IPF, which is also known as usual interstitial pneumonia (UIP), is the most common idiopathic interstitial pneumonia. Cigarette smoking is a risk factor for IPF. Common respiratory symptoms include exertional dyspnea and a nonproductive cough. Physical examination is notable for inspiratory crackles at the lung bases. Clubbing may occur. High-resolution chest CT scans show subpleural reticular opacities predominantly in the lower lung fields, which are associated with honeycombing in advanced disease. Surgical lung biopsy is usually required to confirm the diagnosis, although pts with classic UIP patterns on CT scan may not require a biopsy. IPF can include acute exacerbations characterized by accelerated clinical deterioration over days to weeks. IPF is poorly responsive to available pharmacologic treatment, although recent studies have suggested benefit from pirfenidone and nintedanib.
Nonspecific Interstitial Pneumonia 
Nonspecific interstitial pneumonia (NSIP) is a histologic pattern that can be observed in connective tissue disease, drug-induced ILD, and chronic HP. NSIP is a subacute restrictive process with similar presentation to IPF. High-resolution CT (HRCT) shows bilateral ground-glass opacities, and honeycombing is rare. Unlike IPF, NSIP pts have a good prognosis and typically respond well to systemic glucocorticoid treatment.
ILD Associated with Connective Tissue Disorders
Pulmonary manifestations may precede systemic manifestations of a connective tissue disorder. In addition to direct pulmonary involvement, it is necessary to consider complications of therapy (e.g., opportunistic infections), respiratory muscle weakness, esophageal dysfunction, and associated malignancies as contributors to pulmonary parenchymal abnormalities in pts with connective tissue disorders.
Progressive systemic sclerosis (scleroderma) commonly includes ILD as well as pulmonary vascular disease. Lung involvement tends to be highly resistant to available treatment.
In addition to pulmonary fibrosis (ILD), RA can involve a range of pulmonary complications, including pleural effusions, pulmonary nodules, and pulmonary vasculitis. ILD in RA pts is more common in men.
Systemic lupus erythematosus (SLE) also can involve a range of pulmonary complications, including pleural effusions, pulmonary vascular disease, pulmonary hemorrhage, and BOOP. Chronic, progressive ILD is not commonly observed.
Except for progressive systemic sclerosis, connective tissue-related ILD is typically treated with systemic glucocorticoids, often along with an immunosuppressive agent.
Cryptogenic Organizing Pneumonia
When the BOOP pathologic pattern occurs without another primary pulmonary disorder, the term cryptogenic organizing pneumonia (COP) is used. COP may present with a flu-like illness. Recurrent and migratory pulmonary opacities are common. Glucocorticoid therapy is often effective.
Desquamative Interstitial Pneumonia and Respiratory Bronchiolitis-Associated ILD
Desquamative interstitial pneumonia (DIP) includes extensive macrophage accumulation in intraalveolar spaces with minimal fibrosis. It is seen almost exclusively in cigarette smokers and improves with smoking cessation. Respiratory bronchiolitis-associated ILD is a subset of DIP that includes bronchial wall thickening, ground-glass opacities, and air trapping on HRCT; it also resolves in most pts after smoking cessation.
Pulmonary Alveolar Proteinosis
PAP is a rare diffuse lung disease, with a male predominance, that involves the accumulation of lipoproteinaceous material in the distal airspaces, rather than a classic ILD. More common in males, PAP usually presents insidiously, with dyspnea, fatigue, weight loss, cough, and low-grade fever. Whole-lung lavage is often of therapeutic benefit.
Pulmonary Infiltrates with Eosinophilia
Several disorders are characterized by pulmonary infiltrates and peripheral blood eosinophilia. Acute eosinophilic pneumonia involves fevers and diffuse pulmonary eosinophilic infiltrates with severe hypoxemia. Chronic eosinophilic pneumonia is often in the differential diagnosis with other ILDs; it includes low-grade fever, cough, dyspnea, and weight loss, with a CXR notable for peripheral lung infiltrates. Eosinophilic pneumonias tend to be rapidly responsive to glucocorticoid therapy. Churg-Strauss syndrome, also known as eosinophilic granulomatosis with polyangiitis, occurs in asthmatics and includes eosinophilic vasculitis with multiorgan system involvement. Parasitic infections can cause Löffler syndrome, which includes migratory pulmonary infiltrates and self-limited clinical symptoms, and tropical eosinophilia. Multiple medications can also cause pulmonary eosinophilia.
A variety of diseases can cause diffuse alveolar hemorrhage, including systemic vasculitic syndromes (e.g., granulomatosis with polyangiitis [Wegener's]), connective tissue diseases (e.g., SLE), and Goodpasture syndrome. Although typically an acute process, recurrent episodes can lead to pulmonary fibrosis. Hemoptysis may not occur initially in one-third of cases. CXR typically shows patchy or diffuse alveolar opacities. The DLCO may be increased. High doses of IV methylprednisolone are typically required, followed by gradual tapering of systemic steroid doses. Plasmapheresis may be effective for Goodpasture syndrome.
Pulmonary Langerhans Cell Histiocytosis
PLCH is a smoking-related diffuse lung disease that typically affects men 20-40 years of age. Presenting symptoms often include cough, dyspnea, chest pain, weight loss, and fever. Pneumothorax occurs in 25% of pts. High-resolution chest CT scan reveals upper-zone-predominant nodular opacities and thin-walled cysts, which are virtually diagnostic of this disorder. Smoking cessation is the key therapeutic intervention.
HP is an inflammatory lung disorder caused by repeated inhalation of an organic antigen in a susceptible individual. Many different antigens have been implicated. Clinical presentations can be acute, with cough, fever, malaise, and dyspnea developing within 4-8 h after exposure; subacute, with cough and dyspnea that can become progressively worse over weeks; and chronic, which can appear similar to IPF. Serum precipitins can be measured as an indicator of an environmental exposure. Although helpful in implicating specific agents, the presence of a specific serum precipitin is not diagnostic since many exposed individuals without HP will have such precipitins; false-negative results can also occur. Diagnosis is made based on symptoms, physical findings, pulmonary function tests (restrictive or obstructive pattern), and radiographic studies (chest CT scans typically show ground-glass opacification in acute and subacute forms) that are consistent with HP; history of exposure to a recognized antigen; and presence of an antibody to that antigen. In some cases, lung biopsy (transbronchial or open lung) may be required to confirm the diagnosis. Treatment involves avoiding exposure to the causative antigen; systemic corticosteroids may be required in subacute or chronic HP.
For a more detailed discussion, see King TE Jr: Interstitial Lung Diseases, Chap. 315, p. 1708; Akuthota P, Wechsler ME: Hypersensitivity Pneumonitis and Pulmonary Infiltrates with Eosinophilia, Chap. 310, p. 1681, in HPIM-19. |
Outline
- Idiopathic Pulmonary Fibrosis
- Nonspecific Interstitial Pneumonia
- ILD Associated with Connective Tissue Disorders
- Cryptogenic Organizing Pneumonia
- Desquamative Interstitial Pneumonia and Respiratory Bronchiolitis-Associated ILD
- Pulmonary Alveolar Proteinosis
- Pulmonary Infiltrates with Eosinophilia
- Alveolar Hemorrhage Syndromes
- Pulmonary Langerhans Cell Histiocytosis
- Hypersensitivity Pneumonitis