Not all nebulizers are created equal: Considerations in choosing a nebulizer for aerosol delivery during mechanical ventilation

MacLoughlin, Ronan; Martín‐Loeches, Ignacio

doi:10.1080/17476348.2023.2183194

Cited by 8 publications

(6 citation statements)

References 104 publications

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“…Aerosol-mediated delivery via inhalation allows for potentially non-invasive direct access to the lung and is suitable across the full range of patient types ranging across patient age, disease type, patient intervention, and patient interface. Appropriate aerosol device selection can influence critical determinants of success such as the total deposition of therapeutic agents and distribution within the lung [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…The delivery of therapeutics directly to the lung via the nebulizer is well established in the critical care setting and concurrent aerosol delivery during mechanical ventilation and other respiratory support interventions offers the potential for safe and effective administration without the need for further interventions, or indeed, the removal of the patient from the critical respiratory supports that they may have been prescribed [ 24 ]. The aerosol-mediated delivery of exosomes has already been shown to facilitate therapeutic outcomes and potential advantages over intravenous administration, where the activation of the complement system and the consequent risk of thrombus formation is a risk factor [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…As was carried out in this study, exosomes can simply be suspended in physiologic saline and administered using an off-the-shelf nebulizer. Moreover, and importantly, nebulizers have been shown to be able to deliver via aerosol during lung protective ventilation strategies, which is a critical consideration in the care of the ARDS patient [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

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Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients

Green,

Shenberg,

Baruch

et al. 2023

Biomedicines

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Rationale: Acute respiratory distress syndrome (ARDS) is a major global health concern with a significant unmet need. EXO-CD24 is delivered via inhalation-reduced cytokines and chemokine secretion and lung injury in ARDS and improved survival in mice models of ARDS, influenza, and sepsis. Objectives: This clinical paper aims to evaluate the potential of EXO-CD24, a novel immunomodulatory treatment, in the compassionate care of critically ill, intubated patients with post-infection-induced acute respiratory distress syndrome (ARDS). Methods: Eleven critically ill patients diagnosed with post-infection ARDS (10 with COVID-19 and one with an adenovirus-associated infection) were administered EXO-CD24 in four medical centers across Israel. The patients had multiple co-morbidities, including cancer, hypertension, diabetes, and ischemic heart disease, and met the criteria for severe ARDS according to the Berlin classification. EXO-CD24 was administered via inhalation, and adverse events related to its use were carefully monitored. Measurements and Main Results: The administration of EXO-CD24 did not result in any recorded adverse events. The median hospitalization duration was 11.5 days, and the overall mortality rate was 36%. Notably, patients treated at the Tel Aviv Medical Center (TASMC) showed a lower mortality rate of 12.5%. The WBC and CRP levels decreased in comparison to baseline levels at hospitalization, and rapid responses occurred even in patients with kidney transplants who were off the ventilator within a few days and discharged shortly thereafter. The production of cytokines and chemokines was significantly suppressed in all patients, including those who died. Among the patients at TASMC, four had kidney transplants and were on immunosuppressive drugs, and all of them fully recovered and were discharged from the hospital. Conclusions: EXO-CD24 holds promise as a potential therapeutic agent for all stages of ARDS, even in severe intubated cases. Importantly, EXO-CD24 demonstrated a favorable safety profile without any apparent side effects with promising efficacy. Furthermore, the potential of EXO-CD24 as a platform for addressing hyper-inflammatory states warrants exploration. Further research and larger-scale clinical trials are warranted to validate these preliminary findings.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients

Green,

Shenberg,

Baruch

et al. 2023

Biomedicines

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“…The delivery of aerosolised medications concurrently allows for the targeted delivery of high localised drug concentrations (3). The aerosolised delivery of these medications is influenced by a myriad of variables such as drug type, patient, ventilation mode, nebuliser choice and placement, and artificial airway choice (4). There are numerous review papers in the literature that have compared the performance of different aerosol generator types (5)(6)(7), their position in the circuit (8)(9)(10)(11)(12), and artificial airway choice (13)(14)(15) on aerosol drug delivery.…”

Section: Introductionmentioning

confidence: 99%

An in vitro study of the effects of respiratory circuit setup and parameters on aerosol delivery during mechanical ventilation

Reilly,

Mac Giolla Eain,

Murphy

et al. 2024

Front. Med.

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IntroductionAerosol therapy is often prescribed concurrently during invasive mechanical ventilation (IMV). This study determines the effects of nebuliser position, circuit humidification source, and most importantly, lung health on the delivery of aerosol in simulated adult and paediatric IMV patients. Furthermore, the influence of closed suction catheters on aerosol delivery is also addressed.MethodsA vibrating mesh nebuliser was used to deliver Albuterol to simulated adult and paediatric IMV patients with differing states of lung health. Four different nebuliser positions and two types of humidification were analysed. Closed suction catheter mounts, a mainstay in IMV therapy, were incorporated into the circuits. The mean ± SD dose of aerosol (%) was assayed from a filter at the distal end of the endotracheal tube.ResultsNebuliser placement and circuit humidification source had no effect on the delivered dose (%) in adults, yet both significantly did in the simulated paediatric patients. The use of closed suction catheter mounts significantly reduced the delivered dose (%) in adults but not in paediatric patients. A simulated healthy lung state generated the largest delivered dose (%), irrespective of nebuliser position in the adult. However, different lung health and nebuliser positions yielded higher delivered doses (%) in paediatrics.ConclusionLung health and respiratory circuit composition significantly affect aerosol delivery in both adult and paediatric IMV patients. Nebuliser placement and respiratory circuit humidification source do not affect the delivered dose in adult but do in paediatric IMV patients.

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“…The delivery of therapeutics directly to the lung via a nebulizer is well established in the critical care setting [ 30 ]. The aerosol-mediated delivery of exosomes has already been shown to facilitate therapeutic outcomes and potential advantages over intravenous administration [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Inhaled CD24-Enriched Exosomes (EXO-CD24) as a Novel Immune Modulator in Respiratory Disease

Shapira,

Schwartz,

Tsiodras

et al. 2023

IJMS

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Acute Respiratory Distress Syndrome (ARDS) is a major health concern with urgent unmet need for treatment options. There are three million new ARDS cases annually, and the disease’s mortality rate is high (35–46%). Cluster of differentiation 24 (CD24), a long-known protein with multifaceted functions, is a small, heavily glycosylated, membrane-anchored protein which functions as an immune checkpoint control. CD24 allows for immune discrimination between Damage-Associated Molecular Patterns and Pathogen-Associated Molecular Patterns derived from pathogens. Exosomes are intraluminal vesicles which play an important role in intercellular communication. Exosomes offer the advantage of targeted delivery, which improves safety and efficacy. The safety and efficacy of EXO-CD24 is promising, as was shown in >180 ARDS patients in phase 1b/2a, phase 2b, and compassionate use. CD24 binds Damage-associated molecular patterns (DAMPs) and inhibits the activation of the NF-ĸB pathway, a pivotal mediator of inflammatory responses. In contrast to anti-inflammatory therapies that are cytokine-specific or steroids that shut down the entire immune system, EXO-CD24 acts upstream, reverting the immune system back to normal activity. Herein, the safety and efficacy of mEXO-CD24 is shown in murine models of several pulmonary diseases (sepsis, allergic asthma, Chronic Obstructive Pulmonary Disease(COPD), fibrosis). EXO CD24 can suppress the hyperinflammatory response in the lungs in several pulmonary diseases with a significant unmet need for treatment options.

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Not all nebulizers are created equal: Considerations in choosing a nebulizer for aerosol delivery during mechanical ventilation

Cited by 8 publications

References 104 publications

Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients

Inhaled Exosomes Genetically Manipulated to Overexpress CD24 (EXO-CD24) as a Compassionate Use in Severe ARDS Patients

An in vitro study of the effects of respiratory circuit setup and parameters on aerosol delivery during mechanical ventilation

Inhaled CD24-Enriched Exosomes (EXO-CD24) as a Novel Immune Modulator in Respiratory Disease

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