Managing Chronic Obstructive Pulmonary Disease

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Experimental Respiratory Research Suite
TRW Ground floor
Construction to be complete by June 30, 2009
Contacts David Proud or Richard Leigh
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Experimental Lung Suite in TRW Building
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Main Facilities

• Pulmonary Function Room
• Includes spirometry, plethysmography, exhaled
  nitric oxide,
• exercise facility.

2. Provocation Room Bronchial challenge with
allergen,methacholine, etc. Also hope be doing
nasal challenges rhinovirus infection.
Facilities include nebulizer/dosimeters,spirometr
y, sputum induction, nasal lavages, nasal
scraping.
3. Bronchoscopy Suite Can perform bronchoalveolar
lavage, bronchial brushings, bronchial biopsies.
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Allergen Challenge
OByrne et al. ARRD 1987 136 740-751
Cockroft et al. ARRD 1987 135 264-267
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ICS attenuate Late Asthmatic Response
Mometasone
0
400

g
100

g
-10
50

g
change in FEV1
-20
Placebo
-30
-40
0
1
2
3
4
5
6
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Time Post Allergen Inhalation (h)
Inman, MD,et al. AJRCCM 2001 164 569-574
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What Types of Samples can be Obtained?

• Nasal
• Lavages can be obtained for cell
  counts/differentials
• mediator assays.
• b) Nasal epithelial scrapings for mRNA analysis.
• c) Nasal Biopsies an option.

• Lung
• Bronchoalveolar lavage - cell counts/differentials
  
• mediator assays..
• Bronchial brushings - mRNA analysis or epithelial
  cultures.
• Biopsies - histology/staining for infiltrating
  cells/markers,
• structural changes (remodelling). Can also use
  for in situ
• hybridization. With laser capture microdissection
  can
• assess mRNA expression.

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Method of Sputum Induction
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Sputum Analysis
Squamous contamination
Suitable material
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Cell Differential
Bronchial Epithelial
Eosinophil
Macrophage
Neutrophil
X400, Congo Red
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Bronchoalveolar Lavage and Biopsy
Fibre-Optic Bronchoscopy
Permits
BAL (lavage)
tissue biopsies

Still considered gold standard
Useful in well designed studies
Unsuitable to monitor severe asthma
Time consuming
Invasive
Associated risks
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Eosinophil infiltrate following allergen challenge
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Bronchial epithelium - mouse airway
Kelly et al. Am J Respir Cell Mol Biol 2005
3299-107
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Bronchial epithelium - mouse airway
Kelly et al. Am J Respir Cell Mol Biol 2005
3299-107
Kelly et al. Am J Respir Cell Mol Biol 2005
3299-107
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Bronchial epithelium - mouse airway
Microdissected epithelium on removed cap
Kelly et al. Am J Respir Cell Mol Biol 2005
3299-107
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Examples of recent/current studies
3 Phase 2 bronchial biopsy studies - Med-Immune
(AstraZeneca) aIL-9 mAb - Novartis omalizumab
(aIgE mAb) - Ception (aIL-5 mAb) Genetech -
severe asthma biopsy - tissue banking Dr Alain
Tremblay - autofluorescence imaging of lung
cancer (Terry Fox) - endo-bronchial valves in
COPD Recently completed a study in
bronchiectasis
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Sustainability
Plan service account for standard operations.
Users charged utilization fee depending on
procedures. Expect all individuals with
pharmaceutical contracts to include costs for
the centre. Should also consider for CIHR
studies if human work planned. Fees previously
paid for using region facilities will now go to
the operations budget. Should be
self-sustaining. Ideal would be to build an
endowment for operations.
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