Obstructive Lung Diseases

By: Shefaa’ Qa’qa’

• Obstructive lung diseases (or airway diseases) are characterized by an increase in resistance to airflow due to partial or complete obstruction at any level from the trachea and larger bronchi to the terminal and respiratory bronchioles.

• In individuals with diffuse obstructive disorders, pulmonary function tests show decreased maximal airflow rates during forced expiration, usually expressed as the forced expiratory volume at 1 second (FEV1) over the forced ventilatory capacity (FVC). An FEV1/FVC ratio of less than 0.7 generally indicates airway obstruction.

• Common obstructive lung diseases include emphysema, chronic bronchitis, asthma, and bronchiectasis.

• Emphysema and chronic bronchitis are often clinically grouped together and referred to as chronic obstructive pulmonary disease (COPD), since the majority of patients have features of both, almost certainly because they share a major trigger—cigarette smoking.

Emphysema

• Emphysema is characterized by irreversible enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls without obvious fibrosis.

• Emphysema is classified according to its anatomic distribution within the lobule (cluster of acini):

(1) centriacinar: m.c,

(2) panacinar

(3) paraseptal

(4) irregular

Centriacinar emphysema: - proximal parts of the acini, formed by respiratory bronchioles, are affected. - The lesions are more common and usually more severe in the upper lobes. - Occurs predominantly in heavy smokers. Panacinar emphysema: - The acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli. - tends to occur more commonly in the lower zones, and it is usually most severe at the bases. - associated with α1-antitrypsin deficiency Distal acinar emphysema: - The distal part of acini is predominantly involved. - more severe in the upper half of the lungs. - It occurs adjacent to areas of fibrosis, scarring, or atelectasis. - This type of emphysema probably underlies many cases of spontaneous pneumothorax in young adults. Irregular emphysema: - The acinus is irregularly involved - almost invariably associated with scarring.

• Pathogenesis:

Inhaled cigarette smoke and other noxious

particles cause lung damage and inflammation, which results in parenchymal destruction (emphysema) and airway disease (bronchiolitis and chronic bronchitis).

• Small airways are normally held open by the elastic recoil of the lung parenchyma, and the loss of elastic tissue in the walls of alveoli that surround respiratory bronchioles reduces radial traction and thus causes the respiratory bronchioles to collapse during expiration. This leads to functional airflow obstruction despite the absence of mechanical obstruction.

• MORPHOLOGY:

- Advanced emphysema produces voluminous lungs, often overlapping the heart and hiding it when the anterior chest wall is removed. Generally, the upper two thirds of the lungs are more everely affected.

- apical blebs or bullae.

• Clinical Course: - Symptoms do not appear until at least one third of the functioning pulmonary parenchyma is damaged. - Dyspnea - Weight loss is common - Classically, the patient with severe emphysema is barrel-

chested and dyspneic, with obviously prolonged expiration, sits forward in a hunched-overposition, and breathes through pursed lips.

- Pink puffers (overventilate and well oxygenated) - Impaired expiratory airflow, best measured through spirometry, is the key to diagnosis.

• Development of cor pulmonale and eventually congestive heart failure, related to secondary pulmonary hypertension, is associated with a poor prognosis.

• pneumothorax.

• Treatment options include: smoking cessation, oxygen therapy, long-acting bronchodilators with inhaled corticosteroids, physical therapy, bullectomy, and, in selected patients, lung volume reduction surgery and lung transplantation.

Chronic Bronchitis

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

• Pathogenesis:

The primary or initiating factor in the genesis of chronic bronchitis is exposure to noxious or irritating inhaled substances such as tobacco smoke (90% of patients are smokers) and dust from grain, cotton, and silica.

- Mucus hypersecretion: The earliest feature of chronic bronchitis is hypersecretion of mucus in the large airways, associated with hypertrophy of the submucosal glands in the trachea and bronchi. It is thought that both the submucosal gland hypertrophy and the increase in goblet cells are protective reactions against tobacco smoke or other pollutants . - Inflammation and fibrosis involving small airways - cigarette smoke interferes with the ciliary action of the respiratory epithelium, preventing the clearance of mucus and increasing the risk of infection.

• MORPHOLOGY: - Although the numbers of goblet cells increase slightly, the major change is in the size of mucous glands . This increase can be assessed by the ratio of the thickness of the mucous gland layer to the thickness of the wall between the epithelium and the cartilage (Reid index). The Reid index (normally 0.4) is increased in chronic bronchitis, usually in proportion to the severity and duration of the disease. - The bronchial epithelium may exhibit squamous metaplasia and dysplasia. There is marked narrowing of bronchioles caused by mucus plugging, inflammation, and fibrosis. In the most severe cases, there may be obliteration of lumen due to fibrosis (bronchiolitis obliterans).

• Clinical Features: The cardinal symptom of chronic bronchitis is a persistent cough productive of sparse sputum. hypercapnia, hypoxemia, and mild cyanosis (“blue bloaters”) Long-standing severe chronic bronchitis commonly leads to cor pulmonale and cardiac failure. Death may also result from further impairment of respiratory function due to superimposed acute infections.

Asthma

• Asthma is a chronic disorder of the conducting airways, usually caused by an immunological reaction, which is marked by episodic bronchoconstriction due to increased airway sensitivity to a variety of stimuli; inflammation of the bronchial walls; and increased mucus secretion.

• bronchoconstriction and airflow limitation that is at least partly reversible, either spontaneously or with treatment.

• Asthma may be categorized as atopic (evidence of allergen sensitization and immune activation, often in a patient with allergic rhinitis or eczema) or non-atopic (no evidence of allergen sensitization).

• In either type, episodes of bronchospasm can have diverse triggers, such as respiratory infections (especially viral infections), exposure to irritants (e.g., smoke, fumes), cold air, stress, and exercise.

• Asthma may also be classified according to the agents or events that trigger bronchoconstriction. These include seasonal, exercise-induced, drug-induced (e.g., aspirin---decrease in prostaglandin E2), and occupational asthma, and asthmatic bronchitis in smokers.

• Atopic Asthma: - This most common type of asthma is a classic example of IgE-mediated (type I) hypersensitivity reaction. - The disease usually begins in childhood and is triggered by environmental allergens, such as dusts, pollens, cockroach or animal dander, and foods. - A positive family history of asthma is common. - a skin test with the offending antigen in these patients results in an immediate wheal-and-flare reaction. - Atopic asthma may also be diagnosed based on high total serum IgE levels or evidence of allergen sensitization by serum radioallergosorbent tests (called RAST), which can detect the presence of IgE antibodies that are specific for individual allergens.

• Non-Atopic Asthma: - Individuals with non-atopic asthma do not have evidence of allergen sensitization and skin test results are usually negative. - A positive family history of asthma is less common in these patients. - Respiratory infections due to viruses (e.g., rhinovirus, parainfluenza virus and respiratory syncytial virus) are common triggers. - Inhaled air pollutants, such as smoking, sulfur dioxide, ozone, and nitrogen dioxide, may also contribute to the chronic airway inflammation and hyperreactivity in some cases. - As already mentioned, in some instances attacks may be triggered by seemingly innocuous events, such as exposure to cold and even exercise.

• Pathogenesis: - Atopic asthma is caused by a TH2 and IgE response to environmental allergens in genetically predisposed individuals. - A fundamental abnormality in asthma is an exaggerated TH2 response to normally harmless environmental antigens. - TH2 cells secrete cytokines that promote inflammation and stimulate B cells to produce IgE and other antibodies. - These cytokines include IL-4, which stimulates the production of IgE; IL-5, which activates locally recruited eosinophils; and IL-13, which stimulates mucus secretion from bronchial submucosal glands.

• IgE binds to the Fc receptors on submucosal mast cells, and repeat exposure to the allergen triggers the mast cells to release granule contents and produce cytokines and other mediators, which collectively induce the early-phase (immediate hypersensitivity) reaction and the late-phase reaction.

• The early reaction is dominated by bronchoconstriction(subepithelial vagal receptors stimulation) , increased mucus production, variable degrees of vasodilation, and increased vascular permeability.

• late-phase reaction is dominated by recruitment of leukocytes, notably eosinophils, neutrophils, and more T cells. Eosinophils are key inflammatory cells found in almost all subtypes of asthma.

• Many mediators produced by leukocytes and epithelial cells have been implicated in the asthmatic response:

leukotrienes C4, D4, and E4,

Acetylcholine

Histamine

Prostaglandin D2

platelet-activating factor

• Genetic Susceptibility:

Susceptibility to atopic asthma is multigenic and often associated with increased incidence of other allergic disorders, such as allergic rhinitis (hay fever) and eczema.

Polymorphisms in the IL13 gene

Polymorphisms in the gene encoding ADAM33, a metalloproteinase.

• Environmental Factors:

Asthma is a disease of industrialized societies where the majority of people live in cities.

hygiene hypothesis: The idea that microbial exposure during early development reduces the later incidence of allergic (and some autoimmune) diseases.

• MORPHOLOGY:

A characteristic finding in sputum or bronchoalveolar lavage specimens is Curschmann spirals, which may result from extrusion of mucus plugs from subepithelial mucous gland ducts or bronchioles.

Also present are numerous eosinophils and Charcot-Leyden crystals; the latter are composed of an eosinophil protein called galectin-10.

• Over time, repeated bouts of allergen exposure and immune reactions result in structural changes in the bronchial wall, referred to as “airway remodeling”, adds an irreversible component to the obstructive disease:

- Thickening of airway wall - Subbasement membrane fibrosis (due to deposition of type I and III collagen) - Increased vascularity - An increase in the size of the submucosal glands and number of airway goblet cells - Hypertrophy and/or hyperplasia of the bronchial wall muscle

• Clinical Course:

Recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or in the early morning. A classic acute asthmatic attack lasts up to several hours.

Rarely, a state of unremitting attacks, called acute severe asthma (formerly known as status asthmaticus), may prove fatal; usually, such patients have had a long history of asthma. The paroxysm persists for days and even weeks, sometimes causing airflow obstruction that is so extreme that marked cyanosis or even death ensues.

• Bronchiectasis:

Bronchiectasis is a disorder in which destruction of smooth muscle and elastic tissue by chronic necrotizing infections leads to permanent dilation of bronchi and bronchioles.

• Because of better control of lung infections, bronchiectasis is now uncommon. It may still develop in association with a variety of conditions, including the following:

- Congenital or hereditary conditions: cystic fibrosis, intralobar sequestration of the lung, immunodeficiency states, and primary ciliary dyskinesia and Kartagener syndromes. - necrotizing pneumonia - Bronchial obstruction, due to tumor, foreign bodies, or mucus impaction. - Allergic bronchopulmonary aspergillosis

primary ciliary dyskinesia : AR disorder, ciliary dysfunction due to defects in ciliary motor proteins.

• Pathogenesis:

Obstruction and infection are the major conditions associated with bronchiectasis. After bronchial obstruction, normal clearing mechanisms are impaired, resulting in pooling of secretions distal to the obstruction and secondary infection and

inflammation. Conversely, severe infections of the bronchi lead to inflammation, often with necrosis, fibrosis, and eventually dilation of airways.

• MORPHOLOGY:

Bronchiectasis usually affects the lower lobes bilaterally, particularly air passages that are vertical, and is most severe in the more distal bronchi and bronchioles.

When tumors or aspiration of foreign bodies lead to bronchiectasis, the involvement may be localized to a single lung segment.

The airways are dilated, sometimes up to four times normal size.

In some instances necrosis destroys the bronchial or bronchiolar walls and forms a lung abscess.

• A large variety of bacteria can be found in the usual case of bronchiectasis. These include staphylococci, streptococci, pneumococci, enteric organisms, anaerobic and microaerophilic bacteria, and (particularly in children) Haemophilus influenzae and Pseudomonas aeruginosa.

• Clinical Course: Bronchiectasis causes severe, persistent cough; expectoration of foul smelling, sometimes bloody sputum; dyspnea and orthopnea in severe cases; and, on occasion, hemoptysis, which may be massive. Paroxysms of cough are particularly frequent when the patient rises in the morning, as the change in position causes collections of pus and secretions to drain into the bronchi. Symptoms are often episodic and are precipitated by upper respiratory tract infections or the introduction of new pathogenic agents. Treatment: antibiotics and physical therapy.