Usual interstitial pneumonia (UIP)
Age 55–60, slight male predominance. Insidious dry cough and dyspnea lasting months to years. Clubbing present at diagnosis in 25–50%. Diffuse fine late inspiratory crackles on lung auscultation. Restrictive ventilatory defect and reduced diffusing capacity on pulmonary function tests. ANA and RF positive in ∼25% in the absence of documented collagen-vascular disease.
|Patchy, temporally and geographically nonuniform distribution of fibrosis, honeycomb change, and normal lung. Type I pneumocytes are lost, and there is proliferation of alveolar type II cells. “Fibroblast foci” of actively proliferating fibroblasts and myofibroblasts. Inflammation is generally mild and consists of small lymphocytes. Intra-alveolar macrophage accumulation is present but is not a prominent feature. ||Diminished lung volume. Increased linear or reticular bibasilar and subpleural opacities. Unilateral disease is rare. High-resolution CT scanning shows minimal ground-glass and variable honeycomb change. Areas of normal lung may be adjacent to areas of advanced fibrosis. Between 2% and 10% have normal chest radiographs and high-resolution CT scans on diagnosis. ||No randomized study has demonstrated improved survival compared with untreated patients. Inexorably progressive. Median survival approximately 3 years, depending on stage at presentation. Nintedanib and pirfenidone reduce rate of decline in lung function. |
Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)1
Age 40–45. Presentation similar to that of UIP though in younger patients. Similar results on pulmonary function tests, but less severe abnormalities. Patients with respiratory bronchiolitis are invariably heavy smokers.
|Increased numbers of macrophages evenly dispersed within the alveolar spaces. Rare fibroblast foci, little fibrosis, minimal honeycomb change. In RB-ILD the accumulation of macrophages is localized within the peribronchiolar air spaces; in DIP1, it is diffuse. Alveolar architecture is preserved. ||May be indistinguishable from UIP. More often presents with a nodular or reticulonodular pattern. Honeycombing rare. High-resolution CT more likely to reveal diffuse ground-glass opacities and upper lobe emphysema. ||Spontaneous remission occurs in up to 20% of patients, so natural history unclear. Smoking cessation is essential. Prognosis clearly better than that of UIP: median survival greater than 10 years. Corticosteroids thought to be effective, but there are no randomized clinical trials to support this view. |
Acute interstitial pneumonia (AIP)
Clinically known as Hamman-Rich syndrome. Wide age range, many young patients. Acute onset of dyspnea followed by rapid development of respiratory failure. Half of patients report a viral syndrome preceding lung disease. Clinical course indistinguishable from that of idiopathic ARDS.
|Pathologic changes reflect acute response to injury within days to weeks. Resembles organizing phase of diffuse alveolar damage. Fibrosis and minimal collagen deposition. May appear similar to UIP but more homogeneous and there is no honeycomb change—though this may appear if the process persists for more than a month in a patient on mechanical ventilation. ||Diffuse bilateral airspace consolidation with areas of ground-glass attenuation on high-resolution CT scan. ||Supportive care (mechanical ventilation) critical but effect of specific therapies unclear. High initial mortality: 50-90% die within 2 months after diagnosis. Not progressive if patient survives. Lung function may return to normal or may be permanently impaired. |
Nonspecific interstitial pneumonia (NSIP)
Age 45–55. Slight female predominance. Similar to UIP but onset of cough and dyspnea over months, not years.
|Nonspecific in that histopathology does not fit into better-established categories. Varying degrees of inflammation and fibrosis, patchy in distribution but uniform in time, suggesting response to single injury. Most have lymphocytic and plasma cell inflammation without fibrosis. Honeycombing present but scant. Some have advocated division into cellular and fibrotic subtypes. ||May be indistinguishable from UIP. Most typical picture is bilateral areas of ground-glass attenuation and fibrosis on high-resolution CT. Honeycombing is rare. ||Treatment thought to be effective, but no prospective clinical studies have been published. Prognosis overall good but depends on the extent of fibrosis at diagnosis. Median survival greater than 10 years. |
Cryptogenic organizing pneumonia (COP, formerly bronchiolitis obliterans organizing pneumonia [BOOP])
Typically age 50–60 but wide variation. Abrupt onset, frequently weeks to a few months following a flu-like illness. Dyspnea and dry cough prominent, but constitutional symptoms are common: fatigue, fever, and weight loss. Pulmonary function tests usually show restriction, but up to 25% show concomitant obstruction.
|Included in the idiopathic interstitial pneumonias on clinical grounds. Buds of loose connective tissue (Masson bodies) and inflammatory cells fill alveoli and distal bronchioles. ||Lung volumes normal. Chest radiograph typically shows interstitial and parenchymal disease with discrete, peripheral alveolar and ground-glass infiltrates. Nodular opacities common. High-resolution CT shows subpleural consolidation and bronchial wall thickening and dilation. ||Rapid response to corticosteroids in two-thirds of patients. Long-term prognosis generally good for those who respond. Relapses are common. |