Idiopathic Pulmonary Fibrosis

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Idiopathic Pulmonary Fibrosis
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Royal (Dick) School of Veterinary Studies
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Hospital For Small Animals
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Summerhall Site-Edinburgh
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The Highlands of Scotland
Poltallach Grave Stones
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Westies on the Web
Austin and Harry
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Idiopathic Pulmonary Fibrosis
What does it mean?
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Idiopathic
Unknown Cause
Pulmonary
Lung
Fibrosis
Formation of Scar Tissue
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Lung Scarring of Unknown Cause
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Cryptogenic Fibrosing Alveolitis
But Just to be awkward, in Europe IPF is known
as
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The Veterinary History of Idiopathic Pulmonary
Fibrosis
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Idiopathic Pulmonary Fibrosis
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How Does IPF in the Dog Compare to IPF in Man?
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The Interstitial Lung Diseases-disease categories
in humans

• Primary Diseases
• Hypersensitivity Disorders, Neoplastic processes,
  Infectious Diseases
• Drug Induced- amiodarone, bleomycin
• Toxin Induced - occupational lung diseases
• Connective Tissue Disorders- RA, SLE
• Idiopathic Pulmonary Fibrosis

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Pulmonary Interstitial Disease List - Human

• Connective Tissue Diseases
• scleroderma
• polymyositis-dermatomyositis
• systemic lupus erythematosus
• rheumatoid arthritis
• mixed connective tissue disease
• ankylosing spondylitis
• Treatment or Drug-Induced
• antibiotics (sulfasalazine)
• antiarrythmmics (amiodarone)
• anti-inflammatory (gold)
• chemotherapeutic agents (bleomycin)
• vitamins
• therapeutic radiation
• oxygen
• paraquat
• crack cocaine inhalation

• Idiopathic Fibrotic Disorders
• acute interstitial pneumonitis
• idiopathic pulmonary fibrosis
• familial idiopathic pulmonary fibrosis
• Bronchiolitis obliterans organising pneumonia
• lymphocytic interstitial pneumonia (Sjogrens
  syndrome)
• autoimmune pulmonary fibrosis (inflammatory bowel
  disease, autoimmune haemolytic anaemia)
• Occupational and Environmental
• silicosis
• asbestosis
• hard metal pneumoconiosis
• coal workers pneumoconiosis
• berylliosis
• aluminium oxide fibrosis
• siderosis (arc welder)
• stanosis (tin)
• bird breeders lung
• farmers lung

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Pulmonary Interstitial Disease List - Human

• Primary (unclassified) Disease)
• sarcoidosis
• eosinophilic granuloma
• amyloidosis
• lipoid pneumonia
• lymphangitic carcinoma
• bronchoalveolar carcinoma
• pulmonary lymphoma
• Gauchers disease
• Neimann-Pick disease
• Hermansky-Pudlak syndrome
• neurofibromatosis
• lymphangioleiomyomatosis

• Primary (unclassified) Disease)
• tuberous sclerosis
• adult respiratory distress syndrome
• AIDS
• bone marrow transplantation
• postinfectious
• respiratory bronchiolitis
• eosinophilic pneumonia
• alveolar proteinosis
• diffuse alveolar haemorrhage syndrome
• alveolar microlithiasis
• metastatic calcification

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The Interstitial Lung Disease-probable disease
categories in dogs and cats

• Primary Lung Disease
• neoplasia
• respiratory infection
• hypersensitivity disorders- PIE, asthma
• Toxins
• paraquat
• Idiopathic Pulmonary Fibrosis
• (cardiogenic and non-cardiogenic pulmonary oedema)

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Am. J. Respir. Crit. Care Med., Volume 161,
Number 2, February 2000, 646-664 AMERICAN
THORACIC SOCIETY Idiopathic Pulmonary Fibrosis
Diagnosis and Treatment International Consensus
Statement
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Many acute and chronic lung disorders with
variable degrees of pulmonary inflammation and
fibrosis are collectively referred to as
interstitial lung diseases (ILDs) or diffuse
parenchymal lung diseases. Idiopathic pulmonary
fibrosis (or cryptogenic fibrosing alveolitis)
(IPF or CFA) is one of several idiopathic
interstitial pneumonias. IPF is now recognized as
a distinct clinical disorder. Despite major
accomplishments in our understanding of the
pathogenesis of lung fibrosis, the diagnosis and
management of patients with IPF continues to pose
significant challenges.
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Incidence and Prevalence of Pulmonary Fibrosis in
WHWT
If you are a West Highland White Terrier The
importance of Pulmonary Fibrosis depends on your
age
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WHWT Health SurveyPrevalence of Targeted Disease
among Surveyed Dogs
Responses to the survey were obtained for 2773
dogs, covering 14 specified diseases.
Pulmonary Fibrosis only had a prevalence of 1.4
and was ranked 7th.
Grayson, JK (2000). West Highland Club of America.
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WHWT Health SurveyRespondents Disease Ranking in
Order of Importance
These are the diseases that concerned the
respondents most. Pulmonary fibrosis is perceived
as a disease of concern.
Grayson, JK (2000). West Highland Club of America.
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WHWT Health SurveyImportance of Pulmonary
Fibrosis in the Over 5 Age Group
Atopic dermatitis is still important, but other
diseases, such as diabetes, dry eye and pulmonary
fibrosis become important in middle-aged dogs
Grayson, JK (2000). West Highland Club of America.
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WHWT Health SurveyPrevalence of targeted
diseases among dogs over 5 year of age. Ranking
based on percentage of dogs with the disease
compared to the total number of dogs with that
disease.
Pulmonary Fibrosis is more important if the dog
is more than 5 years old.
Grayson, JK (2000). West Highland Club of America.
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WHWT Health SurveyRelationship between age and
onset of disease(percentage of dogs with a
disease at set time points)
Grayson, JK (2000). West Highland Club of America.
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The Clinical Features of IPF in West Highland
White terriers
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Idiopathic Pulmonary FibrosisThe UK Experience

• Clinical Features
• Age of onset
• middle to old age dogs
• median age at diagnosis 9 years (range
  4.5-13years)
• Development and progression
• gradual onset
• progressive deterioration
• median survival from clinical signs first being
  noticed 15.5 months (range 3-41 months)
• median survival from diagnosis 7 months (range
  1-36 months)

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Idiopathic Pulmonary Fibrosis

• Clinical Signs
• dyspnoea, tachypnoea
• exercise intolerance
• cough
• crackles on auscultation
• otherwise normal

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Diagnosis of IPF

• The characteristic clinical presentation
• The breed association
• The presence of Pulmonary Crackles
• Use of Diagnostic Tests
• imaging
• bronchoscopy and airway cytology
• pathology
• other test blood gas analysis, haematology,
  biochemistry

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Diagnostic ImagingRadiographyHigh resolution
Computed Tomography
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Radiography Mild IPF
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Radiography Severe IPF
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Radiography Very severe IPF
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High Resolution Computed Tomography Panel(HRCT)
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Normal Lung CT
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Normal Caudal Lung Field
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Torag Pattersonmild ground glass appearance
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Radiography and CTModerately Affected Case of IPF
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Radiography and CTSeverely Affected Case of IPF
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Moderate to Severe IPF
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Severe IPF
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IPF-Bronchoscopy
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Idiopathic Pulmonary FibrosisPathology
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Pathology of IPF

• A requirement if definitive diagnosis is to be
  made.
• Invasive technique and so rarely under-taken
• Changes in the dog not completely described.
• Changes in human IPF described but difficult to
  identify.
• Diffuse and patchy
• Variable findings
• May not improve diagnosis
• May not affect therapy considerations.
• Pathological score correlates with survival.
• There is still disagreement about the
  classification of IPF
• The relative risk of lung cancer in IPF patients
  is 7 times that for smokers.

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Idiopathic Pulmonary FibrosisNormal Histology
and Abnormal Histopathology
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Idiopathic Pulmonary FibrosisTherapy
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Idiopathic Pulmonary Fibrosis

• Anti-inflammatory therapy
• glucocorticosteroids
• azathioprine, cyclophosphamide
• Additional Therapy
• bronchodilators
• antibacterial therapy
• colchicine

The response is variable but usually poor, with
inevitable progressive deterioration
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Aetiology of Idiopathic Pulmonary Fibrosis

• Aetiology (unknown)
• Inflammatory reaction ?
• Fibrotic reaction ?
• Immune mediated ?
• Higher numbers of T cells (BALF) because of
  antigen stimulation.
• Circulating auto-antibodies have been detected,
  but does not mean it is an auto-immune disease.
• Exposure to toxins ?

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Human IPF ControversyIs inflammation important?
Inflammation mechanisms are a minor component of
IPF Gauldie, J, Am J Resp Crit Care Med, 2002
Inflammation mechanisms are not a minor component
of IPF Streiter, RM, Am J Resp Crit Care Med, 2002
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Inheritance and Genes
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The Genetics StoryIs the disease inherited?

• A breed-associated disease
• Human Familial Form
• 68 kindreds worldwide have been reported (2002).
• family clusters in Eastern Finland have shared
  ancestry from 16th century.
• Both youngsters and adults are affected.
• Likely to be an autosomal dominant trait with
  reduced penetrance.

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To Determine the Genetics Basis of IPF..You
have to have an accurate Phenotype
You have to be able to identify affected
individuals
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Molecular Genetics and IPF
Use of Microarray Technology to recognise those
genes that are switched on.

• Identification of the genes involved allows
• drug targeting of the products of those genes
• gene therapy

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Microarray scale
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Developments in Human IPF

• Elucidate Aetiology
• Develop Novel Diagnostic Techniques
• Identify Molecular Targets for New Drugs
• Identify Inhibitors of Fibrogenesis
• Use of Molecular Genetics Microarray to identify
  Genes
• Set up National Consortium of Clinical Centres of
  Excellence

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The Future-Canine IPF

• Improve diagnostics
• earlier diagnosis
• high resolution CT scanning
• lung biopsy
• Improve Therapy
• controlled drug studies
• adopt ideas from human medicine
• Epidemiology
• determine exact incidence and prevalence of the
  disease
• pedigree analysis to identify patterns of
  inheritance
• Molecular genetics

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