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A. Teredesai LSRO Meeting, Dec., 13, 2001 INBIFO/CRC Slide 1 Review of Histopathological Changes in the Respiratory Tract of Rat Induced by Inhalation of the Mainstream Smoke of Standard Reference Cigarette 1R4F
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Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

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Page 1: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

A. TeredesaiLSRO Meeting, Dec., 13, 2001

INBIFO/CRCSlide 1

Review of Histopathological Changes inthe Respiratory Tract of Rat Induced byInhalation of the Mainstream Smoke ofStandard Reference Cigarette 1R4F

Page 2: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 2 INBIFO/CRC12_2001.ppt

Outline

• Goal

• Anatomy and Histology

• Histotechnical Work

• Results– INBIFO

– Literature

Page 3: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 3 INBIFO/CRC12_2001.ppt

Goal

• Overview of the methods and procedures regardingthe histotechnical work and histopathologicalevaluation as well as an overview of thehistopathological changes following subchronicexposure to cigarette smoke

Page 4: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 4 INBIFO/CRC12_2001.ppt

Rationales

• Inhalation studies, special emphasis on thehistopathology of the target organs, i.e., respiratorytract organs

• Regulatory guidelines (OECD, EPA)

• Human relevance - association of tobacco smokeinhalation with laryngeal and bronchial cancers inhumans

Page 5: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 5 INBIFO/CRC12_2001.ppt

Rat Respiratory Tract

Page 6: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 6 INBIFO/CRC12_2001.ppt

Nose

• Anatomy– vestibule

– cartilagenous septum that divides the nasal cavity into2 halves

– dorsal, middle, and ventral meatuses

– turbinates or conchae

• Histology– 3 basic epithelial types

– squamous epithelium

– respiratory epithelium

– olfactory epithelium

Page 7: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 7 INBIFO/CRC12_2001.ppt

Anatomy

• Larynx consists of 5 cartilages– epiglottis

– thyroid

– cricoid

– arytenoid

– u-shaped

Page 8: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 8 INBIFO/CRC12_2001.ppt

Histology

• 4 types of epithelium– squamous

– respiratory

– pseudostratified cuboidal

– squamoid

Page 9: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC12_2001.ppt

Trachea

• Anatomy– connects the larynx with the lungs

– 15 incomplete cartilaginous rings dorsally interconnected byligaments

– tracheal bifurcation at the level of 6th rib into a smaller leftand larger right extrapulmonary main bronchus

• Histology– pseudostratified respiratory epithelium

– ciliated cells

– serous cells

– mucous (goblet) cells

– basal cells

Page 10: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 10 INBIFO/CRC12_2001.ppt

Lung

• Left lung

• Right lung

2 lobes10 segmental bronchi

1 lobe12 to 13 segmental bronchi

3 lobes10 segmental bronchi

4 lobes14 to 15 segmental bronchifew subsegmental bronchi

Man Rat

Page 11: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 11 INBIFO/CRC12_2001.ppt

Cells of the Pulmonary Parenchyma

• Alveolar type I epithelial cells

• Alveolar type II epithelial cells

• Pulmonary endothelial cells

• Interstitial cells

• Macrophages

Page 12: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 12 INBIFO/CRC12_2001.ppt

Tissue Sectioning Method

• Sections at pre-established levels– nose: Young (1981)

– larynx: Lewis (1980)

– trachea: INBIFO

– lung: Lamb and Reid (1969)

• Purpose– adequate morphological evaluation

– uniform histological examination

– ensure correct comparison within and among studies

Page 13: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 13 INBIFO/CRC12_2001.ppt

Histopathological Evaluation

• Recording of findings in a consistent manner

• Use of standardized dictionary of criteria

• Consistent scoring system

• Evaluation in a blinded fashion, i.e., without theknowledge of treatment groups

Page 14: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 14 INBIFO/CRC12_2001.ppt

Results INBIFO

• Study reference– subchronic cigarette smoke inhalation studies

• Experimental condition– “nose only” mode

– TPM concentration range 40 to 200 µg TPM/l

– exposure duration: 6 h/d, 7 d/week for 21 or 90 days

Page 15: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 15 INBIFO/CRC12_2001.ppt

Histopathology

• Nose– respiratory epithelium (levels 1 and 2)

– reserve cell hyperplasia

– squamous metaplasia

– goblet cell hypertrophy/hyperplasia

– olfactory epithelium (levels 2, 3, and 4)– ulceration

– atrophy

– squamous metaplasia

Page 16: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 16 INBIFO/CRC12_2001.ppt

Nasal Septum, Level 1, Normal

Page 17: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 17 INBIFO/CRC12_2001.ppt

Nasal Septum, Level 1, Goblet CellHypertrophy/Hyperplasia

Page 18: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 18 INBIFO/CRC12_2001.ppt

Nasal Septum, Level 1, Goblet CellHypertrophy/Hyperplasia, AB-PAS Stain

Page 19: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 19 INBIFO/CRC12_2001.ppt

Dorsolateral Wall, Nose Level 1, Normal

Page 20: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 20 INBIFO/CRC12_2001.ppt

Dorsolateral Wall, Nose Level 1,Squamous Metaplasia

Page 21: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 21 INBIFO/CRC12_2001.ppt

Maxilloturbinate Tip, Nose Level 1,Normal

Page 22: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 22 INBIFO/CRC12_2001.ppt

Maxilloturbinate Tip, Nose Level 1,Hyperplasia

INBIFO/CRC CONFIDENTIAL

Page 23: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 23 INBIFO/CRC12_2001.ppt

Dorsomedial Region, Nose Level 2,Normal Olfactory Epithelium (low power)

Page 24: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 24 INBIFO/CRC12_2001.ppt

Dorsomedial Region, Nose Level 2,Normal Olfactory Epithelium (high power)

INBIFO/CRC CONFIDENTIAL

Page 25: Review of Histopathological Changes in the Respiratory ...LSRO Meeting Dec., 13, 2001 Slide 9 INBIFO/CRC 12_2001.ppt Trachea • Anatomy – connects the larynx with the lungs –

LSRO Meeting Dec., 13, 2001 Slide 25 INBIFO/CRC12_2001.ppt

Dorsomedial Region, Nose Level 2,Olfactory Epithelium, Atrophy