Human Lung Responses to Respiratory Pathogens

Study Overview
=================
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.

Official Title
-----------------
Human Lung Responses to Respiratory Pathogens

Conditions
-----------------
Respiratory Infection

Intervention / Treatment
-----------------
* Dietary Supplement: Vitamin D3 (cholecalciferol)
* Dietary Supplement: Placebo Sugar Pill


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3 (cholecalciferol)<br>Vitamin D3 (1000 international units) daily for 3 months. | Dietary Supplement: Vitamin D3 (cholecalciferol)<br> <br> |
| Placebo Comparator: Sugar capsule<br>Placebo comparator made of sugar in a capsule | Dietary Supplement: Placebo Sugar Pill<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vitamin D, Respiratory infection, Innate immunity