Essential respiratory medicine. Shanthi Paramothayan

Chapter 6. Obstructive airways disease

Learning objectives

 To understand the aetiology and epidemiology of asthma

 To learn about the diagnosis and differential diagnosis of asthma

 To understand the management of acute and chronic asthma

 To recognise the risk factors for fatal asthma

 To understand the aetiology and epidemiology of chronic obstructive pulmonary disease (COPD)

 To understand the diagnosis and differential diagnosis of COPD

 To understand the management and prognosis of COPD

 To understand the management of acute exacerbation of COPD

 To have some understanding of the diagnosis and management of a-1 antitrypsin deficiency (a-1ATD)

 To understand the diagnosis and management of allergic bronchopulmonary aspergillosis (ABPA)

 To understand the diagnosis and management of vocal cord dysfunction

 To understand the diagnosis and management of hyperventilation syndrome


a-1AT a-1 antitrypsin

a-1ATD a-1 antitrypsin deficiency

ABG arterial blood gas

ABPA allergic bronchopulmonary aspergillosis

ACQ Asthma Control Questionnaire

ADAPT Antitrypsin Deficiency Assessment and Programme for Treatment

AHR airway hyper-responsiveness

BHR bronchial hyper-responsiveness

BiPAP bilevel positive airway pressure

CAP community acquired pneumonia

CAT COPD Assessment Test

CBT cognitive behavioural therapy

CO carbon monoxide

CO2 carbon dioxide

COPD chronic obstructive pulmonary disease

CXR chest X-ray

DNA deoxyribonucleic acid

ECRHS European Community Respiratory Health Survey

EGPA eosinophilic granulomatosis with polyangiitis

FEV1 forced expiratory volume in one second

FVC forced vital capacity

GINA Global Initiative for Asthma

GOLD Global Initiative for Chronic Obstructive Lung Disease

GP General Practitioner

HAD Hospital Anxiety and Depression questionnaire

HDM house dust mite

HDU high dependency unit

HRCT high-resolution computed tomography

HV hyperventilation

ICS inhaled corticosteroid

ICU intensive care unit

Ig immunoglobulin

IgE immunoglobin E

ISAAC International Study of Asthma and Allergy in Children

JVP jugular venous pressure

KCO transfer coefficient

LABA long-acting β2-agonist

LTOT long term oxygen therapy

LVRS lung volume reduction surgery

MRC Medical Research Council

NICE National Institute for Health and Care Excellence

NIV non-invasive ventilation

NO nitric oxide

NO2 nitric dioxide

NRAD National Review of Asthma Deaths

NRT nicotine replacement therapy

NSAIDS non-steroidal anti-inflammatory drugs

O3 ozone

OCS oral corticosteroids

PEF peak expiratory flow

PVFM paradoxical vocal fold motion

QOL quality of life

RAST radioallergosorbent test

RV residual volume

SABA short-acting β2-agonist

SIGN Scottish Intercollegiate Guidelines Network

SO2 sulphur dioxide

Th1 T-helper lymphocytes 1

Th2 T-helper lymphocytes 2

TLC total lung capacity

TLCO transfer factor for carbon monoxide (diffusing capacity)

UK United Kingdom

VATS video-assisted thoracoscopic surgery

VCD vocal cord dysfunction


Diseases that cause airway obstruction include asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis. Bronchiectasis is a suppurative lung disease associated with frequent infective exacerbations. This is discussed in Chapter 12.

Asthma and COPD are common conditions that account for a significant amount of morbidity in the general population, requiring frequent visits to the General Practitioner (GP). Patients with these conditions present with breathlessness, which is worse on exertion, a cough, and chest tightness. These symptoms may be present all the time, as in COPD, or may be intermittent and variable, as in asthma. Patients with asthma and COPD are prone to exacerbations, usually triggered by infection, often requiring hospitalisation.

The differential diagnosis for obstructive airways disease includes a-1 antitrypsin deficiency (a-1 ATD), allergic bronchopulmonary aspergillosis (ABPA), hyperventilation (HV), and vocal cord dysfunction (VCD). The diagnosis of these conditions can be made by taking a detailed history, clinical examination, appropriate radiology (CXR, HRCT), spirometry, and lung function testing with reversibility. Other investigations, such as a methacholine challenge, measurement of immunoglobulin E and aspergillus IgG levels can clarify the diagnosis.



Asthma is a reversible, obstructive airways disease caused by inflammation, hyper-responsiveness, and narrowing of the bronchial tree in a susceptible individual, secondary to a variety of stimuli.


The exact prevalence of asthma worldwide is unknown because of historic differences in definition, diagnostic criteria, and methods of data collection. The International Study of Asthma and Allergies in Children (ISAAC) and the European Community Respiratory Health Survey (ECRHS) have been monitoring the prevalence of asthma worldwide and have reported an increase since the 1960s, with significant variation between countries. The increased prevalence is mainly in urbanised Western countries, and there are several hypotheses as to the possible reasons for this trend.

The estimated incidence of asthma is 2.6— 4/1000 individuals per year in the United Kingdom (UK) and the prevalence is 3—34% worldwide. This equates to approximately 8% of adults and 20% of children with asthma. Mortality from asthma is 4/100 000 in the UK, with 1500 deaths every year.

Children with asthma are usually atopic, have had bronchial hyper-responsiveness (BHR) and wheezing for at least 12 months, and demonstrate variability in peak expiratory flow readings. Many children with evidence of BHR and wheeze, particularly those under 5 years of age, are incorrectly diagnosed as having asthma. Viral respiratory tract infections and passive smoking, particularly maternal cigarette smoking, are risk factors for BHR and wheezing. There is some evidence that neonates who go on to develop asthma later in life have worse lung function in infancy.

Airway hyper-responsiveness (AHR), which includes BHR, is an abnormally exaggerated response to stimuli such as infection, cold air, or exercise, resulting in the contraction of the bronchial smooth muscle. The degree of bronchoconstriction can be measured by the dose of methacholine or histamine required to cause a 20% fall in forced expiratory volume in one second (FEV1) as discussed in Chapter 4.

Not all individuals with AHR will develop asthma, but because many will have symptoms of dry cough and wheeze when exposed to these triggers, it can be difficult to differentiate between AHR and mild asthma. In adults, the main differential diagnosis for asthma is chronic bronchitis; therefore, adult patients with a history of cigarette smoking should have investigations, including a chest X-ray (CXR) and spirometry with reversibility testing, to establish the correct diagnosis.

A family history of asthma is an important risk factor for developing asthma, even in non-atopic children, with 60% of the susceptibility to asthma being inherited. Twin studies have shown a 19% concordance in monozygotic twins and 4.8% concordance in dizygotic twins. The prevalence of asthma is greater in boys compared to girls, reaching a peak at puberty. The prevalence of asthma in females gradually increases with age, so that it is equal to that in men between the ages of 20 and 40, thereafter becoming more common in females. The reason for this difference is not clear. It has been postulated that it may reflect smaller relative airway size, increased atopy, and differences in the reporting of symptoms in boys.

The aetiology of asthma is multifactorial; airway inflammation occurs when a genetically susceptible individual with atopy is exposed to certain environmental factors. Atopy is the tendency to produce high amounts of immunoglobulin E (IgE) when exposed to small amounts of an antigen. These patients will demonstrate positive reactions to antigens on skin prick testing. Atopic individuals have a high prevalence of asthma, allergic rhinitis, urticaria, and eczema.

Atopy and asthma show polygenic inheritance and genetic heterogeneity, with gene linkages on chromosome 11q13. The genes responsible for the different components of asthma, such as IgE production, BHR and cytokine production, are found on chromosomes 5q, 7, 11q, 12q, 16, 17, and 21q. The ADAM33 gene on chromosome 70p13, which is a disintegrin and a metalloprotease gene, is involved in the structural airway components of asthma, such as airway remodelling. Expression of this gene may lead to the development of chronic persistent asthma, with irreversible airway obstruction and excess decline in FEV1 over time.

Environmental factors appear to be important in the development of asthma. The ISAAC study found an increased association between wheeze and atopy in developed, urbanised countries. As people spend more time inside, concentrations of indoor allergens become more important than outdoor allergens. This is particularly important in young children as allergen exposure early in life may be important in determining sensitisation. Exposure to the house dust mite (HDM) Dermatophagoidespteronyssinus (found in high concentrations in carpets, soft furnishings, and bedding) in early life may be associated with an increased likelihood of sensitisation to HDM by preschool age. Sensitisation to pet-derived allergens (cat, dog, rabbit) is also common.

There is some evidence that exposure to bacterial and viral antigens in very early life may result in allergen sensitisation and the development of asthma. There appears to be a link between exposure to respiratory syncytial virus, human rhinovirus, mycoplasma pneumonia infections, and the development of asthma.

The hygiene hypothesis, in contrast, postulates that lack of childhood infections results in altered T-cell function and a tendency to develop asthma. Some epidemiological studies have shown that close contact with animals in early life may decrease the prevalence of asthma and allergy, perhaps by the provocation of immune tolerance. The results of studies on domestic allergen avoidance, which are very difficult to conduct, are inconsistent. Atmospheric pollution can worsen asthma, but there is no evidence that it is a cause of asthma. Occupational asthma accounts for 15% of cases of asthma and is discussed in Chapter 15.

Atopic individuals produce IgE antibodies to specific allergens which can be measured in the serum. Skin prick testing can also be used to demonstrate allergy to a specific allergen. A video demonstrating how skin prick testing is performed is found in the supplementary material (www.wiley. com/go/Paramothayan/Essential_Respiratory_ Medicine). Serum levels of IgE correlate better with AHR and asthma severity than skin prick testing which correlates better with allergic rhinitis. It is common for atopic individuals to be sensitive to more than one allergen. Individuals with asthma are highly likely to have other atopic conditions, such as allergic rhinitis and atopic dermatitis (eczema).

Approximately a third of children with atopic dermatitis will go on to develop asthma in adolescence.

Pathophysiology of asthma

Airway inflammation, caused by various cytokines, results in reversible obstruction throughout the tracheobronchial tree. The reversibility distinguishes asthma from COPD. In a sensitised, atopic individual, inhalation of an allergen results in a two-phase response consisting of an early reaction, reaching its climax in about 20 minutes, and a late reaction, developing 6—12 hours later. In the early response, T-helper lymphocytes have an important role in the regulation of the inflammatory response. Th2 cells secrete pro-inflammatory interleukins, which leads to the release of high levels of allergen-specific IgE antibodies by plasma cells. The IgE antibodies bind to receptors on mast cells and eosinophils and stimulate them to release preformed mediators, including histamine, prostaglandins, platelet-activating factor, tryptase, major basic protein, eosinophil cationic protein, eosinophil protein X, heparin, and cysteinyl leukotrienes. These mediators cause bronchoconstriction within minutes.

The late phase reaction is the result of infiltration of the smooth muscle layer by eosinophils, basophils, neutrophils, monocytes, and dendritic cells, which cause patchy desquamation of the epithelial cells. There is also an increase in the number of mucus glands, goblet cell hyperplasia and hypertrophy, and hyperplasia of the airway smooth muscle. Cytokines released by Th2 Helper cells results in further contraction of the airway smooth muscle, increased permeability of the blood vessels, and increased mucus secretion. Acute inflammation results in oedema and mucus-plugging of the bronchial tree. In contrast, the Th1 cells produce cytokines that down-regulate the atopic response.

Narrowing of bronchi of different calibres results in polyphonic wheezing. Narrowing of the smaller airways with a diameter of less than 2 cm leads to closure of these airways at low lung volumes, resulting in air trapping, an increase in residual volume (RV), an increase in total lung capacity (TLC), and dynamic hyperinflation. High-resolution computed tomography (HRCT) images of the thorax can demonstrate the heterogeneous narrowing of the airways. Bronchoconstriction can also occur through reflex neural mechanisms.

Figure 6.1 Pathophysiology of asthma.

While eosinophils are associated with acute asthma, neutrophils are more prevalent in steroid- dependent asthma, and are associated with chronic, persistent airway inflammation and structural changes. With increased severity and chronicity of asthma, there is remodelling of the airways, with collagen deposition and fibrosis of the airway wall, resulting in fixed narrowing and a decreased response to bronchodilator medication (Figure 6.1).

Clinical presentation

Asthma is a variable, reversible condition and therefore it can be difficult to make a reliable diagnosis between exacerbations when the individual is well. Chronic asthma can result in progressive disease and irreversible airway obstruction.

Clinical history: Patients with asthma present with symptoms of cough, chest tightness, breathlessness, and wheeze. These symptoms are variable and intermittent and may be precipitated by triggers at home or at work. There may be diurnal variation in symptoms, with peak flow measurements usually worse in the mornings compared to the evenings. The differential diagnosis of a patient with breathlessness and wheeze includes bronchiectasis, COPD, allergic bronchopulmonary aspergillosis (ABPA), a-1 antitrypsin deficiency (a-1 ATD), and left ventricular failure.

Cough-variant asthma is common. Patients will present with a persistent dry cough, particularly at night, but with no breathlessness or wheeze. Clinical examination, a CXR, and spirometry may be normal in these individuals. The differential diagnosis of a dry cough in a non-smoker with a normal CXR includes acid reflux, post nasal drip, use of non-steroidal anti-inflammatory drugs, use of angiotensin converting enzyme (ACE) inhibitors for the treatment of hypertension, inhaled foreign body, and post-infectious cough. Vocal cord dysfunction (VCD) and hyperventilation (HV) can be difficult to differentiate from asthma and are discussed later in this chapter.

The clinician should ask the patient about a history of atopy, which includes hay fever, allergic rhinitis, and eczema, and about a family history of atopy. They should document in detail any environmental factors that may be triggering the asthma, both at home and at work. A history of smoking and passive smoking is important.

Clinical examination may be normal in between exacerbations. In patients with severe chronic asthma, there may be signs of hyperinflation as described in Chapter 5. Individuals with childhood asthma, especially if undertreated, may develop a chest deformity. During an acute asthma attack, the patient will be breathless at rest, with increased pulse and respiratory rates, and polyphonic expiratory and inspiratory wheeze due to the narrowing of bronchi of different sizes. In life-threatening asthma, the patient may become cyanosed, have a silent chest, and become bradycardic.

Box 6.1 lists the investigations that may be required in a patient presenting with symptoms of unexplained cough and or breathlessness. Some of these investigations are to rule out other causes of these symptoms and are described in Chapter 4.

Box 6.1 Investigations in suspected asthma.

 Blood tests: Full blood count, IgE, radioallergosorbent test (RAST) if a specific allergy is suspected

 Skin prick test to allergens: tree pollen, grass pollen, dog, cat, horse, feather, HDM, aspergillus fumigatus



 Peak expiratory flow (PEF) and PEF homework


 Full lung function test with reversibility

 Methacholine provocation test

 Exhaled nitric oxide (FeNO)

 Sputum analysis

 Nose and throat examination



Patients with atopy and asthma often have a mildly raised peripheral blood eosinophilia and raised IgE. Results of skin prick testing must be interpreted carefully as a positive result merely indicates that the patient is sensitised to that allergen and has the potential to develop symptoms when exposed to that allergen. RAST measures the level of circulating IgE to an antigen, for example, cat. Skin prick test positivity to aspergillus fumigatus and positive aspergillus fumigatus IgE and IgG suggests allergic bronchopulmonary aspergillosis (ABPA). Further investigations, including an HRCT and sputum samples for aspergillus, would be indicated. Eosinophilic granulomatosis with polyangiitis (EG PA), formerly known as Churg-Strauss syndrome, can masquerade as asthma, and should be suspected if there is a very high eosinophilic count in peripheral blood and the patient appears to be steroid- dependent. This condition is discussed in Chapter 11.

PEF measurements may show diurnal variation in asthma (Figure 6.2), with a lower value in the morning compared to the evening. PEF homework, which means that the patient keeps a record of their PEF measurements taken in the mornings and the evenings for several weeks, can be helpful. A 20% or greater variability between mornings and evenings suggests asthma.

Spirometry will be obstructive, with a reduced FEV and an FEV /FVC ratio of less than 70%.

Figure 6.2 Diagram of PEF chart in poorly controlled asthma showing diurnal variation.

See Chapter 4 for the interpretation of spirometry. Improvement in symptoms and in spirometry 20 minutes after a bronchodilator is administered (200 μg inhaled salbutamol or 2.5 mg of nebulised salbutamol) is diagnostic of asthma if the FEVincreases by at least 15% of the baseline value or by more than 200 ml. Spirometry values are also used to establish the severity of asthma, which determines the management. Patients with chronic asthma and COPD will have little or no reversibility when given bronchodilators, as they have a fixed obstruction.

Full lung function tests with reversibility can give additional information. In those with chronic asthma, the residual volume (RV) and total lung capacity (TLC) will be increased due to air trapping, but there will be no impairment of gas exchange, so the transfer factor for carbon monoxide (TLCO) will be normal. There may be evidence of small airway disease with a reduction in FEV 25%, FEV 50% and FEV 75%.

Spirometry and lung function tests may be normal in patients with mild asthma in between exacerbations and in those with cough-variant asthma. Additional hyper-reactivity testing with methacholine or histamine can be diagnostic. This is described in Chapter 4. The concentration of the drug that results in a 20% decrease in FEV1 can be calculated. Exercise can also be used to provoke airway hyperresponsiveness. Exhaled NO levels are increased in patients with asthma and bronchiectasis but will be normal in VCD and hyperventilation, so can be useful in differentiating between these conditions.

The CXR may be normal in mild asthma (Figure 6.3), but may be hyperinflated in chronic asthma, with increased lung volumes and flat diaphragms. The CXR may appear normal in patients with mild bronchiectasis and ABPA, so an HRCT should be considered if these conditions are suspected (Figure 6.4 shows a HRCT in asthma). Differential cell count from induced sputum may show an eosinophilia in asthma. The presence of aspergillus may suggest ABPA.

Nose and throat examinations can be helpful when a patient presents with a persistent dry cough as this will detect evidence of acid reflux, oral candida, and post nasal drip. Nasal polyps may suggest asthma, which is often associated with sensitivity to aspirin. Abnormal adduction of vocal cords during inspiration, made worse by exercise, suggests VCD. Ultrasound of the vocal cords can also show abnormal adduction during inspiration suggestive of VCD.

Figure 6.3 CXR in asthma.

Figure 6.4 HRCT in asthma.

Bronchoscopy with lavage for microbiology may be helpful if an infection is suspected. It is also important to exclude an inhaled foreign body which can be a cause of persistent cough and monophonic wheeze, especially in children. Therapeutic suctioning can clear mucus plugging which can occasionally result in lobar collapse in asthma, resulting in persistent cough, wheeze, and breathlessness.

The algorithm for the diagnosis of asthma is given in Appendix 6.A.

Management of asthma: The aim is to obliterate the symptoms of asthma so that the individual has a good quality of life, with normal exercise tolerance, and no exacerbations. This can be achieved by avoiding allergens that trigger exacerbations and using the appropriate inhaled therapy.

The aim of inhaled therapy is to reduce the need for reliever inhaler with no limitation in physical activity. Well-controlled asthma means that the patient requires short-acting β2-agonist (SABA) less than two days in a week, and less than two nights a month. Appropriate inhaled therapy should achieve the best lung function possible with the minimum of side effects. There should be no more than one exacerbation per year requiring OCS and no hospital admissions.

Inhaled therapy should be prescribed as recommended by NICE/Scottish Intercollegiate Guidelines Network (SIGN), with a stepwise increase in therapy. If the asthma is poorly controlled, then treatment should be ‘stepped up’. When there is better control, then ‘stepping-down’ therapy can be considered. The mechanism of action of the drugs used to treat asthma, their side effects and interactions, inhaler devices, and nebulisers are discussed in Chapter 3. The management of asthma is given in Appendix 6.B. Step 1: mild, intermittent symptoms. Reliever short-acting β2-agonist (SABA) such as salbuta- mol or terbutaline used as and when required. If the patient requires them more than twice a day, then move to step 2.

Step 2: Regular prevention therapy. Add ICS 200—800 μg day-1.

Step 3: Add-on therapy. Commence long-acting β2-agonist (LABA), or increase dose of inhaled corticosteroid (ICS) to 800 μg day-1, or consider leukotriene inhibitor.

Step 4: Persistent poor control. Consider increasing dose of ICS further, or add theophylline. Step 5: Severe symptoms, frequent or continuous use of OCS. Use lowest dose of OCS, maintain ICS at 2000 μg day-1

ICS are the most effective preventative drugs in adults and children for maintaining control in asthma. They should be prescribed to all who have had exacerbations or nocturnal asthma, and those using β-2 agonist more than twice a day. A reasonable starting dose is 400 μg day-1 for adults and should be titrated for effective control.

Patients at Step 4 or Step 5 should be referred to the respiratory physician. Other conditions, such as ABPA or bronchiectasis, will need to be excluded. Individuals with poor asthma control despite treatment with adequate doses of inhaled corticosteroid (ICS), long-acting β2-agonist

(LABA), and leukotriene inhibitor may require a higher dose of ICS, up to 2000 μg day-1. Oral theophylline, a weak bronchodilator, can be introduced at Step 4, usually at a dose of 400 mg daily. The mechanism of action of theophylline, contraindications for its use, side effects, and drug interactions are discussed in Chapter 3.

Some patients with severe asthma appear to be steroid-dependent and experience worsening of their symptoms when the dose of OCS is reduced below a dose of 10 mg daily. Conditions such as EGPA, COPD, and ABPA should be excluded. Compliance and inhaler technique should always be checked.

Patients with allergic asthma have high concentrations of IgE which leads to the secretion of cytokines and mediators which cause bronchoconstriction. Omalizumab (Xolair) is a recombinant humanised immunoglobulin G1 monoclonal antibody that binds to the circulating IgE, forming immune complexes that are cleared by the reticuloendothelial system. Omalizumab prevents IgE from binding to receptors on mast cells, eosinophils, and basophils, thus reducing the effect of the late phase response, with decreased production of cytokines. Omalizumab is indicated for the treatment of patients with asthma who are not controlled at Step 5, who require frequent courses of OCS, and who have high levels of IgE. It is given subcutaneously in a hospital setting as there is a risk of anaphylaxis in 1-2/1000.

There is evidence to support the hypothesis that vitamin D deficiency can worsen the control of asthma. Therefore, patients with vitamin D deficiency should be prescribed supplements. Bronchial thermoplasty, a procedure available in a few centres, is a technique whereby radio-frequency waves are used to apply heat through a bronchoscope to reduce the amount of smooth muscle in the bronchial wall mucosa, resulting in reduced bronchoconstriction. This has been shown to improve asthma control in some patients with severe asthma who are not well controlled with other treatments. The long term benefits and risks of this treatment are not fully understood.

Role of doctor or asthma nurse: Patients with asthma should have regular reviews (at least once every six months) by a trained healthcare professional. He/She should assesses their symptoms, their compliance with therapy, any over-use of short-acting β2-agonist (SABA), possible under-use of ICS, conduct spirometry, and assess their inhaler technique. The patient should have a self-management plan which describes what medication to take, how to increase the medication when symptoms deteriorate, and what to do if they experience an exacerbation. The management plan should include the role of PEF monitoring, with advice to take oral corticosteroids (OCS) and seek medical help if their PEF drops below 75% of their best or predicted PEF. Patients should be aware of environmental triggers and should avoid these as much as possible. Patients who smoke should be advised to quit, and nicotine replacement therapy (NRT) prescribed, as discussed in Chapter 3. Patients with asthma should have an annual influenza vaccination and a pneumococcal vaccination. Regular review by a doctor or specialist nurse has been shown to improve daily control of asthma symptoms with a reduction in the risk of near-fatal or fatal asthma exacerbation. Patients with moderately severe or severe asthma should have a supply of OCS to take in an emergency.

The Global Initiative for Asthma (GINA) suggests asking the following questions to assess symptom control over the past four weeks as listed in Box 6.2. There are other validated questionnaires to assess symptom control, including the Asthma Control Questionnaire (ACQ-5) score and the ACT score.

Box 6.2 GINA assessment of symptoms control.

1. Daytime asthma symptoms more than 2 x week

2. Any night-time waking 2 x week due to asthma

3. Reliever needed for asthma >2 x week

4. Any limitation of normal activity due to asthma


None of the above: asthma is well controlled. 1—2 of the above: asthma partly controlled. 1—4 of the above: asthma poorly controlled.

Box 6.3 lists some of the recognised triggers for acute asthma.

Box 6.3 Triggers for acute asthma.



• Animal-derived allergen

• Cigarette smoking

• Bird-derived allergen

• Passive cigarette smoking

• House dust mite (HDM)

• Fireplace smoke

• Pollen

• Chlorine (household cleaners, swimming pools)

• Grass

• Paints

• Mould

• New furnishings releasing volatile compounds

• Atmospheric pollution

• Exercise

• Ozone (SO2, NO2, O3)

• Cold air

• Perfumes, hair sprays


• Aspirin

• β-blockers


• Sulphite (wine, vinegar, dried fruit)


• Viral respiratory tract infection

• Bacterial respiratory tract infection


• Premenstrual

• Pregnancy

• Stress

Avoidance of triggers: Patients should be advised to either avoid or reduce exposure to any triggers that have been identified. If a skin prick test or RAST test confirms allergy to an animal, then exposure should be removed or limited. If the patient is allergic to HDM, then they should be advised to remove carpets and reduce the amount soft furnishings which harbour HDM. Mattress and pillow protectors can be purchased which may help. Individuals with any drug reaction should avoid those medications. Patients should be advised to avoid scented perfumes, air sprays, hair sprays, and aerosols.

Thunderstorms can trigger an asthma exacerbation by lifting allergens into the air and by disrupting pollen grains into smaller allergenic particles, which are more easily inhaled. High pressure, with warm, dry, still air, results in an accumulation of airborne pollutants, including particulates, such as ozone (O3), nitric dioxide (NO2), and sulphur dioxide (SO2), as well as pollen and fungal spores, which can trigger an asthma attack. Desert dust contains crystalline silica and can be transported across large parts of the globe in a storm. Temperature and humidity may play a role in exercise-induced asthma. Inhalation of cold, dry air can result in bronchoconstriction caused by water loss and cooling of the airways after a rapid flow of blood into the airway blood vessels, resulting in oedema. Hot, humid air can also lead to broncho- constriction mediated by the vagal system.

If the trigger to an asthma attack cannot be avoided, then the patient should be advised to take a dose of bronchodilator, for example, prior to exercise. Patients should be advised to warm up gradually before exercise. Leukotriene antagonists are recommended for patients with exercise- induced asthma. For those with severe atopy, antihistamines might help with symptom control.

Worsening of asthma symptoms prior to or during menstruation has been reported in 20-40% of women with asthma. It is postulated that this is due to the increase in the levels of oestrogen and progesterone. Aspirin sensitivity may be more prevalent in women with perimenstrual asthma. Hormonal treatment with the oral contraceptive pill has not been found to be helpful. Although no clear trial data exists, leukotriene antagonists may be helpful in this group of patients. During pregnancy, asthma can get worse in a third of patients, remain the same in a third, and get worse in a third.

Management of asthma is the same as in the nonpregnant individual.

Non-selective β-blockers (for example, those prescribed in eye drops), aspirin, and NSAIDs are responsible for acute exacerbation in 3-5% of adults. Those with nasal polyposis are at a higher risk of aspirin sensitivity. Depression and chronic stress can worsen the control of asthma. Parental depression and stress are associated with severe asthma in children.

Viral infections, especially influenza and respiratory syncytial virus, are common causes of asthma exacerbations. Therefore, patients with asthma should be advised to have the influenza vaccination. Food allergies can cause asthma if the aerolised allergen, in the form of steam, vapour, or sprays is inhaled. Sulphite sensitivity can cause asthma symptoms, but not in an IgE-mediated way.

Prognosis of asthma: Most patients with asthma remain reasonably stable with only one or two exacerbations every year which can be managed with oral corticosteroids (OCS) and antibiotics if there is evidence of a bacterial respiratory tract infection. In the UK, 20% of patients with asthma account for 80% of the overall costs of managing asthma, amounting to one billion pounds every year.

Acute asthma exacerbation can be severe and life-threatening. Approximately 1500 people die each year from acute asthma in the UK. Many of these deaths are preventable, as published in the National Review of Asthma Deaths (NRAD) in 2012. Near-fatal exacerbations can occur in those even with mild asthma and can be of slow or rapid onset. Deaths occur for the following reasons: failure to recognise the severity of the asthma attack, delay in starting appropriate treatment, underprescription of inhaled corticosteroids, discharging the patient too early, and delay in referring the patient to the intensive care unit (ICU). Deaths also occur because of poor compliance by the patient and because patients and doctors often under-estimate the risk of a fatal asthma attack. The term ‘brittle asthma’ is used to describe those with significant diurnal PEF variability despite adequate treatment and those who suffer sudden, unexpected exacerbations. Box 6.4 lists those patients who have risk factors for fatal asthma. Box 6.5 lists the presentation of patients with a severe asthma exacerbation who require careful assessment and possible admission. Box 6.6 describes the clinical features of acute, severe asthma and life-threatening asthma.

Box 6.4 Risk factors for fatal asthma.

• Recent exacerbation

• Sensitivity to NSAID and aspirin

• Recent hospital admission

• Poor perception of dyspnoea

• Previous ICU admission with intubation

• Over-use of SABA

• Requiring >3 types of asthma medication

• Under-use of ICS

• Dependence on OCS

• Delay in seeking medical help

• Poor compliance

• Brittle asthma

Box 6.5 Patients requiring admission to hospital from asthma.

 Worsening symptoms of breathlessness, wheeze, and cough

 Nocturnal symptoms of breathlessness, wheeze, and cough

 Increasing use of β2-agonist reliever

 Poor response to OCS

 Peak expiratory flow <75% predicted or best


 Living alone

 Previous near-fatal asthma

 Brittle asthma

 Psychological problems, including evidence of poor compliance


These features suggest impending respiratory arrest.

Management of acute asthma: The doctor should take a thorough history if possible, noting the important points described above. Treatment should be commenced without delay. Auscultation of the chest and blood pressure measurement should be done periodically to ensure that there is improvement. Oxygen saturation should be monitored continuously and serial ABG measurements made. Box 6.7 lists the urgent investigations usually done in the emergency department. Box 6.8 describes the medication given to a patient with acute severe asthma exacerbation.

Box 6.6 Features of acute severe asthma and life-threatening asthma.

Acute severe asthma

• Peak expiratory flow

(PEF) <50% predicted

• Pulse rate >110 beats min-1

• Unable to complete sentences in one breath

• Polyphonic wheeze

• Respiratory rate >25 breaths min-1

• paCO2 normal and rising on serial ABG

Life-threatening asthma

• PEF < 35%> predicted or unrecordable

• SpO2 < 92%> on air

• Feeble respiratory effort

• Exhaustion

• Cyanosis

• Confusion

• Silent chest

• Rising PaCO2

• Bradycardia

• Hypotension

Monitoring of patients with severe acute asthma: Patients who present with symptoms of a severe asthma exacerbation should be monitored closely in the high dependency unit (HDU) or ICU and will require regular clinical assessment and urgent review by a senior doctor. The oxygen saturation should be maintained above 92% and high flow oxygen can be given if required. Serial ABG measurements should be done as indicated by the patient’s clinical status. Patients with acute asthma will have a high respiratory rate and therefore become hypocapnic as they blow off CO2. A normal or rising PaCO2 (>4.6kPa) and a pH of less than 7.35 would be cause for concern. If the patient does not improve within 1 hour of initial management, then intubation and ventilation may be required to prevent respiratory arrest.

Box 6.7 Urgent investigations for acute asthma.

 Chest X-ray to exclude consolidation, pneumothorax, and pleural effusion

 Oxygen saturation with continuous monitoring

 Baseline ABG on air if SpO2 < 92% with repeat ABG test to monitor PaCO2 level and pH

 ECG every 30 minutes

 Blood tests to measure full blood count, urea and electrolytes, C-reactive protein, and aminophylline level if on aminophylline

Referral to the intensive care team and the on-call anaesthetist should be made urgently. Noninvasive ventilation (BiPAP) is not usually indicated for patients with respiratory failure secondary to asthma.

It is essential that patients who present with severe asthma and are admitted to hospital are assessed carefully prior to discharge. Box 6.9 lists key points to consider before discharge.

National Review of Asthma Deaths (NRAD): A confidential enquiry into over 200 asthma deaths in 2012 concluded that many of these deaths were preventable. Most of the deaths of young people occurred in the summer and in the winter of elderly patients. Most patients who died had chronic, severe asthma which was not being appropriately managed, with insufficient inhaled or oral steroids, and excessive use of SABA and LABA on their own. Nearly half the deaths occurred in patients who had had a previous hospital admission. These high-risk patients were not being reviewed regularly and had not been referred to a specialist. There was a lack of compliance from some patients, lack of education about their condition, with only 23% having a written self-management plan. Many of these patients had an underlying psychological problem. During an exacerbation, there was a failure by the patient and health care professional to recognise the severity of the condition and manage it appropriately. The majority developed their symptoms of asthma exacerbation over a 48-hour period, which means that there should have been sufficient time to intervene.

Box 6.8 Immediate treatment for acute asthma.

 Oxygen 40-60% given via a Hudson mask to maintain SpO2 between 94% and 98%. Patients with asthma do not usually retain CO2 secondary to oxygen therapy. Continuous monitoring of oxygen saturation

 Salbutamol 2.5-5 mg via oxygen-driven nebuliser at a flow rate of 6 L min-1. Repeat dose at 15- minute intervals if no improvement. Continuous nebulisation if required. When a nebuliser is not available, salbutamol can be given via a large volume spacer

 Ipratropium bromide (atrovent), 500 μg at 6-hourly intervals, driven via oxygen-driven nebuliser at a flow rate of 6 L min-1. The combination of salbutamol and ipratropium bromide results in a much greater bronchodilatation than salbutamol alone

 Corticosteroids can be given orally (prednisolone 40-50 mg daily) or intravenously (hydrocortisone 200 mg initially and then 100 mg 6 hourly). Prednisolone should be given as quickly as possible and continued for at least two weeks; a tapering reduction in dose is not required. Steroids have been shown to reduce mortality in asthma exacerbation

 Intravenous magnesium sulfate 2 g (8 mmol) in 250 ml sodium chloride 0.9% over 1 hour. It causes relaxation of airway smooth muscle

 Intravenous fluids with potassium supplements if necessary, as hypokalaemia can develop secondary to β2-agonist usage

 Intravenous aminophylline, 250 mg in 100 ml sodium chloride 0.9% over 30 minutes as a loading dose, followed by an infusion (750 mg/24 hours); blood concentration of aminophylline should be monitored if the infusion is continued for over 24 hours. Bolus of aminophylline should not be given to patients who are already on oral preparations of this drug. Lower doses should be used in patients with heart failure, hepatic failure, and in those taking drugs which are cytochrome P450 enzyme inhibitors, such as cimetidine, ciprofloxacin, and erythromycin

 Antibiotics if symptoms and signs of a bacterial respiratory tract infection

 Intravenous β2-agonist, salbutamol 3-20 pg min-1 or terbutaline 1.5-5 pg min-1 infusion, can be considered for patients with life-threatening asthma who are not improving despite management so far listed. There is no strong evidence that the intravenous route is better than the inhaled route. Cardiac monitoring will be required as intravenous β2-agonists can cause cardiac arrhythmias

 Intravenous methylprednisolone, 80 mg in 100 ml sodium chloride 0.9% over 1 hour, can be given if patient not responding to the above treatments and can be repeated daily for up to three days

 Intubation and ventilation if patient shows signs of life-threatening asthma

Box 6.9 Checklist prior to discharge.

 The PEF should be more than 75% of their predicted or best and PEF diurnal variability should be less than 25%

 The nebulised therapy should have been stopped for at least 24 hours and the patient stable on their discharge medication for at least 24 hours

 The patient should be on appropriate inhalers (ICS and LABA) and the inhaler technique must be checked

 The patient should be discharged home on a short course of oral prednisolone

 The patient should be given a peak flow meter and a self-management plan

 The side effects of the drugs prescribed should be discussed

 The patient should be strongly advised to stop smoking and referred to a smoking cessation clinic

 The patient should be advised to have an annual influenza vaccination

 The patient should be advised to avoid triggers which cause exacerbation

 Follow-up appointment with the GP, community or hospital respiratory teams should be organised within two weeks of discharge


Chronic asthma: A proportion of patients with asthma go on to develop irreversible airway obstruction, which is less responsive to OCS. These patients will have chronic symptoms of breathlessness, cough, and wheeze, and it can be difficult to distinguish them from those with COPD. These individuals develop structural changes in the airways, with permanent damage to the epithelium, increase in the number of goblet cells, thickening of the lamina reticularis (the sub-basement membrane), increased smooth muscle mass and formation of extracellular matrix. This process is called remodelling and causes distortion of the airways. Management is as for asthma and COPD.

Chronic obstructive pulmonary disease (COPD)

COPD is characterised by progressive airflow obstruction which is not fully reversible and does not change markedly over several months. In 90% of cases, COPD develops because of damage caused by cigarette smoking. The total number of cigarettes smoked daily over the number of years, which can be calculated as the number of pack years, indicates the risk of developing COPD. Cigar and pipe smoking also increase the risk of COPD, but to a lesser extent than cigarette smoking. Other risk factors for developing COPD include passive smoking, occupational exposure to dusts, coal mining, air pollution, and smoke from indoor cooking fires. a-1 antitrypsin deficiency (a-1ATD) accounts for 1% of cases of COPD. This is discussed later in this chapter.

COPD increases with age, being particularly prevalent in those over the age of 65 years. The ageing process itself results in a decline in FEV1 of about 30 ml/year after the age of 30, but smoking accelerates this decline (Figure 6.5).

Only 15—25% of individuals who smoke develop COPD, therefore genetic factors which confer susceptibility are implicated. Exactly what these are is unclear. COPD is commoner in urban areas compared to rural areas and is more prevalent in lower socio-economic groups, particularly in those with poor nutrition.

Figure 6.5 Decline in lung function with smoking.

Worldwide, COPD is responsible for considerable morbidity and mortality. The number of young people who have started smoking has increased in Eastern Europe, China, and India in the past few decades. It is predicted that by 2020 COPD will be the third commonest cause of death worldwide. In the UK, approximately three million people have COPD, 15% of men and 5% of women. Many individuals with COPD are undiagnosed and therefore not treated. COPD exacerbations are responsible for a third of hospital admissions, and COPD causes around 30 000 deaths every year in the UK. It is a huge economic burden on the NHS, estimated as almost one billion pounds every year. COPD has a significant effect on patients’ quality of life and their ability to continue with their normal activities.

Pathophysiology of COPD: Patients with COPD present primarily with symptoms of chronic bronchitis (chronic productive cough) and emphysema (severe breathlessness on exertion) (Figure 6.6). Cigarette smoke activates neutrophils in the lungs which invade the bronchial mucosa and secrete proteases, including elastase and collagenase, which damage the alveoli, resulting in the formation of bullae. In healthy lungs, enzymes that counteract these proteases, such as the enzyme a-1 AT, maintain a balance, so that healthy lung tissue is not damaged. However, in the lungs of smokers, the increased production of proteases compared to anti-proteases results in the destruction of the alveolar sacs, with the formation of large bullae, particularly in the upper zones of the lungs. This progresses to the development of widespread emphysema. Much of the alveolar surface of the lung is destroyed and not available for gas exchange; this can be measured as a reduction in TLCO and KCO. The ventilation/perfusion mismatch results in an increase in the alveolar- arterial gradient (A-a gradient) and hypoxaemia. Hypoxic pulmonary vasoconstriction results in raised pulmonary artery pressure and, over time, leads to pulmonary hypertension and right heart failure (cor pulmonale).

Patients with chronic bronchitis develop inflammation of the airways with fixed structural changes. There is an increase in the number of goblet cells and hypertrophy of the goblet cells, resulting in the production of viscous mucus which is hard to clear. This mucus acts as a culture medium for infective organisms. Damage to cilia affects the host defence mechanisms, which also predisposes to recurrent respiratory tract infections. Recurrent infections lead to further inflammation of the lungs, and a decline in lung function.

Figure 6.6 Pathophysiology of COPD.

Mechanical changes result in increased airway resistance and a loss of the elastic recoil of the lungs, so that they collapse on expiration, causing air trapping and hyperinflation. This increases the work of breathing; therefore, the patient needs to use accessory muscles of breathing to overcome the resistance and adopts pursed-lip breathing to force the air out.

Clinical presentation of COPD: Box 6.10 lists the symptoms and signs of COPD. In mild COPD, clinical examination may be normal but as the condition gets worse, signs will become apparent, especially during an exacerbation. Patients who develop type 2 respiratory failure may show signs of CO2 retention. Patients with severe COPD may have the signs of cor pulmonale, which is right heart failure secondary to chronic lung disease. This will result in pulmonary hypertension.

It is important to determine the extent of breathlessness as this correlates with the severity of COPD. Baseline measurement can be helpful in determining the prognosis and in assessing the impact of any treatment. The Medical Research Council (MRC) Dyspnoea Scale is commonly used and is described in Box 6.11. Other measures which can be used to determine the extent of breathlessness include the shuttle test and the 6- minute walk test, which are described in Chapter 4. There are several validated questionnaires which can be used to assess overall function, quality of life (QOL), and impact of the disease. The St. George’s Respiratory Questionnaire is a validated, comprehensive, disease-specific, health-related score used in many trials, but too lengthy to use in routine clinical practice. The COPD Assessment Test (CAT), which is an 8-item measure of the patient’s symptoms, can be used to assess and monitor patients’ symptoms at each clinic visit.

A diagnosis of COPD should be suspected in any individual over the age of 40 years who presents with symptoms of breathlessness and has a history of cigarette smoking. Spirometry showing an FEV1/FVC ratio of less than 70% predicted post administration of a short-acting bronchodilator confirms the diagnosis of COPD. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) and NICE define severity of COPD as Mild, Moderate, Severe, and Very Severe, based on the spirometry values when the FEV1/FVC is less than 70% predicted.

Box 6.10 Symptoms and signs of COPD.


 Breathlessness on exertion (dyspnoea)


 Frequent lower respiratory tract infections

 Chronic productive cough


 Tachypnoea (respiratory rate > 25 breaths min-1)

 Tachycardia (> 100 beats min-1)

 Barrel chest

 Use of accessory muscles

 Increased anteroposterior diameter of thoracic cage

 Pursed-lip breathing


 Prolonged expiratory phase of respiration

 Polyphonic expiratory wheeze

 CO2 retention: confusion, irritability, flapping tremor, bounding pulse, papilloedema

 Cor pulmonale: raised JVP, peripheral oedema

 Pulmonary hypertension: loud P2 and right ventricular heave

 Reduced muscle mass




FEV1 > 80%


FEV1 50-79%


FEV1 30-49%

Very severe

FEV1 < 30%

Other investigations in the diagnosis of COPD: To establish that the airway obstruction is irreversible, spirometry should be done after giving a SABA. Reversibility testing after a trial of corticosteroids is not recommended in the diagnosis of COPD. Full lung function tests will show that the total lung capacity (TLC) and the residual volume (RV) are increased due to air trapping and static hyperinflation. The destruction of alveoli, with a reduction in surface area for gas exchange, will result in a reduction in transfer factor for CO (TLCO) and transfer coefficient (KCO). Interpretation of the lung function test in COPD is discussed in Chapter 4.

Box 6.11 MRC dyspnoea scale.


Grade 1

breathless only on strenuous exertion

Grade 2

breathless when walking up a slight hill

Grade 3

breathless when walking on flat ground

Grade 4

breathless on walking 100 metres

Grade 5

breathless on dressing or undressing

Pulse oximetry may be normal in mild COPD, but may gradually drop to below 90%, initially on exertion, and then at rest. Patients experiencing an exacerbation will frequently have a low oxygen saturation. Patients who have oxygen saturation less than 92% when breathing room air will require the measurement of arterial blood gas (ABG) to ascertain the PaO2 and PaCO2 levels. Patients with oxygen saturation level below 90%, and who are found to be in type 1 or type 2 respiratory failure, will require careful oxygen therapy to prevent respiratory acidosis (see Chapter 13).

A CXR is recommended in all patients presenting with symptoms suggestive of COPD to exclude other conditions which can present with similar symptoms, including community acquired pneumonia, pneumothorax, lung cancer, pulmonary embolus, and heart failure. In COPD, particularly if the patient has emphysema, the CXR will show hyperinflation, with flat diaphragms, increased retrosternal airspace, and an elongated cardiac shadow (Figure 6.7). When there is significant bullous disease, the lung fields may appear black. An HRCT will show centrilobular emphysema, predominantly in the upper zones when due to cigarette smoking (Figure 6.8). a-1ATD is associated with pan acinar emphysema in the lower lobes and is discussed later in this chapter.

Figure 6.7 CXR in COPD showing hyperinflation.

Box 6.12 Smoking cessation actions.

ASK: identify smokers at every visit


every patient who smokes to quit


assess their willingness to quit


provide access to counselling and prescribe pharmacotherapy



Figure 6.8 HRCT showing a large bulla in left lung in severe emphysema.

A patient presenting for the first time with symptoms of breathlessness should have full blood count, and urea and electrolytes measured. Patients with severe, long-standing COPD can develop secondary polycythaemia due to chronic hypoxia. This can exacerbate the development of pulmonary hypertension.

Objective measurement of exercise capacity with the shuttle walk test or 6-minute walk test can be of prognostic value and an important component of the body mass index, airflow obstruction, dyspnea and exercise (BODE) index, which is used when selecting patients for lung volume reduction surgery or lung transplantation. Exercise capacity falls significantly in the year before death. Measurement of inspiratory, expiratory, and quadricep muscle strength is not normally indicated in routine clinical practice but may be part of the investigations required prior to transplantation.

The aim of management of COPD is to prevent progression of the disease, relieve symptoms, improve the quality of life, reduce morbidity, and prevent hospital admissions. It includes lifestyle changes, most importantly smoking cessation, pharmacological treatment, pulmonary rehabilitation, nutrition, and psychological support. Patients with severe COPD may require long term oxygen therapy (LTOT). Some patients, especially those who are under the age of 60 years with no significant co-morbidities, should be referred for consideration of lung transplantation. Patients with chronic type 2 respiratory failure can be managed with domiciliary non-invasive ventilation (NIV) and LTOT. There should be recognition of severe, end-stage COPD. The doctor should have a discussion with the patient and their family members about palliation, referral to the hospice, and ‘Do Not Attempt Resuscitation (DNAR)’ decisions.

Smoking cessation is the only intervention that reduces the progression of the disease and the risk of death. The earlier the diagnosis of COPD is made, and the earlier the patient stops smoking, the better the outcome. The GOLD guidelines recommend that all healthcare professionals should ensure that they ask the 5 A questions as listed in Box 6.12.

The pharmacological agents used to help people to stop smoking are discussed in Chapter 3.

Large, multi-centre, international studies have concluded that inhaled therapy improves symptoms, improves QOL, and reduces the number of exacerbations and hospital admissions. These trials have not shown that inhaled therapy reduces the decline in lung function or reduces mortality. Benefit from inhaled therapy is seen mainly in those with moderate and severe COPD.

Inhaled therapy includes SABA, such as salbutamol and terbutaline, LABA, such as salmeterol and formoterol, short-acting anticholinergic drugs, such as ipratropium bromide, long-acting anticholinergic drugs, such as tiotropium and aclidinium and inhaled corticosteroids (ICS).

SABA and LABA improve symptoms and reduce the risk of exacerbations, especially when they are combined. Combining bronchodilators with different modes of pharmacological action gives sustained bronchodilation with fewer side effects. LABA are more effective at symptom control and in reducing exacerbations than the shortacting drugs. ICS are also recommended for patients with moderate or severe COPD (FEV1 < 60% predicted) who have experienced at least two exacerbations in the previous year, although the dose-response relationships is unknown in COPD. ICS, when combined with a LABA, has been shown to improve symptoms, quality of life (QOL), and reduce frequency of exacerbations and hospital admissions. They do, however, increase the risk of non-fatal pneumonia. A combination of ICS, LABA, and LAMA (often called triple therapy) is recommended for those with severe COPD.

The flowchart of inhaled therapy in COPD (see Appendix 6.C) describes the management of mild and severe COPD as per the NICE Guidelines. The pharmacology of the inhaled drugs, their side effects, drug interactions, and the devices used to deliver these drugs is discussed in Chapter 3.

Roflumilast, a phosphodiesterase-4 inhibitor, has been shown to reduce exacerbations in those with moderate and severe COPD. Theophylline, a phosphodiesterase-5 inhibitor, can also be considered in those with moderate and severe COPD who are still symptomatic despite optimal inhaled therapy. Slow-release preparations are used in COPD, but theophylline has a narrow therapeutic range with a high risk of toxicity which is dose- related. A mucolytic drug, such as carbocisteine, can improve the symptom of chronic, productive cough in some, but not all, patients.

Pulmonary rehabilitation has been shown to be an effective intervention when a patient is discharged from hospital after an acute exacerbation. Pulmonary rehabilitation improves breathlessness, exercise tolerance, muscle strength, and QOL, especially in those with dyspnoea and a Medical Research Council (MRC) score of 3—5. Pulmonary rehabilitation includes exercises to strengthen the deconditioned muscles of the arms, legs, and muscles of respiration. An eight- week programme, comprising of aerobic exercises three times a week, is carried out by trained nurse specialists and physiotherapists. The exercise programme should be continued for maximum and ongoing benefit.

Relaxation techniques, including yoga and cognitive behavioural therapy (CBT), can help the patient gain more control of their breathing and reduce the symptom of dyspnoea. Chest physiotherapy and postural drainage, including the use of a flutter valve, can help expectorate the thick secretions that are part of the symptomatology of COPD.

Patients with severe COPD are often in a catabolic state and appear cachectic due to the increased work of breathing. The BODE index, which is a measure of body mass index (BMI), airflow obstruction, dyspnoea, and exercise capacity, can be of prognostic value and used in determining patients suitable for lung transplantation. Nutritional support improves muscle strength and health status as measured by the St. George’s Respiratory Questionnaire.

Chronic illnesses predispose to anxiety and depression. The Hospital Anxiety and Depression (HAD) questionnaire can be used to assess this. Patients should be referred for psychological support. Patients with respiratory conditions often run support groups, such as the ‘Breathe Easy Club’, which many find beneficial. It is recommended that all patients over the age of 65 with COPD and those with FEV1 < 40% are offered the influenza and pneumonia vaccinations which will reduce the risk of serious respiratory illnesses and death.

LTOT should be commenced in patients who develop pulmonary hypertension and hypoxia. The ECG will show right axis deviation and a dominant R wave in V1 indicating right ventricular hypertrophy. An echocardiogram can estimate the pulmonary artery pressure and the function of the right heart. Type 1 respiratory failure, with a PaO2 < 7.3 kPa at rest or a PaO2 of <8 kPa with evidence of peripheral oedema, polycythaemia, or pulmonary hypertension, are indications for starting LTOT. Two measurements of the ABG should be done three weeks apart when the patient has recovered from an exacerbation and is stable. Patients on LTOT should be encouraged to use it for at least 15 hours in a 24-hour period (including while they are asleep) as this improves survival. LTOT is not a treatment for breathlessness and should be used with caution in those who continue to smoke. NIV together with LTOT can be considered in patients with chronic type 2 respiratory failure secondary to COPD. LTOT is discussed in more detail in Chapter 3.

There are several surgical treatments for severe emphysema. Bullectomy is the removal of redundant lung tissue which allows adjacent lung parenchyma to expand more effectively by reducing static hyperinflation. Lung volume reduction surgery (LVRS) is recommended for those with emphysema affecting the upper lobes and low exercise capacity but with no significant co-morbidities. LVRS can be done as a video-assisted thoracoscopic surgery (VATS) procedure. LVRS decreases hyperinflation, improves elastic recoil and airflow limitation and the efficiency of respiratory muscle, thus reducing air trapping. These procedures improve symptoms, QOL, and survival compared to medical treatment alone if suitable patients are selected. Bronchoscopic lung volume reduction, which involves the placement of a valve into the bronchus, is a non-surgical alternative for patients with heterogeneous emphysema on CT, FEV1 between 15% and 45%, and hyperinflation (TLC > 100% predicted and RV > 150% predicted). Patients who are appropriately selected show improvement in symptoms and exercise tolerance but appear to have an increased frequency of exacerbations and haemoptysis.

Patients who have heterogeneous emphysema, with FEV1 of less than 20%, TLCO <20%, and a BODE index of 5—10, should be referred for consideration of a single lung transplant if they are less than 65 years or for a double lung transplant if they are less than 60 years. They must have stopped smoking for at least six months, be able to participate in a pulmonary rehabilitation programme, have no significant co-morbidities, and be motivated.

Patients with COPD should be regularly reviewed by either a doctor or a nurse who assesses their clinical state, documents any exacerbations, checks spirometry to determine the rate of decline, reviews medication and the side effects of medication, and checks the inhaler technique. Attention should be paid to the patient’s nutrition and mental state and referral to dietician and psychiatrist made as appropriate. Patients with COPD often have co-morbidities which should be diagnosed and treated. Lung cancer is the commonest cause of death in patients with mild COPD.

Diagnosis of exacerbation of COPD: an exacerbation results in worsening symptoms of breathlessness, cough, and systemic symptoms, such as fever, reduced appetite, and reduced mobility. Exacerbations are commonly due to viral or bacterial infections, changes in the weather, and atmospheric pollution. Exacerbations are commoner in the winter months.

The frequency of exacerbations has prognostic implications. Risk factors for exacerbations and hospital admissions include severe COPD (the lower the FEV1, the more likely to have an exacerbation), and previous exacerbations. Patients with a certain phenotype appear to have an increased risk of experiencing exacerbations. A cohort of patients present to hospital with apparent exacerbation for psychosocial reasons. Each true exacerbation results in a decline in lung function, with more than 55 ml/year of lung capacity lost compared to 30 ml/year which occurs as part of the ageing process. The all-cause mortality three years after hospitalisation approaches 50%. Preventing exacerbations and treating exacerbations aggressively will improve the prognosis of patients with COPD.

Management of exacerbation of COPD: these patients are often brought to hospital by ambulance and managed initially in the emergency department as they can be critically unwell. They will be tachypnoeic, tachycardic and hypoxic and may develop type 1 or type 2 respiratory failure, with a risk of respiratory arrest. The differential diagnosis of this presentation includes pneumothorax (see Chapter 10), lung cancer (see Chapter 9), pulmonary embolism (see Chapter 11) and cardiac causes, including arrhythmias and heart failure.

A national COPD audit has shown that patients referred to the respiratory team and managed in a respiratory unit fare better than those under nonspecialist teams. Some patients with severe COPD exacerbation may need to be in the HDU or the ICU. Box 6.13 lists the management of exacerbation of COPD.

Box 6.13 Management of exacerbation of COPD.

 Controlled oxygen (through venturi mask)

 Nebulised short-acting β2-agonist

 Nebulised short-acting anticholinergic bronchodilator

 Systemic corticosteroids (oral or intravenous)

 Aminophylline (oral or intravenous)

 Mucolytic agent

 Chest physiotherapy

 Antibiotics if evidence of bacterial infection





 Non-invasive ventilation

 Intubation and ventilation if reversible cause



Patients with an exacerbation of COPD are often hypoxic and in respiratory failure. As many of these patients are at risk of developing type 2 respiratory failure, controlled oxygen therapy via a venturi mask is indicated based on the arterial blood gas result. Ideally, the baseline ABG should be taken on air, but if the patient is very hypoxic, then the baseline ABG should be taken on oxygen, but note should be made of the exact amount of inspired oxygen so that the ABG result can be interpreted accurately. This is also important when monitoring the patient’s ABG results. Oxygen should be prescribed on the drug chart so that the oxygen saturation is kept between 88% and 92%. The ABG should be checked after 30 minutes to ensure that there is no acute CO2 retention. Patients with an exacerbation of COPD and type 2 respiratory failure will require non-invasive ventilation (NIV) using BiPAP.

Nebulised salbutamol should be given at least four times in 24 hours but can be given every few hours. A dose of 2.5 mg or 5 mg can be used, depending on the size of the patient. The nebuliser solution should be driven by 6 L air, with supplemental oxygen given through a nasal cannula for those who are hypoxic. The main side effects of β2-agonists are tremor, tachycardia, and hypokalaemia. Some patients cannot tolerate salbutamol, and terbutaline is an alternative SABA.

Nebulised ipratropium bromide, a short-acting, antimuscarinic, anticholinergic drug, should be given at a dose of 500 μg every six hours, driven by 6 L air and supplemental oxygen as required. While on nebulised SAMA, any LAMA that they usually take should be stopped. Systemic corticosteroids should be prescribed as they shorten the recovery time and decrease the risk of relapse. 40 mg of oral prednisolone given for five days is as effective as intravenous hydrocortisone, which can be given to those who are unable to take oral medication. The patient should continue to take their usual ICS during this period.

Aminophylline can be given orally at a dose of 225 mg twice a day, or intravenously with a loading dose of 5 mg kg-1 to a maximum of 500 mg over 30 minutes via a rate-controlled device if the patient is not already on aminophylline. Aminophylline can cause tachycardia and cardiac arrhythmias, therefore cardiac monitoring and checking the blood level of aminophylline are important. The side effects and drug interactions are discussed in Chapter 3.

Mucolytic agents can help expectorate viscous mucus, but long term studies in COPD have not been conclusive, with little evidence of a significant benefit. Carbocisteine, 750 mg three times daily, could be prescribed to patients with viscous sputum who have difficulty expectorating. In stable COPD, only those who appear to be benefitting should continue with it. Saline nebulisers, an Acapella device, and chest physiotherapy may be more effective in clearing sputum than carbo- cisteine alone. N-acetyl cysteine, which has antioxidant properties, has not been shown to be beneficial in this group of patients.

Patients who have symptoms of a bacterial chest infection, with an increase in the volume of sputum and change in the colour of the sputum, should be given antibiotics dictated by local guidelines. Many of these patients will have a raised white cell count, with a neutrophilia, and raised CRP. The differential diagnosis for this presentation includes community acquired pneumonia: patients with community acquired pneumonia (CAP) will have clinical signs of consolidation and radiological evidence of consolidation. If the

patient has symptoms and signs of a bacterial chest infection, sputum should be sent for culture if possible. Haemophilus influenzae, Streptococcus pneumonia, and Moraxella catarrhalis are common pathogens in COPD as they often colonise the respiratory tract. Some 50% of patients with COPD have bacteria colonisation in the lower respiratory tract when they are stable. Exacerbation may be due to the acquisition of new strains of bacteria. Treatment of bacterial infections with antibiotics leads to faster recovery time and reduces the risk of relapse after discharge.

If the patient develops acute type 2 respiratory failure with acidosis (pH < 7.35), they must be started on BiPAP and monitored closely on a respiratory ward or HDU by a team experienced in the management of type 2 respiratory failure. A decision regarding the ceiling of care and resuscitation should be made after careful consideration of the facts, discussion with the respiratory physician, intensivist, the patient, and their family members. The management of type 2 respiratory failure is discussed in Chapter 13.

Patients with severe, end-stage COPD, who are not responding to treatment, should be referred to the palliative care team and should be placed on the end-of-life register. They may benefit from opioids to ease breathlessness.

Discharging a patient admitted with an exacerbation of COPD: patients should be off their nebulised treatment and have oxygen saturation above 88% on exertion. They should be on appropriate inhaled therapy and their inhaler technique should be checked. They should be discharged home on a reducing course of oral prednisolone at a rate of 5 mg every three to seven days. Some patients with COPD will require a longer course of prednisolone than those with asthma. Patients who are hypoxic will require assessment for long term oxygen therapy (LTOT) three weeks after discharge when they are stable. It is dangerous for patients who continue to smoke to have oxygen at home. Patients should be strongly encouraged to stop smoking, should be offered nicotine replacement therapy (NRT), and referred to the smoking cessation clinic.

NICE guidelines recommend pulmonary rehabilitation, so all patients referred with an exacerbation should be mobilised early and referred for pulmonary rehabilitation. These patients should have an annual influenza vaccination and pneumococcal vaccination every 10 years. For those patients who have recurrent exacerbations despite optimal treatment, bronchiectasis should be excluded (see Chapter 12). A three-month trial of prophylactic Azithromycin, given three times a week, may decrease the frequency of exacerbations in this group. This should be prescribed cautiously in those with liver function abnormalities, tinnitus, or hearing loss.

a-1 Antitrypsin Deficiency

Clinical presentation: patients with a-1 antitrypsin deficiency (a-1ATD) present with symptoms of progressively worsening breathlessness, wheeze, and infective exacerbations. Results of investigations will be consistent with a diagnosis of COPD, with obstruction on spirometry and little reversibility. The CXR and HRCT will show predominantly basal emphysema.

a-1ATD is the cause of emphysema in 1—2% of cases. It should be suspected in anyone younger than 40 with a family history of emphysema, and emphysema predominantly affecting the lung bases. It is often under-diagnosed. Typically, these individuals are not heavy smokers, but even minimal smoking increases the risk of developing emphysema. The WHO recommends that all patients under the age of 40, and all adolescents with asthma, are investigated for a-1ATD.

Pathophysiology: a-1 AT is a 52 kDa serine protease inhibitor which is synthesised in the liver and secreted into the bloodstream. It binds irreversibly to trypsin (and other enzymes) and inactivates them. Neutrophil elastase digests damaged, ageing cells and bacteria, and is important in the healing process of normal lungs. a-1AT inactivates elastase and protects the lungs from too much damage. Low levels of a-1 AT result in alveolar damage and the formation of bullae. Smoking activates neutrophil elastase and inactivates a-1AT, so worsens alveolar damage and the development of emphysema.

Genetics of a-1ATD: a-1ATD is a relatively common inherited condition with a frequency of 1 : 2500 worldwide and 1 : 2000 in Caucasians. The gene for a-1AT is on chromosome 14 and mutations at the protease inhibitor (Pi) locus lead to a single amino acid substitution which results in reduced levels of the enzyme in the serum. Glutamine to lysine mutation on position 342 results in PiZ genotype and glutamine to valine mutation on 264 results in PiS.

Box 6.14 Enzyme activity in a-1ATD.


100% activity of




a-1AT (normal)










a-1ATD is an autosomal recessive condition with co-dominant inheritance, so that each allele is responsible for 50% of the circulating a-1AT level. Phenotypic expression is variable. Those who are heterozygous are carriers and do not manifest the disease, but those who are homozygous will develop the condition. Approximately 80 allelic variants have been described. Normal a-1AT gene is called M. Abnormal variants are A—L or N—Z, and produce different amounts of the protein. Box 6.14 lists the levels of enzyme activity with the different alleles. A serum concentration <15—20% of normal values suggests homozygous a-1ATD.

Some 95% of Caucasians have PiMM and 1 in 20 are PiMZ. 95% of deficiency states resulting in clinical manifestations are PiZZ; 60—70% with PiZZ develop emphysema at a young age, and this is made more likely by smoking.

a-1ATD is the commonest cause of liver disease in infants and children, affecting 10%. It also affects 15% of adults, being more common in men than in women. The abnormal protein accumulates in hepatocytes, causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Liver function tests will show a cholestatic picture and a liver biopsy will show characteristic PAS-positive (periodic acid Schiff) inclusions in hepatocytes.

Diagnosis of a-1ATD: clinicians should have a low threshold for investigating patients who present with early onset emphysema and who have a family history of emphysema. a-1AT concentrations in blood, measured by quantitative immuno- precipitation, will show low levels, the normal range is 1.10—2.10. a-1AT phenotype can be measured by isoelectric focusing and DNA studies can confirm the diagnosis. The WHO recommends screening in areas with a high prevalence of the disease and for those with a family history.

Management of a-1ATD: smoking cessation should be strongly advised. Management is as for COPD, as outlined earlier in this chapter. Some patients will progress rapidly to requiring LTOT. Single or double lung transplantation are options in those with progressive disease. Augmentation therapy with a-1AT protein, which can be inhaled as an aerosol spray or given intravenously, is recommended for those with emphysema and will reduce the decline in FEV1. It is not helpful in liver disease. Recombinant a-1 AT given weekly has not yet been shown to confer significant clinical benefit. Patients with a-1 AT liver disease should avoid alcohol and should be vaccinated for hepatitis A and B. Liver transplantation should be considered.

Patients with a-1AT deficiency should be referred to a recognised national centre, such as the Antitrypsin Deficiency Assessment and Programme for Treatment (ADAPT), and be enrolled onto a Registry so that they can participate in trials, have assessment of their carrier status, and be referred for genetic counselling.

Allergic bronchopulmonary aspergillosis (ABPA)

ABPA should be suspected in patients with a long history of asthma that does not respond to standard therapy. Patients will present with breathlessness, a cough productive of thick, mucopurulent sputum plugs, and recurrent infections. The differential diagnosis includes COPD and bronchiectasis. CT thorax will show the characteristic central bronchiectasis (Figure 6.9).

ABPA is not an infection, but an exaggerated T-helper cell reaction to aspergillus fumigatus. Blood tests will show peripheral eosinophilia (see Chapter 7 for causes of eosinophilia), very high plasma IgE levels, and precipitating and specific antibodies to Aspergillus fumigatus. Skin prick tests will be positive for aspergillus and sputum may also grow aspergillus.

Management of ABPA is as for bronchiectasis (see Chapter 12). In addition, patients should receive antifungal treatment for 16 weeks, either voriconazole or itraconazole, and a high dose of prednisolone, with careful monitoring of liver function test.

Figure 6.9 HRCT in ABPA showing proximal bronchiectasis.

Vocal cord dysfunction

Definition: Vocal cord dysfunction (VCD), or paradoxical vocal fold motion (PVFM), occurs due to abnormal movement of the vocal cords. During normal breathing, the true vocal cords abduct during inspiration, allowing air to enter the trachea and partially adduct during expiration. In VCD, there is an abnormal adduction of the vocal cords on inspiration.

Clinical presentation: VCD is commoner in women compared to men and can affect patients of all ages. Patients with VCD complain of breathlessness and persistent wheeze at rest and on exertion. They may also complain of throat tightness, dysphonia, a choking sensation, dysphagia, and rhinosinusitis. They often have a diagnosis of asthma or COPD but continue to complain of symptoms despite optimal treatment with inhalers. Patients present to the emergency department with what appears to be loud wheeze and stridor. Auscultation of the chest will not reveal any wheeze as in acute asthma. As this condition is often not recognised, patients with VCD often have unnecessary treatments, including high doses of corticosteroids, intubation, and ventilation. Clinical observation will reveal inspiratory stridor. VCD can occur secondary to a variety of conditions. Box 6.15 lists some of these.

Diagnosis: the differential diagnosis of VCD is listed in Box 6.16. Clinical history and examination will suggest VCD. Laryngoscopy or bronchoscopy are the diagnostic tests of choice. These investigations will show abnormal adduction of the vocal cords during inspiration which may be exacerbated after exertion. Examination will also exclude a subglottic stricture and tracheal stenosis. Ultrasound of the vocal cords may be diagnostic if there is no concern about a stricture or tumour.

Methacholine challenge will be normal and will exclude asthma. Flow volume loops will show evidence of extra-thoracic airway obstruction, with flattening of the inspiratory loop.

Management of VCD: VCD should be managed with a combination of reassurance, education, behavioural therapy, and speech therapy. Amitriptyline, used ‘off licence’, at a starting dose of10 mg, taken two hours before going to sleep, appears to relax the vocal cords, with improvement over 7—28 days. The dose can be increased weekly by 10 mg, to a maximum dose of 70 mg. Most patients respond to a dose of between 10 mg and 40 mg over three to six months, and the dose can be reduced once the vocal cords relax. Amitriptyline will also correct the insomnia which is associated with this condition. The main side effects occur at higher doses and include dry mouth and fatigue. Caution is also advised in using amitriptyline in patients with severe prostatic hypertrophy. Patients should be advised to drive with care because of possible drowsiness.

Hyperventilation syndrome (HV)

Hyperventilation (HV) syndrome is a condition associated with an increase in minute ventilation, so that the patient presents with intermittent episodes of breathlessness. As there are no clear diagnostic criteria, it is difficult to estimate the incidence and prevalence. The diagnosis is often made after excluding other causes of breathlessness. The differential diagnosis of hyperventilation syndrome includes panic attacks and anxiety disorders, although it is not clear whether the psychological condition is primary or secondary. The prevalence of hyperventilation is higher in those with underlying psychological problems than it is in the normal population, and a detailed clinical history may reveal a psychological cause. It is commoner in women compared to men. Box 6.17 lists the common symptoms of hyperventilation syndrome.

Patients presenting with hyperventilation report difficulty taking a breath in, and may be found to take slow, deep breaths. Patients with panic or anxiety disorder will breathe rapidly and take shallow breaths. They will also report these symptoms after exercise and the extent of their symptoms will not correlate to the level of the exercise. These patients also report symptoms of anxiety and fear. The control of breathing is discussed in Chapter 2.

It is postulated that patients who present with hyperventilation have increased sensitivity to COand an increased respiratory drive when feeling anxious or distressed. This results in reduced PaCO2, respiratory alkalosis, and a reduction in cerebral blood flow which leads to paraesthesia, headache, and light-headedness. Respiratory alkalosis results in changes to the level of ionised calcium, and reduced binding to albumin, which can result in tetany.

Diagnosis of hyperventilation syndrome: acute respiratory and cardiac conditions will need to be excluded with a detailed history, examination, and investigations as discussed in Chapter 5. The history will be one of intermittent breathlessness, with no clear pattern, and normal physical examination and investigations. A clinical presentation suggestive of hyperventilation and no features to suggest an alternative diagnosis is sufficient to make the diagnosis. However, most patients will have a CXR, ECG, spirometry, and measurement of oxygen saturation at rest and on exertion, to rule out other conditions. Convincing the patient that there is no other serious medical condition can be difficult.

Management of hyperventilation syndrome: the main management is with psychological therapies, including behavioural therapy and breathing retraining as part of pulmonary rehabilitation. Patients who present with an episode of acute hyperventilation should be reassured after excluding other causes. They should be taken to a quiet area and an attempt should be made to keep them calm and breathe at a normal rate. A small dose of a sedative drug may be beneficial. As patients who are hyperventilating will be hypocapnic, breathing into a paper bag has long been advocated as part of the management, as this results in an increase in the CO2 level in the blood. However, this cannot be recommended as there is a significant risk of hypoxia. Referral to a psychiatrist for management of anxiety and depression should be considered. β- blockers and benzodiazepines may be beneficial in some patients. Yoga and Buteyko techniques may be helpful in reducing hyperventilation by reducing the respiratory rate.

 Obstructive airways diseases are common causes of morbidity and mortality worldwide.

 Atopy is an inherited tendency to produce large amounts of IgE when exposed to an allergen.

 Asthma is an atopic condition in which exposure to an allergen results in an exacerbation in a genetically susceptible individual.

 Asthma is a reversible condition caused by airway inflammation; the reversibility distinguishes it from COPD.

 Acute asthma exacerbations are managed with nebulisers, systemic steroids, magnesium sulfate, high flow oxygen, and intravenous aminophylline.

 Patients with acute asthma should be monitored closely with regular clinical assessments, including serial ABG measurements.

 Patients who are not improving or deteriorating, with normalising of the PaCO2, should be referred urgently for intubation and ventilation.

 Chronic asthma can develop in patients who have been under-treated; these patients will respond less to bronchodilators as there are fixed, structural changes in the airways.

 There are approximately 1500 asthma deaths in the UK every year.

 Most deaths from asthma are preventable: inadequate use of preventative inhalers, over-use of SABA, lack of recognition of deterioration by patient and doctor, poor compliance.

 COPD is a significant cause of morbidity and mortality worldwide.

 The risk factors for COPD include cigarette smoking, passive smoking, occupational exposure to dusts, and atmospheric pollution.

 The diagnosis of COPD is made when the FEV1/FVC ratio is less than 70% on spirometry.

 COPD severity can be categorised by spirometry as mild, moderate, severe, and very severe.

 The severity of COPD guides management, predicts the frequency of exacerbations and the risk of death.

 Smoking cessation is the most important intervention for patients with COPD.

 Inhaled therapy with SABA, LABA, SAA, LAM, and ICS should be offered in all cases, depending on symptoms and FEV1. A combination of inhalers is more effective than individual drugs.

 Pulmonary rehabilitation should be offered to patients with COPD with an MRC score of 3 or more and improves symptoms, exercise tolerance, and QOL.

 Mucolytic agents can be useful in some patients with COPD, but the evidence for their use is minimal.

 Roflumilast, a phosphodiesterase-4 inhibitor, improves symptoms and prognosis in patients with severe COPD.

 Theophylline, a non-selective phosphodiesterase inhibitor, has a moderate bron- chodilator effect, so could be considered in addition to inhaled therapy but the drug has a narrow therapeutic range and has significant side effects and drug interactions.

 a-1ATD is an inherited condition with autosomal codominance. Patients with homozygous disease develop basal emphysema and liver disease.

 Management of a-1ATD is as for emphysema. Intravenous augmentation therapy and lung transplantation can also be considered.

 Vocal cord dysfunction is a common condition which is often misdiagnosed as acute asthma.

 The diagnosis of VCD is made by observing the movement of the vocal cords during inspiration.

 Management of VCD is with speech and language therapy and amitriptyline.

 Hyperventilation is associated with anxiety and is commoner in women than in men.

 Hyperventilation should be managed with reassurance, CBT, β-blockers, and benzodiazepines.


6.1 Which of the following investigations is most likely to be abnormal in a patient with mild asthma?


B Eosinophil count in peripheral blood

C Exhaled NO

D Methacholine challenge

E Spirometry

Answer: D

CXR and spirometry are likely to be normal in mild asthma in between exacerbations. The eosinophil count and exhaled NO, which is a measure of airway inflammation, are likely to be normal. Methacholine provocation test is the most sensitive of these investigations at detecting airway hyper-responsiveness.

6.2 Which of the following is recommended in the management of asthma?

A Desensitisation to allergen

B Leukotriene receptor inhibitor at Step 2 of the guidelines

C Non-invasive ventilation for respiratory failure

D Pulmonary rehabilitation

E Vaccination against influenza virus

Answer: E

Patients with asthma are usually atopic and should avoid any allergens that cause an exacerbation, but desensitisation is not recommended. Leukotriene receptor inhibitor should be considered in those who have not responded to adequate doses of ICS and LABA, especially those with high IgE and exercise-induced and aspirin-sensitive asthma, so at Step 3. Patients who develop type 1 respiratory failure will require intubation if they do not improve with management. Pulmonary rehabilitation is indicated for patients with COPD and not asthma.

6.3 Which of the following is a feature of life-threatening asthma?

A PaCO2 <4 kPa

B PEF >75% predicted

C Polyphonic wheeze

D Silent chest

E Tachycardia

Answer: D

Patients with asthma initially present with polyphonic wheeze and type 1 respiratory failure. As they are tachypnoeic, they will blow off CO2, which may be low. If there is inadequate treatment or no response to treatment, the patient will tire. In life-threatening asthma, the PaCO2 will rise, and may be at the higher end of the normal range, >4.5 kPa. At this stage, there is little air entering or leaving the lungs, so-called ‘silent chest’. The patient is likely to be bradycardic.

6.4 Which of the following is a risk factor on its own for fatal asthma?

A Moderately severe asthma

B Lower respiratory tract infection

C No hospital admissions with asthma

D Poor perception of dyspnoea

E Under-use of SABA

Answer: D

Patients with mild, moderate, and severe asthma are at risk of fatal asthma if their condition is inadequately treated, if they have poor perception of their symptoms and if they do not understand how to manage it. Lower respiratory tract infections may exacerbate asthma, but is not a risk factor for a fatal asthma attack by itself. Under-use of SABA indicates good control of symptoms as does no previous hospital admissions. NRAD found that patients who had a poor perception of dyspnoea were at risk of death.

6.5 Which of the following investigations is essential in the diagnosis of COPD?

A Arterial blood gas.



D Spirometry

E Reversibility testing

Answer: D

The diagnosis of COPD is made when a symptomatic patient has FEV1 <80% predicted or FEV1/FVC <70%. ABG, CXR, and HRCT may be normal in mild COPD. Reversibility testing is not indicated in COPD, although it may be useful in patients in whom there is uncertainty about whether they have asthma or COPD.

6.6 Which of the following has been shown to have NO benefit in a patient with COPD?

A Aminophylline B Inhaled corticosteroids

C Leukotriene antagonist

D Pulmonary rehabilitation

E Smoking cessation

Answer: C

There is strong evidence for the benefit of smoking cessation and pulmonary rehabilitation in patients with COPD. Inhaled corticosteroids, together with LABA, have been shown in large, multi-centre trials to improve the symptoms and reduce the frequency of exacerbations in those with moderate and severe COPD. Aminophylline appears to have a bronchodilator effect and can be used in those who are symptomatic despite the use of inhaled therapy. Leukotriene antagonists have no role in COPD but are used in Step 3 of asthma management.

6.7 Which of the following is indicated for the management of acute exacerbation of COPD?


B High flow oxygen

C Intravenous salbutamol

D Intravenous magnesium sulfate

E Non-invasive ventilation

Answer: E

CPAP is a way to deliver oxygen in severe type 1 respiratory failure. CPAP and high flow oxygen are not indicated in hypoxic patients with COPD because of the risk of CO2 retention and the development of type 2 respiratory failure. Intravenous salbutamol and magnesium sulfate are not used in an acute exacerbation of COPD, but can be occasionally used, with caution, in an exacerbation of asthma. NIV is the treatment of choice in a patient who develops type 2 respiratory failure because of COPD exacerbation.

6.8 Which of the following statements about a-1ATD is true?

A a-1ATD is an autosomal dominant condition

B a-1ATD never occurs in children

C Augmentation therapy with intravenous protein does not improve lung function

D Emphysema mainly affects the upper lobes of the lungs

E Lung transplantation is the best treatment for severe disease

Answer: E

a-1ATD affects 10% of neonates, presenting with liver disease. It is the commonest cause of liver disease in this age group and presents with abnormal liver function tests. It is an autosomal recessive condition with co-dominance. Intravenous a-1 AT improves lung function, but transplantation is the best option for severe disease. The emphysema affects the lower lobes, unlike the emphysema in COPD, which affects the upper lobes.

6.9 Which of the following statements about ABPA is true?

A Chest physiotherapy is not required

B Corticosteroids are not indicated

C CXR will show cavitation with a fungal ball

D IgE level in blood will be very high

E Treatment is with standard antibiotics as used for community acquired pneumonia

Answer: D

Patients with ABPA present with breathlessness, cough, and wheeze. Management is as for bronchiectasis, so includes chest physiotherapy. CXR may appear normal but HRCT will show proximal bronchiectasis. A cavitating lesion with a fungal ball is seen with aspergilloma, not ABPA. The IgE levels will be very high (>1000iU). Antifungal treatment is recommended (voriconazole, itraconazole).

6.10 Which of the following statements about VCD is true?

A Methacholine challenge will be abnormal

B Patients with VCD cough up a lot of purulent sputum

C Patients with VCD should be treated with high doses of corticosteroids

D Sub-glottic stricture should be excluded

E The vocal cords are paralysed in VCD

Answer: D

Patients with VCD are often mis-diagnosed as having asthma or COPD and receive high doses of steroids which do not improve the symptoms. Methacholine challenge will be normal as there is no airway hyperresponsiveness or bronchoconstriction. These patients do not cough up sputum. Subglottic strictures and tracheal stenosis should be excluded at bronchoscopy. There is no paralysis of the vocal cords, but abnormal adduction during inspiration.

Appendix 6.A Diagnosis of asthma

Figure 6.A.1 Diagnostic algorithm for presentation with respiratory symptoms.

Appendix 6.B Management of asthma

Figure 6.B.1 Summary of asthma management in adults.

Appendix 6.C Management of COPD

Figure 6.C.1 Diagnostic algorithm for inhaled therapy.


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