Airway Hyperresponsiveness

This lecture was mostly a recap of the PHAR3303 lectures on asthma, which I've written about here and here.

What is airway hyperresponsiveness?

Airway hyperresponsiveness means that the airway responds more strongly to a bronchoconstrictor like histamine or to some other respiratory challenge as compared to a healthier airway. Respiratory challenges can be direct, such as when you use histamine or methacholine (an acetylcholine analogue) that directly stimulates H1 or M3 receptors, respectively. Respiratory challenges can also be indirect, such as when you provoke bronchoconstriction through inflammatory pathways. Inhaling hypertonic saline or exercising can do this as these stimuli cause the airways to dry out.

How is it measured? Can you calculate a PC20?

One measure of airway hyperresponsiveness is a PC20, or the provocative concentration of agonist producing a 20% fall in FEV₁. To calculate a PC20, first calculate what the patient's FEV₁ will be after a 20% decrease (e.g. if your patient's FEV₁ is 3.4L, multiply that by 0.8 to get 2.72L). Next, find out what concentration of agonist you need to decrease the FEV₁ to that level.

What are the broad factors that determine airway narrowing?

There are several factors, including the density and affinity of receptors that might trigger airway narrowing and the prevalence of smooth muscle that can produce force. There are also factors that provide mechanical opposition to airway narrowing. For example, parenchymal tethering is the phenomenon in which the alveoli "tether" the airways open (i.e. when the alveoli are inflated, they tug on and open the airways).

Name potential mechanisms producing airway hyperresponsiveness?

Thickening of the ASM layer?

See previous post: Airway pathology in asthma. Thickness of the airway smooth muscle can also be compared to the perimeter of the basement membrane (Pbm), which gives a standard index of airway size.

Poor bronchodilatory response to deep inspiration?

See previous post: Smooth muscle response to stretch