The Lung PCA: A Multi-Dimensional Atlas of Pulmonary Premalignancy

Inclusion Criteria Prerequisites for Inclusion in Either Study Group: 1. Provision of signed and dated informed consent form. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. Male or female, aged \> 18 years. Pre-Screening Inclusion Criteria: Patients that have consented to the pre-screening with any of the clinical histories described below, will be asked to provide a screening sputum sample and undergo a bronchoscopy. The bronchoscopy is contingent on the identification of moderate or worse bronchial epithelial atypia by sputum cytology. Those patients with moderate or worse atypia on sputum cytology will be offered bronchoscopic examination and tissue sampling. If findings from the bronchoscopy meet Main Study Group inclusion criteria, the patients will be offered a chance to enroll in the main study. The following criteria will be used to identify potential pre-screening enrollees: 1. A current or ex-smoker with a \> 20 pack-year history of smoking. 2. History of non-small cell lung cancer (stage I, II, or IIIA) with\> 10 pack-year history of smoking and no evidence of active disease at least 1 year after definitive treatment. 3. History of head and neck cancer (stage I, II, III, or IVA) with \> 10 pack-year history of smoking and no evidence of active disease at least 1 year after definitive treatment. Main Study Group Inclusion Criteria: Enrollment in the main study group can occur via two routes. If inclusion criteria described below are already present from results of a prior bronchoscopy the patient may be enrolled directly. The second route will involve evaluation of results obtained in the pre-screening arm. When a prescreening bronchoscopy shows biopsy histologic findings that meet the pre-requisites shown below, the patient will be offered enrollment in the Main Study Group where they will be offered three more bronchoscopic examinations including the baseline bronchoscopy and those performed at one and two years after the baseline bronchoscopy. Note: the pre-screening bronchoscopy cannot represent the main study group baseline bronchoscopy as costs associated with specialized specimen collection in the main study group (single cell processing, etc.) cannot be covered in the pre-screening bronchoscopy. The qualifying additional pre-requisites for enrollment in the Main Study Group are: 1. Participants must be able and willing to undergo a total of at least three bronchoscopies. 2. Prior results from bronchoscopic analyses (via previous results or from pre-screening cohort bronchoscopies) must meet either of the following criteria to qualify patients as potential Main Study Group enrollees: * Pre-existing bronchoscopic documentation of persistence of or progression to high grade dysplasia at two or more airway sites. * Endobronchial dysplasia (squamous metaplasia/mild dysplasia, score \> 3) at \> 3 airway sites. * High grade bronchial dysplasia (moderate dysplasia or worse, score \> 5) Exclusion Criteria Patients will not eligible if any one of the following conditions are present: 1. Clinically apparent bleeding diathesis. 2. Cardiac dysrhythmia that is potentially life threatening, such as ventricular tachycardia, multifocal premature ventricular contractions or supraventricular tachycardias with a rapid ventricular response. Well-controlled atrial fibrillation or rare (\< 2/minute) premature ventricular contractions are not exclusionary. 3. Hypoxemia (less than 90% saturation with supplemental oxygen) prior to bronchoscopy. 4. Evidence of clinically active coronary artery disease, including myocardial infarction within 6 weeks, anginal chest pain, or poorly controlled congestive heart failure, or any other serious medical condition which would preclude a patient from undergoing a bronchoscopy. 5. Acute bronchitis or pneumonia within 8 weeks, except if these are considered clinically to be possibly a result of lung cancer. 6. Inability to give informed consent.