Clinical Skills for Respiratory Medicine PDF

28 Clinical skills for respiratory medicine Function of the respiratory system Anatomy Physiology Respiratory disease Veronica White and Prina Ruparelia...

28 Clinical skills for respiratory medicine Function of the respiratory system Anatomy Physiology Respiratory disease Veronica White and Prina Ruparelia 927 930 930 932 Pleural disease Pleural effusion Pneumothorax Tumours of the Respiratory Tract 972 972 973 975 Clinical approach to the patient with respiratory Bronchiectasis 982 disease 936 Cystic fibrosis 983 Investigation of respiratory disease 939 Interstitial Lung Diseases 985 Diseases of the upper respiratory tract 945 Sarcoidosis 985 Obstructive respiratory disease 949 Idiopathic pulmonary fibrosis 988 Asthma 949 Hypersensitivity pneumonitis 989 Chronic obstructive pulmonary disease 955 Rare interstitial lung diseases 991 Obstructive sleep apnoea 960 Lung and Heart–Lung Transplantation 994 Smoking 963 Occupational Lung Disease 995 Respiratory infection 963 Miscellaneous Respiratory Disorders 997 Pneumonia 963 Disorders of the Diaphragm 997 Tuberculosis 967 Mediastinal Lesions 998 include bronchoscopy, endobronchial ultrasound scanning and CORE SKILLS AND KNOWLEDGE pleural interventions. Key skills in respiratory medicine include: Respiratory medicine is an exciting and varied specialty caring managing respiratory emergencies, including type 1 and type for patients with a range of acute and chronic conditions. One- 2 respiratory failure, massive pleural effusion, pneumothorax third of visits to primary care are due to a respiratory complaint, and large-volume haemoptysis and respiratory conditions are the reason for one-quarter of interpreting basic examination findings and respiratory in- medical admissions to hospital. vestigations, i.e. chest X-rays (Fig. 28.1), arterial blood gas Respiratory physicians provide a large amount of inpatient analysis and spirometry, with confidence care, for acute problems such as pneumonia or exacerbations understanding common treatments for respiratory condi- of chronic obstructive pulmonary disease and other chronic tions, including inhaled and nebulized medications, home respiratory conditions. Outpatient care is given in general clin- oxygen therapy and non-invasive ventilation. ics (for the initial investigation and diagnosis of patients with Respiratory medicine can be learned through attending gen- respiratory symptoms) and in more specialist ones (for long- eral and subspecialty respiratory clinics (e.g. lung cancer, tuber- term follow-up of individual conditions). In specialist clinics, culosis or sleep clinics), observing specialist investigations such care is shared with community teams and nurse specialists as lung function measurement or bronchoscopy, attending clin- to promote the health and quality of life of patients, through ics and home visits with specialist nurses, and at every opportu- education, self-management and admission-avoidance strate- nity interpreting arterial blood gases and using the results to alter gies. Practical procedures performed by respiratory physicians oxygen delivery or assisted ventilation systems. CLINICAL SKILLS FOR RESPIRATORY MEDICINE ! History Smoking: smoking history (duration of smoking and number of cigarettes smoked per day), and also attempts made to give The following features of the medical history are especially relevant up, including use of nicotine replacement substances such as in respiratory disease: e-cigarettes. Respiratory symptoms: cough, sputum production, breathless- Recreational drug use: especially smoked cannabis. ness, chest pain, haemoptysis, wheeze. Specify acuity of onset, Family history: respiratory conditions such as emphysema, change over time, change in symptoms with location. bronchiectasis or cystic fibrosis. Systemic symptoms: weight loss, malaise, night sweats. Childhood history: prematurity, childhood infections such as Occupational exposure: all previous occupations, with a spe- whooping cough or measles. cific focus on exposure to asbestos, to organic materials such as Travel history: may be relevant in assessing risk factors for hay, mushrooms or cotton, or to animals. Establish any relation- tuberculosis.! ship of symptoms to work. 927 28 928 Respiratory disease Examination ! ! ↑↑  Clinical skills for respiratory medicine 929 28 1. Preliminaries Patient details: Compare where available to previous X-ray images - Which patient, how old, when was this image taken? X-ray details: - Is it a posteroanterior or anteroposterior projection? - Is the patient rotated? - Is there adequate penetration? - Has the patient taken an adequate breath? 2. Trachea The trachea should be widely patent and should be The trachea may be pulled towards areas of fibrosis or central in the chest collapse It may be pushed away by masses, a goitre, lymphadenopathy, large pleural effusion or a tension pneumothorax 3. Mediastinum The aortic notch should be just visible The mediastinum is widened by lymphadenopathy, The left hilum should be slightly higher than the right masses such as thymoma, and aortic aneurysm The hila should be symmetrical in size The hila may be pulled up or down by collapsed lobes, or enlarged by the presence of a tumour 4. Heart size Heart size should be less than 50% of the thoracic Cardiomegaly may be caused by hypertension, valvular width on a PA chest film disease, heart failure or cardiomyopathy Assess heart borders Loss of right heart border may suggest right middle lobe pathology Loss of left heart border suggests lingular pathology 5. Diaphragm The right hemidiaphragm is usually higher than the left Air or gas under the diaphragm indicates a perforated Look for air/gas under the diaphragm and for elevation abdominal viscus of the diaphragm on either side A hemidiaphragm may be pulled up from above by lobar collapse, or pushed up from below by a large mass 6. Pleura The costophrenic angles should be clearly visible Loss of the costophrenic angle is usually due to the presence Look for lung markings extending to the chest wall of pleural effusions Look for evidence of a lung edge Larger pleural effusions may cause a ‘white out’ on one side Loss of lung markings or a visible lung edge suggests a pneumothorax 7. Lungs Is there consolidation of the upper lobe (stops at Areas of consolidation may often be restricted to a lobe and horizontal fissure), middle lobe/lingula (heart edge are usually caused by pneumonia. An air bronchogram unclear) or lower lobe (diaphragm unclear)? (airways outlined) or evidence of cavitation may be seen Inspect each part of the lung looking for round Rounded shadows may be caused by cancer, inflammatory shadows lesions, such as tuberculosis or fungal disease Inspect the lung parenchyma for interstitial changes Interstitial changes may be caused by pulmonary oedema or fibrosis 8. Bones Inspect all ribs for evidence of fractures Think of systemic diseases: Faint bones imply osteopenia - Osteoporosis may cause osteopenia or fractures Are there lytic lesions? - Solid organ cancers or myeloma can cause lytic lesions 9. Soft tissue Observe the soft tissue around the rib cage Air within the skin suggests surgical emphysema 10. Miscellaneous Look for any externally applied devices Nasogastric tubes should bisect the carina and cross the diaphragm Chest drains should terminate in the pleural space Central venous catheters should end just above the right atrium Pacemaker wires, and sternotomy wires imply cardiac disease Fig. 28.1 A systematic ten-step approach to chest X-ray interpretation. 28 930 Respiratory disease Box 28.1 Core content in respiratory medicine The ‘top 10’ respiratory Respiratory failure conditions Atopy Acute and chronic cough The ‘treatment ladder’ approach Asthma to asthma and COPD Chronic obstructive pulmonary Management of chest drains disease (COPD) Diagnosis and staging of lung Pneumonia cancer! Pulmonary tuberculosis The ‘top 10’ respiratory Pneumothorax medications Pleural effusions Oxygen Lung cancer β2 agonists Bronchiectasis Antimuscarinics Interstitial lung disease! Oral and inhaled corticosteroids The ‘top 10’ concepts in Combination inhalers respiratory medicine Antihistamines Smoking cessation Leukotriene receptor antagonists Self-management of chronic Mucolytics Fig. 28.2 Branches of a terminal bronchiole ending in the alveo- conditions Monoclonal antibodies lar sacs. Admission avoidance Antifibrotics Home oxygen therapy The right main bronchus divides into the upper lobe bronchus Multidisciplinary cancer care and the intermediate bronchus, which further subdivides into the middle and lower lobe bronchi. On the left the main bronchus FUNCTION OF THE RESPIRATORY divides into upper and lower lobe bronchi only. Each lobar bronchus SYSTEM further divides into segmental and subsegmental bronchi. There are about 25 divisions in all between the trachea and the alveoli. The respiratory system has several key functions, the principal ones The first seven divisions are bronchi that have: being to extract oxygen from the external environment and to dis- walls consisting of cartilage and smooth muscle pose of carbon dioxide. This requires the lungs to function as effi- an epithelial lining with cilia and goblet cells cient bellows, bringing in fresh air and delivering it to the alveoli, and submucosal mucus-secreting glands expelling used air at an appropriate rate. Gas exchange is achieved endocrine cells. by exposing thin-walled capillaries to the alveolar gas and matching The next 16–18 divisions are bronchioles that have: ventilation to blood flow through the pulmonary capillary bed. The no cartilage and a muscular layer that progressively becomes excretion of carbon dioxide by the lungs is involved in acid–base thinner homeostasis. a single layer of ciliated cells but very few goblet cells The lungs expose a large surface area of body tissue to the granulated Clara cells that produce a surfactant-like substance. external environment in order to achieve gas exchange, and hence The ciliated epithelium is a key defence mechanism. Each cell they can be damaged by dusts, gases and infective agents. Host bears approximately 200 cilia beating at 1000 beats per minute defence is therefore a key priority for the lung and is achieved by a (b.p.m.) in organized waves of contraction. Mucus, which contains combination of structural and immunological defences. macrophages, cell debris, inhaled particles and bacteria, is moved The pulmonary circulation also acts as a blood pool reservoir by the cilia towards the larynx at about 1.5 cm/min (the ‘mucociliary that can allow the body to respond readily to increased oxygen escalator’; see later). demands in exercise. The lungs act as a filtration system for small The bronchioles finally divide within the acinus into smaller pulmonary emboli. The pulmonary circulation also plays a role in respiratory bronchioles that have alveoli arising from the surface innate immunity: for example, in de-priming neutrophils. (Fig. 28.2). Each respiratory bronchiole supplies approximately 200 Finally, the lungs have a role in speech, as the passage of air alveoli via alveolar ducts. The term ‘small airways’ refers to bron- through the vocal cords is necessary for phonation. chioles of less than 2 mm; the average lung contains about 30 000 of these.! Alveoli Anatomy There are approximately 300 million alveoli in each lung. Their total surface area is 40–80 m2. The epithelial lining consists mainly of Nose, pharynx and larynx type I pneumocytes (Fig. 28.3). These cells have an extremely thin See pages 907 and 909.! 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 Trachea, bronchi and bronchioles the movements of fluid in and out of the alveoli. Alveoli are not com- The trachea is 10–12 cm in length. It lies slightly to the right of the pletely airtight; many have holes in the alveolar wall, allowing com- midline and divides at the carina into right and left main bronchi. munication between alveoli of adjoining lobules (pores of Kohn). The carina lies under the junction of the manubrium sterni and the Type II pneumocytes are slightly more numerous than type I second right costal cartilage. The right main bronchus is more verti- cells but cover less of the epithelial lining. They are found generally cal than the left and inhaled material is therefore more likely to end in the borders of the alveolus and contain distinctive lamellar vacu- up in the right lung. oles, which are the source of surfactant. Type I pneumocytes are  Function of the respiratory system 931 28 derived from type II cells. Large alveolar macrophages are present bronchial tree for some distance before reflecting back to join the within the alveoli and assist in defending the lung.! parietal pleura. In health, the pleurae are in apposition, apart from a small quantity of lubricating fluid.! Lungs The lungs are separated into lobes by invaginations of the pleura, Diaphragm which are often incomplete. The right lung has three lobes, whereas The diaphragm is covered by parietal pleura above and peritoneum the left lung has two. The positions of the oblique fissures and the below. The diaphragmatic muscle fibres arise from the lower ribs right horizontal fissure are shown in Fig. 28.4. The upper lobe lies and insert into the central tendon. Motor and sensory nerve fibres mainly in front of the lower lobe and therefore physical signs on the go separately to each half of the diaphragm via the phrenic nerves. right side in the front of the chest are due to lesions of the upper Fifty per cent of the muscle fibres are of the slow-twitch type with a lobe or the middle lobe.! low glycolytic capacity; they are relatively resistant to fatigue.! Pleura Pulmonary vasculature and lymphatics The pleura is a layer of connective tissue covered by a simple The lung has a dual blood supply, receiving deoxygenated blood squamous epithelium. The visceral pleura covers the surface of the from the right ventricle via the pulmonary artery and oxygenated lung, lines the interlobar fissures, and is continuous at the hilum blood via the bronchial circulation. with the parietal pleura, which lines the inside of the hemithorax. The pulmonary artery divides to accompany the bronchi. The At the hilum, the visceral pleura continues alongside the branching arterioles accompanying the respiratory bronchioles are thin-walled and contain little smooth muscle. The pulmonary venules drain lat- erally to the periphery of the lobules, pass centrally in the interlobu- lar 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 veins, forming part of the normal physiological shunt. Lymphatic channels lie in the interstitial space between the alve- olar cells and the capillary endothelium of the pulmonary arterioles. The tracheobronchial lymph nodes are arranged in five main groups: pulmonary, bronchopulmonary, subcarinal, superior tracheo- bronchial and paratracheal. For practical purposes, these form a con- tinuous network of nodes from the lung substance up to the trachea.! Nerve supply to the lung The innervation of the lung remains incompletely understood. Para- sympathetic and sympathetic fibres (from the vagus and sympa- thetic 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- Fig. 28.3 The structure of alveoli, showing the pneumocytes and adrenergic non-cholinergic (NANC) fibres, which use a range of capillaries. neurotransmitters. Three muscarinic receptor subtypes have been Fig. 28.4 Surface anatomy of the chest. (A) Anterior. (B) Lateral. 28 932 Respiratory disease identified: M1 receptors on parasympathetic ganglia, a smaller num- Control of respiration ber of M2 receptors on muscarinic nerve terminals, and M3 recep- Coordinated respiratory movements result from rhythmical dis- tors on airway smooth muscle. The parietal pleura is innervated charges arising in an anatomically ill-defined group of intercon- from intercostal and phrenic nerves but the visceral pleura has no nected neurones in the reticular substance of the brainstem, known innervation. as the respiratory centre. Motor discharges from the respiratory centre travel via the phrenic and intercostal nerves to the respiratory Further reading musculature. Albert RK, Spiro SG, Jett JR. Clinical Respiratory Medicine, 4th edn. Chicago: Ventilation is controlled by a combination of neurogenic and Mosby; 2012.! chemical factors (Fig. 28.5). 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 arte- Physiology rial blood are usually above the level that triggers respiratory drive. Typical normal values are shown in Box 28.2. Nose Breathlessness on physical exertion is normal and not con- The major functions of nasal breathing are: sidered a symptom unless the level of exertion is very light, such to heat and moisten the air as when walking slowly. Surveys of healthy Western populations to remove particulate matter. reveal that over 20% of the general population report themselves Nasal secretions contain immunoglobulin A (IgA) antibodies, as breathless on relatively minor exertion. Although breathlessness lysozyme and interferons. In addition, the cilia of the nasal epithe- is a very common symptom, the sensory and neural mechanisms lium move the mucous gel layer rapidly back to the oropharynx, underlying it remain obscure. The sensation of breathlessness is where it is swallowed. Bacteria have little chance of settling in the derived from at least three sources: nose. Mucociliary protection is less effective against viral infections changes in lung volume, sensed by receptors in thoracic wall because viruses bind to receptors on epithelial cells. The majority muscles signalling changes in their length of rhinoviruses bind to an adhesion molecule, intercellular adhesion tension developed by contracting muscles, sensed by Golgi molecule 1 (ICAM-1), which is shared by neutrophils and eosino- tendon organs phils. Many noxious gases, such as sulphur dioxide, are almost central perception of the sense of effort.! completely removed by nasal breathing.! Airways of the lungs Breathing From the trachea to the periphery, the airways decrease in size but Lung ventilation can be considered in two parts: increase in number. Overall, the cross-sectional area available for the mechanical process of inspiration and expiration airflow increases as the total number of airways increases. The air- the control of respiration to a level appropriate for metabolic flow rate is greatest in the trachea and slows progressively towards needs. the periphery (since the velocity of airflow depends on the cross- sectional area). In the terminal airways, gas flow occurs solely by Mechanical process diffusion. The resistance to airflow is very low (0.1–0.2 kPa/L in a The lungs have an inherent elastic property that causes them to normal tracheobronchial tree), steadily increasing from the small to tend to collapse away from the thoracic wall, generating a nega- the large airways. tive pressure within the pleural space. The strength of this retractive Airways expand as the lung volume increases. At full inspiration force relates to the volume of the lung: at higher lung volumes the (total lung capacity, TLC) they are 30–40% larger in calibre than at lung is stretched more, and a greater negative intrapleural pressure full expiration (residual volume, RV). In chronic obstructive pulmo- is generated. Lung compliance is a measure of the relationship nary disease (COPD) the small airways are narrowed but this can be between this retractive force and lung volume. At the end of a quiet partially compensated by breathing closer to TLC. expiration the retractive force exerted by the lungs is balanced by the tendency of the thoracic wall to spring outwards. At this point, Control of airway tone respiratory muscles are resting. The volume of air remaining in Bronchomotor tone is maintained by vagal efferent nerves and can the lung after a quiet expiration is called the functional residual be reduced by atropine or β-adrenoceptor agonists. Adrenoceptors capacity (FRC; see Fig. 28.15). on the surface of bronchial muscles respond to circulating cate- Inspiration from FRC is an active process: a negative intrapleural cholamines; there is no direct sympathetic innervation. Airway tone pressure is created by descent of the diaphragm and movement of shows a circadian rhythm, which is greatest at 04.00 and lowest the ribs upwards and outwards through contraction of the intercos- in the mid-afternoon. Tone can be increased transiently by inhaled tal muscles. During tidal breathing in healthy individuals, inspiration stimuli acting on epithelial nerve endings, which trigger reflex is almost entirely due to contraction of the diaphragm. More vigor- bronchoconstriction via the vagus. These stimuli include cigarette ous inspiration requires the use of accessory muscles of ventila- smoke, solvents, inert dust and cold air. Airway responsiveness to tion (sternomastoid and scalene muscles). Respiratory muscles are these stimuli increases following respiratory tract infections, even in similar to other skeletal muscles but are less prone to fatigue. How- healthy subjects. In asthma the airways are very irritable, and as the ever, inspiratory muscle fatigue contributes to respiratory failure in circadian rhythm remains the same, asthmatic symptoms are usu- patients with severe chronic airflow limitation and in those with pri- ally worse in the early morning.! mary neurological and muscle disorders. At rest or during low-level exercise, expiration is passive and Airflow results from the natural tendency of the lung to collapse. Forced Movement of air through the airways results from a difference expiration involves activation of accessory muscles, chiefly those of between atmospheric pressure and the pressure in the alveoli; alve- the abdominal wall, which help to push up the diaphragm.! olar pressure is negative in inspiration and positive in expiration.  Function of the respiratory system 933 28 Fig. 28.5 Chemical and neurogenic factors in the control of ventilation. The strongest stimulant to ventilation is a rise in PaCO2, which increases [H+] in cerebrospinal fluid. Sensitivity to this may be lost in chronic obstructive pulmonary disease. In these patients, hypoxaemia is the chief stimulus to respira- tory 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). Box 28.2 Normal values for respiratory physiology expiration, both of which reduce the tendency for airway collapse. To compensate, they increase flow rates during inspiration, where In a typical normal adult at rest: there is relatively less flow limitation. Pulmonary blood flow is about 5 L/min The volume that can be forced in from the residual volume in This carries 11 mmol/min (250 mL/min) of O2 to tissues 1 second (FIV1) will always be greater than that which can be forced Ventilation is about 6 L/min out from TLC in 1 second (FEV1). Thus, the ratio of FEV1 to FIV1 This removes 9 mmol/min (200 mL/min) of CO2 from the body is less than 1. The only exception to this is when there is signifi- Normal pressure of oxygen in arterial blood (PaO2) is 11–13 kPa Normal pressure of carbon dioxide in arterial blood (PaCO2) is cant obstruction to the airways outside the thorax, such as tracheal 4.8–6.0 kPa tumour or retrosternal goitre. Expiratory airway narrowing is pre- vented by tracheal resistance, and expiratory airflow becomes more effort-dependent. During forced inspiration, this same resistance During quiet breathing the pleural pressure is negative throughout causes such negative intraluminal pressure that the trachea is com- the breathing cycle. With vigorous expiratory efforts (e.g. cough) pressed by the surrounding atmospheric pressure. Inspiratory flow the pleural pressure becomes positive (up to 10 kPa). This com- thus becomes less effort-dependent, and the ratio of FEV1 to FIV1 presses the central airways, but the smaller airways do not close off is greater than 1. This phenomenon, and the characteristic flow– because the driving pressure for expiratory flow (alveolar pressure) volume loop, are diagnostic of extrathoracic airways obstruction is also increased.! (Fig. 28.6C).! Flow–volume loops Ventilation and perfusion relationships The relationship between maximal flow rates and lung volume is For optimum gas exchange there must be a match between ventila- demonstrated by the maximal flow–volume (MFV) loop (Fig. 28.6A). tion of the alveoli (V̇ ) and their perfusion (Q̇). However, in reality there In subjects with healthy lungs, maximal flow rates are rarely is variation in the (V̇A/ Q̇) ratio in both normal and diseased lungs (Fig. achieved even during vigorous exercise. However, in patients with 28.7). In the normal lung, both ventilation and perfusion are greater at severe COPD, limitation of expiratory flow occurs even during tidal the bases than at the apices but the gradient for perfusion is steeper, breathing at rest (Fig. 28.6B). To increase ventilation, these patients so the net effect is that ventilation exceeds perfusion towards the have to breathe at higher lung volumes and allow more time for apices while perfusion exceeds ventilation at the bases. Other 28 934 Respiratory disease Fig. 28.6 Flow–volume loops. (A–B) Maximal flow–volume loops, showing the relationship between maximal flow rates on expiration and inspiration. (A) Normal subject. (B) 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 dependent only on effort, the shape of the maximal inspiratory flow–vol- ume loop is quite different, and inspiratory flow remains at a high rate throughout the manoeuvre. (C–D) Flow–volume loops in 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 (compare A, B), greatly reducing effort tolerance. causes of mismatch include direct shunting of deoxygenated blood through hyperventilation will not increase blood oxygen content. through the lung without passing through alveoli (e.g. the bronchial This means that hypoxaemia due to physiological shunting cannot circulation) and areas of lung that receive no blood (e.g. anatomical be compensated for by hyperventilation. deadspace, bullae and areas of under-perfusion during acceleration In individuals who have mild degrees of mismatch the PaO2 and and deceleration, e.g. in aircraft and high-performance cars). PaCO2 will still be normal at rest. Increasing the requirements for An increased physiological shunt results in arterial hypoxaemia gas exchange by exercise will widen the mismatch and the PaO2 since it is not possible to compensate for some of the blood being will fall. Mismatch is by far the most common cause of arterial under-oxygenated by increasing ventilation of the well-perfused hypoxaemia.! areas. An increased physiological deadspace just increases the work of breathing and has less impact on blood gases since the Alveolar stability normally perfused alveoli are well ventilated. In more advanced dis- Pulmonary alveoli are polygonal spaces within a sponge-like matrix. ease this compensation cannot occur, leading to increased alveolar Surface tension acting at the curved internal surface tends to cause and arterial PCO2 (PaCO2), together with hypoxaemia, which cannot the alveoli to decrease in size. The surface tension within the alveoli be compensated for by increasing ventilation. would make the lungs extremely difficult to distend, were it not for Hypoxaemia occurs more readily than hypercapnia because of the presence of surfactant, which reduces surface tension so that the different ways in which oxygen and carbon dioxide are carried alveoli remain stable.! in the blood. Carbon dioxide is carried in three forms (in bicarbon- ate, in carbamino compounds and in simple solution) but the vol- Defence mechanisms of the respiratory tract ume carried is proportional to the partial pressure of CO2. Oxygen is Pulmonary disease often results from a failure of the normal host carried in chemical combination with haemoglobin in the red blood defence mechanisms of the healthy lung (Fig. 28.8). These can be cells, with a non-linear relationship between the volume carried and divided into physical, physiological, humoral and cellular mechanisms. the partial pressure. Alveolar hyperventilation reduces the alveolar PCO2 (PACO2) and diffusion leads to a proportional fall in the carbon Physical and physiological mechanisms dioxide content of the blood (PaCO2). However, as the haemoglo- Humidification bin is already saturated with oxygen, increasing the alveolar PO2 This prevents dehydration of the epithelium.!  Function of the respiratory system 935 28 Fig. 28.7 Relationships between ventilation and perfusion: Fig. 28.8 Defence mechanisms present at the epithelial surface. 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 Congenital defects in mucociliary transport (cystic fibrosis and ventilation (physiological shunting). COPD, chronic obstructive immotile cilia syndrome) lead to recurrent infections and eventually pulmonary disease. to bronchiectasis.! Particle removal The respiratory microbiome Over 90% of particles of more than 10 µm in diameter are removed in It has always been thought that the lower respiratory tract is sterile. the nostril or nasopharynx. This includes most pollen grains, which Recent evidence has shown that there is a resident bacterial flora are typically greater than 20 µm in diameter. Particles between 5 and that is very similar to that of the mouth. The composition of the 10 µm become impacted at the carina. Particles of less than 1 µm respiratory microbiome is determined by three factors: tend to remain airborne: thus the particles capable of reaching the microbial immigration, e.g. by inhalation, or microaspiration deep lung are those in the 1–5 µm range.! from the gastrointestinal tract local growth conditions for the bacteria, e.g. temperature, pH, Particle expulsion nutrients, concentration and activation of local inflammatory This is facilitated by coughing, sneezing or gagging.! cells, and epithelial cell interactions microbial elimination by the usual mechanisms, i.e. the muco- Respiratory tract secretions ciliary escalator, coughing and the innate and adaptive humoral The mucus of the respiratory tract is a gelatinous substance consisting mechanisms. of water and highly glycosylated proteins (mucins). The mucus forms All of these factors will change in both acute and chronic lung a thick gel that is relatively impermeable to water and floats on a liquid conditions when there is an increase in pathological bacteria. This or sol layer found around the cilia of the epithelial cells (see Fig. 28.8). respiratory tract dysbiosis causes a dysregulation of the local The gel layer is secreted from goblet cells and mucus glands as dis- immune response and favours the growth of bacteria: for example, tinct globules that coalesce increasingly in the central airways to form in the exacerbation of chronic diseases in which inflammation is a more or less continuous mucus blanket. In addition to the mucins, perpetuated. The background composition of the bacterial micro- the gel contains various antimicrobial molecules (lysozyme, defensins), biome in different conditions might favour exacerbations.! specific antibodies (IgA) and cytokines, which are secreted by cells in airways and are incorporated into the mucus gel. Bacteria, viruses and other particles become trapped in the mucus and are either inactivated Humoral and cellular mechanisms or simply expelled before they can do any damage. Under normal Non-specific soluble factors conditions the tips of the cilia engage with the undersurface of the gel Alpha-antitrypsin (α1-antiprotease, see p. 1302) in lung se- phase and by coordinated movement they push the mucus blanket cretions is derived from plasma. It inhibits chymotrypsin and upwards and outwards to the pharynx, where it is either swallowed or trypsin, and neutralizes proteases, including neutrophil elastase. coughed up. One of the major long-term effects of cigarette smoking Antioxidant defences include enzymes such as superoxide dis- is a reduction in mucociliary transport. This contributes to recurrent mutase and low-molecular-weight antioxidant molecules (ascor- infection and prolongs contact with carcinogenic material. Air pollut- bate, urate) in the epithelial lining fluid. ants, local and general anaesthetics, and products of bacterial and viral Lysozyme is an enzyme found in granulocytes that has bacteri- infection also reduce mucociliary clearance. cidal properties. 28 936 Respiratory disease Lactoferrin is synthesized from epithelial cells and neutrophil bronchi and diaphragm. Afferent receptors go to the cough centre in granulocytes, and has bactericidal properties. the medulla, where efferent signals are generated to the expiratory Interferons are produced by most cells in response to viral in- musculature. Smokers often have a morning cough with a little spu- fection and are potent modulators of lymphocyte function. tum. A productive cough is the cardinal feature of chronic bronchitis, Complement in secretions is also derived from plasma. In as- while dry coughing, particularly at night, can be a symptom of asthma sociation with antibodies, it plays a major role in cytotoxicity. or acid reflux. Cough also occurs in asthmatics after mild exertion or Surfactant protein A (SPA) is one of four species of surfactant forced expiration. Cough can have no definable pathology; psycho- protein that opsonize bacteria or particles, enhancing phagocy- logical causes may be blamed but there is only limited evidence. tosis by macrophages. A worsening cough is the most common presenting symptom Defensins are bactericidal peptides present in the azurophil of lung cancer. The normal explosive character of the cough is lost granules of neutrophils. when a vocal cord is paralysed, usually as a result of lung cancer infil- Dimeric secretory IgA targets specific antigens (see p. 1155).! trating the left recurrent laryngeal nerve. Cough can be accompanied by stridor in whooping cough or in laryngeal or tracheal obstruction.! Innate and adaptive immunity These mechanisms act as a defence against microbes, inorganic Sputum substances such as asbestos, particulate matter such as dust, and Approximately 100 mL of mucus is produced daily in a healthy, non- other antigens. They aid opsonization so that macrophages can smoking individual. This flows gradually up the airways, through the better ingest foreign material. larynx, and is then swallowed. Excess mucus is expectorated as With infection, neutrophils migrate out of pulmonary capillar- sputum. Cigarette smoking is the most common cause of excess ies into the air spaces and phagocytose and kill microbes with, for mucus production. example, antimicrobial proteins (lactoferrin), degradative enzymes Mucoid sputum is clear and white but can contain black specks (elastase) and oxidant radicals. In addition, neutrophil extracellular resulting from the inhalation of carbon. Yellow or green sputum is due traps ensnare and kill extracellular bacteria. Neutrophils also gener- to the presence of cellular material, including bronchial epithelial cells, ate a variety of mediators, such as tumour necrosis factor alpha or neutrophil or eosinophil granulocytes. Yellow sputum is not neces- (TNF-α), interleukin 1 (IL-1), and chemokines that attract further sarily due to infection, since granulocytes in the sputum, as seen in inflammatory cells that assist with adaptive immunity. asthma, can give the same appearance. The production of large quan- Microbes are detected by host cells by pattern recognition tities of yellow or green sputum is characteristic of bronchiectasis.! receptors, such as toll-like receptors. These act via nuclear fac- tor kappa B (NF-κB) transcription factors in the epithelial cells to Haemoptysis produce adhesion molecules, chemokines and colony stimulating Haemoptysis (blood-stained sputum) varies from small streaks of factors to initiate inflammation. Inflammation is necessary for innate blood to massive bleeding. The most common cause of mild haem- immunity and host defence but can lead to lung damage; there is a optysis is acute infection (Box 28.3), particularly in exacerbations fine line between defence and injury. of COPD, but this should not be assumed without investigation. Other common causes are pulmonary infarction (e.g. secondary Further reading to pulmonary embolism), bronchial carcinoma and tuberculosis. Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med Pink, frothy sputum is seen in pulmonary oedema, while in bron- 2010; 363:2233–2247. Kiley JP, Caler EV. The lung microbiome: a new frontier in pulmonary medicine. chiectasis the blood is often mixed with purulent sputum. Massive Ann Am Thorac Soc 2014; 11(Suppl 1):S66–S70.! haemoptysis (>200 mL of blood in 24 h) is usually due to bronchi- ectasis or tuberculosis, but can also be caused in later stages of lung cancer. Although a diagnosis can often be made from a chest X-ray CLINICAL APPROACH TO THE (e.g. bronchiectasis, tuberculosis), a normal chest X-ray does not PATIENT WITH RESPIRATORY exclude serious disease. However, if the chest X-ray is normal, CT DISEASE scanning and bronchoscopy are diagnostic in only about 5% of patients with haemoptysis.! Clinical features of respiratory disease Runny, blocked nose and sneezing Box 28.3 Causes of haemoptysis Nasal symptoms are extremely common; ‘runny nose’ (rhinorrhoea), Malignancy and benign lung tumours, including lung metastasis nasal blockage and attacks of sneezing can be caused by allergic rhi- Pulmonary infection, including bacterial pneumonia, tuberculosis, lung nitis (see p. 945) and by common colds (p. 945). Nasal secretions are abscesses and fungal infection usually thin and runny in allergic rhinitis but thicker and discoloured Bronchiectasis, including cystic fibrosis with viral infections. Nose bleeds and blood-stained nasal discharge Pulmonary emboli are common and rarely indicate serious pathology. However, a blood- Congestive heart failure stained nasal discharge associated with nasal obstruction and pain Pulmonary fibrosis may be the presenting feature of a nasal tumour (see p. 908). Nasal Pulmonary vasculitis, e.g. Goodpasture’s syndrome, microscopic polyangiitis polyps typically present with nasal blockage and loss of smell.! Severe pulmonary hypertension Arteriovenous malformation Cough Chest trauma and foreign bodies Cough (see also p. 908) is the most common symptom of lower respi- Endometriosis ratory tract disease. It is caused by mechanical or chemical stimulation Anticoagulation, coagulopathy of cough receptors in the epithelium of the pharynx, larynx, trachea, Drugs, e.g. cocaine, thrombolytics  Clinical Approach to the Patient with Respiratory Disease 937 28 Box 28.4 Causes of breathlessness Box 28.6 Signs to look for in the hands Acute Metabolic acidosis Clubbing Airways obstruction Pain Pallor Anaphylaxis Pontine haemorrhage! Warm, well-perfused palms (CO2 retention) Asthma Chronic Cyanosis Pneumothorax COPD Flap Pulmonary embolus Pleural effusion Tremor Myocardial infarction Malignancy Tobacco staining Pulmonary oedema Chronic pulmonary emboli Bruising and/or thin skin Arrhythmias Restrictive lung disorders Pulse rate and character Anxiety! Congestive cardiac failure Subacute Valvular dysfunction Pneumonia Cardiomyopathy localize it. Localized anterior chest pain with tenderness of a cos- Exacerbation of COPD Anaemia tochondral junction is caused by costochondritis. Shoulder tip pain Angina Neuromuscular disorders suggests irritation of the diaphragmatic pleura, while central chest Cardiac tamponade Deconditioning pain radiating to the neck and arms is likely to be cardiac. Retroster- nal soreness is associated with tracheitis, and malignant invasion of COPD, chronic obstructive pulmonary disease. the chest wall causes a constant, severe, dull pain.! Box 28.5 Medical Research Council grading of dyspnoea (breathlessness scale) Examination of the respiratory system 1. Not troubled by breathlessness, except on strenuous exercise Nose 2. Short of breath when hurrying or walking up a slight hill See page 907.! 3. Walks slower than contemporaries on the level because of breathless- ness, or has to stop for breath when walking at own pace Chest 4. Stops for breath after about 100 m or after a few minutes on the level 5. Too breathless to leave the house, or breathless when dressing or undressing Inspection Observe the patient as they enter the room or move around the bed. Are they simply breathless at rest? Do they have a cough or are they Breathlessness wheezy? Assessment should be made of mental alertness, cyano- Dyspnoea (breathlessness) is a sense of awareness of increased sis, breathlessness at rest, use of accessory muscles, shape of the respiratory effort that is unpleasant and recognized by the patient as chest wall, any deformity or scars on the chest and movement on inappropriate. Patients often complain of tightness in the chest; this both sides. Kyphosis and scoliosis of the spine can cause asymmetry must be differentiated from angina (Box 28.4). The degree of breath- of the chest. CO2 intoxication causes coarse tremor or flap of the out- lessness should be assessed in relation to the patient’s lifestyle. stretched hands. Prominent veins on the chest may imply obstruction For example, a moderate degree of breathlessness will be totally of the superior vena cava. The patient’s face may reveal signs of anae- disabling if the patient has to climb many flights of stairs to reach mia, or there may be a Horner’s syndrome due to a Pancoast tumour. home. Breathlessness can be graded using the Medical Research Respiratory rate and rhythm may be altered; the normal respi- Council grading of dyspnoea (Box 28.5). ratory rate is 14–16 breaths per minute. Tachypnoea is an increased Orthopnoea (see p. 1028) is breathlessness on lying down. respiratory rate. Apnoea is the absence of breathing; some patients While it is classically linked to heart failure, it is partly due to the have episodes of apnoea during sleep. weight of the abdominal contents pushing the diaphragm up into the Hands should be inspected for evidence of tobacco staining on thorax. Such patients may also become breathless on bending over. the fingers, clubbing or a fine tremor (Box 28.6). Tachypnoea and hyperpnoea are, respectively, an increased Cyanosis (see p. 1030) is a dusky discoloration of the skin and rate of breathing and an increased level of ventilation. These may mucous membranes, due to the presence of more than 50 g/L of be appropriate responses (e.g. during exercise). desaturated haemoglobin. When it has a central cause, cyanosis Hyperventilation is inappropriate overbreathing. This may is visible on the tongue (especially the underside) and lips. Patients occur at rest or on exertion, and results in a lowering of the alveolar with central cyanosis will also be cyanosed peripherally. Peripheral and arterial PCO2 (see Box 25.33). cyanosis without central cyanosis is caused by a reduced peripheral Paroxysmal nocturnal dyspnoea (see p. 1028) describes acute circulation and is noted on the fingernails and skin of the extremi- episodes of breathlessness at night, typically due to heart failure.! ties, with associated coolness of the skin. Finger clubbing is present when the normal angle between the Wheezing base of the nail and the nail fold is lost (Fig. 28.9). The base of Wheezing is a common complaint and results from airflow limitation due the nail is fluctuant owing to increased vascularity, and there is an to any cause. The symptom of wheezing is not diagnostic of asthma; increased curvature of the nail in all directions, with expansion of other causes include vocal cord dysfunction, bronchiolitis and COPD. the end of the digit. Some causes of clubbing are given in Box 28.7. Conversely, wheeze may be absent in the early stages of asthma.! Clubbing is not a feature of uncomplicated COPD.! Chest pain Palpation and percussion The most common type of chest pain reported in respiratory dis- The position of the trachea and apex beat should be checked. The ease is a localized sharp pain, often termed pleuritic. It is made supraclavicular fossa, cervical chains and axilla are examined for worse by deep breathing or coughing and the patient can usually enlarged lymph nodes. The distance between the sternal notch and 28 938 Respiratory disease the cricoid cartilage (3–4 finger-breadths in full expiration) is reduced In rib fractures, compression of the chest laterally and anteroposte- in patients with severe airflow limitation. Chest expansion should riorly produces localized pain. On percussion, liver dullness is usu- be checked; a tape measure may be used if precise or serial mea- ally detected anteriorly at the level of the sixth rib. Liver and cardiac surements are needed, such as in ankylosing spondylitis. Local dullness disappear when the lungs are over-inflated (Box 28.8).! discomfort over the sternochondral joints suggests costochondritis. Auscultation The patient is asked to take deep breaths through the mouth. Inspi- ration 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 hiss- ing components of breath are not attenuated and can be heard as Fig. 28.9 Clubbing deformity. The finger on the right is clubbed ‘bronchial breathing’. Similar sounds may be heard over areas of compared with the normal-shaped finger on the left. (From Hochberg localized fibrosis or bronchiectasis. Bronchial breathing is accom- MC, Gravallese EM, Silman AJ et al. Rheumatology, 7th edn. Elsevier panied by whispering pectoriloquy (whispered, high-pitched sounds Inc.; 2019; Fig. 213.2.) can be heard distinctly through a stethoscope).! Added sounds Box 28.7 Some causes of finger clubbing Wheeze. Wheeze results from vibrations in the collapsible part of the Respiratory airways when the large and medium-sized bronchi become constricted. Bronchial carcinoma, including hypertrophic pulmonary osteoarthropathy It is usually heard during expiration and is commonly, but not invariably, Chronic suppurative lung disease: present in asthma and COPD. In acute severe asthma, wheeze may – Bronchiectasis not be heard, as airflow may be insufficient to generate the sound. – Lung abscess Wheezes may be monophonic (single large airway obstruction) or poly- – Empyema phonic (narrowing of many small airways). An end-inspiratory wheeze Idiopathic lung fibrosis or ‘squeak’ may be heard in obliterative bronchiolitis. Pleural and mediastinal tumours (e.g. mesothelioma) Crackles. These brief crackling sounds are probably produced Cryptogenic organizing pneumonia! by opening of previously closed bronchioles; early inspiratory crack- Cardiovascular les are associated with diffuse airflow limitation, while late inspi- Cyanotic heart disease Subacute infective endocarditis ratory crackles are characteristically heard in pulmonary oedema, Atrial myxoma! lung fibrosis and bronchiectasis. Miscellaneous Pleural rub. This creaking or groaning sound is usually well Congenital – no disease localized (said to sound like a foot crunching through fresh-fallen Cirrhosis snow). It indicates inflammation and roughening of the pleural sur- Inflammatory bowel disease faces, which normally glide silently over one another, and is heard in Thyroid acropachy association with lung infections and consolidation. Box 28.8 Physical signs of respiratory disease Pathological process Mediastinal displacement Percussion note Breath sounds Vocal resonance Added sounds Consolidation (i.e. lobar None Dull Bronchial Increased Fine crackles pneumonia) Collapse Major bronchus Towards lesion Dull Diminished or absent Reduced or absent None Peripheral bronchus Towards lesion Dull Bronchial Increased Fine crackles Fibrosis Localized Towards lesion Dull Bronchial Increased Coarse crackles Generalized (e.g. None Normal Vesicular Increased Fine crackles idiopathic lung fibrosis) Pleural effusion Away from lesion (in Stony dull Vesicular reduced or Reduced or absent None (>500 mL) massive effusion) absent Large pneumothorax Away from lesion Normal or hyper- Reduced or absent Reduced or absent None resonant Asthma None Normal Vesicular Normal Expiratory polyphonic Prolonged expiration wheeze Chronic obstructive None Normal Vesicular Normal Expiratory polyphonic pulmonary disease Prolonged expiration wheeze and coarse crackles Bronchiectasis None Normal Vesicular Normal Coarse crackles  Clinical Approach to the Patient with Respiratory Disease 939 28 Box 28.9 The chest X-ray Check Centring of the image. The distance between each clavicular head and the spinal processes should be equal. Penetration. Make sure the image is not too dark and adjust the contrast. View: – Postero-anterior (PA) views are used for routine images; the X-ray source is behind the patient. – Anteroposterior (AP) views are used only in patients who are unable to stand or cannot be taken to the radiology department; the cardiac outline appears bigger and the scapulae cannot be moved out of the way. – Lateral views were used to localize pathology but have been replaced by CT scans.! Look at Shape and bony structure of the chest wall Centrality of the trachea Elevation/flatness of the diaphragm Shape, size and position of the heart Shape and size of the hilar shadows Shape and size of any lung abnormalities Fig. 28.10 Collapse of the left upper lobe. Chest X-ray showing Vascular shadowing increased opacification in the left upper and mid zone with evidence of left-sided volume loss. Vocal resonance. Healthy lung attenuates high-frequency notes, as compared to the lower-pitched components of speech. Box 28.10 Causes of lung collapse Consolidated lung has the reverse effect, transmitting high frequen- Enlarged tracheobronchial lymph nodes due to malignant disease or cies well; the spoken word then takes on a bleating quality. Whis- tuberculosis pered (and therefore high-pitched) speech can be clearly heard over Inhaled foreign bodies (e.g. peanuts) in children, usually in the right main consolidated areas, as compared to healthy lung. Low-frequency bronchus sounds such as ‘ninety-nine’ are well transmitted across healthy Bronchial casts or plugs (e.g. allergic bronchopulmonary aspergillosis) lung to produce vibration that can be felt over the chest wall. Con- Retained secretions postoperatively and in debilitated patients solidated lung transmits these low-frequency noises less well, and pleural fluid severely dampens or obliterates the vibrations alto- gether. Tactile vocal fremitus is the palpation of this vibration, usually Collapse and consolidation by placing the edge of the hand on the chest wall. For all practical Simple pneumonia is easy to recognize (see Fig. 28.28) but a care- purposes, this duplicates the assessment of vocal resonance and is ful search should be made for any evidence of collapse (Fig. 28.10 not routinely performed as part of the chest examination.! and Box 28.10). Loss of volume or crowding of the ribs is the best indicator of lobar collapse. The lung lobes collapse in characteristic Cardiovascular system examination directions: This gives additional information about the lungs (see p. 1029).! The lower lobes collapse downwards and towards the mediasti- num. Additional bedside tests The left upper lobe collapses forwards against the anterior chest Review the patient’s observation chart, particularly oxygen satura- wall. tions and the concentration of additional oxygen that the patient may The right upper lobe collapses upwards and inwards, giving the be receiving. Inspect any sputum pots. Since so many patients with appearance of an arch over the remaining lung. respiratory disease have airflow limitation, airflow should be routinely The right middle lobe collapses anteriorly and inwards, obscur- measured using a peak flow meter or spirometer. This is a much more ing the right heart border. useful assessment of airflow limitation than any physical sign.! If a whole lung collapses, the mediastinum will shift towards the side of the collapse. Uncomplicated consolidation does not cause mediastinal shift Investigation of respiratory disease or loss of lung volume, and so any of these features should raise the suspicion of an endobronchial obstruction.! Imaging Imaging is essential in the investigation of most chest symptoms. Some diseases, such as tuberculosis or lung cancer, may be undetectable Pleural effusion on clinical examination but may be obvious on the chest X-ray. Con- Pleural effusions (see Fig. 28.31) need to be larger than 500 mL versely, asthma or chronic bronchitis may be associated with a normal to cause much more than blunting of the costophrenic angle. On chest X-ray. Always try to obtain previous images for comparison. an erect film, they produce a characteristic shadow with a curved upper edge rising into the axilla. If they are very large, the whole of Chest X-ray one hemithorax may be opaque, with mediastinal shift away from See Box 28.9 and Fig. 28.1. the effusion.! 28 940 Respiratory disease Box 28.11 Causes of round shadows (>3 cm) in the lung Carcinoma Metastatic tumours (usually multiple shadows) Lung abscess (usually with fluid level) Encysted interlobar effusion (usually in horizontal fissure) Hydatid cysts (often with a fluid level) Arteriovenous malformations (usually adjacent to a vascular shadow) Aspergilloma Rheumatoid nodules Tuberculoma (may be calcification within the lesion) Bronchial carcinoid Cylindroma Chondroma Lipoma! Other shadows related to mediastinum Pericardium Oesophagus Can be characterised by performing a lateral chest X-ray Spinal cord Fibrosis Localized fibrosis produces streaky shadowing, and the accompa- nying loss of lung volume causes mediastinal structures to move to the same side. More generalized fibrosis can lead to a honeycomb appearance (see p. 988), seen as diffuse shadows containing mul- tiple circular translucencies a few millimetres in diameter.! Round shadows Lung cancer is the most common cause of large round shadows but many other aetiologies are recognized (Box 28.11).! Miliary mottling This term, derived from the Latin for millet, describes numerous min- ute opacities, 1–3 mm in size. The most common causes are tubercu- losis, pneumoconiosis, sarcoidosis, idiopathic pulmonary fibrosis and pulmonary oedema (see Fig. 30.15), although pulmonary oedema is usually perihilar and accompanied by larger, fluffy shadows. Pulmo- nary microlithiasis is a rare but striking cause of miliary mottling.! Computed tomography Computed tomography (CT) provides excellent images of the lungs and mediastinal structures (Fig. 28.11). It is essential in staging bron- chial 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 periph- eral masses. Staging scans should assess liver and adrenals, which are common sites for metastatic disease. Mediastinal structures are Fig. 28.11 Computed tomography scans of the lung. (A) Axial shown more clearly after injecting intravenous contrast medium. CT image of the thorax on lung settings. (1) Right hilum; (2) left hilum; High-resolution CT (HRCT) samples lung parenchyma with (3) right main bronchus; (4) left main bronchus; (5) right lung; (6) left 1–2 mm thickness scans at 10–20 mm intervals and is used to assess lung; (7) bronchus; (8) blood vessel. (B) Axial CT image of the thorax diffuse inflammatory and infective parenchymal processes. HRCT on soft tissue settings. (1) Right lung; (2) left lung; (3) ascending aorta; scanning does not require any intravenous contrast. It is valuable in: (4) descending aorta; (5) pulmonary trunk; (6) right pulmonary artery; evaluation of diffuse disease of the lung parenchyma, includ- (7) left pulmonary artery; (8) vertebra; (9) rib; (10) scapula. (C) CT chest demonstrates a right upper lobe carcinoma that is invading the ing sarcoidosis, hypersensitivity pneumonitis, occupational lung mediastinum (black arrow) and prominent mediastinal lymph nodes disease and any other form of interstitial pulmonary fibrosis (white arrow). diagnosis of bronchiectasis, having a sensitivity and specificity of >90% distinction of emphysema from diffuse parenchymal lung dis- Multi-slice CT scanners can produce detailed images in two or ease or pulmonary vascular disease as a cause of a low gas three dimensions in any plane. This detail is particularly useful for transfer factor with otherwise normal lung function the detection of pulmonary emboli. Pulmonary nodules and airway suspected opportunistic lung infection in immunocompromised disease are more easily defined, reducing the need for HRCT. patients CT pulmonary angiography (CTPA) is used to investigate for diagnosis of lymphangitis carcinomatosa. pulmonary embolism and enables visualization of the pulmonary  Clinical Approach to the Patient with Respiratory Disease 941 28 arteries. Contrast is injected and images are taken in timed fashion, heavily loculated with adhesions or organized (more gelatinous). so that the contrast agent is in the pulmonary circulation.! Ultrasound assists in determining the best site for aspiration and it is recommended that any invasive pleural procedure, such as pleu- Magnetic resonance imaging ral aspiration and intercostal chest drain placement, is performed Magnetic resonance imaging (MRI) with electrocardiography (ECG) with ultrasound screening. Ultrasound-guided biopsy is used for gating allows accurate imaging of the heart and aortic aneurysms. lung masses that abut the pleura or pleural masses, if appropriate. MRI has been used in staging lung cancer and assessing tumour It is also used in bronchoscopy (endobronchial ultrasound, EBUS) invasion in the mediastinum and chest wall and at the lung apex to stage and sample mediastinal lymph nodes (see p. 944).! because it produces good images in the sagittal and coronal planes. Vascular structures can be clearly differentiated, as flowing blood Respiratory function tests produces a signal void on MRI. Traditionally, MRI has been less use- In clinical practice, airflow limitation can be assessed by relatively ful than CT in parenchymal lung disease; however, it may have a simple tests that have good intra-subject repeatability (Box 28.12). place in interstitial lung disease assessment in the future.! Results must be compared with predicted values for healthy sub- jects, as normal ranges vary with sex, age, height and ethnic group. Positron emission tomography–computed Moreover, there is considerable variation between healthy individu- tomography als of the same size and age; the standard deviation for the PEFR PET-CT combines a CT scan and positron emission tomography. is approximately 50 L/min, and for the FEV1 approximately 0.4 L. Positron-emitting isotopes such as 18fluorodeoxyglucose (18FDG) Repeated measurements of lung function are useful for assessing are used as contrast and are taken up rapidly by metabolically active the progression of disease in individual patients. tissue such as lung cancers. PET imaging is used for lung cancer staging prior to curative treatment such as surgery or radiotherapy. Tests of ventilatory function FDG-PET can also be useful in determining an appropriate site for a These tests are used mainly to assess the degree of airflow limita- biopsy and can often assist with differentiating benign from malig- tion during expiration. nant tumours; however, inflammatory lesions may also be FDG-avid.! Spirometry Scintigraphic imaging The patient takes a maximum inspiration followed by a forced expi- Isotopic lung scans were widely used for the detection of pulmonary ration (for as long as possible) into the spirometer. The spirometer emboli but are now performed less often, owing to the widespread measures the 1-second forced expiratory volume (FEV1) and the use of CTPA. They are discussed in more detail on page 1005.! total volume of exhaled gas (forced vital capacity, FVC). Both FEV1 and FVC are related to height, age, sex and ethnicity, and help to Ultrasound differentiate between an obstructive and a restrictive pattern of Two-dimensional transthoracic ultrasound is a technique used for respiratory compromise (Fig. 28.12; Box 28.13). assessing a pleural effusion. Ultrasound confirms the presence of In chronic airflow limitation (particularly COPD and asthma), the pleural fluid and provides details about the nature of the effusion, total lung capacity (TLC) is usually increased, yet there is nearly such as whether it is a simple pleural effusion (single collection), always some reduction in the FVC. This is because collapse of small Box 28.12 Respiratory function and exercise tests Test Use Advantages Disadvantages PEFR Monitoring changes in airflow limitation in Portable Effort-dependent asthma Can be used at the bedside Poor measure of chronic airflow limitation FEV, FVC, FEV1/FVC Assessment of airflow limitation Reproducible Bulky equipment but smaller (the best single test) Relatively effort-independent portable machines available Flow–volume curves Assessment of flow at lower lung volumes Recognizes patterns of flow–volume Sophisticated equipment needed Detection of large-airway obstruction, both curves for different diseases for full test but expiratory intra- and extrathoracic (e.g. tracheal loop possible with compact stenosis, tumour) spirometry Airways resistance Assessment of airflow limitation Sensitive Technique difficult to perform Lung volumes Differentiation between restrictive and Effort-independent, complements FEV1 Sophisticated equipment needed obstructive lung disease Gas transfer Assessment and monitoring of extent of Non-invasive (compared with lung Sophisticated equipment needed interstitial lung disease and emphysema biopsy or radiation from repeated chest X-rays and CT) Blood gases Assessment of respiratory failure Can detect early lung disease when Invasive measured during exercise Pulse oximetry Postoperative, sleep studies and respiratory Continuous monitoring Measures saturation only failure Non-invasive Exercise tests (6-min Practical assessment for disability and No equipment required Time-consuming walk) effects of therapy Learning effect At least two walks required Cardiorespiratory Early detection of lung/heart disease Differentiates breathlessness due to Expensive and complicated assessment Fitness assessment lung or heart disease equipment required CT, computed tomography; FEV, forced expiratory volume; FEV1, forced expiratory volume in 1 sec; FVC, forced vital capacity; PEFR, peak expiratory flow rate. 28 942 Respiratory disease airways causes obstruction to airflow before the normal residual volume (RV) is reached. This trapping of air within the lung is a char- acteristic feature of these diseases.! Peak expiratory flow rate Peak expiratory flow rate (PEFR) is an extremely simple and cheap test. Subjects take a full inspiration to total lung capacity and then blow out forcefully into the peak flow meter (Fig. 28.13). The best of three attempts is recorded. Although reproducible, PEFR is mainly dependent on the flow rate in larger airways and it may be falsely reassuring in patients with moderate airflow limitation. PEFR is mainly used to diagnose asthma, and to monitor exacerbations of asthma and response to treatment. Regular measurements of peak flow rates on waking, during the afternoon and before going to bed demonstrate the wide diurnal variations in airflow limitation that characterize asthma and allow objective assessment of response to treatment (Fig. 28.14).! Other ventilatory function tests Measurement of airways resistance in a body box (plethysmograph) is more sensitive but the equipment is expensive and the neces- sary manoeuvres are too exhausting for many patients with chronic airflow limitation.! Fig. 28.12 Spirometry: volume–time curves. (A) Normal patterns Flow–volume loops for age and sex. (B) Restrictive pattern (FEV1 and FVC reduced). (C) Plotting flow rates against expired volume (flow–volume loops, see Airflow limitation (FEV1 only reduced). FEV1, forced expiratory volume