Contrasting Inflammatory Responses in Severe and Non-severe Community-acquired Pneumonia

Fernández-Botrán, Rafael; Uriarte, Silvia M.; Arnold, Forest W.; Rodriguez-Hernandez, Lisandra; Rane, Madhavi J.; Peyrani, Paula; Wiemken, Timothy; Kelley, Robert; Uppatla, Srinivas; Cavallazzi, Rodrigo; Blasi, Francesco; Morlacchi, Letizia Corinna; Aliberti, Stefano; Jonsson, Colleen B.; Ramirez, Julio A.; Bordón, José

doi:10.1007/s10753-014-9840-2

Cited by 55 publications

(62 citation statements)

References 29 publications

(41 reference statements)

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“…The two phases of our experiment allowed us to compare the differences in cytokines, chemokines, and organ involvement during the systemic inflammatory response with and without antibiotic therapy [36]. All of these data suggest that the inflammatory response observed in our experimental pneumonia baboon model translates to findings observed in humans [36–39]. …”

Section: Discussionmentioning

confidence: 96%

A Non-Human Primate Model of Severe Pneumococcal Pneumonia

Reyes¹,

Restrepo²,

Hinojosa³

et al. 2016

PLoS ONE

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RationaleStreptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia.ObjectiveTo develop a non-human primate model of pneumococcal pneumonia.MethodsSeven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily.ResultsChallenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines.ConclusionsWe have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes.

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Section: Discussionmentioning

confidence: 96%

A Non-Human Primate Model of Severe Pneumococcal Pneumonia

Reyes¹,

Restrepo²,

Hinojosa³

et al. 2016

PLoS ONE

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“…Evidence from the sepsis [30][31][32][33][34], ARDS [7,35,36], and trauma [37,38] literature suggests that degree of elevation in inflammatory cytokines (e.g., TNF, IL-1β, IL-6) on ICU admission and during ICU stay correlates with disease severity and hospital mortality, and that persistent elevation of cytokines at hospital discharge is associated with adverse long-term outcomes [39].…”

Section: Dysfunction Of the Hpa Axis During Critical Illnessmentioning

confidence: 99%

“…In non-ICU patients, even after a few days of glucocorticoid treatment, removal without tapering leads to adrenal suppression (measured with corticotropin test) in 45% of patients with gradual recovery over a period of 14 days [62]. Ample experimental and clinical evidence [29][30][31][32][33][34][35][36] shows that premature discontinuation of glucocorticoids in patients with severe sepsis or ARDS frequently (25-40%) leads to rebound systemic inflammation and clinical relapse (hemodynamic deterioration, recrudescence of ARDS, or worsening multiple organ dysfunction). Experimental animal sepsis models have demonstrated an early marked increase in ACTH levels that returns to baseline values at around 72 h [63].…”

Section: Altered Crh/acth Synthesismentioning

confidence: 99%

Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)

et al. 2017

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“…Patients with severe CAP had higher levels of inflammatory cytokines in the blood but lower levels of inflammatory cytokines in the sputum as compared with patients with nonsevere CAP. 19 The presence of chronic local inflammation could have a protective effect against pathogen growth in the lung although this is hypothetical and one could also argue that chronic lung inflammation may lead to immune-senescence with detrimental effects. Third, perhaps the diagnosis of COPD prompts physicians to take a more proactive approach in this group of patients with CAP.…”

Section: Discussionmentioning

confidence: 99%

The presence of COPD does not influence clinical outcomes in hospitalized patients with community-acquired pneumonia.

Silva¹,

Gearhart²,

Maciel³

et al. 2017

JRI

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Introduction: Community acquired pneumonia (CAP) is a leading cause of death worldwide. Chronic obstructive pulmonary disease (COPD) is a well-established risk factor for development of CAP. What is not as clear is the impact of COPD on the outcomes of patients with CAP. In this study, we compared the outcomes of CAP in COPD and non-COPD patients. Methods: This was a retrospective cohort study. We conducted an analysis of the CommunityAcquired Pneumonia Organization (CAPO) international cohort study database, which includes patients with CAP admitted to several hospitals throughout the world. Patients were categorized into two groups based on the status of COPD: COPD positive or negative. Outcomes were time to clinical stability, length of hospital stay, and in-hospital mortality. Regression models were used to assess the independent effect of COPD on the outcomes. Results: This study included 7,325 patients. Of these, 1,869 (25.5%) had COPD. Patients with COPD had higher severity of illness (pneumonia severity index class V: 15% vs 9%; P <0.001). Accelerated failure time models with adjustment for co-variates showed no significant difference in the probability of clinical stability (P = 0.451) and of discharge (P = 0.232) in COPD vs. non-COPD patients. There was no difference in the crude in-hospital mortality between COPD and non-COPD patients (9% vs 9%; P = 0.37). Conclusion: Our study results show that COPD should not be considered a risk factor for poor outcomes in hospitalized patients with CAP.

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Contrasting Inflammatory Responses in Severe and Non-severe Community-acquired Pneumonia

Cited by 55 publications

References 29 publications

A Non-Human Primate Model of Severe Pneumococcal Pneumonia

A Non-Human Primate Model of Severe Pneumococcal Pneumonia

Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)

The presence of COPD does not influence clinical outcomes in hospitalized patients with community-acquired pneumonia.

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