Jyongsu Huang

Pharyngeal Cross-Sectional Area and Pharyngeal Compliance in Normal Males and Females

Obstructive sleep apnea syndrome is ascribed to pharyngeal dysfunction, but there are only a few reports about the normal morphological values in this anatomical region. We measured the pharyngeal cross-sectional area and the compliance (collapsibility), using the acoustic reflection technique with air breathing, in 181 healthy subjects (age 21–69 years). We assessed their sex-related differences, and the effects of age, body size and body postures on these parameters. The pharyngeal cross-sectional area, defined as the region from the fauces to the glottis, posturally changed with successive decreases in the sitting, left lateral decubitus and supine positions. The area was significantly greater in male than in female subjects in the sitting position (p < 0.01), but no difference was present in the recumbent positions. The pharyngeal cross-sectional area did not correlate with either age or body size. The specific pharyngeal compliance was greater in the males than in the females (p < 0.01) and increased with age only in the male subjects.

Altered lung surfactant system in a Rab38-deficient rat model of Hermansky-Pudlak syndrome

Several Long-Evans rat substrains carrying the phenotype of oculocutaneous albinism and bleeding diathesis are a rat model of Hermansky-Pudlak syndrome (HPS). The mutation responsible for the phenotype (Ruby) was identified as a point mutation in the initiation codon of Rab38 small GTPase that regulates intracellular vesicle transport. As patients with HPS often develop life-limiting interstitial pneumonia accompanied by abnormal morphology of alveolar type II cells, we investigated lung surfactant system in Long-Evans Cinnamon rats, one strain of the Ruby rats. The lungs showed conspicuous morphology of type II cells containing markedly enlarged lamellar bodies. Surfactant phosphatidylcholine and surfactant protein B were increased in lung tissues and lamellar bodies but not in alveolar lumen. Expression levels of mRNA for surfactant proteins A, B, C, and D were not altered. Isolated type II cells showed aberrant secretory pattern of newly synthesized [(3)H]phosphatidylcholine, i.e., decreased basal secretion and remarkably amplified agonist-induced secretion. [(3)H]phosphatidylcholine synthesis and uptake by type II cells were not altered. Thus Rab38-deficient type II cells appear to carry abnormality in lung surfactant secretion but not in synthesis or uptake. These results suggest that aberrant lung surfactant secretion may be involved in the pathogenesis of interstitial pneumonia in HPS.

Pulmonary surfactant transport in alveolar type II cells.

Abstract:  Pulmonary surfactant (PS) is a mixture of several lipids (mainly phosphatidylcholine; PC) and four apoproteins (A, B, C and D). The classical hypothesis of PS transport suggests that PS is synthesized in the endoplasmic reticulum and transported to the lamellar body (LB) via the Golgi apparatus. However, recent studies have raised questions regarding this single route. This study examined, independently, the intracellular trafficking route of three different components of PS, that is, PC, SP‐A and SP‐B. Alveolar type II cells were isolated from Sprague–Dawley rats or Japanese white rabbits. The cells were cultured with either [3H]choline or [35S]methionine/cysteine with or without brefeldin A, which disassembles the Golgi apparatus. LB was purified from disintegrated cells with sucrose density gradient centrifugation. [3H]PC was extracted from radiolabeled media, cells, and the LB fraction with Bligh–Dyers method. [35S]SP‐A or [35S]SP‐B was immunoprecipitated from each sample with a specific antibody. [3H]PC was transported and stored to the LB via a Golgi‐independent pathway. [35S]SP‐A was transported to the Golgi apparatus, underwent glycosylation, and was then constitutively secreted. The secreted [35S]SP‐A was re‐uptaken into the LB. [35S]SP‐B was transported and stored to the LB via the Golgi‐dependent pathway. These results indicate that, rather than a single route, surfactant components take different pathways to reside in the LB. These different pathways may reflect the different nature and role of each surfactant component such as surface tension‐lowering activity and innate host defense.

A three-microphone acoustic reflection technique using transmitted acoustic waves in the airway.

The acoustic reflection technique noninvasively measures airway cross-sectional area vs. distance functions and uses a wave tube with a constant cross-sectional area to separate incidental and reflected waves introduced into the mouth or nostril. The accuracy of estimated cross-sectional areas gets worse in the deeper distances due to the nature of marching algorithms, i.e., errors of the estimated areas in the closer distances accumulate to those in the further distances. Here we present a new technique of acoustic reflection from measuring transmitted acoustic waves in the airway with three microphones and without employing a wave tube. Using miniaturized microphones mounted on a catheter, we estimated reflection coefficients among the microphones and separated incidental and reflected waves. A model study showed that the estimated cross-sectional area vs. distance function was coincident with the conventional two-microphone method, and it did not change with altered cross-sectional areas at the microphone position, although the estimated cross-sectional areas are relative values to that at the microphone position. The pharyngeal cross-sectional areas including retropalatal and retroglossal regions and the closing site during sleep was visualized in patients with obstructive sleep apnea. The method can be applicable to larger or smaller bronchi to evaluate the airspace and function in these localized airways.

High-Frequency Ventilation by Bilateral Phrenic Nerve Stimulation in Dogs

We succeeded in achieving good gas exchange by oscillatory phrenic nerve stimulation (PNS) in dogs. In 7 out of 14 dogs, adequate gas exchange was attained by PNS at 3, 4 and 5 pulses per sec (pps). VE increased with stimulation frequency up to 4 or 5 pps, but decreased above 6 pps. We also applied sinusoidal oscillation using a piston pump at the trachea in the same dogs to analyze the mechanical properties of the respiratory system. The V/P ratio, oscillatory volume divided by driving pressure, decreased markedly at 6 Hz while the pleural pressure remained constant up to 10 Hz. These facts indicate that the fall in VE is due to mechanical properties of the airway and lung, and not due to failure of the ventilatory pump system. We conclude that frequencies of 3-5 pps in high-frequency ventilation are optimal for maintaining effective gas transport when the diaphragma is used as the oscillatory generator.