Usual Interstitial Pneumonia and Acute Exacerbation. Andrew Synn, HMSIII Gillian Lieberman, MD, BIDMC Radiology November 2008

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1 Usual Interstitial Pneumonia and Acute Exacerbation Andrew Synn, HMSIII Gillian Lieberman, MD, BIDMC Radiology November 2008

2 Agenda Brief clinical history of our patient Review of usual interstitial pneumonia/idiopathic pulmonary fibrosis Radiologic approach to evaluating suspected idiopathic pulmonary fibrosis Clinical course of our patient and imaging of acute exacerbation of idiopathic pulmonary fibrosis 2

3 Our Patient JB: Clinical History JB is a 60M with a one-year history of progressive SOB and dry cough Pulse oximetry during exercise demonstrated desaturation to 84% PFTs showed mild/moderate restriction CXR was obtained 3

4 Our Patient JB: Initial chest radiograph Findings: Slightly increased interstitial lung markings Low lung volumes (arrow on 8 th posterior rib) Given clinical suspicion for IPF, recommend CT PA chest radiograph, patient JB. Image source: BIDMC (PACS) 4

5 UIP: Terminology and Clinical Terminology: Presentation Usual interstitial pneumonia (UIP) is a histopathologic term Idiopathic pulmonary fibrosis (IPF) is the clinical syndrome associated with idiopathic UIP Common clinical presentation: Male, > 50 y.o. Progressively worsening dyspnea and nonproductive cough over >6 mo Dry, bibasilar, inspiratory rales Restrictive physiology on PFTs 5

6 Pathogenesis: UIP: Pathogenesis Unknown primary insult that leads to fibrotic response Sequence of events: currently under revision Previously thought to be due to chronic inflammation leading to widespread fibrosis However, inflammation is not a prominent histopathologic finding in the large majority of cases of IPF/UIP Currently thought to be result of repeated acute lung injury with aberrant wound healing, and resultant exuberant fibroblastic proliferation 6

7 UIP: Risk Factors Risk Factors: Age Rare below age of 40 67% of patients are over 60 years of age at presentation Male gender Caucasian Smoking Risk appears to increase with increasing pack-year history Familial syndromes have been described (rare) 7

8 UIP: Treatment and Prognosis Treatment: For many years, corticosteroids were mainstay of therapy However, IPF is poorly responsive to steroids Correlates with recent findings that IPF shows only minimal inflammation Anti-fibrotic agents currently under investigation Pirfenidone, bosentan Prognosis: generally quite poor Mean survival 2-3 years after diagnosis 20% 5-year survival rate 8

9 UIP: Diagnosis and DDx Diagnosis: Radiography plays an important role! UIP may be diagnosed without biopsy in patients with characteristic history, physical, and imaging findings Correct diagnosis is important as other causes of fibrosis may be treatable and/or reversible Surgical biopsy required for definitive diagnosis DDx: Diseases that may have UIP pattern (but are not idiopathic): Drug-induced fibrosis, environmental exposures, infections, and connective tissue diseases Other diseases: NSIP, hypersensitivity pneumonitis 9

10 UIP: Menu of Radiographic Tests Menu of tests used to approach suspected IPF: CXR Chest CT 10

11 CXR for Evaluating UIP Chest radiograph remains an appropriate initial radiographic test for suspected IPF Cost-effective, widely available, less radiation Sensitive Only 5-10% of interstitial lung diseases with have normal chest radiograph throughout course May be normal early in disease process Non-specific findings In general, CXR correlates poorly with histopathologic pattern, anatomic distribution of disease, and the severity of disease 11

12 Companion Patient #1: UIP on CXR Increased interstitial markings (nonspecific) Peripheral honeycombing (specific for UIP) Apico-basilar gradient (relatively specific for UIP) PA chest radiograph, companion pt. #1. Image source: BIDMC (PACS) 12

13 Chest CT for Evaluating UIP For further characterization of UIP, noncontrast chest CT is the most sensitive and specific radiologic modality High resolution CT (HRCT) uses very thin image slices (1mm) to obtain higher resolution of the lung parenchyma In appropriate clinical setting, HRCT findings may be sufficiently characteristic to preclude the need for surgical biopsy in IPF 13

14 Characteristic Findings of UIP on Chest CT Characteristic findings: Reticular opacities Subpleural, macrocystic honeycombing and traction bronchiectasis Apicobasilar gradient Heterogeneity Findings that suggest alternative diagnosis: Lack of any of above findings Extensive ground glass opacities Nodularity 14

15 Our Patient JB: UIP on Axial CT Subpleural honeycombing Traction bronchiectasis Reticular opacities Focal ground glass opacities Enlarged mediastinal LN Large areas of relatively preserved lung Non-contrast, axial chest CT, patient JB. Image source: BIDMC (PACS) 15

16 Our Pt JB: UIP on Axial CT Apico-basilar gradient is clearly demonstrated on inferior section Subpleural honeycombing Reticular opacities Ground glass opacities Non-contrast, axial chest CT, patient JB. Image source: BIDMC (PACS) 16

17 Companion Patient #2: Severe UIP on Axial CT Honeycombing Reticular opacities Extensive ground glass opacities Traction bronchiectasis Non-contrast, axial chest CT, companion pt. #2 Image source: Lynch DA, et. al. 17

18 Companion Patient #3: UIP on Coronal CT Honeycombing Reticular opacities Ground glass opacities Traction bronchiectasis Obvious apico-basilar gradient Non-contrast, coronal chest CT, companion pt. #3 Image source: Mueller-Mang C, et. al. 18

19 Our Patient JB: Clinical Course and Deterioration Mr. JB was enrolled in an investigational study and remained clinically stable for 8 months However, over a three week period, Mr. JB experienced a rapid decline in respiratory status Oxygen saturation low 80s on 5L O2 NC Admitted to the BIDMC MICU 19

20 Our Patient JB: Acute Exacerbation of UIP on Axial CT Contrast-enhanced, axial chest CT, patient JB Image source: BIDMC (PACS) More extensive honeycombing Increased reticular opacities and central involvement Substantial extension of diffuse ground glass opacity affecting all lobes of the lung 20

21 Our Patient JB: Acute Exacerbation of UIP on Sagittal CT Sagittal reconstruction Similar findings to previous image Marked loss of lung volumes Contrast-enhanced, sagittal chest CT, patient JB Image source: BIDMC (PACS) 21

22 Acute Exacerbation of IPF Abrupt (< 4 weeks) and unexpected worsening of underlying lung disease without obvious cause Rule out infections, PE, PTX, or CHF Mortality during episode % May account for up to 50% of deaths attributable to IPF Chest CT findings: new, diffuse opacities Pattern of diffuse alveolar damage on background of UIP 22

23 Summary (1) IPF is a chronic, fibrosing interstitial pneumonia of unknown cause Has a characteristic clinical and radiographic presentation CXR is the usual initial imaging modality Non-specific findings HRCT Specific and sensitive for UIP 23

24 Summary (2) Classic findings on HRCT: Reticular opacities Honeycombing Traction bronchiectasis Apico-basilar gradient Heterogeneity These findings on HRCT are diagnostic for UIP when combined with appropriate clinical presentation 24

25 Summary (3) Acute exacerbation of IPF: Rapid decline in pulmonary function Findings on HRCT: Diffuse, rapid worsening of reticular and alveolar opacities Pattern of DAD on the background of IPF Very high mortality rate 25

26 Acknowledgments Dr. Peter LaCamera of BIDMC Pulmonology for his help in case acquisition and radiographic interpretation Dr. David Roberts of BIDMC Pulmonology for his help in case acquisition Dr. Gillian Lieberman, BIDMC Radiology Maria Levantakis, BIDMC Radiology Larry Barbaras, Webmaster 26

27 References Chesnutt MS, Murray JA, Prendergrast TJ. "Chapter 9. Pulmonary Disorders" (Chapter). McPhee SJ, Papadakis MA, Tierney LM, Jr.: Current Medical Diagnosis & Treatment Husain AN, Kumar V. Chapter 15. The Lung (Chapter). Kumar V, Abbas AK, Fausto N: Robbins and Cotran: Pathologic Basis of Disease, 7th Edition. Johkoh T, et. al. Idiopathic Interstitial Pneumonias: Diagnostic Accuracy of Thin-Section CT in 129 Patients. Radiology. 1999;211: Kim DS, Collard HR, King TE. Classification and Natural History of the Idiopathic Interstitial Pneumonias. Proc Am Thorac Soc. 2006;3: Lynch DA, et. al. Idiopathic Interstitial Pneumonias: CT Features. Radiology. 2005;236: Martinez FJ, et. al. The Clinical Course of Patients with Idiopathic Pulmonary Fibrosis. Ann Intern Med. 2005;142: Mueller-Mang C, Grosse C, Schmid K, Stiebellehner L, Bankier AA. What Every Radiologist Should Know about Idiopathic Interstitial Pneumonias. Radiographics. 2007;27: Prendergast TJ, Ruoss SJ. "Chapter 9. Pulmonary Disease" (Chapter). McPhee SJ, Ganong WF: Pathophysiology of Disease, 5th Edition. 27

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