The association of preexisting severe asthma with COVID-19 outcomes.

PURPOSE OF REVIEW: Three years after the emergence of coronavirus disease 2019 (COVID-19), many studies have examined the association between asthma and COVID-related morbidity and mortality, with most showing that asthma does not increase risk. However, the U.S. Centers for Disease Control (CDC) currently suggests that patients with severe asthma may, nonetheless, be particularly vulnerable to COVID-19-related morbidity. RECENT FINDINGS: With respect to poor COVID-19 outcomes, our search yielded nine studies that quantified associations with severe asthma, seven that considered use of monoclonal antibodies (mAB), and 14 that considered inhaled corticosteroids (ICS) use. mAb and ICS use have been used as measures of severe asthma in several studies. Severe asthma was significantly associated with poor COVID-19 outcomes. The results for mAb and ICS were mixed. SUMMARY: An increased risk of poor COVID-19 outcomes in patients with severe asthma is possible. However, these studies remain sparse and suffer from several methodological limitations that hinder their interpretation. Additional evidence is needed to provide clear, cogent guidance for health agencies seeking to inform patients with asthma about potential risks due to COVID-19.

Asthma in Adult Patients with COVID-19. Prevalence and Risk of Severe Disease.

Rationale: Health outcomes of people with coronavirus disease (COVID-19) range from no symptoms to severe illness and death. Asthma, a common chronic lung disease, has been considered likely to increase the severity of COVID-19, although data addressing this hypothesis have been scarce until very recently.Objectives: To review the epidemiologic literature related to asthma's potential role in COVID-19 severity.Methods: Studies were identified through the PubMed (MEDLINE) and medRxiv (preprint) databases using the search terms "asthma," "SARS-CoV-2" (severe acute respiratory syndrome coronavirus 2), and "COVID-19," and by cross-referencing citations in identified studies that were available in print or online before December 22, 2020.Measurements and Main Results: Asthma prevalence data were obtained from studies of people with COVID-19 and regional health statistics. We identified 150 studies worldwide that allowed us to compare the prevalence of asthma in patients with COVID-19 by region, disease severity, and mortality. The results of our analyses do not provide clear evidence of increased risk of COVID-19 diagnosis, hospitalization, severity, or mortality due to asthma.Conclusions: These findings could provide some reassurance to people with asthma regarding its potential to increase their risk of severe morbidity from COVID-19.

A narrative review on trans-nasal pulmonary aerosol delivery.

The use of trans-nasal pulmonary aerosol delivery via high-flow nasal cannula (HFNC) has expanded in recent years. However, various factors influencing aerosol delivery in this setting have not been precisely defined, and no consensus has emerged regarding the optimal techniques for aerosol delivery with HFNC. Based on a comprehensive literature search, we reviewed studies that assessed trans-nasal pulmonary aerosol delivery with HFNC by in vitro experiments, and in vivo, by radiolabeled, pharmacokinetic and pharmacodynamic studies. In these investigations, the type of nebulizer employed and its placement, carrier gas, the relationship between gas flow and patient's inspiratory flow, aerosol delivery strategies (intermittent unit dose vs continuous administration by infusion pump), and open vs closed mouth breathing influenced aerosol delivery. The objective of this review was to provide rational recommendations for optimizing aerosol delivery with HFNC in various clinical settings.

Guidance on Mitigating the Risk of Transmitting Respiratory Infections During Nebulization by the COPD Foundation Nebulizer Consortium.

BACKGROUND: Nebulizers are used commonly for inhaled drug delivery. Because they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The COVID-19 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures. However, evidence supporting the increased risk of disease transmission with nebulized treatments is inconclusive, and inconsistent guidelines and differing opinions have left uncertainty regarding their use. Many clinicians opt for alternative devices, but this practice could impact outcomes negatively, especially for patients who may not derive full treatment benefit from handheld inhalers. Therefore, it is prudent to develop strategies that can be used during nebulized treatment to minimize the emission of fugitive aerosols, these comprising bioaerosols exhaled by infected individuals and medical aerosols generated by the device that also may be contaminated. This is particularly relevant for patient care in the context of a highly transmissible virus. RESEARCH QUESTION: How can potential risks of infections during nebulization be mitigated? STUDY DESIGN AND METHODS: The COPD Foundation Nebulizer Consortium (CNC) was formed in 2020 to address uncertainties surrounding administration of nebulized medication. The CNC is an international, multidisciplinary collaboration of patient advocates, pulmonary physicians, critical care physicians, respiratory therapists, clinical scientists, and pharmacists from research centers, medical centers, professional societies, industry, and government agencies. The CNC developed this expert guidance to inform the safe use of nebulized therapies for patients and providers and to answer key questions surrounding medication delivery with nebulizers during pandemics or when exposure to common respiratory pathogens is anticipated. RESULTS: CNC members reviewed literature and guidelines regarding nebulization and developed two sets of guidance statements: one for the health care setting and one for the home environment. INTERPRETATION: Future studies need to explore the risk of disease transmission with fugitive aerosols associated with different nebulizer types in real patient care situations and to evaluate the effectiveness of mitigation strategies.

The 2023 GOLD Report: Updated Guidelines for Inhaled Pharmacological Therapy in Patients with Stable COPD.

Over the past 22 years, annual GOLD Reports have documented important changes in guidance and recommendations for uniformly treating patients with chronic obstructive pulmonary disease (COPD) with the goal of improving outcomes in patients suffering from this condition. The most recent GOLD Report, released in 2023, shows continued refinement in several areas, including more precise definitions of COPD and exacerbations of COPD, a new set of parameters to assess exacerbation severity, an updated COPD assessment tool, updated guidelines for initial and follow-up treatment, new information regarding the association between pharmacological triple therapy and reduction in mortality, and new discussions of inhaler device choice and adherence to COPD medications. Whereas we do not address all of the new or updated material in GOLD's 2023 Report, we summarize key changes in GOLD's recommendations regarding inhalation therapy for stable COPD and frame these changes in the context of previous GOLD recommendations.

In Vitro Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler.

Background: Dry powder inhalers (DPIs) require patients to impart sufficient energy through inhalation to ensure adequate dose emission, medication deaggregation, and resultant particle sizes suitable for lung deposition. There is an ongoing debate regarding the level of inspiratory effort, and therefore inspiratory flow rate, needed for optimal dose delivery from DPIs. Materials and Methods: The delivered dose (DD) and fine particle fraction (FPF) for each component of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg and FF/UMEC/VI 200/62.5/25 µg ELLIPTA DPIs were assessed at flow rates of 30, 60, and 90 L/min. Electronic lung (eLung) (eLung; an electronic breathing simulator) assessments were conducted to replicate inhalation profiles representing a wide range of inhalation parameters and inhaled volumes achieved by patients with chronic obstructive pulmonary disease (COPD) or asthma of all severity levels. Timing and duration of dose emission were assessed using a particle detector located at the entrance of an anatomical throat cast attached to the eLung. Results: During DD assessment, a mean of >80% of the nominal blister content (nbc) was emitted from the ELLIPTA DPI at all flow rates. In Next Generation Impactor assessments, the observed mean DD across flow rates for FF/UMEC/VI 100/62.5/25 µg ranged from 85.9% to 97.0% of nbc and 84.0% to 93.5% for FF/UMEC/VI 200/62.5/25 µg. In eLung assessments, 82.8% to 95.5% of nbc was delivered across the PIF range, 43.5 to 129.9 L/min (COPD), and 85.1% to 92.3% across the PIF range, 67.4 to 129.9 L/min (asthma). The FPF (mass <5 µm; % nbc) for each component was comparable across all flow rates and inhalation profiles. Dose emission timings indicated that near-complete dose emission occurs before reaching PIF. Conclusions: Dose delivery assessments across all flow rates and inhalation profiles indicate that patients with all severity levels of COPD or asthma can achieve the required inspiratory effort for efficient delivery of all components of FF/UMEC/VI from the ELLIPTA DPI. Dose emission profiles suggest rapid and near-complete dose delivery from the ELLIPTA DPI before reaching PIF.

Aerosol therapy in adult critically ill patients: a consensus statement regarding aerosol administration strategies during various modes of respiratory support.

BACKGROUND: Clinical practice of aerosol delivery in conjunction with respiratory support devices for critically ill adult patients remains a topic of controversy due to the complexity of the clinical scenarios and limited clinical evidence. OBJECTIVES: To reach a consensus for guiding the clinical practice of aerosol delivery in patients receiving respiratory support (invasive and noninvasive) and identifying areas for future research. METHODS: A modified Delphi method was adopted to achieve a consensus on technical aspects of aerosol delivery for adult critically ill patients receiving various forms of respiratory support, including mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula. A thorough search and review of the literature were conducted, and 17 international participants with considerable research involvement and publications on aerosol therapy, comprised a multi-professional panel that evaluated the evidence, reviewed, revised, and voted on recommendations to establish this consensus. RESULTS: We present a comprehensive document with 20 statements, reviewing the evidence, efficacy, and safety of delivering inhaled agents to adults needing respiratory support, and providing guidance for healthcare workers. Most recommendations were based on in-vitro or experimental studies (low-level evidence), emphasizing the need for randomized clinical trials. The panel reached a consensus after 3 rounds anonymous questionnaires and 2 online meetings. CONCLUSIONS: We offer a multinational expert consensus that provides guidance on the optimal aerosol delivery techniques for patients receiving respiratory support in various real-world clinical scenarios.

Aerosol drug delivery: developments in device design and clinical use.

Aerosolised drugs are prescribed for use in a range of inhaler devices and systems. Delivering drugs by inhalation requires a formulation that can be successfully aerosolised and a delivery system that produces a useful aerosol of the drug; the particles or droplets need to be of sufficient size and mass to be carried to the distal lung or deposited on proximal airways to give rise to a therapeutic effect. Patients and caregivers must use and maintain these aerosol drug delivery devices correctly. In recent years, several technical innovations have led to aerosol drug delivery devices with efficient drug delivery and with novel features that take into account factors such as dose tracking, portability, materials of manufacture, breath actuation, the interface with the patient, combination therapies, and systemic delivery. These changes have improved performance in all four categories of devices: metered dose inhalers, spacers and holding chambers, dry powder inhalers, and nebulisers. Additionally, several therapies usually given by injection are now prescribed as aerosols for use in a range of drug delivery devices. In this Review, we discuss recent developments in the design and clinical use of aerosol devices over the past 10-15 years with an emphasis on the treatment of respiratory disorders.

The role of nebulized therapy in the management of COPD: evidence and recommendations.

Current guidelines recommend inhalation therapy as the preferred route of drug administration for treating chronic obstructive pulmonary disease (COPD). Previous systematic reviews in COPD patients found similar clinical outcomes for drugs delivered by handheld inhalers - pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs) - and nebulizers, provided the devices were used correctly. However, in routine clinical practice critical errors in using handheld inhalers are highly prevalent and frequently result in inadequate symptom relief. In comparison with pMDIs and DPIs, effective drug delivery with conventional pneumatic nebulizers requires less intensive patient training. Moreover, by design, newer nebulizers are more portable and more efficient than traditional jet nebulizers. The current body of evidence regarding nebulizer use for maintenance therapy in patients with moderate-to-severe COPD, including use during exacerbations, suggests that the efficacy of long-term nebulizer therapy is similar, and in some respects superior, to that with pMDI/DPIs. Therefore, despite several known drawbacks associated with nebulized therapy, we recommend that maintenance therapy with nebulizers should be employed in elderly patients, those with severe disease and frequent exacerbations, and those with physical and/or cognitive limitations. Likewise, financial concerns and individual preferences that lead to better compliance may favor nebulized therapy over other inhalers. For some patients, using both nebulizers and pMDI/DPI may provide the best combination of efficacy and convenience. The impact of maintenance nebulizer treatment on other relevant clinical outcomes in patients with COPD, especially the progressive decline in lung function and frequency of exacerbations, needs further investigation.

Aerosol-Generating Procedures and Virus Transmission.

During the early phase of the COVID-19 pandemic, many respiratory therapies were classified as aerosol-generating procedures. This categorization resulted in a broad range of clinical concerns and a shortage of essential medical resources for some patients. In the past 2 years, many studies have assessed the transmission risk posed by various respiratory care procedures. These studies are discussed in this narrative review, with recommendations for mitigating transmission risk based on the current evidence.

Microbiome Profiles of Nebulizers in Hospital Use.

Background: Nebulizers are used to provide treatment to respiratory patients. Concerns over nosocomial infection risks from contaminated nebulizers raise the critical need to identify all microbial populations in nebulizers used by patients. However, conventional culture-dependent techniques are inadequate with the ability to identify specific microbial populations only. Therefore, the aims of this study were to acquire complete profiles of microbiomes in nebulizers used by in-patients with culture-independent high-throughput sequencing and identify sources of microbial contaminants for the development of effective practices to reduce microbial contamination in nebulizer devices. Methods: This study was conducted at the University of Tennessee Medical Center in Knoxville, TN. Nebulizers were collected between May 2018 and October 2018 from inpatients admitted to the floors for pneumonia or chronic obstructive pulmonary disease exacerbations. Nebulizers were sampled for 16S rRNA gene-based amplicon sequencing to profile nebulizer microbiomes and perform phylogenetic analysis. A Bayesian community-wide culture-independent microbial source tracking technique was used to quantify the contribution of human-associated microbiota as potential sources of nebulizer contamination. Results: Culture-independent sequencing detected diverse microbial populations in nebulizers, represented by 18 abundant genera. Stenotrophomonas was identified as the most abundant genus, accounting for 12.4% of the nebulizer microbiome, followed by Rhizobium, Staphylococcus, Streptococcus, and Ralstonia. Phylogenetic analysis revealed the presence of multiple phylotypes with close relationship to potential pathogens. Contributing up to 15% to nebulizer microbiomes, human-associated microbiota was not identified as the primary sources of nebulizer contamination. Conclusion: Culture-independent sequencing was demonstrated to be capable of acquiring comprehensive profiles of microbiomes in nebulizers used by in-patients. Phylogenetic analysis identified differences in pathogenicity between closely related phylotypes. Microbiome profile-enabled community-wide culture-independent microbial source tracking suggested greater importance of environmental sources than human sources as contributors to nebulizer microbiomes, providing important insight for the development of effective strategies for the monitoring and control of nebulizer devices to mitigate infection risks in the hospital.

Mitigating Fugitive Aerosols During Aerosol Delivery via High-Flow Nasal Cannula Devices.

BACKGROUND: Aerosol delivery via high-flow nasal cannula (HFNC) has attracted clinical interest in recent years. However, both HFNC and nebulization are categorized as aerosol-generating procedures (AGPs). In vitro studies raised concerns that AGPs had high transmission risk. Very few in vivo studies examined fugitive aerosols with nebulization via HFNC, and effective methods to mitigate aerosol dispersion are unknown. METHODS: Two HFNC devices (Airvo 2 and Vapotherm) with or without a vibrating mesh nebulizer were compared; HFNC alone, surgical mask over HFNC interface, and HFNC with face tent scavenger were used in a random order for 9 healthy volunteers. Fugitive aerosol concentrations at sizes of 0.3-10.0 µm were continuously measured by particle sizers placed at 1 and 3 ft from participants. On a different day, 6 of the 9 participants received 6 additional nebulizer treatments via vibrating mesh nebulizer or small-volume nebulizer (SVN) with a face mask or a mouthpiece with/without an expiratory filter. In vitro simulation was employed to quantify inhaled dose of albuterol with vibrating mesh nebulizer via Airvo 2 and Vapotherm. RESULTS: Compared to baseline, neither HFNC device generated higher aerosol concentrations. Compared to HFNC alone, vibrating mesh nebulizer via Airvo 2 generated higher 0.3-1.0 µm particles (all P < .05), but vibrating mesh nebulizer via Vapotherm did not. Concentrations of 1.0-3.0 µm particles with vibrating mesh nebulizer via Airvo 2 were similar with vibrating mesh nebulizer and a mouthpiece/face mask but less than SVN with a mouthpiece/face mask (all P < .05). Placing a surgical mask over HFNC during nebulization reduced 0.5-1.0 µm particles (all P < .05) to levels similar to the use of a nebulizer with mouthpiece and expiratory filter. In vitro the inhaled dose of albuterol with vibrating mesh nebulizer via Airvo 2 was ≥ 6 times higher than vibrating mesh nebulizer via Vapotherm. CONCLUSIONS: During aerosol delivery via HFNC, Airvo 2 generated higher inhaled dose and consequently higher fugitive aerosols than Vapotherm. Simple measures, such as placing a surgical mask over nasal cannula during nebulization via HFNC, could effectively reduce fugitive aerosol concentrations.

Efficacy of Various Mitigation Devices in Reducing Fugitive Emissions from Nebulizers.

BACKGROUND: Fugitive aerosol concentrations generated by different nebulizers and interfaces in vivo and mitigation of aerosol dispersion into the environment with various commercially available devices are not known. METHODS: Nine healthy volunteers were given 3 mL saline with a small-volume nebulizer (SVN) or vibrating mesh nebulizer (VMN) with a mouthpiece, a mouthpiece with an exhalation filter, an aerosol mask with open ports for SVN and a valved face mask for VMN, and a face mask with a scavenger (Exhalo) in random order. Five of the participants received treatments using a face tent scavenger (Vapotherm) and a mask with exhalation filter with SVN and VMN in a random order. Treatments were performed in an ICU room with 2 particle counters positioned 1 and 3 ft from participants measuring aerosol concentrations at sizes of 0.3-10.0 µm at baseline, before, during, and after each treatment. RESULTS: Fugitive aerosol concentrations were higher with SVN than VMN and higher with a face mask than a mouthpiece. Adding an exhalation filter to a mouthpiece reduced aerosol concentrations of 0.3-1.0 µm in size for VMN and 0.3-3.0 µm for SVN (all P < .05). An Exhalo scavenger over the mask reduced 0.5-3.0 µm sized particle concentrations for SVN (all P < .05) but not VMN. Vapotherm scavenger and filter face mask reduced fugitive aerosol concentrations regardless of the nebulizer type. CONCLUSIONS: SVN produced higher fugitive aerosol concentrations than VMN, whereas face masks generated higher aerosol concentrations than mouthpieces. Adding an exhalation filter to the mouthpiece or a scavenger to the face mask reduced aerosol concentrations for both SVN and VMN. Vapotherm scavenger and filter face mask reduced fugitive aerosols as effectively as a mouthpiece with an exhalation filter. This study provides guidance for reducing fugitive aerosol emissions from nebulizers in clinical practice.

Integrating digital inhalers into clinical care of patients with asthma and chronic obstructive pulmonary disease.

Modernizing inhaled medications through digital technology can help address persistent problems of non-adherence and poor inhaler technique in patients with obstructive lung diseases. With a growing body of supportive clinical studies, advances in digital inhaler sensors and platforms, greater support from payers and healthcare organizations, significant growth with these technologies is expected. While all digital (smart) inhalers record adherence, these are distinguished by their compatibility with commercial inhalers, capabilities to guide inhaler technique, use of patient-reported outcomes, and user-friendliness for both the healthcare professional (HCP) and patient. Due to the complexity and novelty of employing digital inhalers, collaboration with multiple entities within health systems is necessary and a well-planned integration is needed. For HCPs and patients, cybersecurity and privacy are critical, it will require review by each healthcare organization. In the US, some payers reimburse for remote monitoring using digital inhalers, but reimbursement is currently unavailable in other countries. There are several models for remote patient care, as employing an active, ongoing digital interface between the HCP and patient or they may choose to only review data at clinical encounters. Personalization of therapies and feedback are key to success. While digital inhaler malfunction uncommonly occurs, patient attrition over a year is significant. Some patients will be challenged to use digital platforms or have the necessary technology. Additional research is needed to address cost-effectiveness, in vivo accuracy of inspiratory measurement capable devices, ability to teach inhaler technique, their application for monitoring lung function, and lastly real-world adoption and implementation in routine clinical practice.

Measuring Peak Inspiratory Flow in Patients with Chronic Obstructive Pulmonary Disease.

Dry powder inhalers (DPIs) are breath actuated, and patients using DPIs need to generate an optimal inspiratory flow during the inhalation maneuver for effective drug delivery to the lungs. However, practical and standardized recommendations for measuring peak inspiratory flow (PIF)-a potential indicator for effective DPI use in chronic obstructive pulmonary disease (COPD)-are lacking. To evaluate recommended PIF assessment approaches, we reviewed the Instructions for Use of the In-Check™ DIAL and the prescribing information for eight DPIs approved for use in the treatment of COPD in the United States. To evaluate applied PIF assessment approaches, we conducted a PubMed search from inception to August 31, 2021, for reports of clinical and real-life studies where PIF was measured using the In-Check™ DIAL or through a DPI in patients with COPD. Evaluation of collective sources, including 47 applicable studies, showed that instructions related to the positioning of the patient with their DPI, instructions for exhalation before the inhalation maneuver, the inhalation maneuver itself, and post-inhalation breath-hold times varied, and in many instances, appeared vague and/or incomplete. We observed considerable variation in how PIF was measured in clinical and real-life studies, underscoring the need for a standardized method of PIF measurement. Standardization of technique will facilitate comparisons among studies. Based on these findings and our clinical and research experience, we propose specific recommendations for PIF measurement to standardize the process and better ensure accurate and reliable PIF values in clinical trials and in daily clinical practice.

Respiratory care year in review 2010: part 1. asthma, COPD, pulmonary function testing, ventilator-associated pneumonia.

The purpose of this paper is to review the recent literature related to asthma, COPD, pulmonary function testing, and ventilator-associated pneumonia. Topics covered related to asthma include genetics and epigenetics; exposures; viruses; diet, obesity and exercise; exhaled nitric oxide; and drug therapy (ß agonists, macrolides, tiotropium and monteleukast). Topics covered related to COPD include childhood disadvantage factors and COPD; vitamin D deficiency and COPD; ß-blockers and COPD; corticosteroid therapy during COPD exacerbations; oxygen administration during pre-hospital transport of patients with COPD exacerbation; and prognosis of patients admitted to the hospital for COPD exacerbation. Topics related to pulmonary function testing include methods and techniques; predicted values; natural history, pulmonary function in health and disease; and the COPD controversy. Finally, the paper includes the following topics related to ventilator-associated pneumonia: the tube, the intubation route, and the cuff; mechanical ventilation; the bundle; and cost. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of Respiratory Care.

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.