Diagnosis and management of asthma
Recognition of asthma is not always straightforward
. It isoften missed in children who present with episodes ofcough, wheeze and dyspnoea. Such 'wheezy bronchitis' inchildhood is almost always asthma. The differential diagnosisof chronic asthma includes 'asthmatic' bronchitis,left heart failure, centrally obstructing tumour or foreignbody, and recurrent pulmonary emboli.
Asthma whichrepeatedly fails to respond symptomatically, or in terms oflung function improvement, to inhaled (3-agonists shouldalways cause the diagnosis to be reconsidered. It maybe difficult or impossible to distinguish late-onset asthmafrom chronic obstructive bronchitis in the elderly smoker.Many of them respond well to bronchodilators andhave a better prognosis than patients with fixed airwaysobstruction.Supervision of chronic asthma is as important as in anyserious chronic condition.
Some hospitals run a very effective'open-door' policy for asthmatics, allowing them toobtain immediate specialist advice whenever their asthmais severe.Education about the nature of the disease, the use ofdrugs and delivery systems, the avoidance of allergens andthe recognition of deteriorating asthma are all important.Asthma can seldom be 'cured'. Long-term therapy isusually required, for prophylaxis or control, and it iscritically important that this simple truth is appreciatedby both the patient and the physician.
Leukotriene antagonists
Leukotrienes are formed by the action of 5-lipoxygenaseand 5-lipoxygenase activating protein (FLAP) on arachidonicacid to form leukotriene A4 (LTA4) which is in turnmetabolized to leukotriene B4 or the cysteinyl leukotrieneC4, leukotriene D4 and leukotriene E4 (LTC4,LTD4, LTE4). Leukotriene B4 is a powerful chemotacticagent, whereas the cysteinyl leukotrienes LTC4, LTD4and LTE4 cause bronchoconstriction, increase mucoussecretion, airway wall oedema, eosinophilia and increasebronchial hyperresponsiveness.
These actions are of interestin the pathogenesis of chronic bronchitis and asthma;in particular, leukotriene B4 inhibition might reduceairway inflammation in chronic bronchitis and thesestudies are being pursued. However it was the role of thecysteinyl leukotrienes that generated most pharmacologicalinterest and there are now specific cysteinyl leukotrienereceptor antagonists such as montelukast, zafirlukast andpranlukast available for clinical use in asthma.
There are data to show that they give good control of symptoms,inhibit exercise induced asthma, and are safe when givenby the oral route. Additive effects to inhaled corticosteroidshave also been demonstrated.
Methyl xanthine derivatives (aminophyllineand theophylline)
Oral use is preferred in routine treatment, and intravenoususe for acute asthma. Divided doses of slow-releasetheophyllines are effective and safe bronchodilators andthey have prophylactic anti-inflammatory activity. These sustained-release formulations are useful when given atnight for the prevention of nocturnal asthma and 'morningtightness'. Although 'therapeutic' serum theophyllinelevels of 10-20 mg/L have been targeted in the past, it islikely that levels as low as 3-5 mg/L have useful antiinflammatoryactions.
If excessive doses are given, or occasionallyeven when blood levels are in the therapeuticrange, side-effects may occur. These include nausea,abdominal pain, headache, tremor, insomnia and palpitations,convulsions and cardiac arrhythmias. The doseadministered should be reduced in elderly patients, thosewith liver disease, and those taking other drugs thatincrease theophylline blood levels (e.g. erythromycin).
Anticholinergics
Anticholinergic agents have proved to be of some value,particularly in older patients with late-onset asthmaor 'asthmatic bronchitis'. Atropine can be delivered byinhalation in its methonitrate form from a nebulizer,although it is more convenient to administer the anticholinergics,ipratropium and oxitropium, as a meteredmetereddoseaerosol. For patients optimally treated with inhaledpYagonists the additional benefit of anticholinergic drugsis seldom important.
Disodium cromoglycate
It has been suggested that cromoglycate acts by 'stabilizing'the mast cell and preventing mediator release.However, modification of neural mechanisms may be equally important. Therapy is only effective when used ona regular prophylactic basis, and it has no intrinsicbronchodilator activity. Younger asthmatics tend to benefit most from its regular use, and it can also be used to 'block'exercise-induced asthma when administered about 20 minutes before planned exertion. Useful nasal andophthalmic preparations are available for the treatment of hay fever. The drug has no serious side-effects.
Corticosteroids
Corticosteroids, probably by their anti-inflammatoryaction, are the most powerful drugs available for the treatmentof asthma. Attitudes towards, and use of, Corticosteroidsfor the long-term management of asthma havebeen dramatically changed by the introduction of powerful,topically active fluorinated Corticosteroids for use bythe inhaled route. Beclomethasone diproprionate, budesonideand fluticasone are most often prescribed. Theyenable asthmatics to be treated with low-dose inhaled corticosteroids,which are not absorbed in sufficient quantitiesto cause adrenal suppression or iatrogenic Cushing's syndrome,and are highly effective when used on a regularbasis in the prophylaxis of asthma. Inhaled corticosteroidcan also be delivered via a nebulizer.
However, high dosesfor prolonged periods can cause side-effects, includingosteoporosis. In some patients inhaled Corticosteroids predisposeto oral Candida infection, but this can usually beeasily controlled.If long-term oral Corticosteroids are essential for thecontrol of asthma, patients should also be on maximumdoses of inhaled Corticosteroids, thereby permitting theoral prednisolone dosage to be reduced by as much as10 mg daily.
Inhaler therapy
Many different inhaler devices are available. They includemetered-dose inhalers (MDI), which traditionally usedCFCs as a propellant, but which now, for environmentalreasons, are being switched to CFC-free inhalers, usingHFA (hydrofluoroalkane) carriers. MDI inhalers may beused with 'spacer' devices to facilitate use and improveairway deposition of the drugs. Breath-activated devicesare useful aids to coordination. Many patients now use drypowder inhalers, which have the twin advantages of easeof use and being environmentally friendly.
Nebulizer therapy
Nebulizers can deliver pYagonists, anticholinergic drugsand, occasionally, Corticosteroids to the airways. They areincreasingly used at home by patients with chronic airwaysobstruction, but in view of the large doses of drug used(particularly pVagonists), such treatment requires carefulassessment and supervision. It is important to documentthat nebulized bronchodilators confer a genuine advantageover maximal treatment with metered-dose inhalers.
Diagnosis and management of asthma
By: Dr Izharul Hasan
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