Prevalence of asthma, atopy and bronchial hyperresponsiveness and their interrelation in a semi-rural area of Chile.

OBJECTIVE: To assess the prevalence of asthma symptoms and their association with sensitisation to eight allergens and bronchial hyperresponsiveness (BHR) to methacholine. SETTING: A random sample of 1232 adults, aged 22 to 28 years, studied in a Chilean semi-rural area. DESIGN: A cross-sectional design for the purpose of this analysis. RESULTS: The prevalence of wheeze was 27.4% (95%CI 24.9-29.9) and waking with breathlessness 13.7% (95%CI 11.8-15.6), higher than the results of a multi-centre European study. Only 7.8% (95%CI 6.3-9.3) had a positive BHR (< or =8 mg/ml) and 26.3% (95%CI 23.8-28.8) were atopic. The Youden index of asthma symptoms in non-atopic subjects varied from 0.184 to 0.259 when using BHR as gold standard for asthma, and increased from 0.379 to 0.504 among those with positive atopy. Only 4.5% reported asthma, and the Youden index was slightly higher in comparison to the asthma symptom groups. CONCLUSION: The prevalence of asthma symptoms in young adults was high, but only a small proportion of these were sensitised or had a positive BHR. We believe that aetiological studies of asthma should analyse subjects with asthma symptoms separately from those with positive atopic status or positive BHR.

Human leukocyte antigens in indigenous (mapuche) people in a regional renal transplantation program in chile.

An active regional transplantation program established in the southern region of Chile has allowed the incorporation of ethnic minorities particularly Mapuche living in this geographic area in the development of a histocompatibility database. To identify possible differences in the human leukocyte (HLA) antigen distribution in Chilean Mapuche compared with non-Mapuche, we reviewed 442 HLA tissue-typing studies. Seventy-eight of 309 recipients (25%) and 18 of 133 donors (13%) were Mapuche. Among recipients, Mapuche people showed a significantly higher frequency of the HLA antigens, A28, B16, DR4, and DR8, and a lower one for A19, B15, and DR1 (P < .05) compared with non-Mapuche individuals. A particularly higher frequency of the haplotype A28, -B16, -DR4 was also evidenced in Mapuche. Besides, these recipients showed a higher frequency of the allele -DR4 when compared with Mapuche donors. A greater frequency of some histocompatibility antigens in patients with chronic renal disease might be attributed to allelic concentration due to a high index of endogamy, but a possible association with the development of progressive renal disease cannot be ignored, especially when a higher prevalence of DR4 was observed among Mapuche recipients.

Comparison of the subcellular distribution of alveolar surfactant in two mammalian species of similar body weight: cat and rabbit.

1. We studied the total amount and subcellular distribution of alveolar surfactant, extracted through bronchoalveolar lavage of anesthetized cats and rabbits. This was correlated to several morphometric and ventilatory variables of these animals. 2. Lung weight was significantly larger in the cat while respiratory frequency and minute ventilation were significantly larger in the rabbit. No significant differences were observed in tidal volume, total lung capacity, P(a)O2, P(a)CO2 and pH(a). 3. While both species had similar protein contents in the bronchoalveolar lavage, rabbits had larger phospholipid contents, mostly distributed in the lighter, more active subfractions. 4. With regard to the estimated values obtained from allometric equations derived for mammals, the rabbit presented a lung weight of nearly one-third of the estimated one, an exceedingly larger minute ventilation (by nearly 60%) and a respiratory frequency twice the calculated one. 5. We suggest that the different distribution of alveolar surfactant in these species may be explained by disparities in their ventilatory demands, the rabbit having a higher respiratory frequency and a larger minute ventilation, performed by a mass of lung tissue lower than that corresponding to its body mass.

Factors affecting distribution of alveolar surfactant during resting ventilation.

Few studies have been done to establish the ventilatory factors affecting alveolar surfactant under resting conditions. Experiments in which ventilatory variables were recorded for 4 h were performed in 12 adult cats breathing spontaneously under pentobarbital sodium anesthesia. After the animals were killed and bronchoalveolar lavages (BALs) were performed, the resulting fluid was subjected to differential centrifugation and determinations of proteins, phospholipids (PL), and disaturated phosphatidylcholine (DSPC). Pellet P1+2 was obtained by two centrifugations at 140 g; the supernatant was centrifuged at 1,000 g to obtain pellet P3 and subsequently at 60,000 g to obtain P4. Pellets P3 and P4 had the higher contents of PL and DSPC. Bivariate and multivariate correlational analyses indicate that 1) total PL in BAL was not related to any of the ventilatory variables studied, 2) PL in P3 and P4 fractions was directly correlated to the physiological range of variations in the frequency of large spontaneous gasps (fL), and 3) PL in P1+2 fraction was inversely related to fL. Cats subjected to bilateral section of carotid nerves, although presenting reduced chemosensory drive and ventilatory chemoreflexes, did not exhibit significant differences in resting ventilatory variables nor in alveolar surfactant components. Present results indicate that the total content of alveolar surfactant is not modified by ventilatory variations within physiological range but that the spontaneous occurrence of large gasps increases the proportion of more active forms of alveolar surfactant. This may mediate the role of augmented breaths in keeping lung compliance and preventing atelectasis under resting ventilatory conditions.

Evaluation of reexpansion pulmonary edema following unilateral pneumothorax in rabbits and the effect of superoxide dismutase.

We investigated the lung injury that occurs following reexpansion of a unilateral pneumothorax and determined the effect of superoxide dismutase (SOD) infused immediately prior to reexpansion on this injury. After 7 days of at least 80% right pneumothorax, rabbits received intravenous infusions of either SOD (n = 7), heat-inactivated SOD (n = 1), or vehicle (n = 7) immediately before lung reexpansion. Lung injury was assessed by measuring the systemic white cell counts, pulmonary blood volumes, extravascular albumin, extravascular lung water, wet/dry weight ratios, and histology 2 h after reexpansion. The reexpanded lung showed increased extravascular albumin, extravascular lung water and wet/dry weight ratios with decreased blood volumes compared to the uninjured lung. SOD delayed the onset of leukopenia and neutropenia at 3 and 7 min after reexpansion, but the white cell counts had decreased to the same level in both groups by 30 min. SOD had no effect on the degree of injury after 2 h. While a single bolus of SOD given immediately before reexpansion delayed the onset of this injury, it did not affect the injury that subsequently developed in the lung.

Pulmonary response to free fatty acid intravenous infusion in the rabbit: role of leukotrienes and the effect of prostacyclin.

Intravenous infusion of free fatty acid (FFA) 20 mg.kg-1.min-1 produces pulmonary edema, hypoxemia, hyperventilation and increase in the alveolar surfactant content in rabbits in less than 15 min. We tried to study the role of leukotrienes (LT) and the effects of PGI2 in pulmonary response to FFA. We used Piriprost an inhibitor of LT synthesis or Epoprostenol (Prostacyclin: PGI2) in 4 series of rabbits treated with FFA or its vehicle. Piriprost given as an aerosol (0.1% W/W in THAM) scarcely modified the morphofunctional changes induced by FFA. The only pulmonary effect prevented by Piriprost was the increase in surfactant content (disaturated phosphatidylcholine: DSPC) in broncho-alveolar lavage gluid (BAL). PGI2 administered in a dose of 0.1 micrograms.kg-1.min-1 5 minutes prior to a 15 min infusion of FFA was also unable to prevent most of the effects of FFA on the lung. Only the increase in DSPC in BAL was prevented by PGI2. Some animals received a smaller dose of FFA, because they died earlier. Piriprost, as well as PGI2, shortened the survival time of rabbits treated with FFA. This decrease in the survival rate of animals treated with FFA could account for the lack of increase in DSPC post-FFA. Since other morphofunctional changes induced by FFA were scarcely modified by both Piriprost or PGI2, our results suggest that it is unlikely that either leukotrienes on PGI2 may have a significant effect on pulmonary disturbances induced by FFA.

Effect of lung collapse on alveolar surfactant in rabbits subjected to unilateral pneumothorax.

To determine whether atelectasis might modify lung surfactant, we injected N2 into the right pleural space of adult rabbits. Daily, under sedation, pleural gas volume and pressure were measured and adjusted to 20 ml/kg and 0 to +2 cm H2O with N2. On the sixth day, pHa, PaCO2, PaO2, and FRC were measured. Pressure-volume diagrams or bronchoalveolar lavages (BAL) were performed separately on right and left lungs. Surfactant subfractions were obtained from BAL fluid, and total protein, LDH, and cell counts were determined. Phospholipid (PL) was assayed in lung homogenate, BAL fluid, and subfractions, and PL composition was determined on the largest BAL subfraction (P4). On the sixth day the pleural gas volume was 19.7 +/- 2.7 (SD) ml/kg, and PaO2 and FRC were significantly decreased. Air volume in excised right lungs at 30 cm H2O was 13.1 +/- 2.8 (SE) ml/kg with pneumothorax (PN) and 22.8 +/- 1.9 (SE) ml/kg in controls. Total PL was decreased 43% in BAL and 59% in P4 of collapsed lungs. Phosphatidylglycerol to phosphatidylinositol (PI) plus phosphatidylserine (PS) ratio of P4 was substantially decreased in both lungs of PN animals. Cell counts, LDH, and protein in BAL did not suggest inflammation or epithelial damage. We conclude that pneumothorax decreases the quantity of alveolar surfactant in the collapsed lung and alters its phospholipid composition toward the fetal pattern in both lungs, possibly due in part to the proliferative response of the lungs to pneumothorax.

[Effect of endotracheal instillation of hydrochloric acid on the contents of alveolar surfactant in rats]. / Efecto de la instilación endotraqueal de ácido clorhídrico sobre el contenido de surfactante alveolar en la rata.

Aspiration of gastric contents to the lung is a cause of Adult Respiration Distress syndrome. We studied the effects of endotracheal instillation of hydrochloric acid (2 ml/kg, 0.1 N solution) in anesthetized rats who were sacrificed 4 or 48 hr later. A control group received 0.9% saline solution instead. Total protein, phospholipids, disaturated phosphatidylcholine (DSPC) and number of cells were determined in the bronchoalveolar lavage fluid. Histologic studies were performed in one rat in each group. HCl caused edema and inflammatory reaction characterized by a rise in protein and cells in the bronchoalveolar fluid 48 hr after endotracheal instillation. This was associated with an increase in total phospholipid and in DSPC. Therefore, the inflammatory response to HCl is associated to an increase in alveolar surfactant 48 hr after instillation.

Role of hypocapnia in the alveolar surfactant increase induced by free fatty acid intravenous infusion in the rabbit.

Intravenous infusion of free fatty acid (FFA) produces an increase in the alveolar surfactant pool of the rabbit and pulmonary edema, hyperventilation, hypoxemia and hypocapnia. Previous studies suggested that alveolar PCO2 would be a regulator of intracellular storages of surfactant. In order to study the role of hypocapnia in the increase of lung surfactant in our experiments we administered 20 mg FFA X kg-1 X min-1 i.v. to rabbits breathing room air (n = 10) or 5% CO2, 21% O2, 74% N2 (n = 7). Disaturated phosphatidylcholine (DSPC) was determined in bronchial-alveolar lavage fluid as index of alveolar surfactant content, 5% CO2 in the inspired air prevented the hypocapnia and blocked the increase in DSPC induced by FFA (p less than 0.01). Pulmonary edema post-FFA was not changed by 5% CO2 administration. We conclude that hypocapnia produced by hyperventilation during FFA infusion would be an important factor in the increase of DSPC observed after FFA infusion.

Effects of free fatty acid infusion on rabbit pulmonary surfactant. Influence of corticosteroids.

We studied the effect of free fatty acids (FFA) i.v. on alveolar lung surfactant content of rabbits. A FFA mixture was given in doses from 0.1 to 20 mg X kg-1 X min-1 during 15 min in seven different experimental series (n = 45). Disaturated phosphatidylcholine (DSPC) content in lung airway lavage fluid was measured as an index of alveolar surfactant pool. DSPC was significantly increased (p less than 0.05) by 86% in the series receiving 20 mg FFA X kg-1 X min-1 as compared to control values (means +/- SD: 4.4 +/- 1.1 mg DSPC X kg-1 body weight). Smaller doses of FFA did not change DSPC, but induced a dose-related pulmonary oedema. All the rabbits receiving 20 mg FFA X kg-1 X min-1 died before completion of the 15 min infusion; they were hypoxaemic, hyperventilated and had a decrease in lung compliance. Hydrocortisone (20 mg X kg-1 i.v.) and methylprednisolone (30 mg X kg-1 i.v.) administered 2 h before FFA blocked the increase of DSPC induced by 20 mg FFA X kg-1 X min-1. Both drugs decreased pulmonary oedema and tended to normalize some of the pulmonary function indices, although they did not modify the lethality. In conclusion, acute i.v. infusion of FFA increased alveolar surfactant pool and produced pulmonary oedema; pretreatment with corticosteroids reduced these effects and protected the lung from some of the noxious effects of FFA.

Sodium cholate interactions with rabbit's pulmonary surfactant.

In order to assay the possibility that sodium cholate interacts with pulmonary surfactant, we obtained bronchoalveolar lavage fluid from lungs of adult rabbits and measured the hysteresis area of surface tension-area loops of the bronchoalveolar lavage fluid in a Wilhelmy surface tension balance, before and after the addition of sodium cholate to reach different concentrations. We observed a biphasic behavior: at a low concentration of sodium cholate (1.5 x 10(5) mol/l; n = 6) the hysteresis area increased (p less than 0.05) as compared to its control (initial) area, meanwhile at a higher concentration (5 x 10(-5) mol/l; n = 6) the hysteresis area decreased (p less than 0.025), revealing a likely interaction of sodium cholate with pulmonary surfactant. We conclude that sodium cholate is able to interact in vitro with lung surfactant.

Thromboxane mediates the increase in alveolar surfactant pool induced by free fatty acid infusion in the rabbit.

Intravenous infusion of free fatty acid (FFA) produces pulmonary edema and an increase in the alveolar surfactant content of the rabbit. In order to identify a likely mediator of this lung response to FFA, we used inhibitors of cyclo-oxygenase (indomethacin, 15 mg X kg-1 i.v., or meclofenamate, 5 mg X kg-1 i.v.) and thromboxane synthetase inhibitors (imidazole, 50 mg X kg-1 i.v. or dazoxiben, 2 mg X kg-1 i.v.) which were administered before FFA, 20 mg X kg-1 X min-1 i.v., in four different experimental series (n = 54). Lung surfactant was measured in bronchial-alveolar lavage fluid by determining disaturated phosphatidylcholine (DSPC). Both kinds of inhibitors blocked the increase in FFA-induced DSPC. They increased the survival rate but they only slightly changed the post-FFA morphofunctional pulmonary alterations. We conclude that the increase in alveolar surfactant induced by FFA is likely mediated by thromboxane. This mediator would seem to play a minor role in the FFA-induced pulmonary edema observed.

Ventilation enhances pulmonary alveolar clearance of radioactive dipalmitoyl phosphatidylcholine in liposomes.

We examined the clearance from lungs of dipalmitoyl phosphatidylcholine (DPPC), the main component of pulmonary surfactant, after instillation in the form of radioactively labeled liposomes (small unilamellar vesicles) in anesthetized rabbits breathing spontaneously. There were 2 protocols: normal ventilation in control animals, and ventilation increased 100% by augmentation of the dead space in experimental animals. Liposomes containing 20% phosphatidylglycerol were also tested in animals breathing normally. We examined the stereospecificity of clearance with levo 14C-DPPC and dextro 3H-DPPC isomers. We measured phospholipid content and plotted curves of radioactivity versus time (0 to 5 h) for alveolar material obtained by lavage and for the whole lung. In the control animals (n = 15), alveolar clearance of 14C-L-DPPC was 7.8%/h, and with increased ventilation (n =13) it was 13.3%/h (p less than 0.025). With phosphatidylglycerol (n = 9) alveolar clearance during normal breathing was 13.9%/h(p less than 0.001). Alveolar clearance rates of 14C-L-DPPC and 3H-D-DPPC were not significantly different. Clearance from the whole lung did not differ between control and experimental animals or between isomers, and it averaged 3.1%/h.

Control of lung surfactant by ventilation, adrenergic mediators, and prostaglandins in the rabbit.

In a previous study, we showed that increasing minute ventilation (VE) in rabbit lung by adding a dead space augmented pulmonary surfactant in the airspaces by a cholinergically mediated mechanism. Using the same model in the present study of 148 rabbits, we found that increasing VE augmented airspace phospholipid, the main component of surfactant, from 2.50 +/- 0.61 (mean +/- SD) mg per g of lung during normal VE to 3.15 +/- 1.22 (mean +/- SD) mg per g of lung during increased VE (P = 0.02). Both blocking beta-adrenergic receptors with propranolol or sotalol and inhibiting prostaglandin synthetase with indomethacin or sodium meclofenamate prevented the expected increase in phospholipid during increased VE (P is less than 0.05). The beta-2 agonist, terbutaline, increased phospholipid by 43 per cent during normal VE (P is less than 0.01), and propranolol blocked this increase (P is less than 0.05). Isoproterenol, arachidonic acid, prostaglandins E1, E2, F2alpha, and a cyclic endoperoxide analog of prostaglandin H2 (U-46619) injected during normal VE failed to increase phospholipid. We concluded that acetylcholine (previous study), beta-adrenergic mediators, and prostaglandins are involved in controlling alveolar surfactant during increased VE.

Ventilatory and cholinergic control of pulmonary surfactant in the rabbit.

Four sets of experiments on surfactant secretion were performed using New Zealand rabbits under light pentobarbital anesthesia. Pa02, Paco2, and pHa remained normal during all experiments. In controls lung lavage yielded 1.62 +/- 0.26 (SD) mg of alveolar phospholipid (PL)/g lung; disaturated phosphatidylcholine comprised 55.5% of total PL. a) Acetylcholine infusion into the left pulmonary artery for 1-4 h caused a 13% increase in alveolar PL of left as compared to right lung. b) Efferent left vagus stimulation for 1 h increased alveolar PL of right and left lungs 31% as compared to controls (P = 0.012). c) Increasing minute ventilation by 100% by augmenting dead space for periods of 1, 2, and 4 h, increased alveolar PL 45% (P = 0.001), 54%, (P = 0.002), and 25% (P = 0.004), respectively, compared to controls. d) Administration of atropine prevented the increase in alveolar PL caused by increased ventilation. These findings show that increased ventilation can stimulate surfactant release through a cholinergically mediated mechanism but do not rule out the participation of other mechanisms.