A recent study sheds light on the variability of elastase levels in both pancreatic sufficient (PS) and pancreatic insufficient (PI) infants with cystic fibrosis (CF) (J Pediatr 2013; 162: 808-12).

After eliminating infants who did not have elastase values prior to 3.5 months and after 9 months, the study consisted of 61 formula-fed infants who had been diagnosed with CF.  Diagnosis was established based on either a positive sweat test or having two known CF mutations.

Background: Pancreatic elastase is produced by pancreatic acinar cells and is not degraded during intestinal transit.  It can be measured while on pancreatic enzyme replacement therapy (PERT) because it is specific for human elastase rather than porcine elastase.  In addition, samples are stable at room temperature for weeks.

Among this cohort, 28 (46%) were homozygous for the F508del mutation. Infants were part of a large docosahexaenoic acid (DHA) study; as such, they were randomized to receive either standard formula or formula supplemented with DHA.  Monthly stool samples were collected.

Results:

• Of 29 infants with initial fecal elastase <50 mcg/g, all had a value <200 mcg/g at one year.  However, 3 had a value >200 mcg/g at some time during the first year of life.
• Of 36 infants with initial elastase <100 mcg/g, 32 had a level <100 mcg/g at 1 year.  Only one infant in this group had a value consistent with PS and this infant had a mutation associated with increased likelihood of PS.
• Of 12 infants with initial values between 100-200 mcg/g, more variability was noted in their multiple samples.  This group accounted for the majority of infants who were reclassified from PI initially to PS after one year of life.  Among all 48 with values <200 mcg/g, 4 were considered PS at final evaluation.  However, 13 had values >200 mcg/g at some point.
• 13 infants were considered PS at initial evaluation with a value >200 mcg/g.  At the study conclusion, 3 had values <180 mcg/g.
• The majority of fluctuation in elastase values occurred during the first 6 months of life.

These results lead to the following conclusions:

1. Fluctuations in elastase levels during the first year of life indicate that some infants with PS become PI and vice versa.  Retesting at one year of life is important.
2. The authors recommend that all CF patients with elastase values below 200 mcg/g receive PERT.
3. One can extrapolate these findings to other populations.  A single normal or abnormal elastase value may not indicate ultimately whether a patient will remain pancreatic insufficient or sufficient. Though, values <50 mcg/g are more likely to indicate persistent PI status.

The authors do provide some speculation regarding these fluctuations.  They note that “a fecal elastase obtained very early in life might not reflect the child’s true functional pancreatic status.  Intestinal mucosal damage can cause secondary pancreatic insufficiency by decreasing signaling of the pancreas from enteroendocrine cells.”

Related blog links:

• Learning a lot from ChiLDREN (part 1) | gutsandgrowth
• Ivacaftor for Cystic Fibrosis | gutsandgrowth

References:

• -JPGN 2007; 44: 219.  Use of elastase in CF.  Pancreas secretes elastase; not degraded & does not cross react with porcine elastase, thus allowing measurement even in individuals on enzyme treatment.  Excellent sensitivity/specificity.
• -J Pediatr 2004; 145: 322 & 285,  A fecal elastase-1   >100mcg/g has a 99% predictive value for excluding pancreatic insufficiency.
• -JPGN 2003; 36: 314, 392.  Fecal elastase-1 is marker for exocrince pancreatic function & enteropathy.
• J Peds 2009; 155: supplement. Clinical practice guidelines for infants/children <2 years of age with CF:

1. -routinely give salt 1/8-1/4tsp/day
2. -measure elastase & supplement if PI
3. -Dose: 2000-5000 units lipase per feed –can go as high as 2500 units/kg (max daily 10000 units/kg/day)
4. -monitor & supplement ADEK
5. -consider 7% saline Rx & azithromycin in symptomatic