In 1935, Hamman and Rich reported four cases of rapidly progressive lung fibrosis with identical histological pattern. Today, acute interstitial pneumonia (AIP) is defined as a rapidly progressive and histologically distinct form of interstitial pneumonia. The patho- logical pattern is an organizing form of diffuse alveolar damage (DAD) that is also found in acute respiratory distress syndrome (ARDS) and other acute interstitial pneumonias of known causes (Table 10.1). The term AIP is reserved for cases of unknown cause.
Histopathologically, the hallmark of early (exudative) phase of DAD is hyaline mem- branes. Their presence is helpful in differentiating DAD from other IIPs. The lung biopsy typically shows widespread injury with uniform temporal appearance, alveolar septal thickening, and alveolar organization. In the late (organizing) phase, loose organizing fibrosis within alveolar septa and hyperplasia of type II pneumocytes is seen (Figure 10.1).
AIP frequently starts as a flu-like illness in patients over a wide age range (average 50 years). Both sexes are equally affected. The initial symptoms are myalgia, headache, sore throat and cough, fever, and dyspnea. The typical signs are tachypnea, tachycardia, fine crackles, and occasional wheezes. Most patients develop hypoxemia and respiratory failure, requiring mechanical ventilation. Curiously, most of the patients are in good health when AIP appears. The occurrence of the illness is not related to any known respiratory disease. The clinical course is progressive although a few patients recover completely.
Pathogenesis of AIP is partially resolved. Initial alveolar epithelial cell damage and death are caused by single insult. The inflammatory mediators (TNF-α, interleukin -1β, and others) are released. The neutrophils migrate into the alveolar spaces. Injured alve- olar epithelial barrier exudes proteins into alveolar space that leads to the formation of hyaline membranes. The hyaline membrane functions as a framework for migration of fibroblasts, myofibroblasts, and inflammatory cells. The result is considerable augmen- tation of lung collagen, with widening of interstitial spaces that often causes obliteration of air sacs.
Diagnosis procedure consists of radiological chest examination, lung function testing, and lung biopsy analysis. Chest radiographs show diffuse, patchy, bilateral alveolar pattern with sparing of costophrenic angles (Figure 10.2a, b). The most common HRCT findings in patients with AIP are ground-glass haziness, bronchial dilatation, intralobu- lar linear opacities, and architectural distortion. The distribution of ground-glass opacifications is diffuse, bilateral, with areas of focal sparing of lung lobules giving a geo- graphical appearance. Consolidation is frequently seen. Lung lavage is helpful in exclud- ing alveolar hemorrhage, hypersensitive pneumonitis, eosinophilic pneumonia, and also serves as a source of adequate and valuable samples to perform thorough microbiolog- ical analyses. Usually neutrophilic alveolitis is associated with scattered atypical type II pneumocytes collected in clusters with extracellular amorphous material (fragments of hyaline membranes).
Other tests, especially serological tests aimed at exclusion of pulmonary vasculitis and connective tissue diseases, are necessary. The exact diagnosis is mandatory, because
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Acute Interstitial Pneumonia
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62 Clinical Atlas of Interstitial Lung Disease
Table 10.1. Clinical conditions associated with diffuse alveolar damage (DAD) pattern.
Idiopathic: acute interstitial pneumonia (AIP) Acute hypersensitive pneumonitis ARDS
Connective tissue disease
Dermatomyositis/polymyosistis, mixed connective tissue disease, microscopic polyangiitis, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis
Drug-induced lung disease
Amiodarone, bleomycin, busulfan, carmustine, crack cocaine, nitrofurantoin Infection
Legionella pneumophilia, Mycoplasma pneumoniae, viruses Inhalants and toxins
Chlorine gas, nitrogen dioxide, oxygen toxicity, phosgene, paraquat
Figure 10.2. Plain radiograph of the chest of a patient with AIP shows diffuse alveolar infiltrates (a) and almost normal finding following successful treatment in the ICU. The patient required mechanical ventilation and received high doses of methylprednisolone and azathioprine. Prior to this event she was a healthy person (b).
Figure 10.1. Acute interstitial pneumonia (AIP). The alveolar septa are widened, with myxomatous and edematous stroma; there is interstital fibroblast proliferation. Marked alveolar type II pneumocyte hyperplasia with scanty exudate in alveolar spaces.
Acute Interstitial Pneumonia 63
some of the diseases that are in the differential diagnosis are treated aggressively with immunosuppressive agents.
Open lung biopsy is the procedure that should be weighted carefully because these patients, especially if they require mechanical ventilation, are at risk of developing serious complications.
There is no effective therapy for patients with AIP. Most of the patients receive par- enteral methylpredinsolone in high doses (2 mg kg−1day−1in divided doses) for several days, subsequently switching to oral preparations. There are sporadic reports on effec- tive therapy with immunosuppressive agents.
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