Airway resistance during normal breathing is primarily influenced by the activity of the vagus nerve, which causes airway constriction, and the release of norepinephrine by sympathetic nerves, which inhibits constriction. Various irritants and triggers, such as smoke, dust, cold air, allergens, and viral infections, can stimulate the vagus nerve, leading to airway constriction and coughing. Substances like histamine, acetylcholine, thromboxane A2, prostaglandin F2, and leukotrienes are released by cells in the airway in response to these triggers, directly causing airway constriction and increased resistance. Inhalation occurs mainly in airways with diameters larger than 2 mm, making measurements of airway resistance ineffective in detecting small airway obstruction.

Multiple factors contribute to airway resistance, with lung volume being a significant determinant. Increasing lung volume widens the airways, resulting in decreased resistance, while decreasing lung volume leads to increased resistance. Airway mucus, edema, and contraction of bronchial smooth muscle also contribute to increased resistance by narrowing the airways. The density and viscosity of the inhaled gas can further impact airway resistance. For instance, diving with increased gas density can worsen airway resistance in individuals with asthma or obstructive pulmonary disease, whereas breathing low-density gases like oxygen-helium mixtures can decrease resistance and aid in treating conditions such as status asthmaticus.

Neural and humoral agents play a role in regulating airway resistance. Methacholine, a derivative of acetylcholine, is used to diagnose airway hyperresponsiveness, a characteristic feature of certain asthma types. Individuals with asthma exhibit airway obstruction at lower concentrations of inhaled methacholine compared to those without the condition.

Measurement of expiratory flow rates and volumes is an essential clinical tool for evaluating respiratory diseases. Typically, patients inhale maximally to total lung capacity and exhale as forcefully as possible to residual volume. Results are displayed as spirograms or flow-volume curves and are compared to predicted values from healthy individuals to identify abnormalities. Normal values vary based on factors such as age, sex, ethnicity, height, and weight. Abnormal values indicate pulmonary dysfunction, enabling early detection of respiratory problems and assessment of disease severity and treatment response.
During normal breathing, approximately 80% of the resistance to airflow at functional residual capacity (FRC) of efferent vagal fibers, either directly or reflexively, increases ) secondary to airway constriction (recall that the vagus nerve innervates airway smooth muscle). In con trast, stimulation of sympathetic nerves and release of the postganglionic neurotransmitter norepinephrine inhibits airway constriction. Reflex stimulation of the vagus nerve by inhalation of smoke, dust, cold air, or other irritants can also result in airway constriction and coughing. Agents such as histamine, acetylcholine, thromboxane A2, prostaglandin F2, and leukotrienes (LTB4, LTC4, and LTD4) are released by resident cells (e.g., mast cells, airway epithelial cells) and recruited cells (e.g., neutrophils, eosinophils) in response to various triggers such as allergens and viral infections. These agents act directly on airway smooth muscle to cause constriction and an increase in airway resistance. Inhalation •Fig. 22.2 Airwayresistance(AWR)andconductance(Cond.)asafunctionoflungvolume.
occurs in airways with diameters greater than 2 mm. Because the small airways contribute so little to total lung resistance, measurement of airway resistance is a poor test for detecting small airway obstruction.
Factors That Contribute to Airway Resistance
In healthy individuals, airway resistance is approximately 1 cm H2O/L • sec. One of the most important factors affecting resistance is lung volume. Increasing lung volume increases the caliber of the airways because it creates a positive transairway pressure. As a result, resistance to airflow decreases with increasing lung volume and increases with decreasing lung volume. If the reciprocal of resistance (i.e., conductance) is plotted against lung volume, the relationship between lung volume and conductance is linear (Fig.
22.2 ). Other factors that increase airway resistance include airway mucus, edema, and contraction of bronchial smooth muscle, all of which decrease the caliber of the airways.
The density and viscosity of the inspired gas also affect airway resistance. When scuba diving, gas density rises and results in an increase in airway resistance; this increase can cause problems for individuals with asthma and obstructive pulmonary disease. Breathing a low-density gas such as an oxygen-helium mixture results in a decrease in airway resistance and has been exploited in the treatment of status asthmaticus, a condition associated with increased airway resistance due to a combination of bronchospasm, airway inflammation, and hypersecretion of mucus.
Neurohumoral Regulation of Airway Resistance
In addition to the effects of disease, airway resistance is regulated by various neural and humoral agents. Stimulation of methacholine, a derivative of acetylcholine, is used to diagnose airway hyperresponsiveness, which is one of the cardinal features of certain asthma phenotypes. Although everyone is capable of responding to methacholine, airway obstruction develops in individuals with asthma at much lower concentrations of inhaled methacholine.
Measurement of Expiratory Flow
Measurement of expiratory flow rates and expiratory volumes is an important clinical tool for evaluating and monitoring respiratory diseases. Commonly used clinical tests have the patient inhale maximally to total lung capacity (TLC) and then exhale as rapidly and completely as possible to residual volume (RV). The test results are displayed either as a spirogram (
Fig. 22.3A ) or as a flow-volume curve/ loop (
Fig. 22.3B ). Results from individuals with suspected lung disease are compared with results predicted from normal healthy volunteers. Predicted or normal values vary with age, sex, ethnicity, height, and to a lesser extent, weight (
Table 22.1 ). Abnormalities in values indicate abnormal pulmonary function and can be used to predict abnormalities in gas exchange. These values can detect the presence of abnormal lung function long before respiratory symptoms develop, and they can be used to determine disease severity and the response to therapy.