The rise and rise of asthmaAustralia has one of the highest rates of asthma in the world. It is a complex disease which is still not fully understood.
Key text
Key textWhat is asthma? Whenever we take a breath, we take air into our lungs through a complicated system of tubes, called airways. These airways empty the exhaust gases from our lungs and resupply them with oxygen-rich fresh air. Asthma is a condition where the airway walls become inflamed. The airways become narrower than usual and partially blocked, and may eventually become permanently damaged. Asthma is a long-lasting problem doctors call it a chronic disease. Sufferers can usually lead relatively normal lives (although they may be a bit breathless and have a frequent cough). Once someone has asthma, symptoms can be set off or made worse by triggers, leading to an asthma attack. People suffering an attack will have some or all of these symptoms:
During an attack, the airways narrow because the muscles in their walls are squeezing them. This is called bronchoconstriction. In addition, more and thicker mucus is secreted into the airways, and their inner lining becomes inflamed and over-sensitive to any irritants. A severe asthma attack, if not treated in time, can prove fatal. Causes of asthma It is hard to know exactly what causes airway inflammation and asthma. Genetic factors play a part. Some people have an underlying predisposition. There is strong evidence that exposure to allergens in early life increases their risk of developing asthma. Asthma is also more likely to occur in someone with relatives who suffer from some form of allergy. Asthma can also be caused by exposure to some occupational sensitisers. What triggers asthma symptoms? Once the airways are inflamed, they become twitchy and oversensitive to different triggers, such as:
But it is not always clear what triggers an asthma attack. Types of asthma Not all asthma is the same. There are two general types, sometimes called extrinsic (allergic) and intrinsic (non-allergic). About two-thirds of asthmatics suffer from allergic asthma and one-third suffer from non-allergic asthma. Both types of asthma can be made worse by polluted air, even if it is not a trigger. This is especially true if the air contains sulfur dioxide, nitrogen oxides and ozone. These gases irritate the airways (as do many components in cigarette smoke), worsening an asthmatic’s condition. Other factors also play a part in asthma. Some studies have suggested that the way we breathe and the depth of our breathing may affect the degree of tightness of the muscles that surround the airways. Prevention and management Unfortunately, there is as yet no real cure for asthma. The drugs used to treat it either prevent the occurrence of an attack, or relieve the symptoms of an attack (Box 1: Treatment options). When asthma is controlled by medication, exercise can be beneficial rather than acting as a trigger. Several top athletes are asthmatics. Incidence in Australia Asthma has been on the rise in Australia for many years. We have the dubious honour of being one of the world’s asthma hot spots. About 10 per cent of Australians have a problem with the disease, and probably about 20 per cent of children suffer from an asthma attack at some stage. Asthma ranks among the top ten reasons for visiting a doctor. There are many theories about why the incidence of asthma is so high here. Ideas range from changes in asthma diagnosis (conditions that used to be classified as something else are now diagnosed as asthma) to the occurrence of house dust mites or large quantities of pollen. Most Australian cities are situated in warm, humid areas ideal conditions for house dust mites to thrive. The mites are so small that they are invisible to the unaided eye, but they breed in dust, carpets, mattresses and pillows. The mites are harmless, but when their droppings are inhaled they can trigger a reaction that makes some people sneeze and causes asthma in others. But house dust mites are not the whole story. The rates of asthma around the world do not follow the known extent of dust mite infestations. Asthma rates are lower in less-developed countries and one authority suggests that the reduction in childhood respiratory diseases in our medically efficient world may cause the immune system in the lungs and airways to over-react when exposed to substances that it should tolerate. Australian research into asthma Throughout Australia, doctors and scientists are studying the causes and treatment of asthma (Box 2: Australian research).
Preventers can stop the airways becoming obstructed. They do this by preventing the inner lining from becoming inflamed and from producing too much mucus. These medicines are therefore called anti-inflammatory agents. Most are corticosteroids (or steroids for short). They must be used carefully because they can cause side-effects. Another type of preventer called cromolyn (or disodium cromoglycate) stops the cells lining the airways from reacting to allergens. Relievers are a different class of drug. They are designed to relieve the symptoms once an attack is underway. They can also be used before exercise to prevent exercise-induced asthma. The majority are called bronchodilators because they dilate the airways. They do this by making the muscles around the airways relax. There are many different types. Most are inhaled so that they reach the airways immediately. Peak-flow meters The peak-flow meter is a way of measuring how the airways are performing. If the peak-flow reading is lower than usual, it is a sign that the airways are becoming partly blocked. In this way the asthmatic can monitor whether extra medication or a visit to the doctor is necessary. Careful and regular use of the prescribed medication is important in asthma. In 1994, 825 Australians died from the disease, but many deaths can be prevented. Of course, an important part of asthma management is to avoid situations that are known to bring on attacks wherever possible. That is the best medicine of all. Related sites
One of the great mysteries of the allergic type of asthma or indeed of any allergic condition is why the body makes such a fuss over totally harmless airborne particles. We know that what we call allergens are simply materials mistaken for invading microbes or their products. It’s a costly mistake: the entire immune system is put on red alert to counter a non-existent threat, and the result is the gamut of symptoms that sufferers must endure. But why? Grass pollen or mite faeces should not be genuine problems for the human body; after all, the majority of people don’t react to them at all. Eosinophils respond to allergens in asthmatics Researchers know that the chief culprit in causing much of the damage in an asthma attack is a fairly rare type of white blood cell called the eosinophil. Eosinophils are designed to be the ‘heavy force’ of the immune system, being equipped to deal with occasional 'big' invaders such as worms. It seems quite bizarre, but in asthmatics these cells are unleashing their strong destructive power onto the patient’s uninfected tissue without any provocation. Perth research on interleukins Why and how are the eosinophils brought into the airways and lungs by allergens? In 1985, a team in London discovered that interleukin (an immune system molecule) was controlling eosinophil production and decided to study it. The head of the team was Professor Colin Sanderson. When he came to Perth in 1993, the project moved with him. Research showed that there were actually two chemical messengers involved in eosinophil control. These are now called interleukin-4 (IL-4) and interleukin-5 (IL-5). (The latter was what Colin Sanderson first identified.) These signalling molecules are secreted into the bloodstream by other cells of the immune system (T cells), and can attract eosinophils to the area. If we could block the release of the interleukins, it might stop the accumulation of eosinophils and many of the resulting symptoms of an asthma attack. The researchers in Perth are finding out what controls the production of IL-5 itself. The aim is to see if there are differences in the regulation of its production between T cells from normal and asthmatic individuals. Preliminary findings suggests that there are differences. Canberra researchers use genetically engineered mice At the Australian National University in Canberra, Mr Simon Hogan, a PhD student in Dr Foster’s team, has developed a ‘mouse model’ of allergic asthma. From these asthmatic mice, Dr Klaus Matthaei and Professor Ian Young, also at the John Curtin School, genetically engineered varieties of mice that lacked the genes for expression of either IL-4 or IL-5. When tested with the usual triggers, it was found that the asthmatic mice that couldn’t make IL-5 didn’t have any eosinophils in their airways and lung tissue, and they showed none of the contraction of the smooth muscle of the airways that characterises a full-blown asthma attack. Although they had some types of white blood cell accumulating, they were virtually symptom-free. But the mice that could not make IL-4 had asthma symptoms, which suggested that this chemical messenger is not as important for controlling eosinophils as IL-5. In a further refinement, designed to prove IL-5’s involvement once and for all, colleague Dr Alistair Ramsay was asked to build a genetically engineered virus to carry the IL-5 gene back into the lungs of the mice lacking IL-5. When the mice were infected with the virus, and Il-5 was synthesised, an allergic trigger produced a full asthma response in mice that previously had produced none when presented with an identical trigger. Applications of the research The knowledge from this work gives us a way out of the asthma maze. Blocking the release of IL-5 or inhibiting its effects such as through a drug that binds to it and inactivates it could be extremely useful. The Perth team is now seeking ways of testing for substances that could be used to inhibit IL-5 production or to inactivate circulating Il-5. The Australian pharmaceutical company AMRAD, in Melbourne, will carry out the process of screening likely candidates. Related sites
Teachers notes
During an asthma attack the smooth muscle lining the air passages of the lungs becomes constricted and the volume of the air that can be exhaled is decreased. Using a large plastic bottle, you can approximately measure, the maximum volume of air that can be exhaled during forced breathing. Materials (for each small group)
Procedure
Questions
Teachers notes Students suffering from respiratory or heart problems should not act as subjects for this activity. Make sure students do not become competitive in their exhaling. This activity should be done in groups of two (or more). While one student is exhaling another is needed to stabilise the bottle. Provide a new length of tubing for each student. You may want students to calculate a class average and determine the standard deviation. Students could compare the average volume exhaled by females with that exhaled by males or they could look for a correlation between volume of air exhaled and height of the student. Remind students the volume they are measuring is the vital capacity of the lungs which is more than that exhaled during normal breathing (tidal volume) but less than the total lung capacity. (Some air always remains in the lungs because the thorax cannot be completely collapsed.) Students can also measure the tidal volume of their lungs using the set-up for this activity. They could use the large plastic bottle or a 500-mL cylinder. The plastic bottle will only give a very approximate reading but will show students that the tidal volume is only small compared to the vital capacity.
Exercise can alter the rate of breathing and the carbon dioxide (CO2 ) content of the exhaled air. This activity will measure the effect of exercise on breathing rate and CO2 levels in exhaled air. Materials (for each small group)
Questions
Teachers notes Students suffering from respiratory or heart problems should not act as subjects for this exercise. Preparation
Summary of data collection At the end of the experiment students should have:
CO2 concentration is measured by titration. When CO2 dissolves in water it forms a 'weak' acid (carbonic acid). By measuring the amount of NaOH needed to neutralise this acidic solution, a relative measure of the amount of CO2 is obtained the more NaOH needed, the more CO2 has been exhaled.
Teachers notes The large airways to the lungs are supported by cartilage. However, the smallest airways (bronchioles) which lead to the air sacs (alveoli) are supported only by smooth muscle. When these muscles tighten or spasm, this makes the opening of the airways much narrower than usual so it is hard to move air in and out of the air sacs. In addition to the effect of the muscles tightening, the thin linings inside the airways swell and thick mucous plugs the airways. The symptoms experienced by an asthma sufferer are: breathlessness, wheezing, chest tightness and coughing.
Australasian Science October 2006, pages 38-40 Genetic links between asthma and obesity (by Cheryl Salome and Michael Rolph) Examines the activity of a gene implicated in metabolic disease and asthma.
June 2005, pages 14-17 The effect of indoor air pollution on children's health (by Krassi Rumchev) Infants and children are more vulnerable to pollutants found in high concentrations in our homes.
May 2004, pages 19-20 The scars of asthma (by Janette Burgess) Explains how the growth of scar-forming tissue is responsible for airways narrowing in asthmatics.
Cosmos August 2005 Worms of endearment (by Abbie Thomas) Describes a possible therapy for allergy sufferers.
Issues June 2006, pages 43-46 Asthma: have we reached the peak? (by John Woods and Philip Thompson) Says that the rise in asthma cases seems to have plateaued and discusses possible reasons for the prevalence of asthma.
New Scientist 29 March 2007 Asthma soothed by airway radio-blasts Looks at a device that heats the muscle lining of airways using radio waves to prevent asthma attacks.
3 March 2007, page 13 Asthma linked to hybrid immune cell (by Aria Pearson) Suggests that a recently discovered class of immune cell may hold the key to new treatments for asthma.
22 October 2005, page 23 Perils of sleeping in a fungal ecosystem Describes the fungal ‘ecosystems’ inhabiting many pillows.
10 September 2005, page 18 Suffering from asthma? Try a dose of worms (by Andy Coghlan) Describes a new therapy for allergy-prone people.
16 April 2005, pages 34-39 Filthy friends and the rise of allergies (by Garry Hamilton) Discusses the theory that commensal microbes regulate the response of the immune system to allergens.
5 June 2004, page 13 Asthma linked to use of antibiotics (by James Randerson) Covers experimental evidence that upsetting the gut flora can provoke an allergic response.
27 March 2004, page 36-39 Take a deep breath (by Phyllida Brown) Describes research to understand the dramatic increase in the prevalence of asthma.
26 May 2001, page 16 Wheezy weather (by Melanie Cooper) Covers Australian research showing why thunderstorms trigger asthma outbreaks.
22 May 2001 Protective parasites (by Richard Black) Looks at the possible role of intestinal worms in the prevention of asthma.
research*eu January 2008 Asthma and allergies: Spotlight on leukotrienes (by Julie Van Rossom) Reports on research into an enzyme involved in allergies.
RTD Info May 2004 The allergy enigma Looks at the epidemiology of allergies and sources of environmental allergens. Also includes boxed information ‘Data on plant proteins’ and ‘Apples, false friends’.
Scientific American 11 July 2002 Researchers identify gene associated with asthma (by Rachael Moeller) Describes research identifying a gene associated with asthma.
June 2000, page 19 Asthma worldwide (by Roger Doyle) Shows increases in the prevalence of asthma and its distribution.
A wide range of information for patients to help them understand and manage their asthma.
National Asthma Council Australia
Up-to-date information about asthma for the general public, patients and health professionals. The Asthma Management Handbook is available on-line at this site.
The Lung Net: Learn about lung health (Australian Lung Foundation)
An excellent collection of fact sheets and illustrations about respiratory diseases and lung function. The fact sheets relating directly to lung function and asthma are: 'The lungs - an overview of how they work'; 'Asthma and scuba diving'; 'Asthma in exercise and sport'; 'Controlling adult asthma'; 'Controlling childhood asthma'; 'Occupational asthma'; 'Corticosteroid therapy in respiratory disorders'; and 'Lung function tests'.
Australian Broadcasting Corporation (transcripts)
Asthma overview (British Broadcasting Corporation, UK)
Provides information about the symptoms, causes, common triggers and treatment of asthma.
Asthma (Health System, University of Virginia, USA)
An explanation, with diagrams (and sounds), of the human airways and what happens during an asthma attack.
How your lungs work (How Stuff Works, USA)
Describes how you breathe, where the air goes, how breathing is controlled and diseases that affect your lungs.
allergens. An allergen is any substance that triggers an allergic reaction. Common respiratory allergens are grass pollen, mould spores or house dust mite faeces (present in dust); other allergens may affect the skin or the digestive system. allergic reaction. Allergies are inappropriate reactions of the immune response to substances (allergens) that normally wouldn’t cause any noticeable effects. Most allergic reactions involve the allergen binding on to special immune system cells and causing these cells to release compounds that affect the surrounding tissue. One such compound is histamine. It causes itching and inflammation. Chemicals that block the effect of histamine are called antihistamines, and they are standard allergy medication. However, they are not particularly effective in asthma. bronchodilators. (Also called 'relievers'.) These are a group of drugs that relax the smooth muscle in the airway walls and hence widen (dilate) the airways. Used to relieve the symptoms of an asthma attack. chronic. Used to describe a medical condition that continues for a long time, often with little change. A chronic disease, such as asthma, may have acute episodes, when the situation worsens for short periods of time. eosinophil. A white blood cell that increases in number as a result of certain parasite infections and allergic diseases. extrinsic. External or a cause coming from outside. In this type of asthma, the cause of an attack is normally the inhalation of an allergen. Extrinsic asthma is more likely than intrinsic to start in childhood, and often the trigger(s) can be identified and dealt with. In extrinsic asthma, the reaction of the airways is like an allergic reaction, and is similar to hayfever and other allergies. house dust mites. Tiny mites (about one-third of a millimetre long) that feed off human skin flakes and bodily secretions. They colonise houses, especially in warm, humid areas. They tend to live in carpets, mattresses, pillows and soft furnishings. Although quite harmless, their droppings contain substances that are allergens. Exposure to the droppings (invisible to the eye) can cause sneezing, itchy, red eyes or asthma attacks. inflamed/inflammation. Inflammation is the process that makes living tissue swell, become painful and turn red. Inflamed tissue contains damaged cells and has a higher than normal blood flow through it that is why it’s red and warm. It is usually ‘infiltrated’ by many cells of the immune system. Compounds released from damaged cells cause fluid and more inflammatory cells to leak out of the blood vessels in the area; this fluid accumulates and may make the tissue swell or block tubes. Inflammation is often associated with infection but it can also be caused by allergic reactions. One of the major inflammatory cells in asthma is the eosinophil, which can damage the airway lining. This can ultimately lead to permanent damage in the airways. Inflammation of the lining of the nose, for example, causes the blocked nose characteristic of colds or of hayfever. Inflammation of the airways occurs in asthma, but is not unique to it. interleukin. A chemical messenger secreted by cells of the immune system. They act by affecting the behaviour of the rest of the immune system. For example, they may attract immune system cells to an area of the body or they may stimulate the development of some cells of the immune system. intrinsic. Instrinsic asthma has no clear connection with allergy. It can start at any age. The triggers are usually infection, polluted air, exercise, or cold temperatures, but some attacks occur without any obvious trigger. nitrogen oxides. Chemical formula NOx. This covers the gases nitric oxide (chemical formula NO) and nitrogen dioxide (chemical formula NO2 ). Both can be toxic but nitrogen dioxide is considered to be of most concern for asthmatics. The main source of the gases in urban areas are motor vehicle exhaust and gas cookers and kerosene heaters indoors. The brown haze sometimes seen over cities is mainly nitrogen oxides. These gases are also partly responsible for the generation of ozone, when acted upon by sunlight in the presence of other chemicals. Although air pollution can cause irritating symptoms and increased asthma symptoms in some people, it is unlikely to be an important cause of asthma in Australia. occupational sensitisers. Chemicals or compounds that causes airway inflammation leading to asthma. These sensitisers occur in particular occupations such as carpentry (eg, western red cedar wood dust is a sensitiser) and commercial spray painting (some duco paints are sensitisers). ozone. Ozone (O3 ) is a form of oxygen. It is a colourless gas that has a very pungent odour. It exists naturally at low concentrations in the stratosphere where it absorbs ultraviolet radiation. In the troposphere it exists naturally at extremely low concentrations. But these concentrations increase when sunlight acts on various gases, coming mainly from vehicle exhausts, and ozone then becomes a pollutant in the troposphere. Ozone is a highly corrosive gas and is poisonous to most organisms. At concentrations as low as 0.00001 per cent (or 10 parts per hundred million) it can irritate the membranes lining the nose, throat and airways and can trigger or exacerbate asthma attacks. smooth muscle. All airways have bronchial smooth muscles in their walls. These muscles are classed as 'smooth' muscle. This means they are not under voluntary control, like the muscles of our legs and arms, but instead respond to circulating hormones and compounds released locally by damaged or inflamed tissue. Many drugs will cause changes in smooth muscle without any effects on our voluntary muscles. Smooth muscle contraction will narrow airways and can also constrict arteries and many other tubes in the body. Smooth muscle relaxation will dilate (widen) these tubes. sulfur dioxide. Sulfur dioxide (chemical formula SO2 ) is an acrid-smelling gas that even at low concentrations irritates the membranes of the nose and respiratory system. It is thought to exacerbate many respiratory diseases, including asthma. Sulfur dioxide is produced whenever sulfur-containing compounds are burnt. Its commonest source in Australia is power-stations burning coal containing slight sulfur impurities. trigger. A stimulus that causes asthma symptoms or an attack. Triggers include irritants such as fumes, cigarette smoke, allergens such as house dust mite or moulds, viral respiratory tract infections, and exercise. Not every asthmatic responds to every trigger. And not every asthmatic responds to the same trigger in the same way on each exposure. Some triggers, such as allergens, can cause worsening airway inflammation. white blood cell. (Also known as leucocytes.) White blood cells are the immune system cells. They can be divided into many different categories on the basis of their function and appearance. Many are not found in the blood at all and those that are may have the ability to crawl out of blood vessels, squeezing between the cells of the vessel walls. While some produce antibodies, others produce cocktails of destructive chemicals, others kill virus-infected cells by punching holes in them, and a further class control the entire immune response. For more information see White blood cells (Puget Sound Blood Center, Washington).
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