Interstitial (Nonidiopathic) Pulmonary Fibrosis Clinical Presentation

The clinical history offered by patients with a DPLD is variable and related to the underlying disease process. Many patients with DPLD, particularly IPF/UIP, may experience acute exacerbations of the disease with subsequent persistent decrement in lung function, which has become increasingly recognized.

• In general, all manifest primarily with respiratory symptoms that may be erroneously attributed to aging, obesity, deconditioning, or recent respiratory tract infection.

  • Dyspnea is the most frequent symptom, but chronic cough, wheezing, hemoptysis, and chest pain can occur.
  • Digital clubbing is common with some diagnoses (eg, IPF and asbestosis) and may first be noted by the patient. When it develops in a patient with known interstitial lung disease, it is usually indicative of advanced fibrosis. However, it may also herald an underlying bronchogenic carcinoma.
• Clinical history may include the following:

  • Incidental diagnosis may be made from a chest radiograph or abnormal screening spirometry findings obtained for unrelated reasons.
  • Diagnosis may occur as a result of screening for high-risk occupational exposure, such as asbestos.
  • Medical attention may be sought for other manifestations of systemic illness that also affect the lungs.
• Broadly, the manifestations of fibrotic lung disease can be grouped as follows:

  • They may be chronic, insidious, and slowly progressive.
  • They may be subacute, with a resolving, remitting, relapsing, or progressive course.
  • They may be acute, with a fulminant, progressive, remitting, or resolving course.
• Disorders with chronic, insidious, and slowly progressive courses are those that clinically resemble IPF and usually share a common pathology (ie, UIP).

  • Many of the rheumatologic/connective-tissue diseases (eg, rheumatoid arthritis; calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia (CREST) syndrome/progressive systemic scleroderma; systemic lupus erythematosus; mixed connective-tissue disease; the pneumoconioses (eg, asbestosis, silicosis); chronic hypersensitivity pneumonitis; and drug-related pulmonary fibrosis (eg, due to bleomycin) generally fit into this category.
  • Development of clinically apparent lung diseases related to occupational exposures (eg, pneumoconiosis) generally occurs many years after the exposure. Radiation fibrosis often develops months to years after radiation exposure.
  • A lag time of months or years can occur between the use of pulmonary toxic medications and the development of fibrotic disease. The effect can be dose-dependent (eg, bleomycin), although, in other cases, the relationship is less clear.
  • Pulmonary manifestations of rheumatologic/connective-tissue disease may develop in advance of, coincident with, or many years after the onset of articular disease.
  • Pulmonary sarcoidosis, although sometimes acute or subacute in onset, in some cases may present insidiously over time.
• Subacute presentations with a variable course are typified by COP.

  • COP often develops weeks or months after the onset of a flulike illness.
  • Patients can present to medical attention with dyspnea or exercise intolerance.
  • The course is variable and may either spontaneously remit or progress.
  • The disorder is thought to be very responsive to steroid therapy, although it may recur when steroids are withdrawn or tapered.
  • In some cases, COP may progress to end-stage fibrotic lung disease.
• Disorders with an acute onset are typified by AIP, which is an idiopathic form of severe lung injury.

  • The histopathology is that of adult respiratory distress syndrome with diffuse alveolar damage.
  • Patients present either with no antecedent history of lung disease or as part of an accelerated phase of underlying interstitial disease.
  • Most patients progress rapidly to respiratory failure.
  • Some patients may improve with steroids or other immunosuppressive therapy.

• Varied etiologies make generalization of physical examination findings difficult for patients with DPLD. However, clinical examination findings noted in patients with idiopathic pulmonary fibrosis are frequently noted in patients with other DPLDs.

  • Patients frequently are dyspneic, which may be more pronounced with activity and generally is associated with an accompanying tachypnea.
  • Central cyanosis may be present if significant hypoxemia and arterial oxygen desaturation are present.
  • Fine end-inspiratory pulmonary rales (Velcro rales) are a common finding and may be difficult to distinguish from those auscultated in patients with congestive heart failure. Pulmonary sarcoidosis and other granulomatous disorders are often an exception.
  • Wheezes may be heard and reflect airway involvement, as in sarcoidosis.
  • A pulmonary squawk has been described with HSP.
  • A right-sided gallop (S₃), an accentuated second heart sound (P₂) with fixed or paradoxic splitting, and a right ventricular lift may be present. These indicate the presence of cor pulmonale.
  • Digital clubbing may accompany many of these disorders, as previously discussed.
• Disease-specific findings include the following:

  • Generalized lymphadenopathy often occurs with sarcoidosis.
  • Cutaneous and articular findings are associated with rheumatologic disease.
  • Gastrointestinal manifestations occur with inflammatory bowel disease.

Numerous causes/diagnoses are included among the DPLDs, many of which can be grouped as follows:

• Those that mimic interstitial lung disease in clinical presentation and chest radiographic findings, including the following:

  • Congestive heart failure
  • Atypical pneumonia (including Pneumocystis species)
  • Lymphangitic spread of cancer
• Those associated with environmental or occupational exposures, including the following:

  • Pneumoconioses (a group of occupational lung diseases related to inhalational exposures to inorganic dusts [eg, silicosis, asbestosis, berylliosis, coal worker's pneumoconiosis {black lung}])
  • HSP caused by exposure to protein antigens (eg, farmer's lung, pigeon-breeder's lung, hot-tub lung)
  • Fibrotic lung disease due to exposure to toxic gases, fumes, aerosols, and vapors (eg, silo-filler's disease)
  • Radiation exposure (ionizing radiation, frequently used in medical therapeutics)
• Those associated with rheumatologic/connective-tissue diseases, such as the following:

  • Scleroderma (CREST syndrome/progressive systemic scleroderma)
  • Rheumatoid arthritis
  • Mixed connective-tissue disease
  • Systemic lupus erythematosus
  • The pulmonary-renal syndromes (ie, Wegner or Goodpasture disease) - Often included with this group; however, predominant manifestation is vasculitis rather than fibrosis
• Those related to drug exposure, including the following:

  • Cytotoxic agents (eg, bleomycin, busulfan, methotrexate)
  • Antibiotics (eg, nitrofurantoin, sulfasalazine)
  • Antiarrhythmics (eg, amiodarone, tocainide)
  • Anti-inflammatory medications (eg, gold, penicillamine)
  • Illicit drugs (eg, crack cocaine, heroin)
• Sarcoidosis and other granulomatous diseases (eg, berylliosis)
• Those related to other systemic illnesses, including the following:

  • Hepatitis C
  • Inflammatory bowel disease
  • Acquired immunodeficiency syndrome
• Idiopathic or rare DPLDs, such as the following:

  • COP (idiopathic)
  • PLCH (rare)
  • Eosinophilic pneumonia
• Inherited DPLDs, including the following:

  • Familial IPF or sarcoidosis
  • Tuberous sclerosis
  • Neurofibromatosis
  • Niemann-Pick disease
  • Gaucher disease
  • Hermansky-Pudlak syndrome
• Certain DPLDs, such as RBILD, DIP, and PLCH, are largely or only seen in current or former smokers.