5070: asthma/COPD

what is obstructive lung disease?

increased resistance to airflow

what are some examples of obstructive lung disease? x 5 things

asthma, emphysema

bronchitis (acute/chronic)

cystic fibrosis, bronchiectasis

what is restrictive lung disease?

decr expansion of the lungs due to alterations in the lung tissue, pleura, chest wall or neuromuscular function

what are some examples of restrictive lung disease?

1. idiopathic pulm fibrosis (interstitial pulm fibrosis)

2. sarcoidosis

3. pneumothorax

4. pneumonia

5. TB

6. MG

what is the def of asthma?

what is it characterized by? x 4 things

a chronic obstructive lung disease

1. airway inflammation

2. reversible airway obstruction

3. airway hyperresponsiveness

4. airway remodeling

is reversible airway obstruction always fully reversible?

how do we measure this?

no

test reversibility by administering a bronchodilator during pulm function tests

what is airway hyperresponsiveness made of? x 2 things

hypersensitivity and hyperreactivity

what is airway hypersensitivity?

bronchial smooth muscle shows increased response to even low doses of stimuli

what is airway hyperreactivity?

bronchial sm constricts much more strongly in response to stimuli

what obstructive lung disease tends to be episodic with acute exacerbations and sx free periods?

asthma

in asthma, spasmodic bronchial contractions are manifested by sx like…. x 4 things

1. paroxysmal diffuse wheezing

2. dyspnea

3. cough

4. sensation of tightness in chest

what does the initial ‘initiation’ phase of asthma consist of ?

when do sx begin?

combo of genetics and environment

in childhood

what is the second phase of asthma pathogenesis? x 2 things

1. damage to lower airways due to inhaled agents

2. stimulated immune response in susceptible individuals

what is the 3rd phase of asthma pathogenesis include?

1. over time, recurrent episodes and aberrant repair

2. leads to sustained presence of inflammatory cells and mediators, airway remodeling, and airway hyperresponsiveness

can asthma be fatal?

when do asthma cases most often form?

yes

most cases develop before age 25

what does gut dysbiosis contribute to in the development of allergies/asthma?

it skews type of helper t-cells toward increased type 2 Th cells

what is atopy associated with?

decreased gut microbiota diversity and decreased butyrate-producing (SCFA) bacteria that keep epithelial cells healthy

what is the genetic component of asthma?

many genetic polymorphisms interacting with many environmental factors and SDOH

what is atopy definition?

what is atopy associated with?

predisposition toward developing allergic hypersensitivity, including IgE antibodies to specific antigens

heightened immune responses to common allergens

what is atopic asthma also known as ?

how common is this type?

allergic asthma

most common

what is similar about allergic and non-allergic asthma?

what is different?

their sx are the same

triggers may differ

what are some non-allergic asthma triggers?

cold air, exercise

infection, related conditions (like GERD)

in atopic asthma, sx are triggered by what?

how is the allergic response mediated?

exposure to an allergen to which the person is sensitized

IgE antibodies

what are the phases of atopic asthma?

when is the second phase?

early and late

late is approx 6 hrs after early

what type of HSR is atopic asthma?

type 1

what are the 4 stages of type 1 HSR?

1. exposure to allergen

2. activation of Th2/B cells switching to IgE

3. IgE binds to mast cells receptors- they are now “primed”

4. subsequent exposure causes 2 IgE antibodies to crosslink

5. mast cell degranulation and release of histamine/other mediatiors

what does repeated exposure to the allergen in a type 2 HSR cause?

subsequent response by primed mast cells that degranulate immediately

what are the vasoactive amines in type 1 HSR ?

mainly histamine

what are the lipid mediators ?

mainly leukotrienes

during the first exposure to an antigen, what is produced?

during the second exposure, what happens?

IgE produced, binds to mast cells

allergen binds to IgE

during atopic asthma, what do type 2 Th cells release?

what does this do in the body?

release IL-4, IL-5, IL-13 cytokines

promote asthma, increase eosinophils, airway hyperresponsiveness, airway remodeling

during atopic asthma, and the release of IL-4, IL-5, and IL-13, what happens to promote airway remodeling? x 3 things

1. goblet cell hyperplasia

2. smooth muscle hypertrophy and hyperplasia

3. subepithelial fibrosis/stiffening of airway

during atopic asthma HSR, what do B lymphocytes start to produce?

what is this considered?

IgE antibodies

class-switching

what are 2 histamine-containing cells that are involved in atopic asthma reactions?

mast cells and basophils

what are the key ‘bad actors’ of the late phase of an asthma attack?

eosinophils

what are 2 classic inflammatory leukocytes involved in atopic asthma reactions?

macrophages and neutrophils

what cell plays a prominent role in the late phase of an atopic asthma attack?

eosinophils

what are the effectors of the early phase of atopic asthma? x 5 things

1. ACh (bronchochonstrictor)

2. histamine

3. leukotrienes

4. lipoxins

5. adenosine

what are the early phase of atopic asthma’s physical sx ? x 4 things

bronchconstriction, edema

mucosal thickening, secretions

what is acetylcholine’s role in the early phase of atopic asthma?

bronchoconstrictor

what is histamine’s role in the early phase of atopic asthma?

bronchoconstrictor, edema, increases mucus viscosity

what is leukotrienes role in the early phase of atopic asthma? x 4 things

promotes bronchoconstriction

vascular permeability and leakiness (edema)

increased mucus secretion

eosinophil recruitment

what are lipoxins role in the early phase of atopic asthma? x 1 things

how are thier number’s changed during this?

anti- inflammatory

this is decreased in asthma

what phase of atopic asthma are eosinophil chemotactic factor involved in?

what does it do?

late phase

attracts additional eosinophils to the region of inflammation

what phase are eotaxins associated with?

what are they relased by, and what do they do?

late phase of atopic asthma

released by epithelial cells, attract eosinophils and mast cells

what phase are eosinophil major basic proteins associated with?

what do they do?

late phase

released into/onto tissues by eosinophils and cause additional tissue damage

ROS are associated with what phase?

what do they do?

late phase

released by eosinophils, also cause tissue damage

during late phase, interleukins released by type 2 Th cells promote what?

eosinophil survival and activity

what inflammatory mediators do eosinophils release? x 4 things

what do they do?

IL-1, IL-6, TNF-a, leukotrienes

perpetuate and amplify the inflammatory response

what is airway remodeling defined as?

persistant cellular and structural changes in the airway wall

during airway remodeling, deposition of collagen and fibrocytes in epithelial basement membrane causes what? x 2 things

thickening and stiffening

during airway remodeling, loss of ciliated epithelial cells causes what? x 2 things

more exposure of airway to allergens, toxins, microbes

during airway remodeling, increased #/size of blood vessels in bronchial tissue causes what?

edema of airways

what is the breathing equation ?

airflow (F) is proportional to pressure (P) gradient (from mouth to alveoli)/ airway resistance (R)

resistance to airflow is normally low/high, and so air moves with a small/large pressure gradient

low

small

what is the primary determinant of resistance in breathing?

radius of the airway

what can decrease the airway radius in asthma? x 3 things

1. bronchoconstriction

2. mucus production

3. inflamed, thickened airway wall

what does the accumulation of air behind closed airways lead to ? x 2 things

air trapping and lung hyperinflation

in some severe cases, complete closure of some airways causes isolation of portions of the lung, which causes what?

what does this produce/lead to?

no gas exchange can occur from blocked alveoli

producing hypoxemia

what must an asthmatic patient do to increase the pressure gradient and maintain adequate airflow through narrowed airways that a non-asthmatic person might not have to? x 2 things

use accessory muscles, contract diaphragm more forcefully

for a person with asthma, is expiration/inspiration more difficult?

which specific type of this is esp difficult?

expiration

active expiration

what powers inspiration?

what does this do?

negative pleural pressure

pulls the airways open at the same time that it expands the alveoli

during expiration in asthma, why is the closing tendency of the airway greatly increased?

what is happening to bronchioles during this?

the extra positive pressure required in the chest to cause expiration

bronchioles are narrowed, and further narrowing resulting from the external pressure creates obstruction during expiration

during expiration in lungs with asthma, what tends to happen?

air tends to get trapped in the lungs

sympathetic B2 adrenergic receptor activation causes what?

bronchodilation

what breaks down cAMP to AMP?

phosphodiesterase

parasympathetic M3 muscarinic (cholinergic) receptor activation causes bronco-WHAT?

bronchoconstriction

what is the def of an asthma attack?

what are sx caused by?

acute worsening of asthma sx on exposure to a trigger

airway narrowing due to bronchospasm (sudden constriction), edema/swelling, increased mucus production and/or increased mucus thickening

an asthma attack has 2 phases, what are they?

early and late phase

what is the pt teaching about an asthma attack? x 2 things

what is the goal here?

1. recognize the s/sx of an impending/worsening attack

2. use rescue inhaler sooner than later

to minimize frequency, duration, severity of asthma attacks

what are 3 breathing sx of an asthma attack

cough, wheeze (high pitched, whistling sound), shortness of breath

during an asthma attack, how might someone’s chest feel?

what are 3 other heart/brain sx someone might experience?

tight

anxiety, tachycardia, palpitations

what are 3 breathing/respiration sx someone might have in an asthma attack?

tachypnea, cyanosis, use of accessory muscles

what is the worst outcome of an asthma attack?

what is this? can it be fatal?

status asthmaticus

an acute exacerbation of asthma that is unresponsive to initial treatment with bronchodilators

yes

what does a wheeze sound like? x 2 things

as status asthmaticus progresses, how might wheezing change?

high-pitched, whistling sound

might disappear as airway constricts, don’t be fooled by this!

what are 2 categorizations of asthma severity?

intermittent or persistent

for the 2 categories of asthma severity, how many times does each experience nighttime awakenings?

</= 2 times/month: intermittent

> 2 times/month: persistent

for the 2 categories of asthma severity, how many times does each experience interference w/ daily activity due to asthma?

none: intermittent

any: persistent

what is a way to measure asthma control?

peak expiratory flow

with what rule can asthma control be assessed with?

Rule of 2s

with what 5 sx is asthma considered to well-controlled?

how many of these criteria must be met for asthma to be considered ‘well-controlled’?

1. reports sx </= 2 days/wk

2. uses rescue inhaler </= 2 d/wk

3. is awakened by sx </= 2x/month

4. reports no interference w/ ADLs

5. normal PFTs between exacerbations

all of these have to be true`

what is the peak flow meter based on of the person’s?

what should this be used in combo with?

based on personal best peak flow

written asthma action plan

what is the green zone of the peak flow meter?

yellow zone?

red zone?

> 80% of personal best

>/= 60% but </=80% of personal best

<60% of personal best

what are pulmonary function tests (PFTs)?

forced expiratory volume in one second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC): FEV1/FVC

what are 2 other methods for measuring lung vol and airflow?

spirometer and plethysmography

what does spirometry measure?

how fast and how much air you breathe out

what is plethysmography?

tool to measure residual volume (RV), total lung capacity (TLC) and any other lung volume that incorporates RV

what is the def of FEV1?

forced expiratory vol in 1 second

what is FVC definition?

what does FVC stand for?

the amount of air which can be forcibly exhaled from the lungs after a maximum inhalation

forced vital capacity

what is the equation for total lung capacity?

FVC + residual volume

what is the def of residual vol?

vol of air remaining in lungs after a maximal exhalation

in what unit is the vol of air expelled after maximal inspiration measured?

liters

in someone with obstructive lung disease, how is FVC affected compared to normal function?

FEV1?

RV ? and why

TLC? and why

decreased

decreased

increased- air trapping

increased- hyperinflation prominent in COPD

compared to normal lung function, the graph of Expiratory volume testing is shifted which direction in obstructive disease?

upwards

what are 2 components of asthma exacerbation?

• deterioration in sx

• decrease in airflow

what does COPD stand for?

chronic obstructive pulmonary disease

what does the GOLD 2023 report stand for?

what does it define COPD as?

global initiative for chronic obstructive lung disease

chronic resp sx due to abnormalities of the airways/alveoli that cause persistent, often progressive, airflow obstruction

is COPD a heterogeneous or homogeneous disease?

heterogeneous

COPD is a common, ________, and _______ disease

preventable and treatable

what are the most common resp sx ? x 3 things

what is the cardinal sx?

dyspnea, cough, and/or sputum production

dyspnea is cardinal sx