Clinical characteristics and outcomes in hospitalized adult influenza patients: an observational study from Norway 2014–2018

Wæhre, Torgun; Tunheim, Gro; Bodin, Johanna; Laake, Ida; Kvale, Dag; Kran, Anne-Marte Bakken; Brekke, Hanne; Løken, Ragnhild; Oftung, Fredrik; Mjaaland, Siri; Dyrhol-Riise, Anne Margarita

doi:10.1080/23744235.2021.2022196

Cited by 4 publications

(5 citation statements)

References 39 publications

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“…And it was estimated that an annual average of 88,100 influenza-associated respiratory deaths occurred in China [3]. Studies found that influenza viruses A-(H3N2-) associated hospitalizations and mortality were the highest among other circulating viruses [4][5][6], because it was easier to progress to severe pneumonia with bilateral pulmonary infiltrates, even consolidation (i.e., "white lung" in imageology), and cause ALI/ARDS [1,3]. Therefore, the further study on cellular and molecular mechanisms of influenzaassociated ALI/ARDS remains urgently needed for more efficient agents and therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

“…Particularly, seasonal influenza-induced ALI/ARDS increasingly contributes to annual global mortality. Recent studies indicated that seasonal influenza epidemics annually affected 10–30% of the human population and cause 3-5 million severe cases and approximately 290,000-650,000 deaths worldwide especially among the elderly with chronic diseases [ 1 , 2 ]. And it was estimated that an annual average of 88,100 influenza-associated respiratory deaths occurred in China [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Melatonin Suppresses Macrophage M1 Polarization and ROS-Mediated Pyroptosis via Activating ApoE/LDLR Pathway in Influenza A-Induced Acute Lung Injury

Kang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Influenza virus infection is one of the strongest pathogenic factors for the development of acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS). However, the underlying cellular and molecular mechanisms have not been clarified. In this study, we aim to investigate whether melatonin modulates macrophage polarization, oxidative stress, and pyroptosis via activating Apolipoprotein E/low-density lipoprotein receptor (ApoE/LDLR) pathway in influenza A-induced ALI. Here, wild-type (WT) and ApoE-/- mice were instilled intratracheally with influenza A (H3N2) and injected intraperitoneally with melatonin for 7 consecutive days. In vitro, WT and ApoE-/- murine bone marrow-derived macrophages (BMDMs) were pretreated with melatonin before H3N2 stimulation. The results showed that melatonin administration significantly attenuated H3N2-induced pulmonary damage, leukocyte infiltration, and edema; decreased the expression of proinflammatory M1 markers; enhanced anti-inflammatory M2 markers; and switched the polarization of alveolar macrophages (AMs) from M1 to M2 phenotype. Additionally, melatonin inhibited reactive oxygen species- (ROS-) mediated pyroptosis shown by downregulation of malonaldehyde (MDA) and ROS levels as well as inhibition of the NLRP3/GSDMD pathway and lactate dehydrogenase (LDH) release. Strikingly, the ApoE/LDLR pathway was activated when melatonin was applied in H3N2-infected macrophages and mice. ApoE knockout mostly abrogated the protective impacts of melatonin on H3N2-induced ALI and its regulatory ability on macrophage polarization, oxidative stress, and pyroptosis. Furthermore, recombinant ApoE3 (re-ApoE3) inhibited H3N2-induced M1 polarization of BMDMs with upregulation of MT1 and MT2 expression, but re-ApoE2 and re-ApoE4 failed to do this. Melatonin combined with re-ApoE3 played more beneficial protective effects on modulating macrophage polarization, oxidative stress, and pyroptosis in H3N2-infected ApoE-/- BMDMs. Our study indicated that melatonin attenuated influenza A- (H3N2-) induced ALI by inhibiting the M1 polarization of pulmonary macrophages and ROS-mediated pyroptosis via activating the ApoE/LDLR pathway. This study suggested that melatonin-ApoE/LDLR axis may serve as a novel therapeutic strategy for influenza virus-induced ALI.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Melatonin Suppresses Macrophage M1 Polarization and ROS-Mediated Pyroptosis via Activating ApoE/LDLR Pathway in Influenza A-Induced Acute Lung Injury

Kang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…In the Northern hemisphere, the excess wintertime mortality was largely explained by influenza before the COVID-19 pandemic [32]. In the subset of patients hospitalized with or for influenza, a significant increase of mortality is also reported with age [33][34][35], 70-80% of in-hospital influenza-related deaths being reported among older adults in Western Europe [3 && ,34]. Risk factors for influenza-related mortality in the elderly are age and comorbidities (including immunosuppression, chronic cardiovascular and liver diseases) [33,36].…”

Section: Mortalitymentioning

confidence: 99%

Burden of influenza in the elderly: a narrative review

Conrad

Valour

Vanhems

2023

Current Opinion in Infectious Diseases

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Purpose of review This review provides an update on specificities of influenza in older adults (≥65-year-old), including epidemiology, burden in terms of hospitalization and mortality, extra-respiratory complications and specific challenges of prevention. Recent findings In the past 2 years, influenza activity was drastically reduced by barrier measures implemented during the COVID-19 pandemic. A recent French epidemiological study covering 2010–2018 epidemic seasons estimated that 75% of costs induced by influenza-associated hospitalizations and complications were attributable to older adults, a population bearing more than 90% of influenza-associated excess mortality. In addition to their age, comorbidities and reduced vaccine response, long-term facility residents are at risk for nosocomial outbreaks. Beyond respiratory complications, influenza triggers acute myocardial infarction and ischemic stroke. Influenza might drive significant functional loss in frail older adults, which can lead to “catastrophic” or severe disability in up to 10% of patients. Vaccination remains the cornerstone of prevention, with enhanced immunization strategies (i.e., high-dose or adjuvanted formulations) to be largely implemented in older adults. Efforts to increase influenza vaccination uptake during the COVID-19 pandemic should be consolidated. Summary Burden of influenza in the elderly is largely under-recognized, especially the cardiovascular complications and the impact on functional status, justifying more effective preventive strategies.

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“…Infectious respiratory diseases caused by influenza virus, respiratory syncytial virus, and SARS-CoV-2 can cause significant illness and are responsible for hundreds of thousands of hospitalizations in the United States annually. 1 Data on in-hospital progression of disease and treatment course are broadly available and used to evaluate severity of illness, 2,3 or the impact of vaccination 4,5 and treatment. [6][7][8] However, the primary cause of admission, particularly in those with baseline multimorbidity, might be due to causes either exacerbated by milder respiratory tract infection (e.g., asthma) or possibly unrelated to infection (e.g., dehydration) rather than acute illness.…”

Section: Introductionmentioning

confidence: 99%

K‐medoids clustering of hospital admission characteristics to classify severity of influenza virus infection

Leis

McSpadden

Segaloff

et al. 2023

Influenza Resp Viruses

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Background Patients are admitted to the hospital for respiratory illness at different stages of their disease course. It is important to appropriately analyse this heterogeneity in surveillance data to accurately measure disease severity among those hospitalized. The purpose of this study was to determine if unique baseline clusters of influenza patients exist and to examine the association between cluster membership and in‐hospital outcomes. Methods Patients hospitalized with influenza at two hospitals in Southeast Michigan during the 2017/2018 (n = 242) and 2018/2019 (n = 115) influenza seasons were included. Physiologic and laboratory variables were collected for the first 24 h of the hospital stay. K‐medoids clustering was used to determine groups of individuals based on these values. Multivariable linear regression or Firth's logistic regression were used to examine the association between cluster membership and clinical outcomes. Results Three clusters were selected for 2017/2018, mainly differentiated by blood glucose level. After adjustment, those in C171 had 5.6 times the odds of mechanical ventilator use than those in C172 (95% CI: 1.49, 21.1) and a significantly longer mean hospital length of stay than those in both C172 (mean 1.5 days longer, 95% CI: 0.2, 2.7) and C173 (mean 1.4 days longer, 95% CI: 0.3, 2.5). Similar results were seen between the two clusters selected for 2018/2019. Conclusion In this study of hospitalized influenza patients, we show that distinct clusters with higher disease acuity can be identified and could be targeted for evaluations of vaccine and influenza antiviral effectiveness against disease attenuation. The association of higher disease acuity with glucose level merits evaluation.

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Clinical characteristics and outcomes in hospitalized adult influenza patients: an observational study from Norway 2014–2018

Cited by 4 publications

References 39 publications

Melatonin Suppresses Macrophage M1 Polarization and ROS-Mediated Pyroptosis via Activating ApoE/LDLR Pathway in Influenza A-Induced Acute Lung Injury

Melatonin Suppresses Macrophage M1 Polarization and ROS-Mediated Pyroptosis via Activating ApoE/LDLR Pathway in Influenza A-Induced Acute Lung Injury

Burden of influenza in the elderly: a narrative review

K‐medoids clustering of hospital admission characteristics to classify severity of influenza virus infection

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