Chapter 15 Respiratory disease
The main role of the respiratory system is to extract oxygen from the external environment and dispose of waste gases, principally carbon dioxide. This requires the lungs to function as efficient bellows, bringing in fresh air and delivering it to the alveoli, and expelling used air at an appropriate rate. Gas exchange is achieved by exposing thin-walled capillaries to the alveolar gas and matching ventilation to blood flow through the pulmonary capillary bed. In doing this, the lungs expose a large area of tissue, which can be damaged by dusts, gases and infective agents. Host defence is therefore a key priority for the lung and is achieved by a combination of structural and immunological defences.
The trachea is 10–12 cm in length. It lies slightly to the right of the midline and divides at the carina into right and left main bronchi. The carina lies under the junction of the manubrium sterni and the second right costal cartilage. The right main bronchus is more vertical than the left and, hence, inhaled material is more likely to end up in the right lung.
The right main bronchus divides into the upper lobe bronchus and the intermediate bronchus, which further subdivides into the middle and lower lobe bronchi. On the left the main bronchus divides into upper and lower lobe bronchi only. Each lobar bronchus further divides into segmental and subsegmental bronchi. There are about 25 divisions in all between the trachea and the alveoli.
The ciliated epithelium is a key defence mechanism. Each cell bears approximately 200 cilia beating at 1000 beats per minute in organized waves of contraction. Each cilium consists of nine peripheral parts and two inner longitudinal fibrils in a cytoplasmic matrix (Fig. 15.1). Nexin links join the peripheral pairs. Dynein arms consisting of ATPase protein project towards the adjacent pairs. Bending of the cilia results from a sliding movement between adjacent fibrils powered by an ATP-dependent shearing force developed by the dynein arms (see also p. 22). Absence of dynein arms leads to immotile cilia. Mucus, which contains macrophages, cell debris, inhaled particles and bacteria, is moved by the cilia towards the larynx at about 1.5 cm/min (the ‘mucociliary escalator’, see below).
The bronchioles finally divide within the acinus into smaller respiratory bronchioles that have alveoli arising from the surface (Fig. 15.2). Each respiratory bronchiole supplies approximately 200 alveoli via alveolar ducts. The term ‘small airways’ refers to bronchioles of <2 mm; the average lung contains about 30 000 of these.
There are approximately 300 million alveoli in each lung. Their total surface area is 40–80 m2. The epithelial lining consists mainly of type I pneumocytes (Fig. 15.3). These cells have an extremely thin layer of cytoplasm, which only offers a thin barrier to gas exchange. Type I cells are connected to each other by tight junctions that limit the movements of fluid in and out of the alveoli. Alveoli are not completely airtight – many have holes in the alveolar wall allowing communication between alveoli of adjoining lobules (pores of Kohn).
Type II pneumocytes are slightly more numerous than type I cells but cover less of the epithelial lining. They are found generally in the borders of the alveolus and contain distinctive lamellar vacuoles, which are the source of surfactant. Type I pneumocytes are derived from type II cells. Large alveolar macrophages are present within the alveoli and assist in defending the lung.
The lungs are separated into lobes by invaginations of the pleura, which are often incomplete. The right lung has three lobes, whereas the left lung has two. The positions of the oblique fissures and the right horizontal fissure are shown in Figure 15.4. The upper lobe lies mainly in front of the lower lobe and therefore physical signs on the right side in the front of the chest are due to lesions of the upper lobe or the middle lobe.
The bronchopulmonary segment is further divided into individual lobules approximately 1 cm in diameter and generally pyramidal in shape, the apex lying towards the bronchiole that supplies it. Within each lobule a terminal bronchus supplies an acinus, and within this structure further divisions of the bronchioles eventually give rise to the alveoli.
The pleura is a layer of connective tissue covered by a simple squamous epithelium. The visceral pleura covers the surface of the lung, lines the interlobar fissures, and is continuous at the hilum with the parietal pleura, which lines the inside of the hemithorax. At the hilum the visceral pleura continues alongside the branching bronchial tree for some distance before reflecting back to join the parietal pleura. In health, the pleurae are in apposition apart from a small quantity of lubricating fluid.
The diaphragm is covered by parietal pleura above and peritoneum below. Its muscle fibres arise from the lower ribs and insert into the central tendon. Motor and sensory nerve fibres go separately to each half of the diaphragm via the phrenic nerves. Fifty per cent of the muscle fibres are of the slow-twitch type with a low glycolytic capacity; they are relatively resistant to fatigue.
The pulmonary artery divides to accompany the bronchi. The arterioles accompanying the respiratory bronchioles are thin-walled and contain little smooth muscle. The pulmonary venules drain laterally to the periphery of the lobules, pass centrally in the interlobular and intersegmental septa, and eventually join to form the four main pulmonary veins.
The bronchial circulation arises from the descending aorta. These bronchial arteries supply tissues down to the level of the respiratory bronchiole. The bronchial veins drain into the pulmonary vein, forming part of the normal physiological shunt.
The tracheobronchial lymph nodes are arranged in five main groups: pulmonary, bronchopulmonary, subcarinal, superior tracheobronchial and paratracheal. For all practical purposes these form a continuous network of nodes from the lung substance up to the trachea.
The innervation of the lung remains incompletely understood. Parasympathetic and sympathetic fibres (from the vagus and sympathetic chain respectively) accompany the pulmonary arteries and the airways. Airway smooth muscle is innervated by vagal afferents, postganglionic muscarinic vagal efferents and vagally derived non-adrenergic non-cholinergic (NANC) fibres which use a range of neurotransmitters including substance P, neurokinins A and B, calcitonin gene-related peptide, vasoactive intestinal polypeptide and various adenine and guanine phosphates. Three muscarinic receptor subtypes have been identified: M1 receptors on parasympathetic ganglia, a smaller number of M2 receptors on muscarinic nerve terminals, and M3 receptors on airway smooth muscle. The parietal pleura is innervated from intercostal and phrenic nerves but the visceral pleura has no innervation.
About 10 000 L of air are inhaled daily. The relatively low flow rates and turbulence of inspired air in the nose mean that few particles greater than 10 microns (µm) diameter pass through the nose. Particles deposited on the nasal mucosa are removed within 15 minutes, compared with 60–120 days for particles that reach the alveoli. Nasal secretion contains IgA antibodies, lysozyme and interferons. In addition, the cilia of the nasal epithelium move the mucous gel layer rapidly back to the oropharynx where it is swallowed. Bacteria have little chance of settling in the nose. Mucociliary protection is less effective against viral infections because viruses bind to receptors on epithelial cells. The majority of rhinoviruses bind to an adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), which is shared by neutrophils and eosinophils. Many noxious gases, such as SO2, are almost completely removed by nasal breathing.
The lungs have an inherent elastic property that causes them to tend to collapse away from the thoracic wall, generating a negative pressure within the pleural space. The strength of this retractive force relates to the volume of the lung: at higher lung volumes the lung is stretched more, and a greater negative intrapleural pressure is generated. Lung compliance is a measure of the relationship between this retractive force and lung volume. At the end of a quiet expiration, the retractive force exerted by the lungs is balanced by the tendency of the thoracic wall to spring outwards. At this point, respiratory muscles are resting. The volume of air remaining in the lung after a quiet expiration is called the functional residual capacity (FRC).
Inspiration from FRC is an active process: a negative intrapleural pressure is created by descent of the diaphragm and movement of the ribs upwards and outwards through contraction of the intercostal muscles. During tidal breathing in healthy individuals, inspiration is almost entirely due to contraction of the diaphragm. More vigorous inspiration requires the use of accessory muscles of ventilation (sternomastoid and scalene muscles). Respiratory muscles are similar to other skeletal muscles but are less prone to fatigue. However, inspiratory muscle fatigue contributes to respiratory failure in patients with severe chronic airflow limitation and in those with primary neurological and muscle disorders.
Coordinated respiratory movements result from rhythmical discharges arising in an anatomically ill-defined group of interconnected neurones in the reticular substance of the brainstem, known as the respiratory centre. Motor discharges from the respiratory centre travel via the phrenic and intercostal nerves to the respiratory musculature.
In healthy individuals, the main driver for respiration is the arterial pH, which is closely related to the partial pressure of carbon dioxide in arterial blood. Oxygen levels in arterial blood are usually above the level which triggers respiratory drive. In a typical normal adult at rest:
Figure 15.5 Chemical and neurogenic factors in the control of ventilation. The strongest stimulant to ventilation is a rise in PaCO2 which increases [H+] in CSF. Sensitivity to this may be lost in COPD. In these patients hypoxaemia is the chief stimulus to respiratory drive; oxygen treatment may therefore reduce respiratory drive and lead to a further rise in PaCO2. An increase in [H+] due to metabolic acidosis as in diabetic ketoacidosis will increase ventilation with a fall in PaCO2 causing deep sighing (Kussmaul) respiration. The respiratory centre is depressed by severe hypoxaemia and sedatives (e.g. opiates) and stimulated by doxapram, large doses of aspirin and pyrexia. COPD, chronic obstructive pulmonary disease.
Breathlessness on physical exertion is normal and not considered a symptom unless the level of exertion is very light, such as when walking slowly. Surveys of healthy western populations reveal that over 20% of the general population report themselves as breathless on relatively minor exertion. Although breathlessness is a very common symptom, the sensory and neural mechanisms underlying it remain obscure. The sensation of breathlessness is derived from at least three sources:
From the trachea to the periphery, the airways decrease in size but increase in number. Overall, the cross-sectional area available for airflow increases as the total number of airways increases. The airflow rate is greatest in the trachea and slows progressively towards the periphery (since the velocity of airflow depends on the cross-sectional area). In the terminal airways, gas flow occurs solely by diffusion. The resistance to airflow is very low (0.1–0.2 kPa/L in a normal tracheobronchial tree), steadily increasing from the small to the large airways.
Airways expand as the lung volume increases. At full inspiration (total lung capacity, TLC) they are 30–40% larger in calibre than at full expiration (residual volume, RV). In chronic obstructive pulmonary disease (COPD), the small airways are narrowed but this can be partially compensated by breathing closer to TLC.
Bronchomotor tone is maintained by vagal efferent nerves and can be reduced by atropine or β-adrenoceptor agonists. Adrenoceptors on the surface of bronchial muscles respond to circulating catecholamines – there is no direct sympathetic innervation. Airway tone shows a circadian rhythm, which is greatest at 04.00 and lowest in the mid-afternoon. Tone can be increased transiently by inhaled stimuli acting on epithelial nerve endings, which trigger reflex bronchoconstriction via the vagus. These stimuli include cigarette smoke, solvents, inert dust and cold air. Airway responsiveness to these stimuli increases following respiratory tract infections even in healthy subjects. In asthma, the airways are very irritable and as the circadian rhythm remains the same, asthmatic symptoms are usually worse in the early morning.
Movement of air through the airways results from a difference between atmospheric pressure and the pressure in the alveoli; alveolar pressure is negative in inspiration and positive in expiration. During quiet breathing, the pleural pressure is negative throughout the breathing cycle. With vigorous expiratory efforts (e.g. cough), the pleural pressure becomes positive (up to 10 kPa). This compresses the central airways, but the smaller airways do not close off because the driving pressure for expiratory flow (alveolar pressure) is also increased.
Figure 15.6 Diagrams showing ventilatory forces. (a) During resting at functional residual capacity. (b) During forced expiration in normal subjects. (c) During forced expiration in a patient with COPD. The respiratory system is represented as a piston with a single alveolus and the collapsible part of the airways within the piston (see text). C, collapse point; PALV, alveolar pressure; PEL, elastic recoil pressure; PPL, pleural pressure.
In forced expiration, as mentioned above, the driving pressure raises both the alveolar pressure and the intrapleural pressure. Between the alveolus and the mouth, there is a point (C in Fig. 15.6b) where the airway pressure equals the intrapleural pressure, and the airway collapses. However, this collapse is temporary, as the transient occlusion of the airway results in an increase in pressure behind it (i.e. upstream) and this raises the intra-airway pressure so that the airways open and flow is restored. The airways thus tend to vibrate at this point of ‘dynamic collapse’.
As lung volume decreases during expiration, the elastic recoil pressure of the lungs decreases and the ‘collapse point’ moves upstream (i.e. towards the smaller airways – see Fig. 15.6c). Where there is pathological loss of recoil pressure (as in chronic obstructive pulmonary disease, COPD), the ‘collapse point’ is located even further upstream and causes expiratory flow limitation. The measurement of the forced expiratory volume in 1 second (FEV1) is a useful clinical index of this phenomenon. To compensate, patients with COPD often ‘purse their lips’ in order to increase airway pressure so that their peripheral airways do not collapse. During inspiration, the intrapleural pressure is always less than the intraluminal pressure within the intrathoracic airways, so increasing effort does not limit airflow. Inspiratory flow is limited only by the power of the inspiratory muscles.
Figure 15.7 (a, b) Maximal flow-volume loops, showing the relationship between maximal flow rates on expiration and inspiration. (a) In a normal subject. (b) In a patient with severe airflow limitation. Flow-volume loops during tidal breathing at rest (starting from the functional residual capacity (FRC)) and during exercise are also shown. The highest flow rates are achieved when forced expiration begins at total lung capacity (TLC) and represent the peak expiratory flow rate (PEFR). As air is blown out of the lung, so the flow rate decreases until no more air can be forced out, a point known as the residual volume (RV). Because inspiratory airflow is only dependent on effort, the shape of the maximal inspiratory flow-volume loop is quite different, and inspiratory flow remains at a high rate throughout the manoeuvre. (c, d) Flow-volume loops of patients with large airway (tracheal) obstruction, showing plateauing of maximal expiratory flow. (c) Extrathoracic tracheal obstruction with a proportionally greater reduction of maximal inspiratory (as opposed to expiratory) flow rate. (d) Intrathoracic large airway obstruction; the expiratory plateau is more pronounced and inspiratory flow rate is less reduced than in (c). In severe airflow limitation the ventilatory demands of exercise cannot be met (cf. a, b), greatly reducing effort tolerance.
In subjects with healthy lungs, maximal flow rates are rarely achieved even during vigorous exercise. However, in patients with severe COPD, limitation of expiratory flow occurs even during tidal breathing at rest (Fig. 15.7b). To increase ventilation these patients have to breathe at higher lung volumes and allow more time for expiration, both of which reduce the tendency for airway collapse. To compensate they increase flow rates during inspiration, where there is relatively less flow limitation.
The volume that can be forced in from the residual volume in 1 second (FIV1) will always be greater than that which can be forced out from TLC in 1 second (FEV1). Thus, the ratio of FEV1 to FIV1 is below 1. The only exception to this occurs when there is significant obstruction to the airways outside the thorax, such as tracheal tumour or retrosternal goitre. Expiratory airway narrowing is prevented by tracheal resistance and expiratory airflow becomes more effort-dependent. During forced inspiration this same resistance causes such negative intraluminal pressure that the trachea is compressed by the surrounding atmospheric pressure. Inspiratory flow thus becomes less effort-dependent, and the ratio of FEV1 to FIV1 exceeds 1. This phenomenon, and the characteristic flow-volume loop, is diagnostic of extrathoracic airways obstruction (Fig. 15.7c).
For optimum gas exchange there must be a match between ventilation of the alveoli () and their perfusion (). However, in reality there is variation in the () ratio in both normal and diseased lungs (Fig. 15.8). In the normal lung both ventilation and perfusion are greater at the bases than at the apices, but the gradient for perfusion is steeper, so the net effect is that ventilation exceeds perfusion towards the apices, while perfusion exceeds ventilation at the bases. Other causes of () mismatch include direct shunting of deoxygenated blood through the lung without passing through alveoli (e.g. the bronchial circulation) and areas of lung that receive no blood (e.g. anatomical deadspace, bullae and areas of underperfusion during acceleration and deceleration, e.g. in aircraft and high performance cars).
Figure 15.8 Relationships between ventilation and perfusion: a schematic diagram showing the alveolar–capillary interface. The centre (b) shows normal ventilation and perfusion. On the left (a) there is a block in perfusion (physiological deadspace), while on the right (c) there is reduced ventilation (physiological shunting).
An increased physiological shunt results in arterial hypoxaemia since it is not possible to compensate for some of the blood being underoxygenated by increasing ventilation of the well-perfused areas. An increased physiological deadspace just increases the work of breathing and has less impact on blood gases since the normally perfused alveoli are well ventilated. In more advanced disease this compensation cannot occur, leading to increased alveolar and arterial PCO2 (PaCO2), together with hypoxaemia which cannot be compensated by increasing ventilation.
Hypoxaemia occurs more readily than hypercapnia because of the different ways in which oxygen and carbon dioxide are carried in the blood. Carbon dioxide can be considered to be in simple solution in the plasma, the volume carried being proportional to the partial pressure. Oxygen is carried in chemical combination with haemoglobin in the red blood cells, with a non-linear relationship between the volume carried and the partial pressure (Fig. 15.5, p. 341). Alveolar hyperventilation reduces the alveolar PCO2 (PACO2) and diffusion leads to a proportional fall in the carbon dioxide content of the blood (PaCO2). However, as the haemoglobin is already saturated with oxygen, there is no significant increase in the blood oxygen content as a result of increasing the alveolar PO2 through hyperventilation. The hypoxaemia of even a small amount of physiological shunting cannot therefore be compensated for by hyperventilation.
In individuals who have mild degrees of mismatch, the PaO2 and PaCO2 will still be normal at rest. Increasing the requirements for gas exchange by exercise will widen the mismatch and the PaO2 will fall. mismatch is by far the most common cause of arterial hypoxaemia.
Pulmonary alveoli are essentially hollow spheres. Surface tension acting at the curved internal surface tends to cause the sphere to decrease in size. The surface tension within the alveoli would make the lungs extremely difficult to distend were it not for the presence of surfactant, an insoluble lipoprotein largely consisting of dipalmitoyl lecithin, which forms a thin monomolecular layer at the air-fluid interface. Surfactant is secreted by type II pneumocytes within the alveolus and reduces surface tension so that alveoli remain stable.
Fluid surfaces covered with surfactant exhibit a phenomenon known as hysteresis; that is, the surface-tension-lowering effect of the surfactant can be improved by a transient increase in the size of the surface area of the alveoli. During quiet breathing, small areas of the lung undergo collapse, but it is possible to re-expand these rapidly by a deep breath; hence the importance of sighs or deep breaths as a feature of normal breathing. Failure of this mechanism, e.g. in patients with fractured ribs – gives rise to patchy basal lung collapse. Surfactant levels may be reduced in a number of diseases that cause damage to the lung (e.g. pneumonia). Lack of surfactant plays a central role in the respiratory distress syndrome of the newborn. Severe reduction in perfusion of the lung impairs surfactant activity and this may explain the characteristic areas of collapse associated with pulmonary embolism.
Pulmonary disease often results from a failure of the normal host defence mechanisms of the healthy lung (Fig. 15.9). These can be divided into physical, physiological, humoral and cellular mechanisms.
Over 90% of particles greater than 10 µm diameter are removed in the nostril or nasopharynx. This includes most pollen grains, which are typically >20 µm in diameter. Particles between 5 and 10 µm become impacted at the carina. Particles smaller than 1 µm tend to remain airborne, thus the particles capable of reaching the deep lung are those in the 1–5 µm range.
The mucus of the respiratory tract is a gelatinous substance consisting of water and highly glycosylated proteins (mucins). The mucus forms a thick gel that is relatively impermeable to water and floats on a liquid or sol layer found around the cilia of the epithelial cells. The gel layer is secreted from goblet cells and mucous glands as distinct globules that coalesce increasingly in the central airways to form a more or less continuous mucus blanket. In addition to the mucins, the gel contains various antimicrobial molecules (lysozyme, defensins), specific antibodies (IgA) and cytokines, which are secreted by cells in airways and get incorporated into the mucus gel. Bacteria, viruses and other particles get trapped in the mucus and are either inactivated or simply expelled before they can do any damage. Under normal conditions the tips of the cilia engage with the undersurface of the gel phase and by coordinated movement they push the mucus blanket upwards and outwards to the pharynx where it is either swallowed or coughed up. While it only takes 30–60 minutes for mucus to be cleared from the large bronchi, it can be several days before mucus is cleared from respiratory bronchioles. One of the major long-term effects of cigarette smoking is a reduction in mucociliary transport. This contributes to recurrent infection and prolongs contact with carcinogenic material. Air pollutants, local and general anaesthetics and products of bacterial and viral infection also reduce mucociliary clearance.
Congenital defects in mucociliary transport lead to recurrent infections and eventually to bronchiectasis. For example, in the ‘immotile cilia’ syndrome there is an absence of the dynein arms in the cilia themselves, while in cystic fibrosis there is ciliary dyskinesia and abnormally thick mucus.
Antioxidant defences include enzymes such as superoxide dismutase and low-molecular-weight antioxidant molecules (ascorbate, urate) in the epithelial lining fluid. In addition, lung cells are protected by an extensive range of intracellular defences, especially members of the glutathione S-transferase (GST) superfamily.
These mechanisms act as a defence against microbes, inorganic substances, e.g. asbestos, particulate matter, such as dust, and other antigens. They act by aiding opsonization so that macrophages can better ingest foreign material.
With infection, neutrophils migrate out of pulmonary capillaries into the air spaces and phagocytose and kill microbes with, for example, antimicrobial proteins (lactoferrin), degradative enzymes (elastase) and oxidant radicals. In addition, neutrophil extracellular traps (NET) ensnare and kill extracellular bacteria. Neutrophils also generate a variety of mediators, e.g. TNF-α, IL-1 and chemokines which activate dendritic cells and B cells and produce the T-cell-activating cytokine IL-12. The latter enhances neutrophil-mediated defence during pneumonia. Dendritic cells are antigen presenting cells and are key to the adaptive immune response (p. 58).
Microbes are detected by host cells by pattern recognition receptors, e.g. toll-like receptors. These act via NF-κB transcription factors in the epithelial cells to produce adhesion molecules, chemokines and colony stimulating factors to initiate inflammation. Inflammation is necessary for innate immunity and host defence but can lead to lung damage: there is a fine line between defence and injury.
Nasal symptoms (see also p. 691) are extremely common and both common colds and allergic rhinitis cause ‘runny nose’ (rhinorrhoea), nasal blockage and attacks of sneezing. In allergic rhinitis, symptoms may be intermittent, following contact with pollens or animal danders, or persistent, especially when house-dust mite is the allergen. Colds are frequent during the winter but if the symptoms persist for weeks the patient probably has perennial rhinitis rather than persistent viral infection.
Nasal secretions are usually thin and runny in allergic rhinitis but thicker and discoloured with viral infections. Nose bleeds and blood-stained nasal discharge are common and rarely indicate serious pathology. However, a blood-stained nasal discharge associated with nasal obstruction and pain may be the presenting feature of a nasal tumour (p. 1051). Nasal polyps typically present with nasal blockage and loss of smell.
Cough (see also p. 822) is the commonest symptom of lower respiratory tract disease. It is caused by mechanical or chemical stimulation of cough receptors in the epithelium of the pharynx, larynx, trachea, bronchi and diaphragm. Afferent receptors go to the cough centre in the medulla where efferent signals are generated to the expiratory musculature. Smokers often have a morning cough with a little sputum. A productive cough is the cardinal feature of chronic bronchitis, while dry coughing, particularly at night, can be a symptom of asthma. Cough also occurs in asthmatics after mild exertion or following forced expiration. Cough can also occur for psychological reasons without any definable pathology.
A worsening cough is the most common presenting symptom of lung cancer. The normal explosive character of the cough is lost when a vocal cord is paralysed, usually as a result of lung cancer infiltrating the left recurrent laryngeal nerve – sometimes termed a bovine cough. Cough can be accompanied by stridor in whooping cough or if there is laryngeal or tracheal obstruction.
Approximately 100 mL of mucus is produced daily in a healthy, non-smoking individual. This flows gradually up the airways, through the larynx, and is then swallowed. Excess mucus is expectorated as sputum. Cigarette smoking is the commonest cause of excess mucus production.
Mucoid sputum is clear and white but can contain black specks resulting from the inhalation of carbon. Yellow or green sputum is due to the presence of cellular material, including bronchial epithelial cells, or neutrophil or eosinophil granulocytes. Yellow sputum is not necessarily due to infection, as eosinophils in the sputum, as seen in asthma, can give the same appearance. The production of large quantities of yellow or green sputum is characteristic of bronchiectasis.
The commonest cause of mild haemoptysis is acute infection, particularly in exacerbations of chronic obstructive pulmonary disease (COPD) but it should not be attributed to this without investigation.
Haemoptysis should always be investigated. Although a diagnosis can often be made from a chest X-ray, a normal chest X-ray does not exclude disease. However, if the chest X-ray is normal, CT scanning and bronchoscopy are only diagnostic in about 5% of patients with haemoptysis.
Dyspnoea is a sense of awareness of increased respiratory effort that is unpleasant and that is recognized by the patient as being inappropriate. Patients often complain of tightness in the chest; this must be differentiated from angina.
Breathlessness should be assessed in relation to the patient’s lifestyle. For example, a moderate degree of breathlessness will be totally disabling if the patient has to climb many flights of stairs to reach home.
Orthopnoea (see p. 675) is breathlessness on lying down. While it is classically linked to heart failure, it is partly due to the weight of the abdominal contents pushing the diaphragm up into the thorax. Such patients may also become breathless on bending over.
Wheezing is a common complaint and results from airflow limitation due to any cause. The symptom of wheezing is not diagnostic of asthma; other causes include vocal chord dysfunction, bronchiolitis and chronic obstructive pulmonary disease (COPD). Conversely, wheeze may be absent in the early stages of asthma.
The most common type of chest pain reported in respiratory disease is a localized sharp pain, often termed pleuritic. It is made worse by deep breathing or coughing and the patient can usually localize it. Localized anterior chest pain with tenderness of a costochondral junction is caused by costochondritis. Shoulder tip pain suggests irritation of the diaphragmatic pleura, while central chest pain radiating to the neck and arms is likely to be cardiac. Retrosternal soreness is associated with tracheitis, while malignant invasion of the chest wall causes a constant, severe, dull pain.
Assess mental alertness, cyanosis, breathlessness at rest, use of accessory muscles, any deformity or scars on the chest and movement on both sides. CO2 intoxication causes coarse tremor or flap of the outstretched hands. Prominent veins on the chest may imply obstruction of the superior vena cava.
Cyanosis (see p. 676) is a dusky colour of the skin and mucous membranes, due to the presence of more than 50 g/L of desaturated haemoglobin. When due to central causes, cyanosis is visible on the tongue (especially the underside) and lips. Patients with central cyanosis will also be cyanosed peripherally. Peripheral cyanosis without central cyanosis is caused by a reduced peripheral circulation and is noted on the fingernails and skin of the extremities with associated coolness of the skin.
Finger clubbing is present when the normal angle between the base of the nail and the nail fold is lost. The base of the nail is fluctuant owing to increased vascularity, and there is an increased curvature of the nail in all directions, with expansion of the end of the digit. Some causes of clubbing are given in Table 15.1. Clubbing is not a feature of uncomplicated COPD.
Check the position of the trachea and apex beat. Examine the supraclavicular fossa for enlarged lymph nodes. The distance between the sternal notch and the cricoid cartilage (three to four finger breadths in full expiration) is reduced in patients with severe airflow limitation. Check chest expansion. A tape measure is used if precise or serial measurements are needed, e.g. in ankylosing spondylitis. Local discomfort over the sternochondral joints suggests costochondritis. In rib fractures, compression of the chest laterally and anteroposteriorly produces localized pain. On percussion, liver dullness is usually detected anteriorly at the level of the sixth rib. Liver and cardiac dullness disappear when lungs are over-inflated (Table 15.2).
Ask the patient to take deep breaths through the mouth. Inspiration should be more prolonged than expiration. Normal breath sounds are caused by turbulent flow in the larynx and sound harsher anteriorly over the upper lobes (particularly on the right). Healthy lungs filter out most of the high-frequency component, and the resulting sounds are called vesicular.
If the lung is consolidated or collapsed, the high-frequency hissing components of breath are not attenuated, and can be heard as ‘bronchial breathing’. Similar sounds may be heard over areas of localized fibrosis or bronchiectasis. Bronchial breathing is accompanied by whispering pectoriloquy (whispered, high-pitched sounds can be heard distinctly through a stethoscope).
Wheeze. Wheeze results from vibrations in the collapsible part of the airways when apposition occurs as a result of the flow-limiting mechanisms. Wheeze is usually heard during expiration and is commonly but not invariably present in asthma and in chronic obstructive pulmonary disease. In acute severe asthma wheeze may not be heard, as airflow may be insufficient to generate the sound. Wheezes may be monophonic (single large airway obstruction) or polyphonic (narrowing of many small airways). An end-inspiratory wheeze or ‘squeak’ may be heard in obliterative bronchiolitis.
Crackles. These brief crackling sounds are probably produced by opening of previously closed bronchioles – early inspiratory crackles are associated with diffuse airflow limitation, while late inspiratory crackles are characteristically heard in pulmonary oedema, lung fibrosis and bronchiectasis.
Vocal resonance. Healthy lung attenuates high-frequency notes, as compared to the lower-pitched components of speech. Consolidated lung has the reverse effect, transmitting high frequencies well; the spoken word then takes on a bleating quality. Whispered (and therefore high-pitched) speech can be clearly heard over consolidated areas, as compared to healthy lung. Low-frequency sounds such as ‘ninety-nine’ are well transmitted across healthy lung to produce vibration that can be felt over the chest wall. Consolidated lung transmits these low-frequency noises less well, and pleural fluid severely dampens or obliterates the vibrations altogether. Tactile vocal fremitus is the palpation of this vibration, usually by placing the edge of the hand on the chest wall. For all practical purposes this duplicates the assessment of vocal resonance and is not routinely performed as part of the chest examination.
Radiology is essential in investigating most chest symptoms. Some diseases such as tuberculosis or lung cancer may be undetectable on clinical examination but are obvious on the chest X-ray. Conversely, asthma or chronic bronchitis may be associated with a normal chest X-ray. Always try to get previous films for comparison.
View. Routine films are taken postero-anterior (PA), i.e. the film is placed in front of the patient with the X-ray source behind. Anteroposterior (AP) films are taken only in very ill patients who are unable to stand up or be taken to the radiology department; the cardiac outline appears bigger and the scapulae cannot be moved out of the way. Lateral chest X-rays were often performed in the past to localize pathology, but CT scans have replaced these.
Simple pneumonia is easy to recognize (see Fig. 15.33) but look carefully for any evidence of collapse (Fig. 15.10, Table 15.3). Loss of volume or crowding of the ribs are the best indicators of lobar collapse. The lung lobes collapse in characteristic directions. The lower lobes collapse downwards and towards the mediastinum, the left upper lobe collapses forwards against the anterior chest wall, while the right upper lobe collapses upwards and inwards, forming the appearance of an arch over the remaining lung. The right middle lobe collapses anteriorly and inward, obscuring the right heart border. If a whole lung collapses, the mediastinum will shift towards the side of the collapse. Uncomplicated consolidation does not cause mediastinal shift or loss of lung volume, so any of these features should raise the suspicion of an endobronchial obstruction.
Pleural effusions (see Fig. 15.45) need to be larger than 500 mL to cause much more than blunting of the costophrenic angle. On an erect film they produce a characteristic shadow with a curved upper edge rising into the axilla. If very large, the whole of one hemithorax may be opaque, with mediastinal shift away from the effusion.
Localized fibrosis causes streaky shadowing, and the accompanying loss of lung volume causes mediastinal structures to move to the same side. More generalized fibrosis can lead to a honeycomb appearance (see p. 849), seen as diffuse shadows containing multiple circular translucencies a few millimetres in diameter.
This term, derived from the Latin for millet, describes numerous minute opacities, 1–3 mm in size. The commonest causes are tuberculosis, pneumoconiosis, sarcoidosis, idiopathic pulmonary fibrosis and pulmonary oedema (see Fig. 14.15), although pulmonary oedema is usually perihilar and accompanied by larger, fluffy shadows. Pulmonary microlithiasis is a rare but striking cause of miliary mottling.
CT provides excellent images of the lungs and mediastinal structures (Fig. 15.11). Narrow slice, high-resolution CT scans show the lung parenchyma well, while thicker slice staging CT scans are used for diagnosis of malignant disease. Mediastinal structures are shown more clearly after injecting intravenous contrast medium.
Figure 15.11 CT scans of the lung. (a) Lung setting – showing normal lung markings. 1, right hilum; 2, mediastinum; 3, left hilum; 4, lung vessels; 5, left main bronchus; 6, right main bronchus; 7, peripheral lung vessels. (b) Mediastinal (soft tissue) setting – showing normal mediastinal structures following intravenous contrast enhancement. 1, rib; 2, descending left pulmonary artery; 3, scapula; 4, subcutaneous fat; 5, left main bronchus; 6, descending aorta; 7, spinal canal; 8, vertebral body; 9, oesophagus; 10, right main bronchus; 11, right pulmonary artery; 12, muscle; 13, right superior pulmonary vein; 14, superior vena cava; 15, costal cartilage; 16, ascending aorta; 17, sternum; 18, thymic remnant; 19, pulmonary trunk; 20, left superior pulmonary vein. (c) Post-contrast scan showing large right upper zone carcinoma with enlarged lymph nodes in the mediastinum surrounding the trachea.
CT is essential in staging bronchial carcinoma by demonstrating tumour size, nodal involvement, metastases and invasion of mediastinum, pleura or chest wall. CT-guided needle biopsy allows samples to be obtained from peripheral masses. Staging scans should assess liver and adrenals, which are common sites for metastatic disease.
High-resolution CT (HRCT) scanning samples lung parenchyma with 1–2 mm thickness scans at 10–20 mm intervals and are used to assess diffuse inflammatory and infective parenchymal processes. It is valuable in:
Multi-slice CT scanners can produce detailed images in two or three dimensions in any plane. This detail is particularly useful for the detection of pulmonary emboli. Pulmonary nodules and airway disease are more easily defined and the technique makes HRCT less necessary.
MRI is less valuable than CT in assessing the lung parenchyma. In the mediastinum, MRI with ECG-gating allows accurate imaging of the heart and aortic aneurysms, and MRI has been used in staging lung cancer, for assessing tumour invasion in the mediastinum, chest wall and at the lung apex, because it produces good images in the sagittal and coronal planes. Vascular structures can be clearly differentiated as flowing blood produces a signal void on MRI.
Tumours take up labelled fluorodeoxyglucose (FDG), which emits positrons that can be imaged and helps to differentiate benign from malignant tumours. In bronchial carcinoma, PET scanning combined with CT is now the investigation of choice for assessing lymph nodes and metastatic disease.