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Pulmonary Fibrosis (PF)

BASICS

  • Definition: Interstitial lung disease (ILD) marked by inflammation, cellular proliferation, and fibrosis within lung interstitium and bronchial walls.
  • If no identifiable cause, classified as idiopathic interstitial pneumonia. Most common is idiopathic pulmonary fibrosis (IPF).
  • IPF: Progressive fibrotic ILD with usual interstitial pneumonia (UIP) pattern on histology/radiology, after exclusion of other causes.

EPIDEMIOLOGY

  • Most common ILD worldwide (25–30% of all ILD).
  • Highest in men >60 years.
  • Incidence: 3–9/100,000 person-years in North America/Europe; <4/100,000 in South America/East Asia.
  • Prevalence: US: 10–60/100,000.

ETIOLOGY & PATHOPHYSIOLOGY

  • Favored model: recurrent alveolar epithelial injury, abnormal repair, and interstitial fibrosis.
  • Nonidiopathic PF: Environmental/occupational exposures, drugs, connective tissue diseases.
  • Genetics:
  • Mutations affecting telomere length increase IPF risk.
  • MUC5B promoter SNP increases IPF risk (mechanism unclear).

RISK FACTORS

  • Family history of IPF
  • Smoking (strongest)
  • GERD, OSA
  • Occupational/environmental: wood/metal dust, farming, birds, hairdressing, stonecutting, air pollution, mold

COMMON ASSOCIATED CONDITIONS

  • Pulmonary hypertension (30–80% of IPF)
  • GERD
  • CTD (RA, systemic sclerosis) in nonidiopathic PF

DIAGNOSIS

History

  • Gradual onset, exertional breathlessness, nonproductive cough
  • Constitutional symptoms uncommon
  • Exposure history

Physical Exam

  • Bibasilar, late inspiratory “Velcro” crackles
  • Clubbing (late), cyanosis (rare)
  • Signs of pulmonary hypertension and RV failure
  • Findings of connective tissue disease

Differential

  • Chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonia, CTD-ILD, cryptogenic organizing pneumonia, post-COVID-19 ILD

Diagnostic Tests

  • Labs: Often normal; exclude CTD with ANA, RF, anti-CCP, etc.
  • CXR: Reduced lung volumes, basal reticular opacities, honeycombing in advanced cases
  • High-Resolution CT (HRCT):
  • UIP: Bilateral, peripheral, basilar reticulation & honeycombing, ± traction bronchiectasis—diagnostic of IPF (no biopsy needed)
  • Probable UIP: Similar features but without honeycombing
  • Atypical: Upper/mid-lung predominance, consolidations, GGO, nodules/cysts → consider other ILD
  • PFTs:
  • Decreased DLCO, TLC, FVC, FEV1 (preserved FEV1/FVC)
  • 6MWD: Reduced distance, exertional hypoxemia
  • Echocardiogram: Assess RV function, pulmonary hypertension
  • BAL/Bronchoscopy: Not routine; to exclude infection/malignancy
  • Surgical Lung Biopsy: Only if diagnosis remains uncertain after clinical/radiologic assessment; contraindicated in high-risk patients
  • Multidisciplinary discussion (pulmonology, radiology, pathology, rheumatology) recommended

TREATMENT

General Measures

  • Smoking cessation
  • Vaccination: Pneumococcus, influenza, SARS-CoV-2
  • Pulmonary rehabilitation
  • Supplemental O₂ if SpO₂ <88%
  • Refer to transplant center early if progression

Medications

  • Nintedanib: Tyrosine kinase inhibitor (VEGF, FGF, PDGF receptor); slows FVC decline, side effect: diarrhea, bleeding risk, LFT monitoring
  • Pirfenidone: Antifibrotic/anti-inflammatory; slows FVC decline, side effects: GI upset, photosensitive rash, LFT abnormalities
  • Warfarin
  • Prednisone + azathioprine + NAC combo
  • Endothelin receptor antagonists (ambrisentan, macitentan, bosentan)
  • Imatinib, sildenafil, NAC monotherapy

Other Therapies

  • Lung transplant: Improves QOL, survival in selected patients; 3-year survival post-transplant ~66%
  • Palliative care for advanced/progressive disease

ONGOING CARE

  • Pulmonary/ILD clinic follow-up
  • Serial HRCT (≥yearly), PFTs (≥6 months)
  • LFTs if on antifibrotics
  • Monitor for acute exacerbations (10–20%/year)—worsening hypoxemia, new bilateral GGO/consolidation not explained by overload/infection; weak glucocorticoid recommendation, avoid mechanical ventilation if possible

PROGNOSIS

  • Median survival: 3.8 years (≥65 years)
  • Acute exacerbations: high morbidity/mortality
  • Complications: Acute exacerbation, VTE, lung cancer, pulmonary hypertension

ICD-10 Codes

  • J84.10 Pulmonary fibrosis, unspecified
  • J84.112 Idiopathic pulmonary fibrosis

CLINICAL PEARLS

  • IPF is the most common idiopathic ILD and is often misdiagnosed or diagnosed late.
  • HRCT is the cornerstone of diagnosis.
  • Two antifibrotic drugs are the only proven therapy for IPF.
  • Early referral for pulmonary, ILD, and transplant evaluation is essential.
  • Oxygen, pulmonary rehab, GERD therapy, and vaccinations should be considered for all.