Small airways may be potential target to modify IPF outcomes

The small airways may be a potential target to modify outcomes in patients with idiopathic pulmonary fibrosis, researchers reported in the American Journal of Respiratory and Critical Care Medicine.

Researchers obtained eight single explanted lungs from patients with end-stage IPF (mean age, 61 years) who had bilateral lung transplantation at the University of Pennsylvania. Eight unused donor lungs were also obtained and matched for age and sex to be used as controls. All lungs were inflated and frozen and scanned to assess large airways. To assess stereological small airways and parenchymal fibrosis, researchers also scanned eight unbiased, systemic uniform random sample lungs with micro-CT.

The lungs obtained from patients with IPF had a greater total number of airways on clinical CT compared with control lungs (561 vs. 196; P < .01), which the researchers said was due to increases in the wall (P < .05) and lumen area (P < .05), which resulted in more visible airways with a lumen greater than 2 mm.

The researchers observed a reduction in the number of terminal (P < .01) and transitional (P < .001) bronchioles and an increase in terminal bronchiole wall area (P < .001) in tissue samples from lungs with IPF without microscopic parenchymal fibrosis compared with controls. There was an increase in airway wall thickness (P < .05) and dilated airway lumens (P < .001) in terminal bronchioles in tissue samples from lungs with IPF with microscopic parenchymal fibrosis; these increases led to honeycomb cyst formations, according to the researchers.

These findings demonstrate that the amount of conducting terminal bronchioles and respiratory transitional bronchioles are significantly reduced and terminal bronchiole airway wall are significantly thickened in areas of the lung without microscopic parenchymal fibrosis.

“This study highlights that a reduction and fibrosis of small airways in IPF likely occurs early in the disease process as these features were present before microscopic parenchymal fibrosis occurs. This finding highlights the potential importance of the small airways for modification of disease outcomes in IPF,” Kohei Ikezoe, MD, PhD, respirologist at the Centre for Heart Lung Innovation at St. Paul’s Hospital at the University of British Columbia, Vancouver, Canada, and colleagues wrote.