Pilot Investigation on the Combined Use of Established Clinical Criteria and Systems Biology for Progressive Pulmonary Fibrosis

Background

After reaching adulthood, the organs of the human body preserve their shape and function over a long period, making directed repair one of the most important mechanisms throughout lifetime. Regular wound healing after an injury consists of a well-ordered sequence of overlapping phases: inflammation, formation of supportive new tissue, re-epithelization and final regeneration of epithelial and endothelial lining cells, and essentially repeats the complex process of organ development. In young adults, damage to an organ is frequently answered by fully regenerative wound healing repeating mechanisms of embryonic organ growth called "primary" wound healing. Repeated damage in younger individuals may cause "secondary" wound healing in form of scar formation serving as a rescue program to maintain surface integrity once epithelial and/or endothelial reorganization has failed.

Organ failure in the ageing organism, however, is different and essentially represents the loss of its capacity to achieve an orderly reactivation of organ development. This different quality of wound healing consists of a combination of chronic inflammation and fibroproliferative, non-regenerative repair. Its pathology refers to a large group of diseases involving every organ of the human body.

In the lung, its most prominent form is characterized by a well-defined histopathology named usual interstitial pneumonia (UIP). Unfortunately, this histopathology, while identifying a particularly aggressive phenotype of the fibroproliferative repair response itself, does not allow for an unambiguous clinical diagnosis, as the UIP "pattern" may be found in different fibrotic diseases of the lung, such as hypersensitivity pneumonitis (HP), especially in its chronic form.

In addition, various mechanisms of inflammation which are partly related to the wound healing response itself, may profoundly intensify the aberrant wound healing response. As a result, the mechanisms leading to this condition and maintaining its characteristic clinical appearance are unknown.