Materiały źródłowe

• #1 Pneumonia Pathology – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK526116/

  There is an intricate balance between the organisms residing in the lower respiratory tract and the local and systemic defense mechanisms (both innate and acquired) which when disturbed gives rise to inflammation of the lung parenchyma, i.e., pneumonia. Common defense mechanisms that are compromised in the pathogenesis of pneumonia include: […] The resident macrophages serve to protect the lung from foreign pathogens. Ironically, the inflammatory reaction triggered by these very macrophages is what is responsible for the histopathological and clinical findings seen in pneumonia. The macrophages engulf these pathogens and trigger signal molecules or cytokines like TNF-a, IL-8, and IL-1 that recruit inflammatory cells like neutrophils to the site of infection. They also serve to present these antigens to the T cells that trigger both cellular and humoral defense mechanisms, activate complement and form antibodies against these organisms. This, in turn, causes inflammation of the lung parenchyma and makes the lining capillaries „leaky,” which leads to exudative congestion and underlines the pathogenesis of pneumonia.

• #2 Overview of Pneumonia – Lung and Airway Disorders – MSD Manual Consumer Version

  https://www.msdmanuals.com/home/lung-and-airway-disorders/pneumonia/overview-of-pneumonia

  Pneumonia is caused by different microorganisms including bacteria, viruses, mycobacteria, fungi, and parasites. Bacterial and viral pneumonias are much more common than mycobacterial, fungal, or parasitic pneumonias. The specific organisms vary depending on the person’s age, health, location, and other factors. More than one microorganism may be involved. For example, influenza (a viral infection) is often complicated by bacterial pneumonia. […] Pneumonia develops when defense mechanisms are not functioning correctly. […] A large amount of bacteria is inhaled and overwhelms normal defenses. […] A particularly infective organism is introduced. […] Usually pneumonia starts after microorganisms are inhaled (aspirated) from the upper airways into the lungs, but sometimes the infection is caused by microorganisms that are inhaled from the air, carried to the lungs by the bloodstream, or invade the lungs directly from a nearby site of infection.

• #3 Pneumonia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/pneumonia/symptoms-causes/syc-20354204

  Most pneumonia occurs when a breakdown in your body’s natural defenses allows germs to invade and multiply within your lungs. To destroy the attacking organisms, white blood cells rapidly accumulate. Along with bacteria and fungi, they fill the air sacs within your lungs (alveoli). […] Pneumonia is an infection that inflames the air sacs in one or both lungs. The air sacs may fill with fluid or pus (purulent material), causing cough with phlegm or pus, fever, chills, and difficulty breathing. A variety of organisms, including bacteria, viruses and fungi, can cause pneumonia. […] Many germs can cause pneumonia. The most common are bacteria and viruses in the air we breathe. Your body usually prevents these germs from infecting your lungs. But sometimes these germs can overpower your immune system, even if your health is generally good.

• #4 Pneumonia – Wikipedia

  https://en.wikipedia.org/wiki/Pneumonia

  Pneumonia frequently starts as an upper respiratory tract infection that moves into the lower respiratory tract. […] It is a type of pneumonitis (lung inflammation). […] The progress of pneumonia is determined by the virulence of the organism; the amount of organism required to start an infection; and the body’s immune response against the infection. […] Most bacteria enter the lungs via small aspirations of organisms residing in the throat or nose. […] Once in the lungs, bacteria may invade the spaces between cells and between alveoli, where the macrophages and neutrophils (defensive white blood cells) attempt to inactivate the bacteria. […] The neutrophils also release cytokines, causing a general activation of the immune system. […] This leads to the fever, chills, and fatigue common in bacterial pneumonia.

• #5 Overview of community-acquired pneumonia in adults – UpToDate

  https://www.uptodate.com/contents/overview-of-community-acquired-pneumonia-in-adults/print

  Traditionally, CAP has been viewed as an infection of the lung parenchyma, primarily caused by bacterial or viral respiratory pathogens. In this model, respiratory pathogens are transmitted from person to person via droplets or, less commonly, via aerosol inhalation (eg, as with Legionella or Coxiella species). Following inhalation, the pathogen colonizes the nasopharynx and then reaches the lung alveoli via microaspiration. When the inoculum size is sufficient and/or host immune defenses are impaired, infection results. Replication of the pathogen, the production of virulence factors, and the host immune response lead to inflammation and damage of the lung parenchyma, resulting in pneumonia. […] With the identification of the lung microbiome, that model has changed. While the pathogenesis of pneumonia may still involve the introduction of respiratory pathogens into the alveoli, the infecting pathogen likely has to compete with resident microbes to replicate. In addition, resident microbes may also influence or modulate the host immune response to the infecting pathogen. If this is correct, an altered alveolar microbiome (alveolar dysbiosis) may be a predisposing factor for the development of pneumonia.

• #6 Pneumonia Pathophysiology

  https://www.thenursingjournal.com/post/pneumonia-pathophysiology

  Pneumonia is an acute respiratory infection of the lung parenchyma caused by one or co-infecting pathogens. These pathogens cause the lung parenchyma (alveoli) to become inflamed and fill with pus and fluid, limiting oxygen intake and making gas exchange ineffective. […] In Pneumonia, however, this screening mechanism would have been damaged by previous or ongoing illnesses and harmful pathogens manage to find their way into the lower respiratory tract. […] In addition, pathogens can also enter the lungs through the circulatory system. Bloodborne pathogens can travel through the body until they reach the pulmonary circulation. There they enter the pulmonary capillary bed and settle at the bottom of the lungs. […] Once the pathogens are stuck, some of the alveoli become inflamed and they fill up with a thick exudate that interferes with the exchange of oxygen and carbon dioxide. Naturally, the body has to fight this off so it sends Neutrophils into the alveoli, but in doing it fills the last few empty spaces of air in the alveoli. Following that, the mucosa starts to swell up causing mucosal oedema and partially occluding the bronchi, and in some cases, if the patient has other respiratory conditions bronchospasm would occur.

• #7 adult-pneumonia-pathogenesis-and-clinical-findings | Calgary Guide

  https://calgaryguide.ucalgary.ca/adult-pneumonia-pathogenesis-and-clinical-findings/adult-pneumonia-2022/

  Adult Pneumonia: Pathogenesis and clinical findings […] Smoking suppressed neutrophil function and damaged lung epithelium […] Chronic lung conditions e.g. COPD, asthma, lung cancer destroys lung tissue and offers pathogen more niduses for infection […] Immune suppression e.g. HIV, sepsis, glucocorticoids, chemotherapy suppression of immune response […] Systemic inflammatory response towards invading microbe […] Systemic cytokine release leads to a disruption in hypothalamic thermoregulation […] Exposure to a pathogen via inhalation, aspiration, contiguous Notes: or hematological mechanism […] Susceptible host and/or virulent pathogen […] Proliferation of microbe in lower airways and alveoli […] Local response by alveolar epithelial cells release chemokines into surrounding tissue to recruit neutrophils to the site of inflammation

• #8 Learn About Pneumonia | American Lung Association

  https://www.lung.org/lung-health-diseases/lung-disease-lookup/pneumonia/learn-about-pneumonia

  Pneumonia is an infection of the lungs that may be caused by bacteria, viruses, or fungi. The infection causes the lungs’ air sacs (alveoli) to become inflamed and fill up with fluid or pus. That can make it hard for the oxygen you breathe in to get into your bloodstream. […] Pneumonia can be caused by a wide variety of bacteria, viruses and fungi in the air we breathe. Identifying the cause of your pneumonia can be an important step in getting the proper treatment. […] People age 65 and over are at increased risk because their immune system is becoming less able to fight off infection as years go by. Infants and children two years of age or younger are also at increased risk because their immune systems are not yet fully developed. […] Chronic lung diseases such as COPD, bronchiectasis, or cystic fibrosis that make the lungs more vulnerable.

• #9 Learn About Pneumonia | American Lung Association

  https://www.lung.org/lung-health-diseases/lung-disease-lookup/pneumonia/learn-about-pneumonia

  A weakened immune system due to HIV/AIDs, an organ transplant, chemotherapy or long-term steroid use. […] Difficulty swallowing, due to stroke, dementia, Parkinson’s disease, or other neurological conditions, which can result in aspiration of food, vomit or saliva into the lungs that then becomes infected. […] Recent viral respiratory infectiona cold, laryngitis, influenza, etc. […] Hospitalization, especially when in intensive care and using a ventilator to breathe. […] Cigarette smoking, which damages the lungs. […] Drug and alcohol abuse, which increase the risk of aspiration pneumonia. […] Exposure to certain chemicals, pollutants or toxic fumes, including secondhand smoke.

• #10 Bacterial Pneumonia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513321/

  Bacterial pneumonia, characterized by inflammation in lung parenchyma and alveolar spaces, is caused by various bacteria, each triggering an intricate interplay with the host immune response. […] The body’s inflammatory response against this invasion leads to the clinical symptoms of pneumonia. […] Pathogenic bacteria have various virulence factors that facilitate the evading host immune responses. […] Alveolar macrophages initiate host inflammatory responses upon bacterial invasion to limit bacterial spread within the human host. The host inflammatory responses are the primary drivers of the clinical manifestations observed in bacterial pneumonia. […] These proinflammatory cytokines are responsible for the leakage of the alveolar-capillary membrane at the inflammation site, facilitating the migration of host leukocytes to the site of bacterial burden in the lungs. This leakage can result in decreased gas exchange and associated fibrosis, causing reduced compliance and manifesting as progressive and severe dyspnea. […] Inflammation within the pleura can trigger somatic receptors of the phrenic nerve within the parietal pleura, causing pleuritic chest pain. […] Localized necrosis from damage to the lung parenchyma and tissue extravasation can result in hemoptysis.

• #11 Pneumonia: Classification, Pathogenesis, Diagnosis, and Management

  https://www.medreport.foundation/post/pneumonia-classification-pathogenesis-diagnosis-and-management

  The pathogenesis of pneumonia begins with the invasion of the alveoli by infectious organisms. […] However, when these defenses are compromised by smoking, viral illness, aspiration, or immunosuppression pathogens can reach the lower respiratory tract. […] Once in the alveoli, microbes multiply and trigger a local inflammatory response. Neutrophils infiltrate the alveolar spaces, leading to consolidation, impaired gas exchange, and the classic clinical manifestations of cough, dyspnea, fever, and sometimes pleuritic chest pain. In viral or atypical pneumonia, the inflammatory process may be more interstitial than alveolar, leading to a more indolent course and diffuse findings on imaging.

• #12 Pediatric Pneumonia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/967822-overview

  In bacterial infections, the alveoli fill with proteinaceous fluid, which triggers a brisk influx of red blood cells (RBCs) and polymorphonuclear (PMN) cells (red hepatization) followed by the deposition of fibrin and the degradation of inflammatory cells (gray hepatization). During resolution, intra-alveolar debris is ingested and removed by the alveolar macrophages. This consolidation leads to decreased air entry and dullness to percussion; inflammation in the small airways leads to crackles. […] Four stages of lobar pneumonia have been described. In the first stage, which occurs within 24 hours of infection, the lung is characterized microscopically by vascular congestion and alveolar edema. Many bacteria and few neutrophils are present. The stage of red hepatization (2-3 days), so called because of its similarity to the consistency of liver, is characterized by the presence of many erythrocytes, neutrophils, desquamated epithelial cells, and fibrin within the alveoli. In the stage of gray hepatization (2-3 days), the lung is gray-brown to yellow because of fibrinopurulent exudate, disintegration of RBCs, and hemosiderin. The final stage of resolution is characterized by resorption and restoration of the pulmonary architecture. Fibrinous inflammation may lead to resolution or to organization and pleural adhesions.

• #13 Pediatric Pneumonia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/967822-overview

  Alveolar diffusion barriers may increase, intrapulmonary shunts may worsen, and ventilation/perfusion (V/Q) mismatch may further impair gas exchange despite endogenous homeostatic attempts to improve matching by regional airway and vascular constriction or dilatation. Because the myocardium has to work harder to overcome the alterations in pulmonary vascular resistance that accompany the above changes of pneumonia, the lungs may be less able to add oxygen and remove carbon dioxide from mixed venous blood for delivery to end organs. The spread of infection or inflammatory response, either systemically or to other focal sites, further exacerbates the situation. […] Viral infections are characterized by the accumulation of mononuclear cells in the submucosa and perivascular space, resulting in partial obstruction of the airway. Patients with these infections present with wheezing and crackles. Disease progresses when the alveolar type II cells lose their structural integrity and surfactant production is diminished, a hyaline membrane forms, and pulmonary edema develops.

• #14 Pneumonia – Wikipedia

  https://en.wikipedia.org/wiki/Pneumonia

  Viruses may reach the lung by a number of different routes. […] Once in the upper airway, the viruses may make their way into the lungs, where they invade the cells lining the airways, alveoli, or lung parenchyma. […] The invasion of the lungs may lead to varying degrees of cell death. […] When the immune system responds to the infection, even more lung damage may occur. […] Primarily white blood cells, mainly mononuclear cells, generate the inflammation. […] As well as damaging the lungs, many viruses simultaneously affect other organs and thus disrupt other body functions. […] Pneumonia can cause respiratory failure by triggering acute respiratory distress syndrome (ARDS), which results from a combination of infection and inflammatory response.

• #15 Pediatric Pneumonia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/967822-overview

  On a macroscopic level, the invading agents and the host defenses all tend to increase airway smooth muscle tone and resistance, mucus secretion, and the presence of inflammatory cells and debris in these secretions. These materials may further increase airway resistance and obstruct the airways, partially or totally, causing airtrapping, atelectasis, and ventilatory dead space. […] In addition, disruption of endothelial and alveolar epithelial integrity may allow surfactant to be inactivated by proteinaceous exudate, a process that may be exacerbated further by the direct effects of meconium or pathogenic microorganisms. […] In the end, conducting airways offer much more resistance and may become obstructed, alveoli may be atelectatic or hyperexpanded, alveolar perfusion may be markedly altered, and multiple tissues and cell populations in the lung and elsewhere sustain injury that increases the basal requirements for oxygen uptake and excretory gas removal at a time when the lungs are less able to accomplish these tasks.

• #16 Pneumonia Pathophysiology

  https://www.thenursingjournal.com/post/pneumonia-pathophysiology

  All of these factors limit the oxygen intake into the affected lung and create an imbalance in the Ventilation-Perfusion Ratio. Since the lungs do not have enough oxygen in them, they cannot fully oxygenate the venous blood entering the pulmonary circulation. The poorly oxygenated blood will then enter the left side of the heart and be pumped around the body. But because it has very little oxygen to distribute Arterial Hypoxemia develops. […] This problem can occur in different areas of the lungs, depending on where the pathogens settle. If it attacks a large portion of one or more lobes it is referred to as Lobular Pneumonia. But if it attacks many different patches along the bronchi and stretches out to the nearest parenchyma it is called Bronchopneumonia.

• #17 Overview of community-acquired pneumonia in adults – UpToDate

  https://www.uptodate.com/contents/overview-of-community-acquired-pneumonia-in-adults

  Traditionally, CAP has been viewed as an infection of the lung parenchyma, primarily caused by bacterial or viral respiratory pathogens. In this model, respiratory pathogens are transmitted from person to person via droplets or, less commonly, via aerosol inhalation (eg, as with Legionella or Coxiella species). Following inhalation, the pathogen colonizes the nasopharynx and then reaches the lung alveoli via microaspiration. When the inoculum size is sufficient and/or host immune defenses are impaired, infection results. Replication of the pathogen, the production of virulence factors, and the host immune response lead to inflammation and damage of the lung parenchyma, resulting in pneumonia. […] […] […] With the identification of the lung microbiome, that model has changed. While the pathogenesis of pneumonia may still involve the introduction of respiratory pathogens into the alveoli, the infecting pathogen likely has to compete with resident microbes to replicate. In addition, resident microbes may also influence or modulate the host immune response to the infecting pathogen. If this is correct, an altered alveolar microbiome (alveolar dysbiosis) may be a predisposing factor for the development of pneumonia.

• #18 Overview of community-acquired pneumonia in adults – UpToDate

  https://www.uptodate.com/contents/overview-of-community-acquired-pneumonia-in-adults/print

  In some cases, CAP might also arise from uncontrolled replication of microbes that normally reside in the alveoli. The alveolar microbiome is similar to oral flora and is primarily comprised of anaerobic bacteria (eg, Prevotella and Veillonella) and microaerophilic streptococci. Hypothetically, exogenous insults such as a viral infection or smoke exposure might alter the composition of the alveolar microbiome and trigger overgrowth of certain microbes. Because organisms that compose the alveolar microbiome typically cannot be cultivated using standard cultures, this hypothesis might explain the low rate of pathogen detection among patients with CAP. […] In any scenario, the host immune response to microbial replication within the alveoli plays an important role in determining disease severity. For some patients, a local inflammatory response within the lung predominates and may be sufficient for controlling infection. In others, a systemic response is necessary to control infection and to prevent spread or complications, such as bacteremia. In a minority, the systemic response can become dysregulated, leading to tissue injury, sepsis, acute respiratory distress syndrome, and/or multiorgan dysfunction. […] The pathogenesis of CAP is discussed in greater detail separately.

• #19 The co-pathogenesis of influenza viruses with bacteria in the lung | Nature Reviews Microbiology

  https://www.nature.com/articles/nrmicro3231

  Mortality from influenza viruses is strongly linked to secondary bacterial invaders. In the most extreme example, more than 95% of the 50 million or more deaths during the 1918 pandemic were complicated by bacterial pneumonia. […] Disruption of lung physiology by respiratory viruses breaches natural barriers to infection and promotes bacterial co-infection. Receptors that can be used by bacteria for adherence and infection are uncovered and upregulated. […] Although they are typically secondary invaders during influenza infections, bacteria express virulence factors that promote viral pathogenesis. This results in increased viral load and decreased clearance. […] This co-pathogenesis is characterized by complex interactions between co-infecting pathogens and the host, leading to the disruption of physical barriers, dysregulation of immune responses and delays in a return to homeostasis. The net effect of this cascade can be the outgrowth of the pathogens, immune-mediated pathology and increased morbidity.

• #20 Recognition and management of respiratory co-infection and secondary bacterial pneumonia in patients with COVID-19 | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/87/11/659

  In COVID-19, respiratory infection with SARS-CoV-2 plus another virus (viral co-infection) or with SARS-CoV-2 plus a bacterial pathogen (combined viral and bacterial pneumonia) has been described. […] Secondary bacterial pneumonia can follow the initial phase of viral respiratory infection or occur during the recovery phase. […] Combined viral and bacterial pneumonia and secondary bacterial pneumonia by Staphylococcus aureus and other common community-acquired pneumonia pathogens have been best studied in seasonal and pandemic influenza and contribute significantly to morbidity and mortality. […] Because no obvious pattern or guidelines exist for viral co-infection, combined viral and bacterial pneumonia, or secondary bacterial pneumonia in the context of SARS-CoV-2, the following commentary is based on existing clinical data and experience with similar viruses such as influenza and SARS-CoV.

• #21 S. pneumoniae sticks to dying lung cells, worsening secondary infection following flu – UAB News

  https://www.uab.edu/news/research-innovation/s-pneumoniae-sticks-to-dying-lung-cells-worsening-secondary-infection-following-flu

  Pneumococcal pneumonia. Computer illustration of Streptococcus pneumoniae (pneumococci) bacteria inside the alveoli of the lungs, causing pneumonia. This novel virulence trait, which increases severity of S. pneumoniae superinfection, involves pneumococcal surface protein A, now identified as an adhesin. […] Now researchers have found a further reason for the severity of this dual infection by identifying a new virulence mechanism for a surface protein on the pneumonia-causing bacteria S. pneumoniae. […] This new mechanism had been missed in the past because it facilitates bacterial adherence only to dead or dying lung epithelial cells, not to living cells. […] Virus killing of lung cells during flu was found to set the stage for S. pneumonia attachment to the airway, thereby worsening disease and pneumonia.

• #22 S. pneumoniae sticks to dying lung cells, worsening secondary infection following flu – UAB News

  https://www.uab.edu/news/research-innovation/s-pneumoniae-sticks-to-dying-lung-cells-worsening-secondary-infection-following-flu

  Orihuela and Briles say their findings provide further explanation for how an infection by influenza A flu virus followed by S. pneumoniae superinfection causes severe pneumonia and a high death rate. […] From this clue, the researchers were able to show that PspA functions as an adhesin to dying host cells, in addition to its several other previously established virulence mechanisms. […] Both influenza A infection and release of the S. pneumoniae toxin pneumolysin cause death of lung epithelial cells. […] PspA-GAPDH-mediated binding to lung cells increased S. pneumoniae localization in the lower airway, and this was enhanced by pneumolysin exposure or co-infection with influenza A virus. […] Our findings support the targeting of regions of PspA for therapeutic and vaccine development against influenza A/Streptococcus pneumoniae superinfections, Orihuela said. […] Thus, our finding of PspA’s role in adherence substantially advances our knowledge on the interactions of S. pneumoniae with its host.

• #23 Mechanism of ambient particulate matter and respiratory infections – Vargas Buonfiglio – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/34673/html

  Air pollution is an important risk factor for respiratory infections. One of the main components of air pollution is particulate matter (PM), a mixture of solid particles and liquid droplets suspended in the air. Acute respiratory infections are one of the leading causes of death worldwide, therefore, it is critical to understand the mechanism by which PM increases the risk of infections. […] There are several proposed mechanisms by which PM can increase respiratory infections. First PM can serve as a carrier of bacteria. Once PM arrives into the airway lands on the airway surface liquid and can quickly adsorb and impair peptides and proteins responsible for the airway antimicrobial activity. Also, PM can decrease mucociliary transport, and dampen the expression of antimicrobial peptides such as defensins. Alveolar macrophages are also responsible for the clearance of particles. PM can inhibit the phagocytic ability of macrophages against pathogenic bacteria such as Pneumococcus pneumoniae. Furthermore, our group and Liu et al. observed that PM promotes bacterial growth of airway pathogens. One mechanism might involve iron in PM, serving as an important nutrient for bacterial growth.

• #24 New cell regeneration mechanism identified to protect lung tissue from acute viral infections – IBioBA

  https://ibioba-mpsp-conicet.gov.ar/index.php/en/2024/01/12/new-cell-regeneration-mechanism-identified-to-protect-lung-tissue-from-acute-viral-infections/

  A paper published in the journal Nature Communications, in which IBioBAs Max Planck Guest Laboratory participated, described a molecular mechanism by which lung tissue repair is induced after damage caused by respiratory infection. […] It is in this line of research that a paper recently published in the journal Nature Communications describes how immune system cells called macrophages promote the regeneration of lung tissue after damage caused by acute influenza virus infection. This tissue repair process involves the Plet1 protein. […] The infectious process induces inflammation in the lung tissue, and the repair of the damaged tissue depends on the correct resolution of the inflammatory process. This is the whole cycle, and macrophages are involved in all phases, explains Maximiliano Ferrero, researcher at the Max Planck Guest Laboratory.

• #25 New cell regeneration mechanism identified to protect lung tissue from acute viral infections – IBioBA

  https://ibioba-mpsp-conicet.gov.ar/index.php/en/2024/01/12/new-cell-regeneration-mechanism-identified-to-protect-lung-tissue-from-acute-viral-infections/

  Less recently, it has also been understood that macrophages are actively involved in the cessation of inflammation (resolution), and the regeneration of damaged tissue, actively promoting the return to homeostasis, says Ferrero, first author of the paper together with two scientists from the German institutions. […] The research team saw that in response to these signals, macrophages produce Plet1: a protein that triggers the proliferation of lung progenitor cells, i.e. activates tissue regeneration. […] What we show in the publication is that Plet1 plays a key role in tissue re-epithelialization. We describe a previously unknown mechanism by which macrophages signal lung alveolar progenitor cells to proliferate and then differentiate into the type of cell that performs gas exchange, fully restoring lung function, says Ferrero.

• #26 New cell regeneration mechanism identified to protect lung tissue from acute viral infections – IBioBA

  https://ibioba-mpsp-conicet.gov.ar/index.php/en/2024/01/12/new-cell-regeneration-mechanism-identified-to-protect-lung-tissue-from-acute-viral-infections/

  In the future, this discovery has the potential to lay the groundwork for the development of drugs to protect the lungs from acute viral lung infections, both influenza and other respiratory viruses, especially in people who are less able to resolve infection or inflammation, such as the elderly. What we hope is that by studying the mechanisms that lead to lung tissue regeneration, we can manipulate them so that in situations where that mechanism fails or is depressed, we can make it faster or more efficient.

• #27 Why do short-lived lung infections lead to long-lasting lung damage? – WashU Medicine

  https://medicine.washu.edu/news/why-do-short-lived-lung-infections-lead-to-long-lasting-lung-damage/

  Researchers at Washington University School of Medicine in St. Louis have found clues to just how lung damage develops in the aftermath of a respiratory infection. […] The findings, published Aug. 24 in the Journal of Clinical Investigation, reveal potential points of intervention to prevent chronic lung damage caused by viral infections. […] Further experiments showed that this process hinges on the protein IL-33. […] To assess the role of IL-33 in post-viral lung damage, the researchers genetically modified mice to lack IL-33 in the basal set of lung stem cells. […] Targeting steps on the pathway between IL-33 and basal cell activation could form the basis of broadly effective therapies to prevent or treat lung disease caused by a variety of viruses and perhaps other forms of injury in the lung and other sites where the body meets the outside world, Holtzman said.

• #28 Pediatric Pneumonia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/967822-overview

  Pulmonary injuries are caused directly and/or indirectly by invading microorganisms or foreign material and by poorly targeted or inappropriate responses by the host defense system that may damage healthy host tissues as badly as or worse than the invading agent. Direct injury by the invading agent usually results from synthesis and secretion of microbial enzymes, proteins, toxic lipids, and toxins that disrupt host cell membranes, metabolic machinery, and the extracellular matrix that usually inhibits microbial migration. […] Indirect injury is mediated by structural or secreted molecules, such as endotoxin, leukocidin, and toxic shock syndrome toxin-1 (TSST-1). Any of these molecules may alter local vasomotor tone and integrity, change the characteristics of the tissue perfusate, and generally interfere with the delivery of oxygen and nutrients and removal of waste products from local tissues.

• #29 Insights gained into respiratory infection pathogenesis using lung tissue metabolomics | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008662

  A complete understanding of the role of metabolism in respiratory infection pathogenesis requires lung tissue analysis. […] Lung metabolomics studies have currently been performed only on a restricted list of pathogens. […] There is therefore a strong need for a spatial component to be added to metabolomic studies of lung infection. […] Given the strong connection between metabolism, tissue damage, and immune responses, such studies have great potential to lead to new ways to manage respiratory infections.

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