Clinical Outcomes and Molecular Phenotypes in Smokers With Parenchymal Lung Disease

Despite the implementation of modern public health interventions, 1 in 5 adults in the United States are either current or former smokers and remain at risk for the development of chronic lung diseases. It is unknown how or why any one individual smoker can develop a wide range of lung diseases including chronic obstructive lung disease and/or pulmonary fibrosis. The purpose of this protocol is to collect clinical data, blood, urine, and bronchoalveolar samples from smokers and non-smokers in an attempt to establish phenotypic clinical profiles that correspond to divergent pathways in the expression of such proteins as the transforming growth factor-beta1 (TGF-beta <=1). The information generated from this study will provide insight into the pathogenesis of smoking-related lung injury and potentially allow for the development of early therapeutic interventions.

Study Overview

• Status: Completed
• Conditions: Pulmonary Fibrosis; Lung Disease

Detailed Description

Despite the implementation of modern public health interventions, 1 in 5 adults in the United States are either current or former smokers and remain at risk for the development of chronic lung diseases. It is unknown how or why any one individual smoker can develop a wide range of lung diseases including chronic obstructive lung disease and/or pulmonary fibrosis. The purpose of this protocol is to collect clinical data, blood, urine, and bronchoalveolar samples from smokers and non-smokers in an attempt to establish phenotypic clinical profiles that correspond to divergent pathways in the expression of such proteins as the transforming growth factor-beta1 (TGF-beta1). The information generated from this study will provide insight into the pathogenesis of smoking-related lung injury and potentially allow for the development of early therapeutic interventions.

• Study Type: Observational
• Enrollment (Actual): 7

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

One hundred thirty-eight study subjects with chronic obstructive pulmonary diseases (COPD) and interstitial lung diseases such as idiopathic pulmonary fibrosis (IPF) along with 85 control subjects will be enrolled in this study.

Description

• INCLUSION CRITERIA: For subjects with lung diseases:
• Men and women age 40-80 years
• Smokers with greater than or equal to 10 pack-year history of ever-smoking

EXCLUSION CRITERIA: For subjects with lung diseases:

Subjects will be excluded from the study if they meet one or more of the following criteria:

• Subjects who are under the age of 40 or over 80 years old
• Women who are pregnant or lactating
• Have known allergies to lidocaine or medications used for moderate sedation
• Active coronary artery disease
• Cerebral-vascular accident within the past 12 months
• Active anticoagulation
• Active infections
• Cancer, or a history of cancer within the previous 5 years of screening (other than adequately treated cutaneous basal cell, squamous cell carcinoma, excised melanoma, or carcinoma in situ of the uterine cervix with no evidence of recurrence).
• Poorly controlled chronic diseases
• Unable to provide consent
• Impaired renal function (including dialysis)

• Contraindications to MRI scan including:

  • electrical implants such as cardiac pacemakers or perfusion pumps
  • ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants
  • ferromagnetic objects such as jewelry or metal clips in clothing
  • pre-existing medical conditions, including a likelihood of developing seizures or anxiety disorders such as claustrophobia, panic attacks or any psychiatric disorder

INCLUSION CRITERIA: For Non-Smoking Controls

• Men and women age 40-80 years
• No prior history of smoking (this is a non-smoking cohort)

EXCLUSION CRITERIA: For Non-Smoking Controls

• Subjects who are under the age of 40 or over 80 years old
• Women who are pregnant or lactating
• Have known allergies to lidocaine or medications used for moderate sedation
• Active coronary artery disease
• Cerebral-vascular accident within the past 12 months
• Active anticoagulation
• Active infections
• Cancer, or a history of cancer within the previous 5 years of screening (other than adequately treated cutaneous basal cell, squamous cell carcinoma, excised melanoma, or carcinoma in situ of the uterine cervix with no evidence of recurrence).
• Poorly controlled chronic diseases
• Unable to provide consent
• Impaired renal function (including dialysis)

• Contraindications to MRI scan including:

  • electrical implants such as cardiac pacemakers or perfusion pumps
  • ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants
  • ferromagnetic objects such as jewelry or metal clips in clothing
  • pre-existing medical conditions, including a likelihood of developing seizures or anxiety disorders such as claustrophobia, panic attacks or any psychiatric disorder

INCLUSION CRITERIA

For Smoking Controls

• Men and women age 40-80 years
• Subjects who have a prior smoking history

EXCLUSION CRITERIA

For Smoking Controls

• Subjects who are under the age of 40 or over 80 years old
• Women who are pregnant or lactating
• Have known allergies to lidocaine or medications used for moderate sedation
• Active coronary artery disease
• Cerebral-vascular accident within the past 12 months
• Active anticoagulation
• Active infections
• Cancer, or a history of cancer within the previous 5 years of screening (other than adequately treated cutaneous basal cell, squamous cell carcinoma, excised melanoma, or carcinoma in situ of the uterine cervix with no evidence of recurrence).
• Poorly controlled chronic diseases
• Unable to provide consent
• Impaired renal function (including dialysis)

• Contraindications to MRI scan including:

  • electrical implants such as cardiac pacemakers or perfusion pumps
  • ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants
  • ferromagnetic objects such as jewelry or metal clips in clothing
  • pre-existing medical conditions, including a likelihood of developing seizures or anxiety disorders such as claustrophobia, panic attacks or any psychiatric disorder

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Lung disease (IPF) and smoking history; 50 IPF and 50 COPD patients, and 30 subjects with early interstitial lung abnormalities seen on previous radiographs
Lung disease COPD and smoking history; 50 IPF and 50 COPD patients, and 30 subjects with early interstitial lung abnormalities seen on previous radiographs
Normal Volunteers- Non-smokers, and Smokers; 50 smoking and 30 non-smoking controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine changes in validated clinical parameters of smokers with interstitial lung abnormalities (ILA) as compared to controls and patients with IPF and COPD.	Determine changes in validated clinical parameters of smokers with interstitial lung abnormalities (ILA) as compared to controls and patients with IPF and COPD	3 years

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 14, 2014
• Primary Completion (ACTUAL): January 1, 2018
• Study Completion (ACTUAL): August 23, 2018

Study Registration Dates

• First Submitted: February 4, 2014
• First Submitted That Met QC Criteria: February 4, 2014
• First Posted (ESTIMATE): February 5, 2014

Study Record Updates

• Last Update Posted (ACTUAL): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 27, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: COPD; Smoking; Natural History; Idiopathic Pulmonary Fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Fibrosis; Lung Diseases; Pulmonary Fibrosis
• Other Study ID Numbers: 140049; 14-H-0049

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No