Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) induces a severe cytokine storm that may cause acute lung injury/acute respiratory distress syndrome (ALI/ARDS) with high clinical morbidity and mortality in infected individuals. Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid isolated and extracted from Stephania cepharantha Hayata. It exhibits various pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, and antiviral activities. The low oral bioavailability of CEP can be attributed to its poor water solubility. In this study, we utilized the freeze-drying method to prepare dry powder inhalers (DPI) for the treatment of acute lung injury (ALI) in rats via pulmonary administration. According to the powder properties study, the aerodynamic median diameter (Da) of the DPIs was 3.2 µm, and the in vitro lung deposition rate was 30.26; thus, meeting the Chinese Pharmacopoeia standard for pulmonary inhalation administration. We established an ALI rat model by intratracheal injection of hydrochloric acid (1.2 mL/kg, pH = 1.25). At 1 h after the model's establishment, CEP dry powder inhalers (CEP DPIs) (30 mg/kg) were sprayed into the lungs of rats with ALI via the trachea. Compared with the model group, the treatment group exhibited a reduced pulmonary edema and hemorrhage, and significantly reduced content of inflammatory factors (TNF-α, IL-6 and total protein) in their lungs (p < 0.01), indicating that the main mechanism of CEP underlying the treatment of ALI is anti-inflammation. Overall, the dry powder inhaler can deliver the drug directly to the site of the disease, increasing the intrapulmonary utilization of CEP and improving its efficacy, making it a promising inhalable formulation for the treatment of ALI.

Best practices for pediatricians in diagnosing and treating asthma

Additionally, they can treat atopic comorbidities such as atopic dermatitis, chronic urticaria, nasal polyps, eosinophilic esophagitis, and hypereosinophilic syndrome, resulting in improved quality of life for our patients. Parents should be made aware of its updated black box warning for possible effects on mental health and behavior changes,3 including but not limited to suicidal ideation. FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair);advises restricting use for allergic rhinitis.

Development of an Individualized Responsive Feeding Coaching Intervention

OBJECTIVES/GOALS: Responsive infant feeding (RIF) promotes healthy dietary patterns and infant weight gain. Research is needed to assist caregivers recognize infant hunger/satiety cues and overcome barriers to using RIF. The Learning Early Infant Feeding Cues (LEIFc) intervention was designed to fill this gap by using a validated coaching approach to promote RIF. METHODS/STUDY POPULATION: Guided by the Obesity-Related Behavioral Intervention Trials (ORBIT) model, this proof-of-concept study tests the feasibility and fidelity of the LEIFc intervention in mother-infant dyads (N=25). Study visits from the 3rd trimester of pregnancy to 4 months postpartum (PP) are conducted in family homes. Use of RIF via subjective (survey) and objective (video) measures is collected at 1 and 4 months PP. Prenatally written and video material on infant feeding and infant hunger/satiety cues is provided. At 2 and 3 months PP, coaching during a feeding session is provided by a trained interventionist using the SS-OO-PP-RR (super, Setting the Stage, Observation & Opportunities, Problem Solving & Planning, Reflection & Review) approach. Qualitative data on LEIFc are provided by the interventionist and participants. RESULTS/ANTICIPATED RESULTS: To date 25 dyads have been enrolled and 4 have completed all study visits. Preliminary analyses showed that subjective measure of awareness of infant cues increased post intervention (pre, M=4.38 vs post, M=4.63). LEIFc has been well accepted by participants including use of the SS-OO-PP-RR approach. Data suggests refinement to LEIFc is needed to include breastfeeding and mental health support as well as a longer duration of intervention through at least 6 months PP. An experienced interventionist is key to success of the research. All lost to follow-up (n=7) have occurred before the first PP visit suggesting that at study visit closer to birth is needed. Enrollment will continue through December 2022 and data collection through April 2023. DISCUSSION/SIGNIFICANCE: After refinement, the LEIFc intervention will be tested in a pilot RCT. The long-term goal is to implement LEIFc in the curricula of federally funded maternal-child home visiting programs who serve vulnerable populations;those that often have infant feeding practices that do not align with recommendations and are less likely to use RIF.

Formulation, Device, and Clinical Factors Influencing the Targeted Delivery of COVID-19 Vaccines to the Lungs.

The COVID-19 pandemic has proven to be an unprecedented health crisis in the human history with more than 5 million deaths worldwide caused to the SARS-CoV-2 and its variants ( https://www.who.int/emergencies/diseases/novel-coronavirus-2019 ). The currently authorized lipid nanoparticle (LNP)-encapsulated mRNA vaccines have been shown to have more than 90% vaccine efficacy at preventing COVID-19 illness (Baden et al. New England J Med 384(5):403-416, 2021; Thomas et al., 2021). In addition to vaccines, other small molecules belonging to the class of anti-viral and anti-inflammatory compounds have also been prescribed to reduce the viral proliferation and the associated cytokine storm. These anti-viral and anti-inflammatory compounds have also been shown to be effective in reducing COVID-19 exacerbations especially in reducing the host inflammatory response to SARS-CoV-2. However, all of the currently FDA-authorized vaccines for COVID-19 are meant for intramuscular injection directly into the systemic circulation. Also, most of the small molecules investigated for their anti-COVID-19 efficacy have also been explored using the intravenous route with a few of them explored for the inhalation route (Ramakrishnan et al. Lancet Respir Med 9:763-772, 2021; Horby et al. N Engl J Med 384(8):693-704, 2021). The fact that the SARS-CoV-2 enters the human body mainly via the nasal and airway route resulting in the lungs being the primary organs of infection as characterized by acute respiratory distress syndrome (ARDS)-mediated cytokine storm in the alveolar region has made the inhalation route gain significant attention for the purposes of targeting both vaccines and small molecules to the lungs (Mitchell et al., J Aerosol Med Pulm Drug Deliv 33(4):235-8, 2020). While there have been many studies reporting the safety and efficacy of targeting various therapeutics to the lungs to treat COVID-19, there is still a need to match the choice of inhalation formulation and the delivery device platform itself with the patient-related factors like breathing pattern and respiratory rate as seen in a clinical setting. In that perspective, this review aims to describe the various formulation and patient-related clinical factors that can play an important role in the judicious choice of the inhalation delivery platforms or devices for the development of inhaled COVID-19 vaccines.

Experiences and behaviours of patients with asthma requesting prescriptions from primary care during medication shortages linked to the COVID-19-lockdown: insights from a qualitative analysis of a UK asthma online community.

BACKGROUND: Inhaler shortages were reported in the UK following declaration of the COVID-19 pandemic, prompting advice against stockpiling. AIM: To understand experiences and behaviours of patients with asthma requesting prescriptions from primary care during asthma medication shortages. DESIGN & SETTINGS: UK asthma online community, between March and December 2020. METHOD: Thematic analysis of posts identified using search terms 'shortage', 'out of stock', 'prescribe' and 'prescription'. RESULTS: 66 participants were identified (46 adults, 2 parents of children with asthma, 18 unstated). Factors leading to increased requests included: stockpiling, early ordering, realising inhalers were out-of-date, and doctors prescribing multiple medication items. Patients' anxieties that could lead to stockpiling included fear of asthma attacks leading to admission and acquiring COVID-19 in hospital, lack of dose counters on some inhalers, and believing a lower amount of drug is delivered in the last actuations. Strategies adopted in relation to shortages or changes in treatment due to out-of-stock medications included starting stockpiling, ordering prescriptions early, contacting medical professionals for advice or alternative prescriptions, getting 'emergency prescriptions', ordering online or privately, seeking medications in different pharmacies, contacting drug manufacturers and keeping track of number of doses left in canisters. We found no evidence of anxiety-triggered asthma symptoms that required medications due to fear of COVID-19. Participants seemed to disregard advice against stock-piling. CONCLUSIONS: Better preparation is a key lesson from COVID-19. Clinicians, the pharmaceutical industry, and policy makers should use insights from this work to plan how to better manage medication shortages in future emergency situations.

Original Article Highlights From This Issue

Administration of biologics is not necessary to be postponed due to SARS-CoV-2 infection.Constant-Load Exercise Versus High-Intensity Interval Training on Aerobic Fitness in Moderate-to-Severe Asthma: A Randomized Controlled Trial Aparecido da Silva et al 2596 What is already known about this topic? Bronchiectasis is expected to worsen the clinical and functional outcomes in patients with asthma, but limited data are available regarding the long-term effects of bronchiectasis on the clinical course of asthma. Data from this large, prospective study translate the OCS-sparing effect of mepolizumab in patients with severe asthma reported across randomized, placebo-controlled trials into real-world clinical effectiveness when used alongside standard of care. [...]these risk factors are not of sufficient magnitude to warrant special measures regarding their vaccination.Assessment of Immediate Allergic Reactions After Immunization With the Pfizer BNT162b2 Vaccine Using Intradermal Skin Testing With the COVID-19 Vaccines Shavit et al 2677 What is already known about this topic?

Do you know when your inhaler is empty?

AimsThe presence of propellant in the metered dose inhalers (MDI) makes it challenging to identify when the inhaler is empty. Studies have shown that up to 86 actuations can be done just with the inhaler propellant after all the medication has been used up.1 Salbutamol, the commonly used inhaler in the UK do not have the dose counter. The National Institute for Health and Care Excellence (NICE) recommends medication review at clinic appointments.2 The Covid-19 pandemic has resulted in significant increase in remote consultations and monitoring brining out its own challenges in maintaining essential asthma care. We aimed to evaluate if patients identify when the inhaler is empty, clinical implications and the method of inhaler disposal.MethodsDesignProspective, multicentre quality improvement project in hospitals who are part of the West mIdlands Paedaitric Severe Asthma Network (WMPSAN). Data collected from children with asthma and other respiratory conditions at hospital visits.Outcome measuresChildren/carers attending hospital were asked how they identify an empty salbutamol inhaler, dose counters in the preventer inhalers and disposal practices were reviewed.ResultsData was collected from 157 children between October 2020 to September 2021. One hundred and seven (68.1%) were boys, the median age was 9.5 years (Interquartile Range IQR 2,15). One hundred and eighteen children (75.2%) had asthma, 19 (12.1%) preschool wheeze, 5 (3.2%) cystic fibrosis and 15 (9.5%) bronchiectasis. In children with asthma or PSW (n=137), median asthma attacks requiring emergency department visits within the last 12 months were 2 (IQR, 0-10) and High Dependency Unit (HDU) admissions were 0.5 (IQR 0,4).Eighty six (54.8%) said they were able to identify an empty inhaler correctly and seventy one (45.2%) were unsure/not aware. One hundred and five (69.9%) sought to identify medication left in the inhaler by shaking it and twenty seven (29.9%) looked for visible aerosol during actuation. Only three patients said that they will look at the dose counter and two actually kept count of actuations delivered.Inhaler technique was checked in 152/157 patients (96.8%) and was found to be satisfactory in 127/152 (83.5%). 138/157 brought a spacer device to the clinic and 127/138 (92%) were using an appropriate spacer for age.Neither the Salamol® or Ventolin® information leaflets contained any information on how to identify when 200 actuations had been performed. Symbicort® and Clenil® brands with dose counters had information on when to change the inhaler by looking at the number on the dose counter. Seretide® and Clenil® (without the dose counter) did not have any information regarding when to change the inhaler.ConclusionPatients cannot reliably identify when their inhaler is empty. Along with focus on inhaler technique and use of spacer device, guidance should be provided on how to identify an empty inhaler as part of essential asthma care.There is urgent need for health regulators to work with the pharmaceutical industry to ensure that all inhalers are manufactured with dose counters and support recycling.ReferencesRubin: Chest:2002.NICE asthma quality standards:2018.

POST COVID-19 PATIENTS’ REHABILITATION – POTENTIAL OF USING HALOTHERAPY IN THE FORM OF GENERALLY ACCESSIBLE INHALATORIA WITH DRY SALT AEROSOL

In the times of the ongoing COVID-19 pandemic and related cases of coronavirus infection with its complications affecting patients effective ways to relieve these symptoms are being searched. The article presents a review of publications on the effectiveness of inhalation with dry salt aerosol, one of the forms of halotherapy, in relation to the alleviation of symptoms of chronic respiratory diseases which often coincide with symptoms after COVID-19. The results of the analyzed studies show the effectiveness of halotherapy in the indicated form in relieving the symptoms of respiratory diseases such as dyspnoea or cough. More and more popular in Poland generally accessible inhalatoria with a dry salt aerosol can be considered as part of rehabilitation for patients after COVID-19. © 2021 by Polish Pharmaceutical Society.

Unnatural Cycles: Anthropogenic Disruption to Health and Planetary Functions

Natural cycles underpin the very stuff of life. In this commentary we consider unnatural cycles: that is, anthropogenic activities which have a circularity, but whose nature is to have a detrimental effect on human health, exacerbating existing problems. Natural cycles have feedback loops, some of which have recently come to light, with an understanding that everything is connected in some way. In health, feedback loops are imperative in homeostatic mechanisms. However, in the unnatural cycle the feedback loops serve to reinforce (and in some cases amplify) negative problems. We offer a commentary on an unnatural cycle moving from air quality to lung function and back to air quality;we call this the lung disease unnatural cycle. We suggest where links occur, and where wider consideration of interactions between various disciplines can lead to breaking this unnatural (or vicious) cycle, changing it to a healthy cycle where individual health can be improved, along with better global scale outcomes. We suggest that many activities within this unnatural cycle occur within silos. However, the improved cycle incorporates joint activities at geological, health, and financial levels, to the mutual benefit of all, breaking the unnatural cycle and improving health, life, and financial costs.

The present and future of inhalation therapy for the management of obstructive airway diseases: Emphasis on pressurized metered-dose inhalers

Inhalation therapy has an ancient history and has been recognized as the most effective and safe way of delivering pharmaceutical compounds directly to the airways for the treatment of respiratory diseases. Nowadays, a great variety of devices exist;nebulizers, soft mist inhalers (SMIs), pressurized Metered Dose Inhalers (pMDIs) and single- or multi-dose Dry Powder Inhalers (DPIs). The choice for the optimal device is patient-specific and depends on the advantages and disadvantages of each device category, and the patients' age and capacity to use them correctly. Factors that determine therapeutic success, apart from the previously mentioned, are: the physician-patient relationship, the patient's opinion, willingness, and preferences for certain medical devices, and proper training on device use. Various sources of evidence indicate that frequent change of devices is associated with treatment failure and should be avoided in order to achieve good therapeutic outcomes. The most frequently used types of inhalation devices for management of chronic and acute obstructive respiratory diseases are the pMDIs. Despite having some environmental footprint and requiring a good technique by the users to achieve reliable therapeutic effects, these devices are essential tools for primary care physicians and pulmonologists. In the COVID-19 era, and despite diametrically opposed opinions on the appropriateness of using nebulizers, most experts recommend against their use in order to reduce the potential risk of spreading the SARS-CoV-2 virus. If required, most experts recommend the use of pMDI via a spacer, except for life threatening exacerbations. The ongoing research, to improve the underlying technologies of these devices, introduce environmentally friendlier propellants and combine these devices with modern applications of telemedicine and artificial intelligence, creates new pathways for the continuous utilization of these inhalation devices in everyday clinical practice.

Treating COPD Patients with Inhaled Medications in the Era of COVID-19 and Beyond: Options and Rationales for Patients at Home.

COVID-19 has affected millions of patients, caregivers, and clinicians around the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads via droplets and close contact from person to person, and there has been an increased concern regarding aerosol drug delivery due to the potential aerosolizing of viral particles. To date, little focus has been given to aerosol drug delivery to patients with COVID-19 treated at home to minimize their hospital utilization. Since most hospitals were stressed with multiple admissions and experienced restricted healthcare resources in the era of COVID-19 pandemic, treating patients with COPD at home became essential to minimize their hospital utilization. However, guidance on how to deliver aerosolized medications safely and effectively to this patient population treated at home is still lacking. In this paper, we provide some strategies and rationales for device and interface selection, delivery technique, and infection control for patients with COPD who are being treated at home in the era of COVID-19 and beyond.

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.

Aerosol drug delivery to tracheotomized patients with COVID-19: Pragmatic suggestions for clinicians.

Because of the wide and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the number of hospitalized patients with coronavirus disease 2019 (COVID-19) has rapidly increased medically complex and resource-intensive treatment requirements in health care settings. Although tracheostomy is frequently needed for critically ill patients requiring extended mechanical ventilation, it has been described as an aerosol-generating procedure that puts health care professionals at an increased risk of viral transmission. In addition, the delivery of aerosolized medications to this patient population has become controversial because of concerns on the transmission of SARS-CoV-2 via droplets. Although aerosol therapy in spontaneously breathing patients with COVID-19 was described in recent publications, innovations in aerosol drug delivery to COVID-19 patients with tracheostomy have not been presented. Therefore, empirically based guidance on how to deliver aerosols safely and effectively to tracheotomized patients with COVID-19 is still lacking. This paper provides recommendations and rationales for device selection, interface selection, delivery techniques, and infection control based on the evolving body of literature.

Impact of COVID-19 on corticosteroids and antibiotics prescribing in England: an interrupted time series analysis.

Inhaled corticosteroids (ICS), prednisolone and antibiotics all play a crucial role in the management of respiratory diseases. The aim of this study was to analyse whether the declaration of the COVID-19 pandemic affected prescribing rates, as public health measures were implemented to reduce transmission of SARS-CoV-2. Monthly practise-level prescribing data published by NHS Digital were analysed. At the point, the COVID-19 outbreak was declared a pandemic, ICS prescriptions rose significantly. This was followed by a decrease in ICS and prednisolone prescribing in the following months. There was no difference in the antibiotic prescribing trend.

Guidance on nebulization during the current COVID-19 pandemic.

Awareness of the risk of airborne transmission of SARS-CoV-2 makes patients hesitant about using inhaled medications that are considered as a potential source of viral transmission and immunosuppression. However, patients with asthma or COPD should continue all prescribed inhaled medications. Apparently, inhalers, including pMDIs, DPIs, or SMIs, have a low risk of contamination although characteristics of drug formulation can precipitate cough, whereas some researchers do not rule out the probability that nebulizer treatments may increase the risk of infection transmission via droplet nuclei and aerosols. Considering that aerosol therapy generates fugitive emissions that are not inhaled by the patient and are released from the device during expiration, several international professional bodies have provided recommendations for drug delivery via inhalers and in particular, nebulizers. Unfortunately, these recommendations are often in conflict with each other and do not clarify whether it is appropriate to use nebulizers during this COVID-19 pandemic. Considering what is available in literature, there are no known infection-related hazards to an uninfected patient and also a patient with COVID-19 that preclude the use of a nebulizer at home, but it fundamental that all patients, regardless of whether or not suffering from COVID-19, always follow some practical advices.

Asthma and COVID-19: In Defense of Evidence-Based SABA.

There have recently been major objections to the use of short-acting beta-agonist (SABA) in episodic acute asthma culminating in a call for replacing SABA with combination of inhaled corticosteroids and long-acting beta-agonists despite little evidence supporting this point of view. It is regrettable to note that this attack on SABA occurs in the midst of an unprecedented demand for, and shortage of, SABA inhalers during the current COVID-19 pandemic, and the worldwide efforts to increase SABA supplies. In this commentary, we defend the well-established role of SABA and argue that the call for the phase out of SABA is inappropriate, since it is not solidly evidence based.

Sterilization plan of the used metered dose inhalers (MDI) to avoid wastage amid COVID-19 pandemic drug shortage.

Background Coronavirus is causing a shortage of critical inhalers needed by patients with Asthma and respiratory illness. Patients with Asthma are at higher risk if they tract the novel Coronavirus. As the coronavirus continues to spread, hospitals are turning to use more salbutamol MDI. Salbutamol MDI has become the line of defence for physicians in the emergency room who are treating patients with Corona Virus Disease 2019 (COVID-19) and have respiratory distress .[Hui et al 2020 ,and Center for Drug Evaluation and Research 2020] During the COVID pandemic, there has been a drastic increase in the use of MDI inhalers; therefore, it led to a decrease in availability and a break in the supply chain. Patients with Asthma are at higher risk if they tract the novel Coronavirus, and an inhaler could be a life or death for them. As the coronavirus continues to spread, hospitals are turning to use more salbutamol Metered Dose inhaler (MDI). Salbutamol MDI is now on short supply as the COVID-19 continues to spread. Salbutamol MDI has become the line of defence for physicians in the emergency room who are treating patients with COVID-19 and have respiratory distress. The current shortage of salbutamol MDI could be a result of stockpiling and hoarding of this life-saving inhaler. That had led to a critical shortage of Salbutamol MDI, and even the case shortage continues with some other alternatives such as Ipratropium MDI and even with long-acting B-agonists such as Salmeterol and Formoterol which also starting to have a limitation on ordering these agents. Coronavirus sparks fear of medication shortage. Coronavirus panic-buying also may have led to a shortage of critical inhalers. We have also got elderly patients with COPD who may need Ventolin MDI and also premature babies who may have caught Respiratory Syncytial Virus (RSV) and need salbutamol MDI to support their lungs have since been compromised, and they rely heavily on Asthma inhalers. Finding a safe and creative strategy is essential during the COVID-19 pandemic.