Idiopathic pulmonary fibrosis, identified histologically as usual interstitial pneumonia, accounts for most cases of idiopathic interstitial pneumonia Overview of Idiopathic Interstitial Pneumonias 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... read more . IPF affects men and women > 50 in a ratio of 2:1, with a markedly increased incidence with each decade of age. Current or former cigarette smoking is most strongly associated with the disorder. There is some genetic predisposition; familial clustering occurs in up to 20% of cases.
Etiology of Idiopathic Pulmonary Fibrosis
A combination of environmental, genetic, and other unknown factors probably contribute to alveolar epithelial cell dysfunction or reprogramming, which leads to abnormal fibroproliferation in the lung. There is ongoing research into the contributions of genetics, environmental stimuli, inflammatory cells, the alveolar epithelium, mesenchyme, and matrix.
Pathology of Idiopathic Pulmonary Fibrosis
The key histologic findings of idiopathic pulmonary fibrosis are subpleural fibrosis with sites of fibroblast proliferation (fibroblast foci) and dense scarring, alternating with areas of normal lung tissue (heterogeneity). Scattered interstitial inflammation occurs with lymphocyte, plasma cell, and histiocyte infiltration. Cystic abnormality (honeycombing) occurs in all patients and increases with advanced disease. A similar histologic pattern uncommonly occurs in cases of interstitial lung diseases of known etiology (see table ).
Symptoms and Signs of Idiopathic Pulmonary Fibrosis
Symptoms and signs of idiopathic pulmonary fibrosis typically develop over 6 months to several years and include dyspnea on exertion and nonproductive cough. Constitutional symptoms, such as low-grade fever and myalgias, are uncommon. The classic sign of IPF is fine, dry, inspiratory crackles (Velcro crackles) at both bases. Clubbing is present in about 50% of cases. The remainder of the examination is normal until disease is advanced, at which time signs of pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension is increased pressure in the pulmonary circulation. It has many secondary causes; some cases are idiopathic. In pulmonary hypertension, pulmonary vessels may become constricted... read more and right ventricular systolic dysfunction Cor Pulmonale Cor pulmonale is right ventricular (RV) enlargement secondary to a lung disorder that causes pulmonary artery hypertension. Right ventricular failure follows. Findings include peripheral edema... read more may develop.
Diagnosis of Idiopathic Pulmonary Fibrosis
High-resolution CT (HRCT)
Sometimes surgical lung biopsy
Diagnosis of idiopathic pulmonary fibrosis is suspected in patients with subacute dyspnea, nonproductive cough, and Velcro crackles on chest examination. However, IPF is commonly overlooked initially because of clinical similarities to other more common diseases, such as bronchitis Acute Bronchitis Acute bronchitis is inflammation of the tracheobronchial tree, commonly following an upper respiratory infection in the absence of chronic lung disorders. The cause is almost always a viral... read more , asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more , and heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more .
Diagnosis requires HRCT and in some cases lung biopsy.
Chest x-ray typically shows diffuse reticular opacities in the lower and peripheral lung zones. Small cystic lesions (honeycombing) and dilated airways due to traction bronchiectasis are additional findings.
HRCT shows diffuse, patchy, subpleural, reticular opacities with irregularly thickened interlobular septa and intralobular lines; subpleural honeycombing; and traction bronchiectasis. This is referred to as the usual interstitial pneumonia (UIP) pattern. Ground-glass opacities affecting > 30% of the lung suggest an alternative diagnosis.
Laboratory testing plays little role in diagnosis, except to exclude potential systemic rheumatic disorders.
Treatment of Idiopathic Pulmonary Fibrosis
Pirfenidone or nintedanib
Oxygen and pulmonary rehabilitation
Sometimes lung transplantation
Pirfenidone and nintedanib are antifibrotic drugs that slow progression of idiopathic pulmonary fibrosis (1 Treatment references Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, causes progressive pulmonary fibrosis. Symptoms and signs develop over months to years and include... read more , 2 Treatment references Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, causes progressive pulmonary fibrosis. Symptoms and signs develop over months to years and include... read more , 3 Treatment references Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, causes progressive pulmonary fibrosis. Symptoms and signs develop over months to years and include... read more ). Supportive measures include oxygen and pulmonary rehabilitation Pulmonary Rehabilitation Pulmonary rehabilitation is the use of supervised exercise, education, support, and behavioral intervention to improve functional capacity and enhance quality of life in patients with chronic... read more . Patients may find that joining a support group helps reduce the stress of the illness.
Many novel therapies for IPF are under development or being tested as treatments for IPF, and patients should be encouraged to participate in clinical trials when appropriate.
Lung transplantation Lung and Heart-Lung Transplantation Lung or heart-lung transplantation is an option for patients who have respiratory insufficiency or failure and who remain at risk of death despite optimal medical treatment. (See also Overview... read more is successful for otherwise healthy patients with IPF, generally those < 65 years old. These patients should be evaluated for lung transplantation at the time of diagnosis.
1.King TE, Bradford WZ, Castro-Bernardini S, et al: A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Eng J Med 370:2083-2092, 2014.
2. Raghu G, Rochwerg B, Zhang Y, et al: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med 192 (2):e3-e19, Jun 15, 2015.
3. Richeldi L, du Bois RM, Raghu G, et al: Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 370:2071–2082, 2014.
Prognosis for Idiopathic Pulmonary Fibrosis
Most patients have moderate to advanced clinical disease at the time of diagnosis and deteriorate despite treatment. The mortality rate is estimated to be 50 to 70% at 5 years. Several prognostic models have been proposed. Among the factors that portend a worse prognosis are older age, male sex, lower forced vital capacity, and lower diffusing capacity for carbon monoxide (DLCO).
Causes of acute deterioration include infections, pulmonary embolism Pulmonary Embolism (PE) Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more , pneumothorax Pneumothorax Pneumothorax is air in the pleural space causing partial or complete lung collapse. Pneumothorax can occur spontaneously or result from trauma or medical procedures. Diagnosis is based on clinical... read more , and heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more . Also, acute exacerbations without an identifiable cause may occur. All acute exacerbations have a high morbidity and mortality.
Lung cancer occurs more frequently in patients with IPF, but cause of death is usually respiratory failure. Because of the poor prognosis of IPF, early discussions with the patient and family about advance care planning Advance Directives Advance directives are legal documents that extend a person's control over health care decisions in the event that the person becomes incapacitated. They are called advance directives because... read more and end-of-life care are important.
Idiopathic pulmonary fibrosis accounts for most idiopathic interstitial pneumonia and tends to affect older people.
Symptoms and signs (eg, subacute dyspnea, nonproductive cough, and Velcro crackles) are nonspecific and usually caused by other, more common disorders.
High-resolution CT can help in diagnosis by showing findings such as diffuse, patchy, subpleural, reticular opacities with irregularly thickened interlobular septa and intralobular lines; subpleural honeycombing; and traction bronchiectasis.
Treat supportively and, if available, use pirfenidone or nintedanib.
Encourage participation in clinical trials and, if patients are < 65 years and otherwise healthy, consider lung transplantation at the time of diagnosis.
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2022;205(9):e18-e47. doi:10.1164/rccm.202202-0399ST
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