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Asthma

Asthma is an allergic reaction in the airways of the lungs, and is one of the most common chronic illnesses affecting all age groups in modern society. Worldwide, it is estimated that 330 million people suffer from asthmaANCHOR. 5.2 million people in BritainANCHOR, including one in ten childrenANCHOR, are currently receiving treatment for asthma. It is the most common reason for admission of children to hospital. If untreated, it causes a lifetime of suffering and can be lethal. Asthma is not just a public health problem for 'developed' countries - over 80% of asthma deaths occurs in low and lower-middle income countriesANCHOR. It is predicted that without urgent action asthma deaths will increase by almost 20% in the next 10 yearsANCHOR.

What is asthma and what causes it?
Inhaled medicines to relieve the symptoms of asthma attacks
Recent treatments
The need for continued research into asthma

Asthma animal research in the news

References

What is asthma and what causes it?

Asthma reactions can be provoked by any one of 200 irritants, or allergens, such as the house dust mite, cat dander, pollen, or certain foods. Attacks can also be brought on by exercise, emotional disturbance and infections like bronchitis. The underlying causes are not known, although there appears to be a genetic component. Prevention, by  avoiding exposure to allergens, would be the ideal solution, but this is far from easy and in many cases is impossible.

While there is no evidence that air pollution causes asthma, it can aggravate the condition in people who are already susceptibleANCHOR. Hence during periods of poor air quality, there is a rise in the number of hospital admissions due to acute asthma attacks.

Asthma is a narrowing of the airways of the lungs, made worse by allergens and eased by medication. The inflamed airways become irritable, leading to bouts of coughing, wheezing, breathlessness and chest tightness. The symptoms can be reversed by treatment, but they can be severe and are sometimes fatal.

Professor Clive Page, Kings College London, gave the 81st Stephen Paget memorial lecture in 2017 on the subject: How animals have contributed to our understanding and treatment of respiratory diseases.

It is a great historical review of how modern asthma drugs came about and it’s worth taking the time to watch in full. A transcript is available here.

 

Inhaled medicines to relieve the symptoms of asthma attacks

 Asthma therapy relies on inhaled medicines both to suppress the underlying inflammation and to relieve airway constriction. The former, used regularly as 'preventers', are glucocorticosteroids such as beclomethasone and budesonide. These drugs are based on cortisol, chemical which occurs naturally in the body. Animal experiments and studies have played a vital role in the discovery and characterisation of the glucocorticosteroids introduced from the 1960s onwards, most of which are given by inhalation to avoid the effects associated with oral steroids such as cortisolANCHOR. Sodium chromoglycate is another type of inhaled 'preventer', and interestingly this was discovered in the late 1970s by the scientist and asthmatic, Roger Altounyan, who conducted many experiments on himselfANCHOR.


The second type of inhaled medicines are the bronchodilators or 'relievers' that bring rapid relief from symptoms. Development of bronchodilators in the late 1960s was one result of the discovery of the existence and action of chemical nerve transmitters by Otto Loewi, working on frogs in the 1930s. He discovered that chemicals such as adrenaline are released by nerves and act on receptors in organs such as the heart and lungsANCHOR. However, later animal experiments revealed that the first bronchodilators were too short acting and stimulated the heartANCHOR. Further animal work led to more specific bronchodilators which were safer and longer-lasting such as salbutamol and terbutaline. These drugs activate ß2 adrenoceptors located in airway smooth muscle causing muscle relaxation and thus opening of the airwaysANCHOR.

Both modern preventer and reliever drugs, are refined and more selective versions of the naturally occurring chemicals. One of the great improvements in the treatment of asthma that occurred during the 1990s was the development thanks to animal testing of reliever inhalers with long duration of action (eg serevent). Studies conducted using the guinea pigANCHOR  were enormously beneficial in selecting reliever drugs that had the right properties that enabled asthmatics to take these medicines twice daily to provide protection against the symptoms of asthma. This is of considerable benefit for those asthmatics who suffer night-time awakenings because of their asthmaANCHOR.

Despite these recent medical advances a problem with these existing asthma therapies is that they are usually administered through an inhaler, which makes it difficult to get the dose right, particularly in very young and elderly patients.

Recent treatments

Work in the 1960s on the lungs of guinea pigs led to a greater understanding of the function of chemicals that are released by tissues when normal biological processes are disturbedANCHOR. In 1979, substances called leukotrienes were discovered to be the principal cause of the symptoms of allergic and inflammatory conditionsANCHOR,ANCHOR.

Animal experiments in guinea pigs and then primates led to the development of leukotriene-receptor antagonistsANCHOR. These drugs, introduced in 1998, were the first new type of treatment of asthma in 20 years. The advantage of this new type of therapy is that they can be taken by the mouth. These drugs are effective on all forms of asthma, from the mildest to the most severe.

Since allergens are known to trigger asthma attacks, researchers investigated whether it would be possible to block the effects of the allergen directly. It is known that allergens bind to a protein on the surface of cells in the airways which initiates an asthma attack. Blocking this receptor might prove to be of benefit in patients with allergic diseases. In the early 1990s an antibody was discovered which could block the ability of allergens to trigger an allergic responseANCHOR. This new type of therapy is now being used in the treatment of patients with severe allergic asthma and can also be used in allergic rhinitisANCHOR. This type of therapy needs to be given as injection and is expensive and so there are limits to how widely this type of treatment can be used.

The need for continued research into asthma

Improved medication means that the death rate from asthma is now falling, but there is still a lot we do not know about asthma and its causes. Over the last decade there has been a growing recognition that asthma is more complex than acute wheezing, and that it should be classified as a chronic inflammatory disease of the lungs. There is a recommendationANCHOR by major medical groups such as the British Thoracic Society and the WHO that asthma should be treated early with anti-inflammatory medication, in preference to the symptomatic use of bronchodilators.

Animal experiments are central to the understanding of asthma as a chronic inflammatory disease and to the evaluation of novel drugs for the treatment of this component of asthma. As a result of the human genome project scientists can examine the role of genes which are switched on in asthma. The gene of interest can be removed from mice and then the effect of this gene 'deletion' in models of 'asthma' can be investigated. These studies have not yet delivered new drugs, but many are in the research and development pipeline and some are currently being investigated in clinical trials, the results of which are not yet known. Such developments should lead to better treatments and show that animals play a vital role in the development of current and future asthma drugs.



Asthma animal research in the news

05/09/16 New asthma medicine relied on primate studies

A new asthma medicine - Benralizumab - an dramatically reduce the regularity of asthma attacks in humans. Two clinical trials suggest that the frequency of attacks can be cut by a third to a half. Prior to human trials, studies in primates showed Benralizumab was found to be effective at reducing the levels of a type of white blood cells which can cause asthma symptoms in humans when they build up in the lungs.

https://www.thesun.co.uk/living/1728895/magic-bullet-jab-offers-new-hope-for-severe-asthma-sufferers/

04/04/16 Study using mice reveals new way lungs respond in asthma attacks 

Scientists at the University of Leicester have identified a new biochemical process that controls how air enters and leaves the lungs during normal lung function and during asthma that could lead to new treatments for the disease. By disrupting these biochemical pathways in a mouse model of asthma the scientists discovered that they could prevent airway narrowing and maintain normal lung function. 5.4 million people in the UK suffer with asthma, with the disease affecting one in every 11 people.

http://www2.le.ac.uk/offices/press/press-releases/2016/april/study-reveals-new-way-lungs-respond-in-asthma-attacks


References

  1. World Health Organization (accessed 12 Jan 2007) Asthma: Facts. http://www.who.int/respiratory/asthma/scope/en/index.html
  2. World Health Organization (accessed 12 Jan 2007) Asthma: Facts. http://www.who.int/respiratory/asthma/scope/en/index.html
  3. Asthma UK (accessed 11 Jan 2007) What is asthma? http://www.asthma.org.uk/all_about_asthma/asthma_basics/index.html
  4. World Health Organization (accessed 12 Jan 2007) Asthma: Facts. http://www.who.int/respiratory/asthma/scope/en/index.html
  5. World Health Organization (accessed 12 Jan 2007) Asthma: Facts. http://www.who.int/respiratory/asthma/scope/en/index.html
  6. Wardlaw AJ (1993) The role of air pollution in asthma Clin & Exper Allergy, 23, 81
  7. Brattsand R & Seroos O (1994) Glucocorticosteroids. In Drugs and the Lung, ed Page, CP, Metzger WJ, Raven Press, New York, 101
  8. Altounyan REC (1980) Review of the clinical activity and mode of action of sodium chromoglycate. Clin Allergy 10, 481
  9. Brittain RT, Dean, CM, Jack, D. (1976) Sympathomimetic bronchodilator drugs. Phamacol Ther 2, 423
  10. Brittain RT, Dean, CM, Jack, D. (1976) Sympathomimetic bronchodilator drugs. Phamacol Ther 2, 423
  11. Spina D (1994) ß2 agonists. In Drugs and the Lung, ed Page, CP, Metzger WJ, Raven Press, New York, 1
  12. Jack D (1991) The 1990 Lilly Prize Lecture. A way of looking at agonism and antagonism: lessons from salbutamol, salmeterol and other beta-adrenoceptor agonists. Br J Clin Pharmacol 31 (5), 501
  13. Lockey RF, DuBuske LM, Friedman B, Petrocella V, Cox F, Rickard K (1999) Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes. Chest 115 (3), 666
  14. Brocklehurst WE (1960) The release of histamine and formation of a slow-reacting substance (SRS-A) during anaphylactic shock. J Physiol 151, 416
  15. Morris HR, Piper PJ, Taylor GW, Tippins JR (1979) Comparative studies on immunologically and non-immunologically produced slow-reacting substances from man, guinea-pig and rat. Br J Pharmacol 67 (2), 179
  16. Murphy RC, Hammarstrom S, Samuelsson B (1979) Leukotriene C: a slow-reacting substance from murine mastocytoma cells. Proc Nat Acad Sci USA 76 (9), 4275
  17. Jones TR, Labelle M, Belley M, Champion E, Charette L, Evans J, Ford-Hutchinson AW, Gauthier JY, Lord A, Masson P et al (1995) Pharmacology of montelukast sodium (Singulair), a potent and selective leukotriene D4 receptor antagonist. Can J Physiol Pharmacol 73 (2), 191
  18. Saban R, Haak-Frendscho M, Zine M, Ridgway J, Gorman C, Presta LG, Bjorling D, Saban M, Jardieu P (1994) Human FcERI-IgG and humanized anti-IgE monoclonal antibody MaE11 block passive sensitization of human and rhesus monkey lung. J Allergy Clin Immunol 94 (5), 836
  19. Holgate S, Casale T, Wenzel S, Bousquet J, Deniz Y, Reisner C (2005) The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation. J Allergy Clin Immunol 115 (3), 459
  20. British Thoracic Society (1993) Guidelines for the management of asthma. Thorax, 48, S1

Related links

 http://www.asthma.org.uk/

http://www.who.int/respiratory/asthma/en/



Last edited: 4 March 2021 15:02

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