Physiology, Airway Resistance

Development

Lung development is traditionally subdivided into 3 main periods: embryonic, fetal, and postnatal. The major airways form during the embryonic period at 4 to 7 weeks. The rest of the airways form during the fetal period, with the bronchial tree developing between 5 and 17 weeks, and the most distal airways form between 16 and 26 weeks.[2] At the start of bronchial tree formation, the lung looks like a tubular gland. At 4 to 7 weeks, outgrowth and branching of the terminal bud occur, creating bronchial buds, which later become bronchi. The bronchial buds then bifurcate, ultimately resulting in the formation of bronchioles. This branching continues, and by approximately 26 weeks, the first 20 generations of airways are evident.[3] Fetal breathing movements begin around week 10 in humans. These breathing movements allow amniotic fluid to move in and out of the lungs, resulting in the stretching of the lung tissue, ultimately increasing the airways' caliber.[4]

Mechanism

The standard airway resistance that is present with the laminar flow of normal breathing is largely a function of the Hagen-Poiseuille equation[1]:

R = 8hl /πr⁴

Where h = viscosity, l = length, and r = radius 

Given this equation, it is clear that the radius is the most important factor in airway resistance and that small changes in radius can lead to significant changes in airway resistance. For example, if the radius of the tube doubles, the resistance decreases by a factor of 16. The medium-sized bronchi collectively have the smallest radius. If we use the principle outlined above, it makes sense that since the medium-sized bronchi collectively have the smallest radius, it would also be the site of greatest airway resistance. Using this same principle, we can also conclude that the terminal bronchioles have the lowest resistance since they have the largest radius.[5] Airway radius is not static and can be significantly altered by airway smooth muscle, which lines all of our conducting airways, except for the trachea, where airway smooth muscle gets confined to the anterior wall.[1] The sympathetic nervous system causes the relaxation of the airway's smooth muscle. Stimulation of beta-2 receptors on airway smooth muscle induces bronchodilation and decreases airway resistance. The parasympathetic nervous system innervates airway smooth muscle, triggering contraction when stimulated. This contraction of airway smooth muscle decreases the lumen, increasing airway resistance.[6] Airway resistance also changes between inspiration and expiration. Most airways within the lung parenchyma are tethered by alveolar attachments that transmit an outward force on these airways, which increases as the lungs expand. This increasing outward force increases airway radius, thus decreasing airway resistance. On expiration, this outward tethering force diminishes, and inward elastic recoil forces increase, causing a decrease in airway radius, which leads to increased airway resistance.[1]

Related Testing

Whole-body plethysmography is the most common method for measuring airway resistance. A plethysmograph is an air-tight chamber the participant sits inside, containing a tube that the patient puts in their mouth. There are 2 transducers within the plethysmograph: 1 located in the chamber that measures chamber pressure and 1 inside the tube that measures mouth pressure. There is also a flowmeter in the tube that measures the flow rate. The patient is asked to breathe normally during the test while the tube is left open. Mouth pressure and flow rate are recorded when the participant breathes into the open tube. A shutter then occludes the tube, and the participant is asked to try to breathe normally. With the participant attempting to breathe against the closed tube, there is no airflow, and mouth pressure approximates alveolar pressure.[7] After obtaining the values for mouth pressure (kPa), alveoli pressure (kPa), and flow rate (L/s), airway resistance (kPa s L) can be calculated using the equation below.

R = (Pm – Pa) / Vo

Where Pm = pressure in the mouth, Pa = pressure in the alveoli, and Vo = flow rate.[8]

Pathophysiology

One of the diseases that highlights the importance of normal airway resistance is asthma. Asthma develops due to chronic inflammation of the conducting airways, particularly the bronchi and bronchioles. This chronic inflammation results in contraction and hypertrophy of the airway smooth muscle, increased mucus production, and thickening of the lamina reticularis (a layer of connective tissue that surrounds the airways). Asthma is characterized as an obstructive lung disease because these maladaptive changes to the airways result in narrowing or even complete occlusion of the airway lumen, which leads to an increase in airway resistance that obstructs air from exiting the lungs.[9] The increased airway resistance associated with asthma is responsible for many signs and symptoms a patient experiences during an asthma exacerbation, including wheezing, dyspnea, chest tightness, and air trapping. Air trapping within the distal segments of the lungs is due to an inability to produce enough expiratory pressure to overcome the airway resistance of the more proximal bronchi and bronchioles. Since this airway resistance cannot be overcome, the air gets trapped in the distal segments of the lungs.[9][10]

Clinical Significance

Multiple medications can reduce airway resistance through various mechanisms. Many of these drugs treat obstructive lung diseases like asthma and COPD. Albuterol is an inhaled short-acting beta-2 agonist that stimulates beta-2 receptors on the surface of airway smooth muscle. The increased sympathetic tone causes the relaxation of airway smooth muscle, which causes dilation of the bronchi and bronchioles, reducing airway resistance. Heliox is often an adjunctive therapy alongside albuterol for reducing airway resistance. With severe airway narrowing, gas velocity increases, and airflow becomes turbulent. This turbulent airflow increases airway resistance. Helium is 7 times less dense than air, and when mixed with oxygen to form heliox, the lower density causes the turbulent airflow to revert to a state of laminar flow, decreasing airway resistance. This return to laminar flow and reduced resistance helps albuterol reach the distal airways, where it can act on distant beta-2 receptors. Also, it helps to maintain ventilation to the distal airways, preventing progression to respiratory failure. Ipratropium is another inhaled agent that works in the opposite way of albuterol. Ipratropium is an anticholinergic agent that works by blocking parasympathetic cholinergic receptors, which results in decreased parasympathetic tone on the airway smooth muscle, which prevents stimulation and contraction of airway smooth muscle, dilating bronchi and bronchioles, and resulting in decreased airway resistance. Inhaled corticosteroids are a common therapy option in the treatment of persistent asthma. They act to decrease airway inflammation and mucus production. This reduction in inflammation and mucus increases the caliber of airways, reducing airway resistance. Since these are inhaled corticosteroids, they have few, if any, systemic side effects.[11]