Medicine – Glaucoma

Glaucoma is a group of progressive optic neuropathies characterised by damage to the optic nerve and retinal nerve fibre layer, producing characteristic visual-field loss. Raised intraocular pressure (IOP) is the most important modifiable risk factor, but glaucoma can occur even when IOP is within the statistically normal range.

The two major forms considered here are acute angle-closure glaucoma and primary open-angle glaucoma. They differ substantially in their presentation, mechanism, urgency, and treatment.

1. Acute Angle-Closure Glaucoma

Acute angle-closure glaucoma is an ophthalmic emergency in which the drainage angle between the iris and cornea suddenly closes, causing a rapid rise in intraocular pressure.

It usually affects one eye during an acute attack, although the fellow eye is often anatomically predisposed and therefore also at future risk.

2. Normal Aqueous Humour Drainage

Aqueous humour is produced by the ciliary body in the posterior chamber.

It normally passes through the pupil into the anterior chamber and then drains mainly through the:

Trabecular meshwork → Schlemm canal → episcleral venous circulation.

A smaller proportion leaves through the uveoscleral pathway.

3. Mechanism of Acute Angle Closure

In susceptible eyes, the peripheral iris can obstruct the trabecular meshwork, preventing normal aqueous humour drainage.

Aqueous humour continues to be produced while its outflow is severely reduced.

The result is:

Blocked aqueous outflow → rapid rise in IOP → corneal oedema + iris ischaemia + optic nerve damage.

Without rapid treatment, permanent visual loss can occur.

4. Effect of Pupil Dilatation

An acute attack is particularly likely when the pupil becomes mid-dilated, because this anatomical position can increase contact between the iris and lens and promote pupillary block in susceptible eyes.

Attacks may therefore occur in dim or dark environments, where physiological pupil dilatation occurs.

Certain medications capable of causing mydriasis may also precipitate angle closure in anatomically predisposed individuals.

Clinical Features of Acute Angle-Closure Glaucoma

5. Painful Red Eye

The classic presentation is a sudden, intensely painful red eye.

The pain can be severe and may radiate around the eye or into the forehead.

6. Reduced Vision

Patients develop rapidly reduced or blurred vision.

They may describe coloured halos around lights, particularly because corneal oedema alters the passage of light through the cornea.

7. Mid-Dilated Pupil

The pupil is classically mid-dilated and poorly reactive or fixed.

Therefore, the traditional description of simply a “dilated pupil” is better remembered as:

Mid-dilated + fixed/sluggish pupil.

8. Hazy Cornea

Markedly elevated intraocular pressure causes corneal oedema, producing a characteristic cloudy or hazy appearance.

The hazy cornea contributes to the patient’s reduced vision and halos around lights.

9. Other Symptoms

The severe autonomic response to acute angle closure may cause headache, nausea, and vomiting.

This is clinically important because patients can occasionally be mistaken for having a neurological or gastrointestinal illness rather than an ophthalmic emergency.

Treatment of Acute Angle-Closure Glaucoma

The immediate objective is to rapidly reduce intraocular pressure, followed by definitive treatment to prevent recurrence.

Urgent ophthalmological assessment is required.

10. Acetazolamide

Acetazolamide is a carbonic anhydrase inhibitor that reduces aqueous humour production by the ciliary body.

It can be given systemically during an acute attack and helps rapidly lower intraocular pressure.

11. Topical β-Blockers

A topical β-blocker such as timolol can reduce aqueous humour production.

This provides an additional mechanism for lowering intraocular pressure.

Systemic absorption can occur, so β-blockers require caution in patients with conditions such as asthma, significant bradycardia, or heart block.

12. Other Pressure-Lowering Treatment

Additional topical pressure-lowering agents may be used according to the clinical situation, including α₂-adrenergic agonists.

In very severe cases, an osmotic agent may occasionally be required when the intraocular pressure remains extremely high.

13. Pilocarpine

Pilocarpine is a muscarinic agonist that causes pupillary constriction (miosis).

This can pull the peripheral iris away from the drainage angle and improve aqueous outflow once the intraocular pressure has started to fall.

A useful correction to the original wording is that pilocarpine does not literally “open the canal of Schlemm.” Its main effect is to alter iris configuration and improve access to the trabecular drainage angle.

It may initially be ineffective when the IOP is extremely high because the ischaemic iris sphincter may not respond.

14. Laser Peripheral Iridotomy

The definitive treatment for pupillary-block angle closure is usually laser peripheral iridotomy.

A small opening is created in the peripheral iris, providing an alternative pathway for aqueous humour to move from the posterior to the anterior chamber.

This equalises pressure across the iris and helps prevent recurrent pupillary block.

The fellow eye frequently receives prophylactic laser iridotomy because it may have similar anatomical risk.

15. Surgical Iridectomy

Surgical peripheral iridectomy can achieve a similar result but is now generally reserved for situations in which laser treatment cannot be performed or is unsuccessful.

Therefore, the modern term to remember first is laser peripheral iridotomy, rather than routine surgical iridectomy.

16. Primary Open-Angle Glaucoma

Primary open-angle glaucoma (POAG) is a chronic progressive optic neuropathy in which the anterior chamber angle remains anatomically open, but aqueous humour drainage through the trabecular pathway is impaired.

Unlike acute angle closure, the disease usually develops slowly and painlessly over many years.

17. Intraocular Pressure

Raised intraocular pressure is an important risk factor.

Historically, an IOP above 21 mmHg was used as an important threshold.

However, this should not be treated as the definition of glaucoma.

Some people have:

IOP >21 mmHg without optic nerve damage → ocular hypertension.

Others develop:

Glaucomatous optic nerve damage despite IOP ≤21 mmHg → normal-tension glaucoma.

Therefore, glaucoma is fundamentally an optic neuropathy, not simply an elevated pressure measurement.

18. Insidious and Asymptomatic Onset

Primary open-angle glaucoma typically develops gradually and without pain.

Central visual acuity may remain normal until relatively late, so patients can have substantial optic nerve damage before noticing symptoms.

This is why screening of at-risk individuals and routine eye examinations are important.

19. Optic Disc Cupping

Progressive loss of retinal ganglion cell axons produces characteristic cupping of the optic disc.

The cup-to-disc ratio may increase, and progressive neuroretinal rim thinning can occur.

The important relationship is:

Retinal ganglion cell loss → optic nerve damage → increased disc cupping → visual-field loss.

Visual-Field Defects

20. Arcuate Scotoma

Glaucoma produces characteristic visual-field abnormalities because damage follows the distribution of retinal nerve fibres.

An arcuate scotoma is a classic defect.

It may extend from the region of the blind spot in an arc toward the nasal visual field.

21. Other Visual-Field Changes

Early abnormalities may include paracentral defects and nasal steps.

As glaucoma progresses, arcuate defects enlarge and peripheral visual fields become increasingly restricted.

Very advanced disease may eventually produce severe tunnel vision and irreversible blindness.

Treatment of Chronic Open-Angle Glaucoma

The objective is to lower intraocular pressure sufficiently to slow or prevent further optic nerve damage.

Treatment does not usually restore optic nerve fibres that have already been lost.

22. Prostaglandin Analogues

Prostaglandin analogues, such as latanoprost, are major first-line medications for primary open-angle glaucoma.

They lower intraocular pressure primarily by increasing aqueous humour outflow, particularly through the uveoscleral pathway.

They are effective and can usually be administered once daily.

23. Topical β-Blockers

Timolol and other topical β-blockers lower IOP by reducing aqueous humour production.

They remain useful treatments but may be unsuitable for some patients because of systemic cardiovascular and respiratory effects.

24. Carbonic Anhydrase Inhibitors

Topical carbonic anhydrase inhibitors such as dorzolamide reduce aqueous humour formation.

They may be used alone or in combination with other pressure-lowering medications.

25. Other Topical Treatments

Other medications include α₂-adrenergic agonists, which can reduce aqueous production and influence aqueous outflow.

Combination preparations are frequently used when a single drug does not adequately control intraocular pressure.

26. Pilocarpine

Pilocarpine can increase conventional aqueous outflow by causing ciliary muscle contraction and altering the trabecular drainage pathway.

Although historically important, it is used much less commonly as routine long-term treatment for primary open-angle glaucoma because modern agents are generally better tolerated.

Laser and Surgical Treatment

27. Laser Trabeculoplasty

Laser trabeculoplasty, particularly selective laser trabeculoplasty (SLT), improves aqueous drainage through the trabecular meshwork.

It is now an important treatment for open-angle glaucoma and may be used as initial therapy or when medication does not provide adequate control, depending on local practice and patient factors.

28. Glaucoma Surgery

When medication and/or laser treatment fail to achieve the required pressure reduction, glaucoma surgery may be necessary.

Procedures such as trabeculectomy create an alternative pathway for aqueous drainage.

Various drainage implants and minimally invasive glaucoma procedures are also available for selected patients.

29. Iridectomy and Open-Angle Glaucoma

The original notes list iridectomy as a treatment for chronic open-angle glaucoma.

This requires correction.

Peripheral iridotomy/iridectomy is principally a treatment for angle-closure mechanisms, particularly pupillary block. It is not routine treatment for primary open-angle glaucoma, where the angle is already open.

30. Acute Angle-Closure Glaucoma – Note Form

Onset: sudden.

Eye involvement: usually unilateral during an acute attack.

Pain: severe painful red eye.

Vision: rapidly reduced or blurred; coloured halos may occur.

Cornea: cloudy or hazy because of corneal oedema.

Pupil: characteristically mid-dilated and poorly reactive.

IOP: markedly elevated.

Mechanism: peripheral iris obstructs the trabecular drainage angle.

Trigger: may occur when the pupil becomes mid-dilated, such as in dim light.

Systemic symptoms: headache, nausea, and vomiting may occur.

Initial treatment: rapid pressure reduction with agents such as systemic acetazolamide and topical pressure-lowering medication.

Pilocarpine: produces miosis and can help reopen the drainage angle after pressure begins to fall.

Definitive treatment: laser peripheral iridotomy.

Fellow eye: often requires prophylactic assessment and treatment because it may have the same anatomical predisposition.

Clinical importance: ophthalmic emergency because permanent visual loss can occur rapidly.

31. Primary Open-Angle Glaucoma – Note Form

Onset: chronic and insidious.

Pain: usually absent.

Symptoms: usually asymptomatic early.

Anterior chamber angle: remains open.

IOP: often elevated but can be within the statistically normal range.

Optic disc: progressive glaucomatous cupping.

Visual field: nasal step, paracentral defects and arcuate scotomas; advanced disease can produce severe peripheral field loss.

Latanoprost: increases aqueous outflow and is an important first-line treatment.

β-blockers: reduce aqueous humour production.

Dorzolamide: carbonic anhydrase inhibitor that reduces aqueous production.

Pilocarpine: historically used but much less common in modern routine treatment.

Laser: selective laser trabeculoplasty can improve trabecular aqueous outflow.

Surgery: trabeculectomy or other glaucoma procedures may be required when adequate pressure control cannot otherwise be achieved.

Iridectomy: not routine treatment for primary open-angle glaucoma.

Key Clinical Pattern

Remember acute angle-closure glaucoma as:

Painful + red + reduced vision + hazy cornea + mid-dilated pupil + very high IOP.

It is an ophthalmic emergency requiring immediate pressure reduction followed by definitive laser peripheral iridotomy.

Remember primary open-angle glaucoma as:

Painless + chronic + initially asymptomatic + progressive optic-disc cupping + characteristic visual-field loss.

The goal of treatment is to lower intraocular pressure and prevent further irreversible optic nerve damage, using therapies such as prostaglandin analogues, other topical pressure-lowering drugs, selective laser trabeculoplasty, and surgery when required.

Medicine – Respiratory Physiology and Pulmonary Function Tests

Pulmonary function tests (PFTs) assess how effectively the respiratory system moves air into and out of the lungs and how efficiently gas exchange occurs. Important measurements include lung volumes, lung capacities, expiratory flow, spirometry, compliance, and gas transfer.

Understanding these measurements is particularly useful for distinguishing obstructive lung disease, such as asthma and COPD, from restrictive lung disease, such as pulmonary fibrosis.

1. Pulmonary Blood Flow

Normal pulmonary blood flow is approximately 5 L/min at rest in a healthy adult.

Because the pulmonary and systemic circulations are connected in series, pulmonary blood flow is normally approximately equal to the cardiac output.

During exercise, pulmonary blood flow increases considerably as cardiac output rises.

2. Alveolar Ventilation

Alveolar ventilation refers to the volume of fresh inspired air reaching the gas-exchanging alveoli each minute.

It is different from total minute ventilation because some inspired air remains within the anatomical dead space and does not participate directly in gas exchange.

The exact normal value varies with tidal volume, respiratory rate, and dead-space volume. A resting value around 4–5 L/min is commonly expected, so the quoted value of approximately 5.25 L/min should be regarded as an approximate physiological value rather than a fixed normal.

Lung Volumes and Capacities

The amount of air within the lungs changes continuously throughout the respiratory cycle.

The major individual lung volumes are tidal volume, inspiratory reserve volume, expiratory reserve volume, and residual volume. Combinations of these individual volumes form capacities such as vital capacity, functional residual capacity, and total lung capacity.

3. Tidal Volume

Tidal volume (TV) is the volume of air inspired or expired during a normal quiet breath.

In a typical resting adult it is approximately 500 mL, although the actual value varies considerably with body size, metabolic demand, and activity.

During exercise, tidal volume increases to meet the body’s greater requirement for ventilation.

4. Inspiratory Reserve Volume

Inspiratory reserve volume (IRV) is the additional volume of air that can be inspired after the end of a normal tidal inspiration.

In other words, after taking a normal breath in, the additional air that can still be forcibly inhaled represents the inspiratory reserve volume.

5. Expiratory Reserve Volume

Expiratory reserve volume (ERV) is the additional volume of air that can be forcibly expired after the end of a normal tidal expiration.

It therefore represents the volume between the resting expiratory level and maximal expiration.

6. Residual Volume

Residual volume (RV) is the volume of gas remaining within the lungs following maximal forced expiration.

Even after breathing out as completely as possible, the lungs do not normally become completely empty.

Residual volume helps prevent complete alveolar collapse and allows gas exchange to continue between individual breaths.

7. Vital Capacity

Vital capacity (VC) is the maximum change in lung volume between complete inspiration and complete expiration.

It can therefore be expressed as:

VC = IRV + TV + ERV

Vital capacity does not include residual volume, because residual volume cannot voluntarily be expired.

Vital Capacity and Total Lung Capacity

The supplied notes describe vital capacity as approximately 75% of total lung capacity.

This can be a useful approximate teaching relationship, but it is not a fixed percentage in every person.

Vital capacity depends on factors such as age, sex, height, body size, respiratory muscle strength, and underlying lung disease.

Vital capacity generally decreases with increasing age as residual volume tends to increase.

8. Functional Residual Capacity

Functional residual capacity (FRC) is the volume of air remaining in the lungs at the end of a normal passive expiration.

It represents the resting equilibrium volume of the respiratory system.

FRC is calculated as:

FRC = ERV + RV

Physiological Importance of FRC

FRC provides a reservoir of gas within the lungs between breaths.

This helps prevent dramatic fluctuations in arterial oxygen and carbon dioxide concentrations during normal respiration.

Changes in lung or chest-wall mechanics can substantially alter FRC.

9. Total Lung Capacity

Total lung capacity (TLC) is the total amount of gas contained within the lungs following maximal inspiration.

It represents the maximum volume to which the lungs can be inflated.

TLC can be expressed as:

TLC = VC + RV

or equivalently:

TLC = IRV + TV + ERV + RV

Normal Total Lung Capacity

The supplied notes give approximately 6–7 L for a normal adult.

This is a reasonable approximate teaching value, but TLC varies considerably according to height, sex, age, body size, and reference population.

For clinical interpretation, measured lung volumes are therefore compared with appropriate predicted values rather than with a single universal normal volume.

10. Measuring Total Lung Capacity

TLC cannot be measured completely by ordinary spirometry because spirometry cannot directly measure residual volume.

Methods used to measure lung volumes containing RV include body plethysmography and gas-dilution techniques such as helium dilution.

Body Plethysmography

Body plethysmography measures thoracic gas volume while the patient sits inside an airtight chamber.

An important advantage is that it can detect gas trapped behind poorly communicating or closed airways.

It is therefore particularly useful when significant air trapping, such as in severe COPD, is suspected.

Helium Dilution

In helium dilution, the patient breathes from a closed system containing a known concentration of helium.

The degree to which the helium becomes diluted allows calculation of the communicating lung volume.

Because helium must communicate with the ventilated airspaces, severe air trapping can cause the technique to underestimate true lung volume.

11. Peak Expiratory Flow

Peak expiratory flow (PEF) is the maximum expiratory flow achieved during a forceful expiration beginning from full inspiration.

It provides a simple measurement of airflow through the large airways.

PEF in Asthma

PEF is particularly useful for monitoring asthma within an individual patient.

Repeated measurements can demonstrate variability in airflow obstruction and can help patients recognise deterioration.

Serial peak-flow measurements may also contribute evidence of variable airflow obstruction when investigating suspected asthma.

Therefore, the statement that PEF is simply “not effective as a diagnostic test” is too absolute. A single PEF measurement is relatively nonspecific, but serial variability can support an asthma diagnosis in the appropriate clinical setting.

12. Lung Compliance

Compliance describes the distensibility of the lungs—that is, how easily lung volume changes in response to a change in pressure.

A highly compliant lung expands relatively easily, whereas a lung with low compliance is stiff and requires greater pressure to produce the same increase in volume.

Compliance in Emphysema

Lung compliance is typically increased in emphysema.

Destruction of alveolar elastic tissue causes loss of elastic recoil, so the lungs inflate easily but have difficulty returning to their original volume during expiration.

This contributes to air trapping and hyperinflation.

Compliance in Pulmonary Fibrosis

Compliance is reduced in pulmonary fibrosis.

Fibrotic tissue makes the lungs abnormally stiff, so greater inspiratory pressure is required to expand them.

Patients therefore tend to breathe with small tidal volumes and a relatively rapid respiratory rate.

Compliance in Pulmonary Oedema

Pulmonary oedema also decreases lung compliance.

Fluid within the interstitial and alveolar compartments makes the lungs stiffer and increases the work of breathing.

Spirometry

Spirometry is one of the most important pulmonary function tests. It measures how much air a patient can forcibly expire and how rapidly that air can be expelled.

The two major measurements are FEV₁ and FVC.

13. Forced Expiratory Volume in One Second

FEV₁ is the volume of air forcibly expired during the first second of a maximal forced expiration starting from full inspiration.

FEV₁ is particularly sensitive to airflow obstruction.

When the airways are narrowed, the patient cannot expel air rapidly, so FEV₁ falls.

14. Forced Vital Capacity

Forced vital capacity (FVC) is the total volume of air that can be forcibly expired after taking a maximal inspiration.

It differs from FEV₁ because FEV₁ measures only the volume expelled during the first second, whereas FVC measures the total forced expiratory volume.

15. FEV₁/FVC Ratio

The FEV₁/FVC ratio describes the proportion of the forced vital capacity that can be expelled during the first second.

It is particularly useful for distinguishing an obstructive spirometric pattern from a possible restrictive pattern.

16. Obstructive Lung Disease

In obstructive lung disease, airflow through the airways is impaired.

Examples include asthma and COPD.

FEV₁ falls substantially because the patient cannot expel air rapidly through narrowed or collapsible airways.

FVC may be normal or reduced, but FEV₁ falls proportionately more than FVC.

The result is a reduced FEV₁/FVC ratio.

FEV₁/FVC in Obstruction

The image uses:

FEV₁/FVC <0.75 → obstructive disorder

This is useful older teaching but should not be treated as a universal modern threshold.

For COPD, a post-bronchodilator FEV₁/FVC <0.70 is commonly used, while pulmonary-function laboratories may use the lower limit of normal (LLN) based on age, sex, height, and reference equations.

The key principle remains:

Obstruction → FEV₁ falls more than FVC → FEV₁/FVC decreases.

17. Bronchodilator Reversibility

When airflow obstruction is identified, spirometry may be repeated after administering a bronchodilator.

A significant improvement in airflow after bronchodilator treatment supports the presence of variable or reversible airflow obstruction, which is particularly characteristic of asthma.

However, reversibility is not completely specific for asthma, and some patients with COPD also demonstrate bronchodilator responsiveness.

18. Restrictive Lung Disease

In a restrictive ventilatory defect, the total volume of the lungs is reduced.

Examples include interstitial pulmonary fibrosis, chest-wall restriction, and some neuromuscular disorders.

Both FEV₁ and FVC may decrease because the patient has a smaller volume of air available to expire.

However, they tend to decrease relatively proportionately.

Therefore, the FEV₁/FVC ratio remains normal or may become increased.

FEV₁/FVC in Restriction

The older notes use:

FEV₁/FVC >0.75 → restrictive disorder

The principle is correct, but a preserved or high FEV₁/FVC ratio alone does not prove restriction.

True pulmonary restriction requires demonstration of a reduced total lung capacity (TLC).

Therefore:

Low FVC + normal/high FEV₁/FVC → suspect restriction.

Reduced TLC → confirms restriction.

19. Obstructive Pattern – Note Form

Main abnormality: difficulty getting air out rapidly.

FEV₁: markedly reduced.

FVC: normal or reduced.

FEV₁/FVC: reduced.

TLC: may be normal or increased.

Residual volume: often increased when air trapping is present.

Examples: asthma and COPD.

Bronchodilator response: substantial reversibility particularly supports asthma, although reversibility can also occur in COPD.

Emphysema: compliance increased because elastic recoil is lost.

20. Restrictive Pattern – Note Form

Main abnormality: inability to fully expand the lungs or respiratory system.

FEV₁: reduced.

FVC: reduced.

FEV₁/FVC: normal or increased.

TLC: reduced and required to confirm true restriction.

Residual volume: often reduced or normal depending on the cause.

Examples: pulmonary fibrosis, severe chest-wall restriction, and neuromuscular disease.

Pulmonary fibrosis: lung compliance is reduced because the lungs become stiff.

21. Lung Volumes – Note Form

Tidal volume (TV): volume inspired or expired during an ordinary quiet breath.

Inspiratory reserve volume (IRV): additional air that can be inspired after a normal inspiration.

Expiratory reserve volume (ERV): additional air that can be expired after a normal expiration.

Residual volume (RV): air remaining after maximal expiration.

Vital capacity (VC): maximum volume that can be moved between maximal inspiration and maximal expiration.

VC = IRV + TV + ERV

Functional residual capacity (FRC): air remaining after a normal passive expiration.

FRC = ERV + RV

Total lung capacity (TLC): total volume of gas in the lungs after maximal inspiration.

TLC = VC + RV

22. Important Relationships to Remember

TLC = VC + RV

VC = IRV + TV + ERV

FRC = ERV + RV

Obstruction → FEV₁ ↓↓↓, FVC normal/↓, FEV₁/FVC ↓

Restriction → FEV₁ ↓, FVC ↓, FEV₁/FVC normal/↑, TLC ↓

Emphysema → compliance ↑

Pulmonary fibrosis → compliance ↓

Pulmonary oedema → compliance ↓

Key Clinical Pattern

For examinations, first look at the FEV₁/FVC ratio.

If the ratio is reduced, think airflow obstruction, particularly asthma or COPD.

If the ratio is normal or increased but FVC is reduced, suspect a restrictive pattern and check the TLC. A reduced TLC confirms true restriction.

Then remember the opposite effects on compliance:

Emphysema → lungs are floppy and easy to inflate → ↑ compliance + ↓ elastic recoil.

Pulmonary fibrosis → lungs are stiff and difficult to inflate → ↓ compliance.

Finally, remember that ordinary spirometry cannot directly measure RV, FRC, or TLC, because all three contain residual volume. These require additional lung-volume measurement techniques such as body plethysmography or gas dilution.

Medicine – Gas Transfer Factor

Gas transfer factor refers to the ability of gases to move from the alveoli across the alveolar–capillary membrane into the pulmonary blood. It is usually measured using carbon monoxide because carbon monoxide binds avidly to haemoglobin and its transfer can therefore be used to estimate the efficiency of pulmonary gas exchange.

The measurement is commonly called TLCO in the UK or DLCO in other settings. A reduced transfer factor may result from destruction or thickening of the alveolar–capillary membrane, loss of pulmonary capillary blood volume, reduced haemoglobin concentration, or removal of functioning lung tissue.

1. Causes of Decreased Transfer Factor

A reduced TLCO/DLCO means that carbon monoxide crosses from the alveoli into the blood less efficiently than expected.

The causes can be divided into pulmonary, cardiovascular, and haematological disorders.

Emphysema

Emphysema is a classic cause of reduced gas transfer.

Destruction of alveolar walls reduces the total surface area available for diffusion and also destroys part of the associated pulmonary capillary bed.

Therefore, even though the lungs may be hyperinflated, their effective gas-exchange surface is substantially reduced.

Interstitial Lung Disease

Interstitial lung disease, including pulmonary fibrosis, reduces gas transfer because the alveolar–capillary membrane becomes thickened and fibrotic.

Oxygen and carbon monoxide must therefore diffuse across a greater distance.

TLCO/DLCO is often one of the earliest pulmonary function abnormalities in interstitial lung disease and may fall before marked spirometric restriction develops.

Pneumonia

Pneumonia can temporarily reduce gas transfer because inflammatory exudate fills alveoli and increases the effective distance between inspired gas and pulmonary capillary blood.

The associated V/Q mismatch and alveolar inflammation further impair oxygen transfer.

Pulmonary Embolism

A pulmonary embolism can reduce TLCO/DLCO because it obstructs part of the pulmonary circulation.

Although alveoli may remain ventilated, blood flow through the corresponding pulmonary capillary bed is reduced or absent.

Therefore, there is less pulmonary capillary blood available to take up carbon monoxide.

Pneumonectomy

Following a pneumonectomy, an entire lung has been removed.

This substantially reduces the total alveolar surface area and pulmonary capillary bed available for gas exchange.

Consequently, the absolute transfer factor is reduced.

2. Cardiovascular Causes of Decreased Transfer Factor

Cardiovascular disorders can reduce gas transfer when they decrease the amount of blood reaching the pulmonary capillary circulation or interfere with the alveolar–capillary interface.

Low Cardiac Output

A low cardiac output can reduce pulmonary capillary blood volume.

With less blood flowing through the pulmonary circulation, there is less haemoglobin available to bind the carbon monoxide used during the test.

This can contribute to a reduced measured TLCO/DLCO.

Pulmonary Oedema

Pulmonary oedema can reduce gas transfer because fluid accumulates within the pulmonary interstitium and sometimes within the alveoli.

This increases the diffusion distance between alveolar gas and the pulmonary capillary blood and therefore impairs gas transfer.

The effect may vary depending on the severity and timing of the oedema.

3. Haematological Cause of Decreased Transfer Factor

Anaemia

Anaemia causes a reduced measured TLCO/DLCO because there is less haemoglobin available to bind carbon monoxide.

The lungs themselves may be structurally normal, but the test reads lower because carbon monoxide uptake depends partly on haemoglobin concentration.

For this reason, modern interpretation of TLCO/DLCO should ideally include correction for haemoglobin concentration.

4. Causes of Increased Transfer Factor

An increased TLCO/DLCO occurs when carbon monoxide uptake by the lungs is greater than expected.

This can result from increased pulmonary blood volume, increased haemoglobin concentration, or the presence of blood within the alveoli.

Pulmonary Haemorrhage

Pulmonary haemorrhage can markedly increase TLCO/DLCO.

When blood enters the alveolar spaces, haemoglobin within that blood binds the inhaled carbon monoxide directly.

This increases the measured uptake of carbon monoxide and therefore produces an artificially high transfer factor.

Anti-GBM Disease

Anti-glomerular basement membrane disease, historically called Goodpasture’s syndrome when pulmonary and renal involvement coexist, can cause diffuse alveolar haemorrhage.

The blood within the alveoli increases the apparent TLCO/DLCO because its haemoglobin absorbs carbon monoxide.

Therefore, an unexpectedly high transfer factor in a patient with haemoptysis, anaemia, and bilateral pulmonary infiltrates may support the possibility of alveolar haemorrhage.

5. Cardiovascular Cause of Increased Transfer Factor

Left-to-Right Shunt

A left-to-right cardiac shunt increases pulmonary blood flow.

The increased volume of blood within the pulmonary capillary bed provides more haemoglobin for carbon monoxide uptake.

Therefore, the measured transfer factor may be increased.

Examples of left-to-right shunts include significant atrial septal defects, ventricular septal defects, and patent ductus arteriosus before pulmonary vascular disease reverses the shunt.

6. Haematological Cause of Increased Transfer Factor

Polycythaemia

Polycythaemia increases the haemoglobin concentration of the blood.

Because more haemoglobin is available to bind inhaled carbon monoxide, TLCO/DLCO may be increased.

As with anaemia, haemoglobin concentration therefore needs to be considered when interpreting gas-transfer measurements.

7. Decreased Transfer Factor – Note Form

Emphysema: destruction of alveolar walls reduces gas-exchange surface area and pulmonary capillary bed.

Interstitial lung disease: thickening and fibrosis of the alveolar–capillary membrane impair diffusion.

Pneumonia: alveolar inflammation and exudate interfere with gas transfer.

Pulmonary embolism: reduced perfusion decreases the functioning pulmonary capillary bed.

Pneumonectomy: removal of lung tissue reduces total surface area available for diffusion.

Low cardiac output: reduced pulmonary capillary blood volume decreases carbon monoxide uptake.

Pulmonary oedema: interstitial/alveolar fluid increases diffusion distance.

Anaemia: reduced haemoglobin means less carbon monoxide can be taken up by blood.

8. Increased Transfer Factor – Note Form

Pulmonary haemorrhage: intra-alveolar blood contains haemoglobin that binds carbon monoxide, increasing the measured TLCO/DLCO.

Anti-GBM disease: diffuse alveolar haemorrhage may therefore produce an abnormally high transfer factor.

Left-to-right shunt: increased pulmonary blood flow increases pulmonary capillary blood volume and carbon monoxide uptake.

Polycythaemia: increased haemoglobin concentration increases carbon monoxide uptake.

9. Useful Interpretation with KCO

TLCO/DLCO is influenced by both the efficiency of gas transfer and the available alveolar volume.

Another measurement, KCO, represents transfer factor adjusted for alveolar volume and can sometimes help explain why the TLCO is reduced.

For example, after pneumonectomy, total TLCO is reduced because there is less lung available, but gas transfer per unit of remaining lung may be relatively preserved.

In emphysema, both destruction of alveolar surface and loss of capillaries mean gas-transfer efficiency itself is impaired, so the KCO is often reduced as well.

Key Clinical Pattern

Think of low TLCO/DLCO as occurring when there is:

Less alveolar surface area → emphysema or lung resection.

A thicker diffusion barrier → interstitial lung disease or pulmonary oedema.

Less pulmonary capillary blood flow → pulmonary embolism or low cardiac output.

Less haemoglobin → anaemia.

Think of high TLCO/DLCO as occurring when there is:

More haemoglobin → polycythaemia.

More pulmonary blood flow → left-to-right shunt.

Blood actually present inside the alveoli → pulmonary haemorrhage.

A particularly useful examination association is:

Haemoptysis + pulmonary infiltrates + unexpectedly raised TLCO/DLCO → consider diffuse alveolar haemorrhage.

Medicine – Causes of Haemoptysis

Haemoptysis means coughing up blood that originates from the lower respiratory tract, usually from the bronchi or lungs. It can range from small blood-streaked sputum to life-threatening pulmonary haemorrhage.

The important clinical priorities are to determine the amount of bleeding, whether the patient is haemodynamically or respiratory compromised, and what the underlying cause is.

1. Lung Cancer

Lung cancer is an important cause of haemoptysis, particularly in older patients and those with a significant smoking history.

Bleeding may occur because a tumour erodes into bronchial mucosa or nearby blood vessels.

Associated warning features include persistent cough, unexplained weight loss, chest pain, recurrent pneumonia, hoarseness, and reduced appetite.

Even small-volume recurrent haemoptysis in a high-risk patient warrants further investigation.

2. Pneumonia

Pneumonia can cause haemoptysis because inflammation damages the airway and alveolar tissues.

The sputum may be blood-streaked or occasionally more heavily blood-stained.

Associated features commonly include fever, productive cough, pleuritic chest pain, dyspnoea, and focal chest signs.

3. Tuberculosis

Pulmonary tuberculosis is a classic cause of haemoptysis.

Bleeding can occur from inflamed or cavitating lung tissue, particularly in post-primary disease.

Typical associated symptoms include chronic cough, weight loss, fever, night sweats, fatigue, and sometimes upper-lobe cavitation on imaging.

Significant bleeding can occur if a pulmonary vessel adjacent to a cavity is eroded.

4. Pulmonary Embolism

A pulmonary embolism (PE) may cause haemoptysis, particularly when there is associated pulmonary infarction.

The amount is usually relatively small rather than massive.

Associated features may include sudden breathlessness, pleuritic chest pain, tachycardia, hypoxaemia, syncope, or signs of deep-vein thrombosis.

5. Bronchiectasis

Bronchiectasis is a common structural cause of recurrent haemoptysis.

Chronically inflamed and abnormally dilated bronchi develop enlarged and fragile bronchial arteries, which can bleed.

Patients often have chronic productive cough, large volumes of purulent sputum, recurrent chest infections, and intermittent haemoptysis.

In some patients, bronchiectasis can cause massive haemoptysis.

6. Aspergilloma

An aspergilloma is a fungal ball, usually composed of Aspergillus hyphae, that colonises a pre-existing lung cavity.

The cavity may have resulted from previous tuberculosis, sarcoidosis, or other cavitating lung disease.

Haemoptysis is a classic presentation and may range from mild to severe.

On imaging, an aspergilloma may appear as a mobile intracavitary mass surrounded by an air crescent.

7. Pulmonary Abscess

A lung abscess is a localized area of suppurative infection with destruction and cavitation of lung tissue.

Inflammation and necrosis can damage nearby blood vessels, producing haemoptysis.

Associated features may include fever, productive cough, foul-smelling sputum, weight loss, and an air-fluid level on imaging.

8. Wegener’s Granulomatosis

The older term Wegener’s granulomatosis is now called granulomatosis with polyangiitis (GPA).

GPA is a necrotising small- and medium-vessel vasculitis that commonly affects the upper respiratory tract, lungs, and kidneys.

Pulmonary involvement may produce nodules, cavitation, pulmonary capillaritis, and diffuse alveolar haemorrhage, leading to haemoptysis.

Associated features can include sinusitis, nasal crusting, otitis, haematuria, renal impairment, and systemic inflammatory symptoms.

9. Goodpasture’s Syndrome

Goodpasture’s syndrome, more precisely called anti-glomerular basement membrane disease, can cause severe pulmonary haemorrhage.

Autoantibodies attack basement membranes in the lungs and kidneys.

Patients may present with haemoptysis, breathlessness, anaemia, haematuria, and rapidly progressive glomerulonephritis.

Pulmonary bleeding may be extensive and can cause life-threatening hypoxaemia.

Causes of Haemoptysis – Note Form

Lung cancer: tumour erosion into bronchial tissue or vessels, especially important in smokers and older patients.

Pneumonia: inflammatory damage to airways and alveoli can cause blood-streaked sputum.

Tuberculosis: cavitation and tissue destruction may produce recurrent or severe haemoptysis.

Pulmonary embolism: haemoptysis may occur with pulmonary infarction, usually together with sudden dyspnoea and pleuritic pain.

Bronchiectasis: chronically inflamed dilated bronchi with fragile bronchial arteries; can cause recurrent or massive bleeding.

Aspergilloma: fungal ball within an old lung cavity; haemoptysis is a classic feature.

Pulmonary abscess: cavitating infection with necrosis and vessel damage.

Granulomatosis with polyangiitis: pulmonary vasculitis and alveolar haemorrhage can cause haemoptysis.

Anti-GBM disease: pulmonary capillary bleeding associated with rapidly progressive renal disease.

Key Clinical Pattern

A useful way to remember haemoptysis is to think in broad groups:

Malignancy → lung cancer.

Infection → pneumonia, tuberculosis, lung abscess.

Structural airway disease → bronchiectasis.

Cavitary fungal disease → aspergilloma.

Vascular/thromboembolic → pulmonary embolism.

Pulmonary–renal syndromes → granulomatosis with polyangiitis and anti-GBM disease.

Large-volume haemoptysis is a medical emergency because the immediate danger is often airway obstruction and asphyxiation, not simply blood loss.

Medicine – Causes of Pleuritic Chest Pain

Pleuritic chest pain is a sharp, stabbing chest pain that is typically worse on inspiration, coughing, sneezing, or movement. It usually occurs when the parietal pleura or another pain-sensitive thoracic structure becomes inflamed or irritated.

The most important initial task is to distinguish benign musculoskeletal causes from potentially serious conditions such as pulmonary embolism, pneumothorax, pneumonia, or pericarditis.

1. Pleurisy

Pleurisy means inflammation of the pleura.

When the inflamed pleural surfaces rub against each other during breathing, the patient develops sharp inspiratory chest pain.

A pleural friction rub may sometimes be heard on auscultation.

Pleurisy is not a single diagnosis in itself; it may occur secondary to infection, pulmonary embolism, autoimmune disease, or other pleural disorders.

2. Pneumonia

Pneumonia can cause pleuritic pain when inflammation extends from the lung parenchyma to the adjacent pleural surface.

The pain is often associated with fever, cough, sputum production, dyspnoea, and focal chest signs.

The pleuritic pain is therefore caused by accompanying pleuritis rather than by the lung tissue itself.

3. Pulmonary Embolism

Pulmonary embolism (PE) is an important and potentially life-threatening cause of pleuritic chest pain.

The pain is often sudden and results from irritation of the pleura by a peripheral pulmonary infarct or inflammatory reaction.

Associated features may include sudden breathlessness, tachycardia, haemoptysis, hypoxaemia, syncope, or signs of deep-vein thrombosis.

A normal chest examination does not exclude PE.

4. Pneumothorax

A pneumothorax occurs when air enters the pleural cavity and causes partial or complete lung collapse.

It classically produces sudden unilateral pleuritic chest pain and acute breathlessness.

Examination may show reduced chest expansion, hyperresonance, and diminished breath sounds on the affected side.

A tension pneumothorax is a medical emergency because increasing intrathoracic pressure can impair venous return and cause cardiovascular collapse.

5. Rib Fracture

A rib fracture causes localized chest-wall pain that is typically worsened by deep inspiration, coughing, or movement.

There is often a history of trauma, although fractures can also occur after severe coughing, particularly in older adults or patients with osteoporosis.

The pain is usually reproducible with direct palpation over the affected rib.

6. Costochondritis

Costochondritis is inflammation of the costochondral or costosternal junctions.

It causes localized anterior chest pain that can mimic pleuritic or cardiac pain.

A useful feature is that the pain is often reproducible by pressing over the affected costochondral junctions.

Unlike true pleural disease, there is no underlying abnormality of the lung or pleura.

7. Pleural Effusion

A pleural effusion can cause pleuritic chest pain, particularly during the early inflammatory phase when the pleural surfaces are irritated.

As the effusion enlarges and physically separates the two pleural surfaces, the pleuritic pain may actually become less prominent.

Large effusions may instead cause progressive breathlessness, reduced breath sounds, and stony dullness to percussion.

8. Pericarditis

Acute pericarditis commonly causes sharp, pleuritic-type central chest pain.

The pain is often worse on inspiration and when lying flat, and may improve when the patient sits forward.

A pericardial friction rub may be present.

Because pericarditis can resemble pleuritic pulmonary pain, associated ECG changes and the clinical context are important.

9. Muscular Chest Pain

Muscular chest-wall pain may occur after exercise, coughing, lifting, trauma, or repetitive movement.

The pain is usually worsened by movement of the chest wall and can often be reproduced by palpation or resisted muscle contraction.

This helps distinguish it from many intrathoracic causes.

Causes of Pleuritic Chest Pain – Note Form

Pleurisy: inflammation of the pleura causing sharp pain on inspiration.

Pneumonia: pleural irritation adjacent to infected lung produces pleuritic pain.

Pulmonary embolism: sudden pleuritic pain, often with breathlessness, tachycardia, or haemoptysis.

Pneumothorax: sudden unilateral pleuritic pain with acute dyspnoea.

Rib fracture: localized pain after trauma or coughing, worsened by breathing and reproducible on palpation.

Costochondritis: localized costosternal pain reproducible by pressure over the chest wall.

Pleural effusion: may cause pleuritic pain early, with breathlessness if the effusion is large.

Pericarditis: sharp pain worse on inspiration or lying flat and often relieved by sitting forward.

Muscular chest pain: movement-related and usually reproducible on examination.

Key Clinical Pattern

Think of pleuritic chest pain as:

Sharp pain + worse with inspiration or cough.

The main serious causes to exclude early are:

Pulmonary embolism, pneumothorax, pneumonia, and pericarditis.

Pain that is reproducible with palpation or movement is more suggestive of a musculoskeletal cause such as rib injury, costochondritis, or muscular strain, although this finding alone does not completely exclude more serious disease.

Medicine – Causes of Breathlessness

Breathlessness, or dyspnoea, is the subjective sensation of uncomfortable or difficult breathing. It is a very common clinical symptom and may result from disorders of the respiratory system, cardiovascular system, or other systemic and functional conditions.

When assessing breathlessness, it is important to determine whether the onset is acute or chronic, whether symptoms occur at rest or on exertion, and whether associated features such as chest pain, cough, wheeze, fever, orthopnoea, haemoptysis, or palpitations are present.

1. Respiratory Causes

Respiratory disease is one of the major causes of breathlessness. Dyspnoea can result from airway obstruction, impaired gas exchange, reduced lung expansion, pulmonary vascular disease, pleural disease, or respiratory muscle dysfunction.

Asthma

Asthma causes episodic breathlessness because reversible bronchoconstriction and airway inflammation narrow the conducting airways.

Patients typically experience wheeze, cough, chest tightness, and variable breathlessness. Symptoms may be triggered by allergens, exercise, respiratory infections, smoke, or certain medications.

Chronic Obstructive Pulmonary Disease

COPD produces gradually progressive breathlessness because of persistent airflow obstruction.

Patients commonly have a history of significant smoking or other inhalational exposure and may experience chronic productive cough, wheeze, exertional dyspnoea, and recurrent exacerbations.

Emphysema additionally causes loss of alveolar surface area, hyperinflation, and impaired gas exchange.

Pneumonia

Pneumonia can cause acute breathlessness because infection produces inflammation and filling of the alveoli with inflammatory exudate.

This interferes with ventilation and gas exchange, producing V/Q mismatch and hypoxaemia.

Associated features commonly include fever, cough, sputum production, pleuritic chest pain, and systemic illness.

Pneumothorax

A pneumothorax occurs when air enters the pleural space and causes partial or complete collapse of the affected lung.

It classically presents with sudden-onset breathlessness and unilateral pleuritic chest pain.

A tension pneumothorax can cause severe respiratory and haemodynamic compromise and requires immediate treatment.

Pulmonary Embolism

Pulmonary embolism (PE) occurs when a thrombus, usually originating from the deep veins of the lower limbs or pelvis, travels to the pulmonary circulation.

It can produce sudden unexplained breathlessness, pleuritic chest pain, tachycardia, hypoxaemia, haemoptysis, or syncope.

Massive PE may cause acute right-heart strain and cardiovascular collapse.

Bronchiectasis

Bronchiectasis is characterised by permanent abnormal dilatation of the bronchi associated with impaired mucus clearance and recurrent infection.

Patients typically experience chronic productive cough, large amounts of purulent sputum, recurrent chest infections, haemoptysis, and varying degrees of breathlessness.

Pulmonary Fibrosis

Pulmonary fibrosis causes progressive scarring and stiffening of the lungs.

Reduced lung compliance increases the work required to breathe, while abnormalities of the alveolar–capillary interface impair oxygen transfer.

The typical presentation is progressive exertional breathlessness, persistent dry cough, and fine bibasal inspiratory crackles.

Lung Cancer

Lung cancer can cause breathlessness through several different mechanisms.

The tumour may obstruct a major bronchus, cause collapse of part of the lung, produce a pleural or pericardial effusion, cause lymphangitic spread, or coexist with underlying COPD.

Other concerning features include persistent cough, haemoptysis, chest pain, unexplained weight loss, and recurrent pneumonia.

Pleural Effusion

A pleural effusion is an abnormal accumulation of fluid within the pleural space.

A sufficiently large effusion compresses the underlying lung and restricts its expansion, producing breathlessness.

Examination may demonstrate reduced breath sounds, reduced chest expansion, and stony dullness to percussion over the affected area.

Pulmonary Hypertension

Pulmonary hypertension causes progressive exertional breathlessness because increased pulmonary vascular resistance impairs the ability of the right ventricle to increase pulmonary blood flow during exercise.

Patients may eventually develop fatigue, exertional chest discomfort, syncope, raised JVP, peripheral oedema, and right-sided heart failure.

Phrenic Nerve Palsy

The phrenic nerve supplies the diaphragm.

Phrenic nerve injury can therefore cause diaphragmatic weakness or paralysis. Unilateral paralysis may cause relatively mild symptoms, whereas bilateral involvement can cause substantial breathlessness and ventilatory impairment.

An elevated hemidiaphragm may be visible on chest imaging in unilateral disease.

2. Cardiac Causes

Cardiovascular disease is another major cause of breathlessness.

Dyspnoea can result from reduced cardiac output, elevated left-sided filling pressures, pulmonary venous congestion, pulmonary oedema, arrhythmias, or impaired ventricular filling.

Angina and Myocardial Ischaemia

Myocardial ischaemia usually causes chest discomfort, but some patients—particularly older adults and people with diabetes—may present predominantly with exertional breathlessness.

Dyspnoea can therefore occasionally represent an anginal equivalent.

Left Ventricular Failure

Left ventricular failure is an important cardiac cause of breathlessness.

Failure of the left ventricle increases left atrial and pulmonary venous pressures, causing pulmonary congestion and potentially pulmonary oedema.

Patients may develop exertional dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, bibasal crackles, and reduced exercise tolerance.

Valvular Heart Disease

Significant valvular heart disease can cause breathlessness by reducing effective cardiac output or increasing pressures within the pulmonary circulation.

Important examples include aortic stenosis, aortic regurgitation, mitral stenosis, and mitral regurgitation.

The image appears to state “atrial stenosis” and “atrial regurgitation”; this should be corrected to aortic stenosis and aortic regurgitation.

Aortic Stenosis

Aortic stenosis obstructs blood flow from the left ventricle into the aorta.

Advanced disease may produce the classic combination of exertional breathlessness, angina, and syncope.

Aortic Regurgitation

Aortic regurgitation causes blood to flow backwards from the aorta into the left ventricle during diastole.

Chronic severe regurgitation eventually causes left ventricular dilatation and failure, producing exertional breathlessness and symptoms of heart failure.

Mitral Stenosis

Mitral stenosis obstructs blood flow from the left atrium into the left ventricle.

The resulting elevation of left atrial and pulmonary venous pressures produces exertional breathlessness, orthopnoea, and sometimes pulmonary oedema or haemoptysis.

Mitral Regurgitation

Mitral regurgitation allows blood to flow backwards from the left ventricle into the left atrium during systole.

Severe disease increases left atrial and pulmonary venous pressures and can eventually cause pulmonary congestion and breathlessness.

Arrhythmias

Both rapid and slow cardiac arrhythmias can cause breathlessness by reducing effective cardiac output.

Patients may also report palpitations, dizziness, chest discomfort, presyncope, or syncope.

Examples include atrial fibrillation, supraventricular tachycardia, ventricular arrhythmias, and severe bradyarrhythmias.

Pericardial Effusion

A pericardial effusion is an accumulation of fluid within the pericardial sac.

Large or rapidly developing effusions may interfere with cardiac filling and cause breathlessness.

If intrapericardial pressure becomes sufficiently high, cardiac tamponade can develop, producing hypotension, raised JVP, tachycardia, and circulatory compromise.

Cardiomyopathy

Cardiomyopathy can impair ventricular contraction, relaxation, or filling.

Reduced cardiac output and increased intracardiac pressures can cause exercise intolerance, fatigue, pulmonary congestion, and progressive breathlessness.

Depending on the underlying condition, cardiomyopathy may be dilated, hypertrophic, restrictive, or another recognised subtype.

3. Other Causes of Breathlessness

Not all breathlessness originates directly from the lungs or heart. Several systemic, mechanical, and functional disorders can produce a sensation of dyspnoea.

Psychogenic and Functional Breathlessness

Anxiety, panic attacks, and dysfunctional breathing patterns can produce significant breathlessness even when cardiopulmonary investigations are normal.

Hyperventilation may be accompanied by light-headedness, tingling around the mouth or fingers, chest tightness, and a sensation of being unable to obtain a satisfying breath.

However, breathlessness should not be attributed to anxiety until important organic causes have been appropriately considered.

Massive Ascites

Massive ascites increases intra-abdominal pressure and pushes the diaphragm upward.

This restricts diaphragmatic movement, reduces lung volumes, and can cause significant breathlessness, particularly when lying flat.

Treating the underlying cause and reducing severe ascites can improve respiratory symptoms.

4. Additional Important Causes

A broader differential diagnosis should also include several common systemic causes that were not shown in the original image.

Anaemia

Anaemia reduces the oxygen-carrying capacity of blood.

Patients may therefore develop exertional breathlessness, fatigue, palpitations, dizziness, and tachycardia, despite having structurally normal lungs.

Obesity and Deconditioning

Severe obesity increases the mechanical work of breathing and may restrict diaphragmatic movement.

Physical deconditioning can also produce disproportionate breathlessness during relatively minor exertion.

Metabolic Acidosis

Conditions causing severe metabolic acidosis, such as diabetic ketoacidosis, stimulate respiratory compensation.

Patients may develop rapid, deep breathing known as Kussmaul respiration, which may be perceived as breathlessness.

5. Causes of Breathlessness – Note Form

Respiratory Causes

Asthma: variable airflow obstruction with wheeze, cough, chest tightness, and episodic breathlessness.

COPD: persistent airflow obstruction causing progressive exertional dyspnoea, cough, sputum, and wheeze.

Pneumonia: alveolar infection and inflammation causing impaired gas exchange and acute breathlessness.

Pneumothorax: sudden breathlessness with pleuritic chest pain due to air within the pleural space.

Pulmonary embolism: often sudden unexplained dyspnoea ± pleuritic pain, tachycardia, haemoptysis, or syncope.

Bronchiectasis: chronic productive cough, recurrent infections, haemoptysis, and breathlessness.

Pulmonary fibrosis: progressive exertional dyspnoea with dry cough and fine inspiratory crackles.

Lung cancer: may cause dyspnoea through airway obstruction, lung collapse, effusion, or extensive pulmonary involvement.

Pleural effusion: pleural fluid compresses the lung and restricts expansion.

Pulmonary hypertension: progressive exertional dyspnoea due to increased pulmonary vascular resistance.

Phrenic nerve palsy: diaphragmatic weakness or paralysis causes impaired ventilation.

Cardiac Causes

Myocardial ischaemia/angina: exertional breathlessness may occasionally be an anginal equivalent.

Left ventricular failure: pulmonary venous congestion produces exertional dyspnoea, orthopnoea, and paroxysmal nocturnal dyspnoea.

Aortic stenosis: exertional dyspnoea, angina, and syncope in advanced disease.

Aortic regurgitation: chronic volume overload eventually causes left ventricular failure and dyspnoea.

Mitral stenosis: raised left atrial pressure produces pulmonary venous congestion and breathlessness.

Mitral regurgitation: severe regurgitation can cause pulmonary congestion and heart failure.

Arrhythmias: impaired cardiac output can cause breathlessness, palpitations, and dizziness.

Pericardial effusion: impaired ventricular filling can cause breathlessness and, when severe, cardiac tamponade.

Cardiomyopathy: impaired cardiac function produces reduced exercise tolerance and dyspnoea.

Other Causes

Psychogenic/functional: anxiety, panic attacks, and dysfunctional breathing may cause breathlessness and hyperventilation.

Massive ascites: upward displacement of the diaphragm restricts lung expansion.

Anaemia: reduced oxygen-carrying capacity causes exertional dyspnoea.

Obesity: increased respiratory workload and reduced lung volumes can cause breathlessness.

Deconditioning: reduced cardiovascular and muscular fitness causes early exertional dyspnoea.

Metabolic acidosis: compensatory hyperventilation can present as rapid, deep breathing.

Key Clinical Pattern

A useful way to approach breathlessness is to divide the differential into three major groups:

Respiratory → asthma, COPD, pneumonia, pneumothorax, PE, bronchiectasis, pulmonary fibrosis, lung cancer, pleural effusion, pulmonary hypertension, and diaphragmatic dysfunction.

Cardiac → myocardial ischaemia, left ventricular failure, valvular heart disease, arrhythmias, pericardial effusion, and cardiomyopathy.

Other → anxiety or dysfunctional breathing, massive ascites, anaemia, obesity, deconditioning, and metabolic disorders.

The time course is particularly useful diagnostically. Sudden breathlessness should raise concern for conditions such as PE, pneumothorax, acute pulmonary oedema, acute severe asthma, or an acute cardiac event, whereas gradually progressive breathlessness is more typical of conditions such as COPD, pulmonary fibrosis, chronic heart failure, pulmonary hypertension, anaemia, or malignancy.

Medicine – Respiratory Failure

Respiratory failure occurs when the respiratory system is unable to maintain adequate gas exchange. This results in inadequate arterial oxygenation, abnormal carbon dioxide elimination, or both.

Respiratory failure is traditionally divided into Type I (hypoxaemic) respiratory failure and Type II (hypercapnic or ventilatory) respiratory failure.

1. Type I Respiratory Failure

Type I respiratory failure is primarily a failure of oxygenation.

It is characterised by significant hypoxaemia with a normal or low arterial carbon dioxide level.

Definition

The traditional arterial blood gas definition is:

PaO₂ <8 kPa (60 mmHg)

with

PaCO₂ normal or low.

Therefore, the main abnormality is a fall in arterial oxygen rather than carbon dioxide retention.

Pathophysiology

Type I respiratory failure commonly results from ventilation–perfusion (V/Q) mismatch.

This means that some areas of the lung receive adequate blood flow but insufficient ventilation, so blood leaving these regions remains poorly oxygenated.

However, V/Q mismatch is not the only mechanism. Type I respiratory failure can also result from intrapulmonary shunting, diffusion impairment, and severe abnormalities of the alveolar–capillary membrane.

Why PaCO₂ Is Usually Normal or Low

Patients with hypoxaemia frequently respond by increasing their respiratory rate and ventilation.

Carbon dioxide diffuses across the alveolar membrane more readily than oxygen and can therefore often still be eliminated effectively.

As a result, PaCO₂ commonly remains normal or becomes reduced because of hyperventilation.

Causes of Type I Respiratory Failure

2. Severe Acute Asthma – Early Stage

During the earlier stages of a severe acute asthma attack, marked airway obstruction causes V/Q mismatch and hypoxaemia.

The patient responds by hyperventilating, so the PaCO₂ is usually low.

A very important clinical point is that a normal or rising PaCO₂ in severe acute asthma is dangerous, because it may indicate respiratory muscle fatigue and progression toward ventilatory failure.

3. Emphysema

Patients with predominantly emphysematous COPD may initially develop hypoxaemia while maintaining sufficient ventilation to prevent significant carbon dioxide retention.

This corresponds to the historical “pink puffer” pattern.

As COPD becomes advanced, however, some patients can develop hypercapnia and therefore progress to Type II respiratory failure.

4. Pneumonia

Pneumonia can produce Type I respiratory failure because infected alveoli become filled with inflammatory exudate.

These alveoli may continue to receive blood but are poorly ventilated, producing severe V/Q mismatch and intrapulmonary shunting.

The result is hypoxaemia, which can become profound in extensive pneumonia.

5. Pulmonary Embolism

A pulmonary embolism (PE) disrupts pulmonary blood flow and produces major abnormalities in ventilation–perfusion matching.

Patients often hyperventilate in response to hypoxaemia and physiological stress.

Consequently, a typical blood gas pattern is low PaO₂ with low PaCO₂, although blood gases vary and cannot by themselves diagnose or exclude PE.

6. Pulmonary Oedema

Pulmonary oedema causes accumulation of fluid within the pulmonary interstitium and alveoli.

This interferes with oxygen transfer and produces V/Q mismatch and shunting.

Acute pulmonary oedema can therefore cause significant Type I hypoxaemic respiratory failure.

7. Interstitial Lung Disease

Interstitial lung disease (ILD) causes thickening and fibrosis of the alveolar–capillary interface.

This impairs oxygen diffusion and may also produce V/Q abnormalities.

Hypoxaemia is often particularly noticeable during exercise, when blood passes through the pulmonary capillaries more rapidly and there is less time available for oxygen equilibration.

Advanced ILD can eventually cause severe resting hypoxaemia.

8. Type II Respiratory Failure

Type II respiratory failure is primarily a failure of alveolar ventilation.

The lungs cannot eliminate carbon dioxide adequately, resulting in hypercapnia together with hypoxaemia.

It is therefore also called hypercapnic respiratory failure or ventilatory failure.

Definition

Traditionally, Type II respiratory failure is characterised by:

PaO₂ <8 kPa (60 mmHg)

and

PaCO₂ >6.0–6.7 kPa (45–50 mmHg), depending on the definition being used.

The older notes use PaCO₂ >6.7 kPa, which represents definite hypercapnia.

Pathophysiology

The fundamental problem in Type II respiratory failure is inadequate alveolar ventilation.

When ventilation is insufficient, the body cannot eliminate the carbon dioxide generated by metabolism.

Therefore:

↓ Alveolar ventilation → ↑ PaCO₂ + ↓ PaO₂

This can result from severe lung disease, abnormalities of the chest wall, neuromuscular weakness, or suppression of the brain’s respiratory drive.

Respiratory Causes of Type II Respiratory Failure

9. COPD

COPD is one of the most important causes of Type II respiratory failure.

Severe airflow obstruction, V/Q mismatch, respiratory muscle loading, and inadequate alveolar ventilation can eventually cause CO₂ retention.

Some patients with advanced COPD develop chronic hypercapnia, while others develop Type II respiratory failure mainly during acute exacerbations.

10. Severe Asthma

Very severe asthma can progress from an initial Type I pattern to Type II respiratory failure.

Initially:

Hyperventilation → low PaCO₂

As respiratory muscles fatigue:

Ventilation falls → PaCO₂ becomes normal

With further deterioration:

PaCO₂ rises → Type II respiratory failure

Therefore, a rising carbon dioxide level in severe asthma is a major warning sign of impending respiratory failure.

11. Bronchiectasis

Advanced bronchiectasis can cause chronic airflow obstruction, extensive V/Q mismatch, and impaired alveolar ventilation.

Patients with severe disease may eventually develop hypoxaemia and hypercapnia, particularly during infective exacerbations.

Thoracic Cage Causes

12. Kyphoscoliosis

Severe kyphoscoliosis restricts expansion of the chest wall.

This produces a restrictive ventilatory defect and can substantially reduce alveolar ventilation.

Advanced disease may therefore cause chronic Type II respiratory failure.

13. Ankylosing Spondylitis

Severe ankylosing spondylitis may restrict movement of the thoracic cage because of involvement and fusion of spinal and costovertebral structures.

When sufficiently advanced, this restriction can contribute to alveolar hypoventilation and hypercapnic respiratory failure.

14. Chest Trauma and Surgery

Severe chest trauma can interfere with effective ventilation because of pain, rib fractures, flail chest, or mechanical disruption of chest-wall movement.

Following major thoracic or abdominal surgery, pain, sedation, and impaired respiratory mechanics can similarly produce hypoventilation.

If ventilation becomes inadequate, PaCO₂ rises and Type II respiratory failure can develop.

Neuromuscular Causes

15. Muscular Dystrophy

Muscular dystrophies can progressively weaken the diaphragm and other respiratory muscles.

As respiratory muscle strength declines, patients become unable to generate sufficient ventilation, particularly during sleep and eventually while awake.

This can produce chronic hypercapnic respiratory failure.

16. Guillain–Barré Syndrome

Guillain–Barré syndrome can cause rapidly progressive respiratory muscle weakness.

Severe weakness of the diaphragm and accessory respiratory muscles may result in inadequate ventilation and acute Type II respiratory failure.

Respiratory function therefore requires close monitoring in patients with significant Guillain–Barré syndrome.

17. Myasthenia Gravis

Severe myasthenia gravis, particularly during a myasthenic crisis, can weaken the respiratory muscles.

Progressive respiratory muscle fatigue may eventually cause alveolar hypoventilation, CO₂ retention, and respiratory failure.

Drug Causes

18. Opioids

Opioids can suppress the respiratory centres within the brainstem.

Respiratory rate and tidal volume decrease, causing reduced alveolar ventilation.

The characteristic sequence is:

Respiratory depression → hypoventilation → CO₂ retention → hypoxaemia

Severe opioid toxicity can therefore cause acute Type II respiratory failure.

19. Benzodiazepines

Benzodiazepines can also depress central nervous system activity and contribute to respiratory depression.

The risk is particularly important when benzodiazepines are combined with opioids, alcohol, or other sedative drugs, or when used in patients who already have significant respiratory disease.

20. Type I Respiratory Failure – Note Form

Main problem: failure of oxygenation.

PaO₂: <8 kPa.

PaCO₂: normal or low.

Main mechanism: usually V/Q mismatch, although shunting and diffusion impairment may also contribute.

Ventilation: generally preserved or increased.

Typical causes: pneumonia, pulmonary embolism, pulmonary oedema, interstitial lung disease, early severe asthma, and some patients with emphysema.

Asthma: early severe attacks usually produce hypoxaemia with a low PaCO₂ because the patient hyperventilates.

21. Type II Respiratory Failure – Note Form

Main problem: failure of alveolar ventilation.

PaO₂: reduced.

PaCO₂: raised, traditionally >6.0–6.7 kPa.

Main mechanism: inadequate alveolar ventilation causes CO₂ retention.

Respiratory causes: COPD, very severe asthma, and advanced bronchiectasis.

Thoracic cage causes: kyphoscoliosis, severe ankylosing spondylitis, and major chest trauma or surgery.

Neuromuscular causes: muscular dystrophy, Guillain–Barré syndrome, and myasthenia gravis.

Drug causes: opioids and sedative drugs such as benzodiazepines.

22. Acute vs Chronic Type II Respiratory Failure

The pH and bicarbonate concentration help determine whether hypercapnic respiratory failure is acute or chronic.

In acute Type II respiratory failure, PaCO₂ rises rapidly and there has been little time for renal compensation. The patient therefore develops respiratory acidosis with a reduced pH.

In chronic Type II respiratory failure, the kidneys retain bicarbonate to compensate for persistent CO₂ retention. Therefore, the bicarbonate is elevated and the pH may be relatively close to normal despite a high PaCO₂.

This distinction is particularly important in patients with advanced COPD.

Key Clinical Pattern

Type I respiratory failure = oxygenation failure.

↓ PaO₂ + normal/↓ PaCO₂

Think particularly of pneumonia, PE, pulmonary oedema, ILD, and early severe asthma.

Type II respiratory failure = ventilation failure.

↓ PaO₂ + ↑ PaCO₂

Think of COPD, very severe asthma, severe bronchiectasis, chest-wall restriction, neuromuscular weakness, and respiratory-depressant drugs.

A particularly important examination point is the change in PaCO₂ during severe asthma:

Early severe asthma → hyperventilation → ↓ PaCO₂

Deterioration/fatigue → PaCO₂ becomes normal

Respiratory muscle failure → ↑ PaCO₂ → Type II respiratory failure

Therefore, a normal or rising PaCO₂ in a patient with severe acute asthma is an ominous sign rather than evidence of improvement.

Medicine – Chronic Asthma

Asthma is a chronic inflammatory disorder of the airways characterised by variable respiratory symptoms and variable expiratory airflow limitation. The airways become hyperresponsive to different stimuli, resulting in episodes of bronchoconstriction that are usually reversible either spontaneously or with treatment.

The characteristic symptoms are wheeze, breathlessness, chest tightness, and cough, which typically vary in intensity over time. Unlike the persistent airflow obstruction of COPD, airflow limitation in asthma is often substantially reversible.

1. Prevalence

Asthma is extremely common and can occur at any age, although it frequently begins during childhood.

Older teaching quotes figures of approximately 20% in children and 15% in adults, but prevalence varies substantially according to country, age group, diagnostic criteria, and population studied. It is therefore better to regard these as approximate historical figures rather than universal incidence rates.

2. Chronic Airway Inflammation

Asthma is fundamentally a chronic inflammatory airway disease.

The bronchial mucosa contains increased numbers of inflammatory cells, including eosinophils, mast cells, and T lymphocytes in many asthma phenotypes.

Inflammation causes airway hyperresponsiveness, mucosal oedema, increased mucus production, and increased sensitivity of bronchial smooth muscle to various stimuli.

3. Variable Airflow Obstruction

A defining characteristic of asthma is that airflow obstruction is variable.

Bronchial smooth-muscle contraction, airway inflammation, mucosal oedema, and mucus production narrow the airways during symptomatic periods.

When the trigger disappears or bronchodilator treatment is administered, airway calibre may improve considerably.

Genetic and Environmental Factors

4. Genetic Predisposition

Asthma has an important genetic component, although it is not inherited through a simple single-gene pattern.

A family history of asthma or other allergic disorders increases the likelihood of developing the condition.

5. Atopy

Atopy describes a genetic tendency to develop exaggerated IgE-mediated responses to common environmental allergens.

Atopic individuals are more likely to develop conditions such as asthma, allergic rhinitis, and atopic eczema.

However, not every patient with asthma is atopic, and several distinct inflammatory asthma phenotypes are now recognised.

6. Environmental Factors

Environmental exposures interact with genetic susceptibility to influence the development and expression of asthma.

Important factors include allergens, respiratory infections, tobacco smoke, occupational exposures, and air pollution.

Pulmonary Function Tests

Objective evidence of variable expiratory airflow limitation is important when establishing the diagnosis of asthma.

7. Peak Expiratory Flow Variability

Serial peak expiratory flow (PEF) measurements may demonstrate significant variation over time.

Older teaching often uses >20–25% variability as evidence supporting asthma. Modern diagnostic thresholds and calculation methods vary between guidelines, so the exact percentage should be interpreted within the appropriate diagnostic protocol.

The important principle is that substantial variability in expiratory airflow supports asthma.

8. FEV₁

During periods of airflow obstruction, the forced expiratory volume in one second (FEV₁) may be reduced.

Between attacks, however, spirometry may return completely to normal, particularly in patients with mild asthma.

9. FEV₁/FVC Ratio

Airflow obstruction causes the FEV₁/FVC ratio to decrease because FEV₁ falls disproportionately compared with forced vital capacity.

Again, the ratio may normalise when asthma is well controlled.

10. Bronchodilator Reversibility

A characteristic feature is an improvement in airflow following administration of a bronchodilator.

Both FEV₁ and peak expiratory flow may increase significantly after inhaled salbutamol or another rapidly acting bronchodilator.

Demonstrating significant bronchodilator reversibility provides objective evidence supporting the diagnosis of asthma.

11. Lung Volumes

During significant airway obstruction, air trapping and hyperinflation may increase residual volume and sometimes total lung capacity.

However, increased lung volumes are not required for the diagnosis, and patients with well-controlled or mild asthma may have completely normal lung volumes.

Triggers of Asthma

Asthma symptoms and acute exacerbations can be triggered by numerous environmental, physiological, and pharmacological factors.

12. Allergens

Exposure to allergens is an important trigger in patients with allergic asthma.

Common allergens include grass and tree pollens, house-dust mites, moulds, and animal dander, particularly from cats and dogs.

Exposure triggers airway inflammation and bronchoconstriction in susceptible individuals.

13. Exercise

Exercise can provoke transient bronchoconstriction, particularly when breathing large volumes of cold or dry air.

Patients may develop cough, wheeze, chest tightness, or breathlessness during or shortly after exercise.

Well-controlled asthma should generally allow patients to remain physically active.

14. Aspirin and NSAIDs

Aspirin and other NSAIDs can provoke severe bronchospasm in susceptible patients.

This is particularly important in aspirin/NSAID-exacerbated respiratory disease, which is associated with asthma and chronic rhinosinusitis with nasal polyps.

Not every patient with asthma needs to avoid NSAIDs; the problem occurs in susceptible individuals.

15. β-Blockers

β-blockers can cause bronchoconstriction by blocking β₂ receptors in bronchial smooth muscle.

Non-selective β-blockers present the greatest concern, although even β₁-selective drugs require appropriate consideration in patients with asthma.

β-blocking ophthalmic preparations can also occasionally cause systemic bronchospasm.

16. Respiratory Infection

Respiratory viral infections are among the most common triggers of asthma exacerbations.

Inflammation produced by infection increases airway hyperresponsiveness and can substantially worsen pre-existing asthma.

17. Gastro-Oesophageal Reflux

Gastro-oesophageal reflux disease (GORD/GERD) frequently coexists with asthma and may worsen respiratory symptoms in some patients.

However, reflux is not necessarily the cause of poor asthma control in every patient who has both conditions.

18. Smoke and Air Pollution

Cigarette smoke, vaping aerosols, environmental pollution, fumes, and other respiratory irritants can aggravate airway inflammation and trigger asthma symptoms.

Smoking can also reduce responsiveness to inhaled corticosteroids and contributes to poorer asthma control.

19. Poor Adherence

Poor adherence to regular controller medication, particularly inhaled corticosteroid-containing treatment, is an important cause of poorly controlled asthma and exacerbations.

Before escalating treatment, clinicians should therefore assess adherence, inhaler technique, ongoing triggers, and whether the diagnosis is correct.

Treatment of Chronic Asthma

Modern asthma treatment differs considerably from the older stepwise regimen in the supplied notes.

The major change is that treatment now emphasises inhaled corticosteroid (ICS)-containing therapy from an early stage, because airway inflammation is present even in patients with apparently mild asthma.

Reliance on a short-acting β₂-agonist such as salbutamol alone is generally no longer preferred in modern adult and adolescent asthma management.

20. Reliever Treatment

Historically, patients with mild asthma were treated with a short-acting β₂-agonist (SABA) such as salbutamol whenever symptoms occurred.

Modern approaches increasingly favour an ICS-containing reliever strategy, commonly using a low-dose inhaled corticosteroid combined with the rapid-onset LABA formoterol, where appropriate and available.

This provides both rapid bronchodilation and anti-inflammatory treatment when symptoms occur.

21. Inhaled Corticosteroids

Inhaled corticosteroids are the foundation of long-term asthma control.

They suppress airway inflammation, reduce symptoms, improve lung function, decrease airway hyperresponsiveness, and importantly reduce the risk of severe exacerbations and asthma-related death.

Examples include budesonide, beclometasone, and fluticasone.

22. Leukotriene Receptor Antagonists

A leukotriene receptor antagonist, such as montelukast, may be useful as additional controller therapy in selected patients.

It may be particularly helpful when asthma coexists with allergic rhinitis or in some patients with exercise- or aspirin/NSAID-associated symptoms.

It is generally less effective than inhaled corticosteroids as the main anti-inflammatory controller treatment.

23. Long-Acting β₂-Agonists

A long-acting β₂-agonist (LABA) may be added when asthma remains inadequately controlled with inhaled corticosteroid therapy.

Examples include formoterol and salmeterol.

Importantly, a LABA should not normally be used without an inhaled corticosteroid in asthma, because LABA monotherapy does not treat the underlying airway inflammation and is associated with safety concerns.

24. ICS–Formoterol Maintenance and Reliever Therapy

An important modern strategy is maintenance-and-reliever therapy (MART) using an ICS–formoterol inhaler.

The same inhaler provides regular maintenance anti-inflammatory treatment and additional doses when symptoms occur.

Because formoterol has a rapid onset of bronchodilation, it can function as both a long-acting controller and a reliever when combined appropriately with an ICS.

Escalation of Treatment

25. Persistent Symptoms

If asthma remains uncontrolled, treatment should be increased gradually while repeatedly checking adherence, inhaler technique, environmental exposures, comorbidities, and diagnostic accuracy.

Increasing the dose of inhaled corticosteroid or adding another controller may be appropriate depending on the treatment pathway being followed.

26. Long-Acting Muscarinic Antagonists

A long-acting muscarinic antagonist (LAMA), such as tiotropium, may be added in selected patients whose asthma remains inadequately controlled despite appropriate ICS/LABA treatment.

This has largely replaced the older concept of routinely adding short-acting ipratropium for long-term asthma control.

27. Theophylline

Theophylline was historically used more frequently as additional therapy for chronic asthma.

Its role is now limited because it has a narrow therapeutic index, important drug interactions, and significant adverse effects, while more effective and safer treatment options are available.

28. Nebulised Bronchodilators

Regular nebulised bronchodilators are not standard routine maintenance therapy for most patients with chronic asthma.

Nebulised therapy is much more commonly used during significant acute exacerbations.

Severe Asthma

29. Specialist Assessment

Patients whose asthma remains uncontrolled despite appropriately prescribed high-level inhaled therapy should undergo specialist assessment.

Before diagnosing severe treatment-resistant asthma, clinicians should confirm the diagnosis and carefully evaluate adherence, inhaler technique, smoking, allergen exposure, occupational factors, obesity, rhinosinusitis, reflux, and other comorbidities.

30. Biological Therapies

Modern treatment of severe asthma includes biological therapies directed at specific inflammatory pathways.

Depending on the asthma phenotype and biomarkers, treatment may target IgE, interleukin-5 or its receptor, interleukin-4/13 signalling, or other inflammatory pathways.

These therapies can substantially reduce exacerbations and the need for systemic corticosteroids in appropriately selected patients.

31. Oral Corticosteroids

Maintenance oral corticosteroids should generally be avoided whenever possible because prolonged systemic steroid exposure can cause major adverse effects.

These include osteoporosis, diabetes, hypertension, weight gain, cataracts, adrenal suppression, infection, and muscle weakness.

They may still be necessary in selected patients with severe refractory asthma, but modern biologic therapies can often reduce the requirement for long-term oral steroids.

32. Treatment Escalation – Note Form

Initial/Mild Asthma

Preferred principle: use an ICS-containing treatment strategy, rather than relying solely on salbutamol.

Reliever: low-dose ICS–formoterol is commonly preferred in appropriate adult/adolescent treatment pathways.

Alternative approaches: regular or symptom-linked low-dose ICS with an appropriate reliever may be used according to the treatment guideline and patient circumstances.

Persistent Asthma

Controller treatment: regular low-dose inhaled corticosteroid-containing therapy.

If symptoms persist: increase anti-inflammatory treatment and/or add a LABA.

Important: LABA therapy in asthma should be combined with an ICS, rather than used alone.

Moderate Asthma

Treatment: combination ICS + LABA therapy.

Option: ICS–formoterol may be used as maintenance-and-reliever therapy (MART) when appropriate.

Before escalation: always reassess inhaler technique, adherence, triggers, and comorbidities.

More Difficult-to-Control Asthma

Treatment: increase ICS-containing therapy according to the appropriate treatment pathway.

Additional options: consider a LAMA or other add-on controller treatment.

Theophylline: now has a limited role because of adverse effects and drug interactions.

Regular nebulisers: not routinely required for chronic stable asthma.

Severe Asthma

Management: specialist respiratory assessment.

Treatment options: phenotype-directed biological therapies may be appropriate.

Oral corticosteroids: intermittent courses may be required for exacerbations, while long-term maintenance therapy should be minimised whenever possible because of significant systemic toxicity.

Key Clinical Pattern

Think of asthma as:

Chronic airway inflammation + bronchial hyperresponsiveness + variable symptoms + variable expiratory airflow obstruction.

Typical symptoms are wheeze, breathlessness, chest tightness, and cough, with objective evidence such as variable peak flow, reduced FEV₁/FVC during obstruction, and improvement following bronchodilator treatment.

Important triggers include allergens, exercise, respiratory infections, smoke, NSAIDs/aspirin in susceptible patients, β-blockers, and poor adherence to controller treatment.

For modern treatment, the key principle is early ICS-containing therapy, followed when necessary by ICS/LABA treatment, MART where appropriate, additional controller therapy, and phenotype-directed biologics for severe asthma, while avoiding unnecessary dependence on SABA-only therapy or long-term oral corticosteroids.

Medicine – Acute Asthma

Acute asthma is a sudden or progressive worsening of asthma symptoms caused by increased bronchial smooth-muscle constriction, airway inflammation, mucosal oedema, and mucus production. Patients develop worsening breathlessness, wheeze, cough, and chest tightness, together with a measurable reduction in expiratory airflow.

A severe asthma attack can progress rapidly to life-threatening respiratory failure, so recognising markers of severity and starting treatment promptly are essential.

1. Mortality

Asthma continues to cause preventable deaths in the UK, although the older figure of approximately 1,500 deaths per year varies between years and should not be regarded as a fixed contemporary number.

Many fatal attacks are associated with delayed recognition of severity, inadequate use of anti-inflammatory treatment, or delayed escalation of emergency care.

Assessment of Acute Asthma

The severity of an acute attack should be assessed using the patient’s clinical appearance, ability to speak, respiratory rate, heart rate, oxygen saturation, peak expiratory flow (PEF), and—when indicated—arterial blood gases.

An important correction to the older notes is that some listed findings, particularly PEF <33%, silent chest, hypoxaemia, and normal or raised PaCO₂, are markers of life-threatening asthma, rather than merely severe asthma.

2. Severe Acute Asthma

In adults, acute severe asthma is suggested by the presence of any of the following major features.

Difficulty Speaking

The patient may be unable to complete sentences in one breath because of severe breathlessness.

Speech becoming increasingly fragmented is an important bedside indication of worsening respiratory distress.

Tachycardia

A heart rate ≥110 beats/minute is a marker of acute severe asthma.

Tachycardia can result from respiratory distress, hypoxaemia, sympathetic activation, and β₂-agonist treatment.

Tachypnoea

A respiratory rate ≥25 breaths/minute is commonly used in modern UK adult criteria for acute severe asthma.

The older threshold of >30/min still indicates substantial respiratory distress but is not the usual current threshold for defining acute severe asthma.

Peak Expiratory Flow

A PEF of 33–50% of the patient’s best or predicted value indicates acute severe asthma.

Peak flow provides an objective measurement of the degree of airflow obstruction and should be recorded whenever the patient is capable of performing the manoeuvre safely.

3. Life-Threatening Asthma

Life-threatening asthma is suggested by particularly severe clinical or physiological abnormalities.

These patients require immediate treatment, senior medical involvement, and consideration of intensive care.

Peak Flow Below 33%

A PEF <33% of the patient’s best or predicted value is a major marker of life-threatening asthma.

This represents very severe expiratory airflow limitation.

Silent Chest

A silent chest is an ominous finding.

Although wheezing is characteristic of asthma, extremely severe airflow obstruction can reduce airflow so dramatically that little or no wheeze is audible.

Therefore, disappearance of wheeze in a deteriorating patient does not necessarily indicate improvement.

Hypoxaemia

Significant hypoxaemia indicates severe impairment of ventilation and gas exchange.

Oxygen saturation should therefore be monitored continuously in a severe attack.

Normal or Raised PaCO₂

A normal or elevated arterial PaCO₂ is a particularly concerning finding in acute asthma.

Early in an asthma attack, patients usually hyperventilate and therefore have a low PaCO₂.

As obstruction becomes extreme and respiratory muscles fatigue, the patient can no longer maintain adequate ventilation. PaCO₂ then returns toward normal and subsequently rises.

Therefore:

Low PaCO₂ → expected during significant acute asthma.

Normal PaCO₂ → concerning for deterioration.

Raised PaCO₂ → severe ventilatory failure and potentially impending respiratory arrest.

Other Life-Threatening Features

Additional warning signs include cyanosis, poor respiratory effort, exhaustion, hypotension, arrhythmia, altered consciousness, and confusion.

These features indicate that the patient may be approaching respiratory failure.

4. Pulsus Paradoxus

Pulsus paradoxus refers to an exaggerated fall in systolic blood pressure during inspiration.

It may occur in severe asthma because large changes in intrathoracic pressure influence ventricular filling.

Although historically included in severity assessment, it is not routinely relied upon in modern acute asthma assessment, because simpler clinical and physiological measurements are more useful.

Management of Acute Severe Asthma

Treatment should begin immediately while severity is being assessed.

The major aims are to correct hypoxaemia, reverse bronchoconstriction, suppress airway inflammation, and recognise patients requiring intensive respiratory support.

5. Oxygen

Patients who are hypoxaemic should receive supplemental oxygen, titrated to an appropriate oxygen saturation.

The older instruction to automatically administer unrestricted high-flow oxygen to every patient has been replaced by controlled oxygen therapy guided by oxygen saturation.

In adults with acute asthma, a target oxygen saturation of approximately 94–98% is commonly used.

6. Nebulised β₂-Agonists

A rapidly acting inhaled β₂-agonist, most commonly salbutamol, is a cornerstone of treatment.

In severe attacks, repeated or continuous nebulised therapy may be required.

Nebulisers can be driven by oxygen when appropriate in significantly hypoxaemic patients.

7. Ipratropium Bromide

Nebulised ipratropium bromide should be added to β₂-agonist treatment in severe or life-threatening asthma.

The combination produces greater bronchodilation than either treatment alone in severe attacks.

8. Systemic Corticosteroids

Systemic corticosteroids should be administered early because acute asthma involves significant airway inflammation as well as bronchoconstriction.

Oral prednisolone is often appropriate when the patient can swallow and absorb medication.

Intravenous hydrocortisone can be used when oral treatment is unsuitable.

Steroids do not produce immediate bronchodilation, but they reduce airway inflammation and decrease the likelihood of ongoing deterioration and relapse.

Additional Treatment

9. Intravenous Magnesium Sulfate

Intravenous magnesium sulfate may be considered in severe or life-threatening asthma that responds inadequately to initial inhaled bronchodilator treatment.

Magnesium has a bronchodilator effect and can be useful in selected severe attacks.

It is not routinely required for every asthma exacerbation.

10. Intravenous Aminophylline

Intravenous aminophylline was historically used more frequently in severe asthma.

It is no longer routinely recommended because the additional bronchodilator benefit is limited and adverse effects, including nausea, vomiting, arrhythmias, and seizures, can occur.

It may occasionally be considered in specialist-managed refractory cases.

11. Intravenous Salbutamol

Intravenous β₂-agonists such as salbutamol are also not routinely used when effective inhaled or nebulised therapy can be delivered.

They may occasionally be considered in highly selected refractory cases under specialist supervision.

12. Antibiotics

Antibiotics are not routinely indicated in acute asthma.

Most asthma exacerbations are not caused by bacterial infection, and purulent-looking sputum alone does not necessarily indicate bacterial disease.

Antibiotics should be given when there is convincing evidence of a bacterial infection, such as bacterial pneumonia.

Respiratory Failure

13. When to Consider Intensive Care

Urgent intensive care assessment should be considered when the patient is deteriorating despite appropriate treatment or develops features such as exhaustion, altered consciousness, worsening hypoxaemia, rising PaCO₂, poor respiratory effort, or haemodynamic instability.

A patient with severe asthma can deteriorate very rapidly.

14. Mechanical Ventilation

Mechanical ventilation may become necessary when respiratory failure develops despite maximal medical treatment.

Important indications include worsening hypercapnia, severe hypoxaemia, exhaustion, reduced consciousness, respiratory arrest, or inability to maintain adequate ventilation.

Intubation and ventilation of a patient with severe asthma are challenging because severe airflow obstruction and air trapping can produce dynamic hyperinflation and dangerously high intrathoracic pressures, so experienced critical-care management is essential.

15. Severe vs Life-Threatening Asthma – Note Form

Acute Severe Asthma

Speech: unable to complete sentences in one breath.

Respiratory rate: ≥25/min.

Heart rate: ≥110/min.

PEF: 33–50% of best or predicted.

Life-Threatening Asthma

PEF: <33% of best or predicted.

Chest examination: silent chest.

Oxygenation: significant hypoxaemia.

PaCO₂: normal or raised.

Cyanosis: may be present.

Respiratory effort: poor or decreasing.

Neurological state: exhaustion, confusion, or reduced consciousness.

Cardiovascular features: hypotension or arrhythmia may develop.

16. Immediate Management – Note Form

Oxygen: controlled supplemental oxygen, generally targeting SpO₂ around 94–98%.

Bronchodilator: repeated or nebulised salbutamol.

Antimuscarinic: add nebulised ipratropium in severe or life-threatening attacks.

Steroids: give systemic corticosteroids early.

Magnesium: consider IV magnesium sulfate if the response to initial treatment is inadequate.

Antibiotics: only when bacterial infection is suspected or confirmed.

Aminophylline/IV salbutamol: not routine; reserve for selected refractory cases with specialist input.

Ventilation: consider urgently if respiratory failure, exhaustion, deteriorating consciousness, worsening hypoxaemia, or rising PaCO₂ develops.

Key Clinical Pattern

In acute asthma, a patient initially tends to hyperventilate and lower their PaCO₂. Therefore, a normal PaCO₂ is not reassuring in a severely breathless asthmatic—it may indicate that respiratory muscles are beginning to fail.

Remember the distinction:

Acute severe asthma → PEF 33–50%, RR ≥25/min, HR ≥110/min, inability to complete sentences.

Life-threatening asthma → PEF <33%, silent chest, hypoxaemia, normal/raised PaCO₂, cyanosis, exhaustion, hypotension, arrhythmia, or altered consciousness.

Initial treatment centres on oxygen when hypoxaemic + repeated inhaled/nebulised β₂-agonist + ipratropium + early systemic corticosteroids, with IV magnesium and critical-care support when the response is inadequate.

Medicine – Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a common, progressive respiratory disorder characterised by persistent airflow limitation that is not fully reversible. The airflow obstruction usually develops gradually over years and reflects a combination of small-airway disease, chronic bronchitis, and emphysema.

COPD is associated with substantial morbidity, recurrent exacerbations, reduced exercise tolerance, impaired quality of life, and increased mortality.

1. Definition

COPD is characterised by chronic respiratory symptoms together with persistent airflow obstruction.

The obstruction does not fluctuate markedly over short periods in the way that asthma often does, although some reversibility can still be present.

Modern diagnosis relies on post-bronchodilator spirometry, rather than simply describing airflow obstruction as “fixed.”

2. Main Cause

The most important risk factor is cigarette smoking.

Long-term exposure to tobacco smoke causes chronic airway inflammation, mucus hypersecretion, small-airway narrowing, and destruction of alveolar tissue.

However, COPD can also occur in never-smokers because of factors such as biomass fuel exposure, occupational dusts and fumes, air pollution, impaired lung development, and α1-antitrypsin deficiency.

3. Chronic Bronchitis and Emphysema

Patients with COPD may have varying proportions of chronic bronchitis, small-airway disease, and emphysema.

These abnormalities frequently overlap, so patients do not usually fall neatly into one category.

4. Chronic Bronchitis

Chronic bronchitis is a clinical definition.

Traditionally, it is defined as a productive cough for at least 3 months in each of 2 consecutive years, after excluding other causes of chronic cough.

The condition reflects chronic mucus hypersecretion and airway inflammation.

5. Emphysema

Emphysema is a pathological condition characterised by permanent enlargement of airspaces distal to the terminal bronchioles with destruction of alveolar walls.

This destruction reduces elastic recoil and causes premature airway collapse during expiration.

Although originally defined pathologically, emphysema can now often be identified and quantified on CT imaging.

Clinical Features

6. Chronic Cough

A chronic cough is common and is often productive of sputum.

Some patients may have cough and sputum production for years before significant breathlessness develops.

7. Breathlessness

Progressive exertional breathlessness is one of the most important symptoms of COPD.

It usually worsens gradually over time and eventually may limit ordinary daily activities.

8. Wheeze

Wheeze may occur because of airflow narrowing and dynamic airway collapse.

Its presence does not automatically indicate asthma, since wheeze is common in COPD as well.

9. Recurrent Exacerbations

Patients may experience recurrent acute exacerbations, characterised by a sustained worsening of respiratory symptoms beyond normal day-to-day variation.

Typical features include increased breathlessness, increased cough, greater sputum volume, and sometimes increased sputum purulence.

Exacerbations may be triggered by viral infections, bacterial infections, air pollution, or other environmental factors.

Spirometry

10. FEV₁/FVC Ratio

The diagnosis of persistent airflow obstruction is based on spirometry.

The modern standard is a post-bronchodilator FEV₁/FVC ratio <0.70.

Older teaching sometimes used thresholds such as <75%, but the fixed 0.70 ratio is more commonly used in modern guidelines, with interpretation adjusted for age when appropriate.

11. FEV₁

FEV₁ is useful for assessing the degree of airflow limitation.

An FEV₁ below 80% predicted may support obstructive lung disease, but COPD diagnosis is not based on FEV₁ alone.

Severity assessment now also considers symptoms, exacerbation frequency, hospitalisations, oxygenation, comorbidities, and functional limitation, not just spirometric percentage bands.

Acute Management

12. Bronchodilators

Acute exacerbations are treated with short-acting bronchodilators, typically a short-acting β₂-agonist such as salbutamol, often with an antimuscarinic such as ipratropium.

Nebulised therapy may be used in more severe attacks.

13. Controlled Oxygen Therapy

Oxygen must be given carefully in patients at risk of hypercapnic respiratory failure.

In many acute COPD exacerbations, the usual target oxygen saturation is 88–92% until arterial blood gas results are available.

The aim is to correct dangerous hypoxaemia without causing excessive worsening of CO₂ retention.

14. Corticosteroids

Short courses of systemic corticosteroids are commonly used in moderate or severe exacerbations because they can shorten recovery time and improve lung function.

They are not used simply as an old-style “steroid reversibility trial” to decide long-term treatment.

15. Antibiotics

Antibiotics may be indicated when there is evidence of bacterial infection, especially with increased sputum purulence, increased sputum volume, or more severe exacerbation requiring ventilation.

Chronic Management

16. Smoking Cessation

Smoking cessation is the single most important intervention for patients who smoke.

It slows the accelerated decline in lung function and reduces exacerbations, cardiovascular risk, and overall mortality.

It is more accurate to say that smoking cessation is the most important modifiable measure rather than the only treatment that can influence disease progression.

17. Vaccination

Patients with COPD should receive appropriate influenza vaccination and pneumococcal vaccination.

Other vaccines may also be indicated depending on age and local recommendations.

18. Short-Acting Bronchodilators

Patients with intermittent symptoms may use a short-acting β₂-agonist (SABA) or a short-acting muscarinic antagonist (SAMA) as required.

These drugs provide rapid symptom relief.

19. Long-Acting Bronchodilators

For persistent symptoms, modern treatment generally relies on long-acting bronchodilators.

These include:

LABA – long-acting β₂-agonists

and

LAMA – long-acting muscarinic antagonists.

Many symptomatic patients benefit from LABA + LAMA combination therapy.

This has largely replaced older stepwise regimens based mainly on repeated short-acting bronchodilator use.

20. Inhaled Corticosteroids

Inhaled corticosteroids (ICS) are not routinely given to every patient with COPD.

They are most useful in selected patients with frequent exacerbations, higher blood eosinophil counts, or coexisting asthma features.

ICS is often used in combination with long-acting bronchodilators rather than as monotherapy.

The older practice of giving a steroid trial and continuing ICS only if FEV₁ improves by >15% is no longer the standard approach.

21. Triple Therapy

Patients with persistent exacerbations despite dual bronchodilation may benefit from triple inhaler therapy:

LABA + LAMA + ICS.

The decision depends on symptoms, exacerbation history, blood eosinophils, pneumonia risk, and other clinical factors.

22. Pulmonary Rehabilitation

Pulmonary rehabilitation is an important non-drug treatment for symptomatic patients.

It combines exercise training, education, breathing strategies, and multidisciplinary support and can improve exercise capacity, breathlessness, and quality of life.

23. Long-Term Oxygen Therapy

Long-term oxygen therapy (LTOT) is indicated in selected patients with persistent severe chronic hypoxaemia.

It is not prescribed simply because the COPD is spirometrically “severe.”

Typical eligibility depends on arterial oxygen tension and complications such as pulmonary hypertension, cor pulmonale, or secondary polycythaemia.

Complications

24. Respiratory Failure

Advanced COPD can cause respiratory failure.

Patients may initially develop hypoxaemia and later progress to type 2 respiratory failure with hypercapnia, especially during exacerbations.

25. Recurrent Exacerbations

Frequent exacerbations accelerate functional decline and are associated with worse quality of life and increased mortality.

Patients with repeated exacerbations may require escalation of inhaled therapy and further investigation for contributing factors.

26. Cor Pulmonale

Chronic hypoxaemia can cause hypoxic pulmonary vasoconstriction, leading to pulmonary hypertension.

Over time, this may produce right-sided heart strain and cor pulmonale.

27. Secondary Polycythaemia

Persistent hypoxaemia stimulates erythropoietin production and may cause secondary polycythaemia.

The resulting increase in red cell mass can increase blood viscosity.

28. Pneumothorax

Patients with emphysema may develop bullae, which can rupture and produce a spontaneous pneumothorax.

This may cause sudden pleuritic chest pain and acute worsening of breathlessness.

29. Lung Cancer

COPD is strongly associated with lung cancer, largely because tobacco exposure is a major shared risk factor.

COPD itself may also be associated with additional cancer risk beyond smoking alone.

30. Osteoporosis

Patients with COPD have an increased risk of osteoporosis.

Contributing factors include smoking, low body weight, reduced physical activity, chronic inflammation, vitamin D deficiency, and repeated or prolonged exposure to systemic corticosteroids.

31. Pink Puffer and Blue Bloater

Older teaching divided COPD patients into “pink puffers” and “blue bloaters.”

The pink-puffer pattern was associated mainly with emphysema, marked breathlessness, relatively preserved ventilation, and normal or low PaCO₂ until later disease.

The blue-bloater pattern was associated more with chronic bronchitis, hypoxaemia, hypercapnia, cyanosis, pulmonary hypertension, and cor pulmonale.

These terms are now regarded as historical rather than formal clinical classifications, because most patients have overlapping features.

Key Clinical Pattern

Think of COPD in a patient, usually with a significant smoking or inhalational exposure history, who has progressive exertional breathlessness, chronic cough with or without sputum, wheeze, and recurrent exacerbations.

The key spirometric finding is persistent post-bronchodilator airflow obstruction with FEV₁/FVC <0.70.

Modern long-term treatment centres on smoking cessation, vaccination, long-acting bronchodilators, pulmonary rehabilitation, selective use of inhaled corticosteroids, prevention of exacerbations, and LTOT when severe chronic hypoxaemia is present.

Important complications include respiratory failure, recurrent exacerbations, pulmonary hypertension and cor pulmonale, secondary polycythaemia, pneumothorax, osteoporosis, and lung cancer.