Trumpet Model Research Articles

Inverse problem to estimate lips parameters values of outward-striking trumpet model for successive playing registers.

The objective of this work is to estimate by inverse problem lip parameters values of trumpet model so that the oscillation thresholds for successive playing registers occur for the same blowing pressure as the one measured on several trumpet players. The lips vibration is modeled through an oscillator including unknown parameters such as resonance frequency, quality factor, surface mass, stiffness, and opening at rest of the lips. The oscillation threshold is calculated through linear stability analysis of the outward-striking model including the nonlinear coupling with the bore of the trumpet. It appears that many combinations of parameter values are suitable to obtain the same blowing pressure at threshold as in the experiments. According to the analysis of the possible parameter values, some hypotheses are formulated about the playing strategies used by the trumpeter to select the different registers of the instrument. In addition to the resonance frequency of the lips, controlling the lips opening at rest appears to be a viable strategy to match experimental oscillation thresholds in terms of blowing pressure. Numerical values for the lips parameters are given and through sound synthesis, allow the successive registers of the trumpet to be played.

Three-dimensional simulations of sound propagation in a trumpet with accurate mouthpiece shank geometry

The length and bore geometry of musical instruments directly influences the quality of sound that can be produced. In brass instruments, nonlinear effects from finite-amplitude wave propagation can lead to wave distortion giving sounds a brassy timbre [3,5,16,22,29]. In this paper, we propose a three-dimensional model to describe nonlinear wave propagation in a trumpet and investigate the importance of the mouthpiece shank geometry. The time pressure waveforms corresponding to B3b and B4b notes at the mouthpiece were recorded at the mouthpiece shank are recorded and used as inputs for our model. To incorporate compressibility and nonlinear effects, the compressible Euler equations are used to describe the evolution of the nonlinear waves. The system was solved numerically using the discontinuous Galerkin method. The numerical results were compared with the waveforms of the musical notes, which were also measured outside the bell of the trumpet, to validate our approach. Simulations were run for both notes in computational trumpets where different bore geometries were modelled. Our results demonstrate that the shape of the narrow region near the mouthpiece greatly influences the wave propagation and must be considered in a trumpet model.

Various reduced-order surrogate models for fluid flow and mass transfer in human bronchial tree.

The bronchial tree plays a main role in the human respiratory system because the air distribution throughout the lungs and gas exchange with blood occur in the airways whose dimensions vary from several centimeters to micrometers. Organization of about 60,000 conducting airways and 33 million respiratory airways in a limited space results in a complex structure. Due to this inherent complexity and a high number of airways, using target-oriented dimensional reduction is inevitable. In addition, there is no general reduced-order model for various types of problems. This necessitates coming up with an appropriate model from a variety of different reduced-order models to solve the desired problem. Lumped formulation, trumpet, or typical path model of whole or parts of bronchial tree are frequently used reduced-order models. On the other hand, using any of these models results in underestimation of flow heterogeneity leading to inaccurate prediction of the systems whose mechanisms depend on the fluid heterogeneity. In this study, a simple robust model combining mechanistic and non-mechanistic modeling approaches of the bronchial tree is proposed which overcomes the limitations of the previous reduced-order models and gives the same results of a detailed mechanistic model for the first time. This model starts from an accurate multi-branching model of conducting and respiratory airways (i.e., the base model) and suggests a proxy model of conducting airway and reduced-order model of respiratory airways based on the base model to significantly reduce computational cost while retaining the accuracy. The combination of these models suggests various reduced-order surrogate models of the human bronchial tree for different problems. The applications and limitations of each reduced-order model are also discussed. The accuracy of the proposed model in the prediction of fluid heterogeneity has been examined by the simulation of multi-breath inert gas washout because the alveolar slope is the reflection of fluid heterogeneity where the computational time decreases from 121h (using the base model) to 4.8s (using the reduced-order model). A parallel strategy for solving the equations is also proposed which decreases run time by 0.18s making the model suitable for real-time applications. Furthermore, the ability of the model has been evaluated in the modeling of asthmatic lung as an instance of abnormal lungs, and in the modeling of O2-CO2 exchange as an instance of nonlinear reacting systems. The results indicate that the proposed model outperforms previous models based on accuracy, robustness, and run time.

A quasi-3D model of the whole lung: airway extension to the tracheobronchial limit using the constrained constructive optimization and alveolar modeling, using a sac-trumpet model.

Existing computational models used for simulating the flow and species transport in the human airways are zero-dimensional (0D) compartmental, three-dimensional (3D) computational fluid dynamics (CFD), or the recently developed quasi-3D (Q3D) models. Unlike compartmental models, the full CFD and Q3D models are physiologically and anatomically consistent in the mouth and the upper airways, since the starting point of these models is the mouth–lung surface geometry, typically created from computed tomography (CT) scans. However, the current resolution of CT scans limits the airway detection between the 3rd–4th and 7th–9th generations. Consequently, CFD and the Q3D models developed using these scans are generally limited to these generations. In this study, we developed a method to extend the conducting airways from the end of the truncated Q3D lung to the tracheobronchial (TB) limit. We grew the lung generations within the closed lung lobes using the modified constrained constructive optimization, creating an aerodynamically optimized network aiming to produce equal pressure at the distal ends of the terminal segments. This resulted in a TB volume and lateral area of ∼165 cc and ∼2000 cm2, respectively. We created a “sac–trumpet” model at each of the TB outlets to represent the alveoli. The volumes of the airways and the individual alveolar generations match the anatomical values by design: with the functional residual capacity at 2611 cc. Lateral surface areas were scaled to match the physiological values. These generated Q3D whole lung models can be efficiently used for conducting multiple breathing cycles of drug transport and deposition simulations.

Impact of breath sampling on exhaled carbon monoxide

The influence of breath sampling on exhaled carbon monoxide (eCO) and related pulmonary gas exchange parameters is investigated in a study with 32 healthy non-smokers. Mid-infrared tunable diode laser absorption spectroscopy and well-controlled online sampling is used to precisely measure mouth- and nose-exhaled CO expirograms at exhalation flow rates (EFRs) of 250, 120 and 60 ml s−1, and for 10 s of breath-holding followed by exhalation at 120 ml s−1. A trumpet model with axial diffusion is employed to fit simulated exhalation profiles to the experimental expirograms, which provides equilibrium airway and alveolar CO concentrations and the average lung diffusing capacity in addition to end-tidal concentrations. For all breathing maneuvers, excellent agreement is found between mouth- and nose-exhaled end-tidal CO (ETCO), and the individual values for ETCO and alveolar diffusing capacity are consistent across maneuvers. The eCO parameters clearly show a dependence on EFR, where the lung diffusing capacity increases with EFR, while ETCO slightly decreases. End-tidal CO is largely independent of ambient air CO and alveolar diffusing capacity. While airway CO is slightly higher than, and correlates strongly with, ambient air CO, and there is a weak correlation with ETCO, the results point to negligible endogenous airway CO production in healthy subjects. An EFR of around 120 ml s−1 can be recommended for clinical eCO measurements. The employed method provides means to measure variations in endogenous CO, which can improve the interpretation of exhaled CO concentrations and the diagnostic value of eCO tests in clinical studies. Clinical trial registration number: 2017/306-31

Regional Deposition: Deposition Models.

Modeling particle deposition in the human lung requires information about the morphology of the lung in terms of simple geometric units, e.g., characterizing bronchial airways by straight cylindrical tubes. Five different regional deposition models are discussed in this section with respect to morphometric lung models and related mathematical modeling techniques: 1) one-dimensional cross-section or "trumpet" model, 2) deterministic symmetric generation or "single-path" model, 3) deterministic asymmetric generation or "multiple-path" model, 4) stochastic asymmetric generation or "multiple-path" model, and 5) single-path computational fluid and particle dynamics (CFPD) model. Current deposition models can predict the following regional deposition quantities relevant for the administration of medical aerosols: 1) regional bronchial and alveolar deposition, 2) generational lung deposition, 3) lobar deposition, 4) generational lobar deposition, and 5) generational surface deposition. Although deposition fractions predicted by the different models depend on the selection of a specific morphometric lung model and a specific set of analytical deposition equations, all models predict the same trends as functions of particle diameter and breathing parameters. In general, the overall agreement between the modeling predictions obtained by the various deposition models and the available experimental evidence indicates that current deposition models correctly predict regional and generational deposition.

Fitting of single-exhalation profiles using a pulmonary gas exchange model—application to carbon monoxide

Real-time breath gas analysis coupled to gas exchange modeling is emerging as promising strategy to enhance the information gained from breath tests. It is shown for exhaled breath carbon monoxide (eCO), a potential biomarker for oxidative stress and respiratory diseases, that a weighted, nonlinear least-squares fit of simulated to measured expirograms can be used to extract physiological parameters, such as airway and alveolar concentrations and diffusing capacities. Experimental CO exhalation profiles are acquired with high time-resolution and precision using mid-infrared tunable diode laser absorption spectroscopy and online breath sampling. A trumpet model with axial diffusion is employed to generate eCO profiles based on measured exhalation flow rates and volumes. The concept is demonstrated on two healthy non-smokers exhaling at a flow rate of 250 ml s−1 during normal breathing and at 120 ml s−1 after 10 s of breath-holding. The obtained gas exchange parameters of the two subjects are in a similar range, but clearly distinguishable. Over a series of twenty consecutive expirograms, the intra-individual variation in the alveolar parameters is less than 6%. After a 2 h exposure to 10 ± 2 ppm CO, end-tidal and alveolar CO concentrations are significantly increased (by factors of 2.7 and 4.9 for the two subjects) and the airway CO concentration is slightly higher, while the alveolar diffusing capacity is unchanged compared to before exposure. Using model simulations, it is found that a three-fold increase in maximum airway CO flux and a reduction in alveolar diffusing capacity by 60% lead to clearly distinguishable changes in the exhalation profile shape. This suggests that extended breath CO analysis has clinical relevance in assessing airway inflammation and chronic obstructive pulmonary disease. Moreover, the novel methodology contributes to the standardization of real-time breath gas analysis.

Modeling Pulmonary Gas Exchange and Single-Exhalation Profiles of Carbon Monoxide.

Exhaled breath carbon monoxide (eCO) is a candidate biomarker for non-invasive assessment of oxidative stress and respiratory diseases. Standard end-tidal CO analysis, however, cannot distinguish, whether eCO reflects endogenous CO production, lung diffusion properties or exogenous sources, and is unable to resolve a potential airway contribution. Coupling real-time breath gas analysis to pulmonary gas exchange modeling holds promise to improve the diagnostic value of eCO. A trumpet model with axial diffusion (TMAD) is used to simulate the dynamics of CO gas exchange in the respiratory system and corresponding eCO concentrations for the first time. The mass balance equation is numerically solved employing a computationally inexpensive routine implementing the method of lines, which provides the distribution of CO in the respiratory tract during inhalation, breath-holding, and exhalation with 1 mm spatial and 0.01 s temporal resolution. Initial estimates of the main TMAD parameters, the maximum CO fluxes and diffusing capacities in alveoli and airways, are obtained using healthy population tissue, blood and anatomical data. To verify the model, mouth-exhaled expirograms from two healthy subjects, measured with a novel, home-built laser-based CO sensor, are compared to single-exhalation profiles simulated using actual breath sampling data, such as exhalation flow rate (EFR) and volume. A very good agreement is obtained in exhalation phases I and III for EFRs between 55 and 220 ml/s and after 10 and 20 s of breath-holding, yielding a unique set of TMAD parameters. The results confirm the recently observed EFR dependence of CO expirograms and suggest that measured end-tidal eCO is always lower than alveolar and capillary CO. Breath-holding allows the observation of close-to-alveolar CO concentrations and increases the sensitivity to the airway TMAD parameters in exhalation phase I. A parametric simulation study shows that a small increase in airway flux can be distinguished from an increase in alveolar flux, and that slight changes in alveolar flux and diffusing capacity have a significantly different effect on phase III of the eCO profiles.

Exhaled Nitric Oxide in Systemic Sclerosis Lung Disease.

Background. Exhaled nitric oxide (eNO) is a potential biomarker to distinguish systemic sclerosis (SSc) associated pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). We evaluated the discriminative validity, feasibility, methods of eNO measurement, and magnitude of differences across lung diseases, disease-subsets (SSc, systemic lupus erythematosus), and healthy-controls. Methods. Consecutive subjects in the UHN Pulmonary Hypertension Programme were recruited. Exhaled nitric oxide was measured at 50 mL/s intervals using chemiluminescent detection. Alveolar and conducting airway NO were partitioned using a two-compartment model of axial diffusion (CMAD) and the trumpet model of axial diffusion (TMAD). Results. Sixty subjects were evaluated. Using the CMAD model, control subjects had lower median (IQR) alveolar NO than all PAH subjects (2.0 (1.5, 2.5) versus 3.14 ppb (2.3, 4.0), p = 0.008). SSc-ILD had significantly lower median conducting airway NO compared to controls (1009.5 versus 1342.1 ml⁎ppb/s, p = 0.04). SSc-PAH had increased median (IQR) alveolar NO compared to controls (3.3 (3.0, 5.7) versus 2.0 ppb (1.5, 2.5), p = 0.01). SSc-PAH conducting airway NO inversely correlated with DLCO (r −0.88 (95% CI −0.99, −0.26)). Conclusion. We have demonstrated feasibility, identified that CMAD modeling is preferred in SSc, and reported the magnitude of differences across cases and controls. Our data supports discriminative validity of eNO in SSc lung disease.

A Lagrangian Approach for Calculating Microsphere Deposition in a One-Dimensional Lung-Airway Model.

Using the open-source software openfoam as the solver, a novel approach to calculate microsphere transport and deposition in a 1D human lung-equivalent trumpet model (TM) is presented. Specifically, for particle deposition in a nonlinear trumpetlike configuration a new radial force has been developed which, along with the regular drag force, generates particle trajectories toward the wall. The new semi-empirical force is a function of any given inlet volumetric flow rate, micron-particle diameter, and lung volume. Particle-deposition fractions (DFs) in the size range from 2 μm to 10 μm are in agreement with experimental datasets for different laminar and turbulent inhalation flow rates as well as total volumes. Typical run times on a single processor workstation to obtain actual total deposition results at comparable accuracy are 200 times less than that for an idealized whole-lung geometry (i.e., a 3D-1D model with airways up to 23rd generation in single-path only).

Increased alveolar nitric oxide concentration is related to nocturnal oxygen desaturation in obstructive sleep apnoea

PurposeTo assess distal/alveolar inflammation in patients with suggestive symptoms of obstructive sleep apnoea (OSA) using exhaled nitric oxide (NO) measured by two-compartment model (2-CM) after correction for axial NO back-diffusion (trumpet model). MethodsNinety five patients suspected for OSA prospectively underwent pulmonary function test, overnight polysomnography (PSG), and exhaled NO measurement. Patients with apnoea–hypopnoea index (AHI) < 5/hour were included in non-OSA group. Exhaled NO was repeatedly measured after PSG in 21 OSA patients and 8 non-OSA subjects. ResultsAlveolar NO concentration (CANO) was significantly higher in OSA patients (n = 71; 4.07 ± 1.7ppb) as compared with non-OSA subjects (n = 24; 2.24 ± 1.06ppb; p < 0.0001) whilst maximal bronchial NO flux (J′awNO) and fractional exhaled NO (FENO) did not differ between the two groups. CANO was strongly associated to AHI (r = 0.701; p < 0.0001) and to recording time with SaO2 < 90% (ST-90%; r = 0.659; p < 0.0001) in OSA patients but not in non-OSA persons. The area under ROC curve for screening patients with OSA and significant nocturnal oxygen desaturation (ST-90% > 1%) was 0.865 ± 0.036 (95% IC, 0.793–0.937; p < 0.0001). CANO at 4.5 ppb could detect these patients with specificity of 94% and sensitivity of 46%. Increase of CANO measured after PSG was significantly related to oxygen desaturation index (ST-90%) in OSA patients. ConclusionsIncreased alveolar NO concentration was related to the severity of nocturnal oxygen desaturation in patients with OSA, linking the distal airway inflammation to intermittent hypoxia. (250 words)

A modified De-Gennes's trumpet model for the prediction of practical adhesion of dynamically- and structurally heterogeneous polymeric networks on solid surfaces

A theoretical model for the prediction of practical adhesion of dynamically- and structurally heterogeneous polymeric networks on solid surfaces.

Alveolar and exhaled NO in relation to asthma characteristics--effects of correction for axial diffusion.

Inflammation in the small airways might contribute to incomplete asthma disease control despite intensive treatment in some subgroups of patients. Exhaled NO (FeNO) is a marker of inflammation in asthma and the estimated NO contribution from small airways (CalvNO ) is believed to reflect distal inflammation. Recent studies recommend adjustments of CalvNO for trumpet model and axial diffusion (TMAD-adj). This study aimed to investigate the clinical correlates of CalvNO , both TMAD-adjusted and unadjusted. Asthma symptoms, asthma control, lung function, bronchial responsiveness, blood eosinophils, atopy and treatment level were assessed in 410 subjects, aged 10-35years. Exhaled NO was measured at different flow-rates and CalvNO calculated, with TMAD-adjustment according to Condorelli. Trumpet model and axial diffusion-adjusted CalvNO was not related to daytime wheeze (P=0.27), FEF50 (P=0.23) or bronchial responsiveness (P=0.52). On the other hand, unadjusted CalvNO was increased in subjects with daytime wheeze (P<0.001), decreased FEF50 (P=0.02) and with moderate-to-severe compared to normal bronchial responsiveness (P<0.001). All these characteristics correlated with increased FeNO (all P<0.05). Unadjusted CalvNO was positively related to bronchial NO flux (J'awNO ) (r=0.22, P<0.001) while TMAD-adjCalvNO was negatively related to J'awNO (r=-0.38, P<0.001). Adjusted CalvNO was not associated with any asthma characteristics studied in this large asthma cohort. However, both FeNO and unadjusted CalvNO related to asthma symptoms, lung function and bronchial responsiveness. We suggest a potential overadjustment by current TMAD-corrections, validated in healthy or unobstructed asthmatics. Further studies assessing axial diffusion in asthmatics with different degrees of airway obstruction and the validity of proposed TMAD-corrections are warranted.

High alveolar concentration of nitric oxide is associated with alveolitis in scleroderma

Alveolar concentration of nitric oxide (CANO) is a non invasive prognostic marker of systemic sclerosis (SSc) lung disease. There is, however, as yet no direct evidence showing concomitant increase of CANO and the presence of inflammatory cells in alveoli. We have therefore measured CANO and performed broncho-alveolar lavage (BAL) in SSc patients. Exhaled NO was measured, by the means of two different models, the two-compartment model (2CM) and the trumpet model with axial diffusion (TMAD), in 22 SSc patients and compared with 15 healthy controls. BAL was performed in all SSc patients. Alveolitis was defined as lymphocytes >14%, polymorphonuclears >4%, or eosinophils >3% on cell count in BAL fluid. Comparisons of CANO levels were made between SSc patients with, and without, alveolitis. Levels of CANO were significantly higher in SSc patients as compared with controls (p<0.001). Median CANO was significantly higher in SSc patients with alveolitis as compared with SSc patients without alveolitis (8.4ppb; 1st and 3rd interquartile range: 6.0–10.5 vs 3.3ppb; 2.2–3.5; p=0.004 for 2CM and 5.4ppb; 3.2–9.2 vs 3.2ppb; 1.4–3.3, p=0.02 for TMAD), while bronchial airway output of NO (J′awNO, p=0.19), and fractional exhaled NO (FENO, p=0.12) were comparable. CANO was consistently high in SSc patients with alveolitis irrespective of the methods chosen (TMAD or 2CM). Our findings showed that increased CANO was associated with alveolitis in patients with SSc. We submit that CANO could be used as a reliable non-invasive surrogate biomarker of alveolitis in scleroderma lung disease.

The fraction of NO in exhaled air and estimates of alveolar NO in adolescents with asthma: Methodological aspects

This study investigated the oral contribution to exhaled NO in young people with asthma and its potential effects on estimated alveolar NO (Calv(NO) ), a proposed marker of inflammation in peripheral airways. Secondary aims were to investigate the effects of various exhalation flow-rates and the feasibility of different proposed adjustments of (Calv(NO) ) for trumpet model and axial diffusion (TMAD). Exhaled NO at flow rates of 50-300 ml/sec, and salivary nitrite was measured before and after antibacterial mouthwash in 29 healthy young people (10-20 years) and 29 with asthma (10-19 years). Calv(NO) was calculated using the slope-intercept model with and without TMAD adjustment. Exhaled NO at 50 ml/sec decreased significantly after mouthwash, to a similar degree in asthmatic and healthy subjects (8.8% vs. 9.8%, P = 0.49). The two groups had similar salivary nitrite levels (56.4 vs. 78.4 µM, P = 0.25). Calv(NO) was not significantly decreased by mouthwash. Calv(NO) levels were similar when flow-rates between 50-200 or 100-300 ml/sec were used (P = 0.34 in asthmatics and P = 0.90 in healthy subjects). A positive association was found between bronchial and alveolar NO in asthmatic subjects and this disappeared after the TMAD-adjustment. Negative TMAD-adjusted Calv(NO) values were found in a minority of the subjects. Young people with and without asthma have similar salivary nitrite levels and oral contributions to exhaled NO and therefore no antibacterial mouthwash is necessary in routine use. TMAD corrections of alveolar NO could be successfully applied in young people with asthma and yielded negative results only in a minority of subjects.

Comments on non-holomorphic modular forms and non-compact superconformal field theories

We extend our previous work arXiv:1012.5721 [hep-th] on the non-compact N=2 SCFT_2 defined as the supersymmetric SL(2,R)/U(1)-gauged WZW model. Starting from path-integral calculations of torus partition functions of both the axial-type (`cigar') and the vector-type (`trumpet') models, we study general models of the Z_M-orbifolds and M-fold covers with an arbitrary integer M. We then extract contributions of the degenerate representations (`discrete characters') in such a way that good modular properties are preserved. The `modular completion' of the extended discrete characters introduced in arXiv:1012.5721 [hep-th] are found to play a central role as suitable building blocks in every model of orbifolds or covering spaces. We further examine a large M-limit (the `continuum limit'), which `deconstructs' the spectral flow orbits while keeping a suitable modular behavior. The discrete part of partition function as well as the elliptic genus is then expanded by the modular completions of irreducible discrete characters, which are parameterized by both continuous and discrete quantum numbers modular transformed in a mixed way. This limit is naturally identified with the universal cover of trumpet model. We finally discuss a classification of general modular invariants based on the modular completions of irreducible characters constructed above.

Clinical study of multiple breath biomarkers of asthma and COPD (NO, CO2, CO and N2O) by infrared laser spectroscopy

Breath analysis is a powerful non-invasive technique for the diagnosis and monitoring of respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). Exhaled nitric oxide (NO) and carbon monoxide (CO) are markers of airway inflammation and can indicate the extent of respiratory diseases. We have developed a compact fast response quantum cascade laser system for analysis of multiple gases by tunable infrared absorption spectroscopy. The ARI breath analysis instrument has been deployed in a study of exhaled breath from patients with asthma or COPD. A total of 173 subjects participated, including both adult and pediatric patients. Patients in asthma or COPD exacerbations were evaluated twice—during the exacerbation and at a follow-up visit—to compare variations in breath biomarkers during these events. The change in exhaled NO levels between exacerbation and ‘well’ visits is consistent with spirometry data collected. Respiratory models are important for understanding the exchange dynamics of nitric oxide and other species in the lungs and airways. At each patient's visit, tests were conducted at four expiratory flow rates. We have applied a trumpet model with axial diffusion to the multi-flow exhaled nitric oxide data, obtaining NO alveolar concentrations and airway fluxes. We found higher airway fluxes for those with more severe asthma and during exacerbation events. The alveolar concentrations from the model were higher in adults with asthma and COPD, but this trend was less clear among the pediatric subjects.

Exhaled nitric oxide, but not serum nitrite and nitrate, is a marker of interstitial lung disease in systemic sclerosis

Nitric oxide metabolites (NOx) in serum, and alveolar concentration of NO (CA NO), are markers of inflammation and alveolitis, respectively, in systemic sclerosis (SSc). We prospectively evaluated the usefulness of both NOx and CA NO to assess lung involvement and skin fibrosis in SSc. Serum NOx, and CA NO measured by two different methods, namely the two-compartment (2CM) and the “trumpet” models (TM), were concomitantly assessed in 65 patients with SSc and 17 healthy controls. Whilst serum NOx remained comparable between groups, CA NO were significantly higher in SSc patients ( n = 65, 6.7 ppb; 4.8–9.7 and 5.9 ppb; 3.9–8.9) as compared with controls ( n = 17, 3.0 ppb; 2.0–3.8 and 1.8 ppb; 1.1–2.9, p < 0.001, p < 0.001) using the 2CM and the TM, respectively). CA NO from SSc patients with interstitial lung disease (ILD) ( n = 26, 8.6 ppb; 6.5–10.9 and 8.5 ppb; 5.9–10.7) or pulmonary arterial hypertension ( n = 12, 7.3 ppb; 6.5–10.4 and 6.9 ppb; 5.4–9.9) were significantly higher as compared with patients without ILD ( n = 27, 4.9 ppb; 3.8–6.5 and 4.7 ppb; 2.8–5.7; p < 0.001 and p < 0.001) using the 2CM and the TM, respectively). CA NO assessed either by the 2CM or the trumpet model were directly related to the extent of ILD and inversely related to DLCO. There was no correlation between NOx and ILD, or DLCO. Neither CA NO nor NOx was correlated with skin fibrosis and no relationship was found between CA NO and NOx. Alveolar concentration of NO, but not serum NOx, closely correlates with the extent of ILD in patients with systemic sclerosis. Neither parameter, however, is related to skin fibrosis.

Simulation of the apparent diffusion of helium-3 in the human acinus

Functional MRI of the lungs with hyperpolarized helium provides an index of apparent diffusion measured over several seconds (ADCsec) that is only 2% of its free diffusion in air (0.88 cm2/s). The potential of ADCsec to noninvasively assess in vivo lung structure of diseased lungs at the length scales corresponding to several seconds is critically dependent on the exact link between ADCsec and lung peripheral structure. To understand the intruigingly small ADCsec, numerical simulations of gas transport were performed in 1) a trumpet model, 2) a symmetrical, and 3) an asymmetrical multiple-branch-point model of the human acinus. For initial gas boluses in different locations of the acinar models, ADCsec was quantified as follows. At different time intervals, we computed a coefficient of variation (CoV) of the concentration distributions within each acinar model. The slope in the semilog plot of log(CoV) vs. time was proportional to the ADCsec generated by the internal model structure, provided that the outer model boundaries were similar across all models (i.e., similar cumulative cross section vs. average path length). The simulations revealed an ADCsec that amounted to approximately 1% of free diffusion in the trumpet model of the acinus, i.e., corresponding to free diffusion within the acinar geometric boundaries. Our simulations show that for initial conditions corresponding to those used in MRI experiments, intra-acinar branching introduces a dramatic diffusion delay, comparable to what is observed experimentally.

Examining axial diffusion of nitric oxide in the lungs using heliox and breath hold

Exhaled nitric oxide (NO) is highly dependent on exhalation flow; thus exchange dynamics of NO have been described by multicompartment models and a series of flow-independent parameters that describe airway and alveolar exchange. Because the flow-independent NO airway parameters characterize features of the airway tissue (e.g., wall concentration), they should also be independent of the physical properties of the insufflating gas. We measured the total mass of NO exhaled (A(I,II)) from the airways after five different breath-hold times (5-30 s) in healthy adults (21-38 yr, n = 9) using air and heliox as the insufflating gas, and then modeled A(I,II) as a function of breath-hold time to determine airway NO exchange parameters. Increasing breath-hold time results in an increase in A(I,II) for both air and heliox, but A(I,II) is reduced by a mean (SD) of 31% (SD 6) (P < 0.04) in the presence of heliox, independent of breath-hold time. However, mean (SD) values (air, heliox) for the airway wall diffusing capacity [3.70 (SD 4.18), 3.56 pl.s(-1).ppb(-1) (SD 3.20)], the airway wall concentration [1,439 (SD 487), 1,503 ppb (SD 644>)], and the maximum airway wall flux [4,156 (SD 2,502), 4,412 pl/s (SD 2,906)] using a single-path trumpet-shaped airway model that considers axial diffusion were independent of the insufflating gas (P > 0.55). We conclude that a single-path trumpet model that considers axial diffusion captures the essential features of airway wall NO exchange and confirm earlier reports that the airway wall concentration in healthy adults exceeds 1 ppm and thus approaches physiological concentrations capable of modulating smooth muscle tone.