The purpose of this study is to see if giving people with CF and ABPA enough vitamin D to make their blood levels of the vitamin higher, will reduce the allergic response in their body and make the symptoms caused by ABPA better.

Many patients with cystic fibrosis (CF) cough up mucus or have throat cultures that grow a common fungus called Aspergillus. In patients with CF, aspergillus is not known to cause direct damage to the lungs, but some patients respond with an allergic reaction that causes them to wheeze, cough, or have difficulty breathing. This allergic reaction is called ABPA. Current treatment for ABPA includes high dose steroids and an "anti-fungal" medicine. Treatment with steroids may be problematic for some people due to its side effects on blood sugar levels and the bones. Steroids are medications that decrease inflammation, including prednisone, medrol, dexamethasone and others.

Ongoing research at UPMC on the study "Mechanisms of Immune Tolerance in ABPA" has studied people with CF and ABPA versus those patients with CF that just grow A. fumigatus (Af) in the sputum, but do not have ABPA. You may have participated in this study. This study has shown that people with CF with the fungus, Af, in their sputum but who do not have ABPA have more of a certain type of cell in their blood that helps the body to regulate or suppress allergic reactions than those people with CF and ABPA.

Recent studies have demonstrated that Vitamin D is a critical factor in the development of these cells that suppress allergic reactions. People with CF, due to their pancreatic insufficiency that causes them to have difficulty absorbing fat, also have lower levels of the fat soluble vitamins which include vitamin D. In the study done at UPMC, "Mechanisms of Immune Tolerance in ABPA", people with CF and ABPA had significantly lower vitamin D levels than people with CF who did not have ABPA.

Inclusion Criteria:

1. Male or female ≥ 12 years of age at enrollment

2. Confirmed diagnosis of CF based on the following criteria:

   1. One or more clinical features consistent with the CF phenotype AND (b or c)
   2. Positive sweat chloride > 60 mEq/liter (by pilocarpine iontophoresis)
   3. two identifiable mutations consistent with CF

3. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

4. Clinically stable at enrollment as assessed by the site investigator

5. Past or present respiratory culture positive for Aspergillus fumigatus

6. IgE ≥ 250 and/or presence of class II or higher aspergillus specific IgE on enrollment

7. Ability to comply with medication use, study visits and study procedures as judged by the site investigator -

Exclusion Criteria:

• 1. Systemic corticosteroids (1 mg/kg if < 20 kg or > 20 mg of prednisone per day),.

  2. Investigational drug use within 30 days of screening 3. Laboratory abnormalities at screening

  a. Serum Calcium > 11 mg/dl b. 25(OH) D > 50 ng/ml at screening. c. Creatinine ≥ 1.5, or estimated GFR <60 by Cockcroft-Gault or MDRD equation. d. LFT≥ 3xULN

  4. History of transplantation or currently on lung transplant list 5. Positive serum pregnancy test at screening (to be performed on all post-menarche females) 6. Pregnant, breastfeeding, or if post-menarche female, unwilling to practice birth control during participation in the study 7. Presence of a condition or abnormality that in the opinion of the site investigator would compromise the safety of the subject or the quality of the data 8. Diagnosis of HIV and a CD4+ T cell count below 500 cells/ml or active hepatitis B or C infection.

  9. Undergoing therapy for non-tuberculous mycobacterial infection

Subjects with CF with a prior history of clinically diagnosed ABPA

6 months

same as clinicaltrials.gov definitions