Idiopathic pulmonary fibrosis

1
Idiopathic pulmonary fibrosis
2
Doctors
Others
Cardiologists
3
Diffuse interstitial lung diseases (ILD)
4
Diffuse interstitial lung diseases (ILD)

• Breathlessness and/or cough
• Bilateral abnormal opacities on chest X-ray or CT
  scan
• Restrictive defect

5
Diffuse interstitial lung diseases (ILD)
6
Diffuse interstitial lung diseases (ILD)
DPLD of known cause (drugs or association,
collagen vascular disease)
Idiopathic interstitial pneumonias
Granulomatous DPLD (sarcoidosis)
Other forms of DPLD (LAM, etc.)
7
Idiopathic interstitial pneumonias

• Diffuse parenchymal lung diseases of unknown
  etiology
• Expansion of the interstitial compartment with an
  inflammatory infiltrate

8
(No Transcript)
9
Idiopathic pulmonary fibrosis
10
Desquamative interstitial pneumonia
Respiratory bronchiolitis-associated
interstitial lung disease
Acute interstitial pneumonia
Lymphocytic interstitial pneumonia
Cryptogenic organizing pneumonia
Non-specific interstitial pneumonia
11
Idiopathic pulmonary fibrosis

• Epidemiology
• Estimated prevalence of 14 to 43 per 100,000
• Estimated incidence of 7 to 16 per 100,000
• Usually 5070 years
• Men gt Women
• Sporadic

12
(No Transcript)
13
Idiopathic pulmonary fibrosis

• Pathogenesis
• Chronic fibroproliferation little or no
  inflammation

14
Pathogenesis of IPF
Migration
Multiple microinjuries
Fibroblastic foci

Reexpansion of the collapsed airspace
15
Idiopathic pulmonary fibrosis

• History
• Slowly progressive exertional dyspnea
  nonproductive cough
• 10 have acute exacerbation increasing
  shortness of breath, worsening gas exchange and
  new ground glass infiltrate on CXR

Kim, DS, Park, JH, Park, BK, et al. Acute
exacerbation of idiopathic pulmonary fibrosis
frequency and clinical features. Eur Respir J
2006 27143.
16
Idiopathic pulmonary fibrosis

• Physical Examination
• Bibasilar late inspiratory crackles (Velcro
  rales)
• Cardiac examination usually normal
• 4075 clubbing of the digits ? advanced
• Cyanosis ? advanced

17
Idiopathic pulmonary fibrosis

• Chest X-ray
• Diffuse reticular opacities, predilection for the
  lower lobes
• Coarse reticular pattern or multiple cystic or
  honeycombed areas ? advanced
• Plural involvement is uncommon

18
Chest X-ray of IPF
19
Chest X-ray of IPF
20
Idiopathic pulmonary fibrosis

• Pulmonary Function Studies
• Elastic resistance ? total lung capacity (TLC),
  functional residual capacity (FRC), residual
  volume (RV)
• Flow resistance ? FEV1 FVC, FEV1/FVC normal or
  ?
• Gas Exchange perform exercise testing with
  serial measurement of arterial blood gases

21
Idiopathic pulmonary fibrosis

• HRCT
• Differentiation of IPF from other interstitial
  lung disease
• For biopsy information

22
Idiopathic pulmonary fibrosis

• HRCT
• Early peripheral and subpleural reticular
  opacities
• Advanced more diffuse reticualr pattern
  prominent in the lower lung zone, thickened
  interlobular septa and intralobular lines, often
  with honeycombing, traction bronchiectasis and
  subpulral fibrosis

23
HRCT of IPF
24
Idiopathic pulmonary fibrosis

• Surgical lung biopsy
• The most definitive method of establishing a
  diagnosis
• Open or thoracoscopic

25
Idiopathic pulmonary fibrosis

• Histology
• Usual interstitial pneumonia (UIP)
• Dense fibrosis causing remodeling of lung
  architecture with frequent "honeycomb" fibrosis
• Fibroblastic foci typically scattered at the
  edges of dense scars
• Patchy lung involvement
• Frequent subpleural and paraseptal distribution

26
Diagnosis of IPF without surgical lung biopsy

• Major criteria

• Minor criteria

• Age gt50 years
• Insidious onset of otherwise unexplained dyspnea
  or exertion
• Duration of illness gt3 months
• Bibasilar, inspiratory crackles (dry or
  "Velcro"-type in quality)

• Exclusion of other known causes of ILD
• Abnormal pulmonary function studies that include
  evidence of restriction and impaired gas exchange
• Bibasilar reticular abnormalities with minimal
  ground glass opacities on HRCT scans
• Transbronchial lung biopsy or BAL showing no
  features to support an alternative diagnosis

• All major 3 minor ? clinical diagnosis of
  IPF

27
Diagnosis of IPF

• Histopathologic diagnosis

• Clinical diagnosis

• Sensitivity62
• Specificity97

• Sensitivity71
• Specificity75

28
Diagnosis of IPF
29
Idiopathic pulmonary fibrosis

• Medical treatment
• No known curative therapy

30
Idiopathic pulmonary fibrosis

• Medical therapy
• Corticosteroids
• Cytotoxic agents
• Antifibrotic agents
• Others

31
Treatment of IPF

• Corticosteroids
• Most commonly used, with other agents
• ? progression from inflammation to fibrosis
• No survival advantage with monotherapy or in
  combination ? chronic fibroproliferation little
  or no inflammation
• S/E insomnia, weight gain, skin changes, or
  irritability

32
Treatment of IPF

• Cytotoxic agents-- azathioprine
• Azathioprine corticosteroids are standard of
  care
• Better lung function and decreased mortality (43
  vs. 77), but not statistically significant
• S/E GI symptoms

Raghu, G, Depaso, WJ, Cain, K, et al.
Azathioprine combined with prednisone in the
treatment of idiopathic pulmonary fibrosis A
prospective, double-blind randomized,
placebo-controlled clinical trial. Am Rev Respir
Dis 1991 144291.
33
Treatment of IPF

• Cytotoxic agents-- cyclophosphamide
• Second-line drug as condition ? with
  azathioprine corticosteroids
• S/E ? all hematologic cell lines
• More patients are stable or improved (38 vs.
  23) and fewer death (14 vs. 45), but not
  statistically significant

Johnson, MA, Kwan, S, Snell, NC, et al.
Randomized controlled trial comparing prednisone
along with cyclophosphamide and low dose
prednisone in combination in cryptogenic
fibrosing alveolitis. Thorax 1989 44280.
34
Treatment of IPF

• Antifibrotic agents--Interferon-gamma

35
Pathogenesis of IPF
Endothelial cells
IL-1, MCP, TNFa, etc.
Proliferation
Migration


IFNg

Inflammatory cells
TGFb, PDGF, etc.
Fibroblasts
Differentiation

damage
Epithelial cells (collapsed airspace)
Multiple microinjuries
Myofibroblasts
damage
Reepithelialization
damage
Basement membrane
Interstitium alveolar spaces
Gelatinases
Collagen

Reexpansion of the collapsed airspace
Permits migration
36
Treatment of IPF

• Antifibrotic agents--Interferon-gamma
• Significant better TLC and oxygenation with IFNg
  prednisolone
• Patients treated with IFN gamma-1b had similar
  survival to those treated with placebo
• S/E flu-like symptoms

Ziesche, R, Hofbauer, E, Wittmann, K, et al. A
preliminary study of long-term treatment with
interferon gamma-1b and low-dose prednisolone in
patients with idiopathic pulmonary fibrosis. N
Engl J Med 1999 3411264.
37
Treatment of IPF

• Antifibrotic agents--Interferon-gamma
• Significant better TLC and oxygenation with IFNg
  prednisolone
• Patients treated with IFN gamma-1b had similar
  survival to those treated with placebo
• S/E flu-like symptoms

Raghu, G, Brown, KK, Bradford, WZ, et al. A
placebo-controlled trial of interferon gamma-1b
in patients with idiopathic pulmonary fibrosis. N
Engl J Med 2004 350125
38
Treatment of IPF

• Antifibrotic agents--pirfenidone

39
Pathogenesis of IPF

Pirfenidone

40
Treatment of IPF

• Antifibrotic agents--pirfenidone
• May help to stabilize lung function
• S/E rash, abdominal discomfort, dyspepsia,
  anorexia, nausea, fatigue, and lethargy.

Raghu, G, Johnson, C, Lockhart, D, Mageto, Y.
Treatment of idiopathic pulmonary fibrosis with a
new antifibrotic agent, pirfenidone. Results of a
prospective, open-label phase II study. Am J
Respir Crit Care Med 1999 1591061.
41
Treatment of IPF

• OthersAcetylcysteine
• Oxidant-antioxidant imbalance may contribute to
  the IPF

42
Pathogenesis of IPF
Endothelial cells
IL-1, MCP, TNFa, etc.
Proliferation
Migration


Inflammatory cells
TGFb, PDGF, etc.
Fibroblasts
Differentiation


damage
Epithelial cells (collapsed airspace)
Multiple microinjuries
Myofibroblasts
damage
Reepithelialization
damage
Basement membrane
Interstitium alveolar spaces
Gelatinases
Collagen

Reexpansion of the collapsed airspace
Permits migration
43
Treatment of IPF

• OthersAcetylcysteine
• Mortality was not significantly changed
• S/E GI symptoms

Demedts, M, Behr, J, Buhl, R, et al. High-dose
acetylcysteine in idiopathic pulmonary fibrosis.
N Engl J Med 2005 3532229.
44
Idiopathic pulmonary fibrosis

• Prognosis
• Most patients die of respiratory failure within 5
  to 10 years after diagnosis.
• 5 year survival after diagnosis 2030
• Median survival after diagnosis 3 years

45
Treatment of IPF

• Lung transplantation
• 32 single lung transplants and 13 bilateral lung
  transplants
• Perioperative mortality 8.9
• 1 and 5 years survival 75.5 and 53.5, better
  than medical therapy
• Offer a viable therapy for patients with IPF

Meyers, BF, Lynch, JP, Trulock, EP, et al. Single
versus bilateral lung transplantation for
idiopathic pulmonary fibrosis A ten-year
institutional experience. J Thorac Cardiovasc
Surg 2000 12099.
46
Treatment of IPF

• Lung transplantation
• lt 60 years, single lung transplantation (SLT) was
  associated with improved survival compared to BLT
• SLT has been the standard procedure for patients
  with IPF

Meyer, DM, Edwards, LB, Torres, F, et al. Impact
of recipient age and procedure type on survival
after lung transplantation for pulmonary
fibrosis. Ann Thorac Surg 2005 79950.
47
Treatment of IPF

• Lung transplantation
• High-dose corticosteroid therapy may be
  associated with ? survival after lung
  transplantation
• Prednisone use gt20 mg/day as a relative
  contraindication

McAnally, KJ, Valentine, VG, LaPlace, SG, et al.
Effect of pre-transplantation prednisone on
survival after lung transplantation. J Heart Lung
Transplant 2006 2567
48
The End