Diminished lung compliance and elevated surfactant lipids and proteins in nutritionally obese young rats.

Dietary-induced obesity is associated with increases in lung weight, lung volume, alveolar surface area, and number of lamellar bodies in alveolar epithelial type II cells. This suggests that alterations in lung compliance and surfactant content may also occur. The effects of dietary-induced obesity on lung function and surfactant composition were studied in newborn male rats raised in (1) small litters until weaning and then fed a high fat diet (Obese Group, n = 23) and (2) normal-sized litters until weaning and subsequently fed a normal rat diet (Control Group, n = 29). At age 8 weeks, lung function was measured in anesthetized, spontaneously breathing rats, and surfactant composition was analyzed in lung tissue and lavage fluid. The 8-week-old obese rats had a higher body weight (31%) and fat pad weight/body weight ratio (224%) than the Control Group. When compared with control animals, obese rats had an increased respiratory rate, reduced tidal volume, and decreased lung compliance (dynamic and specific). Disaturated phosphatidylcholine (DSPC) in lung tissue and surfactant pellets (large aggregates) and SP-A and SP-B levels in large aggregates were higher in obese than control rats. Phospholipid, DSPC, and triglyceride contents were also elevated in lung tissue in obese rats, suggesting intracellular lipid accumulation, but low relative to alveolar surface area. Thus, alterations in lung function and surfactant lipids and proteins occur in dietary-induced obesity in young rats. We speculate that intrapulmonary lipid deposition and possible surfactant deficiency relative to alveolar surface area may contribute to the reduction in lung compliance in obese rats.

Alveolar enlargement in obesity-induced hyperplastic lung growth.

Structural changes underlying obesity-induced pulmonary cellular hyperplasia were evaluated by lung morphometry and stereology in 8-wk-old male Long-Evans rats made obese by nursing in small litters with subsequent feeding of a high-fat diet. Control animals were raised in normal-sized litters and then fed standard rat chow. Compared with controls, obese rats had significant elevations in body weight (31%), fat pad weight (158%), fat pad weight-to-body weight ratio (97%), snout-to-anus length (8%), snout-to-tail length (7%), serum insulin concentration (64%), fixed lung volume (56%), and the ratios of lung volume to body weight (18%) and lung volume to body length3 (24%). Lungs of obese rats had enlarged alveoli, with significant increases in mean (182%) and total (71%) alveolar volume, mean chord length (28%), and mean (89%) and total (25%) alveolar surface area. Surface density (24%), surface-to-volume2/3 ratio (24%), and numerical density (43-53%) of alveoli in obese rats were significantly diminished compared with lungs of control rats. Unchanged were total alveolar number and alveolar volume density. Measurements of perihilar and subpleural alveoli within the obese and control groups were indistinguishable. These results indicate the presence of alveolar enlargement with relatively diminished respiratory surface area in lungs of young rats made obese by diet. This relative decrease in gas-exchanging area may contribute to physiological and functional alterations present in obesity.

Obesity-induced hyperplastic lung growth.

The effects of overnutrition on lung growth were studied in newborn male Long-Evans rats made obese by nursing in small litters with subsequent feeding of a high fat diet. Control rats were nursed in normal-sized litters and then fed standard rat chow. The animals were killed at 8 wk of age. When compared with control rats, obese rats had significant increases in body weight (24%); fat pad weight (118%); fat pad weight/body weight ratio (77%); snout-to-anus length (11%); total lung weight (11%); lung content of DNA (19%), protein (22%), RNA (22%), total lipids (31%), cholesterol (20%), and triglycerides (141%); and the lung triglyceride/DNA ratio (217%). Serum levels of insulin (71%), total lipids (60%), cholesterol (64%), and triglycerides (90%) were also elevated in obese rats as compared with those in control rats. Unchanged were the ratios of lung protein/DNA, RNA/DNA, lipid/DNA, and cholesterol/DNA; lung phospholipid content; and serum concentrations of glucose and phospholipids. The results indicate the presence of cellular hyperplasia in lungs of young rats made obese by diet. Lipid deposition in the obese lungs suggests metabolic alterations in pulmonary composition occurring with obesity.

Alterations in plasma amino acid levels in children with asthma: a preliminary investigation.

Concentrations of plasma amino acids and cortisol were measured in 27 children with status asthmaticus, moderate, or mild asthma and in 7 controls without lung disease. Individuals with conditions potentially altering amino acid levels were excluded. Measurements were made at 8 A.M. and 4 P.M. on the same day. Of the 24 amino acids analyzed, threonine, serine, citrulline, tyrosine, proline, alanine, cystine, isoleucine, ornithine, lysine, and arginine were decreased at 8 A.M. or 4 P.M. and plasma cortisol was elevated at 4 P.M. in patients with status asthmaticus when compared with the other groups (p less than 0.05). Normal diurnal variations of amino acids and cortisol were preserved in all groups. Sequential daily determinations in eight patients with status asthmaticus showed progressive increases in total and many individual amino acids as symptoms subsided. These studies demonstrate a decrease of certain gluconeogenic amino acids in the plasma in status asthmaticus. This diminution could reflect the need for maintenance of normal glucose concentrations in status asthmaticus. The decrease in gluconeogenic amino acid levels may play a role in the severity of asthma.

Ethanol and fetal nutrition: effect of chronic ethanol exposure on rat placental growth and membrane-associated folic acid receptor binding activity.

Rat placental composition and specific folate receptor activity were measured at 20 days gestation in dams exposed to chronic high doses of ethanol (6%, vol/vol) throughout gestation and in isocalorically pair-fed controls. Ethanol-exposed fetuses were smaller (ethanol = 3.28 +/- 0.08 vs. control = 4.01 +/- 0.10 g, p less than 0.001), but their placentae were larger (experimental = 0.534 +/- 0.02 vs. control = 0.399 +/- 0.01 g, p less than 0.001). The increased weight appears to be secondary to hyperplasia as total DNA was increased while the wet/dry, RNA/DNA, and protein/DNA ratios were not different. Despite larger placentae, specific folate receptor activity was significantly reduced in the ethanol-exposed tissue, whether expressed relative to membrane protein, placental weight, or total placental binding. These results confirm that ethanol exposure is placentotoxic and suggest an additional mechanism by which ethanol may lead to intrauterine growth retardation; namely, decreased folate receptor activity.

Effect of intrauterine ethanol exposure on fetal lung growth.

Lung weight, DNA, RNA, protein, and total body weight were analyzed in fetuses from 14 pregnant Sprague-Dawley rats fed a nutritionally complete liquid diet containing v/v 6% ethanol (ethanol group). Each ethanol rat was matched with an isocalorically pair-fed animal (control group) who received the same liquid diet with carbohydrate substituted for ethanol. The rats were killed on day 20 of gestation. The mean maternal blood ethanol concentration at 0700 h on day 20 was 170 +/- 22 (SE) mg/dl. Compared to controls, ethanol fetuses had reduced body weight (21%), lung dry weight (39%), lung wet weight/body weight ratio (10%), DNA (21%), RNA (25%), protein (28%), and protein/DNA ratio (8%) (p less than 0.05). The results indicate that prenatal ethanol exposure inhibits cellular growth in the fetal lung, resulting in hypoplastic lungs which have fewer and smaller cells. The effect on the lung appears to be greater than on the body as a whole. These hypoplastic lungs may be predisposed to the development of pulmonary disease and may explain observations of more frequent and severe lower respiratory infections in children with prenatal ethanol exposure.

Apparent resurgence of tuberculosis in urban children.

An apparent increase in incidence of pulmonary and extrapulmonary forms of tuberculosis was observed in children in an inner-city community in New York City. This occurred during years in which the case rates of tuberculosis declined in the city and the nation. Two unusual presentations of childhood tuberculosis are described. This experience suggests that physicians should be more aware of the diagnosis of tuberculosis in children and that routine tuberculin skin testing with 5 TU of purified protein derivative (PPD) should be continued, with emphasis on testing in high-risk areas. Adequate funding of detection and treatment programs may prevent reemergence of this disease.

Effect of lung collapse on compensatory lung growth.

The effect of unilateral lung collapse on compensatory lung growth was studied in 3-wk-old (young) and 10-wk-old (adult) male Long-Evans rats. Under light halothane anesthesia, left lung collapse was produced by injection of dental plastic through a thracheostomy cannula. The rats were killed either 5 days or 4 wk later. At 5 days postcollapse, the 3-wk-old rats had an increase in DNA over sham controls (21%) (P less than 0.05), with no significant change in the protein/DNA ratio. At 4 wk postcollapse, increases in DNA over shamoperated controls were observed in both the 3-wk-old (58%) and the 10-wk-old (28%) rats, whereas the protein/DNA ratio at both ages was significantly less than that of sham controls (P less than 0.05). Thus, unilateral lung collapse stimulates growth of the contralateral lung by cellular hyperplasia, not hypertrophy, both in the young and adult rat. The hyperplasia begins within 5 days after collapse and is greater by 4 wk. The extent of hyperplasia is greater in the young than in the adult rat.