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1.
JCI Insight ; 7(3)2022 02 08.
Article in English | MEDLINE | ID: covidwho-1705325

ABSTRACT

BackgroundAdenovirus-vectored (Ad-vectored) vaccines are typically administered via i.m. injection to humans and are incapable of inducing respiratory mucosal immunity. However, aerosol delivery of Ad-vectored vaccines remains poorly characterized, and its ability to induce mucosal immunity in humans is unknown. This phase Ib trial evaluated the safety and immunogenicity of human serotype-5 Ad-vectored tuberculosis (TB) vaccine (AdHu5Ag85A) delivered to humans via inhaled aerosol or i.m. injection.MethodsThirty-one healthy, previously BCG-vaccinated adults were enrolled. AdHu5Ag85A was administered by single-dose aerosol using Aeroneb Solo Nebulizer or by i.m. injection. The study consisted of the low-dose (LD) aerosol, high-dose (HD) aerosol, and i.m. groups. The adverse events were assessed at various times after vaccination. Immunogenicity data were collected from the peripheral blood and bronchoalveolar lavage samples at baseline, as well as at select time points after vaccination.ResultsThe nebulized aerosol droplets were < 5.39 µm in size. Both LD and HD of AdHu5Ag85A administered by aerosol inhalation and i.m. injection were safe and well tolerated. Both aerosol doses, particularly LD, but not i.m., vaccination markedly induced airway tissue-resident memory CD4+ and CD8+ T cells of polyfunctionality. While as expected, i.m. vaccination induced Ag85A-specific T cell responses in the blood, the LD aerosol vaccination also elicited such T cells in the blood. Furthermore, the LD aerosol vaccination induced persisting transcriptional changes in alveolar macrophages.ConclusionInhaled aerosol delivery of Ad-vectored vaccine is a safe and superior way to elicit respiratory mucosal immunity. This study warrants further development of aerosol vaccine strategies against respiratory pathogens, including TB and COVID-19.Trial registrationClinicalTrial.gov, NCT02337270.FundingThe Canadian Institutes for Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada funded this work.


Subject(s)
Aerosols/pharmacology , COVID-19/prevention & control , SARS-CoV-2/drug effects , Tuberculosis Vaccines/immunology , Tuberculosis/prevention & control , Administration, Inhalation , Adolescent , Adult , Aerosols/administration & dosage , Antibodies, Neutralizing/blood , BCG Vaccine/immunology , COVID-19/immunology , Female , Humans , Immunity, Mucosal/drug effects , Immunity, Mucosal/immunology , Male , Middle Aged , Mycobacterium tuberculosis/immunology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Tuberculosis/immunology , Vaccination/methods , Young Adult
2.
Drug Deliv ; 29(1): 10-17, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1577575

ABSTRACT

Aerosol therapy is used to deliver medical therapeutics directly to the airways to treat respiratory conditions. A potential consequence of this form of treatment is the release of fugitive aerosols, both patient derived and medical, into the environment and the subsequent exposure of caregivers and bystanders to potential viral infections. This study examined the release of these fugitive aerosols during a standard aerosol therapy to a simulated adult patient. An aerosol holding chamber and mouthpiece were connected to a representative head model and breathing simulator. A combination of laser and Schlieren imaging was used to non-invasively visualize the release and dispersion of fugitive aerosol particles. Time-varying aerosol particle number concentrations and size distributions were measured with optical particle sizers at clinically relevant positions to the simulated patient. The influence of breathing pattern, normal and distressed, supplemental air flow, at 0.2 and 6 LPM, and the addition of a bacterial filter to the exhalation port of the mouthpiece were assessed. Images showed large quantities of fugitive aerosols emitted from the unfiltered mouthpiece. The images and particle counter data show that the addition of a bacterial filter limited the release of these fugitive aerosols, with the peak fugitive aerosol concentrations decreasing by 47.3-83.3%, depending on distance from the simulated patient. The addition of a bacterial filter to the mouthpiece significantly reduces the levels of fugitive aerosols emitted during a simulated aerosol therapy, p≤ .05, and would greatly aid in reducing healthcare worker and bystander exposure to potentially harmful fugitive aerosols.


Subject(s)
Aerosols , COVID-19 , Drug Delivery Systems , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Nebulizers and Vaporizers , Respiratory Therapy , Aerosols/administration & dosage , Aerosols/adverse effects , COVID-19/prevention & control , COVID-19/transmission , Computer Simulation , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Equipment Design , Humans , Infection Control/methods , Models, Biological , Particle Size , Respiratory Therapy/adverse effects , Respiratory Therapy/instrumentation , Respiratory Therapy/methods , SARS-CoV-2
4.
Drug Deliv ; 28(1): 1496-1500, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1309552

ABSTRACT

COVID-19 can cause serious respiratory complications resulting in the need for invasive ventilatory support and concurrent aerosol therapy. Aerosol therapy is considered a high risk procedure for the transmission of patient derived infectious aerosol droplets. Critical-care workers are considered to be at a high risk of inhaling such infectious droplets. The objective of this work was to use noninvasive optical methods to visualize the potential release of aerosol droplets during aerosol therapy in a model of an invasively ventilated adult patient. The noninvasive Schlieren imaging technique was used to visualize the movement of air and aerosol. Three different aerosol delivery devices: (i) a pressurized metered dose inhaler (pMDI), (ii) a compressed air driven jet nebulizer (JN), and (iii) a vibrating mesh nebulizer (VMN), were used to deliver an aerosolized therapeutic at two different positions: (i) on the inspiratory limb at the wye and (ii) on the patient side of the wye, between the wye and endotracheal tube, to a simulated intubated adult patient. Irrespective of position, there was a significant release of air and aerosol from the ventilator circuit during aerosol delivery with the pMDI and the compressed air driven JN. There was no such release when aerosol therapy was delivered with a closed-circuit VMN. Selection of aerosol delivery device is a major determining factor in the release of infectious patient derived bioaerosol from an invasively mechanically ventilated patient receiving aerosol therapy.


Subject(s)
Aerosols , COVID-19 , Disease Transmission, Infectious/prevention & control , Metered Dose Inhalers , Nebulizers and Vaporizers , Respiration, Artificial/methods , Respiratory Therapy , Aerosols/administration & dosage , Aerosols/adverse effects , COVID-19/physiopathology , COVID-19/therapy , COVID-19/transmission , Combined Modality Therapy , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Drug Delivery Systems/standards , Humans , Occupational Exposure/prevention & control , Research Design , Respiratory Therapy/adverse effects , Respiratory Therapy/instrumentation , Respiratory Therapy/methods , Risk Management , SARS-CoV-2
5.
Sci Adv ; 7(22)2021 05.
Article in English | MEDLINE | ID: covidwho-1247309

ABSTRACT

Globally, there is an urgency to develop effective, low-cost therapeutic interventions for coronavirus disease 2019 (COVID-19). We previously generated the stable and ultrapotent homotrimeric Pittsburgh inhalable Nanobody 21 (PiN-21). Using Syrian hamsters that model moderate to severe COVID-19 disease, we demonstrate the high efficacy of PiN-21 to prevent and treat SARS-CoV-2 infection. Intranasal delivery of PiN-21 at 0.6 mg/kg protects infected animals from weight loss and substantially reduces viral burdens in both lower and upper airways compared to control. Aerosol delivery of PiN-21 facilitates deposition throughout the respiratory tract and dose minimization to 0.2 mg/kg. Inhalation treatment quickly reverses animals' weight loss after infection, decreases lung viral titers by 6 logs leading to drastically mitigated lung pathology, and prevents viral pneumonia. Combined with the marked stability and low production cost, this innovative therapy may provide a convenient and cost-effective option to mitigate the ongoing pandemic.


Subject(s)
COVID-19/drug therapy , COVID-19/prevention & control , SARS-CoV-2/drug effects , Single-Domain Antibodies/administration & dosage , Administration, Inhalation , Aerosols/administration & dosage , Animals , Disease Models, Animal , Female , Male , Mesocricetus , Pandemics/prevention & control , Pneumonia, Viral/drug therapy , Pneumonia, Viral/prevention & control , Viral Load/drug effects
6.
Pediatr Pulmonol ; 55(2): 322-329, 2020 02.
Article in English | MEDLINE | ID: covidwho-1064412

ABSTRACT

OBJECTIVES: Transnasal pulmonary aerosol delivery using high-flow nasal cannula (HFNC) devices has become a popular route of aerosol administration in toddlers. Clinically, albuterol is administered using an infusion pump or unit doses. However, little evidence is available to compare the two administration strategies. METHODS: A toddler manikin (15 kg) with appropriate anatomic airway was connected with collecting filter to a simulator of distressed breathing. HFNC device with mesh nebulizer placed at the inlet of a humidifier at 37°C, with the gas flow set at 25 and 3.75 L/min. Five milligrams of albuterol was delivered in all experiments. With infusion pump administration, albuterol concentrations of 5 and 1 mg/mL were delivered at 4 and 20 mL/hr for 15 minutes. With unit dose administration, 1 mL (5 mg/mL) and 2 mL (2.5 mg/mL) of albuterol were nebulized. Additional tests with mouth open and nebulizers via mask were using 5 mg/1 mL for mesh nebulizer and 5 mg/3 mL for jet nebulizer (n = 3). The drug was eluted from the filter and assayed with UV spectrophotometry (276 nm). RESULTS: The inhaled dose was higher with unit dose than infusion pump administration with gas flows of 25 L/min (2.66 ± 0.38 vs 1.16 ± 0.28%; P = .004) and 3.75 L/min (10.51 ± 1.29 vs 8.58 ± 0.68%; P = .025). During unit dose administration, compared with closed-mouth breathing, open-mouth breathing generated a higher inhaled dose at 3.75 L/min and lower inhaled dose at 25 L/min. Compared to the nebulizers via mask with both open and closed-mouth breathing, nebulization via HFNC at 3.75 L/min generated greater inhaled dose, while HFNC at 25 L/min generated lower inhaled dose. CONCLUSIONS: During transnasal aerosol delivery, the inhaled dose was higher with medication administrated using unit dose than using an infusion pump.


Subject(s)
Albuterol/administration & dosage , Bronchodilator Agents/administration & dosage , Cannula , Administration, Inhalation , Aerosols/administration & dosage , Albuterol/therapeutic use , Bronchodilator Agents/therapeutic use , Child, Preschool , Equipment Design , Humans , Humidifiers , Infusion Pumps , Lung , Manikins , Nebulizers and Vaporizers , Respiration
7.
PLoS One ; 16(2): e0244127, 2021.
Article in English | MEDLINE | ID: covidwho-1067399

ABSTRACT

INTRODUCTION: Olfactory dysfunction (OD) affects a majority of COVID-19 patients, is atypical in duration and recovery, and is associated with focal opacification and inflammation of the olfactory epithelium. Given recent increased emphasis on airborne transmission of SARS-CoV-2, the purpose of the present study was to experimentally characterize aerosol dispersion within olfactory epithelium (OE) and respiratory epithelium (RE) in human subjects, to determine if small (sub 5µm) airborne aerosols selectively deposit in the OE. METHODS: Healthy adult volunteers inhaled fluorescein-labeled nebulized 0.5-5µm airborne aerosol or atomized larger aerosolized droplets (30-100µm). Particulate deposition in the OE and RE was assessed by blue-light filter modified rigid endoscopic evaluation with subsequent image randomization, processing and quantification by a blinded reviewer. RESULTS: 0.5-5µm airborne aerosol deposition, as assessed by fluorescence gray value, was significantly higher in the OE than the RE bilaterally, with minimal to no deposition observed in the RE (maximum fluorescence: OE 19.5(IQR 22.5), RE 1(IQR 3.2), p<0.001; average fluorescence: OE 2.3(IQR 4.5), RE 0.1(IQR 0.2), p<0.01). Conversely, larger 30-100µm aerosolized droplet deposition was significantly greater in the RE than the OE (maximum fluorescence: OE 13(IQR 14.3), RE 38(IQR 45.5), p<0.01; average fluorescence: OE 1.9(IQR 2.1), RE 5.9(IQR 5.9), p<0.01). CONCLUSIONS: Our data experimentally confirm that despite bypassing the majority of the upper airway, small-sized (0.5-5µm) airborne aerosols differentially deposit in significant concentrations within the olfactory epithelium. This provides a compelling aerodynamic mechanism to explain atypical OD in COVID-19.


Subject(s)
Aerosols/analysis , Anosmia/etiology , COVID-19/complications , Olfactory Mucosa/physiopathology , Adult , Aerosols/administration & dosage , Anosmia/physiopathology , Anosmia/virology , COVID-19/physiopathology , COVID-19/virology , Host-Pathogen Interactions , Humans , Olfactory Mucosa/virology , SARS-CoV-2/physiology , Smell
8.
PLoS One ; 16(2): e0246543, 2021.
Article in English | MEDLINE | ID: covidwho-1063221

ABSTRACT

Dental turbines and scalers, used every day in dental operatories, feature built-in water spray that generates considerable amounts of water aerosol. The problem is that it is not exactly known how much. Since the outbreak of COVID-19, several aerosol safety recommendations have been issued-based on little empirical evidence, as almost no data are available on the exact aerosol concentrations generated during dental treatment. Similarly, little is known about the differences in the efficacy of different commercially available aerosol control systems to reduce in-treatment aerosol load. In this in vitro study, we used spectrometry to explore these questions. The time-dependent effect of conventional airing on aerosol concentrations was also studied. Everyday patient treatment situations were modeled. The test setups were defined by the applied instrument and its spray direction (high-speed turbine with direct/indirect airspray or ultrasonic scaler with indirect airspray) and the applied aerosol control system (the conventional high-volume evacuator or a lately introduced aerosol exhaustor). Two parameters were analyzed: total number concentration in the entire measurement range of the spectrometer and total number concentration within the 60 to 384 nm range. The results suggest that instrument type and spray direction significantly influence the resulting aerosol concentrations. Aerosol generation by the ultrasonic scaler is easily controlled. As for the high-speed turbine, the efficiency of control might depend on how exactly the instrument is used during a treatment. The results suggest that scenarios where the airspray is frequently directed toward the air of the operatory are the most difficult to control. The tested control systems did not differ in their efficiency, but the study could not provide conclusive results in this respect. With conventional airing through windows with a standard fan, a safety airing period of at least 15 minutes between treatments is recommended.


Subject(s)
Aerosols/adverse effects , Dental Instruments/virology , Dentistry/methods , Aerosols/administration & dosage , Aerosols/analysis , COVID-19/etiology , Equipment Design , Humans , Particle Size , SARS-CoV-2/isolation & purification
9.
Otolaryngol Head Neck Surg ; 163(4): 702-704, 2020 10.
Article in English | MEDLINE | ID: covidwho-999412

ABSTRACT

Otolaryngologists are at increased risk for exposure to suspected aerosol-generating procedures during the ongoing coronavirus disease 2019 (COVID-19) pandemic. In the present study, we sought to quantify differences in aerosol generation during common ventilation scenarios. We performed a series of 30-second ventilation experiments on porcine larynx-trachea-lung specimens. We used an optical particle sizer to quantify the number of 1- to 10-µm particles observed per 30-second period (PP30). No significant aerosols were observed with ventilation of intubated specimens (10.8 ± 2.4 PP30 vs background 9.5 ± 2.1, P = 1.0000). Simulated coughing through a tracheostomy produced 53.5 ± 25.2 PP30, significantly more than background (P = .0121) and ventilation of an intubated specimen (P = .0401). These data suggest that undisturbed ventilation and thus intubation without stimulation or coughing may be safer than believed. Coughing increases aerosol production, particularly via tracheostomy. Otolaryngologists who frequently manage patient airways and perform tracheostomy are at increased risk for aerosol exposure and require appropriate personal protective equipment, especially during the ongoing COVID-19 pandemic.


Subject(s)
Aerosols/administration & dosage , Betacoronavirus , Coronavirus Infections/epidemiology , Disease Transmission, Infectious/prevention & control , Personal Protective Equipment/standards , Pneumonia, Viral/epidemiology , Respiration, Artificial/methods , Tracheostomy/methods , COVID-19 , Coronavirus Infections/transmission , Humans , Pandemics , Pneumonia, Viral/transmission , SARS-CoV-2
10.
J Pharm Sci ; 110(3): 1316-1322, 2021 03.
Article in English | MEDLINE | ID: covidwho-943677

ABSTRACT

Under pandemic-caused emergency, evaluation of the potential of existing antiviral drugs for the treatment of COVID-19 is relevant. Triazavirin, an antiviral drug developed in Russia for per-oral administration, is involved in clinical trials against SARS-CoV-2 coronavirus. This virus has affinity to epithelial cells in respiratory tract, so drug delivery directly in lungs may enhance therapeutic effect and reduce side effects for stomach, liver, kidneys. We elaborated ultrasonic method of triazavirin aerosol generation and investigated the inhalation delivery of this drug in mice. Mean particle size and number concentration of aerosol used in inhalation experiments are 560 nm and 4 × 105 cm-3, respectively. Aerosol mass concentration is 1.6 × 10-4 mg/cm3. Inhalation for 20 min in a nose-only chamber resulted in 2 mg/kg body delivered dose and 2.6 µg/mL triazavirin concentration in blood plasma. Elimination rate constant determined in aerosol administration experiments was ke = 0.077 min-1, which agrees with the value measured after intravenous delivery, but per-oral administration resulted in considerably lower apparent elimination rate constant of pseudo-first order, probably due to non-linear dependence of absorption rate on triazavirin concentration in gastrointestinal tract. The bioavailability of triazavirin aerosol is found to be 85%, which is about four times higher than for per-oral administration.


Subject(s)
Aerosols/administration & dosage , Antiviral Agents/administration & dosage , Azoles/administration & dosage , Nebulizers and Vaporizers , Triazines/administration & dosage , Administration, Inhalation , Administration, Oral , Aerosols/pharmacokinetics , Animals , Antiviral Agents/blood , Antiviral Agents/pharmacokinetics , Azoles/blood , Azoles/pharmacokinetics , Biological Availability , COVID-19/drug therapy , Drug Delivery Systems/instrumentation , Drug Elimination Routes , Equipment Design , Humans , Male , Mice , Triazines/blood , Triazines/pharmacokinetics , Triazoles
11.
Otolaryngol Head Neck Surg ; 163(1): 98-103, 2020 07.
Article in English | MEDLINE | ID: covidwho-913959

ABSTRACT

The correct selection and utilization of respiratory personal protective equipment is of the utmost importance in the current COVID-19 pandemic. This is especially true for health care workers exposed to high-risk aerosol-generating procedures, including otolaryngologists, ophthalmologists, neurosurgeons, maxillofacial surgeons, and laparoscopic surgeons. This communication provides a review of approved forms of respiratory protection and compares their characteristics, including surgical masks, N95 respirator, elastomeric respirators, powered air-purifying respirators, and controlled air-purifying respirators. For standard airborne precautions, N95 respirator are appropriate for respiratory protection. However, high-risk aerosol-generating procedures may create aerosolization of high viral loads that represent increased risk to health care workers. In these situations, enhanced respiratory protection with filters certified as 99, 100, or HEPA (high-efficiency particulate air) may be appropriate.


Subject(s)
Aerosols/administration & dosage , Betacoronavirus , Coronavirus Infections/epidemiology , Disease Transmission, Infectious/prevention & control , Pandemics , Personal Protective Equipment/standards , Pneumonia, Viral/epidemiology , Respiratory Protective Devices/standards , COVID-19 , Coronavirus Infections/transmission , Humans , Pneumonia, Viral/transmission , Risk Factors , SARS-CoV-2
12.
Am J Respir Crit Care Med ; 202(8): 1115-1124, 2020 10 15.
Article in English | MEDLINE | ID: covidwho-727210

ABSTRACT

Rationale: Aerosol generation with modes of oxygen therapy such as high-flow nasal cannula and noninvasive positive-pressure ventilation is a concern for healthcare workers during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The amount of aerosol generation from the respiratory tract with these various oxygen modalities is unknown.Objectives: To measure the size and number concentration of particles and droplets generated from the respiratory tract of humans exposed to various oxygen delivery modalities.Methods: Ten healthy participants with no active pulmonary disease were enrolled. Oxygen modalities tested included nonhumidified nasal cannula, face mask, heated and humidified high-flow nasal cannula, and noninvasive positive-pressure ventilation. Aerosol generation was measured with each oxygen mode while participants performed maneuvers of normal breathing, talking, deep breathing, and coughing. Testing was conducted in a negative-pressure room. Particles with a diameter between 0.37 and 20 µm were measured using an aerodynamic particle spectrometer.Measurements and Main Results: Median particle concentration ranged from 0.041 to 0.168 particles/cm3. Median diameter ranged from 1.01 to 1.53 µm. Cough significantly increased the number of particles measured. Measured aerosol concentration did not significantly increase with the use of either humidified high-flow nasal cannula or noninvasive positive-pressure ventilation. This was the case during normal breathing, talking, deep breathing, and coughing.Conclusions: Oxygen delivery modalities of humidified high-flow nasal cannula and noninvasive positive-pressure ventilation do not increase aerosol generation from the respiratory tract in healthy human participants with no active pulmonary disease measured in a negative-pressure room.


Subject(s)
Aerosols/administration & dosage , Betacoronavirus , Coronavirus Infections/therapy , Oxygen Inhalation Therapy/methods , Pneumonia, Viral/therapy , Adult , COVID-19 , Cannula , Coronavirus Infections/epidemiology , Female , Healthy Volunteers , Humans , Male , Noninvasive Ventilation/methods , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2
13.
Otolaryngol Head Neck Surg ; 163(5): 934-937, 2020 11.
Article in English | MEDLINE | ID: covidwho-611164

ABSTRACT

The impact of the COVID-19 pandemic on otolaryngology practice is nowhere more evident than in acute airway management. Considerations of preventing SARS-CoV-2 transmission, conserving personal protective equipment, and prioritizing care delivery based on acuity have dictated clinical decision making in the acute phase of the pandemic. With transition to a more chronic state of pandemic, heightened vigilance is necessary to recognize how deferral of care in patients with tenuous airways and COVID-19 infection may lead to acute airway compromise. Furthermore, it is critical to respect the continuing importance of flexible laryngoscopy in diagnosis. Safely managing airways during the pandemic requires thoughtful multidisciplinary planning. Teams should consider trade-offs among aerosol-generating procedures involving direct laryngoscopy, supraglottic airway use, fiberoptic intubation, and tracheostomy. We share clinical cases that illustrate enduring principles of acute airway management. As algorithms evolve, time-honored approaches for diagnosis and management of acute airway pathology remain essential in ensuring patient safety.


Subject(s)
Aerosols/administration & dosage , Airway Management/methods , Betacoronavirus , Coronavirus Infections/therapy , Disease Transmission, Infectious/prevention & control , Personal Protective Equipment , Pneumonia, Viral/therapy , Adult , Aged , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Female , Humans , Infant , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , SARS-CoV-2
17.
Respir Med ; 167: 105987, 2020 06.
Article in English | MEDLINE | ID: covidwho-101982

ABSTRACT

The COVID-19, the disease caused by a novel coronavirus and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe. It has caused outbreaks of illness due to person-to-person transmission of the virus mainly via close contacts and droplets produced by an infected person's cough or sneeze. Exhaled droplets from infected patients with COVID-19 can be inhaled into the lungs and leads to respiratory illness such as pneumonia and acute respiratory distress syndrome. Although aerosol therapy is a mainstay procedure used to treat pulmonary diseases at home and healthcare settings, it has a potential for fugitive emissions during therapy due to the generation of aerosols and droplets as a source of respiratory pathogens. Delivering aerosolized medications to patients with COVID-19 can aggravate the spread of the novel coronavirus. This has been a real concern for caregivers and healthcare professionals who are susceptible to unintended inhalation of fugitive emissions during therapy. Due to a scarcity of information in this area of clinical practice, the purpose of this paper is to explain how to deliver aerosolized medications to mild-, sub-intensive, and intensive-care patients with COVID-19 and how to protect staff from exposure to exhaled droplets during aerosol therapy.


Subject(s)
Coronavirus Infections/drug therapy , Drug Delivery Systems/methods , Pneumonia, Viral/drug therapy , Administration, Inhalation , Aerosols/administration & dosage , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/epidemiology , Drug Delivery Systems/standards , Humans , Infection Control/methods , Nebulizers and Vaporizers , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2
18.
Eur J Pharm Sci ; 147: 105290, 2020 Apr 30.
Article in English | MEDLINE | ID: covidwho-3102

ABSTRACT

Dehydroandrographolide succinate (DAS) injection, which was approved in China for the treatment of viral pneumonia and upper respiratory tract infections, is often off-label used for nebulization therapy to avoid the adverse drug reactions associated with the injection. However, the aerodynamic properties and pulmonary fate of nebulized DAS was largely uninvestigated. In this study, the main objectives were to evaluate the in vitro aerodynamic deposition profiles of nebulizer generated aerosols and comparatively investigate the local drug availability and anti-inflammatory efficacy of DAS between intratracheal and intravenous dosing. The in vitro evaluation of aerodynamic characteristics and droplet size distribution showed more than 50% aerosol particles with size being <5 µm, allowing the aerosols to reach the lower respiratory tract. Following intratracheal administration, the drug underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 47.3%. Compared to the intravenous delivery, the intratracheal administration dramatically increased the drug availability in the lung tissue in rats by more than 80-fold, leading to an improved and prolonged local anti-inflammatory efficacy in a lipopolysaccharide induced lung injury model in mice. The present results demonstrated that inhalation delivery of DAS is a convenient and effective alternative to intravenous injections.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacokinetics , Diterpenes/administration & dosage , Diterpenes/pharmacokinetics , Pneumonia/drug therapy , Administration, Inhalation , Administration, Intravenous , Aerosols/administration & dosage , Animals , Anti-Inflammatory Agents/blood , Biological Availability , Diterpenes/blood , Lung/drug effects , Male , Mice , Mice, Inbred BALB C , Models, Animal , Nebulizers and Vaporizers , Rats , Rats, Wistar
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