Materiały źródłowe

• #1 Bronchiolitis – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bronchiolitis/symptoms-causes/syc-20351565

  Bronchiolitis happens when a virus infects the bronchioles, which are the smallest airways in the lungs. The infection makes the bronchioles swollen and irritated. Mucus collects in these airways, which makes it difficult for air to flow freely in and out of the lungs. […] Bronchiolitis is usually caused by the respiratory syncytial virus (RSV). RSV is a common virus that infects just about every child by 2 years of age. Outbreaks of RSV infection often happen during the colder months of the year in some locations or the rainy season in others. A person can get it more than once. Bronchiolitis also can be caused by other viruses, including those that cause the flu or the common cold. […] The viruses that cause bronchiolitis are easily spread. You can get them through droplets in the air when someone who is sick coughs, sneezes or talks. You also can get them by touching shared items such as dishes, doorknobs, towels or toys and then touching your eyes, nose or mouth.

• #2 Respiratory Syncytial Virus Bronchiolitis in Children | AAFP

  https://www.aafp.org/pubs/afp/issues/2017/0115/p94.html

  Bronchiolitis is a common lower respiratory tract infection in infants and young children, and respiratory syncytial virus (RSV) is the most common cause. […] Although the exact mechanism is unclear, it is likely that direct viral cytotoxic injury has a role in the pathogenesis of RSV infections. This leads to necrosis of the epithelial cells of the small airways, and the sloughed cells and mucus cause plugging of the bronchioles that leads to hyperinflation and atelectasis.

• #3 Bronchiolitis-updated | Calgary Guide

  https://calgaryguide.ucalgary.ca/bronchiolitis-updated/bronchiolitis-updated/

  Bronchiolitis: Pathogenesis and clinical findings Viral pathogen, most commonly respiratory syncytial virus (RSV) but can be others such as rhinovirus, adenovirus, parainfluenza, influenza, and coronaviruses initially colonizes the nasopharyngeal mucosa […] Virus travels via the epithelium to the lower airways to the terminal bronchioles (small airways) […] RSV-fusion protein facilitates fusion of the virus to the host cell and directs viral penetration as well as facilitates fusion of the infected cell with its healthy neighbors […] Cytokines are released into circulation thermo-regulatory set-point at the hypothalamus […] Protein and fluid leak into nasopharyngeal interstitium […] Capillary permeability […] Protein and fluid leak into the bronchiole interstitium, accumulating around airway walls

• #4 Pediatric Bronchiolitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519506/

  Most viral pathogens enter the body through the nasopharynx and oral or conjunctival mucosal surfaces. RSV, the most common cause of bronchiolitis, initially replicates in the nasopharynx before spreading to respiratory tract cells lining the terminal bronchioles. RSV primarily infects type I alveolar pneumocytes, with some involvement of type II alveolar pneumocytes, while sparing basal cells. Aspiration of upper respiratory tract secretions and subsequent cell-to-cell spread typically leads to lower respiratory tract involvement within 1 to 3 days of the initial upper respiratory infection. […] Infection of the respiratory tract cells lining the terminal bronchioles leads to cellular damage and activates local inflammatory responses. The virus-induced inflammation triggers the release of cytokines and chemokines, resulting in edema, increased mucus production, and the recruitment of additional inflammatory cells to the respiratory tract.

• #5 Pediatric Bronchiolitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519506/

  Most viral pathogens enter the body through the nasopharynx and oral or conjunctival mucosal surfaces. RSV, the most common cause of bronchiolitis, initially replicates in the nasopharynx before spreading to respiratory tract cells lining the terminal bronchioles. RSV primarily infects type I alveolar pneumocytes, with some involvement of type II alveolar pneumocytes, while sparing basal cells. Aspiration of upper respiratory tract secretions and subsequent cell-to-cell spread typically leads to lower respiratory tract involvement within 1 to 3 days of the initial upper respiratory infection. […] Infection of the respiratory tract cells lining the terminal bronchioles leads to cellular damage and activates local inflammatory responses. The virus-induced inflammation triggers the release of cytokines and chemokines, resulting in edema, increased mucus production, and the recruitment of additional inflammatory cells to the respiratory tract.

• #6 Pathophysiology and pathogenesis or viral bronchiolitis. Recent advances and perspectives.

  https://www.medigraphic.com/cgi-bin/new/resumenI.cgi?IDARTICULO=6295

  After an incubation period of two to eight days, respiratory syncytial virus (RSV), parainfluenza viruses and rhinoviruses replicate in the nasopharyngeal epithelium and spread to the lower respiratory tract one to three days later. The inflammation response to viral bronchiolitis is characterized by necrosis and sloughing of the small airways epithelium, with edema and increased secretion of mucus, which occludes the flow of terminal airways. The resulting clinical manifestations are the hallmark of bronchiolitis: wheezing, alveolar hyperinflation and atelectasis. […] About 50 percent of the infants hospitalized with RSV have subsequent wheezing episodes with recruitment of TH-2 cells, eosinophils and release of soluble mediators, such as histamine, kinins, and leukotrienes. Severe wheezing has been correlated with increased IgE antibodies levels and the release of cells and inflammatory mediators that may further affect neural pathways with bronchial hyperreactivity, which are common features of viral bronchiolitis and allergic asthma. […] Research studies have raised the question of whether the current epidemic of asthma could be diminished by controlling RVS and parainfluenza virus infections.

• #7 Bronchiolitis – McMaster Pathophysiology Review

  https://www.pathophys.org/bronchiolitis/

  Direct viral inoculation of respiratory epithelium leads to inflammation of small airways. The mechanisms by which RSV spreads along the respiratory tract are still not fully known, but likely include cell-to-cell transfer along intracytoplasmic bridges or aspiration of nasopharyngeal secretions. […] RSV can also damage cells of the structural airway and impair immune cells residing in the lungs. […] The hosts inflammatory response contributes to the pathophysiology and symptomatology: Host cells recognize RSV via toll-like receptors, and secrete inflammatory cytokines (e.g. IFN-, IL-1, IL-4, IL-8). These effectors influence the local tissue environment directly, and also further the inflammatory process by drawing immune cells from the periphery. Many cytokines have known roles in the pathogenesis of RSV bronchiolitis, and some are even implicated in sustaining the infection. For example, the helper T cells main cytokine, IL-17, enhances RSV infection by increasing mucus production, inhibiting CD8 T cell activation, and reducing viral clearance.

• #8 Pediatric Bronchiolitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519506/

  Most viral pathogens enter the body through the nasopharynx and oral or conjunctival mucosal surfaces. RSV, the most common cause of bronchiolitis, initially replicates in the nasopharynx before spreading to respiratory tract cells lining the terminal bronchioles. RSV primarily infects type I alveolar pneumocytes, with some involvement of type II alveolar pneumocytes, while sparing basal cells. Aspiration of upper respiratory tract secretions and subsequent cell-to-cell spread typically leads to lower respiratory tract involvement within 1 to 3 days of the initial upper respiratory infection. […] Infection of the respiratory tract cells lining the terminal bronchioles leads to cellular damage and activates local inflammatory responses. The virus-induced inflammation triggers the release of cytokines and chemokines, resulting in edema, increased mucus production, and the recruitment of additional inflammatory cells to the respiratory tract.

• #9 Bronchiolitis – Armando Hasudungandownloadbookprintpencilchevron-leftchevron-righttwitterfacebookhand-o-rightfilterchainlist-ulenvelopelinkedinangle-rightangle-upyoutubexinginstagramlong-arrow-uppaper-planepinterest-pwhatsappcommentingaddress-book-ox-twit

  https://armandoh.org/disease/paediatrics-bronchiolitis/?srsltid=AfmBOopLDfEVmgEzDf31xcugmxMXaCN8ZHqqExpfCaNraBRtgeAO4qaI

  An RSV infection begins with replication of the virus in the nasopharynx. The virus spreads to the small bronchiolar epithelium lining the small airways within the lungs, and a lower respiratory tract infection can begin in one to three days. If a lower respiratory tract infection occurs, it causes edema, increased mucus production, and eventual necrosis and regeneration of these epithelial cells. This leads to small airway obstruction, air trapping, and increased airway resistance.

• #10 Bronchiolitis-updated | Calgary Guide

  https://calgaryguide.ucalgary.ca/bronchiolitis-updated/bronchiolitis-updated/

  Bronchiolitis: Pathogenesis and clinical findings Viral pathogen, most commonly respiratory syncytial virus (RSV) but can be others such as rhinovirus, adenovirus, parainfluenza, influenza, and coronaviruses initially colonizes the nasopharyngeal mucosa […] Virus travels via the epithelium to the lower airways to the terminal bronchioles (small airways) […] RSV-fusion protein facilitates fusion of the virus to the host cell and directs viral penetration as well as facilitates fusion of the infected cell with its healthy neighbors […] Cytokines are released into circulation thermo-regulatory set-point at the hypothalamus […] Protein and fluid leak into nasopharyngeal interstitium […] Capillary permeability […] Protein and fluid leak into the bronchiole interstitium, accumulating around airway walls

• #11 Pediatric Bronchiolitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519506/

  Most viral pathogens enter the body through the nasopharynx and oral or conjunctival mucosal surfaces. RSV, the most common cause of bronchiolitis, initially replicates in the nasopharynx before spreading to respiratory tract cells lining the terminal bronchioles. RSV primarily infects type I alveolar pneumocytes, with some involvement of type II alveolar pneumocytes, while sparing basal cells. Aspiration of upper respiratory tract secretions and subsequent cell-to-cell spread typically leads to lower respiratory tract involvement within 1 to 3 days of the initial upper respiratory infection. […] Infection of the respiratory tract cells lining the terminal bronchioles leads to cellular damage and activates local inflammatory responses. The virus-induced inflammation triggers the release of cytokines and chemokines, resulting in edema, increased mucus production, and the recruitment of additional inflammatory cells to the respiratory tract.

• #12 Bronchiolitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441959/

  Bronchiolitis is a common lung infection in young individuals. The viral infection involves the lower respiratory tract and can present with signs of mild to moderate respiratory distress. Bronchiolitis is a mild, self-limited infection in the majority of children but may sometimes progress to respiratory failure in infants. […] The clinical features of bronchiolitis are primarily due to airway obstruction and diminished lung compliance. The virus infects the epithelial cells in the airways and induces an inflammatory reaction that leads to ciliary dysfunction and cell death. The accumulated debris, edema of the airways, and narrowing of the airways due to the release of cytokines eventually lead to symptoms and lowered lung compliance. […] Typical features include: Air trapping, Increased mucus production, Atelectasis, Labored breathing, Decreased ventilation.

• #13 Bronchiolitis – McMaster Pathophysiology Review

  https://www.pathophys.org/bronchiolitis/

  Direct viral inoculation of respiratory epithelium leads to inflammation of small airways. The mechanisms by which RSV spreads along the respiratory tract are still not fully known, but likely include cell-to-cell transfer along intracytoplasmic bridges or aspiration of nasopharyngeal secretions. […] RSV can also damage cells of the structural airway and impair immune cells residing in the lungs. […] The hosts inflammatory response contributes to the pathophysiology and symptomatology: Host cells recognize RSV via toll-like receptors, and secrete inflammatory cytokines (e.g. IFN-, IL-1, IL-4, IL-8). These effectors influence the local tissue environment directly, and also further the inflammatory process by drawing immune cells from the periphery. Many cytokines have known roles in the pathogenesis of RSV bronchiolitis, and some are even implicated in sustaining the infection. For example, the helper T cells main cytokine, IL-17, enhances RSV infection by increasing mucus production, inhibiting CD8 T cell activation, and reducing viral clearance.

• #14 Pediatric Bronchiolitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519506/

  Dead bronchial epithelial and inflammatory cells slough into the inflamed, mucus-filled airways, further exacerbating small airway obstruction. Infants are particularly prone to airway obstruction due to the small caliber of their airways, which can result in wheezing and air trapping. Atelectasis of the lung parenchyma and resulting hypoxemia further contribute to varying levels of respiratory distress. […] The pathology of bronchiolitis involves necrosis of airway epithelial cells, along with proliferation of the bronchiolar epithelium and cellular infiltration of monocytes and T cells affecting both bronchial and pulmonary arterioles. Neutrophilic infiltration can also be observed between the vascular structures and small airways. Airway obstruction and air trapping result in increased airway resistance. Additionally, neutrophilia is frequently observed in pediatric cases following bronchoalveolar lavage.

• #15 Pediatric Bronchiolitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519506/

  Dead bronchial epithelial and inflammatory cells slough into the inflamed, mucus-filled airways, further exacerbating small airway obstruction. Infants are particularly prone to airway obstruction due to the small caliber of their airways, which can result in wheezing and air trapping. Atelectasis of the lung parenchyma and resulting hypoxemia further contribute to varying levels of respiratory distress. […] The pathology of bronchiolitis involves necrosis of airway epithelial cells, along with proliferation of the bronchiolar epithelium and cellular infiltration of monocytes and T cells affecting both bronchial and pulmonary arterioles. Neutrophilic infiltration can also be observed between the vascular structures and small airways. Airway obstruction and air trapping result in increased airway resistance. Additionally, neutrophilia is frequently observed in pediatric cases following bronchoalveolar lavage.

• #16 Bronchiolitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/961963-overview

  Proliferation of goblet cells results in excessive mucus production, whereas epithelial regeneration with nonciliated cells impairs elimination of secretions. […] Lymphocytic infiltration may result in submucosal edema. […] Cytokines and chemokines, released by infected respiratory epithelial cells, amplify the immune response by increasing cellular recruitment into infected airways. […] The inflammation, edema, and debris result in obstruction of bronchioles, leading to hyperinflation, increased airway resistance, atelectasis, and ventilation-perfusion mismatching. […] Infants are affected most often because of their small airways, high closing volumes, and insufficient collateral ventilation. […] Recovery begins with regeneration of bronchiolar epithelium after 3-4 days; however, cilia do not appear for as long as 2 weeks. […] Infection is spread by direct contact with respiratory secretions. […] Virtually all children experience RSV infection within the first 3 years of life, but a previous infection does not convey complete immunity.

• #17 Bronchiolitis – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/respiratory-disorders-in-young-children/bronchiolitis

  The virus spreads from the upper respiratory tract to the medium and small bronchi and bronchioles, causing epithelial necrosis and initiating an inflammatory response. The developing edema and exudate result in partial obstruction, which is most pronounced on expiration and leads to alveolar air trapping. Complete obstruction and absorption of the trapped air may lead to multiple areas of atelectasis, which can be exacerbated by breathing high inspired oxygen concentrations. […] Edema and exudate in medium and small bronchi and bronchioles cause partial obstruction and air trapping; atelectasis and/or pneumonia cause hypoxemia in more severe cases.

• #18 Bronchiolitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/961963-overview

  Bronchiolitis is an acute inflammatory injury of the bronchioles that is usually caused by a viral infection. […] Bronchiolar injury and the consequent interplay between inflammatory and mesenchymal cells can lead to diverse pathologic and clinical syndromes. […] The effects of bronchiolar injury may begin 18 to 24 hours after the infection and include the following: Increased mucus secretion, bronchial obstruction and constriction, alveolar cell death, mucus debris, viral invasion, air trapping, atelectasis, reduced ventilation that leads to ventilation-perfusion mismatch, labored breathing. […] Complex immunologic mechanisms play a role in the pathogenesis of bronchiolitis. […] Necrosis of the respiratory epithelium is one of the earliest lesions in bronchiolitis and occurs within 24 hours of acquisition of infection.

• #19 Bronchiolitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/961963-overview

  Bronchiolitis is an acute inflammatory injury of the bronchioles that is usually caused by a viral infection. […] Bronchiolar injury and the consequent interplay between inflammatory and mesenchymal cells can lead to diverse pathologic and clinical syndromes. […] The effects of bronchiolar injury may begin 18 to 24 hours after the infection and include the following: Increased mucus secretion, bronchial obstruction and constriction, alveolar cell death, mucus debris, viral invasion, air trapping, atelectasis, reduced ventilation that leads to ventilation-perfusion mismatch, labored breathing. […] Complex immunologic mechanisms play a role in the pathogenesis of bronchiolitis. […] Necrosis of the respiratory epithelium is one of the earliest lesions in bronchiolitis and occurs within 24 hours of acquisition of infection.

• #20 Pediatric Bronchiolitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519506/

  Dead bronchial epithelial and inflammatory cells slough into the inflamed, mucus-filled airways, further exacerbating small airway obstruction. Infants are particularly prone to airway obstruction due to the small caliber of their airways, which can result in wheezing and air trapping. Atelectasis of the lung parenchyma and resulting hypoxemia further contribute to varying levels of respiratory distress. […] The pathology of bronchiolitis involves necrosis of airway epithelial cells, along with proliferation of the bronchiolar epithelium and cellular infiltration of monocytes and T cells affecting both bronchial and pulmonary arterioles. Neutrophilic infiltration can also be observed between the vascular structures and small airways. Airway obstruction and air trapping result in increased airway resistance. Additionally, neutrophilia is frequently observed in pediatric cases following bronchoalveolar lavage.

• #21 Bronchiolitis – Clinical features – Management – TeachMePaeds

  https://teachmepaediatrics.com/respiratory/lower-respiratory-tract/bronchiolitis/

  Bronchioles are airways in the lungs which are less than 2mm wide and do not contain cartilage or submucosal glands. There are several physiological changes which occur in response to viral infection: […] The combination of mucus, oedema and increased cells in the bronchioles leads to a ball-valve effect resulting in hyperinflation, increased airway resistance, atelectasis (lung collapse) and ventilation-perfusion mismatch, which together result in the clinical features typically seen in bronchiolitis (1).

• #22 The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis

  https://www.mdpi.com/1999-4915/12/8/808

  The prevailing view is that severe bronchiolitis results from excessive inflammation and consequent immunopathology, rather than virus-induced cytology. Neutrophils are the dominant inflammatory cell in the airways of paediatric patients with RSV bronchiolitis, accounting for up to 80% of the cellular infiltrate at peak symptomatology, and yet the precise contribution of neutrophils to antiviral immunity remains ill-defined. […] Here, we review the multifaceted roles of the neutrophil in host defence, antiviral immunity, and immunopathogenesis in the context of viral LRIs. We find that neutrophils make an important contribution to innate antiviral immunity and help to optimise the induction of an effective adaptive immune response. However, as a consequence of their ability to initiate and amplify the magnitude of an inflammatory reaction, it is clear that a failure to adequately regulate this response can lead to excessive collateral damage and a loss of tissue function, leading to significant morbidity from an RSV infection.

• #23 The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis

  https://www.mdpi.com/1999-4915/12/8/808

  The prevailing view is that severe bronchiolitis results from excessive inflammation and consequent immunopathology, rather than virus-induced cytology. Neutrophils are the dominant inflammatory cell in the airways of paediatric patients with RSV bronchiolitis, accounting for up to 80% of the cellular infiltrate at peak symptomatology, and yet the precise contribution of neutrophils to antiviral immunity remains ill-defined. […] Here, we review the multifaceted roles of the neutrophil in host defence, antiviral immunity, and immunopathogenesis in the context of viral LRIs. We find that neutrophils make an important contribution to innate antiviral immunity and help to optimise the induction of an effective adaptive immune response. However, as a consequence of their ability to initiate and amplify the magnitude of an inflammatory reaction, it is clear that a failure to adequately regulate this response can lead to excessive collateral damage and a loss of tissue function, leading to significant morbidity from an RSV infection.

• #24 The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis

  https://www.mdpi.com/1999-4915/12/8/808

  The prevailing view is that severe bronchiolitis results from excessive inflammation and consequent immunopathology, rather than virus-induced cytology. Neutrophils are the dominant inflammatory cell in the airways of paediatric patients with RSV bronchiolitis, accounting for up to 80% of the cellular infiltrate at peak symptomatology, and yet the precise contribution of neutrophils to antiviral immunity remains ill-defined. […] Here, we review the multifaceted roles of the neutrophil in host defence, antiviral immunity, and immunopathogenesis in the context of viral LRIs. We find that neutrophils make an important contribution to innate antiviral immunity and help to optimise the induction of an effective adaptive immune response. However, as a consequence of their ability to initiate and amplify the magnitude of an inflammatory reaction, it is clear that a failure to adequately regulate this response can lead to excessive collateral damage and a loss of tissue function, leading to significant morbidity from an RSV infection.

• #25 The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis

  https://www.mdpi.com/1999-4915/12/8/808

  We postulate that neutrophils promote lung pathophysiology during RSV bronchiolitis through the production of pro-inflammatory cytokines and the releasing of cytotoxic molecules. These products, released through distinct cellular processes (e.g., NETosis, degranulation) contribute to mucus hyperproduction, airway epithelial cell death and sloughing, and oedema. […] Collectively, these findings suggest that neutrophils can contribute to pathogenesis; however, a limitation of modelling RSV in mice is that the virus replicates poorly, and hence this is not a particularly tractable system to assess the beneficial properties of neutrophils, such as their antiviral activities. […] Therefore, excessive neutrophilic inflammation in infants with severe RSV bronchiolitis may contribute to the onset of type 2 inflammation and cause long-term defects in lung development that predispose susceptible infants to the development of asthma in later childhood. […] We discuss these questions in the sections below.

• #26 Frontiers | Something Is Changing in Viral Infant Bronchiolitis Approach

  https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.865977/full

  A strong induction of antiviral type I and type III interferons and interferon-induced genes is the primary response of the RSV infected mucosa, but RSV has developed the capacity to evade this innate interferon (INF) response through RSV-NS1/2 proteins, which are able to reduce both IFN-I and INF-III responses. […] In conclusion, bronchiolitis is due to direct viral cytotoxic injury in conjunction with a robust host inflammatory response, but the relative contribution remains uncertain and is probably related to the type of virus involved and to the variability of the individual immune response. […] To conclude, there is evidence that some phenotypes of bronchiolitis are more strongly associated with asthma features and are also linked to higher risk for asthma development. In these populations, use of bronchodilators might have a better impact.

• #27 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  In infected cells, the transcription of viral genes should encode NS1 and NS2 proteins initially, which are essential for host infection, and their function is to inhibit the type interferon (IFN-) response and other components of the immune system. […] NS1, which has previously been studied more deeply than NS2, is a major participant in immunosuppression. […] It is reported that NS1 can bind and inhibit various molecules in the signal cascade of IFN- response in retinoic acid-inducible gene I (RIG-I) or Toll-like receptor (TLR) pathway. […] The NS1 and NS2 complexes are transported to mitochondria to form degradosome, which can degrade a variety of proteins in the IFN- pathway, such as STAT2, TRAF3 (TNF receptor-associated factor 3), TBK1 (TANK-binding kinase 1) and RIG-I. […] A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load.

• #28 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  In infected cells, the transcription of viral genes should encode NS1 and NS2 proteins initially, which are essential for host infection, and their function is to inhibit the type interferon (IFN-) response and other components of the immune system. […] NS1, which has previously been studied more deeply than NS2, is a major participant in immunosuppression. […] It is reported that NS1 can bind and inhibit various molecules in the signal cascade of IFN- response in retinoic acid-inducible gene I (RIG-I) or Toll-like receptor (TLR) pathway. […] The NS1 and NS2 complexes are transported to mitochondria to form degradosome, which can degrade a variety of proteins in the IFN- pathway, such as STAT2, TRAF3 (TNF receptor-associated factor 3), TBK1 (TANK-binding kinase 1) and RIG-I. […] A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load.

• #29 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20240719/Discovery-of-key-RSV-immune-evasion-mechanism-offers-hope-for-new-treatments.aspx

  RSV causes a significant disease burden in the global population, with an estimated 33.1 million cases each year, and is the leading cause of infant bronchiolitis and viral pneumonia. […] Working with human airway epithelial cells, the team of scientists has discovered that RSV suppresses a key biological pathway in our cells (called „the JAK/STAT pathway”) and prevents key „immune system igniters” from moving into the nuclei of cells. […] So when RSV prevents interferon from communicating to these genes the virus slams the brakes on our immune response, which can result in the virus taking hold and quite quickly causing very serious medical issues. […] Our discovery is an exciting revelation because it identifies the JAK/STAT pathway as a prime target for therapeutic immune restoration. […] We predict such a therapeutic could make a significant impact in treating RSV and even clear an RSV infection, which would represent a much-needed solution for both children and the elderly, who are very vulnerable to this dangerous virus.

• #30

  https://link.springer.com/article/10.1007/s00134-002-1256-z

  Respiratory syncytial virus (RSV) bronchiolitis resulting in respiratory insufficiency is frequently encountered during the winter season in paediatric intensive care units. […] This review evaluates potential determinants described in severe RSV bronchiolitis with special attention to the role of immaturity of immune responses during infancy. […] In general, infants at this early age have maturation-related deficient cellular immunity. […] Several studies show an association between decreased cellular immunity and severe RSV bronchiolitis, indeed suggesting that a maturation-related defect of the cellular immune system facilitates severe RSV. […] In conclusion, immaturity of the physiological functions in healthy pre-term infants and neonates, in particular the immune system, appears to be an important factor in the pathogenesis of RSV bronchiolitis resulting in mechanical ventilation.

• #31 Why does bronchiolitis only affect infants? | Institut Pasteur

  https://www.pasteur.fr/en/home/press-area/press-documents/why-does-bronchiolitis-only-affect-infants?language=fr

  In a study published in the prestigious Immunity journal on February 21, 2017, researchers from the Institut Pasteur in Paris and in Shanghai, Bictre Hospital (AP-HP), Paris-Sud University and the CNRS (French National Center for Scientific Research) reported on the discovery of a new group of B lymphocytes, which are only present in infants and are the preferential target of the virus responsible for bronchiolitis. This shows why this infection of the lower respiratory tract mainly affects newborns so severely, in contrast to older children. […] In this context, Richard Lo-Mans group at the Institut Pasteur (Human Histopathology Unit) together with Prof. Pierre Tissiress team at Bictre Hospital (AP-HP NICU) and Paris-Sud University, and the Institut Pasteur of Shanghai, newly identified a B lymphocyte population only found in very young children (under 1 year old) which is preferentially infected by the RSV virus.

• #32 Why does bronchiolitis only affect infants? | Institut Pasteur

  https://www.pasteur.fr/en/home/press-area/press-documents/why-does-bronchiolitis-only-affect-infants?language=fr

  However, the B lymphocytes discovered by the scientists have regulatory properties, which tend to reduce the inflammation and immune response to the virus. By infecting these specific B lymphocytes named nBreg (for neonatal regulatory B lymphocytes) in infants, RSV activates nBregs that decrease viral clearance and thus contribute to the disease severity. […] More specifically, the researchers have described a mechanism whereby the RSV virus infects the nBreg lymphocytes. This mechanism draws on a dual recognition system between the virus and the immune cell. The initial recognition occurs through contact between a protein on the surface of the virus (F protein) and a specific antibody on the surface of the nBreg cell. Lymphocyte activation and expression of CX3CR1 which in turn recognizes the viral G protein leads to viral infection. By infecting this cell, the virus can then inhibit the antiviral immune response, by expressing the anti-inflammatory response genes. Thanks to this mechanism, the RSV virus therefore uses the infant immune system to persist in its host.

• #33 Why does bronchiolitis only affect infants? | Institut Pasteur

  https://www.pasteur.fr/en/home/press-area/press-documents/why-does-bronchiolitis-only-affect-infants?language=fr

  However, the B lymphocytes discovered by the scientists have regulatory properties, which tend to reduce the inflammation and immune response to the virus. By infecting these specific B lymphocytes named nBreg (for neonatal regulatory B lymphocytes) in infants, RSV activates nBregs that decrease viral clearance and thus contribute to the disease severity. […] More specifically, the researchers have described a mechanism whereby the RSV virus infects the nBreg lymphocytes. This mechanism draws on a dual recognition system between the virus and the immune cell. The initial recognition occurs through contact between a protein on the surface of the virus (F protein) and a specific antibody on the surface of the nBreg cell. Lymphocyte activation and expression of CX3CR1 which in turn recognizes the viral G protein leads to viral infection. By infecting this cell, the virus can then inhibit the antiviral immune response, by expressing the anti-inflammatory response genes. Thanks to this mechanism, the RSV virus therefore uses the infant immune system to persist in its host.

• #34 SciELO Brazil – Bronchiolitis, respiratory syncytial virus, and recurrent wheezing: what is the relationship? Bronchiolitis, respiratory syncytial virus, and recurrent wheezing: what is the relationship?

  https://www.scielo.br/j/rhc/a/WHK4pM6CzNCYWgSsL4PH3jh/

  Various follow-up studies of children hospitalized with bronchiolitis caused by respiratory syncytial virus have demonstrated that a significant proportion of infants (50%) have recurrent wheezing during childhood. […] The first suggests that some children could have an individual predisposition to bronchiolitis caused by respiratory syncytial virus and recurrent wheezing. […] Another hypothesis proposes that respiratory syncytial virus could be directly responsible for recurrent wheezing. During an episode of bronchiolitis, the damage in the airway mucosa caused by the vital inflammatory response to infection contributes to sensitivity to other allergens or exposes irritant receptors, resulting in recurrent wheezing. […] The most significant works that evaluated sequels in children with RSV bronchiolitis are summarized in Table 1.

• #35 SciELO Brazil – Bronchiolitis, respiratory syncytial virus, and recurrent wheezing: what is the relationship? Bronchiolitis, respiratory syncytial virus, and recurrent wheezing: what is the relationship?

  https://www.scielo.br/j/rhc/a/WHK4pM6CzNCYWgSsL4PH3jh/

  Various follow-up studies of children hospitalized with bronchiolitis caused by respiratory syncytial virus have demonstrated that a significant proportion of infants (50%) have recurrent wheezing during childhood. […] The first suggests that some children could have an individual predisposition to bronchiolitis caused by respiratory syncytial virus and recurrent wheezing. […] Another hypothesis proposes that respiratory syncytial virus could be directly responsible for recurrent wheezing. During an episode of bronchiolitis, the damage in the airway mucosa caused by the vital inflammatory response to infection contributes to sensitivity to other allergens or exposes irritant receptors, resulting in recurrent wheezing. […] The most significant works that evaluated sequels in children with RSV bronchiolitis are summarized in Table 1.

• #36 The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis

  https://www.mdpi.com/1999-4915/12/8/808

  We postulate that neutrophils promote lung pathophysiology during RSV bronchiolitis through the production of pro-inflammatory cytokines and the releasing of cytotoxic molecules. These products, released through distinct cellular processes (e.g., NETosis, degranulation) contribute to mucus hyperproduction, airway epithelial cell death and sloughing, and oedema. […] Collectively, these findings suggest that neutrophils can contribute to pathogenesis; however, a limitation of modelling RSV in mice is that the virus replicates poorly, and hence this is not a particularly tractable system to assess the beneficial properties of neutrophils, such as their antiviral activities. […] Therefore, excessive neutrophilic inflammation in infants with severe RSV bronchiolitis may contribute to the onset of type 2 inflammation and cause long-term defects in lung development that predispose susceptible infants to the development of asthma in later childhood. […] We discuss these questions in the sections below.

• #37 Respiratory Syncytial Virus (RSV) Pathophysiology

  https://pro.campus.sanofi/us/respiratory-syncytial-virus/articles/rsv-physiopathology

  RSV pathology is characterized by infection of respiratory epithelial cells, which triggers a variety of immune and inflammatory events. […] For some infants, the initial RSV infection will progress into RSV bronchiolitis. […] The pathophysiology of RSV bronchiolitis involves inflammation of the distal bronchial airways, which ultimately leads to distal airway obstruction. […] Although the exact mechanism of RSV bronchiolitis pathophysiology is unclear, its thought that viral cytotoxicity causes necrosis of the epithelial cells, with subsequent sloughing and mucus production plugging the bronchioles and leading to lung hyperinflation and atelectasis. […] RSV progresses to bronchiolitis in some infants largely because of an immature immune system and lack of functionally RSV-protective maternal transplacental antibodies.

• #38 Pathophysiological mechanisms for the respiratory syncytial virus-reactive airway disease link | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/rr185

  We have proposed that interactions between neural and immunoinflammatory mechanisms may cause inflammation well after the initial RSV infection is cleared. […] RSV upregulates the expression of the gene that encodes the NK1 receptor subtype, which mediates the inflammatory and immunomodulatory effects of substance P, thereby potentiating neurogenically mediated airway inflammation. […] RSV infection interferes with this physiologic decline, promoting a large increase in the expression of both NGF and neurotrophin receptors. […] Accordingly, selective NGF blockade inhibits neurogenically mediated inflammation during RSV infection, and the magnitude of this inhibitory effect is more prominent in younger animals. […] In summary, we propose that remodeling of the submucosal neural network and the deriving cluster of neuroimmune interactions may link RSV infections that occur during critical developmental 'windows’ with RAD in childhood. […] If this is the case then it is possible that inhibition of RSV penetration or replication in the lower respiratory tract could reduce the frequency of childhood RAD.

• #39 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20240719/Discovery-of-key-RSV-immune-evasion-mechanism-offers-hope-for-new-treatments.aspx

  RSV causes a significant disease burden in the global population, with an estimated 33.1 million cases each year, and is the leading cause of infant bronchiolitis and viral pneumonia. […] Working with human airway epithelial cells, the team of scientists has discovered that RSV suppresses a key biological pathway in our cells (called „the JAK/STAT pathway”) and prevents key „immune system igniters” from moving into the nuclei of cells. […] So when RSV prevents interferon from communicating to these genes the virus slams the brakes on our immune response, which can result in the virus taking hold and quite quickly causing very serious medical issues. […] Our discovery is an exciting revelation because it identifies the JAK/STAT pathway as a prime target for therapeutic immune restoration. […] We predict such a therapeutic could make a significant impact in treating RSV and even clear an RSV infection, which would represent a much-needed solution for both children and the elderly, who are very vulnerable to this dangerous virus.

• #40 Bronchodilators for Bronchiolitis | AAFP

  https://www.aafp.org/pubs/afp/issues/2015/0901/od1.html

  Bronchiolitis is a common viral infection of childhood that is most often caused by respiratory syncytial virus. Bronchiolitis causes significant inflammation in the lower respiratory tract, which leads to large amounts of secretions and debris that obstruct small airways leading to wheezing on examination. […] Although bronchiolitis is not caused by the same mechanism that leads to wheezing in asthma, the similarity in presentation has led to the common use of bronchodilators to treat bronchiolitis. […] Based on these findings, it is hard to know with certainty whether any patients are harmed by bronchodilators in the setting of bronchiolitis. However, given their cost, lack of efficacy, and potential to cause adverse effects, it is clear that bronchodilators should not be used routinely for the treatment of bronchiolitis, at least in children without a history of wheezing.

• #41 Bronchodilators for Bronchiolitis | AAFP

  https://www.aafp.org/pubs/afp/issues/2015/0901/od1.html

  One important point to understand in examining the literature on the benefits of bronchodilators in bronchiolitis is that some older studies did not exclude patients with a history of wheezing. These studies likely included many patients with asthma who would be expected to improve with bronchodilators. Several newer studies have excluded patients with a history of wheezing. When only these studies are pooled, any apparent benefit from bronchodilators disappears. It must be remembered that these newer findings do not apply to patients with a history of wheezing. Such patients may have asthma and therefore might benefit from bronchodilators. […] The American Academy of Pediatrics Subcommittee on the Diagnosis and Management of Bronchiolitis has published guidelines that have been endorsed by the American Academy of Family Physicians. These guidelines explicitly state that bronchodilators and epinephrine should not be used in the management of bronchiolitis.

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