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 8 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 8 histologic subtypes of idiopathic interstitial pneumonia, in decreasing order of frequency, are
Idiopathic pulmonary fibrosis (identified histologically as usual interstitial pneumonia)
Respiratory bronchiolitis–associated interstitial lung disease (RBILD)
These subtypes are characterized by varying degrees of interstitial inflammation and fibrosis (1). 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 table 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 |
|---|---|---|---|---|---|---|
More frequently men > 50 (> 60% smoke) | Chronic (> 12 months) | Basal-predominant reticular abnormality with volume loss and honeycombing | Peripheral, subpleural, and basal reticular honeycombing Traction bronchiectasis or bronchiolectasis Architectural distortion | Systemic rheumatic disorders, particularly rheumatoid arthritis | Usual 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 | Desquamative 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 | |
People of any age, usually aged 40–50 (< 50% smoke) | Subacute (< 3 months) | Patchy bilateral consolidation | Peribronchial Patchy consolidation, nodules, or both | Alveolar cell carcinoma Chronic eosinophilic pneumonia Infection Nonspecific interstitial pneumonia Sarcoidosis | 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 Infection Nonspecific interstitial pneumonia | Respiratory bronchiolitis–associated interstitial lung disease |
People of any age† | Abrupt (1–2 weeks) | Progressive, diffuse ground-glass opacification | Diffuse consolidation, ground-glass opacification, often with lobular sparing Traction bronchiectasis later | Acute respiratory distress syndrome Hydrostatic edema | Diffuse alveolar damage | |
Mostly women, of any age† | Chronic (> 12 months) | Reticular opacities Nodules | Diffuse pattern Centrilobular nodules Ground-glass opacification Septal and bronchovascular thickening Thin-walled cysts | Lymphangitic carcinoma Sarcoidosis Systemic rheumatic disorders | Lymphocytic interstitial pneumonia | |
No sex predilection, median age of 57 years | Chronic (> 12 months) | Bilateral apical irregular pleural thickening | Dense subpleural consolidation Traction bronchiectasis Architectural distortion Upper lobe volume loss | Asbestosis Hypersensitivity pneumonitis Nonspecific interstitial pneumonia Radiation-induced lung disease Sarcoidosis Systemic rheumatic disorders | Pleuroparenchymal fibroelastosis | |
* Disorders listed in order of decreasing frequency. | ||||||
† History of smoking unknown. | ||||||
General reference
1. Travis WD, Costabel U, Hansell DM, et al: An Official American Thoracic Society/European Respiratory Society Statement: Update of the International Multidisciplinary Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med 188 (6):733–748, 2013.
Symptoms and Signs of Idiopathic Interstitial Pneumonias
Symptoms and signs of idiopathic interstitial pneumonias 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 of Idiopathic Interstitial Pneumonias
High-resolution CT (HRCT)
Pulmonary function tests
Laboratory tests
Sometimes lung biopsy
Idiopathic interstitial pneumonia 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 table 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 people who smoke or formerly smoked)
Current and prior drug use
Detailed review of home and work environments, including those of family members
A chronologic listing of the patient's 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 potential 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 systemic rheumatic disease, vasculitis, or environmental exposure. Such tests may include antinuclear antibodies, rheumatoid factor, and other more specific serologic tests for systemic rheumatic diseases (eg, anti-cyclic citrullinated peptide [CCP], ribonucleoprotein [RNP], anti-Ro [SSA], anti-La [SSB], scleroderma antibody [Scl70], anti-Jo-1 antibody, myositis antibody panel).
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 interstitial idiopathic pneumonias. Bronchoalveolar lavage helps narrow the differential diagnosis in some patients and can exclude other processes, such as infection. The usefulness of this procedure in the initial clinical assessment and follow-up of most patients with these diseases has not been established.
Cryobiopsy, a technique that quickly freezes the lung tissue immediately prior to removal, is an aid to diagnosis of certain interstitial lung diseases. The tissue yield is higher than that of transbronchial biopsy but lower than surgical lung biopsy. Risks of the procedure include bleeding and pneumothorax. Transbronchial cryobiopsy can be considered as an alternative to surgical lung biopsy in centers with experience performing it and interpreting its results.
Surgical lung biopsy is needed to confirm the diagnosis when the history and HRCT are nondiagnostic. Biopsy of multiple sites with video-assisted thoracoscopic surgery (VATS) procedure is preferred.
Treatment of Idiopathic Interstitial Pneumonias
Varies by disorder
Sometimes antifibrotics or corticosteroids
Sometimes lung transplantation
Treatment varies by disorder (see table Treatment and Prognosis of Idiopathic Interstitial Pneumonias). Smoking cessation is always recommended to avoid potentially accelerating disease progression and to limit respiratory comorbidities.
idiopathic pulmonary fibrosis and can be considered in progressive forms of other types of pulmonary fibrosis.
Corticosteroids are typically recommended for cryptogenic organizing pneumonia, lymphocytic 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 |
|---|---|---|
Lung transplantation | Mortality rate: 50–70% in 5 years | |
Smoking cessation | 70% survival at 10 years | |
Mortality rate: widely variable, but generally better than idiopathic pulmonary fibrosis; in purely cellular disease (rare), extremely low | ||
Corticosteroids | 5-year survival rate is > 90% | |
Respiratory bronchiolitis–associated interstitial lung disease | Smoking cessation | Mortality rate: Rare with smoking cessation |
Supportive care; often corticosteroids | Mortality rate: > 50% in < 6 months | |
Corticosteroids | Not well defined | |
Appropriate treatment unknown; often corticosteroids | 5-year survival rates approximately 25 to 60% | |
* Listed in order of decreasing frequency. | ||
Key Points
There are 8 histologic subtypes of idiopathic interstitial pneumonia.
Symptoms, signs, and chest x-ray findings are nonspecific.
Diagnose idiopathic interstitial pneumonia initially based primarily on history and high-resolution CT (HRCT).
When clinical evaluation and HRCT are not diagnostic, do surgical lung biopsy.
Treatment and prognosis vary by subtype.
