PASSMEDICINE NOTES

RESPIRATORY MEDICINE
CONTENTS
No Topic Page
1 RESPIRATORY PHYSIOLOGY: LUNG VOLUMES
2 TRANSFER FACTOR
3 OXYGEN DISSOCIATION CURVE
4 PULMONARY FUNCTION TESTS
5 FLOW VOLUME LOOP
6 RESPIRATORY ACIDOSIS
7 RESPIRATORY ALKALOSIS
8 CHEST X-RAY: CAVITATING LUNG LESION
9 CHEST X-RAY: LUNG METASTASES
10 ASTHMA: DIAGNOSIS
11 ASTHMA: MANAGEMENT IN ADULTS
12 ACUTE ASTHMA: FEATURES
13 ASTHMA: OCCUPATIONAL
14 LEUKOTRIENE RECEPTOR ANTAGONISTS
15 OMALIZUMAB
16 COPD: CAUSES
17 COPD: INVESTIGATION AND DIAGNOSIS
18 ACUTE EXACERBATION OF COPD
19 COPD: STABLE MANAGEMENT
20 COPD: LONG-TERM OXYGEN THERAPY
21 OXYGEN THERAPY
22 SMOKING CESSATION
23 ACUTE RESPIRATORY DISTRESS SYNDROME
24 MIDDLE EAST RESPIRATORY SYNDROME
25 NON-INVASIVE VENTILATION
26 PLEURAL EFFUSION: CAUSES
27 PLEURAL EFFUSION: INVESTIGATION AND MANAGEMENT
28 PNEUMONIA: ASSESSMENT AND MANAGEMENT
29 KLEBSIELLA
30 CRYPTOGENIC ORGANIZING PNEUMONIA
31 PSITTACOSIS
32 TUBERCULOSIS
33 PNEUMOTHORAX: FEATURES
34 PNEUMOTHORAX: MANAGEMENT
35 CHEST DRAIN
36 OBSTRUCTIVE SLEEP APNOEA/HYPOPNOEA SYNDROME
37 PULMONARY HYPERTENSION: CAUSES AND CLASSIFICATION
38 ALPHA-1 ANTITRYPSIN DEFICIENCY
39 KARTAGENER'S SYNDROME
40 LOFGREN'S SYNDROME
41 ATELECTASIS
42 BRONCHIECTASIS: CAUSES
43 BRONCHIECTASIS: MANAGEMENT
44 LUNG CANCER: RISK FACTORS
45 LUNG CANCER: INVESTIGATION
46 LUNG CANCER: PARANEOPLASTIC FEATURES
47 LUNG CANCER: NON-SMALL CELL MANAGEMENT
48 LUNG CANCER: SMALL CELL
49 LUNG CANCER: CARCINOID
50 LUNG CANCER: REFERRAL
51 SARCOIDOSIS
52 BILATERAL HILAR LYMPHADENOPATHY
53 SARCOIDOSIS: INVESTIGATION
54 SARCOIDOSIS: MANAGEMENT
55 SARCOIDOSIS: PROGNOSTIC FEATURES
56 SILICOSIS
57 ASBESTOS AND THE LUNG
58 MESOTHELIOMA
59 RHEUMATOID ARTHRITIS: RESPIRATORY MANIFESTATIONS
60 LUNG FIBROSIS
61 IDIOPATHIC PULMONARY FIBROSIS
62 EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (CHURG-STRAUSS SYNDROME)
63 GRANULOMATOSIS WITH POLYANGIITIS (WEGENER'S GRANULOMATOSIS)
64 MICROSCOPIC POLYANGIITIS
65 PULMONARY EOSINOPHILIA
66 EXTRINSIC ALLERGIC ALVEOLITIS
67 ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS
68 ALTITUDE RELATED DISORDERS
69 DRUGS USED IN RESPIRATORY MEDICINE
RESPIRATORY PHYSIOLOGY: LUNG VOLUMES

The diagram below demonstrates the lung volumes which may be measured:

Tidal volume (TV)

 volume inspired or expired with each breath at rest
 500ml in males, 350ml in females

Inspiratory reserve volume (IRV) = 2-3 L

 maximum volume of air that can be inspired at the end of a normal tidal inspiration
 inspiratory capacity = TV + IRV

Expiratory reserve volume (ERV) = 750ml

 maximum volume of air that can be expired at the end of a normal tidal expiration

Residual volume (RV) = 1.2L

 volume of air remaining after maximal expiration
 increases with age
 RV = FRC - ERV

Functional residual capacity (FRC)

 the volume in the lungs at the end-expiratory position
 FRC = ERV + RV

Vital capacity (VC) = 5L

 maximum volume of air that can be expired after a maximal inspiration
 4,500ml in males, 3,500 mls in females
 decreases with age
 VC = inspiratory capacity + ERV

Total lung capacity (TLC) is the sum of the vital capacity + residual volume

Physiological dead space (VD)

 VD = tidal volume * (PaCO2 - PeCO2) / PaCO2
 where PeCO2 = expired air CO2

TRANSFER FACTOR

The transfer factor describes the rate at which a gas will diffuse from alveoli into blood. Carbon
monoxide is used to test the rate of diffusion. Results may be given as the total gas transfer (TLCO)
or that corrected for lung volume (transfer coefficient, KCO)

Causes of a raised TLCO Causes of a lower TLCO

 asthma  pulmonary fibrosis

 pulmonary haemorrhage (Wegener's,  pneumonia
Goodpasture's)  pulmonary emboli
 left-to-right cardiac shunts  pulmonary oedema
 polycythaemia  emphysema
 hyperkinetic states  anaemia
 male gender, exercise  low cardiac output

KCO also tends to increase with age. Some conditions may cause an increased KCO with a normal or
reduced TLCO
 pneumonectomy/lobectomy
 scoliosis/kyphosis
 neuromuscular weakness
 ankylosis of costovertebral joints e.g. ankylosing spondylitis
OXYGEN DISSOCIATION CURVE

The oxygen dissociation curve describes the relationship between the percentage of saturated
haemoglobin and partial pressure of oxygen in the blood. It is not affected by haemoglobin
concentration

Basics
 shifts to left = for given oxygen tension there is increased saturation of Hb with oxygen i.e.
decreased oxygen delivery to tissues
 shifts to right = for given oxygen tension there is reduced saturation of Hb with oxygen i.e.
enhanced oxygen delivery to tissues

Shifts to Left = Lower oxygen delivery Shifts to Right = Raised oxygen delivery
HbF, methaemoglobin, carboxyhaemoglobin Raised [H+] (acidic)
Low [H+] (alkali) Raised pCO2
Low pCO2 Raised 2,3-DPG*
Low 2,3-DPG Raised temperature
Low temperature

The L rule

Shifts to L → Lower oxygen delivery, caused by

 Low [H+] (alkali)

 Low pCO2
 Low 2,3-DPG
 Low temperature

Another mnemonic is 'CADET, face Right!' for CO2, Acid, 2,3-DPG, Exercise and Temperature

*2,3-diphosphoglycerate

PULMONARY FUNCTION TESTS

Pulmonary function tests can be used to determine whether a respiratory disease is obstructive or
restrictive. The table below summarises the main findings and gives some example conditions:
Obstructive lung disease Restrictive lung disease
FEV1 - significantly reduced FEV1 - reduced
FVC - reduced or normal FVC - significantly reduced
FEV1% (FEV1/FVC) - reduced FEV1% (FEV1/FVC) - normal or increased
Asthma Pulmonary fibrosis
COPD Asbestosis
Bronchiectasis Sarcoidosis
Bronchiolitis obliterans Acute respiratory distress syndrome
Infant respiratory distress syndrome
Kyphoscoliosis e.g. ankylosing spondylitis
Neuromuscular disorders
Severe obesity

FLOW VOLUME LOOP

A normal flow volume loop is often described as a 'triangle on top of a semi circle'

Flow volume loops are the most suitable way of assessing compression of the upper airway

RESPIRATORY ACIDOSIS

Respiratory acidosis may be caused by a number of conditions:

 COPD
 decompensation in other respiratory conditions e.g. life-threatening asthma / pulmonary
oedema
 neuromuscular disease
 obesity hypoventilation syndrome
 sedative drugs: benzodiazepines, opiate overdose

RESPIRATORY ALKALOSIS

Common causes
 anxiety leading to hyperventilation
 pulmonary embolism
 salicylate poisoning*
 CNS disorders: stroke, subarachnoid haemorrhage, encephalitis
 altitude
 pregnancy

*salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation
of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of
salicylates (combined with acute renal failure) may lead to an acidosis

CHEST X-RAY: CAVITATING LUNG LESION

Differential
 abscess (Staph aureus, Klebsiella and Pseudomonas)
 squamous cell lung cancer
 tuberculosis
 Wegener's granulomatosis
 pulmonary embolism
 rheumatoid arthritis
 aspergillosis, histoplasmosis, coccidioidomycosis

CHEST X-RAY: LUNG METASTASES

Lung metastases are seen with a wide variety of cancers including:

 breast cancer
 colorectal cancer
 renal cell cancer
 bladder cancer
 prostate cancer

Multiple, round well-defined lung secondaries are often referred to as 'cannonball metastases'.
They are most commonly seen with renal cell cancer but may also occur secondary to
choriocarcinoma and prostate cancer.

Calcification in lung metastases is uncommon except in the case of chondrosarcoma or

osteosarcoma.
Chest x-ray showing cannonball metastases secondary to renal cell cancer. Multiple well defined nodules
are noted distributed in both lung fields
ASTHMA: DIAGNOSIS

NICE released guidance on the management of asthma in 2017. These followed on quickly from the
2016 British Thoracic Society (BTS) guidelines. Given previous precedents where specialist societies
or Royal colleges eventually default/contribute to NICE, we have followed the NICE guidance for the
notes and questions.

NICE guidance has radically changed how asthma should be diagnosed. It advocates moving anyway
from subjective/clinical judgements are more towards objective tests.

There is particular emphasis on the use of fractional exhaled nitric oxide (FeNO). Nitric oxide is
produced by 3 types of nitric oxide synthases (NOS). One of the types is inducible (iNOS) and levels
tend to rise in inflammatory cells, particularly eosinophils. Levels of NO therefore typically correlate
with levels of inflammation.

Other more established objective tests such as spirometry and peak flow variability are still
important.

All patients >= 5 years should have objective tests. Once a child with suspected asthma reaches the
age of 5 years objective tests should be performed to confirm the diagnosis.

Diagnostic testing
Patients >= 17 years
 patients should be asked if their symptoms are better on days away from work/during holidays.
If so, patients should be referred to a specialist as possible occupational asthma
 all patients should have spirometry with a bronchodilator reversibility (BDR) test
 all patients should have a FeNO test

Patients 5-16 years

 all patients should have spirometry with a bronchodilator reversibility (BDR) test
 a FeNO test should be requested if there is normal spirometry or obstructive spirometry with a
negative bronchodilator reversibility (BDR) test

Patients < 5 years

- diagnosis should be made on clinical judgement

Specific points about the tests

FeNO
 in adults level of >= 40 parts per billion (ppb) is considered positive
 in children a level of >= 35 parts per billion (ppb) is considered positive

Spirometry
 FEV1/FVC ratio less than 70% (or below the lower limit of normal if this value is available) is
considered obstructive

Reversibility testing
 in adults, a positive test is indicated by an improvement in FEV1 of 12% or more and increase in
volume of 200 ml or more
 in children, a positive test is indicated by an improvement in FEV1 of 12% or more

ASTHMA: MANAGEMENT IN ADULTS

NICE released guidance on the management of asthma in 2017. These followed on quickly from the
2016 British Thoracic Society (BTS) guidelines. Given previous precedents where specialist societies
or Royal colleges eventually default/contribute to NICE, we have followed the NICE guidance for the
notes and questions.

One of the key changes is in 'step 3' - patients on a SABA + ICS whose asthma is not well controlled
should be offered a leukotriene receptor antagonist, not a LABA

NICE do not follow the stepwise approach of the previous BTS guidelines. However, to try to make
the guidelines easier to follow we've added our own steps:

Step Notes
1 Short-acting beta agonist (SABA)

Newly-diagnosed asthma
2 SABA + low-dose inhaled corticosteroid (ICS)

Not controlled on previous step

OR
Newly-diagnosed asthma with
symptoms >= 3 / week or night-
time waking
3 SABA + low-dose ICS + leukotriene receptor antagonist (LTRA)
4 SABA + low-dose ICS + long-acting beta agonist (LABA)

Continue LTRA depending on patient's response to LTRA

5 SABA +/- LTRA

Switch ICS/LABA for a maintenance and reliever therapy (MART),

that includes a low-dose ICS
Step Notes
6 SABA +/- LTRA + medium-dose ICS MART

OR consider changing back to a fixed-dose of a moderate-dose

ICS and a separate LABA
7 SABA +/- LTRA + one of the following options:

 increase ICS to high-dose (only as part of a fixed-dose

regime, not as a MART)
 a trial of an additional drug (for example, a long-acting
muscarinic receptor antagonist or theophylline)
 seeking advice from a healthcare professional with
expertise in asthma

Maintenance and reliever therapy (MART)

 a form of combined ICS and LABA treatment in which a single inhaler, containing both ICS and a
fast-acting LABA, is used for both daily maintenance therapy and the relief of symptoms as
required
 MART is only available for ICS and LABA combinations in which the LABA has a fast-acting
component (for example, formoterol)

It should be noted that NICE does not advocate changing treatment in patients who have well-
controlled asthma simply to adhere to the latest guidance.

Table showing examples of inhaled corticosteroid doses

Frustratingly, the definitions of what constitutes a low, moderate or high-dose ICS have also
changed. For adults:
 <= 400 micrograms budesonide or equivalent = low dose
 400 micrograms - 800 micrograms budesonide or equivalent = moderate dose
 > 800 micrograms budesonide or equivalent= high dose.

ACUTE ASTHMA: FEATURES

Acute asthma is nearly always seen in patients who've got a history of asthma.

Features
 worsening dyspnoea, wheeze and cough that is not responding to salbutamol
 maybe triggered by a respiratory tract infection
Patients with acute severe asthma are stratified into moderate, severe or life-threatening

Moderate Severe Life-threatening

PEFR 50-75% best or predicted PEFR 33 - 50% best or predicted PEFR < 33% best or predicted
Speech normal Can't complete sentences Oxygen sats < 92%
RR < 25 / min RR > 25/min Silent chest, cyanosis or feeble
Pulse < 110 bpm Pulse > 110 bpm respiratory effort
Bradycardia, dysrhythmia or
hypotension
Exhaustion, confusion or coma

In addition, a normal pCO2 in an acute asthma attack indicates exhaustion and should, therefore, be
classified as life-threatening.

Note that a patient having any one of the life-threatening features should be treated as having a
life-threatening attack.

British Thoracic Society guidelines

 magnesium sulphate recommended as next step for patients who are not responding (e.g. 1.2 -
2g IV over 20 mins)
 little evidence to support use of IV aminophylline (although still mentioned in management
plans)
 if no response consider IV salbutamol

ASTHMA: OCCUPATIONAL

Patients may either present with concerns that chemicals at work are worsening their asthma or
you may notice in the history that symptoms seem better at weekends / when away from work.

Exposure to the following chemicals is associated with occupational asthma:

 isocyanates - the most common cause. Example occupations include spray painting and foam
moulding using adhesives
 platinum salts
 soldering flux resin
 glutaraldehyde
 flour
 epoxy resins
 proteolytic enzymes

Serial measurements of peak expiratory flow are recommended at work and away from work.
Referral should be made to a respiratory specialist for patients with suspected occupational asthma.

LEUKOTRIENE RECEPTOR ANTAGONISTS

Basics
 e.g. Montelukast, zafirlukast
 have both anti-inflammatory and bronchodilatory properties
 should be used when patients are poorly controlled on high-dose inhaled corticosteroids and a
long-acting b2-agonist
 particularly useful in aspirin-induced asthma
 associated with the development of Churg-Strauss syndrome

OMALIZUMAB

Omalizumab is a new drug that is available for the management of severe asthma. As it's name
suggests it's a monoclonal antibody that specifically binds to free human immunoglobulin E (IgE).

Omalizumab is given as a subcutaneous injection every 2 to 4 weeks.

Where does omalizumab fit into current management?

NICE updated their technology appraisal of omalizumab in 2013. A copy of the criteria is given
below. The emphasis in bold has been added.

Omalizumab is recommended as an option for treating severe persistent confirmed allergic IgE-
mediated asthma as an add on to optimised standard therapy in people aged 6 years and older:
 who need continuous or frequent treatment with oral corticosteroids (defined as 4 or more
courses in the previous year)

Optimised standard therapy is defined as a full trial of and, if tolerated, documented compliance
with inhaled high-dose corticosteroids, long-acting beta agonists, leukotriene receptor antagonists,
theophyllines, oral corticosteroids, and smoking cessation if clinically appropriate.

Adverse effects
 abdominal pain
 headache
 fever
 Churg-Strauss syndrome: may present with eosinophilia, vasculitic rash, worsening respiratory
symptoms and peripheral neuropathy
COPD: CAUSES

Smoking!

Alpha-1 antitrypsin deficiency

Other causes
 cadmium (used in smelting)
 coal
 cotton
 cement
 grain

COPD: INVESTIGATION AND DIAGNOSIS

NICE recommend considering a diagnosis of COPD in patients over 35 years of age who are smokers
or ex-smokers and have symptoms such as exertional breathlessness, chronic cough or regular
sputum production.

The following investigations are recommended in patients with suspected COPD:

 post-bronchodilator spirometry to demonstrate airflow obstruction: FEV1/FVC ratio less than
70%
 chest x-ray: hyperinflation, bullae, flat hemidiaphragm. Also important to exclude lung cancer
 full blood count: exclude secondary polycythaemia
 body mass index (BMI) calculation

The severity of COPD is categorised using the FEV1*:

Post-bronchodilator FEV1/FVC FEV1 (of predicted) Severity

< 0.7 > 80% Stage 1 - Mild**
< 0.7 50-79% Stage 2 - Moderate
< 0.7 30-49% Stage 3 - Severe
< 0.7 < 30% Stage 4 - Very severe

Measuring peak expiratory flow is of limited value in COPD, as it may underestimate the degree of
airflow obstruction.
*note that the grading system has changed following the 2010 NICE guidelines. If the FEV1 is greater
than 80% predicted but the post-bronchodilator FEV1/FVC is < 0.7 then this is classified as Stage 1 -
mild

**symptoms should be present to diagnose COPD in these patients

ACUTE EXACERBATION OF COPD

Acute exacerbations of COPD are one of the most common reasons why people present to hospital
in developed countries.

Features
 increase in dyspnoea, cough, wheeze
 there may be an increase in sputum suggestive of an infective cause
 patients may be hypoxic and in some cases have acute confusion

The most common bacterial organisms that cause infective exacerbations of COPD are:
 Haemophilus influenzae (most common cause)
 Streptococcus pneumoniae
 Moraxella catarrhalis

Respiratory viruses account for around 30% of exacerbations, with the human rhinovirus being the
most important pathogen.

NICE guidelines from 2010 recommend the following:

 increase frequency of bronchodilator use and consider giving via a nebuliser
 give prednisolone 30 mg daily for 7-14 days
 it is common practice for all patients with an exacerbation of COPD to receive antibiotics. NICE
do not support this approach. They recommend giving oral antibiotics 'if sputum is purulent or
there are clinical signs of pneumonia'
 the BNF recommends one of the following oral antibiotics first-line: amoxicillin or clarithromycin
or doxycycline.

COPD: STABLE MANAGEMENT

NICE updated its guidelines on the management of chronic obstructive pulmonary disease (COPD) in
2018.

General management
 > smoking cessation advice: including offering nicotine replacement therapy, varenicline or
bupropion
 annual influenza vaccination
 one-off pneumococcal vaccination
 pulmonary rehabilitation to all people who view themselves as functionally disabled by COPD
(usually Medical Research Council [MRC] grade 3 and above)

Bronchodilator therapy
 a short-acting beta2-agonist (SABA) or short-acting muscarinic antagonist (SAMA) is first-line
treatment
 for patients who remain breathless or have exacerbations despite using short-acting
bronchodilators the next step is determined by whether the patient has 'asthmatic
features/features suggesting steroid responsiveness'

There are a number of criteria NICE suggest to determine whether a patient has asthmatic/steroid
responsive features:
 any previous, secure diagnosis of asthma or of atopy
 a higher blood eosinophil count - note that NICE recommend a full blood count for all patients as
part of the work-up
 substantial variation in FEV1 over time (at least 400 ml)
 substantial diurnal variation in peak expiratory flow (at least 20%)

Interestingly NICE do not recommend formal reversibility testing as one of the criteria. In the
guidelines they state that 'routine spirometric reversibility testing is not necessary as part of the
diagnostic process or to plan initial therapy with bronchodilators or corticosteroids. It may be
unhelpful or misleading...'. They then go on to discuss why they have reached this conclusion. Please
see the guidelines for more details.

No asthmatic features/features suggesting steroid responsiveness

 add a long-acting beta2-agonist (LABA) + long-acting muscarinic antagonist (LAMA)
o if already taking a SAMA, discontinue and switch to a SABA

Asthmatic features/features suggesting steroid responsiveness

 LABA + inhaled corticosteroid (ICS)
 if patients remain breathless or have exacerbations offer triple therapy i.e. LAMA + LABA + ICS
o if already taking a SAMA, discontinue and switch to a SABA
 NICE recommend the use of combined inhalers where possible

Oral theophylline
 NICE only recommends theophylline after trials of short and long-acting bronchodilators or to
people who cannot used inhaled therapy
 the dose should be reduced if macrolide or fluoroquinolone antibiotics are co-prescribed
Oral prophylactic antibiotic therapy
 azithromycin prophylaxis is recommended in select patients
 patients should not smoke, have optimised standard treatments and continue to have
exacerbations
 other prerequisites include a CT thorax (to exclude bronchiectasis) and sputum culture (to
exclude atypical infections and tuberculosis)
 LFTs and an ECG to exclude QT prolongation should also be done as azithromycin can prolong
the QT interval

Mucolytics
 should be 'considered' in patients with a chronic productive cough and continued if symptoms
improve

Cor pulmonale
 features include peripheral oedema, raised jugular venous pressure, systolic parasternal heave,
loud P2
 use a loop diuretic for oedema, consider long-term oxygen therapy
 ACE-inhibitors, calcium channel blockers and alpha blockers are not recommended by NICE

Factors which may improve survival in patients with stable COPD

 smoking cessation - the single most important intervention in patients who are still smoking
 long term oxygen therapy in patients who fit criteria
 lung volume reduction surgery in selected patients

COPD: LONG-TERM OXYGEN THERAPY

The 2018 NICE guidelines on COPD clearly define which patients should be assessed for and offered
long-term oxygen therapy (LTOT). Patients who receive LTOT should breathe supplementary oxygen
for at least 15 hours a day. Oxygen concentrators are used to provide a fixed supply for LTOT.

Assess patients if any of the following:

 very severe airflow obstruction (FEV1 < 30% predicted). Assessment should be 'considered' for
patients with severe airflow obstruction (FEV1 30-49% predicted)
 cyanosis
 polycythaemia
 peripheral oedema
 raised jugular venous pressure
 oxygen saturations less than or equal to 92% on room air

Assessment is done by measuring arterial blood gases on 2 occasions at least 3 weeks apart in
patients with stable COPD on optimal management.
Offer LTOT to patients with a pO2 of < 7.3 kPa or to those with a pO2 of 7.3 - 8 kPa and one of the
following:
 secondary polycythaemia
 peripheral oedema
 pulmonary hypertension

In terms of smoking, NICE advise the following:

 do not offer LTOT to people who continue to smoke despite being offered smoking cessation
advice and treatment, and referral to specialist stop smoking services.

NICE suggest that a structured risk assessment is carried out before offering LTOT, including:
 the risks of falls from tripping over the equipment
 the risks of burns and fires, and the increased risk of these for people who live in homes where
someone smokes (including e‑cigarettes)

OXYGEN THERAPY

The British Thoracic Society updated its guidelines on emergency oxygen therapy in 2017. The
following selected points are taken from the guidelines. Please see the link provided for the full
guideline.

In patients who are critically ill (anaphylaxis, shock etc) oxygen should initially be given via a
reservoir mask at 15 l/min. Hypoxia kills. The BTS guidelines specifically exclude certain conditions
where the patient is acutely unwell (e.g. myocardial infarction) but stable.

Oxygen saturation targets

 acutely ill patients: 94-98%
 patients at risk of hypercapnia (e.g. COPD patients): 88-92% (see below)
 oxygen should be reduced in stable patients with satisfactory oxygen saturation

Management of COPD patients

 prior to availability of blood gases, use a 28% Venturi mask at 4 l/min and aim for an oxygen
saturation of 88-92% for patients with risk factors for hypercapnia but no prior history of
respiratory acidosis
 adjust target range to 94-98% if the pCO2 is normal

Situations where oxygen therapy should not be used routinely if there is no evidence of hypoxia:
 myocardial infarction and acute coronary syndromes
 stroke
 obstetric emergencies
 anxiety-related hyperventilation

SMOKING CESSATION

NICE released guidance in 2008 on the management of smoking cessation. General points include:
 patients should be offered nicotine replacement therapy (NRT), varenicline or bupropion - NICE
state that clinicians should not favour one medication over another
 NRT, varenicline or bupropion should normally be prescribed as part of a commitment to stop
smoking on or before a particular date (target stop date)
 prescription of NRT, varenicline or bupropion should be sufficient to last only until 2 weeks after
the target stop date. Normally, this will be after 2 weeks of NRT therapy, and 3-4 weeks for
varenicline and bupropion, to allow for the different methods of administration and mode of
action. Further prescriptions should be given only to people who have demonstrated that their
quit attempt is continuing
 if unsuccessful using NRT, varenicline or bupropion, do not offer a repeat prescription within 6
months unless special circumstances have intervened
 do not offer NRT, varenicline or bupropion in any combination

Nicotine replacement therapy

 adverse effects include nausea & vomiting, headaches and flu-like symptoms
 NICE recommend offering a combination of nicotine patches and another form of NRT (such as
gum, inhalator, lozenge or nasal spray) to people who show a high level of dependence on
nicotine or who have found single forms of NRT inadequate in the past

Varenicline
 a nicotinic receptor partial agonist
 should be started 1 week before the patients target date to stop
 the recommended course of treatment is 12 weeks (but patients should be monitored regularly
and treatment only continued if not smoking)
 has been shown in studies to be more effective than bupropion
 nausea is the most common adverse effect. Other common problems include headache,
insomnia, abnormal dreams
 varenicline should be used with caution in patients with a history of depression or self-harm.
There are ongoing studies looking at the risk of suicidal behaviour in patients taking varenicline
 contraindicated in pregnancy and breast feeding

Bupropion
 a norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonist
 should be started 1 to 2 weeks before the patients target date to stop
 small risk of seizures (1 in 1,000)
 contraindicated in epilepsy, pregnancy and breast feeding. Having an eating disorder is a relative
contraindication

Pregnant women
NICE recommended in 2010 that all pregnant women should be tested for smoking using carbon
monoxide detectors, partly because 'some women find it difficult to say that they smoke because
the pressure not to smoke during pregnancy is so intense.'. All women who smoke, or have stopped
smoking within the last 2 weeks, or those with a CO reading of 7 ppm or above should be referred to
NHS Stop Smoking Services.

Interventions
 the first-line interventions in pregnancy should be cognitive behaviour therapy, motivational
interviewing or structured self-help and support from NHS Stop Smoking Services
 the evidence for the use of NRT in pregnancy is mixed but it is often used if the above measures
failure. There is no evidence that it affects the child's birthweight. Pregnant women should
remove the patches before going to bed
 as mentioned above, varenicline and bupropion are contraindicated
ACUTE RESPIRATORY DISTRESS SYNDROME

Acute respiratory distress syndrome (ARDS) is caused by the increased permeability of alveolar
capillaries leading to fluid accumulation in the alveoli, i.e. non-cardiogenic pulmonary oedema. It is a
serious condition that has a mortality of around 40% and is associated with significant morbidity in
those who survive.

Causes
 infection: sepsis, pneumonia
 massive blood transfusion
 trauma
 smoke inhalation
 acute pancreatitis
 cardio-pulmonary bypass

Clinical features are typically of an acute onset and severe:

 dyspnoea
 elevated respiratory rate
 bilateral lung crackles
 low oxygen saturations

A chest x-ray and arterial blood gases are the key investigations.

Criteria (American-European Consensus Conference)

 acute onset (within 1 week of a known risk factor)
 pulmonary oedema: bilateral infiltrates on chest x-ray ('not fully explained by effusions,
lobar/lung collapse or nodules)
 non-cardiogenic (pulmonary artery wedge pressure needed if doubt)
 pO2/FiO2 < 40kPa (200 mmHg)

Management
 due to the severity of the condition patients are generally managed in ITU
 oxygenation/ventilation to treat the hypoxaemia
 general organ support e.g. vasopressors as needed
 treatment of the underlying cause e.g. antibiotics for sepsis
 certain strategies such as prone positioning and muscle relaxation have been shown to improve
outcome in ARDS
MIDDLE EAST RESPIRATORY SYNDROME

Middle East respiratory syndrome (MERS) is caused by the betacoronavirus MERS-CoV.

At the present time, MERS-CoV is limited to the Arabian Peninsula and its surrounding countries,
although due to an incubation period of 2-14 days travellers returning from this region may present
with MERS in other parts of the world.

Contact with camels (including camel products such as milk) is a significant risk factor for MERS-CoV.

The clinical syndrome of MERS is varied, ranging from very only mild symptoms through to life-
threatening multi-organ failure.

NON-INVASIVE VENTILATION

The British Thoracic Society (BTS) published guidelines in 2002 on the use of non-invasive ventilation
in acute respiratory failure. Following these the Royal College of Physicians published guidelines in
2008.

Non-invasive ventilation - key indications

 COPD with respiratory acidosis pH 7.25-7.35*
 type II respiratory failure secondary to chest wall deformity, neuromuscular disease or
obstructive sleep apnoea
 cardiogenic pulmonary oedema unresponsive to CPAP
 weaning from tracheal intubation

Recommended initial settings for bi-level pressure support in COPD

 Expiratory Positive Airway Pressure (EPAP): 4-5 cm H2O
 Inspiratory Positive Airway Pressure (IPAP): RCP advocate 10 cm H20 whilst BTS suggest 12-15
cm H2O
 back up rate: 15 breaths/min
 back up inspiration:expiration ratio: 1:3

*the BTS guidelines state that NIV can be used in patients who are more acidotic (i.e. pH < 7.25) but
that a greater degree of monitoring is required (e.g. HDU) and a lower threshold for intubation and
ventilation should be used
PLEURAL EFFUSION: CAUSES

Pleural effusions may be classified as being either a transudate or exudate according to the protein
concentration.

Transudate (< 30g/L protein)

 heart failure (most common transudate cause)
 hypoalbuminaemia (liver disease, nephrotic syndrome, malabsorption)
 hypothyroidism
 Meigs' syndrome

Exudate (> 30g/L protein)

 infection: pneumonia (most common exudate cause), TB, subphrenic abscess
 connective tissue disease: RA, SLE
 neoplasia: lung cancer, mesothelioma, metastases
 pancreatitis
 pulmonary embolism
 Dressler's syndrome
 yellow nail syndrome

Features
 dyspnoea, non-productive cough or chest pain are possible presenting symptoms
 classic examination findings include dullness to percussion, reduced breath sounds and reduced
chest expansion

PLEURAL EFFUSION: INVESTIGATION AND MANAGEMENT

The British Thoracic Society (BTS) produced guidelines in 2010 covering the investigation of patients
with a pleural effusion.

Imaging
 posterioranterior (PA) chest x-rays should be performed in all patients
 ultrasound is recommended: it increases the likelihood of successful pleural aspiration and is
sensitive for detecting pleural fluid septations
 contrast CT is now increasingly performed to investigate the underlying cause, particularly for
exudative effusions

Pleural aspiration
 as above, ultrasound is recommended to reduce the complication rate
 a 21G needle and 50ml syringe should be used
 fluid should be sent for pH, protein, lactate dehydrogenase (LDH), cytology and microbiology

Light's criteria was developed in 1972 to help distinguish between a transudate and an exudate. The
BTS recommend using the criteria for borderline cases:
 exudates have a protein level of >30 g/L, transudates have a protein level of <30 g/L
 if the protein level is between 25-35 g/L, Light's criteria should be applied. An exudate is likely if
at least one of the following criteria are met:
o pleural fluid protein divided by serum protein >0.5
o pleural fluid LDH divided by serum LDH >0.6
o pleural fluid LDH more than two-thirds the upper limits of normal serum LDH

Other characteristic pleural fluid findings:

 low glucose: rheumatoid arthritis, tuberculosis
 raised amylase: pancreatitis, oesophageal perforation
 heavy blood staining: mesothelioma, pulmonary embolism, tuberculosis

Pleural infection
All patients with a pleural effusion in association with sepsis or a pneumonic illness require
diagnostic pleural fluid sampling
 if the fluid is purulent or turbid/cloudy a chest tube should be placed to allow drainage
 if the fluid is clear but the pH is less than 7.2 in patients with suspected pleural infection a chest
tube should be placed

Management of recurrent pleural effusion

Options for managing patients with recurrent pleural effusions include:
 recurrent aspiration
 pleurodesis
 indwelling pleural catheter
 drug management to alleviate symptoms e.g. opioids to relieve dyspnoea
PNEUMONIA: ASSESSMENT AND MANAGEMENT

Primary care setting

NICE recommends that patients should initially be assessed in primary care using the CRB65 criteria:

Criterion Marker
C Confusion (abbreviated mental test score <= 8/10)
R Respiration rate >= 30/min
B Blood pressure: systolic <= 90 mmHg and/or diastolic <= 60 mmHg
65 Aged >= 65 years

Patients are stratified for risk of death as follows:

 0: low risk (less than 1% mortality risk)
 1 or 2: intermediate risk (1-10% mortality risk)
 3 or 4: high risk (more than 10% mortality risk).

NICE recommend, in conjunction with clinical judgement:

 for all other patients, particularly those with a CRB65 score of 2 or more.

NICE also mention point-of-care CRP test. This is currently not widely available but they make the
following recommendation with reference to the use of antibiotic therapy:
CRP < 20 mg/L - do not routinely offer antibiotic therapy
CRP 20 - 100 mg/L - consider a delayed antibiotic prescription
CRP > 100 mg/L - offer antibiotic therapy

Secondary care setting

Note that in hospital, once blood tests are available the CURB65, rather than the CRB65, can be
used. This adds an extra criterion of urea > 7 mmol/L:

Criterion Marker
C Confusion (abbreviated mental test score <= 8/10)
U urea > 7 mmol/L
R Respiration rate >= 30/min
B Blood pressure: systolic <= 90 mmHg and/or diastolic <= 60 mmHg
65 Aged >= 65 years

NICE recommend, in conjunction with clinical judgement:

 consider home-based care for patients with a CURB65 score of 0 or 1 - low risk (less than 3%
mortality risk)
 consider hospital-based care for patients with a CURB65 score of 2 or more - intermediate risk
(3-15% mortality risk)
 consider intensive care assessment for patients with a CURB65 score of 3 or more - high risk
(more than 15% mortality risk)

Investigations
 chest x-ray
 in intermediate or high-risk patients NICE recommend blood and sputum cultures,
pneumococcal and legionella urinary antigen tests
 CRP monitoring is recommend for admitted patients to help determine response to treatment

Management of low-severity community acquired pneumonia

 amoxicillin is first-line
 if penicillin allergic then use a macrolide or tetracycline
 NICE now recommend a 5 day course of antibiotics for patients with low severity community
acquired pneumonia

Management of moderate and high-severity community acquired pneumonia

 dual antibiotic therapy is recommended with amoxicillin and a macrolide
 a 7-10 day course is recommended
 NICE recommend considering a beta-lactamase stable penicillin such as co-amoxiclav,
ceftriaxone or piperacillin with tazobactam and a macrolide in high-severity community acquired
pneumonia

Discharge criteria and advice post-discharge

NICE recommend that patients are not routinely discharged if in the past 24 hours they have had 2
or more of the following findings:
 temperature higher than 37.5°C
 respiratory rate 24 breaths per minute or more
 heart rate over 100 beats per minute
 systolic blood pressure 90 mmHg or less
 oxygen saturation under 90% on room air
 abnormal mental status
 inability to eat without assistance.

They also recommend delaying discharge if the temperature is higher than 37.5°C.

NICE recommend that the following information is given to patients with pneumonia in terms of
how quickly their symptoms should symptoms should resolve:

Time Progress
1 week Fever should have resolved
4 weeks Chest pain and sputum production should have substantially reduced
Time Progress
6 weeks Cough and breathlessness should have substantially reduced
3 months Most symptoms should have resolved but fatigue may still be present
6 months Most people will feel back to normal.

KLEBSIELLA

Klebsiella pneumoniae is a Gram-negative rod that is part of the normal gut flora. It can cause a
number of infections in humans including pneumonia (typically following aspiration) and urinary
tract infections.

Features of Klebsiella pneumonia

 more common in alcoholic and diabetics
 may occur following aspiration
 'red-currant jelly' sputum
 often affects upper lobes

Prognosis
 commonly causes lung abscess formation and empyema
 mortality is 30-50%

A human neutrophil interacting with Klebsiella pneumoniae (pink), a multidrug-resistant bacterium that
causes severe hospital infections. Credit: NIAID
CRYPTOGENIC ORGANIZING PNEUMONIA

Cryptogenic organizing pneumonia (COP) is a diffuse interstitial lung disease that affects the distal
bronchioles, respiratory bronchioles, alveolar ducts and alveolar walls. It affects around 2 people
per 100,000. The aetiology is unknown.

Males and females are equally affected and tend to present in the 5th or 6th decade of life and is
not associated with smoking. Patients typically present with a cough, shortness of breath, fever and
malaise. Symptoms can be present for weeks or months. There is often a history of non-response to
antibiotics. Haemoptysis is rare. Clinical examination is often normal but inspiratory crackles can be
heard. Wheeze and clubbing are rare.

Bloods show a leukocytosis and an elevated ESR and CRP. Imaging typically shows bilateral patchy or
diffuse consolidative or ground glass opacities. Lung function tests are most commonly restrictive
but can be obstructive or normal. The transfer factor is reduced.

Treatment is watch and wait if mild or high dose oral steroids if severe.

PSITTACOSIS

Psittacosis is infection caused by Chlamydia psittaci. The most common presentation is as a cause of
atypical pneumonia. Psittacosis should be suspected in a combination of typical fever with a history
of bird contact (reported in 84%) or a presentation with pneumonia and severe headache or
organomegaly and failure to respond to penicillin-based antibiotics.

Epidemiology
 Psittacosis is present throughout the world, including the United Kingdom
 It is more common in young adults

Pathology
 Chlamydia psittaci is an obligate intracellular bacterium
 Transmission is typically from birds or bird secretions including urine and faeces, typically
occurring after cleaning bird cages
 Many birds have been implicated in transmission, including pet birds and wild birds
 Transmission from other animals or humans is possible but very rare and no strong female or
male predisposition has been noted
 It is rare; in the US there are roughly 10 cases reported annually
Patients typically present with a subacute onset of:
 Flu-like symptoms (90%): fever, headache and myalgia
 Respiratory symptoms (82%): dyspnoea, dry cough and chest pain

Signs:
 Chest: unilateral crepitations and vesicular breathing (common), evidence of pleural effusion
(uncommon)
 Abdomen: hepatomegaly and splenomegaly (rare)

Investigations:
 Raised inflammatory markers
 Chest X-ray: consolidation (90%)
 Confirmation with serology (usually as part of atypical pneumonia screening)

Treatment:
 1st-line: tetracyclines e.g. doxycycline
 2nd-line: macrolides e.g. erythromycin

TUBERCULOSIS

Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis that most commonly affects
the lungs. Understanding the pathophysiology of TB can be difficult - the key is to differentiate
between primary and secondary disease.

Primary tuberculosis
A non-immune host who is exposed to M. tuberculosis may develop primary infection of the lungs.
A small lung lesion known as a Ghon focus develops. The Ghon focus is composed of tubercle-laden
macrophages. The combination of a Ghon focus and hilar lymph nodes is known as a Ghon complex

In immunocompotent people the intially lesion usually heals by fibrosis. Those who are
immunocompromised may develop disseminated disease (miliary tuberculosis).

Secondary (post-primary) tuberculosis

If the host becomes immunocompromised the initial infection may become reactivated.
Reactivation generally occurs in the apex of the lungs and may spread locally or to more distant
sites. Possible causes of immunocomprise include:
 immunosuppressive drugs including steroids
 HIV
 malnutrition

The lungs remain the most common site for secondary tuberculosis. Extra-pulmonary infection may
occur in the following areas:
 central nervous system (tuberculous meningitis - the most serious complication)
 vertebral bodies (Pott's disease)
 cervical lymph nodes (scrofuloderma)
 renal
 gastrointestinal tract

Miliary tuberculosis

Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause TB. Credit: NIAID
PNEUMOTHORAX: FEATURES

Risk factors
 pre-existing lung disease: COPD, asthma, cystic fibrosis, lung cancer, Pneumocystis pneumonia
 connective tissue disease: Marfan's syndrome, rheumatoid arthritis
 ventilation, including non-invasive ventilation
 catamenial pneumothorax is the cause of 3-6% of spontaneous pneumothoraces occurring in
menstruating women. It is thought to be caused by endometriosis within the thorax

Symptoms tend to come on suddenly. Features include:

 dyspnoea
 chest pain: often pleuritic
 sweating
 tachypnoea
 tachycardia

PNEUMOTHORAX: MANAGEMENT

The British Thoracic Society (BTS) published updated guidelines for the management of spontaneous
pneumothorax in 2010. A pneumothorax is termed primary if there is no underlying lung disease
and secondary if there is.

Primary pneumothorax
Recommendations include:
 if the rim of air is < 2cm and the patient is not short of breath then discharge should be
considered
 otherwise aspiration should be attempted
 if this fails (defined as > 2 cm or still short of breath) then a chest drain should be inserted
 patients should be advised to avoid smoking to reduce the risk of further episodes - the lifetime
risk of developing a pneumothorax in healthy smoking men is around 10% compared with
around 0.1% in non-smoking men

Secondary pneumothorax
Recommendations include:
 if the patient is > 50 years old and the rim of air is > 2cm and/or the patient is short of breath
then a chest drain should be inserted.
 otherwise aspiration should be attempted if the rim of air is between 1-2cm. If aspiration fails
(i.e. pneumothorax is still greater then 1cm) a chest drain should be inserted. All patients should
be admitted for at least 24 hours
 if the pneumothorax is less the 1cm then the BTS guidelines suggest giving oxygen and admitting
for 24 hours
 regarding scuba diving, the BTS guidelines state: 'Diving should be permanently avoided unless
the patient has undergone bilateral surgical pleurectomy and has normal lung function and chest
CT scan postoperatively.'

Iatrogenic pneumothorax
Recommendations include:
 less likelihood of recurrence than spontaneous pneumothorax
 majority will resolve with observation, if treatment is required then aspiration should be used
 ventilated patients need chest drains, as may some patients with COPD

CHEST DRAIN

A chest drain is a tube inserted into the pleural cavity which creates a one-way valve, allowing
movement of air or liquid out of the cavity.

Chest drain insertion is indicated in cases of:

 Pleural effusion
 Pneumothorax not suitable for conservative management or aspiration
 Empyema
 Haemothorax
 Haemopneumothorax
 Chylothorax
 In some cases of penetrating chest wall injury in ventilated patients

Insertion of a chest drain is relatively contraindicated in patients with any of the following:
 INR > 1.3
 Platelet count < 75
 Pulmonary bullae
 Pleural adhesions

Please note, all of the above represent only relative contraindications, addressing respiratory
compromise in an emergency situation should always be on an individual case basis.

Once patient consent has been obtained and patient imaging assessed, the patient should be
positioned in a supine position or at a 45º angle. The patient's forearm may be positioned behind
the patient's head to allow easy access to the axilla. Identify the 5th intercostal space in the
midaxillary line. Alternatively, positioning may be determined by ultrasound guidance, British
Thoracic Society Guidance 'strongly recommend' use of ultrasound guidance in all cases of fluid
within the pleura. The area should be anaesthetised using local anaesthetic injection (lidocaine, up
to 3mg/kg). The drainage tube should then be inserted using a Seldinger technique. The drain tubing
should then be secured using either a straight stitch or with an adhesive dressing.

Positioning can be confirmed by aspiration of fluid from the drainage tubing, by 'swinging' of the
fluid within the drain tubing when the patient inspires and on chest x-ray.

Complications that may occur and which the patient should be advised of in the process of obtaining
consent:
 Failure of insertion - the drain may be abutting the apical pleura, in which case it should be
pulled back, or may be subcutaneous or in rare cases could enter the abdominal cavity. In both
latter cases, the drain should be removed and re-sited.
 Bleeding - around the site of the drain or into the pleural space
 Infection
 Penetration of the lung
 Re-expansion pulmonary oedema

Re-expansion pulmonary oedema may be preceded by the onset of a cough and/or shortness of
breath. In the event of concerns regarding re-expansion pulmonary oedema, the chest drain should
be clamped and an urgent chest x-ray should be obtained. To avoid re-expansion pulmonary
oedema, it is recommended that the drain tubing should be clamped regularly in the event of rapid
fluid output i.e. drain output should not exceed 1L of fluid over a short period of time (less than 6
hours).

Removal of the chest drain is dependent upon the indication for insertion:
 In cases of fluid drainage from the pleural cavity, the drain should be removed when there has
been no output for > 24 hours and imaging shows resolution of the fluid collection.
 In cases of pneumothorax, the drain should be removed when it is no longer bubbling
spontaneously or when the patient coughs and ideally when imaging shows resolution of the
pneumothorax.
 Drains inserted in cases of penetrating chest injury should be reviewed by the specialist to
confirm an appropriate time for removal.
OBSTRUCTIVE SLEEP APNOEA/HYPOPNOEA SYNDROME

Predisposing factors
 obesity
 macroglossia: acromegaly, hypothyroidism, amyloidosis
 large tonsils
 Marfan's syndrome

The partner often complains of excessive snoring and may report periods of apnoea.

Consequence
 daytime somnolence
 compensated respiratory acidosis
 hypertension

Assessment of sleepiness
 Epworth Sleepiness Scale - questionnaire completed by patient +/- partner
 Multiple Sleep Latency Test (MSLT) - measures the time to fall asleep in a dark room (using EEG
criteria)

Diagnostic tests
 sleep studies (polysomnography) - ranging from monitoring of pulse oximetry at night to full
polysomnography where a wide variety of physiological factors are measured including EEG,
respiratory airflow, thoraco-abdominal movement, snoring and pulse oximetry

Management
 weight loss
 continuous positive airway pressure (CPAP) is first line for moderate or severe OSAHS
 intra-oral devices (e.g. mandibular advancement) may be used if CPAP is not tolerated or for
patients with mild OSAHS where there is no daytime sleepiness
 the DVLA should be informed if OSAHS is causing excessive daytime sleepiness
 limited evidence to support use of pharmacological agents
PULMONARY HYPERTENSION: CAUSES AND CLASSIFICATION

Pulmonary hypertension may be defined as a sustained elevation in mean pulmonary arterial

pressure of greater than 25 mmHg at rest. It has recently been reclassified by the WHO:

Group 1: Pulmonary arterial hypertension (PAH)

- idiopathic*
- familial
- associated conditions: collagen vascular disease, congenital heart disease with systemic to
pulmonary shunts, HIV**, drugs and toxins, sickle cell disease
- persistent pulmonary hypertension of the newborn

Group 2: Pulmonary hypertension with left heart disease

- left-sided atrial, ventricular or valvular disease such as left ventricular systolic and diastolic
dysfunction, mitral stenosis and mitral regurgitation

Group 3: Pulmonary hypertension secondary to lung disease/hypoxia

- COPD
- interstitial lung disease
- sleep apnoea
- high altitude

Group 4: Pulmonary hypertension due to thromboembolic disease

Group 5: Miscellaneous conditions

- lymphangiomatosis e.g. secondary to carcinomatosis or sarcoidosis

*previously termed primary pulmonary hypertension

**the mechanism by which HIV infection produces pulmonary hypertension remains unknown
ALPHA-1 ANTITRYPSIN DEFICIENCY

Alpha-1 antitrypsin (A1AT) deficiency is a common inherited condition caused by a lack of a protease
inhibitor (Pi) normally produced by the liver. The role of A1AT is to protect cells from enzymes such
as neutrophil elastase. It classically causes emphysema (i.e. chronic obstructive pulmonary disease)
in patients who are young and non-smokers.

Genetics
 located on chromosome 14
 inherited in an autosomal recessive / co-dominant fashion*
 alleles classified by their electrophoretic mobility - M for normal, S for slow, and Z for very slow
 normal = PiMM
 homozygous PiSS (50% normal A1AT levels)
 homozygous PiZZ (10% normal A1AT levels)

Features
 patients who manifest disease usually have PiZZ genotype
 lungs: panacinar emphysema, most marked in lower lobes
 liver: cirrhosis and hepatocellular carcinoma in adults, cholestasis in children

Investigations
 A1AT concentrations
 spirometry: obstructive picture

Management
 no smoking
 supportive: bronchodilators, physiotherapy
 intravenous alpha1-antitrypsin protein concentrates
 surgery: lung volume reduction surgery, lung transplantation

*trusted sources are split on which is a more accurate description

KARTAGENER'S SYNDROME

Kartagener's syndrome (also known as primary ciliary dyskinesia) was first described in 1933 and
most frequently occurs in examinations due to its association with dextrocardia (e.g. 'quiet heart
sounds', 'small volume complexes in lateral leads')

Pathogenesis
 dynein arm defect results in immotile cilia
Features
 dextrocardia or complete situs inversus
 bronchiectasis
 recurrent sinusitis
 subfertility (secondary to diminished sperm motility and defective ciliary action in the fallopian
tubes)

LOFGREN'S SYNDROME

Lofgren's syndrome is an acute form sarcoidosis characterised by bilateral hilar lymphadenopathy

(BHL), erythema nodosum, fever and polyarthralgia.

It typically occurs in young females and carries an excellent prognosis.

ATELECTASIS

Atelectasis is a common postoperative complication in which basal alveolar collapse can lead to
respiratory difficulty. It is caused when airways become obstructed by bronchial secretions.

Features
 it should be suspected in the presentation of dyspnoea and hypoxaemia around 72 hours
postoperatively

Management
 positioning the patient upright
 chest physiotherapy: breathing exercises

BRONCHIECTASIS: CAUSES

Bronchiectasis describes a permanent dilatation of the airways secondary to chronic infection or

inflammation. There are a wide variety of causes are listed below:

Causes
 post-infective: tuberculosis, measles, pertussis, pneumonia
 cystic fibrosis
 bronchial obstruction e.g. lung cancer/foreign body
 immune deficiency: selective IgA, hypogammaglobulinaemia
 allergic bronchopulmonary aspergillosis (ABPA)
 ciliary dyskinetic syndromes: Kartagener's syndrome, Young's syndrome
 yellow nail syndrome

Chest x-ray showing tramlines, most prominent in the left lower zone
CT chest showing widespread tram-track and signet ring signs

BRONCHIECTASIS: MANAGEMENT

Bronchiectasis describes a permanent dilatation of the airways secondary to chronic infection or

inflammation. After assessing for treatable causes (e.g. immune deficiency) management is as
follows:
 physical training (e.g. inspiratory muscle training) - has a good evidence base for patients with
non-cystic fibrosis bronchiectasis
 postural drainage
 antibiotics for exacerbations + long-term rotating antibiotics in severe cases
 bronchodilators in selected cases
 immunisations
 surgery in selected cases (e.g. Localised disease)

Most common organisms isolated from patients with bronchiectasis:

 Haemophilus influenzae (most common)
 Pseudomonas aeruginosa
 Klebsiella spp.
 Streptococcus pneumoniae
LUNG CANCER: RISK FACTORS

Smoking
 increases risk of lung ca by a factor of 10

Other factors
 asbestos - increases risk of lung ca by a factor of 5
 arsenic
 radon
 nickel
 chromate
 aromatic hydrocarbon
 cryptogenic fibrosing alveolitis

Factors that are NOT related

 coal dust

Smoking and asbestos are synergistic, i.e. a smoker with asbestos exposure has a 10 * 5 = 50 times
increased risk

LUNG CANCER: INVESTIGATION

Chest x-ray
 this is often the first investigation done in patients with suspected lung cancer
 in around 10% of patients subsequently diagnosed with lung cancer the chest x-ray was reported
as normal

CT
 is the investigation of choice to investigate suspected lung cancer

Bronchoscopy
 this allows a biopsy to be taken to obtain a histological diagnosis sometimes aided by
endobronchial ultrasound

PET scanning
 is typically done in non-small cell lung cancer to establish eligibility for curative treatment
 uses 18-fluorodeoxygenase which is preferentially taken up by neoplastic tissue
 has been shown to improve diagnostic sensitivity of both local and distant metastasis spread in
non-small cell lung cancer
Bloods
 raised platelets may be seen

LUNG CANCER: PARANEOPLASTIC FEATURES

Small cell
 ADH
 ACTH - not typical, hypertension, hyperglycaemia, hypokalaemia, alkalosis and muscle weakness
are more common than buffalo hump etc
 Lambert-Eaton syndrome

Squamous cell
 parathyroid hormone-related protein (PTH-rp) secretion causing hypercalcaemia
 clubbing
 hypertrophic pulmonary osteoarthropathy (HPOA)
 hyperthyroidism due to ectopic TSH

Adenocarcinoma
 gynaecomastia
 hypertrophic pulmonary osteoarthropathy (HPOA)

Hypertrophic pulmonary osteoarthropathy is a proliferative periostisis involving that typically involves the
long bones. It is often painful.
*whilst it is traditionally taught that HPOA is most common with squamous cell carcinoma some
studies indicate that adenocarcinoma is the most common cause e.g.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049689/

LUNG CANCER: NON-SMALL CELL MANAGEMENT

Management
 only 20% suitable for surgery
 mediastinoscopy performed prior to surgery as CT does not always show mediastinal lymph
node involvement
 curative or palliative radiotherapy
 poor response to chemotherapy

Surgery contraindications
 assess general health
 stage IIIb or IV (i.e. metastases present)
 FEV1 < 1.5 litres is considered a general cut-off point*
 malignant pleural effusion
 tumour near hilum
 vocal cord paralysis
 SVC obstruction

* However if FEV1 < 1.5 for lobectomy or < 2.0 for pneumonectomy then some authorities advocate
further lung function tests as operations may still go ahead based on the results

LUNG CANCER: SMALL CELL

Features
 usually central
 arise from APUD* cells
 associated with ectopic ADH, ACTH secretion
 ADH → hyponatraemia
 ACTH → Cushing's syndrome
 ACTH secretion can cause bilateral adrenal hyperplasia, the high levels of cortisol can lead to
hypokalaemic alkalosis
 Lambert-Eaton syndrome: antibodies to voltage gated calcium channels causing myasthenic like
syndrome
Management
 usually metastatic disease by time of diagnosis
 patients with very early stage disease (T1-2a, N0, M0) are now considered for surgery. NICE
support this approach in their 2011 guidelines
 however, most patients with limited disease receive a combination of chemotherapy and
radiotherapy
 patients with more extensive disease are offered palliative chemotherapy

CT scan showing small cell lung cancer with multiple pulmonary nodules and extensive mediastinal nodal
metastases.

*an acronym for

 Amine - high amine content
 Precursor Uptake - high uptake of amine precursors
 Decarboxylase - high content of the enzyme decarboxylase

LUNG CANCER: CARCINOID

The vast majority of bronchial adenomas are carcinoid tumours, arising from the amine precursor
uptake and decarboxylation (APUD) system, like small cell tumours. Lung carcinoid accounts 1% of
lung tumours and for 10% of carcinoid tumours. The term bronchial adenoma is being phased out.
Lung carcinoid
 typical age = 40-50 years
 smoking not risk factor
 slow growing: e.g. long history of cough, recurrent haemoptysis
 often centrally located and not seen on CXR
 'cherry red ball' often seen on bronchoscopy
 carcinoid syndrome itself is rare (associated with liver metastases)

Management
 surgical resection
 if no metastases then 90% survival at 5 years

LUNG CANCER: REFERRAL

The 2015 NICE cancer referral guidelines gave the following advice:

Refer people using a suspected cancer pathway referral (for an appointment within 2 weeks) for
lung cancer if they:
 have chest x-ray findings that suggest lung cancer
 are aged 40 and over with unexplained haemoptysis

Offer an urgent chest x-ray (to be performed within 2 weeks) to assess for lung cancer in people
aged 40 and over if they have 2 or more of the following unexplained symptoms, or if they have
ever smoked and have 1 or more of the following unexplained symptoms:
 cough
 fatigue
 shortness of breath
 chest pain
 weight loss
 appetite loss

Consider an urgent chest x-ray (to be performed within 2 weeks) to assess for lung cancer in people
aged 40 and over with any of the following:
 persistent or recurrent chest infection
 finger clubbing
 supraclavicular lymphadenopathy or persistent cervical lymphadenopathy
 chest signs consistent with lung cancer
 thrombocytosis
SARCOIDOSIS
Sarcoidosis is a multisystem disorder of unknown aetiology characterised by non-caseating
granulomas. It is more common in young adults and in people of African descent

Features
 acute: erythema nodosum, bilateral hilar lymphadenopathy, swinging fever, polyarthralgia
 insidious: dyspnoea, non-productive cough, malaise, weight loss
 skin: lupus pernio
 hypercalcaemia: macrophages inside the granulomas cause an increased conversion of vitamin D
to its active form (1,25-dihydroxycholecalciferol)

Syndromes associated with sarcoidosis

Lofgren's syndrome is an acute form of the disease characterised by bilateral hilar
lymphadenopathy (BHL), erythema nodosum, fever and polyarthralgia. It usually carries an excellent
prognosis

In Mikulicz syndrome* there is enlargement of the parotid and lacrimal glands due to sarcoidosis,
tuberculosis or lymphoma

Heerfordt's syndrome (uveoparotid fever) there is parotid enlargement, fever and uveitis secondary
to sarcoidosis

*this term is now considered outdated and unhelpful by many as there is a confusing overlap with
Sjogren's syndrome

BILATERAL HILAR LYMPHADENOPATHY

The most common causes of bilateral hilar lymphadenopathy are sarcoidosis and tuberculosis.

Other causes include:

 lymphoma/other malignancy
 pneumoconiosis e.g. berylliosis
 fungi e.g. histoplasmosis, coccidioidomycosis

SARCOIDOSIS: INVESTIGATION

There is no one diagnostic test for sarcoidosis and hence diagnosis is still largely clinical. ACE levels
have a sensitivity of 60% and specificity of 70% and are therefore not reliable in the diagnosis of
sarcoidosis although they may have a role in monitoring disease activity. Routine bloods may show
hypercalcaemia (seen in 10% if patients) and a raised ESR

A chest x-ray may show the following changes:

stage 0 = normal
stage 1 = bilateral hilar lymphadenopathy (BHL)
stage 2 = BHL + interstitial infiltrates
stage 3 = diffuse interstitial infiltrates only
stage 4 = diffuse fibrosis

Other investigations*
 spirometry: may show a restrictive defect
 tissue biopsy: non-caseating granulomas
 gallium-67 scan - not used routinely

Chest x-ray and CT scan showing stage 2 sarcoidosis with both bilateral hilar lymphadenopathy + interstitial
infiltrates. The reticulonodular opacities are particularly noted in the upper zones. Remember that pulmonary
fibrosis (which this case has not yet progressed to) may be divided into conditions which predominately
affect the upper zones and those which predominately affect the lower zones - sarcoidosis is one of the
former. The CT of the chest demonstrates diffuse areas of nodularity predominantly in a peribronchial
distribution with patchy areas of consolidation particularly in the upper lobes. There is some surrounding
ground glass opacities. No gross reticular changes to suggest fibrosis.
*the Kveim test (where part of the spleen from a patient with known sarcoidosis is injected under
the skin) is no longer performed due to concerns about cross-infection

SARCOIDOSIS: MANAGEMENT

Sarcoidosis is a multisystem disorder of unknown aetiology characterised by non-caseating

granulomas. It is more common in young adults and in people of African descent.

Indications for steroids

 patients with chest x-ray stage 2 or 3 disease who are symptomatic. Patients with asymptomatic
and stable stage 2 or 3 disease who have only mildly abnormal lung function do not require
treatment
 hypercalcaemia
 eye, heart or neuro involvement

SARCOIDOSIS: PROGNOSTIC FEATURES

Sarcoidosis is a multisystem disorder of unknown aetiology characterised by non-caseating

granulomas. It is more common in young adults and in people of African descent. Sarcoidosis remits
without treatment in approximately two-thirds of people

Factors associated with poor prognosis

 insidious onset, symptoms > 6 months
 absence of erythema nodosum
 extrapulmonary manifestations: e.g. lupus pernio, splenomegaly
 CXR: stage III-IV features
 black people

SILICOSIS
Silicosis is a fibrosing lung disease caused by the inhalation of fine particles of crystalline silicon
dioxide (silica). It is a risk factor for developing TB (silica is toxic to macrophages).

Occupations at risk of silicosis

 mining
 slate works
 foundries
 potteries
Features
 fibrosing lung disease
 'egg-shell' calcification of the hilar lymph nodes

Chest x-ray from a patient with silicosis. Note the bilateral diffuse upper lobe reticular shadowing
superimposed with occasional scattered mass like opacities. These features are in keeping with silicosis and
progressive massive fibrosis (PMF)

CT scan from a patient with silicosis showing upper zone predominant mass-like scarring with calcification
and volume loss. Hilar and mediastinal lymph node calcification also noted. No cavitary changes are seen.
There is a left pleural effusion.
ASBESTOS AND THE LUNG

Asbestos can cause a variety of lung disease from benign pleural plaques to mesothelioma.

Pleural plaques
Pleural plaques are benign and do not undergo malignant change. They are the most common form
of asbestos related lung disease and generally occur after a latent period of 20-40 years.

Pleural thickening
Asbestos exposure may cause diffuse pleural thickening in a similar pattern to that seen following
an empyema or haemothorax. The underlying pathophysiology is not fully understood.

Asbestosis
The severity of asbestosis is related to the length of exposure. This is in contrast to mesothelioma
where even very limited exposure can cause disease. The latent period is typically 15-30 years.
Asbestosis typically causes lower lobe fibrosis. As with other forms of lung fibrosis the most
common symptoms are shortness-of-breath and reduced exercise tolerance.

Mesothelioma
Mesothelioma is a malignant disease of the pleura. Crocidolite (blue) asbestos is the most
dangerous form.

Possible features
 progressive shortness-of-breath
 chest pain
 pleural effusion

Patients are usually offered palliative chemotherapy and there is also a limited role for surgery and
radiotherapy. Unfortunately the prognosis is very poor, with a median survival from diagnosis of 8-
14 months.

Lung cancer
Asbestos exposure is a risk factor for lung cancer and also has a synergistic effect with cigarette
smoke.

MESOTHELIOMA

Mesothelioma is a cancer of the mesothelial layer of the pleural cavity that is strongly associated
with asbestos exposure. In a small percentage of cases, other mesothelial layers such as those in the
abdomen may be affected.
Features
 Dyspnoea, weight loss, chest wall pain
 Clubbing
 30% present as painless pleural effusion
 Only 20% have pre-existing asbestosis
 History of asbestos exposure in 85-90%, latent period of 30-40 years

Basics
 Malignancy of mesothelial cells of pleura
 Metastases to contralateral lung and peritoneum
 Right lung affected more often than left

Investigation/diagnosis
 suspicion is normally raised by a chest x-ray showing either a pleural effusion or pleural
thickening
 the next step is normally a pleural CT
 if a pleural effusion is present fluid should be sent for MC&S, biochemistry and cytology (but
cytology is only helpful in 20-30% of cases)
 local anaesthetic thoracoscopy is increasingly used to investigate cytology negative exudative
effusions as it has a high diagnostic yield (around 95%)
 if an area of pleural nodularity is seen on CT then an image-guided pleural biopsy may be used

Management
 Symptomatic
 Industrial compensation
 Chemotherapy, Surgery if operable
 Prognosis poor, median survival 12 months

RHEUMATOID ARTHRITIS: RESPIRATORY MANIFESTATIONS

A variety of respiratory problems may be seen in patients with rheumatoid arthritis:

 pulmonary fibrosis
 pleural effusion
 pulmonary nodules
 bronchiolitis obliterans
 complications of drug therapy e.g. methotrexate pneumonitis
 pleurisy
 Caplan's syndrome - massive fibrotic nodules with occupational coal dust exposure
 infection (possibly atypical) secondary to immunosuppression
LUNG FIBROSIS

It is important in the exam to be able to differentiate between conditions causing predominately

upper or lower zone fibrosis. It should be noted that the more common causes (idiopathic
pulmonary fibrosis, drugs) tend to affect the lower zones

Fibrosis predominately affecting the upper zones

hypersensitivity pneumonitis (also known as extrinsic allergic alveolitis)
coal worker's pneumoconiosis/progressive massive fibrosis
silicosis
sarcoidosis
ankylosing spondylitis (rare)
histiocytosis
tuberculosis

Fibrosis predominately affecting the lower zones

idiopathic pulmonary fibrosis
most connective tissue disorders (except ankylosing spondylitis) e.g. SLE
drug-induced: amiodarone, bleomycin, methotrexate
asbestosis

Acronym for causes of upper zone fibrosis:

CHARTS

 C - Coal worker's pneumoconiosis

 H - Histiocytosis/ hypersensitivity pneumonitis
 A - Ankylosing spondylitis
 R - Radiation
 T - Tuberculosis
 S - Silicosis/sarcoidosis

IDIOPATHIC PULMONARY FIBROSIS

Idiopathic pulmonary fibrosis (IPF, previously termed cryptogenic fibrosing alveolitis) is a chronic
lung condition characterised by progressive fibrosis of the interstitium of the lungs. Whilst there are
many causes of lung fibrosis (e.g. medications, connective tissue disease, asbestos) the term IPF is
reserved when no underlying cause exists.

IPF is typically seen in patients aged 50-70 years and is twice as common in men.

Features
 progressive exertional dyspnoea
 bibasal fine end-inspiratory crepitations on auscultation
 dry cough
 clubbing

Diagnosis
 spirometry: classically a restrictive picture (FEV1 normal/decreased, FVC decreased, FEV1/FVC
increased)
 impaired gas exchange: reduced transfer factor (TLCO)
 imaging: bilateral interstitial shadowing (typically small, irregular, peripheral opacities - 'ground-
glass' - later progressing to 'honeycombing') may be seen on a chest x-ray but high-resolution CT
scanning is the investigation of choice and required to make a diagnosis of IPF
 ANA positive in 30%, rheumatoid factor positive in 10% but this does not necessarily mean that
the fibrosis is secondary to a connective tissue disease. Titres are usually low

Management
 pulmonary rehabilitation
 very few medications have been shown to give any benefit in IPF. There is some evidence that
pirfenidone (an antifibrotic agent) may be useful in selected patients (see NICE guidelines)
 many patients will require supplementary oxygen and eventually a lung transplant

Prognosis
 poor, average life expectancy is around 3-4 years

Chest X-ray shows sub-pleural reticular opacities that increase from the apex to the bases of the lungs
Chest X-ray and CT scan from a patient who presented with dyspnoea. The x-ray shows reitcular opacities
predominantly in the bases. In addition the CT demonstrates honeycombing and traction bronchiectasis
CT scan showing advanced pulmonary fibrosis including 'honeycombing'

CT scan showing advanced pulmonary fibrosis including 'honeycombing'

EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (CHURG-
STRAUSS SYNDROME)

Eosinophilic granulomatosis with polyangiitis (EGPA) is now the preferred term for Churg-Strauss
syndrome. It is an ANCA associated small-medium vessel vasculitis.

Features
 asthma
 blood eosinophilia (e.g. > 10%)
 paranasal sinusitis
 mononeuritis multiplex
 pANCA positive in 60%

Comparison of granulomatosis with polyangiitis and Churg-Strauss syndrome

Leukotriene receptor antagonists may precipitate the disease.

GRANULOMATOSIS WITH POLYANGIITIS (WEGENER'S

GRANULOMATOSIS)

Granulomatosis with polyangiitis is now the preferred term for Wegener's granulomatosis. It is an
autoimmune condition associated with a necrotizing granulomatous vasculitis, affecting both the
upper and lower respiratory tract as well as the kidneys.
Features
 upper respiratory tract: epistaxis, sinusitis, nasal crusting
 lower respiratory tract: dyspnoea, haemoptysis
 rapidly progressive glomerulonephritis ('pauci-immune', 80% of patients)
 saddle-shape nose deformity
 also: vasculitic rash, eye involvement (e.g. proptosis), cranial nerve lesions

Investigations
 cANCA positive in > 90%, pANCA positive in 25%
 chest x-ray: wide variety of presentations, including cavitating lesions
 renal biopsy: epithelial crescents in Bowman's capsule

Management
 steroids
 cyclophosphamide (90% response)
 plasma exchange
 median survival = 8-9 years

Chest x-ray from a young patient with granulomatosis with polyangiitis. Whilst the changes are subtle it
demonstrates a number of ill-defined nodules the largest of which projects over the dome of the right
hemidiaphragm. This nodule appears to have a central lucency suggesting cavitation
CT of the same patient showing the changes in a much more obvious way, confirming the presence of at
least 2 nodules, the larger of the two having a large central cavity and and air-fluid level

MICROSCOPIC POLYANGIITIS

Microscopic polyangiitis is a small-vessel ANCA vasculitis.

Features
 renal impairment: raised creatinine, haematuria, proteinuria
 fever
 other systemic symptoms: lethargy, myalgia, weight loss
 rash: palpable purpura
 cough, dyspnoea, haemoptysis
 mononeuritis multiplex

Investigations
 pANCA (against MPO) - positive in 50-75%
 cANCA (against PR3) - positive in 40%
PULMONARY EOSINOPHILIA

Pulmonary eosinophilia describes a situation where there are increased numbers of eosinophils in
the lung airways and parenchyma. This is generally associated with a blood eosinophilia.

Causes of pulmonary eosinophilia

 Churg-Strauss syndrome
 allergic bronchopulmonary aspergillosis (ABPA)
 Loffler's syndrome
 eosinophilic pneumonia
 hypereosinophilic syndrome
 tropical pulmonary eosinophilia
 drugs: nitrofurantoin, sulphonamides
 less common: Wegener's granulomatosis

Loffler's syndrome
 transient CXR shadowing and blood eosinophilia
 thought to be due to parasites such as Ascaris lumbricoides causing an alveolar reaction
 presents with a fever, cough and night sweats which often last for less than 2 weeks.
 generally a self-limiting disease

Acute eosinophilic pneumonia

 highly responsive to steroids

Tropical pulmonary eosinophilia

 associated with Wuchereria bancrofti infection

EXTRINSIC ALLERGIC ALVEOLITIS

Extrinsic allergic alveolitis (EAA, also known as hypersensitivity pneumonitis) is a condition caused
by hypersensitivity induced lung damage due to a variety of inhaled organic particles. It is thought to
be largely caused by immune-complex mediated tissue damage (type III hypersensitivity) although
delayed hypersensitivity (type IV) is also thought to play a role in EAA, especially in the chronic
phase.

Examples
 bird fanciers' lung: avian proteins
 farmers lung: spores of Saccharopolyspora rectivirgula (formerly Micropolyspora faeni)
 malt workers' lung: Aspergillus clavatus
 mushroom workers' lung: thermophilic actinomycetes*
Presentation
 acute: occur 4-8 hrs after exposure, SOB, dry cough, fever
 chronic

Investigation
 chest x-ray: upper/mid-zone fibrosis
 bronchoalveolar lavage: lymphocytosis
 blood: NO eosinophilia

*here the terminology is slightly confusing as thermophilic actinomycetes is an umbrella term

covering strains such as Micropolyspora faeni

Chest x-ray and CT scan from a middle-aged woman who presented with dyspnoea. The CT demonstrates
multuple centrilobular ground glass nodules consistent with hypersensitivity pneumonitis
ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS

Allergic bronchopulmonary aspergillosis results from an allergy to Aspergillus spores. In the exam
questions often give a history of bronchiectasis and eosinophilia.

Features
 bronchoconstriction: wheeze, cough, dyspnoea. Patients may have a previous label of asthma
 bronchiectasis (proximal)

Investigations
 eosinophilia
 flitting CXR changes
 positive radioallergosorbent (RAST) test to Aspergillus
 positive IgG precipitins (not as positive as in aspergilloma)
 raised IgE

Management
 steroids
 itraconazole is sometimes introduced as a second-line agent

Chest x-ray of a 40-year-old woman with ABPA demonstrating a mass overlying the left hilum. In the right
upper parahilar region a few ring shadow / tram track opacities are also noted, suggestive of bronchiectasis
CT scan from the same patient. CT reveals a branching lesion in the superior segment of the left lower lobe
with classic finger in glove appearance which represents of mucous filling dilated bronchi (i.e. bronchocoeles).
Bronchocoeles are a common feature of allergic bronchopulmonary aspergillosis (ABPA)
ALTITUDE RELATED DISORDERS

There are three main types of altitude related disorders: acute mountain sickness (AMS), which may
progress to high altitude pulmonary edema (HAPE) or high altitude cerebral edema (HACE). All three
conditions are due to the chronic hypobaric hypoxia which develops at high altitudes

Acute mountain sickness is generally a self-limiting condition. Features of AMS start to occur above
2,500 - 3,000m, developing gradually over 6-12 hours and potentially last a number of days:
 headache
 nausea
 fatigue

Prevention and treatment of AMS

 the risk of AMS may actually be positively correlated to physical fitness
 gain altitude at no more than 500 m per day
 acetazolamide (a carbonic anhydrase inhibitor) is widely used to prevent AMS and has a
supporting evidence base
 treatment: descent

A minority of people above 4,000m go onto develop high altitude pulmonary oedema (HAPE) or
high altitude cerebral oedema (HACE), potentially fatal conditions
 HAPE presents with classical pulmonary oedema features
 HACE presents with headache, ataxia, papilloedema

Management of HACE
 descent
 dexamethasone

Management of HAPE
 descent
 nifedipine, dexamethasone, acetazolamide, phosphodiesterase type V inhibitors*
 oxygen if available

*the relative merits of these different treatments has only been studied in small trials. All seem to
work by reducing systolic pulmonary artery pressure
DRUGS USED IN RESPIRATORY MEDICINE

Drug Mechanism of action Notes

Salbutamol Beta receptor agonist • Short-acting inhaled bronchodilator. Relaxes
bronchial smooth muscle through effects on beta
2 receptors
• Used in asthma and chronic obstructive
pulmonary disease (COPD).
• Salmeterol has similar effects but is long-acting
Corticosteroids Anti-inflammatory • Inhaled corticosteroids are used as mainterance
therapy
• Oral or intravenous corticosteroids are used
following an acute exacerbation of asthma or
COPD
Ipratropium Blocks the muscarinic • Short-acting inhaled bronchodilator. Relaxes
acetylcholine receptors bronchial smooth muscle
• Used primarily in COPD
• Tiotropium has similar effects but is long-acting
Methylxanthines Non-specific inhibitor of • Given orally or intravenously
(e.g. theophylline) phosphodiesterase resulting • Has a narrow therapeutic index
in an increase in cAMP
Monteleukast, Blocks leukotriene receptors • Usually taken orally
zafirlukast • Useful in aspirin-induced asthma