Pathogenesis of pleural infection: <scp>A</scp> complex warfare

Popowicz, Natalia; Idell, Steven; Lee, Gary

doi:10.1111/resp.13171

Cited by 5 publications

(5 citation statements)

References 15 publications

(25 reference statements)

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“…In previous meta-analyses, it was concluded that there was equivocal evidence supporting the use of IPFT for these patients (8,9), with a more recent study unable to assess the impact of IPFT (10). Among factors contributing to the uncertainty, IPFT dosing remains empiric, and bioactivity of currently used IPFT agents was not confirmed in prior clinical trial testing in adults with empyema/CPE (19,20,25).…”

Section: Discussionmentioning

confidence: 99%

Phase I trial of the single-chain urokinase intrapleural LTI-01 in complicated parapneumonic effusions or empyema

Beckert¹,

Brockway²,

Simpson³

et al. 2019

JCI Insight

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Conflict of interest: Lung Therapeutics Inc. (LTI) sponsored the trial. SI serves as a Founder and Chief Scientific Officer of LTI and a member of the Board of Directors of LTI, which provided funding for preparation of the drug product and for the trial. He has an equity position (first-tier conflict of interest) in the company, as does the University of Texas Horizon Fund and the UTHSCT. He has a conflict-of-interest plan acknowledging and managing these declared conflicts of interest through the UTHSCT and the UT System. He is an inventor on a patent (USPTO 7332469) held by the UT Board of Regents and licensed to LTI. AAK and GF have received funding from LTI for this study, and they and KS likewise have conflict-of-interest management plans at the UTHSCT. KPS has an equity position in LTI. AAK, GF, and SI are inventors on patent USPTO 10,175,255 B2. NR and YCGL serve as key opinion leaders for LTI, and NR is paid for input to the company. SS is a paid consultant for LTI, and JG received payment as medical monitor for the study from LTI. LB has a potential conflict of interest, having more than $50,000 funding support for personnel and laboratory work for this study from LTI. AMS received funding in the fiscal year prior to submission greater than $50,000 from GSK for 2 funded COPD trials. YCGL has led clinical trials for which Rocket Ltd. provided pleural drainage kits for patients without charge. YCGL has served as advisor to LTI and CareFusion/BD.

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Section: Discussionmentioning

confidence: 99%

Phase I trial of the single-chain urokinase intrapleural LTI-01 in complicated parapneumonic effusions or empyema

Beckert¹,

Brockway²,

Simpson³

et al. 2019

JCI Insight

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“…PAI-1 neutralising antibodies have been shown to enhance the effectiveness of low doses of intrapleural fibrinolytic therapy [93]. This has paved the way for a single-chain urokinase plasminogen activator (scuPA), a fibrinolysin that is processed to a PAI-1 resistant form, and is currently in a phase 1 trial for patients with loculated pleural infections [94,95].…”

Section: The Effect Of Intrapleural Enzyme Therapy (Iet)mentioning

confidence: 99%

Pleural infection: a closer look at the etiopathogenesis, microbiology and role of antibiotics

Bedawi

Hassan

McCracken

et al. 2019

Expert Review of Respiratory Medicine

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BACKGROUND: Pleural infection is a condition that continues to pose a significant challenge to respiratory physicians. We hypothesise that the main barriers to progress include a limited understanding of the pathogenesis, microbiology and role of antibiotics in the pleural space. DATA SOURCE: PubMed was searched for articles related to adult pleural infection using the terms 'pleural infection', 'empyema' and 'parapneumonic'. The search focused on developments in the last ten years, with any older citations only used to display context or lack of progress. Tuberculous pleural infection was excluded. RESULTS: We summarise our latest understanding of the pathogenesis of pleural infection, including recent advances in diagnostics and biomarkers. We discuss our understanding of the pleural microbiome, which differs inherently to that of the lung, and rationalise the current use of antibiotics in treating this condition. 2 Pneumonia vs Pleural Infection 2.1 The pathogenesis of pneumonia Pneumonia can be defined as an infectious process resulting from the invasion and overgrowth of microorganisms in lung parenchyma, breakdown of host defences and provocation of intra-alveolar exudates[8]. The causes can be divided into intrinsic and extrinsic factors. Extrinsic factors include exposure to a causative agent, pulmonary irritants or direct injury. Intrinsic factors are related to the host relating to loss of upper airway reflexes, which allows aspiration of contents and microorganisms from the upper airways into the lung. Underlying disease, loss of mechanical respiratory defences with the use of sedatives, tracheal intubation, and antibiotic treatment are all determinant factors for change in the normal flora of the upper respiratory tract. Once these bacteria find their way to down to the lung parenchyma , a combination of factors may lead to bacterial pneumonia. These include virulence of infecting organism, status of local defences and overall health of the patient. Susceptibility to infection is usually increased in patients of advanced age, or those with chronic disease, due to impairment of the immune response. Dysfunction of defence mechanisms, such as is seen in smokers, patients with chronic obstructive pulmonary disease and tumours, can also lead to greater susceptibility. 2.2 The evolution of the parapneumonic effusion 2.2.1 The exudative phase The interval between aspiration of organisms and the development of pneumonia varies from a few days up to one week. Pneumonia typically begins in dependent lobes at the periphery of the lung, and if untreated, spreads centripetally towards the hilum. If left untreated for the subsequent 2-5 days, a 'simple' parapneumonic effusion will develop and this is known as the "exudative" phase[9]. The development of the initial effusion is due to increased permeability of the pleural membranes in response to inflammation in the underlying lung parenchyma, which is thought to result in transfer of the interstitial fluid across the visceral pleura. Indirect clinical evidence sugg...

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“…18 The pathobiology of pleural infection involves complex interplay between different cells of immunity, mediators of inflammation, the coagulation cascade and the offending organism(s), only a small part of which we understand thus far. 19 The pathophysiological model for pleural infection mainly describes the sequence of events from aspiration of oropharyngeal flora into lung parenchyma where infection ensues to invade the pleura space. These stages do not necessarily happen in primary pleural infection, where the organism spreads via the haematogenous route.…”

Section: Pathogenesismentioning

confidence: 99%

Recent developments in the management of pleural infection: A comprehensive review

Bedawi

Hassan

Rahman

2018

Clinical Respiratory J

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Pathogenesis of pleural infection: A complex warfare

Abstract: http://onlinelibrary.wiley.com/doi/10.1111/resp.13148/abstract

Cited by 5 publications

References 15 publications

Phase I trial of the single-chain urokinase intrapleural LTI-01 in complicated parapneumonic effusions or empyema

Phase I trial of the single-chain urokinase intrapleural LTI-01 in complicated parapneumonic effusions or empyema

Pleural infection: a closer look at the etiopathogenesis, microbiology and role of antibiotics

Recent developments in the management of pleural infection: A comprehensive review

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