Human Lung Responses to Respiratory Pathogens

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Infection
• Intervention / Treatment: Dietary supplement: Vitamin D3 (cholecalciferol); Dietary supplement: Placebo Sugar Pill

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Vitamin D3 (cholecalciferol); Vitamin D3 (1000 international units) daily for 3 months.	Dietary supplement: Vitamin D3 (cholecalciferol)
PLACEBO_COMPARATOR: Sugar capsule; Placebo comparator made of sugar in a capsule	Dietary supplement: Placebo Sugar Pill

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

Collaborators and Investigators

• Sponsor: University of Iowa
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General Publications

• Vargas Buonfiglio LG, Cano M, Pezzulo AA, Vanegas Calderon OG, Zabner J, Gerke AK, Comellas AP. Effect of vitamin D3 on the antimicrobial activity of human airway surface liquid: preliminary results of a randomised placebo-controlled double-blind trial. BMJ Open Respir Res. 2017 Jun 4;4(1):e000211. doi: 10.1136/bmjresp-2017-000211. eCollection 2017.
• Gerke AK, Pezzulo AA, Tang F, Cavanaugh JE, Bair TB, Phillips E, Powers LS, Monick MM. Effects of vitamin D supplementation on alveolar macrophage gene expression: preliminary results of a randomized, controlled trial. Multidiscip Respir Med. 2014 Mar 26;9(1):18. doi: 10.1186/2049-6958-9-18.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (ACTUAL): July 1, 2010
• Study Completion (ACTUAL): October 1, 2010

Study Registration Dates

• First Submitted: October 17, 2013
• First Submitted That Met QC Criteria: October 17, 2013
• First Posted (ESTIMATE): October 23, 2013

Study Record Updates

• Last Update Posted (ACTUAL): March 29, 2018
• Last Update Submitted That Met QC Criteria: February 28, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Vitamin D; Respiratory infection; Innate immunity
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Respiratory Tract Infections; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: DMID 06-0003; N01AI30040-11-0-0 (NIH)