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Cystic Fibrosis & Vitamin D Lindsay Esposito Evidence-Based Medicine Integration of the best research evidence with clinical expertise, and the patient’s unique values and circumstances • Purpose: improve patient outcomes by providing clinicians with highest grade evidence available • Pros: results have been shown in a large number of people • Cons: individuals are different, funding issues, outdated, unsupported claims, constant change Ask relevant question Acquire best evidence Appraise validity Apply results to patients Assess effectiveness CF: Background • Inherited autosomal recessive disorder • Epithelial cells and exocrine glands secrete abnormal mucus • Affects respiratory tract, sweat, salivary, intestine, pancreas, liver, reproductive tract CF: Symptoms • • • • • • Increase number of greasy stools Abdominal Cramping EFAD High risk for malnutrition Increased energy expenditure Individualize throughout life span CF: MNT Focus • • • • • • Enzyme therapy Energy Macronutrients Antioxidants Vitamins/Minerals Feeding Strategies CF: Treatment • Airway Clearing Techniques – Postural drainage and percussion • Pancreatic enzyme supplements • Inhaled medications • Antibiotics • Implanted devices – Ports and PICCs Cystic Fibrosis • Most common lethal autosomal-recessive genetic disease among Caucasian • Affects 60,000 individuals worldwide, occurs in 1 in every 2500 live births • Leads to death or lung transplantation in more than 1000 people annually Cystic Fibrosis • Greatest single cause: respiratory disease • Medical improvements/treating pulmonary infections • Recognition of bone disease which increases with age • Vitamin D: maximizes calcium absorption from the lumen of the gut Possible Causes of Low Vitamin D • • • • • • Decreased GI absorption Impaired hydroxylation Reduced sun exposure Increased use of sunscreen Season influence Geographical location Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis patients Robert K Lark, Gayle E Lester, David A Ontjes, Angelina D Blackwood, Bruce W Hollis, Margaret M Hensler, Robert M Aris • • • • • • • Osteoporosis diminishes quality of life Vitamin D and low bone mineral density 10 Control and 10 CF CF patients matched with control based on age, gender, sex 2500 micrograms Vit D2 with meals CF took pancreatic enzymes Baseline blood samples at specific hour intervals Results • Vitamin D absorption significantly lower and variable in CF • Ergocalciferol (D2) vs. cholecalciferol (D3) • Large dose of vitamin D2 did not raise serum 25(OH)D significantly • Don’t absorb vitamin D2 efficiently less substrate for 25hydroxylase enzyme • Rapid metabolic clearance • CF: absorbed less than ½ oral vit D2 than controls over time Discussion • • • • • • Vitamin D malabsorption correlated to low BMD Do not convert into more active form like controls >25 micrograms oral Vit D/d for adequate repletion Individualize dosage More vitamin D analogs Further research needed Study 1 Rating • • • • A Randomized, well-controlled study Generalizable Other studies mentioned confirm results and conclusions – Need more research on exact dose – Current dose of 20 micrograms vit D/day not adequate Cholecalciferol significantly increases 25hydroxyvitamin D concentrations in adults with cystic fibrosis Anne Stephenson, Michelle Brotherwood, Ronalee Robert, Eshetu Atenafu, Mary Corey, Elizabeth Tullis • Guidelines for Vit D not proven and effectiveness untreated • 360 adults with CF • Determine prevalence of 25(OH)D and effectiveness of supplementation with cholecalciferol • Counseled on compliance or additional oral cholecalciferol • Baseline 25(OH)D less than or equal to 50 nmol/L Results • 69% had 25(OH)D baseline concentrations less than or equal to 50 nmol/l, despite already having cholecalciferol • Current dosage 400-800 IU cholecalciferol/d inadequate to normalize serum concentrations • Lowest 25(OH)D seen in young: Lower BMI and less pulmonary function (more at risk) • Cholecalciferol increases with maximum response in those with lowest baseline concentrations Discussion • Recent recommendations from CFF: 25(OH)D greater than 75 nmol/L • Highest risk in those with severe CF • Brief, casual exposure to sun • Additional 1000 IU/d • Most effective way to normalize concentrations is uncertain Study 2 Rating • • • • B Well-conducted cohort study Large population size Retrospective study design, not randomized controlled • Exact date of intervention not recorded • Dosage results not recorded • Randomized clinical trial needed to determine dosage and treatment duration References • • Lark, Robert K., Gayle E. Lester, David A. Ontjes, Angelia D. Blackwood, Bruce W. Hollis, Margaret M. Hensler, and Robert M. Aris. “Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis pateints1’2’3.” The American Journal of Clinical Nutrition 73.3 (2001): 602-606. American Society for Clinical Nutrition, March 2001. Web. 24 Oct. 2015. Stephenson, Anne, Michelle Brotherwood, Ronalee Robert, Eschetu Atenafu, Mary Corey, and Elizabeth Tullis. “Cholecalciferol Significantly Increases 25hydroxyvitamin D Concentrations in Adults with Cystic Fibrosis1,2.” The American Journal of Clinical Nutrition 85.5 (2007): 1307-1311. American Society for Clinical Nutrition, May 2007. Web. 24 Oct. 2015. Questions