Scientific Article June 2014

COPD: chronic obstructive pulmonary disease Part 2

Try to answer the following questions from the material in the article. The numbers in brackets refer to the number
of information points you should try to include in your answer.

1) Para 19: Describe how a transgenic sheep such as Tracey could have been produced (5).
Isolate gene for A1AT;
restriction enzymes;
transfer to a vector;
ref. to a virus or liposomes;
add to sheep cells/embryo cells/zygote/fertilised egg;
select cells containing new DNA ref. to marker (gene) - (in vector);
ref to using female zygote/embryo (milk production)

2) People with COPD caused by A1AT deficiency can be treated by drinking the milk from transgenic sheep
like Tracey. Do you agree with this statement? Why? (2)
A1AT needs to get to the lungs;
enzyme/protein digested in the stomach

3) Gene therapy is another alternative treatment method for people suffering from COPD due to A1AT
deficiency. Describe how you would treat these patients using this method (3).
Isolate normal/unmutated allele of A1AT;
ref. to restriction enzymes;
Add to a vector liposomes or virus;
Add to patient inhaler or injection;
Need for repeated treatments.

4) Para 20: A preferred method of COPD diagnosis is by physically measuring the diameter of various regions
of the lung airways. How could this be easily done? (1)
Using an X-ray/CT/MRI scan

5) Para 24: Describe how to calculate persons BMI (1)
BMI = weight in kg/(height in m)
2

6) What advice might you be given if your BMI was over 30 (and assuming you are not an Olympian athlete!)
(2)
Lose weight;
Exercise more;
Eat less fat-rich foods; eq

7) Para 25: Describe how a doctor would use a spirometer to get some consistent background readings of
tidal volume (with the patient at rest) for assessing a patients lung function (4)
Ref. to calibrating the spirometer/kymograph (for air volume);
allow patient to acclimatise (to breathing through the tubes);
collect several breaths (breathing normally);
definition of tidal volume as volume of air breathed in or out during a normal breath;
repeat experiment to calculate an average tidal volume (not measure several breaths from the same
trace)

8) Para 25: How would the doctor measure FVC, using a spirometer? (3)
tell patient to breathe in as deeply as possible/maximum inhalation;
then breathe out as much as possible/force air out/keep breathing out;
FVC is the volume from the peak of inhalation to the trough of the exhalation
as much air as possible/force remaining air out/keep breathing out

9) Can you draw a sample spirometer trace showing several normal breaths, followed by a breath for
measuring FVC. Indicate tidal volume and FVC on your spirometer trace (N.B. the trace does not have to
be to scale. (3)
sample trace showing inhalation and exhalations (two minimum) dont need to be labelled as such
tidal volume correctly labelled;
FVC correctly drawn and labelled

10) Para 27: What are the disadvantages in using X-rays to screen for lung diseases? (2)
doesnt show soft tissue clearly/in detail/only shows denser structures, such as bones;
risk of causing mutations/cant be given repeatedly

11) Para 27: Describe another imaging technique you have learned about which may give better results. How
does this technique work? How is it better than using X-rays? What are the disadvantages of this
technique? (4)

CT scan:
- multiple X-rays; 3D image generated; ref. to a contrast material to make certain structures show up
more clearly
- generates a 3D image
- disadvantages: high radiation dose; only for denser tissues; adverse reaction to the contract material

MRI scan:
- uses a magnetic field to allow detection of molecules containing e.g. hydrogen; 3D image is generated
- generates a 3D image; doesnt use radiation/safer
- requires patient to stay still in an enclosed space; cant use if the patient has certain metal
prosthetics/pacemakers etc

12) The inhalers used to treat COPD differ in the way in which they act. Beta-2 agonists bind to a receptor
protein on the cell surface membrane (Beta-2 adrenergic receptor). How would this mechanism of action
differ from the steroid inhalers (para 42) in affecting gene expression, leading to the effect of the drug? (4)
(B2 agonists bind receptor) and this causes activation/changes to proteins/enzymes in the
membrane/cytoplasm;
other proteins/enzymes in the cytoplasm are subsequently changed;
until transcription factors are modified (affecting transcription)
steroids are hydrophobic and can pass through membrane;
bind to a (nuclear) protein;
complex acts as a transcription factor

13) Antimuscarinic inhalers (para 40) block the activity of a group of acetylcholine receptors found on post-
synaptic membranes. Acetylcholine is known to cause contraction of smooth muscle, such as that found in
the bronchi. Describe how antimuscarinic inhalers work to relieve the symptoms of COPD. (3)
inhaler drugs bind to post-synaptic Ach receptors;
block Ach from binding;
prevent smooth muscle contraction;
allow airways to dilate

14) Para 44: In the near future, your doctor may be able to predict how well you will respond to different
medicines before you start to take them. Describe how the work on the Humane Genome Project and
subsequent projects have made this possible. (3)
(All) human genes identified;
can identify mutations/variations/SNPs within genes;
may affect e.g. enzyme activity/levels of enzymes or proteins/binding of drugs/breakdown rate of drug;
allow correct dose of drug to be prescribed;
allow any side-effects to be predicted/avoided

15) Para 45: mucolytics are also used in the treatment of another genetic lung condition, cystic fibrosis. Why
are mucolytics useful as a treatment for this condition? (2 short answer, or 7 full answer)
CF: thick mucus generated in all mucus-lined tubes;
needs to be cleared;
easier if it is runnier

(can explain why it is thicker than normal CFTR protein doesn't work/wrong conformation/missing;
Cl
-
ions don't move out of cell;
mutated CFTR doesnt inhibit Na
+
channel;
Na
+
ions pass into cell from tube duct;
water follows by osmosis;
mucus becomes thicker than normal)

16) Para 57 mentions the importance of self-care. If COPD has been caused by someone smoking, should
other, healthy people be forced to pay for a health service (hospitals, doctors, nurses, drugs, rehabilitation,
etc) that is used to treat such people? Should they have free access to such services if the condition has
been created by their own actions? (2)
Ethical arguments are relevant duty of care; treating a disease (addiction); etc

17) Para 62: Describe how a vaccine against flu (caused by the influenza virus) or pneumococcalbacteria
would work. Why do people have to be given a yearly flu vaccination each autumn? (10)
Vaccine contains pure antigen/dead or weak microbe etc;
antigens/microbe phagocytosed;
antigen presentation from APC/macrophage;
(specific) Helper T-Cell activated and divides:
memory T
H
cells produced;
cytokines produced;
Killer T cells activated;
kill infected cells (displaying antigen);
B cells activated;
plasma cells formed;
antibody production increases;

Flu virus mutates/changes antigens every year/regularly;
not immune to the new antigens

18) There are many ongoing clinical trials for new drugs and treatments for COPD. One current trial is
comparing different combinations of bronchodilators and steroids against a placebo treatment. This trial is
both randomised and double-blind. What is meant by the following terms and why are they each important?
a) randomised b) double-blind and c) placebo-controlled? (3)

a) randomised patients are assigned into treatment or placebo groups on a random basis/not chosen
b) double-blind neither the patient nor the doctor know what treatment the patient is getting. This
removes any bias in or recording the results
c) placebo-controlled this allows us to see if there is any improvement even without an active drug
being taken (can be due to the placebo effect). A placebo is a pill or injection without any active
ingredient e.g. a white sugar pill or tablet, or a saline/water injection