Mr. Jones is a 60-year-old man referred to a pulmonologist after preadmission testing for a total knee replacement. His chest radiograph proves abnormal, showing bilateral reticular opacities. His knee surgery is cancelled, and he is referred to a lung practitioner.
A review of systems during the lung practitioner's assessment reveals Mr. Jones' progressive shortness of breath the past year. On visual assessment, he has digital clubbing with cyanosis of his fingertips and lips. On auscultation, he has bibasilar crackles. The lung practitioner orders several tests, which reveal pulmonary fibrosis.
Pulmonary fibrosis is one of many interstitial lung diseases that scar lung tissue. An incurable, restrictive lung disease, it causes scarring and fibrosis between the alveoli (chronic interstitial inflammation). Scarring and stiffening of the alveoli decreases transport of oxygen across the alveolar membrane.
One clear sign of pulmonary fibrosis on CT scan is honeycombing and scarring, which irreversibly lessen elasticity and lung compliance.1
Pulmonary fibrosis is known by different names, including idiopathic pulmonary fibrosis (IPF), defined by progressive dyspnea and declining pulmonary function test.2 Chest radiographs display interstitial infiltrations and biopsy shows fibrosis, inflammation or both.
Idiopathic interstitial pneumonias fall into eight categories.
- Desquamative interstitial pneumonia (DIP): A rare form of fibrosis. Average age at onset is 42. Of these patients, 90% have a smoking history, and 75% respond to steroids.
- Bronchiolitis obliterans
- Organizing pneumonia
- Cryptogenic organizing pneumonia (CFA)
- Respiratory bronchiolitis interstitial lung disease (RBILD): Takes on the same process of DIP. Average age at onset is 36.1,2
- Acute interstitial pneumonia (AIP): Acute onset with rapid progression of shortness of breath and respiratory failure. Life expectancy is 6 months.
- Nonspecific interstitial pneumonia (NSIP): More common in women. Average age at onset is 49. Inflammation is more common than fibrosis.
- Lymphangioleiomyomatosis (LAM): A rare form of pulmonary fibrosis affecting only women. Average age at onset is 34.
Other disease processes can cause pulmonary fibrosis, including lupus, rheumatoid arthritis, scleroderma and sarcoidosis.
Studies show that 13 to 20 people per 100,000 develop interstitial lung diseases, including an IPF prevalence of 7.4 women per 100,000 and 10.7 men per 100,000.1
Pulmonary fibrosis typically affects adults 40 to 70 years of age. About two-thirds are over age 60. The mean age at diagnosis is 66. Incidence increases after age 75, to 175 per 100,000. Overall death increases at age 75, as well, with the mean length of survival following diagnosis at 3 to 5 years.1
Unfortunately, pulmonary fibrosis patients, not knowing their condition for years, attribute shortness of breath to other causes, such as weight gain, aging and lack of exercise. As a result, the condition is often diagnosed in the late stages after a comparatively minor medical event, for example, flu requiring hospitalization. After diagnosis, life expectancy for most patients is 2 to 4 years, with the 5-year survival rate at 30% to 50%.1
There are six known risk factors for pulmonary fibrosis:
- cigarette smoking
- environmental factors
- genetic predisposition
- chronic aspiration
- infectious agents
- some prescription medications.1
While cigarette smoking plays a role in the development of pulmonary fibrosis, it has actually extended survival in some patients, compared with nonsmokers or former smokers.3
A likely explanation is that these patients may seek medical attention earlier for smoking-related symptoms.3 These patients also can have more digital clubbing and less crackling on examination, increased incidence of pulmonary hypertension on chest radiograph and decreased spirometry and diffusion capacities on pulmonary function tests.3
Environmental factors that increase the risk of developing pulmonary fibrosis include exposure to solvents and to dust from metal and wood, and atopy.4
Genetic predisposition also may be a factor. No specific genetic markers have been linked to IPF, but there have been cases of two immediate family members having IPF, though this is currently being researched.
Chronic aspiration is another risk factor for IPF. These patients tend to aspirate secondary to gastric reflux disease. However, it is still not clear how chronic aspiration leads to IPF.
Several infectious diseases can lead to IPF, including Legionnaires disease, herpes virus, parainfluenza 3 virus, HIV-1, hepatitis C, cytomegalovirus, measles and the Epstein Barr virus.1,5 Some studies evaluated DNA markers of CMV, EBV, HHV-7 and 8 and have shown that patients with these viruses were at an increased risk for pulmonary fibrosis.5
Antidepressants and tricyclic medications may lead to pulmonary fibrosis.6 Dothiepin and imipramine have shown to increase incidence of IPF, but how these medications affect the disease process is not known.6
Other medications may cause pulmonary fibrosis using different mechanisms. They include amiodarone, amphotericin B, nitrofurantoin, methotrexate, bleomycin, vinca and alkaloids. Prolonged use of amiodarone leads to pulmonary toxicity. Chemotherapeutic medications, e.g., bleomycin and vinca alkaloids, can cause pulmonary fibrosis in 10% of the population. Methotrexate, standard dosaging in patients with arthritis and nitrofurantoin, also can cause pulmonary fibrosis.7 Other medications can lead to pulmonary fibrosis, with high doses or chronic use related to the disease process.
IPF does not have a known etiology unless the causative agent is biopsied from the lung.
A new hypothesis outlines how pulmonary fibrosis developes: First, the patient is exposed to a stimulus, which initiates lung injury that can cause inflammation depending on the patient's dominant inflammatory phenotype. Eventually, the lung tissue begins to heal causing fibrosis.2 Some of the factors modifying the patient's "fibrotic" response are a history of smoking, environmental exposures and viral infections.
Pulmonary fibrosis is caused by stimuli, or exposure to a substance that triggers a triad of responses.2 First, the stimulus is introduced causing chronic inflammation within the lung tissue, which releases cytokines that eventually lead to lung injury. This is caused by development of increased fibroblast activity, which leads to fibrosis of the lung parenchyma.2,8