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1.
Neurosci Lett ; 783: 136743, 2022 Jul 13.
Article in English | MEDLINE | ID: mdl-35716964

ABSTRACT

Meningitis occurs when S. pneumonia invade the blood-brain barrier, provoking inflammatory host response and neurological injury. Nucleotide-binding oligomerization domain 2 (NOD2) has been identified to promote microglial activation and autophagy during pneumococcal meningitis, but the mechanism remains unclear. In the present study, we investigated the passway of NOD2-mediated autophagy activation and the role of autophagy in inflammatory damage of murine microglia and mouse meningitis model. We demonstrated that autophagy was activated during S. pneumonia infection, and NOD2-RIP2 signaling was involved in the process. Treatment of microglia with GSK583, the RIP2 kinase inhibitor resulted in reduced autophagy-related protein and p-ULK1, indicating that RIP2 regulated autophagy in a kinase-dependent manner by phosphorylating ULK1. In addition, microglia with ULK1 knockdown exhibited enhanced production of ROS, leading to IL-1ß and IL-18 release and cellular pyroptosis. Similar to the in vitro results, NOD2-RIP2 signaling induced autophagy in the brain in a mouse meningitis model. Moreover, ULK1 or RIP2 silencing significantly increased pyroptosis of brain and induced more inflammatory damage of pneumococcal meningitis mice. Taken together, our study demonstrate that NOD2-RIP2 signaling is involved in the activation of autophagy by promoting ULK1 phosphorylation, which alleviates microglial ROS damage and pyroptosis during S. pneumonia infection.


Subject(s)
Meningitis, Pneumococcal , Pneumonia , Animals , Autophagy , Meningitis, Pneumococcal/metabolism , Mice , Microglia/metabolism , Nod2 Signaling Adaptor Protein/metabolism , Pneumonia/metabolism , Pyroptosis , Reactive Oxygen Species/metabolism , Receptor-Interacting Protein Serine-Threonine Kinase 2/metabolism , Streptococcus/metabolism
2.
Cells ; 11(12)2022 06 10.
Article in English | MEDLINE | ID: mdl-35741013

ABSTRACT

Preeclampsia (PE) is an obstetric complication associated with significant health implications for the fetus and mother. Studies have shown a correlation between lung disease development and PE. Gas6 protein is expressed in the lung and placenta, and binds to the AXL Tyrosine kinase receptor. Recently, our laboratory utilized Gas6 to induce preeclamptic-like conditions in rats. Our objective was to determine the role of Gas6/AXL signaling in the maternal lung during PE development. Briefly, pregnant rats were divided into control, Gas6, or Gas6 + R428 (an AXL inhibitor). Immunofluorescence was performed to determine AXL expression. Bronchoalveolar lavage fluid (BALF) was procured for the assessment of inflammatory cell secretion. Western blot was performed to detect signaling molecules and ELISA determined inflammatory cytokines. We observed increased proteinuria and increased blood pressure in Gas6-treated animals. AXL was increased in the lungs of the treated animals and BALF fluid revealed elevated total protein abundance in Gas6 animals. Extracellular-signal regulated kinase (ERK) and protein kinase B (AKT) signaling in the lung appeared to be mediated by Gas6 as well as the secretion of inflammatory cytokines. We conclude that Gas6 signaling is capable of inducing PE and that this is associated with increased lung inflammation.


Subject(s)
Pneumonia , Pre-Eclampsia , Animals , Cytokines , Female , Humans , Intercellular Signaling Peptides and Proteins , Pneumonia/complications , Proto-Oncogene Proteins/metabolism , Rats
3.
Chin J Nat Med ; 20(6): 443-457, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35750384

ABSTRACT

Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis. Hence, regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis. However, the underlying mechanism is unclear. Dendrobium nobile (Shihu) exhibits anti-inflammatory and immune activities. Hence, in this study, we investigated the mechanism via which Shihu may improve allergic rhinitis. Mouse models of allergic rhinitis with intestinal flora dysbiosis (Model-D, antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy) and normal intestinal flora with allergic rhinitis (Model-N, ovalbumin-induced allergy) were established. The effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed. Allergic symptoms, infiltration of hematoxylin and eosin in the lungs and nose, and the release of various factors [interleukin (IL)-2, IL-4, IFN-γ, IL-6, IL-10, and IL-17] in the lungs were evaluated. The results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis. However, treatment with the Shihu extract effectively reversed these symptoms. Besides, the Shihu extract inhibited the PI3K/AKT/mTOR pathway and increased the level of Forkhead box protein in the lungs. Additionally, the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved regulator T cell differentiation. Furthermore, in the Model-D group, the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora. Screening was performed to determine which intestinal flora was positively correlated with Treg differentiation using Spearman's correlation analysis. In conclusion, we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using Traditional Chinese Medicine to improve allergic rhinitis.


Subject(s)
Dendrobium , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Pneumonia , Rhinitis, Allergic , Animals , Cytokines/metabolism , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Dysbiosis/chemically induced , Dysbiosis/drug therapy , Inflammation/drug therapy , Mice , Mice, Inbred BALB C , Ovalbumin , Phosphatidylinositol 3-Kinases , Rhinitis, Allergic/drug therapy , Rhinitis, Allergic/metabolism
4.
BMJ Open ; 12(6): e062428, 2022 Jun 24.
Article in English | MEDLINE | ID: mdl-35750458

ABSTRACT

INTRODUCTION: Community-acquired pneumonia (CAP), frequently encountered in both outpatient and inpatient settings, is the leading cause of infectious disease-related mortality. While equipoise regarding the optimal duration of antimicrobial therapy to treat CAP remains, recent studies suggest shorter durations of therapy may achieve optimal outcomes. We have therefore planned a systematic review and meta-analysis evaluating the impact of shorter versus longer durations of antibiotic therapy for patients with CAP. METHODS AND ANALYSIS: We searched Ovid MEDLINE, Embase, CINAHL and Cochrane Central Register of Controlled Trials from inception to September 2021 for randomised controlled trials evaluating shorter versus longer duration of antibiotics. Eligible studies will compare durations with a minimum difference of two days of antibiotic therapy, irrespective of antibiotic agent, class, route, frequency or dosage, and will report on any patient-important outcome of benefit or harm. Paired reviewers working independently will conduct title and abstract screening, full-text screening, data extraction and risk of bias (RoB) evaluation using a modified Cochrane RoB 2.0 tool. We will perform random-effects modelling for meta-analyses, with study weights generated using the inverse variance method, and will assess certainty in effect estimates using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The Instrument for assessing the Credibility of Effect Modification Analyses (ICEMAN) tool will inform assessments of credibility of subgroup effects based on severity of illness, drug class, duration of therapy, setting of CAP acquisition and RoB. ETHICS AND DISSEMINATION: The results will be of importance to general practitioners and internists managing CAP, and may directly inform international clinical guidance. Where concerns regarding antimicrobial resistance continue to grow internationally, this evidence summary may motivate new recommendations regarding shorter durations of therapy. We intend to disseminate our findings via national and international conferences, and publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021283990.


Subject(s)
Community-Acquired Infections , Pneumonia , Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/drug therapy , Humans , Meta-Analysis as Topic , Pneumonia/drug therapy , Systematic Reviews as Topic
5.
Sci Rep ; 12(1): 10741, 2022 Jun 24.
Article in English | MEDLINE | ID: mdl-35750716

ABSTRACT

Data are limited on the prevalence and outcome of anemia and its risk on mortality among children under five years of age hospitalized for pneumonia/severe pneumonia. Thus, we conducted a secondary analysis of data extracted from Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh to address the evidence gap. Among 3468 children fulfilling the study criteria,1712 (49.4%) had anemia. If children aged ≤ 1.0, > 1.0 to 2.0, > 2.0 to < 6.0, and ≥ 6.0 to 59 months had blood hemoglobin (Hb) value of ≤ 10.7 g/dL, ≤ 9.4 g/dL, ≤ 9.5 g/dL, and ≤ 11 g/dl respectively; we considered them anemic. The trend of prevalence of anemia was found to be inversely related to increasing age (Chi-square for linear trend analysis was done to understand the relation of anemia with increasing age, which was = 6.96; p = 0.008). During hospitalization anemic children more often developed respiratory failure (7.2% vs. 4.4%, p < 0.001) and fatal outcome (7.1.0% vs. 4.2%, p < 0.001) than the children who did not have anemia. After adjusting for potential confounders, such as female sex, lack of immunization, abnormal mental status, severe acute malnutrition, dehydration, hypoxemia, severe sepsis, and bacteremia using multivariable logistic regression analysis, anemia was found to be independently associated with fatal outcome (OR = 1.88, 95% CI 1.23-2.89, p = 0.004). Thus, future interventional studies on the early management of anemia may be warranted to understand whether the intervention reduces the morbidity and deaths in such children.


Subject(s)
Anemia , Pneumonia , Bangladesh/epidemiology , Child , Child, Preschool , Developing Countries , Female , Hospitalization , Humans , Infant , Pneumonia/complications , Prevalence , Risk Factors
7.
Mol Med ; 28(1): 72, 2022 Jun 25.
Article in English | MEDLINE | ID: mdl-35752760

ABSTRACT

BACKGROUND: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are clinical syndromes characterized by acute lung inflammation, pulmonary edema and hypoxemia, with up to 50% mortality rate without effective pharmacological therapy. Following the acute inflammation, repair and remodeling occurs which in some cases resulting in lung fibrosis. The pathophysiology of ALI/ARDS remains incompletely understood. Lipopolysaccharide (LPS)-induced ALI in mice have been widely used as a model to study human ALI/ARDS. Isthmin 1 (ISM1) is a secreted protein highly abundant in mouse lung. We have previously reported that upon intratracheal LPS instillation, ISM1 expression in the lung is further upregulated. Recently, we also reported that ISM1 is an anti-inflammatory protein in the lung with Ism1-/- mice presenting spontaneous chronic low-grade lung inflammation and obvious emphysema at young adult stage. However, what role ISM1 plays in ALI/ARDS and lung fibrosis remain unclear. METHODS: Using Ism1-/- mice and intratracheal LPS-induced ALI, and local delivery of recombinant ISM1 (rISM1), we investigated the role ISM1 plays in ALI and post-ALI lung fibrosis using flow cytometry, Western blot, antibody array, immunohistochemistry (IHC), immunofluorescent and other histological staining. RESULTS: We reveal that ISM1 deficiency in mice led to an intensified acute lung inflammation upon intratracheal LPS challenge, with a heightened leukocyte infiltration including neutrophils and monocyte-derived alveolar macrophages, as well as upregulation of multiple pro-inflammatory cytokines/chemokines including tumor necrosis factor α (TNF-α). Although innate immune cells largely subsided to the baseline by day 7 post-LPS challenge in both wild-type and Ism1-/- mice, Ism1-/- lung showed increased post-ALI fibrosis from day 9 post-LPS treatment with increased myofibroblasts, excessive collagen accumulation and TGF-ß upregulation. The heightened lung fibrosis remained on day 28 post-LPS. Moreover, intranasal delivered recombinant ISM1 (rISM1) effectively suppressed LPS-induced acute lung inflammation and ALI, and rISM1 suppressed LPS-induced NF-κB activation in cultured mouse alveolar macrophages. CONCLUSION: Together with our previous report, this work further established ISM1 as an endogenous anti-inflammation protein in the lung, restraining excessive host inflammatory response to LPS-triggered ALI and suppressing post-ALI lung fibrosis likely through suppressing NF-κB activation and pro-inflammatory cytokine/chemokine production.


Subject(s)
Acute Lung Injury , Pneumonia , Pulmonary Fibrosis , Respiratory Distress Syndrome , Acute Lung Injury/metabolism , Animals , Anti-Inflammatory Agents , Cytokines/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Lipopolysaccharides/pharmacology , Lung/pathology , Mice , NF-kappa B/metabolism , Pneumonia/metabolism , Pulmonary Fibrosis/metabolism
8.
Comput Intell Neurosci ; 2022: 5607358, 2022.
Article in English | MEDLINE | ID: mdl-35755768

ABSTRACT

Objective: Using data investigation, the microbiology of bacterial infection in patients with pulmonary infection was discussed, and its clinical characteristics were analyzed. Methods: The clinical data of 160 patients with pulmonary infection in our hospital from March 2019 to March 2021 were collected and analyzed. Blood samples were collected and cultured, and the pathogens were identified. The distribution, constituent ratio, and drug resistance of pathogens in elderly patients with pulmonary infection were analyzed. Logistics regression analysis was adopted to analyze the risk factors of pulmonary infection. Results: Of the 160 patients with pulmonary infection, 107 were males (66.88%) and 53 were females (33.13%). The age ranged from 12 to 97 years old, with an average of 63.82 ± 12.64 years old. Sevent-six patients (47.50%) were over 65 years old. Urban patients accounted for 71.88%, and rural patients accounted for 28.13%, of which workers accounted for 46.25%, and farmers and cadres each accounted for about 4%. 85.62% of smokers have smoked for more than 4 years. Eighty-five patients had chronic diseases such as coronary heart disease, hypertension, diabetes, and cerebrovascular disease. Heart failure occurred in 10.00%, old tuberculosis in 11.25%, and new tuberculosis in 5.63%. The average hospital stay of the patients was 14.93 days, and the improvement rate was 91.25%. Eleven patients died. Among the 160 patients with pulmonary infection, COPD, pneumonia, and lung cancer accounted for the highest proportions, and idiopathic pulmonary fibrosis, bronchitis dilatation, tuberculosis, and bronchial asthma also played an important role. Pathogenic bacteria were detected in 104 of the 160 elderly patients with pulmonary infection, and the detection rate was 65.00%. A total of 444 strains of pathogenic bacteria were detected, including 328 strains of Gram-negative bacteria (73.87%, mainly Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Serratia marcescens), 28 strains of Gram-positive bacteria (6.30%, mainly Staphylococcus aureus), and 88 strains of fungi (20.00%, mainly Candida albicans). Regarding Klebsiella pneumoniae in elderly patients with pulmonary infection, the drug resistance rates were 59.72% for amoxicillin-clavulanate potassium, 52.78% for ampicillin sodium-sulbactam sodium, and 51.39% for cefazolin sodium. Regarding Pseudomonas aeruginosa, the drug resistance rates were 29.31% for ticarcillin sodium-potassium clavulanate, 27.59% for piperacillin sodium, and 24.14% for gentamicin. Regarding Stenotrophomonas maltophilia, the drug resistance rates were 79.55% for ceftazidime, 38.64% for chloramphenicol, and 31.82% for levofloxacin. Regarding Serratia marcescens, the drug resistance rates from high to low were 74.42% for cefotaxime, 72.09% for moxifloxacin, and 69.77% for gentamicin. Regarding Staphylococcus aureus in elderly patients with pulmonary infection, the drug resistance rates were 100.00% for penicillin, 61.54% for erythromycin, 61.54% for clarithromycin, and 61.54% for azithromycin. Regarding Candida albicans, the drug resistance rates from high to low were 22.41% for caspofungin, 15.52% for itraconazole, and 9.09% for fluconazole. The results of univariate analysis of pulmonary bacterial infection indicated that there were no significant differences in sex and body mass index between nonbacterial infection group and bacterial infection group (P > 0.05). There were significant differences in terms of dust or harmful gas exposure, family member smoking, chronic lung disease history, age, smoking, family cooking, hospital stay, and indwelling catheter (P < 0.05). Exposure to dust or harmful gases, family cooking, age, history of chronic lung disease, indwelling catheter, and length of hospital stay were risk factors for pulmonary bacterial infection (P < 0.05). Conclusion: Gram-negative bacteria are the main pathogens in elderly patients with pulmonary infection. Antibiotics should be administered reasonably according to the results of the drug sensitivity test. Older age, history of chronic lung disease, catheter indwelling, and length of stay are the risk factors for pulmonary bacterial infection.


Subject(s)
Bacterial Infections , Lung Diseases , Pneumonia , Adolescent , Adult , Aged , Aged, 80 and over , Bacteria , Bacterial Infections/complications , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Child , Drug Resistance, Bacterial , Dust , Female , Gentamicins , Gram-Negative Bacteria , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Pseudomonas aeruginosa , Staphylococcus aureus , Young Adult
9.
Front Immunol ; 13: 868973, 2022.
Article in English | MEDLINE | ID: mdl-35757724

ABSTRACT

Introduction: Immunoglobulins (Igs) play a pivotal role in host defense and prevention of pneumonia. Aging influences serum Ig levels, but the association between Igs and pneumonia in community-dwelling older individuals remains unknown. We evaluated the association of serum IgA, IgG, and IgM with pneumonia and lung function in middle-aged and older individuals. Methods: We performed Cox and negative binomial regression analyses for the association of Igs with incident pneumonia and pneumonia-related mortality, and recurrent pneumonia respectively. We performed logistic regression analyses for the association between Igs and lung function values. Associations were adjusted for age, sex, smoking, comorbidities, and serum C-reactive protein. Results: We included 8,766 participants (median age 62.2 years, 57% women, median follow-up 9.8 years). Higher IgA (hazard ratio [HR]: 1.15; 95% confidence interval [95% CI]: 1.00-1.32) and IgG (HR: 1.13; 95% CI: 1.06-1.19) were associated with an increased pneumonia risk. Higher IgG was associated with an increased risk of pneumonia-related mortality (HR: 1.08; 95% CI: 1.01-1.16) and recurrent pneumonia (incidence rate ratio: 1.04; 95% CI: 1.00-1.09). Higher IgA and IgG were also associated with lower forced expiratory volume in one second (FEV1), lower forced vital capacity (FVC), and an increased odds of preserved ratio impaired spirometry (PRISm, i.e. FEV1 <80% and FEV1/FVC ratio ≥70%). No association was seen with an obstructive spirometry pattern. Discussion: Higher serum IgA and IgG levels were associated with pneumonia, pneumonia-related mortality, and PRISm in middle-aged and older individuals from the general population. Future studies should validate our findings and elucidate underlying pathophysiology.


Subject(s)
Lung , Pneumonia , Aged , Cohort Studies , Female , Humans , Immunoglobulin A , Immunoglobulin G , Male , Middle Aged , Pneumonia/epidemiology
10.
Wiad Lek ; 75(5 pt 1): 1175-1179, 2022.
Article in English | MEDLINE | ID: mdl-35758498

ABSTRACT

OBJECTIVE: The aim: To assess national trends in the morbidity of pneumonia in children aged 0-6 years, 7-14 years and 15-17 years in the period from 1993 to 2017 and mathematically predict the dynamics of the morbidity in 2025. PATIENTS AND METHODS: Materials and methods: Data from the Center for Medical Statistics of the Ministry of Health of Ukraine for the period 1993-2017 were used to calculate the morbidity rate of pneumonia in children aged 0-6 years, 7-14 and 15-17 years. RESULTS: Result: The period from 1993 to 2017 is characterized by high incidence of pneumonia in children in Ukraine (from 6.74 to 8.21 per 1000). In children aged 0-6 years, the morbidity 1000 ranged from 11.45 to 11.17, in children aged 7-14 years - from 4.65 to 6.46, in adolescents aged 15-17 years - from 1.99 to 10.47 . In Ukraine, the morbidity rate has significantly exceeded the that in European countries. In 2025, the morbidity of children under 6 years old in Ukraine may make up 3.84 per 1,000. CONCLUSION: Conclusions: In Ukraine, a significant increase in the morbidity rate of pneumonia in adolescents is predicted by 2025. It is necessary to develop a national strategy to improve the health of children and adolescents to implement policy and management measures in the health care system, aimed at effective prevention and quality treatment of pneumonia in children and adolescents.


Subject(s)
Pneumonia , Adolescent , Child , Child, Preschool , Europe , Humans , Incidence , Morbidity , Pneumonia/epidemiology , Prognosis , Ukraine/epidemiology
11.
Drug Des Devel Ther ; 16: 1793-1809, 2022.
Article in English | MEDLINE | ID: mdl-35719213

ABSTRACT

Purpose: Idiopathic pulmonary fibrosis is a chronic and irreversible fibrotic interstitial pneumonia of unknown etiology and therapeutic strategies are limited. Emerging evidence suggests that the continuous activation of the central nucleotide-binding oligomerization-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is involved in the pathogenesis of pulmonary fibrosis. Ginsenoside Rb1 (G-Rb1) is the most abundant component in the traditional Chinese herb ginseng and has anti-inflammatory and anti-fibrotic activities. The purpose of this study was to explore whether G-Rb1 exerts anti-inflammatory and anti-fibrotic activities in vivo and in vitro by suppressing the activation of the NLRP3 inflammasome and NF-κB pathway. Methods: Forty-eight male C57BL/6 mice were randomly divided into four groups (n=12/group) as follows: control, bleomycin (BLM), BLM/G-Rb1, and G-Rb1. A pulmonary fibrosis model was developed via an intratracheal injection of BLM. Six mice from each group were euthanized on days 3 and 21. The degree of pulmonary fibrosis was examined by histological evaluation and assessing α-smooth muscle actin levels. THP-1 cells were differentiated into macrophages, and stimulated by lipopolysaccharide and adenosine triphosphate. Activation of the NLRP3 inflammasome and NF-κB pathway was determined by Western blotting. Interleukin-1 beta and interleukin-18 levels were measured by ELISA. MRC-5 cells were cultured in the conditioned medium of the treated macrophages, after which markers of myofibroblasts were determined by Western blotting. Results: G-Rb1 ameliorated BLM-induced pulmonary inflammation and fibrosis in mice, and suppressed NLRP3 inflammasome activation and the NF-κB pathway in lung tissues. Moreover, interleukin-1 beta secreted after NLRP3 inflammasome activation in macrophages promoted fibroblast differentiation. G-Rb1 inhibited lipopolysaccharide- and adenosine triphosphate-induced NLRP3 inflammasome activation in macrophages and disturbed the crosstalk between macrophages and fibroblasts. Conclusion: G-Rb1 ameliorates BLM-induced pulmonary inflammation and fibrosis by suppressing NLRP3 inflammasome activation and the NF-κB pathway. Hence, G-Rb1 is a potential novel therapeutic drug for idiopathic pulmonary fibrosis.


Subject(s)
Idiopathic Pulmonary Fibrosis , Pneumonia , Adenosine Triphosphate/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Bleomycin/adverse effects , Fibrosis , Ginsenosides , Idiopathic Pulmonary Fibrosis/drug therapy , Inflammasomes/metabolism , Interleukin-1beta/metabolism , Leucine/therapeutic use , Lipopolysaccharides/pharmacology , Male , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Nucleotides/metabolism , Pneumonia/chemically induced , Pneumonia/drug therapy , Pneumonia/metabolism , Pyrin Domain , Signal Transduction
12.
Adv Respir Med ; 90(3): 219-229, 2022.
Article in English | MEDLINE | ID: mdl-35731114

ABSTRACT

Immune-checkpoint inhibitors (ICIs) have revolutionized treatment of solid malignancies, leading in some cases to durable responses. However, an unchecked immune response might lead to mild to severe immune-related adverse events (irAEs). Pulmonary toxicity, though often referred to as Immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis), covers a broad and overlapping spectrum of pulmonary manifestations and has been described in < 10% of patients receiving ICI either alone or in combination. However, the actual numbers in real-world populations are high, and are likely to increase as the therapeutic indications for ICIs continue to expand to include other malignancies. Drug withdrawal is the mainstay of treatment for ICI-pneumonitis. However, a good number of patients with higher grades of toxicity may need corticosteroids. Patients with refractory disease need additional immunosuppressive agents. In this brief review, we succinctly discuss the incidence, risk factors, mechanisms, clinical and radiologic manifestations, diagnosis and summarize the current management strategies of ICI-pneumonitis.


Subject(s)
Neoplasms , Pneumonia , Humans , Incidence , Neoplasms/complications , Neoplasms/drug therapy , Pneumonia/etiology , Risk Factors
13.
BMJ Case Rep ; 15(6)2022 Jun 22.
Article in English | MEDLINE | ID: mdl-35732376

ABSTRACT

A man in his 60s with stage 3 squamous cell carcinoma of the left lung status postchemotherapy and radiation therapy presented with mixed septic and obstructive shock with multiorgan dysfunction. Initial electrocardiogram showed sinus tachycardia and diffuse concaved ST elevation. Transthoracic echocardiogram revealed pericardial effusion with tamponade physiology. CT thorax was notable for dense left lung consolidation with pleural effusion. Emergent pericardiocentesis and percutaneous balloon pericardiotomy were performed which successfully drained 500 mL of purulent pericardial fluid. A left chest tube was placed and revealed a large volume of empyema. Both pericardial and pleural fluid cultures yielded similar strains of Streptococcus anginosus The patient was initially treated with empiric broad-spectrum intravenous antibiotics which were eventually de-escalated to intravenous ceftriaxone based on microbiology culture and sensitivity. Unfortunately, the patient developed pulseless electrical activity arrest on day 10 of intensive care unit stay and expired despite cardiopulmonary resuscitation.


Subject(s)
Cardiac Tamponade , Pericardial Effusion , Pericarditis , Pneumonia , Cardiac Tamponade/etiology , Cardiac Tamponade/therapy , Humans , Male , Mediastinitis , Pericardial Effusion/etiology , Pericardiocentesis/adverse effects , Pericarditis/drug therapy , Pericarditis/therapy , Pneumonia/complications , Sclerosis , Streptococcus anginosus
14.
J Exp Med ; 219(8)2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35708626

ABSTRACT

Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.7%) aged 1.5-13 yr with critical (7 children), severe (3), and moderate (2) pneumonia and 4 of the 15 known clinically recessive and biochemically complete inborn errors of type I IFN immunity: X-linked recessive TLR7 deficiency (7 children) and autosomal recessive IFNAR1 (1), STAT2 (1), or TYK2 (3) deficiencies. Fibroblasts deficient for IFNAR1, STAT2, or TYK2 are highly vulnerable to SARS-CoV-2. These 15 deficiencies were not found in 1,224 children and adults with benign SARS-CoV-2 infection without pneumonia (P = 1.2 × 10-11) and with overlapping age, sex, consanguinity, and ethnicity characteristics. Recessive complete deficiencies of type I IFN immunity may underlie ∼10% of hospitalizations for COVID-19 pneumonia in children.


Subject(s)
COVID-19 , Interferon Type I , Pneumonia , Adult , COVID-19/genetics , Child , Humans , Inheritance Patterns , SARS-CoV-2
15.
Crit Care Med ; 50(7): 1153-1155, 2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35726980
16.
J Trop Pediatr ; 68(4)2022 Jun 06.
Article in English | MEDLINE | ID: mdl-35727140

ABSTRACT

BACKGROUND: Pneumonia acquired in the community is a leading cause of hospitalization and death in under-five children. Predicting mortality in children remains a challenge. There is a need of consolidated scoring system to predict mortality in under-five children in developing nations. METHODS: This is a hospital-based prospective nested case-control study, conducted in a tertiary care teaching hospital of north India. Included were under-five hospitalized children due to WHO defined severe community acquired pneumonia (CAP). Those who did not survive were categorized as cases, while those who were discharged were categorized as controls. RESULTS: The mortality rate among the recruited 180 hospitalized children with severe CAP was 9.4%. The mortality in under-five children was higher among infants, children who resided in rural areas and were unimmunized or partially immunized for the present age. Mortality was also statistically significantly higher among under-five children with weight for age and weight for length/height below -2Z score; SpO2 < 90% at room air at admission, cyanosis, convulsion, high C-reactive protein (CRP), blood culture positive sepsis and end point consolidation. These predictors were found to be independent risk factors for the mortality after analyzing in multivariate model while presence of wheeze and exclusive breast feeding for first six months of life were found to be protective. The receiver operating characteristic (ROC) curve for respiratory index of severity in children (RISC) score has area under curve (AUC) 0.91 while AUC of RISC score with King George's Medical University (KGMU) modification has 0.88 for prediction of mortality. At the cut-off level of 3, the sensitivity of the RISC score in predicting mortality was 94.1% while the specificity was 73.6%. However, the sensitivity of the RISC score with KGMU modification in predicting mortality at cut-off level of 3 was 88.4% with a specificity of 74.8%. CONCLUSION: Various predictors for mortality under-five children are young age, malnutrition, cyanosis, high CRP, blood culture positive sepsis and end point consolidation. It is also possible to predict mortality using RISC score which comprises simple variables and can be easily used at centers of periphery. Similar accuracy had been also found through the use of an age independent modified score (RISC score with KGMU modification).Lay summaryPneumonia is a primary cause of hospitalization as well as death among the children under the age of five. A variety of severity or mortality predicting scores have been produced for adults, but such scores for children are scarce. Furthermore, their utility in developing nations has not been proven. This is a hospital-based prospective study. Included were children under five (2 to 59 months) hospitalized due to severe community acquired pneumonia (CAP) defined as per World Health Organization (WHO) and were not hospitalized in last 14 days elsewhere. Those who did not survive were classified as cases while those who were discharged were classified as controls. A total of 200 consecutively hospitalized children with severe CAP based on WHO were screened and 180 children were recruited. Among recruited children, the percentage of mortality was 9.4% while 90.6% were discharged. The mortality was higher among children younger than 12 months, those belonged to rural area and were unimmunized or partially immunized for the present age. Mortality was also higher among under-five children with severe malnutrition, anemia, SpO2 < 90% at room air at admission, cyanosis, convulsion, thrombocytopenia, high CRP, blood culture positive sepsis and end point consolidation. After assessing in a multivariate model, these predictors were determined to be independent risk factor for death, while wheezing and exclusive breast feeding throughout the first six months of life were found to be protective. The receiver operating characteristic (ROC) curve for respiratory index of severity in children (RISC) score has an area under curve (AUC) of 0.91 while AUC of RISC score with King George's Medical University (KGMU) modification was 0.88 for the prediction of death in under-five children hospitalized due to severe CAP.


Subject(s)
Community-Acquired Infections , Malnutrition , Pneumonia , Sepsis , Adult , C-Reactive Protein , Case-Control Studies , Child , Community-Acquired Infections/diagnosis , Cyanosis , Hospitalization , Humans , Infant , Pneumonia/diagnosis , Prospective Studies , Retrospective Studies , Seizures , Severity of Illness Index , World Health Organization
17.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(5): 485-491, 2022 May.
Article in Chinese | MEDLINE | ID: mdl-35728849

ABSTRACT

OBJECTIVE: To compare and analyze the clinical features of patients with severe coronavirus disease 2019 (sCOVID-19) and severe community acquired pneumonia (sCAP) who meet the diagnostic criteria for severe pneumonia of the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS). METHODS: A retrospective comparative analysis of the clinical records of 116 patients with sCOVID-19 admitted to the department of critical care medicine of Wuhan Third Hospital from January 1, 2020 to March 31, 2020 and 135 patients with sCAP admitted to the department of critical care medicine of Shanghai First People's Hospital from January 1, 2010 to December 31, 2017 was conducted. The basic information, diagnosis and comorbidities, laboratory data, etiology and imaging results, treatment, prognosis and outcome of the patients were collected. The differences in clinical data between sCOVID-19 and sCAP patients were compared, and the risk factors of death were analyzed. RESULTS: The 28-day mortality of sCOVID-19 and sCAP patients were 50.9% (59/116) and 37.0% (50/135), respectively. The proportion of arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ≤ 250 mmHg (1 mmHg ≈ 0.133 kPa) in sCOVID-19 patients was significantly higher than that of sCAP [62.1% (72/116) vs. 34.8% (47/135), P < 0.01]. The possible reason was that the proportion of multiple lung lobe infiltration in sCOVID-19 was significantly higher than that caused by sCAP [94.0% (109/116) vs. 40.0% (54/135), P < 0.01], but the proportion of sCOVID-19 patients requiring mechanical ventilation was significantly lower than that of sCAP [45.7% (53/116) vs. 60.0% (81/135), P < 0.05]. Further analysis of clinical indicators related to patient death found that for sCOVID-19 patients PaO2/FiO2, white blood cell count (WBC), neutrophils (NEU), neutrophil percentage (NEU%), neutrophil/lymphocyte ratio (NLR), total bilirubin (TBil), blood urea nitrogen (BUN), albumin (ALB), Ca2+, prothrombin time (PT), D-dimer, C-reactive protein (CRP) and other indicators were significantly different between the death group and the survival group, in addition, the proportion of receiving mechanical ventilation, gamma globulin, steroid hormones and fluid resuscitation in death group were higher than survival group. Logistic regression analysis showed that the need for mechanical ventilation, NLR > 10, TBil > 10 µmol/L, lactate dehydrogenase (LDH) > 250 U/L were risk factors for death at 28 days. For sCAP patients, there were significant differences in age, BUN, ALB, blood glucose (GLU), Ca2+ and D-dimer between the death group and the survival group, but there was no significant difference in treatment. Logistic regression analysis showed that BUN > 7.14 mmol/L and ALB < 30 g/L were risk factors for 28-day death of sCAP patients. CONCLUSIONS: The sCOVID-19 patients in this cohort have worse oxygen condition and symptoms than sCAP patients, which may be due to the high proportion of lesions involving the lungs. The indicators of the difference between the death group and the survival group were similar in sCOVID-19 and sCAP patients. It is suggested that the two diseases have similar effects on renal function, nutritional status and coagulation function. But there were still differences in risk factors affecting survival. It may be that sCOVID-19 has a greater impact on lung oxygenation function, inflammatory cascade response, and liver function, while sCAP has a greater impact on renal function and nutritional status.


Subject(s)
COVID-19 , Community-Acquired Infections , Pneumonia , China , Community-Acquired Infections/diagnosis , Humans , Oxygen , Prognosis , Retrospective Studies
18.
BMJ Open ; 12(6): e057957, 2022 Jun 21.
Article in English | MEDLINE | ID: mdl-35728910

ABSTRACT

OBJECTIVE: To identify aetiologies of childhood community-acquired pneumonia (CAP) based on a comprehensive diagnostic approach. DESIGN: 'Partnerships for Enhanced Engagement in Research-Pneumonia in Paediatrics (PEER-PePPeS)' study was an observational prospective cohort study conducted from July 2017 to September 2019. SETTING: Government referral teaching hospitals and satellite sites in three cities in Indonesia: Semarang, Yogyakarta and Tangerang. PARTICIPANTS: Hospitalised children aged 2-59 months who met the criteria for pneumonia were eligible. Children were excluded if they had been hospitalised for >24 hours; had malignancy or history of malignancy; a history of long-term (>2 months) steroid therapy, or conditions that might interfere with compliance with study procedures. MAIN OUTCOMES MEASURES: Causative bacterial, viral or mixed pathogen(s) for pneumonia were determined using microbiological, molecular and serological tests from routinely collected specimens (blood, sputum and nasopharyngeal swabs). We applied a previously published algorithm (PEER-PePPeS rules) to determine the causative pathogen(s). RESULTS: 188 subjects were enrolled. Based on our algorithm, 48 (25.5%) had a bacterial infection, 31 (16.5%) had a viral infection, 76 (40.4%) had mixed bacterial and viral infections, and 33 (17.6%) were unable to be classified. The five most common causative pathogens identified were Haemophilus influenzae non-type B (N=73, 38.8%), respiratory syncytial virus (RSV) (N=51, 27.1%), Klebsiella pneumoniae (N=43, 22.9%), Streptococcus pneumoniae (N=29, 15.4%) and Influenza virus (N=25, 13.3%). RSV and influenza virus diagnoses were highly associated with Indonesia's rainy season (November-March). The PCR assays on induced sputum (IS) specimens captured most of the pathogens identified in this study. CONCLUSIONS: Our study found that H. influenzae non-type B and RSV were the most frequently identified pathogens causing hospitalised CAP among Indonesian children aged 2-59 months old. Our study also highlights the importance of PCR for diagnosis and by extension, appropriate use of antimicrobials. TRAIL REGISTRATION NUMBER: NCT03366454.


Subject(s)
Community-Acquired Infections , Haemophilus influenzae type b , Pneumonia , Respiratory Syncytial Virus, Human , Virus Diseases , Child , Child, Hospitalized , Child, Preschool , Community-Acquired Infections/microbiology , Humans , Indonesia/epidemiology , Infant , Pneumonia/etiology , Prospective Studies , Virus Diseases/complications
19.
Life Sci Alliance ; 5(10)2022 Oct.
Article in English | MEDLINE | ID: mdl-35728946

ABSTRACT

We evaluated the efficacy of ceftazidime or colistin in combination with polyclonal IgM-enriched immunoglobulin (IgM-IG), in an experimental pneumonia model (C57BL/6J male mice) using two multidrug-resistant Pseudomonas aeruginosa strains, both ceftazidime-susceptible and one colistin-resistant. Pharmacodynamically optimised antimicrobials were administered for 72 h, and intravenous IgM-IG was given as a single dose. Bacterial tissues count and the mortality were analysed. Ceftazidime was more effective than colistin for both strains. In mice infected with the colistin-susceptible strain, ceftazidime reduced the bacterial concentration in the lungs and blood (-2.42 and -3.87 log10 CFU/ml) compared with colistin (-0.55 and -1.23 log10 CFU/ml, respectively) and with the controls. Colistin plus IgM-IG reduced the bacterial lung concentrations of both colistin-susceptible and resistant strains (-2.91 and -1.73 log10 CFU/g, respectively) and the bacteraemia rate of the colistin-resistant strain (-44%). These results suggest that IgM-IG might be useful as an adjuvant to colistin in the treatment of pneumonia caused by multidrug-resistant P. aeruginosa.


Subject(s)
Pneumonia , Pseudomonas Infections , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Ceftazidime/pharmacology , Ceftazidime/therapeutic use , Colistin/pharmacology , Colistin/therapeutic use , Drug Resistance, Multiple, Bacterial , Immunoglobulin M , Male , Mice , Mice, Inbred C57BL , Pneumonia/drug therapy , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa
20.
Int J Chron Obstruct Pulmon Dis ; 17: 1299-1310, 2022.
Article in English | MEDLINE | ID: mdl-35686213

ABSTRACT

Background: Fibrinogen is increasingly being studied as an inflammatory biomarker in chronic obstructive pulmonary disease (COPD), but there are limited data on the role of fibrinogen in assessing the severity of acute exacerbation of COPD (AECOPD). This study aimed to explore whether circulating fibrinogen could be used as a surrogate to measure the severity and predict the prognosis of AECOPD. Methods: A total of 535 AECOPD patients diagnosed at our center from January 2016 to June 2021 were retrospectively enrolled in this study. The electronic medical record of each patient was retrieved to collect data on baseline characteristics and laboratory parameters, as well as the use of noninvasive positive-pressure ventilation (NPPV) and prognosis. Multiple linear regression analysis was used to identify independent factors associated with circulating fibrinogen values. Receiver-operating characteristic curve and multivariate logistic regression analysis were applied to further verify the use of fibrinogen to predict NPPV failure. Results: Compared to patients with fibrinogen <4 g/L, patients with increased fibrinogen levels (>4 g/L) tended to have elevated inflammatory response and higher incidence of DVT/PTE, emphysema, pneumonia, and atherosclerosis. In addition, fibrinogen levels in NPPV-failure patients were significantly higher than non-NPPV patients and NPPV-success ones. The presence of emphysema, pneumonia, and history of long-term oxygen therapy and higher CRP levels and leukocyte counts were independent risk factors associated with increased fibrinogen levels in AECOPD. Furthermore, our data indicated that fibrinogen could be considered as a reliable biomarker to predict NPPV failure (AUC, 0.899, 95% CI 0.846-0.952), with an OR of 7.702 (95% CI 2.984-19.875; P<0.001). Conclusion: The level of circulating fibrinogen can be used to measure severity of AECOPD, and among AECOPD patients managed with NPPV, fibrinogen >3.55 g/L can independently predict NPPV failure.


Subject(s)
Emphysema , Pneumonia , Pulmonary Disease, Chronic Obstructive , Biomarkers , Emphysema/complications , Fibrinogen , Humans , Pneumonia/complications , Prognosis , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/therapy , Retrospective Studies
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