Autoimmune pulmonary alveolar proteinosis in an adolescent girl with rapidly progressive dyspnea

Autoimmune pulmonary alveolar proteinosis (PAP) is a rare disease, especially in pediatrics, but important to consider, as it may avoid unnecessary and/or invasive investigations and delayed diagnosis. This case report highlights an adolescent girl with rapid onset dyspnea but an unremarkable physical exam and initial testing. However, due to a high index of suspicion, a chest computed tomography (CT) scan was done, revealing a "crazy paving" pattern, which then prompted expedited assessment. This finding, however, is not as specific as often discussed and has a broad differential diagnosis, which will be reviewed in detail as part of this case. Furthermore, this report demonstrates a diagnostic approach for PAP that avoids lung biopsy, previously considered to be required for diagnosis of PAP, but is increasingly becoming unnecessary with more advanced blood tests and understanding of their sensitivity and specificity. Additionally, management strategies for PAP will be briefly discussed.Copyright © 2022 Canadian Thoracic Society.

Respiratory support for adult patients with COVID-19

The COVID-19 pandemic is creating unique strains on the healthcare system. While only a small percentage of patients require mechanical ventilation and ICU care, the enormous size of the populations affected means that these critical resources may become limited. A number of non-invasive options exist to avert mechanical ventilation and ICU admission. This is a clinical review of these options and their applicability in adult COVID-19 patients. Summary recommendations include: (1) Avoid nebulized therapies. Consider metered dose inhaler alternatives. (2) Provide supplemental oxygen following usual treatment principles for hypoxic respiratory failure. Maintain awareness of the aerosol-generating potential of all devices, including nasal cannulas, simple face masks, and venturi masks. Use non-rebreather masks when possible. Be attentive to aerosol generation and the use of personal protective equipment. (3) High flow nasal oxygen is preferred for patients with higher oxygen support requirements. Non-invasive positive pressure ventilation may be associated with higher risk of nosocomial transmission. If used, measures special precautions should be used reduce aerosol formation. (4) Early intubation/mechanical ventilation may be prudent for patients deemed likely to progress to critical illness, multi-organ failure, or acute respiratory distress syndrome (ARDS).Copyright © 2020 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of the American College of Emergency Physicians.

Aerosol Medication Use in COVID-19 Pandemic

Administration of aerolized drugs to patients diagnosed with COVID-19 leads to the risk of transmission of patient-generated infectious aerosols to healthcare providers.While the COVID-19 pandemic is ongoing, in order to provide the best treatment for patients and at the same time to protect healthcare providers at the highest level, it is necessary to increase access to information and pay maximum attention to preventive measures.Copyright © 2020 Bilimsel Tip Yayinevi. All rights reserved.

Delivery of Epinephrine by Metered-Dose Inhaler for the Treatment of Croup in Children

Study Objective: Croup, also known as laryngotracheobronchitis, is a common pediatric presentation in the emergency department. When children present with moderate or severe croup, epinephrine, either racemic or L-isomer, given by nebulization is considered standard of care. Since the beginning of the SARS-CoV-2 pandemic, many medical institutions have moved away from the delivery of medications by nebulization whenever possible in order to prevent aerosolization of the SARS-CoV-2 virus and infecting others in close proximity. Delivery of respiratory medication by metered-dose inhaler (MDI) was the most commonly adopted method to replace nebulization. Primatene MIST (Armstrong Pharmaceuticals) is an over-the-counter, L-epinephrine MDI. In February 2021, the Pediatric Service Line Pharmacy and Therapeutics Committee of the Northwell Health system approved the use of Primatene MIST in children >= 1 years old presenting to the emergency department with croup as an alternative to nebulized epinephrine. We aim to demonstrate that L-epinephrine administered by MDI is safe and effective in children presenting with moderate croup. Study Design/Methods: We conducted a single-center retrospective chart review study of children 1 to 17 years of age who presented to the emergency department at Cohen Children's Medical Center and were evaluated for suspected croup from March 2021 until May 2022. As part of a surveillance and later reapproval process by the Pediatric Service Line Pharmacy and Therapeutics Committee of the Northwell Health system for Primatene MIST, data was prospectively collected and entered into a REDCap database. This included Westley Croup Score, requirement of additional doses of epinephrine, adverse events, disposition, and return within 48 hours. During the initial rollout, eligible patients were administered 4 puffs through an attached spacer. Following safety review, dosing was increased to 6 puffs. Result(s): A total of 24 pediatric patients with croup received Primatene MIST. The mean age was 3.3 years (SD:2.3 years) and 75% were male. Of the 16 patients who had respiratory viral testing, 19% tested positive for SARS-CoV-2 virus. The median Westley Croup Scores at presentation was 3 (IQR:2,3;Range:2-5), 0 (IQR:0,1;Range:0-4) at 30 minutes and 0 (IQR:0,1;Range:0-3) at 120 minutes following Primatene MIST administration. A second dose of epinephrine (nebulized or MDI) was administered to 7 patients (29.2%;CI:14.9%-49.2%). Only 1 patient (4.2%) was admitted and 1 (4.2%) returned within 48 hours. There were no reported adverse events. Conclusion(s): Epinephrine administered by MDI is a safe and effective treatment for moderate croup. It should be considered as an alternative to nebulized epinephrine when there are concerns for infectious aerosolization. No, authors do not have interests to disclose Copyright © 2022

Oral inhalation of cannabidiol delivered from a metered dose inhaler to alleviate cytokine production induced by SARS-CoV-2 and pollutants.

Cannabidiol (CBD) was formulated as a metered dose inhaler (CBD-MDI) and evaluated in vitro for its efficacy as an inhaled dosage form against inflammation caused by the SARS-CoV-2 virus, lipopolysaccharide (LPS) from Escherichia coli, silica particles, nicotine, and coal tar. A CBD-MDI formulation was prepared with 50 mg of CBD in 10 mL for a CBD dose of 250 µg/puff. The formulation ingredients included CBD, absolute ethanol as a cosolvent, and HFA-134a as the propellant. High aerosol performance of CBD-MDI was obtained with mass median aerodynamic diameter of 1.25 ± 0.01 µm, geometric standard deviation of 1.75 ± 0.00, emitted dose of 244.7 ± 2.1 µg, and fine particle dose of 122.0 ± 1.6 µg. The cytotoxicity and anti-inflammatory effectiveness of CBD-MDI were performed in alveolar macrophage (NR8383) and co-culture of alveolar macrophage (NR8383) and human lung adenocarcinoma (A549) cell line. CBD delivered from an MDI was safe on respiratory cells and did not trigger an immune response in alveolar macrophages. CBD-MDI effectively reduced the generation of cytokines in immune cells treated with viral antigen S-RBD, bacterial antigen LPS, silica particles, and coal tar. The efficacy of CBD-MDI was comparable to budesonide. Furthermore, the findings demonstrated that the use of CBD-MDI was more effective in treatment rather than prevention when inflammation was induced by either a viral or bacterial stimulant.

A Retrospective Review of an Inhaler to Nebulizer Therapeutic Interchange Program Across a Health System.

BACKGROUND: The hospitals of the Saint Alphonsus Health System (SAHS) have implemented a metered dose inhaler (MDI) to nebulization therapeutic interchange program in which all orders for albuterol/ipratropium and inhaled corticosteroid/long-acting beta agonists (ICS/LABA) MDIs are therapeutically interchanged to nebulizers by pharmacy. OBJECTIVES: The primary outcome measure is to assess the percent of albuterol/ipratropium and ICS/LABA inhalers therapeutically interchanged to nebulized solutions. Secondary outcomes include assessment of readmission rates, the percentage of patients discharged with the appropriate MDI, and a financial analysis of the implementation of the therapeutic interchange program. METHODS: This retrospective observational cohort study was approved by the system's institutional review board and conducted between October 15, 2019, and February 15, 2020. Adult patients with history of asthma or COPD admitted to one of the SAHS hosptials with an order placed for ipratropium/albuterol, fluticasone/salmeterol, mometasone/formoterol, or budesonide/formoterol MDIs were eligible for inclusion. Patients were excluded if they were presumed to have or tested positive for COVID-19. RESULTS: Therapeutic interchanges were successfully completed in 94.3% of the orders included in this evaluation. Discharge discrepancies occurred in 14.3% of orders assessed. No correlation was found between discharge discrepancies and 30-day readmissions. The MDI to nebulized solution interchanges saved $13,908.16 in medication cost in the sample population. CONCLUSION: The first phase of implementing the SAHS inhaler to nebulizer therapeutic interchange program was operationally and clinically successful. The program is projected to continue to reduce medication waste and provide cost savings for the health system.

Powder characterisation: A critical tool for the evolution of inhaled drug delivery

In this article, Jamie Clayton, Operations Director at Freeman Technology, and Joana Pinto, PhD, Senior Scientist, and Sarah Zellnitz, PhD, Senior Scientist, both of Research Center Pharmaceutical Engineering’s Area II – Advanced Products & Delivery section, discuss the benefits of multi-faceted powder characterisation in dry powder inhalation formulations and how it can support efforts to achieve net zero emissions.

The Potential Use of Cyclosporine Ultrafine Solution Pressurised Metered- Dose Inhaler in the Treatment of COVID-19 Patients.

INTRODUCTION: Serious COVID-19 respiratory problems start when the virus reaches the alveolar level, where type II cells get infected and die. Therefore, virus inhibition at the alveolar level would help preventing these respiratory complications. METHOD: A literature search was conducted to collect physicochemical properties of small molecule compounds that could be used for the COVID-19 treatment. Compounds with low melting points were selected along with those soluble in ethanol, hydrogen-bond donors, and acceptors. RESULTS: There are severe acute respiratory syndrome coronavirus inhibitors with physicochemical properties suitable for the formulation as an ultrafine pressurised metered-dose inhaler (pMDI). Mycophenolic acid, Debio 025, and cyclosporine A are prime candidates among these compounds. Cyclosporine A (hereafter cyclosporine) is a potent SARS-CoV-2 inhibitor, and it has been used for the treatment of COVID-19 patients, demonstrating an improved survival rate. Also, inhalation therapy of nebulised cyclosporine was tolerated, which was used for patients with lung transplants. Finally, cyclosporine has been formulated as a solution ultrafine pMDI. Although vaccine therapy has started in most countries, inhalation therapies with non-immunological activities could minimise the spread of the disease and be used in vaccine-hesitant individuals. CONCLUSION: Ultrafine pMDI formulation of cyclosporine or Debio 025 should be investigated for the inhalation therapy of COVID-19.

Evaluation of Aerosol Drug Delivery Options during Adult Mechanical Ventilation in the COVID-19 Era.

Drug delivery devices used for aerosol therapy during mechanical ventilation to ease the symptoms of respiratory diseases provide beneficial treatment but can also pose challenges. Reflecting the significant changes in global guidance around aerosol usage and lung-protective ventilation strategies, seen in response to the COVID-19 pandemic, for the first time, we describe the drug delivery performance of commonly used devices under these conditions. Here, vibrating mesh nebuliser (VMN), jet nebuliser (JN) and pressurised metered-dose inhaler (pMDI) performance was assessed during simulated adult mechanical ventilation. Both standard test breathing patterns and those representatives of low tidal volume (LTV) ventilation with concurrent active and passive humidification were investigated. Drug delivery using a VMN was significantly greater than that with a JN and pMDI for both standard and LTV ventilation. Humidification type did not affect the delivered dose across all device types for standard ventilation. Significant variability in the pMDI dosing was evident, depending on the timing of actuation and the adapter type used. pMDI actuation synchronised with inspiration resulted in a higher delivered drug dose. The type of adapter used for pMDI actuation influenced drug delivery, with the highest dose observed using the CombiHaler.

An in vitro visual study of fugitive aerosols released during aerosol therapy to an invasively ventilated simulated patient.

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.

[Evaluation of Valved Holding Chambers Simulating Repurposing Use of Ciclesonide Metered-dose Inhaler by Patients with Pneumonia].

Achieving appropriate inhalation in patients with coronavirus disease 2019 (COVID-19) is a common challenge in the use of repurposed metered-dose inhaler (MDI) formulations. The purpose of this study was to evaluate the effect of five valved holding chambers (VHCs) on the inhalation of ciclesonide from Alvesco MDI. The aerodynamic particle size distribution of ciclesonide discharged from Alvesco MDI was evaluated using a Next Generation Impactor in the presence and absence of VHCs. The use of VHCs retained or slightly increased the amount of ciclesonide in the fine particle diameter range (aerodynamic particle size below 3 µm) (FPD) and reduced the amount at the induction port after coordinated inhalation. However, the use of VHC reduced the FPD of the formulation by increasing the time between the MDI discharge and the pump suction by various degrees among the five VHCs. These results indicated that use of the VHCs and minimizing the inhalation delay time should ensure sufficient inhalation of ciclesonide particles.

Homemade valved holding chambers for children with airway hyperresponsiveness: A randomized crossover trial.

BACKGROUND: During the COVID-19 pandemic, a metered-dose inhaler (MDI) with a valved holding chamber (VHC) is a preferred route of bronchodilator delivery. We have developed a new homemade VHC, made of a paper coffee cup, and a drinking water bottle. This study was conducted to compare the bronchodilator response in children with airway hyperresponsiveness after the use of our homemade VHC and that of a standard commercial one. METHODS: In a randomized, two-period, two-sequence crossover trial, we recruited 20 children, aged 6-15 years, who had a greater than 12% increase in FEV1 after inhaled salbutamol. They were randomized into Group A and B. Group A used our VHC on the first day and Aerochamber® on the second day. Group B used the same VHCs but in alternate sequence. Spirometries were performed before and after 400 µg of salbutamol, MDI was administered via those VHCs. RESULTS: Baseline demographic data and spirometric values did not have statistically significant differences between group A and B and between the first and second day (p > .05). After giving salbutamol MDI, both VHCs produced significant increases in FVC, FEV1 , and FEF25-75% (p < .005). The improvement in FEV1 did not significantly differ between our homemade VHC and Aerochamber® (p > .05). CONCLUSION: Our homemade VHC is effective for an MDI bronchodilator delivery. Since it is very cheap and easy to make, it may be used as a disposable device to minimize airborne transmission especially when commercial VHC is not available.

Approach to childhood asthma in the era of COVID-19: The official statement endorsed by the Saudi Pediatric Pulmonology Association (SPPA).

Coronaviruses are a large family of viruses that infect humans, which may result in mild symptoms similar to those of the common cold. COVID-19 is most recent subtype similar or even worse than the two previous pandemic strains which were the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). The first cases of COVID-19 emerged in December 2019. Since then, the virus causing the disease has infected more than four million people around the globe and led to hundreds of thousands deaths. We think addressing the management of asthma in the era of this pandemic is important for several reasons: high prevalence of asthma in Saudi Arabia, further, majorities were uncontrolled disease. The statement will provide special instructions and answers to common questions of physicians dealing with asthmatic children during this pandemic.