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Stattin K, Eriksson M, Frithiof R, Kawati R, Crockett D, Hultström M, Lipcsey M. Alcohol consumption has a J-shaped association with bacterial infection and death due to infection, a population-based cohort study. Sci Rep 2025; 15:7333. [PMID: 40025055 PMCID: PMC11873035 DOI: 10.1038/s41598-025-90197-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 02/11/2025] [Indexed: 03/04/2025] Open
Abstract
The aim of this study is to investigate the association between alcohol consumption and the risk of bacterial infection and its dose-response association. Participants in the Swedish Mammography Cohort and Cohort of Swedish Men answered lifestyle questionnaires in 1997 and have since been followed in national registers. The risks of acquiring infection, intensive care unit (ICU) admission and dying due to infection were assessed with Cox regression. Among 58,078 cohort participants followed for 23 years, 23,035 participants were diagnosed with an infection and 4,030 died from infection. Alcohol consumption exhibited a J-shaped association with the risk of acquiring infection and dying due to infection: compared to consuming 5-10 g of alcohol per day, consuming < 0.5 g/day and consuming > 30 g/day were both associated with higher risk of acquiring infection, ICU admission and dying due to infection, whereas alcohol consumption between 5 and 30 g/day was not associated with acquiring infection, ICU admission or death due to infection. In conclusion, moderate alcohol consumption was not associated with infection, but both very low and high levels of consumption were associated with acquiring infection, ICU admission and death. If replicated, this suggests that reduction of alcohol consumption might reduce mortality from bacterial infections.
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Affiliation(s)
- Karl Stattin
- Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Akademiska sjukhuset, ingång 70, 751 85, Uppsala, Sweden.
| | - Mikael Eriksson
- Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Akademiska sjukhuset, ingång 70, 751 85, Uppsala, Sweden
| | - Robert Frithiof
- Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Akademiska sjukhuset, ingång 70, 751 85, Uppsala, Sweden
| | - Rafael Kawati
- Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Akademiska sjukhuset, ingång 70, 751 85, Uppsala, Sweden
| | - Douglas Crockett
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Michael Hultström
- Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Akademiska sjukhuset, ingång 70, 751 85, Uppsala, Sweden
- Department of Medical Cell Biology, Integrative Physiology, Uppsala University, Uppsala, Sweden
| | - Miklos Lipcsey
- Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Akademiska sjukhuset, ingång 70, 751 85, Uppsala, Sweden
- Hedenstierna Laboratory, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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Colling KP, Kraft AK, Harry ML. Comparing Outcomes and Infection Risk in Medical, Surgical, and Trauma Intensive Care Patients with Alcohol Use Disorder. Surg Infect (Larchmt) 2025. [PMID: 39866118 DOI: 10.1089/sur.2024.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2025] Open
Abstract
Introduction: Alcohol is the most frequently abused drug in the United States, and alcohol use disorder (AUD) is a common comorbidity in intensive care units (ICUs). Patients and Methods: We performed a retrospective chart review of patients admitted to an ICU between January 2017 and March 2019 at a tertiary hospital serving a large rural population. Patients with diagnoses of AUDs were included. Patients were excluded if they did not require ICU care. Patient demographics, hospital course, infection type, culture results, and mortality were evaluated. We compared medical, surgical, and trauma ICU patient outcomes and infections. Results: In total, 527 patients met inclusion and exclusion criteria. Trauma ICU patients had the least pre-existing comorbidities, and surgical ICU patients had the longest lengths of stay. There was no difference in in-hospital mortality between ICU groups; however, surgical and medical ICU patients had significantly greater rates of in-hospital mortality compared with trauma ICU patients. Infections were common across all ICU types, occurring in 40% of patients. There was no difference in infection rate between ICU types. In multi-variable analysis controlling for age, gender, liver failure, chronic kidney disease, thrombocytopenia, complications, and blood transfusions, infection remained an independent predictor of in-hospital mortality (adjusted odds ratio 3.3, 95% confidence interval 1.7-6.4). Septic shock occurred in 57% of infections and was associated with an increased risk of mortality (38% vs. 2%, p < 0.001). Pneumonia was the most common infection occurring in 28% of the cohort, followed by bacteremia (7%), skin/soft tissue infections (6%), urinary tract infection (5%), intra-abdominal infections (4%), and C. difficile (2%). Conclusions: AUDs in all types of ICU patients are associated with high rates of infections and high morbidity and mortality.
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Affiliation(s)
| | - Alexandra K Kraft
- Department of Surgery, University of Minnesota Medical Center, Duluth, Minnesota, USA
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Chen YH, Ren CY, Liao Y. Analysis of risk factors for hospital-acquired pneumonia in schizophrenia. Front Psychiatry 2024; 15:1414332. [PMID: 39220180 PMCID: PMC11362047 DOI: 10.3389/fpsyt.2024.1414332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 07/31/2024] [Indexed: 09/04/2024] Open
Abstract
Background Hospital-acquired pneumonia is one of the most important causes of recurrent illness, disease progression, and even death during hospitalization. Patients with schizophrenia have the special characteristics of their disease, and at the same time, the occurrence of hospital-acquired pneumonia is more common among patients with schizophrenia due to the prolonged stay in closed wards, accompanied by various factors such as age, gender, and nutritional status. Methods The PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database (CBM) databases were searched with a timeframe of build to February 2024 to collect studies on factors influencing hospital-acquired pneumonia in patients with schizophrenia. Two researchers independently screened the literature, extracted data, and analyzed them. Results A total of 5 papers including 85246 patients were included in the literature, which suggested that benzodiazepines (especially the use of clozapine), combination of antipsychotics, mood stabilizers, modified electroconvulsive therapy (MECT), duration of hospitalization, underlying diseases, hyperglycemia, and salivation/dysphagia were important risk factors for hospital-acquired pneumonia in schizophrenia patients, and that advanced age, smoking and alcohol drinking Older age, smoking and drinking habits, malnutrition, and underlying diseases are also risk factors for hospital-acquired pneumonia. Conclusions Patients with schizophrenia are at a higher risk of developing hospital-acquired pneumonia, so identifying the risk factors associated with hospital-acquired pneumonia and evaluating them comprehensively and promptly during hospitalization facilitates the development of early interventions, which are essential for improving the prognosis of patients with schizophrenia.
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Affiliation(s)
- Yu-hang Chen
- Department of Operations Management, Chongqing Mental Health Center, Chongqing, China
| | - Cong-ying Ren
- Department of Hospital Infection Control, Chongqing Mental Health Center, Chongqing, China
| | - Yu Liao
- Cardiology Department, People’s Hospital of Chongqing Rongchang District, Chongqing, China
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Kessel K, Forsblom E, Ruotsalainen E, Järvinen A. Staphylococcus aureus bacteremia in alcoholics. PLoS One 2024; 19:e0298612. [PMID: 38771740 PMCID: PMC11108141 DOI: 10.1371/journal.pone.0298612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 01/27/2024] [Indexed: 05/23/2024] Open
Abstract
BACKGROUND Alcoholism associates with increased Staphylococcus aureus bacteremia incidence and mortality. The objective was to compare disease progression, treatment and prognosis of Staphylococcus aureus bacteremia in alcoholics versus non-alcoholics. METHODS The study design was a multicenter retrospective analysis of methicillin-sensitive Staphylococcus aureus bacteremia with 90-day follow-up. Patients were stratified as alcoholics or non-alcoholics based on electronic health record data. Altogether 617 Staphylococcus aureus bacteremia patients were included of which 83 (13%) were alcoholics. RESULTS Alcoholics, versus non-alcoholics, were younger, typically male and more commonly had community-acquired Staphylococcus aureus bacteremia. No differences in McCabe´s classification of underlying conditions was observed. Higher illness severity at blood culture sampling, including severe sepsis (25% vs. 7%) and intensive care unit admission (39% vs. 17%), was seen in alcoholics versus non-alcoholics. Clinical management, including infectious disease specialist (IDS) consultations and radiology, were provided equally. Alcoholics, versus non-alcoholics, had more pneumonia (49% vs. 35%) and fewer cases of endocarditis (7% vs. 16%). Mortality in alcoholics versus non-alcoholics was significantly higher at 14, 28 and 90 days (14% vs. 7%, 24% vs. 11% and 31% vs. 17%), respectively. Considering all prognostic parameters, male sex (OR 0.19, p = 0.021) and formal IDS consultation (OR 0.19, p = 0.029) were independent predictors of reduced mortality, whereas ultimately or rapidly fatal comorbidity in McCabe´s classification (OR 12.34, p < 0.001) was an independent predictor of mortality in alcoholics. CONCLUSIONS Alcoholism deteriorates Staphylococcus aureus bacteremia prognosis, and our results suggests that this is predominantly through illness severity at bacteremia onset. Three quarters of Staphylococcus aureus bacteremia patients we studied had identified deep infection foci, and of them alcoholics had significantly less endocarditis but nearly half of them had pneumonia.
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Affiliation(s)
- Klaus Kessel
- Division of Infectious Diseases, Inflammation Center, Helsinki University Hospital, Helsinki, Finland
| | - Erik Forsblom
- Division of Infectious Diseases, Inflammation Center, Helsinki University Hospital, Helsinki, Finland
| | - Eeva Ruotsalainen
- Division of Infectious Diseases, Inflammation Center, Helsinki University Hospital, Helsinki, Finland
| | - Asko Järvinen
- Division of Infectious Diseases, Inflammation Center, Helsinki University Hospital, Helsinki, Finland
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Shen M, Zhao H, Han M, Su L, Cui X, Li D, Liu L, Wang C, Yang F. Alcohol-induced gut microbiome dysbiosis enhances the colonization of Klebsiella pneumoniae on the mouse intestinal tract. mSystems 2024; 9:e0005224. [PMID: 38345382 PMCID: PMC10949497 DOI: 10.1128/msystems.00052-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 01/12/2024] [Indexed: 03/20/2024] Open
Abstract
Chronic alcohol consumption, an important risk factor for diseases and deaths, can cause intestinal microbiota dysbiosis and increase the infection of some opportunistic pathogens. However, the current studies on the effects of alcohol-induced intestinal microbiota dysbiosis on gut colonization of Klebsiella pneumoniae are still scarce. In the present study, we established a binge-on-chronic alcohol model in mice to identify the characteristics of alcohol-induced intestinal microbiome and metabolite dysbiosis using multi-omics and explored the effects and potential mechanisms of these dysbioses on the intestinal colonization of K. pneumoniae. The results show that chronic alcohol consumption alters the diversity and composition of gut microbiota (including bacteria and fungi), decreases the complexity of the interaction between intestinal bacteria and fungi, disturbs the gut metabolites, and promotes the colonization of K. pneumoniae on the gut of mice. The relevance analyses find that alcohol-induced gut microbiome dysbiosis has a strong correlation with the alteration of secondary bile acids. In vitro results suggest that the high concentration of lithocholic acid, a secondary bile acid, could significantly inhibit the proliferation of K. pneumoniae, and the adhesion of K. pneumoniae to Caco-2 cells. Our results indicate that alcohol-induced microbiome dysbiosis contributes to decreased levels of secondary bile acids, which was one of the main reasons affecting the colonization of K. pneumoniae in mice's intestines. Some secondary bile acids (e.g., lithocholic acid) might be a potential drug to prevent the colonization and spread of K. pneumoniae.IMPORTANCEAlcohol is one of the most commonly misused substances in our lives. However, long-term heavy drinking will increase the colonization of some opportunistic pathogens (e.g., Klebsiella pneumoniae) in the body. Here, we revealed that binge-on-chronic alcohol consumption disrupted the balance between gut bacteria and fungi, induced the gut microbiome and metabolites dysbiosis, and promoted the colonization of K. pneumoniae in the intestine of mice. In particular, alcohol-taking disrupted intestinal bile acid metabolism and reduced the lithocholic acid concentration. However, a high concentration of lithocholic acid can protect against intestinal colonization of K. pneumoniae by inhabiting the bacterial growth and adhesion to the host cell. Hence, regulating the balance of gut microbiota and intestinal bile acid metabolism may be a potential strategy for reducing the risk of K. pneumoniae infection and spread.
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Affiliation(s)
- Mengke Shen
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
- Department of Pathogenic Biology and Immunology, Sanquan College of Xinxiang Medical University, Xinxiang, China
| | - Huajie Zhao
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
| | - Meiqing Han
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
| | - Lin Su
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
| | - Xiaojian Cui
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
| | - Duan Li
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
| | - Liang Liu
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
| | - Chuansheng Wang
- The Second Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China
| | - Fan Yang
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
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Burnham EL, Pomponio R, Perry G, Offner PJ, Ormesher R, Peterson RA, Jolley SE. Prevalence of Alcohol Use Characterized by Phosphatidylethanol in Patients With Respiratory Failure Before and During the COVID-19 Pandemic. CHEST CRITICAL CARE 2024; 2:100045. [PMID: 38818345 PMCID: PMC11138642 DOI: 10.1016/j.chstcc.2023.100045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/01/2024]
Abstract
BACKGROUND Alcohol misuse is overlooked frequently in hospitalized patients, but is common among patients with pneumonia and acute hypoxic respiratory failure. Investigations in hospitalized patients rely heavily on self-report surveys or chart abstraction, which lack sensitivity. Therefore, our understanding of the prevalence of alcohol misuse before and during the COVID-19 pandemic is limited. RESEARCH QUESTION In critically ill patients with respiratory failure, did the proportion of patients with alcohol misuse, defined by the direct biomarker phosphatidylethanol, vary over a period including the COVID-19 pandemic? STUDY DESIGN AND METHODS Patients with acute hypoxic respiratory failure receiving mechanical ventilation were enrolled prospectively from 2015 through 2019 (before the pandemic) and from 2020 through 2022 (during the pandemic). Alcohol use data, including Alcohol Use Disorders Identification Test (AUDIT)-C scores, were collected from electronic health records, and phosphatidylethanol presence was assessed at ICU admission. The relationship between clinical variables and phosphatidylethanol values was examined using multivariable ordinal regression. Dichotomized phosphatidylethanol values (≥ 25 ng/mL) defining alcohol misuse were compared with AUDIT-C scores signifying misuse before and during the pandemic, and correlations between log-transformed phosphatidylethanol levels and AUDIT-C scores were evaluated and compared by era. Multiple imputation by chained equations was used to handle missing phosphatidylethanol data. RESULTS Compared with patients enrolled before the pandemic (n = 144), patients in the pandemic cohort (n = 92) included a substantially higher proportion with phosphatidylethanol-defined alcohol misuse (38% vs 90%; P < .001). In adjusted models, absence of diabetes, positive results for COVID-19, and enrollment during the pandemic each were associated with higher phosphatidylethanol values. The correlation between health care worker-recorded AUDIT-C score and phosphatidylethanol level was significantly lower during the pandemic. INTERPRETATION The higher prevalence of phosphatidylethanol-defined alcohol misuse during the pandemic suggests that alcohol consumption increased during this period, identifying alcohol misuse as a potential risk factor for severe COVID-19-associated respiratory failure. Results also suggest that AUDIT-C score may be less useful in characterizing alcohol consumption during high clinical capacity.
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Affiliation(s)
- Ellen L Burnham
- Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO
| | - Raymond Pomponio
- Department of Medicine, Biostatistics and Informatics, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora CO
| | - Grace Perry
- Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO
| | - Patrick J Offner
- Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO
| | - Ryen Ormesher
- Colorado School of Public Health, and Internal Medicine, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora CO
| | - Ryan A Peterson
- Department of Medicine, Biostatistics and Informatics, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora CO
| | - Sarah E Jolley
- Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO
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Sophonsri A, Lou M, Ny P, Minejima E, Nieberg P, Wong-Beringer A. Machine learning to identify risk factors associated with the development of ventilated hospital-acquired pneumonia and mortality: implications for antibiotic therapy selection. Front Med (Lausanne) 2023; 10:1268488. [PMID: 38170135 PMCID: PMC10759933 DOI: 10.3389/fmed.2023.1268488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 11/28/2023] [Indexed: 01/05/2024] Open
Abstract
Background Among patients with nosocomial bacterial pneumonia, those who decompensated to requiring mechanical ventilation (vHABP) faced the highest mortality followed by ventilator-associated pneumonia (VABP) and non-ventilated hospital-acquired pneumonia (nvHABP). The objectives of this study were to identify risk factors associated with the development and mortality of vHABP and to evaluate antibiotic management. Methods A multicenter retrospective cohort study of adult inpatients with nosocomial pneumonia during 2014-2019 was performed. Groups were stratified by vHABP, nvHABP, and VABP and compared on demographics, clinical characteristics, treatment, and outcomes. Multivariable models were generated via machine learning to identify risk factors for progression to vHABP as well as pneumonia-associated mortality for each cohort. Results 457 patients (32% nvHABP, 37% vHABP, and 31% VABP) were evaluated. The vHABP and nvHABP groups were similar in age (median age 66.4 years) with 77% having multiple comorbidities but more vHABP patients had liver disease (18.2% vs. 7.7% p = 0.005), alcohol use disorder (27% vs. 7.1%, p < 0.0001), and were hospitalized within the past 30 days (30.4% vs. 19.5%, p = 0.02). An immediate need for ventilatory support occurred in 70% of vHABP patients on the day of diagnosis. Mortality was the highest in vHABP followed by VABP and nvHABP groups (44.6% vs. 36% vs. 14.3%, p < 0.0001). Nearly all (96%) vHABP patients had positive cultures, with Gram-negative pathogens accounting for 58.8% whereby 33.0% were resistant to extended-spectrum β-lactams (ESBLs), ceftriaxone (17.5%), fluoroquinolones (20.6%), and carbapenems (12.4%). Up to half of the vHABP patients with ESBL-Enterobacterales or P. aeruginosa did not receive an effective empiric regimen; over 50% increase in mortality rate was observed among patients whom effective therapy was initiated past the day of pneumonia diagnosis. Risk factors associated with vHABP development were alcohol use disorder, APACHE II score, vasopressor therapy prior to infection, and culture positive for ESBL-Enterobacterales whereas history of hospitalization in the past 30 days, active malignancy, isolation of ceftriaxone-resistant pathogens or Pseudomonas aeruginosa, and vasopressor therapy were risk factors for vHABP-associated mortality. Conclusion Patients with vHABP experienced an acute and severe decompensation upon diagnosis. The risk factors identified in this study could provide actionable data for clinicians to identify those at risk for vHABP at the onset of pneumonia and to target antimicrobial stewardship efforts to improve treatment success.
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Affiliation(s)
- Anthony Sophonsri
- Department of Clinical Pharmacy, University of Southern California, Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, United States
| | - Mimi Lou
- Department of Clinical Pharmacy, University of Southern California, Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, United States
| | - Pamela Ny
- Department of Pharmacy, Huntington Hospital, Pasadena, CA, United States
| | - Emi Minejima
- Department of Clinical Pharmacy, University of Southern California, Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, United States
- Department of Pharmacy, Los Angeles General Medical Center, Los Angeles, CA, United States
| | - Paul Nieberg
- Department of Medicine – Infectious Diseases, Huntington Hospital, Pasadena, CA, United States
| | - Annie Wong-Beringer
- Department of Clinical Pharmacy, University of Southern California, Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, United States
- Department of Pharmacy, Huntington Hospital, Pasadena, CA, United States
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Easley KF, Edenfield RC, Lott MEJ, Reed RC, Das Sarma J, Mehta AJ, Staitieh BS, Lipp EK, Cho IK, Johnson SK, Jones CA, Bebin-Blackwell AG, Levy JM, Tompkins SM, Easley CA, Koval M. Chronic alcohol use primes bronchial cells for altered inflammatory response and barrier dysfunction during SARS-CoV-2 infection. Am J Physiol Lung Cell Mol Physiol 2023; 325:L647-L661. [PMID: 37786945 PMCID: PMC11498272 DOI: 10.1152/ajplung.00381.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 07/26/2023] [Accepted: 09/15/2023] [Indexed: 10/04/2023] Open
Abstract
Alcohol use disorder (AUD) is a significant public health concern and people with AUD are more likely to develop severe acute respiratory distress syndrome (ARDS) in response to respiratory infections. To examine whether AUD was a risk factor for more severe outcome in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we examined early responses to infection using cultured differentiated bronchial epithelial cells derived from brushings obtained from people with AUD or without AUD. RNA-seq analysis of uninfected cells determined that AUD cells were enriched for expression of epidermal genes as compared with non-AUD cells. Bronchial epithelial cells from patients with AUD showed a significant decrease in barrier function 72 h postinfection, as determined by transepithelial electrical resistance. In contrast, barrier function of non-AUD cells was enhanced 72 h after SARS-CoV-2 infection. AUD cells showed claudin-7 that did not colocalize with zonula occludens-1 (ZO-1), indicative of disorganized tight junctions. However, both AUD and non-AUD cells showed decreased β-catenin expression following SARS-CoV-2 infection. To determine the impact of AUD on the inflammatory response to SARS-CoV-2 infection, cytokine secretion was measured by multiplex analysis. SARS-CoV-2-infected AUD bronchial cells had enhanced secretion of multiple proinflammatory cytokines including TNFα, IL-1β, and IFNγ as opposed to non-AUD cells. In contrast, secretion of the barrier-protective cytokines epidermal growth factor (EGF) and granulocyte macrophage-colony stimulating factor (GM-CSF) was enhanced for non-AUD bronchial cells. Taken together, these data support the hypothesis that AUD is a risk factor for COVID-19, where alcohol primes airway epithelial cells for increased inflammation and increased barrier dysfunction and increased inflammation in response to infection by SARS-CoV-2.NEW & NOTEWORTHY Alcohol use disorder (AUD) is a significant risk factor for severe acute respiratory distress syndrome. We found that AUD causes a phenotypic shift in gene expression in human bronchial epithelial cells, enhancing expression of epidermal genes. AUD cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had higher levels of proinflammatory cytokine secretion and barrier dysfunction not present in infected non-AUD cells, consistent with increased early COVID-19 severity due to AUD.
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Affiliation(s)
- Kristen F Easley
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
| | - R Clayton Edenfield
- Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia, United States
- Regenerative Bioscience Center, University of Georgia, Athens, Georgia, United States
| | - Megan E J Lott
- Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia, United States
| | - Ryan C Reed
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
| | - Jayasri Das Sarma
- Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, India
- Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
| | - Ashish J Mehta
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
- Atlanta Veterans Affairs Health Care System, Decatur, Georgia, United States
| | - Bashar S Staitieh
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
| | - Erin K Lipp
- Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia, United States
| | - In Ki Cho
- Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia, United States
- Regenerative Bioscience Center, University of Georgia, Athens, Georgia, United States
| | - Scott K Johnson
- Center for Vaccines and Immunology, University of Georgia, Athens, Georgia, United States
| | - Cheryl A Jones
- Center for Vaccines and Immunology, University of Georgia, Athens, Georgia, United States
| | | | - Joshua M Levy
- Department of Otolaryngology, Emory University School of Medicine, Atlanta, Georgia, United States
- National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States
| | - S Mark Tompkins
- Center for Vaccines and Immunology, University of Georgia, Athens, Georgia, United States
| | - Charles A Easley
- Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia, United States
- Regenerative Bioscience Center, University of Georgia, Athens, Georgia, United States
| | - Michael Koval
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
- Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, United States
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9
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Martins FRB, de Oliveira MD, Souza JAM, Queiroz-Junior CM, Lobo FP, Teixeira MM, Malacco NL, Soriani FM. Chronic ethanol exposure impairs alveolar leukocyte infiltration during pneumococcal pneumonia, leading to an increased bacterial burden despite increased CXCL1 and nitric oxide levels. Front Immunol 2023; 14:1175275. [PMID: 37275853 PMCID: PMC10235596 DOI: 10.3389/fimmu.2023.1175275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 05/05/2023] [Indexed: 06/07/2023] Open
Abstract
Ethanol abuse is a risk factor for the development of pneumonia caused by Streptococcus pneumoniae, a critical pathogen for public health. The aim of this article was to investigate the inflammatory mechanisms involved in pneumococcal pneumonia that may be associated with chronic ethanol exposure. Male C57BL6/J-Unib mice were exposed to 20% (v/v) ethanol for twelve weeks and intranasally infected with 5x104 CFU of S. pneumoniae. Twenty-four hours after infection, lungs, bronchoalveolar lavage and blood samples were obtained to assess the consequences of chronic ethanol exposure during infection. Alcohol-fed mice showed increased production of nitric oxide and CXCL1 in alveoli and plasma during pneumococcal pneumonia. Beside this, ethanol-treated mice exhibited a decrease in leukocyte infiltration into the alveoli and reduced frequency of severe lung inflammation, which was associated with an increase in bacterial load. Curiously, no changes were observed in survival after infection. Taken together, these results demonstrate that chronic ethanol exposure alters the inflammatory response during S. pneumoniae lung infection in mice with a reduction in the inflammatory infiltrate even in the presence of higher levels of the chemoattractant CXCL1.
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Affiliation(s)
- Flávia Rayssa Braga Martins
- Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Maycon Douglas de Oliveira
- Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Jéssica Amanda Marques Souza
- Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Celso Martins Queiroz-Junior
- Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Francisco Pereira Lobo
- Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Mauro Martins Teixeira
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | | | - Frederico Marianetti Soriani
- Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
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10
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Swanson GR, Schwartz BA, Joyce C, Keshavarzian A. Binge drinking alcohol and circadian misalignment in night shift nurses is associated with decreased resiliency to COVID-19 infection. Alcohol Clin Exp Res 2023; 47:908-918. [PMID: 37526580 DOI: 10.1111/acer.15052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 02/20/2023] [Accepted: 02/27/2023] [Indexed: 08/02/2023]
Abstract
BACKGROUND Nurses and other first responders are at high risk of exposure to the SARS-CoV2 virus, and many have developed severe COVID-19 infection. A better understanding of the factors that increase the risk of infection after exposure to the virus could help to address this. Although several risk factors such as obesity, diabetes, and hypertension have been associated with an increased risk of infection, many first responders develop severe COVID-19 without established risk factors. As inflammation and cytokine storm are the primary mechanisms in severe COVID-19, other factors that promote an inflammatory state could increase the risk of COVID-19 in exposed individuals. Alcohol misuse and shift work with subsequent misaligned circadian rhythms are known to promote a pro-inflammatory state and thus could increase susceptibility to COVID-19. To test this hypothesis, we conducted a prospective, cross-sectional observational survey-based study in nurses using the American Nursing Association network. METHOD We used validated structured questionnaires to assess alcohol consumption (the Alcohol Use Disorders Identification Test) and circadian typology or chronotype (the Munich Chronotype Questionnaire Shift -MCTQ-Shift). RESULTS By latent class analysis (LCA), high-risk features of alcohol misuse were associated with a later chronotype, and binge drinking was greater in night shift workers. The night shift was associated with more than double the odds of COVID-19 infection of the standard shift (OR 2.67, 95% CI: 1.18 to 6.07). Binge drinkers had twice the odds of COVID-19 infection of those with low-risk features by LCA (OR: 2.08, 95% CI: 0.75 to 5.79). CONCLUSION Working night shifts or binge drinking may be risk factors for COVID-19 infection among nurses. Understanding the mechanisms underlying these risk factors could help to mitigate the impact of COVID-19 on our at-risk healthcare workforce.
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Affiliation(s)
- Garth R Swanson
- Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois, USA
- Section of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - Benjamin A Schwartz
- Section of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA
| | - Cara Joyce
- Department of Medicine, Loyola University Stritch School of Medicine, Chicago, Illinois, USA
| | - Ali Keshavarzian
- Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, Illinois, USA
- Section of Digestive Diseases, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA
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11
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Muralidharan A, Bauer CD, Katafiasz DM, Strah HM, Siddique A, Reid SP, Bailey KL, Wyatt TA. Synergistic Detrimental Effects of Cigarette Smoke, Alcohol, and SARS-CoV-2 in COPD Bronchial Epithelial Cells. Pathogens 2023; 12:498. [PMID: 36986420 PMCID: PMC10056639 DOI: 10.3390/pathogens12030498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 03/09/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023] Open
Abstract
Lung conditions such as COPD, as well as risk factors such as alcohol misuse and cigarette smoking, can exacerbate COVID-19 disease severity. Synergistically, these risk factors can have a significant impact on immunity against pathogens. Here, we studied the effect of a short exposure to alcohol and/or cigarette smoke extract (CSE) in vitro on acute SARS-CoV-2 infection of ciliated human bronchial epithelial cells (HBECs) collected from healthy and COPD donors. We observed an increase in viral titer in CSE- or alcohol-treated COPD HBECs compared to untreated COPD HBECs. Furthermore, we treated healthy HBECs accompanied by enhanced lactate dehydrogenase activity, indicating exacerbated injury. Finally, IL-8 secretion was elevated due to the synergistic damage mediated by alcohol, CSE, and SARS-CoV-2 in COPD HBECs. Together, our data suggest that, with pre-existing COPD, short exposure to alcohol or CSE is sufficient to exacerbate SARS-CoV-2 infection and associated injury, impairing lung defences.
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Affiliation(s)
- Abenaya Muralidharan
- Department of Pathology and Microbiology, College of Medicine, The University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Christopher D. Bauer
- Pulmonary, Critical Care, and Sleep Medicine Division, Department of Internal Medicine, College of Medicine, the University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Dawn M. Katafiasz
- Pulmonary, Critical Care, and Sleep Medicine Division, Department of Internal Medicine, College of Medicine, the University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Heather M. Strah
- Pulmonary, Critical Care, and Sleep Medicine Division, Department of Internal Medicine, College of Medicine, the University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Aleem Siddique
- Department of Surgery, College of Medicine, the University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - St Patrick Reid
- Department of Pathology and Microbiology, College of Medicine, The University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Kristina L. Bailey
- Pulmonary, Critical Care, and Sleep Medicine Division, Department of Internal Medicine, College of Medicine, the University of Nebraska Medical Center, Omaha, NE 68198, USA
- Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA
| | - Todd A. Wyatt
- Pulmonary, Critical Care, and Sleep Medicine Division, Department of Internal Medicine, College of Medicine, the University of Nebraska Medical Center, Omaha, NE 68198, USA
- Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA
- Department of Environmental, Agricultural & Occupational Health, College of Public Health, the University of Nebraska Medical Center, Omaha, NE 68198, USA
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12
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Muralidharan A, Bauer C, Katafiasz DM, Pham D, Oyewole OO, Morwitzer MJ, Roy E, Bailey KL, Reid SP, Wyatt TA. Malondialdehyde acetaldehyde adduction of surfactant protein D attenuates SARS-CoV-2 spike protein binding and virus neutralization. Alcohol Clin Exp Res 2023; 47:95-103. [PMID: 36352814 PMCID: PMC9878066 DOI: 10.1111/acer.14974] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 11/01/2022] [Accepted: 11/06/2022] [Indexed: 11/11/2022]
Abstract
BACKGROUND Over 43% of the world's population regularly consumes alcohol. Although not commonly known, alcohol can have a significant impact on the respiratory environment. Living in the time of the COVID-19 pandemic, alcohol misuse can have a particularly deleterious effect on SARS-CoV-2-infected individuals and, in turn, the overall healthcare system. Patients with alcohol use disorders have higher odds of COVID-19-associated hospitalization and mortality. Even though the detrimental role of alcohol on COVID-19 outcomes has been established, the underlying mechanisms are yet to be fully understood. Alcohol misuse has been shown to induce oxidative damage in the lungs through the production of reactive aldehydes such as malondialdehyde and acetaldehyde (MAA). MAA can then form adducts with proteins, altering their structure and function. One such protein is surfactant protein D (SPD), which plays an important role in innate immunity against pathogens. METHODS AND RESULTS In this study, we examined whether MAA adduction of SPD (SPD-MAA) attenuates the ability of SPD to bind SARS-CoV-2 spike protein, reversing SPD-mediated virus neutralization. Using ELISA, we show that SPD-MAA is unable to competitively bind spike protein and prevent ACE2 receptor binding. Similarly, SPD-MAA fails to inhibit entry of wild-type SARS-CoV-2 virus into Calu-3 cells, a lung epithelial cell line, as well as ciliated primary human bronchial epithelial cells isolated from healthy individuals. CONCLUSIONS Overall, MAA adduction of SPD, a consequence of alcohol overconsumption, represents one mechanism of compromised lung innate defense against SARS-CoV-2, highlighting a possible mechanism underlying COVID-19 severity and related mortality in patients who misuse alcohol.
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Affiliation(s)
- Abenaya Muralidharan
- Department of Pathology and Microbiology, College of MedicineUniversity of Nebraska Medical CenterOmahaNebraskaUSA
| | - Christopher Bauer
- Department of Internal Medicine, College of MedicineUniversity of Nebraska Medical CenterOmahaNebraskaUSA
| | - Dawn M. Katafiasz
- Department of Internal Medicine, College of MedicineUniversity of Nebraska Medical CenterOmahaNebraskaUSA
| | - Danielle Pham
- Department of Internal Medicine, College of MedicineUniversity of Nebraska Medical CenterOmahaNebraskaUSA
| | - Opeoluwa O. Oyewole
- Department of Pathology and Microbiology, College of MedicineUniversity of Nebraska Medical CenterOmahaNebraskaUSA
| | - M. Jane Morwitzer
- Department of Pathology and Microbiology, College of MedicineUniversity of Nebraska Medical CenterOmahaNebraskaUSA
| | - Enakshi Roy
- Department of Pathology and Microbiology, College of MedicineUniversity of Nebraska Medical CenterOmahaNebraskaUSA
| | - Kristina L. Bailey
- Department of Internal Medicine, College of MedicineUniversity of Nebraska Medical CenterOmahaNebraskaUSA
- Veterans Affairs Nebraska‐Western Iowa Health Care SystemOmahaNebraskaUSA
| | - St Patrick Reid
- Department of Pathology and Microbiology, College of MedicineUniversity of Nebraska Medical CenterOmahaNebraskaUSA
| | - Todd A. Wyatt
- Department of Internal Medicine, College of MedicineUniversity of Nebraska Medical CenterOmahaNebraskaUSA
- Veterans Affairs Nebraska‐Western Iowa Health Care SystemOmahaNebraskaUSA
- Department of Environmental, Agricultural and Occupational Health, College of Public HealthUniversity of Nebraska Medical CenterOmahaNebraskaUSA
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13
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Forsyth CB, Voigt RM, Swanson GR, Bishehsari F, Shaikh M, Zhang L, Engen P, Keshavarzian A. Alcohol use disorder as a potential risk factor for COVID-19 severity: A narrative review. Alcohol Clin Exp Res 2022; 46:1930-1943. [PMID: 36394508 PMCID: PMC9722573 DOI: 10.1111/acer.14936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/25/2022] [Accepted: 08/31/2022] [Indexed: 11/19/2022]
Abstract
In Dec. 2019-January 2020, a pneumonia illness originating in Wuhan, China, designated as coronavirus disease 2019 (COVID-19) was shown to be caused by a novel RNA coronavirus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). People with advanced age, male sex, and/or underlying health conditions (obesity, type 2 diabetes, cardiovascular disease, hypertension, chronic kidney disease, and chronic lung disease) are especially vulnerable to severe COVID-19 symptoms and death. These risk factors impact the immune system and are also associated with poor health, chronic illness, and shortened longevity. However, a large percent of patients without these known risk factors also develops severe COVID-19 disease that can result in death. Thus, there must exist risk factors that promote exaggerated inflammatory and immune response to the SARS-CoV-2 virus leading to death. One such risk factor may be alcohol misuse and alcohol use disorder because these can exacerbate viral lung infections like SARS, influenza, and pneumonia. Thus, it is highly plausible that alcohol misuse is a risk factor for either increased infection rate when individuals are exposed to SARS-CoV-2 virus and/or more severe COVID-19 in infected patients. Alcohol use is a well-known risk factor for lung diseases and ARDS in SARS patients. We propose that alcohol has three key pathogenic elements in common with other COVID-19 severity risk factors: namely, inflammatory microbiota dysbiosis, leaky gut, and systemic activation of the NLRP3 inflammasome. We also propose that these three elements represent targets for therapy for severe COVID-19.
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Affiliation(s)
- Christopher B. Forsyth
- Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, Chicago, IL 60612
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612
- Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612
| | - Robin M. Voigt
- Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, Chicago, IL 60612
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612
- Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612
| | - Garth R. Swanson
- Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, Chicago, IL 60612
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612
- Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612
| | - Faraz Bishehsari
- Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, Chicago, IL 60612
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612
- Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612
| | - Maliha Shaikh
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
| | - Lijuan Zhang
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
| | - Phillip Engen
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
| | - Ali Keshavarzian
- Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, Chicago, IL 60612
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612
- Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612
- Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612
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14
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Carlson RW, Girgla N, Davis J, Moradi A, Cooper T. Pneumonia is a common and early complication of the Severe Alcohol Withdrawal Syndrome (SAWS). Heart Lung 2022; 55:42-48. [PMID: 35468360 DOI: 10.1016/j.hrtlng.2022.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 03/25/2022] [Accepted: 04/03/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND Pneumonia (PNA) may complicate the Severe Alcohol Withdrawal Syndrome (SAWS), with ICU admission, mechanical ventilation (MV), prolonged length of stay (LOS), and adverse events. OBJECTIVES To examine the onset, features and courses of PNA in patients with SAWS to aid management. METHODS A 33 month contiguous review of SAWS and PNA was conducted at an urban public hospital. RESULTS There were 279 episodes of Alcohol Withdrawal Syndrome (AWS) among 255 patients. Males predominated (91%) with a mean age of 45.8 years (range 23-73), of whom 31% (87/279) developed SAWS with ICU management. Direct ICU admission occurred for 62 patients; 25 were transferred for delirium, seizures, escalating sedation, PNA or other complications. PNA was identified for 34 ICU direct admissions and 13 ward patients. Ten transfers to the ICU also developed PNA for an ICU total of 44/87 (51%), of whom 82% (36/44) required MV. Another 10 ICU patients without PNA received MV for high dose sedation or respiratory failure. Most ICU patients (72/87 (83%)), including all with MV, required IV infusion of sedation. MV prolonged LOS, but LOS for PNA with MV was similar to all MV. ICU transfers had longer LOS with greater use of MV than direct admits (p<0.05). PNA was identified before ICU admission or transfer for 73% (32/44 (p<0.05)), and usually before intubation. Most PNA was Community Acquired Pneumonia (CAP) with P. Pneumoniae frequently cultured. CONCLUSIONS PNA with SAWS is predominately CAP and occurs early. Focused ICU admission with respiratory support are priorities of initial management.
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Affiliation(s)
- Richard W Carlson
- Department of Medicine, Valleywise Medical Center, Phoenix, AZ, United States; College of Medicine, University of Arizona, Phoenix, AZ, United States; Mayo Clinic Alix School of Medicine, Scottsdale, AZ, United States.
| | - Navkaran Girgla
- Department of Medicine, Valleywise Medical Center, Phoenix, AZ, United States; Creighton University Arizona Education Health Alliance, AZ, United States
| | - Jesse Davis
- Department of Medicine, Addiction Medicine Fellowship, University of Washington, Seattle, WA, United States
| | - Ali Moradi
- Department of Medicine, Valleywise Medical Center, Phoenix, AZ, United States; Creighton University Arizona Education Health Alliance, AZ, United States
| | - Tracy Cooper
- Valleywise Medical Center, Phoenix, AZ, United States
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15
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Hulsebus HJ, Najarro KM, McMahan RH, Boe DM, Orlicky DJ, Kovacs EJ. Ethanol Intoxication Impairs Respiratory Function and Bacterial Clearance and Is Associated With Neutrophil Accumulation in the Lung After Streptococcus pneumoniae Infection. Front Immunol 2022; 13:884719. [PMID: 35603143 PMCID: PMC9116899 DOI: 10.3389/fimmu.2022.884719] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 04/11/2022] [Indexed: 11/27/2022] Open
Abstract
Alcohol consumption is commonplace in the United States and its prevalence has increased in recent years. Excessive alcohol use is linked to an increased risk of infections including pneumococcal pneumonia, mostly commonly caused by Streptococcus pneumoniae. In addition, pneumonia patients with prior alcohol use often require more intensive treatment and longer hospital stays due to complications of infection. The initial respiratory tract immune response to S. pneumoniae includes the production of pro-inflammatory cytokines and chemokines by resident cells in the upper and lower airways which activate and recruit leukocytes to the site of infection. However, this inflammation must be tightly regulated to avoid accumulation of toxic by-products and subsequent tissue damage. A majority of previous work on alcohol and pneumonia involve animal models utilizing high concentrations of ethanol or chronic exposure and offer conflicting results about how ethanol alters immunity to pathogens. Further, animal models often employ a high bacterial inoculum which may overwhelm the immune system and obscure results, limiting their applicability to the course of human infection. Here, we sought to determine how a more moderate ethanol exposure paradigm affects respiratory function and innate immunity in mice after intranasal infection with 104 colony forming units of S. pneumoniae. Ethanol-exposed mice displayed respiratory dysfunction and impaired bacterial clearance after infection compared to their vehicle-exposed counterparts. This altered response was associated with increased gene expression of neutrophil chemokines Cxcl1 and Cxcl2 in whole lung homogenates, elevated concentrations of circulating granulocyte-colony stimulating factor (G-CSF), and higher neutrophil numbers in the lung 24 hours after infection. Taken together, these findings suggest that even a more moderate ethanol consumption pattern can dramatically modulate the innate immune response to S. pneumoniae after only 3 days of ethanol exposure and provide insight into possible mechanisms related to the compromised respiratory immunity seen in alcohol consumers with pneumonia.
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Affiliation(s)
- Holly J Hulsebus
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.,Immunology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Kevin M Najarro
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Rachel H McMahan
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Devin M Boe
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.,Immunology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - David J Orlicky
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Elizabeth J Kovacs
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.,Immunology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
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16
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Nissen CG, Mosley DD, Kharbanda KK, Katafiasz DM, Bailey KL, Wyatt TA. Malondialdehyde Acetaldehyde-Adduction Changes Surfactant Protein D Structure and Function. Front Immunol 2022; 13:866795. [PMID: 35669781 PMCID: PMC9164268 DOI: 10.3389/fimmu.2022.866795] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 04/13/2022] [Indexed: 11/23/2022] Open
Abstract
Alcohol consumption with concurrent cigarette smoking produces malondialdehyde acetaldehyde (MAA)-adducted lung proteins. Lung surfactant protein D (SPD) supports innate immunity via bacterial aggregation and lysis, as well as by enhancing macrophage-binding and phagocytosis. MAA-adducted SPD (SPD-MAA) has negative effects on lung cilia beating, macrophage function, and epithelial cell injury repair. Because changes in SPD multimer structure are known to impact SPD function, we hypothesized that MAA-adduction changes both SPD structure and function. Purified human SPD and SPD-MAA (1 mg/mL) were resolved by gel filtration using Sephadex G-200 and protein concentration of each fraction determined by Bradford assay. Fractions were immobilized onto nitrocellulose by slot blot and assayed by Western blot using antibodies to SPD and to MAA. Binding of SPD and SPD-MAA was determined fluorometrically using GFP-labeled Streptococcus pneumoniae (GFP-SP). Anti-bacterial aggregation of GFP-SP and macrophage bacterial phagocytosis were assayed by microscopy and permeability determined by bacterial phosphatase release. Viral injury was measured as LDH release in RSV-treated airway epithelial cells. Three sizes of SPD were resolved by gel chromatography as monomeric, trimeric, and multimeric forms. SPD multimer was the most prevalent, while the majority of SPD-MAA eluted as trimer and monomer. SPD dose-dependently bound to GFP-SP, but SPD-MAA binding to bacteria was significantly reduced. SPD enhanced, but MAA adduction of SPD prevented, both aggregation and macrophage phagocytosis of GFP-SP. Likewise, SPD increased bacterial permeability while SPD-MAA did not. In the presence of RSV, BEAS-2B cell viability was enhanced by SPD, but not protected by SPD-MAA. Our results demonstrate that MAA adduction changes the quaternary structure of SPD from multimer to trimer and monomer leading to a decrease in the native anti-microbial function of SPD. These findings suggest one mechanism for increased pneumonia observed in alcohol use disorders.
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Affiliation(s)
- Claire G. Nissen
- Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States
| | - Deanna D. Mosley
- Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States
| | - Kusum K. Kharbanda
- Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States
- Research Service Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, United States
| | - Dawn M. Katafiasz
- Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States
| | - Kristina L. Bailey
- Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States
- Research Service Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, United States
| | - Todd A. Wyatt
- Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States
- Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States
- Research Service Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, United States
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17
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Hammond A, Halliday A, Thornton HV, Hay AD. Predisposing factors to acquisition of acute respiratory tract infections in the community: a systematic review and meta-analysis. BMC Infect Dis 2021; 21:1254. [PMID: 34906101 PMCID: PMC8670045 DOI: 10.1186/s12879-021-06954-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 12/02/2021] [Indexed: 12/17/2022] Open
Abstract
Background Preventing respiratory tract infections (RTIs) could have profound effects on quality of life, primary care workload, antibiotic prescribing and stewardship. We aimed to identify factors that increase and decrease RTI acquisition within Organisation for Economic Cooperation and Development (OECD) member countries. Methods Systematic search of Medline, Embase, Cochrane and ISI Web of Knowledge for studies conducted up to July 2020 reporting predisposing factors for community RTI acquisition. Pooled odds ratios were calculated using a random-effects model. Results 23 studies investigated risk factors associated with community-acquired pneumonia (n = 15); any RTI (n = 4); influenza like illness (n = 2); and lower RTI (n = 2). Demographic, lifestyle and social factors were: underweight BMI (pooled odds ratio (ORp 2.14, 95% CI 1.58 to 2.70, p = 0.97); male sex (ORp 1.30, 95% CI 1.27 to 1.33, p = 0.66); contact with pets (ORp 1.35, 95% CI 1.16 to 1.54, p = 0.72); contact with children (ORp 1.35, 95% CI 1.15 to 1.56, p = 0.05); and ex-smoking status (ORp 1.57, 95% CI 1.26 to 1.88, p = 0.76). Health-related factors were: chronic liver condition (ORp 1.30, 95% CI 1.09 to 1.50, p = 0.34); chronic renal condition (ORp 1.47, 95% CI 1.09 to 1.85, p = 0.14); and any hospitalisation in previous five years (ORp 1.64, 95% CI 1.46 to 1.82, p = 0.66). Conclusions We identified several modifiable risk factors associated with increased likelihood of acquiring RTIs in the community, including low BMI, contact with children and pets. Modification of risk factors and increased awareness of vulnerable groups could reduce morbidity, mortality and antibiotic use associated with RTIs. PROSPERO registration CRD42019134176. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06954-3.
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Affiliation(s)
- Ashley Hammond
- Centre for Academic Primary Care, NIHR School for Primary Care Research, Bristol Medical School, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK.
| | - Alice Halliday
- School of Cellular and Molecular Medicine, Biomedical Sciences Building, University of Bristol, University Walk, Bristol, BS8 1TD, UK
| | - Hannah V Thornton
- Centre for Academic Primary Care, NIHR School for Primary Care Research, Bristol Medical School, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK
| | - Alastair D Hay
- Centre for Academic Primary Care, NIHR School for Primary Care Research, Bristol Medical School, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK
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18
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Bhalla S, Sharma B, Smith D, Boley R, McCluskey C, Ilyas Y, Afshar M, Balk R, Karnik N, Keshavarzian A. Investigating Unhealthy Alcohol Use As an Independent Risk Factor for Increased COVID-19 Disease Severity: Observational Cross-sectional Study. JMIR Public Health Surveill 2021; 7:e33022. [PMID: 34665758 PMCID: PMC8575002 DOI: 10.2196/33022] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 10/11/2021] [Accepted: 10/14/2021] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Unhealthy alcohol use (UAU) is known to disrupt pulmonary immune mechanisms and increase the risk of acute respiratory distress syndrome in patients with pneumonia; however, little is known about the effects of UAU on outcomes in patients with COVID-19 pneumonia. To our knowledge, this is the first observational cross-sectional study that aims to understand the effect of UAU on the severity of COVID-19. OBJECTIVE We aim to determine if UAU is associated with more severe clinical presentation and worse health outcomes related to COVID-19 and if socioeconomic status, smoking, age, BMI, race/ethnicity, and pattern of alcohol use modify the risk. METHODS In this observational cross-sectional study that took place between January 1, 2020, and December 31, 2020, we ran a digital machine learning classifier on the electronic health record of patients who tested positive for SARS-CoV-2 via nasopharyngeal swab or had two COVID-19 International Classification of Disease, 10th Revision (ICD-10) codes to identify patients with UAU. After controlling for age, sex, ethnicity, BMI, smoking status, insurance status, and presence of ICD-10 codes for cancer, cardiovascular disease, and diabetes, we then performed a multivariable regression to examine the relationship between UAU and COVID-19 severity as measured by hospital care level (ie, emergency department admission, emergency department admission with ventilator, or death). We used a predefined cutoff with optimal sensitivity and specificity on the digital classifier to compare disease severity in patients with and without UAU. Models were adjusted for age, sex, race/ethnicity, BMI, smoking status, and insurance status. RESULTS Each incremental increase in the predicted probability from the digital alcohol classifier was associated with a greater odds risk for more severe COVID-19 disease (odds ratio 1.15, 95% CI 1.10-1.20). We found that patients in the unhealthy alcohol group had a greater odds risk to develop more severe disease (odds ratio 1.89, 95% CI 1.17-3.06), suggesting that UAU was associated with an 89% increase in the odds of being in a higher severity category. CONCLUSIONS In patients infected with SARS-CoV-2, UAU is an independent risk factor associated with greater disease severity and/or death.
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Affiliation(s)
- Sameer Bhalla
- Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States
| | - Brihat Sharma
- Addiction Data Science Laboratory, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States
| | - Dale Smith
- Addiction Data Science Laboratory, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States
| | - Randy Boley
- Addiction Data Science Laboratory, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States
| | - Connor McCluskey
- Addiction Data Science Laboratory, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States
| | - Yousaf Ilyas
- Addiction Data Science Laboratory, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States
| | - Majid Afshar
- Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI, United States
| | - Robert Balk
- Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United States
| | - Niranjan Karnik
- Addiction Data Science Laboratory, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center, Chicago, IL, United States
| | - Ali Keshavarzian
- Center for Circadian Rhythm and Alcohol-Induced Tissue Injury, Rush University Medical Center, Chicago, IL, United States
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19
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Navarro-Torné A, Montuori EA, Kossyvaki V, Méndez C. Burden of pneumococcal disease among adults in Southern Europe (Spain, Portugal, Italy, and Greece): a systematic review and meta-analysis. Hum Vaccin Immunother 2021; 17:3670-3686. [PMID: 34106040 PMCID: PMC8437551 DOI: 10.1080/21645515.2021.1923348] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/07/2021] [Accepted: 04/23/2021] [Indexed: 12/18/2022] Open
Abstract
The aim was to summarize pneumococcal disease burden data among adults in Southern Europe and the potential impact of vaccines on epidemiology. Of 4779 identified studies, 272 were selected. Invasive pneumococcal disease (IPD) incidence was 15.08 (95% CI 11.01-20.65) in Spain versus 2.56 (95% CI 1.54-4.24) per 100,000 population in Italy. Pneumococcal pneumonia incidence was 19.59 (95% CI 10.74-35.74) in Spain versus 2.19 (95% CI 1.36-3.54) per 100,000 population in Italy. Analysis of IPD incidence in Spain comparing pre-and post- PCV7 and PCV13 periods unveiled a declining trend in vaccine-type IPD incidence (larger and statistically significant for the elderly), suggesting indirect effects of childhood vaccination programme. Data from Portugal, Greece and, to a lesser extent, Italy were sparse, thus improved surveillance is needed. Pneumococcal vaccination uptake, particularly among the elderly and adults with chronic and immunosuppressing conditions, should be improved, including shift to a higher-valency pneumococcal conjugate vaccine when available.
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20
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Hietanen S, Kaakinen T, Ala-Kokko T, Herajärvi J, Auvinen J, Niittyvuopio M, Liisanantti J. Alcohol consumption is associated with a later need for ICU admission: a Northern Finland Birth Cohort 1966-study. J Public Health (Oxf) 2021; 43:551-557. [PMID: 32561923 DOI: 10.1093/pubmed/fdaa085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 04/27/2020] [Accepted: 05/26/2020] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Alcohol-related problems are common in intensive care unit (ICU) admitted patients. The aim of the present study is to assess the impact of alcohol consumption on the need of intensive care in 19 years follow-up period. METHODS The study population consists of Northern Finland Birth Cohort 1966 participants, who responded alcohol-related questions at 31 years of age and Intensive Care Unit (ICU admissions from 1997 to 2016. RESULTS There were a total of 8379 assessed people and 136 (1.6%) of them were later admitted to ICU. A total of 44 (32.4%) of the ICU-admitted persons had their alcohol consumption at the highest quartile of the cohort (P = 0.047). These patients had a lower number of malignancy-related admissions (3.6% versus 14.0%, P = 0.027), neurological admissions (14.3 versus 30.6%, P = 0.021), and were more often admitted due to poisonings (12.5% versus 5.0%, P = 0.07). There were no differences in 28-day post-ICU mortality but long-term mortality of ICU-admitted patients with lower alcohol consumption was higher than non-ICU-admitted population. CONCLUSION Among ICU-admitted population, there was higher alcohol consumption at age of 31 years. People in the lower alcohol consumption quartiles were more often admitted to ICU due to malignancy-related causes and they had higher long-term mortality.
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Affiliation(s)
- Siiri Hietanen
- Central Osthrobotnian Hospital, Department of Cardiology, 67200 Kokkola, Finland.,Oulu University Hospital, Department of Anesthesiology, 90029 Oulu, Finland
| | - Timo Kaakinen
- Oulu University Hospital, Department of Anesthesiology, 90029 Oulu, Finland.,MRC Oulu, Research Group of Surgery, Anesthesiology and Intensive Care Medicine, University of Oulu, 90220 Oulu Finland
| | - Tero Ala-Kokko
- Oulu University Hospital, Department of Anesthesiology, 90029 Oulu, Finland.,MRC Oulu, Research Group of Surgery, Anesthesiology and Intensive Care Medicine, University of Oulu, 90220 Oulu Finland
| | - Johanna Herajärvi
- MRC Oulu, Research Group of Surgery, Anesthesiology and Intensive Care Medicine, University of Oulu, 90220 Oulu Finland
| | - Juha Auvinen
- Center for Life Course Health Researc, University of Oulu, 90220 Oulu, Finland.,Oulunkaari Health Center, 91100 Ii, Finland
| | - Miikka Niittyvuopio
- Oulu University Hospital, Department of Anesthesiology, 90029 Oulu, Finland.,MRC Oulu, Research Group of Surgery, Anesthesiology and Intensive Care Medicine, University of Oulu, 90220 Oulu Finland
| | - Janne Liisanantti
- Oulu University Hospital, Department of Anesthesiology, 90029 Oulu, Finland.,MRC Oulu, Research Group of Surgery, Anesthesiology and Intensive Care Medicine, University of Oulu, 90220 Oulu Finland
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21
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Sivaraman V, Richey MM, Nasir ABM. Alcohol, Cannabis and Crossfading: Concerns for COVID-19 Disease Severity. BIOLOGY 2021; 10:779. [PMID: 34440011 PMCID: PMC8389695 DOI: 10.3390/biology10080779] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/22/2021] [Accepted: 08/10/2021] [Indexed: 11/17/2022]
Abstract
Risk factors for severe COVID-19 pathology are currently being investigated worldwide. The emergence of this highly infectious respiratory disease has plagued the world, with varying severity across populations of different age, race, and socio-economic level. These data suggest that other environmental or social factors may contribute to this disease's severity. Using a mouse model, we identify heavy alcohol and cannabinoid consumption as risk factors for increased pulmonary pathology in the setting of exposure to a microbial pulmonary pathogen (K. pneumoniae). We present observational evidence that pneumonia patients admitted to North Carolina hospitals have longer lengths of stay when they endorse alcohol use or have conditions considered alcohol attributable. We are concerned that the observed increase in alcohol and legal cannabinoid sales during lockdown and quarantine may contribute to increased pulmonary pathology among patients who become infected with COVID-19.
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Affiliation(s)
- Vijay Sivaraman
- Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA
- Julius Chambers Biomedical and Biotechnological Research Institute, North Carolina Central University, Durham, NC 27707, USA
| | - Morgan M. Richey
- Department of Epidemiology, Gillings School of Global Public Health, UNC Chapel Hill, Chapel Hill, NC 27514, USA;
| | - ABM Nasir
- Business School, North Carolina Central University, Durham, NC 27707, USA;
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22
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Shkeiri R, Saliba W, Stein N, Najjar R, Weber G, Dror SK, Mishan PS, Adir Y, Shteinberg M. Exploring factors associated with acquisition and chronicity of infection in bronchiectasis: A population-based study. Respir Med 2021; 185:106487. [PMID: 34139580 DOI: 10.1016/j.rmed.2021.106487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/23/2021] [Accepted: 05/24/2021] [Indexed: 11/17/2022]
Abstract
INTRODUCTION Chronic infection is associated with adverse outcomes among people with bronchiectasis. However, it is not known which factors are associated with a bacterial infection, and with persistence of an infection after the first episode. We aimed to determine factors associated with a new infection and with chronicity of Pseudomonas aeruginosa (PA) and H. influenzae (HI), the most common organisms in bronchiectasis infection. METHODS Using an Israeli population database, we identified individuals diagnosed with bronchiectasis. Cox proportional hazard models were used to assess risk factors for first isolation and Logistic regression for chronicity of infection after a first isolation of PA and HI. RESULTS We included 1305 people with a median of 5 respiratory samples per individual. PA was initially isolated in 297 people, of whom 97 (33%) developed chronic PA infection. HI was newly identified in 169 people, of whom 39 (23%) developed chronic infection (p = 0.029). Factors associated with increased risk of a new infection with PA were COPD (HR 1.87 [1.52-2.28], previous isolation of HI (HR 1.38 [1.07-1.78]), and alcohol abuse (HR 2.22 [1.13-4.3]). Younger age was associated with increased risk of HI infection, while COPD was associated with a lower risk of HI infection. Prescription of an anti- PA antibiotic was associated with chronic PA after a new infection (OR = 1.8 [1.09-2.9], p = 0.02). A landmark analysis showed that survival was worse in people with chronic PA infection vs. single or intermittent infection (Log rank: p = 0.034) CONCLUSIONS: Younger age and presence of PCD are associated with a new isolation of HI. A new infection with PA is associated with previous HI infection, PCD, COPD, and alcohol abuse. Unexpectedly, treatment with appropriate anti-PA antimicrobials was not associated with a reduced risk of chronicity.
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Affiliation(s)
- Rashed Shkeiri
- Pulmonology Institute Carmel Medical Center, Haifa, Israel
| | - Walid Saliba
- Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Nili Stein
- Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel
| | - Ronza Najjar
- Infectious Diseases Unit, Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Gabriel Weber
- Infectious Diseases Unit, Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Shifra Ken- Dror
- Clinical Microbiological Laboratory, Central Laboratories Haifa & Western Galilee, Clalit Health Services, Haifa, Israel
| | | | - Yochai Adir
- Pulmonology Institute Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Michal Shteinberg
- Pulmonology Institute Carmel Medical Center, Haifa, Israel; CF Center, Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
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23
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Alberca RW, Rigato PO, Ramos YÁL, Teixeira FME, Branco ACC, Fernandes IG, Pietrobon AJ, Duarte AJDS, Aoki V, Orfali RL, Sato MN. Clinical Characteristics and Survival Analysis in Frequent Alcohol Consumers With COVID-19. Front Nutr 2021; 8:689296. [PMID: 34150832 PMCID: PMC8206498 DOI: 10.3389/fnut.2021.689296] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 04/29/2021] [Indexed: 12/15/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can generate a systemic disease named coronavirus disease-2019 (COVID-19). Currently, the COVID-19 pandemic has killed millions worldwide, presenting huge health and economic challenges worldwide. Several risk factors, such as age, co-infections, metabolic syndrome, and smoking have been associated with poor disease progression and outcomes. Alcohol drinking is a common social practice among adults, but frequent and/or excessive consumption can mitigate the anti-viral and anti-bacterial immune responses. Therefore, we investigated if patients with self-reported daily alcohol consumption (DAC) presented alteration in the immune response to SARS-CoV-2. We investigated 122 patients with COVID-19 (101 male and 46 females), in which 23 were patients with DAC (18 men and 5 women) and 99 were non-DAC patients (58 men and 41 women), without other infections, neoplasia, or immunodeficiencies. Although with no difference in age, patients with DAC presented an increase in severity-associated COVID-19 markers such as C-reactive protein (CRP), neutrophil count, and neutrophil-to-lymphocyte ratio. In addition, patients with DAC presented a reduction in the lymphocytes and monocytes counts. Importantly, the DAC group presented an increase in death rate in comparison with the non-DAC group. Our results demonstrated that, in our cohort, DAC enhanced COVID-19-associated inflammation, and increased the number of deaths due to COVID-19.
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Affiliation(s)
- Ricardo Wesley Alberca
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
| | - Paula Ordonhez Rigato
- Technical Division of Medical Biology, Immunology Center, Adolfo Lutz Institute, São Paulo, Brazil
| | - Yasmim Álefe Leuzzi Ramos
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
| | - Franciane Mouradian Emidio Teixeira
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil.,Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Anna Cláudia Calvielli Branco
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil.,Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Iara Grigoletto Fernandes
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
| | - Anna Julia Pietrobon
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil.,Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Alberto Jose da Silva Duarte
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
| | - Valeria Aoki
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
| | - Raquel Leão Orfali
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
| | - Maria Notomi Sato
- Laboratorio de Dermatologia e Imunodeficiencias (LIM-56), Departamento de Dermatologia, Faculdade de Medicina FMUSP, Instituto de Medicina Tropica, Universidade de São Paulo, São Paulo, Brazil
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24
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Gu M, Samuelson DR, Taylor CM, Molina PE, Luo M, Siggins RW, Shellito JE, Welsh DA. Alcohol-associated intestinal dysbiosis alters mucosal-associated invariant T-cell phenotype and function. Alcohol Clin Exp Res 2021; 45:934-947. [PMID: 33704802 PMCID: PMC8283808 DOI: 10.1111/acer.14589] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 02/23/2021] [Accepted: 02/24/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Chronic alcohol consumption is associated with a compromised innate and adaptive immune responses to infectious disease. Mucosa-associated invariant T (MAIT) cells play a critical role in antibacterial host defense. However, whether alcohol-associated deficits in innate and adaptive immune responses are mediated by alterations in MAIT cells remains unclear. METHODS To investigate the impact of alcohol on MAIT cells, mice were treated with binge-on-chronic alcohol for 10 days and sacrificed at day 11. MAIT cells in the barrier organs (lung, liver, and intestine) were characterized by flow cytometry. Two additional sets of animals were used to examine the involvement of gut microbiota on alcohol-induced MAIT cell changes: (1) Cecal microbiota from alcohol-fed (AF) mice were adoptive transferred into antibiotic-pretreated mice and (2) AF mice were treated with antibiotics during the experiment. MAIT cells in the barrier organs were measured via flow cytometry. RESULTS Binge-on-chronic alcohol feeding led to a significant reduction in the abundance of MAIT cells in the barrier tissues. However, CD69 expression on tissue-associated MAIT cells was increased in AF mice compared with pair-fed (PF) mice. The expression of Th1 cytokines and the corresponding transcriptional factor was tissue specific, showing downregulation in the intestine and increases in the lung and liver in AF animals. Transplantation of fecal microbiota from AF mice resulted in a MAIT cell profile aligned to that of AF mouse donor. Antibiotic treatment abolished the MAIT cell differences between AF and PF animals. CONCLUSION MAIT cells in the intestine, liver, and lung are perturbed by alcohol use and these changes are partially attributable to alcohol-associated dysbiosis. MAIT cell dysfunction may contribute to alcohol-induced innate and adaptive immunity and consequently end-organ pathophysiology.
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Affiliation(s)
- Min Gu
- Department of Internal Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Science Center, New Orleans, LA, USA
| | - Derrick R. Samuelson
- Department of Internal Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Science Center, New Orleans, LA, USA
- Department of Internal Medicine, Division of Pulmonary, Critical Care, & Sleep, University of Nebraska Medical Center, Omaha, NE, USA
| | - Christopher M. Taylor
- Department of Microbiology, Immunology, & Parasitology, Louisiana State University Health Science Center, New Orleans, LA, USA
| | - Patricia E. Molina
- Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA, USA
- Comprehensive Alcohol-HIV/AIDS Research Center, Louisiana State University Health Science Center, New Orleans, LA, USA
| | - Meng Luo
- Department of Microbiology, Immunology, & Parasitology, Louisiana State University Health Science Center, New Orleans, LA, USA
| | - Robert W. Siggins
- Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA, USA
- Comprehensive Alcohol-HIV/AIDS Research Center, Louisiana State University Health Science Center, New Orleans, LA, USA
| | - Judd E. Shellito
- Department of Internal Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Science Center, New Orleans, LA, USA
- Department of Microbiology, Immunology, & Parasitology, Louisiana State University Health Science Center, New Orleans, LA, USA
| | - David A. Welsh
- Department of Internal Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Science Center, New Orleans, LA, USA
- Department of Microbiology, Immunology, & Parasitology, Louisiana State University Health Science Center, New Orleans, LA, USA
- Comprehensive Alcohol-HIV/AIDS Research Center, Louisiana State University Health Science Center, New Orleans, LA, USA
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25
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Melliez H, Mary-Krause M, Guiguet M, Carrieri P, Abgrall S, Enel P, Gallien S, Duval X, Duvivier C, Pavie J, Siguier M, Freire-Maresca A, Tattevin P, Costagliola D. Risk of Severe Bacterial Infection in People Living Human Immunodeficiency Virus Infection in the Combined Antiretroviral Therapy Era. J Infect Dis 2021; 222:765-776. [PMID: 32253435 DOI: 10.1093/infdis/jiaa154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 04/01/2020] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Severe bacterial infections are the first cause of morbidity in people with human immunodeficiency virus (PWH). We aimed to assess their incidence and to analyze their determinants. METHODS We studied human immunodeficiency virus (HIV)-1-infected individuals aged at least 15 years and prospectively followed between 2006 and 2015 in the French Hospital Database on HIV. The Andersen and Gill model was used to calculate the adjusted hazard ratios (HRs), focusing on heavy alcohol use and neutrophil function-altering comorbidities. RESULTS Of 25 795 participants, 1414 developed 1883 severe bacterial infections. Between 2006 and 2009 and 2013 and 2015, the incidence fell from 13.2 (95% confidence interval [CI], 12.3-14.1) to 7.1 (95% CI, 6.3-7.8) per 1000 person-years. Heavy alcohol use was associated with an increased risk of severe bacterial infection (HR = 1.3, 95% CI = 1.1-1.7 for 40-80 g/day and HR = 1.6, 95% CI = 1.2-2.1 for >80 g/day), as were diabetes, chronic kidney disease, and end-stage liver disease (HR = 1.2, 95% CI = 1.0-1.4 when 1 comorbidity; HR = 2.3, 95% CI = 1.6-3.4 when more than 1 comorbidity), and nonacquired immune deficiency syndrome-defining malignancy (HR = 2.0; 95% CI, 1.6-2.4). CONCLUSIONS Heavy alcohol use was associated with an increased risk of severe bacterial infection, as were neutrophil function-altering comorbidities. Controlled-drinking approaches should be promoted and comorbidity management should be strengthened in PWH.
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Affiliation(s)
- Hugues Melliez
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.,Hôpital Gustave Dron, Service Universitaire des Maladies Infectieuses et du Voyageur, Tourcoing, France.,Hôpital de la Région de Saint-Omer, Service de Médecine Interne, Helfaut, France
| | - Murielle Mary-Krause
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
| | - Marguerite Guiguet
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
| | - Patrizia Carrieri
- Aix Marseille University, INSERM, IRD, SESSTIM, Sciences Economiques et Sociales de la Santé et Traitement de l'Information Médicale, Marseille, France.,ORS PACA, Observatoire Régional de la Santé Provence-Alpes-Côte d'Azur, Marseille, France
| | - Sophie Abgrall
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.,Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Antoine Béclère, Service de Médecine Interne et Immunologie Clinique, Clamart, France
| | - Patricia Enel
- Hôpital de la Conception, Service d'Information Médicale, Marseille, France
| | - Sébastien Gallien
- AP-HP, Hôpital Henri Mondor, Service d'Immunologie Clinique et Maladies Infectieuses, Créteil, France
| | - Xavier Duval
- AP-HP, Hôpital Bichat-Claude Bernard, Service des Maladies Infectieuses et Tropicales, Paris, France
| | - Claudine Duvivier
- Institut Pasteur, Centre Médical de l'Institut Pasteur, Centre d'Infectiologie Necker-Pasteur, Paris, France
| | - Juliette Pavie
- AP-HP, Hôpital Européen Georges Pompidou, Service d'Immunologie Clinique, Paris, France
| | - Martin Siguier
- AP-HP, Service des Maladies Infectieuses, Hôpital Saint-Louis, Paris, France
| | | | - Pierre Tattevin
- Hôpital Pontchaillou, Service de des Maladies Infectieuses et Réanimation Médicale, Rennes, France
| | - Dominique Costagliola
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
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26
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Bailey KL, Samuelson DR, Wyatt TA. Alcohol use disorder: A pre-existing condition for COVID-19? Alcohol 2021; 90:11-17. [PMID: 33080339 PMCID: PMC7568767 DOI: 10.1016/j.alcohol.2020.10.003] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 10/02/2020] [Accepted: 10/05/2020] [Indexed: 02/07/2023]
Abstract
Alcohol misuse is long established as a contributor to the pathophysiology of the lung. The intersection of multi-organ responses to alcohol-mediated tissue injury likely contributes to the modulation of lung in response to injury. Indeed, the negative impact of alcohol on susceptibility to infection and on lung barrier function is now well documented. Thus, the alcohol lung represents a very likely comorbidity for the negative consequences of both COVID-19 susceptibility and severity. In this review, we present the known alcohol misuse ramifications on the lung in the context of the current coronavirus pandemic.
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Affiliation(s)
- Kristina L Bailey
- Research Service, Department of Veterans Affairs Omaha-Western Iowa Health Care System, Omaha, NE, 68105, United States; Pulmonary, Critical Care and Sleep, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5910, United States.
| | - Derrick R Samuelson
- Pulmonary, Critical Care and Sleep, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5910, United States.
| | - Todd A Wyatt
- Research Service, Department of Veterans Affairs Omaha-Western Iowa Health Care System, Omaha, NE, 68105, United States; Pulmonary, Critical Care and Sleep, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5910, United States; Department of Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center, Omaha, NE, 68198-5910, United States.
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Harpaz D, Marks RS, Kushmaro A, Eltzov E. Environmental pollutants induce noninherited antibiotic resistance to polymyxin B in Escherichia coli. Future Microbiol 2020; 15:1631-1643. [PMID: 33251814 DOI: 10.2217/fmb-2020-0172] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: The mechanisms behind antibiotic resistance by bacteria are important to create alternative molecules. Objective: This study focuses on the impact of environmental pollutants on bacterial resistance to antibiotics. Materials & methods: The effect of various environmental pollutants on noninherited bacterial resistance to antibiotics was examined. Results: The tolerance to the polymyxin-B antibiotic was shown to be conferred to Escherichia coli, by pretreatment with subinhibitory concentrations of environmental toxicants. The cell survival to a sublethal dosage of antibiotics was tested. Exposure to low concentrations of toxic compounds (500 ppb copper, 2% [v/v] ethanol or 0.5 μg/ml trimethoprim) stimulated the bacterial heat shock systems and led to increased tolerance to polymyxin B. Conclusion: Environmental pollutants induce a temporary bacterial noninheritable resistance to antibiotic.
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Affiliation(s)
- Dorin Harpaz
- Institute of Biochemistry, Food science & Nutrition, Faculty of Agriculture, Food & Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel.,Department of Postharvest Science, Institute of Postharvest and Food Sciences, The Volcani Center, Agricultural Research Organization, Rishon LeZion 7505101, Israel
| | - Robert S Marks
- Avram & Stella Goldstein-Goren Department of Biotechnology Engineering, Faculty of Engineering Science, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel.,The Ilse Katz Center for Meso & Nanoscale Science & Technology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
| | - Ariel Kushmaro
- Avram & Stella Goldstein-Goren Department of Biotechnology Engineering, Faculty of Engineering Science, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel.,The Ilse Katz Center for Meso & Nanoscale Science & Technology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
| | - Evgeni Eltzov
- Department of Postharvest Science, Institute of Postharvest and Food Sciences, The Volcani Center, Agricultural Research Organization, Rishon LeZion 7505101, Israel
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Lange KW, Nakamura Y. Lifestyle factors in the prevention of COVID-19. GLOBAL HEALTH JOURNAL 2020; 4:146-152. [PMID: 33520339 PMCID: PMC7834031 DOI: 10.1016/j.glohj.2020.11.002] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 10/19/2020] [Accepted: 10/20/2020] [Indexed: 02/07/2023] Open
Abstract
Confinement to the home and psychological distress due to the coronavirus disease 2019 (COVID-19) pandemic may lead to harmful health behaviors, such as overeating, sedentary behavior with reduced physical activity, elevated alcohol and tobacco use and increased screen time causing impaired sleep. All of these behaviors are associated with non-communicable diseases and can interfere with immunity. While no foods, single nutrients or dietary supplements are capable of preventing infection with COVID-19, a balanced diet containing sufficient amounts of macronutrients and diverse micronutrients is a prerequisite of an optimally functioning immune system. High-energy "Western" diets and obesity are major risk factors for a more severe course of COVID-19. Alcohol use and tobacco also have detrimental effects on the immune system. Therefore, population-wide body weight control, reduction of smoking rates and limitation of alcohol consumption are important preventive measures. Furthermore, sufficient restorative sleep is needed for adequate immune functioning. Appropriate lifestyle changes in regard to nutrition, exercise, sleep, smoking and alcohol intake may help shift the population distribution of infection risk and aid in preventing severe COVID-19 disease. Large-scale surveys should explore the effects of lifestyle changes, and the provision of reliable lifestyle information and effective interventions to individuals and communities during the pandemic is a pressing need.
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Çelikhisar H, Daşdemir Ilkhan G, Arabaci Ç. Prognostic factors in elderly patients admitted to the intensive care unit with community-acquired pneumonia. Aging Male 2020; 23:1425-1431. [PMID: 32543939 DOI: 10.1080/13685538.2020.1775192] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE We aimed to determine the clinical, radiological and laboratory findings that may indicate poor prognosis in severe community acquired pneumonia (CAP) requiring intensified care to reduce the risk of death. METHODS The medical histories, demographic characteristics and laboratory values of over 65 years old patients admitted to the intensive care unit (ICU) and diagnosed with CAP were recorded. RESULTS Total of 86 patients were included in the study. Among those patients 39 were discharged from the ICU with health but 47 were expired. Diastolic blood pressure was significantly lower in expired patients (p = 0.044). In multivariate analysis, older age (>78 years) (p = 0.004), at admission elevated blood glucose (>108 mg/dL) levels (p = 0.048), decreased serum albumin (<3.5 g/dL) levels (p = 0.043), elevated serum procalcitonin levels (>0.63 μg/L) (p = 0.034) and in blood gas analysis decreased pH (<7.35) (p = 0.042)and increased lactate (>2mmol/L) (p = 0.001) were the significant risk factors for in-ICU mortality. CONCLUSIONS At old age, blood glucose and procalcitonin levels increased at the time of admission, serum albumin levels decreased, pH decreased in blood gas analysis and lactate levels increased, and significant mortality determinants in CAP patients over 65 years of age who applied to the intensive care unit.
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Affiliation(s)
- Hakan Çelikhisar
- Department of Chest Deseases, İzmir Metropolitan Municipality Hospital, İzmir, Turkey
| | - Gülay Daşdemir Ilkhan
- Department of Chest Diseases, Okmeydanı Training and Research Hospital, Istanbul, Turkey
| | - Çiğdem Arabaci
- Department of Microbiology, Okmeydanı Training and Research Hospital, Istanbul, Turkey
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Systemic Inflammatory Response and Outcomes in Community-Acquired Pneumonia Patients Categorized According to the Smoking Habit or Presence of Chronic Obstructive Pulmonary Disease. J Clin Med 2020; 9:jcm9092884. [PMID: 32906593 PMCID: PMC7564982 DOI: 10.3390/jcm9092884] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 08/27/2020] [Accepted: 09/04/2020] [Indexed: 01/01/2023] Open
Abstract
The systemic inflammatory response (SIR) may help to predict clinical progression, treatment failure, and prognosis in community-acquired pneumonia (CAP). Exposure to tobacco smoke may affect the SIR; the role of smoking in CAP has not been consolidated. We evaluated the SIR and outcomes of hospitalized CAP patients stratified by smoking habits and the presence of COPD. This retrospective analysis was conducted at the Hospital Clinic of Barcelona. Baseline, clinical, microbiological, and laboratory variables were collected at admission, using C-reactive protein (CRP) levels as a marker of SIR. The study outcomes were pleural complications, hospital stay, non-invasive and invasive mechanical ventilation (IMV), and intensive care unit (ICU) admission. We also considered the in-hospital and 30-day mortality. Data were grouped by smoking habit (non-, former-, and current-smokers) and the presence of COPD. Current smokers were younger, had fewer comorbidities, and fewer previous pneumonia episodes. CRP levels were higher in current smokers than in other groups. Current smokers had a higher risk of pleural complications independent of CRP levels, the presence of pleuritic pain, and a higher platelet count. Current smokers more often required IMV and ICU admission. Current smokers have a greater inflammatory response and are at increased risk of pleural complications.
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31
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Bailey KL, Smith H, Mathai SK, Huber J, Yacoub M, Yang IV, Wyatt TA, Kechris K, Burnham EL. Alcohol Use Disorders Are Associated With a Unique Impact on Airway Epithelial Cell Gene Expression. Alcohol Clin Exp Res 2020; 44:1571-1584. [PMID: 32524622 PMCID: PMC7484391 DOI: 10.1111/acer.14395] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 05/28/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Alcohol use disorders (AUDs) and cigarette smoking both increase risk for the development of community-acquired pneumonia (CAP), likely through adverse effects on proximal airway mucociliary clearance and pathogen recognition. Smoking-related alterations on airway gene expression are well described, but little is known about the impact of AUDs. We measured gene expression in human airway epithelial cells (AECs), hypothesizing that AUDs would be associated with novel differences in gene expression that could alter risk for CAP. METHODS Bronchoscopy with airway brushings was performed in participants with AUDs and controls to obtain AECs. An AUD Identification Test was used to define AUD. RNA was extracted from AECs, and mRNA expression data were collected on an Agilent micro-array. Differential expression analyses were performed on the filtered and normalized data with correction for multiple testing. Enrichment analyses were performed using clusterProfiler. RESULTS Expression data from 19 control and 18 AUD participants were evaluated. After adjustment for smoking, AUDs were associated with significant differential expression of 520 AEC genes, including genes for ribosomal proteins and genes involved in protein folding. Enrichment analyses indicated significant differential expression of 24 pathways in AUDs, including those implicated in protein targeting to membrane and viral gene expression. Smoking-associated AEC gene expression differences mirrored previous reports, but differed from those associated with AUDs. CONCLUSIONS AUDs have a distinct impact on AEC gene expression that may influence proximal airway function independent of smoking. Alcohol-associated alterations may influence risk for CAP through modifying key mechanisms important in protecting proximal airway integrity.
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Affiliation(s)
- Kristina L. Bailey
- University of Nebraska Medical Center, Department of Internal Medicine. Division of Pulmonary, Critical Care, Sleep and Allergy
- VA Nebraska-Western Iowa Health Care System
| | - Harry Smith
- University of Colorado Anschutz Medical Campus, Department of Biostatistics and Informatics, Colorado School of Public Health
| | - Susan K. Mathai
- Baylor University Medical Center, Center for Advanced Heart & Lung Disease
| | - Jonathan Huber
- University of Colorado Anschutz Medical Campus, Department of Medicine, Division of Allergy & Clinical Immunology
| | - Mark Yacoub
- University of Colorado Anschutz Medical Campus, Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine
| | - Ivana V. Yang
- University of Colorado Anschutz Medical Campus, Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine
- University of Colorado Anschutz Medical Campus, Department of Medicine, Division of Biomedical Informatics and Personalized Medicine
| | - Todd A. Wyatt
- VA Nebraska-Western Iowa Health Care System
- University of Nebraska Medical Center, Department of Environmental, Agricultural, & Occupational Health
| | - Katerina Kechris
- University of Colorado Anschutz Medical Campus, Department of Biostatistics and Informatics, Colorado School of Public Health
- University of Colorado Anschutz Medical Campus, Department of Medicine, Division of Biomedical Informatics and Personalized Medicine
| | - Ellen L. Burnham
- University of Colorado Anschutz Medical Campus, Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine
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Chronic Alcohol Ingestion Worsens Survival and Alters Gut Epithelial Apoptosis and CD8+ T Cell Function After Pseudomonas Aeruginosa Pneumonia-Induced Sepsis. Shock 2020; 51:453-463. [PMID: 29664837 DOI: 10.1097/shk.0000000000001163] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Mortality is higher in septic patients with a history of alcohol use disorder than in septic patients without a history of chronic alcohol usage. We have previously described a model of chronic alcohol ingestion followed by sepsis from cecal ligation and puncture in which alcohol-fed septic mice have higher mortality than water-fed septic mice, associated with altered gut integrity and increased production of TNF and IFNγ by splenic CD4 T cells without alterations in CD8 T cell function. The purpose of this study was to determine whether this represents a common host response to the combination of alcohol and sepsis by creating a new model in which mice with chronic alcohol ingestion were subjected to a different model of sepsis. C57Bl/6 mice were randomized to receive either alcohol or water for 12 weeks and then subjected to Pseudomonas aeruginosa pneumonia. Mice were sacrificed either 24 hours after the onset of sepsis or followed for survival. Alcohol-fed septic mice had significantly higher 7-day mortality than water-fed septic mice (96% vs 58%). This was associated with a 5-fold increase in intestinal apoptosis in alcohol-fed septic animals, accompanied by an increase in the pro-apoptotic protein Bax. Serum IL-6 levels were higher and IL-2 levels were lower in alcohol-fed septic mice. In contrast, CD8 T cell frequency was lower in alcohol-fed mice than water-fed septic mice, associated with increased production of IFNγ and TNF in stimulated splenocytes. No significant differences were noted in CD4 T cells, lung injury or bacteremia. Mice with chronic alcohol ingestion thus have increased mortality regardless of their septic insult, associated with changes in both the gut and the immune system.
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Gaydos J, McNally A, Burnham EL. The impact of alcohol use disorders on pulmonary immune cell inflammatory responses to Streptococcus pneumoniae. Alcohol 2019; 80:119-130. [PMID: 30195043 DOI: 10.1016/j.alcohol.2018.08.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 08/29/2018] [Accepted: 08/31/2018] [Indexed: 12/11/2022]
Abstract
Community-acquired pneumonia due to Streptococcus pneumoniae occurs commonly in alcohol use disorders (AUDs). Pneumonia in the AUD patient is associated with poorer outcomes, and specific therapies to mitigate disease severity in these patients do not exist. Numerous investigations have attributed increased severity of pneumonia in AUDs to aberrant function of the alveolar macrophage (AM), a lung immune cell critical in host defense initiation. No studies have examined the response of human AMs to S. pneumoniae in AUDs. We hypothesized that the inflammatory mediators released by AMs after S. pneumoniae stimulation would differ quantitatively in individuals with AUDs compared to non-AUD participants. We further postulated that AM inflammatory mediators would be diminished after exposure to the antioxidant, N-acetylcysteine (NAC). For comparison, responses of peripheral blood mononuclear cells (PBMCs) to pneumococcal protein were also examined. Otherwise healthy participants with AUDs and smoking-matched controls underwent bronchoalveolar lavage and peripheral blood sampling to obtain AMs and PBMCs, respectively. Freshly collected cells were cultured with increasing doses of heat-killed S. pneumoniae protein, with and without exposure to N-acetylcysteine. Cell culture supernatants were collected, and inflammatory mediators were measured, including interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. IFN-γ and IL-6 were significantly higher in unstimulated AM cell culture supernatants from subjects with AUDs. After stimulation with pneumococcal protein, a dose-response and time-dependent increase in pro-inflammatory cytokine production by both AMs and PBMCs was also observed; differences were not observed between AUD and non-AUD subjects. Addition of NAC to pneumococcal-stimulated AMs and PBMCs was generally associated with diminished cytokine production, with the exception of IL-1β that was elevated in AM culture supernatants from subjects with AUDs. Our observations suggest that AUDs contribute to basal alterations in AM pro-inflammatory cytokine elaboration, but did not support consistent differences in pneumococcal-stimulated AM or PBMC inflammatory mediator secretion that were referable to AUDs.
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Michelin L, Weber FM, Scolari BW, Menezes BK, Gullo MC. Mortality and costs of pneumococcal pneumonia in adults: a cross-sectional study. ACTA ACUST UNITED AC 2019; 45:e20180374. [PMID: 31644703 PMCID: PMC8653114 DOI: 10.1590/1806-3713/e20180374] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 03/14/2019] [Indexed: 12/27/2022]
Abstract
Objective Pneumococcal pneumonia is a significant cause of morbidity and mortality among adults. The study’s main aim was to evaluate the in-hospital mortality and related costs of community-acquired pneumococcal pneumonia in adults. Methods This cross-sectional study used medical records of adult patients with pneumococcal pneumonia hospitalized in a university hospital in Brazil from October 2009 to April 2017. All patients aged ≥ 18 years diagnosed with pneumococcal pneumonia were included. Risk factors, intensive care unit admission, length of hospital stay, in-hospital mortality, and direct and indirect costs were analyzed. Results In total, 186 patients were selected. The mean in-hospital mortality rate was 18% for adults aged < 65 years and 23% for the elderly (≥ 65 years). Bacteremic pneumococcal pneumonia affected 20% of patients in both groups, mainly through chronic respiratory disease (adjusted OR: 3.07, 95% CI: 1.23–7.65, p < 0.01). Over 7 years, annual total direct and indirect costs were USD 28,188 for adults < 65 years (USD 1,746 per capita) and USD 16,350 for the elderly (USD 2,119 per capita). Conclusion Pneumococcal pneumonia remains an important cause of morbidity and mortality among adults, significantly affecting direct and indirect costs. These results suggest the need for prevention strategies for all adults, especially for patients with chronic respiratory diseases.
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Affiliation(s)
| | | | - Bruna W Scolari
- Programa de Pós-graduação em Ciências da Saúde, Universidade de Caxias do Sul, Caxias do Sul (RS), Brasil
| | | | - Maria Carolina Gullo
- Departamento de Ciências Econômicas, Universidade de Caxias do Sul, Caxias do Sul (RS), Brasil
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Tanzella G, Motos A, Battaglini D, Meli A, Torres A. Optimal approaches to preventing severe community-acquired pneumonia. Expert Rev Respir Med 2019; 13:1005-1018. [PMID: 31414915 DOI: 10.1080/17476348.2019.1656531] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Introduction: Community-acquired pneumonia (CAP) has the highest rate of mortality of all infectious diseases, especially among the elderly. Severe CAP (sCAP) is defined as a CAP in which intensive care management is required and is associated with an unfavorable clinical course. Areas covered: This review aims to identify prevention strategies for reducing the incidence of CAP and optimized management of sCAP. We highlight the main prevention approaches for CAP, focusing on the latest vaccination plans and on the influence of health-risk behaviors. Lastly, we report the latest recommendations about the optimal approach for sCAP when CAP has already been diagnosed, including prompt admission to ICU, early empirical antibiotic therapy, and optimization of antibiotic use. Expert opinion: Despite improvements in the diagnosis and treatment of sCAP, more efforts are needed to combat preventable causes, including the implementation and improvement of vaccine coverage, anti-tobacco campaigns and correct oral hygiene. Moreover, future research should aim to assess the benefits of early antimicrobial therapy in primary care. Pharmacokinetic studies in the target population may help clinicians to adjust dosage regimens in critically ill patients with CAP and thus reduce rates of treatment failure.
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Affiliation(s)
- Giacomo Tanzella
- Division of Animal Experimentation, Department of Pulmonary and Critical Care Medicine, Hospital Clinic , Barcelona , Spain.,Department of Surgical Sciences and Integrated Diagnostics (DISC), San Martino Policlinico Hospital , Genoa , Italy
| | - Ana Motos
- Division of Animal Experimentation, Department of Pulmonary and Critical Care Medicine, Hospital Clinic , Barcelona , Spain.,Centro de Investigación Biomédica en Red Enfermedades Respiratorias , Madrid , Spain.,Institut d'Investigacions Biomèdiques August Pi I Sunyer , Barcelona , Spain.,Faculty of Medicine, University of Barcelona , Barcelona , Spain
| | - Denise Battaglini
- Division of Animal Experimentation, Department of Pulmonary and Critical Care Medicine, Hospital Clinic , Barcelona , Spain.,Department of Surgical Sciences and Integrated Diagnostics (DISC), San Martino Policlinico Hospital , Genoa , Italy
| | - Andrea Meli
- Division of Animal Experimentation, Department of Pulmonary and Critical Care Medicine, Hospital Clinic , Barcelona , Spain.,University of Milan , Milan , Italy
| | - Antoni Torres
- Division of Animal Experimentation, Department of Pulmonary and Critical Care Medicine, Hospital Clinic , Barcelona , Spain.,Centro de Investigación Biomédica en Red Enfermedades Respiratorias , Madrid , Spain.,Institut d'Investigacions Biomèdiques August Pi I Sunyer , Barcelona , Spain.,Faculty of Medicine, University of Barcelona , Barcelona , Spain
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Kjærgaard N, Bodilsen J, Justesen US, Schønheyder HC, Andersen CØ, Ellermann-Eriksen S, Dzajic E, Chen M, Møller JK, Dessau RB, Frimodt-Møller N, Jarløv JO, Nielsen H. Community-acquired meningitis caused by beta-haemolytic streptococci in adults: a nationwide population-based cohort study. Eur J Clin Microbiol Infect Dis 2019; 38:2305-2310. [PMID: 31440914 DOI: 10.1007/s10096-019-03678-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 08/09/2019] [Indexed: 10/26/2022]
Abstract
The objective of this study was to examine the clinical presentation of community-acquired beta-haemolytic streptococcal (BHS) meningitis in adults. This is a nationwide population-based cohort study of adults (≥ 16 years) with BHS meningitis verified by culture or polymerase chain reaction of the cerebrospinal fluid (CSF) from 1993 to 2005. We retrospectively evaluated clinical and laboratory features and assessed outcome by Glasgow Outcome Scale (GOS). We identified 54 adults (58% female) with a median age of 65 years (IQR 55-73). Mean incidence rate was 0.7 cases per 1,000,000 person-years. Alcohol abuse was noted among 11 (20%) patients. Group A streptococci (GAS) were found in 17 (32%) patients, group B (GBS) in 18 (34%), group C (GCS) in four (8%) and group G (GGS) in 14 (26%). Patients with GAS meningitis often had concomitant otitis media (47%) and mastoiditis (30%). Among patients with GBS, GCS or GGS meningitis, the most frequent concomitant focal infections were bone and soft tissue infections (19%) and endocarditis (16%). In-hospital mortality was 31% (95% CI 19-45), and 63% (95% CI 49-76) had an unfavourable outcome at discharge (GOS < 5). BHS meningitis in adults is primarily observed among the elderly and has a poor prognosis. GAS meningitis is primarily associated with concomitant ear-nose-throat infection.
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Affiliation(s)
- Nicolai Kjærgaard
- Department of Infectious Disease, Aalborg University Hospital, Mølleparkvej 4, DK-9000, Aalborg, Denmark.
| | - Jacob Bodilsen
- Department of Infectious Disease, Aalborg University Hospital, Mølleparkvej 4, DK-9000, Aalborg, Denmark
| | - Ulrik Stenz Justesen
- Department of Clinical Microbiology, Odense University Hospital, J. B. Winsløws Vej 4, DK-5000, Odense, Denmark
| | - Henrik Carl Schønheyder
- Department of Clinical Microbiology, Aalborg University Hospital, Hobrovej 18-22, DK-9000, Aalborg, Denmark
| | | | - Svend Ellermann-Eriksen
- Department of Clinical Microbiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200, Aarhus N, Denmark
| | - Esad Dzajic
- Department of Clinical Microbiology, Sydvestjysk Sygehus, Finsensgade 35, DK-6700, Esbjerg, Denmark
| | - Ming Chen
- Department of Clinical Microbiology, Hospital of Southern Jutland, Sydvang 1, DK-6400, Sonderborg, Denmark
| | - Jens Kjølseth Møller
- Department of Clinical Microbiology, Sygehus Lillebælt, Kabbeltoft 25, DK-7100, Vejle, Denmark
| | - Ram Benny Dessau
- Department of Clinical Microbiology, Slagelse Hospital, Ingemannsvej 30, DK-4200, Slagelse, Denmark
| | - Niels Frimodt-Møller
- Department of Clinical Microbiology, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark
| | - Jens Otto Jarløv
- Department of Clinical Microbiology, Herlev Hospital, Herlev Ringvej 75, DK-2730, Herlev, Denmark
| | - Henrik Nielsen
- Department of Infectious Disease, Aalborg University Hospital, Mølleparkvej 4, DK-9000, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Søndre Skovvej 15, DK-9000, Aalborg, Denmark
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Gupta NM, Lindenauer PK, Yu PC, Imrey PB, Haessler S, Deshpande A, Higgins TL, Rothberg MB. Association Between Alcohol Use Disorders and Outcomes of Patients Hospitalized With Community-Acquired Pneumonia. JAMA Netw Open 2019; 2:e195172. [PMID: 31173120 PMCID: PMC6563577 DOI: 10.1001/jamanetworkopen.2019.5172] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
IMPORTANCE Patients with alcohol use disorder (AUD) are at elevated risk of developing pneumonia, but few studies have assessed the outcomes of pneumonia in patients with AUD. OBJECTIVES To compare the causes, treatment, and outcomes of pneumonia in patients with and without AUD and to understand the associations of comorbid illnesses, alcohol withdrawal, and any residual effects due to alcohol itself with patient outcomes. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted of 137 496 patients 18 years or older with pneumonia who were admitted to 177 US hospitals participating in the Premier Healthcare Database from July 1, 2010, to June 30, 2015. Statistical analysis was conducted from October 27, 2017, to August 20, 2018. EXPOSURE Alcohol use disorders identified from International Classification of Diseases, Ninth Revision, Clinical Modification codes. MAIN OUTCOMES AND MEASURES Pneumonia cause, antibiotic treatment, inpatient mortality, clinical deterioration, length of stay, and cost. Associations of AUD with these variables were studied using generalized linear mixed models. RESULTS Of 137 496 patients with community-acquired pneumonia (70 358 women and 67 138 men; mean [SD] age, 69.5 [16.2] years), 3.5% had an AUD. Patients with an AUD were younger than those without an AUD (median age, 58.0 vs 73.0 years; P < .001), more often male (77.3% vs 47.8%; P < .001), and more often had principal diagnoses of aspiration pneumonia (10.9% vs 9.8%; P < .001), sepsis (38.6% vs 30.7%; P < .001), or respiratory failure (9.3% vs 5.5%; P < .001). Their cultures more often grew Streptococcus pneumoniae (43.7% vs 25.5%; P < .001) and less frequently grew organisms resistant to guideline-recommended antibiotics (25.0% vs 43.7%; P < .001). Patients with an AUD were treated more often with piperacillin-tazobactam (26.2% vs 22.5%; P < .001) but equally as often with anti-methicillin-resistant Staphylococcus aureus agents (32.9% vs 31.8%; P = .11) compared with patients without AUDs. When adjusted for demographic characteristics and insurance, AUD was associated with higher mortality (odds ratio, 1.40; 95% CI, 1.25-1.56), length of stay (risk-adjusted geometric mean ratio, 1.24; 95% CI, 1.20-1.27), and costs (risk-adjusted geometric mean ratio, 1.33; 95% CI, 1.28-1.38). After additional adjustment for differences in comorbidities and risk factors for resistant organisms, AUD was no longer associated with mortality but remained associated with late mechanical ventilation (odds ratio, 1.28; 95% CI, 1.12-1.46), length of stay (risk-adjusted geometric mean ratio, 1.04; 95% CI, 1.01-1.06), and costs (risk-adjusted geometric mean ratio, 1.06; 95% CI, 1.03-1.09). Models segregating patients undergoing alcohol withdrawal showed that poorer outcomes among patients with AUD were confined to the subgroup undergoing alcohol withdrawal. CONCLUSIONS AND RELEVANCE This study suggests that, compared with hospitalized patients with community-acquired pneumonia but without AUD, those with AUD less often harbor resistant organisms. The higher age-adjusted risk of death among patients with AUD appears to be largely attributable to differences in comorbidities, whereas greater use of health care resources may be attributable to alcohol withdrawal.
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Affiliation(s)
- Niyati M. Gupta
- Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, Cleveland, Ohio
| | - Peter K. Lindenauer
- Institute for Healthcare Delivery and Population Science, Department of Medicine, University of Massachusetts Medical School-Baystate, Springfield
- Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester
| | - Pei-Chun Yu
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Peter B. Imrey
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
- Mellon Center for MS Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, Ohio
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio
| | - Sarah Haessler
- Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School-Baystate, Springfield
| | - Abhishek Deshpande
- Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, Cleveland, Ohio
| | | | - Michael B. Rothberg
- Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, Cleveland, Ohio
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Belz M, Rehling N, Schmidt U, Wiltfang J, Kis B, Wolff-Menzler C. Bacterial infections among patients with psychiatric disorders: Relation with hospital stay, age, and psychiatric diagnoses. PLoS One 2018; 13:e0208458. [PMID: 30513128 PMCID: PMC6279031 DOI: 10.1371/journal.pone.0208458] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 11/17/2018] [Indexed: 11/17/2022] Open
Abstract
The prevalence of infections is supposed to be higher in older patients and to extend the length of hospital stays. This study aimed, first, to test this supposition within a large psychiatric population which we divided into four clusters of psychiatric ICD-10 diagnoses: F00-F03 (dementias), F10 (substance disorders), F20-29 (schizophrenia, schizophreniform and other non-mood psychotic disorders), F32-F33 (major depressive disorders). Second, despite the increasing evidence for the role of infections in psychiatric disorders, it is, to the best of our knowledge, largely unknown whether the rates of infections with pathogens of the four most frequent germ families differ between psychiatric diseases. Thus, in a retrospective study, the results of clinical routine examinations (pap smear, analysis of midstream urine, stool) dependent on symptoms in 8545 patients of a German psychiatric clinic were analyzed in a 12-year dataset. Results show that a longer hospital stay was associated with an increased number of microbiological tests, but led to no significant difference between positive vs. negative findings. Consistent with previous studies, patients with infections were older than patients without infections. For the F10 diagnosis cluster we found a significantly reduced (F10: Staphylococcaceae) and for the F20-29 cluster a heightened risk of infections (Staphylococcaceae, Corynebacteriaceae). Furthermore, patients belonging to the F00-F03 cluster exhibited elevated rates of infections with all four germ families. The latter can be ascribed to patients' age as we found higher age to be associated with these infections, independently of the presence of dementia. Our results suggest that different psychiatric diagnoses are associated with a heightened or lowered risk of bacterial infections and, furthermore, that clinical routine infection-screenings for elderly psychiatric patients seems to be reasonable.
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Affiliation(s)
- Michael Belz
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), Göttingen, Lower-Saxony, Germany
| | - Nico Rehling
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), Göttingen, Lower-Saxony, Germany
| | - Ulrike Schmidt
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), Göttingen, Lower-Saxony, Germany
| | - Jens Wiltfang
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), Göttingen, Lower-Saxony, Germany.,German Center for Neurodegenerative Diseases (DZNE), Goettingen, Lower-Saxony, Germany.,Institute for Biomedicine (iBiMED), Medical Sciences Department, University of Aveiro, Aveiro, Portugal
| | - Bernhard Kis
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), Göttingen, Lower-Saxony, Germany
| | - Claus Wolff-Menzler
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen (UMG), Göttingen, Lower-Saxony, Germany
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Mörs K, Kany S, Hörauf JA, Wagner N, Neunaber C, Perl M, Marzi I, Relja B. Suppression of the interleukin-1ß-induced inflammatory response of human Chang liver cells by acute and subacute exposure to alcohol: an in vitro study. Croat Med J 2018; 59:46-55. [PMID: 29740988 PMCID: PMC5941294 DOI: 10.3325/cmj.2018.59.46] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Aim To evaluate protective immunosuppressive dose and time-dependent effects of ethanol in an in vitro model of acute inflammation in human Chang liver cells. Method The study was performed in 2016 and 2017 in the research laboratory of the Department of Trauma, Hand and Reconstructive Surgery, the University Hospital of the Goethe-University Frankfurt. Chang liver cells were stimulated with either interleukin (IL)-1β or IL-6 and subsequently treated with low-dose ethanol (85 mmol/L) or high-dose ethanol (170 mmol/L) for one hour (acute exposure) or 72 hours (subacute exposure). IL-6 and IL-1β release were determined by enzyme-linked immunosorbent assay. Neutrophil adhesion to Chang liver monolayers, production of reactive oxygen species, and apoptosis or necrosis were analyzed. Results Contrary to high-dose ethanol, acute low-dose ethanol exposure significantly reduced IL-1β-induced IL-6 and IL-6-induced IL-1β release (P < 0.05). Subacute ethanol exposure did not change proinflammatory cytokine release. Acute low-dose ethanol exposure significantly decreased inflammation-induced formation of reactive oxygen species (P < 0.05) and significantly improved cell survival (P < 0.05). Neither acute nor subacute high-dose ethanol exposure significantly changed inflammation-induced changes in reactive oxygen species or survival. Acute and subacute ethanol exposure, independently of the dose, significantly decreased neutrophil adhesion to inflamed Chang liver cells (P < 0.05). Conclusion Acute treatment of inflamed Chang liver cells with ethanol showed its immunosuppressive potential. However, the observed effects were limited to low-dose setting, indicating the relevance of ethanol dose in the modulation of inflammatory cell response.
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Affiliation(s)
| | | | | | | | | | | | | | - Borna Relja
- Borna Relja, Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe-University, 60590 Frankfurt, Germany,
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Stoyle G, Fawcett P, Malagon I. The use of VV-ECMO in patients with drug dependencies. J Artif Organs 2018; 21:293-299. [PMID: 29464442 DOI: 10.1007/s10047-018-1026-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2017] [Accepted: 02/16/2018] [Indexed: 10/18/2022]
Abstract
The purpose of this study is to determine the effect of illicit drug and alcohol dependencies on mortality, length of stay, and complications in patients who have been supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO) following respiratory failure not responsive to conventional methods of ventilation. 584 VV-ECMO referrals received at Wythenshawe Hospital were reviewed for evidence of drug dependency. 13 patients were identified as being drug-dependent and having undergone treatment with VV-ECMO. A matched cohort of 13 non-drug-dependent patients was identified using date of birth, pre-ECMO Murray Score, and primary diagnosis. The outcomes were compared. 19 more complications were found amongst the drug-dependent patients compared with the non-drug-dependent cohort (39 vs 20). A mean difference of 1.46 complications per patient was calculated (p = 0.005). Mortality after 180 days was reported in 4 of the drug-dependent patients, compared with one in the matched cohort. Length of stay on ECMO was increased on average by 1.93 days amongst the drug-dependent patients (p = 0.557); however, the sample size was not great enough to achieve statistical significance. Patients with drug dependencies undergoing VV-ECMO have more complications when compared with a cohort of patients with no proven or suspected drug dependencies. Differences in morbidity and mortality were not statistically significant.
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Affiliation(s)
- George Stoyle
- Wythenshawe Hospital, Manchester University Foundation Trust, Wythenshawe, Manchester, UK.
- The University of Manchester, Manchester, UK.
| | - Peter Fawcett
- Wythenshawe Hospital, Manchester University Foundation Trust, Wythenshawe, Manchester, UK
| | - Ignacio Malagon
- Wythenshawe Hospital, Manchester University Foundation Trust, Wythenshawe, Manchester, UK.
- The University of Manchester, Manchester, UK.
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Mahendra M, Jayaraj BS, Limaye S, Chaya SK, Dhar R, Mahesh PA. Factors influencing severity of community-acquired pneumonia. Lung India 2018; 35:284-289. [PMID: 29970765 PMCID: PMC6034384 DOI: 10.4103/lungindia.lungindia_334_17] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality in India. There is a need to understand the risk factors associated with severity of CAP in our population. This study was part of the international global initiative for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia study to evaluate MRSA. METHODS A total of 100 consecutive cases of pneumonia admitted to the Department of Pulmonary Medicine in a tertiary care hospital were recruited in the study during March-July 2015. The severity of pneumonia was assessed based on the CURB-65 score. Individuals with pneumonia and CURB-65 score >2 were compared with subjects with CURB-65 score ≤2. Individuals were also evaluated for the causative organism and its resistance pattern with specific reference to the presence of MRSA. RESULTS Mean age of patients was 54.03 years, 66% were men. Patients were managed either in the intensive care unit (42%) or wards/high dependency unit (58%), 22% needed noninvasive ventilation and 18% needed mechanical ventilation within 24 h of admission. On multivariate analysis, prior respiratory infection (within last 1 year), obesity (body mass index >30), and alcoholism, old age (>60 years) were independently associated risk factors for severe pneumonia. There were no cases of MRSA. In 34% of cases, organisms could be identified. Most common organisms were Klebsiella (8%), influenza (8%), and Pseudomonas (5%). CONCLUSION Prior respiratory infection, obesity, alcoholism, and old age (>60 years) were observed to be important risk factors for severe CAP. Prospective studies should evaluate effect of weight reduction and cessation of alcohol consumption on recurrences of pneumonia in this population and on the severity of pneumonia.
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Affiliation(s)
- M Mahendra
- Department of Pulmonary Medicine, Shimoga Institute of Medical Sciences, Shivamogga, Karnataka, India
| | - BS Jayaraj
- Department of Pulmonary Medicine, JSS Medical College, JSS University, Mysore, Karnataka, India
| | - Sneha Limaye
- Department of Clinical Trials, Respiratory Research Network of India(CRF), Pune, Maharashtra, India
| | - SK Chaya
- Department of Pulmonary Medicine, JSS Medical College, JSS University, Mysore, Karnataka, India
| | - Raja Dhar
- Department Of Respiratory Medicine, Fortis Hospital, Kolkata, West Bengal, India
| | - PA Mahesh
- Department of Pulmonary Medicine, JSS Medical College, JSS University, Mysore, Karnataka, India
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A Peculiar Case of Invasive Streptococcus pneumoniae. Case Rep Infect Dis 2018; 2017:1530507. [PMID: 29464129 PMCID: PMC5804339 DOI: 10.1155/2017/1530507] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 11/12/2017] [Accepted: 11/29/2017] [Indexed: 11/23/2022] Open
Abstract
Patients commonly present to the emergency department with acute respiratory distress; however, the differentials are broad and at times difficult to distinguish. We describe a case of severe community-acquired pneumonia (CAP) secondary to invasive Streptococcus pneumoniae. The patient was intubated within 3 h of presentation and suffered multiorgan failure within 72 h of intensive care unit (ICU) admission. This case is a stark illustration of how the most common bacteria associated with CAP can be fatal and highlights the associated markers of severity. It also outlines other potential complications including a very rare phenomenon of cardiomyopathy with myocarditis associated with S. pneumoniae bacteraemia.
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Kochhar G, Edge P, Blomme C, Wu XR, Lopez R, Ashburn J, Shen B. Clostridium difficle Enteropathy Is Associated With a Higher Risk for Acute Kidney Injury in Patients With an Ileostomy-A Case-Control Study. Inflamm Bowel Dis 2018; 24:402-409. [PMID: 29361091 DOI: 10.1093/ibd/izx034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is traditionally considered a colon-affecting disease with frequent pseudomembrane formation. However, multiple case reports have documented the existence of CDI in the small bowel, and the literature on outcome of C difficile enteropathy (CDE) is sparse. The aims of our study are to identify risk factors and to assess patient-related outcomes associated with CDE. METHODS This is a case-control study involving 112 patients at our tertiary care center. Patients with an ileostomy who tested positive for C difficile toxins were assigned to the study group (n = 34). The control group included patients with an ileostomy who tested negative for the C difficile toxins (n = 78). Via chart review, we collected data on baseline characteristics, laboratory values, potential risk factors, and outcome measures. RESULTS Patients in the study and control groups were comparable in baseline and laboratory characteristics. In univariate analysis, CDE was associated with a history of smoking (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.06-4.3; P = 0.034), the presence of alcohol use (HR, 3.7; 95% CI, 1.05-12.8; P = 0.042), and older median age at the time of ileostomy (HR, 1.2; 95% CI, 1.07-1.3; P = 0.001). In multivariate analysis, no significant association between established CDI risk factors (eg, prior exposure to antibiotics and the use of proton pump inhibitors or histamine 2 receptor blockers) and the risk for the CDE was found. Only a history of alcohol intake was found to be associated with CDE (HR, 3.9; 95% CI, 1.09-14.1; P = 0.036). No significant difference in mortality was found in the study and control groups (2.9% vs 1.3%, P = 0.52), but patients with CDE were more likely to have acute kidney injury (AKI) than those without CDE (odds ratio, 4.0; 95% CI, 1.2-13.0. P = 0.023). CONCLUSIONS We identified a history of alcohol use a risk factor for CDE. Furthermore, CDE was found be associated with an increased risk for developing AKI.
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Affiliation(s)
- Gursimran Kochhar
- Department of Gastroenterology and Hepatology, the Cleveland Clinic Foundation, Cleveland, Ohio
| | - Preston Edge
- Department of Gastroenterology and Hepatology, the Cleveland Clinic Foundation, Cleveland, Ohio
| | - Courtney Blomme
- Department of Gastroenterology and Hepatology, the Cleveland Clinic Foundation, Cleveland, Ohio
| | - Xian-Rui Wu
- Department of Colorectal Surgery, the Cleveland Clinic Foundation, Cleveland, Ohio
| | - Rocio Lopez
- Department of Quantitative Sciences, the Cleveland Clinic Foundation, Cleveland, Ohio
| | - Jean Ashburn
- Department of Colorectal Surgery, the Cleveland Clinic Foundation, Cleveland, Ohio
| | - Bo Shen
- Department of Gastroenterology and Hepatology, the Cleveland Clinic Foundation, Cleveland, Ohio
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Regionally compartmentalized resident memory T cells mediate naturally acquired protection against pneumococcal pneumonia. Mucosal Immunol 2018; 11:220-235. [PMID: 28513594 PMCID: PMC5693795 DOI: 10.1038/mi.2017.43] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Accepted: 04/10/2017] [Indexed: 02/04/2023]
Abstract
As children age, they become less susceptible to the diverse microbes causing pneumonia. These microbes are pathobionts that infect the respiratory tract multiple times during childhood, generating immunological memory. To elucidate mechanisms of such naturally acquired immune protection against pneumonia, we modeled a relevant immunological history in mice by infecting their airways with mismatched serotypes of Streptococcus pneumoniae (pneumococcus). Previous pneumococcal infections provided protection against a heterotypic, highly virulent pneumococcus, as evidenced by reduced bacterial burdens and long-term sterilizing immunity. This protection was diminished by depletion of CD4+ cells prior to the final infection. The resolution of previous pneumococcal infections seeded the lungs with CD4+ resident memory T (TRM) cells, which responded to heterotypic pneumococcus stimulation by producing multiple effector cytokines, particularly interleukin (IL)-17A. Following lobar pneumonias, IL-17-producing CD4+ TRM cells were confined to the previously infected lobe, rather than dispersed throughout the lower respiratory tract. Importantly, pneumonia protection also was confined to that immunologically experienced lobe. Thus regionally localized memory cells provide superior local tissue protection to that mediated by systemic or central memory immune defenses. We conclude that respiratory bacterial infections elicit CD4+ TRM cells that fill a local niche to optimize heterotypic protection of the affected tissue, preventing pneumonia.
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Hietanen S, Ala-Kokko T, Ohtonen P, Käkelä R, Niemelä S, Liisanantti JH. Treatment Profile and 1-Year Mortality Among Nontraumatic Intensive Care Unit Patients With Alcohol-Related Health Problems. J Intensive Care Med 2017; 35:244-250. [DOI: 10.1177/0885066617740071] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background: Long-term excessive use of alcohol leads to severe complications, which often require treatment in an intensive care unit (ICU). The aim of this study was to report on the associations between alcohol-related health problems and treatment profile, as well as 1-year mortality among patients with nontrauma-related ICU admissions. Methods: Information on the history of alcohol-related health problems or excessive alcohol use and ICU treatment was collected retrospectively from electronic medical records and ICU patient data management systems at Oulu University Hospital, Finland. Information on 1-year mortality was obtained from the Finnish Population Register Center. Results: According to the medical records, in a total of 899 admissions, 32.9% (n = 296) of patients had a history of alcohol-related problems. In the alcohol group, intoxications were more frequent and respiratory and cardiovascular causes were less frequent, compared to those without alcohol-related problems. Patients without alcohol-related problems had a higher rate of previous comorbidities compared with the alcohol group. There were no differences concerning age, severity of illness scores, length of stay, or intensive care outcome. Mortality during the 1-year follow-up was 32.8% in total: 35.1% among those without alcohol-related history and 28.0% in the alcohol group ( P = .041). The difference in mortality appeared during the first month following admission and remained throughout the follow-up period. The highest 1-year mortality (59.3%) was observed among patients with alcohol-related liver disease. Conclusion: Every third patient admitted to ICU used alcohol excessively or had alcohol-related diseases, and those patients with alcohol-related liver disease had the poorest 1-year survival rate. We found higher long-term mortality in nonalcohol-related admissions, which can be explained by the case mix, including a lower rate of chronic diseases, such as malignancies and coronary artery disease, and a higher rate of low-risk admission diagnoses in the alcohol group.
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Affiliation(s)
- Siiri Hietanen
- Division of Intensive Care Medicine, Department of Anesthesiology, Oulu University Hospital, Oulu, Finland
- Research Group of Surgery, Anesthesiology and Intensive Care, Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Tero Ala-Kokko
- Division of Intensive Care Medicine, Department of Anesthesiology, Oulu University Hospital, Oulu, Finland
- Research Group of Surgery, Anesthesiology and Intensive Care, Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Pasi Ohtonen
- Department of Operative Care, Oulu University Hospital, Oulu, Finland
| | - Riikka Käkelä
- Division of Intensive Care Medicine, Department of Anesthesiology, Oulu University Hospital, Oulu, Finland
- Research Group of Surgery, Anesthesiology and Intensive Care, Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Solja Niemelä
- Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland
- Department of Psychiatry, Lapland Hospital District, Rovaniemi, Finland
| | - Janne H. Liisanantti
- Division of Intensive Care Medicine, Department of Anesthesiology, Oulu University Hospital, Oulu, Finland
- Research Group of Surgery, Anesthesiology and Intensive Care, Medical Research Center Oulu, University of Oulu, Oulu, Finland
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Marrie TJ, Tyrrell GJ, Majumdar SR, Eurich DT. Invasive Pneumococcal Disease: Still Lots to Learn and a Need for Standardized Data Collection Instruments. Can Respir J 2017; 2017:2397429. [PMID: 28424565 PMCID: PMC5382326 DOI: 10.1155/2017/2397429] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 02/23/2017] [Accepted: 03/05/2017] [Indexed: 01/25/2023] Open
Abstract
Background. Large studies of invasive pneumococcal disease (IPD) are frequently lacking detailed clinical information. Methods. A population-based 15-year study of IPD in Northern Alberta. Results. 2435 patients with a mean age of 54.2 years formed the study group. Males outnumbered females and Aboriginal and homeless persons were overrepresented. High rates of smoking, excessive alcohol use, and illicit drug use were seen. Almost all (87%) had a major comorbidity and 15% had functional limitations prior to admission. Bacteremia, pneumonia, and meningitis were the most common major manifestations of IPD. Almost half of the patients had alteration of mental status at the time of admission and 22% required mechanical ventilation. Myocardial infarction, pulmonary embolism, and new onset stroke occurred in 1.7, 1.3, and 1.1% of the patients, respectively; of those who had echocardiograms, 35% had impaired ventricular function. The overall in-hospital mortality was 15.6%. Conclusions. IPD remains a serious infection in adults. In addition to immunization, preventative measures need to consider the sociodemographic features more carefully. A standard set of data need to be collected so that comparisons can be made from study to study. Future investigations should target cardiac function and pulmonary embolism prevention in this population.
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Affiliation(s)
- T. J. Marrie
- Department of Medicine, Dalhousie University, Halifax, NS, Canada
| | - G. J. Tyrrell
- The Division of Diagnostic and Applied Microbiology, Department of Laboratory Medicine and Pathology, University of Alberta and The Provincial Laboratory for Public Health, Edmonton, AB, Canada
| | - Sumit R. Majumdar
- Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Dean T. Eurich
- School of Public Health, University of Alberta, Edmonton, AB, Canada
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Bacterial meningitis in alcoholic patients: A population-based prospective study. J Infect 2017; 74:352-357. [PMID: 28065808 DOI: 10.1016/j.jinf.2017.01.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2016] [Revised: 12/07/2016] [Accepted: 01/02/2017] [Indexed: 11/23/2022]
Abstract
OBJECTIVES To study clinical features and outcome of community-acquired bacterial meningitis in alcoholic patients. METHODS Patients with a history of alcoholism were selected from our nationwide, prospective cohort on community-acquired bacterial meningitis performed from March 2006 to October 2014. Data on patient history, symptoms and signs on admission, treatment, and outcome were prospectively collected. RESULTS Of 1359 included episodes, 88 episodes (6%) occurred in 88 alcoholic patients. Seizures as presenting symptom were present in 18% alcoholic patients, and 23% presented with co-existing pneumonia. Causative organisms were Streptococcus pneumoniae in 76%, Listeria monocytogenes in 8%, and Neisseria meningitidis in 6% of patients. A high rate of systemic complications occurred with respiratory failure in 40% and endocarditis in 9% of patients. Outcome was unfavorable in 58% of alcoholic patients, and 25% died. Alcoholism was associated with unfavorable outcome in a multivariate analysis (OR 1.96; 95% CI 1.12-3.46; P = 0.019), but not with death (OR 0.76; 95% CI 0.35-1.68; P = 0.762). CONCLUSION Alcoholic bacterial meningitis patients often have an unfavorable outcome, which appears to result from a high rate of systemic complications, mainly respiratory failure. Seizures are common in alcoholic patients and warrant caution of development of an alcohol withdrawal syndrome.
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Yeligar SM, Chen MM, Kovacs EJ, Sisson JH, Burnham EL, Brown LAS. Alcohol and lung injury and immunity. Alcohol 2016; 55:51-59. [PMID: 27788778 DOI: 10.1016/j.alcohol.2016.08.005] [Citation(s) in RCA: 82] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 07/07/2016] [Accepted: 08/24/2016] [Indexed: 02/06/2023]
Abstract
Annually, excessive alcohol use accounts for more than $220 billion in economic costs and 80,000 deaths, making excessive alcohol use the third leading lifestyle-related cause of death in the US. Patients with an alcohol-use disorder (AUD) also have an increased susceptibility to respiratory pathogens and lung injury, including a 2-4-fold increased risk of acute respiratory distress syndrome (ARDS). This review investigates some of the potential mechanisms by which alcohol causes lung injury and impairs lung immunity. In intoxicated individuals with burn injuries, activation of the gut-liver axis drives pulmonary inflammation, thereby negatively impacting morbidity and mortality. In the lung, the upper airway is the first checkpoint to fail in microbe clearance during alcohol-induced lung immune dysfunction. Brief and prolonged alcohol exposure drive different post-translational modifications of novel proteins that control cilia function. Proteomic approaches are needed to identify novel alcohol targets and post-translational modifications in airway cilia that are involved in alcohol-dependent signal transduction pathways. When the upper airway fails to clear inhaled pathogens, they enter the alveolar space where they are primarily cleared by alveolar macrophages (AM). With chronic alcohol ingestion, oxidative stress pathways in the AMs are stimulated, thereby impairing AM immune capacity and pathogen clearance. The epidemiology of pneumococcal pneumonia and AUDs is well established, as both increased predisposition and illness severity have been reported. AUD subjects have increased susceptibility to pneumococcal pneumonia infections, which may be due to the pro-inflammatory response of AMs, leading to increased oxidative stress.
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Affiliation(s)
- Samantha M Yeligar
- Department of Medicine, Emory University and Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA
| | - Michael M Chen
- Burn and Shock Trauma Research Institute, Alcohol Research Program, Integrative Cell Biology Program, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA
| | - Elizabeth J Kovacs
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO 80045, USA
| | - Joseph H Sisson
- Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Ellen L Burnham
- Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA
| | - Lou Ann S Brown
- Department of Pediatrics, Emory University, Atlanta, GA 30322, USA.
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Kashiura M, Sugiyama K, Akashi A, Hamabe Y. Diverticulitis-induced pylephlebitis possibly misdiagnosed as biliary duct obstruction. Acute Med Surg 2016; 3:404-406. [PMID: 29123823 DOI: 10.1002/ams2.205] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 03/07/2016] [Indexed: 12/29/2022] Open
Abstract
Case A 59-year-old Asian man presented to our emergency department with hypogastrium pain, loss of appetite, and diarrhea. On admission, he was hypotensive and jaundiced. Laboratory test results revealed thrombocytopenia, hypercreatininemia, and hyperbilirubinemia. Color Doppler sonography showed no blood flow in the right and left branches of the portal vein, which seemed similar to biliary obstruction. Enhanced computed tomography showed portal vein thrombi, consistent with pylephlebitis; a broad-spectrum antibiotic and an anticoagulant were administered. Outcome The patient died of multiple organ failure 22 h post-admission. An autopsy revealed suppurative thrombi in the portal vein, multiple liver abscesses, and diverticulitis in the sigmoid colon. Conclusion Pylephlebitis, a rare complication of intra-abdominal infections, is associated with high rates of morbidity and mortality. Ultrasonography findings mimic those of biliary obstruction. Enhanced computed tomography is useful for diagnosing this condition.
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Affiliation(s)
- Masahiro Kashiura
- Tertiary Emergency Medical Center Tokyo Metropolitan Bokutoh Hospital Sumida-ku Tokyo Japan
| | - Kazuhiro Sugiyama
- Tertiary Emergency Medical Center Tokyo Metropolitan Bokutoh Hospital Sumida-ku Tokyo Japan
| | - Akiko Akashi
- Tertiary Emergency Medical Center Tokyo Metropolitan Bokutoh Hospital Sumida-ku Tokyo Japan
| | - Yuichi Hamabe
- Tertiary Emergency Medical Center Tokyo Metropolitan Bokutoh Hospital Sumida-ku Tokyo Japan
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Holter JC, Ueland T, Jenum PA, Müller F, Brunborg C, Frøland SS, Aukrust P, Husebye E, Heggelund L. Risk Factors for Long-Term Mortality after Hospitalization for Community-Acquired Pneumonia: A 5-Year Prospective Follow-Up Study. PLoS One 2016; 11:e0148741. [PMID: 26849359 PMCID: PMC4746118 DOI: 10.1371/journal.pone.0148741] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 01/22/2016] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Contributors to long-term mortality in patients with community-acquired pneumonia (CAP) remain unclear, with little attention paid to pneumonia etiology. We examined long-term survival, causes of death, and risk factors for long-term mortality in adult patients who had been hospitalized for CAP, with emphasis on demographic, clinical, laboratory, and microbiological characteristics. METHODS Two hundred and sixty-seven consecutive patients admitted in 2008-2011 to a general hospital with CAP were prospectively recruited and followed up. Patients who died during hospital stay were excluded. Demographic, clinical, and laboratory data were collected within 48 hours of admission. Extensive microbiological work-up was performed to establish the etiology of CAP in 63% of patients. Mortality data were obtained from the Norwegian Cause of Death Registry. Cox regression models were used to identify independent risk factors for all-cause mortality. RESULTS Of 259 hospital survivors of CAP (median age 66 years), 79 (30.5%) died over a median of 1,804 days (range 1-2,520 days). Cumulative 5-year survival rate was 72.9% (95% CI 67.4-78.4%). Standardized mortality ratio was 2.90 for men and 2.05 for women. The main causes of death were chronic obstructive pulmonary disease (COPD), vascular diseases, and malignancy. Independent risk factors for death were the following (hazard ratio, 95% CI): age (1.83 per decade, 1.47-2.28), cardiovascular disease (2.63, 1.61-4.32), COPD (2.09, 1.27-3.45), immunocompromization (1.98, 1.17-3.37), and low serum albumin level at admission (0.75 per 5 g/L higher, 0.58-0.96), whereas active smoking was protective (0.32, 0.14-0.74); active smokers were younger than non-smokers (P < 0.001). Microbial etiology did not predict mortality. CONCLUSIONS Results largely confirm substantial comorbidity-related 5-year mortality after hospitalization for CAP and the impact of several well-known risk factors for death, and extend previous findings on the prognostic value of serum albumin level at hospital admission. Pneumonia etiology had no prognostic value, but this remains to be substantiated by further studies using extensive diagnostic microbiological methods in the identification of causative agents of CAP.
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Affiliation(s)
- Jan C. Holter
- Department of Internal Medicine, Drammen Hospital, Vestre Viken Health Trust, Drammen, Norway
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- * E-mail:
| | - Thor Ueland
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway
| | - Pål A. Jenum
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Medical Microbiology, Drammen Hospital, Vestre Viken Health Trust, Drammen, Norway
| | - Fredrik Müller
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Microbiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Cathrine Brunborg
- Oslo Center of Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway
| | - Stig S. Frøland
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway
- Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Einar Husebye
- Department of Internal Medicine, Drammen Hospital, Vestre Viken Health Trust, Drammen, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Lars Heggelund
- Department of Internal Medicine, Drammen Hospital, Vestre Viken Health Trust, Drammen, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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