Respiratory Infection
Conditions
Keywords
Vitamin D, Respiratory infection, Innate immunity
Brief summary
For most individuals, the lung has a remarkable ability to deal with exposure to a variety of inhaled bacteria. Some individuals, however, do have recurrent bacterial infections, usually in the form of acute or chronic bronchitis and, in some instances, pneumonia. The reasons for this variability in bacterial infections between otherwise healthy subjects, between types of lung disease, and within the same type of lung disease are poorly understood. Variability in susceptibility to bacterial infections is partially explained by differences in exposure to infectious agents, genetic susceptibility and innate (or early) immune responses. It is of interest that the incidence and severity of bacterial infections is greatest during the winter months. Other than viral infections, there are few variables that change with season. Vitamin D is one known immune modulator with a seasonal periodicity. The hypothesis of this study is that levels of vitamin D are an important determinant of the innate defense of the lung against inhaled bacteria. The investigators further postulate that vitamin D has effects on the innate immune function of both alveolar macrophages and lung epithelial cells.
Interventions
DIETARY_SUPPLEMENTVitamin D3 (cholecalciferol)
DIETARY_SUPPLEMENTPlacebo Sugar Pill
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
University of Iowa
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Signed informed consent form Age 18 - 60 Healthy nonsmoker, healthy smoker Forced expiratory volume in 1 second (for smokers) \> 60% predicted.
Exclusion criteria
* Pregnant or breastfeeding * Medications (with the exception of hormonal birth control, thyroid medication or prespecified over the counter medications), including multi-vitamins and any preparation that contains vitamin D * Asthma * Heart disease * Diabetes * Previous positive tuberculin skin test, or previous diagnosis of tuberculosis * Recent respiratory tract infection * History of multiple bouts of pneumonia * Allergies to caines, atropine, or a history of adverse reaction to narcotics * Other factors that increase the risk of bronchoscopy * Evidence of acute bronchitis within the past 2 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antimicrobial Activity by Airway Surface Liquid (ASL) as Measured by Relative Light Units (RLU) | 3 months | We investigated the effect of vitamin D3 supplementation on airway surface liquid antimicrobial activity using a bioluminescent bacterial challenge. We challenged airway surface liquid samples with bioluminescent bacteria and measured live bacteria by relative light units (RLU) after 2 minutes as a surrogate of antimicrobial activity. We interpreted a reduction in live bacteria after challenge in relative light units as increased antimicrobial activity |
Countries
United States
Participant flow
Recruitment details
Subjects were included if they were 18-60 years old and able to understand and sign a consent form. All study procedures were performed at the University of Iowa Hospitals and Clinics bronchoscopy lab and clinical research unit between May 2008 and July 2010.
Pre-assignment details
Subjects were included if they were 18-60 years.Subjects were excluded if taking a multivitamin or vitamin D supplement within the previous three months, pregnant or breastfeeding,had a vaccination within one month, significant comorbid conditions, respiratory infection, history of positive tuberculin skin test, or use of antibiotics recently.
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D ASL Analysis of airway surface liquid in those taking Vitamin D | 21 |
| Placebo ASL Analysis of airway surface liquid in those taking placebo. | 19 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Low protein concentration in sample | 20 | 25 |
| Overall Study | Unable to complete bronchoscopy | 4 | 6 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Vitamin D ASL | Total | Placebo ASL |
|---|---|---|---|
| Age, Continuous | 25.8 years STANDARD_DEVIATION 7.6 | 26 years STANDARD_DEVIATION 10 | 29.4 years STANDARD_DEVIATION 13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 36 Participants | 16 Participants |
| Sex: Female, Male Female | 6 Participants | 14 Participants | 8 Participants |
| Sex: Female, Male Male | 15 Participants | 26 Participants | 11 Participants |
| Smokers | 5 Participants | 12 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 19 |
| other Total, other adverse events | 0 / 21 | 0 / 19 |
| serious Total, serious adverse events | 0 / 21 | 0 / 19 |
Outcome results
Primary
Antimicrobial Activity by Airway Surface Liquid (ASL) as Measured by Relative Light Units (RLU)
We investigated the effect of vitamin D3 supplementation on airway surface liquid antimicrobial activity using a bioluminescent bacterial challenge. We challenged airway surface liquid samples with bioluminescent bacteria and measured live bacteria by relative light units (RLU) after 2 minutes as a surrogate of antimicrobial activity. We interpreted a reduction in live bacteria after challenge in relative light units as increased antimicrobial activity
Time frame: 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitamin D3 | Antimicrobial Activity by Airway Surface Liquid (ASL) as Measured by Relative Light Units (RLU) | -581 Relative Light Units (RLU) |
| Sugar Capsule | Antimicrobial Activity by Airway Surface Liquid (ASL) as Measured by Relative Light Units (RLU) | -485 Relative Light Units (RLU) |