Impulse Oscillometry Versus Spirometry to Detect Bronchiolitis Obliterans Syndrome in Bilateral Lung Transplant Recipients: A Prospective Diagnostic Study.

BACKGROUND: Chronic lung allograft dysfunction (CLAD), and especially bronchiolitis obliterans syndrome (BOS), remain dominant causes of morbidity and mortality after lung transplantation. Interest is growing in the forced oscillation technique, of which impulse oscillometry (IOS) is a form, as a tool to improve our understanding of these disorders. However, data remain limited and no longitudinal studies have been published, meaning there is no information regarding any capacity IOS may have for the early detection of CLAD. METHODS: We conducted a prospective longitudinal study enrolling a consecutive sample of adult bilateral lung transplant recipients with healthy lung allografts or CLAD and performed ongoing paired IOS and spirometry tests on a clinically determined basis. We assessed for correlations between IOS and spirometry and examined any predictive value either modality may hold for the early detection of BOS. RESULTS: We enrolled 91 patients and conducted testing for 43 mo, collecting 558 analyzable paired IOS and spirometry tests, with a median of 9 tests per subject (interquartile range, 5-12) and a median testing interval of 92 d (interquartile range, 62-161). Statistically significant moderate-to-strong correlations were demonstrated between all IOS parameters and spirometry, except resistance at 20 Hz, which is a proximal airway measure. No predictive value for the early detection of BOS was found for IOS or spirometry. CONCLUSIONS: This study presents the first longitudinal data from IOS after lung transplantation and adds considerably to the growing literature, showing unequivocal correlations with spirometry but failing to demonstrate a predictive value for BOS.

Evidence for endothermic ancestors of crocodiles at the stem of archosaur evolution.

Physiological, anatomical, and developmental features of the crocodilian heart support the paleontological evidence that the ancestors of living crocodilians were active and endothermic, but the lineage reverted to ectothermy when it invaded the aquatic, ambush predator niche. In endotherms, there is a functional nexus between high metabolic rates, high blood flow rates, and complete separation of high systemic blood pressure from low pulmonary blood pressure in a four-chambered heart. Ectotherms generally lack all of these characteristics, but crocodilians retain a four-chambered heart. However, crocodilians have a neurally controlled, pulmonary bypass shunt that is functional in diving. Shunting occurs outside of the heart and involves the left aortic arch that originates from the right ventricle, the foramen of Panizza between the left and right aortic arches, and the cog-tooth valve at the base of the pulmonary artery. Developmental studies show that all of these uniquely crocodilian features are secondarily derived, indicating a shift from the complete separation of blood flow of endotherms to the controlled shunting of ectotherms. We present other evidence for endothermy in stem archosaurs and suggest that some dinosaurs may have inherited the trait.

The pattern of surfactant cholesterol during vertebrate evolution and development: does ontogeny recapitulate phylogeny?

Pulmonary surfactant is a complex mixture of phospholipids (PLs), neutral lipids and proteins that lines the inner surface of the lung. Here it modulates surface tension, thereby increasing lung compliance and preventing the transudation of fluid. In humans, pulmonary surfactant is comprised of approximately 80% PLs, 12% neutral lipids and 8% protein. In most eutherian (i.e. placental) mammals, cholesterol (Chol) comprises approximately 8-10% by weight or 14-20 mol% of both alveolar and lamellar body surfactant. It is regarded as an integral component of pulmonary surfactant, yet few studies have concentrated on its function or control. The lipid composition is highly conserved within the vertebrates, except that surfactant of teleost fish is dominated by cholesterol, whereas tetrapod pulmonary surfactant contains a high proportion of disaturated phospholipids (DSPs). The primitive Australian dipnoan lungfish Neoceratodus forsterii demonstrates a 'fish-type' surfactant profile, whereas the other derived dipnoans demonstrate a surfactant profile similar to that of tetrapods. Homology of the surfactant proteins within the vertebrates points to a single evolutionary origin for the system and indicates that fish surfactant is a 'protosurfactant'. Among the terrestrial tetrapods, the relative proportions of DSPs and cholesterol vary in response to lung structure, habitat and body temperature (Tb), but not in relation to phylogeny. The cholesterol content of surfactant is elevated in species with simple saccular lungs or in aquatic species or in species with low Tb. The DSP content is highest in complex lungs, particularly of aquatic species or species with high Tb. Cholesterol is controlled separately from the PL component in surfactant. For example, in heterothermic mammals (i.e. mammals that vary their body temperature), the relative amount of cholesterol increases in cold animals. The rapid changes in the Chol to PL ratio in response to various physiological stimuli suggest that these two components have different turnover rates and may be packaged and processed differently. In mammals, the pulmonary surfactant system develops towards the end of gestation and is characterized by an increase in the saturation of PLs in lung washings and the appearance of surfactant proteins in amniotic fluid. In general, the pattern of surfactant development is highly conserved among the amniotes. This conservation of process is demonstrated by an increase in the amount and saturation of the surfactant PLs in the final stages (>75%) of development. Although the ratios of surfactant components (Chol, PL and DSP) are remarkably similar at the time of hatching/birth, the relative timing of the maturation of the lipid profiles differs dramatically between species. The uniformity of composition between species, despite differences in lung morphology, birthing strategy and relationship to each other, implies that the ratios are critical for the onset of pulmonary ventilation. The differences in the timing, on the other hand, appear to relate primarily to birthing strategy and the onset of air breathing. As the amount of cholesterol relative to the phospholipids is highly elevated in immature lungs, the pattern of cholesterol during development and evolution represents an example of ontogeny recapitulating phylogeny. The fact that cholesterol is an important component of respiratory structures that are primitive, when they are not in use or developing in an embryo, demonstrates that this substance has important and exciting roles in surfactant. These roles still remain to be explored.

Ubiquitous expression of a gene encoding for uncoupling protein isolated from the thermogenic inflorescence of the dead horse arum Helicodiceros muscivorus.

Uncoupling proteins (UCPs) are a family of mitochondrial inner membrane proteins that have been implicated in heat production in mammalian cells. The inflorescences of several members of the arum lily family (Araceae) have also been shown to produce heat during flowering, but the involvement of UCP-mediated heat production in plants is not known. In this work a gene has been isolated termed HmUCPa that encodes for a putative uncoupling protein from Helicodiceros muscivorus, a highly thermogenic arum lily. RT-PCR analysis revealed that the expression of HmUCPa was ubiquitously found, both in thermogenic male florets and appendix, and the non-thermogenic female florets, spathe and club-shaped organs of the spadix. These results suggest that HmUCPa is not primarily involved in organ-specific heat production in H. muscivorus.

Ontogeny of the pulmonary surfactant and antioxidant enzyme systems in the viviparous lizard, Tiliqua rugosa.

The antioxidant enzyme (AOE) system protects the lung from oxidative damage. The pulmonary surfactant (PS) system lowers the interfacial pressure within the lung, improving lung compliance and aiding lung clearance. In mammals, the AOE and PS systems develop in tandem during the final 10%-20% of gestation. Here, we investigated the development of these systems in the viviparous skink, Tiliqua rugosa. The content of total phospholipid (PL), disaturated phospholipid (DSP), and cholesterol (Chol) increased in lung washings from foetal lizards with advancing gestational age. Similarly, the relative saturation of the PLs increased throughout gestation, with mid-stage 40 foetuses having a DSP/PL equivalent to newborns and adults. Maternal lizards had significantly less total PL, DSP, and Chol than nongravid and newborn lizards; however, the relative composition did not differ from nongravid animals. This presumably results from compression of the lungs under the bulk of the developing foetus. The Chol/PL and Chol/DSP ratios declined early in development such that mid-stage 40 embryos had comparable ratios to both newborns and adults. Thus, it appears that the PS system matures in a similar manner in skinks and in mammals. However, the composition of surfactant is complete some weeks before parturition, probably to enable improved survivorship of the precocial young in the event of premature birth. Unlike the surfactant lipids, the AOEs, catalase, superoxide dismutase, and glutathione peroxidase did not differ appreciably throughout gestation. It appears therefore that like the surfactant lipids the AOE system is in readiness for air breathing throughout the latter stages of gestation, possibly in preparation for premature birth. Unlike mammals, the PS and AOE systems develop independently from one another.

The pulmonary surfactant system matures upon pipping in the freshwater turtle Chelydra serpentina.

Pulmonary surfactant (PS), a mixture of phospholipids (PL), neutral lipids and surfactant proteins (SP), lowers surface tension within the lung, which increases lung compliance and improves the removal of fluid at birth. Here, we have examined the expression of thyroid transcription factor-1 (TTF-1) and the surfactant protein SP-B, and also the composition of pulmonary surfactant lipids in the developing lung of the turtle Chelydra serpentina. Lavage and lung tissue were collected from late embryonic, pipped and hatchling turtles. TTF-1, a regulator of gene expression of surfactant proteins and cell differentiation in mammals, was detected using immunohistochemistry in epithelia of the gas-exchange area and conducting airways during late development. Expression declined in hatchlings. SP-B was detected in subsets of cells within the respiratory epithelium at all stages sampled. The same cell types also stained for TTF-1. Turtle surfactant lipids matured toward the end of incubation. Maximal secretion of both total phospholipids and disaturated phospholipid (DSP) occurred at the time of pipping, coincident with the onset of breathing. The DSP/PL ratio increased after pipping, whereas cholesterol levels (Chol) increased prior to pipping. This resulted in a decrease in the Chol/PL and Chol/DSP ratios after pipping. Thus, TTF-1 and SP-B appear to be highly conserved within the vertebrates. Maturation of surfactant phospholipid content occurred with the commencement of pulmonary ventilation.