ILAs in CT Lung Cancer Screening Population
Condition: Interstitial Lung Disease; IPF
MeSH terms: Lung Diseases; Lung Diseases, Interstitial
Study type: Observational

Summary: 
      Interstitial Lung Abnormalities (ILA) have been previously defined as nondependent changes
      affecting more than 5% of any lung zone on computed tomography (CT) scans of the lung.
      Several studies suggest that the prevalence of ILA in participants in non-pulmonary research
      studies ranges anywhere from 7-9%. Work over the last decade has shown that, despite previous
      characterization as an asymptomatic research finding, ILA has significant clinical and
      biological consequences. These include reduced exercise capacity, functional limitations,
      decreased lung volumes, increased mortality, and in some cases histopathology similar to
      Idiopathic Pulmonary Fibrosis (IPF). ILA have been detected in lung cancer screening cohorts,
      where the prevalence of ILA is estimated to be between (10%-20%) to those noted in other
      research cohorts. Given that a significant proportion of those will have progression, CT lung
      cancer screening (CTLS) cohorts represent an ideal catchment population for future research
      and clinical trials. Lahey Hospital and Medical Center was one of the earliest clinical
      centers to develop a CTLS program in the country. Investigators propose to qualitatively
      characterize ILA in a large clinical CTLS population.
    

Detailed description: 
      Investigators propose a retrospective, single-center study with following aims:

        1. Characterize the prevalence and incidence of ILA at baseline and 5 year follow-up,
           respectively, and associated imaging phenotypes in CTLS cohort.

        2. Baseline qualitative ILA features associated with clinical outcomes: Lung Cancer,
           Hospitalization, and Mortality.

        3. Baseline qualitative ILA features associated with progressive ILA and fibrotic lung
           disease.

        4. Clinical opportunity: to determine the % of CTLS patients with ILA who are at risk for
           progressive and development of fibrotic lung disease and who would benefit from
           specialized care referral and potential enrollment in clinical trials utilizing proven
           antifibrotic therapies

      Patient Selection:

      All clinical CT Lung Cancer Screening (CTLS) patients at Lahey Hospital and Medical Center
      (LHMC), Burlington, MA from January 1st, 2012 through September 30th, 2014 who had an in
      network primary care physician (n=1703). Patients with T4 screening scans will be scored for
      progression (n=653). To qualify for our study, patients had to satisfy the National
      Comprehensive Cancer Network (NCCN) Guidelines® Lung Cancer Screening Version 1.2012
      high-risk criteria for lung cancer. Based on the NCCN Guidelines®, individuals eligible for
      lung cancer screening can be classified into NCCN group 1 and 2 as previously described.
      Patients in both groups were asymptomatic and had a physician order for CTLS, were free of
      lung cancer for ≥ 5 years, and had no known metastatic disease.

      Clinical Variables:

      Clinical variables were collected prospectively as part of the CTLS program and stored in a
      centralized data repository. Additional clinical variables not already available in this data
      repository will be collected retrospectively by manual review of the electronic medical
      record or pulled directly from the EMR and stored utilizing a custom-designed database
      (FileMaker ProVersion 11; Filemaker Inc, Santa Clara, California). Data was obtained through
      September 30th, 2019, patient demographics, past medical history, PFTs, immunization records,
      whether the patient was managed by a pulmonologist, and for hospital admissions with
      principal admission diagnoses. Hospital admissions will be collected using Lahey
      administrative coding data. Principal admission diagnoses of COPD, PNA, and CHF will be
      characterized based on diagnosis codes per 2018 Center for Medicare and Medicaid Services
      (CMS) condition-specific measures.

      CT Imaging:

      Clinically acquired, CTLS examinations which were performed on ≥64-row multidetector CT
      scanners (LightSpeed VCT and Discovery VCT [GE Medical Systems, Milwaukee, Wisconsin];
      Somatom Definition [Siemens AG, Erlangen, Germany]; iCT [Philips Medical Systems, Andover,
      Massachusetts]) at 100 kV and 30 to 100 mA, depending on the scanner and the availability of
      iterative reconstruction software. Axial images were obtained at 1.25- to 1.5-mm thickness
      with 50% overlap and reconstructed with both soft tissue and lung kernels.

      Qualitative ILA Scoring:

      CT images will be scored utilizing Philips Intellispace PACS version 4.4 with clinical grade
      monitors. Scoring will be performed independently by two thoracic radiologists as described
      previously. Scores that are discordant between the two radiologists will be scored by a third
      by a pulmonologist with expertise in ILD.

      ILA: The presence of ILA features will be scores as (Yes/No/Indeterminate). Indeterminate
      will be defined as features identified unilaterally/focal involvement.

      ILA features that will be scored include: A) non dependent ground glass, B) reticular
      abnormalities, C) traction bronchiectasis and D) honeycombing.

      A) Non Dependent ground glass: (Yes/No/Indeterminate) defined as hazy increased attenuation
      of the lung with preservation of bronchial and vascular margins.

      B) Reticular abnormalities: (Yes/No/Indeterminate) defined as a collection of innumerable
      small linear opacities that, by summation, produce an appearance resembling a net.

      C) Traction Bronchiectasis: (Yes/No/Indeterminate) defined Traction bronchiectasis and
      traction bronchiolectasis respectively represents irregular bronchial and bronchiolar
      dilatation caused by surrounding retractile pulmonary fibrosis.

      D) Honeycombing: (Yes/No/Indeterminate) defined on CT as clustered cystic air spaces,
      typically of comparable diameters on the ordered of 3-10 mm but occasionally as large as 2.5
      cm.

      Pattern: The overall pattern/Type of ILA findings will also be scored as the following:
      Subpleural, centrilobular, mixed or consistent with ILD (see UIP below).

      Subpleural: Defined as less than 1 cm from the pleural surface.

      Centrilobular: Defined as region of the bronchiolovascular core of the secondary pulmonary
      lobule.

      Location: Overall location ILA will then be scored as Upper lobe, lower lobe or diffuse.

      Extent: Overall extent of disease will be scored as Mild, Moderate and Marked.

      Usual Interstitial Pneumonia: Finally, the subset of scans that have evidence of fibrotic
      disease defined as traction bronchiectasis/honeycombing will then be classified as consistent
      with usual interstitial pneumonia (UIP) (Yes/Probable/No) based on Fleischner Criteria. UIP
      defined as Honey-combing with basal and subpleural distribution.

      Progression: The subset of patients who have had their T4 (5 year post baseline) screening
      scanned will be independently scored as above and in addition will be compared to their
      baseline scans and scored for progression: Stable, improved, and progressed.
    

Intervention name(s): Retrospective observational study
Intervention type(s): Other
Intervention description(s): No intervention to occur
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        All clinical CTLS patients at Lahey Hospital and Medical Center (LHMC), Burlington, MA from
        January 1st, 2012 through September 30th, 2014 who had an in network primary care physician
        (n=1703). Patients with T4 screening scans will be scored for progression (n=653). To
        qualify for our study, patients had to satisfy the National Comprehensive Cancer Network
        (NCCN) Guidelines® Lung Cancer Screening Version 1.2012 high-risk criteria for lung cancer.
        Based on the NCCN Guidelines®, individuals eligible for lung cancer screening can be
        classified into NCCN group 1 and 2 as previously described.21 Patients in both groups were
        asymptomatic and had a physician order for CTLS, were free of lung cancer for ≥ 5 years,
        and had no known metastatic disease.
      
Keywords: Interstitial Lung Disease; Interstitial Lung Abnormalities