The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance

Abstract

Acute respiratory distress syndrome (ARDS) continues to be a major healthcare problem, affecting >190 000 people in the USA annually, with a mortality of 27–45%, depending on the severity of the illness and comorbidities. Despite advances in clinical care, particularly lung protective strategies of mechanical ventilation, most survivors experience impaired health-related quality of life for years after the acute illness. While most patients survive the acute illness, a subset of ARDS survivors develops a fibroproliferative response characterised by fibroblast accumulation and deposition of collagen and other extracellular matrix components in the lung. Historically, the development of severe fibroproliferative lung disease has been associated with a poor prognosis with high mortality and/or prolonged ventilator dependence. More recent studies also support a relationship between the magnitude of the fibroproliferative response and long-term health-related quality of life. The factors that determine which patients develop fibroproliferative ARDS and the cellular mechanisms responsible for this pathological response are not well understood. This article reviews our current understanding of the contribution of pulmonary dysfunction to mortality and to quality of life in survivors of ARDS, the mechanisms driving pathological fibroproliferation and potential therapeutic approaches to prevent or attenuate fibroproliferative lung disease.

Allograft inflammatory factor-1 in the pathogenesis of bleomycin-induced acute lung injury

“…A study has reported that fibroproliferative activity is present in the early phase in lungs of patients with ARDS (30). Histology has also indicated that fibroproliferation is present in the early phase in the lungs of patients with ARDS (31,32).…”

Mechanisms of Lung Fibrosis Resolution

“…14 Studies assessing long-term outcomes in acute respiratory distress syndrome survivors report persistent lung dysfunction and computed tomographic abnormalities in only subsets of subjects, suggesting significant fibrosis resolution for most patients. 15,16 In summary, animal models of fibrosis in the kidney, liver, and lung indicate the potential to reverse a substantial fibrotic burden and return to near predisease function after the fibrogenic insult is extinguished. The concept of fibrosis reversal in solid organs is supported in human disease, where liver cirrhosis caused by hepatitis infection demonstrates marked resolution after antiviral treatment.…”

Overview of current lung imaging in acute respiratory distress syndrome

“…Although there is a tendency to divide the types of organisation in different entities, the lung's response to injury is quite limited, with a similar pattern regardless of the underlying cause [9]. While excessive fibroproliferation is clearly detrimental, an appropriate fibroproliferative response may have beneficial consequences in guiding lung repair; bronchoscopy with bronchoalveolar lavage as well as CT scan could both add useful information for the early detection of fibroproliferative activity [58].…”