Chapter 13: Obstructive lung diseases (emphysema, chronic bronchitis and asthma) Flashcards
Diffuse pulmonary diseases can be classified into two categories. Which two? What are they characterized by?
- obstructive airway disease, characterized by an increase in resistance to air flow caused by partial or complete obstruction at any level 2. restrictive disease, characterized by reduced expansion of lung parenchyma and decreased total lung capacity
What are the major diffuse obstructive disorders?
Emphysema, chronic bronchitis, bronchiectasis and asthma
What is the forced vital capacity (FVC) and expiratory flow rate (FEV1) in obstructive disorders?
FVC: Normal or slightly decreased FEV1: Significantly decreased
What is the forced vital capacity (FVC) and expiratory flow rate (FEV1) in restrictive disorders?
FVC: reduced FEV1: Normal or reduced proportionately
What is emphysema characterized by?
Permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls without significant fibrosis
What are the four major types of emphysema?
(1) centriacinar, (2) panacinar, (3) distal acinar, and (4) irregular (you can read about these types on p498-500, I did not include them)
Inhaled cigarette smoke and other noxious particles cause lung damage and inflammation, which, particularly in patients with a genetic predisposition, result in parenchymal destruction (emphysema) and airway disease (bronchiolitis and chronic bronchitis). Factors that influence the development of emphysema include:
- Inflammatory cells and mediators
- Protease–anti-protease imbalance
- Oxidative stress
- Airway infection (how these play a role in the pathogenesis can be found on p 500)
What are the symptoms of obstructive lung diseases?
Dyspnea usually is the first symptom; it begins insidiously but is steadily progressive. In patients with underlying chronic bronchitis or chronic asthmatic bronchitis, cough and wheezing may be the initial complaints. Weight loss is common and may be severe enough to suggest an occult malignant tumor.
What are conditions that are related to emphysema?
• Compensatory emphysema • Obstructive overinflation • Bullous emphysema • Mediastinal (interstitial) emphysema
How is chronic bronchitis diagnosed?
Chronic bronchitis is diagnosed on clinical grounds: it is defined by the presence of a persistent productive cough for at least 3 consecutive months in at least 2 consecutive years
What is the distinctive feature of chronic bronchitis?
Hypersecretion of mucus, beginning in the large airways (by smoking/pollutants)
Are eosinophils seen in chronic bronchitis?
No, they are seen in asthma
What inflammatory cells are seen in chronic bronchitis?
infiltration of macrophages, neutrophils, and lymphocytes
Whereas the defining mucus hypersecretion is primarily a reflection of involvement of large bronchi, the airflow obstruction in chronic bronchitis results from…
(1) small airway disease, induced by mucous plugging of the bronchiolar lumen, inflammation, and bronchiolar wall fibrosis, and (2) coexistent emphysema. In general, while small airway disease (chronic bronchiolitis) is an important component of early, mild airflow obstruction, chronic bronchitis with significant airflow obstruction almost always is complicated by emphysema.
What are the clinical features of chronic bronchitis?
The course of chronic bronchitis is quite variable. In some patients, cough and sputum production persist indefinitely without ventilatory dysfunction, while others develop COPD with significant outflow obstruction marked by hypercapnia, hypoxemia, and cyanosis
What clinical symptoms does asthma cause?
Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or early in the morning
What are the hallmarks of asthma?
Intermittent, reversible airway obstruction; chronic bronchial inflammation with eosinophils; bronchial smooth muscle cell hypertrophy and hyperreactivity; and increased mucus secretion
Many cells play a role in the inflammatory response of asthma, which in particular?
eosinophils, mast cells, macrophages, lymphocytes, neutrophils, and epithelial cells
What are major factors contributing to the development of asthma?
genetic predisposition to type I hypersensitivity (atopy), acute and chronic airway inflammation, and bronchial hyperresponsiveness to a variety of stimuli
Asthma may be classified in atopic or non-atopic. What do they mean?
Atopic: evidence of allergen sensitization Nonatopic: no evidence of allergen sensitization
What may episodes of bronchospasm be triggered by?
Diverse exposures, such as respiratory infections (especially viral), airborne irritants (e.g., smoke, fumes), cold air, stress, and exercise. There also are varying patterns of inflammation—eosinophilic (most common), neutrophilic, mixed inflammatory, and pauci-granulocytic—that are associated with differing etiologies, immunopathologies, and responses to treatment.
Explain which helper cells and cytokines play a role in the classic atopic form of asthma
The classic atopic form is associated with excessive type 2 helper T (TH2) cell activation. Cytokines produced by TH2 cells account for most of the features of atopic asthma— IL-4 and IL-13 stimulate IgE production, IL-5 activates eosinophils, and IL-13 also stimulates mucus production. IgE coats submucosal mast cells, which on exposure to allergen release their granule contents and secrete cyto- kines and other mediators. Mast cell–derived mediators produce two waves of reaction: an early (immediate) phase and a late phase (I don’t think you should know this, since it wasn’t discussed in the lecture)
What is the early and late phase reaction in atopic asthma?
- The early-phase reaction is dominated by bronchoconstriction, increased mucus production, and vasodilation. Bronchoconstriction is triggered by mediators released from mast cells, including histamine, prosta- glandin D2, and leukotrienes LTC4, D4, and E4, and also by reflex neural pathways.
- The late-phase reaction is inflammatory in nature. Inflammatory mediators stimulate epithelial cells to produce chemokines (including eotaxin, a potent chemoattractant and activator of eosinophils) that promote the recruitment of TH2 cells, eosinophils, and other leukocytes, thus amplifying an inflammatory reaction that is initiated by resident immune cells. (I don’t think you should know this, since it wasn’t discussed in the lecture)
What is atopic asthma?
This is the most common type of asthma and is a classic example of type I IgE–mediated hypersensitivity reaction (It usually begins in childhood. A positive family history of atopy and/or asthma is common, and the onset of asthmatic attacks is often preceded by allergic rhinitis, urticaria, or eczema. Attacks may be triggered by allergens in dust, pollen, animal dander, or food, or by infections)
Explain non-atopic asthma
Patients with nonatopic forms of asthma do not have evidence of allergen sensitization, and skin test results usually are negative. A positive family history of asthma is less common. Respiratory infections due to viruses (e.g., rhino- virus, parainfluenza virus) and inhaled air pollutants (e.g., sulfur dioxide, ozone, nitrogen dioxide) are common trig- gers. It is thought that virus-induced inflammation of the respiratory mucosa lowers the threshold of the subepithelial vagal receptors to irritants. Although the connections are not well understood, the ultimate humoral and cellular mediators of airway obstruction (e.g., eosinophils) are common to both atopic and nonatopic variants of asthma, so they are treated in a similar way.
What are, besides atopic and non-atopic, other types of asthma?
Drug-induced and occupational asthma
For a very very nice representation of what asthma looks like, see fig 13.10 on p 504
This picture is so big, I am too chicken to add it due to copyright sorry (it’s for your own understanding)
What are the clinical features of asthma?
An attack of asthma is characterized by severe dyspnea and wheezing due to bronchoconstriction and mucus plugging, which leads to trapping of air in distal airspaces and progressive hyperinflation of the lungs. In the usual case, attacks last from 1 to several hours and subside either spontaneously or with therapy. Intervals between attacks are characteristically free from overt respiratory difficulties, but persistent, subtle deficits can be detected by pulmonary function tests
How is asthma treated?
With anti-inflammatory drugs, particularly glucocorticoids and bronchodilators such as beta-adrenergic drugs and leukotriene inhibitors (recall that leukotrienes are potent bronchoconstrictors)
