Pretreatment with adalimumab reduces ventilator-induced lung injury in an
            experimental model

Correger, Enrique; Marcos, Josefina; Laguens, Graciela; Stringa, Pablo; Cardinal-Fernández, Pablo; Blanch, Lluís

doi:10.5935/0103-507x.20200010

Cited by 8 publications

(3 citation statements)

References 29 publications

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“…Prolonged mechanical ventilation is necessary for patients that develop severe disease symptoms, but can cause secondary lung injuries in some cases, leading to complications such as edema, pulmonary inflammation and abnormal surfactant function, decreasing lung compliance and reducing gas exchange 19 . In the recovery phase, patients may experience residual lung damage, such as parenchymal consolidation, in which the alveolar walls develop fibrosis due to parenchymal repair processes, directly affecting respiratory function 1 , 19 , 20 .…”

Section: Factors That Influence Functional Capacity After Covid-19mentioning

confidence: 99%

Functional capacity and rehabilitation strategies in Covid-19 patients: current knowledge and challenges

Frota

Vieira

Soares

et al. 2021

Rev. Soc. Bras. Med. Trop.

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Covid-19 is a novel infectious disease whose spectrum of presentation ranges from absence of symptoms to widespread interstitial pneumonia associated with severe acute respiratory syndrome (SARS), leading to significant mortality. Given the systemic pattern of Covid-19, there are many factors that can influence patient's functional capacity after acute infection and the identification of such factors can contribute to the development of specific rehabilitation strategies. Pulmonary impairment is the primary cause of hospitalization due to Covid-19, and can progress to SARS as well as increase length of hospitalization. Moreover, cardiac involvement is observed in approximately 30% of hospitalized patients, with an increased risk of acute myocarditis, myocardial injury, and heart failure, which may compromise functional capacity in the long-term. Thromboembolic complications have also been reported in some patients with Covid-19 and are associated with a poor prognosis. Musculoskeletal complications may result from long periods of hospitalization and immobility, and can include fatigue, muscle weakness and polyneuropathy. Studies that address the functional capacity of patients after Covid-19 infection are still scarce. However, based on knowledge from the multiple systemic complications associated with Covid-19, it is reasonable to suggest that most patients, especially those who underwent prolonged hospitalization, will need a multiprofessional rehabilitation program. Further studies are needed to evaluate the functional impact and the rehabilitation strategies for patients affected by Covid-19.

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Section: Factors That Influence Functional Capacity After Covid-19mentioning

confidence: 99%

Functional capacity and rehabilitation strategies in Covid-19 patients: current knowledge and challenges

Frota

Vieira

Soares

et al. 2021

Rev. Soc. Bras. Med. Trop.

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“…Typical histological evidence of ALI assesses neutrophilic infiltration of the interstitium and the alveolar space, formation of hyaline membranes and edema of the alveolar walls. These histological findings are summarized in the lung injury score initially introduced by Matute-Bello et al [ 17 ] Most investigators use an adapted form of the score [ 18 – 20 ]. Since the evidence of hemorrhage is regarded as a somewhat relevant feature we included it in the adapted histological score.…”

Section: Discussionmentioning

confidence: 99%

Unilateral acute lung injury in pig: a promising animal model

et al. 2022

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Background Acute lung injury (ALI) occurs in 23% unilateral. Models of unilateral ALI were developed and used previously without clearly demonstrating the strictly unilateral nature and severity of lung injury by the key parameters characterizing ALI as defined by the American Thoracic Society (ATS). Thus, the use of unilateral ALI remained rare despite the innovative approach. Therefore, we developed a unilateral model of ALI and focused on the crucial parameters characterizing ALI. This model can serve for direct comparisons between the injured and intact lungs within single animals, thus, reducing the number of animals required for valid experimental conclusions. Methods We established the model in nine pigs, followed by an evaluation of key parameters in six pigs (main study). Pigs were ventilated using an adapted left double-lumen tube for lung separation and two ventilators. ALI was induced in the left lung with cyclic rinsing (NaCl 0.9% + Triton® X-100), after which pigs were ventilated for different time spans to test for the timing of ALI onset. Ventilatory and metabolic parameters were evaluated, and bronchoalveolar lavage (BAL) was performed for measurements of inflammatory mediators. Finally, histopathological specimens were collected and examined in respect of characteristics defining the lung injury score (LIS) as suggested by the ATS. Results After adjustments of the model (n = 9) we were able to induce strictly left unilateral ALI in all six pigs of the evaluation study. The median lung injury score was 0.72 (IQR 0.62–0.79) in the left lung vs 0.14 (IQR 0.14–0.16; p < 0.05) in the right lung, confirming unilateral ALI. A significant and sustained drop in pulmonary compliance (Cdyn) of the left lung occurred immediately, whereas Cdyn of the right lung remained unchanged (p < 0.05). BAL fluid concentrations of interleukin-6 and -8 were increased in both lungs. Conclusions We established a model of unilateral ALI in pigs, confirmed by histopathology, and typical changes in respiratory mechanics and an inflammatory response. This thoroughly evaluated model could serve as a basis for future studies and for comparing pathophysiological and pharmacological changes in the uninjured and injured lung within the same animal.

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“…Although it is used to modify inflammatory responses in rheumatic diseases such as rheumatoid arthritis and ankylosing spondylitis [8], and inflammatory bowel diseases such as Crohn's disease [9], increasing evidence now shows the efficacy of adalimumab in more pathological conditions. Adalimumab, ameliorates cognitive impairment by attenuating neuroinflammation in the mouse model of Alzheimer's disease [10], reduces methotrexate-induced organ toxicity with toxic side effects on tissues and organs [11], limits the production of proinflammatory cytokines in the experimental animal model of acute lung injury, and improves tissue inflammation [12], prevents cognitive impairment and neuroinflammation caused by chronic cerebral hypoperfusion [13], reduces pulmonary edema and histological damage due to mechanical ventilation [14], alleviates endotoxininduced cardiac damage by modulating cytokine secretion [15], protective effect by reducing blood sugar and cytokine secretion in obese diabetic rats [16], prevents lipid peroxidation caused by spinal cord trauma in rats [17]. It contributes to the regulation of cognitive and emotional processes in response to antiinflammatory therapy with adalimumab in patients suffering from inflammatory bowel disease [18].…”

Section: Introductionmentioning

confidence: 99%

The Antinociceptive Effect of Adalimumab, a TNF-Alpha Inhibitor, in a Mice Model of Inflammatory Pain

ÖZ>

Şimşek

2022

Türk Doğa Ve Fen Dergisi

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The aim of this study, evaluate the nociceptive effect of adalimumab, a TNF-alpha inhibitor, on formalin-induced inflammatory pain in mice. The antinociceptive activity of adalimumab was determined on adult male BALB-C mice (6 mice in each group) by a formalin-induced inflammatory pain model and hot plate test applied. Diclofenac, which we used as a positive control, showed anti-nociceptive activity in both phases of the formalin test. The effect of the hot plate test at the thirtieth minute was statistically significantly different. Adalimumab was not effective in the neuronal phase of the formalin test but showed an antinociceptive effect in the inflammatory phase. Changes due to adalimumab in the hot plate test did not reach statistical significance. The findings of this study showed that adalimumab, which we applied as a single dose, had antinociceptive activity in the inflammatory phase of the formalin test. This result indicated that the peripheral analgesic effect of adalimumab is stronger.

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Pretreatment with adalimumab reduces ventilator-induced lung injury in an experimental model

Cited by 8 publications

References 29 publications

Functional capacity and rehabilitation strategies in Covid-19 patients: current knowledge and challenges

Functional capacity and rehabilitation strategies in Covid-19 patients: current knowledge and challenges

Unilateral acute lung injury in pig: a promising animal model

The Antinociceptive Effect of Adalimumab, a TNF-Alpha Inhibitor, in a Mice Model of Inflammatory Pain

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