Progress in the management of IPF-related acute exacerbations: a goal for patients, respirologists and intensivists

To the Editor:

We read with interest the illuminating review on the pharmacological management of idiopathic pulmonary fibrosis (IPF) recently published in the European Respiratory Journal [1]. Raghu [1] did not detail the pharmacological management of acute exacerbations (AEs). AEs often lead to the question of whether to transfer the patient to the intensive care unit (ICU) for respiratory support, whether this is invasive mechanical ventilation (IMV) or not, and to the choice of adequate pharmacological agent(s) [2]. This is a critical issue for respirologists and intensivists as it is estimated that ∼3 million patients suffer from this disease worldwide [3]. When making the decision of whether to transfer to the ICU, it should be kept in mind that ≤46% of IPF-related deaths are preceded by an AE, with the majority of patients dying within the first month and most of the remaining within a year [2, 4].

The 2011 guidelines from the American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) suggested that IMV might only be reasonable in a minority of patients (weak recommendation, low-quality evidence) [5]. This point was not discussed in the updates published in 2015 [6]. French experts published their recommendations in 2017 [7]. ICU management in a patient with IPF-related AEs appears to be justified when there is a pulmonary transplant, when a reversible cause of exacerbation has been identified, or if the research has not been carried out [7]. It should only be used after discussion with the patients and their relatives (ideally in advance).

The identification of patients who can best benefit from admission to the ICU remains a challenge. The Glasgow Prognostic Score was recently demonstrated to be advantageous in the classification of patients with IPF-related AEs into three disease stages with distinct mortality risk over 1–3 years [8]. Its usefulness in the decision to transfer the patient to the ICU requires validation in prospective cohorts performed in the era of new pharmacological treatments described by Raghu [1].

The data on the symptomatic management of IPF-related AEs (i.e. respiratory support) were recently reviewed by Kondoh et al. [2]. Only four out of five studies published since 2008 included patients in the ICU (182 patients). Data on oxygenation with “new” techniques are lacking. Humidified high-flow nasal cannula oxygen could perhaps be used for long periods, possibly when waiting for lung transplantation [9]. Recent findings suggest that noninvasive ventilation failure could be deleterious as it increases the risk of ventilator-induced lung injury [10]. Extracorporeal oxygenation seems to be available to patients who are waiting for an impending lung transplant [11]. These only detail the supportive care and not the medical advances described by Raghu [1], which are, in our opinion, fundamental.

As briefly discussed, research continues in the pharmacological management of IPF-related AEs [1]. It still typically includes high-dose corticosteroids and/or immunosuppressant and broad-spectrum antibiotics, despite the scarcity of data supporting the usefulness of these therapies [2]. A placebo-controlled randomised phase III trial evaluating the efficacy of cyclophosphamide in conjunction with corticosteroids in IPF-related AEs was recently approved in France (EXAFIP; registered at ClinicalTrials.gov with the identifier number NCT02460588). A number of other novel therapeutic approaches (nintedanib, pirfenidone, polymyxin B direct haemoperfusion, thrombomodulin, rituximab, plasma exchange, intravenous immunoglobulin) have been evaluated or are still being evaluated; however, preliminary results are disappointing or are based on too small series [2]. We believe that Raghu [1] emphasises above all the lack of relevant data on the pharmacological management of IPF-related AEs and the need for further studies.