Human Physiology, 14th edition (2016)

Respiratory Physiology 545

Clinical Investigation CLUES

Peter is a smoker and has asthma, and he had a low

FEV 1 measurement.

• How is FEV 1 measured and what does it indicate?


• What could explain his low FEV 1 and what can he
  do about it?

Asthma

The dyspnea, wheezing, and other symptoms of asthma are
produced by an obstruction of air flow through the bronchioles
that occurs in episodes, or “attacks.” This obstruction is caused
by inflammation, mucous secretion, and bronchoconstriction.
Inflammation of the airways is characteristic of asthma, and
itself contributes to increased airway responsiveness to agents
that promote bronchiolar constriction. Bronchoconstriction
further increases airway resistance and makes breathing dif-
ficult. The increased airway resistance of asthma may be pro-
voked by allergic reactions in which immunoglobulin E (IgE)
is produced (chapter 15, section 15.6), by exercise (in exercise-
induced bronchoconstriction), by breathing cold, dry air, or by
aspirin (in a minority of asthmatics).
Atopic (allergic) asthma, the most common form of asthma,
is a chronic inflammatory disorder of the airways characterized by

CLINICAL APPLICATION

Asthma medications fall into different categories. Quick-

acting beta agonists (such as albuterol ), which stimulate the

b 2 -adrenergic receptors in the pulmonary smooth muscle to

dilate the bronchioles (chapter 9, section 9.3), are used for res-

cue during an asthma attack. Long-acting beta agonists also

stimulate the b 2 -adrenergic receptors, but their effects last for

12 or more hours. These are generally combined with a gluco-

corticoid to inhibit inflammation, and are used more for asthma

control over a period of weeks rather than for rescue from an

attack. Inhaled or even intravenous corticosteroids are some-

times given for serious asthma attacks. Leukotriene receptor

antagonists, including montelukast ( Singulair ), are pills now

often used for long-term alleviation of asthma symptoms.

Clinical Investigation CLUES

Peter uses an inhaler when he has an asthma attack and

a different inhaler that he sometimes takes for a month.

• What is asthma, and how is it produced?


• What drugs are in his inhalers, and how do they
  work to treat asthma?

hyper-responsiveness of the airways to inhaled allergens. Activa-

tion of helper T lymphocytes by an allergen causes the release of

cytokines that lead to the production of IgE antibodies (chapter 15,

section 15.3) and pulmonary eosinophilia (high numbers of eosin-

phils). Mast cells also become more abundant in the lungs.

When the person is again exposed to the same allergen, the

allergen bonds to IgE on the surface of mast cells and basophils,

causing these cells to release chemicals that promote inflamma-

tion (chapter 15; see fig. 15.23). These include histamine, leukot-

rienes and prostaglandins (chapter 11; see fig. 11.34), and others

that stimulate the bronchoconstriction and mucous secretion of

asthma. With repeated exposures to allergens, there is sustained

infiltration of eosinophils and basophils, increased numbers of

mast cells, increased goblet cells that secrete more mucus, and

increased bronchiolar smooth muscle mass. This is accompanied

by hyper-responsiveness to allergens and airway irritants.

There is evidence that early exposure to diverse microbes and

their products, as may occur when children grow up on farms, can

protect children against later asthma. This supports the concept

that the incidence of asthma has increased because of population

movements to cities, causing children to be exposed to more ster-

ile urban environments. This, combined with increased exposure

to air pollutants from traffic, could be responsible for the increased

prevalence of asthma observed over the last several decades.

Emphysema

Alveolar tissue is destroyed in the chronic, progressive con-

dition called emphysema, which results in fewer but larger

alveoli ( fig.  16.17 ). This reduces the surface area for gas

exchange. Because alveoli exert a lateral tension on bronchio-

lar walls to keep them open, the loss of alveoli in emphysema

reduces the ability of the bronchioles to remain open during

expiration. Collapse of the bronchioles as a result of the com-

pression of the lungs during expiration produces air trapping,

which further decreases the efficiency of gas exchange in the

alveoli.

The most common cause of emphysema is cigarette smok-

ing. Cigarette smoke directly and indirectly causes the release of

inflammatory cytokines, which promote inflammation by attract-

ing and activating macrophages, neutrophils, and T lymphocytes

within lung tissue. Proteinases (protein-digesting enzymes)—

including matrix metalloproteinases (chapter 6) secreted from

alveolar macrophages and elastase from neutrophils—cause

destruction of the extracellular matrix. Proteinase degradation

of the extracellular matrix is aided by the inactivation of such

molecules as a 1 -antitrypsin, which normally protect the lungs

from destruction by proteinases. This destruction of the extracel-

lular matrix results in the loss of alveoli and enlargement of the

remaining alveoli that is characteristic of emphysema.

Chronic Obstructive Pulmonary

Disease (COPD)

Chronic obstructive pulmonary disease (COPD) is charac-

terized by chronic inflammation with narrowing of the airways