World's First Experience of the Low-Dose Radionuclide Inhalation Therapy in the Treatment of COVID-19-Associated Viral Pneumonia: Phase 1/2 Clinical Trial.

OBJECTIVE: Previously, low-dose radiation therapy was used for pneumonia treatment. We aimed to investigate the safety and effectiveness of carbon nanoparticles labeled with Technetium isotope (99mTc) in a form of ultradispersed aerosol in combination with standard COVID-19 therapy. The study was a randomized phase 1 and phase 2 clinical trial of low-dose radionuclide inhalation therapy for patients with COVID-19 related pneumonia. METHODS: We enrolled 47 patients with confirmed COVID-19 infection and early laboratory signs of cytokine storm and randomized them into the Treatment and Control groups. We analyzed blood parameters reflecting the COVID-19 severity and inflammatory response. RESULTS: Low-dose 99mTc-labeled inhalation showed a minimal accumulation of radionuclide in lungs in healthy volunteers. We observed no significant differences between the groups before treatment in WBC-count, D-dimer, CRP, Ferritin or LDH levels. We found that Ferritin and LDH levels significantly raised after the 7th day follow-up only in the Control group (p < 0.0001 and p = 0.0005, respectively), while mean values of the same indicators did not change in patients in the Treatment group after the radionuclide treatment. D-dimer values also lowered in the radionuclide treated group, however, this effect was not statistically significant. Furthermore, we observed a significant decrease in CD19+ cell counts in patients of the radionuclide-treated group. CONCLUSION: Inhalation low-dose radionuclide therapy of 99mTc aerosol affects the major prognostic indicators of COVID-19- related pneumonia restraining inflammatory response. Overall, we identified no evidence of major adverse events in the group receiving radionuclide.

Optimizing Respiratory Therapy Resources by De-Implementing Low-Value Care.

BACKGROUND: Our institution was experiencing a respiratory therapy staffing crisis during the COVID-19 pandemic, in part due to excessive workload. We identified an opportunity to reduce burden by limiting use of 3% hypertonic saline and/or N-acetylcysteine nebulizer therapies (3%HTS/NAC). METHODS: Leveraging the science of de-implementation, we established a policy empowering respiratory therapists to discontinue 3%HTS/NAC not meeting the American Association for Respiratory Care (AARC) Clinical Practice Guideline: Effectiveness of Pharmacologic Airway Clearance Therapies in Hospitalized Patients. After a 3-month period of educating physicians and advanced practice practitioners the policy went to into effect. Outcomes measured included monthly number of treatments, orders, and full-time employees associated with administering nebulized 3%HTS/NAC. RESULTS: Post policy activation, the monthly mean 3%HTS/NAC treatments were significantly reduced to 547.5 ± 284.3 from 3,565.2 ± 596.4 (P < .001) as were the associated monthly mean of full-time employees, 0.8 ± 0.41 from 5.1 ± 0.86 (P < .001). The monthly mean 3%HTS/NAC orders also fell to 93.8 ± 31.5 from 370.0 ± 46.9 (P < .001). Monthly mean non-3%HTS/NAC treatments remained stable; post policy was 3,089.4 ± 611.4 and baseline 3,279.6 ± 695.0 (P = 1.0). CONCLUSIONS: Implementing a policy that empowers respiratory therapists to promote adherence to AARC Clinical Guidelines reduced low-value therapies, costs, and staffing needs.

Isocratic ion pair chromatography for estimation of novel combined inhalation therapy that blocks coronavirus replication in chronic asthmatic patients.

A rapid and sensitive isocratic ion-pair chromatographic method was developed for the accurate analysis of ternary mixtures of formoterol, tiotropium, and ciclesonide in their novel combined inhalation that is widely used for the symptomatic treatment of patients with chronic obstructive disease. Analytical separation was performed using a C8 column and ion pair mobile phase composed of acetonitrile: acidified deionized water (55: 45% v/v) containing 0.025% sodium dodecyl sulfate. The pH was adjusted to 3.0 using orthophosphoric acid and eluted isocratically at 2.0 mL/min and 40 °C applying UV detection at 237 nm. The calibration ranges were found to be 0.3-9.0 µg/mL for formoterol, 0.45-13.5 µg/mL for tiotropium, and 10.0-300.0 µg/mL concerning ciclesonide. The proposed method exhibited good repeatability, accuracy, and sensitivity (R.S.D. < 2.0%). The approach is rapid (run time does not exceed 15 min) and achieves satisfactory resolution (resolution factors = 7.45 and 5.3 between formoterol and tiotropium and tiotropium and ciclesonide respectively). The sensitivity and the efficiency of the proposed method permit their successful estimation with a recovery percentage ± SD of 99.33% ± 0.43 for formoterol, 99.15% ± 0.60 for tiotropium, and 99.90% ± 0.41 for ciclesonide.

Higher Risk of Acute Respiratory Distress Syndrome and Risk Factors among Patients with COVID-19: A Systematic Review, Meta-Analysis and Meta-Regression.

OBJECTIVE: To estimate the global risk and risk factors associated with acute respiratory distress syndrome (ARDS) among patients with COVID-19: Design: A systematic review, meta-analysis and meta-regression. SETTING AND PARTICIPANTS: Hospitals or nursing homes and patients with acute respiratory distress syndrome after COVID-19. METHODS: The literature review was systematically conducted on Embase, MEDLINE, CINAHL, and Web of Science, in addition to manual searches and reference list checking from 1 January 2019 to 2 March 2022. The search terms included coronavirus, acute respiratory syndrome, acute respiratory distress syndrome and observational studies. Three reviewers independently appraised the quality of the studies and extracted the relevant data using the Joanna Briggs Institute abstraction form and critical appraisal tools. A study protocol was registered in PROSPERO (CRD42022311957). Eligible studies were meta-analyzed and underwent meta-regression. RESULTS: A total of 12 studies were included, with 148,080 participants. The risk ratio (RR) of ARDS was 23%. Risk factors were age ≥ 41-64 years old (RR = 15.3%, 95% CI =0.14-2.92, p = 0.03); fever (RR = 10.3%, 95% CI = 0.03-2.03, p = 0.04); multilobe involvement of the chest (RR = 33.5%, 95% CI = 0.35-6.36, p = 0.02); lymphopenia (RR = 25.9%, 95% CI = 1.11-4.08, p = 0.01); mechanical ventilation with oxygen therapy (RR = 31.7%, 95% CI = 1.10-5.25, p = 0.002); European region (RR = 16.3%, 95% CI = 0.09-3.17, p = 0.03); sample size ≤ 500 (RR = 18.0%, 95% CI = 0.70-2.89, p = 0.001). CONCLUSIONS AND IMPLICATIONS: One in four patients experienced ARDS after having COVID-19. The age group 41-64 years old and the European region were high-risk groups. These findings can be used by policymakers to allocate resources for respiratory care facilities and can also provide scientific evidence in the design of protocols to manage COVID-19 worldwide.

Perceptions of inspiratory muscle training in adults recovering from COVID-19.

Post COVID-19 condition can occur following infection with SARS-CoV-2 and is characterised by persistent symptoms, including fatigue, breathlessness and cognitive dysfunction, impacting everyday functioning. This study explored how people living with post COVID-19 experienced an eight-week inspiratory muscle training (IMT) rehabilitation programme. Individualised semi-structured interviews with 33 adults (29 female; 49 ± 10 years; 6-11 months post-infection) explored expectations of IMT prior to the intervention, and post intervention interviews explored perceptions of IMT and its impact on recovery. Inductive thematic analysis was used to analyse the data. IMT helped many to feel proactive in managing their symptoms and was associated with perceived improvements in respiratory symptoms, exercise and work capacity, and daily functioning. IMT was well perceived and offers significant potential for use as part of a holistic recovery programme, although it is important to consider the complex, varied symptoms of post COVID-19, necessitating an individually tailored rehabilitation approach.

A Pre-Pandemic Evaluation of the State of Staffing and Future of the Respiratory Care Profession: Perceptions of Louisiana Respiratory Therapists.

BACKGROUND: Workforce development for the respiratory therapy (RT) profession is a growing concern. Upcoming staffing difficulties are expected due to retirement, attrition from the profession, and decreased enrollment in accredited RT programs nationwide. This study assessed respiratory therapists' perceptions of staffing needs and future trajectory of the RT profession. METHODS: This cross-sectional study utilized a modified 39-question survey tool delivered via e-mail to 618 Louisiana members of the American Association for Respiratory Care (AARC) between November 2019-February 2020. RESULTS: The response rate was 19% (118/618). Although 50% of respondents perceived understaffing, 77.6% indicated the importance to remain in the RT profession. A majority (93.1%) agreed on the importance of maintaining an active membership in the AARC. Respondents working in a hospital setting perceived understaffed work environments more often than other groups. Salary was most important to the employee (33.6%, 39/116), followed equally by room for growth (14.7%, 17/116) and scope of practice (14.7%, 17/116). For the future of the profession, the ability to assess patients and develop care plans and the ability to receive reimbursement for services were indicated as most important factors. Most (69.8%) agreed that the entry-level minimum should be increased to the bachelor's degree, and 21.6% agreed the master's degree in RT should be supported to increase scope of practice. CONCLUSIONS: This study indicated a consistent perception of understaffed work environments in respiratory care, and respondents expressed a perceived importance of remaining in the RT profession. This study also indicated support for raising the entry-level standard in RT and a desire for higher education to achieve professional growth and advancement.

Physiotherapy practice for hospitalized patients with COVID-19.

OBJECTIVE: To identify the indications for physiotherapy and to evaluate physiotherapy practices in patients with COVID-19 admitted to the ICU (on mechanical ventilation) or to the ward (spontaneously breathing). METHODS: An online, 50-item survey was completed by physiotherapists who had been treating hospitalized patients with COVID-19 in Brazil. RESULTS: Of the 644 physiotherapists who initiated the survey, 488 (76%) completed it. The main reasons for indications for physiotherapy in both settings reported as "very frequently" and "frequently" both in the ICU and the ward by most respondents were oxygenation improvement (> 95%) and prevention of general complications (> 83%). Physical deconditioning was considered an infrequent indication. When compared with mobilization strategies, the use of respiratory interventions showed great variability in both work settings, and techniques considered effective were underutilized. The most frequently used respiratory techniques in the ICU were positioning (86%), alveolar recruitment (73%), and hard/brief expiratory rib cage compression (46%), whereas those in the ward were active prone positioning (90%), breathing exercises (88%), and directed/assisted cough (75%). The mobilization interventions reported by more than 75% of the respondents were sitting on the edge of the bed, active and resistive range of motion exercises, standing, ambulation, and stepping in place. CONCLUSIONS: The least common reason for indications for physiotherapy was avoidance of deconditioning, whereas oxygenation improvement was the most frequent one. Great variability in respiratory interventions was observed when compared with mobilization therapies, and there is a clear need to standardize respiratory physiotherapy treatment for hospitalized patients with COVID-19.

Virtual respiratory therapy delivered through a smartphone app: a mixed-methods randomised usability study.

INTRODUCTION: A new smartphone app (QUT Inspire) has been developed to detect inspiratory sound and deliver virtual incentive spirometry (ISy), a respiratory therapy technique used in postoperative recuperation, management of some chronic conditions and with potential applications in SARS-CoV-2 rehabilitation. The aim of this study was to compare the usability of this new app with a clinical ISy device as measured by effectiveness, efficiency and satisfaction. METHODS: In this mixed-methods randomised usability study, healthy volunteers (aged 39.2±12.2 years, n=24) compared inspirations using the QUT Inspire app and a Triflo II clinical ISy device. A post-test questionnaire and a semi-structured interview explored dimensions of usability regarding the new app. RESULTS: The duration of inspirations performed using the QUT Inspire app (7.3±2.0 s) were comparable with use of the Triflo II ISy device (7.5±2.3 s). No artefacts arising from the order of device testing were identified. App users held their phones adjacent but not proximal to their mouths (13.6±6.4 cm), notwithstanding instructions to keep the phone less than 5 cm away for optimal breath sound detection. The use of onscreen text or video instructional materials did not result in a significant reduction in this distance. Participants reported clear preferences for the app (100%, n=24) to motivate persistence with repeated inspirations. App gamification features such as a timer (75%, n=18) and breath counter (83.3%, n=20) were well regarded. Analysis of semi-structured interviews identified four main themes arising from this study: visual reward from responsive app animations, clinical look and feel influencing credibility, perceived effort affecting engagement and selective adoption of gamification features. CONCLUSION: This study demonstrates that a virtual ISy app can be effective, efficient and have high satisfaction. Improvements informed by this research include use of additional phone sensors to optimise sound detection and minimising the distance that phones are held from the user's mouth. Further research in randomised controlled trials are needed to evaluate performance of this app in clinical contexts where ISy is currently employed.

[Aerosol Therapy in Intensive Care Unit]. / Aerosoltherapie auf Intensivstation.

Inhalation therapy is a cornerstone especially in pulmonary diseases or comorbidities, either in invasive or noninvasive mechanical ventilation. In pediatric patients, mainly in respiratory failure of the premature born child inhalation of surfactant is crucial in the therapy. Additional drugs given by inhalation are antibiotics, mucoactive substances and drugs that treat pulmonary hypertension. This article describes main deposition mechanisms of inhalation therapies and presents recommendations for correct performance of inhalation therapy in invasively as well as noninvasively ventilated patients in ICU. Also safety aspects for patients and medical staff during aerosol therapy in the Corona pandemic era are discussed.

Conceptual model of low-cost improvised bubble continuous positive airway pressure device for adults and its potential use in the COVID-19 pandemic.

Low-cost improvised continuous positive airway pressure (CPAP) device is safe and efficacious in neonatal respiratory distress. There is a great necessity for similar device in adults, and this has been especially made apparent by the recent Coronavirus Disease 2019 (COVID-19) pandemic, which is unmasking the deficiencies of healthcare system in several low-resource countries. We propose a simplified and inexpensive model of improvised CPAP in adults using locally available resources including aquarium air pumps and a novel pressure release mechanism. Although the safety and efficacy of improvised CPAP in adults are not established, the conceptual model we propose has the potential to serve as a lifesaving technology in many low-resource settings during this ongoing pandemic and thus calls for expedited research.

Nitric Oxide Inhalation Therapy Attenuates Postoperative Hypoxemia in Obese Patients with Acute Type A Aortic Dissection.

Objective: To investigate the differences between inhaled nitric oxide (iNO) treatment and conventional therapy in the treatment of postoperative hypoxemia in obese patients with acute type A aortic dissection (ATAAD). Methods: ATAAD patients diagnosed and treated with emergency surgery in our hospital from June 2017 to December 2019 were retrospectively analyzed. Patients with postoperative hypoxemia were divided into the iNO group and control group. Propensity score matching was used to analyze clinical characteristics and results of the two groups. Results: A total of 218 ATAAD patients with BMI ≥ 25 were treated with surgery. Among them, 115 patients developed refractory hypoxemia (64 in the control group and 51 in the iNO group). Patients in the iNO group had significantly shorter invasive mechanical ventilation time, intensive care unit (ICU) stay, and hospital stay. After 6 h of iNO treatment, the PaO2/FiO2 ratio in the iNO group increased significantly, and this ratio was higher than that in the control group at 6, 12, 24, 48, and 72 h after treatment. Conclusion: Low-dose iNO could improve oxygenation and shorten mechanical ventilation and ICU stay in patients with hypoxemia after ATAAD surgery, but without significant side effects or increase in postoperative mortality or morbidity. These findings provide a basis for a randomized multicenter controlled trial to assess the efficacy of iNO in the treatment of hypoxemia after ATAAD surgery.

Mechanisms of the Effects of Short-Term Inhalations of Xe and O2 Gas Mixture in the Rehabilitation of Post-COVID Ventilation Failure.

The article presents a theoretical rationale and a clinical case of relief of post-COVID ventilation failure by inhalation of Xe and O2 gas mixture. Pneumonitis of coronavirus etiology transforms saturated phospholipids of surfactant into a solid-ordered phase, which disrupts surface tension, alveolar pneumatization, and alveolar-capillary gas exchange. Using molecular modeling (B3LYP/lanl2dz; GAUSSIAN09), we demonstrated that Xe atom due to the van der Waals dispersion interaction increases the distance between the phospholipid acyl chains providing a phase transition from the solid-ordered to liquid phase and restored the surface-active monolayer surfactant film. A clinical case confirmed that short-term inhalations of the Xe and O2 gas mixture relieved manifestations of ventilation insufficiency and increased SpO2 and pneumatization of the terminal parts of the lungs.

Aerosol release, distribution, and prevention during aerosol therapy: a simulated model for infection control.

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.