CF Infants Research Articles

Acylcarnitine is Low in Cord Blood in Cystic Fibrosis

Carnitine metabolites (total, free, short and long chain) were analyzed in cord blood of cystic fibrosis (n = 5), non-CF siblings (n = 7), and controls (n = 8). Total acylcarnitine (short and long chain combined) was significantly lower (less than 0.001) in CF compared to both control groups. Total and free carnitine showed no significant differences between the three groups. These findings are compatible with disturbed fatty acid metabolism in utero and may be related to the increased energy expenditure characteristic of CF infants.

The pathophysiology of the pancreatic defect in cystic fibrosis.

Studies of the postnatal development of the pancrease in CF infants show a failure of acinar development and an increase in lumen volume with accumulation of secretory material within the pancreatic ducts. Our evaluation of functional changes within the exocrine pancreas are consistent with the pathologic findings. Impaired pancreatic fluid secretion appears to be a primary phenomenon of CF. We have shown that pancreatic secretions from CF patients also contain significantly higher concentrations of protein in comparison with pancreatic function-matched controls. Since total protein output is not increased, hyperconcentration of protein appears to be a direct result of a primary defect of fluid secretion. Protein hyperconcentration appears to predispose CF patients to protein precipitation and obstruction within small pancreatic ducts which, in turn, produces pancreatic acinar atrophy and fibrosis Our studies suggest that both bicarbonate and chloride transport within pancreatic ducts account for deficient fluid secretion in the pancreas of CF subjects.

OUTCOME OF MECHANICALLY VENTILATED INFANTS WITH CYSTIC FIBROSIS (CP) AND RESPIRATORY FAILURE

Previous studies have documented a 75-85% mortality rate in infants (≤12 mos.) with CF who initially presented with respiratory failure requiring mechanical ventilation (RFMV). Five infants with CF and RFMV as their initial presentation were cared for between the years 1980-86 at Children's Hospital of Wisconsin. Clinical presentation of each case (age, physical exam, ABGs, CXR findings, tracheal cultures, days ventilated) was similar to previously reported studies of infants with CF and RFMV. The purpose of this study was to compare the outcome of these infants with age matched CF infants who never had RFMV. Three age matched controls with CF and born between the years 1980-86 were selected at random for each case. Most recent Schwachman's scores (SS) were obtained independently by two investigators. Interobserver differences in SS were not significant. All study cases were alive from 1-6 years after the episode of RFMV. Their most recent mean SS was 82.0 (range 79-95). In comparison, the recent mean SS of the controls was 78.0 (range 50-95). There was no difference between group SS (t=0.54, NS). We conclude that the outcome of infants with CF whose initial presentation is RFMV is not as grave as once thought, if indicated, infants with CF and respiratory failure should be ventilated.

Abnormalities of circulating immunoreactive pancreatic anionic trypsinogen in cystic fibrosis: An assay artifact due to cross-reacting serum antibodies

In patients with CF, serum pancreatic cationic trypsinogen has proven to be useful for newborn diagnostic screening and also as a test of pancreatic function in the older patient. However, an assay for serum anionic trypsinogen is of no value as a test of pancreatic function in CF due to an apparent artifactual elevation of this enzyme in some patients. In this study, we evaluated the extent of the abnormality in the anionic trypsinogen assay and also elucidated the nature of the interfering material. CF patients were grouped according to the presence (pancreatic insufficiency) or absence (pancreatic sufficiency) of steatorrhea. In CF infants, both serum cationic and anionic trypsinogen levels were greatly elevated. Serum cationic trypsinogen declined with age in patients with pancreatic insufficiency, reaching low or undetectable levels after 6 years. In contrast, serum anionic trypsinogen levels remained normal or elevated in 33% of those over 6 years of age. There was no age-related change in either cationic or anionic trypsinogen among the CF patients with pancreatic sufficiency, and the majority had normal or elevated levels. Serum samples from selected CF patients were separated into IgG and non-IgG fractions using Staph. Protein A columns. Immunoreactive cationic and anionic trypsinogen were detectable in the non-IgG fractions of sera from CF infants and older patients with pancreatic sufficiency. In older CF patients with undetectable serum cationic and anionic trypsinogen, no immunoreactive material was detectable in either the IgG or non-IgG fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption of a New Semielemental Diet in Infants with Cystic Fibrosis

Summary:A new semielemental formula made up of whey protein hydrolysate, medium‐chain triglyceride as 50% of fat, and glucose polymer was studied in 21 cystic fibrosis infants to determine whether its intestinal absorption was better than that of standard milk‐based formula. Each experiment lasted 10 days, during which the patient was fed for 5 days on one formula and immediately afterwards for 5 days on the alternative formula, without any pancreatic enzyme replacement. Fat and nitrogen absorption were assessed by 3‐day balance studies, stool fat was assayed by a modified Van de Kamer method, and stool nitrogen by an automatic method. Ten infants with very severely impaired digestive function (coefficient of fat absorption on normal diet ≤75%) showed a highly significant improvement in fat and nitrogen absorption, leading to a significant gain in weight when fed on semielemental diet compared with standard diet. No significant improvement was observed in fat and nitrogen absorption or in weight gain in the 11 infants with less severe malabsorption (coefficient of fat absorption on normal diet >75%). These results were obtained over a short period and have to be confirmed over a prolonged period of study with pancreatic enzyme supplementation. However, they suggest that such a semielemental diet should be effective for short‐term treatment in selected CF infants who have difficulty in starting to thrive adequately.

1850 FLOW LIMITATION IN INFANTS WITH CYSTIC FIBROSIS DURING A PULMONARY EXACERBATION

We evaluated nine CF infants, mean age 18 months (5.5-28), during pulmonary exacerbation (PE) and again at follow-up (FU), mean 3.4 months (1-6) post PE. During sleep, we measured 1) respiratory rate (RR), 2) function residual capacity (FRC) by helium dilution, 3) mixing index (MI) and 4) size corrected flows at FRC (VmaxFRC/FRC). Clinical scores (CS), 0-25 (healthy), were based upon cough, cyanosis retractions, breath sounds, and clubbing. During PE, 5 infants required hospitalization (H) and 4 were outpatients (OP). The H group had significantly lower (P<.03) VmaxFRC/FRC (.19 vs .80). Five of 5 H and none of OP infants reached flow limitation during tidal breathing, but RR, FRC/kg, and MI between groups were not significantly different (NSD). Between PE and FU, paired t-test for combined H and O groups demonstrated increase in VmaxFRC/FRC, +.49 (P<.01), and decrease in FRC/kq. -3 (P<.04), but NSD in RR or MI. There was a significant linear regression between CS and VmaxFRC/FRC (r=.80). We conclude that pulmonary function changes during PE in CF infants can effectively be assessed from partial expiratory flow volume curves and that flow limitation during tidal breathing is associated with severe lung disease.

Immunoreactive trypsin in cystic fibrosis.

Since the first observation in 1979 that CF infants have elevated blood IRT, studies in various centres have enabled us to more fully understand the importance of this phenomenon. There is increasing evidence to show that mass newborn screening for CF using the IRT assay is practical and is capable of detecting essentially all CF newborns at a cost comparable to existing screening programs for other disorders such as Hypothyroidism. Although the elevated IRT levels seen in infancy in CF soon decrease, IRT levels in older CF patients appear to quite closely reflect the capability of that patient to secrete pancreatic enzymes and can be helpful in separating CF patients whose ability to secrete enzymes is preserved, from those with diminished exocrine pancreatic function. In all CF patients there appears to be an altered relationship between pancreatic exocrine secretion and circulating IRT levels as compared to control patients. This is probably one further manifestation of a secretory obstructive defect which although not uniformly severe, is common to all CF patients.

Sudden infant death syndrome (SIDS) in south australia

Sudden Infant Death Syndrome (SIDS) is a significant cause of death of infants, representing 15-20% of infant mortality and being responsible for about 60% of deaths of babies aged 1 to 7 mth in South Australia. The incidence of SIDS in South Australia is 1.7/1000 live births. The age limits usually recognized for SIDS are 2 wk to 2 yr. Most deaths (90%) in this series occurred between 1 and 7 mth of age, with a maximum at 2 to 4. SIDS was found to be commoner in winter than in summer, in babies of low birth weight, and in twins. Clinical findings at the time of death varied; in many, nothing abnormal was found. Respiratory infection is common in children of the SIDS age group; 56% of a control group of babies reaching 4 mth of age had respiratory tract infection in the previous 4 wk. At autopsy in SIDS, a mild degree of bronchiolitis, upper respiratory tract infection or otitis media is often found. However, infection should not be indicated as a cause of death unless it is felt that it was sufficiently severe to have been the probable cause of death. The importance of prompt counselling of parents cf infants dying of SIDS cannot be over emphasized, since most, left to their own devices, will wonder whether they could have prevented the death. They need to realize that the cause of death was SIDS, and not any of the factors frequently noted in association with SIDS. By admitting that the cause of SIDS is unknown, an important step towards recognition of the cause may have been taken. Sudden Infant Death Syndrome (SIDS) is a significant cause of death of infants, representing 15-20% of infant mortality and being responsible for about 60% of deaths of babies aged 1 to 7 mth in South Australia. The incidence of SIDS in South Australia is 1.7/1000 live births. The age limits usually recognized for SIDS are 2 wk to 2 yr. Most deaths (90%) in this series occurred between 1 and 7 mth of age, with a maximum at 2 to 4. SIDS was found to be commoner in winter than in summer, in babies of low birth weight, and in twins. Clinical findings at the time of death varied; in many, nothing abnormal was found. Respiratory infection is common in children of the SIDS age group; 56% of a control group of babies reaching 4 mth of age had respiratory tract infection in the previous 4 wk. At autopsy in SIDS, a mild degree of bronchiolitis, upper respiratory tract infection or otitis media is often found. However, infection should not be indicated as a cause of death unless it is felt that it was sufficiently severe to have been the probable cause of death. The importance of prompt counselling of parents cf infants dying of SIDS cannot be over emphasized, since most, left to their own devices, will wonder whether they could have prevented the death. They need to realize that the cause of death was SIDS, and not any of the factors frequently noted in association with SIDS. By admitting that the cause of SIDS is unknown, an important step towards recognition of the cause may have been taken.