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Clinics in Chest Medicine Dec 2023The immunocompromised host is at an increased risk for pulmonary and extrapulmonary NTM infections. Where data are available in these specific populations, increased... (Review)
Review
The immunocompromised host is at an increased risk for pulmonary and extrapulmonary NTM infections. Where data are available in these specific populations, increased mortality is observed with NTM disease. Prior to starting therapy for NTM disease, providers should ensure diagnostic criteria are met as treatment is long and often associated with significant side effects and toxicities. Treatment should involve 2 to 4 agents and be guided by cultures and antimicrobial susceptibilities. Drug interactions are important to consider, especially in those with HIV or transplant recipients. Whenever possible, immunosuppression should be reduced or changed.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Lung; Immunocompromised Host; Lung Diseases
PubMed: 37890919
DOI: 10.1016/j.ccm.2023.06.007 -
Seminars in Respiratory and Critical... Feb 2024Imaging plays an important role in the various forms of -related pulmonary disease. Depending on the immune status of the patient, three forms are described with...
Imaging plays an important role in the various forms of -related pulmonary disease. Depending on the immune status of the patient, three forms are described with distinct imaging characteristics: invasive aspergillosis affecting severely immunocompromised patients, chronic pulmonary aspergillosis affecting less severely immunocompromised patients but suffering from a pre-existing structural lung disease, and allergic bronchopulmonary aspergillosis related to respiratory exposure to species in patients with asthma and cystic fibrosis. Computed tomography (CT) has been demonstrated more sensitive and specific than chest radiographs and its use has largely contributed to the diagnosis, follow-up, and evaluation of treatment in each condition. In the last few decades, CT has also been described in the specific context of cystic fibrosis. In this particular clinical setting, magnetic resonance imaging and the recent developments in artificial intelligence have shown promising results.
Topics: Humans; Cystic Fibrosis; Artificial Intelligence; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Lung; Aspergillus
PubMed: 38286137
DOI: 10.1055/s-0043-1776998 -
Cell Feb 2024BA.2.86, a recently identified descendant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sublineage, contains ∼35 mutations in the...
BA.2.86, a recently identified descendant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sublineage, contains ∼35 mutations in the spike (S) protein and spreads in multiple countries. Here, we investigated whether the virus exhibits altered biological traits, focusing on S protein-driven viral entry. Employing pseudotyped particles, we show that BA.2.86, unlike other Omicron sublineages, enters Calu-3 lung cells with high efficiency and in a serine- but not cysteine-protease-dependent manner. Robust lung cell infection was confirmed with authentic BA.2.86, but the virus exhibited low specific infectivity. Further, BA.2.86 was highly resistant against all therapeutic antibodies tested, efficiently evading neutralization by antibodies induced by non-adapted vaccines. In contrast, BA.2.86 and the currently circulating EG.5.1 sublineage were appreciably neutralized by antibodies induced by the XBB.1.5-adapted vaccine. Collectively, BA.2.86 has regained a trait characteristic of early SARS-CoV-2 lineages, robust lung cell entry, and evades neutralizing antibodies. However, BA.2.86 exhibits low specific infectivity, which might limit transmissibility.
Topics: Humans; Antibodies, Neutralizing; Antibodies, Viral; Caspases; COVID-19; Lung; SARS-CoV-2; Virus Internalization; Spike Glycoprotein, Coronavirus
PubMed: 38194966
DOI: 10.1016/j.cell.2023.12.025 -
PLoS Pathogens Aug 2023Pseudomonas aeruginosa (P.a.) infection accounts for nearly 20% of all cases of hospital acquired pneumonia with mortality rates >30%. P.a. infection induces a robust...
Pseudomonas aeruginosa (P.a.) infection accounts for nearly 20% of all cases of hospital acquired pneumonia with mortality rates >30%. P.a. infection induces a robust inflammatory response, which ideally enhances bacterial clearance. Unfortunately, excessive inflammation can also have negative effects, and often leads to cardiac dysfunction with associated morbidity and mortality. However, it remains unclear how P.a. lung infection causes cardiac dysfunction. Using a murine pneumonia model, we found that P.a. infection of the lungs led to severe cardiac left ventricular dysfunction and electrical abnormalities. More specifically, we found that neutrophil recruitment and release of S100A8/A9 in the lungs activates the TLR4/RAGE signaling pathways, which in turn enhance systemic inflammation and subsequent cardiac dysfunction. Paradoxically, global deletion of S100A8/A9 did not improve but aggravated cardiac dysfunction and mortality likely due to uncontrolled bacterial burden in the lungs and heart. Our results indicate that P.a. infection induced release of S100A8/9 is double-edged, providing increased risk for cardiac dysfunction yet limiting P.a. growth.
Topics: Animals; Mice; Pseudomonas aeruginosa; Heart; Inflammation; Pseudomonas Infections; Lung; Heart Diseases
PubMed: 37624851
DOI: 10.1371/journal.ppat.1011573 -
Nature Communications May 2024SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia and disrupted lung iron...
SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia and disrupted lung iron homeostasis in COVID-19 patients imply that ferroptosis, an iron-dependent cell death, may occur. Immunostaining and lipidomic analysis in COVID-19 lung autopsies reveal increases in ferroptosis markers, including transferrin receptor 1 and malondialdehyde accumulation in fatal cases. COVID-19 lungs display dysregulation of lipids involved in metabolism and ferroptosis. We find increased ferritin light chain associated with severe COVID-19 lung pathology. Iron overload promotes ferroptosis in both primary cells and cancerous lung epithelial cells. In addition, ferroptosis markers strongly correlate with lung injury severity in a COVID-19 lung disease model using male Syrian hamsters. These results reveal a role for ferroptosis in COVID-19 pulmonary disease; pharmacological ferroptosis inhibition may serve as an adjuvant therapy to prevent lung damage during SARS-CoV-2 infection.
Topics: Ferroptosis; COVID-19; Animals; Humans; Male; Lung; SARS-CoV-2; Mesocricetus; Female; Iron; Middle Aged; Disease Models, Animal; Aged; Lung Injury; Iron Overload; Adult; Cricetinae
PubMed: 38769293
DOI: 10.1038/s41467-024-48055-0 -
Pediatric Radiology Apr 2024Pulmonary infection is the leading cause of infectious morbidity and mortality in children with immune defects. We provide a comprehensive review of lung infections in... (Review)
Review
Pulmonary infection is the leading cause of infectious morbidity and mortality in children with immune defects. We provide a comprehensive review of lung infections in immunocompromised children, with a focus on imaging findings and imaging-based management. We include an overview of the immune defences of the respiratory tract, the aetiologies of immune defects in children, the features of specific infections and important differential diagnoses and describe diagnostic strategies using imaging and non-imaging-based techniques.
Topics: Child; Humans; Respiratory Tract Infections; Pneumonia; Immunocompromised Host; Lung
PubMed: 37589764
DOI: 10.1007/s00247-023-05735-1 -
International Journal of Molecular... Nov 2023Lung infections are one of the most common causes of death and morbidity worldwide. Both bacterial and viral lung infections cause a vast number of infections with... (Review)
Review
Lung infections are one of the most common causes of death and morbidity worldwide. Both bacterial and viral lung infections cause a vast number of infections with varying severities. Extracellular vesicles (EVs) produced by different cells due to infection in the lung have the ability to modify the immune system, leading to either better immune response or worsening of the disease. It has been shown that both bacteria and viruses have the ability to produce their EVs and stimulate the immune system for that. In this review, we investigate topics from EV biogenesis and types of EVs to lung bacterial and viral infections caused by various bacterial species. , and infections are covered intensively in this review. Moreover, various viral lung infections, including SARS-CoV-2 infections, have been depicted extensively. In this review, we focus on eukaryotic-cell-derived EVs as an important component of disease pathogenesis. Finally, this review holds high novelty in its findings and literature review. It represents the first time to cover all different information on immune-cell-derived EVs in both bacterial and viral lung infections.
Topics: Humans; Extracellular Vesicles; Pneumonia; Virus Diseases; Lung; COVID-19
PubMed: 38003329
DOI: 10.3390/ijms242216139 -
Frontiers in Immunology 2023Respiratory syncytial virus (RSV) commonly infects the upper respiratory tract (URT) of humans, manifesting with mild cold or flu-like symptoms. However, in infants and...
Respiratory syncytial virus (RSV) commonly infects the upper respiratory tract (URT) of humans, manifesting with mild cold or flu-like symptoms. However, in infants and the elderly, severe disease of the lower respiratory tract (LRT) often occurs and can develop into chronic airway disease. A better understanding of how an acute RSV infection transitions to a LRT chronic inflammatory disease is critically important to improve patient care and long-term health outcomes. To model acute and chronic phases of the disease, we infected wild-type C57BL/6 and toll-like receptor 7 knockout (TLR7 KO) mice with RSV and temporally assessed nasal, airway and lung inflammation for up to 42 days post-infection. We show that TLR7 reduced viral titers in the URT during acute infection but promoted pronounced pathogenic and chronic airway inflammation and hyperreactivity in the LRT. This study defines a hitherto unappreciated molecular mechanism of lower respiratory pathogenesis to RSV, highlighting the potential of TLR7 modulation to constrain RSV pathology to the URT.
Topics: Animals; Mice; Asthma; Bronchi; Inflammation; Mice, Inbred C57BL; Respiratory Syncytial Virus Infections; Toll-Like Receptor 7; Mice, Knockout
PubMed: 37795093
DOI: 10.3389/fimmu.2023.1240552 -
Expert Review of Respiratory Medicine 2024Hypercapnia is developed in patients with acute and/or chronic respiratory conditions. Clinical data concerning hypercapnia and respiratory infections interaction is... (Review)
Review
INTRODUCTION
Hypercapnia is developed in patients with acute and/or chronic respiratory conditions. Clinical data concerning hypercapnia and respiratory infections interaction is limited.
AREAS COVERED
Currently, the relationship between hypercapnia and respiratory infections remains unclear. In this review, we summarize studies on the effects of hypercapnia on models of pulmonary infections to clarify the role of elevated CO2 in these pulmonary pathologies. Hypercapnia affects different cell types in the alveoli, leading to changes in the immune response. In vitro studies show that hypercapnia downregulates the NF-κβ pathway, reduces inflammation and impairs epithelial wound healing. While in vivo models show a dual role between short- and long-term effects of hypercapnia on lung infection. However, it is still controversial whether the effects observed under hypercapnia are pH dependent or not.
EXPERT OPINION
The role of hypercapnia is still a controversial debate. Hypercapnia could play a beneficial role in mechanically ventilated models, by lowering the inflammation produced by the stretch condition. But it could be detrimental in infectious scenarios, causing phagocyte dysfunction and lack of infection control. Further data concerning hypercapnia on respiratory infections is needed to elucidate this interaction.
Topics: Humans; Hypercapnia; Lung; Inflammation; Pulmonary Alveoli; Respiratory Tract Infections
PubMed: 38489161
DOI: 10.1080/17476348.2024.2331767 -
Clinics in Chest Medicine Dec 2023The diagnosis of nontuberculous mycobacterial (NTM) pulmonary disease is based on three criteria: patient's symptoms, radiographic findings, and microbiologic results.... (Review)
Review
The diagnosis of nontuberculous mycobacterial (NTM) pulmonary disease is based on three criteria: patient's symptoms, radiographic findings, and microbiologic results. The microbiologic criterion is the most complicated because it requires more than one positive sputum acid-fast bacilli culture. Clinicians are challenged to apply the diagnostic criteria in the context of variable patient symptoms, NTM pathogenicity, and host susceptibility. The decision to treat NTM pulmonary disease entails assessment of the risks and benefits of therapy and the patient's wishes and ability to receive treatment.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Lung; Sputum; Lung Diseases
PubMed: 37890914
DOI: 10.1016/j.ccm.2023.07.003