Pulmonary Vascular Dysfunctions in Cystic Fibrosis.

Cystic fibrosis (CF) is an inherited disorder caused by a deleterious mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Given that the CFTR protein is a chloride channel expressed on a variety of cells throughout the human body, mutations in this gene impact several organs, particularly the lungs. For this very reason, research regarding CF disease and CFTR function has historically focused on the lung airway epithelium. Nevertheless, it was discovered more than two decades ago that CFTR is also expressed and functional on endothelial cells. Despite the great strides that have been made in understanding the role of CFTR in the airway epithelium, the role of CFTR in the endothelium remains unclear. Considering that the airway epithelium and endothelium work in tandem to allow gas exchange, it becomes very crucial to understand how a defective CFTR protein can impact the pulmonary vasculature and overall lung function. Fortunately, more recent research has been dedicated to elucidating the role of CFTR in the endothelium. As a result, several vascular dysfunctions associated with CF disease have come to light. Here, we summarize the current knowledge on pulmonary vascular dysfunctions in CF and discuss applicable therapies.

Effect of airflow and material models on tissue displacement for surgical planning of pharyngeal airways in pediatric down syndrome patients.

Pharyngeal narrowing in obstructive sleep apnea (OSA) results from flow-induced displacement of soft tissue. The objective of this study is to evaluate the effect of airflow parameters and material model on soft tissue displacement for planning surgical treatment in pediatric patients with OSA and Down syndrome (DS). Anatomically accurate, three-dimensional geometries of the pharynx and supporting tissue were reconstructed for one pediatric OSA patient with DS using magnetic resonance images. Six millimeters of adenoid tissue was virtually removed based on recommendations from the surgeon, to replicate the actual adenoidectomy. Computational simulations of flow-induced obstruction of the pharynx during inspiration were performed using patient-specific values of tissue elasticity for pre and post-operative airways. Sensitivity of tissue displacement to selection of turbulence model, variation in inspiratory airflow, nasal airway resistance and choice of non-linear material model was evaluated. The displacement was less sensitive to selection of turbulence model (10% difference) and more sensitive to airflow rate (20% difference) and nasal resistance (30% difference). The sensitivity analysis indicated that selection of Neo-Hookean, Yeoh, Mooney-Rivlin or Gent models would result in identical tissue displacements (less than 1% difference) for the same flow conditions. Change in pharyngeal airway resistance between the rigid and collapsible models was nearly twice for the pre-operative case as compared to the post-operative scenario. The tissue strain at the site of obstruction in the velopharyngeal airway was lowered by approximately 84% following surgery. Inclusion of tissue elasticity resulted in better agreement with the actual surgical outcome compared to a rigid wall assumption, thereby emphasizing the importance of pharyngeal compliance for guiding treatment in pediatric OSA patients.

Computational Modeling of Airway Obstruction in Sleep Apnea in Down Syndrome: A Feasibility Study.

Current treatment options are successful in 40% to 60% of children with persistent obstructive sleep apnea after adenotonsillectomy. Residual obstruction assessments are largely subjective and do not clearly define multilevel obstruction. We endeavor to use computational fluid dynamics to perform virtual surgery and assess airflow changes in patients with Down syndrome and persistent obstructive sleep apnea. Three-dimensional airway models were reconstructed from respiratory-gated computed tomography and magnetic resonance imaging. Virtual surgeries were performed on 10 patients, mirroring actual surgeries. They demonstrated how surgical changes affect airflow resistance. Airflow and upper airway resistance was calculated from computational fluid dynamics. Virtual and actual surgery outcomes were compared with obstructive apnea-hypopnea index values. Actual surgery successfully treated 6 of 10 patients (postoperative obstructive apnea-hypopnea index <5). In 8 of 10 subjects, both apnea-hypopnea index and the calculated upper airway resistance after virtual surgery decreased as compared with baseline values. This is a feasibility and proof-of-concept study. Further studies are needed before using these techniques in surgical planning.

Planning human upper airway surgery using computational fluid dynamics.

The study advances the idea of using computational fluid dynamics in the process of planning surgical treatment modalities for patients with obstructive airway disorders. It is hypothesized that the a priori knowledge of the functional outcome of surgical intervention on the flow and airway resistance can guide the surgeon in choosing an effective surgical strategy. Computed tomography images spanning the respiratory tract of an adult patient with a combined glottic and subglottic stenosis are used to reconstruct three-dimensional geometrical models of the airway. Computational fluid dynamics is used to obtain airway flow patterns during inspiration and expiration in these models. Numerical predictions about flow velocity, pressure distribution on the airway lumen, wall shear stress, and airway resistance are obtained so that the relevance of each individual stenotic level is quantified. Four different virtual surgeries in different combinations are assessed in order to remedy the constricted airway. The virtual surgery based airway models are evaluated by comparisons with the pre-treatment flow modeling results. The predicted numerical data revealed that the removal of the constriction at the level of the vocal folds will have the most significant effect on the airway resistance. The flow simulations offer a quantitative method of evaluating the airway resistance in patients with combined glottic and subglottic stenoses. Predictions of airway resistances and other numerical calculations from different virtual surgeries give additional inputs for the surgeon, in deciding the most appropriate surgery on a case-by-case basis.

Patterns in pharyngeal airflow associated with sleep-disordered breathing.

OBJECTIVE: To establish the feasibility of a noninvasive method to identify pharyngeal airflow characteristics in sleep-disordered breathing. METHODS: Four patients with sleep-disordered breathing who underwent surgery or used positive airway pressure devices and four normal healthy controls were studied. Three-dimensional CT imaging and computational fluid dynamics modeling with standard steady-state numerical formulation were used to characterize pharyngeal airflow behavior in normals and pre-and post-treatment in patients. Dynamic flow simulations using an unsteady approach were performed in one patient. RESULTS: The pre-treatment pharyngeal airway below the minimum cross-sectional area obstruction site showed airflow separation. This generated recirculation airflow regions and enhanced turbulence zones where vortices developed. This interaction induced large fluctuations in airflow variables and increased aerodynamic forces acting on the pharyngeal wall. At post-treatment, for the same volumetric flow rate, airflow field instabilities vanished and airflow characteristics improved. Mean maximum airflow velocity during inspiration reduced from 18.3±5.7 m/s pre-treatment to 6.3±4.5 m/s post-treatment (P=0.002), leading to a reduction in maximum wall shear stress from 4.8±1.7 Pa pre-treatment to 0.9±1.0 Pa post-treatment (P=0.01). The airway resistance improved from 4.3±1.4 Pa/L/min at pre-treatment to 0.7±0.7 Pa/L/min at post-treatment (P=0.004). Post-treatment airflow characteristics were not different from normal controls (all P ≥ 0.39). CONCLUSION: This study demonstrates that pharyngeal airflow variables may be derived from CT imaging and computational fluid dynamics modeling, resulting in high quality visualizations of airflow characteristics of axial velocity, static pressure, and wall shear stress in sleep-disordered breathing.

Large eddy simulation of the pharyngeal airflow associated with obstructive sleep apnea syndrome at pre and post-surgical treatment.

Obstructive Sleep Apnea Syndrome (OSAS) is the most common sleep-disordered breathing medical condition and a potentially life-threatening affliction. Not all the surgical or non-surgical OSAS therapies are successful for each patient, also in part because the primary factors involved in the etiology of this disorder are not completely understood. Thus, there is a need for improving both diagnostic and treatment modalities associated with OSAS. A verified and validated (in terms of mean velocity and pressure fields) Large Eddy Simulation approach is used to characterize the abnormal pharyngeal airflow associated with severe OSAS and its interaction with the airway wall in a subject who underwent surgical treatment. The analysis of the unsteady flow at pre- and post-treatment is used to illustrate the airflow dynamics in the airway associated with OSAS and to reveal as well, the changes in the flow variables after the treatment. At pre-treatment, large airflow velocity and wall shear stress values were found at the obstruction site in all cases. Downstream of obstruction, flow separation generated flow recirculation regions and enhanced the turbulence production in the jet-like shear layers. The interaction between the generated vortical structures and the pharyngeal airway wall induced large fluctuations in the pressure forces acting on the pharyngeal wall. After the surgery, the flow field instabilities vanished and both airway resistance and wall shear stress values were significantly reduced.