Chronic Obstructive Airways Disease

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Chronic Obstructive Airways Disease

• Gerard Flaherty
• B.Sc.(Hons.), M.B., B.Ch., B.A.O., M.R.C.P.I.
• Specialist Registrar in General
  Medicine/Endocrinology

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Lecture Outline

• Definition of COAD
• Diagnostic criteria
• Classification of severity
• Epidemiology
• Chronic bronchitis
• Emphysema
• Bronchiectasis
• Bronchial asthma

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Definition of COAD

• COAD is a disease state characterised by airflow
  limitation that is not fully reversible. The
  airflow limitation is usually both progressive
  and associated with an abnormal inflammatory
  response of the lungs to noxious particles or
  gases.

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Epidemiology of COAD

• Prevalence and morbidity data greatly
  underestimate the total burden of COAD.
• Prevalence of 9.34/1,000 in men and 7.33/1,000 in
  women (Global Burden of Disease Study, 1990).
• Morbidity increases with age and is greater in
  men than in women.
• Currently the 4th leading cause of death in the
  world.
• Economic burden per capita cost of COAD in UK of
  US65 (1996).

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Risk Factors for COAD

• Host factors
• Alpha-1-antitrypsin deficiency
• Asthma and airway hyperresponsiveness
• Disordered lung development

• Environmental factors
• Tobacco smoke
• Occupational dusts/chemicals
• Air pollution
• Childhood infections
• Lower socioeconomic status

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Diagnosis of COAD

• Considered in patients with cough, sputum
  production, or dyspnoea /- risk factors.
• Confirmed by spirometry.
• FEV1/FVC lt70 postbronchodilator FEV1 lt80 of
  predicted value.
• A low peak expiratory flow has poor specificity
  for the diagnosis of COAD.

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Spirometry

• Normal flow-volume loop
• Flow-volume loop in severe COAD

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Classification of Severity
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Respiratory Failure

• Results when gas exchange is inadequate,
  resulting in hypoxia with PaO2 lt8kPa.
• Type I Hypoxia with normal/low PaCO2.
• Caused by ventilation/perfusion mismatch, e.g.,
  Life-threatening asthma, Emphysema.
• Type II Hypoxia with hypercapnia (PaCO2
  gt6.5kPa).
• Caused by alveolar hypoventilation, e.g., Chronic
  bronchitis.
• Oxygen therapy must be controlled in type II
  respiratory failure due to the risk of further
  hypercapnia if the hypoxic drive to ventilation
  is abrogated by excessive oxygen.

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Chronic Bronchitis

• Persistent cough with sputum production for at
  least 3 months in consecutive years
• Simple / Chronic asthmatic / Obstructive
• Most frequent in middle-aged men
• Higher incidence in urban dwellers
• May coexist with emphysema
• Presents with exertional dyspnoea and frequent
  respiratory tract infections

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Chronic BronchitisPathogenesis

• Chronic irritation by inhaled substances
• Respiratory infections
• 4-10 times more common in heavy smokers
• Hypersecretion of mucus in large airways
• Submucosal gland hypertrophy
• Increase in goblet cells in small airways
• Excessive mucus ? airway obstruction
• Cigarette smoke predisposes to infection

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Chronic BronchitisMorphology

• Gross
• Hyperaemia and oedema of mucous membranes
• Excessive secretions /- casts

• Histology
• Hypertrophy of submucosal smooth muscle
• Hyperplasia of submucosal glands of
  trachea/bronchi
• Increased Reid index (gt0.4)
• Squamous metaplasia and dysplasia of epithelium
• Loss of ciliary activity
• Narrowing of bronchioles /- bronchiolitis
  obliterans

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Chronic BronchitisHistology
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Chronic BronchitisComplications

• ?PaO2 ?PaCO2 .Respiratory failure
• Respiratory tract infections (H. influenzae,
  Strep. Pneumoniae)
• Pulmonary hypertension ? Cor pulmonale
• Atypical metaplasia / dysplasia of respiratory
  epithelium.Bronchogenic carcinoma

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Emphysema

• Abnormal permanent enlargement of the airspaces
  distal to the terminal bronchiole, accompanied by
  destruction of their walls
• Types (1) centrilobular
• (2) panlobular
• (3) paraseptal
• (4) irregular
• Associated with heavy cigarette smoking

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Emphysema

• Presents with progressive dyspnoea, reduced
  exercise tolerance, wheeze and weight loss
• Signs of hyperinflation
• Loss of elastic support ? Airways collapse on
  expiration ? Obstructive pattern on spirometry
• Respiratory acidosis
• Cor pulmonale (rarely)
• Pneumothorax

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Emphysema
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EmphysemaPathogenesis

• Protease-antiprotease hypothesis
• Homozygous alpha-1-antitrypsin deficiency is
  associated with panlobular emphysema, especially
  in smokers
• Emphysema results from the destructive effect of
  high protease (elastase) activity in patients
  with low antiprotease activity
• Smoking stimulates release of elastase from
  neutrophils

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EmphysemaPathogenesis
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EmphysemaMorphology

• Gross
• Panlobular resp. bronchiole ? terminal alveoli.
  Lower gt Upper lobes
• Centrilobular ? respiratory bronchioles. Upper gt
  Lower
• Paraseptal ? distal acinus. Upper gt Lower
• Irregular ? associated with scarring, e.g.,
  Tuberculosis

• Histology
• Destruction of septal walls
• Fusion of adjacent alveoli
• Blebs / bullae
• Compressed blood vessels
• /- Bronchitis

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EmphysemaSubtypes
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EmphysemaGross
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EmphysemaHistology
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Bronchiectasis

• A chronic necrotising infection of the bronchi
  and bronchioles associated with abnormal
  permanent dilation of these airways
• Presents with cough, productive of large amounts
  of foul-smelling, purulent sputum, hamoptysis and
  digital clubbing
• Pooled secretions in lower lobes ? respiratory
  tract infections

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BronchiectasisAetiology

• Bronchial obstruction
• Tumour, foreign bodies, mucous impaction
• Asthma / Chronic bronchitis
• Infection
• Tuberculosis, Staphylococcus aureus, ABPA,
  Measles, Pertussis
• Congenital
• Congenital bronchiectasis, Cystic fibrosis,
  Intralobar sequestration, Immunodeficiency,
  Kartageners syndrome, Yellow nail syndrome

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Cystic FibrosisGenetic defect
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BronchiectasisPathogenesis

• Bronchial obstruction ? Atelectasis
• Dilatation of walls of patent airways
• Infection ? Bronchial wall inflammation ?
  weakened walls ? further dilation
• Cystic fibrosis squamous metaplasia with
  impaired mucociliary action, infection, necrosis
  of bronchial and bronchiolar walls
• Kartageners syndrome absent dynein arms in
  cilia ? lack of ciliary activity

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BronchiectasisMorphology

• Gross
• Usually both lower lobes
• May be localised
• Dilated airways
• Cylindroid
• Fusiform
• Saccular
• Cystic pattern on cut surface of lungs

• Histology
• Acute and chronic inflammation
• Desquamation of epithelium
• Necrotising ulceration
• Squamous metaplasia
• Necrosis ? lung abscess
• Fibrosis

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BronchiectasisComputed Tomography
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BronchiectasisGross
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BronchiectasisHistology
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BronchiectasisComplications

• Pneumonia
• Lung abscess
• Empyema
• Septicaemia
• Cor pulmonale
• Metastatic cerebral abscesses
• Secondary Amyloidosis

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Bronchial Asthma

• Hyper-reactive bronchioles, leading to episodic,
  reversible bronchoconstriction
• Bronchospasm ? cough, dyspnoea, wheeze
• Status asthmaticus may be fatal
• Types (1) Extrinsic (eg, atopic, occupational,
  ABPA) type 1 reaction
• (2) Intrinsic (eg, respiratory infections,
  aspirin, exercise)

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Bronchial AsthmaPathogenesis

• Atopic Asthma
• Exposure of presensitised IgE-coated mast cells
  to antigen causes acute immediate response
• Chemical mediators (histamine, cytokines, PAF,
  leukotrienes)
• Late-phase reaction

• Nonatopic Asthma
• Virus-induced inflammation of respiratory mucosa
  lowers threshold of vagal receptors to irritants
• Aspirin-sensitive asthma a/w rhinitis/nasal
  polyps
• Occupational asthma

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Bronchial Asthma
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Dermatophagoides pteronyssinus (House dust mite)
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Bronchial AsthmaMorphology

• Gross
• Overdistended lungs
• Mucous plugs occlude bronchioles
• Histology
• Thickened basement membrane
• Oedema
• Inflammatory infiltrate
• Numerous eosinophils
• Hyperplasia of submucosal glands
• Bronchial wall muscle hypertrophy
• Curschmanns spirals
• Charcot-Leyden crystals (eosinophil membrane
  protein)

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Bronchial AsthmaHistology
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Bronchial AsthmaComplications

• Status asthmaticus
• Pneumothorax
• Bronchiectasis
• Cor pulmonale

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