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Pulmonary Pathology Online

Pathology of Bronchial Asthma

Dr Sampurna Roy MD

 

                                                                                                                      

 

Bronchial asthma is a chronic relapsing inflammatory disorder with increased responsiveness of tracheobroncheal tree to various stimuli, resulting in paroxysmal contraction of bronchial airways.

It refers to a condition of subjects with widespread narrowing of the bronchial airways which changes in severity over short periods of time, either spontaneously or under treatment, and is not due to cardiovascular disease.

The following points are worth noting:

Most asthmatic patients, even when apparently well, have persistent airflow obstruction and morphologic lesions.

This explains why asthma is placed in the category of chronic airflow obstruction.

A substantial proportion of patients with the usual clinical features of chronic airflow obstruction, predominantly middle-aged male smokers with chronic bronchitis and airflow obstruction, frequently also have increased airway reactivity - that is, an asthmatic component.

Asthma in most patients is readily recognized as acute attacks of airflow obstruction, often easy to treat.

In between the paroxysmal acute attacks, patients are normal.

Status asthmaticus is a long-lasting and severe asthma episode that does not respond to standard treatment.

It occurs when asthma symptoms - difficulty breathing, wheezing, and coughing - fail to improve with emergency medication treatment.

Status asthmaticus is a medical emergency that can lead to death.  

In addition, many patients with chronic bronchitis have evidence of bronchial reactivity, and some may exhibit a distinct overlap with asthma.

Finally, any airway insult may produce bronchial hyperreactivity.

Types of Asthma: Asthma is classically divided into extrinsic asthma and intrinsic asthma.

(1) Extrinsic atopic - allergen, reagin-mediated.

(2) Intrinsic non-reaginic (idiopathic) or precipitated by various factors.

Extrinsic asthma is most commonly an immunologic phenomenon and occurs as a response to inhaled antigens.

It is strongly related to allergic skin test reactivity and is usually found in children.

The prognosis is good.

Intrinsic asthma is a disease of adults and its prognosis is significantly worse.

The causative factor may not be apparent and skin reactivity is uncommon.

"Asthmatic bronchitis" is a disputed term and should be confined to patients  with chronic airflow obstruction who have clear-cut episodes of acute worsening of airflow obstruction.

These may also be regarded as patients with "intrinsic asthma".

Another way of looking at asthma is to divide it into more specific categories :

Antigen induced asthma is the most common form of asthma.

About one third to one half of all patients with asthma have known or suspected reactions to antigens.

Most antigens are air-borne and must be present in the environment for a considerable time to induce hyperreactivity.

Common allergens include pollen, animal hair or fur, and insect contamination of house dust.

Patients with antigen-induced asthma have classic extrinsic asthma.

Occupation-related substances:

Asthma may be associated with inhalation of a number of occupation-related substances.

More than 80 different occupations have been identified where such a substance occurs.

In some instances, these substances may provoke asthma by obvious hypersensitivity mechanisms.

(Example:  in animal handlers, bakers, and workers with wood and vegetable dusts, metal salts, pharmaceutical agents, and industrial chemicals).

In others, the asthma may be due to release of histamine-like substances, a mechanism noted in byssinosis ("brown lung"), an occupational lung disease in cotton workers. 

Occupational exposure may directly affect the autonomic nervous system.

For example, organic phosphorous insecticides act as anti-cholinesterases and produce overactivity of the parasympathetic nervous system.

Toluene diisocyanate is thought to have a beta-adrenergic antagonist action.

Irritant gases:

Irritant gases, such as hydrochloric acid, ammonia, and heated plastic fumes, have a direct effect of the airways.

At high doses almost all those exposed develop acute bronchitis and bronchoconstriction, where as at low doses these substances produce only bronchoconstriction in sensitive people.

Environmental pollution:

Environmental pollution is associated with bronchospasm, usually during episodes of massive air pollution.

Usually patients with preexisting lung conditions are affected, but new cases of asthma do occur.

Sulfur dioxide, oxides of nitrogen, and ozone are commonly implicated environmental pollutants.

Drugs:

Although drug-induced bronchospasm occurs most commonly in patients with known asthma, the agents themselves may produce asthma.

The best-known of these is aspirin, but several other anti-inflammatory agents have been implicated.

Viral Respiratory Tract Infections:

Viral respiratory tract infections trigger attacks in young asthmatics and may cause the first attack.

In children under the age of 2 years the respiratory syncytial virus is the usual agent, whereas in older children rhinovirus, influenza , and parainfluenza are the common inciting organisms.

Exercise:

Exercise may induce attacks of asthma in patients who already have the disease; some degree of bronchospasm is usual in such subjects.

Exercise-induced asthma is related to the magnitude of heat loss from the epithelium of the airways to the intra-thoracic gas.

The more rapid the ventilation (severity of exercise) and the colder and drier the air breathed, the more likely the asthma is to be precipitated. 

Note:  Other patients with typical chronic airflow obstruction have variable airflow obstruction that responds to bronchodilators or have airway hyperreactivity.

Such patients are not usually categorized as having asthma.

However, occasionally a patient who has otherwise typical chronic airflow obstruction may show unexpected reversibility when treated with bronchodilators or corticosteroids. 

Such patients, whose number is small, have been referred to as "hidden asthmatics".

It is important to recognize them because of the therapeutic implications of Asthma.

Asthma is uncommon, affecting 7% to 10% of children and 5% of adults.

It is most common in young children, least common in adolescence, and increases in frequency in adult life.

Typically, childhood asthma disappears in adolescence or early adult life and has a good prognosis.

Nevertheless, because deaths during acute attacks can occur, acute asthma should be regarded as a medical emergency, and prolonged difficulty in breathing - that is, status asthmaticus - must be terminated.

Most information on status asthmaticus has been derived from autopsies on patients who have died from the disease, and the findings are dramatic.

The airways are filled with thick tenacious adherent mucous plugs, and the lungs are greatly distended with air.

Histologic examination shows that the mucous plugs contain stripes of epithelium and many eosinophils, the extruded granules of which coalesce to form needle-like crystals (Charcot-Leyden crystals).

In some cases the mucoid exudates forms a cast of the airways.

These casts or whorled mucous plugs which may be coughed up, are known as "Curschmannís spirales".

Crystaloid debris of eosinophils membranes  (Charcot-Leyden crystals) are seen within airways.

Compact clusters of epithelial cells ("Creola bodies") are also seen in the sputum.

The epithelium displays a loss of the normal pseudostratified appearance and may be denuded, with only the basal cells remaining.

The basal cells are hyperplastic, and squamous metaplasia is seen.

An increase in goblet cells (goblet cell metaplasia) is also apparent.

Characteristically, the epithelial basement membrane is thickened, owing to an increase in collagen deep to the true basal lamina.

One of the most characteristic features of status asthmaticus is the prominence of bronchial smooth muscle, which reflects muscle hyperplasia.

The lamina propria contains numerous eosinophils.

Edema and thickening of the bronchial walls are common.

All these lesions may also be seen in apparently well asthmatics, but in these patients the lesions are less severe.

Other changes are seen in asthma:

- Bronchiectasis may occur in unusual locations, such as the upper lobe, probably because of bronchial obstruction by mucous plugs.

- Although asthma is primarily a disease of the central airways, peripheral airways may be abnormal, with increased airway muscle and goblet cell metaplasia.

- Emphysema is not a complication of long-standing asthma.

 A disagreement often arises between pathologists and clinicians concerning the relative importance of mucous plugs and bronchospasm.

Pathologists see fatal cases and favour the significance of the dramatic mucous plugs.

Clinicians are impressed by the rapid reversibility of airflow obstruction and thus stress the importance of bronchospasm.

It seems reasonable to assume that plugs may play a more significant role in status asthmaticus, where as bronchospasm may be more important in attacks of asthma.

Pathogenesis of Asthma:

The etiology and pathogenesis of asthma are complex.

The two primary features of asthma - bronchial muscle contraction and mucus secretion - are under nervous system control.

- Stimulation of the parasympathetic nervous system, represented by the vagus nerve, leads to bronchial constriction and hypersecretion of mucus.

- The sympathetic nervous system,through beta-adrenergic receptors, mediates bronchial dilatation and, less certainly, diminished mucus secretion.

- In addition, there is the nonadrenergic inhibitory system that causes relaxation of the airway smooth muscle.

- Numerous mediators released from inflammatory cells or from mast cells result in bronchoconstriction, including histamine ; bradykinin ; and thromboxane A.

- Some of these mediators also increase capillary permeability. Other agents are chemoattractants, for example, eosinophil and neutrophil chemotactic factors of anaphylaxis and leukotriene B4.

- The simplest theory of asthma invokes hypersensitivity.  The patient becomes sensitized to an antigen, the antibodies to which are IgE of the mast cells.

The inhaled antigen binds to its IgE antibody, after which the mast cells release their contents.

These in turn produce bronchial smooth muscle contraction, edema, and release of other mediators that amplify the response.

In addition, the products of mast cells stimulate irritant receptors, which induces reflex bronchial constriction and mucus hypersecretion via the vagus nerve.

How do the antigens sensitize the mast cells and how do the antigens reach them to trigger the reaction?

- Since bronchial epithelial cells are connected by tight junctions, loosening of the junctions may be a prerequisite for the appearance of asthma.

- Such loosening may reflect damage caused by infections, environmental irritants, and tobacco smoke.

- Mast cells and afferent nerves are present in the surface epithelium.

- Thus, when the antigen binds to its antibody, epithelial leakiness is amplified and a reflex stimulation occurs.

- Easier access to the submucosa is then possible, and both direct and reflex actions on smooth muscle occur.

- Other possible factors are inherent defects, including leakiness of the epithelium ; inadequate sympathetic nervous system inhibitory action (beta-adrenergic blockade); and excessive cholinergic reactivity.

Atopic (allergic) and Nonatopic Asthma:

Atopic (allergic) Asthma: This is the most common type.

It is triggered by environmental antigens (dust, pollen, food). Often the family has a positive history of atopy.

This is a classic type-I  IgE - mediated hypersensitivity reaction.

Acute phase : There is binding of antigen by IgE coated mast cells causing release of primary mediators (Example: leukotrienes) and secondary mediators (Example:  cytokines, neuro-peptides).

These mediators cause broncho-spasm, edema, mucus secretion, and recruitment of leukocytes.

Late phase reaction : It is mediated by recruited leukocytes (eosinophils, lymphocytes, neutrophils, monocytes) causing persistent bronchospasm and edema, leukocytic infiltration and loss of damaged epithelial cells.

Nonatopic Asthma (nonreaginic): It is often triggered by respiratory infections, chemical irritants, and drugs, usually without a family history and with little or no evidence of IgE mediated hypersensitivity.

The primary cause of increased airway reactivity is unknown.

In summary, the pathogenesis of asthma involves two extremes :

i) At one extreme, it is mediated entirely through allergens inspite of a healthy epithelium.

ii) At the other, a variety of non-specific stimuli acts on the severely compromised epithelium.

In most cases, there is probably a combination of the two.

In any event it seems that there is a final common pathway for all types of asthma, as evidenced by similarity of lesions.

 

Further reading:

Acute severe asthma: recent advances.

Severe acute asthma: its management in emergency visits and intensive care.

Airway inflammation assessed by invasive and noninvasive means in severe asthma: eosinophilic and noneosinophilic phenotypes.

Abnormalities of the bronchial arteries in asthma.

Airway smooth muscle and asthma.

Structural changes in the airways in asthma: observations andconsequences.

Acute severe asthma.

Relation between clinical severity of bronchial asthma and degree of airway inflammation assessed by the eosinophilic leukocyte count in induced sputum. 

 

 

Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)

 


 

 

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