Interstitial lung diseases

Last updated: August 16, 2022

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Interstitial lung diseases (ILDs) are a diverse group of rare, highly morbid pulmonary disorders characterized by inflammation and progressive scarring (fibrosis) of the lungs. The most common types of ILD are idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), chronic hypersensitivity pneumonitis, and smoking-related ILD. Cough and progressive exertional dyspnea are the most common symptoms. Bibasilar inspiratory crackles or rales are typically heard on auscultation. While most forms of ILD have similar clinical features, different types of ILD have unique epidemiological and radiographic features. A multidisciplinary approach is ideal for distinguishing IPF from other types of ILD, based on a thorough medical history and HRCT findings. Bronchoscopy or surgical lung biopsy is sometimes necessary to confirm the diagnosis. Smoking cessation, removal of exposures, symptom management, and advance care planning are central to the management of all forms of ILD. Long-term treatment of IPF may include antifibrotic agents. Corticosteroids should only be used to treat select cases of acute exacerbations of IPF. For other causes of ILD, treatment may involve systemic immunomodulators targeting the underlying cause (e.g., rheumatoid arthritis). Advanced stages of ILD can result in pulmonary hypertension and right heart failure. Lung transplantation is the only curative treatment.

Idiopathic interstitial pneumonias (IIPs)

Secondary to a known cause

Exposure-related (environmental and occupational)

Secondary to underlying disease

Idiopathic pulmonary fibrosis (IPF)

Acute interstitial pneumonia (AIP)

  • Definition: a severe, acute ILD that can rapidly progress to respiratory failure
  • Epidemiology: most commonly affects individuals without preexisting lung conditions
  • Diagnostics: histologically characterized by diffuse alveolar damage

Cryptogenic organizing pneumonia (COP)

Nonspecific interstitial pneumonia (NSIP)

Desquamative interstitial pneumonia (DIP)

  • Definition: a rare type of ILD characterized by lung inflammation due to intraalveolar mononuclear infiltration
  • Epidemiology: affects men 40–50 years of age with a history of smoking
  • Diagnostics
    • Imaging studies show ground-glass opacities in the lower pulmonary lobes, usually without peripheral reticular opacities
    • Histologically characterized by intraalveolar accumulation of macrophages and thickening of alveolar septa

Respiratory bronchiolitis-interstitial lung disease (RB-ILD)

Lymphocytic interstitial pneumonia (LIP)

  • Definition: a rare ILD characterized by lymphocytic infiltration of the alveolar and alveolar septa
  • Epidemiology: affects adults (especially women) of all ages
  • Etiology: Associated with autoimmune (e.g., Sjögren disease, SLE) disorders, lymphoproliferative disorders, and HIV infection
  • Diagnostics: histologically characterized by diffuse alveolar and interstitial infiltration with plasma cells and polyclonal lymphocytes

Idiopathic pleuroparenchymal fibroelastosis (IPPFE)

  • Definition: a rare ILD characterized by pleural and subpleural fibrosis
  • Epidemiology: affects nonsmoker individuals between 50 and 60 years of age
  • Diagnostics
    • Imaging studies show pleural and subpleural thickening of the upper pulmonary lobes on imaging studies
    • Histological findings include intraalveolar fibrosis and elastosis of the alveolar walls
Overview of pneumoconioses [5][6]
Type Etiology Population at risk Clinical features Chest x-ray
Asbestosis
  • Asbestos miners and millers
  • Brake linings and insulation manufactures
  • Ship construction workers
  • Demolishers
  • Firefighters
  • Plumbers
  • Roofers
  • Diffuse bilateral infiltrates predominantly in the lower lobes
  • Interstitial fibrosis
  • Calcified pleural plaques (usually indicate benign pleural disease)
  • Supradiaphragmatic and pleural reticulonodular opacities/plaques
Silicosis
  • Crystalline silica dust
  • Miners
  • Workers of quarries, pottery production, sandblasting, glass manufacturers
  • Construction workers
  • Eggshell calcifications
  • Large number of rounded, solitary, small (< 1 cm) opacities particularly in the upper lobe of the lungs
  • Bilateral diffuse ground-glass opacities
Aluminosis [7][8]
  • Aluminum dust
  • Welders (e.g., automobile industry)
  • Nodular or diffuse infiltrates (predominantly affect the upper lung fields)
  • Small cystic radiolucencies (honeycombing) [8]
Anthracosis [9][10]
  • Carbon dust and sooty air
  • Urban population
  • Coal miners
  • Heterogeneous pulmonary infiltrates, with/without mass lesion
Coal workers' pneumoconiosis [9][10]
  • Fine nodular opacifications (< 1 cm) in upper lung zone
Berylliosis
  • Beryllium
  • Workers in manufacturing industries where alloys are frequently used (often high-tech)
    • Aerospace engineering
    • Ceramics industries
    • Dental material production
    • Nuclear and electronics plants
    • Dye manufacturing
    • Foundries
Pulmonary siderosis [13][14]
  • Welders, iron miners, foundry workers
  • Usually asymptomatic
  • Occasionally, presents with features similar to COPD
  • Complications: pulmonary fibrosis (rarely occurs)
  • Small, round, patchy shadows on x-ray
Organic dust toxic syndrome
  • Organic dust contaminated with mycotoxins (e.g., from moldy grain or hay)
  • Farmers working with grain, hay, silage, and confined animals (e.g., swine and poultry)
  • N/A
Byssinosis [15]
  • Mainly dust from raw cotton
  • Less commonly: flax, jute, hemp, and sisal dust
  • Textile industry workers
  • Symptoms diminish with prolonged exposure but manifest again with increased severity upon reexposure after a period nonexposure, e.g., a weekend.
  • Acute byssinosis
  • Chronic byssinosis
    • Disappearance of cyclical symptoms
    • Chronic productive cough
  • Complications: pulmonary fibrosis
  • Diffuse haziness, predominantly in the lower lobes of the lungs.

Although coal is mined from under the earth, the upper lobes of the lungs are primarily affected.

Features

Advanced disease

Approach [3][18][19]

Multidisciplinary care helps increase diagnostic accuracy. [3][21]

Laboratory studies [3][19][20]

Evaluation for CTD-ILD [21]

Additional studies [22]

All patients should be screened for rheumatic and autoimmune diseases. [3][21]

High-resolution CT (HCRT) chest [3][19][22][23][24]

Usual interstitial pneumonia (UIP) pattern is highly specific for IPF.

  • Typical UIP pattern findings [25]
  • Other findings may be classified into:
    • Probable UIP
    • Indeterminate for UIP
    • Alternative diagnosis
  • Interpretation
    • If UIP pattern is present, a definitive diagnosis can be made without histopathologic confirmation.
    • If other patterns are present, further evaluation is required to determine the cause.

In patients with IPF, the extent of abnormalities on HRCT correlates with the severity of functional impairment. [24]

X-ray chest [19]

Findings are not sufficient for a diagnosis but can raise clinical suspicion for ILD. [19]

  • Normal in approx. 10% of patients
  • Predominantly basilar increase in reticular opacities (sign of fibrosis)
  • Patients may have nodular or mixed patterns.

Pulmonary function tests (PFTs)

PFTs can help assess disease severity but do not identify a specific cause of ILD. [20]

Invasive testing [19][26]

Obtain invasive testing if the diagnosis remains unclear and results will affect management.

If HRCT shows a pattern of definite UIP, invasive testing is not usually necessary for diagnostic confirmation. [3]

Approach [22][28]

  • Offer supportive management, including preventive measures.
  • Refer all patients to pulmonology for:
  • Identify and treat common comorbidities, e.g., GERD, pulmonary hypertension, major depressive order. [22][25][29]
  • Initiate early advance care planning while patients are still able to participate in decision-making. [30]

ILD is a chronic, progressive, life-limiting condition. Encourage advance care planning and early engagement with palliative care. [28]

Supportive management [22]

Treatment of IPF [22]

Do not start patients with IPF on immunosuppressive therapy; immunomodulation may worsen outcomes. [28]

Treatment of non-IPF ILD

Lung transplantation is the only curative option for ILD.

Management of acute exacerbation of IPF (AE-IPF) [39][40]

AE-IPF is characterized by acute respiratory deterioration accompanied by new widespread alveolar abnormalities and it may be idiopathic or triggered. [40]

AE-IPF has an in-hospital mortality rate of ∼ 50%. An elevated APACHE score, the need for mechanical ventilation, and hypoxemia are all associated with increased mortality in hospitalized patients with ILD. [41]

We list the most important complications. The selection is not exhaustive.

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