Interstitial Lung Disease

Madelaine Behrens

---

Background

• Heterogenous group of parenchymal lung diseases that involve scarring or fibrosis, affecting the lung interstitium, alveoli, and pulmonary capillaries

  • Leads to loss of lung volume and compliance and impaired gas exchange

  • Radiologic appearance not specific for underlying cause. No cause -> IIP

Etiologies

• ILD is divided into primary (idiopathic) causes and secondary causes

• Idiopathic: idiopathic pulmonary fibrosis, eosinophilic pneumonia, idiopathic NSIP, organizing pneumonia, acute interstitial pneumonia, etc

• Secondary

  • Systemic:

    • Connective tissue disease: RA, Sjogrens, dermatomyositis, polymyositis SLE, MCTD, scleroderma

    • Granulomatous disease: sarcoidosis, TB

    • Vasculitis: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, amyloidosis, lymphangioleiomyomatosis

  • Exposure

    • Pneumoconiosis (inorganic) – exposure to coal mines, silica, asbestos, organic solvents, heavy metals, solder, hair dressing chemicals

    • Hypersensitivity pneumonitis (organic)- farm exposures, chicken coops, pesticide, stored grains, mold (ex: water damage in home, hot tubs)

    • Iatrogenic – amiodarone, immunotherapies, TKI, TNF-a inhibitors, nitrofurantoin, radiation

Evaluation

• Dry cough is the most common symptom of ILD. Productive coughs are uncharacteristic

• Dry cough is the most common symptom of ILD. Productive coughs are uncharacteristic

• Dyspnea (especially on exertion) is also typical of many progressive ILDs.

• Occupational and environmental exposures: pets, dust, hay, grass, molds, organic/inorganic compounds

• Medications, smoking history, radiation history, family history lung disease

• Autoimmunity and vasculitis symptoms: dysphagia, arthritis, myalgia, rash, Raynaud’s phenomenon, hematuria, hemoptysis, mononeuritis multiplex

• High resolution CT (image of choice): evaluates the lung parenchyma while pt is supine and prone (to rule out atelectasis), and with inspiratory and expiratory cuts (to identify air trapping - mosaicism worse with expiration)

• Chest Imaging:

  • CXR – could find peripheral reticular opacities

  • HRCT protocol is used for diagnosis: evaluates the lung parenchyma while pt is supine, prone, with inspiratory and expiratory cuts

  • There are two morphologic features on HRCT

    • Usual Interstitial Pneumonia (UIP): basilar predominant fibrosis, honey combing, and traction bronchiectasis. Minimal GGOs. Pattern seen in IPF.

    • Non-Specific Interstitial Pneumonia (NSIP): Marked by subpleural sparing, increased reticular patterns, and mosaic attenuation due to air trapping. Minimal or absent honeycombing

• Labs without Pulmonology consult

  • ESR, CRP, ANA w/ reflex ENA, RF, CCP
  • CBC with diff: evaluate eosinophilia or cytopenias concerning for autoimmune disease

• Labs in conjunction with Pulmonology

  • Myositis panel: 70% of those with anti-synthetase syndrome will have primary lung pathology without myositis findings, anti-Scl-70 and anti-RNP most commonly
  • Hypersensitivity pneumonitis panel: should be sent to a highly specialized lab since not all labs use an immunoprecipitation technique (crucial)
  • Histo antigen, blasto antigen, aspergillus galactomannan, 1-3-β-D-glucan, sputum GMS; consider NTM and HIV
  • PFTs: usually restrictive lung disease
  • Spirometry: expect to see ↓ FEV1 and FVC with FEV1/FVX >0.7
  • Lung volumes: ↓ TLC, RV, and/or FRC
  • DLCO: Gas exchange is generally impaired and worsens with disease progression

• Bronchoscopy and biopsy

  • BAL is not diagnostic ILD: may help understand the underlying inflammatory response (eosinophilic PNA, lymphocytosis of >40% in hypersensitivity pneumonitis) and rule out infection (particularly in organizing PNA)
  • Consider when there is diagnostic uncertainty: indeterminate or non-UIP patterns, more GGOs than anticipated, air trapping indicated HP, or concern for superimposed infection
  • Transbronchial lung biopsy (TBLB) is usually nondiagnostic in ILD outside of sarcoidosis or HP. Cryobiopsy can be considered an alternative to surgical lung biopsy for histopathology

• Other tests to consider

  • 6-minute walk test: prognostic value o TTE to evaluate for pHTN
  • SLP evaluation for indolent aspiration

Management

• Acute exacerbation (AE-ILD)

• Definition: acute lung injury (new onset bilateral pulmonary infiltrates, PaO2 /FiO2 ≤ 300, and PAWP ≤ 18) in the absence of heart failure, pulmonary infection, pulmonary embolism (PE), aspiration, or drug reaction

• Chest CT is imaging standard, both to diagnose and also rule out other etiologies of AHRF

• Treat any underlying trigger, support with supplemental oxygen and respiratory therapy

• Generally, UIP pattern (i.e. end-stage fibrosis) is NOT steroid responsive acutely or chronically.

• Consult pulmonology and rheumatology if CTD-ILD to guide immunosuppression.

• Chronic therapy

  • Antifibrotics

    • Main utility is in pts with IPF

    • Tyrosine kinase inhibition: nintedanib (INBUILD & INPULSIS trials): decreases rate of decline in FVC, no reduction on mortality

      • Adverse effects: abdominal pain, nausea, vomiting, diarrhea, anorexia, weight loss, elevated AST and ALT

    • TGF-beta inhibition: pirfenidone (RELIEF & ASCEND trials): May slow rate of decline of DLCO and 6MWT distance, no mortality reduction

      • Adverse effects: GI discomfort and photosensitivity

  • Immunosuppression

    • MUST rule out infection prior to use
    • Steroid/immunosuppression responsive (generally): COP, NSIP (cellular subtype), CT- ILD, inflammatory HP, granulomatous inflammation (sarcoidosis, silicosis, berylliosis, etc.), eosinophilic pneumonia, vasculitis-associated ILDs
    • Not steroid responsive: IPF, fibrotic HP
    • There is increased mortality in IPF with azathioprine/prednisone. NAC (PANTHER- IPF trial)

  • Other considerations

    • Smoking cessation
    • Drug removal: consider discontinuing amiodarone, checkpoint inhibitor, etc
    • Hypersensitivity pneumonitis: antigen exposure elimination
    • Eosinophilic pneumonia: steroids; biologics can be used (send to Allergy clinic)
    • Consider lung transplant eval for progressive or rapidly decompensating fibrotic lung disease
    • Pulmonary rehabilitation is crucial (trend towards mortality benefit)