Supplemental oxygen and exercise performance in patients with cystic fibrosis with severe pulmonary disease.

Patients with cystic fibrosis (CF) and advanced pulmonary disease have pulmonary limitation of exercise, often associated with arterial oxygen desaturation. Improving oxygenation during exercise by providing supplemental oxygen may improve exercise performance in these patients. To test this, we performed graded exercise stress tests in 22 CF patients with severe pulmonary disease (mean PaO2, 64 +/- 2 mm Hg [+/- SE]; PaCO2 46 +/- 2 mm Hg; RV/TLC, 57 +/- 4 percent; FEV1, 38 +/- 4 percent of predicted; FEF25-75%, 13 +/- 2 percent of predicted; median age, 26 years) and compared them to 21 controls (RV/TLC, 27 +/- 4 percent; FEV1, 112 +/- 2 percent of predicted; FEF25-75%, 80 +/- 4 percent of predicted; median age, 29 years). Each subject performed graded exercise stress tests while breathing FIO2 of 0.21 and FIO2 of 0.30. Subjects were blinded to the composition of the inspired gas, and the order of testing was randomized. We found that CF subjects exercised longer, had a higher maximal VO2, higher O2 pulse, and less arterial oxygen desaturation when receiving supplemental O2. Control subjects exercised longer when breathing supplemental O2 but had no significant change in maximal VO2, O2 pulse, or SaO2. Both CF and control subjects had increased end-tidal PCO2 when exercising while breathing supplemental O2. We conclude that CF patients with advanced pulmonary disease have increased exercise tolerance and aerobic capacity when exercising while breathing supplemental O2.

Variable weight training in cystic fibrosis.

A six-month pilot study of variable weight training (VWT) was undertaken to assess its impact on body weight, pulmonary function, muscle size and strength, and social function in 12 adolescent and adult patients with moderately severe cystic fibrosis. Exercise for patients with cystic fibrosis (CF) has often been recommended as an adjunct to physical therapy, although aerobic exercise has not resulted in weight gain in CF. Compared to a three-month control period, six months of VWT resulted in significant increase in weight (2.88 kg, p less than .02), muscle size (1.6 to 1.8 cm upper arm, p less than .01), strength (increase from 16 to 32 muscle groups at normal strength, p less than .005), and decrease in residual volume (1.77 L, p less than .03) and RV/TLC (12.4 percent, p less than .02). There was no significant improvement in other measures of pulmonary or social function. VWT appears to be a form of exercise in which even moderately ill CF patients can engage safely, leading to desired weight gain and increased strength. These results warrant further study of the effects of VWT on pulmonary function and CF morbidity.

Breast-feeding by a mother with cystic fibrosis.

A 20-year-old white women with cystic fibrosis who breast-fed her normal infant is described. Extensive breast milk analysis revealed normal sodium and chloride concentrations but elevated total protein and low total fat content; IgG and IgM levels were low to absent. The infant tolerated breast-feeding well, with normal growth and without infections, but the nutritional status of the mother appeared to be adversely affected. This case illustrates that breast-feeding by a mother with cystic fibrosis appears to be feasible but is fraught with difficulties.

The quantity of natural surfactant necessary to prevent the respiratory distress syndrome in premature lambs.

Premature lambs at 118 to 122 days of gestation were delivered by caesarean section and received before the first breath 0, 19, 53 or 64 mg natural surfactant total lipid (TL) per kg body weight (BW). The seven lambs receiving no surfactant died within 40.1 +/- 7.5 min, whereas the lambs treated with surfactant survived the 2-hr experimental period. Nineteen mg surfactant TL per kg BW preserved lung function; the pH and blood gas measurements were similar to those measured in lambs receiving 53 mg TL per kg BW or more surfactant. Pressure volume and surface tension characteristics were significantly improved after the administration of 19 mg of surfactant, but surface activity was still poor when compared to lambs receiving 53 mg TL per kg BW or more surfactant. The dose of surfactant (53 mg TL per kg BW) that resulted in good surface activity measurements in vitjro was similar to other estimates of the amount of surfactant necessary to cover the alveolar space.

Circulating immune complexes in cystic fibrosis.

Recurrent respiratory infections associated with "mucoid" Pseudomonas aeruginosa characterize the advanced stages of cystic fibrosis. To determine if chronic antigenic stimulation is associated with circulating immune complexes (CIC), we assayed the sera of 20 hospitalized patients using the technique of precipitation with 4% polyethylene glycol. Elevated CIC levels, defined by > 310 micrograms IgG per ml, were found in 18 of 20 patients, (range, 350 to 3200 micrograms/ml). Serum, supernatant, and resuspended precipitates were assayed for hemagglutinating antibodies against pseudomonas lipopolysaccharide (LPS or endotoxin) and exotoxin A antigens. Both serum anti-LPS (range, 1:64 to 1:2048) and antitoxin titers (range, 1:64 to 1:16, 384) were markedly elevated and higher than titers in supernatants and resuspended precipitates, indicating antibody excess. "Enrichment" ratios for antibodies present in CIC were calculated by proportion of titer to immunoglobulin in the precipitated complex relative to these values in serum. Mean enrichment ratios of 13.1 and 13.9 were obtained for LPS antibody before and after 2 mercaptoethanol reduction, but the mean enrichment ratio for antitoxin was only 2.07. Serially diluted supernatants and precipitates were boiled for 1 hr and tested for endotoxin-like activity by the limulus test. At > 1:8 dilutions, precipitates were positive, and supernatants were negative. These findings indicate that CIC's are common in advanced cystic fibrosis, and analysis of the precipitated complexes demonstrates significant (> 13-fold) enrichment of antibodies against LPS but not exotoxin antigens, as well as endotoxin-like activity in boiled precipitates.

The effect of cimetidine on maldigestion in cystic fibrosis.

Ten patients (6 to 27 years of age) who had severe pancreatic exocrine insufficiency due to cystic fibrosis were studied to determine whether cimetidine would improve dietary fat and nitrogen absorption. When a constant diet was consumed and oral pancreatic enzymes were administered, the addition of cimetidine (150 or 200 mg taken orally one-half hour before meals) signficantly reduced fecal fat excretion from 25.3 +/- 2.9 to 17.3 +/- 2.1 gm/24 hours and fecal nitrogen excretion from 4.5 +/- 0.6 to 3.4 +/- 0.5 gm/24 hours (P less than 0.05). Lower doses of cimetidine resulted in less significant reductions of steatorrhea and azotorrhea. Cimetidine may be a useful adjunct to oral pancreatic enzyme therapy in patients with cystic fibrosis who continue to have steatorrhea and azotorrhea with enzyme therapy alone.

Influence of pH on elastic deformability of the human erythrocyte membrane.

Fresh human blood was diluted 1:5000 in buffered saline-sucrose solution and titrated to a pH varying from 4.5 to 10.5 with 0.1 N HCl or 0.1 N NaOH. Circular regions of the membrane of individual cells were then deformed at 25 degrees C by aspiration into a micropipette having an internal tip diameter of 0.9-1.4 micron. A membrane surface elasticity modulus, mu (dyn/cm), was computed from the relationship between length of the aspirated membrane and the deforming pressure according to a two-dimensional membrane model. Surface elasticity increases with decreasing pH and with time after the cell suspension is acidified, rising several orders of magnitude with a t1/2 of 1--5 h as pH is lowered from 7.2 to 4.6. This increase in mu is only partially reversible. pH greater than 7.2 had little effect on mu. Membrane surface elasticity is not affected by variations in external [Ca2+] over the range of 0--50 mM, tonicity of the suspension medium from 275--400 mosM, or age of 0--50 h. Addition of 50 mM NaHCO3 to the medium increases the rate of change of mu at a given pH. These results suggest that the elastic properties of the red cell membrane are largely determined by interactions among structural proteins located on the cytoplasmic surface of the membrane and that these interactions are initiated by changes in intracellular pH.

Effects of continuous positive airway pressure after oleic acid-induced lung injury in dogs.

The physiologic effects of continuous positive airway pressure (CPAP) of 5,10,15, and 20 cm H2O during spontaneous ventilation were studied in six anesthetized dogs with simulated respiratory distress syndrome (RDS) induced by iv infusion of oleic acid and in three normal controls. After oleic acid, mean PaO2 dropped to 63.6 +/- 3.1 mm Hg while breathing 100% oxygen and mean shunt fraction was 48.3 +/- 3.0%. PaO2 and shunt fraction improved significantly at the two highest levels of CPAP (e.g.,PaO2 271.3 +/- 41.3 mm Hg and shunt fraction 17.8 +/-2.2% at 20 cm H2O CPAP). Mean mixed venous PO2 rose from 37.4 +/- 1.5 mm Hg with no CPAP TO 60.8 +/- 3.1 mm Hg at 20 cm H2O CPAP. Tissue oxygenation appeared to improve during CPAP, since cardiac output, oxygen delivery, and serum lactate were not significantly affected and mixed venous PO2 rose significantly. However, significant hypoventilation occurred at all but the lowest level of CPAP, mean PaCO2 rising from 44.1 +/- 1.8 mm Hg with no CPAP to 77.6 +/-6.8 mm Hg at 20 cm H2O CPAP. The hypoventilation during CPAP is consistent with increased work of breathing due to a combination of decreased lung compliance and increased dead space ventilation due to rapid, shallow breathing.

Effects of tracheal instillation of natural surfactant in premature lambs. I. Clinical and autopsy findings.

Ten pairs of twin lambs 118--122 days of gestation were given either natural surfactant or diluent endotracheally before the first breath. By using the premature twin lamb model, we have been able to show that instillation of natural surfactant produced 100% survival for the duration of the study period (2 hr); stable blood gases on room air; lungs that became increasingly compliant while on the respirator; generally well aerated lungs at autopsy; good lung pressure-volume relationships; normal lung surface tension measurements; and histologic evidence of good alveolar expansion with large amounts of free intraluminal phospholipid, no epithelial damage, and no hyaline membranes. It is concluded that tracheal instillation of natural surfactant into the premature lamb protects the lungs from developing many features characteristic of the respiratory distress syndrome.

Amikacin therapy of exacerbations of Pseudomonas aeruginosa infections in patients with cystic fibrosis.

Amikacin, a new semisynthetic aminoglycoside antibiotic with activity against Pseudomonas aeruginosa, was used to treat 22 acute exacerbations of chronic pulmonary infections in 18 patients with cystic fibrosis. Patients ranged from 5 to 32 years of age and had mucoid P. aeruginosa isolated from sputum. The amikacin dose was usually 7.5 mg/kg every eight hours but was increased to 10 mg/kg and/or carbenicillin was added in selected cases depending on clinical course. Although P. aeruginosa was not eliminated from our patients' sputum except in two cases, there was a good clinical response in 19 of 22 courses. Significant improvement in chest x-ray films, spirometry, or arterial oxygen tension was documented in 11 of 17 courses. One instance of serum creatinine level elevation could not be attributed to this antibiotic. Two patients showed minimal (15 dB) unilateral high-frequency hearing loss on serial audiograms. Activity against many gentamicin-resistant strains and high blood levels are among the attractive properties of amikacin. Amikacin is clinically effective in treating Pseudomonas-associated pulmonary infections complicating cystic fibrosis.

Absorption of digoxin in children with cystic fibrosis.

The absorption of digoxin in cystic fibrosis was evaluated in 16 subjects by assessing the relationship between dosage expressed in mug/kg/day and serum digoxin concentration. The results indicate that the same relationship exists between maintenance dosage and serum levels in these patients and in patients without cystic fibrosis. Thus, no evidence of impaired absorption was found.