Background
Bronchial Asthma is a chronic inflammatory disorder of the respiratory tract which is characterized by chronic inflammation associated with hyper-sensitivity of the airways which results in recurrent episodes of dyspnoea, wheezing, cough and chest tightness. Various treatment modalities used in managing bronchial asthma include use of bronchodilators like β- adrenoreceptor and anticholinergic drugs or less selective adrenergic receptor agonists, Leukotriene receptor antagonists, mast cell stabilizers, Inhaled or oral corticosteroids, monoclonal antibodies, bronchial thermoplasty and Macrolide Antibiotics.
Methodology
PubMed and MeSH databases where searched for the relevant review and research articles and analysed for their outcomes to gain a clearer understanding of these modalities.
Result
A clearer understanding of the working and effectiveness of the use of Bronchodilators in Asthma is gained with appropriate guidelines and recommendations for their uses in different scenarios.
Conclusion
A much clearer understanding of the uses of bronchodilators is gained which helps in supporting the theory that their use can be helpful in supplementing the treatment and prophylaxis of Bronchial Asthma. Bronchodilators clearly have a role to play in the prophylaxis of Bronchial Asthma. Studies depict and give support to the idea that Bronchodilators are effective as an individual therapy and also in combination therapy with inhaled corticosteroids and other pharmacological modalities. Going forward more targeted study is required for bronchodilators working and benefits for gaining a clearer consensus which would help in better incorporation of these modalities in the management of Bronchial Asthma.
Introduction
Overview
Bronchial asthma a chronic inflammatory disorder of the airway is characterised by hyper-responsiveness of the airways on exposure to various factors like bacterial or viral microorganisms, allergens or other environmental or genetic factors. It may occur as recurrent episodes associated with breathlessness, cough, wheezing and chest tightness. These incidents of the disease are primarily associated with extensive but variable obstruction of the airflow in the lungs which is either reversible instantaneously or through treatment. Asthma characteristically displays diurnal pattern with symptoms and lung function being worst in the early morning particularly when poorly controlled. The symptoms like cough and wheeze may disturb the sleep. Patients with mild intermittent asthma are generally asymptomatic between exacerbations whereas patients with persistent asthma complain of ongoing breathlessness or wheeze which may be variable, with symptoms fluctuating over the course of one day, or day to day or from month to month.
Cough may present as a dominant symptom in few patients and lack of breathlessness and wheezing may lead to a delay in the diagnosis of the disease. Asthma may be mistaken commonly for cold or persistent chest infection. The development and the course of asthma and its response to various treatments is influenced by the genetic and various environmental factors like potential indoor and outdoor allergen, microbial exposure, diet, breast feeding, tobacco smoke, air pollution and obesity. Asthma being a chronic condition is controlled with appropriate treatment in majority of patients. The goal of the treatment should be to obtain and maintain complete control but the aims may be adjusted according to the circumstances and the patient. The prognosis in cases of bronchial asthma is good, especially in mild disease cases amongst children. Poor outcomes like deaths in cases of bronchial asthma over the past decades have come down due to better diagnostic facilities, various treatment plans and improved patient care involved in the disease. Moderate to severe disability worldwide is seen in a very few cases. Almost half of the cases of asthma diagnosed specially in childhood don’t have the diagnosis of asthma in the later parts of their life. Airway undergoes remodelling in these patients, but it is certainly not known if these changes are harmful or beneficial in a long run. Early diagnosis and treatment involving a combination therapy of Bronchodilators and corticosteroids is known to prevent the decline in lung function.
Treatment
The pharmacological medications used in treating bronchial asthma can be divided into either ‘controllers’ or ‘relievers’. Controller medicines have an anti-inflammatory actions and involves the use of drugs like inhaled corticosteroids, leukotriene receptor antagonists, mast cell stabilizers or monoclonal antibodies or the long acting bronchodilators to mention a few control the inflammation of the respiratory tract and are basically used as maintenance therapy drugs of the disease. They are administered on a regular basis, even if the patient is in an asymptomatic state of the disease. On the other hand, the reliever medications act by relieving the acute symptoms but do not control respiratory tract inflammation. Hence, they are to be taken on an as and when required basis for instantaneous relief during the periods of symptomatic deterioration. Bronchodilators with rapid onset of action like short acting beta adrenergic agonists are the most favoured reliever.
Bronchodilators are the medications used in the therapy that dilates the bronchi and bronchioles in the lungs thereby reducing the resistance in the respiratory system which leads to increased airflow to the lungs. Bronchodilators are recommended in the treatment of breathing disorders like asthma and COPD. Bronchodilators are usually classified short acting or long acting bronchodilators. Short acting bronchodilator medications provide rapid relief from state of acute bronchoconstriction. Long acting bronchodilators acts by controlling the symptoms and prevent their reappearance and are usually used as the maintenance therapy drugs.
Short-acting β2-adrenergic agonists: These are also known as the rapid-relief or the ‘rescue’ medications which offer early onset of action resulting in time being relief from the symptoms of asthma or exacerbations. They usually start taking effect within 20 minutes or less from the time of administration, and the effects can last up to five to six hours. They are used via an inhaler and are favoured for treating sudden and severe or the new asthma symptoms. When used 15 to 20 minutes in advance of time, these medications also prevent asthma symptoms prompted due to exercise or exposure to cold air. Few short-acting β-agonists, such as salbutamol and albuterol are selective to the β2-adrenergic receptors of the lungs; hence are called β2-adrenergic agonists and can relieve symptoms like bronchospasms without the unwanted cardiac adverse effects of nonselective β-agonists like epinephrine by acting on β2 – receptors.
Long-acting β-adrenergic agonists (LABA): These are generally the long acting β2-adrenergic agonists drug classes which is generally prescribed in cases such as moderate or severe persistent asthma in which is administered as an inhalational form. They are anticipated to decrease the need for shorter-acting β2 agonists such as salbutamol and albuterol as their duration of action lasts approximately about 12 hours as compared to that of the 4 to 6 hours of the short acting β2-adrenergic agonists. With an exception of formoterol all the long-acting β2 agonists are unadvised in the treatments involving acute asthma exacerbations because its onset of action being slow compared to that of drugs such as salbutamol. Long-acting beta-agonists substantially improve pulmonary function, symptoms and quality of life and reduce the use of rescue medications and exacerbation episodes of asthma. Since Long-acting beta-agonists have no effect on controlling the respiratory tract inflammation, their use as a single therapy drug is discouraged in asthma. Long-acting beta-agonists are excellent bronchodilators and lead to wide-ranging symptomatic improvement. Nevertheless, they allow airway inflammation to advance unchecked sub-clinically, and this may lead to poorer long-term outcomes.
Anticholinergics: Anticholinergics are the therapeutic agents that act by blocking in the central and the peripheral nervous system the actions or the effects of the neurotransmitter acetylcholine. They go about acting by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in the nerve cells thereby inhibiting the parasympathetic nerve impulses. The involuntary actions of the smooth muscles in the lungs and many other parts of the body are carried out by the nerve fibres belonging to the parasympathetic system. Depending upon on their specific targets located in the central and peripheral nervous system the anticholinergic drugs are divided into three classes of drugs.
Few examples of anticholinergics include tiotropium and ipratropium bromide. Ipratropium bromide available only as an inhalant is used in the treatment of asthma and belonging to the group of short-acting anticholinergics it acts by improving the lung functioning and thereby results in decreased risks of exacerbations in patients symptomatic with asthma. Although, it does not put an end to an ongoing episode of asthma attack. When used alone it will not have any effects on the asthmatic symptoms and therefore it is typically paired with a short-acting β2-adrenergic agonist for a better desired effects. Even though it is believed to be a relief or rescue medication, it takes about an hour for this drug to start exerting its effects on the lungs. Therefore, it plays a secondary role in management of acute asthma. The most common side effect of this drug is the dryness of throat. When used in combination with short-acting β2-adrenergic agonists these anticholinergic medications have shown to decrease hospital admissions among children and adults for treatment of acute asthma exacerbation episodes.
Tiotropium a long-acting anti-muscarinic agent is predominantly used as a first line drug in treatment of patients with COPD. Tiotropium is currently used as an additional agent for treating patients inadequately controlled with Inhaled corticosteroid or Inhaled corticosteroid–Long acting beta adrenergic agonist combination therapy. Clinically the advantage of adding tiotropium to an Inhaled corticosteroid therapy in patients with poorly controlled asthma has shown to be similar to that of adding of a Long acting bronchodilators. Nonetheless, when added to an ongoing therapy with an Inhaled corticosteroid–Long acting beta adrenergic combination therapy, tiotropium leads to a better functioning of the pulmonary system and also a fewer episodes of exacerbation. Therefore, tiotropium can be used as an additional drug for poorly controlled patients despite moderate to high dose Inhaled corticosteroid–Long acting beta adrenergic agonist combination therapy.
Approach in treating of Bronchial Asthma:
Asthma maybe managed using a single drug therapy or via multi drug therapy. Conventionally inhaled corticosteroids are used along with long acting beta adrenergic agonists with short acting beta adrenergic agonists used as a rescue drug or a reliever drug. New management strategy known as SMART treatment involves usage of long acting beta adrenergic drug along with inhaled corticosteroid with an inhaled corticosteroid or formoterol being used as a rescuer or a reliever drug.
The approach contemplated in treating of patients with stable or well controlled asthma is based on the severity of the presentation of symptoms along with their response to already advised medications.
Step I: Needed reliever- This is the lowest step in asthma treatment and is beneficial only for those patients who encounter intermittent symptoms usually less than twice a month, and are asymptomatic in between these episodes. They can be managed only with a reliever drugs taken as and when required. A short acting beta adrenergic agonists like salbutamol are the agents of choice for managing these patients.
Step II: Single controller medications- This is often used in patients having recurrent or consistent episodes of the symptoms ranging usually between from twice a month or twice a week are not advised to be managed using only reliever medications. They should use a controller drug along with a reliever drug on an as and when required basis. Low doses of Inhaled Corticosteroid are favoured as the controller medication, although Leukotriene-1 receptor antagonist monotherapy can be prescribed as an alternative to those who are unable to use Inhaled corticosteroid. Single drug therapy using either methylxanthines or Long acting beta agonists is opposed.
Step III: Dual controller medications- If asthma continues to be poorly controlled despite the usage of low doses of Inhaled corticosteroids as mentioned in the above step 2 or if symptoms continue to occur more than twice a week or during night then the therapy needs to be amplified. The preferred approach is adding a Long acting beta adrenergic agonist to a low dose Inhaled corticosteroid which the patient is already using. Another possibility includes increasing the Inhaled corticosteroid dose to double or merging a Leukotriene-1 receptor antagonists or theophylline with an Inhaled corticosteroid. However, these possibilities are not as efficient as adding a Long acting beta adrenergic agonists to Inhaled corticosteroid. Single inhaler therapy approach can also be used, using a formoterol (long-acting β2 agonists) based combinations.
Step IV: Two or more controller medications- It is a complex management step in treating patients with uncontrolled asthma despite using the step III therapy, and represents all the orderly increases# in drugs before a patient is deemed as a candidate for oral corticosteroid therapy or various other drug therapies. The favoured treatment option for these patients is continue using an Inhaled corticosteroid–Long acting beta adrenergic agonist combination and increasing the dose of the Inhaled corticosteroid to medium and high doses subsequently. High doses of Inhaled corticosteroid can be used for 3 months, and then decreased if there is no clinical progress. If a patient was not using a Long acting beta adrenergic agonist at step III then it must be supplemented before any further modifications in the management. If the patient remains poorly controlled in spite of using a moderate-to high dose Inhaled corticosteroid–Long acting beta adrenergic agonist combination, tiotropium or Leukotirene-1 receptor antagonist and/or methylxanthines can be added. This therapy is highly customized, based on inclinations of the doctor and patients along with the availability, tolerability and cost of the medications.
Step V: add-on medications- Patients who do not respond to all of the above treatment approaches, a trial of oral corticosteroids or other specific treatment modalities like monoclonal antibodies such as omalizumab can be contemplated. Even though no clinical trial has precisely reviewed the role oral corticosteroids play in patients having difficult-to-control asthma, they can be contemplated in such a situation at the lowest possible dose and for the shortest amount of time required to achieve asthma control due to their many adverse effects.
Conclusion
Bronchodilators is a useful option for both management and prophylaxis of Bronchial asthma but are underused at this moment of time. The studies that have been done so far do shed light on their efficacy in preventing further episodes of exacerbation of the disease. Bronchodilator’s have been shown to be more effective in combination therapy with inhaled corticosteroids and other pharmacological modalities Guidelines do exist recommending their use but differ from each other. Though the results of present studies show significant evidence of their efficacy, further studies should be conducted to obtain a clearer insight of their prophylactic efficiency and a model needs to be formulated to ensure their implementation.
