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

Abstract

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.

Figures

Figure 1

Clinical scenarios for the idiopathic pulmonary fibrosis (IPF) patient presenting in the emergency department with subacute/acute dyspnea. (a) Progression to the final end of the disease. (b) 'True' IPF exacerbation. (c) IPF exacerbation due to treatable causes. Acute exacerbation (AE) criteria are presented in [7]. For details about laboratory tests and blood/sputum/bronchoalveolar lavage (BAL) tests, see the 'Clinical and laboratory assessment' section. Cardiac echo, cardiac echocardiography; CTPA, computed tomography pulmonary angiography; HRCT, high-resolution computed tomography; ICU, intensive care unit; PE, pulmonary embolism; PH, pulmonary hypertension; PNX, pneumothorax; proBNP, pro-brain natriuretic peptide.

Figure 2

Idiopathic pulmonary fibrosis (IPF) progressing to the final end. Roentgenograms of a 57-year-old female (a) 6 years before diagnosis (normal) and (b) at the time of diagnosis of IPF. The latter reveals a bilateral reticular pattern. (c) High-resolution computed tomography shows mild reticulation. (d) Roentgenogram of the patient 24 months after diagnosis demonstrates worsening of the reticular pattern superimposed on a ground-glass pattern. The patient was admitted with severe breathlessness and productive cough. Her symptoms were severely aggravated in the last 9 months and she was hospitalized many times. She had received corticosteroids and mycophenolate mofetil, which were discontinued months prior to this roentgenogram because of lower respiratory tract infections. At the time of the roentgenogram, she was receiving only proton pump inhibitors. She deteriorated further despite best supportive care and died while on palliation treatment. Our putative diagnosis was IPF progressing to the final end.

Figure 3

Idiopathic pulmonary fibrosis (IPF) 'idiopathic' exacerbation. (a-c) High-resolution computed tomography in an IPF patient at three different parenchymal levels shows diffuse areas of ground-glass attenuation, bronchiolectasis, and honeycombing. The patient was a 71-year-old male physician recently diagnosed with IPF. He was self-administering high-dose oral corticosteroids for months and presented severe deterioration of dyspnea and cough and developed severe acute respiratory failure. Despite empirical treatment with broad-spectrum antimicrobials, he deteriorated and was intubated. He died in the intensive care unit 4 weeks later. Extensive work-up disclosed no causative factors.

Figure 4

Exacerbation of idiopathic pulmonary fibrosis (IPF) due to treatable causes. (a) High-resolution computed tomography (HRCT) shows minimal evidence of apical interstitial lung disease. (b) HRCT shows, at the lung bases, ground-glass opacities upon extensive peripheral thickening of intralobular septa. The patient was a 65-year-old male with IPF and initiated treatment with high doses of corticosteroids. (c) Four months later, HRCT denotes diffuse ground-glass with irregular reticulation. Note the extensive lipomatosis of the mediastinum due to chronic steroid use. Owing to deterioration of dyspnea, he was admitted to another hospital, where bronchoalveolar lavage (BAL) was performed and the immunosuppressive treatment was intensified. A few weeks later, he was admitted to our department with respiratory failure, severe corticosteroid-related myopathy, diabetes mellitus, severe dyspnea, and purulent sputum. Clinical examination disclosed herpes simplex virus keratitis in the left eye, and BAL cultures grew positive for Pseudomonas aeruginosa. Corticosteroids were tapered, and antimicrobial and antiviral treatment was initiated. Both eye and lower respiratory tract infections subsided, and the patient was discharged home a few weeks later. (d) Eighteen months after the exacerbation, the ground-glass opacities completely resolved as did the lipomatosis of the mediastinum. The patient is still alive and at home.

Figure 5

Different clinical settings characterized by diffuse alveolar damage (DAD) pathology. This non-proportional figure denotes the incoherence of the clinical significance of acute respiratory distress syndrome (ARDS), acute interstitial pneumonia (AIP), and idiopathic pulmonary fibrosis (IPF) exacerbations in which DAD, despite being the common denominator, develops upon different histology substrates (UIP in IPF exacerbations, normal lungs in AIP, and normal or diseased lungs in ARDS) and, according to current definitions, presents at different time intervals: 7 days for ARDS, 4 weeks for IPF exacerbations, and 2 months for AIP. This incoherence led also to a different pharmacologic approach, which proved to be unsuccessful at least in AIP and in IPF true exacerbations. ALI, acute lung injury.