OBSTRUCTIVE AIRWAYS DISEASE

&

SMOKING-ASSOCIATED

INTERSTITIAL LUNG DISEASE

• Chronic bronchitis

• Chronic bronchiolitis (Small Airways Disease)

• Emphysema

• Bronchiectasis

• Bronchial asthma

OBSTRUCTIVE AIRWAYS DISEASE

All characterized by airflow limitation, but involvedifferent mechanisms and parts of the respiratorytree

• Chronic bronchitis - hypersecretory • Chronic bronchiolitis - obstructive• Emphysema - destructive

NB Cigarette smoking Frequently co-exist – but 2 clinical syndromes

“Blue bloater vs. Pink puffer”

OBSTRUCTIVE AIRWAYS DISEASE

“Persistent or recurrent excess of secretion in the bronchial tree on most days for at least 3 months in the year, over 2 years”

• Middle-aged & elderly, M > F• Mucoid sputum – H. Inf, Strep pneum., Bran. Cat• Cigarette smoke, air pollution, dust exposure – cadmium,

smog• At PM - bronchi filled with mucous / pus• Enlargement of submucosal glands (Reid Index) shift to pure mucous from mixed sero-mucinous type• Inceased nos of goblet cells in epithelium, at expense of

ciliated cells and Clara cells

OBSTRUCTIVE AIRWAYS DISEASE – Chronic Bronchitis

Obstructive Airways Disease

Normal

Chronicbronchitis

Bronchialmucusglandhyperplasia

OBSTRUCTIVE AIRWAYS DISEASE Acute on chronic bronchitis

OBSTRUCTIVE AIRWAYS DISEASE

Loss of airway ‘tapering’ in chronic bronchitis

• Airways < 2mm = small bronchi, proximal bronchioles

• Bronchiolar goblet cell metaplasia – loss of clara cells – loss of protease inhibitor

• Chronic inflammation & fibrosis – focal stenoses

• Hypoxic pulmonary vasoconstriction – hypertension – cor pulmonale

• Compensatory polycythaemia

OBSTRUCTIVE AIRWAYS DISEASE – Small Airway Disease

• Emphysema is a condition of the lung characterized by abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis

• Airflow limitation is due to premature closure of airways because of diminished elastic recoil

OBSTRUCTIVE AIRWAYS DISEASE – Emphysema

Morphologic types according to part of acinus affected

• Centriacinar – cigs, UL

• Panacinar - 1-AT defficiency, LL

• Paraseptal - septal / subpleural

OBSTRUCTIVE AIRWAYS DISEASE – Emphysema

OBSTRUCTIVE AIRWAYS DISEASE

CENTRILOBULAR EMPHYSEMA SEPTAL EMPHYSEMA

OBSTRUCTIVE AIRWAYS DISEASE

PARASEPTAL EMPHYSEMA Large solitary bullaeThese may grow largeenough to cause respiratory failure by compressing adjacent‘normal’ lung. Corrective bullectomy or ‘lung reduction’ may returnpulmonary function to normal

OBSTRUCTIVE AIRWAYS DISEASE

PANACINAR EMPHYSEMA

OBSTRUCTIVE AIRWAYS DISEASE

PANACINAR EMPHYSEMA

Proteases (elastase) vs. Antiproteases• Neutrophils & macrophages - sources of elastase –

increased in smokers / infection / inflamm• Smoking stimulates release and enhances activity of

elastase • Oxidants in cig smoke inhibit native 1-AT activity 1-AT defficiency - unopposed elastase activity 1-AT specified by proteinase inhibitor (Pi) locus –

chrom 14, polymorphism – 70 different variantsPiMM – normal, Z and S mutants NB medical relevance

OBSTRUCTIVE AIRWAYS DISEASE – Emphysema - pathogenesis

• Asthma - characterized by hyperreactive airways leading to episodic, reversible bronchconstriction, owing to increased responsiveness of the tracheobronchial tree to various stimuli

• Extrinsic / Atopic / Allergic = allergy to exogenous substances

• Intrinsic / idiosyncratic / Non-atopic = no exogenous factors identified

OBSTRUCTIVE AIRWAYS DISEASE – Bronchial Asthma

• Commoner

• Childhood, M>F

• Less severe as age – but 30% symptoms as adults

• Assoc eczema, rhinitis

• Environmental triggers

• Type I (IgE-mediated) hypersensitivity reaction

OBSTRUCTIVE AIRWAYS DISEASE – Atopic Asthma

• Adult onset• Chronic, tending to worsen with age• Triggered by respiratory tract infxn –

viral• Family hx – uncommon• Serum IgE – normal• Virus-induced inflammation may lower

threshold of receptors to irritants

OBSTRUCTIVE AIRWAYS DISEASE – Nonatopic Asthma

• Sputum – yellow – MPO

• Eosinophils, Charcot-Leyden crystals, Curschmann’s spirals and Creola bodies

• Lungs at PM – Status Asthmaticus – overdistension, mucous plugging

• Micro – luminal mucous & eo, goblet cell hyperplasia, infiltration by eosinophils, BM thickening, bronchial smooth muscle hyperplasia, hypertrophy

OBSTRUCTIVE AIRWAYS DISEASE – Asthma

OBSTRUCTIVE AIRWAYS DISEASE

a b

(a) Curschmann spiral

(b) Creola body

OBSTRUCTIVE AIRWAYS DISEASE

Hyperinflatedlungs in statusasthmaticus

OBSTRUCTIVE AIRWAYS DISEASE

Sticky mucusplugs in status asthmaticus

“SMOKING-ASSOCIATED” INTERSTITIAL LUNG DISEASE

• Respiratory-bronchiolitis (RB)

• Desquamative interstitial pneumonia (DIP)

• Langerhan’s cell histiocytosis (LCH) Eosinophilic granuloma (EG) Histiocytosis X (HX)

RESPIRATORY (SMOKERS) BRONCHIOLITIS (RB) and DIP

• Cough & dyspnoea• LL interstitial infiltrates, restrictive PFTs• Patchy disease• Accumulation of macrophages containing

yellow-brown pigment in lumens of distal bronchioles, alveolar ducts & spaces

• Mild interstitial thickening• DIP – diffuse filling of alveolar spaces • ?different ends of the spectrum of one disease

• Pulmonary LCH – smokers

• Cough, dyspnoea, fever, malaise, spontaneous pneumothorax

• Imaging – UL, cysts and nodules

• Micro: discrete stellate nodules, bronchocentric

• Langerhan’s cells, histiocytes, eosinophils,

• Langerhan’s cells – large histiocytes – “groovy” nuclei

• Cysts, stellate or starfish-shaped scars

• H&E diagnosis, IHC has replaced EM as a diagnostic tool

LANGERHAN’S CELL HISTIOCYTOSIS (LCH) EOSINOPHILIC GRANULOMA (EG) HISTIOCYTOSIS X (HX)