Extrathoracic Airways Research Articles

Exploring the role of electrostatic deposition on inhaled aerosols in alveolated microchannels

Large amounts of net electrical charge are known to accumulate on inhaled aerosols during their generation using commonly-available inhalers. This effect often leads to superfluous deposition in the extra-thoracic airways at the cost of more efficient inhalation therapy. Since the electrostatic force is inversely proportional to the square of the distance between an aerosol and the airway wall, its role has long been recognized as potentially significant in the deep lungs. Yet, with the complexity of exploring such phenomenon directly at the acinar scales, in vitro experiments have been largely limited to upper airways models. Here, we devise a microfluidic alveolated airway channel coated with conductive material to quantify in vitro the significance of electrostatic effects on inhaled aerosol deposition. Specifically, our aerosol exposure assays showcase inhaled spherical particles of 0.2, 0.5, and 1.1 μm that are recognized to reach the acinar regions, whereby deposition is typically attributed to the leading roles of diffusion and sedimentation. In our experiments, electrostatic effects are observed to largely prevent aerosols from depositing inside alveolar cavities. Rather, deposition is overwhelmingly biased along the inter-alveolar septal spaces, even when aerosols are charged with only a few elementary charges. Our observations give new insight into the role of electrostatics at the acinar scales and emphasize how charged particles under 2 µm may rapidly overshadow the traditionally accepted dominance of diffusion or sedimentation when considering aerosol deposition phenomena in the deep lungs.

An Epidemiological Study of Lung Cancer and Selected Other Cancers among Namibian Uranium Workers.

The Rössing Uranium Limited (RUL) open-cast uranium mine in Namibia has operated since 1976. Studies of underground uranium miners from Europe and North America have shown increased cancer risks (principally lung cancer). We explored the association between radiation doses and selected cancers in RUL mineworkers. Employees with at least one-year of continuous employment between 1976 and 2010 were included. Incident cancer cases [lung, extra-thoracic airways (ETA), leukemia, brain and kidney] occurring before the end of 2015 were identified from the Namibian and South African National Cancer Registries, and RUL's occupational health provider. Using a case-cohort design, data on exposure and confounding factors were collected for all cancer cases among the study cohort and a stratified random sample (sub-cohort) of the cohort, including cases. Radiation doses were estimated based on annual dose records held by RUL. In total, 76 cancer cases (32 lung, 18 ETA, 8 leukemia, 9 brain, 9 kidney) and a sub-cohort of 1,121 sampled from 7,901 RUL employees were included. A weighted Cox model, adjusted for available known confounders, produced a rate ratio (95% CI) for lung cancer of 1.42 (0.42, 4.77) and 1.22 (0.26, 5.68), respectively, for medium and higher cumulative lung dose categories compared to the lower category, and 1.04 (0.95, 1.13) for a dose increase of 10 mSv. This study faced considerable challenges with respect to case ascertainment, exposure estimates, and ensuring accuracy of key variables. Persuasive consistent evidence for elevated cancer risk was not found for radiation or other exposures studied at the Rössing uranium mine.

In vitro-in silico correlation of three-dimensional turbulent flows in an idealized mouth-throat model.

There exists an ongoing need to improve the validity and accuracy of computational fluid dynamics (CFD) simulations of turbulent airflows in the extra-thoracic and upper airways. Yet, a knowledge gap remains in providing experimentally-resolved 3D flow benchmarks with sufficient data density and completeness for useful comparison with widely-employed numerical schemes. Motivated by such shortcomings, the present work details to the best of our knowledge the first attempt to deliver in vitro-in silico correlations of 3D respiratory airflows in a generalized mouth-throat model and thereby assess the performance of Large Eddy Simulations (LES) and Reynolds-Averaged Numerical Simulations (RANS). Numerical predictions are compared against 3D volumetric flow measurements using Tomographic Particle Image Velocimetry (TPIV) at three steady inhalation flowrates varying from shallow to deep inhalation conditions. We find that a RANS k-ω SST model adequately predicts velocity flow patterns for Reynolds numbers spanning 1'500 to 7'000, supporting results in close proximity to a more computationally-expensive LES model. Yet, RANS significantly underestimates turbulent kinetic energy (TKE), thus underlining the advantages of LES as a higher-order turbulence modeling scheme. In an effort to bridge future endevours across respiratory research disciplines, we provide end users with the present in vitro-in silico correlation data for improved predictive CFD models towards inhalation therapy and therapeutic or toxic dosimetry endpoints.

How SARS-CoV-2 Omicron droplets transport and deposit in realistic extrathoracic airways

The SARS-CoV-2 Omicron variant is more highly transmissible and causes a higher mortality rate compared to the other eleven variants despite the high vaccination rate. The Omicron variant also establishes a local infection at the extrathoracic airway level. For better health risk assessment of the infected patients, it is essential to understand the transport behavior and the toxicity of the Omicron variant droplet deposition in the extrathoracic airways, which is missing in the literature. Therefore, this study aims to develop a numerical model for the Omicron droplet transport to the extrathoracic airways and to analyze that transport behavior. The finite volume method and ANSYS Fluent 2020 R2 solver were used for the numerical simulation. The Lagrangian approach, the discrete phase model, and the species transport model were employed to simulate the Omicron droplet transport and deposition. Different breathing rates, the mouth and nose inhalation methods were employed to analyze the viral toxicity at the airway wall. The results from this study indicated that there was a 33% of pressure drop for a flow rate at 30 l/min, while there was only a 3.5% of pressure drop for a 7.5 l/min. The nose inhalation of SARS-CoV-2 Omicron droplets is significantly more harmful than through the mouth due to a high deposition rate at the extrathoracic airways and high toxicity in the nasal cavities. The findings of this study would potentially improve knowledge of the health risk assessment of Omicron-infected patients.

A critical analysis of the CFD-DEM simulation of pharmaceutical aerosols deposition in extra-thoracic airways

Recent advances in the characterization of the human respiratory system and in multi-phase flow dynamics in complex geometries have led numerical simulations to play an expanding role for exploring aerosol deposition mechanisms in the lungs. However, the development of an efficient numerical and mathematical description is far from unique, and determining which aspects of the modelling are critical and which details are essentially irrelevant is indeed a difficult task. With the aim of addressing this lack of a rationalized framework, we propose a systematic analysis of pharmaceutical aerosols deposition in the extra-thoracic airways, focusing on several important modelling aspects whose related assumptions and approximations have not always been sufficiently discussed and clarified. We consider the importance of intrinsic time dependent fluctuations of the air flow, highlighting how their contribution in aerosol deposition is as important as the particle-turbulence interaction one. We show how sensitive the turbulence intensity can be to the meshing strategy and how aerosol deposition can be influenced by the latter choice. We demonstrate how a swirling air jet can enhance extra-thoracic deposition compared to a straight one, and how different the deposition patterns can be in case a realistic inhalation profile and aerosol plume are employed.

Fate of inhaled aerosols under the influence of glottal motion in a realistic in silico human tracheobronchial tree model

Despite the prevalence of inhalation therapy in the treatment of various respiratory diseases, predicting and optimizing lung deposition fractions of inhaled drugs for maximal efficacy remains challenging due to the complex anatomical structures of the extra-thoracic airways, notably the glottal region. One of the widespread speculations in current insilico simulations lies in assuming a static glottis during inhalation, while in reality inhalation leads to significant glottis cross-sectional area expansion. The present work attempts to explore, insilico, the influence of transient movement of the glottal structures on inhalation therapy outcomes. To this end, we adopted a CT-based realistic human tracheobronchial tree (TB) model and explored transient airflows and deposition outcomes for a broad range of inhaled aerosols (i.e., dp=1-12 μm) under a dry powder inhaler (DPI) maneuver. Three different glottal expansion ratios, spanning static to 40 percent cross-sectional area expansion have been considered for the analysis. Our findings point to the tangible impact of glottal motion on airflow and particle deposition along the respiratory tract for a DPI maneuver, where a static glottis underpredicts the total particle deposition in the TB model for lower sized particles (dp≤ 3 μm) compared to predictions for all dynamic glottal motions. In contrast, for larger size particles (i.e., 5 ≤dp≤ 10 μm), a static glottis yields lower total deposition in the TB model compared with dynamic glottal motions. Our study also underlines that regional deposition of smaller micron-sized particles is most affected by glottal deformation in the conducting airways.

Influence of Complete Denture Use on Respiratory Capacity: A Systematic Review

This study aimed to determine whether the use of complete dentures has an influence on the respiratory capacity, assessed by the spirometry examination. A systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis and registered in the International Prospective Register of Systematic Reviews (CRD42021255224). The PICO question (population/exposure/comparison/outcome) was "Does the use of complete dentures influence the respiratory capacity of a toothless subject?" A search strategy was adapted for the PubMed/MEDLINE, The Cochrane Library, OpenGrey, Lilacs, Scopus, and Embase databases. Inclusion criteria were prospective and retrospective studies. The new castle ottawa (NOS) scale and the Methodological Index for Non-randomized studies were selected to assess the quality of the included studies. Four studies were selected, totalizing the evaluation of 242 participants, aged ranging from 40 to 73 years old. Two studies concluded that the use of complete dentures can negatively affect the respiratory capacity. One study stated that it did not interfere regardless of its use during spirometric measurements, and the other reported that dental prosthesis was required in cases of evaluation of the extrathoracic airways. The use of complete dentures did not represent relevant changes from the reference values for pulmonary function in the spirometry test. Considering the results of this review, it is not yet possible to establish a clinical protocol for the use of complete dentures during the test. Oral rehabilitation with conventional complete dentures is widely used for the treatment of edentulism, especially in elderly patients. In addition, with aging, many complex changes in immunity and respiratory function contribute to the increase in the development of lung diseases. Therefore, it is important to establish a guidance regarding the use or not of the removable dental prostheses in the respiratory capacity test through spirometry examination.

Fine Particle Fraction: The Good and the Bad.

Fine particle fraction (FPF) is defined in general terms as the fraction or percentage of the drug mass contained in an aerosol cloud that may be small enough to enter the lungs and exert a clinical effect. An aerodynamic diameter of 5 μm represents the approximate border between "fine" and "coarse" particles, but there is no universally agreed upon definition of FPF in terms of an aerodynamic particle size range. FPF alone does not adequately describe a heterodisperse aerodynamic particle size distribution, and it needs to be combined with another measure or measures indicating the width of the distribution. When determined using techniques specified in United States and European Pharmacopeias, FPF is measured by cascade impactors that have straight-sided ninety degree inlets through which air is drawn at a constant rate. It is not the purpose of in vitro tests to predict in vivo behavior, and FPF is primarily a measure of aerosol quality. Despite this, FPF broadly predicts the amount of drug from an inhaler device depositing in the lungs, but it systematically overestimates whole lung deposition and may not correctly predict the relative lung depositions for two inhalers of different types. The relationship between FPF and both drug pharmacokinetics and clinical response is incompletely understood at the present time, and more studies are needed to investigate these relationships. Modifications to impactor technologies, including inlets that mimic the human extrathoracic airways and the use of realistic breathing patterns, would be expected to improve the predictive power of in vitro tests for drug delivery in vivo.

Evaluation of the polyhedral mesh style for predicting aerosol deposition in representative models of the conducting airways

A critical factor affecting the accuracy of Computational Fluid Dynamic (CFD) simulations and the time required to conduct them is construction of the computational mesh. This study aimed to evaluate the relatively new polyhedral mesh style for simulating aerosol deposition in the upper conducting airways compared with established meshing techniques and experimental data. Hexahedral and polyhedral mesh solutions were compared in two benchmark geometries: 1) a 90°-bend with flow characteristics similar to the extrathoracic airways of an adolescent child, and 2) a double bifurcation representing bifurcations B3–B5 in an adult. Both 4-block and 5-block hexahedral meshes were used in the 90°-bend to capture the potential of fully-structured hexahedral meshes. In the 90°-bend, polyhedral elements matched polydisperse in vitro deposition data with 20% relative error (RE; averaged across the particle sizes considered), which is an improvement on the accuracy of the 4-block hexahedral mesh (35% RE) and is similar to the accuracy of the 5-block hexahedral mesh (19% RE). In the double bifurcation, deposition fraction relative differences evaluated between polyhedral and hexahedral meshes ranged from 0.3% to 28.6% for the different particle sizes assessed, which is an order of magnitude improvement compared with previous studies that considered hexahedral vs. hybrid tetrahedral-prism meshes for the same flow field. Solution convergence time with polyhedral elements was found to be 50%–140% higher than with hexahedral meshes of comparable size. While application dependent, the increase in simulation time observed with polyhedral meshes will likely be outweighed by the ease and convenience of polyhedral mesh construction. It was concluded that the polyhedral mesh style, with sufficient resolution especially near the walls, is an excellent alternative to the highly regarded hexahedral mesh style for predicting upper airway aerosol transport and deposition, providing a powerful new tool for the assessment of respiratory aerosol dosimetry.

A Novel Strategy for the Assessment of Radon Risk Based on Indicators.

Among the physical pollutants affecting indoor air, the radioactive gas radon may turn out to be the most hazardous. Health effects related to radon exposure have been investigated for several decades, providing major scientific evidence to conclude that chronic exposures can cause lung cancer. Additionally, an association with other diseases, such as leukemia and cancers of the extra-thoracic airways, has been advanced. The implementation of a strategy to reduce the exposure of the population and minimize the health risk, according to the European Directive 59/2013/Euratom on ionizing radiations, is a new challenge in public health management. Starting from an understanding of the general state-of-the-art, a critical analysis of existing approaches has been conducted, identifying strengths and weaknesses. Then, a strategy for assessing the radon exposure of the general population, in a new comprehensive way, is proposed. It identifies three main areas of intervention and provides a list of hazard indicators and operative solutions to control human exposure. The strategy has been conceived to provide a supporting tool to authorities in the introduction of effective measures to assess population health risks due to radon exposure.

Deposition distribution of the new coronavirus (SARS-CoV-2) in the human airways upon exposure to cough-generated droplets and aerosol particles

The new coronavirus disease 2019 (COVID-19) has been emerged as a rapidly spreading pandemic. The disease is thought to spread mainly from person-to-person through respiratory droplets produced when an infected person coughs, sneezes, or talks. The pathogen of COVID-19 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It infects the cells binding to the angiotensin-converting enzyme 2 receptor (ACE2) which is expressed by cells throughout the airways as targets for cellular entry. Although the majority of persons infected with SARS-CoV-2 experience symptoms of mild upper respiratory tract infection, in some people infections of the acinar airways result in severe, potentially fatal pneumonia. However, the induction of COVID-19 pneumonia requires that SARS-CoV-2 reaches the acinar airways. While huge efforts have been made to understand the spread of the disease as well as the pathogenesis following cellular entry, much less attention is paid to how SARS-CoV-2 from the environment reach the receptors of the target cells. The aim of the present study is to characterize the deposition distribution of SARS-CoV-2 in the airways upon exposure to cough-generated droplets and aerosol particles. For this purpose, the Stochastic Lung Deposition Model has been applied. Particle size distribution, breathing parameters supposing normal breathing through the nose, and viral loads were taken from the literature. We found that the probability of direct infection of the acinar airways due to inhalation of particles emitted by a bystander cough is very low. As the number of viruses deposited in the extrathoracic airways is about 7 times higher than in the acinar airways, we concluded that in most cases COVID-19 pneumonia must be preceded by SARS-CoV-2 infection of the upper airways. Our results suggest that without the enhancement of viral load in the upper airways, COVID-19 would be much less dangerous. The period between the onset of initial symptoms and the potential clinical deterioration could provide an opportunity for prevention of pneumonia by blocking or significantly reducing the transport of viruses towards the acinar airways. Therefore, even non-specific treatment forms like disinfection of the throat and nasal and oral mucosa may effectively keep the viral load of the upper airways low enough to avoid or prolong the progression of the disease. In addition, using a tissue or cloth in order to absorb droplets and aerosol particles emitted by own coughs of infected patients before re-inhalation is highly recommended even if they are alone in quarantine.

Dry powder inhaler aerosol deposition in a model of tracheobronchial airways: Validating CFD predictions with in vitro data.

Effective drug delivery into the lungs plays an important role in management of pulmonary diseases that affect millions all around the world. The main objective of this investigation is to study airflow structure, as well as transport and deposition of micron-size particles at different inhalation flow rates in a realistic model of human tracheobronchial airways. The airway model was developed based on computed tomography (CT) images of a healthy 48-years-old female, which includes extrathoracic, trachea, and bronchial airways up to fourth generations. Computational fluid dynamics (CFD) simulations were performed to predict transport and deposition of inhaled particles and the results were compared to our previous in vitro experiments. Airflow structure was studied through velocity contours and streamlines in the extrathoracic region, where the onset of turbulence, reverse flow and subsequently vortex formation, and laryngeal jet are found to be critical phenomenons in the formation of airflow and deposition patterns. The deposition data was presented by deposition efficiency (DE) and deposition fraction (DF) against impaction parameter and Stokes number. At all of the inhalation flow rates, highest values of deposition fractions were devoted to the mouth-throat (MT), tracheobronchial tree (TB), and trachea (Tra), respectively (At 60L/min: MT=6.7%, TB=5.3%, Tra=1.9%). The numerical deposition data showed a good agreement with the experimental deposition data in most of the airway regions (e.g. less than 10% difference between the deposition fractions in the tracheobronchial region). Enhancing inhalation flow rate in all of the airway regions led to an uptrend in deposition rate due to the increase of particles inertia and turbulence level. In addition, the increase of particle deposition with enhancing inhalation flow rate in all of the sections including extrathoracic, trachea, and tracheobronchial tree suggesting that inertial impaction is the dominant deposition mechanism due to the increase of inertial force. In conclusion, the validated CFD model provided an opportunity to cover the limitations of our previous experimental investigation on aerosol deposition of commercial inhalers and became an efficient method for further studies.

3D Assessment of Endodontic Lesions with a Low-Dose CBCT Protocol.

Background: Cone beam computed tomography (CBCT) is often used in different fields of dental science, especially in complex anatomical districts like the endodontic one. The aim of this study is to propose a low-dose CBCT protocol useful in cases of endodontic lesions. Methods: The device used was a MyRay Hyperion X9-11x5; the low dose setting of the machine was 90 Kv, 27 mAs, CTDI/Vol 2.89 mGy. The absorbed organ doses have been evaluated with an anthropomorphic phantom loaded with thermoluminescent dosimeters positioned at the level of sensitive organs like brain, bone marrow, salivary glands, thyroid, esophagus, oral mucosa, extrathoracic airways, and lymph nodes. Equivalent and effective doses have been calculated; the last one has been calculated using the recommendations approved by the Main Commission of ICRP (International Commission Radiological Protection) in March 2007. For the assessment of image quality, five senior clinicians, independent and experienced clinicians, were asked to state if CBCT scans were accurate enough to assess endodontic lesions. Results: The use of a low-dose CBCT acquisition produced the lowest organ dose (5.01 microSv) at the level of the esophagus. Image quality has been considered accurate enough for endodontic diagnostic needs. Conclusions: CBCT low-dose protocol can be used over the standard one in endodontic special cases because it provides a significantly lower radiation dose to the patients while ensuring good image quality. However, further studies are necessary to evaluate the opportunity of low-dose CBCT exams in endodontic clinical practice.

Effect of Inspiratory Maneuvers on Lung Deposition of Tobramycin Inhalation Powder: A Modeling Study.

Background: Tobramycin inhalation powder (TIP) and tobramycin inhalation solution (TIS) are considered equally effective for the treatment of chronic pulmonary Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients. The impact of TIP inhalation maneuvers on distribution of tobramycin is unknown. We hypothesized that (1) fast TIP inhalations result in greater extrathoracic and reduced small airway concentrations compared with slow or uninstructed TIP inhalations; (2) slow TIP inhalations result in greater small airway concentrations than TIS inhalations. The aim of the study was to assess TIP and TIS deposition with computational fluid dynamics (CFD). Methods: Uninstructed, instructed fast, and instructed slow TIP inhalations of CF patients on maintenance TIP therapy, and inhalations during nebulization of saline with PARI LC Plus® were recorded at home. Drug deposition was determined using TIP and TIS aerosol characteristics together with CFD simulations based on airway geometries from chest computed tomography scans. The drug concentration was assessed in extrathoracic, central, large, and small airways. Results: Twelve patients aged 12-45 years were included, and 144 CFD simulations were performed. In all individual analyses, the tobramycin concentrations were well above the threshold for effective dose of 10 times minimal inhibitory concentration throughout the bronchial tree. Extrathoracic concentrations were comparable between fast and uninstructed TIP inhalations, while slow inhalations resulted in reduced extrathoracic concentrations compared with uninstructed TIP inhalations (p = 0.024). Small airway concentrations were comparable between fast and uninstructed TIP inhalations, while slow TIP inhalations resulted in greater small airway concentrations than uninstructed TIP inhalations (p < 0.001). Small airway concentrations of TIS were comparable with those of slow TIP inhalations (p = 0.065), but greater than those of fast and uninstructed TIP inhalations (p < 0.001). Conclusion: All TIS and TIP inhalation maneuvers resulted in high enough concentrations, however, inhaling TIS or inhaling TIP slowly results in the greatest small airway deposition.

Euler-Lagrange Prediction of Diesel-Exhaust Polydisperse Particle Transport and Deposition in Lung: Anatomy and Turbulence Effects

In clinical assessments, the correlation between atmospheric air pollution and respiratory damage is highly complicated. Epidemiological studies show that atmospheric air pollution is largely responsible for the global proliferation of pulmonary disease. This is particularly significant, since most Computational Fluid Dynamics (CFD) studies to date have used monodisperse particles, which may not accurately reflect realistic inhalation patterns, since atmospheric aerosols are mostly polydisperse. The aim of this study is to investigate the anatomy and turbulent effects on polydisperse particle transport and deposition (TD) in the upper airways. The Euler-Lagrange approach is used for polydisperse particle TD prediction in both laminar and turbulent conditions. Various anatomical models are adopted to investigate the polydisperse particle TD under different flow conditions. Rossin-Rammler diameter distribution is used for the distribution of the initial particle diameter. The numerical results illustrate that airflow rate distribution at the right lung of a realistic model is higher than a non-realistic model. The CFD study also shows that turbulence effects on deposition are higher for larger diameter particles than with particles of smaller diameter. A significant amount of polydisperse particles are also shown to be deposited at the tracheal wall for CT-based model, whereas particles are mostly deposited at the carinal angle for the non-realistic model. A comprehensive, polydisperse particle TD analysis would enhance understanding of the realistic deposition pattern and decrease unwanted therapeutic aerosol deposition at the extrathoracic airways.

Wheezing in Childhood- not Always Asthma -Review

Wheezing in infancy and childhood is a common condition; however it is not a single disorder and can be due to causes other than asthma. Wheezing is a musical, expiratory sound due to narrowing and hyper responsiveness of the intra-thoracic and extra thoracic airways. Not all wheezing is asthma. Wheezing-associated respiratory illnesses in children are often described as asthma; however while most children with asthma show symptoms of wheezing. Wheezing, coughing and breathlessness are common in young children, and can all be symptoms of conditions other than asthma. Bronchiolitis refers to a first episode of wheezing, with respiratory distress triggered by a viral infection. Episodic wheezing refers to discrete episodes of wheezing without intermittent symptoms. Unremitting wheezing refers to distinct episodes of wheezing with intermittent symptoms, such as coughing or wheezing at night or in response to exercise, crying, laughter, mist, or cold air. Environmental conditions that increase the rate of bacterial and viral infections are risk factors for transient wheezing, but its relationship to asthma remains unclear. Children with frequent simple colds and other common childhood infections in infancy are less likely to develop persistent wheezing in later childhood. Many preschool children with viral induced wheezing will outgrow these symptoms, and do not have asthma. Generally, asthma is identified by the presence of cough, wheeze and breathing difficulty, together with features of atopy (or a family history of atopy or asthma) and impaired lung function evidenced by spirometry. It is important to explain to parents/ carers that wheezing in an infant or preschooler does not mean the child will have asthma or allergies by primary school age. In preschool-aged children with recurrent wheeze (e.g. four or more episodes per year), consider using the Asthma Predictive Index, to estimate whether children are likely to have asthma during primary school years. Asthma Prediction Index has some major criteria and minor criteria. Major criteria are diagnosis of asthma in one or both parent, Diagnosis of atopic dermatitis during the first 3 yr. of life, Sensitization against &gt;1 allergen, Minor criteria- Milk, egg, or peanut sensitization. Associated with respiratory infections, Eosinophilia &gt;4%. In the first 3 years of life if anyone who have 1 major criteria or 2 minor criteria is present in one episode, the possibility of asthma in 6-13 years is 59% but 2 episodes possibility is 77%. Investigation -Chest X-Ray, spirometry, CT scan of Chest and Fiberoptic Bronchoscope. It is usually not necessary if history of “classic” asthma or, patient response to salbutamol and or steroid; then only spirometry should be done. But need other investigation when Chronic cough (&gt;1 month), recurrent pneumonia, persistent signs or symptoms are seen despite therapy. Bronchomalacia, esophageal dilatation, foreign body aspiration, vocal cord dysfunction, viral pneumonia allergic rhinitis, bronchiectasis, cystic fibrosis, heart failure, acute chest syndrome of sickle cell anemia, use of beta blockers, etc. All these conditions described can present with wheezing and certainly do not characterize asthma. Here we reported six case series having wheeze but ultimate diagnosis was not asthma.

Effect of delayed pMDI actuation on the lung deposition of a fixed-dose combination aerosol drug

Lack of coordination between the beginning of the inhalation and device triggering is one of the most frequent errors reported in connection with the use of pMDI devices. Earlier results suggested a significant loss in lung deposition as a consequence of late actuation. However, most of our knowledge on the effect of poor synchronization is based on earlier works on CFC devices emitting large particles with high initial velocities. The aim of this study was to apply numerical techniques to analyse the effect of late device actuation on the lung dose of a HFA pMDI drug emitting high fraction of extrafine particles used in current asthma and COPD therapy. A computational fluid and particle dynamics model was combined with stochastic whole lung model to quantify the amount of drug depositing in the extrathoracic airways and in the lungs. High speed camera measurements were also performed to characterize the emitted spray plume. Our results have shown that for the studied pMDI drug late actuation leads to reasonable loss in terms of lung dose, unless it happens in the second half of the inhalation period. Device actuation at the middle of the inhalation caused less than 25% lung dose reduction relative to the value characterizing perfect coordination, if the inhalation time was between 2 and 5 s and inhalation flow rate between 30 and 150 L/min. This dose loss is lower than the previously known values of CFC devices and further support the practice of triggering the device shortly after the beginning of the inhalation instead of forcing a perfect synchronization and risking mishandling and poor drug deposition.

Deposition of carbon nanotubes in the human respiratory tract: a theoretical approach

Background: The study aims to describe the behavior of single-wall and multi-wall carbon nanotubes (SWCNT, MWCNT) in the human respiratory tract (HRT). Based on a theoretical deposition model, possible accumulation of these particles in different lung regions is subject to a detailed investigation. Predictions made by the theoretical approach should help to develop appropriate risk assessments for highly anisometric ultrafine particles. Methods: Particle geometry expressed by the aspect ratio was approximated by using the aerodynamic diameter concept. Transport and deposition of SWCNT and MWCNT in the HRT was simulated with the help of a random-walk model based on the Monte-Carlo method. Random particle paths were computed for a stochastic lung architecture. For the simulation of particle deposition, empirical and analytical equations describing the physical processes exerting on the particles (i.e., Brownian motion, impaction, interception, and gravitational settling) were used. Simulations were conducted for adult lungs and two different breathing conditions. Results: For sitting breathing (low tidal volume and breathing frequency), SWCNT exhibit a total deposition of 77.7%, with 34.3% being accumulated in the extrathoracic airways, 35.1% being deposited in the thoracic airways (lung generation 1–27), and 8.3% being targeted to the alveoli. MWCNT show a total deposition of 23.1%, whereby extrathoracic deposition amounts to 10.2%, bronchial deposition to 10.1, and alveolar deposition to 2.8%. For heavy-work breathing (high tidal volume and breathing frequency), total deposition of SWCNT is decreased (67.2%) and regional deposition is significantly modified (extrathoracic: 4.5%, bronchial: 43.5%, alveolar: 19.2%). Total deposition of MWCNT is reduced (15.4%), resulting in a remarkable change of extrathoracic (1.1%), bronchial (8.1%), and alveolar deposition (6.2%). Conclusions: Inhalation of SWCNT and MWCNT may bear considerable health risks, as high numbers of inspired particles are deposited in lung regions (distal bronchioles, alveoli) being predisposed to various pulmonary diseases.

Inertial and gravitational effects on aerosol deposition in the conducting airways

In most inhaled drug delivery applications, aerosol deposition in the upper airways occurs primarily via impaction. However, the effects of gravity become important as particle size increases and flow rate decreases. Sedimentation can therefore be significant in the smaller airways of the tracheobronchial tree, where velocities decrease due to the large increase in cross-sectional area, as well as the larger airways at low inhalation flow rates. In order to assess the relative importance of impaction and sedimentation, particle transport and deposition is examined under different steady inhalation conditions in a mouth-throat and a bifurcation model, using direct numerical simulations. The results are also compared to computations without the effect of gravity on the particles. Two important parameters characterize particle motion: (i) the Stokes number, Stk, and (ii) the ratio of the gravitational settling velocity to the fluid velocity, Vg*. The ratio of these two parameters is the Froude number, which measures the relative importance of inertial to gravitational forces. Instantaneous definitions of the Stokes number, non-dimensional settling velocity and Froude number are derived, based on the local flow properties, which provide a more accurate representation of the particle trajectories compared to the reference parameters based on characteristic flow scales. Results show that, in certain regions of the flow, the instantaneous Froude number can be three to four orders of magnitude smaller than the reference value. In these regions, deposition via sedimentation is shown to be significant, and the reference parameter underestimates gravitational effects. In the extrathoracic airways, particles with high Vg* deposit primarily in the mouth, via sedimentation, while particles with high Stk deposit mainly in the larynx and trachea, via impaction. In the bifurcation, different orientation angles of the airway geometry are shown to result in non-negligible variation in deposition. Impaction is the dominant mechanism for deposition on the carinal ridge, while sedimentation occurs along airway walls at an angle to the gravity direction. In the daughter branches, both impaction and sedimentation contribute to deposition.

Scaling an idealized infant nasal airway geometry to mimic inertial filtration of neonatal nasal airways

Idealized extrathoracic airways are a valuable tool for the development and testing of pharmaceutical aerosol delivery devices. These airways are designed to mimic the average filtration properties of the extrathoracic airways of the population on which they are based. We have investigated the ability to scale a previously developed infant nasal airway to generate a model with the correct filtration properties to mimic the neonatal population. Prospective scale factors were identified based on the dimensions of realistic nasal replicas, and based on 50th percentile body mass, body length, and head circumference. Inertial deposition was measured for four geometrically similar idealized nasal airway models. These data were compared to deposition in nasal airway replicas based on computed tomography (CT) images of seven infants between the ages of 5 and 79 days. Isotropically scaling the model that mimics the infant population (average age approximately 9 months) by 0.75 produced a model that mimics the neonatal population (average age approximately 1 month). This scale factor was consistent with the ratio of model characteristic diameters (airway volume divided by surface area, DV/As) and with the ratio of 50th percentile body lengths for the two average ages. A predictive correlation based on Reynolds and Stokes numbers was identified that provides deposition efficiency of this geometry for DV/As between 1.20mm and 0.72mm. This equation can be used to provide expected deposition characteristics of our idealized nasal model before construction at scales not specifically considered here.