A new study suggests that an acute exacerbation — the sudden worsening of respiratory symptoms — in idiopathic pulmonary fibrosis (IPF) may actually be a systemic circulatory disorder resulting in multiple organ injury. Large cells expressing (or positive for) scavenger receptor A (SRA⁺) and tumor necrosis factor-α (TNF-α⁺) also may play important roles in this process.

The study, “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,” was published in the journal BCM Pulmonary Medicine.

IPF is considered as “interstitial pneumonia limited to the lung,” and acute exacerbations considerably increase disease progression. The researchers sought to further characterize the mechanisms and pathophysiology of acute IPF exacerbations. While previous studies have reported diffuse alveolar damage in the lungs of patients who have died from an acute exacerbation of IPF, they haven’t addressed characteristics of peripheral blood and systemic organs at autopsy.

The research team examined peripheral blood cells and systemic organ tissues in 14 patients who had died with acute exacerbation of IPF or connective tissue disease (CTD)-associated interstitial lung disease (ILD). The group compared clinical characteristics of peripheral blood prior to acute exacerbation, after the disease diagnosis and related acute exacerbation, and again at autopsy. Organs examined at autopsy included the lungs, heart, liver, kidney, and stomach tissues.

Multiple organ injury, defined as damage to two or more organs, was found in nine of the patients, and diffuse alveolar damage in all 14 patients. In heart tissue, necrosis (cell death) was observed, as well as an accumulation of neutrophils (a type of white blood cells) and platelets in blood capillaries in all cases.

Researchers also noted the presence of large SRA⁺ and TNF-α⁺ cells in peripheral blood at autopsy in all 14 cases.

Liver cell necrosis was observed in nine cases (64.3%) as was necrosis of kidney epithelial cells (9 cases, 64.3%), and shallow gastric ulcers were found in four cases (28.6%).

The research team previously found cells positive for SRA and TNF-α at autopsy in the systemic circulation of patients who had died with multiple organ dysfunction syndrome (MODS), including those with acute respiratory distress syndrome (ARDS), which is considered a systemic multi-organ disease.

Based on the findings, the researchers concluded that 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,” and highlighted the importance of these cells in the pathophysiology of acute exacerbation.