Chronic Obstructive Pulmonary Disease

Question 1

COPD

Answer 1

obstructive lung disease resulting from cigarette smoking and other toxic chemicals

airflow limitation that is not fully reversible, usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases

third leading cause of death in adults in the US, increasing in prevalence

Question 2

causal risk factors of COPD

Answer 2

cigarette smoking

occupational exposures

genetic risk (alpha-1-antitrypsin deficiency)

Question 3

genetic factors that predispose COPD

Answer 3

alpha-1-antitrypsin deficiency - PiZZ or PiMZ + smoking

single nucleotide polymorphisms - Type IV collagen alpha3, solute carrier familly 11 member 1 (SLC11A1), interleukin-1B

MMP-9 and CCL-1 increase severity and exacerbation risk

Question 4

alpha-1-antitrypsin deficiency

Answer 4

coded by single gene on chromosome 14

PiZZ patients are severely deficient

PiSZ, Pi null-null, and Pi null-Z are also deficient

normal phenotyp eis PiMM

cigarette smoking is the most important risk factor

increased risk of cirrhosis and lung cancer as well

Question 5

mechanisms of airflow obstruction in COPD

Answer 5

1) loss of tethering of airways due to emphysema - alveolar destruction resulting in decreased elastic recoil and airway collapse
2) remodeling of the small airways which causes plugging
3) increased mucous secretion which decreases the internal airway caliber and increases

Question 6

inflammatory cells involved in COPD

Answer 6

epithelial cells and alveolar macrophages activate fibroblasts,CD8+ lymphocytes, neutrophils, and monoytes

COPD is a nuetrophilic disease

Question 7

alveolar macrophages in COPD

Answer 7

orchestrate much of the inflammatory process

release mediators that attract neutrophils, monocytes, and CD8+ lymphocytes

release elastolytic enzymes and generate ROS

Question 8

neutrophils in COPD

Answer 8

attracted by IL-8, LTB4 from macrophages and PMNs

release ROS and MPO which contribute to ongoing inflammatory response

serine proteases lik eneutrophil elastase contribute to destruction of th elung parenchyma

increased numbers of sputum neutrophils are associated with declining lung function

Question 9

CD8+ lymphocytes in COPD

Answer 9

found in the airway walls, vessels, and lymph nodes of smokers with COPD

increased number associated with worse lung function

suggest that an antigenic process in the lung leads to abnormal inflammatory responses

perpetuate the inflammatory response by releasing chemoattractants

Question 10

changes in the large airways in COPD

Answer 10

leads to chronic bronchitis

neutrophils in sputum

squamous metaplasia of epithelium, no basement membrane thickening

increased macrophages

increased CD8+ lymphocytes

mucous gland hyperplasia

goblet cell hyperplasia

mucous hypersecretion

Question 11

changes in the small airways in COPD

Answer 11

remodeling of the airways

inflammatory exudate in lumen

disrupted alveolar attachments

thcikened wall with inflammatory cells - macrophages, CD8+ cells, fibroblasts

peribronchial fibrosis

Question 12

changes in lung parenchyma in COPD

Answer 12

emphysema

alveolar wall destruction

loss of elasticity

destruction of pulmonary capillary bed

increased number of inflammatory cells - macrophages, CD8+ lymphocytes

Question 13

Describe the flow-volume and volume-time cirves in COPD.

Answer 13

flow-volume curve more concave, can’t reach the same peak outflow

volume-time curve flatter and takes longer to get closer to FVC

Question 14

Mechanisms of Airflow Limitation in COPD

Answer 14

mucus hypersecretion (luminal obstruction)

disrupted alveolar attachments (emphysema)

mucosal and peribronchial inflammation and fibrosis (obliterative bronchiolitis

Question 15

GOLD classification of mild COPD

Answer 15

FEV1/FVC < 70%

FEV1 >/= 80% predicted

Question 16

GOLD classification of moderate COPD

Answer 16

FEV1/FVC < 70%

FEV1 between 50% and 80%<!--= FEV1 < 80% predicted</p-->

Question 17

GOLD classification of severe COPD

Answer 17

FEV1/FVC < 70%

between 50% and 30% <!--= FEV1 < 50% predicted</p-->

Question 18

GOLD classification of very severe COPD

Answer 18

FEV1/FVC < 70%

FEV1 < 30% predicted

Question 19

maximal inspiration and expiration in COPD

Answer 19

IC is decreased, RV is increased, FRC is increased

Question 20

respiratory response to exercise in COPD

Answer 20

Lungs stay overinflated, more volume and less inspiration each breath

Can breath up to TLC, everything is shifted upward, IC is smaller

RR goes up

EELV goes up, dynamic lung hyperinflation, IC goes down

Question 21

grade 0 mMRC dyspnea

Answer 21

breathless with strenuous exercise

Question 22

grade 1 mMRC dyspnea

Answer 22

short of breath when hurrying onf the level or walking up a slight hill

Question 23

grade 2 mMRC dyspnea

Answer 23

walk slower than people of the same age level because of breathlessness

have to stop for breath when walking at my own pace on the level

Question 24

grade 3 mMRC dyspnea

Answer 24

stop for breath after walking about 100 meters of after a few minutes on the level

Question 25

grade 4 mMRC dyspnea

Answer 25

too breathless to leave the house

breathless when drssing or undressing

Question 26

treatment options for COPD

Answer 26

long acting beta agonists (can be used safely by itself) - salmeterol or formoterol

ultra long-acting beta-agonist - indacaterol

long-acting anti-muscarinic - tiotropium

beta agonist + inhaled corticosteroid - salmeterol + fluticasone or formoterol + budesonide

Question 27

definition of a COPD exacerbation

Answer 27

an event in the natural course of the disease characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD

Question 28

consequences of COPD exacerbations

Answer 28

faster decline in lung function

poorer quality of life

higher mortality

greater airway inflammation

Question 29

COPD exacerbation treatment

Answer 29

oxygen

inhaled bronchodilators

systemic corticosteroids

antibiotics

ventilatory support (either NIV or intubation)

Question 30

Describe the progression of disease in COPD.

Answer 30

lung inflammatory cells present in greater numbers due to smoking or other toxic chemicals, release of toxic oxygen species

activation of NF-kB and increase in TNF alpha and IL-8 lead to neutrophil recruitment

what results is bronchitis, mucus hypersescretion, bronchospasm, destruction of alveolar walls, and small airway remodeling resulting in peribronchiolar fibrosis and formation of airway lymphoid follicles

decrease in anti-proteases lead to lung damage

Question 31

chronic bronchitis

Answer 31

a set of symptoms defined as the presence of a productive cough for three months in each of two successive years

patients are also short of breath and wheeze