Interstitial Lung Disease¶
Chapter 304 | Part 7: Disorders of the Respiratory System
KEY CLINICAL POINTS¶
- ILD encompasses >200 heterogeneous conditions affecting lung parenchyma with varying inflammation/fibrosis.
- IPF is the most common ILD of unknown cause, with 50% 3-5 year mortality.
- Diagnosis requires integration of clinical data, imaging (HRCT), lab tests, and histopathology.
- Antifibrotic therapies (pirfenidone, nintedanib) improve survival in IPF.
- Genetic factors (e.g., MUC5B promoter variant) contribute to familial and sporadic ILD.
1. DEFINITION & OVERVIEW¶
Interstitial Lung Disease (ILD) refers to a group of disorders characterized by inflammation and fibrosis of lung parenchyma. ILDs are classified into known and unknown causes, with genetic factors increasingly recognized in both categories. The hallmark of ILD is progressive dyspnea and impaired gas exchange.
Table 304-1 Common Interstitial Lung Disease (ILD) Findings¶
| Clinical Symptoms | Exposures | HRCT Findings | Histopathology | Prognosis |
|---|---|---|---|---|
| Gradual onset of SOB, dry cough. More common in older adults. | Idiopathic but many exposed to smoke. Genetic findings may explain >1/3 risk. | Bilateral subpleural reticular changes, traction bronchiectasis, honeycombing. | UIP pattern including fibroblastic foci, honeycombing. | 50% 3-5 year mortality. |
| Subacute onset of SOB, dry cough. Frequently associated with other conditions. | Can be idiopathic but should prompt consideration for associated conditions. | Peripheral subpleural ground-glass and reticular patterns. | Cellular or fibrotic pattern of NSIP. | 18% 5 year mortality. |
| Can be asymptomatic, or have SOB and cough. | Strong association with smoking. | Diffuse patchy centrilobular ground glass nodules. | Respiratory bronchiolitis with adjacent inflammatory changes. | 25% 7 year mortality. |
| Gradual onset of SOB, dry cough. Fatigue, skin thickening, exaggerated cold response. | Mostly unknown; some debate about solvent and silicate exposures. | Can have UIP or NSIP patterns, dilated esophagus, pulmonary vascular enlargement. | Both UIP or NSIP patterns can occur. | 20–30% 10 year mortality. |
| Clinical Symptoms | Exposures | HRCT Findings | Histopathology | Prognosis |
|---|---|---|---|---|
| Can be asymptomatic, or have SOB and cough. Can also have fatigue, palpitations, eye, skin, and joint findings. | Mostly unknown, although silicate dusts thought to play a role in some cases. | Can have mediastinal and hilar lymphadenopathy. | Noncaseating granulomas. | Generally low but varies by state. |
1.1 Classification¶
ILD is divided into known causes (occupational, drug-induced, CTD-associated) and unknown causes (idiopathic interstitial pneumonias). Genetic variants (e.g., MUC5B, TERT) contribute to both familial and sporadic forms.
1.2 Diagnostic Approach¶
Multidisciplinary evaluation combining clinical history, HRCT, pulmonary function tests, and biopsy is essential. HRCT is the primary imaging modality, with UIP pattern diagnostic for IPF.
2. EPIDEMIOLOGY¶
IPF prevalence increases with age (50–200:100,000), most common in >60 years. Sarcoidosis and CTD-associated ILD are more common in women. Smoking is a major risk factor for RB-ILD and DIP.
2.1 Age and Sex¶
IPF peaks in 60–80 years, more common in men. Sarcoidosis and CTD-associated ILD are more common in women. LAM is predominantly in young women.
2.2 Genetic Factors¶
MUC5B promoter variant (20% Caucasians, 35–45% IPF patients) and telomere-related genes (TERT, RTEL1) contribute to familial and sporadic ILD.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Causes include occupational exposures (asbestos, silica), medications (amiodarone, methotrexate), CTDs (RA, scleroderma), and genetic factors. Pathogenesis involves epithelial injury, inflammatory cytokines, and fibroblast activation.
3.1 Known Causes¶
Occupational (asbestosis, silicosis), drug-induced (amiodarone, nitrofurantoin), CTD-associated (RA, scleroderma), and infections (HP, sarcoidosis).
3.2 Unknown Causes¶
Idiopathic interstitial pneumonias (IPs) including IPF, NSIP, and others. Genetic variants (MUC5B, TERT) and environmental factors contribute.
4. CLINICAL FEATURES¶
Progressive dyspnea on exertion is the most common symptom. Dry cough is prevalent in IPF. Physical findings include fine crackles, digital clubbing, and signs of cor pulmonale.
4.1 Symptomatology¶
Dyspnea (exertional), dry cough, fatigue. Hemoptysis may indicate DAH (Goodpasture’s, GPA, LAM).
4.2 Physical Exam¶
Fine crackles at lung bases, digital clubbing, skin thickening (scleroderma), joint swelling (RA).
5. DIFFERENTIAL DIAGNOSIS¶
Differentiate from COPD, pneumonia, heart failure, and CTDs. Acute exacerbations of IPF mimic ARDS. Sarcoidosis must be distinguished from other granulomatous diseases.
5.1 Common Mimics¶
COPD, pneumonia, heart failure, sarcoidosis, CTDs, and malignancies.
5.2 Acute Exacerbations¶
Acute IPF exacerbations present with rapid decline in lung function, similar to ARDS. Eosinophilic GPA and HP may mimic infections.
6. INVESTIGATIONS & DIAGNOSIS¶
Chest CT (HRCT) is the primary diagnostic tool. Pulmonary function tests show restrictive patterns. Biopsy (VATS) and serologic tests for CTDs are critical for definitive diagnosis.
6.1 Imaging¶
HRCT findings: UIP pattern (IPF), NSIP, ground-glass opacities (DIP), nodules (sarcoidosis).
6.2 Laboratory¶
Serologic tests for CTDs (anti-CCP, ANCA), inflammatory markers, and genetic testing (MUC5B, TERT).
7. MANAGEMENT & TREATMENT¶
Treatment varies by ILD type: antifibrotics (IPF), immunosuppression (CTD-associated), oxygen therapy, and lung transplantation for advanced cases. Avoidance of smoking and toxic exposures is critical.
7.1 Pharmacologic¶
Antifibrotics (pirfenidone, nintedanib), corticosteroids, cytotoxic agents (azathioprine), biologics (rituximab).
7.2 Surgical¶
Lung transplantation for end-stage ILD. VATS biopsy for diagnostic confirmation.
8. PROGNOSIS & COMPLICATIONS¶
IPF has 50% 3-5 year survival. Complications include pulmonary hypertension, respiratory failure, and increased mortality in acute exacerbations (>85% mortality).
8.1 Survival¶
IPF: 50% 3-5 year mortality. Sarcoidosis: variable, with 20–30% 10 year mortality.
8.2 Complications¶
Pulmonary hypertension, respiratory failure, acute exacerbations, and progression to fibrosis.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Avoid immunosuppressants. Pediatrics: DIP and LAM may occur in children. Elderly: Higher risk of IPF and drug toxicity.
9.1 Pregnancy¶
Avoid corticosteroids and immunosuppressants. Monitor for fetal complications.
9.2 Pediatrics¶
DIP and LAM may present in children with familial pulmonary fibrosis.
10. KEY POINTS & CLINICAL PEARLS¶
- HRCT is essential for ILD diagnosis. 2. IPF is the most common ILD with 50% 3-5 year mortality. 3. Genetic variants (MUC5B, TERT) contribute to ILD. 4. Antifibrotics improve survival in IPF. 5. Multidisciplinary approach is critical for accurate diagnosis.