Usual Interstitial Pneumonia/Idiopathic Pulmonary Fibrosis

Etiology, Prevalence, and Epidemiology

Idiopathic pulmonary fibrosis (IPF) has been defined as “a specific form of chronic fibrosing interstitial pneumonia limited to the lung and associated with the histologic and/or CT appearance of usual interstitial pneumonia (UIP).” IPF is the most common idiopathic interstitial lung disease. Data from the late 1980s estimated a prevalence of 20 per 100,000 for men and 13 per 100,000 for women, and an incidence of 11 per 100,000 per year in men and 7 per 100,000 per year in women. However, more recent data has shown that prevalence and incidence of IPF have increased, with a prevalence of 42.7 to 63 per 100,000 and an incidence of 16.3 to 17.4 per 100,000 per year, which may reflect the average increased life expectancy in that span of time. Most patients with IPF are older than 50 years, and approximately 80% are older than 65 years. Indeed, age older than 75 years has been shown to have an extremely high positive predictive value in IPF diagnosis. IPF has been reported worldwide in rural and urban settings. IPF is likely more common in Caucasians, although this has not been definitively proven. IPF is more common in smokers; the odds ratio of IPF in smokers compared with lifelong nonsmokers in various studies ranges from 1.6 to 2.9. Occasionally, clusters of IPF may occur in families. Although the prevalence of familial IPF is unknown, it has been estimated to account for 0.5% to 2.2% of patients with IPF.

Clinical Presentation

Symptoms are nonspecific and include progressive dyspnea, nonproductive cough, weight loss, and fatigue. Dyspnea is usually the main symptom and typically is present for more than 6 months before initial diagnosis. Diagnosis is delayed by more than 1 year in up to half of patients. Finger clubbing occurs in 25% to 50% of patients. Auscultation typically reveals late inspiratory crackles (so-called Velcro rales). Cyanosis and signs of pulmonary hypertension and cor pulmonale are late manifestations.

The clinical course of IPF is typically one of relentless progressive increase in the extent of fibrosis and severity of clinical manifestations. The course of individual patients varies, however, and some patients remain stable for extended periods without treatment. Acute deterioration with an abrupt and unexpected worsening of symptoms may occur secondary to infection, pulmonary embolism, pneumothorax, or heart failure. Often, no identifiable cause for the acute decline is identified, however, and these episodes are called “acute exacerbation” or “accelerated phase” of IPF.

Acute exacerbations of IPF are defined as an acute, clinically significant respiratory deterioration characterized by new widespread alveolar abnormality and are considerably more common than previously recognized. In one retrospective study of 168 patients with IPF, 21% of patients died over a median period of 76 weeks, and 47% of these deaths followed an acute deterioration in the patient's clinical status. In a second study of 147 patients with biopsy-proven IPF, the 1-year frequency of acute exacerbation was 8.5%, and the 2-year frequency was 9.6%. As pointed out by the authors, however, the actual incidence of acute exacerbation could have been underestimated in their study because some of the patients were lost to follow-up and because the study included only patients with biopsy-proven IPF. In an autopsy series of 25 patients, 15 (60%) deaths in patients with IPF or nonspecific interstitial pneumonia (NSIP) associated with connective tissue disease were due to diffuse alveolar damage and consistent with acute exacerbation. The reported mortality rates from acute exacerbation range from 20% to 86%. Diagnostic criteria for acute exacerbation of IPF have recently been revised and include:

• 1.

  Previous or concurrent diagnosis of IPF

• 2.

  Acute worsening or development of dyspnea typically of less than 1 month in duration

• 3.

  CT findings of bilateral ground-glass opacities and/or consolidation superimposed on a background pattern consistent with usual IPF

• 4.

  Deterioration not fully explained by cardiac failure or fluid overload

Pathophysiology