The diagnosis of asthma in adults.
Asthmatics fear the hallmark breathlessness, chest pain and cough. Yet symptoms alone are not always a reliable means of diagnosing and monitoring asthma. For instance, breathlessness on exercise may be unreliable as a guide to severity if adults walk more slowly as breathing becomes more difficult. Furthermore, asthma symptoms correlate poorly with objective measurements of lung function and the severity of the underlying inflammation. Indeed, some people with severe asthma report fewer and less intense symptoms than people with milder asthma.
Moreover, at any given severity, older people typically feel that their symptoms are more severe than younger people. Ekici and collaborators found that older people with asthma (average age 67 years) show similar lung function to younger people (average age 42 years). However, most older people with asthma reported feeling more breathless when they exercised. Older people also tend to feel that a similar exacerbation is more severe compared to the perception of younger patients. On the other hand, older people are typically less able to perceive bronchoconstriction following exposure to chemicals than younger asthmatics. So older people may not appreciate the seriousness of the attack.
Other factors complicate the relationship between symptoms and asthma severity. For example, older people may regard limitations to their activity as inevitable (because of their asthma, age or both) and not necessarily a marker of poor control. For instance, a review in The Lancet reports that up to a third of older people report feeling breathless – but around 70 per cent of these regard breathlessness as a normal part of ageing, so they don’t report symptoms that they regard as ‘normal’ to their GP or asthma nurse. This leads to under-treatment, and therefore to more severe symptoms.
Finally, asthma’s symptoms overlap with those of other diseases common in older people, which complicates diagnosis and treatment. For example, the Lancet review reports that 14 per cent of people over the age of 75 years wheezed. COPD, heart failure, acute bronchitis, bronchiectasis (abnormal widening of the airways), cancer and pulmonary embolism (caused when a clot blocks a blood vessel supplying the lung) can cause wheeze. Partly because of these problems, doctors have not diagnosed asthma in about half of the elderly people who suffer from the condition. As a consequence, the patients endure unnecessary symptoms.
Lung function tests
Because of the weak association between severity and symptoms, doctors use ‘lung function tests’ to diagnose asthma, monitor response to treatment and offer an early warning of an impending attack. Several factors influence lung function, including the following:
- Lung capacity is about a fifth to a quarter lower in women compared with men, even if they’re the same height and weight.
- Normally, lung function increases until early adolescence and then remains stable until the patient’s mid-30s. Lung function then declines, partly because lungs become less elastic as we get older.
- People who developed asthma for the first time aged over 60 years showed a more rapid decline in FEV1 – (42 ml a year) than those without asthma (2 ml a year) or those who already had asthma (15 ml a year).
To allow for such factors, doctors usually express the results of lung function tests as a percentage of those predicted for other people of the same age, sex and height based on measurements in thousands of healthy people. Doctors generally regard normal lung function as being within 85 per cent of the predicted average value.
Peak flow measures the maximum rate at which air moves when you exhale. This indirectly indicates the airway’s diameter when you breathe out. Despite the fact that you exhale for only a second or two, doctors measure peak flow in litres per minute.
Peak flow measurements can offer valuable insights into your asthma. For instance, an improvement of 60 litres a minute (l/min) or at least 20 per cent after taking a short-acting bronchodilator strongly suggests asthma. Furthermore, when diagnosing asthma your doctor or nurse may ask you to measure your peak flow in the morning and evening (sometimes more frequently) for, usually, a couple of weeks. Asthma patients tend to show a greater variation in their measurements over the course of a day (called the diurnal or circadian variation) than healthy people and those with some other diseases. In asthma, the diurnal variation is more than 20 per cent and appears to be especially marked in people with intrinsic, compared to allergic, asthma.
Keeping a peak flow record
If you keep a peak flow record, either to aid diagnosis or to monitor your disease, it is worth noting symptoms and any triggers (such as exercise or factors at work). This may help you identify a cause. If your symptoms get worse when vacuuming or making beds, you could be allergic to house dust mites or dander, for example. Symptoms that improve when you are away from home for a week or more, then relapse when you return, may suggest you’re reacting to an allergen in the house. If the doctor suspects occupational asthma, you may take peak flow measurements at and away from work – such as every two hours over four weeks. However, the duration depends on your particular circumstances, such as how long your symptoms take to improve when you are away from work. It’s important to note the hours you’re at work, to allow for shift patterns, for example.
In general, asthma symptoms do not emerge until peak flow declines by 25 per cent or more from your personal best. So, regularly measuring peak flow can offer an early warning of an impending exacerbation and helps ensure your asthma is well controlled. In general, if peak flow is commonly a third or more below your best, your asthma may be poorly controlled. For example, if your predicted peak flow is 500 l/min:
- a value of 400 l/min means that your asthma may still be well controlled;
- if peak flow drops to 300 l/min you may need to change your treatment (usually by increasing the dose of your inhaled steroid or taking a short course of oral steroid) as part of a self-management plan to restore good control.
Likewise, an increase in the normal circadian variation – the difference between the peak and the trough – may indicate poor control, increased severity or both. Nevertheless, peak flow charts may not always accurately reflect asthma’s severity. For example:
- Abdominal fat can hinder the diaphragm’s descent and, as a result, peak flow declines. So, carrying excessive weight can undermine the chart’s accuracy.
- Some healthy people from non-white ethnic groups have different normal peak flow rates from those of Caucasians. Current charts may not account fully for such ethnic differences.
- Factors other than asthma, including tobacco smoke and some other irritants, can influence peak flow.
- Several diseases other than asthma can increase diurnal variation.
Spirometry measures the volume of air expelled in one breath over time, when you breathe out as hard as you can after breathing in as deeply as possible. The forced vital capacity (FVC) is the total volume of air expelled forcefully until no more air can be breathed out. In healthy people, FVC is around 60 per cent of the lungs’ total capacity. The remainder represents the residual volume – the amount of air in the airways after a breath.
As you breathe out, the volume of air exhaled initially increases rapidly and then levels off. In general, healthy people take around four seconds to expel a full breath, and usually expel at least 75 per cent of the breath in the first second. Lung disease can reduce this proportion of the breath exhaled, so spirometry allows doctors to calculate ‘forced expiratory volume in one second’ (FEV1).
Doctors calculate the ratio between FEV1 and FVC. In healthy people, the FEV1:FVC ratio is 0.75 (or 75 per cent). People with asthma have narrow airways, so they exhale more slowly and FEV1 declines. FVC also declines, but to a lesser extent than FEV1. For example, an FEV1:FVC ratio of 75 per cent or less of the predicted level is a more sensitive indicator of airway obstruction than peak flow. Indeed, the ratio may decline (indicating obstruction) when FEV1 is normal.
In general, spirometry offers a more accurate measure of lung function than peak flow, depends less on the person’s effort and is more reproducible than peak flow. Normal spirometry while you experience symptoms means that it’s unlikely you have asthma. On the other hand, spirometry may be normal when you don’t have symptoms, so you may have to undergo repeated measurements at the surgery or clinic.
To aid diagnosis, doctors may measure your lung function using the spirometer before and after a dose of short-acting bronchodilator. An improvement in FEV1 of more than 200 to 400 ml (or more than 15 per cent) suggests that the airway’s obstruction is reversible, and therefore makes it more likely that you suffer from asthma rather than, for example, chronic obstructive pulmonary disease (COPD). However, remodelling means that the lung function of those with chronic severe asthma may not improve to this extent after bronchodilators. In such cases, an improvement after a trial of oral steroids (which potently reduce inflammation) for 14 days often clinches the diagnosis (inflammation is far more important in asthma than COPD).
As we’ve noted several times, asthmatic airways constrict when exposed to non-specific triggers such as cold air, dust, aerosol sprays and tobacco smoke. Doctors use this bronchial hyper-reactivity to help diagnose asthma using challenge tests. For example, a chemical called methacholine constricts the airways. The doctor gradually increases the dose of methacholine a person with suspected asthma inhales until FEV1 declines by 20 per cent. Most asthmatics – around 95 per cent – need a much lower dose of methacholine to constrict their bronchi by 20 per cent than people with healthy lungs. Other challenge tests use histamine, cold air, saline (a salt solution), exercise or adenosine.
However, a challenge test isn’t necessarily definitive. Some people with healthy lungs, smokers and many with chronic bronchitis, bronchiectasis or cystic fibrosis show abnormal challenge tests. Moreover, McGrath and Fahy found that 27 per cent of adults diagnosed with asthma by their doctor had a negative methacholine test. Those whose symptoms emerged during adulthood, those with normal FEV1 and those who did not require oral steroids were especially likely to show negative methacholine tests. Nevertheless, 60 per cent of those with a negative test reported experiencing asthma-like symptoms (cough, dyspnoea – shortness of breath – chest tightness or wheeze) at least once a week. Indeed, 39 per cent said they had visited an A&E department for asthma-like symptoms and 13 per cent had been hospitalized for asthma.
In some cases of suspected occupational asthma, the doctor will ask you to inhale one or more suspected triggers under very carefully controlled conditions. To reduce the risk of a severe attack, the dose is generally lower than the level encountered at work. Nevertheless, challenge tests can be dangerous – there’s always the risk that the test will trigger a serious, even life-threatening exacerbation – so specialized centres perform these tests and have equipment and trained staff at hand in case you should develop a severe reaction. During the test, you’ll probably also inhale an inert material. You won’t know which substance is which until after the test. This allows the doctor to account for any psychological reaction. Not surprisingly, people can be nervous when they undergo challenge tests. And stress can affect your respiration, a point we’ll return to in the last chapter.
Because allergies commonly cause asthma, doctors may suggest tests that determine whether your immune system is sensitized to a particular allergen. These tests are more useful to rule out a cause rather than to determine that, for example, grass pollen specifically causes your allergy. If you don’t show a positive reaction, the allergen probably isn’t responsible. On the other hand, if you test positive that doesn’t necessarily mean the allergen is responsible. You may be sensitive – in other words, produce IgE to the allergen – without the immune reaction being sufficiently severe to trigger asthma.
Skin prick tests
Skin prick tests are the longest-established immune investigation. The English scientist Charles Blakely performed the first skin prick test – on himself – in 1869. Blakely wanted to test his idea that pollen caused his hay fever. The test has changed little in more than 140 years.
During a skin prick test, the doctor or nurse uses a fine needle to press a small amount of the suspected allergen into your skin on the inside of your forearm. The needle is held almost parallel to the skin and doesn’t go very deep. (I’ve had this done several times. It doesn’t hurt. Really!) A swelling (weal) surrounded by a red flare 15 minutes or so later suggests you’re sensitive to that allergen.
The test includes two ‘controls’: the fluid used to suspend the allergen (called the vehicle) and histamine, to deliberately provoke weal and flare. A reaction to histamine shows the test is working correctly and helps doctors evaluate the results. Some elderly people may show a less marked response to a skin prick test than younger ones, for example. The control ensures that the vehicle doesn’t provoke symptoms.
Another type of immune investigation measures levels of IgE circulating in your blood, either the total amount or the concentration specific for a particular allergen. A high level of IgE suggests that an allergy may underlie your asthma. However, a positive test is much more common than symptoms. For example, between 8 and 35 per cent of young adults in Europe show IgE to grass pollen. Nevertheless, the test can rule out allergens and forms one piece in the jigsaw of tests that doctors use to decide whether you’re suffering from allergic asthma.
At least half of people aged 65 years and over have three or more co-morbidities, some of which – including COPD, congestive heart failure and vocal cord dysfunction – can mimic asthma’s symptoms. Other less common asthma mimics include cystic fibrosis, cancer and bronchiectasis. However, some people have both asthma and other diseases that cause similar symptoms, and this considerably complicates diagnosis and treatment. An asthmatic smoker may show signs of COPD, for example. Similarly, heart disease remains the UK’s leading killer and many asthmatics suffer a heart attack – simply because both conditions are common. Heart attack (myocardial infarction) survivors are at risk of heart failure, one symptom of which is ‘cardiac asthma’. So you may undergo tests to examine other possible causes, such as chest X-rays or an echocardiogram to exclude heart failure. In this section, we’ll look at three of the most common diseases that can complicate the diagnosis of asthma in adults.
The diseases formerly known as chronic bronchitis and emphysema
COPD encompasses several conditions that limit airflow, including ‘chronic bronchitis’ and ‘emphysema’. Around 15 per cent of men and 5 per cent of women in the UK suffer from chronic bronchitis, which Bourke defines as a productive cough ‘on most days for at least three months of two successive years’. Smoking or other triggers leave the airways of COPD patients inflamed and swollen, which blocks the flow of air and damages the lung. Meanwhile, goblet cells pump out more mucus. Because of the damage to the mucociliary escalator, the mucus isn’t cleared, leaving a plug in the airway. The mucus is an ideal habitat for many bacteria, so COPD patients often experience regular infections (acute bronchitis).
Emphysema arises from the alveoli’s gradual destruction. Alveoli and small airways depend on the support of the surrounding tissues to remain open. Emphysema destroys this support. That’s one reason why the airways of people with emphysema become obstructed and collapse when they exhale. This traps air, which can stretch the lungs. Breathing using ‘hyperinflated’ lungs takes much more effort. Emphysema also damages other elastic tissues – such as elastin – in the lungs. As emphysema progresses, alveoli form into large, irregular pockets with holes in their walls. Not surprisingly, these changes hinder the transfer of carbon dioxide and oxygen.
Chronic obstructive pulmonary disease (COPD)
Doctors estimate that three million people in the UK suffer from COPD. Of these, two million remain undiagnosed. For example, smokers may attribute cough and phlegm to tobacco rather than COPD and so don’t seek medical help. While the symptoms can seem similar, asthma essentially arises from inflamed, hyper-reactive airways. Contraction of the muscle surrounding the airways causes the obstruction, a very different process from COPD.
Traditionally, doctors have regarded asthma as reversible: in other words, attacks abate when exposure to the trigger ends or after the patient uses a bronchodilator. In contrast, they consider COPD to be largely irreversible. However, drugs can at least partially reverse the airway obstruction in many people with COPD, while remodelling can mean that people with severe asthma do not show totally reversible obstruction.
The risk factors for COPD and asthma also overlap. While smoking is the leading risk factor for COPD, many asthmatics smoke. Furthermore, bacterial infections trigger between a third and half of all COPD exacerbations, Hoshino and collaborators note. But respiratory infections are also a problem for people with asthma.
Nevertheless, COPD usually has a poorer prognosis than asthma. According to the National Institute for Health and Clinical Excellence (NICE), COPD kills approximately 30,000 people each year in the UK. According to NICE, 78 per cent of men and 72 per cent of women with mild COPD that does not require continuous drug treatment survive for a minimum of five years. But five-year survival declines to 30 and 24 per cent respectively in people with severe COPD who require oxygen or nebulized therapy.
So, it’s important to get the diagnosis right (see Table 1 below) and several clues help doctors differentiate COPD and asthma. For example:
- Asthma often has a sudden onset. COPD typically develops more gradually, typically over between 10 and 40 years, although people with sedentary lifestyles may not notice breathlessness until considerable portions of their lung function is gone.
- Asthma tends to wax and wane. While the airflow obstruction in COPD is slowly progressive, the severity does not change markedly over several months.
- Cough and sputum are more common with COPD than in asthma.
- Wheeze, a marked diurnal variation in symptoms and peak flow, and bronchial hyper-responsiveness are more common with asthma than COPD.
- Cold air is a more important trigger in asthma than COPD. Almost all asthmatics (96 per cent) show hyper-responsiveness when they inhale cold air, compared to just 10 per cent of those with COPD.
While these patterns offer important clues, doctors can’t rely on a single feature to distinguish the diseases. Indeed, Dima and colleagues found that combining lung function, assessing sputum production after inhaling a saline aerosol and determining airway hyper-responsiveness helped differentiate asthma from COPD.
|Smoker or ex-smoker||Possible||Nearly all|
|Symptoms emerged before 35 years of age||Often||Rarely|
|Chronic productive cough||Uncommon||Common|
|Night-time waking with breathlessness or wheeze||Common||Uncommon|
|Significant diurnal or day-to-day symptom variability||Common||Uncommon|
Against this background, NICE suggests that doctors should consider whether COPD is responsible for symptoms in those aged 35 years and over who are present or former smokers (or have another risk factor) and suffer from any of the following:
- breathlessness when they exercise;
- chronic cough;
- regular sputum production;
- frequent bouts of winter ‘bronchitis’;
(Doctors should exclude other causes of chronic cough, including tuberculosis and bronchiectasis.)
Stanley’s smoker’s cough
Stanley, who’s just celebrated his 68th birthday, started work at 16 years of age as an apprentice paint-sprayer in a car factory. When the site shut down, he retrained as a baker. An active trade unionist, he was well aware of the risks of occupational asthma in his previous jobs but, unlike some of his co-workers, he didn’t develop symptoms. However, a few months ago, Stan sought his GP’s advice as sometimes he feels breathless walking down to the local social club or working in his allotment. One of Stan’s grandsons keeps nagging him to quit smoking. And even after more than half a century smoking, he wants to set a good example to his other grandchildren. ‘If I can quit, they can,’ he says. Stan admits to having a dreadful smoker’s cough and catching ‘cold after cold’. His doctor suspects COPD. But a trial of inhaled steroids and salmeterol markedly improves Stan’s breathlessness and his peak flow returns to 89 per cent of his predicted level. Stanley has late-onset asthma – and he quits smoking.
Smoking and other causes of COPD
Smoking is the most common cause of COPD. Indeed, NICE points out, smoking causes around 85 per cent of COPD-related deaths. Furthermore, Løkke and colleagues found that at least 25 per cent of people develop moderate or severe COPD after smoking for 25 years. Indeed, 30 to 40 per cent of smokers in this study showed mild COPD or worse.
Nevertheless, some smokers never develop COPD. On the other hand, some lifelong non-smokers also suffer from COPD. Lamprecht and co-workers reported that, of people aged at least 40 years who had never smoked, 6.6 per cent suffered mild COPD and 5.6 per cent moderate to severe COPD. Indeed, people who had never smoked comprised 23.3 per cent of patients with moderate to severe COPD.
As non-smokers can develop COPD, factors other than tobacco must contribute. For instance, the immune system normally differentiates our tissue from that of invading pathogens. Occasionally, however, immunological civil war breaks out and the immune system produces antibodies against healthy tissues – so called auto-immunity. Rheumatoid arthritis, multiple sclerosis and type 1 (‘juvenile’) diabetes, for example, arise when autoantibodies attack joints, the fatty stealth surrounding nerve cells in the brain and the pancreas respectively. A growing body of evidence suggests that COPD patients produce autoantibodies against elastin and the cell layer lining the airways. Núñez and colleagues found abnormal levels of two antibodies linked to autoimmunity in 34 and 26 per cent of COPD patients respectively, compared to 3 and 6 per cent of controls.
Certain factors – including coalmine and silica dust, and metal fumes – can cause occupational COPD, which occasionally proves fatal. Coggon and colleagues estimated that occupational COPD accounted for approximately 172 extra deaths a year in men aged 20 to 79 years from England and Wales during 1979–90 (excluding 1981) and 83 extra deaths during 1991–2000.
Furthermore, 1 to 2 per cent of people with emphysema inherit a deficiency in a protein called alpha-1-antitrypsin (AAt), which protects the lung’s elastic structures. In smokers who lack AAt, emphysema can begin in their 30s and 40s. In most smokers, emphysema begins to produce symptoms between the ages of 40 and 60 years. Nevertheless, smoking remains the most important cause of COPD.
Heart failure and cardiac asthma
Heart failure can cause nocturnal cough and other symptoms reminiscent of asthma. During a heart attack, a blockage in blood vessels supplying the heart starves the cardiac muscle of oxygen and nutrients, and the area of the heart supplied by the blocked vessels dies. As a result, the heart pumps less effectively – a condition called heart failure.
Heart failure causes fluid to accumulate in the lungs (pulmonary oedema), which inhibits the transfer of oxygen across the thin lining of the alveoli. In some, this causes symptoms – including shortness of breath, coughing and wheezing – that are similar to asthma. While congestive heart failure commonly causes nocturnal symptoms, these tend to occur between one and two hours after lying down, rather than in the early morning as is typical of asthma. Furthermore, many people with heart failure show ankle swelling and weight gain, which are not associated with asthma.
Treatments for heart failure reduce pulmonary oedema and therefore alleviate the symptoms of cardiac asthma. But overusing asthma treatments, such as bronchodilators, can exacerbate heart failure and, because beta-agonists stimulate the heart, provoke dangerous abnormal heart rhythms. However, asthma and heart disease are common and some people develop both conditions.
Vocal cord dysfunction
In some studies, up to 40 per cent of people referred to specialists with recalcitrant asthma suffered from vocal cord dysfunction (VCD). Newman and colleagues found that 56 per cent of people hospitalized with VCD also had asthma. So 44 per cent had VCD without asthma – and VCD seems to be especially common in young women. However, doctors often confused VCD and asthma. Indeed, in patients with VCD alone, doctors misdiagnosed asthma for, on average, almost five years and 81 per cent regularly received oral steroids, which, as we’ll see in the next chapter, can cause serious side effects.
VCD can hinder airflow. So, like asthma sufferers, VCD patients wheeze. However, some important clues help distinguish VCD from asthma:
- People with VCD are more likely than asthma sufferers to experience throat tightness or changes in their voice.
- Typically, people with VCD experience more problems inhaling than exhaling.
- Symptoms that are predominantly due to VCD tend to be most common during the day. Attacks tend to emerge and resolve abruptly.
- Inhaled bronchodilators have little effect, or even exacerbate, VCD.
- Patients with asthma are more likely than those with VCD to produce sputum.