Acute exacerbation of idiopathic pulmonary fibrosis: lessons learned from acute respiratory distress syndrome?

Abstract

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by progressive loss of lung function and poor prognosis. The so-called acute exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical ventilation in the intensive care unit (ICU). AE-IPF shares several pathophysiological features with acute respiratory distress syndrome (ARDS), a very severe condition commonly treated in this setting.A review of the literature has been conducted to underline similarities and differences in the management of patients with AE-IPF and ARDS.During AE-IPF, diffuse alveolar damage and massive loss of aeration occurs, similar to what is observed in patients with ARDS. Differently from ARDS, no studies have yet concluded on the optimal ventilatory strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding, a protective ventilation strategy with low tidal volume and low driving pressure could be recommended similarly to ARDS. The beneficial effect of high levels of positive end-expiratory pressure and prone positioning has still to be elucidated in AE-IPF patients, as well as the precise role of other types of respiratory assistance (e.g., extracorporeal membrane oxygenation) or innovative therapies (e.g., polymyxin-B direct hemoperfusion). The use of systemic drugs such as steroids or immunosuppressive agents in AE-IPF is controversial and potentially associated with an increased risk of serious adverse reactions.Common pathophysiological abnormalities and similar clinical needs suggest translating to AE-IPF the lessons learned from the management of ARDS patients. Studies focused on specific therapeutic strategies during AE-IPF are warranted.

Keywords: Acute respiratory distress syndrome; Diffuse alveolar damage; Idiopathic pulmonary fibrosis; Mechanical ventilation; Respiratory failure.

Fig. 1

During AE-IPF, lung inflammation is driven by upregulation of macrophage activation pathways. M1 pathway classically activated by Th1 cytokines (IFN-γ) leads to increased IL-8 and CXCL1 expression and neutrophil recruitment though CXCR2 receptor. M2 pathway activated by type II alveolar epithelial cell injury might perpetuate lung fibrosis boosting collagen deposition, fibroblast proliferation, and epithelial–mesenchymal transition. AE-IPF acute exacerbation of idiopathic pulmonary fibrosis, DAD diffuse alveolar damage, IL interleukin, INF interferon

Fig. 2

Mechanisms of ventilation-induced lung injury in patients with AE-IPF. El elastance of lung, Etot elastance of respiratory system, Paw airway pressure

Fig. 3

a Patient with AE-IPF during assisted spontaneous breathing with end-expiratory positive pressure of 4 cmH₂O and pressure support of 10 cmH₂O. Note ΔPes of 30 cmH₂O due to respiratory drive hyperactivity. b Thorax CT scan performed on same patient as (a), showing anterior left pneumothorax probably due to high transpulmonary pressure. Note homogeneous increase of parenchymal density. c Patient with AE-IPF during assisted spontaneous breathing with end-expiratory positive pressure of 4 cmH₂O and pressure support of 10 cmH₂O. Note ΔPes of 5 cmH₂O due to normal activation of respiratory drive. d Thorax CT scan performed on same patient as (b) showing nonhomogeneous opacities in lung parenchyma. Pes esophageal pressure. Paw airway pressure