Oral Iloprost for the Prevention of Lung Cancer In Former Smokers

Inclusion Criteria:

* Participants must be former smokers (\> 12 months abstinent and confirmed by serum cotinine) with at least a 30 pack-year cigarette history who are at high risk for the development of lung cancer with at least one of the following:

  * Stage I or II lung cancer survivors, surgically treated with curative intent, who have remained disease free for \> 12 months. Participants may have been treated with adjuvant chemotherapy or targeted therapy \[(e.g. Osimertinib for epidermal growth factor receptor (EGFR) mutation)\], if appropriate, provided they are \> 12 months from the last systemic adjuvant therapy dose.
  * Patients with chronic obstructive pulmonary disease (COPD), defined as either airflow obstruction (forced expiratory volume in 1 second \[FEV1\]/forced vital capacity \[FVC\] \< 0.70) on spirometry or emphysema (as commented on in a Radiology report) on CT scan.
  * Patients who display a ground glass opacity (GGO) on CT with a largest diameter =\< 10 mm and \>= 4 mm on axial imaging. The GGO must either be documented to have remained the same size or slowly progressing, but not regressing, over a 6-month period of observation by serial CT scan such that further workup beyond observation is not planned. A solid component of =\< 1/3 of the axial diameter may be present, providing the treating physician(s) do not plan on workup for resection within the next 6 months, taking both the character of the lesion and its rate of growth into consideration.
  * Patients who have had a previous endobronchial biopsy with mild World Health Organization (WHO) score 4 or greater dysplasia
* Participants must be able to safely undergo bronchoscopy in the judgement of the investigator
* Participants must have a biopsy showing mild (grade 4 on WHO score) or greater dysplasia on the baseline bronchoscopy
* Participants must be at least 50 years old. Because no dosing or adverse event (AE) data are currently available on the use of iloprost in participants \<18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable.
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Leukocytes \>= 3,000/microliter
* Platelets \>= 100,000/microliter
* Total bilirubin =\< 2.0 mg/dl
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x institutional upper limit of normal (ULN)
* Creatinine =\< 2.0 mg/dl
* The effects of iloprost on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because prostacyclins are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* The use of any tobacco product or inhalational nicotine delivery device in the past year
* Taking any anticoagulant agent with the exception of aspirin
* Taking any antiplatelet agent
* Receiving any other investigational agents or the previous use of iloprost
* Participants may not have received radiation therapy directed to the thorax or head and neck or immunotherapy, including checkpoint inhibitors
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to iloprost
* A requirement of supplemental oxygen (O2) of \>= 4 liter/minute to maintain an oxygen saturation of \>= 90% at rest
* A biopsy on baseline bronchoscopy with a dysplasia score of 7 or 8 (carcinoma in situ or invasive cancer)
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study because iloprost is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with iloprost breastfeeding should be discontinued if the mother is treated with iloprost.
* Due to the risk for hypotension due to vasodilator effect of iloprost, participants must not have a blood pressure \< 95 mm Hg systolic
* Participants must not have a current or prior invasive cancer within the past 12 months. History of the following cancers, curatively treated by surgery or locally ablative means, at any time prior to screening is allowed: non-melanoma skin cancer and cervical carcinoma in situ. Participants with prostate cancer undergoing active surveillance are allowed.
* Participants being treated with hormonal or immune therapies, including intravesicular bacillus calmette-guerin (BCG), are excluded
* Survivors of curatively treated stage III non-small cell lung cancer (NSCLC) or any stage lung small cell carcinoma (SCLC) are excluded
* Patients with known metastatic cancer of any kind are excluded
* Participants with known underlying bleeding disorders are excluded