Respiratory: Anatomy, Physiology and Pharmacology

🫁 Respiratory anatomy, physiology and pharmacology -the lungs have one job: to get oxygen into the blood and carbon dioxide out. Understanding the airways, the mechanics of breathing, ventilation–perfusion matching and the oxygen dissociation curve explains most respiratory symptoms, blood gases and treatments. Most respiratory drugs either open the airways, reduce airway inflammation, clear mucus, slow fibrosis or treat infection.
Your four questions for every drug: How does it work? What is it used for? What are the important side effects and safety issues? What does it interact with, and how is it monitored?

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The Airways

• Upper airway -nose (warms, humidifies and filters air), pharynx, larynx (vocal cords -the narrowest point in adults; in young children the narrowest point is below the cords, at the cricoid).
• Trachea -about 10–12 cm long, from C6 to the carina at about T4/T5 (level of the sternal angle); C-shaped cartilage rings, open at the back.
• Main bronchi:
  • Right main bronchus -wider, shorter and more vertical -inhaled foreign bodies and aspiration go to the right lung more often (lower lobe when upright; posterior segment of the upper lobe and apical segment of the lower lobe when lying down).
  • Left main bronchus -longer, more horizontal, passes under the aortic arch.
• Branching -about 23 generations: lobar → segmental bronchi → bronchioles → terminal bronchioles (end of the conducting zone -no gas exchange) → respiratory bronchioles → alveolar ducts → alveoli (the respiratory zone; about 300–500 million alveoli, surface area about 70 m²).
• Cartilage is present down to the small bronchi; bronchioles have no cartilage and rely on smooth muscle and surrounding lung tissue to stay open (they collapse in emphysema -air trapping).
• Airway smooth muscle -contracts in asthma (bronchospasm); controlled by the vagus (muscarinic M3 receptors -constrict) and circulating adrenaline (beta-2 receptors -relax).

Lungs, Lobes and Segments

• Right lung -three lobes (upper, middle, lower), divided by the oblique and horizontal fissures; 10 bronchopulmonary segments.
• Left lung -two lobes (upper and lower), one oblique fissure; the lingula (part of the upper lobe) is the equivalent of the right middle lobe; the cardiac notch makes room for the heart.
• Bronchopulmonary segments -each has its own bronchus and artery, so a segment can be removed surgically.
• Hilum -where the main bronchus, pulmonary artery, pulmonary veins, bronchial vessels, lymph nodes and nerves enter the lung (enlarged hilar nodes -sarcoidosis, TB, lymphoma, lung cancer).
• Lobes on examination and X-ray:
  • From the front, you mainly hear the upper lobes (and right middle lobe on the right).
  • From the back, you mainly hear the lower lobes.
  • Right middle lobe pneumonia blurs the right heart border; lingula blurs the left heart border; lower lobe disease blurs the diaphragm (the "silhouette sign").
• Lymphatics drain to hilar and mediastinal nodes (important in lung cancer staging).

Pleura and Surface Anatomy

• Pleura -two layers with a thin film of fluid between them (the pleural space, normally about 10–20 mL):
  • Visceral pleura -covers the lung; no pain fibres.
  • Parietal pleura -lines the chest wall, diaphragm and mediastinum; pain-sensitive (intercostal nerves -localised pleuritic pain; the central diaphragm via the phrenic nerve -pain referred to the shoulder tip).
  • The pleural space has negative pressure, which keeps the lung expanded; air (pneumothorax) or fluid (effusion) lets the lung collapse.
• Surface markings ("6, 8, 10" for the lungs; pleura about two ribs lower):
  • Lung lower edge -6th rib in the mid-clavicular line, 8th in the mid-axillary line, 10th at the back.
  • Pleura lower edge -8th, 10th and 12th ribs (the gap is the costodiaphragmatic recess where effusions collect).
  • Lung apex -about 2–3 cm above the medial third of the clavicle (at risk with subclavian lines -pneumothorax).
  • Oblique fissure -from about T3 at the back to the 6th costal cartilage at the front; horizontal fissure (right) -along the 4th costal cartilage.
• Intercostal neurovascular bundle -runs in the groove under each rib (vein, artery, nerve -"VAN" from top to bottom) -so needles and drains are inserted just above the rib below.
• Safe triangle for chest drains -lateral border of pectoralis major, lateral border of latissimus dorsi, a line at the level of the nipple (5th intercostal space), and the base of the axilla.

Muscles of Breathing

• Diaphragm -the main muscle of breathing (about 70% of quiet inspiration); dome-shaped; contracts and flattens to enlarge the chest.
  • Supplied by the phrenic nerves (C3, C4, C5 -"C3, 4, 5 keeps the diaphragm alive") -high cervical spinal cord injury stops breathing.
  • Openings -IVC at T8, oesophagus at T10, aorta at T12.
  • Diaphragm weakness -orthopnoea, breathlessness lying flat or in water, paradoxical inward movement of the abdomen on breathing in, FVC falls on lying down.
• External intercostals -lift the ribs ("bucket handle" and "pump handle" movements).
• Accessory muscles of inspiration -sternocleidomastoid, scalenes, trapezius -used in respiratory distress (a sign of increased work of breathing).
• Expiration -normally passive (elastic recoil of the lungs); active in exercise, coughing and airway obstruction (internal intercostals, abdominal muscles).
• Upper airway muscles (genioglossus) keep the throat open -they relax in sleep, alcohol and sedation (obstructive sleep apnoea).

Blood Supply of the Lungs

• Two blood supplies:
  • Pulmonary circulation -the whole cardiac output passes through the lungs from the right ventricle; low pressure (mean about 15 mmHg) and low resistance; returns oxygenated blood to the left atrium via the pulmonary veins.
  • Bronchial circulation -small systemic arteries from the aorta supply the airways and lung tissue; source of massive haemoptysis (treated by bronchial artery embolisation).
• Because of the dual supply, pulmonary infarction is uncommon after PE (usually with small peripheral clots -pleuritic pain and haemoptysis).
• Hypoxic pulmonary vasoconstriction -small pulmonary arteries constrict in areas with low oxygen, diverting blood to better-ventilated lung (the opposite of systemic arteries). Widespread chronic hypoxia (COPD, altitude, sleep apnoea) causes pulmonary hypertension and right heart failure (cor pulmonale).
• Recruitment and distension -the pulmonary circulation opens more vessels as cardiac output rises (e.g. in exercise), so pressure barely rises.
• Lymphatics clear fluid from the interstitium -fluid leaks into the alveoli when capillary pressure is high (heart failure) or capillaries are damaged (ARDS).

Cells of the Airways and Alveoli

• Ciliated columnar epithelium -lines the airways down to the bronchioles; cilia beat mucus upwards (the mucociliary escalator); damaged by smoking; abnormal in primary ciliary dyskinesia.
• Goblet cells and submucosal glands -produce mucus (increased in chronic bronchitis and asthma).
• Club cells (Clara cells) -in the bronchioles; secrete protective proteins.
• Type I pneumocytes -flat cells forming about 95% of the alveolar surface; very thin barrier for gas exchange; easily damaged.
• Type II pneumocytes -make surfactant and can divide to repair the alveoli.
• Surfactant -lowers surface tension so small alveoli don't collapse at the end of breathing out (Laplace's law); deficient in premature babies (respiratory distress syndrome) and damaged in ARDS.
• Alveolar macrophages -engulf dust and microbes ("dust cells").
• Mast cells and eosinophils -key in allergic (type 2) asthma; release histamine, leukotrienes and other mediators.
• Neuroendocrine (Kulchitsky) cells -origin of carcinoid tumours and small cell lung cancer.

Lung Development

• The lungs develop from a bud of the foregut (so a tracheo-oesophageal fistula can occur with oesophageal atresia).
• Airways branch through the first two trimesters; gas-exchanging sacs form from about 24 weeks; alveoli keep multiplying until about age 8.
• Surfactant production starts around 24 weeks and is usually enough by about 34–36 weeks.
• Antenatal corticosteroids (dexamethasone or betamethasone) speed lung maturation -offered for threatened preterm birth (from 24 weeks to 33+6 weeks, and considered up to 35+6 weeks).
• Congenital diaphragmatic hernia -abdominal organs in the chest compress the developing lung (pulmonary hypoplasia).
• Oligohydramnios (e.g. kidney agenesis, ruptured membranes) also causes pulmonary hypoplasia -the fetus needs to "breathe" amniotic fluid for lungs to grow.

Mechanics of Breathing

• Inspiration -the diaphragm and intercostals enlarge the chest → pleural pressure becomes more negative → alveolar pressure falls below atmospheric pressure → air flows in.
• Expiration -elastic recoil of the lungs pushes air out (passive at rest).
• Compliance -how easily the lungs stretch (change in volume per change in pressure):
  • Low compliance (stiff lungs) -pulmonary fibrosis, oedema, ARDS, pneumonia; also chest wall problems (obesity, kyphoscoliosis) -restrictive pattern; small, fast breaths.
  • High compliance (floppy lungs) -emphysema (loss of elastic tissue) -lungs over-inflate and air is trapped.
• Airway resistance:
  • Mostly in the medium-sized bronchi (not the small airways, because there are so many of them in parallel).
  • Resistance rises sharply as airways narrow -by Poiseuille's law, resistance is proportional to 1/radius⁴ (halving the radius increases resistance 16 times).
  • Increased by bronchospasm, mucus, oedema, and loss of airway support (emphysema) -obstructive pattern.
• Dynamic airway compression -on forced expiration, pressure around the airways rises and squeezes them shut (worse in emphysema -hence pursed-lip breathing, which keeps airways open).
• Work of breathing -rises with stiff lungs or narrow airways; signs include tachypnoea, accessory muscle use, recession and tripod positioning; exhaustion leads to type 2 respiratory failure.
• Laminar and turbulent flow -turbulent flow in large airways and at narrowings produces sounds (stridor, wheeze); heliox (helium–oxygen, low density) reduces turbulent resistance in upper airway obstruction.

Lung Volumes

Volume	Meaning	Typical adult value
Tidal volume (TV)	Air moved in a normal breath	About 500 mL (6–8 mL/kg)
Inspiratory reserve volume	Extra air that can be breathed in after a normal breath	About 3 L
Expiratory reserve volume	Extra air that can be breathed out after a normal breath	About 1.1 L
Residual volume (RV)	Air left after maximal expiration (can't be measured by spirometry)	About 1.2 L
Vital capacity (VC)	Maximal breath out after maximal breath in (FVC when forced)	About 4.5–5 L
Functional residual capacity (FRC)	Air in the lungs at the end of a normal breath out (RV + ERV) -the body's oxygen store between breaths	About 2.3 L
Total lung capacity (TLC)	All the air in the lungs after maximal inspiration	About 6 L

• Obstruction (COPD, asthma) -air trapping: raised RV, FRC and TLC (hyperinflation).
• Restriction (fibrosis, obesity, chest wall, neuromuscular) -reduced TLC, VC and FRC.
• FRC falls when lying flat, in obesity, pregnancy and anaesthesia -so oxygen stores fall and hypoxia comes on faster (pre-oxygenate before intubation).
• Spirometry measures FEV1 and FVC; RV, FRC and TLC need body plethysmography or gas dilution (see the Respiratory Investigations chapter).

Ventilation and Dead Space

• Minute ventilation = tidal volume × respiratory rate (about 500 mL × 12 = 6 L/min).
• Anatomical dead space -the conducting airways (no gas exchange) -about 150 mL (roughly 2 mL/kg).
• Alveolar ventilation = (tidal volume − dead space) × rate -this is what removes CO2.
• Fast, shallow breathing is inefficient -e.g. 25 breaths of 200 mL = 5 L/min minute ventilation, but only (200 − 150) × 25 = 1.25 L/min alveolar ventilation → CO2 rises (seen in exhaustion, neuromuscular weakness, opioid toxicity).
• Physiological dead space = anatomical plus alveolar dead space (alveoli that are ventilated but not perfused -e.g. PE, emphysema, low cardiac output).
• PaCO2 is inversely proportional to alveolar ventilation -halve the ventilation, double the CO2. So a high PaCO2 always means inadequate alveolar ventilation (type 2 respiratory failure).
• Regional differences -in an upright person, the lung bases receive more ventilation and more blood flow than the apices (gravity); TB favours the apices (high oxygen, less blood flow).

Gas Exchange

• Diffusion across the alveolar–capillary membrane follows Fick's law -faster with a larger surface area, a bigger pressure difference, and a thinner membrane:
  • Less surface area -emphysema, lung resection, PE (less perfused capillary bed).
  • Thicker membrane -fibrosis, oedema.
  • Measured by gas transfer (TLCO/DLCO) using carbon monoxide.
• CO2 diffuses about 20 times more easily than oxygen -so diffusion problems cause hypoxaemia (especially on exercise) long before CO2 rises.
• Blood normally spends about 0.75 seconds in the capillary but equilibrates in about 0.25 seconds -there's reserve, used up in exercise (desaturation on walking in ILD).
• Alveolar gas equation -estimates the oxygen in the alveoli:
  • PAO2 = FiO2 × (atmospheric pressure − water vapour pressure) − PaCO2 ÷ 0.8.
  • On room air at sea level: PAO2 ≈ 20 − (PaCO2 × 1.25) kPa (about 13.7 kPa if PaCO2 is 5 kPa).
• A–a gradient = PAO2 − PaO2 -normally under about 2 kPa in young adults (rises with age):
  • Normal gradient with low PaO2 -hypoventilation (lungs healthy -e.g. opioids, neuromuscular weakness) or low inspired oxygen (altitude).
  • Raised gradient -a lung problem: V/Q mismatch, shunt or diffusion impairment.

Ventilation–Perfusion Matching

• For efficient gas exchange, ventilation (V) and blood flow (Q) must match -the overall V/Q ratio is about 0.8.
• Low V/Q (perfused but poorly ventilated) -asthma, COPD, pneumonia, atelectasis -the commonest cause of hypoxaemia; corrects with extra oxygen.
• Shunt (V/Q = 0 -perfused but not ventilated at all) -collapsed or fluid-filled alveoli (pneumonia, ARDS, oedema), intracardiac shunts, pulmonary AVMs -hypoxaemia that responds poorly to oxygen; needs PEEP or CPAP to open alveoli.
• Dead space (V/Q = infinity -ventilated but not perfused) -PE, emphysema, low cardiac output; raises the work of breathing.
• Hypoxic pulmonary vasoconstriction limits V/Q mismatch by diverting blood away from poorly ventilated areas.
• Why some drugs worsen oxygenation -bronchodilators and vasodilators can release hypoxic vasoconstriction, briefly worsening V/Q and saturations.
• Why high-flow oxygen raises CO2 in COPD -mainly by releasing hypoxic vasoconstriction (more blood to poorly ventilated areas → more dead space) and the Haldane effect (oxygenated haemoglobin carries less CO2) -not mainly by abolishing "hypoxic drive".
• Positioning -in one-sided lung disease, lying with the good lung down improves oxygenation (more blood flow to the better lung).

Causes of Hypoxaemia

Mechanism	A–a gradient	Response to oxygen	Examples
V/Q mismatch	Raised	Good	Asthma, COPD, pneumonia, PE
Shunt	Raised	Poor	ARDS, severe pneumonia, pulmonary oedema, AVMs, cyanotic heart disease
Diffusion impairment	Raised (especially on exercise)	Good	Pulmonary fibrosis, emphysema
Hypoventilation	Normal (and CO2 is high)	Good (but CO2 stays high)	Opioids, neuromuscular disease, chest wall disease, obesity hypoventilation
Low inspired oxygen	Normal	Good	High altitude, aircraft cabins

• Type 1 respiratory failure -PaO2 under 8 kPa with normal or low PaCO2 (V/Q mismatch, shunt, diffusion).
• Type 2 respiratory failure -PaO2 under 8 kPa with PaCO2 over 6.0 kPa (hypoventilation -COPD, neuromuscular, sedation, exhaustion).
• Tissue hypoxia without hypoxaemia -anaemia, carbon monoxide poisoning, low cardiac output, cyanide (cells can't use oxygen).

Oxygen Transport

• Most oxygen (about 98%) is carried bound to haemoglobin; only a little is dissolved in plasma. Each gram of haemoglobin carries about 1.34 mL of oxygen when fully saturated.
• Oxygen content ≈ 1.34 × Hb (g/L ÷ 10) × saturation -so anaemia reduces oxygen delivery even with normal saturations.
• Oxygen dissociation curve -S-shaped (haemoglobin binds oxygen more easily as more is bound -cooperative binding):
  • The flat upper part -saturation stays high even if PaO2 falls a bit (safety margin); also why giving more oxygen to someone at 97% adds little.
  • The steep part (below about 8 kPa / 90%) -small falls in PaO2 cause big falls in saturation; tissues can unload oxygen easily.
  • P50 (PaO2 at 50% saturation) -about 3.5 kPa.
  • Rough guide -PaO2 8 kPa ≈ 90%; PaO2 5.3 kPa ≈ 75% (mixed venous blood).
• Right shift (oxygen released more easily to tissues) -raised CO2, acidosis (Bohr effect), raised temperature, raised 2,3-DPG (anaemia, altitude, chronic hypoxia), exercise.
• Left shift (haemoglobin holds on to oxygen) -fetal haemoglobin (helps the fetus take oxygen from the mother), carbon monoxide, alkalosis, low temperature, low 2,3-DPG (stored blood), methaemoglobin.
• Carbon monoxide -binds haemoglobin about 240 times more strongly than oxygen and shifts the curve left -pulse oximetry reads falsely normal; measure carboxyhaemoglobin on a blood gas; give 100% oxygen (shortens CO half-life from about 5 hours to about 1 hour).
• Methaemoglobinaemia (dapsone, local anaesthetics like prilocaine and benzocaine, nitrites) -iron oxidised so it can't carry oxygen; chocolate-brown blood, oximetry about 85% regardless; treat with methylene blue.
• Cyanosis -visible when there is about 50 g/L of deoxygenated haemoglobin -may be absent in anaemia, and seen earlier in polycythaemia.

Carbon Dioxide Transport

• CO2 is carried in three forms:
  • Bicarbonate (about 70%) -CO2 + water → carbonic acid → H+ + HCO3− (fast in red cells via carbonic anhydrase); bicarbonate moves out of the cell in exchange for chloride (the "chloride shift").
  • Bound to haemoglobin as carbamino compounds (about 20–25%).
  • Dissolved in plasma (about 5–10%).
• Haldane effect -deoxygenated haemoglobin carries more CO2; when blood is oxygenated in the lungs, CO2 is released. Giving high-flow oxygen to someone with COPD releases CO2 from haemoglobin, adding to hypercapnia.
• CO2 and pH -rising CO2 makes blood more acidic (respiratory acidosis); the kidneys compensate over days by keeping bicarbonate.
• CO2 is a vasodilator in the brain -high CO2 causes headache, bounding pulse, warm hands, flapping tremor, drowsiness and raised intracranial pressure; low CO2 (hyperventilation) causes cerebral vasoconstriction, dizziness and tingling (and is used briefly to lower intracranial pressure).
• Acetazolamide (carbonic anhydrase inhibitor) -causes a mild metabolic acidosis that stimulates breathing (used for altitude sickness).

Control of Breathing

• Respiratory centres in the medulla and pons set the rhythm; the cortex allows voluntary control (breath-holding, speech).
• Central chemoreceptors (medulla) -respond to CO2 via changes in pH of the cerebrospinal fluid -the main minute-to-minute drive to breathe.
• Peripheral chemoreceptors (carotid bodies -glossopharyngeal nerve; aortic bodies -vagus) -respond mainly to low oxygen (especially PaO2 under about 8 kPa), and also to acidosis and CO2.
• Chronic hypercapnia (some COPD patients) -the central response to CO2 is blunted as bicarbonate rises, so low oxygen becomes relatively more important -but the main reason oxygen raises CO2 is V/Q change and the Haldane effect (see above).
• Lung receptors -stretch receptors (Hering–Breuer reflex), irritant receptors (cough, bronchoconstriction), J receptors (stimulated by oedema and fibrosis -breathlessness and fast breathing).
• Things that reduce the drive to breathe -opioids, benzodiazepines, alcohol, anaesthetics, gabapentinoids, brainstem stroke, hypothyroidism, sleep.
• Things that increase it -metabolic acidosis (Kussmaul breathing in DKA), hypoxia, fever, anxiety, pain, PE, salicylates, progesterone (pregnancy), stimulants.
• Breathing patterns:
  • Cheyne–Stokes -waxing and waning breathing with pauses -heart failure, stroke, opioids, altitude.
  • Kussmaul -deep, sighing breaths -metabolic acidosis.
  • Apneustic and ataxic breathing -brainstem damage.

Acid–Base Balance

• Henderson–Hasselbalch -pH depends on the ratio of bicarbonate (kidneys) to CO2 (lungs). The lungs adjust CO2 in minutes; the kidneys adjust bicarbonate over 2–5 days.
• Four primary disturbances:
  • Respiratory acidosis -high CO2 (hypoventilation -COPD, opioids, neuromuscular). Acute -low pH, normal bicarbonate; chronic -near-normal pH, high bicarbonate (renal compensation).
  • Respiratory alkalosis -low CO2 (hyperventilation -anxiety, PE, pneumonia, pain, early salicylate poisoning, pregnancy, altitude).
  • Metabolic acidosis -low bicarbonate (DKA, lactic acidosis, AKI, diarrhoea); the lungs compensate by blowing off CO2 (Kussmaul breathing); check the anion gap.
  • Metabolic alkalosis -high bicarbonate (vomiting, diuretics); the lungs compensate by breathing less (CO2 rises -limited by hypoxia).
• Acute-on-chronic respiratory acidosis (COPD exacerbation) -high bicarbonate (chronic) but pH under 7.35 (acute rise in CO2) -consider NIV if pH is under 7.35 and PaCO2 over 6.5 kPa despite optimal treatment.
• Compensation never overcorrects -if the pH is on the "wrong side", there's a second primary disturbance.
• Step-by-step blood gas interpretation is covered in the Respiratory Investigations and Respiratory Emergencies chapters.

Lung Defences

• Nose and upper airway -filtering and humidification; large particles trapped.
• Cough and sneeze reflexes -impaired by stroke, sedation, neuromuscular disease, rib fractures, pain -leading to aspiration pneumonia.
• Mucociliary escalator -damaged by smoking, viral infections, dehydration; abnormal in cystic fibrosis (thick mucus from CFTR defect) and primary ciliary dyskinesia (bronchiectasis, sinusitis, infertility, situs inversus in Kartagener syndrome).
• Immune defences -secretory IgA, alveolar macrophages, neutrophils, surfactant proteins, lymphocytes.
  • Antibody deficiency -recurrent bacterial chest infections and bronchiectasis.
  • T-cell deficiency (HIV, steroids, transplant drugs) -PCP, TB, fungal and viral infections.
  • Neutropenia -bacterial and fungal (Aspergillus) infections.
• Alpha-1 antitrypsin -made in the liver; protects lung tissue from neutrophil elastase; deficiency causes early emphysema (lower lobes) and liver disease.

Exercise, Altitude, Pregnancy and Sleep

• Exercise -minute ventilation can rise more than tenfold; in healthy people, the heart (not the lungs) usually limits exercise; lung disease limits it through breathlessness, desaturation and hyperinflation.
• Altitude -the oxygen fraction stays at 21%, but barometric pressure falls, so inspired oxygen falls:
  • Hypoxia → hyperventilation → respiratory alkalosis → kidneys excrete bicarbonate over days (acclimatisation); more 2,3-DPG; polycythaemia over weeks.
  • Hypoxic pulmonary vasoconstriction → pulmonary hypertension → risk of high-altitude pulmonary oedema.
  • Aircraft cabins are pressurised to the equivalent of about 1,500–2,400 m (PaO2 falls to about 8 kPa in healthy people) -see the fitness-to-fly guidance.
• Pregnancy -progesterone increases breathing (tidal volume up) → mild respiratory alkalosis (PaCO2 about 4 kPa) with compensated low bicarbonate; FRC falls as the uterus pushes up the diaphragm; breathlessness is common; a "normal" PaCO2 of 5.5 kPa in late pregnancy may mean the mother is tiring (e.g. severe asthma).
• Sleep -less drive to breathe, relaxed upper airway muscles, less response to CO2 -worsens sleep apnoea, hypoventilation in obesity, neuromuscular disease and COPD (REM sleep is the most vulnerable time).
• Ageing -loss of elastic recoil, stiffer chest wall, weaker muscles, a wider A–a gradient, and lower PaO2 (about 0.5 kPa less per decade after middle age is common).
• Diving -pressure rises 1 atmosphere for every 10 m; risks include barotrauma, pneumothorax, decompression illness, and air embolism.

Normal Values

Measure	Typical adult value
Respiratory rate	12–20 breaths/min
Oxygen saturation (air)	94–98% (88–92% target if at risk of hypercapnia)
pH	7.35–7.45
PaO2 on air	10–13 kPa (lower in older people)
PaCO2	4.7–6.0 kPa
Bicarbonate	22–26 mmol/L
Base excess	−2 to +2 mmol/L
Lactate	Under 2 mmol/L
A–a gradient	Under about 2 kPa (young adults; rises with age)
Tidal volume	About 500 mL (6–8 mL/kg)
Anatomical dead space	About 150 mL
FEV1/FVC ratio	Above the lower limit of normal (traditionally over 0.7)
Mean pulmonary artery pressure	20 mmHg or less
Pleural fluid (normal)	About 10–20 mL; pH about 7.6

Inhaler Devices and Technique

• Why inhalers -deliver drug straight to the airways: fast action, lower doses, fewer systemic side effects. Poor technique is the commonest reason inhalers "don't work" -check it at every review.
• Pressurised metered-dose inhaler (pMDI) -"puffer"; needs coordination of pressing and breathing in slowly and deeply, then holding the breath for about 10 seconds.
  • Use with a spacer -improves lung delivery and reduces mouth deposition (oral thrush); essential for children and in acute attacks (as effective as nebulisers in most).
  • Spacers -wash monthly, air-dry; replace every 6–12 months.
• Dry powder inhaler (DPI) (e.g. Turbohaler, Accuhaler, Ellipta) -breath-activated; needs a quick, forceful breath in; less suitable in severe attacks, young children and frail people with weak breaths.
• Soft mist inhaler (Respimat) -slow-moving mist; less coordination needed.
• Nebulisers -for severe attacks and people who can't use inhalers; driven by oxygen in asthma, but by air in COPD with hypercapnia (with supplemental nasal oxygen as needed).
• Environmental impact -pMDIs contain propellant gases with a high carbon footprint; DPIs or soft mist inhalers are lower-carbon alternatives where clinically suitable.
• Counting doses -patients should know when their inhaler is running out (dose counters).

Bronchodilators

• Beta-2 agonists -stimulate beta-2 receptors on airway smooth muscle → raise cAMP → relaxation.
  • SABA (short-acting) -salbutamol, terbutaline: work in minutes, last 4–6 hours; reliever.
  • LABA (long-acting) -salmeterol (slow onset, 12 hours), formoterol (fast onset, 12 hours -allows use as a reliever in MART/AIR), vilanterol, olodaterol, indacaterol (24 hours).
  • Side effects -tremor, tachycardia and palpitations, hypokalaemia (high doses), lactic acidosis (high-dose nebulised or IV salbutamol), headache, muscle cramps.
  • LABA alone must never be used in asthma -always with an inhaled steroid (increased risk of severe attacks and death).
• Antimuscarinics -block muscarinic (M3) receptors → less vagal bronchoconstriction and mucus secretion.
  • SAMA -ipratropium (in acute asthma and COPD exacerbations).
  • LAMA -tiotropium, umeclidinium, glycopyrronium, aclidinium -once or twice daily; mainly COPD; also add-on in severe asthma.
  • Side effects -dry mouth, constipation, urinary retention (prostate enlargement), blurred vision, and acute angle-closure glaucoma (nebulised drug escaping a face mask into the eyes -use a mouthpiece or goggles).
  • Don't use a LAMA and ipratropium together regularly.
• Theophylline -see Montelukast and Theophylline.

Inhaled Corticosteroids

• Mechanism -switch off inflammatory genes in airway cells → less eosinophilic (type 2) inflammation, less airway hyper-responsiveness; prevent attacks and reduce death in asthma.
• Examples -beclometasone, budesonide, fluticasone (propionate and furoate), mometasone, ciclesonide. Doses are graded as low, moderate or high (devices aren't interchangeable dose-for-dose -prescribe by brand).
• Uses -the foundation of asthma treatment (all adults now use ICS-containing treatment -no SABA-only treatment); COPD with asthmatic features or frequent exacerbations with raised blood eosinophils.
• Local side effects -oral thrush, hoarse voice (dysphonia) -reduce by using a spacer and rinsing the mouth after use.
• Systemic side effects (mainly at high doses) -adrenal suppression (steroid emergency card for high doses), osteoporosis, cataracts and glaucoma, skin thinning and bruising, growth slowing in children (small), raised glucose.
• Pneumonia -increased risk with ICS in COPD (especially fluticasone).
• Step down -once asthma is well controlled for 3 months, reduce to the lowest effective dose.

Combination Inhalers, AIR and MART

• ICS + LABA -budesonide–formoterol, beclometasone–formoterol, fluticasone–salmeterol, fluticasone furoate–vilanterol.
• Asthma (BTS/NICE/SIGN 2024) in adults and young people aged 12 and over:
  • AIR (anti-inflammatory reliever) -as-needed low-dose ICS–formoterol for mild asthma, instead of a SABA alone.
  • MART (maintenance and reliever therapy) -the same ICS–formoterol inhaler taken regularly and also as the reliever; escalate to moderate-dose MART if not controlled.
  • Then -check FeNO and eosinophils, add a LTRA or LAMA, refer for specialist care.
  • Formoterol is used because its onset is fast; salmeterol combinations can't be used as relievers.
  • Maximum daily doses of ICS–formoterol must be explained (e.g. no more than 12 puffs a day of budesonide–formoterol 200/6 in most adults -check the product).
• LABA + LAMA (e.g. umeclidinium–vilanterol, tiotropium–olodaterol) -first-line regular treatment for most people with COPD who remain breathless (NICE NG115).
• Triple therapy (LABA + LAMA + ICS in one inhaler -e.g. fluticasone furoate–umeclidinium–vilanterol, beclometasone–formoterol–glycopyrronium) -COPD with continued exacerbations (especially with raised eosinophils or asthmatic features); severe asthma.
• Fewer devices are better -use one inhaler type where possible to avoid technique confusion.

Montelukast and Theophylline

• Montelukast (leukotriene receptor antagonist):
  • Blocks cysteinyl leukotriene receptors → less bronchoconstriction and inflammation.
  • Uses -add-on in asthma, exercise-induced and aspirin-exacerbated asthma, allergic rhinitis with asthma, preschool wheeze (trial).
  • MHRA warning -neuropsychiatric reactions: sleep disturbance, nightmares, agitation, depression, behaviour changes and suicidal thoughts (children and adults) -warn patients and families and stop if they occur.
  • Rarely associated with eosinophilic granulomatosis with polyangiitis (often unmasked as steroids are reduced).
• Theophylline and aminophylline (methylxanthines):
  • Phosphodiesterase inhibition and adenosine receptor blockade → bronchodilatation; now rarely used.
  • Narrow therapeutic range -plasma level about 10–20 mg/L (55–110 micromol/L); check 4–6 hours after an oral dose, and before and during IV aminophylline.
  • Metabolised by CYP1A2 -levels raised by ciprofloxacin, clarithromycin, erythromycin, fluvoxamine, cimetidine, heart failure, liver disease, viral infection, stopping smoking; lowered by smoking, rifampicin, carbamazepine, phenytoin, alcohol.
  • Toxicity -nausea and vomiting, tachycardia, arrhythmias, seizures, hypokalaemia, hyperglycaemia, agitation -TOXBASE; activated charcoal (repeat doses), correct potassium, treat seizures.
  • Don't give an IV loading dose of aminophylline to someone already taking oral theophylline.

Oral and IV Steroids and Magnesium

• Acute asthma -prednisolone 40–50 mg once daily for at least 5 days (IV hydrocortisone if unable to swallow); no need to taper short courses.
• COPD exacerbation -prednisolone 30 mg daily for 5 days (NICE NG115).
• Other uses -sarcoidosis, organising pneumonia, hypersensitivity pneumonitis, some ILDs, ABPA, eosinophilic lung diseases, airway swelling.
• Side effects of repeated or long courses -hyperglycaemia (check glucose), hypertension, mood disturbance and insomnia, infection, osteoporosis (bone protection for 3 months or more), adrenal suppression (steroid card; don't stop suddenly after 3 weeks or more), weight gain, cataracts, peptic ulcers. Two or more courses a year in asthma means poor control -review and refer.
• Magnesium sulfate -smooth muscle relaxant; IV 1.2–2 g over 20 minutes in acute severe or life-threatening asthma not responding to initial treatment (single dose); also used in some COPD exacerbations. Watch for hypotension and flushing.

Biologics for Severe Asthma

Drug	Target	Used for
Omalizumab	IgE	Severe allergic asthma (raised IgE, sensitised to perennial allergens); also chronic urticaria
Mepolizumab, reslizumab	IL-5 (eosinophil growth and survival)	Severe eosinophilic asthma; mepolizumab also for EGPA and some nasal polyps
Benralizumab	IL-5 receptor (depletes eosinophils)	Severe eosinophilic asthma
Dupilumab	IL-4 receptor alpha (blocks IL-4 and IL-13)	Severe type 2 asthma (raised eosinophils or FeNO); also eczema, nasal polyps; can cause conjunctivitis and a rise in eosinophils
Tezepelumab	TSLP (an "upstream" alarmin)	Severe asthma including non-eosinophilic types

• Given by injection every 2–8 weeks under specialist severe asthma services (NICE TAs), for people with frequent exacerbations or needing maintenance oral steroids despite optimal inhaled treatment and good adherence.
• Reduce exacerbations and oral steroid use; response is reviewed at about 12 months.
• Risks -injection reactions, rare anaphylaxis (omalizumab), parasitic infections (anti-eosinophil drugs -screen travellers).

Mucolytics and CF Modulators

• Carbocisteine (and acetylcysteine) -thin mucus; for chronic productive cough in COPD; stop if no benefit after 4 weeks; avoid with active peptic ulcer.
• Hypertonic saline (nebulised 6–7%) -draws water into the airways; used in bronchiectasis and CF; can cause bronchospasm (give a bronchodilator first and test the first dose).
• Dornase alfa -enzyme that breaks down DNA from dead neutrophils in CF sputum.
• Mannitol (inhaled dry powder) -in CF.
• CFTR modulators -correct the faulty CFTR protein in cystic fibrosis:
  • Elexacaftor–tezacaftor–ivacaftor (Kaftrio, with ivacaftor) -for people with at least one F508del mutation (most people with CF) -large improvements in lung function, weight and survival.
  • Ivacaftor alone -for gating mutations (e.g. G551D).
  • Monitoring -LFTs (raised transaminases), eye checks in children (cataracts), mood; many CYP3A4 interactions (e.g. rifampicin, clarithromycin, azole antifungals).
• Airway clearance -physiotherapy techniques (active cycle of breathing, oscillating devices) are the mainstay in bronchiectasis and CF.
• Long-term macrolides (azithromycin) -anti-inflammatory and fewer exacerbations in bronchiectasis, CF and COPD (selected patients); check ECG (QT), hearing, LFTs, and exclude non-tuberculous mycobacteria first.

Antifibrotic Drugs

• Pirfenidone and nintedanib -slow the decline in lung function (FVC) in idiopathic pulmonary fibrosis; nintedanib is also used in progressive pulmonary fibrosis from other causes (NICE TAs). They don't reverse existing fibrosis.
• Pirfenidone -side effects: photosensitivity rash (sunscreen, cover up), nausea, loss of appetite and weight, fatigue; raised LFTs (monitor monthly at first).
• Nintedanib (tyrosine kinase inhibitor) -side effects: diarrhoea (very common -loperamide), nausea, raised LFTs; bleeding risk (care with anticoagulants); teratogenic.
• Avoid immunosuppression with steroids and azathioprine in IPF (harmful); steroids and immunosuppressants are used in inflammatory ILDs (e.g. CTD-ILD, hypersensitivity pneumonitis, NSIP).

Oxygen as a Drug

• Prescribe oxygen with a target saturation (BTS):
  • 94–98% for most acutely ill patients.
  • 88–92% for those at risk of hypercapnic respiratory failure -COPD, severe obesity, neuromuscular disease, chest wall deformity, cystic fibrosis, bronchiectasis -until a blood gas is available.
  • Critical illness (shock, cardiac arrest, major trauma, sepsis) -start with high-flow oxygen via a reservoir mask (15 L/min), then titrate.
• Delivery devices:
  • Nasal cannulae (1–4 L/min) -about 24–40%.
  • Venturi masks -fixed oxygen percentages (24%, 28%, 35%, 40%, 60%) -preferred when CO2 retention is a risk.
  • Simple face mask (5–10 L/min) -40–60%.
  • Non-rebreathe reservoir mask (15 L/min) -60–90%.
  • High-flow nasal oxygen -up to 60 L/min, warm and humidified, precise FiO2, some PEEP effect.
• Harms of too much oxygen -hypercapnia and acidosis in at-risk patients; possible harm in MI and stroke without hypoxia (don't give routinely); absorption collapse; retinopathy in premature babies; lung toxicity at very high concentrations.
• Home oxygen:
  • Long-term oxygen therapy (LTOT) -for stable patients with PaO2 under 7.3 kPa on air, or 7.3–8 kPa with polycythaemia, peripheral oedema or pulmonary hypertension; at least 15 hours a day; improves survival in COPD.
  • Smoking (and vaping near oxygen) is a serious fire and burns risk -assess before prescribing; home fire safety checks.

⚠️ Safety Pearl: Oxygen is a drug -prescribe it with a target range. In COPD, aim for 88–92% using a Venturi mask, and get a blood gas; but never withhold oxygen from a severely hypoxic patient for fear of CO2 retention.

Antibiotics and TB Drugs

• Community-acquired pneumonia (NICE NG138, BTS) -choose by severity (CURB-65) and local policy:
  • Low severity -amoxicillin for 5 days (doxycycline or clarithromycin if penicillin-allergic).
  • Moderate -amoxicillin plus clarithromycin (atypical cover).
  • High severity -co-amoxiclav plus clarithromycin (IV), or per local guidance.
  • Clarithromycin -QT prolongation; CYP3A4 inhibitor (raises statin, warfarin and theophylline effects). Doxycycline -avoid in pregnancy and under 12; photosensitivity; take upright with water.
• COPD exacerbation -antibiotics if sputum is purulent or there are signs of pneumonia (amoxicillin, doxycycline or clarithromycin).
• TB drugs -standard treatment for drug-sensitive pulmonary TB: RIPE (rifampicin, isoniazid, pyrazinamide, ethambutol) for 2 months, then rifampicin and isoniazid for 4 months:
  • Rifampicin -orange-red urine, tears and sweat (stains contact lenses); potent enzyme inducer (reduces the effect of the combined pill, warfarin, DOACs, antiretrovirals, steroids, methadone); hepatitis; flu-like symptoms.
  • Isoniazid -peripheral neuropathy (give pyridoxine), hepatitis (slow acetylators), enzyme inhibitor.
  • Pyrazinamide -hepatotoxicity, raised urate and gout, joint pains.
  • Ethambutol -optic neuritis (reduced visual acuity and red–green colour vision) -check vision before and during; reduce dose in renal impairment.
  • Check LFTs, U&E and vision at baseline; directly observed therapy if adherence is a concern; notify UKHSA (see the Respiratory Infection and TB chapter).
• Antifungals -voriconazole (aspergillosis -visual disturbance, photosensitivity, skin cancer risk, many interactions); itraconazole (ABPA, chronic aspergillosis).
• Co-trimoxazole -treatment and prophylaxis of Pneumocystis pneumonia; high potassium, rash, marrow suppression.
• Antivirals -oseltamivir for influenza in at-risk people (within 48 hours); COVID-19 antivirals in eligible high-risk patients.

Pulmonary Hypertension Drugs

• Used for pulmonary arterial hypertension (group 1) and CTEPH, only in specialist centres (see the Pulmonary Vascular and Sleep chapter). They target three pathways:
• Nitric oxide pathway -PDE5 inhibitors (sildenafil, tadalafil -never with nitrates; headache, flushing); riociguat (soluble guanylate cyclase stimulator -also for CTEPH; don't combine with PDE5 inhibitors).
• Endothelin pathway -endothelin receptor antagonists (bosentan, ambrisentan, macitentan) -teratogenic (effective contraception and monthly pregnancy tests), liver toxicity (monthly LFTs with bosentan), anaemia, oedema.
• Prostacyclin pathway -epoprostenol (continuous IV infusion -line infections, rebound if interrupted), iloprost (inhaled), treprostinil, selexipag (oral receptor agonist).
• Calcium channel blockers (high dose) -only for the small number who respond to vasoreactivity testing.
• Plus diuretics, anticoagulation in some, oxygen if hypoxic.

Drugs That Affect Breathing

• Respiratory depressants -opioids, benzodiazepines, Z-drugs, gabapentin and pregabalin, alcohol, barbiturates, anaesthetic agents. Combinations are especially dangerous (MHRA warnings on opioids with benzodiazepines or gabapentinoids). Highest risk -COPD, sleep apnoea, obesity hypoventilation, neuromuscular disease, older people, kidney or liver failure.
• Reversal -naloxone for opioids (titrated in small IV doses in palliative or chronic opioid users to avoid severe pain and withdrawal; short half-life -infusion may be needed); flumazenil for benzodiazepines (rarely used -seizure risk).
• Drugs that cause bronchospasm -beta-blockers (especially non-selective -propranolol, timolol eye drops), NSAIDs and aspirin (aspirin-exacerbated respiratory disease -asthma with nasal polyps), adenosine, some contrast agents and anaesthetic drugs.
• Cough -ACE inhibitors (dry cough in about 10%; switch to an ARB).
• Respiratory stimulants -doxapram (rarely used now; NIV is preferred); acetazolamide (altitude, some central sleep apnoea).
• Neuromuscular blockers and drugs that worsen myasthenia -aminoglycosides, magnesium, beta-blockers, fluoroquinolones, macrolides -can precipitate respiratory failure in myasthenia gravis.

Drugs That Damage the Lungs

Drug	Lung problem
Amiodarone	Pneumonitis and fibrosis (dose-related; baseline chest X-ray and lung function)
Methotrexate	Acute hypersensitivity pneumonitis (cough, fever, breathlessness -stop and seek advice)
Nitrofurantoin	Acute pneumonitis (within days) or chronic fibrosis (long-term use -older women on prophylaxis)
Bleomycin	Pulmonary fibrosis (dose-related; avoid high oxygen concentrations later)
Busulfan, cyclophosphamide, other chemotherapy	Pneumonitis and fibrosis
Immune checkpoint inhibitors (pembrolizumab, nivolumab)	Immune pneumonitis -urgent assessment; steroids
Ergot derivatives (cabergoline, bromocriptine)	Pleural and pulmonary fibrosis
Beta-blockers, NSAIDs	Bronchospasm
ACE inhibitors	Cough; angioedema
Opioids, benzodiazepines, gabapentinoids	Respiratory depression
Anticoagulants and antiplatelets	Haemoptysis; alveolar haemorrhage
Drugs causing lupus-like pleurisy (hydralazine, procainamide, isoniazid)	Pleuritis and effusions
Smoking, vaping, cocaine (crack lung)	COPD, cancer, ILD; acute lung injury

• Pneumotox (www.pneumotox.com) lists drug-induced lung diseases; see the Interstitial Lung Disease chapter.

Drug Reference Table

Drug	Key points
Salbutamol (SABA)	Beta-2 agonist reliever; tremor, tachycardia, low potassium, lactic acidosis at high doses.
Formoterol / salmeterol (LABA)	Never alone in asthma; formoterol's fast onset allows AIR and MART.
Ipratropium (SAMA)	Acute asthma and COPD; dry mouth; glaucoma risk with face-mask nebulisers.
Tiotropium / umeclidinium (LAMA)	COPD maintenance; urinary retention, dry mouth.
Budesonide / beclometasone / fluticasone (ICS)	Asthma foundation; thrush and hoarseness -spacer, rinse; pneumonia risk in COPD; steroid card at high doses.
Budesonide–formoterol	AIR (as needed) or MART in asthma; know the maximum daily puffs.
LABA–LAMA / triple therapy	COPD first-line regular treatment / COPD with exacerbations.
Montelukast	LTRA add-on; neuropsychiatric side effects (MHRA).
Theophylline / aminophylline	Level 10–20 mg/L; ciprofloxacin and clarithromycin raise levels; smoking lowers; toxicity -vomiting, arrhythmias, seizures.
Prednisolone	Asthma attack 40–50 mg for at least 5 days; COPD exacerbation 30 mg for 5 days.
Magnesium sulfate (IV)	Acute severe asthma -1.2–2 g over 20 minutes.
Omalizumab / mepolizumab / benralizumab / dupilumab / tezepelumab	Biologics for severe asthma (specialist).
Carbocisteine	Mucolytic for productive COPD; avoid with peptic ulcer.
Azithromycin (long-term)	Fewer exacerbations in bronchiectasis and COPD; ECG (QT), hearing, LFTs; exclude NTM.
Elexacaftor–tezacaftor–ivacaftor	CFTR modulator for CF (F508del); LFTs, CYP3A4 interactions.
Pirfenidone / nintedanib	Antifibrotics for IPF; photosensitivity / diarrhoea; LFTs.
Oxygen	Target 94–98% (88–92% if hypercapnia risk); LTOT if PaO2 under 7.3 kPa; fire risk.
Amoxicillin / clarithromycin / co-amoxiclav	Pneumonia by severity; clarithromycin -QT and CYP3A4 interactions.
Rifampicin / isoniazid / pyrazinamide / ethambutol	TB: orange secretions and enzyme induction / neuropathy (pyridoxine) / gout and hepatitis / optic neuritis.
Sildenafil / bosentan / epoprostenol	Pulmonary arterial hypertension (specialist); no nitrates with sildenafil; bosentan -liver, teratogenic.
Naloxone	Reverses opioid respiratory depression; short-acting -may need repeat or infusion.
Acetazolamide	Altitude sickness prevention; metabolic acidosis stimulates breathing.

Spot the Answer

Clue	Answer
Peanut inhaled by a toddler -which side?	Right main bronchus (wider, shorter, more vertical)
Aspiration pneumonia in a patient lying flat	Posterior segment of right upper lobe or apical segment of right lower lobe
Shoulder tip pain with a subphrenic abscess	Diaphragmatic pleura irritation (phrenic nerve C3–5)
Where to insert a chest drain	Safe triangle, just above the rib below (avoid the neurovascular bundle)
Premature baby at 28 weeks with grunting and ground-glass lungs	Surfactant deficiency (respiratory distress syndrome)
Raised TLC, RV and FRC	Hyperinflation and air trapping (COPD)
Hypoxaemia that barely improves on 60% oxygen	Shunt (e.g. ARDS, pulmonary AVM)
Low PaO2, high PaCO2, normal A–a gradient after an opioid overdose	Hypoventilation with healthy lungs
SpO2 99% in a headache-stricken family with a faulty boiler	Carbon monoxide poisoning -oximetry falsely normal
SpO2 stuck at 85% and brown blood after dapsone	Methaemoglobinaemia -methylene blue
Curve shift with fever, acidosis and raised CO2	Right shift (oxygen released more easily)
COPD patient on 15 L/min oxygen becomes drowsy	Oxygen-induced hypercapnia -Venturi mask, target 88–92%, ABG
pH 7.28, PaCO2 9.5 kPa, bicarbonate 34	Acute-on-chronic respiratory acidosis -consider NIV
Tremor and potassium 2.9 after back-to-back salbutamol nebulisers	Beta-2 agonist effects -monitor potassium
Eye pain and blurred vision after nebulised ipratropium by mask	Acute angle-closure glaucoma
Oral thrush and hoarse voice on an inhaler	ICS -use a spacer and rinse the mouth
Nightmares and low mood in a child on a new asthma tablet	Montelukast neuropsychiatric reaction
Vomiting and seizure in a theophylline user given ciprofloxacin	Theophylline toxicity (CYP1A2 inhibition)
Severe eosinophilic asthma on maintenance prednisolone	Refer for biologic (e.g. mepolizumab, benralizumab)
Orange urine and a failed contraceptive pill on TB treatment	Rifampicin (enzyme inducer)
Tingling feet on TB treatment	Isoniazid neuropathy -pyridoxine
Loss of red–green colour vision on TB treatment	Ethambutol optic neuritis
Severe sunburn-like rash on an IPF drug	Pirfenidone photosensitivity
Breathless with lung fibrosis on long-term nitrofurantoin	Drug-induced pulmonary fibrosis

Exam-style Scenarios

1. A 70-year-old man with COPD is brought in breathless and is given 15 L/min oxygen by the ambulance crew. An hour later he is drowsy. ABG: pH 7.24, PaO2 18 kPa, PaCO2 10.2 kPa, bicarbonate 33.
Answer: Acute-on-chronic hypercapnic respiratory failure, worsened by excessive oxygen.

• Reduce oxygen to a Venturi mask (24–28%), target 88–92% -don't stop oxygen abruptly.
• Mechanism -release of hypoxic pulmonary vasoconstriction (worse V/Q) and the Haldane effect, plus some loss of hypoxic drive.
• Bronchodilators, steroids, antibiotics if indicated; repeat ABG; NIV if pH stays under 7.35 with PaCO2 over 6.5 kPa.

2. A 45-year-old with severe pneumonia has PaO2 6.8 kPa on 60% oxygen. Chest X-ray shows dense consolidation of the whole right lung.
Answer: Shunt -blood passes through unventilated lung, so extra oxygen helps little.

• Lie him with the good (left) lung down.
• CPAP or high-flow oxygen with PEEP to recruit alveoli; critical care review for intubation if worsening.
• Antibiotics per severity (co-amoxiclav plus clarithromycin).

3. A 26-year-old woman with asthma uses salbutamol 3–4 times a week and wakes at night with cough. She has no preventer.
Answer: Uncontrolled asthma -move to ICS-containing treatment (BTS/NICE/SIGN 2024).

• Start low-dose MART with budesonide–formoterol (or AIR if symptoms are mild).
• Check inhaler technique; explain maximum daily doses; written asthma action plan.
• Explain why LABA must never be used without an ICS; review in 8–12 weeks.

4. A 62-year-old man on theophylline for COPD is given ciprofloxacin for a UTI. Three days later he has vomiting, palpitations and a seizure.
Answer: Theophylline toxicity -ciprofloxacin inhibits CYP1A2.

• Stop theophylline; check theophylline level, potassium and glucose; ECG monitoring.
• Treat seizures with benzodiazepines; correct hypokalaemia; repeat-dose activated charcoal (TOXBASE).
• Choose a non-interacting antibiotic; consider stopping theophylline long term.

5. A 35-year-old woman with newly diagnosed pulmonary TB starts standard treatment. She takes the combined pill and wears contact lenses.
Answer: Counselling for RIPE treatment.

• Rifampicin -orange urine and tears (stains soft lenses); makes the pill ineffective -use a copper IUD or other non-hormonal method.
• Isoniazid -take pyridoxine; report tingling; hepatitis symptoms (nausea, jaundice) for any drug.
• Ethambutol -report any change in vision; baseline visual acuity and colour vision, LFTs, U&E, HIV test.

Key Points

• The right main bronchus is wider, shorter and more vertical -inhaled objects go right.
• Right lung has 3 lobes, left has 2 plus the lingula; silhouette sign localises shadowing.
• Parietal pleura is pain-sensitive; diaphragmatic pleura refers pain to the shoulder tip (C3–5).
• Insert needles and drains just above the rib (neurovascular bundle runs below each rib); use the safe triangle.
• Diaphragm: phrenic nerves C3, 4, 5; weakness causes orthopnoea and a fall in FVC lying down.
• Surfactant from type II pneumocytes -enough by about 34–36 weeks; antenatal steroids speed it.
• Emphysema increases compliance; fibrosis reduces it; resistance rises with 1/radius⁴.
• PaCO2 reflects alveolar ventilation -high CO2 means hypoventilation.
• Hypoxaemia causes: V/Q mismatch (commonest), shunt (oxygen-resistant), diffusion, hypoventilation (normal A–a gradient), low inspired oxygen.
• Oxygen dissociation curve shifts right with CO2, acid, heat and 2,3-DPG; left with HbF and CO.
• CO poisoning gives falsely normal oximetry; methaemoglobinaemia gives about 85% regardless.
• Oxygen raises CO2 in COPD mainly via V/Q change and the Haldane effect; target 88–92%.
• Central chemoreceptors sense CO2; peripheral chemoreceptors sense low oxygen.
• Check inhaler technique at every review; use a spacer with pMDIs.
• Never use LABA alone in asthma; AIR or MART with ICS–formoterol (BTS/NICE/SIGN 2024).
• COPD: LABA–LAMA first; triple therapy for exacerbations; ICS increases pneumonia risk.
• Antimuscarinics: dry mouth, urinary retention, glaucoma.
• Montelukast: neuropsychiatric effects; theophylline: narrow range, CYP1A2 interactions.
• Prednisolone 40–50 mg for at least 5 days in asthma attacks; 30 mg for 5 days in COPD exacerbations.
• TB drugs: rifampicin (orange, enzyme inducer), isoniazid (neuropathy -pyridoxine), pyrazinamide (gout, liver), ethambutol (eyes).
• Drugs damaging lungs: amiodarone, methotrexate, nitrofurantoin, bleomycin, checkpoint inhibitors.

Guidelines and Further Reading

• BTS/NICE/SIGN NG245: Asthma -diagnosis, monitoring and chronic asthma management (2024)
• NICE NG115: Chronic obstructive pulmonary disease in over 16s
• BTS Guideline for oxygen use in healthcare and emergency settings
• NICE NG138: Pneumonia (community-acquired) -antimicrobial prescribing
• NICE NG33: Tuberculosis
• NICE TAs: Biologics for severe asthma; pirfenidone and nintedanib for IPF and progressive fibrosis; CFTR modulators
• MHRA Drug Safety Updates: Montelukast; opioids with benzodiazepines and gabapentinoids
• West JB: Respiratory Physiology -The Essentials
• Pneumotox: drug-induced respiratory disease
• BNF -for current doses