Computational fluid-particle dynamics modeling of ultrafine to coarse particles deposition in the human respiratory system, down to the terminal bronchiole.

BACKGROUND AND OBJECTIVES: Suspended respirable airborne particles are associated with human health risks and especially particles within the range of ultrafine (< 0.1 µm) or fine (< 2.5 µm) have a high possibility of penetrating the lung region, which is concerned to be closely related to the bronchial or alveoli tissue dosimetry. Nature complex structure of the respiratory system requires much effort to explore and comprehend the flow and the inhaled particle dynamics for precise health risk assessment. Therefore, this study applied the computational fluid-particle dynamics (CFPD) method to elucidate the deposition characteristics of ultrafine-to-coarse particles in the human respiratory tract from nostrils to the 16th generation of terminal bronchi. METHODS: The realistic bronchi up to the 8th generation are precisely and perfectly generated from computed tomography (CT) images, and an artificial model compensates for the 9th-16th bronchioles. Herein, the steady airflow is simulated at constant breathing flow rates of 7.5, 15, and 30 L/min, reproducing human resting-intense activity. Then, trajectories of the particle size ranging from 0.002 - 10 µm are tracked using a discrete phase model. RESULTS: Here, we report reliable results of airflow patterns and particle deposition efficiency in the human respiratory system validated against experimental data. The individual-related focal point of ultrafine and fine particles deposition rates was actualized at the 8th generation; whilst the hot-spot of the deposited coarse particles was found in the 6th generation. Lobar deposition characterizes the dominance of coarse particles deposited in the right lower lobe, whereas the left upper-lower and right lower lobes simultaneously occupy high deposition rates for ultrafine particles. Finally, the results indicate a higher deposition in the right lung compared to its counterpart. CONCLUSIONS: From the results, the developed realistic human respiratory system down to the terminal bronchiole in this study, in coupling with the CFPD method, delivers the accurate prediction of a wide range of particles in terms of particle dosimetry and visualization of site-specific in the consecutive respiratory system. In addition, the series of CFPD analyses and their results are to offer in-depth information on particle behavior in human bronchioles, which may benefit health risk assessment or drug delivery studies.

Effect of Electronic Cigarette Liquid pH on Retention of 11C-Nicotine in a Respiratory Tract Model.

INTRODUCTION: Based on our preliminary 11C-nicotine positron emission tomography (PET) imaging studies in humans, we speculated that greater deposition of nicotine in the respiratory tract from electronic cigarettes compared to combustible cigarettes could result from the alkaline pH of typical aerosol-producing electronic cigarette liquids (e-liquids). To address this hypothesis, we assessed the effect of e-liquid pH on the retention of nicotine in vitro using 11C-nicotine, PET, and a human respiratory tract model of nicotine deposition. AIMS AND METHODS: A single 2-second 35-mL puff was delivered to a human respiratory tract cast from a 2.8-Ohm cartomizer at 4.1 volts. Immediately after the puff, a 2-second 700-mL air wash-in volume was administered. E-liquids (glycerol and propylene glycol 50/50 vol/vol) containing 24 mg/mL nicotine were mixed with 11C-nicotine. Deposition (retention) of nicotine was assessed using a GE Discovery MI DR PET/CT scanner. Eight e-liquids with different pH values (range 5.3-9.6) were investigated. All experiments were performed at room temperature and at a relative humidity of 70%-80%. RESULTS: Retention of nicotine in the respiratory tract cast was pH dependent and the pH-sensitive component of the retention was well described by a sigmoid curve. In total, 50% of the maximal pH-dependent effect was observed at pH 8.0, which is close to the pKa2 of nicotine. CONCLUSIONS: The retention of nicotine in the respiratory tract conducting airways is dependent on the e-liquid pH. Lowering the e-liquid pH reduces retention of nicotine. Nonetheless, reduction of the pH below 7 has little effect, consistent with the pKa2 of protonated nicotine. IMPLICATIONS: Similar to combustible cigarettes, the retention of nicotine in the human respiratory tract from consumption of electronic cigarettes may have some health consequences and affect nicotine dependence. Here we demonstrated that the retention of nicotine in the respiratory tract is dependent on the e-liquid pH, and lowering pH reduces retention of nicotine in conducting airways of the respiratory tract. Therefore, e-cigarettes with low pH values would result in reduced respiratory tract nicotine exposure and faster delivery of nicotine to the central nervous system (CNS). The latter can be associated with e-cigarette abuse liability and the effectiveness of e-cigarettes as substitutes for combustible cigarettes.

Respiratory Tract Deposition of E-Cigarette Particles.

Total and regional deposition of inhaled electronic cigarette (E-cig) particles in the respiratory tract (RT) depends on both physical properties of the inhaled particles and biological factors of users, for example, breathing pattern or puff profile, airway anatomy, and regional ventilation. Accurate particle sizing of E-cig aerosols is essential for predicting particle deposition in the RT. Studies using a variety of sizing methods have shown mass median aerodynamic diameters ranging from 0.2 to 1.2 um and secondary count diameters in the ultrafine range (<0.1 µm). Incorporating these particle sizes into a multiple-path particle dosimetry (MPPD) model shows 10% to 45% total lung deposition by mass and 30% to 80% for ultrafine particles depending on the breathing patterns. These predictions are consistent with experimental measures of deposition fraction of submicron and ultrafine particles. While box-mod-type E-cig devices allow for full "direct-lung" inhalations of aerosol, the more recent pod-based, and disposable E-cigs (e.g., JUUL, Puff Bar, Stig) deliver the aerosol as a "mouth-to-lung" puff, or bolus, that is inhaled early in the breath followed to various degrees by further inhalation of ambient air. Measurement of realistic ventilation patterns associated with these various devices may further improve deposition predictions. Finally, while in vivo measures of RT deposition present a challenge, a recent methodology to radiolabel E-cig particles may allow for such measurements by gamma scintigraphy. Supported by NIH/NHLBI R01HL139369. © 2022 American Physiological Society. Compr Physiol 12: 1-10, year.

Nomograms for predicting difficult airway based on ultrasound assessment.

BACKGROUND: Accurate prediction of the difficult airway (DA) could help to prevent catastrophic consequences in emergency resuscitation, intensive care, and general anesthesia. Until now, there is no nomogram prediction model for DA based on ultrasound assessment. In this study, we aimed to develop a predictive model for difficult tracheal intubation (DTI) and difficult laryngoscopy (DL) using nomogram based on ultrasound measurement. We hypothesized that nomogram could utilize multivariate data to predict DTI and DL. METHODS: A prospective observational DA study was designed. This study included 2254 patients underwent tracheal intubation. Common and airway ultrasound indicators were used for the prediction, including thyromental distance (TMD), modified Mallampati test (MMT) score, upper lip bite test (ULBT) score temporomandibular joint (TMJ) mobility and tongue thickness (TT). Univariate and the Akaike information criterion (AIC) stepwise logistic regression were used to identify independent predictors of DTI and DL. Nomograms were constructed to predict DL and DTL based on the AIC stepwise analysis results. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of the nomograms. RESULTS: Among the 2254 patients enrolled in this study, 142 (6.30%) patients had DL and 51 (2.26%) patients had DTI. After AIC stepwise analysis, ULBT, MMT, sex, TMJ, age, BMI, TMD, IID, and TT were integrated for DL nomogram; ULBT, TMJ, age, IID, TT were integrated for DTI nomogram. The areas under the ROC curves were 0.933 [95% confidence interval (CI), 0.912-0.954] and 0.974 (95% CI, 0.954-0.995) for DL and DTI, respectively. CONCLUSION: Nomograms based on airway ultrasonography could be a reliable tool in predicting DA. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR-RCS-14004539 ), registered on 13th April 2014.

Impact of lung structure on airway opening index during mechanical versus manual chest compressions in a porcine model of cardiac arrest.

OBJECTIVES: The exhaled CO2 signal provides guidance during cardiopulmonary resuscitation. The Airway opening index (AOI) has been recently used to quantify chest-compression (CC) induced expired CO2 oscillations. We aimed to determine whether levels of intrathoracic pressures developed during CC or parameters related to lung structure may affect AOI. METHODS: Secondary analysis of a randomized animal study (n = 12) in a porcine model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) during ambulance transport. Animals were randomized to 18-min of manual or mechanical CCs. Changes in AOI and right atrial pressure (ΔRAP) were recorded during CCs in animals undergoing manual (n = 6) or mechanical (n = 6) CCs. Lung CT scan and measurement of the respiratory system compliance (Cpl,rs) were performed immediately after return of spontaneous circulation. RESULTS: Animals undergoing mechanical CCs had a lower AOI compared to animals treated with manual CCs (p < 0.001). AOI negatively correlated with the swings of intrathoracic pressure, as measured by the change in ΔRAP (ρ=-0.727, p = 0.007). AOI correlated with the lung density (ρ=-0.818, p = 0.001) and with the Cpl,rs (ρ = 0.676, p = 0.016). Animals with cardiopulmonary resuscitation associated lung edema (CRALE) (i.e. mean CT≥-500 HU) showed lower levels of AOI compared to animals without it (29 ± 12 % versus 50 ± 16 %, p = 0.025). CONCLUSIONS: Animals undergoing mechanical CCs had lower levels of AOI compared to animals undergoing manual CCs. A higher swing of intrathoracic pressure during CC, a denser and a stiffer lung were associated with an impaired CO2 exhalation during CC as observed by a lower AOI.

Pediatric Lower Respiratory Tract Infections: Imaging Guidelines and Recommendations.

Lower respiratory tract infection (LRTI) remains a major cause of morbidity and mortality in children. Various organisms cause LRTI, including viruses, bacteria, fungi, and parasites, among others. Infections caused by 2 or more organisms also occur, sometimes enhancing the severity of the infection. Medical imaging helps confirm a diagnosis but also plays a role in the evaluation of acute and chronic sequelae. Medical imaging tests help evaluate underlying pathology in pediatric patients with recurrent or long-standing symptoms as well as the immunocompromised.

Use of cone beam computed tomography imaging for airway measurement to predict obstructive sleep apnea.

Objective: This retrospective chart review examined whether airway parameters were correlated with scores on the STOP-Bang questionnaire.Methods: Minimal upper airway area, upper airway volume, minimal retropalatal area, retropalatal volume, minimal retroglossal area, and retroglossal volume were calculated from cone beam computed tomography (CBCT) images. Patients were grouped based on their STOP-Bang scores (<3 or ≥3) for obstructive sleep apnea (OSA), and airway parameters were compared across the 2 groups.Results: Thirty-one (43%) of 72 patients with a minimal upper airway area of <110 mm2 had STOP-Bang scores of ≥3. Most patients (90%) with STOP-Bang scores of ≥3 had minimal retropalatal areas of <110 mm2. Differences were found between groups for minimal upper airway area (p = 0.03), upper airway volume (p = 0.04), and minimal retropalatal area (p = 0.001).Discussion: To assess OSA risk, dentists should compare CBCT images with STOP-Bang scores.

Image Correlation-Based Method to Assess Ciliary Beat Frequency in Human Airway Organoids.

Ciliary movements within the human airway are essential for maintaining a clean lung environment. Motile cilia have a characteristic ciliary beat frequency (CBF). However, CBF measurement with current video microscopic techniques can be error-prone due to the use of the single-point Fourier transformation, which is often biased for ciliary measurements. Herein, we describe a new video microscopy technique that harnesses a metric of motion-contrast imaging and image correlation for CBF analysis. It can provide objective and selective CBF measurements for individual motile cilia and generate CBF maps for the imaged area. The measurement performance of our methodology was validated with in vitro human airway organoid models that simulated an actual human airway epithelium. The CBF determined for the region of interest (ROI) was equal to that obtained with manual counting. The signal redundancy problem of conventional methods was not observed. Moreover, the obtained CBF measurements were robust to optical focal shifts, and exhibited spatial heterogeneity and temperature dependence. This technique can be used to evaluate ciliary movement in respiratory tracts and determine whether it is non-synchronous or aperiodic in patients. Therefore, our observations suggest that the proposed method can be clinically adapted as a screening tool to diagnose ciliopathies.

Clinical Picture and Risk Factors of Severe Respiratory Symptoms in COVID-19 in Children.

Children with COVID-19 develop moderate symptoms in most cases. Thus, a proportion of children requires hospital admission. The study aimed to assess the history, clinical and laboratory parameters in children with COVID-19 concerning the severity of respiratory symptoms. The study included 332 children (median age 57 months) with COVID-19. History data, clinical findings, laboratory parameters, treatment, and outcome, were evaluated. Children were compared in the groups that varied in the severity of symptoms of respiratory tract involvement. Children who required oxygen therapy represented 8.73%, and intensive care 1.5% of the whole cohort. Comorbidities were present in 126 patients (37.95%). Factors increasing the risk of oxygen therapy included comorbidities (odds ratio (OR) = 92.39; 95% confidence interval (95% CI) = (4.19; 2036.90); p < 0.00001), dyspnea (OR = 45.81; 95% CI (4.05; 518.21); p < 0.00001), auscultation abnormalities (OR = 34.33; 95% CI (2.59; 454.64); p < 0.00001). Lactate dehydrogenase (LDH) > 280 IU/L and creatinine kinase > 192 IU/L were parameters with a good area under the curve (0.804-LDH) and a positive predictive value (42.9%-CK). The clinical course of COVID-19 was mild to moderate in most patients. Children with comorbidities, dyspnea, or abnormalities on auscultation are at risk of oxygen therapy. Laboratory parameters potentially useful in patients evaluated for the severe course are LDH > 200 IU/L and CK > 192 IU/L.

The influence of gravity on respiratory kinematics during phonation measured by dynamic magnetic resonance imaging.

Respiratory kinematics are important for the regulation of voice production. Dynamic MRI is an excellent tool to study respiratory motion providing high-resolution cross-sectional images. Unfortunately, in clinical MRI systems images can only be acquired in a horizontal subject position, which does not take into account gravitational effects on the respiratory apparatus. To study the effect of body posture on respiratory kinematics during phonation, 8 singers were examined both in an open-configuration MRI with a rotatable gantry and a conventional horizontal MRI system. During dynamic MRI the subjects sang sustained tones at different pitches in both supine and upright body positions. Sagittal images of the respiratory system were obtained at 1-3 images per second, from which 6 anatomically defined distances were extracted to characterize its movements in the anterior, medium and posterior section of the diaphragm as well as the rip cage (diameter at the height of the 3rd and 5th rip) and the anterior-posterior position of the diaphragm cupola. Regardless of body position, singers maintained their general principles of respiratory kinematics with combined diaphragm and thorax muscle activation for breath support. This was achieved by expanding their chest an additional 20% during inspiration when singing in the supine position but not for sole breathing. The diaphragm was cranially displaced in supine position for both singing and breathing and its motion range increased. These results facilitate a more realistic extrapolation of research data obtained in a supine position.

Multi-disciplinary management of patients with benign airway strictures: A review.

Histologically benign airway strictures are frequently misdiagnosed as asthma or COPD and may present with severe symptoms including respiratory failure. A clear understanding of pathophysiology and existing classification systems is needed to determine the appropriate treatment options and predict clinical course. Clinically significant airway strictures can involve the upper and central airways extending from the subglottis to the lobar airways. Optimal evaluation includes a proper history and physical examination, neck and chest computed tomography, pulmonary function testing, endoscopy and serology. Available treatments include medical therapy, endoscopic procedures and open surgery which are based on the stricture's extent, location, etiology, morphology, severity of airway narrowing and patient's functional status. The acuity of the process, patient's co-morbidities and operability at the time of evaluation determine the need for open surgical or endoscopic interventions. The optimal management of patients with benign airway strictures requires the availability, expertise and collaboration of otolaryngologists, thoracic surgeons and interventional pulmonologists. Multidisciplinary airway teams can facilitate accurate diagnosis, guide management and avoid unnecessary procedures that could potentially worsen the extent of the disease or clinical course. Implementation of a complex airway program including multidisciplinary clinics and conferences ensures that such collaboration leads to timely, patient-centered and evidence-based interventions. In this article we outline algorithms of care and illustrate therapeutic techniques based on published evidence.

Clinical Prediction Models for Suspected Pediatric Foreign Body Aspiration: A Systematic Review and Meta-analysis.

Importance: Although various clinical prediction models (CPMs) have been described for diagnosing pediatric foreign body aspiration (FBA), to our knowledge, there is still no consensus regarding indications for bronchoscopy, the criterion standard for identifying airway foreign bodies. Objective: To evaluate currently available CPMs for diagnosing FBA in children. Data Sources: Performed in Ovid MEDLINE, Ovid Embase, PubMed, Web of Science, and CINAHL database with citation searching of retrieved studies. Study Selection: Prediction model derivation and validation studies for diagnosing FBA in children were included. Exclusion criteria included adult studies; studies that included variables that were not available in routine clinical practice and outcomes for FBA were not separate or extractable. Data Extraction and Synthesis: We followed the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies and the Prediction Model Risk of Bias Assessment Tool framework. Data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was the diagnosis of FBA as confirmed by bronchoscopy. Characteristics of CPMs and individual predictors were evaluated. The final model presentation with available measures of performance was provided by narrative synthesis. A meta-analysis of individual predictor variables and prediction models was performed. Results: After screening 4233 articles, 7 studies (0.2%; 1577 patients) were included in the final analysis. There were 6 model derivation studies and 1 validation study. Air trapping (odds ratio [OR], 8.3; 95% CI, 4.4-15.5), unilateral reduced air entry (OR, 4.8; 95% CI, 3.5-6.5), witnessed choking (OR, 3.1; 95% CI, 1.0-9.6), wheezing (OR, 2.5; 95% CI, 1.2-5.2), and suspicious findings suggestive of FBA on radiography (OR, 18.5; 95% CI, 5.0-67.7) were the most commonly used predictor variables. Model performance varied, with discrimination scores (C statistic) ranging from 0.74 to 0.88. The pooled weighted C statistic score of all models was 0.86 (95% CI, 0.80-0.92). All studies were deemed to be at high risk of bias, with overfitting of models and lack of validation as the most pertinent concerns. Conclusions and Relevance: This systematic review and meta-analysis suggests that existing CPMs for FBA in children are at a high risk of bias and have not been adequately validated. No current models can be recommended to guide clinical decision-making. Future CPM studies that adhere to recognized standards for development and validation are required.

Comparing infectivity and virulence of emerging SARS-CoV-2 variants in Syrian hamsters.

BACKGROUND: Within one year after its emergence, more than 108 million people acquired SARS-CoV-2 and almost 2·4 million succumbed to COVID-19. New SARS-CoV-2 variants of concern (VoC) are emerging all over the world, with the threat of being more readily transmitted, being more virulent, or escaping naturally acquired and vaccine-induced immunity. At least three major prototypic VoC have been identified, i.e. the United Kingdom, UK (B.1.1.7), South African (B.1.351) and Brazilian (B.1.1.28.1) variants. These are replacing formerly dominant strains and sparking new COVID-19 epidemics. METHODS: We studied the effect of infection with prototypic VoC from both B.1.1.7 and B.1.351 variants in female Syrian golden hamsters to assess their relative infectivity and virulence in direct comparison to two basal SARS-CoV-2 strains isolated in early 2020. FINDINGS: A very efficient infection of the lower respiratory tract of hamsters by these VoC is observed. In line with clinical evidence from patients infected with these VoC, no major differences in disease outcome were observed as compared to the original strains as was quantified by (i) histological scoring, (ii) micro-computed tomography, and (iii) analysis of the expression profiles of selected antiviral and pro-inflammatory cytokine genes. Noteworthy however, in hamsters infected with VoC B.1.1.7, a particularly strong elevation of proinflammatory cytokines was detected. INTERPRETATION: We established relevant preclinical infection models that will be pivotal to assess the efficacy of current and future vaccine(s) (candidates) as well as therapeutics (small molecules and antibodies) against two important SARS-CoV-2 VoC. FUNDING: Stated in the acknowledgment.

Diagnostic Imaging of the Respiratory Tract of the Reptile Patient.

Detailed information is given about technique and image interpretation of radiography and computed tomography of the respiratory tract in reptiles. MRI and sonography are mentioned when supporting differential diagnoses. Various diseases and imaging pitfalls are described with multiple figures and graphics. One focus is on lung compression in chelonians, which may be misinterpreted as pneumonia in dyspneic patients without the help of imaging tools.

Development of in-airway laser absorption spectroscopy for respiratory based measurements of cardiac output.

Respiratory approaches to determining cardiac output in humans are securely rooted in mass balance and therefore potentially highly accurate. To address existing limitations in the gas analysis, we developed an in-airway analyser based on laser absorption spectroscopy to provide analyses every 10 ms. The technique for estimating cardiac output requires both a relatively soluble and insoluble tracer gas, and we employed acetylene and methane for these, respectively. A multipass cell was used to provide sufficient measurement sensitivity to enable analysis directly within the main gas stream, thus avoiding errors introduced by sidestream gas analysis. To assess performance, measurements of cardiac output were made during both rest and exercise on five successive days in each of six volunteers. The measurements were extremely repeatable (coefficient of variation ~ 7%). This new measurement technology provides a stable foundation against which the algorithm to calculate cardiac output can be further developed.

Experimental tracking and numerical mapping of novel coronavirus micro-droplet deposition through nasal inhalation in the human respiratory system.

It is essential to study the viral droplet's uptake in the human respiratory system to better control, prevent, and treat diseases. Micro-droplets can easily pass through ordinary respiratory masks. Therefore, the SARS-COV-2 transmit easily in conversation with a regular mask with 'silent spreaders' in the most physiological way of breathing through the nose, indoor and at rest condition. The results showed that the amount of deposited micro-droplets in the olfactory epithelium area is low. Also, due to receptors and long droplet residence time in this region, the possibility of absorption increases in the cribriform plate. This phenomenon eventually could lead to brain lesion damage and, in some cases, leads to stroke. In all inlet flow rates lower than 30 L/min inlet boundary conditions, the average percentage of viral contamination for upper respiratory tract is always less than 50% and more than 50% for the lungs. At 6L/min and 15L/min flow rates, the average percentage of lung contamination increases to more than 87%, which due to the presence of the Coronavirus receptor in the lungs, the involvement of the lungs increases significantly. This study's other achievements include the inverse relationship between droplets deposition efficiency in some parts of the upper airway, which have the most deformation in the tract. Also, the increased deformities per minute applied to the trachea and nasal cavity, which is 1.5 times more than usual, could lead to chest and head bothers.

Prospective Evaluation of Free-Breathing Fast T2-Weighted MultiVane XD Sequence at 3-T MRI for Large Airway Assessment in Pediatric Patients.

OBJECTIVE. The purpose of our study was to prospectively evaluate the technical feasibility of the free-breathing fast T2-weighted MultiVane XD sequence (sequence with non-Cartesian k-space filling using radial rectangular blades) at 3-T MRI for large airway assessment in pediatric patients. SUBJECTS AND METHODS. Forty consecutive pediatric patients (23 boys and 17 girls; age range, 5-15 years) referred for MRI examination for indications not related to neck, chest, or large airway disorders were enrolled in this prospective research study. All children underwent MRI in three planes using a free-breathing fast T2-weighted MultiVane XD sequence at 3-T MRI. The MR images were assessed by two pediatric radiologists independently for visualization of the large airways at six levels. The quality of the MR images was assessed and graded. Interobserver agreement between two radiologists was assessed using the kappa test, McNemar test, and intraclass correlation coefficients. RESULTS. High-quality MR images of the large airways were obtained in at least one plane in 38 MRI examinations (95.0%) by reviewer 1 and 37 MRI examinations (92.5%) by reviewer 2. Best-quality MR images with the least artifacts were seen in the sagittal plane followed by the coronal plane and the axial plane. The kappa test of agreement showed almost-perfect agreement between the two radiologists for MR image quality in the sagittal (κ = 1), coronal (κ = 0.96), and axial (κ = 0.81) planes. The McNemar test and intraclass correlation coefficients revealed similar results. CONCLUSION. The free-breathing fast T2-weighted MultiVane XD sequence at 3-T MRI is a technically feasible and promising new MRI technique for evaluating the large airways of pediatric patients in daily clinical practice.

Using µCT in live larvae of a large wood-boring beetle to study tracheal oxygen supply during development.

How respiratory structures vary with, or are constrained by, an animal's environment is of central importance to diverse evolutionary and comparative physiology hypotheses. To date, quantifying insect respiratory structures and their variation has remained challenging due to their microscopic size, hence only a handful of species have been examined. Several methods for imaging insect respiratory systems are available, in many cases however, the analytical process is lethal, destructive, time consuming and labour intensive. Here, we explore and test a different approach to measuring tracheal volume using X-ray micro-tomography (µCT) scanning (at 15 µm resolution) on living, sedated larvae of the cerambycid beetle Cacosceles newmannii across a range of body sizes at two points in development. We provide novel data on resistance of the larvae to the radiation dose absorbed during µCT scanning, repeatability of imaging analyses both within and between time-points and, structural tracheal trait differences provided by different image segmentation methods. By comparing how tracheal dimension (reflecting metabolic supply) and basal metabolic rate (reflecting metabolic demand) increase with mass, we show that tracheal oxygen supply capacity increases during development at a comparable, or even higher rate than metabolic demand. Given that abundant gas delivery capacity in the insect respiratory system may be costly (due to e.g. oxygen toxicity or space restrictions), there are probably balancing factors requiring such a capacity that are not linked to direct tissue oxygen demand and that have not been thoroughly elucidated to date, including CO2 efflux. Our study provides methodological insights and novel biological data on key issues in rapidly quantifying insect respiratory anatomy on live insects.

Why do we lack a specific magic anti-COVID-19 drug? Analyses and solutions.

The Coronavirus 2019 (COVID-19) pandemic represents the greatest worldwide public health crisis of recent times. The lack of proven effective therapies means that COVID-19 rages relatively unchecked. Current anti-COVID-19 pharmacotherapies are drugs originally designed for other diseases, and administered orally or intravascularly. Thus, they can have various adverse effects. A specific anti-Coronavirus drug should not only target the virus per se, but also treat the related respiratory and cardiovascular symptoms. Here, we examine the advantages and disadvantages of current anti-COVID-19 pharmacotherapies, and analyze the reasons why in the era of big data we have not yet established specific coronavirus therapies and related technical bottlenecks. Finally, we present our design of a novel nebulized S-nitrosocaptopril that is under development for targeting both coronaviruses and their related symptoms.