Asthma

According to Kumar(2009), asthma is a common chronic disorder of the airways of which the pathophysiology is multifaceted and still not completely understood. King and Moores(2008) explain that asthma is probably not a single disease, but rather multiple separate syndromes that overlap. These involve a complex interaction of the following components:
• Airway inflammation
• Intermittent airflow obstruction
• Bronchial hyperresponsiveness -compared to normal, the smooth muscle in an asthmatic bronchiole is hyperreactive and constricts in response to a variety of stimuli that would not normally trigger bronchoconstriction.
Barnes (2003) explains that atopy, the genetic predisposition for the development of an immunoglobulin E (IgE)-mediated response to common aeroallergens, is the strongest identifiable predisposing factor for developing asthma. IgE is a type of antibody that binds to allergens and triggers the release of substances from mast cells that can cause inflammation. The surfaces of mast cells contain special receptors for binding IgE and when activated release an array of chemicals such as histamine, tryptase, cytokines, chemokines and growth factors that contribute to all stages of asthma including the late asthmatic response and more chronic aspects of asthma. NAEPP(2007) add that other important factors are T helper lymphocytes (also known as CD4+ T cells because they express the CD4 protein on their surface) which show evidence of activation and the release of their cytokines plays a key part in the migration and activation of mast cells (IL-3, IL-4, IL-9 and IL-13) and eosinophils (IL-3, IL-5, GM-CSF). Interleukins (abbreviated IL) are a group of cytokines (cell signalling proteins) which activate and recruit further immune cells and lead to underlying airway inflammation

Diagram from NAEPP (2007)
According to Waugh (2010), the mucous membrane and muscle layers of the bronchi become thickened and the mucous glands enlarge, reducing airflow in the lower respiratory tract. The walls swell and thicken with inflammatory exudate and there is an influx of inflammatory cells, especially eosinophils.
Busse and Sedgwick(1992) explain that eosinophils are granular leukocytes, a type of white blood cells that are one of the immune system components which are found in large numbers in the bronchial wall and secretions of asthmatics. Filipović and Cekić(2001) add that eosinophils are a rich source of cytotoxic proteins, lipid mediators, oxygen free radicals and cytokines which promote obstruction, injury, and bronchial hyperresponsivenes and thus causing airway inflammation.

Cross-section of the airway wall (Waugh 2010)

Monteseirín(2009) recognises the importance of eosinophils he claims that evidence supports an important role for neutrophils in asthma. Neutrophils are another granular leukocytes that play an essential role in the immune system, acting as the first line of defence against bacterial and fungal infections in asthma. Neutrophils are the first cells recruited to the site of the allergic reaction and are an important factor in asthma especially in sudden-onset, fatal asthma exacerbations
Jeffrey(2004) states that in chronic asthma, inflammation may be accompanied in some patients by irreversible airflow limitation as a result of airway wall remodelling that may involve alterations in structural cells and tissues in the large and small airways. These structural changes lead to hypertrophy of smooth muscle which narrows the airways and increase reactivity to allergens, infections and irritants.
Common Triggers of asthma (compiled from GINA(2011) unless otherwise noted)
Allergens:
• Seasonal allergens such as pollens
• Indoor allergens – moulds, faeces of house dust mite or cockroaches
• Pets or animals with fur
Infections(viral respiratory illness)
• Rhinovirus
• Influenza
• Respiratory syncytial virus (RSV)
• Parainfluenza
• Human metapneumovirus
• Sinus infections

Irritants:
• Cigarette smoke
• Coal and wood smoke
• Perfumes
• Cleaning products
• Aerosol chemicals
• Exhaust fumes especially diesel particulates (Brostoff and Gamlin (1999)
• Air pollution such as high ozone levels and sulphur dioxide (Brostoff and Gamlin (1999)
• Weather changes
• Exercise
• Strong emotional expressions
• Drugs such as aspirin and beta-blockers. NSIDs such as ibuprofen
Diet: (Stephenson 2011)
• Eggs
• Milk
• Wheat
• Fish
Paul’s recent wheezing attack could have been initially brought on by being exposed to working in very dusty environment, especially the mouldy wooden rafters. The fact that his body was also infected by a cold would have contributed in weakening his resistance. The cold weather and fumes from the nearby lorries were also triggers. The stress he has being experiencing and lack of sleep will also have weakened Paul’s immune system and reduced his ability to fight off illness.

b) Signs and symptoms
GINA(2011) reports that coughing and wheezing are the most common symptoms of childhood asthma, particularly a nocturnal cough, but breathlessness, chest tightness or pressure, and chest pain also are reported. GINA point out that although wheezing is the hallmark of asthma, a cough is often sole presenting complaint and that the most common cause of chronic cough in children older than 3 years is asthma.
BTS/SIGN(2012) explain that clinical features that increase the probability that episodic respiratory symptoms are due to asthma, both in children and adults, would be when a patient presents with more than one of the following symptoms: wheeze, cough, difficulty breathing, chest tightness – particularly if these symptoms
• are frequent and recurrent
• are worse at night and in the early morning
• occur in response to, or are worse after, exercise or other triggers, such as exposure to pets, cold or damp air, or with emotions or laughter
• occur apart from colds
• In adults: symptoms after taking aspirin or beta blockers
Probability of asthma in children and adults increases if there is:
• Personal history of atopic disorder
• Family history of atopic disorder and/or asthma
• Widespread wheeze heard on auscultation. The wheezing is a high-pitched, expiratory sound produced when air forced through narrow airways and tends to be polyphonic (varied in pitch)
BTS/SIGN(2012 warn that many of the signs and symptoms of asthma present in other illnesses and so asthma can be easily confused with other diseases such as cystic fibrosis, bronchiectasis and protracted bronchitis among others.
Paul’s symptoms
Martin and Banks-Schlegel(1998) explain that there are several reasons why asthma can get worse in the night such as an increased exposure to allergens eg house dust mite; cooling of the airways; being in a reclining position leading to accumulation of secretions in the airways (drainage from sinuses or postnasal drip). (Barnes et al(1980) have traced diurnal changes in the plasma levels of cortisol, epinephrine and histamine which might cause inflammation and lead to bronchospasm. They also point out that there is a circadian pattern in lung function both in asthmatics and non-asthmatics, with best function occurring at approximately 4 PM and the worst at around 4 AM. In non-asthmatics the peak-to-trough swings in peak expiratory flow rate are only 5 to 8% compared to a variation which can reach 50% or more in asthmatics.

Signs and symptoms giving cause for concern
NHS website details signs of a severe asthma attack:
• The reliever inhaler does not help symptoms at all.
• The symptoms of wheezing, coughing, tight chest are severe and constant.
• Patient is struggling for breath or too breathless to speak.
• Patient’s pulse is racing.
• Patient feels agitated or restless.
• Patient’s lips or fingernails look blue.

Warning Features (compiled from Stephenson(2011) unless otherwise noted.
1) Any new onset of difficulty breathing such as increased respiratory rate, nocturnal wheeze or noisy breathing in a child (less than 8 years old). In the case of mild breathlessness it may be helpful to refer primarily to exclude or confirm a diagnosis of asthma.
In people with pre-existing lung disease such as asthma:
2) Features of progressive upper respiratory infection (cough and fever or new production of yellow/green phlegm each persisting for more than 3 days).

3) Features of progression of infection to the lower respiratory tract. Moderate to severe breathlessness with malaise suggests the involvement of the bronchi or lower air passages. Usually accompanied by cough and fever, but may be the only symptom of an infection in the elderly or immunocompromised. Breathlessness is a feature of lower respiratory tract narrowing or infection and should be taken seriously, especially in the elderly immunocompromised and those with pre-existing lung disease (such as asthma. Respiratory rate of more than 30 respirations per minute is a marker of significant breathlessness.

4) Features of severe asthma: BTS/SIGN(2012) in their ‘Levels of severity of acute asthma exacerbations table’, they categorise acute severe asthma to be any one of:
– PEF 33-50% best or predicted
– respiratory rate ≥25/min
– heart rate ≥110/min
– inability to complete sentences in one breath.
Cyanosis is a very serious sign.

5) Progressive swelling of the soft tissues of the face and neck (angio-oedema) and/or urticaria (nettle rash). Angioedema can result from acute allergic reaction and can precede life threatening asthma. Refer urgently if any features of respiratory distress (itchy throat/wheeze).

C) Management
Paul’s breathing rate is 30 breaths per minute and according to the latest guidelines from BTS/SIGN(2012) this would be categorised as acute severe asthma. In their criterias for referral they advise that any patients with features of acute severe or life threatening asthma should be referred to hospital, so I would immediately call an ambulance.
Western Medicine
BTS/SIGN (2012) advocate a stepwise approach where the idea is to balance treatment giving the least amount of medication, but at the same time keeping the symptoms under control and so treatment should be regularly reassessed and moved up/down to the next step to find and maintain the lowest controlling step.
They further break this stepwise management of asthma into 3 categories:
• Adults and adolescents aged over 12
• Children aged 5-12 years
• Children under 5 years
Step 1 is classified as mild intermittent asthma where only intermittent usage is required to relieve symptoms. In all age groups the quickest acting treatment with the fewest side-effects is an inhaled short acting Beta-2 (β2) agonist as required. Longmore et al(2010) explain that β2 adrenoceptor agonists such as Salbutamol relax bronchial smooth muscle.
Step 2 For all ages treatment is to add an inhaled steroid (Longmore et al(2010) mention beclometasone) as well as the β2 agonist. In all cases the lowest appropriate dosage should be used, but general starting dosages are often given. In children a leukotriene receptor agonist should be used if inhaled steroids cannot be used.
Age Initial starting dose Range
Adults and adolescents 400mcg 200 – 800mcg
5-12 years 200mcg 200 – 400mcg
under 5 years Lowest appropriate dose 200 – 400mcg

Step 4 In all but young children add an inhaled long-acting β2 agonist (LABA) (Longmore et al(2010) mention salmeterol) to existing treatment. This step should be carefully monitored :
• If there is a good response LABA should be continued.
• If some or no benefit, but control still inadequate then increase inhaled steroid dose (Adults to 800mcg, Children to 400mcg, per day).
• If no benefit and control is still inadequate after steroid increase then leukotriene receptor antagonist or oral theophylline would be tried.
In young children on inhaled steroids, the addition of a leukotriene receptor antagonist(LRA) would be considered and vice versa.
Children under 2 years would be referred to a respiratory paediatrician which is step 4 for all children under 5.
Step 4 Adults increase inhaled steroid to 2000mcg, children to 800mcg. Adults add 4th drug, LRA, oral theophylline or β2 agonist tablet.
Step 5 Adults and children add daily steroid tablet to other medication. Refer children to a respiratory paediatrician and adults to specialist care.
Lifestyle and other advice
BTS/SIGN (2012) advises that people who smoke when they have asthma should be encouraged to stop. Parents with asthma should be advised about the dangers of smoking to themselves and their children with asthma and offered appropriate support to stop smoking.
If an asthma patient is obese then weight reduction will improve lung function, symptoms, morbidity and health status and so BTS/SIGN(2012) recommend weight reduction in obese patients with asthma to promote general health and to improve asthma control. Other dietary advice is not so clear cut – reducing salt intake, supplementation with omega n-3 fatty acids such as fish oils, probiotics, vitamin C, vitamin E or selenium shows no clinical benefits in people with asthma.
Gøtzsche and Johansen(2010) in their Cochrane review conclude that ‘Chemical and physical methods aimed at reducing exposure to house dust mite allergens cannot be recommended’ as no real evidence was found that this helped.
Peak Flow
GINA (2011) describes a peak flow meter as a portable device that measures air flow, or peak expiratory flow rate (PEFR). It monitors a person’s ability to breathe out air, measuring the airflow through the bronchi and thus the degree of obstruction in the airways. Ideally the peak flow should be in the normal range for the person’s height and sex, and also should show very little variability at different times of the day.
It can be used to:
• Determine the severity of asthma
• Check the response to treatment during an acute asthma episode
• Monitor progress in treatment of chronic asthma and provide information for any changes in therapy
• Detect worsening lung function and avoid a possible serious asthma flare-up

Diagram from CMS Disk(2010)
The following instructions come from a Mini-Wright Peak flow meter instruction leaflet.
• Insert a clean mouthpiece into the meter, if not already fitted.
• Ensure the pointer is set at zero (L/MIN position)
• Hold the Peak Flow Meter so that your fingers are clear of the scale and slot.
• Do not obstruct the holes at the end of the Peak Flow Meter.
• Stand up if possible.
• Take a deep breath, place the Peak Flow Meter in the mouth and hold horizontally, closing the lips around the mouthpiece, then blow as hard and as fast as you can.
• Do not cough, spit or let your tongue block the mouthpiece
• Note the number on the scale indicated by the pointer.
• Return the pointer to zero (L/MIN position) and repeat the procedure twice more to obtain three readings.
• Mark the highest of the three readings on your Peak Flow Diary

d) TCM interpretation
According to Zhu and Wang(2011) , long-retained Phlegm is thought to be the main pathogenic factor in asthma, known as xiao-chuan in China. Xiao means wheezing and chuan means breathlessness. Climatic changes, emotional factors, overstrain and diet will provide the latent Phlegm which then ascends with Qi and obstructs the trachea and causes asthma. There can be Cold Phlegm or Phlegm Heat and either can Obstruct the Lungs. Recurrent asthma will result in simultaneously deficiency of the Lungs, Spleen, Kidneys and Heart. The main syndromes for these are Lung-Spleen Qi deficiency, Lung-Kidney Yin deficiency and Heart-Kidney Yang deficiency.
Xiezu (1993) describes Shi type asthma which results from dysfunction of the Lung in descending due to invasion of exogenous Wind-Cold or disturbance of Phlegm-Heat. Xu type asthma is due to either Lung deficiency or Kidney deficiency which fails to perform its function of receiving Qi.
Maciocia(2011) however differentiates between Breathlessness (Chuan), Wheezing(Xiao) and allergic asthma. His first 2 categories have syndromes which agree with classical TCM definitions, but he feels there are gaps in the traditional pathology in relation to allergic asthma and instead of Phlegm in this case, he advocates Wind as being the main pathogenic factor. He says that asthma symptoms manifest with the character of Wind – Wind contracts causing bronchospasm; it may come and go- accounting for the paroxysmal nature of asthma and changes rapidly. It also helps to explain why asthmatics breathe well in between attacks.
In an interesting article Samuels(2000) points out that the well and well-documented phenomenon In Western medicine, nocturnal worsening of asthma is a well-known and well-documented phenomenon of peak flow values being at their lowest at 04:00 am with peak flow values at their highest at 4pm correspond exactly with the middle of the high point and low point of the Lungs two-hour peak period which occurs between 03:00-05:00 am. However on first thought, this idea might seem puzzling. If the peak time for the Lung is between 3 and 5am, shouldn’t asthma symptoms be better? I have not been able to find anything that explain this peculiarity, but on reflection I believe that because the Lungs are already compromised with asthma, they cannot handle the surge of Qi that comes at this time and so instead of being better, they can be actually worse.
Paul’s asthma is worse when he is stressed because as Maciocia(2010) explains emotional stress and strains can weaken the Lung and Spleen with Lung function being obstructed which leads to breathlessness. Spleen Qi is weakened and so does not transform and transport fluids properly leading to Phlegm. Also emotional stress can cause Liver-Yang or Liver-Fire to rise and on rising it can invade the Lung and obstruct the descending of Lung-Qi.

References
Barnes PJ. Pathophysiology of asthma Eur Respir Mon, 2003, 23, 84–113.
BTS/SIGN(2012) – British Thoracic Society. Scottish Intercollegiate Guidelines Network. British guidelines on asthma management. Thorax 2008; Revised January 2012
Brostoff, Prof. J, Gamlin.L,1999 The Complete Guide to Asthma, Bloomsbury Publishing, London
Busse WW, Sedgwick JB. Eosinophils in asthma Ann Allergy. 1992 Mar;68(3):286-90.
CICM (2010), CMS Disk
Filipović,M, Cekić,S The Role Of Eosinophils In Asthma Medicine and Biology Vol.8, No 1, 2001, pp. 6 – 10
GINA Global Initiative for Asthma Report, Global Strategy for Asthma Management and Prevention 2011 – pdf downloaded from http://www.ginasthma.org/guidelines-gina-report-global-strategy-for-asthma.html on 30/6/12
Gøtzsche PC, Johansen HK House dust mite control measures for asthma (Review) The Cochrane Library 2010, Issue 1
Jeffery K. Remodelling and inflammation of bronchi in asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc 2004; 1:176–183
King CS and Moores LK, Clinical Asthma Syndromes and Important Asthma Mimics Respiratory Care May 2008 Vol 53 No 5
Kumar P and Clark M L (2009) Clinical Medicine (Kumar and Clark’s Clinical Medicine). 7th Edition. Spain: Saunders Ltd
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Maciocia, Giovanni (2011) The Practice of Chinese Medicine, 2nd edition reprinted London, Churchill Livingstone
Martin RJ and Banks-Schlegel S, Chronobiology of Asthma, Am. J. Respir. Crit. Care Med. September 1, 1998 vol. 158 no. 3 1002-1007
Monteseirin J. Neutrophils and asthma. J. Investig. Allergol. Clin. Immunol. 2009;19:340–354.
NAEPP – National Asthma Education and Prevention Program, Third Expert Panel on the Diagnosis and Management of Asthma. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda (MD): National Heart, Lung, and Blood Institute (US); 2007 Aug. Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma. Available from: http://www.ncbi.nlm.nih.gov/books/NBK7223/ accessed 27/6/12
http://www.nhs.uk/Conditions/Asthma/Pages/Symptoms.aspx Last reviewed: 20/08/2010 accessed 27/6/12
Samuels N. Chronotherapy in Traditional Chinese Medicine, Am J Chin Med. 2000;28(3-4):419-23
Stephenson, C (2011) The Complementary Therapist’s Guide to Conventional Medicine, 1st Edition, Oxford: Churchill Livingstone
Waugh, A, (2010). Ross and Wilson Anatomy and Physiology in Health and Illness, 11th Edition. Churchill Livingstone.
Xiezu, B (1993) Essentials of Chinese Acupuncture, Beijing,Foreign Languages Press; 2nd edition
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