Chronic Obstructive Lung Disease or Pulmonary Disorder

Chronic Obstructive Lung Disease

1. Chronic Obstructive Pulmonary Disease Dr. Vijay David Raj R

2. Types Obstructive lung diseases consists of four diseases namely  ( i ) Emphysema,  (ii) Chronic bronchitis,  (iii) Asthma and  (iv) Bronchiectasis. 

3. Chronic Bronchitis Chronic bronchitis is defined clinically as  persistent cough with sputum production (chronic productive cough) for at least 3 months in at least 2 consecutive years in the absence of any other identifiable cause.

4. Causes Cigarette smoking: It is the most important risk factor.  Air pollutants: Sulfur dioxide, nitrogen dioxide.  Toxic industrial inhalants: Occupational dust exposure.  Respiratory tract infection: It may initiate and promote chronic bronchitis.

5. pathogenesis Irritation by inhaled air pollutants:  Irritants cause inflammation → infiltration by CD8+ T lymphocytes, macrophages and neutrophils. Hypersecretion of mucus:  Hyperplasia/Hypertrophy of Submucosal Glands : Occurs in the larger airways such as the trachea and bronchi. Triggered by inhaled environmental irritants and proteases released by neutrophils, including elastase, cathepsin, histamine, and IL-13. Results in the enlargement and increased activity of submucosal glands. Leads to hypersecretion of mucus, contributing to airway obstruction. Increase of Goblet Cells in Small Airways : Particularly affects small bronchi and bronchioles. Goblet cells produce excessive mucus. Excessive mucus production can lead to mucus plugging of the bronchial lumen. Mucus plugging triggers inflammation and fibrosis of the bronchial wall, further contributing to airway obstruction. Chronic inflammation and accompanying fibrosis involving small airways can produce chronic airway obstruction.

6. Infection may be secondary rather than primary and probably important in maintaining and producing acute exacerbations.  Infection may cause direct damage to airway epithelium and interferes with ciliary action of the respiratory epithelium → defective clearance of bacteria by leukocytes.

7. Morphology Gross Airways (large and small) changes include: Mucous membrane: It shows hyperemia, swelling and edema. It appears dusky red.  Lumen: They are filled with excessive mucus or mucopurulent secretion. 

8. microscopy Hyperplasia and hypertrophy of mucus-secreting glands in the submucosa: results in hypersecretion of mucus.   Reid index: It is the ratio of the thickness of the mucous gland layer to the thickness of the wall between the base of the surface epithelium and the inner limit of the cartilage plates. It is useful for detecting the increase in the size and number of the mucus glands. Reid index (normally 0.4) is increased in chronic bronchitis.  Chronic inflammation of the airways with predominant infiltration by lymphocytes.  Marked narrowing of bronchioles:  In severe cases, there may be obliteration of lumen due to fibrosis (bronchiolitis obliterans).

9. Clinical Features Usually affects middle-aged men who are heavy smokers.  Early symptoms: Persistent productive cough (sputum) for many years.  Later stage: – Dyspnea on exertion Blue bloaters: Patients develop hypercapnia, hypoxemia, and mild cyanosis. Such patients are called ‘blue bloaters’.

10. complications Progression to chronic obstructive pulmonary disease (COPD). Longstanding cases lead to cor pulmonale with cardiac failure.  May develop squamous metaplasia and dysplasia of the respiratory epithelium → a rich soil for cancerous transformation.

11. asthma Asthma is a chronic inflammatory disorder of the bronchial tree (airways) in which breathing is periodically rendered difficult by widespread narrowing of the bronchi (reversible bronchoconstriction). It is clinically, characterized by recurrent episodes of wheezing, breathlessness, tightness of the chest and cough.

12. Characteristics Episodes of bronchoconstriction—Partly reversible, either spontaneously or after treatment.  Inflammation of the bronchial walls.  Increased mucus secretion.

13. types

14. Atopic Most common type of asthma that usually begins in childhood.  Family history of asthma or allergic diseases (e.g. eczema, urticaria, or hay fever) is common.  Classic example of type I IgE -mediated hypersensitivity reaction.  Exogenous substances (allergens) causing asthma can be recognized.

15. Non atopic No causative exogenous factors can be identified and it does not show allergen sensitization.  Skin tests are usually negative.   Family history of asthma is less common.  Respiratory infections due to viruses (e.g. rhinovirus, parainfluenza virus).  Inhaled air pollutants (e.g. smoke, fumes).  Drug-induced Asthma Many drugs may trigger asthma (e.g. aspirin-sensitive asthma). Aspirin inhibits cyclooxygenase pathway of arachidonic acid metabolism → produces leukotrienes (bronchoconstrictor) → causes asthma. Occupational Asthma Triggering occupational agents: • Fumes (epoxy resins, plastics). • Organic and chemical dusts (wood, cotton, platinum). • Gases (toluene). • Other chemicals (formaldehyde, penicillin products)

16. pathogenesis Genetic predisposition: Type I hypersensitivity (atopy) reaction and exposure to environmental trigger. One of the susceptibility locus is on the chromosome 5 (5q) → several genes involved in regulation of IgE synthesis and mast cell and eosinophil growth and differentiation. 

17. Airway hyper-responsiveness:  It is an abnormality in which there is excessive tendency for airways to contract (bronchoconstrictor) too easily in response to multiple inhaled triggers that usually does not have any effect on normal individuals. Hygiene Hypothesis:   proposes that individuals with lack of infections in early childhood are more prone to asthma than children brought up on farms who are exposed to a high level of endotoxin. 

18. Gross Airways (bronchi and bronchioles) are occluded by plugs of thick, tenacious mucus.  In patients who die due to status asthmaticus, the lungs are greatly distended due to overinflation, and shows small areas of atelectasis (collapse).

19. microscopy Mucus plug contains desquamated epithelial cells and eosinophils and forms spiral-shaped cast of the airways and are called Curschmann spirals. These may be found in the sputum.  Numerous eosinophils are found in the walls of the the bronchi and bronchioles.  Charcot–Leyden crystals , which are crystalloid derived from an eosinophil lysophospholipase binding protein called galectin-10  Airway remodeling: An increase in size and number (hypertrophy/hyperplasia) of the submucosal glands. • Hypertrophy and/or hyperplasia of the bronchial wall smooth muscle. • Increased vascularity. • Deposition of subepithelial collagen accompanied by fibrosis and thickening of the basement membrane.

20. Clinical details Acute asthmatic attack usually lasts up to several hours. In some mild degree of chest tightness, dyspnea, wheezing and cough with or without sputum production, may constantly present. Between the asthmatic attacks, patients may be asymptomatic.  Status asthmaticus: It is the most severe form of asthma that persists for days and even weeks. The bronchoconstriction does not respond to the drugs. It may cause severe airflow obstruction leading to severe cyanosis and even death.

21. bronchiectasis Bronchiectasis is a disorder characterized by irreversible (permanent)dilation of bronchi and bronchioles. The dilatation of bronchi and bronchioles is caused by destruction of the muscle and elastic tissue of bronchial wall.

22. Causes Chronic Respiratory Infections: C hronic necrotizing infections. • Bacteria, Viruses, Fungi  Cystic Fibrosis:  genetic disorder characterized by abnormal transport of chloride ions, leading to thick, sticky mucus. Primary Ciliary Dyskinesia (PCD):  Kartagener syndrome leading to impaired mucociliary clearance in the respiratory tract, sinuses, and reproductive organs. Common features include chronic respiratory infections, sinusitis, bronchiectasis, and situs inversus (reversal of the normal positions of organs). Young’s syndrome: Patients develop bronchiectasis, sinusitis and obstructive azoospermia. The cause is not known. Obstructive Lung Diseases like asthma and chronic bronchitis.

23. Autoimmune diseases: e.g. rheumatoid arthritis, Sjögren’s syndrome, systemic lupus erythematosus, inflammatory bowel disease.  Immune-mediated disease: e.g. allergic bronchopulmonary aspergillosis. Obstructive causes: Tumour or Foreign body Causes

24. pathogenesis Obstruction: It impairs clearing mechanisms of the lung → results in accumulation of secretions distal to the obstruction → leads to secondary infection → inflammation → weakens and dilates airway.  Chronic persistent necrotizing infection: Chronic infection in the bronchi or bronchioles → increased bronchial secretion → obstruction of airways by secretions → inflammation and fibrosis of the airway walls → weakening and dilatation of airways. 

25. gross

26. Gross Saccular (cystic) bronchiectasis: It is characterized by markedly dilated bronchi which end blindly in dilated sacs. Cylindrical (tubular) bronchiectasis: It shows uniform and moderate dilation.  Fusiform: Characterized by fusiform dilatation.  Varicose bronchiectasis: It shows irregular dilations and constrictions. They resemble varicose veins when seen by radiologic bronchography.

27. microscopy Dilatation of bronchi and bronchioles and destruction of their wall due to severe inflammation.  Dense infiltration of chronic inflammatory cells: It mainly consists of lymphocytes and plasma cells within the walls of the bronchi and bronchioles.  Fibrosis of the bronchial and bronchiolar wall: It occurs in the chronic cases→ may result in partial or complete obliteration of bronchiolar lumens.

28. Clinical features Severe persistent productive cough Sputum is foul-smelling, sometimes bloody. Symptoms are precipitated by upper respiratory tract infections.  Paroxysms of cough occur when the patient rises in the morning. This is because, the changes in position lead to drainage of collections of pus and secretions into the bronchi.