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Definition of Asthma :

  • Asthma is a heterogenous disease.
  • The disease is characterized by chronic airway inflammation.
  • Asthma is also characterized by variable expiratory airflow obstruction.
  • The clinical symptoms include wheezing, shortness of breath, chest tightness and cough which varies in time and intensity.

Symptoms frequency :

  • The symptomatic episodes usually occur at night or in the early morning and are produced by the bronchoconstriction.
  • The symptoms is at least partly reversible spontaneously or with treatment.
  • Sometimes rarely, an unremitting attack called Acute Severe Asthma may occur.
  • This was formerly called Status Asthmaticus and may be Fatal.
  • The above condition usually takes place in patients having a long history of the Disease.
  • Between the attacks the patients may be asymptomatic.

Demographic details :

  • There has been a significant increase in the incidence of the disease in the Western countries over the past 40 to 50 years.
  • However, the prevalence of Asthma continues to increase in lower income countries and in some ethnic groups in which the prevalence was previously low.

Etiology and Types :

  • Asthma has different types of phenotypes.
  • All the different phenotypes have different underlying pathogenic mechanisms.
  • Moreover it may be categorized as Atopic , Non – Atopic Asthma, Drug – induced, or occupational asthma etc. based upon the triggering agents .

Atopic Asthma :

  • It is the classical example of IgE – mediated hypersensitivity ( type 1 ) reaction.
  • This type of disease begins usually in the childhood.
  • The triggering agents are environmental allergens such as dusts, pollens, cockroach or animal dander, and also foods.
  • Moreover all the above factors frequently act in synergy with all the other proinflammatory factors in the environment.
  • The proinflammatory factors are usually respiratory viral infections.
  • The patients usually have positive family history of the disease.
  • And also the skin test with offending antigen usually produces an immediate wheal and flare reaction.
  • The diagnosis as Atopic asthma comes to a conclusion often based on high total serum IgE levels.
  • The arrival of diagnosis is also on the basis of evidence of allergen sensitization by serum radioallergosorbent tests ( RASTs ).
  • The above test can detect the presence of IgE antibodies that are specific for individual allergens.

Non – Atopic Asthma :

  • Individuals suffering from non-atopic asthma usually do not have any evidence of allergen sensitization.
  • And these individuals usually have their skin test negative.
  • The patients also usually have negative family history.
  • Respiratory infections due to viruses like rhinovirus, parainfluenza virus and respiratory influential virus are the common triggering agents.
  • Inhaled pollutants like tobacco smoke, sulfur dioxide, ozone, and nitrogen dioxide may also contribute to the chronic inflammation and hyperactivity in some cases.
  • In some cases the condition may also be triggered by exposure to cold and even exercise.

Drug – induced Asthma :

  • Several pharmacologic agents provoke asthma.
  • Aspirin – sensitive asthma is uncommon in individuals with recurrent history of rhinitis and nasal polyps.
  • These individuals are highly sensitive to small doses of aspirin and other non-steroidal anti inflammatory drugs.
  • These sort of patients not only experience the attacks of asthma but they also experience the attacks of Urtricaria.
  • Aspirin like medications triggers the episodes of Asthma in these sorts of patients by inhibiting the cyclooxygenase pathway of Arachidonic acid metabolism , leading to decrease prostaglandin E2.
  • Normally Prostaglandin E2 inhibits the enzymes that generate the proinflammatory factors such as Leukotrienes B4, C4, D4 and E4.
  • These above mediators is commonly believed to have central roles in the Aspirin – induced asthma.

Occupational asthma :

  • This form of asthma may be triggered by may be triggered by fumes like epoxy resins and plastic.
  • These may be also be triggered by agents organic and chemical dusts like wood cotton and platinum and also gases like toluene or other sorts of chemicals like formaldehyde and penicillin products.
  • Only minute amount of quantity is required to trigger the condition.
  • The underlying mechanisms may vary according to the stimulus and also vary according to the type – I hypersensitivity reactions.
  • It also vary according to the release of Bronchoconstrictor substances and hypersensitivity responses of unknown origin.

Pathogenesis :

  • Atopic asthma is the most common of the disease, is caused by a Th2 mediated IgE response to environmental allergens in genetically predisposed individuals.
  • Airway inflammation is central to the disease pathophysiology and causes airway dysfunction partly through the release of potent inflammatory mediators.
  • The pathophysiology is also mediated through the re modelling of the airway wall.
  • As the disease progresses, there is increase in the local secretion of growth factors, that induces the mucous gland enlargement, smooth muscle proliferation, angiogenesis and Fibrosis.
  • Varying combination of these processes help explain the different subtypes of the disease.
  • A fundamental abnormality in asthma is an exaggerated Th2 response to normally harmless environmental antigens.

Histopathology :

  • Morphology :
    • In patients dying of acute severe asthma ( Status Asthmaticus ), the lungs are overinflated and contain small areas of atelectasis.
    • The most striking gross finding is occlusion of bronchi and bronchioles by thick, tenacious mucus plugs, which often contain shed epithelium.
    • A characteristic findings in sputum or bronchoalveolar lavage specimens of patients with atopic asthma in Curschmann spirals, which may result from extrusion of mucus plugs from subepithelial mucus gland ducts or bronchioles.
    • Also present are numerous eosinophils and Charcoat – Leyden crystals composed of eosinophil – derived protein galectin -10.
    • The other histologic findings of the disease is characteristic remodeling of airway.
      • Thickening of airway wall
      • Sub – basement membrane fibrosis ( due to deposition of type I and type III collagens )
      • Increased vascularity
      • Increase in the size of submucosal glands and number of airway goblet cells.
      • Hypertrophy and/or hyperplasia of the bronchial wall muscle with the extracellular matrix.
Histopathology findings in asthma
Bronchus from asthmatic patient showing goblet cell hyperplasia ( green arrow ), sub – basement membrane fibrosis ( black arrow ), eosinophilic inflammation ( yellow arrow ), and muscle hypertrophy ( Blue arrow )

Environmental factors :

  • Asthma is a disease of industrializing societies where the majority of people live in cities.
  • Two ideas has been proposed to explain the association of environment and asthma.
  • First, industrialized environments contain many airborne pollutants that can serve as allergens to initiate the Th2 response.
  • Secondly, the city life tends to limit the exposure of very young children to certain antigens, particularly the microbial antigens, and exposure to such antigens may protect children from asthma and atopy.
  • The idea that microbial exposure during early life reduces the later incidence of allergic diseases has been popularized as hygiene hypothesis.
  • Moreover, infections do not cause asthma on their own, but they may be the important co – factors.
  • But overtime repeated bouts of allergen exposure and immune reactions result in structural changes in the bronchial wall, referred to as airway remodeling.

Clinical features of Asthma :

  • Chest tightness
  • Dyspnea
  • Wheezing
  • Coughing
  • Extreme airflow obstruction – some cases – Cyanosis

Diagnosis :

  • Demonstration of an increased airflow obstruction
  • Difficulty with Exhalation – Prolonged Expiration, Wheeze
  • Atopic asthma – identification of eosinophilia in the peripheral blood and also eosinophils, Curschmann spirals, and Charcot – Leyden crystals in the sputum.

Treatment of Asthma :

  • Bronchodilators
  • Glucocorticoids
  • Leukotriene antagonists
  • And also IL-5 blocking antibodies

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