Shortness of Breath

Question 1

Mrs Finnegan is a 78-year-old widow who presents to your clinic complaining of increasing shortness of breath. She describes that for the past 4 months she has gradually become increasingly short of breath when she walks back up the hill to her bungalow after going to the shops. She is finally seeking medical help because she now finds herself short of breath when she does her gardening. Her sister (a lifelong smoker) died of lung cancer aged 73, and given that Mrs Finnegan used to smoke, she is especially concerned that she may have lung cancer.
In broad terms, what pathological processes could cause shortness of breath?

Answer 1

Shortness of breath essentially means either that not enough oxygen is getting around the body or that there is a cause for increased respiratory drive. This could be due to:

1) Insufficient oxygen getting into the lungs:
2) Insufficient oxygen getting from the air into the blood (ventilation–perfusion mismatch):
3) Insufficient oxygen getting around the body:
4) Increased respiratory drive per se:

Question 2

Give some examples of diseases where insufficient oxygen is getting into the lungs

Answer 2

− Obstructed airways (obstructive lung disease impairing airflow, e.g.
asthma, chronic obstructive pulmonary disease (COPD), lung cancer, or
upper airway obstruction, e.g. anaphylaxis)
− Decreased lung compliance (restrictive lung disease limiting inspiratory
volumes, e.g. pulmonary fibrosis)
− Decreasedlungspace(e.g.pneumothorax,lungcollapse)
− Weakdiaphragm(e.g.Guillain–Barrésyndrome,myastheniagravis)
− Chest wall that cannot inflate properly (e.g. obesity, kyphoscoliotic
spine)

Question 3

Give some examples of where there is a ventilation-perfusion mismatch

Answer 3

− Pulmonary oedema (e.g. heart failure, liver failure, nephrotic syndrome)
− Pneumonia
− Pulmonaryembolism(PE;areaoflungisnotperfused,sonoexchangecan
occur)
− Pulmonary fibrosis

Question 4

Give some examples where there is increased respiratory drive per se

Answer 4

− Hystericalhyperventilation

− Acidaemia(e.g.diabeticketoacidosis)

Question 5

Good history-taking begins with listening to whatever the patient has to tell you, followed by open questions to avoid leading the patient’s answers. You can then move on to specific questions that can help narrow your differential diagnosis.
What specific questions might you ask someone who presents with shortness of breath?

Answer 5

About the shortness of breath
• Timing of onset? This is crucial because vascular (e.g. PE) and mechanical (e.g. pneumothorax, foreign body) pathologies typically present suddenly. At the other end of the spectrum, it may take weeks or months before diseases such as lung cancer or pulmonary fibrosis cause noticeable dyspnoea.
• Alleviating or exacerbating factors? Most shortness of breath will be worse on exertion. However, heart failure will also be worse on lying flat; asthma will usually be worse at certain times of the year (e.g. due to pollen allergy), in cer- tain places (e.g. in dusty environments, or when the pets are around), during intense cardiovascular exercise (e.g. running), or in the early hours of the morn- ing. Psychogenic hyperventilation will be worse at times of anxiety and stress.

Question 6

Which risk factors should you enquire about

Answer 6

• Smoking? Never forget to ask about smoking and to quantify this in terms of ‘pack years’ smoked (1 pack = 20 cigarettes; 20 cigarettes a day for a year = 1 pack year).
• Pets? The patient may be allergic to pets, especially new ones.
• Occupational history? Ask about jobs – there are still lots of people who have been exposed to asbestos, silica dust, and coal particulates in past jobs and who are at risk of pneumoconioses.
• Medications? Certain drugs can cause pulmonary fibrosis, e.g. amiodarone, methotrexate, cyclophosphamide, bleomycin, hydralazine, busulphan.
• Nutritional status? Even in today’s Western societies, some patients present with malnourishment – typically elderly patients who live alone on a ‘tea and toast’ diet or homeless people with alcoholism who fail to maintain an ade- quate diet. Such patients are at risk of anaemia and thus shortness of breath.

Question 7

Describe what you should ask about the cough

Answer 7

• Cough? A cough points strongly towards a respiratory pathology. The nature of the cough is important: Is it productive? What colour is the sputum? Is there any blood? When does the cough occur? What does the cough sound like? A per- sistent, productive cough over the last few days suggests pneumonia; a persist- ent, productive cough on most days of the past 3 months and spanning years suggests chronic bronchitis; a dry cough present mainly during the episodes of shortness of breath or at night suggests asthma, but may also be a feature of left ventricular failure; blood-stained sputum may suggest a PE, lung cancer, or a cavitating pneumonia. Certain pathologies are associated with characteristic- sounding coughs – for those of you with a veterinary bent, croup is said to sound like a barking seal, whereas recurrent laryngeal nerve palsy (sometimes associated with lung cancer) can produce a bovine cough.

Question 8

What other associated symptoms should you ask about

Answer 8

• Chest pain? If there is chest pain, is it pleuritic? Pleuritic chest pain can suggest pneumonia, a PE, or a pneumothorax, because these often involve the parietal pleura. Non-pleuritic chest pain could indicate a cardiovascular pathology.
• Muscular weakness or fatigue? Neuromuscular diseases (e.g. Guillain– Barré syndrome, myasthenia gravis, Lambert–Eaton syndrome, polymyositis, motor neuron disease) will usually be accompanied by muscular weakness or fatigueability.
• Tender limbs? Pulmonary emboli can originate from anywhere in the venous system. Patients usually only notice deep vein thrombosis (DVT) if it occurs in a limb as this will usually cause inflammation – a swollen red, tender, warm, shiny looking limb. It is often stated that clots forming below the knee pose less risk of embolizing to the lungs, but autopsy studies have shown that approximately 35% of fatal PEs originate from calf DVTs.
• Weight loss? Night sweats? Loss of appetite? These are ‘red flag’ signs that suggest that a highly metabolic, systemic inflammatory process is going on – often a cancer. Always ask these questions, regardless of the presentation.
• Loss of blood? Anaemia can cause or exacerbate shortness of breath, so always ask about heavy menstrual bleeding (in women) and melaena

Question 9

How would the speed of onset influence your differential diagnosis? Think of which pathologies present over seconds to minutes, hours to days, and weeks to months.
Which of these conditions must you exclude, due to their need for urgent treatment or poor prognosis?

Answer 9

Seconds to minutes:
Acute asthma attack Anaphylaxis Laryngeal oedema
(secondary to burns or
chemical irritation) PE
Pneumothorax
Flash pulmonary oedema Laryngotracheobronchitis
(croup)
Hysterical hyperventilation Inhaled foreign body Tension pneumothorax
Acute epiglottitis/ supraglottitis

Question 10

Which diseases will take hours to days to manifest

Answer 10

Pneumonia Bronchitis Heart failure Pleural effusion
Post-operative atelectasis Chronic, multiple
pulmonary emboli Altitude sickness Guillain–Barré syndrome Myasthenia gravis Acute respiratory
distress syndrome Lung collapse (e.g.
secondary to bronchial carcinoma)

Question 11

Which diseases will take weeks to months to manifest

Answer 11

COPD
Chronic asthma Heart failure Pulmonary fibrosis Anaemia Bronchiectasis
Physical
deconditioning
Obesity
Pulmonary hypertension Mesothelioma Pulmonary tuberculosis Kyphoscoliosis Ankylosing spondylitis Motor neuron disease

Question 12

We already know that Mrs Finnegan’s dyspnoea has developed over several months.
What key clues on history and examination will help you differentiate between the potential diagnoses? Try to think of key clues for the most common diagnoses in the ‘weeks to months’ column above.

Answer 12

Explore key features of these chronic culprits

Question 13

What are the key features of COPD

Answer 13

• COPD
− RememberthatCOPDisabrackettermencompassingchronicbronchitis
and emphysema.
− History of chronic bronchitis (a clinical diagnosis, based on the presence of
a cough, productive of sputum (~10 mL daily), on most days of 3 months for
2 consecutive years) and permanent, largely irreversible, shortness of breath.
− Presence of risk factors suggesting a cause for COPD:
− Smoking (usually more than 20 pack years)
− Occupationalexposuretolungirritants,e.g.incoalminers,tunnelworkers
− α -Antitrypsin deficiency (liver failure, family history). 1
− Signs of COPD:
− Hyperexpandedchest
− Breathingthroughpursedlips
− Reduced air entry/chest expansion
− Hyper-resonant percussion note (particularly resonance over the heart
and liver).

Question 14

What are the key features of chronic asthma

Answer 14

• Chronic asthma
− History of transient, reversible cough, wheeze and shortness of breath –
often worse at night, during exercise, or when exposed to allergens or cold
− Presence of associated atopic conditions personally or in family members
(eczema, hayfever, allergies, nasal polyps)
− Symptoms may be exacerbated by drugs such as non-steroidal anti-
inflammatory drugs (NSAIDs), aspirin, β-blockers (including those in eye
drops used for glaucoma)
− Wheeze on auscultation of the lungs.

Question 15

What are the key features of pulmonary fibrosis

Answer 15

• Pulmonary fibrosis
− History of exposure to asbestos, silica, or coal (pneumoconioses causing
fibrosis), exposure to drugs (e.g. methotrexate)
− Signs on examination include:
− Clubbing(inusualinterstitialpneumonitis)
− Reduced air entry/chest expansion
− Late inspiratory, fine crackles (often heard throughout the chest rather
than just the lung bases as in pulmonary oedema).

Question 16

What are the key features of heart failure

Answer 16

Heart failure
− History of shortness of breath on exertion, orthopnoea (breathless when
lying flat), paroxysmal nocturnal dyspnoea (waking up short of breath)
− Presence of risk factors suggesting a cause for heart failure:
− Ischaemic heart disease (smoking, diabetes mellitus, hypercholestero- laemia, hypertension, South Asian descent, strong family history)
− Other atherosclerotic disease (e.g. stroke, transient ischaemic attack (TIA), limb claudication)
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                     10 − Hypertension(cancauseheartfailurebyitself,intheabsenceofischaemic heart disease) − Valvulardisease(e.g.rheumaticfever,endocarditis,Marfan’ssyndrome) − Cardiomyopathy − Signs on examination include: − Displacedapexbeat − Third and fourth heart sounds − Crackles in both lung bases − Raisedjugularvenouspressure(JVP),hepatomegaly,peripheraloedema (ankles, sacrum).

Question 17

What are the key features of anaemia

Answer 17

Anaemia
− History of bleeding (menorrhagia, melaena, haematochezia) or malnutri-
tion (‘tea and toast’ diet in elderly, poor diet of homeless). Fatigue as well as
shortness of breath on exertion
− Signs of peripheral (fingers) or central (tongue) cyanosis. Specific signs
such as koilonychia, glossitis, and angular stomatitis (all rare). Checking for conjunctival pallor is routinely done but is unreliable.

Question 18

Describe some key features of the other chronic culprits

Answer 18

• Bronchiectasis would be suggested by a history of productive cough and recurrent chest infections, or a history of cystic fibrosis.
• Obesity, kyphoscoliosis, ankylosing spondylitis can be excluded on inspection.
• Physical deconditioning is a diagnosis of exclusion.

Question 19

Your history-taking reveals that Mrs Finnegan is a retired office worker who is diabetic and takes ‘aspirin, a pill for the diabetes, and a water tablet for blood pressure’. Her past medical history is significant for an anterior myocardial infarction (MI) 5 years ago, after which she received a single vessel coronary artery bypass graft (CABG). Her parents ‘died of old age’ and her only sister died of lung cancer. She smoked about 10 cigarettes a day from her early 20s until her late 60s. She has slept propped up with several pillows for the last few years as this is ‘more comfortable’. She becomes short of breath when gardening or walking uphill, but feels much better if she stops to catch her breath for a minute. She has not had any cough, chest pain, or dark or bloody faeces or urine. She has not lost any weight, had any night sweats, or noticed any change in appetite. However, she is worried that she may have lung cancer like her sister and was hoping you might be able to do some test to rule that out.
On examination, there are no signs of cyanosis or anaemia. Her blood pressure is 155/80 mmHg and her heart rate is 85 bpm and regular. There is no cervical lymphadenopathy. Her JVP is elevated to 6 cm above the angle of Louis and her apex is most prominent lateral of the mid-clavicular line, in the sixth intercostal space. There is a median sternotomy scar from her CABG 5 years ago. There are no heaves or thrills, and auscultation reveals no murmurs. Chest expansion is symmetrical and resonant to percus- sion. The trachea is central and breath sounds are heard throughout both lungs, albeit with crackles in both lung bases. Her liver is not enlarged or tender but there is pitting oedema in both ankles. Abdominal examination is normal. Neurological examination is also normal.
Mrs Finnegan’s history and examination are consistent with a particular diagnosis for her shortness of breath, but this should be confirmed or refuted with basic investigations.
Given the history and examination, what is the most likely cause of Mrs Finnegan’s shortness of breath?

Answer 19

Mrs Finnegan is an elderly lady with shortness of breath and significant risk factors for both cardiovascular disease (ex-smoker, hypertension, diabetes mellitus, previous MI) and respiratory disease (>20 pack years of smoking). However, she gives a clear history of predictable shortness of breath on exercise that is relieved by rest. She has orthopnoea, and has a displaced apex beat, bilateral pulmonary oedema, and ankle oedema. Put together, this all suggests that Mrs Finnegan likely has congestive heart failure that is causing reduced cardiac output, pulmonary oedema, and peripheral oedema.

Question 20

What investigations would you like to do

Answer 20

• Full blood count (FBC): looking for anaemia.
• Blood cholesterol, glucose, and HbA1c: abnormal cholesterol levels (total >5 mM, low-density lipoprotein (LDL) >3 mM or high-density lipoprotein (HDL) <1 mM) and abnormal glucose levels (random >11.1 mM or fasting >7 mM) will give clues about risk factors for ischaemic heart disease, the main cause of heart failure. Mrs Finnegan is a known diabetic, so her HbA1c level will be useful as this is a measure of her glucose control over the preceding 60 days (non-diabetic HbA1c <6.5%).
• Thyroid function tests (TFTs): hyperthyroidism can cause a tachyarrhythmia and high-output cardiac failure.
• Urea and electrolytes (U&Es): if you think the patient might have excess fluid and therefore there is a chance you might start diuretics to offload some fluid, you need a baseline of electrolyte levels and renal function. It is best to take all the bloods now, both to avoid putting a needle in the patient twice and because an earlier baseline is better.

Question 21

Describe some other investigations that yo u could perform

Answer 21

If the history were suggestive of lung pathology (rather than cardiac pathology) as the cause of breathlessness, you might consider performing:
• Peak expiratory flow rate (PEFR). This can be used to stratify the severity of an asthma attack in chronic asthma.

Spirometry. This is used to distinguish between obstructive and restrictive lung disease. In obstructive airways disease (e.g. asthma, COPD, bronchiecta- sis), the bronchi are narrowed by mucus such that less air can be forcibly exhaled during a single second (forced expiratory volume in 1 second; FEV1 <70% of predicted), but the total lung capacity is not reduced (forced vital capacity; FVC >70%). In restrictive airways disease (e.g. pulmonary fibrosis), the total lung volume is reduced (FVC <70%) but the amount of air that can be exhaled in the first second remains the same (FEV1 >70%).

Question 22

What does the PA erect X-ray show

Answer 22

Remember to go through radiographs systematically.
• Check the patient details are correct: none are shown here for confidentiality.
• Check the radiograph is technically adequate: full coverage, good penetration, not rotated, adequate inspiration. This radiograph is rotated to the right.
• Present your findings logically. Mrs Finnegan’s radiograph shows a reticular pat- tern of opacification throughout both lung fields, which is much denser in the lower zones bilaterally. There is upper lobe diversion of the pulmonary veins in both lung fields. The heart shadow is significantly enlarged. There are faintly visible sternal sutures (from her CABG) and a small amount of fluid in the transverse fissure.

Question 23

Mrs Finnegan’s ECG shows pathological Q waves in leads V –V . Her FBC is normal. Her glucose is 6.2 mM
14
and her HbA1c is 6.8%. Her total cholesterol = 6.2 mM, LDL = 3.1 mM and HDL = 1.1 mM.
What is the diagnosis for Mrs Finnegan? Can you identify any risk factors for this diagnosis in her history and investigations?

Answer 23

Mrs Finnegan is probably suffering from congestive cardiac failure as she has signs of both left ventricular failure (bibasal crackles suggestive of pulmonary oede- ma, and a displaced apex beat as well as a chest radiograph showing bilateral pulmo- nary oedema) and right ventricular failure (peripheral oedema and a raised JVP).
Heart failure is a syndrome, not a true pathological diagnosis. Mrs Finnegan’s heart failure could be due to any number of causes (e.g. hypertension, valvular dis- ease, alcohol-induced cardiomyopathy) but it is important to remember that the most common cause of heart failure is ischaemic heart disease and that this patient has significant risk factors for this pathology:
• She smoked 10 cigarettes (half a pack) every day for 40 years = 20 pack years.
• She has diabetes mellitus.
• Her total cholesterol (6.2 mM) and LDL (3.1 mM) are elevated.
• Her hypertension is not well controlled (155/80 mmHg). National Institute for Health and Clinical Excellence (NICE) guidelines recommend a target blood pressure of <140/85 mmHg for most people, <130/80 mmHg for diabetics or <125/75 mmHg for patients with proteinuria.
The absence of angina in Mrs Finnegan does not exclude ischaemic heart disease since patients with diabetes mellitus may have ‘silent’ ischaemia.

Question 24

How does Mrs Finnegan’s diagnosis explain her symptoms (shortness of breath on exertion, orthop- noea) and signs (displaced apex beat, crackles in the lungs, peripheral oedema, raised JVP)?

Answer 24

Each symptom in turn

Question 25

How does it explain the SOB

Answer 25

Shortness of breath. The failing heart can’t pump enough blood out. This is espe- cially true if venous return to the heart is increased (e.g. exercise, lying down) and the heart is forced to work harder (e.g. exercise). Back pressure forces fluid out from the pulmonary vasculature into the alveoli, causing ‘wet lungs’ and a feeling of shortness of breath (some patients will say it feels like drowning). A combination of decreased lung compliance, decreased gas exchange, and airways obstruction are the important drivers of dyspnoea in most left ventricular failure patients.

Question 26

How does it explain the orthopnea

Answer 26

Orthopnoea. Lying down increases venous return to the heart, which is already struggling to pump out all the blood reaching it. This makes conges- tion of blood in the pulmonary vessels even worse, forcing more fluid out into the lungs and therefore causing shortness of breath. This is why patients with heart failure often sleep propped up with pillows.

Question 27

How does it explain the displaced apex beat

Answer 27

Displaced apex beat. The failing heart can’t pump out all of the blood reach- ing it, so it gradually but inexorably dilates, leading to a displaced (and weak) apex beat. This can be thought of as a volume-overloaded heart. Do not con- fuse this with hypertrophy, which is caused by hypertension or aortic stenosis. Here, the heart has to pump harder and thus grows concentrically, leading to
10
How does Mrs Finnegan’s diagnosis explain her symptoms (shortness of breath on exertion, orthop- noea) and signs (displaced apex beat, crackles in the lungs, peripheral oedema, raised JVP)?
10
an undisplaced but forceful or heaving apex beat. This can be thought of as a pressure-overloaded heart. Ultimately, a pressure-overloaded heart can also dilate and fail, but this occurs later in the disease process.

Question 28

How does it explain the crackles in the lungs

Answer 28

Crackles in the lungs. The build-up of blood in the pulmonary vessels forces fluid out of the vasculature into the alveoli. The alveoli are usually kept open by sur- factant, but the interstitial fluid dilutes this and results in increased alveolar sur- face tension, leading to collapse of the alveoli. As the patient breathes in deeply, the alveoli eventually ‘pop open’ – the crackles you can hear with the stethoscope.

Question 29

How does it explain the peripheral oedema

Answer 29

Peripheral oedema. This is caused mainly because the failing heart cannot pump all of the blood reaching it (venous return), so one gets back pressure in the venous system. This is further compounded by salt and water retention due to activation of the renin–angiotensin–aldosterone system by a low cardiac output. The resultant pressure in the venous system often manifests as a raised JVP and/or a tender, enlarged liver. The increased blood pressure in the venous system also forces fluid out into the surrounding tissues, particularly in plac- es where the venous pressure is highest, i.e. the dependent parts of the body (ankles in someone who has been standing, sacrum in someone who has been in bed). A raised JVP and hepatomegaly are not always clinically apparent.

Question 30

What second-line investigations should be arranged for Mrs Finnegan?

Answer 30

• Echocardiography to assess ventricular function and confirm low cardiac out- put and heart failure, assess valve patency, and look for areas of dyskinesia.
• Coronary angiography if you suspect this lady’s heart is failing because of coronary artery disease. This is quite likely in Mrs Finnegan’s case given her history of previous MI and risk factors for atherosclerotic disease.

Question 31

Mrs Finnegan went for echocardiography. This showed anterior akinesia and a left ventricular ejection frac- tion of 36%. Coronary angiography showed patent graft vessels but an occluded left anterior descending artery, plus severe stenosis of the right coronary and circumflex arteries. Based on this, it is fair to pro- ceed based on a working diagnosis of congestive heart failure secondary to ischaemic heart disease.
What drug treatments would you offer this lady? Don’t worry about specific drugs. Try to think what types of drug might help with: (1) her symptoms (too much fluid in lungs and limbs), (2) the pathologi- cal mechanism involved in heart failure, and (3) the underlying cause of the problem (atherosclerosis, in her case).

Answer 31

Explain each one

Question 32

Describe the symptomatic relief that you would offer

Answer 32

1) Symptomatic relief: her symptoms are largely due to her left ventricular fail- ure (pulmonary oedema). You should treat this as follows:
− In those patients presenting with acute pulmonary oedema (i.e. not our
patient) – sit upright, give oxygen, and reduce cardiac pre-load with vasodi-
lators such as morphine, nitrates, and furosemide.
− Chronically–withaloopdiureticsuchasfurosemide,whichmaybecom-
bined with the potassium-sparing diuretic spironolactone.

Question 33

What would you offer based on the pathophysiological mechanism

Answer 33

2) Pathophysiological mechanism: reduced cardiac output activates two physiological systems that actually worsen the situation in heart failure: the
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Shortness of breath

                    sympathetic and the renin–angiotensin systems. Greater sympathetic acti- vation increases heart rate and contractility via β-adrenergic receptors. This increases the heart’s oxygen demand, which may already be compromised in heart failure (particularly if secondary to ischaemic heart disease), and at high- er heart rates filling time and therefore cardiac output may be further reduced. Activation of the renin–angiotensin system results in increased water reten- tion, leading to fluid overload. Logically, therefore, addressing the unhelpful response of these two systems is associated with improved mortality: − Reduce the oxygen demand of the heart: heart failure is usually due to not enough blood reaching the hard-working myocytes, which start to die. One way of treating this is to use a β-blocker which slows the heart beat, although β-blockers must never be used if patient is in acute LVF. The patient won’t like it (as a slower beating heart will make them feel tired and lethargic) but the many double-blinded, randomized controlled trials have shown that the patient will live longer. The trick is to start with a small dose of β-blocker and increase it very slowly.

Inhibit the renin–angiotensin–aldosterone system: angiotensin-con- verting enzyme (ACE) inhibitors limit activation of the renin–angiotensin– aldosterone pathway, thus reducing reabsorption of sodium and water from the kidneys. Several double-blinded, randomized controlled trials have now shown that ACE inhibitors reduce mortality in heart failure. Angiotensin II receptor blockers (ARBs) may be used as an alternative to ACE inhibitors. NICE guidelines suggest that aldosterone antagonists such as spironolactone can also be used.

Question 34

What would you offer to treat the underlying cause

Answer 34

3) Underlying cause: the most common cause of heart failure is atherosclerosis of the coronary arteries and you should consider addressing this. There are various ways of preventing atherosclerosis getting worse (and maybe even helping the body start to reverse it): statins to reduce cholesterol levels and prevent progression of the atheroma; aspirin to reduce the risk of thrombosis leading to heart ischaemia or infarction; and medication for diabetes mellitus if the patient is diabetic, as uncontrolled diabetes leads to hyperglycaemia which accelerates atherosclerosis.

Question 35

What therapies could be used for advanced heart failure

Answer 35

In advanced heart failure, treatments can include digoxin, cardiac resynchroniza- tion therapy (biventricular pacemakers), implantable cardioversion devices (ICDs), mechanical assist devices, or heart transplantation.
Also, in addition to drug treatments, your management should include conserva- tive measures, such as advice to adopt a healthy (low-salt) diet, minimizing alcohol intake, and taking regular exercise.

Question 36

Mrs Finnegan told you that she was concerned she may have lung cancer, because she used to smoke and her sister died of lung cancer.
Can you reassure Mrs Finnegan that she does not have lung cancer?

Answer 36

It is important to address a patient’s concerns and expectations. If these issues are not addressed, patients will go away unsatisfied and worried. This is not only unethi- cal, as you could prevent the unnecessary agitation, but potentially uneconomical, as they may seek a second opinion.

Mrs Finnegan does not give a history suggesting any warning signs for lung cancer (dry cough, haemoptysis, hoarse voice, loss of weight, poor appetite, night sweats). Head and neck examination revealed no lymphadenopathy or Horner’s syndrome. Her chest radiograph showed no ‘coin lesions’ that could indicate a tumour. But despite all this, it would be unwise to categorically inform the patient that ‘she does not have lung cancer’ because one cannot be 100% sure that she doesn’t have a small tumour which we simply haven’t picked up. Given her 20-pack-year smoking his- tory, it is probably wiser to explain that although she is at an increased risk of lung cancer because of her previous smoking, you could not see any tumours on her cur- rent chest radiograph nor were there any signs in her history or examination that are suggestive of cancer. Explain that you cannot rule out cancer 100% with any tests, but that you have found no evidence of it at the moment and her current symptoms are much more likely to be due to heart failure.

Question 37

Mr Humbolt is a 52-year-old gentleman who underwent a partial hepatectomy for primary hepatic car- cinoma 24 hours ago. On the ward round, Mr Humbolt complains of a ‘painful, rattling cough’. His pulse is 105 bpm regular, blood pressure 125/75 mmHg, respiratory rate 18/min and temperature 37.1oC. Chest expansion is reduced bilaterally and there are crackles in both lung bases. The base of the right lung is dull to percussion and has reduced breath sounds on auscultation.
What reasons can you think of for this patient’s breathlessness? What is the most likely diagnosis in this patient?

Post-operative causes of breathlessness

Answer 37

• Atelectasis (alveolar collapse). Pain sometimes prevents patients from breath- ing adequately and expectorating any mucus in their lungs. The mucus eventu- ally plugs the bronchioles, preventing air entry, and areas of lung collapse as the trapped air is gradually absorbed into the surrounding tissues. In some coun- tries this is prevented by having post-operative patients blow bubbles though a straw placed in a bottle of water, which encourages forceful expiration.
• Pneumonia. This is fairly common post-operatively for a combination of fac- tors: poor clearance of mucus due to pain, aspiration of gastric contents, infec- tion from operative intubation, and a somewhat weakened immune response from the physiological stress of surgery.
• Pulmonary oedema. This can be due to heart failure and/or excessive fluids peri-operatively.
• PE. DVT is very common after surgery due to the combination of trauma and immobility, and classically occurs 10 days post-operation. Large DVTs can be prevented by using compression stockings on the legs, mobilizing patients as early as possible, and using low-molecular weight heparin.
• Anaemia. Patients may be anaemic if there was significant blood loss during surgery.
• Pneumothorax. This should always be considered if the patient has had any interventions near the chest either during the surgery or around the time of surgery (e.g. insertion of central venous line, intercostal anaesthetic block).

Question 38

What is the rattling cough suggestive of

Answer 38

The ‘rattling cough’ is highly suggestive of mucus trapped in the lungs. The reduced chest expansion, crackles, and dull percussion all suggest a collapse of a segment of lung, most notably on the right. This picture would fit with post-operative atelectasis, caused by the patient not breathing out deeply enough to clear his lungs of mucus. This can be prevented with adequate analgesia. Nonetheless, it is important to confirm this diagnosis and exclude the others listed above so this patient would require a chest radiograph (look- ing for collapse, consolidation from pneumonia, oedema, or a pneumothorax), FBC (look- ing for anaemia or a raised white cell count (WCC) from infection such as pneumonia), and C-reactive protein (CRP) levels (which will be raised in infection or tissue damage but is useful to monitor as a sign of improvement or deterioration). The most important treatment for post-operative atelectasis is physiotherapy, analgesia and oxygen.

Question 39

Maggie is a 16-year-old student referred to the respiratory physicians for her recurrent shortness of breath. She describes how she has found herself getting short of breath over the last few months. This mainly occurs in the evenings, and is often associated with a dry cough. In between these episodes, she describes herself as being fine, although she admits that she feels ‘a bit unfit because I’m breathless when I go for even a gentle run with my dad’. She denies any weight loss, fevers, dark faeces, or changes in menstruation. She thinks her father suffers with eczema, and is sure that her brother and father have mild hayfever, as does she. She lives at home with her family, none of whom smoke, and a pet dog.
What is the most likely cause of shortness of breath in Maggie? How can this be confirmed? What long-term management will Maggie require?

Answer 39

Maggie has intermittent episodes of shortness of breath that are worse in the evenings and on exercising. Some episodes are associated with a dry cough but in between episodes she is apparently fine. She also has a family history of atopic indi- viduals, with several members including herself having hayfever and/or eczema. The picture of reversible, intermittent shortness of breath and cough in someone with a family history of atopy is strongly suggestive of asthma.

Question 40

What is asthma a disease of

Answer 40

Asthma is a disease caused by a hypersensitive immune reaction in the bron- chi, which leads to excessive mucus production and bronchoconstriction. The combination leads to an obstructive airways disease which can be confirmed on spirometry. This should show a relatively normal FVC but a significantly reduced forced expiratory ratio (FER) – as the problem is not lung capacity but obstruction affecting the speed at which air can get out of the lungs. (For the precise diagnostic criteria see Chapter 7.)

Question 41

Summarise the management of asthma

Answer 41

Management of asthma is based on three different mechanisms:
1) Avoidance of trigger(s). These can include smoke, allergens (e.g. dust mites, pollen, pets), or exercising in cold air, but often no obvious trigger is known.
2) Bronchodilation. Dilatation of the bronchi can be achieved by either increas- ing sympathetic stimulation to the lungs (e.g. β -agonists or phosphodiesterase
2
inhibitors = theophyllines) or decreasing parasympathetic stimulation to the
lungs (e.g. antimuscarinics). These compounds can be inhaled in short-acting
forms for acute attacks, or in long-acting forms for prophylaxis. β -Agonists 2
can also be given intravenously (IV) if needed.
3) Reduction of immune response in lungs. This can be achieved using inhaled or, in severe cases, oral corticosteroids.

Question 42

Mr Marley is a 67-year-old retired musician. He has been referred to the respiratory physicians by his GP because of persistent shortness of breath and recurrent chest infections. You enter the room to find him standing, with his arms propped against the edge of the table. His breathing is laboured and he has a rattling cough. He finally sits down and explains that he always feels short of breath, and his wife has noticed that he often wheezes. He coughs up phlegm every day, and says he has been doing so for at least 2 years almost non-stop, although it is worse in winter. He knows this is all because of his lifetime habit of smoking – he has smoked about 30 cigarettes a day for over 40 years.
On examination, you find there is peripheral and central cyanosis. His breathing is laboured, with inter- costal recession and an audible wheeze. His chest appears slightly hyperinflated and chest percussion fails to reveal the usual dullness over the liver and heart. The rest of the examination is normal.
Spirometry in the clinic reveals FVC = 70% of expected and FER = 60% of expected.
What is the likely diagnosis? How should this be managed?

Answer 42

Mr Marley is a patient with >20 pack years of smoking who has had a productive
cough every day for >3 consecutive months a year for at least 2 years (chronic bron-
chitis) and hyperinflated lungs (suggesting emphysema). The combination of chron-
ic bronchitis and emphysema in a lifelong smoker is highly suggestive of COPD.
This is a disease caused by the persistent toxicity of smoke, which leads to goblet
cell hyperplasia (and thus excessive mucus production), damaged ciliated epithelial
cells (which usually clear mucus), and inhibition of α -antitrypsin (and thus active 1
trypsin, which degrades the interstitial matrix proteins, leading to loss of elasticity of the lungs and alveoli merging into bullae). The result is lungs with decreased com- pliance (hence the decreased FER), less surface area (hence the decreased FVC), and lots of mucus that cannot be cleared. As a consequence, patients suffer chronically from poor gas exchange in their lungs and recurrent infections.

Question 43

How is COPD diagnosed

Answer 43

According to British Thoracic Society (BTS) guidelines, COPD can only be diag- nosed if spirometry shows FEV1 <80% predicted and FEV1:FVC (FER) ratio <70% predicted. Notice that spirometry in COPD patients often shows both a reduced FER (due to obstructed airways) and a reduced FVC (although the lungs are hyper- inflated, their lack of elasticity means they shift a smaller volume of air as much remains trapped in the lungs). This is not the case in asthma, where usually only the FER is affected. Notice also that the shortness of breath in COPD is persistent and largely irreversible. Again, this is not the case in asthma, where patients are not short of breath between attacks.

Question 44

How is COPD managed

Answer 44

• Smoking cessation. This is the single most important factor in limiting the progression of the disease.
• Effective inhaled therapy. As in asthma, short- and long-acting β -agonists 2
and/or antimuscarinics can be used to control symptoms and improve exercise tolerance in patients. Inhaled corticosteroids should be added to long-acting bronchodilators to decrease exacerbation frequency in patients with an FEV1 less than or equal to 50% predicted who have had two or more exacerbations requiring treatment with antibiotics or oral corticosteroids in a 12-month period.
• Pulmonary rehabilitation (for all patients who need it). A programme of physiotherapy, exercise, education, etc. This increases exercise tolerance and quality of life.
• Non-invasive ventilation (NIV). This is the treatment of choice when medical therapy fails to control persistent hypercapnic ventilatory failure during exacerbations.
• Long-term oxygen. Patients who are hypoxic with an arterial partial pressure of oxygen (PaO2) <7.3 kPa on air, or <8.0 kPa and pulmonary hypertension, should use long-term oxygen for 15 hours each day. This prevents progression to cor pulmonale but does not improve symptoms. Ambulatory oxygen can be given to those who desaturate whilst walking, whilst short-burst oxygen is for psychological benefit only.
• Manage exacerbations. Appropriate use of inhaled steroids, bronchodilators, and vaccines should be used to reduce the incidence of exacerbations. The impact of exacerbations should be minimized by:
− Giving self-management advice on responding promptly to the symptoms
of an exacerbation
− Startingappropriatetreatmentwithoralcorticosteroidsand/orantibiotics
− Use of non-invasive ventilation when indicated
− Useofhospital-at-homeorassisted-dischargeschemes.

Question 45

Mr Marley (from the previous case) is admitted to hospital 5 months after he is diagnosed with COPD by the respiratory physicians. He has become very short of breath, confused, and unable to complete full sentences. His daughter explains that he has been deteriorating gradually over the past week and was due to see the respiratory physicians again next week. He is immediately given high-flow 100% oxygen. An arterial blood gas (ABG) is performed and shows PaO2 = 6.2 kPa, PaCO2 = 7.3 kPa, pH = 7.28, bicarbo- nate = 33 mM, base excess = –1 (on 15 L of O2). The emergency physicians request a chest radiograph, which shows no signs of consolidation (pneumonia) or pulmonary oedema. His ECG, FBC, and serum biochemistry are normal.
What is the problem? How would you proceed?

Answer 45

Mr Marley’s arterial blood gas shows type II respiratory failure (PaO2 <8 kPa and PaCO2 >6.5 kPa). With his history and ABG results (indicating a degree of metabolic compensation but with an acute acidosis), this is an acute-on-chronic picture.
Type II respiratory failure is a medical emergency. Untreated, the rising CO2 will narcose the patient, who will fall into an irreversible coma and die.

Question 46

What does treatment for the acute acidosis involve

Answer 46

1) Controlled oxygen therapy. The high CO2 that defines type II respiratory failure often means that patients no longer rely on CO2 levels to stimulate breathing. If you give 100% oxygen, you risk causing a respiratory arrest so this must be stopped in Mr Marley’s case. Instead, give controlled oxygen (24–28% using a special connector on the oxygen mask) aiming for oxygen saturations of 80–90%. Perform repeated arterial blood gases, looking for a drop in PaCO2.
2) Improve ventilation. If the CO2 does not drop with controlled oxygen therapy, ensure the airway is fully patent and involve the intensive therapy unit (ITU) physicians as the patient will need assisted ventilation (e.g. non-invasive ven- tilation) and/or respiratory stimulants (e.g. doxapram).
3) Treat the underlying cause. Assess for reversible causes of reduced gas exchange (e.g. pneumothorax, pneumonia, pulmonary oedema, PE) and reversible causes of reduced ventilation (e.g. airway obstruction due to reduced consciousness, opiate medication).
10

Question 47

Miss Chanda is a 27-year-old factory worker from Zambia who has been referred to the medical admis- sions unit of her hospital because of severe shortness of breath, which has been present for the last few days. She finds she is always breathless but it is worse with even mild exertion such as walking. She has felt very weak for the last few days and has had a dry cough and fever. On hindsight, she thinks she has probably been losing weight for the past few months. Her past medical history is unremarkable and she takes no regular medications.
On examination, Miss Chanda has a temperature of 37.6°C and a respiratory rate of 25/min. Her JVP is not raised, there is no peripheral oedema, and both heart sounds are present without any added sounds. There are fine crackles heard over the entirety of both lung fields. The rest of the examination is entirely normal. Her oxygen saturations are 90% on air but the attending nurse comments that when Miss Chan- da came back from walking to the toilet, her saturations had dropped to 82%. A chest radiograph shows diffuse interstitial shadowing throughout both lung fields.
What is the likely diagnosis? What tests will you arrange?

Answer 47

The clinical picture of dry cough, shortness of breath, low oxygen saturation/ desaturation on exercise, and diffuse interstitial shadowing throughout the lungs on a chest radiograph in a young patient from Africa should always make you sus- picious of Pneumocystis jiroveci pneumonia (previously known as Pneumocystis carinii pneumonia, or PCP). Pneumocystis is an opportunistic organism that rarely causes problems in healthy adults but commonly causes pneumonia in immunosup- pressed patients. Indeed, Pneumocystis pneumonia is a common complication of patients with AIDS. It is diagnosed by performing microscopy (+ silver staining) and culture on sputum and broncho-alveolar lavage samples.
If you suspect Pneumocystis pneumonia, you should arrange to test for two other infections:
• HIV testing. Offer Miss Chanda an HIV test. If this is positive, you will need to check her CD4+ lymphocyte levels, as these dictate the need for antiretro- viral therapy.
• Tuberculosis testing, as this is a frequent cause of pulmonary pathology in HIV-positive patients. Testing is by microscopy (+ Ziehl–Neelsen staining) and culture of sputum and broncho-alveolar lavage samples.

Question 48

Mrs Betty is a 48-year-old magistrate who attends your clinic complaining of persistent breathless- ness that has been getting worse over the last year. It is worst when she takes her dog for a brisk walk, but is always present, even at rest. She denies any cough, weight loss, or night sweats. She smokes ‘the odd cigarette’ at social events, but never more than five cigarettes a month. A recent blood test ordered by her referring GP shows:
RBC
WCC
Hb
ESR
HbA1c
Blood glucose Total cholesterol LDL
HDL
4.7 × 1012 cells/L 8 × 109 cells/L 11.5 g/dL
72 mm/h
5%
4.8 mM 4.3 mM 2.2 mM 2.1 mM
(Hb, haemoglobin; ESR, erythrocyte sedimentation rate)
Her past medical history includes rheumatoid arthritis, for which she takes methotrexate.
On examination, you notice swelling of the metacarpophalangeal joints (MCPJs) and ulnar deviation
of her fingers on both hands. Her pulse is 80 bpm and regular, her blood pressure is 120/80 mmHg and she is apyrexial. There are no signs of peripheral or central cyanosis, anaemia, or lymphadenopathy. Her trachea is central and her apex beat undisplaced. Heart sounds I and II are present with no added sounds, and no carotid bruits. Her lungs expand symmetrically and show normal resonance to percus- sion. However, very fine crackles can be heard all over her lung fields. She has no peripheral oedema and her abdominal and neurological examinations are entirely normal.
Flow spirometry reveals FVC = 65% and FEV1 = 88%. An ECG shows sinus rhythm with no abnormalities

What is the most likely cause of Mrs Betty’s shortness of breath? How would you confirm this?

Answer 48

Mrs Betty does not have any features that are strongly suggestive of the ‘most likely’ or ‘must exclude’ diagnoses listed in Table 10.1. Her flow spirometry suggests a restrictive lung pathology as her expiratory rate is normal (FEV1 >70%) but her lung capacity is reduced (FVC <70% predicted value) – in other words, the problem is not getting air out but how much air her lungs can hold. The fine crackles heard all over her lungs, combined with her flow spirometry and absence of another obvi- ous diagnosis, suggest that Mrs Betty has pulmonary fibrosis. Pulmonary fibrosis can be caused by congenital diseases (e.g. neurofibromatosis, Gaucher disease), systemic inflammatory diseases (e.g. rheumatoid arthritis, ankylosing spondylitis, sarcoidosis), chemical irritation (e.g. silica, asbestos, coal dust, chlorine), drugs (e.g. methotrexate, amiodarone), allergic reations (e.g. bird-funcier’s lung), radia- tion, or the cause may not be known (e.g. cryptogenic fibrosing alveolitis/usual interstitial pneumonitis).

Question 49

How would you confirm the diagnosis of pulmonary fibrosis

Answer 49

The best way to confirm Mrs Betty’s postulated diagnosis of pulmonary fibrosis is a high-resolution chest computed tomography (CT) scan. Radiologists can diagnose pulmonary fibrosis with high sensitivity and specificity by looking for characteristic linear reticular opacities and a ground-glass appearance of the lung.
10
Short cases 199
Short case
200 Shortness of breath
Mrs Betty should switch from methotrexate to another immunosuppresive agent in order to control her rheumatoid arthritis. Whilst this is unlikely to improve her condition significantly, it will at least prevent further deterioration, particularly if the fibrosis was mainly due to the methotrexate rather than the rheumatoid arthritis (which explains her elevated ESR).

Question 50

Claire is a 15-year-old student who presents to her GP complaining of general fatigue and shortness of breath when she exercises. She has recently found herself feeling unusually tired towards the end of the day and complains that she is more breathless than usual during her netball training. She does not smoke, denies any cough, and is never woken at night feeling short of breath. She has never travelled further than Italy, and is otherwise fit and well. She has no family history of respiratory disease. When specifically asked, she reveals with some embarrassment that her periods are ‘a bit heavy’ but she denies her faeces ever being dark or bloody. Physical examination is unremarkable. Spirometry reveals an FVC = 90% and FER = 88%.
What tests should the GP arrange? What is the most likely diagnosis?

Answer 50

This patient does not have any features of heart failure (no clinical features and a bit young), aortic stenosis (no murmur), asthma (no cough, no wheeze, nor- mal spirometry), COPD (young with no family history to suggest α -antitrypsin,
1 non-smoker, no cough), Guillain–Barré syndrome (no recent infection, normal
spirometry), lung collapse (no physical signs), or pneumothorax (no physical signs). However, she does complain of fatigue and admits to having menorrhagia (heavy menstrual periods). It is therefore very likely that this patient is anaemic, as the most common cause for anaemia in menstruating women is menorrhagia. The GP should order an FBC (which will probably reveal a microcytic hypochromic anaemia, compatible with an iron-deficiency anaemia) and clotting studies (to rule out a clotting disorder that may be causing or exacerbating her menorrhagia). If a gynaecologist referral does not reveal any abnormality causing the menorrhagia, the patient will probably benefit from pharmacological treatment. NICE guidelines recommend a levonorgestrel-releasing intrauterine device (LNG-IUD) or the com- bined oral contraceptive pill.
10

Question 51

Mr Andreyov is a 42-year-old investment banker who presents to your clinic complaining of shortness of breath. He says the sensation of breathlessness is always present. He doesn’t think it is connected, but mentions that he has found it increasingly difficult to type at his computer recently and he has noticed some twitching of his thighs that he initially put down to stress. He has no relevant past medical history and is not on any medication. He has never smoked and drinks approximately 10 units of wine a week with evening meals. He sleeps well and has not noticed any change in his appetite nor any bloody or dark faeces or urine. He is worried he may be developing heart problems because he admits his diet is not very healthy and he doesn’t exercise enough.
Cardiovascular, respiratory, and abdominal examination is unremarkable. Neurological examination reveals that the first dorsal interossei on both hands are wasted. In addition, you note fasciculations over both his thighs, reduced power (4/5) on knee flexion, and an upgoing plantar reflex. Flow spirometry reveals FVC = 60% and FER = 80%.
What important diagnosis should you consider in this patient?

Answer 51

Mr Andreyov has presented with shortness of breath and a history suggestive of weakness/poor coordination in distal muscle groups of his upper limbs. He has wast- ing of his hand muscles (suggesting a lower motor neuron or muscular pathology). He also has fasciculations in his right leg (suggesting a lower motor neuron pathol- ogy) but an upgoing plantar reflex (suggesting an upper motor neuron pathology). The combination of upper and lower motor neuron pathology signs in any patient should always arouse the suspicion of motor neuron disease and warrants referral to a neurologist. The shortness of breath is likely to be due to diaphragmatic weak- ness, usually a late sign of this disease.

Question 52

Mr O’Hara is a 62-year-old retired paratrooper who presents to your clinic complaining of shortness of breath. He first noticed this a month ago when he was jogging, but says he now feels breathless with minimal exertion. He has not had a cough and has never smoked. He drinks a few pints of ale every weekend. His only past medical history is a fractured right tibia 20 years ago and hypertension for which he takes a thiazide diuretic and an ACE inhibitor. He has not noticed any changes in his bowel habit or urine, but admits that he has probably lost weight over the past few months.
On examination, you can feel several enlarged lymph nodes in the right anterior cervical chain of his neck. His right lung shows decreased expansion and is dull to percussion in the bases. Vocal fremitus is markedly reduced on the right. His cardiovascular, abdominal, and neurological examinations are all normal.
What diagnosis should you consider for Mr O’Hara? What are your next steps?

Answer 52

Mr O’Hara gives a history of worsening shortness of breath and weight loss. His respiratory examination reveals lymphadenopathy of the neck and signs consistent with a right-sided pleural effusion. The combination of weight loss, lymphaden- opathy, and pleural effusion should make you think of a malignant pleural effusion caused by infiltration of the pleural space by metastatic cancer cells.
Your next step should be to arrange a chest radiograph. If this confirms a right- sided pleural effusion, the effusion should be sampled (thoracocentesis) to deter- mine if the fluid in the pleural space is due to changes in osmotic forces (transudate, with protein <25 g/L) or due to infiltration of the pleural space by metastatic cancer cells, infectious agents or inflammatory proteins (exudate, with protein >35 g/L). A finding of protein between 25 and 35 g/L is considered indeterminate and you should then use Light’s criteria (see Chapter 8).
You should also arrange for a lymph node fine needle aspiration (FNA), as Mr O’Hara’s history of weight loss should alert you to the possibility of a malignancy. Mr O’Hara’s chest radiograph showed a massive pleural effusion in his right lung. Thoracocentesis showed it to be an exudate, with low glucose and abnormal-looking lymphocytes. A lymph node biopsy confirmed the presence of binucleated lym-
phocytes (Reed–Sternberg cells), which are diagnostic of Hodgkin’s lymphoma.

Question 53

The notes of a patient you are asked to see state that his past medical history is of ‘asthma/COPD’. Is such a diagnosis possible?

Answer 53

It is obviously possible to have both COPD and asthma at the same time, but it is much more likely that a clear diagnosis has simply not been made. Asthma and COPD are very different diseases and should not be confused:
• Asthma is a reversible and transient obstruction of the airways caused by excessive mucus production, airway inflammation, and constriction of the bronchi. Flow spirometry shows only obstructive changes (i.e. drop in FEV1 <70% but normal FVC, that is, a reduced rate of air flow but a normal lung capacity). It is usually accompanied by a cough and is often worse at night. It is often linked to triggers such as pollen, dust mites, or cold air and is common in patients who are atopic (i.e. who suffer from multiple diseases caused by excessive IgE-mediated hypersensitivity, such as eczema, hayfever, or urticaria).
• COPD is an irreversible and progressive obstruction of the airways. There is a history of chronic bronchitis and/or emphysema. Flow spirometry shows obstructive changes (i.e. drop in FEV1 <70%) but often also a degree of restrictive change (i.e. FVC <70%). Patients are usually older and have a smoking history of >20 pack years.

Question 54

Which different classes of inhaled drugs are used in obstructive airways disease (asthma and/or COPD)? What is the mechanism of action of each drug?

Answer 54

Short-acting bronchodilators
− Salbutamol (UK: blue, ‘Ventolin’): selective β -agonist. Acts on a G-protein-coupled receptor, activat-
2
ing adenylate cyclase and increasing the formation of cAMP, leading to relaxation of the smooth
muscle lining the airways.
− Ipratropium (UK: white + green, ‘Atrovent’): antimuscarinic/cholinergic. Antagonizes muscarinic ace-
tylcholine receptors in the airways, preventing parasympathetic-mediated smooth muscle contrac-
tion. Often used in COPD, but less often in asthma.
− Salbutamol + ipratropium (UK: white + orange, ‘Combivent’).
2) Inhaled steroids
− For example beclometasone, budesonide (UK: brown inhalers), fluticasone (UK: orange inhaler). Work
by affecting intracellular transcription of various proteins to reduce inflammation in the airways. Used in asthma and COPD as second-line treatment.
3) Long-acting bronchodilators
− Salmeterol, formoterol: long-acting β -agonist (LABA). Mechanism like the short-acting variant.
2
− Tiotropium: long-acting anticholinergic (LACA). Mechanism like the short-acting variant. Used in
COPD but not asthma.
− Long-acting bronchodilators can also be combined with inhaled steroids, e.g. budesonide + formoterol
(UK: red, ‘Symbicort’) or fluticasone + salmeterol (UK: purple, ‘Seretide’).
) Oxygen. Don’t forget that this is a drug! It may be given acutely, e.g. in an ambulance or in hospital, or
long-term, e.g. in severe COPD.
Oral drugs are also sometimes used, including oral steroids, xanthine derivatives (theophylline, aminophyl- line), leukotriene antagonists (montelukast), and cromones (sodium cromoglycate, nedocromil sodium).

Question 55

What is the difference between bronchitis and pneumonia, and between broncho- and lobar pneumonia?

Answer 55

Both are lower respiratory tract illnesses, but bronchitis is a disease of the airways whereas pneumonia is a disease of the alveoli. In bronchitis, airways inflammation leads to excess mucus production and partial airway obstruction. In pneumonia, pus accumulates in the alveoli impairing gas exchange and appearing as consolida- tion on a chest radiograph.
Pneumonia can be classified by the pattern of anatomical involvement. In bronchopneumonia, focal areas are affected in a patchy distribution that may involve one or more lobes. Lobar pneumonia, as the name suggests, involves most or all of a single lobe.

Question 56

Why do we get short of breath at altitude? What is the pharmacological mechanism of action of the altitude 10 sickness drug acetazolamide (‘Diamox’)? How might this influence breathlessness at altitude?

Answer 56

At altitude, there is a lower partial pressure of oxygen in the environment. Thus there is a smaller concen- tration gradient driving oxygen from air in the alveoli into the blood. As a result there is a reduction in gas exchange, leading to hypoxia. This causes breathlessness and compensatory hyperventilation to correct the hypoxia. The hyperventilation causes a respiratory alkalosis, which makes one feel lightheaded. One either feels breathless (from hypoxia) or dizzy (from hyperventilation).
Acetazolamide inhibits carbonic anhydrase, an enzyme that catalyses the conversion of CO2 and H2O into
–+
HCO3 and H . There are two theories as to how this might alleviate breathlessness. The first suggests the inhi-
bition of carbonic anhydrase leads to a build-up of CO2, stimulating the respiratory centre and increasing the ventilatory drive. The other theory suggests that the inhibition of carbonic anhydrase in the kidneys leads to a bicarbonaturia and hence a metabolic acidosis, which offsets the respiratory alkalosis due to hyperven- tilation at altitude. The acidosis caused by acetazolamide enables one to hyperventilate at altitude (thus reducing hypoxia and shortness of breath) without becoming lightheaded from the alkalosis that would otherwise result from hyperventilating.

Question 57

There has been a large decrease in the incidence of epiglottitis in recent years, particularly in children. How can you explain this?

Answer 57

Historically, epiglottitis primarily affected children and was a severe, sometimes fatal, condition. It is nearly always due to bacterial infection by Haemophilus influenzae B (HiB). The development and introduction of a HiB vaccine into the UK vaccination schedule in the mid-1990s has led to a decrease in both meningitis (another condition often caused by HiB) and epiglottitis.

Question 58

What is the difference between type I and type II respiratory failure? What are some of the causes?

Answer 58

Respiratory failure is defined as impairment of pulmonary gas exchange sufficient to result in hypoxaemia (PaO2 <8 kPa or 60 mmHg) and/or hypercapnia (PaCO2 >6 kPa or 45 mmHg). It is divided into two types depend- ing on whether CO2 is expelled (and therefore normal or low) or retained (and therefore raised):
Type I respiratory failure
• Pathology: this is a problem with one gas (oxygen), i.e. hypoxaemic respiratory failure. It is caused by a ventilation–perfusion mismatch in the lungs, with ventilation of the unaffected alveoli normal. Compensatory hyperventilation increases CO2 removal but not O2 saturation as blood leaving the unaffected alveoli is already saturated.
• Causes: any lung disease, e.g. asthma, COPD, pneumonia, pulmonary fibrosis, pulmonary oedema. Type II respiratory failure
• Pathology: this is a problem with two gases (oxygen and carbon dioxide), i.e. hypercapnic respiratory failure (low PaO2 and a raised PaCO2). This is caused by ventilatory failure, i.e. impairment of the respira- tory ‘bellows’, resulting in alveolar hypoventilation.
• Causes:
− Decreased respiratory drive, e.g. opiates, central neurological damage (stroke, head trauma)
− Impaired lung movements, e.g. chest wall deformity (as in Duchenne’s muscular dystrophy for
example), neuromuscular impairment (as in motor neuron disease) − Lung pathology, e.g. long-standing COPD, pulmonary fibrosis.

Question 59

What is the difference between a ‘pink puffer’ and a ‘blue bloater’?

Answer 59

Note that these terms are not synonymous with type I and type II respiratory failure! They are outdated terms but still used on the wards sometimes to describe two distinct clinical pictures that arise in chronic lung disease (e.g. COPD), although this is of course a simplification and every patient will be different:
• ‘Pink puffers’ respond to hypercapnia and hypoxaemia by increasing their respiratory rate, resulting in normal PaO2 levels and a ‘pink’ appearance. As a result of the hard work to maintain their oxygena- tion, they often have a barrel-shaped, hyperinflated chest and may breathe through pursed lips. They nonetheless complain of shortness of breath on mild exertion. Broadly speaking, their prognosis is better than that of ‘blue bloaters’.
• In ‘blue bloaters’ the presence of chronically high PaCO2 levels results in desensitization of the respira- tory centre to PaCO2 and chronic cyanosis, giving them a ‘blue’ appearance. They are chronic CO2 retain- ers, becoming reliant on their hypoxic (rather than hypercapnic) drive. They are often bloated because of widespread peripheral oedema caused by right heart failure secondary to the lung problems (cor pulmonale). In general, their prognosis is poor.

Question 60

What is Eisenmenger’s syndrome

Answer 60

Eisenmenger’s syndrome describes the situation where a left to right cardiac shunt becomes a right to left (or bidirectional) shunt. It follows a sequence of events beginning with a left to right cardiac shunt, due to, for example, a ventricular and/or atrial septal defect, patent ductus arteriosus. Over time this causes progres- sive pulmonary hypertension as the delicate pulmonary vasculature is subjected to blood emerging from the left ventricle, via the shunt, at greater pressures than normal pulmonary pressures. Eventually the pulmonary hypertension provides enough resistance to reverse the direction of the shunt.
Ultimately it leads to heart failure and can only be cured by heart–lung transplant. Women of childbearing age must be warned about the increased mortality in pregnancy (over 50%) and strongly advised against it. This condition has become relatively rare in the UK due to early surgical correction of cardiac defects (indeed this is the rationale behind early correction of such defects).

Question 61

Which muscles are responsible for inspiration and expiration: (a) at rest and (b) during exercise or respiratory distress?

Answer 61

) At rest
Diaphragm
External intercostals

(Passive – natural elastic recoil of lung)
(b) During exercise/ respiratory distress
Diaphragm
External intercostals Scalene Sternocleidomastoids

Natural elastic recoil of lung PLUS: Internal intercostals
Abdominal muscles (rectus and
transversus abdominus, internal and external obliques)

Question 62

What is the differential diagnosis for bibasal crepitations? Which features in the history and examination will
help you to distinguish them?

Answer 62

Pulmonary oedema:
Displaced apex, raised JVP, ankle oedema
Pulmonary fibrosis:
Reduced expansion, clubbing, crepitations that do not vary with cough
Bronchiectasis:
Chronic productive cough, wheeze, and crepitations that vary with cough, clubbing
     10
208 Shortness of breath

Cause of crepitations Key clue
Pneumonia ;Acute productive cough, fever, chest pain, bronchial breathing, dull percussion

Question 63

What is your differential diagnosis for shortness of breath in a post-operative patient? What key clues will help you identify the most likely cause? How will you manage each cause?

Answer 63

Pulmonary oedema
Displaced apex, raised JVP, ankle oedema, frothy sputum ± evidence of MI on ECG or biochemically (troponins)
Sit patient up, furosemide, oxygen, morphine, nitrates

PE
Fever, tachycardia, signs of DVT in leg. Onset typically 10 days after surgery
LMWH, start warfarin, TED (anti-embolism) stockings to prevent more DVTs
Atelectasis
Crepitations, mild fever, fruity and painful cough. Onset typically during first 48 h after surgery
Analgesia, oxygen, and lung physiotherapy

Pneumonia Productive cough, fever, chest pain, bronchial breathing, dull percussion,
increased vocal resonance, consolidation on chest radiograph
LMWH, low-molecular weight heparin.
Antibiotics

Pneumothorax
Area of lung with decreased air entry, hyper-resonance and air in pleural space on chest radiograph
Chest drain

Question 64

Once a patient has been diagnosed with chronic heart failure, there are several medications that can help
reduce their mortality. What are the key trials demonstrating mortality benefit in chronic heart failure?

Answer 64

ACE inhibitors: the SAVE1 and SOLVD2 trials both showed that ACE inhibitors can significantly reduce mortality from chronic heart failure, from 8–28% depending on how symptomatic the patient is (more symptomatic patients gain more benefit). In patients who cannot tolerate ACE inhibitors because of their side-effects (e.g. cough), the ELITE II3 study and Valsartan Heart Failure Trial4 have shown that angiotensin II receptor blockers (A2RB) are as effective as ACE inhibitors in reducing mortality. How- ever, a third trial (RESOLVD5) had to be stopped because of increased mortality in the group receiving the A2RB.
β-Blockers: Several trials6 including CIBIS-II7 and MERIT-HF8 have shown that β-blockers reduce mortality from chronic heart failure by about 25%.
Spironolactone: the RALES9 trial found that the aldosterone receptor spironolactone reduced mortality from chronic heart failure by about 30%.