Terminal Diffuse Alveolar Damage in Relation to Interstitial Pneumonias

Abstract

Acute exacerbations of idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis (IPF/CFA) are rare and typically terminal events, but their relationship to underlying patterns of idiopathic interstitial pneumonias is unknown. We reviewed autopsy material from patients who died of diffuse alveolar damage in the clinical setting of pulmonary fibrosis, both idiopathic and with background fibrosing alveolitis with connective tissue disorders (FA-CTDs), and compared them with cases of acute interstitial pneumonia. Of 15 patients with acute exacerbations of IPF/CFA (n = 12) or FA-CTD (n = 3), 12 had a background pattern of usual interstitial pneumonia and 3 had fibrotic nonspecific interstitial pneumonia. All cases of fibrotic nonspecific interstitial pneumonia were seen in association with FA-CTD. The cause of acute exacerbations is unknown, but our data suggest that toxic effects of oxygen and triggering infection are unlikely causes. In patients with CTDs, it remains uncertain whether the acute exacerbation is related to the fibrosis, the associated CTD, or a combination of these factors. Acute exacerbations of IPF/CFA may be a more common terminal event than previously thought.

Seasonal Variation

“…6 -9 Analysis of a recently completed controlled treatment trial 10 found that 89% of the deaths occurring in the placebo arm were considered to be due to IPF progression; of these deaths, half were categorized as acute with decompensation occurring over 4 weeks or less, with the other half considered subacute with worsening occurring over weeks to months. These accelerated declines 32,33 and acute exacerbations of IPF (and other fibrotic lung diseases) 34 have recently gained attention due to their high direct mortality rate, their unpredictable nature (as they do not appear to be related to the level of pulmonary function derangement), 10,11,35 and the lack of effective therapy. 11 Under these conditions, the absence of an underlying mechanism is even more frustrating.…”

“…[13][14][15]21,22,25,26 The absence of a code for infection when infection is actually present may result from either of two causes: (1) the failure to clinically consider or to systematically evaluate for it; or (2) the presence of an infectious agent that is difficult to identify or previously unknown. However, the absence of a clearly recognized infection in PF deaths is supported by autopsy studies 33,36 in which it is rare to find a specific infection and the underlying pathology of the lung is often underlying fibrosis with superimposed diffuse alveolar damage, a pattern not unique to pneumonia. In PF, it could be that an infectious agent activates or accelerates the fibrotic process without causing classic infection.…”

Two Cases of Acute Exacerbation of Interstitial Pneumonia Treated with Polymyxin B-immobilized Fiber Column Hemoperfusion Treatment

“…Acute exacerbations of IPs have been described to have high mortality during short course (3,6,7). Recent reports have suggested that PMX hemoperfusion treatment may be effective in patients with ALI/ARDS and acute exacerbation of IPF (8,9,11).…”

Presence of large scavenger receptor A-positive cells in systemic circulation: A potential prognostic indicator for idiopathic pulmonary fibrosis, connective tissue disease-associated interstitial lung disease, acute exacerbation and risk factor for acute exacerbation

“…Diffuse alveolar damage is frequently observed in patients who have died from an AE of IPF [14][15][16], but pathological findings of systemic organs were not described in these reports. Autopsy was performed in 14 of 47 Group D patients and we reported that 1) Multiple organ injury (including diffuse alveolar damage) was confirmed in all cases, 2) Large SRA + cells and TNF-α + cells in systemic circulation were considered to play central roles in multiple organ injury.…”

“…The rest of fresh peripheral blood samples obtained for the examination of differential white blood counts during the hospitalization were examined (median times [range], 4 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]). Peripheral blood was collected into tubes containing EDTA (Vacutainer plastic, EDTA 2K; Becton Dickinson, Franklin Lakes, NJ, USA).…”