Exhaled Aerosol Pattern Discloses Lung Structural Abnormality: A Sensitivity Study Using Computational Modeling and Fractal Analysis

Xi, Jinxiang; Xiuhua, A.; Kim, Jong-Won; McKee, Edward E.; Lin, En-Bing

doi:10.1371/journal.pone.0104682

Cited by 24 publications

(22 citation statements)

References 61 publications

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“…With the advent of nanotechnology, studies of the biological consequences and fate of nanoparticles using animal models are increasing. Inhaled particles have been shown to deposit variably between the upper and lower respiratory regions (Asgharian et al, 2014, Xi et al, 2014). Depending on particle size, shape, density, and hygroscopicity, inhaled particles deposit in different regions via different mechanisms, such as gravitational settling, impaction, and interception and diffusion (Brain and Valberg, 1979, Heyder, 1982, Brain et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary distribution of nanoceria: comparison of intratracheal, microspray instillation and dry powder insufflation

Molina¹,

Konduru²,

Hirano³

et al. 2016

Inhalation Toxicology

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Particles can be delivered to the respiratory tract of animals using various techniques. Inhalation mimics environmental exposure but requires large amounts of aerosolized NPs over a prolonged dosing time, varies in deposited dose among individual animals, and results in nasopharyngeal and fur particle deposition. Although less physiological, intratracheal (IT) instillation allows quick and precise dosing. Insufflation delivers particles in their dry form as an aerosol. We compared the distribution of neutron-activated 141CeO2 nanoparticles (5 mg/kg) in rats after 1) IT instillation, 2) left intrabronchial instillation, 3) microspraying of nanoceria suspension, and 4) insufflation of nanoceria dry powder. Blood, tracheobronchial lymph nodes, liver, gastrointestinal tract, feces and urine were collected at 5 minutes and 24 hours post-dosing. Excised lungs from each rat were dried at room temperature while inflated at a constant 30 cm water pressure. Dried lungs were then sliced into 50 pieces. The radioactivity of each lung piece and other organs was measured. The evenness index (El) of each lung piece was calculated [EI=(μCi/mgpiece)/(μCi/mglung)]. The degree of EI value departure from 1.0 is a measure of deposition heterogeneity. We showed that the pulmonary distribution of nanoceria differs among modes of administration. Dosing by IT or microspraying resulted in similar spatial distribution. Insufflation resulted in significant deposition in the trachea and in more heterogeneous lung distribution. Our left intrabronchial instillation technique yielded a concentrated deposition into the left lung. We conclude that animal dosing techniques and devices result in varying patterns of particle deposition that will impact biokinetic and toxicity studies.

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Section: Introductionmentioning

confidence: 99%

Pulmonary distribution of nanoceria: comparison of intratracheal, microspray instillation and dry powder insufflation

Molina¹,

Konduru²,

Hirano³

et al. 2016

Inhalation Toxicology

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“…Even mild asymmetries in the branching patterns of successive generations can create large variations in ventilation at the terminal segments, resulting in inefficiency of gas exchange (15,16). Indeed, exhaled aerosol patterns demonstrate fractal behavior, suggesting an influence of fractal patterns on airflow and particle deposition (31). Although branching morphogenesis is initiated early in utero during embryogenesis, the patterns might influence deposition of cigarette smoke and other environmental agents, and potentiate a series of events controls, but AFD was substantially lower in these cases compared with controls (20).…”

Section: Discussionmentioning

confidence: 99%

Airway fractal dimension predicts respiratory morbidity and mortality in COPD

Bodduluri

Puliyakote

Gerard

et al. 2018

Journal of Clinical Investigation

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BACKGROUND. Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling. Characterization of airway changes on computed tomography has been challenging due to the complexity of the recurring branching patterns, and this can be better measured using fractal dimensions. METHODS. We analyzed segmented airway trees of 8,135 participants enrolled in the COPDGene cohort. The fractal complexity of the segmented airway tree was measured by the Airway Fractal Dimension (AFD) using the Minkowski-Bougliand boxcounting dimension. We examined associations between AFD and lung function and respiratory morbidity using multivariable regression analyses. We further estimated the extent of peribronchial emphysema (%) within 5 mm of the airway tree, as this is likely to affect AFD. We classified participants into 4 groups based on median AFD, percentage of peribronchial emphysema, and estimated survival. RESULTS. AFD was significantly associated with forced expiratory volume in one second (FEV 1 ; P < 0.001) and FEV 1 /forced vital capacity (FEV 1 /FVC; P < 0.001) after adjusting for age, race, sex, smoking status, pack-years of smoking, BMI, CT emphysema, air trapping, airway thickness, and CT scanner type. On multivariable analysis, AFD was also associated with respiratory quality of life and 6-minute walk distance, as well as exacerbations, lung function decline, and mortality on longitudinal follow-up. We identified a subset of participants with AFD below the median and peribronchial emphysema above the median who had worse survival compared with participants with high AFD and low peribronchial emphysema (adjusted hazards ratio [HR]: 2.72; 95% CI: 2.20-3.35; P < 0.001), a substantial number of whom were not identified by traditional spirometry severity grades. CONCLUSION. Airway fractal dimension as a measure of airway branching complexity and remodeling in smokers is associated with respiratory morbidity and lung function change, offers prognostic information additional to traditional CT measures of airway wall thickness, and can be used to estimate mortality risk. TRIAL REGISTRATION. ClinicalTrials.gov identifier: NCT00608764.

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“…13c. The multifractal spectrum measured the level of time variation in local regularity of a signal [63]. From Fig.…”

Section: Resultsmentioning

confidence: 99%

Numerical study of dynamic glottis and tidal breathing on respiratory sounds in a human upper airway model

Wang

Talaat

et al. 2017

Sleep Breath

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Background Human snores are caused by vibrating anatomical structures in the upper airway. The glottis is a highly variable structure and a critical organ regulating inhaled flows. However, the effects of the glottis motion on airflow and breathing sound are not well understood, while static glottises have been implemented in most previous in silico studies. The objective of this study is to develop a computational acoustic model of human airways with a dynamic glottis and quantify the effects of glottis motion and tidal breathing on airflow and sound generation. Methods Large eddy simulation and FW-H models were adopted to compute airflows and respiratory sounds in an image-based mouth-lung model. User-defined functions were developed that governed the glottis kinematics. Varying breathing scenarios (static vs. dynamic glottis; constant vs. sinusoidal inhalations) were simulated to understand the effects of glottis motion and inhalation pattern on sound generation. Pressure distributions were measured in airway casts with different glottal openings for model validation purpose. Results Significant flow fluctuations were predicted in the upper airways at peak inhalation rates or during glottal constriction. The inhalation speed through the glottis was the predominating factor in the sound generation while the transient effects were less important. For all frequencies considered (20–2500 Hz), the static glottis substantially underestimated the intensity of the generated sounds, which was most pronounced in the range of 100–500 Hz. Adopting an equivalent steady flow rather than a tidal breathing further underestimated the sound intensity. An increase of 25 dB in average was observed for the life condition (sine-dynamic) compared to the idealized condition (constant-rigid) for the broadband frequencies, with the largest increase of approximately 40 dB at the frequency around 250 Hz. Conclusion Results show that a severely narrowing glottis during inhalation, as well as flow fluctuations in the downstream trachea, can generate audible sound levels.

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Exhaled Aerosol Pattern Discloses Lung Structural Abnormality: A Sensitivity Study Using Computational Modeling and Fractal Analysis

Cited by 24 publications

References 61 publications

Pulmonary distribution of nanoceria: comparison of intratracheal, microspray instillation and dry powder insufflation

Pulmonary distribution of nanoceria: comparison of intratracheal, microspray instillation and dry powder insufflation

Airway fractal dimension predicts respiratory morbidity and mortality in COPD

Numerical study of dynamic glottis and tidal breathing on respiratory sounds in a human upper airway model

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