Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 μm in size were examined for endotracheal and and up to 5 μm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model

Establishing a large prospective clinical cohort in people with head and neck cancer as a biomedical resource: head and neck 5000

BACKGROUND: Head and neck cancer is an important cause of ill health. Survival appears to be improving but the reasons for this are unclear. They could include evolving aetiology, modifications in care, improvements in treatment or changes in lifestyle behaviour. Observational studies are required to explore survival trends and identify outcome predictors. METHODS: We are identifying people with a new diagnosis of head and neck cancer. We obtain consent that includes agreement to collect longitudinal data, store samples and record linkage. Prior to treatment we give participants three questionnaires on health and lifestyle, quality of life and sexual history. We collect blood and saliva samples, complete a clinical data capture form and request a formalin fixed tissue sample. At four and twelve months we complete further data capture forms and send participants further quality of life questionnaires. DISCUSSION: This large clinical cohort of people with head and neck cancer brings together clinical data, patient-reported outcomes and biological samples in a single co-ordinated resource for translational and prognostic research

Microvascular maturation of the septal capillary layers takes place in parallel to alveolarization in human lungs.

Primary and secondary septa formed during lung development contain a double-layered capillary network. To improve gas-exchange the capillary network is remodeled into a single-layered one, a process that is called microvascular maturation (MVM). It takes place during classical and continued alveolarization. Classical alveolarization is defined as a formation of new septa from immature septa and continued alveolarization as a formation from mature septa. Until now, MVM was never quantitatively evaluated in human lungs. To correlate alveolarization and MVM, and to determine the transition point from classical to continued alveolarization, the degree of MVM was stereologically estimated. In 12 human lungs (0.1-15 years) the alveolar surface area of immature and mature septa was estimated stereologically by intersection counting. A MVM-quotient (RMVM) was defined as the mature alveolar surface area over total alveolar surface area. The MVM-quotient increased logarithmically over age and showed a bi-phasic increase similar to alveolarization. It did not reach 100% maturity in these samples. A linear correlation between the MVM-quotient and the logarithm of the number of alveoli was observed. We conclude that MVM increased logarithmically and biphasically in parallel to alveolarization until alveolarization ceased. However, at 2-3 years of age three quarters of the alveolar microvasculature are mature. This result may explain a previous postulate that MVM is finished at this age. We hypothesize that as long as alveolarization takes place, MVM will take place in parallel. We propose that the transition from classical to continued alveolarization takes place between the ages of 1-3 years in humans

The Basement Membrane Zone in Asthma: The Supracellular Anchoring Network.

Thickening of the basement membrane zone (BMZ) is a characteristic feature of airway remodeling in the lungs of asthmatics. However the significance of a thickened BMZ in the pathology of the asthmatic airway is not known. In this review we show that the columnar epithelium is linked to the reticular BMZ through the supracellular anchoring network. We discuss the evidence that changes in the width of the BMZ in control airways are part of a supracellular anchoring mechanism for increasing the strength of attachment between the airway epithelium and the extracellular matrix (ECM). We then review the effects of asthma on this anchoring mechanism. We conclude that both thickening of the BMZ and sloughing of columnar epithelium (creola bodies) in asthma represent abnormalities in the supracellular anchoring network attaching the airway epithelium to the ECM. Future research directed toward studying the regulation and development of the supracellular anchoring network may help better understand sloughing of columnar epithelium and the significance of reticular BMZ thickening in the asthmatic airway

Pulmonary vagal reflexes and breathing pattern are not altered in elastase-induced emphysema in rats

The role of nonmyelinated and myelinated vagal afferents in pulmonary reflexes and breathing pattern was examined in elastase-treated emphysemic rats. Fourteen to 17 days after intratracheal instillation of 1 IU/gm of porcine pancreatic elastase or 0.5 mL of saline, elastase-treated rats had a decreased alveolar surface area to volume of parenchyma (Sv) (42.44 ± 1.7 vs. 31.51 ± 1.1 mm /mm ), increased quasistatic compliance (QSC) (1.05 ± 0.06 vs. 1.25 ± 0.09 mL/cm H O), functional residual capacity (FRC) (4.31 ± 0.10 vs. 5.88 ± 0.37 mL), residual volume (RV) (3.02 ± 0.14 vs. 4.27 ± 0.31 mL), and total lung capacity (TLC) (14,04 ± 0.28 vs. 15.58 ± 0.54 mL). There were no changes in the strength of the pulmonary chemoreflex, the strength of the Hering-Breuer inflation reflex, or breathing pattern before or after vagal perineural capsaicin treatment (VPCT) or vagotomy. There were, however, significant negative correlations between Sv and TLC, FRC and RV, and a near significant (p \u3c .09) negative correlation between Sv and QSC, but no significant correlations between Sv and indices of either the pulmonary chemoreflex or Hering-Breuer inflation reflex. The results indicate that pulmonary vagal nonmyelinated and myelinated reflex activity and breathing pattern are not affected by elastase-induced emphysema in rats. 2 3

Contribution of vagal afferents to breathing pattern in rats with lung fibrosis

In anesthestized male Wistar rats with bleomycin-induced lung fibrosis we examined the influence of lung vagal non-myelinated and myelinated afferents in setting breathing pattern. Fourteen days after intratracheal instillation of bleomycin, lung compliance, total lung capacity (TLC) and inspiratory capacity were reduced while functional residual capacity and residual volume were increased. Baseline tidal volume (V(T)) was decreased and frequency (fR) increased in the bleomycin treated rats compared with controls. Selective vagal C-fiber blockade did not affect fR or V(T) in any group. Vagotomy resulted in an increase in V(T) and decrease in fR in both groups with the percent increase in V(T)/TLC and decrease in fR being significantly greater in the bleomycin rats compared with controls. Vagotomy also attenuated the significantly elevated P(CO2) in the bleomycin treated rats suggesting that bleomycin-induced alterations in breathing pattern contribute to blood gas abnormalities. We conclude that vagal myelinated afferents contribute to the rapid shallow breathing in bleomycin treated rats

ASU VETS Center Newsletter

September 1, 2013Volume 1, Issue 1 or the Angelo State University VETS (Veterans Educational and Transitional Services) Center newsletter.Texas Workforce Commission College Credit for Heroes Gran

Organized lymphatic tissue (BALT) in lungs of rhesus monkeys after air pollutant exposure.

The presence of bronchus-associated lymphoid tissue (BALT) and its size in humans largely depends upon age. It is detected in 35% of children less than 2 years of age, but absent in the healthy adult lung. Environmental gases or allergens may have an effect on the number of BALT. Lungs of rhesus macaque monkeys were screened by histology for the presence, size, and location of BALT after exposure to filtered air for 2, 6, 12, or 36 months or 12 and 36 months to ozone or 2, 12, or 36 months of house dust mite or a combination of ozone and house dust mite for 12 months. In the lungs of monkeys housed in filtered air for 2 months, no BALT was identified. After 6, 12, or 36 months, the number of BALT showed a significantly increased correlation with age in monkeys housed in filtered air. After 2 months of episodic house dust mite (HDM) exposure, no BALT was found. Monkeys exposed to HDM or HDM + ozone did not show a significant increase in BALT compared to monkeys housed in filtered air. However, monkeys exposed to ozone alone did show significant increases in BALT compared to all other groups. In particular, there were frequent accumulations of lymphocytes in the periarterial space of ozone exposed animals. In conclusion, BALT in rhesus monkeys housed under filtered air conditions is age-dependent. BALT significantly increased in monkeys exposed to ozone in comparison with monkeys exposed to HDM