Human Respiratory Tract Research Articles

A quasi-realistic computational model development and flow field study of the human upper and central airways.

The impact of drug delivery and particulate matter exposure on the human respiratory tract is influenced by various anatomical and physiological factors, particularly the structure of the respiratory tract and its fluid dynamics. This study employs computational fluid dynamics (CFD) to investigate airflow in two 3D models of the human air conducting zone. The first model uses a combination of CT-scan images and geometrical data from human cadaver to extract the upper and central airways down to the ninth generation, while the second model develops the lung airways from the first Carina to the end of the ninth generation using Kitaoka's deterministic algorithm. The study examines the differences in geometrical characteristics, airflow rates, velocity, Reynolds number, and pressure drops of both models in the inhalation and exhalation phases for different lobes and generations of the airways. From trachea to the ninth generation, the average air flowrates and Reynolds numbers exponentially decay in both models during inhalation and exhalation. The steady drop is the case for the average air velocity in Kitaoka's model, while that experiences a maximum in the 3rd or 4th generation in the quasi-realistic model. Besides, it is shown that the flow field remains laminar in the upper and central airways up to the total flow rate of 15l/min. The results of this work can contribute to the understanding of flow behavior in upper respiratory tract.

SARS-CoV-2 and Influenza Co-Infection: Fair Competition or Sinister Combination?

The COVID-19 pandemic remains a serious public health problem globally. During winter influenza seasons, more aggressive SARS-CoV-2 infections and fatalities have been documented, indicating that influenza co-infections may significantly impact the disease outcome of COVID-19. Both influenza and SARS-CoV-2 viruses share many similarities in their transmission and their cellular tropism for replication in the human respiratory tract. However, the complex intricacies and multi-faceted dynamics of how the two pathogens interact to ensure their survival in the same lung microenvironment are still unclear. In addition, clinical studies on influenza co-infections in COVID-19 patients do not provide conclusive evidence of how influenza co-infection mechanistically modifies disease outcomes of COVID-19. This review discusses various viral as well as host factors that potentially influence the survival or synergism of these two respiratory pathogens in the infected lung microenvironment.

Characterization of trace elements of size-resolved particulate matter, development of emission factors and human health impacts associated with stationary diesel engine exhausts

The mass concentration of diesel particulate matter (DPM) and its elemental constituents (twenty-four) emitted from stationary diesel engine exhaust at ten different sizes (56 nm to 18 µm) increased with rise in engine-operating load. The maximum value of DPM concentration varied from 10.3 ± 2.4 mg/Nm3 at 0 % load to 20.4 ± 6.5 mg/Nm3 at 100 % load at size-bin of 0.10–0.18 μm. The elements of S, Ca, K, Al, Na, Mg, Fe, and Zn contributed as the major components to DPM mass with more than 90 % to total elements at six engine-operating loads. Ca, K, Al, Na, and Mg also showed higher values of EFs compared to Fe, Zn, As, Cr and Ni. Compared to Cu, Mn, Co, Se, Pb, Ba, Sr, fuel-based emission factor (EF) of Ti, Ga, Cd, Bi, and Te showed lower side of the estimated values. The levels of hazardous particulate elements generated from stationary diesel engine exhausts was a matter of concern from human health point of view as these elements showed better potential in causing significant cancer and non-cancer diseases through long-term exposure. The elements in DPM revealed significant deposition in the pulmonary and alveolar region of the human respiratory tract.

Exploring the pediatric nasopharyngeal bacterial microbiota with culture-based MALDI-TOF mass spectrometry and targeted metagenomic sequencing.

The human upper respiratory tract is an important source of disease-causing and antibiotic-resistant bacteria. However, understanding the interactions and stability of these bacterial populations is technically challenging. We used a combination of approaches to determine colonization patterns over a 3-month period in 101 Cambodian children. The combined approach was feasible to implement, and each component gave complementary data to enable a better understanding of the complex patterns of bacterial colonization.

Meta-analysis of the human upper respiratory tract microbiome reveals robust taxonomic associations with health and disease

BackgroundThe human upper respiratory tract (URT) microbiome, like the gut microbiome, varies across individuals and between health and disease states. However, study-to-study heterogeneity in reported case–control results has made the identification of consistent and generalizable URT-disease associations difficult.ResultsIn order to address this issue, we assembled 26 independent 16S rRNA gene amplicon sequencing data sets from case–control URT studies, with approximately 2–3 studies per respiratory condition and ten distinct conditions covering common chronic and acute respiratory diseases. We leveraged the healthy control data across studies to investigate URT associations with age, sex, and geographic location, in order to isolate these associations from health and disease states.ConclusionsWe found several robust genus-level associations, across multiple independent studies, with either health or disease status. We identified disease associations specific to a particular respiratory condition and associations general to all conditions. Ultimately, we reveal robust associations between the URT microbiome, health, and disease, which hold across multiple studies and can help guide follow-up work on potential URT microbiome diagnostics and therapeutics.

A Study to Evaluate the Anti Bacterial Activity of Squilla Maritima Against Streptococcus Pneumonia in - Vitro

This study aims to evaluate the antibacterial properties of Squilla maritima, a homoeopathic medicine, against Streptococcus pneumonia, a common pathogen in the human upper respiratory tract. The Agar Well-Diffusion test will be used to screen the bacteria at 30C and 200C potencies. Result: Squilla maritime 30C (0.8±0.1), 200C (0.6±0.1) cm. showed inhibitory activity against Streptococcus pneumonia by Agar well-diffusion assay. Squilla maritima 30 showed maximum Growth inhibitory zone (GIZ) against Streptococcus pneumonia. But Vehicle control (Dispensing alcohol or ethanol 90%) showed 10mm of Growth inhibitory zone which is more than squilla 30C. Conclusion: This experiment showed that the homoeopathic medicine Squilla maritima has antibacterial property against Streptococcus pneumonia which is less effective than dispensing alcohol.

Human Airway Organoids and Multimodal Imaging-Based Toxicity Evaluation of 1-Nitropyrene.

Despite significant advances in understanding the general health impacts of air pollution, the toxic effects of air pollution on cells in the human respiratory tract are still elusive. A robust, biologically relevant in vitro model for recapitulating the physiological response of the human airway is needed to obtain a thorough understanding of the molecular mechanisms of air pollutants. In this study, by using 1-nitropyrene (1-NP) as a proof-of-concept, we demonstrate the effectiveness and reliability of evaluating environmental pollutants in physiologically active human airway organoids. Multimodal imaging tools, including live cell imaging, fluorescence microscopy, and MALDI-mass spectrometry imaging (MSI), were implemented to evaluate the cytotoxicity of 1-NP for airway organoids. In addition, lipidomic alterations upon 1-NP treatment were quantitatively analyzed by nontargeted lipidomics. 1-NP exposure was found to be associated with the overproduction of reactive oxygen species (ROS), and dysregulation of lipid pathways, including the SM-Cer conversion, as well as cardiolipin in our organoids. Compared with that of cell lines, a higher tolerance of 1-NP toxicity was observed in the human airway organoids, which might reflect a more physiologically relevant response in the native airway epithelium. Collectively, we have established a novel system for evaluating and investigating molecular mechanisms of environmental pollutants in the human airways via the combinatory use of human airway organoids, multimodal imaging analysis, and MS-based analyses.

Transport and deposition of microplastics and nanoplastics in the human respiratory tract

Recent studies have unveiled the presence of nano- and microplastics (NMPs) within both human and avian respiratory systems, prompting an exploration into the interactions between these particles and the human respiratory system. Experimental evidence has strongly suggested that these plastic particles amplify human susceptibility to a spectrum of lung disorders, including chronic obstructive pulmonary disease, fibrosis, dyspnea, asthma, and the formation of frosted glass nodules. To advance the understanding, this study employs computational fluid-particle dynamics (CFPD) to study the transfer and deposition of poly-dispersed 1-100 nm nanoplastics and 1-100 μm microplastics under three breathing conditions. Notably, this investigation utilized a computerized tomography-based full respiratory tract model, comprehensively spanning regions from the nasal cavity to the 13th generation of the bronchial tree, providing a highly detailed representation of the anatomical complexities of the human respiratory system. The outcomes reveal distinctive deposition patterns of spherical, cylindrical, and tetrahedral NMPs in the human respiratory tract, elucidating the significant impact of breathing rate, pinpointing specific deposition hotspots, and highlighting the critical role of particle size in governing transport and deposition behavior. This study establishes a link between the behavior of nanoplastics within the respiratory tract and its consequential impact, providing insights that extend across three critical domains. Firstly, in environmental health, the research contributes to understanding NMP-related air pollution. Secondly, within respiratory medicine, the findings shed light on NMPs' role in respiratory disorders. Finally, this study guides the formulation of regulations addressing permissible NMP levels and mitigating associated health and environmental risks.

Exploring Clinical Predictors of Severe Human Metapneumovirus Respiratory Tract Infections in Children: Insights from a Recent Outbreak.

Human metapneumovirus (hMPV) is an important pathogen that causes both upper (URTIs) and lower respiratory tract infections (LRTIs) in children. The virus can be implicated in severe bronchiolitis and pneumonia, necessitating hospitalization, with certain cases requiring intensive care unit intervention. As part of a retrospective observational study, we aimed to identify indicators of severe hMPV respiratory tract infections in children referred to the University Children's Hospital Ljubljana and the Department of Infectious Diseases Ljubljana, Slovenia, during a recent outbreak. We analyzed clinical data from November 2022 to January 2023 and compared the characteristics of children presenting with URTIs and LRTIs. We also examined the characteristics of children with hMPV LRTIs, distinguishing between children with and without LRTI-associated hypoxemia. Of 78 hMPV-PCR-positive pediatric patients (mean age 3.1 years; 60.3% boys), 36% had a URTI, and 64% had an LRTI. Hospitalization was required in 64% (50/78), with 42% (21/50) requiring oxygen therapy. LRTI-associated hypoxemia was more common in patients with atopy who showed dyspnea, tachypnea, crackles, and wheezing on lung auscultation. In a multivariable logistic regression analysis, wheezing detected on lung auscultation was a significant predictive factor for hypoxemic hMPV-LRTI. Specifically, children presenting with wheezing were found to be ten times more likely to experience hypoxemia. Prematurity and chronic conditions did not influence the presentation or severity of hMPV infection. This study highlights wheezing and atopy as crucial indicators of severe hMPV LRTI in children, emphasizing the importance of early recognition and intervention.

Effect of Nasal Inhalation on Drug Particle Deposition and Size Distribution in the Upper Airway: With Soft Mist Inhalers.

Delivery of drugs to the lungs is commonly achieved using nasal and/or oral breathing-assisted techniques. The route of inhalation can substantially change the fate of inhaled droplets. The Respimat® Soft Mist™ Inhaler (SMI) is a commercially available efficient inhaler with 40-60% effectiveness. In the present study, we used computational fluid dynamics (CFD) with a custom setup to investigate the effect of a combined oral/nasal inhalation route on the SMI's regional droplet deposition, size distribution, and flow field. Our setup used a modified induction port (MIP) to mimic nasal inhalation inside the human respiratory tract. Six different oral/nasal flow rate ratios inside the MIP were applied (total flow rate of 30l/min). An overall good agreement was achieved between simulation outcomes and in vitro results. Our results confirmed that the combined inhalation route affects the flow field, altering the MIP's droplet deposition and size distribution. The lowest depositional loss, mainly in the mouth area, was observed at oral/nasal flow rate ratios of O/N = 1 and O/N = 2 with 3% and 7.7% values, respectively. Droplets with a 2-5µm diameter range showed the highest droplet mass inside the MIP at all combined flow rates. We observed less intense vortexes followed by a lower level of turbulent kinetic energy at the oral/nasal ratio of 1. Increasing the relative humidity (RH) at oral/nasal flow rate ratios of 0.07, 1, and 14 led to an increase in droplet deposition at the outlet of the MIP.

The influence of COVID-19 pandemic on deposited dose of outdoor particulate matter in human respiratory tract: A case study from Krakow, Southern Poland

The influence of COVID-19 pandemic on deposited dose of outdoor particulate matter in human respiratory tract: A case study from Krakow, Southern Poland

Fungal community shows more variations by season and particle size than bacteria

The global concern regarding the health risk associated with airborne microorganisms has prompted research in this field. However, there is a lack of systematic investigation into the particle-size distribution of airborne bacterial and fungal communities associated with seasons, which determines where they are deposited in the human respiratory tract. To address this gap, we conducted a study in Nanchang, located in central China, where we collected both coarse and fine particles during summer and winter seasons. The results demonstrated that microbial community exhibited obvious seasonal and particle-size variations except bacterial community in fine particles. Certain taxa (e.g., Bacteroidales, Ktedonobacterales, Capnodiales) displayed either seasonal and/or particle-size preferences. Furthermore, airborne microorganisms in coarse particles were more sensitive to season and particle size compared to those in fine particles, with fungal community being more susceptible than bacterial community. The susceptibility can be attributed to their high vulnerability to air pollutants and meteorological conditions, primarily PM2.5 and PM10. Additionally, a greater relative abundance of pathogenic fungi was observed in fine particles, even though microbial diversity in coarse particles was noticeably higher than that in fine particles. Furthermore, some predominant pathogens such as Alternaria, Nigrospora, and Escherichia-Shigella not only had particle size and/or seasonal preferences, but also were strongly correlated with environmental factors. This study advances our understanding of atmospheric pathogenic microorganisms and highlights the fungal health threat.

Fate of inhaled electronic nicotine delivery systems (ENDS) puff constituents in the human respiratory tract

Published research on the fate of a puff from electronic nicotine delivery systems (ENDS) in the lungs is limited; more information would better inform human exposure and potential adverse outcomes from ENDS use. An ENDS puff is a mixture of multiple constituents in droplet and vapor form, including propylene glycol, vegetable glycerin, nicotine, water, and flavor chemicals. Understanding the complexity of the puff aids in developing mechanistic models that can account for the physical, physiological, and thermodynamic processes of the puff while traveling and depositing in lung airways. Previously, we developed a mathematical model to predict deposition and uptake of ENDS constituents in the oral cavity. In this study, we formulated the model for lung airways to extend to the entire respiratory tract and made adjustments to mechanisms such as phase change and nicotine protonation to study effects on droplet pH and nicotine evaporation. We conducted model simulations for two representative inhalation profiles relevant to ENDS users: mouth-to-lung and direct-to-lung inhalation. Simulation results showed that vapor uptake during ENDS use was the primary mechanism of the overall tissue dose for higher vapor pressure constituents. Nicotine protonation was unaffected by the ratio of propylene glycol to vegetable glycerin but changes to vanillin molarity impacted droplet pH and free nicotine fraction. The largest uptake and deposition occurred in the deep lung, where constituents more efficiently reach the arterial blood. Predicted total respiratory tract retention of higher vapor pressure constituents such as nicotine, propylene glycol, and benzaldehyde were 94–95%, whereas retention of lower volatility constituents such as vegetable glycerin and vanillin was 82–83%. Results also indicated regional uptake differences for the constituents evaluated in the two inhalation scenarios. Predictions from the ENDS deposition model can be linked to physiologically based pharmacokinetic (PBPK) models to determine the fate of puff constituents such as nicotine in other tissues and organs of the body and provides further basis for evaluating flavor chemicals and puff constituents based on user-specific exposure characteristics as well as internal dose to inform risk assessment of ENDS.

Characterisation of a capsular polysaccharide from Moraxella nonliquefaciens CCUG 348T

Moraxella nonliquefaciens is a commensal of the human upper respiratory tract (URT) but on rare occasions is recovered in cases of ocular, septic and pulmonary infections. Hence there is interest in the pathogenic determinants of M. nonliquefaciens, of which outer membrane (OM) structures such as fimbriae and two capsular polysaccharide (CPS) structures, →3)-β-D-GalpNAc-(1→5)-β-Kdop-(2→ and →8)-α-NeuAc-(2→, have been reported in the literature. To further characterise its surface virulence factors, we isolated a novel CPS from M. nonliquefaciens type strain CCUG 348T. This structure was elucidated using NMR data obtained from CPS samples that were subjected to various degrees of mild acid hydrolysis. Together with GLC-MS data, the structure was resolved as a linear polymer composed of two GalfNAc residues consecutively added to Kdo, →3)-β-D-GalfNAc-(1→3)-α-D-GalfNAc-(1→5)-α-(8-OAc)Kdop-(2→.Supporting evidence for this material being CPS was drawn from the proposed CPS biosynthetic locus which encoded a potential GalfNAc transferase, a UDP-GalpNAc mutase for UDP-GalfNAc production and a putative CPS polymerase with predicted GalfNAc and Kdo transferase domains. This study describes a unique CPS composition reported in Moraxella spp. and offers genetic insights into the synthesis and expression of GalfNAc residues, which are rare in bacterial OM glycans.

Particulate matter deposition in the human respiratory system: A health risk assessment at a technical university

Introduction: This study quantified Particulate Matter (PM) deposition and its clearance in the Human Respiratory Tract (HRT) at different microenvironments of a university. The university is located adjacent to the National Highway (NH 334) and main bus stop of the city, thus highly affected by PM pollution.
 Materials and methods: The deposition calculations were performed using a widely accepted MPPD 3.04 model. Three seasons (summer, winter and monsoon), seven microenvironments (including three Lecture Hall Complexes (LHCs), a library, two laboratories and outdoor), and different activity patterns associated with each microenvironment were considered.
 Results: The deposited mass of coarse fraction (PM2.5-10) in different HRT regions follows the order: pulmonary (0.5%)<tracheobronchial (2%)<head
 (or extrathoracic region) (97.5%). In the case of lobar region, because of the larger volume of lower lobes, they received higher deposition (53%) than the middle (8%) and upper lobes (39%). Further, the sitting activity level was found to be most critical for lobar deposition. The total deposited mass in the HRT was maximum outdoors and minimum at the library. The difference in winter and monsoon deposition was 100% for PM2.5-10, 75% for PM1-2.5 and 126% for PM1. The clearance rate of PM1 is such that 1.5 % of particles in the tracheobronchial and 64% in the pulmonary region remained even after six months.
 Conclusion: The results implied that physical activity levels, mode of inhalation and particle size significantly influence regional deposition. For instance, heavy exercise causes greater deposition in the head region, whereas sitting activity contributes to higher pulmonary and tracheobronchial deposition.

Multidimensional assessment of the biological effects of electronic cigarettes on lung bronchial epithelial cells

Cigarette smoke (CS) exposure is known to cause injury to respiratory tract epithelial cells and is a contributing factor in the development of chronic obstructive pulmonary disease and lung cancer. Electronic cigarettes (e-cigarettes) are gaining popularity as a potential substitute for conventional cigarettes due to their potential for aiding smoking cessation. However, the safety of e-cigarettes remains uncertain, and scientific evidence on this topic is still limited. In this study, we aimed to investigate the effects of CS and e-cigarette smoke (ECS) of different flavors on human lung bronchial epithelial cells. Real-time smoke exposure was carried out using an air–liquid interface system, and cell viability was assessed. RNA-Seq transcriptome analysis was performed to compare the differences between CS and ECS. The transcriptome analysis revealed a significantly higher number of differentially expressed genes in CS than in ECS. Moreover, the impact of mint-flavored e-cigarettes on cells was found to be greater than that of tobacco-flavored e-cigarettes, as evidenced by the greater number of differentially expressed genes. These findings provide a reference for future safety research on traditional cigarettes and e-cigarettes, particularly those of different flavors. The use of omics-scale methodologies has improved our ability to understand the biological effects of CS and ECS on human respiratory tract epithelial cells, which can aid in the development of novel approaches for smoking cessation and lung disease prevention.

Impact of altitude on the dosage of indoor particulates entering an individual’s small airways

The complexity of indoor particulate exposure intensifies at higher altitudes owing to the increased lung capacity that residents develop to meet the higher oxygen demands. Altitude variations impact atmospheric pressure and alter particulate dynamics in ambient air and the human respiratory tract, complicating particulate inhalation. This study assessed the fraction of PM2.5 and PM10 entering small airways. This assessment covered an altitude range from 400 m above sea level to 3650 m, and an in vitro respiratory tract model was used. The experimental results confirmed that with increasing altitude, the penetration fractions of PM2.5 and PM10 significantly increased from 0.133 ± 0.031 and 0.141 ± 0.045 to 0.404 ± 0.159 and 0.353 ± 0.132, respectively. Additionally, the computational fluid dynamics simulation results revealed that among particles with sizes of 0.1 to 10 µm, the 7.5-μm particles exhibited the most substantial reduction in deposition in the upper airway, displaying a decrease of 6.27%. Our findings underscore the health risks faced by low-altitude residents during acclimatization to higher altitudes, as they experience heightened exposure to particulate matter sources.

Heme sequestration by hemophilin from Haemophilus haemolyticus reduces respiratory tract colonization and infection with non-typeable Haemophilus influenzae.

The microbiome provides a critical layer of protection against infection with bacterial pathogens. This protection is accomplished through a variety of mechanisms, including interference with pathogen growth and adherence to host cells. In terms of immune defense, another way to prevent pathogens from establishing infections is by limiting the availability of nutrients, referred to as nutritional immunity. Restricting pathogen access to iron is a central component of this approach. Here, we uncovered an example where these two strategies intersect to impede infection with the respiratory tract bacterial pathogen Haemophilus influenzae. Specifically, we find that a non-pathogenic (commensal) bacterium closely related to H. influenzae called Haemophilus haemolyticus improves protection against H. influenzae by limiting the ability of this pathogen to access iron. These findings suggest that beneficial members of the microbiome improve protection against pathogen infection by effectively contributing to host nutritional immunity.

Effective density of inhaled environmental and engineered nanoparticles and its impact on the lung deposition and dosimetry

BackgroundAirborne environmental and engineered nanoparticles (NPs) are inhaled and deposited in the respiratory system. The inhaled dose of such NPs and their deposition location in the lung determines their impact on health. When calculating NP deposition using particle inhalation models, a common approach is to use the bulk material density, ρb, rather than the effective density, ρeff. This neglects though the porous agglomerate structure of NPs and may result in a significant error of their lung-deposited dose and location.ResultsHere, the deposition of various environmental NPs (aircraft and diesel black carbon, wood smoke) and engineered NPs (silica, zirconia) in the respiratory system of humans and mice is calculated using the Multiple-Path Particle Dosimetry model accounting for their realistic structure and effective density. This is done by measuring the NP ρeff which was found to be up to one order of magnitude smaller than ρb. Accounting for the realistic ρeff of NPs reduces their deposited mass in the pulmonary region of the respiratory system up to a factor of two in both human and mouse models. Neglecting the ρeff of NPs does not alter significantly the distribution of the deposited mass fractions in the human or mouse respiratory tract that are obtained by normalizing the mass deposited at the head, tracheobronchial and pulmonary regions by the total deposited mass. Finally, the total deposited mass fraction derived this way is in excellent agreement with those measured in human studies for diesel black carbon.ConclusionsThe doses of inhaled NPs are overestimated by inhalation particle deposition models when the ρb is used instead of the real-world effective density which can vary significantly due to the porous agglomerate structure of NPs. So the use of realistic ρeff, which can be measured as described here, is essential to determine the lung deposition and dosimetry of inhaled NPs and their impact on public health.Graphical abstract

Flow Rate and Wall Shear Stress Characterization of a Biomimetic Aerosol Exposure System.

Current in vitro emissions and exposure systems lack biomimicry, use unrealistic flow conditions, produce unrealistic dose, and provide inaccurate biomechanical cues to cell cultures, limiting ability to correlate in vitro outcomes with in vivo health effects. A biomimetic in vitro system capable of puffing aerosol and clean air inhalation may empower researchers to investigate complex questions related to lung injury and disease. A biomimetic aerosol exposure system (BAES), including an electronic cigarette adapter, oral cavity module (OCM), and bifurcated exposure chamber (BEC) was designed and manufactured. The fraction of aerosol deposited in transit to a filter pad or lost as volatiles was 0.116±0.021 in a traditional emissions setup versus 0.098 ± 0.015 with the adapter. The observed flowrate was within 5% of programed flowrate for puffing (25 mL/s), puff-associated respiration (450 mL/s), and tidal inhalation (350 mL/s). The maximum flowrate observed in the fabricated BAES was 450 mL/s, exceeding the lower target nominal wall shear stress of 0.025 Pa upstream of the bifurcation and fell below the target of 0.02 Pa downstream. This in vitro system addresses several gaps observed in commercially available systems and may be used to study many inhaled aerosols. The current work illustrates how in silico models may be used to correlate results of an in vitro study to in vivo conditions, rather than attempting to design an in vitro system that performs exactly as the human respiratory tract.