering that filtering face piece respirators (FFPs) reduced the penetration of fine particulates ranging from 80% (FFP1) to 99% (FFP3), their global use during the coronavirus disease 2019 pandemic could protect people against outdoor and indoor allergenic components. 4 Promoting warm and humid environment, indoor activities (ie, tele-working, cooking, and indoor sports) could improve the exposition of airborne fungal spores in damp houses, increasing the incidence of asthma and allergic diseases. 7 Because of the fear of contagion, people may avoid mass transit and increase their commuting by individual car, which may in turn promote air pollution-and the release of the highly allergenic fine particulate matter.


id: cord-032811-sdbj26ca
title: Reply
author: Hosoki, Koa
date: 2020-09-29
txt: ./txt/cord-032811-sdbj26ca.txt
cache: ./cache/cord-032811-sdbj26ca.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522701/
doi: 10.1016/j.jaci.2020.09.008
abstract: nan
summary:
  They suggest that suppression of angiotensin-converting enzyme-2 (ACE-2) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could impair the hydrolysis of des-Arg 9 -bradykinin and stimulate the bradykinin receptor type 1 (BKB1) pathway to induce leakage of fluid into the lungs. 4 However, other studies suggest that SARS-CoV-2 may upregulate the expression of ACE-2 in patients with coronavirus disease 2019 (COVID-19) or influenza pneumonia in alveolar epithelial cells, endothelial cells, and lymphocytes in perivascular tissue than in uninfected control autopsy lung. 7 We favor a third hypothesis, where excessive and prolonged secretion of type I and type III IFNs in the airways contributes to loss of lung epithelial barrier function during COVID-19 and other RNA virus infections (Fig 1, A) . Because IFN-l contributes to loss of lung epithelial barrier function, 8 we hypothesize that entry of SARS-CoV-2 via ACE-2 can stimulate secretion of IFN-l and induce leakage of fluid into the lungs (Fig 1, A) .


id: cord-034640-ygtbuy4k
title: Corrigenda
author: nan
date: 2020-11-04
txt: ./txt/cord-034640-ygtbuy4k.txt
cache: ./cache/cord-034640-ygtbuy4k.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640884/
doi: 10.1016/j.jaci.2020.08.023
abstract: nan
summary:
  key: cord-034640-ygtbuy4k authors: nan cord_uid: ygtbuy4k This is highlighted by preliminary findings in a recent study demonstrating the efficacy of dexamethasone in reducing mortality in critically ill patients with COVID-19, but showing no benefit in those not requiring respiratory support. 4 Furthermore, our study 5 demonstrated a ''''dose-response,'''' with greater degrees of respiratory allergy being associated with larger reductions in angiotensin-converting enzyme 2 gene expression in the nasal epithelium, and the impact of suppressing type 2 inflammation in these individuals is not currently known. SARS-CoV-2 reverse genetics reveals a variable infection gradient in the respiratory tract Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2 The names were shown as Gregori Silvia, PhD, and Aiuti Alessandro, MD, PhD. The first and last names of both authors were inadvertently reversed and should be Silvia Gregori


id: cord-252950-eiphxwmn
title: Type I IFN immunoprofiling in COVID-19 patients
author: Trouillet-Assant, Sophie
date: 2020-04-29
txt: ./txt/cord-252950-eiphxwmn.txt
cache: ./cache/cord-252950-eiphxwmn.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jaci.2020.04.029
doi: 10.1016/j.jaci.2020.04.029
summary:
  COVID patients in ICU present a high mortality rate and immunoprofiling reveals heterogeneous IFN-α2 production with about 20% of critically-ill patients unable to produce IFN-α2, highlighting the immune response heterogeneity and opening avenues for targeted therapies. 42 Capsule summary: 43 COVID patients in ICU present a high mortality rate and immunoprofiling reveals heterogeneous α2 production with about 20% of critically-ill patients unable to produce IFN-α2, highlighting the 45 immune response heterogeneity and opening avenues for targeted therapies. Various immunosuppressive drugs, including IL-6 blockers or JAK-STAT signaling inhibitors have been 56 suggested for the treatment of SARS-COV-2 infection 2 whereas additional clinical trials are evaluating 57 the use of recombinant interferon to foster host antiviral response. To date, IFN-I response has not been evaluated in COVID-19 60 patients and its contribution to the viral control and inflammation is unknown. We further explored a larger cohort of 26 critically ill COVID patients from one of the intensive care 75 unit (ICU) at Hospices Civils de Lyon (Lyon, France).

abstract:
  COVID patients in ICU present a high mortality rate and immunoprofiling reveals heterogeneous IFN-α2 production with about 20% of critically-ill patients unable to produce IFN-α2, highlighting the immune response heterogeneity and opening avenues for targeted therapies.


id: cord-255794-55ubow92
title: IL-6 serum levels predict severity and response to Tocilizumab in COVID-19: an observational study
author: Galván-Román, José María
date: 2020-09-30
txt: ./txt/cord-255794-55ubow92.txt
cache: ./cache/cord-255794-55ubow92.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0091674920313294?v=s5
doi: 10.1016/j.jaci.2020.09.018
summary:
  Since 120 interleukin-6 (IL-6) is a relevant cytokine in ARDS, the blockade of its receptor with 121 Tocilizumab (TCZ) could reduce mortality and/or morbidity in severe Objective 123 To determine whether baseline IL-6 serum levels can predict the need for IMV and the 124 response to TCZ. Retrospective observational study performed in hospitalized patients diagnosed of Clinical information and laboratory findings, including IL-6 levels, were collected 128 approximately 3 and 9 days after admission to be matched with pre-and post-administration The recent exponential increase in cases of severe acute respiratory syndrome caused by 181 coronavirus 2 (SARS-CoV-2) has led the World Health Organization to declare a pandemic. To determine the variables associated with the need for IMV, we performed a multivariable 296 logistic regression analysis that was first modeled by adding all the variables with a p value 297 lower than 0.15 in the bivariable analysis, namely total lymphocyte count, D-dimer, LDH, 298 PaO 2 /FiO 2 , COPD, obesity, hypertension, C-reactive protein, and IL-6 (high vs low).

abstract:
  Background COVID-19 patients can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation (IMV). Since interleukin-6 (IL-6) is a relevant cytokine in ARDS, the blockade of its receptor with Tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective To determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods Retrospective observational study performed in hospitalized patients diagnosed of COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with pre- and post-administration of TCZ. Multivariable logistic and linear regressions, and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio (PaO2/FiO2) or mortality. Results One hundred and forty-six patients were studied, predominantly male (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels>30 pg/ml was the best predictor for IMV (OR:7.1; p<0.001). Early administration of TCZ was associated with improvement of oxygenation (PaO2/FiO2) in patients with high IL-6 (p=0.048). Patients with high IL-6 not treated with TCZ showed high mortality (HR: 4.6; p=0.003), as well as those with low IL-6 treated with TCZ (HR: 3.6; p=0.016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusion Baseline IL-6>30 pg/ml predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.


id: cord-256788-h4iv8crq
author: Sumino, Kaharu
date: 2012-03-27
txt: ./txt/cord-256788-h4iv8crq.txt
cache: ./cache/cord-256788-h4iv8crq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/22460071/
doi: 10.1016/j.jaci.2012.02.033
summary:
  9 In that regard a decrease in IFN-g production from cord blood mononuclear cells (CBMCs) stimulated by PHA or allergens has been associated with increased risk for acute respiratory tract illness during infancy. We assessed whether each of these immune end points could predict the development of respiratory tract illness during the first year of life in a prospective birth cohort of children at high risk for asthma and allergic disease. Together, these findings reinforce the association of a decreased IFN-g response to RSV with the development of increased viral respiratory tract infections in the first year of life. In this study we provide evidence that a decreased antiviral interferon response at the time of birth is selectively associated with an increase in acute respiratory tract infections in the first year of life among infants at high risk for asthma and allergic disease.

title:
  Antiviral IFN-γ responses of monocytes at birth predict respiratory tract illness in the first year of life

abstract:
  BACKGROUND: Viral respiratory tract infections are the leading cause of acute illness during infancy and are closely linked to chronic inflammatory airway diseases later in life. However, the determinants of susceptibility to acute respiratory tract infections still need to be defined. OBJECTIVE: We investigated whether the individual variation in antiviral response at birth determines the risk for acute respiratory tract illness in the first year of life. METHODS: We studied 82 children who were enrolled in a birth cohort study of inner-city children with at least 1 parent with allergy or asthma. We cultured cord blood monocytes and assessed IFNG and CCL5 mRNA production at 24 hours after inoculation with respiratory syncytial virus. We also monitored the frequency of acute respiratory tract illness at 3-month intervals and analyzed nasal lavage samples for respiratory tract viruses at the time of illness during the first year. RESULTS: Respiratory tract infection was reported for 88% of subjects, and respiratory tract viruses were recovered in 74% of symptomatic children. We observed a wide range of antiviral responses in cord blood monocytes across the population. Furthermore, a decrease in production of IFNG (but not CCL5) mRNA in response to respiratory syncytial virus infection of monocytes was associated with a significant increase in the frequency of upper respiratory tract infections (r = −0.42, P < .001) and the prevalence of ear and sinus infections, pneumonias, and respiratory-related hospitalizations. CONCLUSION: Individual variations in the innate immune response to respiratory tract viruses are detectable even at birth, and these differences predict the susceptibility to acute respiratory tract illness during the first year of life.


id: cord-258093-6fn8ei9f
author: Hanania, Nicola A.
date: 2011-08-25
txt: ./txt/cord-258093-6fn8ei9f.txt
cache: ./cache/cord-258093-6fn8ei9f.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/21872730/
doi: 10.1016/j.jaci.2011.06.048
summary:
  The aging lung Large, longitudinal, and more complete studies to determine the effects of aging on the function of the respiratory system Improved knowledge about lung structure-function relationships in older age using techniques of imaging and measures of lung function not requiring effort (eg, high-resolution computed tomographic scanning and forced oscillation) Improved assessment of lung processes underlying airflow limitation attributable to aging versus COPD or asthma, especially in asthmatic patients who smoke Studies to examine the effects of aging in ethnic groups and the role of gender Epidemiology, effect, diagnosis, and management Determine the true prevalence and cost of asthma in the older population Develop a uniform definition of asthma to be applied to health care records that will distinguish asthma from COPD and mixed asthma/COPD Evaluate evidence-based treatment algorithms for older asthmatic patients, such as those developed by the National Heart, Lung, and Blood Institute and Global Initiative For Asthma guidelines 7 Assess the effect of asthma treatment, including direct medical costs of care, indirect costs of care, and value of treatment in improving quality of life 8, 9 Assess the effect of comorbid conditions, especially COPD and congestive heart failure, on asthma 9 Characterize phenotypes of elderly asthma with regard to responses to therapy and long-term outcomes based on age of onset, duration of disease, and environmental triggers Develop algorithms for electronic medical record systems that are asthma-specific Evaluate effects of current asthma medications in older patients compared with younger patients Identify pharmacogenetic determinants of response to asthma medications in older adults Identify simpler and safer drug delivery systems and schedules for older adults Develop simple methods to differentiate COPD from asthma exacerbations in older adults

title:
  Asthma in the elderly: Current understanding and future research needs—a report of a National Institute on Aging (NIA) workshop

abstract:
  Asthma in the elderly is underdiagnosed and undertreated, and there is a paucity of knowledge on the subject. The National Institute on Aging convened this workshop to identify what is known and what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of asthma in the elderly. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger patients, but comorbid illnesses and the psychosocial effects of aging might affect the diagnosis, clinical presentation, and care of asthma in this population. At least 2 phenotypes exist among elderly patients with asthma; those with longstanding asthma have more severe airflow limitation and less complete reversibility than those with late-onset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiologic mechanisms of asthma in the elderly are likely to be different from those seen in young asthmatic patients, and these differences might influence the clinical course and outcomes of asthma in this population.


id: cord-259927-xh9cw9ao
title: Promising approaches for the treatment and prevention of viral respiratory illnesses
author: Papadopoulos, Nikolaos G.
date: 2017-07-21
txt: ./txt/cord-259927-xh9cw9ao.txt
cache: ./cache/cord-259927-xh9cw9ao.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0091674917311132
doi: 10.1016/j.jaci.2017.07.001
summary:
  When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Here we provide an overview of the options and highlight some of the most promising approaches in vRTI treatment, including symptomatic medication, immunomodulatory drugs, antiviral agents, and natural products, as well as in vRTI prevention, ranging from vaccines to immunostimulators and public health policies. Early in vivo evidence suggested that azithromycin has anti-inflammatory and antiviral effects through induction of interferon-stimulated gene mRNA expression and reduced viral replication and release in patients with asthma and chronic obstructive lung disease. mAb therapies to viral infections, such as EBV (rituximab) or RSV (palivizumab), provide passive immunization and are licensed, whereas similar agents targeting influenza and other viruses are in preclinical development.

abstract:
  Viral respiratory tract infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of viral species and subtypes have been associated with these conditions, with influenza viruses, respiratory syncytial virus, and rhinoviruses being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Strategies targeting all these aspects are developing concurrently, and several novel and promising approaches are emerging. In this perspective we overview the entire range of options and highlight some of the most promising approaches, including new antiviral agents, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, and vaccines and public health policies toward prevention. Wide-scale prevention through immunization appears to be within reach for respiratory syncytial virus and promising for influenza virus, whereas additional effort is needed in regard to rhinovirus, as well as other respiratory tract viruses.


id: cord-260700-u12aa739
author: Kainulainen, Leena
date: 2010-06-10
txt: ./txt/cord-260700-u12aa739.txt
cache: ./cache/cord-260700-u12aa739.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0091674910006652
doi: 10.1016/j.jaci.2010.04.016
summary:
  title: Recurrent and persistent respiratory tract viral infections in patients with primary hypogammaglobulinemia OBJECTIVE: We conducted a prospective 12-month follow-up study of respiratory tract infections in 12 adult patients with primary hypogammaglobulinemia. METHODS: Nasal swab samples and induced sputum samples were taken at the onset of acute respiratory tract infection and every 3 months thereafter. CONCLUSIONS: Despite adequate immunoglobulin replacement therapy, patients with primary hypogammaglobulinemia have increased susceptibility to respiratory tract viral infections. Using modern diagnostic techniques, we wanted to study the occurrence of respiratory tract infections, especially viral infections, in patients with primary hypogammaglobulinemia who were receiving regular immunoglobulin replacement therapy. If the spouse of the patient had acute symptoms of respiratory tract infection, she or he took nasal swabs at home according to the instructions of the research nurse and sent the vials by post. First, despite adequate immunoglobulin replacement therapy, most patients with primary hypogammaglobulinemia had increased susceptibility to respiratory tract viral infections.

title:
  Recurrent and persistent respiratory tract viral infections in patients with primary hypogammaglobulinemia

abstract:
  BACKGROUND: The occurrence of respiratory tract viral infections in patients with primary hypogammaglobulinemia has not been studied. OBJECTIVE: We conducted a prospective 12-month follow-up study of respiratory tract infections in 12 adult patients with primary hypogammaglobulinemia. METHODS: Nasal swab samples and induced sputum samples were taken at the onset of acute respiratory tract infection and every 3 months thereafter. Samples were tested for bacteria and viruses. PCR tests were performed for 15 respiratory tract viruses. In case the results for rhinovirus were positive, follow-up nasal swab samples were taken every 2 weeks until rhinoviral PCR results became negative. Patients completed symptom diaries, which were collected every month. The spouses of the patients served as healthy control subjects. RESULTS: During the 12-month period, the 12 patients had 65 episodes of acute respiratory tract infections, and the 11 spouses had 12 acute episodes (P < .001). Respiratory tract viruses were found in sputum in 54% of the infections. Rhinovirus was the most common virus. In more than half of our patients, rhinoviral PCR results stayed positive for more than 2 months. The most long-acting persistence with the same rhinovirus was 4 months. CONCLUSIONS: Despite adequate immunoglobulin replacement therapy, patients with primary hypogammaglobulinemia have increased susceptibility to respiratory tract viral infections. Rhinoviral infections are frequent and prolonged.


id: cord-264311-t81r2l3r
author: Toivonen, Laura
date: 2019-01-14
txt: ./txt/cord-264311-t81r2l3r.txt
cache: ./cache/cord-264311-t81r2l3r.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0091674919300211
doi: 10.1016/j.jaci.2018.12.1004
summary:
  To address the knowledge gap, we examined the association between rhinovirus species and the nasopharyngeal airway microbiota determined by 16S rRNA gene sequencing in 774 infants with severe bronchiolitis. Briefly, 1016 infants (age <1 year) hospitalized for bronchiolitis were enrolled in 17 sites across 14 US states (see Table E1 in this article''s Online in PBMC-engrafted mice (n 5 14-16 per group) without or with injection of neutrophils and subsequent intranasal challenge with birch pollen extract (BPE) or PBS. 7 Our observations-for example, the association between RV-C and higher likelihood of Moraxella-dominant microbiota-corroborate these earlier findings, and extend them by applying 16S rRNA gene sequencing to the airway samples of a large multicenter prospective cohort of infants with severe bronchiolitis. Despite this complexity, the identification of the association between specific virus species and airway microbiota in infants with bronchiolitis is important given their relation to subsequent respiratory health in children.

title:
  Association between rhinovirus species and nasopharyngeal microbiota in infants with severe bronchiolitis

abstract:
  Among 774 infants with severe bronchiolitis, rhinovirus species related to distinct nasopharyngeal microbiota. Infants with rhinovirus-A were more likely to have Haemophilus-dominant microbiota profile, while those with rhinovirus-C were more likely to have Moraxella-dominant profile.


id: cord-265054-52eqdlef
title: Respiratory viral infections drive chemokine expression and exacerbate the asthmatic response
author: Schaller, Matthew
date: 2006-08-03
txt: ./txt/cord-265054-52eqdlef.txt
cache: ./cache/cord-265054-52eqdlef.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/16890750/
doi: 10.1016/j.jaci.2006.05.025
summary:
  By this same theory, it has been demonstrated that chemokine levels produced during respiratory syncytial virus infection determine host responses to later immune stimuli in the lung, with the potential to augment the asthmatic response. 3 These studies are supported by clinical investigations that demonstrate that a relatively low number of influenza cases, versus RSV or rhinovirus infections, actually cause exacerbation of asthma and acute bronchiolitis in adults. A comparative study examining the effects of respiratory viruses on CXCL8 production found that although levels of CXCL8 protein in the nasal lavage fluid (NLF) of influenza virusand rhinovirus-infected patients correlated with a higher symptom score, this was not the case for RSV-infected patients. The recruitment of allergen-responsive T cells to the lung and draining lymph nodes has been linked to CCR1 in a murine model of RSV-induced exacerbation of allergic asthma (Schaller and Lukacs, unpublished data).

abstract:
  A number of investigations have linked respiratory vial infections and the intensity and subsequent exacerbation of asthma through host response mechanisms. For example, it is likely that the immune-inflammatory response to respiratory syncytial virus can cause a predisposition toward an intense inflammatory reaction associated with asthma, and adenovirus might cause exacerbation of the immune response associated with chronic obstructive pulmonary disease. In each of these situations, the host's immune response plays a critical mechanistic role through the production of certain cytokines and chemokines. Specific aspects of these augmented immune responses are determined by the biology of the virus, the genetic variability of the host, and the cytokine-chemokine phenotype of the involved tissue. For instance, the type 1/type 2 cytokine ratio in the airways during infection with rhinovirus determines how long the viral infection endures. By this same theory, it has been demonstrated that chemokine levels produced during respiratory syncytial virus infection determine host responses to later immune stimuli in the lung, with the potential to augment the asthmatic response. Further research in this area will clarify cytokines, chemokines, or cell targets, which will provide the basis for next-generation therapies.


id: cord-269776-hj1s3ipp
author: Agostoni, Angelo
date: 2004-09-11
txt: ./txt/cord-269776-hj1s3ipp.txt
cache: ./cache/cord-269776-hj1s3ipp.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0091674904017579
doi: 10.1016/j.jaci.2004.06.047
summary:
  Concerning HAE-I and HAE-II, just as variations in serum concentrations of APP appear to determine which individuals in a normal population develop angioedema with a second perturbation of kinin metabolism, such as the use of ACE inhibitors, 96 it could be speculated that variations in either kinin activation or inactivation pathways might contribute to the differences in severity of angioedema in individuals with a pre-existing perturbation in kinin metabolism, such as a mutation in C1-INH (as occurs in HAE). 13, 14, 27 This increase in plasma bradykinin was demonstrated both for patients with HAE with C1-INH deficiency and for patients with drug-associated angioedema who had an angioedematous attack in conjunction with ACE inhibitor treatment. The patient''s daughter had recurrent skin angioedema and gastrointestinal pain attacks since age 12 years; therefore, with a normal C1-INH concentration and activity in both mother and daughter, a diagnosis of HAE type III was assumed.

title:
  Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond

abstract:
  Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.


id: cord-270635-l8380adr
title: COVID-19: unanswered questions on immune response and pathogenesis
author: Maggi, Enrico
date: 2020-05-08
txt: ./txt/cord-270635-l8380adr.txt
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mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S009167492030631X?v=s5
doi: 10.1016/j.jaci.2020.05.001
summary:
  It is generally accepted that only achieving a better understanding of the interactions between the virus and host immune response and of the pathogenesis of infection is crucial to identify valid therapeutic tools to control virus entry, replication and spread as well as to impair its lethal effects. On this basis, we also touch important aspects regarding the immune response in asymptomatic subjects, the immune-evasion of SARS-CoV-2 in severe patients and differences in disease severity by age and gender. This implies to be able to answer many questions on the virus itself, on the pathogenesis of infection, on the 81 host immune response and to identify therapeutic tools to control virus entry into the cells, its replication and 82 spread as well as its lethal effects. Humoral Immune Responses SARS-CoV 3 -Seroconversion few days after the disease onset and specific IgG detectable in most patients by 14 days.

abstract:
  Abstract The novel coronavirus disease 2019 (COVID-19) has rapidly increased in pandemic scale since it first appeared in Wuhan, China, in December 2019. In these troubled days the scientific community is asking rapid replies to prevent and combat the emergency. It is generally accepted that only achieving a better understanding of the interactions between the virus and host immune response and of the pathogenesis of infection is crucial to identify valid therapeutic tools to control virus entry, replication and spread as well as to impair its lethal effects. Based on the recent research progress of SARS-CoV-2 and the results on previous coronaviruses, in this contribution we underscore some of the main unsolved problems, mostly focusing on pathogenetic aspects and host immunity to the virus. On this basis, we also touch important aspects regarding the immune response in asymptomatic subjects, the immune-evasion of SARS-CoV-2 in severe patients and differences in disease severity by age and gender.


id: cord-272214-rwkfev8j
author: Kaplan, Allen P.
date: 2020-10-28
txt: ./txt/cord-272214-rwkfev8j.txt
cache: ./cache/cord-272214-rwkfev8j.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0091674920315025
doi: 10.1016/j.jaci.2020.10.025
abstract: nan
summary:
  46 47 There are two general pathways for the production of bradykinin, the first being the release of 48 cellular tissue kallikrein which cleaves low molecular weight kininogen (LK) to release lys-49 bradykinin (Fig. 1) . An alternative process requires 85 carboxypeptidase activity (carboxypeptidase N in plasma and carboxypeptidase M on pulmonary 86 vascular endothelial cells) to first remove the C-terminal arg from either bradykinin (plasma 87 cascade) or lys-bradykinin (tissue kallikrein product) (Fig. 1) . Studies of gene expression in 97 bronchoalveolar lavage specimens of COVID-19 patients(5), when compared to normal control 98 specimens, reveal upregulation of multiple components that lead to bradykinin production and 99 expression for C1-INH was decreased 33-fold which would render the plasma bradykinin 102 cascade labile and overreactive as we see in C1-INH deficiency (types I and II HAE) in which 103 enzymes not adequately inhibited by C1-INH include both forms of activated factor XII, plasma 104 kallikrein, and C1r.

title:
  Pathways for Bradykinin Formation and Interrelationship with Complement as a Cause of Edematous Lung in COVID-19 Patients


id: cord-281566-6v5zfue6
title: Host-microbial interactions in patients with chronic rhinosinusitis
author: Hamilos, Daniel L.
date: 2013-11-28
txt: ./txt/cord-281566-6v5zfue6.txt
cache: ./cache/cord-281566-6v5zfue6.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24290275/
doi: 10.1016/j.jaci.2013.06.049
summary:
  12 Our group found that cultured airway epithelial cells from patients with CRSsNP had an exaggerated response to stimulation with the combination of double-stranded RNA (a Toll-like receptor [TLR] 3 agonist and surrogate for viral infection) plus cigarette smoke extract, with exaggerated production of RANTES and hBD-2. Ramanathan et al 3 showed that culturing human sinonasal epithelial cells in the presence of the T H 2 cytokines IL-4 or IL-13 for 36 hours reduced expression of antimicrobial innate immune genes by using real-time PCR, ELISA, and flow cytometry, including TLR9, hBD-2, and SP-A. This has been shown in cultured airway epithelial cells and dispersed T lymphocytes from NPs. Fungi are commonly detected in the attached mucus of sinus tissues in patients with CRS 47,165 and can induce eosinophil activation and degranulation. Th2 cytokines associated with chronic rhinosinusitis with polyps down-regulate the antimicrobial immune function of human sinonasal epithelial cells Th2 cytokines associated with chronic rhinosinusitis with polyps down-regulate the antimicrobial immune function of human sinonasal epithelial cells

abstract:
  There has been considerable investigation of host-microbial interactions in patients with chronic rhinosinusitis (CRS) in hopes of elucidating mechanisms of disease and better treatment. Most attention has been paid to bacterial infection and potential underlying defects in innate immunity. Bacterial biofilm is present in most patients with CRS undergoing surgical intervention, and its presence is associated with more severe disease and worse surgical outcomes. A role for viral or fungal infection in patients with CRS is less clear. There is no evidence for a primary defect in mucociliary clearance in most patients with CRS. Decreased levels of certain antimicrobial proteins, most notably lactoferrin, have been found in sinus secretions, whereas levels of other antimicrobial proteins have been found to be normal. No primary defects in Toll-like receptors have been found in patients with CRS, although a 50% reduced expression of Toll-like receptor 9 was reported in patients with recalcitrant nasal polyps. A polymorphism in a bitter taste receptor was recently associated with refractory CRS and persistent Pseudomonas aeruginosa infection. A downregulation of innate immunity by maladaptive T(H)2 tissue inflammation has also been described in patients with recalcitrant nasal polyps, suggesting a link to persistent infection. To date, an effective means of restoring host-microbial balance and mitigating disease in patients with CRS remains elusive.


id: cord-284053-tna7e9dw
title: Type 2 Inflammation Modulates ACE2 and TMPRSS2 in Airway Epithelial Cells
author: Kimura, Hiroki
date: 2020-05-15
txt: ./txt/cord-284053-tna7e9dw.txt
cache: ./cache/cord-284053-tna7e9dw.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0091674920306473?v=s5
doi: 10.1016/j.jaci.2020.05.004
summary:
  Objective To extend our work in interleukin (IL)-13 biology to determine if airway epithelial cell expression of two key mediators critical for SARS-CoV-2 infection, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) are modulated by IL-13. Methods We determined effects of IL-13 treatment on ACE2 and TMPRSS2 expression ex vivo in primary airway epithelial cells from participants with and without type 2 asthma obtained by bronchoscopy. Here, we demonstrate that interleukin (IL)-13, a cytokine associated 115 with type 2 (T2) asthma, suppresses ACE2 receptor expression and significantly 116 increases TMPRSS2 expression in airway epithelial cells from participants with T2 117 asthma and atopy. In addition, participants who are defined as T2 high based upon three gene 246 signatures (CLCA1, POSTN, SERPINB2) (17) also demonstrate lower nasal epithelial 247 ACE2 expression compared to the T2 low and healthy control groups (Fig 2C) .

abstract:
  Abstract Background SARS-CoV-2 has dramatically changed our world, country, communities and families. There is controversy regarding risk factors for severe COVID-19 disease. It has been suggested that asthma and allergy are not highly represented as co-morbid conditions associated with COVID-19. Objective To extend our work in interleukin (IL)-13 biology to determine if airway epithelial cell expression of two key mediators critical for SARS-CoV-2 infection, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) are modulated by IL-13. Methods We determined effects of IL-13 treatment on ACE2 and TMPRSS2 expression ex vivo in primary airway epithelial cells from participants with and without type 2 asthma obtained by bronchoscopy. We also examined expression of ACE2 and TMPRSS2 in two datasets containing gene expression data from nasal and airway epithelial cells from children and adults with asthma and allergic rhinitis. Results IL-13 significantly reduced ACE2 and increased TMPRSS2 expression ex vivo in airway epithelial cells. In two independent datasets, ACE2 expression was significantly reduced and TMPRSS2 was significantly increased in the nasal and airway epithelial cells in type 2 asthma and allergic rhinitis. ACE2 expression was significantly negatively associated with type 2 cytokines while TMPRSS2 expression was significantly positively associated with type 2 cytokines. Conclusion IL-13 modulates ACE2 and TMPRSS2 expression in airway epithelial cells in asthma. This deserves further study with regard to any effects asthma and atopy may render in the setting of COVID-19 infection.


id: cord-284576-nemh4wdo
author: Sims, Jonathan T.
date: 2020-09-10
txt: ./txt/cord-284576-nemh4wdo.txt
cache: ./cache/cord-284576-nemh4wdo.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jaci.2020.08.031
doi: 10.1016/j.jaci.2020.08.031
summary:
  Methods Blood samples from adult patients hospitalized with COVID-19 were analyzed using high-throughput and ultrasensitive proteomic platforms and compared with ageand sex-matched healthy controls to provide insights into differential regulation of 185 markers. Objective: To identify and characterize the host inflammatory response to SARS-CoV-2 59 infection, we assessed levels of proteins related to immune responses and cardiovascular 60 disease, in patients stratified as mild, moderate, and severe, versus matched healthy controls. Objective: To identify and characterize the host inflammatory response to SARS-CoV-2 59 infection, we assessed levels of proteins related to immune responses and cardiovascular 60 disease, in patients stratified as mild, moderate, and severe, versus matched healthy controls. Furthermore, in a limited series of patients who were sampled 69 frequently confirming reliability and reproducibility of our assays, we demonstrate that 70 intervention with baricitinib attenuates these circulating biomarkers associated with the cytokine 71 The COVID-19 pandemic created an overwhelming need to define host-derived molecular 96 mediators of disease severity evident in hospitalized patients.

title:
  Characterization of the Cytokine Storm Reflects Hyperinflammatory Endothelial Dysfunction in COVID-19

abstract:
  Background Physicians treating COVID-19 patients increasingly believe that the hyperinflammatory acute stage of COVID-19 results in a cytokine storm. The circulating biomarkers seen across the spectrum of COVID-19 have not been characterized compared to healthy controls, but such analyses are likely to yield insights into the pursuit of interventions that adequately reduce the burden of these cytokine storms. Objective To identify and characterize the host inflammatory response to SARS-CoV-2 infection, we assessed levels of proteins related to immune responses and cardiovascular disease, in patients stratified as mild, moderate, and severe, versus matched healthy controls. Methods Blood samples from adult patients hospitalized with COVID-19 were analyzed using high-throughput and ultrasensitive proteomic platforms and compared with age- and sex-matched healthy controls to provide insights into differential regulation of 185 markers. Results Results indicate a dominant hyperinflammatory milieu in the circulation and vascular endothelial damage markers within COVID-19 patients, and strong biomarker association with patient response as measured by Ordinal scale. As patients progress, we observe statistically significant dysregulation of IFNγ, IL-1RA, IL-6, IL-10, IL-19, MCP-1, -2, -3, CXCL9, CXCL10, CXCL5, ENRAGE and PARP-1. Furthermore, in a limited series of patients who were sampled frequently confirming reliability and reproducibility of our assays, we demonstrate that intervention with baricitinib attenuates these circulating biomarkers associated with the cytokine storm. Conclusion These wide-ranging circulating biomarkers show an association with increased disease severity and may help stratify patients and selection of therapeutic options. They also provide insights into mechanisms of SARS-CoV-2 pathogenesis and the host response.


id: cord-286477-0euaaspo
title: Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan
author: Li, Xiaochen
date: 2020-04-12
txt: ./txt/cord-286477-0euaaspo.txt
cache: ./cache/cord-286477-0euaaspo.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0091674920304954
doi: 10.1016/j.jaci.2020.04.006
summary:
  This study aims to describe and compare the 141 epidemiological, demographic, clinical, laboratory and radiological characteristics as well as the 142 complications, treatment and outcomes of hospitalized patients with nonsevere and severe 143 COVID-19. Comparison of findings between nonsevere and severe cases in 223 the patients with positive viral nucleic acid test pre-admission showed essentially the similar 224 differences to that in the total patients (see Table E1 in the Online Repository). In the follow-up period, the complications of COVID-19 were assessed , including acute 297 respiratory distress syndrome (ARDS) (38.3%), cardiac injury (21.7%), liver dysfunction (19.3%), 298 acute kidney injury (17.3%), bacteremia (7.7%), diffuse intravascular coagulation (7.7%), and 299 hyperglycemia (33.2%) ( This study provided a comprehensive data on the epidemiological, demographic, clinical, 338 laboratory, and radiological characteristics as well as the complications, treatment, and outcomes 339 of hospitalized patients with nonsevere and severe COVID-19 in Wuhan.

abstract:
  Abstract Background In December 2019, COVID-19 outbreak occurred in Wuhan. Data on the clinical characteristics and outcomes of patients with severe COVID-19 are limited. Objective The severity on admission, complications, treatment, and outcomes of COVID-19 patients were evaluated. Methods Patients with COVID-19 admitted to Tongji Hospital from January 26, 2020 to February 5, 2020 were retrospectively enrolled and followed-up until March 3, 2020. Potential risk factors for severe COVID-19 were analyzed by a multivariable binary logistic model. Cox proportional hazard regression model was used for survival analysis in severe patients. Results We identified 269 (49.1%) of 548 patients as severe cases on admission. Elder age, underlying hypertension, high cytokine levels (IL-2R, IL-6, IL-10, and TNF-a), and high LDH level were significantly associated with severe COVID-19 on admission. The prevalence of asthma in COVID-19 patients was 0.9%, markedly lower than that in the adult population of Wuhan. The estimated mortality was 1.1% in nonsevere patients and 32.5% in severe cases during the average 32 days of follow-up period. Survival analysis revealed that male, elder age, leukocytosis, high LDH level, cardiac injury, hyperglycemia, and high-dose corticosteroid use were associated with death in patients with severe COVID-19. Conclusions Patients with elder age, hypertension, and high LDH level need careful observation and early intervention to prevent the potential development of severe COVID-19. Severe male patients with heart injury, hyperglycemia, and high-dose corticosteroid use may have high risk of death.


id: cord-287063-kheek4lx
title: Influence of maternal asthma on the cause and severity of infant acute respiratory tract infections
author: Carroll, Kecia N.
date: 2012-02-14
txt: ./txt/cord-287063-kheek4lx.txt
cache: ./cache/cord-287063-kheek4lx.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S009167491200139X
doi: 10.1016/j.jaci.2012.01.045
summary:
  In this investigation that included mother-infant dyads enrolled in the Tennessee Children''s Respiratory Initiative (TCRI), we tested the hypothesis that a familial atopic predisposition was associated with viral cause and increased severity of viral acute respiratory tract infection (ARI) during infancy. In our next set of analyses we examined whether having a mother with asthma (first defined by maternal self-report and then using the atopic asthma and nonatopic asthma classifications) was associated with increased severity of the infant''s HRV-or RSV-induced ARI. [5] [6] [7] 12, 22 Because of the known differential risk of early childhood asthma after RSV-and HRV-induced infant infections, we were interested in studying whether a familial predisposition to asthma and allergies was associated with the viral cause of the infant''s ARI and the severity of the ARI.

abstract:
  BACKGROUND: Respiratory syncytial virus (RSV) and rhinovirus infections are the most common significant infant respiratory tract illnesses and are associated with increased but differential risks of childhood asthma. OBJECTIVE: We sought to determine whether maternal asthma is associated with higher odds of infant respiratory tract infection with rhinovirus versus RSV and increased infection severity. METHODS: Mother-infant dyads were enrolled from 2004-2008 during an infant respiratory tract infection (104 with rhinovirus and 279 with RSV). Mothers were classified into mutually exclusive groups (atopic asthma, nonatopic asthma, and no asthma). We determined viral cause using PCR and the severity of the infant’s respiratory tract infection using the bronchiolitis severity score. Adjusted relative odds of maternal asthma with viral cause were calculated by using logistic regression. Proportional odds models assessed the association of maternal asthma and infant infection severity. RESULTS: Infants with a mother with atopic asthma compared with infants whose mothers did not have asthma were more likely to have rhinovirus versus RSV infection (adjusted odds ratio, 2.42; 95% CI, 1.19-4.90). Similarly, among infants with rhinovirus, having a mother with atopic asthma was associated with increased infection severity (adjusted odds ratio, 3.10; 95% CI, 1.21-7.98). This relationship was not seen among infants with RSV. CONCLUSIONS: Clinically significant rhinovirus infection during infancy was more strongly associated with having a mother with atopic asthma than clinically significant RSV infection. Having a mother with atopic asthma was associated with increased severity of infant rhinovirus but not RSV infections. Infants with rhinovirus were more likely to have a familial atopic predisposition, which might partly explain the subsequent increased asthma risk.


id: cord-302886-5zjghwkq
title: Compartmental immunophenotyping in COVID-19 ARDS: A case series
author: Ronit, Andreas
date: 2020-10-23
txt: ./txt/cord-302886-5zjghwkq.txt
cache: ./cache/cord-302886-5zjghwkq.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0091674920313178
doi: 10.1016/j.jaci.2020.09.009
summary:
  OBJECTIVE: Our aim was to phenotype leukocyte subpopulations and the cytokine milieu in the lungs and blood of critically ill patients with COVID-19 acute respiratory distress syndrome (ARDS). Although the available evidence favors the presence of severe immunopathology during COVID-19 ARDS, the compartmental transmission of immunoinflammatory processes between blood and lungs remains unexplored, and characterization of distinct leukocyte subpopulations and their cytokine mediators could thus potentially reveal both novel therapeutic targets and guide the timing of treatment. In the present study, we immunophenotyped bronchoalveolar lavage fluid (BALF) and blood of mechanically ventilated patients with moderate-to-severe COVID-19 ARDS. [33] [34] [35] A recent study performed genome-wide transcriptome sequencing of RNA obtained from BALF in 3 patients with COVID-19 with unknown disease severity; it reported different expression of 1004 genes, including a high expression of cytokines such as MCP-1, IP-10, MIP-1A, and MIP-1B. In conclusion, our study provides novel phenotypic insight into the cell composition and inflammatory mediators simultaneously present in the lungs and blood in patients with COVID-19 ARDS.

abstract:
  BACKGROUND: Severe immunopathology may drive the deleterious manifestations that are observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood. OBJECTIVE: Our aim was to phenotype leukocyte subpopulations and the cytokine milieu in the lungs and blood of critically ill patients with COVID-19 acute respiratory distress syndrome (ARDS). METHODS: We consecutively included patients less than 72 hours after intubation following informed consent from their next of kin. Bronchoalveolar lavage fluid was evaluated by microscopy; bronchoalveolar lavage fluid and blood were assessed by 10-color flow cytometry and a multiplex cytokine panel. RESULTS: Four mechanically ventilated patients (aged 40-75 years) with moderate-to-severe COVID-19 ARDS were included. Immature neutrophils dominated in both blood and lungs, whereas CD4 and CD8 T-cell lymphopenia was observed in the 2 compartments. However, regulatory T cells and T(H)17 cells were found in higher fractions in the lung. Lung CD4 and CD8 T cells and macrophages expressed an even higher upregulation of activation markers than in blood. A wide range of cytokines were expressed at high levels both in the blood and in the lungs, most notably, IL-1RA, IL-6, IL-8, IP-10, and monocyte chemoattactant protein-1, consistent with hyperinflammation. CONCLUSION: COVID-19 ARDS exhibits a distinct immunologic profile in the lungs, with a depleted and exhausted CD4 and CD8 T-cell population that resides within a heavily hyperinflammatory milieu.


id: cord-303135-rx21ajiw
title: Perspective: COVID-19, implications of nasal diseases and consequences for their management
author: Jian, Li
date: 2020-05-01
txt: ./txt/cord-303135-rx21ajiw.txt
cache: ./cache/cord-303135-rx21ajiw.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jaci.2020.04.030
doi: 10.1016/j.jaci.2020.04.030
abstract: nan
summary:
  This leads us to the question whether treatment in patients with allergic rhinitis, normally INCS, or in severe patients with CRSwNP, nowadays including biologics to suppress type 2 immune reactions, should be continued in case of a SARS-CoV-2 infection. SARS-CoV-2 may also infect patients with severe asthma and CRSwNP, who might be under treatment with a type 2 biologic drug such as dupilumab, omalizumab, or mepolizumab. However, we begin to recognize that diseases of the upper airways or their management by corticosteroids and biologics do not seem to increase the risk of infection nor the risk for severe COVID-19. In research perspective, because the airway passage of nose and nasopharynx is the main entry for respiratory viruses including the SARS-CoV 2, the expression and its regulation of the ACE2 receptor and the TMPRSS2 protease are key topics for research and targets for interventions. SARS-CoV-2 entry genes are most highly expressed in nasal goblet and ciliated cells within human airways


id: cord-304140-4l574k3q
author: IJspeert, Hanna
date: 2014-01-11
txt: ./txt/cord-304140-4l574k3q.txt
cache: ./cache/cord-304140-4l574k3q.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0091674913018484
doi: 10.1016/j.jaci.2013.11.028
summary:
  METHODS: We included 22 patients with similar RAG1 mutations (c.519delT or c.368_369delAA) resulting in N-terminal truncated RAG1 protein with residual recombination activity but presenting with different clinical phenotypes. 9 Different RAG mutations can result in a broad spectrum of clinical phenotypes, including severe combined immunodeficiency (SCID), RAG deficiency (RAGD) with skin inflammation and ab T-cell expansion (classical Omenn syndrome [OS]), RAGD with skin inflammation but without T-cell expansion (incomplete OS), RAGD with maternofetal transfusion, RAGD with gd T-cell expansion, late-onset SCID, RAGD with granulomas, and RAGD with CD4 cytopenia and thymus hypoplasia. This suggests that receptor editing in this group of patients with RAGD was slightly impaired, which can either be a result of reduced recombination activity caused by the RAG1 mutation or by low B-cell numbers leading to reduced selection against autoreactive B cells.

title:
  Similar recombination-activating gene (RAG) mutations result in similar immunobiological effects but in different clinical phenotypes

abstract:
  BACKGROUND: V(D)J recombination takes place during lymphocyte development to generate a large repertoire of T- and B-cell receptors. Mutations in recombination-activating gene 1 (RAG1) and RAG2 result in loss or reduction of V(D)J recombination. It is known that different mutations in RAG genes vary in residual recombinase activity and give rise to a broad spectrum of clinical phenotypes. OBJECTIVE: We sought to study the immunologic mechanisms causing the clinical spectrum of RAG deficiency. METHODS: We included 22 patients with similar RAG1 mutations (c.519delT or c.368_369delAA) resulting in N-terminal truncated RAG1 protein with residual recombination activity but presenting with different clinical phenotypes. We studied precursor B-cell development, immunoglobulin and T-cell receptor repertoire formation, receptor editing, and B- and T-cell numbers. RESULTS: Clinically, patients were divided into 3 main categories: T(−)B(−) severe combined immunodeficiency, Omenn syndrome, and combined immunodeficiency. All patients showed a block in the precursor B-cell development, low B- and T-cell numbers, normal immunoglobulin gene use, limited B- and T-cell repertoires, and slightly impaired receptor editing. CONCLUSION: This study demonstrates that similar RAG mutations can result in similar immunobiological effects but different clinical phenotypes, indicating that the level of residual recombinase activity is not the only determinant for clinical outcome. We postulate a model in which the type and moment of antigenic pressure affect the clinical phenotypes of these patients.


id: cord-304320-1oaobtlx
author: Lee, Pui Y.
date: 2020-08-25
txt: ./txt/cord-304320-1oaobtlx.txt
cache: ./cache/cord-304320-1oaobtlx.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jaci.2020.07.033
doi: 10.1016/j.jaci.2020.07.033
summary:
  One patient developed Multisystem Inflammatory Syndrome in Children (MIS-C) in the setting of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Discussion Heterozygous loss-of-function SOCS1 mutations are associated with enhanced interferon signaling and increased immune cell activation, thereby predisposing to infection-associated autoimmune cytopenias. 2, 4 In a recent study detailing 88 outcomes of whole-genome sequencing for patients with primary immunodeficiency, SOCS1 89 haploinsufficiency was briefly described in two individuals with recurrent bacterial infections and 90 severe multi-systemic autoimmunity. Individuals with Evans syndrome (ES) present with immune thrombocytopenia (ITP), 93 autoimmune hemolytic anemia (AIHA), and/or immune neutropenia arising from either primary 94 or secondary causes. Patient 1 presented at five months of age with fever, otitis media, oral ulcers, and developed ITP (61 x 10 3 platelets/µL, normal 215-448 x 10 3 platelets/µL; Fig. 1A ). At two years 107 of age, in addition to ITP and immune neutropenia, he developed a warm antibody AIHA with a 108 hemoglobin of 4.4 g/dL (normal 10.5-13.0 g/dL).

title:
  Immune dysregulation and Multisystem Inflammatory Syndrome in Children (MIS-C) in individuals with haploinsufficiency of SOCS1

abstract:
  Abstract Objectives To identify the mechanisms underlying the development of infection-driven autoimmune cytopenias. Background We studied two unrelated patients with immune thrombocytopenia and autoimmune hemolytic anemia in the setting of acute infections. One patient developed Multisystem Inflammatory Syndrome in Children (MIS-C) in the setting of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods Whole exome sequencing was performed on both patients and the impact of the identified variants were validated by functional assays using the patients’ peripheral blood mononuclear cells (PBMCs). Results Each patient was found to have a unique heterozygous truncation variant in SOCS1. Suppressor of Cytokine Signaling 1 (SOCS1) is an essential negative regulator of type I and type II interferon (IFN) signaling. The patients’ PBMCs showed increased levels of STAT1 phosphorylation and a transcriptional signature characterized by increased expression of type I and type II interferon stimulated genes and pro-apoptotic genes. The enhanced IFN signature exhibited by the patients’ unstimulated PBMCs parallels the hyperinflammatory state associated with MIS-C, suggesting the contributions of SOCS1 in regulating the inflammatory response characteristic of MIS-C. Discussion Heterozygous loss-of-function SOCS1 mutations are associated with enhanced interferon signaling and increased immune cell activation, thereby predisposing to infection-associated autoimmune cytopenias.


id: cord-304549-e8q8mck4
title: Genetic and environmental interaction in allergy and asthma()()
author: Holgate, Stephen T.
date: 2005-11-02
txt: ./txt/cord-304549-e8q8mck4.txt
cache: ./cache/cord-304549-e8q8mck4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/10588993/
doi: 10.1016/s0091-6749(99)70005-9
summary:
  Abnormal signaling between the epithelium, which is in contact with the environment, and the underlying (myo)fibroblasts and dendritic cells indicating reactivation of the epithelial mesenchymal trophic unit, which is involved in fetal lung development and branching, provide a basis for asthma that encapsulates both T(H)2 polarization and airway wall remodeling. Asthma is a complex disorder involving a combination of genetic and environmental interactions that culminate in a specific type of inflammation involving mast cells, eosinophils, and macrophages and polarization of T cell-mediated immunity toward enhanced production of cytokines encoded in a cluster on the long arm of chromosome 5. Two fundamental approaches are being used to discover susceptibility genes in asthma and atopy: linkage analysis with functional cloning and association analysis for mutations of "candidate" genes thought to be involved in disease pathogenesis. 55 In susceptible mice genetic linkage has shown that ozone-induced lung inflammation is directed by genes encoded on chromosome 17, including the strong candidate TNF-α, a pleiotropic cytokine generated during oxidant-induced cell injury.

abstract:
  Asthma is an inflammatory disorder of the airways involving coordinate up-regulation of T(H)2-type cytokines encoded in a cluster on chromosome 5q(31-33) on T cells and inflammatory cells. There is also a requirement for local airway susceptibility factors that, together with T(H)2 polarization, results in hyperresponsiveness, variable airflow obstruction, and, over time, remodeling of the airway wall. Asthma has strong genetic and environmental components that interact both in the induction and subsequent expression of the disease phenotypes. Multiple genes are involved and probably interact. Whole genome screens are beginning to identify gene-rich regions of special relevance to asthma and atopy, although a novel disease-related gene has yet to be discovered from these. By contrast, there are a plethora of candidate genes whose function in relation to disease pathophysiologic mechanisms and response to treatment are known. Two examples are polymorphisms involving IL-4 receptors and the enzymes controlling cysteinyl leukotriene production. Abnormal signaling between the epithelium, which is in contact with the environment, and the underlying (myo)fibroblasts and dendritic cells indicating reactivation of the epithelial mesenchymal trophic unit, which is involved in fetal lung development and branching, provide a basis for asthma that encapsulates both T(H)2 polarization and airway wall remodeling. (J Allergy Clin Immunol 1999;104:1139-46.)


id: cord-313058-nrrl4kjc
author: Rivas, Magali Noval
date: 2020-10-16
txt: ./txt/cord-313058-nrrl4kjc.txt
cache: ./cache/cord-313058-nrrl4kjc.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0091674920314147
doi: 10.1016/j.jaci.2020.10.008
abstract: nan
summary:
  title: COVID-19 Associated Multisystem Inflammatory Syndrome in Children (MIS-C): a novel disease that mimics Toxic Shock Syndrome. As of mid-September, the novel severe acute respiratory syndrome coronavirus 2 26 (SARS-CoV-2) has infected more than 30 million people, resulting in approximately one 27 million deaths worldwide, including over 200,000 deaths in the USA alone. Exacerbation of the COVID-19 immune response manifested by extensive cytokines 33 release, called cytokine storm, may lead to multisystem inflammatory syndrome that is 34 fatal in 28% of cases 1 . Interestingly, SAg-induced TSS has been associated with long-term 94 neuropsychologic deficits in adults, including cognitive decline 10 , and we identified a 95 homology between the SAg motif of SARS-CoV-2 and neurotoxin-like sequences which 96 are able to bind the TCR 5 . Clinical 131 Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome 132 Temporally Associated With SARS-CoV-2

title:
  COVID-19 Associated Multisystem Inflammatory Syndrome in Children (MIS-C): a novel disease that mimics Toxic Shock Syndrome. The superantigen hypothesis


id: cord-314640-vik5rgnq
title: Aminopeptidase activity in human nasal mucosa()()()()
author: Ohkubo, Kimihiro
date: 2005-11-02
txt: ./txt/cord-314640-vik5rgnq.txt
cache: ./cache/cord-314640-vik5rgnq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/9819290/
doi: 10.1016/s0091-6749(98)70013-2
summary:
  Several aminopeptidase (Ap) activities were defined by (1) substrate specificity with leucine-enkephalin (leu-Ap) and alanine-nitroanilide (ala-Ap), (2) inhibitor studies with puromycin and bestatin, (3) enzyme activity histochemistry (zymography), (4) immunohistochemistry, and (5) gel electrophoresis. To begin defining the physiology of aminopeptidases in airways, we have used multiple assays to characterize aminopeptidase activity in soluble and membrane fractions of human nasal mucosa. Enkephalin-degrading aminopeptidase activity was expressed as picomoles of leuenkephalin metabolized per minute per milligram of protein for extracts, or as picomoles of leu-enkephalin metabolized per minute per milliliter for nasal lavage fluid samples. Alanine aminopeptidase (Ala-Ap) assay samples (25 µL) were added to cuvettes containing 1.65 mL of 10 mmol/L tris HCl buffer (pH 7.4), 1 µmol/L phosphoramidon, and 10 µmol/L captopril, mixed thoroughly, and incubated for 1 minute.

abstract:
  Background: Aminopeptidases activate bradykinin and degrade many inflammatory peptides. Objective: The objective of this study was to identify the types of aminopeptidase activities in human nasal mucosa. Methods: Human nasal mucosa was homogenized (n = 12), and cytoplasmic (S2) and membrane-rich (P2) fractions were obtained. Several aminopeptidase (Ap) activities were defined by (1) substrate specificity with leucine-enkephalin (leu-Ap) and alanine-nitroanilide (ala-Ap), (2) inhibitor studies with puromycin and bestatin, (3) enzyme activity histochemistry (zymography), (4) immunohistochemistry, and (5) gel electrophoresis. Human volunteers had methacholine, histamine, and allergen nasal provocations to determine the mechanisms controlling nasal aminopeptidase secretion in vivo. Results: P2 was the largest reservoir of puromycin-resistant aminopeptidase activity (630 pmol leu-enk/min/mg protein). S2 contained 32 pmol leu-enk/min/mg activity, with 80% representing puromycin-resistant activity and 20% puromycin-sensitive aminopeptidase (PS-Ap). Ala-Ap was detected in both P2 and S2 fractions and was localized by zymography to epithelial and gland cells. Anti–rat brain–soluble PS-Ap IgG detected immunoreactive material in epithelium, glands, and endothelium. In nasal provocation studies, leu-AP correlated with glandular exocytosis but not vascular leak. Conclusions: The predominant aminopeptidase in human nasal epithelial and submucosal gland cells was membrane-bound puromycin-resistant aminopeptidase. A novel soluble puromycin-resistant aminopeptidase and lower amounts of soluble PS-Ap were also detected. (J Allergy Clin Immunol 1998;102:741-50.)


id: cord-323695-jkik03lb
author: Paolo, Gisondi
date: 2020-11-05
txt: ./txt/cord-323695-jkik03lb.txt
cache: ./cache/cord-323695-jkik03lb.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S009167492031558X?v=s5
doi: 10.1016/j.jaci.2020.10.032
summary:
  Objective investigating the incidence of hospitalization and death for COVID-19 in a large sample of patients with plaque psoriasis receiving biologic therapies compared with the general population. Materials and methods This is a retrospective multicenter cohort study including patients with chronic plaque psoriasis (n=6,501) being treated with biologic therapy and regularly followed up at the Divisions of Dermatology of several main hospitals in the Northern Italian cities of Verona, Padua, Vicenza, Modena, Bologna, Piacenza, Turin, and Milan. Incidence rates (IR) of hospitalization and death per 10,000 person-months with exact mid-p 95% confidence intervals (CI) and standardized incidence ratios (SIR) were estimated in the psoriasis patients and compared with the general population in the same geographic areas. We would not advise biologic discontinuation in patients on treatment since more than 6 months and not infected with SARS-CoV-2 to prevent hospitalization and death from COVID-19. In this study, we evaluated the incidence of hospitalization and death for COVID-19 in a large sample of patients with plaque psoriasis receiving biologic therapies compared with the general population.

title:
  Incidence rates of hospitalization and death from COVID-19 in patients with psoriasis receiving biological treatment: a Northern Italy experience

abstract:
  Introduction Whether biologic therapies enhance the risk of COVID-19 or affect the disease outcome in patients with chronic plaque psoriasis remains to be ascertained. Objective investigating the incidence of hospitalization and death for COVID-19 in a large sample of patients with plaque psoriasis receiving biologic therapies compared with the general population. Materials and methods This is a retrospective multicenter cohort study including patients with chronic plaque psoriasis (n=6,501) being treated with biologic therapy and regularly followed up at the Divisions of Dermatology of several main hospitals in the Northern Italian cities of Verona, Padua, Vicenza, Modena, Bologna, Piacenza, Turin, and Milan. Incidence rates (IR) of hospitalization and death per 10,000 person-months with exact mid-p 95% confidence intervals (CI) and standardized incidence ratios (SIR) were estimated in the psoriasis patients and compared with the general population in the same geographic areas. Results The IR of hospitalization for COVID-19 was 11.7 (95% CI: 7.2-18.1) per 10,000 person-months in psoriasis patients and 14.4 (95% CI: 14.3-14.5) in the general population; the IR of death from COVID-19 was 1.3 (95% CI: 0.2-4.3) and 4.7 (95% CI: 4.6-4.7) in psoriasis patients and the general population, respectively. The SIR of hospitalization and death in psoriasis patients compared with the general population was 0.94 (95% CI: 0.57-1.45; p=0.82) and 0.42 (95% CI: 0.07-1.38; p=0.19) respectively. Conclusions Our data did not show any adverse impact of biologics on COVID-19 outcome in psoriasis patients. We would not advise biologic discontinuation in patients on treatment since more than 6 months and not infected with SARS-CoV-2 to prevent hospitalization and death from COVID-19.


id: cord-327076-qq5499qg
author: Siniorakis, Eftychios
date: 2020-09-29
txt: ./txt/cord-327076-qq5499qg.txt
cache: ./cache/cord-327076-qq5499qg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33019963/
doi: 10.1016/j.jaci.2020.09.004
abstract: nan
summary:
  title: COVID-19 and upper respiratory tract: Collecting swab specimens from patients inhaling corticosteroids Correspondence COVID-19 and upper respiratory tract: Collecting swab specimens from patients inhaling corticosteroids Q 1 To the Editor: Jian et al 1 in a recent article refer to the immune reaction of the upper respiratory tract (URT) in patients infected by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 (coronavirus disease 2019 [COVID-19] pandemic). The authors wonder about the consequences of inhaled corticosteroids (ICSs) on immune reaction. With the URT sprayed by ICSs, we are wondering about the diagnostic accuracy of specimens collected. With this in mind, swabbing the URT of coronavirus-infected patients under an ICS regimen renders the quality of the viral load collected questionable. With all this scepticism in our minds, we are preparing ourselves to cope with the intricacies of triaging in a COVID-19 era, performing with responsibility the swabbing techniques, ensuring specimens of high diagnostic accuracy.

title:
  COVID-19 and upper respiratory tract: Collecting swab specimens from patients inhaling corticosteroids


id: cord-328210-qhl429fm
author: Gelardi, Matteo
date: 2020-06-24
txt: ./txt/cord-328210-qhl429fm.txt
cache: ./cache/cord-328210-qhl429fm.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0091674920306783
doi: 10.1016/j.jaci.2020.04.049
abstract: nan
summary:
  title: The clinical relevance of the clinical cytological grading in patients with chronic rhinosinusitis with nasal polyps The clinical relevance of the clinical cytological grading in patients with chronic rhinosinusitis with nasal polyps Smell dysfunction is a common symptom and has a diagnostic value in the workup of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) as recently outlined by Mullol et al. As a consequence, a clinical cytological grading (CCG), including the documentation of possible asthma, allergy, or aspirin sensitivity comorbidity, and the presence of eosinophils and/or mast cells in the nose, has been proposed as a precision medicine-based approach in the management of patients with CRSwNP. Non-surgical management of chronic rhinosinusitis with nasal polyps based on clinical cytological grading: a precision medicine-based approach Olfactory dysfunction in patients with chronic rhinosinusitis with nasal polyps is associated with clinical-cytological grading severity

title:
  The clinical relevance of the clinical cytological grading in patients with chronic rhinosinusitis with nasal polyps


id: cord-334801-p5mxc694
title: COVID-19 risk stratification algorithms based on sTREM-1 and IL-6 in emergency department
author: Van Singer, Mathias
date: 2020-10-09
txt: ./txt/cord-334801-p5mxc694.txt
cache: ./cache/cord-334801-p5mxc694.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33045281/
doi: 10.1016/j.jaci.2020.10.001
summary:
  We evaluated the accuracy of clinical signs and these biomarkers in predicting 30-day intubation/mortality, and oxygen requirement by calculating the area under the receiver operating characteristic curve (AUROC) and by classification and regression tree analysis. sTREM-1-and IL-6-based algorithms are 54 highly sensitive to identify patients with adverse outcome and could serve as early triage The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to 84 surges of patients that can overwhelm health systems (1) (2) (3) (4) . Current prediction 90 models to support clinical decision making for Coronavirus disease (COVID-19) patients 91 were developed based on demographics, clinical signs and symptoms, imaging techniques, 92 biomarkers or a combination of these variables, however most are poorly validated and at risk 93 of bias (10). 282 The CRT analysis performed with all clinical signs, severity scores and biomarkers to predict Since we could also use this triage tool to identify patients at high risk of poor outcomes, we 290 tested this algorithm to predict 7-and 30-day intubation/death.

abstract:
  Background The COVID-19 pandemic has led to surges of patients presenting to emergency departments (ED) and potentially overwhelming health systems. Objective This study aimed to assess the predictive accuracy of host biomarkers at clinical presentation to the ED for adverse outcome. Methods Prospective observational study of PCR-confirmed COVID-19 patients in the ED of a Swiss hospital. Concentrations of inflammatory and endothelial dysfunction biomarkers were determined at clinical presentation. We evaluated the accuracy of clinical signs and these biomarkers in predicting 30-day intubation/mortality, and oxygen requirement by calculating the area under the receiver operating characteristic curve (AUROC) and by classification and regression tree analysis. Results Of 76 COVID-19 patients included, 24 were outpatients or hospitalized without oxygen requirement, 35 hospitalized with oxygen requirement and 17 intubated/died. We found that soluble triggering receptor expressed on myeloid cells (sTREM-1) had the best prognostic accuracy for 30-day intubation/mortality (AUROC 0.86; 95% CI 0.77-0.95) and interleukin-6 (IL-6) measured at presentation to the ED had the best accuracy for 30-day oxygen requirement (AUROC 0.84; 95% CI 0.74-0.94) .An algorithm based on respiratory rate and sTREM-1 predicted 30-day intubation/mortality with 94% sensitivity and 0.1 NLR. An IL-6-based algorithm had 98% sensitivity and 0.04 negative likelihood ratio (NLR) for 30-day oxygen requirement. Conclusion sTREM-1 and IL-6 concentrations in COVID-19 in the ED have good predictive accuracy for intubation/mortality and oxygen requirement. sTREM-1- and IL-6-based algorithms are highly sensitive to identify patients with adverse outcome and could serve as early triage tools.


id: cord-341650-f8orw6ro
author: Li, Hailan
date: 2020-09-17
txt: ./txt/cord-341650-f8orw6ro.txt
cache: ./cache/cord-341650-f8orw6ro.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jaci.2020.09.002
doi: 10.1016/j.jaci.2020.09.002
abstract: nan
summary:
  title: Regarding "Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial" Regarding ''''Ruxolitinib in Q 1 treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, singleblind, randomized controlled trial'''' Q 2 To the Editor: We read with great interest the article titled ''''Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial'''' by Cao et al. 1 The study, which finally included 41 patients, evaluated the efficacy and safety of ruxolitinib for severe COVID-19 cases. First, the duration from illness onset to randomization, 22 days for the control group and 20 days for the ruxolitinib group, was not appropriate because according to literature reports, 2-4 the course (from illness onset to discharge) of severe patients was about 27 to 30 days. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): a multicenter, singleblind, randomized controlled trial Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study

title:
  Regarding “Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial”


id: cord-344759-7zs389m9
author: Shilts, Meghan H.
date: 2020-07-03
txt: ./txt/cord-344759-7zs389m9.txt
cache: ./cache/cord-344759-7zs389m9.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0091674920309520?v=s5
doi: 10.1016/j.jaci.2020.06.023
abstract: nan
summary:
  128 129 One hundred and five (~34%) of the 309 infants with RSV-only ARIs enrolled in INSPIRE had 130 ≥1 nasal wash with 16S rRNA sequencing and immune mediator data available -obtained as Page 7 part of separate projects 5, 6 -and were thus included in our study. Cluster #1 also mainly included 147 infants with a higher relative abundance of Haemophilus in their nasopharynx (Figure 1) In unadjusted analyses, the nasopharyngeal relative abundance of Haemophilus was positively 152 correlated with the levels of 39 (~75%) of the 52 local immune mediators after controlling for 153 multiple comparisons (Figure 2A and Table E3 in the Online Repository). 8, 9 195 196 Our study has multiple strengths, including the population-based design of the parent study, the 197 close surveillance during the infants'' first winter viral season to capture their initial RSV ARI, 198 the use of next-generation sequencing and high-throughput immune assays, and the use of 199 statistical analysis adjusting for potential confounders.

title:
  Nasopharyngeal Haemophilus and Local Immune Response during Infant Respiratory Syncytial Virus Infection


id: cord-346835-gg3xespb
author: Navel, Valentin
date: 2020-04-26
txt: ./txt/cord-346835-gg3xespb.txt
cache: ./cache/cord-346835-gg3xespb.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0091674920305753
doi: 10.1016/j.jaci.2020.04.026
abstract: nan
summary:
  title: Will environmental impacts of social distancing due to the SARS-CoV-2 pandemic decrease allergic disease? The burden of climatic change and air pollution represents a massive challenge for Humanity, affecting the development of allergic diseases and upsetting the exposome. 1 Air pollution, a causative factor of climate change, contributes to nine million deaths by years, 2 and more than 500 million people have an allergic disease around the world. Air pollution is a causative factor for both various symptoms such as bronchospasm, rhinorrhea, eye redness, and irritation, as well as various allergic diseases such as asthma, chronic rhinitis, nasal polyposis, atopic dermatitis, seasonal or perennial allergic conjunctivitis, and vernal or atopic keratoconjunctivitis. 7 Similar decrease was measured in most megalopolis of developing countries around the world where containment was set for limiting the spreading of the SARS-CoV-2 ( Figure 1 ). Climate Change and the Impact on Respiratory and Allergic Disease Effects on asthma and respiratory allergy of Climate change and air pollution

title:
  Will environmental impacts of social distancing due to the SARS-CoV-2 pandemic decrease allergic disease?


id: cord-347512-veavzt6d
title: Elevated plasma sTIM-3 levels in severe Covid-19 patients
author: Ueland, Thor
date: 2020-09-21
txt: ./txt/cord-347512-veavzt6d.txt
cache: ./cache/cord-347512-veavzt6d.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0091674920313142
doi: 10.1016/j.jaci.2020.09.007
summary:
  Methods We analyzed plasma levels of myeloperoxidase (MPO, neutrophil activation), soluble (s) CD25 and soluble T cell immunoglobulin mucin domain-3 (sTIM-3) (markers of T cell activation and exhaustion) and sCD14 and sCD163 (markers of monocyte/macrophage activation) in 39 COVID-19 infected patients at hospital admission and two additional times during the first 10 days in relation to the need for ICU treatment. Results Our major findings were: (i) Severe clinical outcome (ICU) was associated with high plasma levels sTIM-3 and MPO suggesting activated and potentially exhausted T cells and activated neutrophils, respectively. Patients admitted to ICU were characterized by high levels of the T cell activation marker sCD25 and sTIM-3 in à priori analysis, and for sTIM-3 also in posthoc testing. In contrast to the T cell markers and MPO, plasma levels of sCD14 and sCD163, reflecting activation of monocytes/macrophages, were similar in ICU and non-ICU patients ( Figure 1 ).

abstract:
  Background The pathogenesis of COVID-19 is still incompletely understood, but seems to involve immune activation and immune dysregulation. Objective We examined parameters of activation of different leukocyte subsets in COVID-19 infected patients in relation to disease severity. Methods We analyzed plasma levels of myeloperoxidase (MPO, neutrophil activation), soluble (s) CD25 and soluble T cell immunoglobulin mucin domain-3 (sTIM-3) (markers of T cell activation and exhaustion) and sCD14 and sCD163 (markers of monocyte/macrophage activation) in 39 COVID-19 infected patients at hospital admission and two additional times during the first 10 days in relation to the need for ICU treatment. Results Our major findings were: (i) Severe clinical outcome (ICU) was associated with high plasma levels sTIM-3 and MPO suggesting activated and potentially exhausted T cells and activated neutrophils, respectively. (ii) In contrast, sCD14 and sCD163 showed no association with need for ICU treatment. (iii) sCD25, sTIM-3 and MPO were inversely correlated with the degree of respiratory failure as assessed by P/F ratio and positively correlated with the cardiac marker N-terminal pro-B-type natriuretic peptide. Conclusion Our findings suggest that neutrophil activation and in particular activated T cells may play an important role in the pathogenesis of COVID-19 infection, suggesting that T cell targeted treatment options and downregulation of neutrophil activation could be of importance in this disorder.


id: cord-349754-v6lll1xy
author: Zhu, Zhaozhong
date: 2020-07-18
txt: ./txt/cord-349754-v6lll1xy.txt
cache: ./cache/cord-349754-v6lll1xy.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jaci.2020.07.004
doi: 10.1016/j.jaci.2020.07.004
summary:
  title: Investigating asthma heterogeneity through shared and distinct genetics: insights from genome-wide cross-trait analysis The genome-wide cross-trait analysis features in several analytical aspects: genetic correlation, cross-trait meta-analysis, Mendelian randomization, polygenic risk score and functional analysis. A major advantage going from phenotypic correlations to genetic 138 correlations is to improve understanding of the mechanism(s)-shared genetic components can 139 be identified at different levels, from whole genome to individual variants, providing insights 140 into the reasons why asthma and coexistent diseases or traits are correlated. 26-29 A genome-wide cross-trait analysis features several analyses: 173 genetic correlation, cross-trait meta-analysis, Mendelian randomization, polygenic risk score, 174 and GWAS functional analysis. Of note, the human leukocyte antigen (HLA) region (chr6: 25-34Mb) was found to be 262 shared in the cross-trait meta-analysis of allergic disease and asthma as well as that between 263 major depressive disorder and asthma. Genome-wide association study (GWAS) An analytical method that tests the association between each genetic variant and a specific phenotype (a disease status or a quantitative trait).

title:
  Investigating asthma heterogeneity through shared and distinct genetics: insights from genome-wide cross-trait analysis

abstract:
  Abstract: Asthma is a heterogeneous respiratory disease reflecting distinct pathobiological mechanisms. These mechanisms are based, at least partly, on different genetic factors shared by many other conditions, such as allergic diseases and obesity. Investigating the shared genetic effects enables better understanding the mechanisms of phenotypic correlations and is less subject to confounding by environmental factors. The increasing availability of large-scale genome-wide association study (GWAS) for asthma has enabled researchers to examine the genetic contributions to the epidemiological associations between asthma subtypes, and those between coexisting diseases/traits and asthma. Studies have found not only shared but also distinct genetic components between asthma subtypes, indicating that the heterogeneity is related to distinct genetics. This review summarizes a recently compiled analytical approach—genome-wide cross-trait analysis—to determine shared and distinct genetic architecture. The genome-wide cross-trait analysis features in several analytical aspects: genetic correlation, cross-trait meta-analysis, Mendelian randomization, polygenic risk score and functional analysis. In this article, we discuss in detail the scientific goals that can be achieved by these analyses, their advantages and limitations. We also make recommendations for future directions: 1) ethnicity-specific asthma GWASs, and 2) application of cross-trait methods to multi-omics data to dissect the heritability found in GWAS. Finally, these analytical approaches are also applicable to complex and heterogeneous traits beyond asthma.


