Two elements are involved in the repair of tissue injury, the replacement of damaged cells and the filling of spaces that result from tissue loss. The lung, unlike other organs, has an abundance of empty spaces in its normal state and, of course, requires them to function. Many forms of lung injury eventuate in pulmonary fibrosis, in which there is both loss and distortion of air spaces resulting in the well-known physiologic abnormalities, restriction of ventilation and impaired gas exchange.
On the basis of morphologic approaches, one can infer that at least 4 processes contribute to the remodeling of lung architecture: interstitial thickening, deposition of connective tissue matrix within air spaces, collapse of air spaces, and wound contraction. Although astute morphologists relying on routine histology have long suspected that organization within air spaces and collapse were involved in particular forms of lung fibrosis, tradition has it that pulmonary fibrosis is mainly an interstitial disease. In fact, electron microscopic and immunohistochemical studies carried out in several laboratories in the past 5 years have renewed interest in processes involving the air spaces.