Interstitial Lung Diseases

A heterogeneous group of disorders that diffusely affect the lung parenchyma.

The interstitial lung diseases (ILDs) are classified together because of their similar clinical, physiologic, pathologic, and radiologic manifestations (see Table 80-1). ILD is usually related to occupational or environmental exposure, especially to inorganic or organic dusts. Sarcoidosis, idiopathic pulmonary fibrosis (IPF), and pulmonary fibrosis associated with connective tissue diseases have an unknown etiology. Limited information exists regarding the incidence and outcomes of these diseases in the elderly.

Deterioration of patients with ILD may be secondary to disease progression, to disease-related complications, or to therapy-associated complications. This latter phenomenon may be especially problematic in elderly patients, whose tolerance of the drugs used to treat ILDs is 2 to 3 times less than that of younger patients.

Symptoms, Signs, and Diagnosis

Although ILDs do not present differently in the elderly, concurrent disease may confuse the diagnosis. The insidious onset of breathlessness or cough is common, as are other nonspecific findings such as fatigue, arthralgias, and myalgias. Frank arthritis, myositis (muscle tenderness, weakness), photosensitivity, visual problems, or Raynaud's phenomenon suggests a systemic process, such as collagen vascular disease, vasculitis, or sarcoidosis.

A detailed drug history is needed to exclude the possibility of drug-induced disease. An occupational/environmental history is needed to evaluate exposure in the workplace (eg, to asbestos or silica) and in the home (eg, to pets [particularly birds], humidifiers, evaporative coolers, or materials used for hobbies).

The physical examination usually reveals resting tachypnea and bibasilar rales. Cardiac test results may be normal, but a thorough search for signs of left ventricular dysfunction and mitral valve disease (both common in the elderly) should be made. Signs of pulmonary hypertension (right-sided gallops or heaves, accentuated pulmonary component of the second heart sound) may occur late in any of the ILDs. Digital clubbing is common in IPF, collagen vascular disease-related ILD, and asbestosis but is uncommon in hypersensitivity pneumonitis, silicosis, sarcoidosis, and idiopathic bronchiolitis obliterans with organizing pneumonia (BOOP). A thorough inspection of mucosal surfaces, skin, and joints may give clues to systemic processes.

The chest x-ray may provide the earliest evidence of ILD by showing reticular or nodular opacities with reduced lung volume. Other abnormalities indicative of ILD include alveolar or ground-glass opacities, septal Kerley B lines, pleural involvement, and mediastinal or hilar adenopathy. High-resolution CT (HRCT) of the chest may show distinctive patterns of various ILDs. HRCT is significantly more sensitive and specific than chest x-ray for diagnosing and assessing the extent of ILD.

Pulmonary function tests often reveal a restrictive pattern of lung dysfunction. The ratio of forced expiratory volume in 1 second to forced vital capacity (FEV₁/FVC) is normal or increased because of increased elastic recoil of the stiff lung parenchyma. Several ILDs (eg, chronic sarcoidosis, chronic hypersensitivity pneumonitis, advanced pulmonary histiocytosis X) cause airway obstruction and normal or increased volumes secondary to air trapping and hyperinflation. Lung compliance is increased in ILD. The diffusing capacity for carbon monoxide (Dlco) is generally reduced, even when corrected for alveolar volume and Hb. Arterial blood gases obtained at rest may be normal early in ILD; hypoxemia and mild hypocarbia are common as the disease progresses.

Multistage and steady-state exercise testing are considered the most sensitive methods for assessing severity. They reveal the patient's functional limitations. In mild to moderate disease, the ratio of dead space volume to tidal volume (Vd/Vt) ventilation is often normal at rest but usually remains stable or decreases with exercise. In advanced disease, the Vd/Vt ratio commonly increases with exercise; if this occurs in milder cases of ILD, however, pulmonary vascular involvement should be suspected.

Routine blood and serologic tests are often unremarkable. Abnormal results of hepatocellular injury tests and high serum calcium levels are clues to the diagnosis of sarcoidosis or metastatic malignancy with pulmonary lymphangitic spread. Renal insufficiency or microscopic hematuria raises the possibility of Wegener's granulomatosis, Goodpasture's syndrome, systemic lupus erythematosus, or systematic necrotizing vasculitis. However, these conditions rarely present in the elderly. Low titers of antinuclear antibodies and rheumatoid factor are nonspecific findings in a number of ILDs, especially IPF. High titers of antinuclear antibodies suggest collagen vascular disease.

Specialized procedures for obtaining lung cells or tissue are often required to confirm a specific diagnosis. These include fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) of subsegmental regions of the lung with or without biopsy. BAL is considered safe for use in elderly patients, although caution should be used when anesthetizing and premedicating patients with sedatives (eg, midazolam). Transbronchial lung biopsy, the least invasive way to obtain lung tissue for diagnosis, is of limited value in diagnosing ILD, because only small pieces of tissue can be obtained. Surgical lung biopsy by means of video-assisted thoracic surgery is the procedure most often used to obtain a definitive diagnosis of ILD. Elderly patients tolerate thoracoscopic biopsy well, incurring much less pain and fewer complications than with traditional open thoracotomy. Complications include postoperative atelectasis with hypoxemia, pneumonia, and persistent bronchopleural fistulas.

Treatment

Diagnosing and treating the disease early helps delay or prevent functional limitation and disability. End-stage fibrosis is irreversible and untreatable, regardless of etiology.

In general, any possible offending agent should be identified and removed before other medical treatment is started. The mainstay of treatment, especially for IPF, sarcoidosis, and pulmonary fibrosis associated with connective tissue diseases, is suppression of inflammatory and cellular immune responses with corticosteroids and immunosuppressants. Supportive care, including physical and pulmonary rehabilitation, psychosocial therapy, and supplemental oxygen therapy, seems to greatly improve quality of life for many patients.

Corticosteroids: Corticosteroids, which are used to suppress active ongoing alveolar and interstitial inflammation and injury, have long been the drug of choice for treating patients with ILD. Unfortunately, only 15 to 20% show improvement by objective measures.

The dosage and duration of corticosteroid therapy depend on the specific disorder. Patients with fibrosing alveolitis (IPF or collagen vascular disease--related ILD) often require up to 6 months to respond. Patients with sarcoidosis or idiopathic BOOP may respond more quickly to lower doses. Some conditions, such as IPF, commonly require therapy for >= 12 months.

Immunosuppressants: Variable success has been achieved with use of immunosuppressants, such as cyclophosphamide or azathioprine (at 1 mg/kg/day lean body weight for 6 to 8 weeks to a maximum dose of 2 mg/kg/day po). Dosing should begin at 50 to 100 mg/day and after the initial dosing period be increased gradually at 4-week intervals in 25-mg increments until the maximum dose is reached. Therapy is usually combined with corticosteroids (prednisone 0.25 mg/kg/day). Immunosuppressants are associated with substantial toxicity and adverse effects, including hemorrhagic cystitis; leukopenia; anorexia, nausea, and vomiting; infection; and development of hematologic malignancies. Therefore, the decision to use immunosuppressants in elderly patients should not be taken lightly.

Patient and End-of-Life Issues

Patients with ILD, especially those with IPF, may stop exercising regularly and may even stop performing normal daily activities because of dyspnea caused by physical exertion. Education in energy management techniques may provide these patients with the means to perform more of their daily activities and improve their quality of life. Patients with severe disease may benefit from a comprehensive pulmonary rehabilitation program.

ILD is often chronic, progressive, and irreversible. Endotracheal intubation and mechanical ventilation for respiratory failure in patients with end-stage ILD should be avoided, because these patients rarely recover adequately to be extubated or discharged from intensive care. Consequently, patients with progressive ILD should be encouraged to issue advance directives indicating their wishes with respect to life-sustaining therapies. There comes a time when symptomatic relief and supportive care are often preferred over aggressive and uncomfortable treatment.