• - 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

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- <=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.