Growth and division of type II pulmonary epithelial cells are important components of the pathway by which the alveolar surface is repaired following several forms of lung injury. These processes, which result in reepithelialization of the denuded alveolar basement membrane, involve loss of type II cell differentiation and transition to a type I epithelium. As in other cells, the extracellular matrix appears to be an important determinant of type II cell differentiation. This effect on the type II cell is exerted by both simple and complex matrices and may be modulated by active synthesis and remodeling of the matrix components by the pneumocytes themselves. In general, laminin or laminin-rich complex surfaces favor cellular differentiation; fibronectin or fibronectin-rich complex matrices accelerate loss of differentiated form and function. In both cases, matrix-initiated changes in the type II cell involve regulation of cell shape and morphology, hormone responsiveness, secretory activity, phospholipid synthesis, protein turnover, and gene expression. These influences of the extracellular matrix, along with the effects of locally acting soluble factors, likely direct the cellular transitions required for restoration of a physiologically competent alveolar surface during the repair of lung injury.

Selection of appropriate treatment is now possible on the basis of prognostic indices. For patients with a "poor" prognosis, therapy should be minimally toxic, for palliative purposes only. For patients with a "good" prognosis, intensive treatment is recommended with combinations comprised from C, A, V, VP-16, and CP. For patients obtaining a remission, consolidation is recommended with radiation treatment if this has not been part of the initial induction program with or without chemotherapy. Consolidation may be intensified by using high-dose chemotherapy in association with autologous bone marrow transplantation or possibly the use of hematopoietic growth factors. The major problem limiting further improvements in survival in this disease remains the emergence of drug resistance, which is now the subject of intensive investigations both in the laboratory and in the clinic.