Welcome to Core IM, a virtual medical community! Core IM strives to empower its colleagues of all levels and backgrounds with clinically applicable information as well as inspire curiosity and critical thinking. Core IM promotes its mission through podcasts and other multimodal dialogues. ACP has teamed up with Core IM to offer continuing medical education, available exclusively to ACP members by completing the CME/MOC quiz.

ILD and High-Risk Medication Prescribing: Gray Matters Segment

Key Insights

1. ILD symptoms and CT findings are nuanced, requiring careful evaluation to avoid misdiagnosis or delayed treatment.
2. Antifibrotics and immunosuppressants are cornerstone therapies, but their use depends on ILD type. 
3. Addressing barriers to care using frameworks like Maslow’s hierarchy can improve patient adherence and outcomes. 

Deep Dive 1: Evaluating Incidental Findings

Why do incidental CT findings matter? 

• Subtle interstitial changes on a CT scan may indicate early fibrosis, atelectasis, aspiration, pulmonary edema, or infection. (Though not exhaustive list)
• What is  ILD protocol CT?
  • High-resolution CT (HRCT) with inspiratory, expiratory, supine and prone images
  • Differentiate fibrosis from mimics
  • Involves:
    • Number of Acquisitions:
      • Supine Position: Inspiratory (volumetric) and expiratory (sequential or volumetric) acquisitions.
      • Prone Position (Optional): Only inspiratory scans, which can be sequential or volumetric.
      • Inspiratory scans should be obtained at full inspiration.

If fibrosis is suspected:

• Refer to pulmonology within 6 months
• Order pulmonary function tests (PFTs) to expedite evaluation.
  • PFTs provide data on disease progression and urgency of intervention.

Deep Dive 2: Categorizing ILD

What is a clinically relevant way to categorize the causes of ILD? 

• Broad groups to aid in diagnosis and treatment. Below is a streamlined overview:
  • Infectious ILDs 
    • Examples: Viral pneumonias, tuberculosis, fungal infections. 
  • Environmental or Medication-Induced ILDs 
    • Environmental exposures examples: tobacco/smoking, asbestos, silica, and other occupational exposures. 
    • Medication-Induced ILD: Common culprits include amiodarone and methotrexate. 
  • Autoimmune-Related ILDs  
    • Associated with systemic rheumatologic conditions, such as systemic sclerosis, rheumatoid arthritis, and polymyositis. 
      • Subtype: Often referred to as connective tissue disease-associated ILDs (CTD-ILDs). 
  • Granulomatous ILDs 
    • Examples: Sarcoidosis, Langerhans cell histiocytosis. 
      • Sarcoidosis:
        • Characterized by non-caseating granulomas. 
        • Requires exclusion of other granulomatous diseases. 
      • Langerhans Cell Histiocytosis: 
        • Often linked to smoking. 
    • Presents with cystic and nodular changes on HRCT.
  • Idiopathic ILDs 
    • Definition: Diagnosed after ruling out all other potential causes. 
    • Examples: 
      • Idiopathic Pulmonary Fibrosis (IPF):
        • Most common form
        • Often managed with antifibrotics. 
      • Nonspecific Interstitial Pneumonia (NSIP):
        • A more inflammatory subtype. 
      • Cryptogenic Organizing Pneumonia (COP):
        • Frequently responds to corticosteroids. 

Deep Dive 3: Treatment for ILD

What are the primary treatment options? 

• Antifibrotics: Pirfenidone and Nintedanib slow the decline in FVC but do not reverse fibrosis. 
  • Indicated for all patients with progressive fibrosis, irrespective of subtype. 
  • Side effects include GI disturbances (e.g., diarrhea) and hepatotoxicity (requires liver enzyme monitoring). 
  • Key takeaways INBUILD trial
    • 1. Efficacy of Nintedanib:
      • Primary Outcome: Reduced annual FVC decline by 107 mL/year compared to placebo in the overall population (-80.8 mL vs. -187.8 mL, p<0.001). 
      • For patients with a UIP-like fibrotic pattern: Decline reduced by 128.2 mL/year (-82.9 mL vs. -211.1 mL, p<0.001). 
      • Patients with other fibrotic patterns showed a reduction of 75.3 mL/year.
    • Secondary Outcomes:
      • No statistically significant improvement in quality of life using the K-BILD questionnaire. 
      • Lower incidence of acute exacerbation or death: 7.8% in nintedanib vs. 9.7% in placebo. 
    • Safety Profile:
      • Most common adverse event: Diarrhea (66.9% in nintedanib vs. 23.9% in placebo). 
      • Liver enzyme elevations were more common in the nintedanib group (13.0% vs. 1.8%). 
      • Discontinuation due to adverse events: 19.6% in the nintedanib group vs. 10.3% in placebo.
• Immunosuppressants:
  • Ex: Mycophenolate and azathioprine
    • Used in non-IPF ILDs. 
  • Avoid in IPF, as shown by increased mortality in the PANTHER trial. 
    • PANTHER trial was a randomized, double-blind, placebo-controlled trial comparing a combination of prednisone, azathioprine, and N-acetylcysteine (NAC) (triple therapy) versus placebo.
      • Patients included had mild-to-moderate IPF with FVC ≥50% and DLCO ≥30% of predicted values.
    • Outcomes:
      • Increased Mortality:
        • Patients in the triple therapy group experienced an 8-fold higher mortality rate compared to placebo (10% vs. 1%, p = 0.01).
        • Deaths were primarily related to respiratory causes or treatment-related complications.
      • Hospitalizations:
        • Rates of all-cause hospitalization were significantly higher in the triple therapy group (30% vs. 9%, p < 0.001).
      • Serious Adverse Events (SAEs):
        • 31% of patients in the triple therapy group reported SAEs, compared to 10% in the placebo group (p = 0.001).
        • These included respiratory complications, infections, and general adverse drug reactions.
    • The PANTHER trial provided definitive evidence that immunosuppressants, particularly azathioprine and prednisone, should not be used in IPF due to their association with increased mortality, hospitalizations, and adverse events. Antifibrotic therapies remain the standard of care for this patient population.
  • What role do steroids play? 
    • Managing acute ILD exacerbations or flares
    • Rapidly progressive or exacerbating ILD, where they can help reduce inflammation and stabilize the patient's condition.

Deep Dive 4: Addressing Barriers to Care

How do you identify and address barriers to care? 

• Use Maslow’s hierarchy of needs to guide assessment:
  • A psychological theory that explains human motivation in five levels, starting from basic survival needs to personal growth.
  • You must meet lower-level needs before focusing on higher ones.
    • Basic Needs: Essentials like food, water, safety, and shelter.
      • Specifically:  Transportation, food security, and health literacy.
    • Social Needs: Relationships, love, and belonging.
    • Self-Worth: Feeling respected and accomplished.
    • Personal Growth: Achieving your full potential and pursuing your passions.
  • Collaborate with PCPs and social workers to address social determinants of health. 

Deep Dive 5: Ethical Considerations in ILD Treatment

How do you balance ethics in ILD care? 

• Utilitarian ethics focus on maximizing outcomes vs.
• Egalitarian ethics emphasize equal care opportunities. 
  • Success in ILD management often hinges on equitable access to resources, rather than identical treatment outcomes for all patients.

What is the role of shared decision-making? 

• Frame treatment as a contract between physician and patient, ensuring both parties collaborate for effective care.

Key Takeaways

1. Evaluate incidental CT findings using ILD protocol CT with prone imaging, and follow up with PFTs. 
2. Categorize ILD broadly (e.g., infections, exposures, idiopathic) to guide therapy. 
3. Treat progressive fibrosis with antifibrotics; use immunosuppressants for non-IPF ILDs. 
4. Address social barriers to care using frameworks like Maslow’s hierarchy to improve patient adherence. 
5. Strive for equitable care opportunities through ethical and collaborative practices. 

Further Resources

• ILD REVIEW - https://pubmed.ncbi.nlm.nih.gov/38648021/
• INBUILD TRIAL https://pubmed.ncbi.nlm.nih.gov/32145830/
• Panther Trial      - https://pmc.ncbi.nlm.nih.gov/articles/PMC4116664/
• Barriers to Care - https://pmc.ncbi.nlm.nih.gov/articles/PMC10913766/

Contributors

Shreya Trivedi, MD, ACP Member – Editor
Alison Trainor, MD – Host, editor, MOC Questions
Jason Freed, MD – Host, editor
Kelly Graham, MD - Expert
Robert Hallowell, MD* – Expert
Jason Krastein, BS - Editor

Reviewers

Robert Koichiro Arao, MD
Armand M. Gottlieb, MD

* Robert Hallowell, MD – Boehringer Ingelheim, Genetech, Vicore - Consultant

Those named above, unless otherwise indicated, have no relevant financial relationships to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.  All relevant relationships have been mitigated.

Release Date:  February 5. 2025

Expiration Date: February 4, 2028

CME Credit

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the American College of Physicians and Core IM.  The American College of Physicians is accredited by the ACCME to provide continuing medical education for physicians.

The American College of Physicians designates this enduring material (podcast) for .5 AMA PRA Category 1 Credit™.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

ABIM Maintenance of Certification (MOC) Points

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to .5 medical knowledge MOC Point in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program.  Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

How to Claim CME Credit and MOC Points

After listening to the podcast, complete a brief multiple-choice question quiz. To claim CME credit and MOC points you must achieve a minimum passing score of 66%. You may take the quiz multiple times to achieve a passing score.