eMedicine Specialties > Radiology > Chest

Idiopathic Pulmonary Fibrosis

Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia
Coauthor(s): Klaus L Irion, MD, PhD, Consulting Staff, The Cardiothoracic Centre Liverpool NHS Trust, The Royal Liverpool University Hospital, UK; Alberto Alonso, MD, MRCP, Specialist Registrar in Radiology, Department of Radiology, Manchester Royal Infirmary, UK; Anitha James, MBBS, DMRD, FRCR, Specialist Registrar, Manchester Radiology Training Scheme, Hospitals NHS Trust, UK; Velauthan Rudralingam, MB, BCh, BAO, FRCS, FRCR, Staff Physician, Gastrointestinal and Body Imaging Block, Hope Hospital and Wytenshawe Hospital, UK
Contributor Information and Disclosures

Updated: Dec 4, 2008

Introduction

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive pulmonary disease of unknown etiology. It is primarily diagnosed on the basis of clinical, physiologic, and radiologic criteria. In its International Consensus statement, the American Thoracic Society defines IPF as a specific chronic interstitial pneumonia that is limited to the lung and that has the histologic appearance of usual interstitial pneumonia (UIP) on open or thoracoscopic biopsy. No specific pathognomonic clinical or pathologic findings are associated with IPF, and the diagnosis is made after other causes of interstitial lung disease are excluded.^{1,2,3,4,5,6,7}

The diagnosis is confirmed with a lung biopsy, but the histology shows striking variation from one region to the next (ie, the disease is characterized by histologic temporal and spatial heterogeneity) (see Images above). It is not unusual to find areas of normal lung next to areas with severe thickening of alveolar walls. Therefore, findings on bronchoscopic or percutaneous lung biopsy are difficult to interpret. Open lung biopsy and video-assisted thoracoscopic lung biopsy are the preferred methods.

IPF usually affects patients 50-70 years of age. Most series report a male preponderance, with a male-to-female ratio of 2:1. Clinical features consist of progressive exertional dyspnea; the presence of interstitial infiltrates, as evidenced on chest radiographs; and physiologic evidence of restriction and impaired gas exchange on pulmonary function testing.

Patients are generally treated with corticosteroids, other immunosuppressants, or both.

The prognosis of patients with IPF is poor; most patients die of respiratory failure. The mean survival is approximately 4 years.

Pathophysiology

The pathologic features of idiopathic pulmonary fibrosis are nonspecific, and the exact pathogenesis is not clear. The disease is thought to evolve from undefined alveolar injuries produced by infectious, oxidative, or immunologic agents that result in a recurring cascade of injury, repair, and subsequent fibrosis.^8,9,10

The histologic findings show a striking variation from region to region, and it is not unusual to find areas of normal lung next to areas with severe thickening of alveolar walls. Biopsy findings with predominant fibrosis and scant inflammatory cells are required to confirm the diagnosis of IPF.

A diagnosis of IPF is considered when a surgical biopsy sample shows changes of usual interstitial pneumonia (UIP). Elements suggesting the diagnosis include the following: (1) other causes of interstitial lung disease, such as those related to drug-related lung disease, asbestosis, chronic hypersensitivity pneumonitis, and collagen-vascular disease, have been excluded; (2) abnormalities of lung function, including restriction and/or impairment of lung gas exchange at rest and at exercise or decreased diffuse lung capacity for carbon dioxide, are present; and (3) abnormalities are seen on conventional chest radiographs or high-resolution CT (HRCT) scans.

The diagnosis of IPF remains elusive in the absence of a lung biopsy. However, major and minor criteria have been suggested for application in the immunocompetent patient. These criteria may obviate biopsy. Major criteria are the exclusion of known causes of interstitial lung disease, abnormal results on lung function tests, bibasilar reticular abnormalities and honeycombing with a minimal ground-glass appearance on HRCT, and a transbronchial lung biopsy or bronchoalveolar lavage sample that shows no features of an alternative diagnosis. Minor criteria are age older than 50 years, unexplained dyspnea of insidious onset, duration of symptoms longer than 3 months, and bibasilar inspiratory crackles.

Potential risk factors include cigarette smoking, exposure to commonly prescribed drugs, chronic aspiration, environmental factors, infections, and predisposing genetic factors.

Frequency

United States

The incidence of idiopathic pulmonary fibrosis has been estimated to be 10.7 cases per 100,000 among men and 7.4 cases per 100,000 among women. The incidence appears to be rising. The prevalence of IPF ranges from 13 cases per 100,000 among women to 20 cases per 100,000 among men, though these rates may be underestimations.

The incidence increases with age. The disease affects individuals 50-70 years of age; it occurs only infrequently in young people and is extremely rare in children.

International

No data suggest that the international prevalence of idiopathic pulmonary fibrosis differs from that in the United States. Studies from England and Wales report a similar prevalence of 6 cases per 100,000 population.

Mortality/Morbidity

The overall prognosis of patients with idiopathic pulmonary fibrosis is not favorable; death often ensues within 4-6 years.

• The course of the disease varies. In some patients, the disease follows a rapidly progressive, fatal course over several months, whereas others experience a deterioration of pulmonary function over a longer period.
• Indicators of a better prognosis are a young age, female sex, short duration of symptoms, nonsevere physiologic or radiologic impairment, increased lymphocyte counts in bronchoalveolar lavage fluids, and ground-glass opacification on HRCT.
• Complications associated with IPF are common and include frequent chest infections, frequent drug intolerance or reactions, respiratory failure, cor pulmonale or right-sided heart failure, pneumothorax, pulmonary embolism, bronchial cancers, and coronary artery disease and strokes.

Race

Idiopathic pulmonary fibrosis has no racial predilection. It has been reported both in rural and urban settings. However, age-adjusted mortality rates appear higher among whites than among blacks.¹¹

Sex

Idiopathic pulmonary fibrosis affects more men than women; the ratio is 2:1. See also Frequency, above.

Age

Idiopathic pulmonary fibrosis affects people 40-70 years of age.

• Approximately two thirds of patients with IPF are older than 60 years at the time of diagnosis; the mean age is 66 years.
• The prevalence is 2.7 cases per 100,000 adults aged 35-44 years; it is approximately 17.5 cases per 100,000 adults older than 75 years.¹²
• Whether a syndrome similar to IPF occurs in children is uncertain.
• See also Frequency, above.

Presentation

None of the clinical features of idiopathic pulmonary fibrosis are pathognomonic. The most common symptom is exertional dyspnea of gradual onset that progresses. Approximately one half of patients have a dry cough early in the course of the disease; a similar number have constitutional symptoms, such as tiredness, weight loss, and arthralgia. Approximately 5% have no presenting symptoms at the time of diagnosis. Patients eventually become severely disabled and oxygen dependent.

Physical examination

Physical examination reveals end-inspiratory rales at the lung bases. Finger clubbing occurs in 20-50% of patients. Signs of pulmonary hypertension and right-sided heart failure may be observed with progressive disease.

Differential diagnosis of IPF

The differential diagnosis of IPF is wide and includes the entities listed in the Differentials section, below.

Preferred Examination

The diagnosis of idiopathic pulmonary fibrosis is made on the basis of the patient's history, clinical findings, pulmonary physiology, and imaging results. The diagnosis is one of exclusion. Nonidiopathic causes must be excluded first because of the important therapeutic implications. After nonidiopathic causes are excluded, further investigation of patients with IPF typically reveals radiographic abnormalities and restrictive lung physiology with decreased diffusion capacity.^13,14,15

Plain chest radiography is usually the first investigation performed for patients with suspected interstitial lung disease. However, the findings on conventional radiography are highly nonspecific.

HRCT defines the underlying lung parenchymal abnormalities better than does plain radiography. Studies have shown that HRCT may obviate surgical lung biopsy in some patients. Raghu et al compared the diagnostic accuracy of clinical evaluation in combination with HRCT with the accuracy of histology of surgical lung-biopsy samples.¹⁶

Clinical assessment in conjunction with careful review of HRCT scans was 60% sensitive and 97% specific for IPF. However, though HRCT may obviate the need for tissue diagnosis in 60% of patients, surgical lung biopsy is still needed in 40%.

For diagnoses other than IPF, a combination of clinical assessment and HRCT is neither sensitive nor specific enough to be relied on without surgical biopsy. Open lung biopsy remains the criterion standard. In immunocompetent patients, the benefit is relatively low because corticosteroid therapy is frequently administered after biopsy. In immunocompromised patients, approaches to therapy change substantially after tissue confirmation, but the mortality rate is high. Therefore, open biopsy should be performed only in patients in whom the diagnosis is likely to change therapy and in patients who have a reasonable prognosis.

Radionuclide scanning with gallium-67 may depict interstitial fibrosis and may show changes early. This feature may be of therapeutic benefit, but the changes are nonspecific and do not obviate the need for lung biopsy.

Limitations of Techniques

Neither imaging nor clinical findings are diagnostic of idiopathic pulmonary fibrosis. The differential diagnosis is wide.

Differential Diagnoses

Other Problems to Be Considered

Other forms of idiopathic interstitial pneumonia

Nonspecific interstitial pneumonia
Respiratory bronchiolitis – associated interstitial lung disease
Desquamative interstitial pneumonitis
Collagen-vascular diseases
Chronic hypersensitivity pneumonitis
Cryptogenic organizing pneumonia
Lymphoid interstitial pneumonia
Acute interstitial pneumonitis

Pulmonary fibrosis related to abnormalities of the connective tissue

Progressive systemic sclerosis
Systemic lupus erythematosus
Rheumatoid arthritis

Therapeutic modalities that may induce pulmonary fibrosis 

Antibiotics (eg, nitrofurantoin)
Cardiovascular drugs (eg, amiodarone)
Antimitotic agents (eg, bleomycin)
Radiation exposure

Causative factors in hypersensitivity pneumonitis (usually the chronic form)

Organic dust
Bacteria
Animal protein
Fungi 

Types of fibrosis associated with occupational exposures

Asbestosis
Silicosis and other pneumoconioses

Lymphocytic interstitial pneumonitis

Sjögren syndrome
Low-grade lymphoma
HIV infection

Other conditions

Chronic aspiration pneumonia
Sarcoidosis
Lymphangioleiomyomatosis
Eosinophilic granuloma

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