Acute Flares in IPF Patients Linked in Study to Multiple Organ Injury

Although previously limited to the pulmonary system, new research suggests that acute exacerbations in idiopathic pulmonary fibrosis (IPF) also involve multiple organ systems. Moreover, two genes, scavenger receptor A (SRA) and TNF-α, are thought to play a role in mediating this systemic tissue damage.

Acute exacerbations is the all-encompassing term a the sudden increase in respiratory symptoms. In IPF patients who die from acute exacerbations, pathologists often observe diffuse alveolar damage in the lungs at autopsy. This type of damage is consistent with the tissue injury observed in the multi-system acute respiratory syndrome (ARDS), and suggests that acute exacerbations in IPF may also be a systemic disease.

For this reason, researchers in Japan assessed how acute exacerbations in IPF, or related connective tissue disease-associated interstitial lung disease (CTD-associated ILD), affect other organ systems. The results were recently published in the journal  BMC Pulmonary Medicine, in the article, “Acute exacerbation of IPF has systemic consequences with multiple organ injury, with SRA+ and TNF-α+ cells in the systemic circulation playing central roles in multiple organ injury.”

Fourteen autopsy cases were examined, 12 IPF and two CTD-associated ILD. The median age of the patients analyzed was 68, and most were men (78.5%). In addition to lung tissues, the heart, liver and kidney were examined for histopathological and cytological abnormalities. Peripheral blood before and after death was also assessed for the presence of SRA⁺ and TNF-α⁺ cells. Cells expressing SRA and TNF-α were previously reported to be present in the systemic circulation of patients who succumb with multiple organ dysfunction syndrome, suggesting a link between their presence and systemic organ dysfunction.

All lungs examined showed diffuse alveolar damage, as expected, and histopathologic and cytologic evidence classified diseased lungs into two major subtypes. Additional pathological abnormalities were observed in the cardiac, liver and renal (kidney) systems.  Specifically, more necrotic tissue, or dead cells, was found in cardiac tissue, as well as in 64.3% of hepatocytes (liver cells) and 64.3% of renal tubular epithelial cells. Gastric ulcers were also observed in 28.6% of the patients.

Additionally, all injured organs displayed an accumulation of neutrophils (a type of white blood cell) and platelets, which indicates a pro-inflammatory immune response, and extensive injury to the endothelial cells in blood capillaries.

When assessing the peripheral blood for SRA⁺ and TNF-α⁺ cells, the researches found a greater number of these cells post-death compared to before death. At autopsy, SRA+ and TNF-α+ cells were observed in all 14 cases; SRA+ cells were found in 11 of the 14 cases (78.6%) before acute exacerbation, and TNF-α+ cells in nine of the 14 cases (64.3%) after disease diagnosis.

The researchers hypothesized that a rapid and substantial release of signaling molecules into the systemic circulatory system activates a pro-inflammatory immune response, ultimately leading to tissue damage and injury.

“Acute exacerbation of IPF and CTD-associated ILD appears to be a systemic disorder that brings about multiple organ injury, with SRA+ cells and TNF-α+ cells in the systemic circulation playing central roles. Our findings illuminate the importance of these cells in the pathophysiology of acute exacerbation,” the researchers concluded.

The team believes that the findings offer a new understanding of the IPF pathology, and may have implications for patients with the disease.