Dataset Information

Macrophage PPAR-? suppresses long-term lung fibrotic sequelae following acute influenza infection.

ABSTRACT: Influenza virus causes a heterogeneous respiratory infectious disease ranging from self-limiting symptoms to non-resolving pathology in the lungs. Worldwide, seasonal influenza infections claim ~500,000 lives annually. Recent reports describe pathologic pulmonary sequelae that result in remodeling the architecture of lung parenchyma following respiratory infections. These dysfunctional recovery processes that disproportionately impact the elderly have been understudied. Macrophages are involved in tissue remodeling and are critical for survival of severe influenza infection. Here, we found intrinsic deficiency of the nuclear receptor PPAR-? in myeloid cells delayed the resolution of pulmonary inflammation following influenza infection. Mice with myeloid cell-specific PPAR-? deficiency subsequently presented with increased influenza-induced deposition of pulmonary collagen compared to control mice. This dysfunctional lung remodeling was progressive and sustained for at least 3 months following infection of mice with myeloid PPAR-? deficiency. These progressive changes were accompanied by a pro-fibrotic gene signature from lung macrophages and preceded by deficiencies in activation of genes involved with damage repair. Importantly similar aberrant gene expression patterns were also found in a secondary analysis of a study where macrophages were isolated from patients with fibrotic interstitial lung disease. Quite unexpectedly, mice with PPAR-? deficient macrophages were more resistant to bleomycin-induced weight loss whereas extracellular matrix deposition was unaffected compared to controls. Therefore PPAR-? expression in macrophages may be a pathogen-specific limiter of organ recovery rather than a ubiquitous effector pathway in response to generic damage.

SUBMITTER: Huang S

PROVIDER: S-EPMC6777801 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Macrophage PPAR-γ suppresses long-term lung fibrotic sequelae following acute influenza infection.

Huang Su S Goplen Nick P NP Zhu Bibo B Cheon In Su IS Son Youngmin Y Wang Zheng Z Li Chaofan C Dai Qigang Q Jiang Li L Xiang Min M Carmona Eva M EM Vassallo Robert R Limper Andrew H AH Sun Jie J

PloS one 20191004 10

Influenza virus causes a heterogeneous respiratory infectious disease ranging from self-limiting symptoms to non-resolving pathology in the lungs. Worldwide, seasonal influenza infections claim ~500,000 lives annually. Recent reports describe pathologic pulmonary sequelae that result in remodeling the architecture of lung parenchyma following respiratory infections. These dysfunctional recovery processes that disproportionately impact the elderly have been understudied. Macrophages are involved ...[more]

PMID: 31584978

Similar Datasets

Project description:ImportanceInfluenza has been associated with the risk of developing Parkinson disease, but the association is controversial.ObjectiveTo examine whether prior influenza and other infections are associated with Parkinson disease more than 10 years after infection.Design, setting, and participantsThis case-control study used data from 1977 to 2016 from the Danish National Patient Registry. All individuals with Parkinson disease, excluding those with drug-induced parkinsonism, were included and matched to 5 population controls on sex, age, and date of Parkinson diagnosis. Data were analyzed from December 2019 to September 2021.ExposuresInfections were ascertained between 1977 and 2016 and categorized by time from infection to Parkinson disease diagnosis. To increase specificity of influenza diagnoses, influenza exposure was restricted to months of peak influenza activity.Main outcomes and measuresParkinson disease diagnoses were identified between January 1, 2000, and December 31, 2016. Crude and adjusted odds ratios (ORs) and 95% CIs were calculated by conditional logistic regression overall and stratified by time between infection and Parkinson disease (5 years or less, more than 5 to 10 years, more than 10 years).ResultsOf 61 626 included individuals, 23 826 (38.7%) were female, and 53 202 (86.3%) were older than 60 years. A total of 10 271 individuals with Parkinson disease and 51 355 controls were identified. Influenza diagnosed at any time during a calendar year was associated with Parkinson disease more than 10 years later (OR, 1.73; 95% CI, 1.11-2.71). When influenza exposure was restricted to months of highest influenza activity, an elevated OR with a wider confidence interval was found (OR, 1.52; 95% CI, 0.80-2.89). There was no evidence of an association with any type of infection more than 10 years prior to Parkinson disease (OR, 1.04; 95% CI, 0.98-1.10). Several specific infections yielded increased odds of Parkinson disease within 5 years of infection, but results were null when exposure occurred more than 10 years prior.Conclusions and relevanceIn this case-control study, influenza was associated with diagnoses of Parkinson disease more than 10 years after infection. These observational data suggest a link between influenza and Parkinson disease but do not demonstrate causality. While other infections were associated with Parkinson disease diagnoses soon after infection, null associations after more than 10 years suggest these shorter-term associations are not causal.

Project description:ObjectiveTo determine acute and long-term clinical, neuropsychological, and return-to-work (RTW) effects of electrical injuries (EIs). This study aims to further contrast sequelae between low-voltage and high-voltage injuries (LVIs and HVIs). We hypothesise that all EIs will result in substantial adverse effects during both phases of management, with HVIs contributing to greater rates of sequelae.DesignRetrospective cohort study evaluating EI admissions between 1998 and 2015.SettingProvincial burn centre and rehabilitation hospital specialising in EI management.ParticipantsAll EI admissions were reviewed for acute clinical outcomes (n=207). For long-term outcomes, rehabilitation patients, who were referred from the burn centre (n=63) or other burn units across the province (n=65), were screened for inclusion. Six patients were excluded due to pre-existing psychiatric conditions. This cohort (n=122) was assessed for long-term outcomes. Median time to first and last follow-up were 201 (68-766) and 980 (391-1409) days, respectively.Outcome measuresAcute and long-term clinical, neuropsychological and RTW sequelae.ResultsAcute clinical complications included infections (14%) and amputations (13%). HVIs resulted in greater rates of these complications, including compartment syndrome (16% vs 4%, p=0.007) and rhabdomyolysis (12% vs 0%, p<0.001). Rates of acute neuropsychological sequelae were similar between voltage groups. Long-term outcomes were dominated by insomnia (68%), anxiety (62%), post-traumatic stress disorder (33%) and major depressive disorder (25%). Sleep difficulties (67%) were common following HVIs, while the LVI group most frequently experienced sleep difficulties (70%) and anxiety (70%). Ninety work-related EIs were available for RTW analysis. Sixty-one per cent returned to their preinjury employment and 19% were unable to return to any form of work. RTW rates were similar when compared between voltage groups.ConclusionsThis is the first investigation to determine acute and long-term patient outcomes post-EI as a continuum. Findings highlight substantial rates of neuropsychological and social sequelae, regardless of voltage. Specialised and individualised early interventions, including screening for mental health concerns, are imperative to improvingoutcomes of EI patients.

Project description:BackgroundFew studies have directly compared the risk and magnitude of post-acute sequelae following COVID-19 and influenza, and most of these studies were conducted before emergence of the Omicron. This study investigated the prevalence of post-COVID conditions and the long-term risk of emergency department (ED) visits, hospitalizations, and deaths in patients with COVID-19 and compared their risk with that of patients with influenza.MethodsA retrospective study based on the TriNetX databases, a global health research network. We identified patients with COVID-19 and influenza who required hospitalization between January 1, 2022, and January 1, 2023. We compared the risk of developing any post-COVID conditions between the two groups and also analyzed each post-COVID-19 condition and all-cause ED visits, hospitalizations, and deaths in both populations during the follow-up 90-180 days.ResultsBefore matching, 7,187 patients with COVID-19 were older (63.9 ± 16.7 vs. 55.4 ± 21.2) and were predominantly male (54.0% vs. 45.4%), and overweight/obese (16.1% vs. 11.2%) than 11,266 individuals with influenza. After propensity score matching, 6,614 patients were identified in each group, resulting in well-balanced baseline characteristics. During follow-up, the COVID-19 group had a higher incidence of any post-COVID-19 condition when compared with the influenza group (17.9% vs. 13.0%), with a hazard ratio (HR) of 1.398 (95% CI, 1.251-1.562). Compared to the influenza group, the COVID-19 group had a significantly higher incidence of abnormal breathing (HR, 1.506; 95% CI, 1.246-1.822), abdominal symptoms (HR, 1.313; HR, 1.034-1.664), fatigue (HR, 1.486; 95% CI, 1.158-1.907), and cognitive symptoms (HR, 1.815; 95% CI, 1.235-2.668). Moreover, the COVID-19 group had a significantly higher risk of the composite outcomes during all-cause ED visits, hospitalizations, and deaths when compared with the influenza group (27.5% vs. 21.7; HR, 1.303; 95% CI, 1.194-1.422).ConclusionsThis study indicates that hospitalized COVID-19 patients are at a higher risk of long-term complications when compared with influenza survivors.

Project description:Critical neurologic disease and injury affect thousands of children annually with survivors suffering high rates of chronic morbidities related directly to the illness and to critical care hospitalization. Postintensive care syndrome (PICS) in patients and families encompasses a variety of morbidities including physical, cognitive, emotional, and psychological impairments following critical care. We conducted a focus group study with parents of children surviving pediatric neurocritical care (PNCC) for traumatic brain injury, stroke, meningitis, or encephalitis to determine outcomes important to patients and families, identify barriers to care, and identify potential interventions to improve outcomes. Sixteen parents participated in four groups across Oregon. Three global themes were identified: (1) PNCC is an intense emotional experience for the whole family; (2) PNCC survivorship is a chronic illness; and (3) PNCC has a significant psychological and social impact. Survivors and their families suffer physical, emotional, psychological, cognitive, and social impairments for many years after discharge. Parents in this study highlighted the emotional and psychological distress in survivors and families after PNCC, in contrast to most PNCC research focusing on physical outcomes. Several barriers to care were identified with potential implications on survivor outcomes, including limited pediatric resources in rural settings, perceived lack of awareness of PICS among medical providers, and the substantial financial burden on families. Parents desire improved education surrounding PICS morbidities for families and medical providers, improved communication with primary care providers after discharge, access to educational materials for patients and families, direction to mental health providers, and family support groups to assist them in dealing with morbidities and accessing appropriate resources. Clinicians and researchers should consider the parent perspectives reported here when caring for and evaluating outcomes for children requiring PNCC.

Project description:Subjects recovering from COVID-19 frequently experience persistent respiratory ailments; however, little is known about the underlying biological factors that may direct lung recovery and the extent to which these are affected by COVID-19 severity. We performed a prospective cohort study of subjects with persistent symptoms after acute COVID-19, collecting clinical data, pulmonary function tests, and plasma samples used for multiplex profiling of inflammatory, metabolic, angiogenic, and fibrotic factors. Sixty-one subjects were enrolled across two academic medical centers at a median of 9 weeks (interquartile range 6-10) after COVID-19 illness: n=13 subjects (21%) mild/non-hospitalized, n=30 (49%) hospitalized/non-critical, and n=18 subjects (30%) hospitalized/intensive care ("ICU"). Fifty-three subjects (85%) had lingering symptoms, most commonly dyspnea (69%) and cough (58%). Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and diffusing capacity for carbon monoxide (DLCO) declined as COVID-19 severity increased (P<0.05), but did not correlate with respiratory symptoms. Partial least-squares discriminant analysis of plasma biomarker profiles clustered subjects by past COVID-19 severity. Lipocalin 2 (LCN2), matrix metalloproteinase-7 (MMP-7), and hepatocyte growth factor (HGF) identified by the model were significantly higher in the ICU group (P<0.05) and inversely correlated with FVC and DLCO (P<0.05), and were confirmed in a separate validation cohort (n=53). Subjective respiratory symptoms are common after acute COVID-19 illness but do not correlate with COVID-19 severity or pulmonary function. Host response profiles reflecting neutrophil activation (LCN2), fibrosis signaling (MMP-7), and alveolar repair (HGF) track with lung impairment and may be novel therapeutic or prognostic targets. The study was funded in part by the NHLBI (K08HL130557 to BDK and R01HL142818 to HJC), the DeLuca Foundation Award (AP), a donation from Jack Levin to the Benign Hematology Program at Yale, and Divisional/Departmental funds from Duke University.

Dataset Information

Macrophage PPAR-? suppresses long-term lung fibrotic sequelae following acute influenza infection.

Publications

Macrophage PPAR-γ suppresses long-term lung fibrotic sequelae following acute influenza infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets