Find information on medical topics, symptoms, drugs, procedures, news and more, written for the health care professional.

* This is a professional Version *

Overview of Idiopathic Interstitial Pneumonias

by Harold R. Collard, MD

Idiopathic interstitial pneumonias (IIPs) are interstitial lung diseases of unknown etiology that share similar clinical and radiologic features and are distinguished primarily by the histopathologic patterns on lung biopsy. Classified into 7 histologic subtypes, all are characterized by varying degrees of inflammation and fibrosis and all cause dyspnea. Diagnosis is based on history, physical examination, high-resolution CT imaging, pulmonary function tests, and lung biopsy. Treatment varies by subtype. Prognosis varies by subtype and ranges from excellent to nearly always fatal.

The 7 histologic subtypes of IIP in decreasing order of frequency are

These subtypes are characterized by varying degrees of interstitial inflammation and fibrosis. All cause dyspnea; diffuse abnormalities on high-resolution CT(HRCT); and inflammation, fibrosis, or both on biopsy. The subtypes are important to distinguish, however, because they have different clinical features (see Key Features of Idiopathic Interstitial Pneumonias) and respond differently to treatment.

Key Features of Idiopathic Interstitial Pneumonias

Disorder

People Most Often Affected

Prodrome

Chest X-ray Findings

High-Resolution CT Findings

CT Differential Diagnosis

Histologic Pattern

Idiopathic pulmonary fibrosis

More frequently men > 50 (> 60% smoke)

Chronic (> 12 mo)

Basal-predominant reticular abnormality with volume loss and honeycombing

Peripheral, subpleural, and basal reticular honeycombing

Traction bronchiectasis or bronchiolectasis

Architectural distortion

Asbestosis

Connective tissue disorders

Hypersensitivity pneumonitis

Usual interstitial pneumonia

Desquamative interstitial pneumonia

More frequently men, aged 30–50 (> 90% smoke)

Subacute to chronic (weeks to years)

Ground-glass opacification

Lower zone, peripheral predominance in most cases

Ground-glass opacification

Reticular lines

Hypersensitivity pneumonitis

Pneumocystis jirovecii

pneumonia

Respiratory bronchiolitis–associated interstitial lung disease

Sarcoidosis

Desquamative interstitial pneumonia

Nonspecific interstitial pneumonia

More frequently women, usually age 40–60 (< 40% smoke)

Subacute to chronic (months to years)

Ground-glass and reticular opacity

Peripheral, basal, symmetric

Reticular opacities

Variable ground-glass opacification

Irregular lines

Cryptogenic organizing pneumonia

Desquamative interstitial pneumonia

Hypersensitivity pneumonitis

Idiopathic pulmonary fibrosis

Nonspecific interstitial pneumonia

Cryptogenic organizing pneumonia

People of any age, usually aged 40–50 (< 50% smoke)

Subacute (< 3 mo)

Patchy bilateral consolidation

Peribronchial

Patchy consolidation, nodules, or both

Alveolar cell carcinoma

Eosinophilic pneumonia

Lymphoma

Infection

Nonspecific interstitial pneumonia

Sarcoidosis

Vasculitis

Organizing pneumonia

Respiratory bronchiolitis–associated interstitial lung disease

Slightly more men, aged 30–50 (> 90% smoke)

Subacute (weeks to months)

Bronchial wall thickening

Ground-glass opacification

Diffuse pattern

Bronchial wall thickening

Centrilobular nodules

Patchy ground-glass opacification

Desquamative interstitial pneumonia

Hypersensitivity pneumonitis

Nonspecific interstitial pneumonia

Infection

Respiratory bronchiolitis–associated interstitial lung disease

Acute interstitial pneumonia

People of any age

Abrupt (1–2 wk)

Progressive, diffuse ground-glass opacification

Diffuse consolidation, ground-glass opacification, often with lobular sparing

Traction bronchiectasis later

Acute eosinophilic pneumonia

Acute respiratory distress syndrome

Hydrostatic edema

Pneumonia

Diffuse alveolar damage

Lymphoid interstitial pneumonia

Mostly women, of any age

Chronic (> 12 mo)

Reticular opacities

Nodules

Diffuse pattern

Centrilobular nodules

Ground-glass opacification

Septal and bronchovascular thickening

Thin-walled cysts

Langerhans cell histiocytosis

Lymphangitic carcinoma

Sarcoidosis

Lymphoid interstitial pneumonia

*Listed in order of decreasing frequency.

History of smoking unknown.

Symptoms and Signs

Symptoms and signs are usually nonspecific. Cough and dyspnea on exertion are typical, with variable onset and progression. Common signs include tachypnea, reduced chest expansion, bibasilar end-inspiratory dry crackles, and digital clubbing.

Diagnosis

  • High-resolution CT (HRCT)

  • Pulmonary function tests

  • Sometimes surgical lung biopsy

IIP should be suspected in any patient with unexplained interstitial lung disease. Clinicians, radiologists, and pathologists should exchange information to determine the diagnosis in individual patients. Potential causes (see Causes of Interstitial Lung Disease) are assessed systematically. For maximum diagnostic yield, history should address the following criteria:

  • Symptom duration

  • Family history of lung disease, especially lung fibrosis

  • History of tobacco use (because some diseases occur mostly among current or former smokers)

  • Current and prior drug use

  • Detailed review of home and work environments, including those of family members.

A chronologic listing of the patient's entire employment history, including specific duties and known exposures to organic and inorganic agents (see Table: Causes of Interstitial Lung Disease), is obtained. The degree of exposure, duration of exposure, latency of exposure, and the use of protective devices is elicited.

Chest x-ray is done and is typically abnormal, but findings are not specific enough to differentiate between the various types. Pulmonary function tests are often done to estimate the severity of physiologic impairment, but they do not help differentiate between the various types. Typical results are restrictive physiology, with reduced lung volumes and diffusion capacity. Hypoxemia is common during exercise and may be present at rest. HRCT, which distinguishes airspace from interstitial disease, is the most useful test and is always done. It provides assessment of the etiology, extent, and distribution of disease, and is more likely to detect underlying or coexisting disease (eg, occult mediastinal adenopathy, cancer, emphysema). HRCT should be done with the patient supine and prone and should include dynamic expiratory imaging to accentuate evidence of small airway involvement.

Laboratory tests are done for patients who have clinical features suggesting a connective tissue disorder, vasculitis, or environmental exposure. Such tests may include antinuclear antibodies, rheumatoid factor, other more specific serologic tests for connective tissue diseases (eg, RNP, SSA, SSB, scl70, Jo-1), hypersensitivity panel (a collection of tests for antibodies to common antigens from microbial, fungal, and animal sources), antineutrophil cytoplasmic antibodies, and anti-basement membrane antibody.

Bronchoscopic transbronchial biopsy can help differentiate certain interstitial lung diseases, such as sarcoidosis and hypersensitivity pneumonitis, but the biopsy does not yield enough tissue to diagnose the IIPs. Bronchoalveolar lavage helps narrow the differential diagnosis in some patients and can provide information about disease progression and response to therapy. The usefulness of this procedure in the initial clinical assessment and follow-up of most patients with these diseases has not been established, however.

Surgical lung biopsy is needed to confirm the diagnosis when the history and HRCT are nondiagnostic. Biopsy of multiple sites with a video-assisted thoracoscopic surgery (VATS) procedure is preferred.

Treatment

  • Varies by disorder

  • Often corticosteroids

  • Sometimes lung transplantation

Treatment varies by disorder (see Treatment and Prognosis of Idiopathic Interstitial Pneumonias*). Smoking cessation is always recommended to avoid potentially accelerating disease progression and to limit respiratory comorbidities. Corticosteroids are typically recommended for cryptogenic organizing pneumonia, lymphoid interstitial pneumonia, and nonspecific interstitial pneumonia but not for idiopathic pulmonary fibrosis. Lung transplantation may be recommended for selected patients with end-stage disorders.

Treatment and Prognosis of Idiopathic Interstitial Pneumonias*

Disorder

Treatment

Prognosis

Idiopathic pulmonary fibrosis

Pirfenidone (in selected countries); lung transplantation

Mortality rate: 50–70% in 5 yr

Desquamative interstitial pneumonia

Smoking cessation

Mortality rate: 5% in 5 yr

Nonspecific interstitial pneumonia

Corticosteroids with or without immunosuppressive therapies (eg azathioprine, mycophenolate mofetil)

Mortality rate: widely variable, but generally better than idiopathic pulmonary fibrosis. In purely cellular disease (rare), extremely low

Cryptogenic organizing pneumonia

Corticosteroids

Complete recovery rate: > 65%

Relapses: In many

Mortality rate: Rare

Respiratory bronchiolitis–associated interstitial lung disease

Smoking cessation

Mortality rate: Rare

Acute interstitial pneumonia

Supportive care

Mortality rate: 60% in < 6 mo

Lymphoid interstitial pneumonia

Corticosteroids

Not well defined

*Listed in order of decreasing frequency.

Key Points

  • There are 7 histologic subtypes of idiopathic interstitial pneumonia

  • Symptoms, signs, and chest x-ray findings are nonspecific.

  • Diagnose IIPs initially based primarily on history and HRCT.

  • When clinical evaluation and HRCT are not diagnostic, do surgical lung biopsy.

  • Treatment varies by subtype.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • ESBRIET
  • IMURAN

* This is a professional Version *