Ventilation Scintigraphy With Radiolabeled Carbon Nanoparticulate Aerosol (Technegas): State-of-the-Art Review and Diagnostic Applications to Pulmonary Embolism During COVID-19 Pandemic.

ABSTRACT: Invented and first approved for clinical use in Australia 36 years ago, Technegas is the technology that enabled ventilation scintigraphy with 99m Tc-labeled carbon nanoparticles ( 99m Tc-CNP). The US Food and Drug Administration (FDA) has considered this technology for more than 30 years but only now is getting close to approving it. Meanwhile, more than 4.4 million patients benefited from this technology in 64 countries worldwide. The primary application of 99m Tc-CNP ventilation imaging is the diagnostic evaluation for suspicion of pulmonary embolism using ventilation-perfusion quotient (V/Q) imaging. Because of 99m Tc-CNP's long pulmonary residence, tomographic imaging emerged as the preferred V/Q methodology. The FDA-approved ventilation imaging agents are primarily suitable for planar imaging, which is less sensitive. After the FDA approval of Technegas, the US practice will likely shift to tomographic V/Q. The 99m Tc-CNP use is of particular interest in the COVID-19 pandemic because it offers an option of a dry radioaerosol that takes approximately only 3 to 5 tidal breaths, allowing the shortest exposure to and contact with possibly infected patients. Indeed, countries where 99m Tc-CNP was approved for clinical use continued using it throughout the COVID-19 pandemic without known negative viral transmission consequences. Conversely, the ventilation imaging was halted in most US facilities from the beginning of the pandemic. This review is intended to familiarize the US clinical nuclear medicine community with the basic science of 99m Tc-CNP ventilation imaging and its clinical applications, including common artifacts and interpretation criteria for tomographic V/Q imaging for pulmonary embolism.

Towards a multi-scale computer modeling workflow for simulation of pulmonary ventilation in advanced COVID-19.

Physics-based multi-scale in silico models offer an excellent opportunity to study the effects of heterogeneous tissue damage on airflow and pressure distributions in COVID-19-afflicted lungs. The main objective of this study is to develop a computational modeling workflow, coupling airflow and tissue mechanics as the first step towards a virtual hypothesis-testing platform for studying injury mechanics of COVID-19-afflicted lungs. We developed a CT-based modeling approach to simulate the regional changes in lung dynamics associated with heterogeneous subject-specific COVID-19-induced damage patterns in the parenchyma. Furthermore, we investigated the effect of various levels of inflammation in a meso-scale acinar mechanics model on global lung dynamics. Our simulation results showed that as the severity of damage in the patient's right lower, left lower, and to some extent in the right upper lobe increased, ventilation was redistributed to the least injured right middle and left upper lobes. Furthermore, our multi-scale model reasonably simulated a decrease in overall tidal volume as the level of tissue injury and surfactant loss in the meso-scale acinar mechanics model was increased. This study presents a major step towards multi-scale computational modeling workflows capable of simulating the effect of subject-specific heterogenous COVID-19-induced lung damage on ventilation dynamics.

One year monitoring of SARS-CoV-2 prevalence in a German cohort of patients with cystic fibrosis.

BACKGROUND: In Germany, the first case of coronavirus disease 2019 (COVID-19) was registered on 28 January 2020. By February 2021, the third wave of the pandemic began. So far, only few data are available on the SARS-CoV-2 prevalence and the clinical impact of an infection in patients with cystic fibrosis (CF). METHODS: From February 2020 until March 2021, we screened 156 CF patients for anti-SARS-CoV-2 IgG antibodies (serology) and the presence of SARS-CoV-2 in deep throat saliva or nasopharyngeal swabs (molecular testing). From patients with confirmed SARS-CoV-2 infection, we recorded symptoms and collected clinical data. RESULTS: In total, 13 patients (8.3%) were tested positive for SARS-CoV-2 infection, most of them during the second and the beginning third wave of the pandemic. Ten positive tested patients described symptoms linked to COVID-19. The most common symptom was cough followed by fatigue and headache. SARS-CoV-2 infection did not impair lung function. No positive tested patient needed to be hospitalized. CONCLUSIONS: SARS-CoV-2 infections in patients with CF are not as rare as initially anticipated, as frequent testing revealed. However, infected patients did not experience more severe clinical courses or worse clinical outcome. Our observation is in line with published reports indicating that individuals with CF are not at higher risk for severe COVID-19.

Abnormal dynamic ventilation function of COVID-19 survivors detected by pulmonary free-breathing proton MRI.

OBJECTIVES: To visualize and quantitatively assess regional lung function of survivors of COVID-19 who were hospitalized using pulmonary free-breathing 1H MRI. METHODS: A total of 12 healthy volunteers and 27 COVID-19 survivors (62.4 ± 8.1 days between infection and image acquisition) were recruited in this prospective study and performed chest 1H MRI acquisitions with free tidal breathing. Then, conventional Fourier decomposition ventilation (FD-V) and global fractional ventilation (FVGlobal) were analyzed. Besides, a modified PREFUL (mPREFUL) method was developed to adapt to COVID-19 survivors and generate dynamic ventilation maps and parameters. All the ventilation maps and parameters were analyzed using Student's t-test. Pearson's correlation and a Bland-Altman plot between FVGlobal and mPREFUL were analyzed. RESULTS: There was no significant difference between COVID-19 and healthy groups regarding a static FD-V map (0.47 ± 0.12 vs 0.42 ± 0.08; p = .233). However, mPREFUL demonstrated lots of regional high ventilation areas (high ventilation percentage (HVP): 23.7% ± 10.6%) existed in survivors. This regional heterogeneity (i.e., HVP) in survivors was significantly higher than in healthy volunteers (p = .003). The survivors breathed deeper (flow-volume loop: 5375 ± 3978 vs 1688 ± 789; p = .005), and breathed more air in respiratory cycle (total amount: 62.6 ± 19.3 vs 37.3 ± 9.9; p < .001). Besides, mPREFUL showed both good Pearson's correlation (r = 0.74; p < .001) and Bland-Altman consistency (mean bias = -0.01) with FVGlobal. CONCLUSIONS: Dynamic ventilation imaging using pulmonary free-breathing 1H MRI found regional abnormity of dynamic ventilation function in COVID-19 survivors. KEY POINTS: • Pulmonary free-breathing1H MRI was used to visualize and quantitatively assess regional lung ventilation function of COVID-19 survivors. • Dynamic ventilation maps generated from 1H MRI were more sensitive to distinguish the COVID-19 and healthy groups (total air amount: 62.6 ± 19.3 vs 37.3 ± 9.9; p < .001), compared with static ventilation maps (FD-V value: 0.47 ± 0.12 vs 0.42 ± 0.08; p = .233). • COVID-19 survivors had larger regional heterogeneity (high ventilation percentage: 23.7% ± 10.6% vs 13.1% ± 7.9%; p = .003), and breathed deeper (flow-volume loop: 5375 ± 3978 vs 1688 ± 789; p = .005) than healthy volunteers.

Electrical impedance tomography clues to detect pulmonary thrombosis in a teenager with COVID-19.

We report a case of pulmonary thrombosis in a teenager during a hypercoagulable state associated with COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). A condition rare in children and adolescents, pulmonary thrombosis underdiagnosis likely increases morbidity and mortality. A pulmonary thrombosis diagnosis requires a high level of suspicion and relies on the combination of clinical presentation, D-dimer elevation, and computed tomography (CT) pulmonary angiography or ventilation/perfusion scans, imaging techniques that are difficult to perform. Electrical impedance tomography (EIT) has gained attention, as it provides real-time ventilation distribution analysis. In addition, lung pulsatility images can be obtained through this technique using electrocardiogram gating to filter out ventilation. In this case report, the reduced EIT pulsatility corresponded to the perfusion defect found on the CT scan, information that was obtained at the bedside without radiation or contrast exposure.

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients.

BACKGROUND: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. METHODS: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. RESULTS: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). CONCLUSIONS: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation.

The effects of wearing facemasks on oxygenation and ventilation at rest and during physical activity.

BACKGROUND: Facemasks are recommended to reduce the spread of SARS-CoV-2, but concern about inadequate gas exchange is an often cited reason for non-compliance. RESEARCH QUESTION: Among adult volunteers, do either cloth masks or surgical masks impair oxygenation or ventilation either at rest or during physical activity? STUDY DESIGN AND METHODS: With IRB approval and informed consent, we measured heart rate (HR), transcutaneous carbon dioxide (CO2) tension and oxygen levels (SpO2) at the conclusion of six 10-minute phases: sitting quietly and walking briskly without a mask, sitting quietly and walking briskly while wearing a cloth mask, and sitting quietly and walking briskly while wearing a surgical mask. Brisk walking required at least a 10bpm increase in heart rate. Occurrences of hypoxemia (decrease in SpO2 of ≥3% from baseline to a value of ≤94%) and hypercarbia (increase in CO2 tension of ≥5 mmHg from baseline to a value of ≥46 mmHg) in individual subjects were collected. Wilcoxon signed-rank was used for pairwise comparisons among values for the whole cohort (e.g. walking without a mask versus walking with a cloth mask). RESULTS: Among 50 adult volunteers (median age 33 years; 32% with a co-morbidity), there were no episodes of hypoxemia or hypercarbia (0%; 95% confidence interval 0-1.9%). In paired comparisons, there were no statistically significant differences in either CO2 or SpO2 between baseline measurements without a mask and those while wearing either kind of mask mask, both at rest and after walking briskly for ten minutes. INTERPRETATION: The risk of pathologic gas exchange impairment with cloth masks and surgical masks is near-zero in the general adult population.

Exhalation Spreading During Nasal High-Flow Therapy at Different Flow Rates.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 is transmitted through aerosols and droplets. Nasal high-flow therapy could possibly increase the spreading of exhalates from patients. The aim of this study is to investigate whether nasal high-flow therapy affects the range of the expiratory plume compared with spontaneous breathing. DESIGN: Interventional experiment on single breaths of a healthy volunteer. SETTING: Research laboratory at the Bauhaus-University Weimar. SUBJECTS: A male subject. INTERVENTIONS: Videos and images from a schlieren optical system were analyzed during spontaneous breathing and different nasal high-flow rates. MEASUREMENTS AND MAIN RESULTS: The maximal exhalation spread was 0.99, 2.18, 2.92, and 4.1 m during spontaneous breathing, nasal high-flow of 20 L/min, nasal high-flow of 40 L/min, and nasal high-flow of 60 L/min, respectively. Spreading of the expiratory plume in the sagittal plane can completely be blocked with a surgical mask. CONCLUSIONS: Nasal high-flow therapy increases the range of the expiratory air up to more than 4 meters. The risk to pick up infectious particles could be increased within this range. Attachment of a surgical mask over the nasal high-flow cannula blocks the expiratory airstream.

Ventilated Patients With COVID-19 Show Airflow Obstruction.

OBJECTIVE: Many patients with coronavirus disease 2019 (COVID-19) need mechanical ventilation secondary to acute respiratory distress syndrome. Information on the respiratory system mechanical characteristics of this disease is limited. The aim of this study is to describe the respiratory system mechanical properties of ventilated COVID-19 patients. DESIGN, SETTING, AND PATIENTS: Patients consecutively admitted to the medical intensive care unit at the University of Iowa Hospitals and Clinics in Iowa City, USA, from April 19 to May 1, 2020, were prospectively studied; final date of follow-up was May 1, 2020. MEASUREMENTS: At the time of first patient contact, ventilator information was collected including mode, settings, peak airway pressure, plateau pressure, and total positive end expiratory pressure. Indices of airflow resistance and respiratory system compliance were calculated and analyzed. MAIN RESULTS: The mean age of the patients was 58 years. 6 out of 12 (50%) patients were female. Of the 21 laboratory-confirmed COVID-19 patients on invasive mechanical ventilation, 9 patients who were actively breathing on the ventilator were excluded. All the patients included were on volume-control mode. Mean [±standard deviation] ventilator indices were: resistive pressure 19 [±4] cmH2O, airway resistance 20 [±4] cmH2O/L/s, and respiratory system static compliance 39 [±16] ml/cmH2O. These values are consistent with abnormally elevated resistance to airflow and reduced respiratory system compliance. Analysis of flow waveform graphics revealed a pattern consistent with airflow obstruction in all patients. CONCLUSIONS: Severe respiratory failure due to COVID-19 is regularly associated with airflow obstruction.

Evaluation of pulmonary ventilation in COVID-19 patients using oxygen-enhanced three-dimensional ultrashort echo time MRI: a preliminary study.

AIM: To evaluate the lung function of coronavirus disease 2019 (COVID-19) patients using oxygen-enhanced (OE) ultrashort echo time (UTE) MRI. MATERIALS AND METHODS: Forty-nine patients with COVID-19 were included in the study. The OE-MRI was based on a respiratory-gated three-dimensional (3D) radial UTE sequence. For each patient, the percent signal enhancement (PSE) map was calculated using the expression PSE = (S100% - S21%)/S21%, where S21% and S100% are signals acquired during room air and 100% oxygen inhalation, respectively. Agreement of lesion detectability between UTE-MRI and computed tomography (CT) was performed using the kappa test. The Mann-Whitney U-test was used to evaluate the difference in the mean PSE between mild-type COVID-19 and common-type COVID-19. Spearman's test was used to assess the relationship between lesion mean PSE and lesion size. Furthermore, the Mann-Whitney U-test was used to evaluate the difference in region of interest (ROI) mean PSE between normal pulmonary parenchyma and lesions. The Kruskal-Wallis test was applied to test the difference in the mean PSE between different lesion types. RESULTS: CT and UTE-MRI reached good agreement in lesion detectability. Ventilation measures in mild-type patients (5.3 ± 5.5%) were significantly different from those in common-type patients (3 ± 3.9%). Besides, there was no significant correlation between lesion mean PSE and lesion size. The mean PSE of COVID-19 lesions (3.2 ± 4.9%) was significantly lower than that of the pulmonary parenchyma (5.4 ± 3.9%). No significant difference was found among different lesion types. CONCLUSION: OE-UTE-MRI could serve as a promising method for the assessment of lung function or treatment management of COVID-19 patients.

Implications of microscale lung damage for COVID-19 pulmonary ventilation dynamics: A narrative review.

The COVID-19 pandemic surges on as vast research is produced to study the novel SARS-CoV-2 virus and the disease state it induces. Still, little is known about the impact of COVID-19-induced microscale damage in the lung on global lung dynamics. This review summarizes the key histological features of SARS-CoV-2 infected alveoli and links the findings to structural tissue changes and surfactant dysfunction affecting tissue mechanical behavior similar to changes seen in other lung injury. Along with typical findings of diffuse alveolar damage affecting the interstitium of the alveolar walls and blood-gas barrier in the alveolar airspace, COVID-19 can cause extensive microangiopathy in alveolar capillaries that further contribute to mechanical changes in the tissues and may differentiate it from previously studied infectious lung injury. Understanding microlevel damage impact on tissue mechanics allows for better understanding of macroscale respiratory dynamics. Knowledge gained from studies into the relationship between microscale and macroscale lung mechanics can allow for optimized treatments to improve patient outcomes in case of COVID-19 and future respiratory-spread pandemics.

A Prospective Study of Voice, Swallow, and Airway Outcomes Following Tracheostomy for COVID-19.

OBJECTIVE: The COVID-19 pandemic has led to unprecedented demands on healthcare with many requiring intubation. Tracheostomy insertion has often been delayed and the enduring effects of this on voice, swallow, and airway outcomes in COVID-19 tracheostomy patients are unknown. The aim of this study was to prospectively assess these outcomes in this patient cohort following hospital discharge. METHODS: All COVID-19 patients who had undergone tracheostomy insertion, and were subsequently decannulated, were identified at our institution and followed up 2 months post-discharge. Patient-reported (PROMS) and clinician-reported outcome measures, endoscopic examination, and spirometry were used to assess voice, swallow, and airway outcomes. RESULTS: Forty-one patients were included in the study with a mean age of 56 years and male:female ratio of 28:13. Average duration of endotracheal intubation was 24 days and 63.4% of tracheostomies were performed at day 21 to 35 of intubation. 53.7% had an abnormal GRBAS score and 30% reported abnormal swallow on EAT-10 questionnaire. 81.1% had normal endoscopic examination of the larynx, however, positive endoscopic findings correlated with the patient self-reported VHI-10 (P = .036) and EAT-10 scores (P = .027). 22.5% had spirometric evidence of fixed upper airway obstruction using the Expiratory-Disproportion Index (EDI) and Spearman correlation analysis showed a positive trend between abnormal endoscopic findings and EDI scores over 50 (P < .0001). CONCLUSION: The preliminary results of this study reveal a high incidence of laryngeal injury among patients who underwent intubation and tracheostomy insertion during the COVID-19 pandemic. As these patients continue to be followed up, the evolution of these complications will be studied. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E1918-E1925, 2021.

Risk factors for COVID-19 patients with cardiac injury: pulmonary ventilation dysfunction and oxygen inhalation insufficiency are not the direct causes.

BACKGROUND: Cardiac injury in patients with coronavirus disease 2019 (COVID-19) has been reported in recent studies. However, reports on the risk factors for cardiac injury and their prognostic value are limited. RESULTS: In total, 15.9% of all cases were defined as cardiac injury in our study. Patients with severe COVID-19 were significantly associated with older age and higher respiratory rates, Sequential Organ Failure Assessment (SOFA) scores, cardiac injury biomarkers and PaO2/FiO2 ratios. Male patients with chest distress and dyspnea were more likely to have severe disease. Patients with cardiac injury were significantly more likely to have a severe condition and have an outcome of death. However, no significant difference was found in respiratory rates, dyspnea or PaO2/FiO2 ratio between patients with or without cardiac injury. In the logistic regression model, pre-existing hypertension and higher SOFA score were independent risk factors for patients with COVID-19 developing cardiac injury. CONCLUSIONS: Our study revealed that cardiac injury was an important predictor for patients having a severe or fatal outcome. Patients with pre-existing hypertension and higher SOFA scores upon admission were more likely to develop cardiac injury. Nevertheless, pulmonary ventilation dysfunction and oxygen inhalation insufficiency were not the main causes of cardiac injury in patients with COVID-19. METHODS: A total of 113 confirmed cases were included in our study. Severe patients were defined according to American Thoracic Society guidelines for community-acquired pneumonia. Cardiac injury was defined as a serum cTnI above the 99th-percentile of the upper reference limit. Patient characteristics, clinical laboratory data and treatment details were collected and analyzed. The risk factors for patients with and without cardiac injury were analyzed.