Clinical review: Idiopathic pulmonary fibrosis acute exacerbations - unravelling Ariadne's thread

Critical Care Clinical review: Idiopathic pulmonary fibrosis acute exacerbations - unravelling Ariadne's thread Spyros A Papiris 0 3 Effrosyni D Manali 0 3 Likurgos Kolilekas 0 3 Konstantinos Kagouridis 0 3 Christina Triantafillidou 0 3 IraklisTsangaris 2 Charis Roussos 1 0 2nd Pulmonary Department, 'Attikon' University Hospital, Athens Medical School, National and Kapodistrian University of Athens , 1 Rimini Street, 12462, Haidari , Greece 1 'Thorax' foundation and 'Evangelismos' General Hospital , 3 Ploutarchou Street, 10675 Athens, Greece and 45-47 Yspilantou Street, 10676 Athens , Greece 2 2nd Department of Critical Care, 'Attikon' University Hospital, Athens Medical School, National and Kapodistrian University of Athens , 1 Rimini Street, 12462, Haidari , Greece 3 2nd Pulmonary Department, 'Attikon' University Hospital, Athens Medical School, National and Kapodistrian University of Athens , 1 Rimini Street, 12462, Haidari , Greece Idiopathic pulmonary fibrosis (IPF) is a dreadful, chronic, and irreversibly progressive fibrosing disease leading to death in all patients affected, and IPF acute exacerbations constitute the most devastating complication during its clinical course. IPF exacerbations are subacute/acute, clinically significant deteriorations of unidentifiable cause that usually transform the slow and more or less steady disease decline to the unexpected appearance of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) ending in death. The histological picture is that of diffuse alveolar damage (DAD), which is the tissue counterpart of ARDS, upon usual interstitial pneumonia, which is the tissue equivalent of IPF. ALI/ ARDS and acute interstitial pneumonia share with IPF exacerbations the tissue damage pattern of DAD. 'Treatment' with high-dose corticosteroids with or without an immunosuppressant proved ineffective and represents the coup de grace for these patients. Provision of excellent supportive care and the search for and treatment of the 'underlying cause' remain the only options. IPF exacerbations require rapid decisions about when and whether to initiate mechanical support. Admission to an intensive care unit (ICU) is a particular clinical and ethical challenge because of the extremely poor outcome. Transplantation in the ICU setting often presents insurmountable difficulties. - death in all patients affected, and IPF exacerbations constitute the most devastating complication during its course [1-6]. IPF exacerbations appear more frequently than previously thought and represent a common terminal event [7,8]. IPF lacks effective treatment, and survival is approximately 3 years [2,6,9,10]. Best supportive care constitutes the only attainable therapeutic strategy and includes a more or less effective attempt to alleviate symptoms and prevent complications and a far more efficacious interventional approach consisting of the withdrawal of corticosteroids and immunosuppressants (commonly administered by clinicians) that are ineffective and harmful [2,9,11]. Transplantation is the only therapeutic option [12]. IPF exacerbations represent acute and clinically significant deteriorations of unidentifiable cause, transforming the slow and more or less steady disease decline [13] to the unexpected appearance of acute lung injury/ acute respiratory distress syndrome (ALI/ARDS) ending in death [6,14]. Occasionally, IPF exacerbations may present in a previously apparently healthy or minimally symptomatic individual and might represent acute progression of an unsuspected or undiagnosed early IPF [3,15]. Definition criteria include IPF diagnosis, unexplained worsening or development of dyspnea within 30 days, new lung infiltrates (mainly ground glass upon honeycomb), and exclusion of any identifiable or treatable cause of lung injury [6]. Surgical lung biopsy per se constitutes a risk factor for their development [16] but, when performed for the investigation of the etiology of exacerbations or in autopsies, discloses a histological picture of diffuse alveolar damage (DAD), which is the ARDS tissue counterpart, upon usual interstitial pneumonia (UIP), which is the IPF tissue equivalent [4,8,17-19]. In IPF, anachronic and reiterative epithelial injury and loss of the alveolar-capillary integrity constitute the initial event and the point of no return that trigger aberrant repair pathways leading to inappropriate, progressive, and heterogeneous lung scarring (UIP) [20-22]. DAD upon UIP might represent massive epithelial and endothelial injury of the lung areas yet preserved from scarring [9,23]. Putative initiators of IPF include viruses, cigarette smoke, gastroesophageal reflux, and occupational exposure to wood and metals [24,25]. Aging, by reducing efficiency in repairing damage, represents a cofactor [26]. The development of DAD upon UIP may relate to a clinically occult infection [14,27], aspiration, or a distinct pathobiological manifestation of IPF [6]. Treatment with high-dose corticosteroids with or without an immunosuppressant proved ineffective and represents the coup de grace for these patients [8]. IPF exacerbations require rapid decisions about when and whether to initiate mechanical support. However, the consideration of admission to an intensive care unit (ICU) is a particular clinical and ethical challenge because of poor outcome [28-32]. Transplantation in this setting presents insurmountable difficulties. Epidemiology and risk factors The incidence of IPF exacerbations varies greatly between studies (from 8.5% to 60%) mainly because of differences in their design [3-6,8,14,16,19,28,29,31-35]: (a) case series and retrospective cohorts [4,17-19], (b) randomized controlled trials of specific treatments for IPF [3], (c) autopsy reviews [8,16,33], and (d) retrospective reviews of ICU admissions [28,29,31,32]. Discrepancies in reported frequencies should be attributed to the difficulty in strictly respecting the definition criteria especially concerning symptom duration (less than 4 weeks) and the definite exclusion of infection [3,6,36]. IPF exacerbations do not appear to be linked to disease duration, functional derangement, age, gender, or smoking history [4,29], although further studies are necessary to confirm early development as well as lack of association with immunosuppression [37]. Exacerbation mortality approaches 100%, questioning the need for ICU admission [2-6,8,14, 16,19,28,29,31-34]. Etiologic and pathogenetic considerations The definition of IPF exacerbations after excluding identifiable causes of lung injury implies that in idiopathic pulmonary fibrosis, idiopathic exacerbations occur [3,4,6]. However, in clinical practice, when such a patient is referred to the emergency department (ED), the attending clinician has to face one of three clinical scenarios [38] (Figure 1). The first scenario is the case in which the physical evolution of IPF comes to the final end in which spontaneous breathing becomes unsupport (...truncated)