Chapter 15: Lung: Obstructive versus Restrictive Pulmonary Diseases Flashcards
1
Q
Based on pulmonary function tests, chronic noninfectious diffuse pulmonary diseases can be
classified in one of two categories:
A
- (1) obstructive diseases (or airway diseases)
- (2) restrictive diseases,
2
Q
What are is an obstructive disease ( airway dse)?
A
(1) obstructive diseases (or airway diseases), 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
3
Q
What is restrictive dse?
A
(2) restrictive
diseases, characterized by reduced expansion of lung parenchyma and decreased total lung
capacity.
4
Q
In individuals with diffuse obstructive disorders, pulmonary function tests show
decreased maximal airflow ratesduringforced expiration, usually measured by___________
A
forced expiratory
volume at 1 second.
5
Q
Expiratory airflow obstruction may be caused by a variety of conditions listed in Table 15-3 .
They are distinguished by _________ and hence different mechanisms for airflow obstruction.
As discussed below, such neat distinctions are not always
possible.
A
distinct anatomic lesions
6
Q
In contrast, restrictive diseases are identified by a reduced total lung capacity, and an
expiratory flow rate that is normal or reduced proportionately.
Restrictive defects occur in two
general conditions:
A
(1) chest wall disorders (e.g., neuromuscular diseases such as poliomyelitis, severe obesity, pleural diseases, and kyphoscoliosis) and
(2) chronic interstitial and infiltrative diseases, such as pneumoconioses and interstitial fibrosis of unknown etiology.
7
Q
TABLE 15-3 – Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
A
Clinical Term :Anatomic Site
- Chronic bronchitis : Bronchus
- Bronchiectasis :Bronchus
- Asthma : Bronchus
- Emphysema: Acinus
- Small-airway disease, bronchiolitis :Bronchiole
8
Q
TABLE 15-3 – Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
Chronic
bronchitis
A
- Anatomic Site: Bronchus
- Major Pathologic Changes: Mucous gland hyperplasia, hypersecretion
- Etiology: Tobacco smoke, air
pollutants - S/Sx: Cough, sputum production
9
Q
TABLE 15-3 – Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
Bronchiectasis
A
Anatomic Site: Bronchus
Major Pathologic Changes: Airway dilation and
scarring
Etiology: Persistent or severe
infections
S/Sx: Cough, sputum production
10
Q
TABLE 15-3 – Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
Asthma
A
Anatomic Site: Bronchus
Major Pathologic Changes: Smooth muscle
hyperplasia, excess
mucus, inflammation
Etiology:Immunological or
undefined causes
S/Sx: Cough, sputum production
11
Q
TABLE 15-3 – Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
Emphysema
A
Anatomic Site: Acinus
Major Pathologic Changes: Airspace enlargement; wall
destruction
Etiology:Tobacco smoke
S/Sx: Dyspnea
12
Q
TABLE 15-3 – Disorders Associated with Airflow Obstruction: The Spectrum of Chronic
Obstructive Pulmonary Disease
Small-airway
disease,
bronchiolitis
A
Anatomic Site: Bronchiole
Major Pathologic Changes: Inflammatory
scarring/obliteration
Etiology:Tobacco smoke, air pollutants, miscellaneous
S/Sx:Cough, dyspnea
13
Q
What is COPD?
A
Emphysema and chronic bronchitis are often clinically grouped together and referred to as
chronic obstructive pulmonary disease (COPD), since many patients have overlapping features
of damage at both the acinar level (emphysema) and bronchial level (bronchitis), almost
certainly because one extrinsic trigger—cigarette smoking—is common to both
In addition,
small-airway disease, a variant of chronic bronchiolitis, is now known to contribute to obstruction both in emphysema and chronic bronchitis.
[11] While asthma is distinguished from chronic
bronchitis and emphysema by thepresence of reversible bronchospasm,some patients with
otherwise typical asthma also develop an irreversible component (
14
Q
A
FIGURE 15-5 Schematic representation of overlap between chronic obstructive lung
diseases.
Conversely,
some patients with otherwise typical COPD have a reversible component. It is clinically common
to label such patients as having COPD/asthma. In a recent study the overlap between these
three disorders was found to be substantial
15
Q
In most patients, COPD is the result of long-term ____________
A
heavy cigarette smoking; about 10% of
patients are nonsmokers.
However, only a minority of smokers develop COPD, the
reason for which is still unknown
16
Q
What is emphysema?
A
EMPHYSEMA
Emphysema is a condition of the lung characterized by irreversible enlargement of the
airspaces distal to the terminal bronchiole, accompanied by destruction of their walls without
obvious fibrosis
Incidence.
There is a clear-cut association between heavy cigarette
smoking and emphysema, and women and African Americans are more susceptible than other
groups.
17
Q
How is emphysema classified?
A
Emphysema is classified according to its anatomic distribution within the lobule
18
Q
Types of Emphysema.
A
Recall that the
lobule is a cluster of acini, the terminal respiratory units.
Although the term emphysema is
sometimes loosely applied to diverse conditions, there are four major types:
- (1) centriacinar ,
- (2) panacinar ,
- (3) paraseptal, and
- (4) irregular .
Of these, only the first two cause clinically significant airflow obstruction ( Fig. 15-6 ).
19
Q
Among the types of emphysema, which among the four causes clinically
significant airflow obstruction
A
(1) centriacinar ,
(2) panacinar
Centriacinar emphysema is far more common than
the panacinar form, constituting more than 95% of cases.
20
Q
A
FIGURE 15-6 Major patterns of emphysema.
A, Normal structure within the acinus.
B, Centriacinar emphysema with dilation that initially affects the respiratory bronchioles.
C, Panacinar emphysema with initial distention of the alveolus and alveolar duct.
21
Q
What is Centriacinar (Centrilobular) Emphysema?
A
In this type of emphysema the central or proximal parts of the acini , formed by respiratory
bronchioles, are affected, whereas distal alveoli are spared.
Thus,
both emphysematous and normal airspaces exist within the same acinus and lobule.
The lesions are more common and usually more severe in the upper lobes, particularly in the apical
segments.
The walls of the emphysematous spaces often contain large amounts of black pigment.
Inflammation around bronchi and bronchioles is common.
In severe centriacinar
emphysema, the distal acinus may also be involved, and differentiation from panacinar
emphysema becomes difficult.
Centriacinar emphysema occurs predominantly in heavy smokers, often in association with chronic bronchitis.
22
Q
What is the more common and more severe area affected in centriacinar emphysema?
A
The lesions are more common and usually more severe in the upper lobes, particularly in the apical
segments.
23
Q
In severe centriacinar
emphysema, the distal acinus may also be involved, and differentiation from panacinar
emphysema becomes difficult.
T or F
A
True
24
Q
What is Panacinar (Panlobular) Emphysema?
A
In this type, the acini are uniformly enlarged from the level of the respiratory bronchiole to the
terminal blind alveoli ( Figs. 15-6C and 15-7B ).
The prefix “pan” refers to the entire acinus but
not to the entire lung.
. This type of emphysemais associated with α1-antitrypsin ( α1-
AT) deficiency
25
What is the difference of centriacinar and panlobular?
In contrast to **centriacinar emphysema**, panacinar emphysema tends to
* *occur more commonly in the lower zones** and in the **anterior margins of the lung**, and it is
* *usually most severe at the bases**
26
What type of emphysema is associated with heavy smoking?
Centriacinar
27
What type of emphysema is associated with a 1 antitrypsin deficiency?
panlobular
28
FIGURE 15-7
A, Centriacinar emphysema. Central areas show marked emphysematous
damage (E), surrounded by relatively spared alveolar spaces.
B, Panacinar emphysema
involving the entire pulmonary lobule.
29
Where does Panacinar (Panlobular) Emphysema commonly occurs?
panacinar emphysema tends to
occur more commonly in the lower zones and in the anterior margins of the lung, and it is
usually most severe at the bases
30
cen**T**rilobular= **T**op ( most common)
Top Gun heavy smoking
pan**L**obular= **L**ow ( most common)
31
What is Distal Acinar (Paraseptal) Emphysema?
In this type, the **proximal portion of the acinus** is **normal** , and the **distal part is predominantly
involved.**
The **emphysema is more striking adjacent to the pleura**, **along the lobular connective**
**tissue septa, and at the margins of the lobules**.
It **occurs adjacent to areas of fibrosis, scarring,
or atelectasis**and is**usually more severe in the upper half of the lungs.**
32
What is the characteristic finding of Distal Acinar (Paraseptal) Emphysema?
The characteristic
findings are of **multiple**, **continuous**, **enlarged airspaces from less than 0.5 cm** to **more than 2.0
cm in diameter**, sometimes**forming cystlike structures.**
This type of emphysema probably
**underlies many of the cases of spontaneous pneumothorax in young adults.**
33
Where is the most common affected area of Distal Acinar (Paraseptal) Emphysema?
It occurs adjacent to areas of fibrosis, scarring,
or atelectasis and is usually more severe in the upper half of the lungs
34
What is Airspace Enlargement with Fibrosis (Irregular Emphysema).?
Irregular emphysema, so named because **the acinus is irregularly involved** , is **almost invariably
associated with scarring**.
Thus, **it may be the most common form of emphysema,** because
careful search of most lungs at autopsy shows one or more scars from a healed inflammatory
process.
In most instances, these foci of irregular emphysema are **asymptomatic and clinically
insignificant.**
35
What is pathogenesis of the Airspace Enlargement with Fibrosis (Irregular Emphysema) ?
COPD is characterized by **mild chronic inflammation throughout the airways, parenchyma, and
pulmonary vasculature**.
Macrophages, **CD8+ and CD4+ T lymphocytes, and neutrophil**s are
increased in various parts of the lung.
**Activated inflammatory cells release a variety of
mediators**, including**leukotriene B4, IL-8, TNF, and others**, that are capable of damaging lung
structures or sustaining neutrophilic inflammation. [20]
Although details of the genesis of the two
common forms of emphysema—**centriacinar and panacinar—remain unsettled,** the **most
plausible hypothesis to account for the destruction of alveolar walls is the proteaseantiprotease
mechanism,**aided and abetted by**imbalance of oxidants and antioxidants**.
The protease-antiprotease imbalance hypothesis is **based on the observation that patients with
a genetic deficiency of the antiprotease α1-antitrypsin have a markedly enhanced tendency to
develop pulmonary emphysema**, which is**compounded by smoking** ( Fig. 15-8 ).
About **1% of all
patients with emphysema have this defect. α1-antitrypsin**, normally present in serum, tissue
fluids, and macrophages, is a **major inhibitor of proteases (particularly elastase)** secreted by
**neutrophils during inflammation**.
α1-antitrypsin is encoded by codominantly expressed genes on
the proteinase inhibitor (Pi) locus on chromosome 14. The Pi locus is extremely polymorphic,
with many different alleles. Most common is the normal (M) allele and the corresponding
phenotype. Approximately 0.012% of the US population is homozygous for the Z allele,
associated with markedly decreased serum levels of α1antitrypsin.
More than 80% of these
individuals develop symptomatic panacinar emphysema, which occurs at an earlier age and with
greater severity if the individual smokes.
36
What is α1-antitrypsin
α1-antitrypsin is encoded by codominantly expressed genes on the **proteinase inhibitor (Pi) locus on chromosome 14.**
The Pi locus is extremely polymorphic,
with many different alleles.
**α1-antitrypsin**, normally present in serum, **tissue
fluids, and macrophages**, is a**major inhibitor of proteases (particularly elastase) secreted by
neutrophils during inflammation**
37
More than 80% of these
individuals develop symptomatic panacinar emphysema, which occurs at an earlier age and with
greater severity if the individual smokes. The following sequence is postulated:
* 1. Neutrophils (the principal source of cellular proteases) are normally sequestered in
peripheral capillaries, including those in the lung, and a few gain access to the alveolar
spaces.
* 2. Any stimulus that increases either the number of leukocytes (neutrophils and
macrophages) in the lung or the release of their protease-containing granules
increases proteolytic activity.
* 3. With low levels of serum α1-antitrypsin, elastic tissue destruction is unchecked and
emphysema results
38
FIGURE 15-8 Pathogenesis of emphysema.
Excessive protease activity and reactive oxygen
species are additive in their effects and contribute to tissue damage.
α1-antitrypsin (α1-AT)
deficiency can be either congenital or “functional” as a result of oxidative inactivation
See
text for details. IL-8, interleukin 8; LTB4, leukotriene B4; TNF, tumor necrosis factor.
39
Thus, emphysema is seen to **result from the destructive effect of high protease activity** in
**subjects with low antiprotease activity**.
The **protease-antiprotease imbalance hypothesis** also
* *helps explain the effect of cigarette smoking in the development of emphysema,** particularly the
* *centriacinar** form in subjects with normal amounts of α1-antitrypsin:
* In smokers, neutrophils and macrophages accumulate in alveoli . The mechanism of inflammation is not entirely clear, but possibly involves the direct chemoattractant effects of nicotine as well as the effects of reactive oxygen species contained in smoke. These activate the transcription factor NF-κB, which switches on genes that encode TNF and chemokines, including IL-8. These, in turn, attract and activate neutrophils
* Accumulated neutrophils are activated and release their granules, rich in a variety of cellular proteases (neutrophil elastase, proteinase 3, and cathepsin G), resulting in tissue damage.
* Smoking also enhances elastase activity in macrophages; macrophage elastase is not
inhibited by α1-antitrypsin) and, indeed, can proteolytically digest this antiprotease. There is increasing evidence that in addition to elastase, matrix metalloproteinases derived from macrophages and neutrophils have a role in tissue destruction.
40
In addition, **smoking has a seminal role in perpetuating the oxidant-antioxidant imbalance** in the pathogenesis of emphysema.
Why?
Normally, the **lung contains a healthy complement of antioxidants** (superoxide dismutase, glutathione) that keep oxidative damage to a minimum.
Tobacco smoke
* *contains abundant reactive oxygen species** (free radicals), which **deplete these antioxidant**
* *mechanisms**, thereby **inciting tissue damage (** Chapter 1 ).
* *Activated neutrophils also add to the**
* *pool of reactive oxygen species in the alveoli.**
A secondary consequence of oxidative injury is
* *inactivation of native antiproteases, r**esulting in **“functional” α1-antitrypsin deficiency even in**
* *patients without enzyme deficiency.**
41
How does emphysema leads to funcitonal ariflow obstruction despite absence of mechanical obstruction?
Since s**mall airways are normally tethered by the elastic** **recoil of the lung parenchyma**, 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.
42
Until recently loss of elastic recoil was considered to be the sole mechanism of airflow
obstruction in emphysema. However, careful studies in young smokers who died in accidents
have revealed that inflammation of small airways, defined as bronchioles less than 2 mm in
diameter, occurs early in the evolution of COPD. Several changes are seen:
1. **goblet cell metaplasia** with **mucus plugging of the lumen**
2. i**nflammatory infiltration of the walls with neutrophils,** **macrophages, B cells** (sometimes
forming follicles), **CD4 and CD8+ T cells**
3. **thickening of the bronchiolar wall** due to smooth muscle hypertrophy and peribronchial
fibrosis
Together these changes narrow the bronchiolar lumen and contribute to airway
obstruction.
43
One of the perplexing features of COPD is that **smoldering inflammation and slow progressive
destruction of the lung parenchyma**often continue**for decades after cessation of smoking**. [22]
While there are no clear answers, there is emerging evidence that the **initial insult in the form of
tobacco smoke**, or other irritants, triggers a**maladaptive, self-perpetuating immune response in
which both innate and adaptive components play a role.**
Fingers are pointing to pathogenic
CD4+TH17 cells similar to those that are involved in other immunemediated inflammatory
diseases such as Crohn disease, but much remains to be known.
44
What is the morphology of emphysema?
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 severely affected**.
Large apical blebs or bullae are more characteristic of
irregular emphysema secondary to scarring and of distal acinar emphysema. Large alveoli
can easily be seen on the cut surface of formalin-inflated fixed lung
45
What is the more characteristic of irregular emphysema?
Large apical **blebs or bulla**e are more characteristic of
irregular emphysema secondary to scarring and of distal acinar emphysema
46
What is the appearance of emphysema microscopically ?
Microscopically, there are abnormally large alveoli **separated by thin septa with only focal
centriacinar fibrosis**.
There is loss of attachments of the alveoli to the outer wall of small
airways.
The **pores of Kohn are so large that septa appear to be floating** or protrude blindly into alveolar spaces with a club-shaped end.
As alveolar walls are destroyed, there is
d**ecrease in the capillary bed**.
With advanced disease, there are even larger **abnormal
airspaces and possibly blebs or bullae, which often deform and compress the respiratory
bronchioles and vasculature of the lung**.
Inflammatory changes in small airways were
described earlier.
47
The clinical manifestations of emphysema do not appear until at least \_\_\_\_\_\_\_\_
one third of the
functioning pulmonary parenchyma is damaged
48
What is the Clinical Course of emphysema?
* **Dyspnea** is usually the first symptom; it begins insidiously but is steadily progressive.
* In some patients, **cough or wheezing** is the **chief complaint,** easily confused with asthma.
* **Cough and expectoration** are extremely variable and **depend on the extent of the associated bronchitis**.
* **Weight loss is common** and can be so severe as to suggest a hidden malignant tumor.
* Classically, **the patient is barrel-chested and dyspneic**, with obviously prolonged expiration, sits forward in a hunched-over position, and breathes through pursed lips.
49
What is the first symptom in emphysema?
Dyspnea is usually the first symptom; it begins
insidiously but is steadily progressive
50
In some patient what is the chief complaint of emphysema?
In some patients, cough or wheezing is the chief
complaint, easily confused with asthma.
51
**Expiratory airflow limitation**, best measured through spirometry, is the **key to diagnosis.**
52
In individuals with **severe emphysema**, **cough is often slight, overdistention is severe, diffusion
capacity is low, and blood gas values are relatively normal at rest.**
Such patients may
overventilate and remain well oxygenated, and therefore are somewhat ingloriously designated
pink puffers (see Table 15-4 ).
Development of cor pulmonale and eventually congestive heart failure, related to secondary pulmonary vascular hypertension, is associated with a poor prognosis.
Death in most patients with emphysema is due to :
* (1) respiratory acidosis and coma,
* (2) right-sided heart failure, and
* (3) massive collapse of the lungs secondary to pneumothorax.
53
Treatment options of emphysema include
* bronchodilators
* , steroids,
* bullectomy,
* and, in selected patients, lung volume reduction surgery and lung transplantation.
* Substitution therapy with α1-AT is being evaluated.
54
TABLE 15-4 -- Emphysema and Chronic Bronchitis
Predominant Bronchitis---- Predominant Emphysema
Age (yr): 40–45 50–75
Dyspnea: Mild; late **Severe; early**
Cough: Early; copious sputum **Late; scanty sputum**
Infections: Common Occasional
Respiratory insufficiency: Repeated **Terminal**
Cor pulmonale: **Common** Rare; terminal
Airway resistance: Increased **Normal or sligh**tly increased
Elastic recoil: Normal **Low**
Chest xray:: Prominent vessels; large heart **Hyperinflation; small heart**
Appearance: Blue bloater Pink puffer
55
Other Forms of Emphysema.
Now we come to some conditions in which the term emphysema is applied less stringently and
to some closely related conditions.
* Compensatory Hyperinflation (Emphysema).
* Obstructive Overinflation.
* Bullous Emphysema.
56
What is Compensatory Hyperinflation (Emphysema)?
This term is sometimes used to **designate dilation of alveoli but not destruction of septal walls** in
**response to loss of lung substance elsewhere.**
It is best exemplified by the hyperexpansion of the residual lung parenchyma that follows surgical removal of a diseased lung or lobe.
57
What is Obstructive Overinflation?
In this condition the **lung expands because air is trapped within it .**
A common cause is **subtotal
obstruction by a tumor or foreign object**.
Another example is **congenital lobar overinflation** in
**infants,** probably **resulting from hypoplasia** of **bronchial cartilage and sometimes associated with
other congenital cardiac and lung abnormalities.**
58
Overinflation in obstructive lesions occurs
either
* (1) because of a **ball-valve action** of the **obstructive agent,** so that air enters on **inspiration but cannot leave on expiration,** or
* (2) because the **bronchus may be totally**
**obstructed** **but ventilation through collaterals** may bring in air from behind the obstruction.
These collaterals **are the pores of Kohn and other direct accessory bronchioloalveolar**
**connections (the canals of Lambert)**.
59
Why is obstructive overinflation can be life threatening emergency?
Obstructive overinflation can be a life-threatening
emergency, because the affected portion distends sufficiently to compress the remaining
normal lung.
60
What is Bullous Emphysema?
Bullous Emphysema.
This is a **descriptive term for large subpleural blebs or bullae** (spaces more than 1 cm in
diameter in the distended state) **that can occur in any form of emphysema** ( Fig. 15-9 ).
They
represent localized accentuations of emphysema and occur near the apex, sometimes in
relation to old tuberculous scarring.
* *On occasion, rupture of the bullae may give rise to
pneumothorax. **
61
FIGURE 15-9 Bullous emphysema with large subpleural bullae (upper left) .
62
What is interstitial emphysema?
The **entrance of air into the connective tissue stroma** **of the lung, mediastinum, or
subcutaneous tissue is** called interstitial emphysema.
In most instances, **alveolar tears in
pulmonary emphysema provide the avenue of entrance of air** into the stroma of the lung, but
**rarely, a wound of the chest that allows air to be sucked in or a fractured rib** that punctures the
lung substance may underlie this disorder.
Alveolar tears usually occur **when there is a
combination of coughing plus some bronchiolar obstruction**, producing**sharply increased
pressures within the alveolar sacs.**
Children with whooping cough and bronchitis, patients with
obstruction to the airways (by blood clots, tissue, or foreign bodies) or who are being artificially
ventilated, and individuals who suddenly inhale irritant gases are at risk.
63
What is CHRONIC BRONCHITIS?
Chronic bronchitis is defined clinically as **persistent cough with sputum production for at least 3
months in at least 2 consecutive year**s,**in the absence of any other identifiable cause**.
Chronic
bronchitis, so **common among habitual smokers** and **inhabitants of smog-laden cities, is not
nearly as trivial as was once thought.**
64
When Chronic bronchitis persistent for years, it may result to three:
* (1) progress to **COPD,**
* (2) lead to **cor pulmonale and heart failure,** or
* (3) cause **atypical metaplasia and dysplasia** of the respiratory epithelium, providing a rich soil for cancerous transformation.
65
What is the primiry intitiating factor in chronic bronchitis?
The **primary or initiating factor** in the genesis of chronic bronchitis seems to be **long-standing
irritation by inhaled substances such as tobacco smoke (90% of patients are smokers)**, and
**dust from grain, cotton, and silica.**
66
What is the pathogenesis of Chronic bronchitis?
The **earliest feature** of chronic bronchitis is **hypersecretion of
mucus in the large airways,**associated with**hypertrophy of the submucosal glands i**n the
**trachea and bronchi**. [24]
Proteases released from neutrophils, such as **neutrophil elastase** and
**cathepsin, and matrix metalloproteinases, stimulate** **this mucus hypersecretion.**
67
As chronic
bronchitis persists, there is also a marked increase in \_\_\_\_\_\_\_\_\_\_\_
**goblet cells** of small airways—small
bronchi and bronchioles—leading to excessive mucus production that contributes to airway
obstruction.
68
It is thought that **both the submucosal gland hypertrophy** and the increase in goblet
cells are protective metaplastic reactions against tobacco smoke or other pollutants (e.g., sulfur
dioxide and nitrogen dioxide)
T or F?
True
69
Although mucus hypersecretion in large airways is the cause of sputum overproduction, it is
now thought that \_\_\_\_\_\_\_\_\_\_**can result in physiologically important and early
manifestations of chronic airway obstruction. [**25,] [26]
**This feature is similar to that describedearlier in emphysema and seems to be a common denominator in COPD.**
accompanying alterations in the small airways of the lung (small bronchi and
bronchioles, less than 2 to 3 mm in diameter)
70
What is the role of infection in chronic bronchitis?
The **role of infection seems to be secondary**.
**It is not responsible for the initiation of chronic
bronchitis**but**is probably significant in maintaining it**and**may be critical in producing acute
exacerbations.**
Cigarette smoke predisposes to infection in more than one way.
It interferes with
ciliary action of the respiratory epithelium, it may cause direct damage to airway epithelium, and
it inhibits the ability of bronchial and alveolar leukocytes to clear bacteria. Viral infections can
also cause exacerbations of chronic bronchitis.
71
What is the morphology of Chronic bronchitis?
Grossly, there is **hyperemia, swelling, and edema** of the mucous membranes,
frequently **accompanied by excessive mucinous or mucopurulent secretions**.
Sometimes,
**heavy casts of secretions** and **pus fill the bronchi and bronchioles.**
The **characteristic
histologic features are chronic inflammation** of the airways (predominantly lymphocytes) and
**enlargement of the mucus-secreting glands** of the trachea and bronchi.
Although the
numbers of goblet cells increase slightly, **the major change is in the size of the mucous
gland (hyperplasia).**
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).**
72
What is Reid index?
This increase in the size of the mucous
gland (hyperplasia) 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
73
What is bronchiolitis obliterans?
obliteration of lumen due to fibrosis (bronchiolitis obliterans).
74
What is the cardinal symptom of chronic bronchitis?
The cardinal symptom of chronic bronchitis is a **persistent cough productive of sputum**
75
What are the clinical features of Chronic bronchitis?
The **cardinal symptom of chronic bronchitis** is a **persistent cough productive of sputum.**
For many years **no other respiratory functional impairment is presen**t, but **eventually dyspnea on
exertion develops.**
With the passage of time, and usually **with continued smoking, other
elements of COPD may appear, including hypercapnia, hypoxemia, and mild cyanosis (“blue
bloaters”).**
Differentiation of pure chronic bronchitis from that associated with emphysema can
be made in the classic case (see Table 15-4 ), but, as has been mentioned, many patients with COPD have both conditions. Longstanding severe chronic bronchitis commonly leads to cor
pulmonale with cardiac failure. Death may also result from further impairment of respiratory
function due to superimposed acute infections.
76
What is asthma?
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 in the early**
* *morning.**
These symptoms are usually **associated with widespread but variable**
* *bronchoconstriction** and **airflow limitation that is at least partly reversible, either spontaneously**
* *or with treatment.**
77
78
What are the hallmarks of asthma?
The hallmarks of the disease are:
* increased airway responsiveness to a variety of stimuli, resulting in **episodic bronchoconstriction**;
* inflammation of the bronchial walls;
* and **increased mucus secretion**.
Some of the stimuli that trigger attacks in patients would have little or no effect in subjects with normal airways.
Many cells play a role in the inflammatory
response, in particular **lymphocytes, eosinophils, mast cells, macrophages, neutrophils, and**
**epithelial cells.**
79
What is status asthmaticus?
Individuals with asthma experience attacks of varying **severity of dyspnea, coughing, and**
**wheezing** due to **sudden episodes of bronchospasm.**
Rarely, ***a state of unremitting attacks,***
called **status asthmaticus**, **proves fatal;** usually, s**uch patients have had a long history of**
**asthma**.
Between the attacks, patients may be virtually asymptomatic. There has been a
significant increase in the incidence of asthma in the Western world in the past four decades.
80
Asthma is categorize into:
1. Atopic Asthma.
2. non-atopic
81
What is atopic asthma?
atopic **(evidence of allergen sensitization**, often in a **patient with a history of allergic rhinitis, eczema)**
82
What is non atopic asthma?
non-atopic (w**ithout evidence of allergen**
**sensitization**
83
```
In either type of athma, **episodes of bronchospasm** can be triggered by **diverse
mechanisms, such as respiratory infections (especially viral infections), environmental exposure
to irritants (e.g., smoke, fumes), cold air, stress, and exercise**
```
**T or F**
True
84
Recent studies have suggested
that the r**ecognition of subphenotypes of asthma based on the pattern of airway inflammation**
may also be useful.
There is emerging evidence for differing patterns of airway inflammation:
* eosinophilic,
* neutrophilic,
* mixed inflammatory,
* and pauci-granulocytic asthma
These subgroups **may differ in their etiology,** **immunopathology, and response to treatment.** [28] Asthma may also b**e classified according to the agents or events that trigger bronchoconstriction.**
These include
**seasonal, exercise-induced, drug-induced** (e.g., aspirin), and **occupational asthma, and asthmatic bronchitis in smokers**
85
What is the most common type of asthma?
Atopic asthma.
86
What is atopic asthma specifically?
This most common type of asthma is a **classic example of type I IgE-mediated hypersensitivity**
**reaction**, discussed in detail in Chapter 6 .
The disease **usually begins in childhood** and is
* *triggered by environmental allergens, such as dusts**, **pollens, roach or animal dander, and**
* *foods.**
A **positive family history of asthma is common,** and a **skin test with the offending antigen**
in these patients **results in an immediate wheal-and-flare reaction**.
87
How else can you diagnose atopic asthma?
Atopic asthma may also be
diagnosed **based on evidence of allergen sensitization** by s**erum radioallergosorbent tests**
**(called RAST)**, which **identify the presence of IgE specific for a panel of allergens.**
88
What is non atopic asthma specifically?
The second group of individuals with asthma **does 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) are
common triggers in non-atopic asthma.**[29]
In these patients **hyperirritability of the bronchial
tree probably underlies their asthma**
It is thought that **virus-induced inflammation of the
respiratory mucosa lowers the threshold of the subepithelial vagal receptors to irritants**.
Inhal**ed
air pollutants, such as sulfur dioxide, ozone, and nitrogen dioxide, may also contribute** to the
chronic airway inflammation and hyperreactivity that are present in some cases.
89
What are the common triggers in non-atopic asthma?
Respiratory infections due to viruses (e.g., rhinovirus, parainfluenza virus) are
common triggers in non-atopic asthma. [29]
90
Describe Drug-Induced Asthma.
Several pharmacologic agents provoke asthma.
* **Aspirin-sensitive asthma** is an uncommon yet
fascinating type, occurring in individuals with **recurrent rhinitis and nasal polyps**. These individuals are **exquisitely sensitive** to **small doses of aspirin** as well as other nonsteroidal antiinflammatory medications, and they experience not only asthmatic attacks but also urticaria.
It is
probable that aspirin triggers asthma in these patients by **inhibiting the cyclooxygenase
pathway of arachidonic acid metabolism without affecting the lipoxygenase route**, thus tipping
the balance toward elaboration of the bronchoconstrictor leukotrienes
91
What is occupational asthma?
This form of asthma is **stimulated by fumes (epoxy resins, plastics)**, **organic and chemical dusts**
* *(wood, cotton, platinum), gases (toluene),** and other c**hemicals (formaldehyde, penicillin**
* *products)**.
* *Minute quantities of chemicals are required to induce the attack**, which usually
* *occurs after repeated exposure.**
The underlying mechanisms vary according to stimulus and include **type I reactions, direct liberation of bronchoconstrictor substances, and hypersensitivity**
**responses of unknown origin.**
92
What are the major etiologic factors in atopic asthma?
The major etiologic factors in atopic asthma are a genetic predisposition to type I
hypersensitivity (“atopy”) and exposure to environmental triggers that remain poorly
defined.
93
It is postulated that inheritance of **susceptibility genes makes individuals prone to
develop strong TH2 reactions**against environmental antigens (allergens) that are ignored or
elicit harmless responses in most individuals.
So what is the pathogenesis after this?
* In the airways the scene for the reaction is set by
**initial sensitization to inhaled allergens**, which **stimulate induction of TH2 cells** ( Fig. 15-10 )
* TH2 cells **secrete cytokine**s that **promote allergic inflammatio**n and **stimulate B cells to produce IgE and other antibodies. T**hese cytokines include I**L-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 and also promotes **IgE production by B cells**.
* As in other allergic reactions ( Chapter 6 )**, IgE coats 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.**
94
What happens in the early reaciton of asthma and it dominated by what?
The early reaction is dominated by:
* bronchoconstriction,
* increased mucus production,
* and variable degrees of vasodilation with increased vascular permeability.
* **Bronchoconstriction** is triggered by **direct stimulation of subepithelial vagal (parasympathetic)** receptors through both central and local reflexes (including those mediated by unmyelinated sensory C fibers).
95
What happens in the late phase of asthma?
The late-phase reaction consists largely of **inflammation with recruitment of leukocytes**, notably
**eosinophils, neutrophils, and more T cells.**
Leukocyte recruitment is stimulated by **chemokines
produced by mast cells, epithelial cells and T cells**, and by other cytokines ( Chapter 2 ).
**Epithelial cells** are known to produce a large variety of cytokines in response to infectious
agents, drugs, and gases as well as to inflammatory mediators. [31]
This **second wave of
mediators stimulates the late reaction**.
For example, eotaxin, produced by airway epithelial cells, is a potent chemoattractant and activator of eosinophils. [32]
The **major basic protein** of
eosinophils, in turn, causes epithelial damage [31] and more airway constriction. [33]
Many
mediators have been implicated in the asthmatic response, but the relative importance of each
putative mediator in actual human asthma has been difficult to establish.
The long list of
“suspects” in acute asthma can be subclassified by the clinical efficacy of pharmacologic
intervention with inhibitors or antagonists of the mediators.
96
The long list of
“suspects” in acute asthma can be subclassified by the clinical efficacy of pharmacologic
intervention with inhibitors or antagonists of the mediators.
* The first (disappointingly small) group includes **putative mediators whose role in
bronchospasm** is clearly supported by efficacy of pharmacologic intervention:
* (1) leukotrienes **C4, D4, and E4,** extremely potent mediators that **cause prolonged
bronchoconstriction**as well as**increased vascular permeability** and increased mucus
secretion, and
* (2) **acetylcholine**, released from intrapulmonary motor nerves, which can cause airway smooth muscle constriction by directly stimulating muscarinic receptors.
* A **second group includes agents p**resent at the scene of the crime and with potent
**asthma-like effects but whose actual role in acute allergic asthma** seems relatively minor
on the basis of lack of efficacy of potent antagonists or synthesis inhibitors:
* (1) **histamine**, a potent bronchoconstrictor;
* (2) **prostaglandin D2,** which elicits
bronchoconstriction and vasodilatation; and (3) **platelet-activating factor** , which causes
aggregation of platelets and release of histamine and serotonin from their granules.
These mediators might yet prove important in other types of chronic or nonallergic
asthma.
* Finally, a large third group comprises the suspects for whom **specific antagonists or
inhibitors are not available or have been insufficiently studied as yet**. These include
numerous **cytokines, such as IL-1, TNF, and IL-6** (some of which exist in a preformed
state within the mast cell granules), [34] chemokines (e.g., eotaxin), neuropeptides,
nitric oxide, bradykinin, and endothelins
97
What is airway remodelling?
Over time, **repeated bouts of allergen exposure** and **immune reactions result in structural
changes in the bronchial wall,**referred to as**“airway remodeling.”**
These changes, described
later in greater detail, **include hypertrophy and hyperplasia of bronchial smooth muscle,**
**epithelial injury,** **increased airway vascularity, increased subepithelial mucus gland**
**hypertrophy/hyperplasia,** and **deposition of subepithelial collagen.**
The complex interactions
between the immune system, airway epithelium, and mesenchymal tissues in the airways are
poorly understood.
Infections with common respiratory pathogens, such as respiratory syncytial
virus and influenza, can exacerbate the chronic changes and cause serious worsening of the
clinical manifestations of the disease.
98
Although infections are often triggers for asthma, paradoxically, **some infections may be
protective.**
Epidemiologic studies first suggested that the incidence of asthma **was greater in
populations not exposed to microbe**s than in those living in an environment with abundant
microbes, and this relationship may explain the increasing incidence of asthma in developed
countries. [35]
These findings have led to the “hygiene hypothesis,” which states that
eradication of infections may promote allergic and other harmful immune responses. Despite a fascination with this idea, there is no plausible explanation for the inverse relationship between
infections and asthma.
99
Asthma is a **complex genetic trai**t in which multiple **susceptibility genes interact** with
**environmental factors to initiate the pathologic** **reaction.**
As in other complex traits ( Chapter 5 ),
there is considerable variability in the expression of these genes and in the combinations of
polymorphisms present in individual patients, and even in the significance and reproducibility of
reported polymorphisms.
Of the more than 100 genes that have been reported to be
associated with the disease, relatively few have been replicated in multiple patient populations.
Many of these affect the immune response or tissue remodeling.
Some genes may influence the
development of asthma, while others modify asthma severity or the patient's response to
therapy. [36] A few of these are discussed below:
* chromosome 5q
* IL-3, IL-4, IL-5, IL-9, and IL-13 and the IL-4
receptor.
* receptor for LPS (CD14)
* IL13 gene
* CD14
* TT genotype of CD14
* class II HLA alleles.
* ADAM-33
* β2-adrenergic receptor gene
* IL-4 receptor gene
* Mammalian chitinase family
100
One of the most replicated susceptibility loci for asthma is on chromosome 5q, near the
gene cluster encoding the cytokines\_\_\_\_\_\_\_\_
IL-3, IL-4, IL-5, IL-9, and IL-13 and the IL-4
receptor
The r**eceptor for LPS (CD14)**, and another candidate gene, the **β2-adrenergic
receptor**, also map here.
101
Why is chromosome 5q is of great interest in asthma?
This region is of great interest because of the connection between several of the genes located here **and the mechanisms of IgE regulation** and
**mast cell and eosinophil growth and differentiation.**
Among the genes in this cluster,
polymorphisms in the **IL13 gene have the strongest and most consistent associations**
**with asthma or allergic disease.**
102
Among the genes in this cluster in **chromosome 5q**
**polymorphisms in the \_\_\_\_\_\_\_\_\_\_\_** gene have the strongest and most consistent associations
with asthma or allergic disease.
**IL13**
103
The **association between asthma** and **other forms of atopy with a polymorphism** in the
gene encoding the monocyte receptor for endotoxin, **CD14,** is **worthy of additional
comments since it is paradigmatic for studies of gene-environment interactions.**
In some
studies, **the TT genotype of CD14 ha**s been associated with \_\_\_\_\_\_\_\_\_\_\_\_
Other studies have revealed the opposite, i.e., an
increased risk for atopy.
Further analysis has revealed that the TT genotype is
**protective against asthma or allergic sensitization in individuals exposed to low**
(household) endotoxin levels, whereas the same genotype is associated with an
increased risk for asthma or allergic sensitization in individuals exposed to high
endotoxin levels (as may occur in those living on farms).
These **differences may relate
to the influence of endotoxin levels on the regulation of TH1 vs. TH2 responses.**
In
individuals with the TT genotype high endotoxin levels skew the response towards TH2
type, thus favoring more brisk IgE production and a predisposition to allergy.
These
studies indicate that the relationship between genotype and phenotype is context
dependent, and help explain some of the discrepant results of association studies in
different populations.
reduced levels of IgE and
reduced risk for asthma and atopy
104
The tendency to produce IgE antibodies against some but not all antigens, such as
ragweed pollen, may be linked to particular \_\_\_\_\_\_\_\_
class II HLA alleles.
105
How does the gene ADAM-33 contribute to asthma?
ADAM-33: ADAM-33 belongs to a **subfamily of metalloproteinases** related to the MMPs
such as collagenases ( Chapter 3 ).
Although the precise function of ADAM-33 remains
to be elucidated, it is **known to be expressed by lung fibroblasts** and **bronchial smooth**
**muscle cells**.
It is speculated that **ADAM-33 polymorphisms** **accelerate proliferation of**
**bronchial smooth muscle cells and fibroblasts**, thus contributing to bronchial
hyperreactivity and subepithelial fibrosis. [39] ADAM-33 is also associated with decline in
lung functions.
106
β2-adrenergic receptor gene:
This also maps to 5q and variations in this gene are
associated wit**h differential in vivo airway hyper-responsiveness** and in **vitro response to
β-agonist stimulation.**
Thus, knowledge of the genotype can be of value in predicting
response to treatment.
107
Mutliple polymorphic variants in the gene encoding the alpha-chain
of the\_\_\_\_\_\_\_\_ are associated with atopy, elevated total serum IgE, and asthma.
IL-4 receptor gene:
108
What is chinatase?
Mammalian chitinase family: Chitinases are enzymes that cleave chitin, a polysaccharide
contained in many human parasites and the cell walls of fungi. In humans the chitinase family includes members with and without enzymic activity.
One member with activity,
acidic mammalian chitinase, is up-regulated in and contributes to TH2 inflammation.
Another chitinase family member with no enzymatic activity, YKL-40, is associated with
asthma. Serum levels of YKL-40 correlate with the severity of asthma.
109
What is the macroscopic finding of status asthmaticus?
In patients dying of status asthmaticus the lungs are **overdistended because of
overinflation**, with**small areas of atelectasis.**
The **most striking macroscopic finding** is
**occlusion of bronchi** and **bronchioles by thick, tenacious mucus plugs.**
110
What is the histological appearance of astma
Histologically, the
* *mucus plugs contain whorls of shed epithelium**, which **give rise to the well-known spiral**
* *shaped mucus plugs called Curschmann spirals** (these **result either from mucus plugging in**
* *subepithelial mucous gland ducts which later become extruded or from plugs in bronchioles).**
**Numerous eosinophils and *Charcot-Leyden crystals are present; the latter are collections
of crystalloid made up of an eosinophil lysophospholipase*binding protein called galectin-**
**The other characteristic histologic findings of asthma, collectively called “airway
remodeling**
111
What is Curschmann spirals?
**these are shaped mucus plugs which contains contain whorls of shed epithelium,**
112
What are Charcot-Leyden crystals?
are collections
of **crystalloid made up of an eosinophil lysophospholipase binding protein called galectin-
10.**
113
The other characteristic histologic findings of asthma, collectively called “**airway
remodeling”**( Fig. 15-10B ), include:
* Overall thickening of airway wall
* • **Sub-basement membrane fibrosis** (due to d**eposition of type I and III collagen beneath the classic basement membrane composed of type IV collagen and laminin) ( Fig. 15- 11 )**
* • I**ncreased vascularity**
* • An **increase in size of the submucosal glands** and m**ucous metaplasia of airway epithelial cells**
* • **Hypertrophy and/or hyperplasia of the bronchial wall muscle** (this has led to the novel therapy of bronchial thermoplasty in which radiofrequency current is applied to the walls of the central airways through a bronchoscopically placed probe, which reduces airway hyper-responsiveness for up to at least a year
114
FIGURE 15-11 Bronchial biopsy specimen from an asthmatic patient showing subbasement
membrane fibrosis, eosinophilic inflammation, and muscle hyperplasia.
115
What is the clinical course of asthma?
Clinical Course.
The **classic acute asthmatic attack lasts up to several hours.**
In some patients these symptoms
of **chest tightness, dyspnea, wheezing, and cough with or without sputum production, persist at**
**a low level constantly**.
In its most severe form, **status asthmaticus,** the severe acute paroxysm persists for days and even weeks, and under these circumstances airflow obstruction might be
so extreme as to cause severe cyanosis and even death. The clinical diagnosis is aided by the
demonstration of an increase in airflow obstruction (from baseline levels), difficulty with
exhalation (prolonged expiration, wheeze), and elevated eosinophil count in the peripheral
blood and the finding of eosinophils, Curschmann spirals, and Charcot-Leyden crystals in the
sputum (particularly in patients with atopic asthma).
In the usual case, with intervals of freedom
from respiratory difficulty, the disease is more discouraging and disabling than lethal, being
more of a problem in adult women than men. With appropriate therapy to relieve the attacks,
most individuals with asthma are able to maintain a productive life.
Up to 50% of childhood
asthma remits in adolescence only to return in adulthood in a significant number of patients.
In
other cases there is a variable decline in baseline lung function.
116
What it Bronchiectasis?
Bronchiectasis is a **disease characterized by permanent dilation of bronchi** and **bronchioles**
**caused by destruction of the muscle** and **elastic tissue, resulting from or associated with
chronic necrotizing infections.**
117
To be considered bronchiectasis the dilation must be
**permanent reversible bronchia**l **dilation often accompanies viral and bacterial pneumonia.**
Because of
better control of lung infections, bronchiectasis is now an uncommon condition
118
Bronchiectasis
develops in association with a variety of conditions, which include the following [44,] [45] :
* Congenital or hereditary conditions, including **cystic fibrosis, intralobar sequestration** of the **lung, immunodeficiency states**, [46] and **primary ciliary dyskinesia** and **Kartagener syndromes**
* • **Postinfectious conditions**, including necrotizing pneumonia caused by bacteria (Mycobacterium tuberculosis, Staphylococcus aureus, Haemophilus influenzae, Pseudomonas), viruses (adenovirus, influenza virus, human immunodeficiency virus [HIV]), and fungi (Aspergillus species)
* • Bronchial obstruction, due to tumor, foreign bodies, and occasionally mucus impaction, in which the bronchiectasis is localized to the obstructed lung segment
* • Other conditions, including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and post-transplantation (chronic lung rejection, and chronic graft-versus-host disease after bone marrow transplantation)
119
What are the major conditions associated with bronchiectasis?
* *Obstruction and infection** are the major conditions associated with bronchiectasis, and it is likely
* *that both are necessary for the development of full-fledged lesions**, although **either may come
first. **
After bronchial obstruction, normal clearing mechanisms are impaired, there is pooling of
secretions distal to the obstruction, and there is inflammation of the airway. Conversely, severe
infections of the bronchi lead to inflammation, often with necrosis, fibrosis, and eventually
dilation of airways.
120
These mechanisms, infection and obstruction, are most readily apparent in the severe form of
bronchiectasis associated with ___________ Chapter 10 ).
cystic fibrosis
In cystic fibrosis the primary defect
in **ion transport leads to defective mucociliary action**, and **accumulation of thick viscid secretions**
**that obstruct the airways.**
This **leads to a marked susceptibility to bacterial infections**, which **further damage the airways**.
**With repeated infections** there is **widespread damage to airway** walls, **with destruction of supporting smooth muscle and elastic tissue, fibrosis, and further
dilatation of bronchi.**
The smaller bronchioles become progressively obliterated as a result of
fibrosis (bronchiolitis obliterans).
121
What is primary ciliary dyskinesia ?
In primary ciliary dyskinesia , an **autosomal recessive syndrome** with variable penetrance and a
frequency of 1 in 15,000 to 40,000 births**, poorly functioning cilia contribute to the retention of
secretions and recurrent infections**that in turn lead to**bronchiectasis**.
There is an **absence or
shortening of the dynein arms**that are**responsible for the coordinated bending of the cilia.**
**Approximately half of the patients with primary ciliary dyskinesia have Kartagener syndrome**
(bronchiectasis, sinusitis, and situs inversus or partial lateralizing abnormality). [48]
The lack of
**ciliary activity interferes with bacterial clearance**, **predisposes the sinuses and bronchi** to
infection, and affects cell motility during embryogenesis, resulting in the situs inversus.
Males
with this condition tend to be infertile, as a result of sperm dysmotility.
122
What is Kartagener syndrome?
Kartagener syndrome
**(bronchiectasis**, **sinusitis**, and **situs inversus or partial lateralizing abnormality**).
123
What is allergic bronchopulmonary aspergillosis?
Allergic bronchopulmonary aspergillosis **is a condition that results from a hypersensitivity**
**reaction to the fungus Aspergillus fumigatus**.
It is also **an important complication of asthma and**
**cystic fibrosis.** [49]
Characteristics are **high serum IgE levels, serum antibodies to Aspergillus,**
**intense airway inflammation with eosinophils, and the formation of mucus plugs,** which play a
primary role in its pathogenesis.
There is evidence that neutrophil-mediated inflammation and a
relative deficiency of anti-inflammatory cytokines such as **IL-10** may also play a role. [50]
Clinically, there are periods of exacerbation and remission that may lead to proximal
bronchiectasis and fibrotic lung disease.
124
What is the histologic morphology of Bronchiectasis?
The histologic findings **vary with the activity** and **chronicity of the disease.**
In the full-blown,
active case there is an **intense acute and chronic inflammatory exudation** within the walls of
the bronchi and bronchioles, associated with desquamation of the lining epithelium and
extensive areas of necrotizing ulceration. **There may be pseudostratification of the columnar
cells or squamous metaplasia**of the remaining epithelium.
In some instances the necrosis
completely destroys the bronchial or bronchiolar walls and forms a lung abscess.
Fibrosis of
the bronchial and bronchiolar walls and peribronchiolar fibrosis develop in the more chronic
cases, leading to varying degrees of subtotal or total obliteration of bronchiolar lumens.
125
Bronchiectasis usually affects the \_\_\_\_\_\_\_\_\_\_\_\_
lower lobes bilaterally, particularly air
passages that are vertical, and is most severe in the more distal bronchi and bronchioles
126
When tumors or aspiration of foreign bodies lead to bronchiectasis, the involvement may be
**sharply localized to a** \_\_\_\_\_\_\_\_\_\_.
single segment of the lung
***\*\*\*The airways are dilated, sometimes up
to four times normal size.***
Characteristically, the bronchi and bronchioles are sufficiently bdilated that they can be followed almost to the pleural surfaces.
By contrast, in the normal
lung, the bronchioles cannot be followed by ordinary gross dissection beyond a point 2 to 3
cm from the pleural surfaces.
On the cut surface of the lung, the transected dilated bronchi
**appear as cysts filled with mucopurulent secretions**
127
In the usual case of bronchiectasis, a mixed flora can be cultured from the involved bronchi,
including **staphylococci, streptococci, pneumococci, enteric organisms, anaerobic and
microaerophilic bacteria, and (particularly in children) Haemophilus influenzae and
Pseudomonas aeruginosa**. [51]
In allergic bronchopulmonary aspergillosis a few fungal
hyphae can be seen on special stains within the muco-inflammatory contents of the
cylindrically dilated segmental bronchi.
In late stages the fungus may infiltrate the bronchial
wall.
128
