Aerosol delivery systems for treating obstructive airway diseases during the SARS-CoV-2 pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes CoronaVirus Disease 2019 (COVID-19), has resulted in a worldwide pandemic and currently represents a major public health crisis. It has caused outbreaks of illness through person-to-person transmission of the virus mainly via close contacts, and droplets produced by an infected person's cough or sneeze. Aerosolised inhaled therapy is the mainstay for treating obstructive airway diseases at home and in healthcare settings, but there is heightened particular concern about the potential risk for transmission of SARS-CoV-2 in the form of aerosolised respiratory droplets during the nebulised treatment of patients with COVID-19. As a consequence of this concern, the use of hand-held inhalers, especially pressurised metered dose inhalers, has risen considerably as an alternative to nebulisers, and this switch has led to inadequate supplies of inhalers in some countries. However, there is no evidence supporting an increased risk of viral transmission during nebulisation in COVID-19 patients. Furthermore, some patients may be unable to adequately use their new device and may not benefit fully from the switch to treatment via hand-held inhalers. Thus, there is no compelling reason to alter aerosol delivery devices for patients with established nebuliser-based regimens. The purpose of this paper is to discuss the current evidence and understanding of the use of aerosolised inhaled therapies during the SARS-CoV-2 pandemic and to provide some guidance on the measures to be taken to minimise the risk of transmitting infection, if any, during aerosol therapies.

Containment of procedure-associated aerosols by an extractor tent: effect on nebulized drug particle dispersal.

BACKGROUND: Several medical procedures involving the respiratory tract are considered as 'aerosol-generating procedures'. Aerosols from these procedures may be inhaled by bystanders, and there are consequent concerns regarding the transmission of infection or, specific to nebulized therapy, secondary drug exposure. AIM: To assess the efficacy of a proprietary high-efficiency-particulate-air-filtering extractor tent on reducing the aerosol dispersal of nebulized bronchodilator drugs. METHODS: The study was conducted in an unoccupied outpatient room at St. James's Hospital, Dublin, Ireland. A novel real-time, fluorescent particle counter, the Wideband Integrated Bioaerosol Sensor (WIBS), monitored room air continuously for 3 h. Baseline airborne particle count and count during nebulization of bronchodilator drug solutions were recorded. FINDINGS: Nebulization within the tent prevented any increase over background level. Nebulization directly into room air resulted in mean fluorescent particle counts of 4.75 x 105/m3 and 4.21 x 105/m3 for Ventolin and Ipramol, respectively, representing more than 400-fold increases over mean background level. More than 99.3% of drug particles were <2 µm in diameter and therefore small enough to enter the lower respiratory tract. CONCLUSION: The extractor tent was completely effective for the prevention of airborne spread of drug particles of respirable size from nebulized therapy. This suggests that extractor tents of this type would be efficacious for the prevention of airborne infection from aerosol-generating procedures during the COVID-19 pandemic.

A narrative review of hydrogen-oxygen mixture for medical purpose and the inhaler thereof.

Recent development regarding mixture of H2 (concentration of ~66%) with O2 (concentration of ~34%) for medical purpose, such as treatment of coronavirus disease-19 (COVID-19) patients, is introduced. Furthermore, the design principles of a hydrogen inhaler which generates mixture of hydrogen (~66%) with oxygen (~34%) for medical purpose are proposed. With the installation of the liquid blocking module and flame arresters, the air pathway of the hydrogen inhaler is divided by multiple isolation zones to prevent any unexpected explosion propagating from one zone to the other. An integrated filtering/cycling module is utilized to purify the impurity, and cool down the temperature of the electrolytic module to reduce the risk of the explosion. Moreover, a nebulizer is provided to selectively atomize the water into vapor which is then mixed with the filtered hydrogen-oxygen mix gas, such that the static electricity of a substance hardly occurs to reduce the risk of the explosion. Furthermore, hydrogen concentration detector is installed to reduce the risk of hydrogen leakage. Result shows that the hydrogen inhaler implementing the aforesaid design rules could effectively inhibit the explosion, even ignition at the outset of the hydrogen inhaler which outputs hydrogen-oxygen gas (approximately 66% hydrogen: 34% oxygen).

Nebulised surfactant for the treatment of severe COVID-19 in adults (COV-Surf): A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: SARS-Cov-2 virus preferentially binds to the Angiotensin Converting Enzyme 2 (ACE2) on alveolar epithelial type II cells, initiating an inflammatory response and tissue damage which may impair surfactant synthesis contributing to alveolar collapse, worsening hypoxia and leading to respiratory failure. The objective of this study is to evaluate the feasibility, safety and efficacy of nebulised surfactant in COVID-19 adult patients requiring mechanical ventilation for respiratory failure. TRIAL DESIGN: This study is a dose-escalating randomized open-label clinical trial of 20 COVID-19 patients. PARTICIPANTS: This study is conducted in two centres: University Hospital Southampton and University College London Hospitals. Eligible participants are aged ≥18, hospitalised with COVID-19 (confirmed by PCR), who require endotracheal intubation and are enrolled within 24 hours of mechanical ventilation. For patients unable to consent, assent is obtained from a personal legal representative (PerLR) or professional legal representative (ProfLR) prior to enrolment. The following are exclusion criteria: imminent expected death within 24 hours; specific contraindications to surfactant administration (e.g. known allergy, pneumothorax, pulmonary hemorrhage); known or suspected pregnancy; stage 4 chronic kidney disease or requiring dialysis (i.e., eGFR < 30); liver failure (Child-Pugh Class C); anticipated transfer to another hospital, which is not a study site, within 72 hours; current or recent (within 1 month) participation in another study that, in the opinion of the investigator, would prevent enrollment for safety reasons; and declined consent or assent. INTERVENTION AND COMPARATOR: Intervention: The study is based on an investigational drug/device combination product. The surfactant product is Bovactant (Alveofact®), a natural animal derived (bovine) lung surfactant formulated as a lyophilized powder in 108 mg vials and reconstituted to 45 mg/mL in buffer supplied in a prefilled syringe. It is isolated by lung lavage and, by weight, is a mixture of: phospholipid (75% phosphatidylcholine, 13% phosphatidylglycerol, 3% phosphatidylethanolamine, 1% phosphatidylinositol and 1% sphingomyelin), 5% cholesterol, 1% lipid-soluble surfactant-associated proteins (SP-B and SP-C), very low levels of free fatty acid, lyso-phosphatidylcholine, water and 0.3% calcium. The Drug Delivery Device is the AeroFact-COVID™ nebulizer, an investigational device based on the Aerogen® Solo vibrating mesh nebulizer. The timing and escalation dosing plans for the surfactant are as follows. Cohort 1: Three patients will receive 10 vials (1080 mg) each of surfactant at dosing times of 0 hours, 8 hours and 24 hours. 2 controls with no placebo intervention. Cohort 2: Three patients will receive 10 vials (1080 mg) of surfactant at dosing times of 0 hours and 8 hours, and 30 vials (3240 mg) at a dosing time of 24 hours. 2 controls with no placebo intervention. Cohort 3: Three patients will receive 10 vials (1080 mg) of surfactant at a dosing time of 0 hours, and 30 vials (3240 mg) at dosing times of 8 hours and 24 hours. 2 controls with no placebo intervention. Cohort 4: Three patients will receive 30 (3240 mg) vials each of surfactant at dosing times of 0 hours, 8 hours and 24 hours. 2 controls. 2 controls with no placebo intervention. The trial steering committee, advised by the data monitoring committee, will review trial progression and dose escalation/maintenance/reduction after each cohort is completed (48-hour primary outcome timepoint reached) based on available feasibility, adverse event, safety and efficacy data. The trial will not be discontinued on the basis of lack of efficacy. The trial may be stopped early on the basis of safety or feasibility concerns. Comparator: No placebo intervention. All participants will receive usual standard of care in accordance with the local policies for mechanically ventilated patients and all other treatments will be left to the discretion of the attending physician. MAIN OUTCOMES: The co-primary outcome is the improvement in oxygenation (PaO2/FiO2 ratio) and pulmonary ventilation (Ventilation Index (VI), where VI = [RR x (PIP - PEEP) × PaCO2]/1000) at 48 hours after study initiation. The secondary outcomes include frequency and severity of adverse events (AEs), Adverse Device Effects (ADEs), Serious Adverse Events (SAEs) and Serious Adverse Device Events (SADEs), change in pulmonary compliance, change in positive end-expiratory pressure (PEEP) requirement of ventilatory support at 24 and 48 hours after study initiation, clinical improvement defined by time to one improvement point on the ordinal scale described in the WHO master protocol (2020) recorded while hospitalised, days of mechanical ventilation, mechanical ventilator free days (VFD) at day 21, length of intensive care unit stay, number of days hospitalised and mortality at day 28. Exploratory end points will include quantification of SARS-CoV-2 viral load from tracheal aspirates using PCR, surfactant dynamics (synthesis and turnover) and function (surface tension reduction) from deep tracheal aspirate samples (DTAS), surfactant phospholipid concentrations in plasma and DTAS, inflammatory markers (cellular and cytokine) in plasma and DTAS, and blood oxidative stress markers. RANDOMISATION: After informed assent, patients fulfilling inclusion criteria will be randomised to 3:2 for the treatment and control arms using an internet-based block randomization service (ALEA tool for clinical trials, FormsVision BV) in combination with electronic data collection. Randomisation will be done by the recruiting centre with a unique subject identifier specific to that centre. BLINDING (MASKING): This is an open-labelled unblinded study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The total sample size is 20 COVID-19 mechanically ventilated patients (12 intervention; 8 control). TRIAL STATUS: Current protocol version is V2 dated 5th of June 2020. The recruitment is currently ongoing and started on the 14th of October 2020. The anticipated study completion date is November 2021. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04362059 (Registered 24 April 2020), EUDAMED number: CIV-GB-20-06-033328, EudraCT number: 2020-001886-35 (Registered 11 May 2020) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

GINA 2020: what's new and why?

The Global initiative against asthma (GINA) 2020 strategy has been released with some changes and updates. GINA recommends the continuation of medications, avoidance of nebulization and spirometry, and ensuring a written asthma action plan in COVID-19 times. GINA 2020 specifies which step of management is to be followed according to the patient's symptoms in an easy flowchart. Clinicians need to be aware of the changes and the evidence behind them.

Respiratory support in patients with COVID-19 (outside intensive care unit). A position paper of the Respiratory Support and Chronic Care Group of the French Society of Respiratory Diseases.

With first cases noted towards the end of 2019 in China, COVID-19 infection was rapidly become a devastating pandemic. Even if most patients present with a mild to moderate form of the disease, the estimated prevalence of COVID-19-related severe acute respiratory failure (ARF) is 15-20% and 2-12% needed intubation and mechanical ventilation. In addition to mechanical ventilation some other techniques of respiratory support could be used in some forms of COVID-19 related ARF. This position paper of the Respiratory Support and Chronic Care Group of the French Society of Respiratory Diseases is intended to help respiratory clinicians involved in care of COVID-19 pandemic in the rational use of non-invasive techniques such as oxygen therapy, CPAP, non-invasive ventilation and high flow oxygen therapy in managing patients outside intensive care unit (ICU). The aims are: (1) to focus both on the place of each technique and in describing practical tips (types of devices and circuit assemblies) aimed to limit the risk of caregivers when using those techniques at high risk spreading of viral particles; (2) to propose a step-by-step strategy to manage ARF outside ICU.