B. Pharm Projects and Review Articles Free download: ASTHMA, A COMPREHENSIVE OUTLOOK

Tuesday, April 21, 2009

ASTHMA, A COMPREHENSIVE OUTLOOK

Abey T Thomas, R. Raju

National College of Pharmacy, Manassery, Calicut

Cite this: Abey T Thomas, R. Raj, "Asthma, a comprehensive outlook", B. Pharm Projects and Review Articles, Vol. 1, pp. 43-79, 2006. (http://farmacists.blogspot.in/)

INTRODUCTION:

Our current understanding of the pathophysiology of asthma and the availability of potent, effective therapies mean that asthma can be well controlled. However, to achieve this goal, optimal therapy must be prescribed and the patient must be taught how and when to use it. Pharmacists, as part of the health care team, help improve the pharmacologic management of asthma by teaching patients about their medications, how to use them, and the importance of using them as prescribed. Alerting physicians to suspected problems, such as under using anti-inflammatory therapy or overusing inhaled bronchodilators, will provide an opportunity for the physician to consider changes in a patient's management plan when appropriate. Acting in these educational and information-sharing roles, pharmacists contribute to improving the control of asthma and enabling patients to live full, active, and productive lives.

DEFINITION:

Asthma is a chronic, episodic disease of the airways, and it is best viewed as a syndrome. In 1997, the National Heart, Lung, and Blood Institute (NHLBI) included the following features as integral to the definition of asthma, recurrent episodes of respiratory symptoms; variable airflow obstruction that is often reversible, either spontaneously or with treatment; presence of airway hyper reactivity; and, importantly, chronic airway inflammation in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. All of these features need not be present in any given asthmatic patient. Although the absolute "minimum criteria" to establish a diagnosis of asthma is not known or widely agreed upon, the presence of airway hyper reactivity is a common finding in patients with current symptoms and active asthma.¹⁴

W H O Definition

Asthma is a chronic disease characterized by recurrent attacks of breathlessness and wheezing, which vary in severity and frequency from person to person. Symptoms may occur several times in a day or week in affected individuals, and for some people become worse during physical activity or at night. During an asthma attack, the lining of the bronchial tubes swell, causing the airways to narrow and reducing the flow of air into and out of the lungs. Recurrent asthma symptoms frequently cause sleeplessness, daytime fatigue, reduced activity levels and school and work absenteeism. Asthma has a relatively low fatality rate compared to other chronic diseases.²

EPIDEMOLOGY:

· According to World Health Organization (WHO) estimates, 300 million people suffer from asthma and 255 000 people died of asthma in 2005. ²

· Asthma is currently a worldwide problem, with increasing prevalence in both children and adults. Total prevalence is estimated to be 7.2% of the world's population (6% in adults, 10% in children).
⁴

· An hospital based study on 20,000 children under the age of 18 years from 1979,1984,1989,1994 and 1999 in the city of Bangalore showed a prevalence of 9%, 10.5%, 18.5%, 24.5% and 29.5% respectively. The increased prevalence correlated well with demographic changes of the city. Further to the hospital study, a school survey in 12 schools on 6550 children in the age group of 6 to 15 years was undertaken for prevalence of asthma and children were categorized into three groups depending upon the geographical situation of the school in relation to vehicular traffic and the socioeconomic group of children. Group I-Children from schools of heavy traffic area showed prevalence of 19.34%, Group II-Children from heavy traffic region and low socioeconomic population had 31.14% and Group III-Children from low traffic area school had 11.15% respectively. (P: I & II; II & III <0.001). A continuation of study in rural areas showed 5.7% in children of 6-15 years. The persistent asthma also showed an increase from 20% to 27.5% and persistent severe asthma 4% to 6.5% between 1994-99. ⁷

· Asthma is found in all countries but it is more prevalent in industrialized countries than in low-income countries. A recent survey estimates that in New Zealand, 25% of children from 13 to 14 years of age have asthma symptoms, 16% in the USA, 13% in Europe and Latin America and 10% in African cities.¹¹

· The total number of people with asthma, however, is already higher in the developing world than in the industrialized countries. There are approximately 3 million asthmatics in Japan and in France, compared to an estimated more than 15 million in India and over 30 million in Africa.¹¹

MORTALITY:

Asthma was not generally considered to be a fatal illness and this was the teaching in medical schools well into the present century. It was not until the rise in deaths from asthma in the 1960s that attitudes began to change.

The increasing death rate during the 1980s has been particularly alarming. As shown in the following figure.⁴

Fig No 1: Rising Asthma Deaths in the World, 1980-1994

MORBIDITY:

About 60% of all asthmatics visit their physician at least once a year regarding their condition. Office visits doubled from 1975-1994 (see table below). Emergency department (ED) visits and hospitalizations are also increasing, with 466,000 hospitalizations in 1993 and 1.9 million ED visits in 1995.

Table No 1:Office Visits (1980-1994) and ED Visits (1992-1995) and Hospitalizations (1980-1994) Due to Asthma
⁴

	Office Visits		ED Visits		Hospitalizations
Age (years)	1994	Increase from 1980 (%)	1995	Increase from 1992* (%)	1994	Increase from 1980 (%)
0-4	1,024,000	98	248,000	-14	97,000	73
5-14	2,004,000	23	322,000	11	67,000	20
15-34	1,876,000	65	566,000	29	78,000	15
35-64	3,982,000	164	630,000	75	139,000	9
>65	1,488,000	119	101,000	13	85,000	8
Total	10,374,000	90	1,867,000	27	466,000	21

*Data unavailable for 1980.

The effect asthma has on an individual's quality of life and the extent to which it may restrict daily activities is often overlooked. Yet, it is an important part of understanding this condition and the benefits that effective treatment can bring. Results from a 1998 survey conducted by the American Lung Association (ALA) highlight these quality-of-life issues.

® Asthma significantly disrupts lives.

87% of parents and 84% of adult patients report that asthma has had a negative impact on their or their child's lives.
23% of adult patients and 36% of parents of asthmatics missed work during the past year because of their asthma (ALA survey).

® Asthma is not under control.

83% of parents and 75% of adult patients reported unscheduled visits to the physician during 1998 because of asthma attacks.

® Asthmatics adapt their lifestyle to accommodate their asthma. And they do not
lead a "normal" life.

61% of all asthma patients and 73% of children report that they limit sports participation or exercise, find it difficult to sleep through the night, and make unplanned trips to the physician or ED.

® Families, with members who have asthma, adapt to accommodate asthma and
lack a "normal" family life.

70% of parents and patients agree that the whole family is affected by one member's asthma, and nearly 50% say asthma limits the range of activities the family can do together.

® Many asthmatics do not know the difference between the controller medications
that keeps symptoms from occurring and the reliever medication that can

alleviate an attack

73% of adult patients and 79% or parents of asthmatics actually named a reliever medication when asked to name a controller medication.

® In children:

Asthma is the most common chronic illness and is the highest ranking chronic condition causing hospitalization
Asthma is the primary chronic illness resulting in school absences (1998 ALA survey); asthmatic children have three times the school absences than those without the disease.⁴

ETIOLOGY:

The complete causes of asthma are unknown. Heredity does seem to play a role, as do allergens and environmental factors. According to the latest Expert Panel Report (EPR) in 1997 from the National Heart, Lung, and Blood Institute's National Asthma Education and Prevention Program, "Atopy, the genetic predisposition for the development of an IgE-mediated response to common aeroallergens, is the strongest identifiable predisposing factor for developing asthma."³

There are two categories of asthma: allergic or extrinsic and idiosyncratic or intrinsic. Allergic asthma is a result of an antigen\antibody reaction on mast cells in the respiratory tract. This reaction causes the release of inflammatory mediators from mast cells, which elicit the clinical response associated with an asthma attack. Idiosyncratic asthma is a result of neurological imbalances in the autonomic nervous system (ANS) in which the alpha and beta-adrenergic as well as the cholinergic sites of the ANS are not properly coordinated. Onset of asthma between the ages of 5 to 15 years usually indicates asthma with an allergic basis.³

Studies suggest a genetic basis for airway hyper responsiveness, including linkage to chromosomes 5q and 11q. However, asthma clearly does not result from a single genetic abnormality, but is rather a complex multigenic disease with a strong environmental contribution. For example, allergic potential to inhalant allergens (dust mites, mold spores, cat dander, etc) more commonly is found in asthmatic children as well as asthmatic adults whose asthma began in childhood, compared with adult-onset asthmatics.³

Exposure to environmental allergens can trigger asthma symptoms. Among the most common allergens are microscopic droppings of dust mites and cockroaches, airborne pollens and molds, plants and plant proteins, enzymes, and pet dander (minute scales of hair, feathers, or skin). Exposure to a variety of occupational irritants (e.g., vapors, dust, gases, fumes, tobacco smoke, air pollution) also can worsen or cause asthma. ⁸

Certain medications may trigger asthma symptoms. These include beta-blockers, used to treat high blood pressure, heart disease, and glaucoma (in eye drops). About 5% to 20% of adults with asthma have attacks triggered by sensitivities or allergies to medications such as aspirin, ibuprofen, indomethacin, and naproxen. Others react to sulfites (chemicals commonly used to preserve foods such as tuna, salads, dried apples and raisins, and beverages such as lemon juice, grape juice, and wine). ⁸

Other factors that may contribute to asthma or worsen symptoms include sinus infections, gastro esophageal reflux disease (GERD), pregnancy, menstruation, and even the time of day. Asthma also can be induced by exercise or cold air. ⁸

¹⁶

® Respiratory infection:

Respiratory syncytial virus (RSV), rhinovirus, influenza,parainfluenza, Mycoplasma pneumonia

® Allergens:

Airborne pollens (grass, trees, weeds), house-dust mites, animal danders, cockroaches, fungal spores.

® Environment:

Cold air, fog, ozone, sulfur dioxide, nitrogen dioxide, tobacco smoke, wood smoke.

® Emotions:

Anxiety, stress, laughter.

® Exercise:

Particularly in cold, dry climate

® Drugs/Preservatives:

Aspirin, NSAIDS (Cyclooxygenase inhibitors), sulfites, benzalkonium chloride, Beta-blockers

.® Occupational stimuli:

Bakers (flour dust); farmers (hay mold); spice and enzyme workers; printers (Arabic gum);

Chemical workers (azo dyes, anthraquinone, polyvinyl chloride); plastic, rubber and wood workers; (Formaldehyde, western cedar, dimethylethanolamine, anhydrides)

PATHOPHYSIOLOGY:

Airway inflammation is the primary problem in asthma. An initial event in asthma appears to be the release of inflammatory mediators (e.g., histamine, tryptase, leukotrienes and prostaglandins) triggered by exposure to allergens, irritants, cold air or exercise. The mediators are released from bronchial mast cells, alveolar macrophages, T lymphocytes and epithelial cells. Some mediators directly cause acute bronchoconstriction, termed the "early-phase asthmatic response." The inflammatory mediators also direct the activation of eosinophils and neutrophils, and their migration to the airways, where they cause injury. This so-called "late-phase asthmatic response" results in epithelial damage, airway edema, mucus hyper secretion and hyper responsiveness of bronchial smooth muscle (Figure No 2 ). Varying airflow obstruction leads to recurrent episodes of wheezing, breathlessness, chest tightness and cough.⁶

Figure No 2: . Pathophysiology of asthma. According to the current view, several inflammatory cells interact in a complex manner and release multiple inflammatory mediators that act on various target cells in the airways to produce the characteristic pathophysiology of asthma.

CLASSIFICATION:

Table No 3: National Asthma Education and Prevention Program, USA: ⁶
Classification*	Symptoms	Night symptoms	Lung function
Step 1: mild intermittent asthma	Symptoms occurring twice a week or less No symptoms and normal PEF between exacerbations Brief exacerbations (lasting a few hours to days) with variable intensity	Symptoms occurring no more than twice a month	FEV₁/FVC is 80% or more of predicted PEF variability of less than 20%
Step 2: mild persistent asthma	Symptoms occurring more than twice a week Exacerbations may affect activity	Symptoms occurring more than twice a month	FEV₁/FVC is 80% or more of predicted PEF variability of 20 to 30%
Step 3: moderate persistent asthma	Daily symptoms Daily use of inhaled short-acting beta agonist Exacerbations affect activity Exacerbations occur more than twice a week and may last for days	Symptoms occurring more than once a week	FEV₁/FVC is greater than 60% but less than 80% of predicted PEF variability of greater than 30%
Step 4: severe persistent asthma	Continual symptoms Limited physical activity Frequent exacerbations	Frequent symptoms	FEV₁/FVC is 60% or less of predicted PEF variability of greater than 30%
PEF = peak expiratory flow; FEV₁= forced expiratory volume in one second; FVC = forced vital capacity; FEV₁/FVC% = FEV₁ as percentage of FVC. *--The initial classification is based on the presence of certain clinical features before treatment. The presence of one of the features of severity is sufficient to place a patient in that category. A patient should be assigned to the most severe grade in which any feature occurs. The characteristics noted in this classification are general and may overlap because asthma is highly variable. Furthermore, a patient's classification may change over time.

Mild Intermittent Asthma

Symptoms of cough, wheeze, chest tightness or difficulty breathing less than twice a week
Flare-ups-brief, but intensity may vary
Nighttime symptoms less than twice a month
No symptoms between flare-ups
Lung function test FEV1 equal to or above 80 percent of normal values
Peak flow less than 20 percent variability AM-to-AM or AM-to-PM, day-to-day.

Mild Persistent Asthma

Symptoms of cough, wheeze, chest tightness or difficulty breathing three to six times a week
Flare-ups-may affect activity level
Nighttime symptoms three to four times a month
Lung function test FEV1 equal to or above 80 percent of normal values
Peak flow less than 20 to 30 percent variability.

Moderate Persistent Asthma

Symptoms of cough, wheeze, chest tightness or difficulty breathing daily
Flare-ups-may affect activity level
Nighttime symptoms 5 or more times a month
Lung function test FEV1 above 60 percent but below 80 percent of normal values
Peak flow more than 30 percent variability.

Severe Persistent Asthma

Symptoms of cough, wheeze, chest tightness or difficulty breathing continual
Nighttime symptoms frequently
Lung function test FEV1 less than or equal to 60 percent of normal values
Peak flow more than 30 percent variability.

The level of asthma severity will determine the types of medicine required to get asthma under control.⁵

Another type of classification commonly seen is ¹⁶

1. Chronic asthma
2. Acute severe asthma
3. Allergic asthma
4. Exercise induced asthma
5. Nocturnal asthma

DIAGNOSIS:

A diagnosis of asthma usually is based on the patient's symptoms, medical history, a physical examination, and laboratory tests that measure pulmonary (lung) function. Doctors typically look for signs that the patient's airflow is obstructed and that the obstruction is at least partially reversible. Factors that trigger symptoms may be evident, such as exercise, cold air, and exposure to an allergen; however, the precipitating factors may not be clearly identified.

Evidence of reversible airway obstruction is often detected in the physical examination or by physiologic testing. Physiologic testing generally is recommended to confirm the diagnosis. During an asthma attack, wheezing can be heard by listening to the chest with a stethoscope. The airway obstruction is considered reversible if the wheezing disappears in response to treatment, or when the suspected triggering factor is removed or resolved.

·     Spirometry
·     Peak Expiratory flow
·     Bronchial Provocation
·     Other Tests

·     Spirometry

The most reliable way to determine reversible airway obstruction is with spirometry, a test that measures the amount of air entering and leaving the lungs. This simple test can be performed in the physician's office.

Spirometry uses a measuring device called a spirometer that is connected by a flexible tube to a disposable cardboard mouthpiece. The patient exhales and inhales deeply, then seals his or her lips around the mouthpiece and blows as forcefully and for as long as possible until all the air is exhaled from the lungs.

Ideally, the patient should exhale for at least 6 seconds. The spirometer measures the amount of air exhaled and the length of time it took to exhale it. The amount of air exhaled in the first second, expressed as "FEV1," is measured and compared to the total amount exhaled. If the amount exhaled in 1 second is disproportionately low to the total exhaled, the patient has an obstruction. To test for reversibility, the patient then inhales a bronchodilator (i.e., a drug that widens the airways in the lungs) and the spirometry is repeated. If the values of the test performed after administration of the bronchodilator are significantly better than the prebronchodilator values, the obstruction is considered reversible.

Sometimes a patient with asthma does not demonstrate reversibility after the inhalation of a bronchodilator. In this case, the patient may be treated for a few weeks with anti-inflammatory medications and then returns for another spirometry test. If the post treatment spirometry results are better than the initial results, the obstruction is considered reversible. ⁸

Fig No 3: How to use a spirometer

· Peak Expiratory flow

Because asthma symptoms vary, it is not unusual for a patient with chronic asthma to have normal spirometry. In such cases, peak expiratory flow (PEF) rate monitoring may be used to demonstrate reversible airway obstruction. A peak flow meter is a portable device that can be carried by the patient. It consists of a small tube with a gauge that measures the maximum force with which one can blow air through the tube.

The patient performs the peak flow meter test twice a day for about 2 weeks and records the results for review in a follow up appointment. The first test should be performed after waking in the morning, before taking bronchodilator medications. The patient should perform the peak expiratory flow maneuver 3 times and record the highest measurement. The second test should be done in the afternoon or early evening after taking a bronchodilator. Peak flows vary during the day and the early morning peak is lower than the evening peak. A variability greater than 20% indicates a reversible airway obstruction. ⁸

Fig No 4: Peak Expiratory flow

· Bronchial Provocation

Occasionally, a patient with a suspected asthma-related airway obstruction does not demonstrate obstruction in spirometry or peak flow monitoring. In this circumstance, the diagnosis of airway obstruction may be provided by bronchial provocation.

Bronchial provocation, also known as bronchoprovocation and bronchial challenge, identifies and characterizes hyperresponsive airways by having the patient inhale an aerosolized chemical, called a broncho-spastic agonist that triggers a hyperresponsive reaction. The chemicals most often used are histamine and methacholine.

Patients perform spirometry without inhaling the agent and then inhale increasingly higher doses of the agent. After each incremental dose inhalation, spirometry is performed. Patients who demonstrate a reduction in FEV1 of 20% with a low dose of methacholine or histamine have nonspecific hyperresponsiveness. Although some patients without asthma demonstrate hyperresponsiveness, most patients with a positive reaction have asthma.

The other common bronchoprovocation test is the exercise challenge test, which is used primarily with patients whose asthma is triggered by exercise. The patient performs spirometry and then exercises, usually on a treadmill or exercise cycle. The exercise test should resemble as closely as possible the conditions under which the symptoms are usually triggered. After the patient exercises, spirometry is repeated. This may be done several times, immediately after exercise and periodically, until there is a drop in the FEV1 greater than 20% or until 30 minutes have elapsed.⁸

· Other Tests
Tests may be employed to exclude other diseases and to evaluate conditions that worsen the asthmatic condition. These include the following:

Chest x-rays are often obtained initially to rule out other health conditions.

Allergy testing, either by skin testing or by measuring antibodies in the blood, sometimes is performed to determine if the asthma is allergy induced, and if so, what specific allergens are involved.
X-rays of the sinuses is often done to exclude sinusitis as a factor.

Evaluation for gastroesophageal reflux disease is often performed to evaluate its contribution to the control of asthma.⁸

Table No 4: Diagnosis of Asthma in Children and Adults¹⁴

Episodic symptoms of airflow obstruction
Difficulty breathing
Chest tightness
Cough (worse at night)
Symptoms occurring or worsening at night, awakening the patient
Symptoms occurring or worsening with exercise, viral infections, changes in weather, strong emotions, or menses; or in the presence of animals, dust mites, mold, smoke, pollen, or chemicals
Wheezing
Airflow obstruction at least partially reversible
Diurnal variation in PEF of more than 20 percent over one to two weeks
Increase of at least 12 percent and 200 mL in FEV₁ after bronchodilator use (indicates reversibility)
Reduced FEV₁ and FEV₁/FVC ratio using spirometry (indicates obstruction)

PEF = peak expiratory flow; FEV₁ = forced expiratory volume in one second; FVC = forced vital capacity.

Adapted from National Asthma Education and Prevention Program

Fig No 5:DIAGNOSISALGORITHM¹⁰

Asthma

Symptoms

Symptom and peak flow diary for 14 days

OR spirometry with bronchodilator

Spirometry shows

Reversibility

NO

NO

Diary shows

Symptoms and PEFR

Variability

YES

YES

PEFR and/or
spirometry shows

Airflow obstruction?

Other diagnosis
NO

Review by

respiratory physician

YES

Oral prednisone x 2 weeks
OR

Inhaled corticosteroid x 4 weeks

COPD
Do not use inhaled

corticosteroids routinely

YES

15%/200mls or

Greater improvement

In FEV1 or PEFR?

NO

Smoker?
NO

YES

+ve

Methacholine,

Saline OR histamine

OR exercise

Challenge

-ve

ASTHMA CONFIRMED
Start appropriate

Treatment
BDP

BUD

COPD

FEV1

ICS

LABAs

MDI

PEFR

ABBREVIATIONS

beclomethasone dipropionate

budesonide

Chronic obstructive pulmonary disease

Forced expiratory volume

Inhaled corticosteroids

Long-acting ß2-agonists

Metered dose inhaler

SYMPTOMS:

People with asthma have symptoms when the airways are narrowed (bronchospasm), swollen (inflamed), or filled with mucus. Common symptoms of asthma include:

Coughing, especially at night

Wheezing
Shortness of breath
Chest tightness, pain, or pressure

The symptoms might also vary from one asthma episode to the next, being mild during one asthma episode and severe during another.

Some people with asthma might have extended symptom-free periods, interrupted by periodic asthma episodes, while others have some symptoms every day. In addition, some people with asthma might only have symptoms during exercise, or when they are exposed to allergens or viral respiratory tract infections.

Mild asthma episodes are generally more common. Usually, the airways open up within a few minutes to a few hours. Severe episodes are less common, but last longer and require immediate medical help. It is important to recognize and treat even mild symptoms to help you prevent severe episodes and keep asthma in better control.¹²

Early warning sign

Early warning signs are changes that happen just before or at the very beginning of an asthma episode. These changes start before the well-known symptoms of asthma and are the earliest signs that a person's asthma is worsening.

In general, these signs are not severe enough to stop a person from going about his or her daily activities. By recognizing these signs, one can stop an asthma episode or prevent one from getting worse. Early warning signs include:
¹²

Frequent cough, especially at night
Losing your breath easily or shortness of breath
Feeling very tired or weak when exercising
Wheezing or coughing after exercise
Feeling tired, easily upset, grouchy, or moody
Decreases or changes in a peak expiratory flow
Signs of a cold, upper respiratory infection, or allergies (sneezing, runny nose, cough, congestion, sore throat, and headache)
Trouble sleeping

Symptoms of worsening asthma

If early warning signs and symptoms are not recognized and treated, the asthma episode can progress and symptoms might worsen. As symptoms worsen, one might have more difficulty performing daily activities and sleeping. Symptoms of worsening asthma include:
¹²

A cough that won't go away (day and night)

Wheezing
Tightness in the chest
Shortness of breath
Poor response to medicines (bronchodilators)

Late, severe symptoms

When asthma symptoms become severe, the patient will be unable to perform regular activities. If one has late, severe symptoms, follow the "Red Zone" or emergency instructions in the Asthma Action Plan immediately. These symptoms occur in life-threatening asthma episodes and the patient needs medical help right away. Late, severe symptoms include:
¹²

Severe wheezing (both when breathing in and out)
Coughing that won't stop
Very rapid breathing
Inability to catch your breath
Chest pain or pressure
Tightened neck and chest muscles (retractions)
Difficulty talking
Inability to perform a peak expiratory flow
Feelings of anxiety or panic
Pale, sweaty face
Blue lips or fingernails

COMPLICATIONS:

Those with asthma are at increased risk of developing problems associated with acid reflux, including the development of gastroesophogeal reflux disease. Avoiding acid reflux can be aided by avoiding food or drink for several hours prior to bedtime and sleeping with the head slightly elevated.⁹

MANAGEMENT OF ASTHMA:

Þ NON PHARMACOLOGICAL ^8,13

There is increasing interest in factors, which, if avoided, might facilitate the management of Asthma, reducing the requirement for pharmacotherapy; and which may have the potential to modify fundamental causes of asthma. However, evidence has been difficult to obtain for many approaches and more studies are required.

This section distinguishes:

Þ PRIMARY PROPHYLAXIS: interventions made before there is any

evidence of disease.

Þ SECONDARY PROPHYLAXIS: interventions made after the onset of

disease to reduce its impact

The distinction is made, as factors that induce the disease in the first place are not necessarily the same as those that
incites a pre-existing problem.

Þ PRIMARY PROPHYLAXIS:

Primary prophylaxis is employed before there is any evidence of disease in an attempt to prevent
its onset. A number of potential strategies are discussed below

¨ ALLERGEN AVOIDANCE:

There is a strong correlation between allergic sensitisation to common aeroallergens and the subsequent development of asthma. There is also a strong association between allergen exposure in early life and sensitisation to these allergens, although it has not been possible to demonstrate an association between allergen exposure and the development of asthma.

The majority of allergen avoidance studies focus on dietary manipulation to prevent atopic
eczema and have paid little attention to aeroallergen avoidance. Two trials in progress are
investigating the consequences of introducing house dust mite reduction in early pregnancy, and
are following up the children born to the participating mothers. Although accurate asthma
phenotyping is not possible in infancy, outcomes at one year of age indicate a modest but
significant reduction in wheezing illnesses.

Allergen avoidance after birth has been studied in a number of controlled (but not double blind
trials). There appears to be transient reduction in the prevalence of atopic eczema in the first two years of life but no evidence of sustained benefit in relation to asthma. A number of
epidemiological studies suggest that close contact with a cat or dog in very early infancy reduces
subsequent prevalence of allergy and asthma. This may be a consequence of high allergen exposure
inducing tolerance.

¨
BREAST-FEEDING

A systematic review and meta-analysis involving 8,183 subjects followed for a mean of four
years revealed a significant protective effect of breast-feeding against the development of asthma.
The effect was greatest in children with a family history of atopy. In contrast, a more recent
study in 1,246 patients found that breast-feeding was associated with a reduced risk of infant
wheeze, but also with an increased risk of asthma at six years.

Breast-feeding should be encouraged and its benefits include a protective effect in relation
to early life wheezing.

¨
MODIFIED INFANT MILK FORMULAE

Trials of modified milk formulae using partial and extensive hydrolysates of whey or casein or
soy formulae compared with conventional formulae have not shown any consistent significant
long-term benefits in relation to asthma. Variation in study design, intervention used co-interventions and outcome definition makes meta-analysis problematical.

¨ OTHER DIETARY MODIFICATIONS

Limited epidemiological evidence suggests that fish oil consumption may protect against asthma
in childhood. Trials of lipid supplementation during pregnancy and postnatally to prevent
atopic disease are in progress.

¨ MICROBIAL EXPOSURE

The "hygiene hypothesis" suggests that early exposure to microbial products will switch off
allergic responses preventing allergic diseases such as asthma. Epidemiological studies comparing
large populations who have or have not had such exposures support the hypothesis. A double
blind placebo trial of the probiotic, Lactobacillus CG, reported a reduced incidence of atopic
eczema but no effect on IgE antibody sensitisation. Small sample size and early outcome age
limit the interpretation of this study. In the absence of good quality intervention studies, no
recommendation can be made at present.

¨
IMMUNOTHERAPY AND PRIMARY PREVENTION

Three observational studies, in over 8,000 patients, have shown that immunotherapy in individuals
with a single allergy reduces the numbers subsequently developing new allergies over a three to
four year follow up compared with contemporaneous untreated controls. No double blind
placebo controlled trials of immunotherapy as primary prevention have been conducted, and at
present immunotherapy cannot be recommended for primary prevention. Preliminary results
from an ongoing parallel group study using contemporaneous untreated children as the control
group for pollen immunotherapy in children with allergic rhinitis suggests a lower rate of onset of
asthma in the treated group.

¨
AVOIDING POLLUTANTS

No evidence was found to support a link between exposure to environmental tobacco smoke and
other air pollutants and the induction of atopic asthma.

An early meta-analysis suggested an association between gas cooking and respiratory illness but
this has not been borne out in larger studies

Increased risk of infant wheeze is associated with smoking during pregnancy and maternal postnatal
smoking. Pregnancy smoking affects an infant's airway function, increasing susceptibility to
wheeze. There are many other adverse effects on the young child of such exposures.

Establishing the correct diagnosis is important. Asthma must be distinguished from chronic obstructive pulmonary disease (COPD) and other causes of airway narrowing which have a different pathogenesis and course, and require different treatment strategies. The features that help to differentiate between asthma and COPD are summarised in Asthmatics who smoke may have coexisting COPD. In these cases treatment for asthma is recommended if the asthmatic component is prominent.

¨
PHARMACOTHERAPY

For completeness, this section on the primary prevention of asthma should mention
pharmacological trials of treatments designed to prevent onset of the disease. Children given
ketotifen (206 infants, in two trials) showed significantly less asthma at one and three-year
follow-up compared with those receiving placebo. In the third study, using cetirizine, ¹⁸

Months' treatment had no effect in the intention to treat population but significantly reduced
asthma in children with atopic dermatitis sensitised to either grass pollen or house dust mite.
Cetirizine had additional benefits for atopic dermatitis alone and reduced the frequency of
urticaria.

SECONDARY PROPHYLAXIS

ALLERGEN AVOIDANCE:

Allergen avoidance measures may be helpful in reducing the severity of existing disease. Increasing allergen exposure in sensitised individuals is associated with an increase in asthma symptoms,bronchial reactivity and deterioration in lung function.

ENVIRONMENTAL FACTORS:

SMOKING:

The association between passive smoking and respiratory health has been extensively reviewed. There is a direct causal relationship between parental smoking and lower respiratory illness in children up to three years of age. Infants whose mothers smoke are four times more likely to develop wheezing illnesses in the first year of life.

AIR POLLUTION:

There is evidence that changing from a high particulate sulphur dioxide (coal burning) environment to a low sulphur dioxide/high diesel particulate environment increases the incidence of asthma and atopy. In the UK, asthma is more prevalent in 12-14 year olds in non-metropolitan rather than metropolitan areas. However, many differences between environments might explain the variation in asthma and allergy risk. There is some laboratory evidence that various pollutants can enhance the response of patients with asthma to allergens, but there is no firm. Epidemiological evidence that this has occurred in the UK or elsewhere.¹⁵

Þ
PHARMACOLOGICAL ^{8, 13,17,18,19}

► MANAGEMENT IN ADULTS

·
AIMS OF MANAGEMENT

The aims of asthma management are to:

Avoid causative and trigger factors
- Abolish symptoms and achieve a normal lifestyle
- Restore normal (or best possible) lung function
- Reduce the risk of severe attacks
- Optimize treatment and minimize side-effects of drugs

These aims are promoted by early recognition of asthma and treatment of airway inflammation with inhaled. corticosteroids. The severity of asthma is assessed and treatment initiated on the principle of "hit early, hit hard" to gain rapid control. This is followed by a step down procedure as shown in the figure no:6

· ASSESSMENT OF ASTHMA SEVERITY

Asthma is assessed on presentation as mild intermittent or chronic persistent asthma that is mild, moderate or severe (Table No:5) when in doubt the patient should be placed in a more severe category. For example a patient who has normal lung function but experiences daytime symptoms more frequently than twice a week or has nocturnal symptoms more than once a month should be assessed as mild chronic persistent asthma. This assessment system is of less value in patients who are already on treatment, but provides a guide to the level of control and the need for additional treatment. Following assessment of severity, the appropriate level of initial treatment is selected.

Table No 5:Assessment of asthma severity at presentation using symptoms (daytime cough, tight chest and wheeze), night waking and lung function (PEF - peak expiratory flow)

INTERMITTENT	CHRONIC PERSISTENT
Mild	Mild	Moderate	Severe
I	II	III	IV
DAYTIME SYMPTOMS: any of cough tight chest wheeze <2/week	DAYTIME SYMPTOMS: any of cough tight chest wheeze 2-4/week	DAYTIME SYMPTOMS: any of cough tight chest wheeze >4/week	DAYTIME SYMPTOMS: any of cough tight chest wheeze continuous
NIGHT SYMPTOMS <1/month	NIGHT SYMPTOMS 2-4/month	NIGHT SYMPTOMS >4/month	NIGHT SYMPTOMS frequent
PEF > 80%	PEF >80%	PEF 60-80%	PEF <60%

CLASSES OF DRUGS

A classification of asthma drugs based on current knowledge of their mode of action is represented in Table No 7. They may be:

 preventors - anti-inflammatory

 relievers – short-acting bronchodilators that provide acute relief of symptoms

 controllers - a sustained bronchodilator action with unproven or mild anti-inflammatory action

Prescribers should be acquainted with the trade names, formulations, dosage and mode of administration of each preparation. In general, duplication of drugs within one group should be avoided. Combinations such as the regular use of controllers like long-acting b₂ agonists (salmeterol or formoterol) with a short-acting b₂ agonist as rescue medication may be used and are discussed below. The combination of a short-acting b₂ agonist inhaler with ipratropium bromide is not recommended for routine use in asthma.

The chlorofluoro carbons (CFC) propellants in pressurised metered dose inhalers (MDIs) are currently being replaced with alternatives like hydrofluoroalkanes (HFA) as part of the global strategy to protect the atmospheric ozone layer.

Table No 6: Classification of drugs used in the maintenance treatment of asthma

PREVENTERS	CONTROLLERS	RELIEVERS
*Anti-inflammatory action to prevent asthma attacks*	*Sustained bronchodilator action but weak or unproven anti-inflammatory effect*	*For quick relief of symptoms and use in acute attacks as PRN dosage only*
Inhaled corticosteroids*	Long-acting b₂ agonists*	Short-acting b₂ agonists*
1. beclomethasone 2. budenoside 3. fluticasone 4. flunisolide 5. triamcinolone	1. salmeterol 2. formoterol	1. salbutamol 2. fenoterol 3. terbutaline 4. hexoprenaline 5. orciprenaline
	Sustained release theophylline tablets
	\| aminophylline	Anti-cholinergics
Oral corticosteroids		ipratropium bromide
1.prednisone
2.prednisolone 3.methylprednisone 4.methylprednisolone	Leukotriene antagonists** 1. montelukast 2. zafirlukast	Short-acting theophyllines several preparations

* Preferred drugs in this class **provisional categorisation

A. PREVENTERS

Anti-inflammatory treatment is recommended for all patients with asthma, except those that are classified as mild intermittent asthma. Inhaled corticosteroids are the most widely studied and recommended drugs in this class. Other drugs like sodium cromoglycate and nedocromil sodium have weak selective anti-inflammatory effects and are of limited clinical value in adult asthma.

¨Corticosteroids

· Inhaled corticosteroids are the mainstay of treatment for patients with chronic persistent asthma. The inhaled route is preferred because delivery direct to the lungs permits the use of lower doses. Several inhaled corticosteroid preparations are available. The equivalent effective doses of currently available inhaled corticosteroid preparations for prescription in asthma are compared to 100mg beclomethasone dipropionate in Table No 8 Through its anti-inflammatory effects inhaled corticosteroids reduce airway inflammation and improve asthma control. In addition they may modify airway remodelling and prevent an accelerated decline in lung function.

Systemic absorption of inhaled corticosteroids arises from oropharyngeal and gastrointestinal absorption and to a lesser extent from drug deposited in the lungs. This may be reduced by the use of a spacer device combined with mouth washing after inhalation. The former increases the fraction delivered to the lung. Both measures reduce the incidence of dysphonia and oropharyngeal candidiasis.

Dry powder formulations result in similar or greater drug delivery to that of MDIs.

Inhaled corticosteroids should be administered twice daily. A low starting dose is 400-500mg / day of BDP equivalent and a dose above 1000mg / day is considered a high dose. At higher doses, the dose-response curve is relatively flat but the risk of side effects such as skin bruising, cataracts and osteoporosis may be increased. Patients requiring long-term use of high dose inhaled corticosteroids should be referred to a pulmonologist. Strategies to minimise osteoporosis such as regular exercise, calcium supplementation and hormonal replacement in post-menopausal women should be considered. An alternative strategy to high dose inhaled corticosteroids is the combination of long-acting b₂ agonists (salmeterol or formoterol) with a lower dose of inhaled corticosteroids. Whilst this is the preferred option, combination with slow release theophyllines may be an alternative.

Common Adverse effects

Hoarseness, oral or pharyngeal candidiasis,adrenal suppression may occur with high doses.

· Nebulised corticosteroids are available but are expensive, require high pressure nebulisers for optimal delivery and are not recommended for routine use for acute or maintenance treatment of asthma.

· Oral corticosteroids may be considered in patients with poorly controlled asthma on high doses of inhaled corticosteroids and controller medications. Such patients should be referred to a pulmonologist for review. Long term oral corticosteroids (>7.5mg prednisone/day) whilst relatively inexpensive, are associated with serious systemic side-effects.

Common adverse effects:

Prolonged use of these results in exaggeration of some of the normal physiological effects of steroids

Mineralocortiocoid effects include:hypertension, potassium loss, muscle weakness, and sodium and water retention. These effects are most notable with fludrocortisone, are significant with hydrocortisone, occur only slightly with prednisolone and methylprednisolone and are negligible with dexamethasone and betamethasone.

Glucocorticoid effects include: precipitation of diabetes, osteoporosis, development o f aparanoic state, depression, euphoria, peptic ulceration, immunosuppression, Cushing's syndrome (moon face, striate and acne), growth suppression in children, worsening of infection: skin thinning, striae atrophicae, increased hair growth, perioral dermatitis and acne.

Adrenal suppression occurs with high doses and/or prolonged treatment. Steroid therapy must be gradually withdrawn in these patients to avoid precipitating and adrenal crisis of hypotension, weight loss, arthralgia and sometimes, death.

Patients with poor asthma control should be assessed for the following:

 Poor compliance and/or poor inhaler technique

 gastro-oesophageal acid reflux disease

 Chronic disease of the nasal sinuses

 Use of b-blockers including b-blocker eye drops

 Use of aspirin and non-steroidal anti-inflammatory drugs

 vocal cord dysfunction

Treatment with short courses of oral prednisone should be considered in the following circumstances in order to prevent severe deterioration and to gain rapid control of asthma:

      Symptoms and /or lung function (PEF / FEV₁) progressively deteriorating over several days and associated with increased use of inhaled rescue medication
      Lack of sustained relief from rescue medication
      repeated drops in PEFR over 1 or more days to below 60% of previous best value
      frequent night time symptoms
      requirement for emergency nebuliser or parenteral bronchodilator treatment

Recommended procedure for the prescription of a short course of oral prednisone

 Prednisone 30-40mg / day for 7-14 days

 Once daily (morning) dosing

 Stop abruptly after course. There is no need to tail off if used for the recommended duration.

 Inhaled steroids for maintenance treatment should be commenced or continued

 A step-up in maintenance treatment is often indicated.

 Oral corticosteroids should not be stopped until symptoms are controlled and the PEF has stabilised

 Patients requiring oral corticosteroids for more than 14 days must be referred to a pulmonologist.

Table No 7: Equivalent effective metered doses of inhaled corticosteroids

STEROID PREPARATION	EQUIVALENT METERED DOSE IN ASTHMA
Beclomethasone dipropionate	100mg
Budesonide	80mg
Flunisolide	100mg
Fluticasone propionate	50mg
Triamcinolone	90mg

B. CONTROLLERS

These are agents that have prolonged bronchodilator action, but weak anti-inflammatory effects and include the long-acting b₂ agonists and the slow release theophyllines. The leukotriene receptor antagonists may be better classed as controllers.

a. Long-acting b₂ agonist (LABA) inhalers

Salmeterol and formoterol are LABA inhaler therapy administered twice daily because of their greater than 12 hour duration of action. They are useful for control of nocturnal symptoms and exercise-induced asthma. They are recommended in step 3 of the treatment guidelines (Fig 1) in preference to increasing the dose of inhaled corticosteroids. This is supported by several studies which have shown that combining low dose steroids with salmeterol or formoterol provides better asthma control compared than doubling the dose of inhaled corticosteroids. LABAs are not suitable for acute relief of asthma exacerbations although formoterol has an acute onset of bronchodilation (within 10-15mins of administration). LABAs should not be used without concurrent anti-inflammatory medication. Side effects of these drugs include palpitations and tremors.

LABAs and slow release theophyllines have replaced short-acting and slow release oral b₂ agonists in the management of chronic persistent asthma.

Common adverse effects:

By inhalation: adverse drug reactions are uncommon.

More commonly (mainly by nebulization, orally or parenterally): fine tremor (usually the hands), nervous tension, headache, peripheral vasodilatation, tachycardia. The adverse reactions often diminish as tolerance develops with continued administration.

With high doses: hypokalaemia, aggravation of angina.

b. Slow release (SR) theophyllines

Some formulations of SR theophyllines have a 12 hour and others a 24 hour duration of action. They have the following advantages:

 Oral administration

 sustained bronchodilator action

 Mild anti-inflammatory actions

 Complementary mode of action to other bronchodilators

Disadvantages include their narrow therapeutic index, wide inter-patient pharmacokinetic variability and side-effects such as palpitations, insomnia, and irritability and gastrointestinal upsets.

Common adverse effects:

Although about 5% of the population experience minor adverse effects: nausea, diarrhoea, nervousness and headache, increasing the serum concentration results in more serious effects.

c. Leukotriene receptor antagonists

Leukotriene receptor antagonists are a new class of asthma drugs that have been shown to improve asthma control and exert their effect within days of commencing treatment. The current recommendation is to classify them as controllers pending further evidence of their effect on inflammatory activity. They may be used in patients with moderate persistent asthma as add-on treatment to inhaled corticosteroids and may be of value in patients with aspirin sensitive asthma. If no benefit is evident after 4 weeks, the leukotriene receptor antagonists should be withdrawn since not all patients respond. Increasing the dose is of no value. Their use as monotherapy in asthma is not advised. Several incidents of the rare asthma-related vasculitis, the Churg-Strauss syndrome, associated with the administration of leukotriene antagonists have been published. It has been postulated that the concurrent reduction in corticosteroids may have unmasked this condition. Physicians should be on the alert to this possibility.⁸

Common adverse effects:

Abdominal pain, headache, diarrhoea, dizziness, upper respiratory tract infections.
Rarely: acute hepatitis (associated with zafirlukast), Churg-Strauss syndrome.
C. RELIEVERS

These include short-acting inhaled b₂ agonists, ipratropium bromide and short-acting theophyllines. They should be used only on a prn basis as rescue medication for chronic persistent asthma. Some patients with severe persistent asthma may need to use b₂agonists up to 6 times per day.

a. Short-acting b₂ agonists

Short-acting b₂ agonists provide relief from acute symptoms of asthma and are usually used as 2 puffs prn. With optimal maintenance therapy their use should be rare (less than once a day). The frequency of their use is a measure of asthma control.

They may only be used as the sole therapy in mild intermittent asthma where the symptoms are mild and the lung function is normal (PEF > 80% predicted), sees Fig 1. Side effects of b₂ agonists include tachycardia, tremor, headache and irritability.

b. Anticholinergics (ipratropium bromide)

These drugs work by inhibiting vagally mediated bronchoconstriction. They are not the preferred relievers in asthma. They may be used in patients, particularly the elderly, who cannot tolerate b₂ agonist side effects. They may also be of value as add on treatments in patients who do not obtain adequate symptom relief with the short-acting b₂ agonists.

Common adverse effects:

Occasionally: dry mouth

Rarely: systemic anticholinergic effects such as urinary retention and constipation

D. ADDITIONAL TREATMENT AND OTHER DRUGS

Antihistamines are not effective in adult asthma.

Immunosuppressives including methotrexate, are rarely of benefit. Patients considered for this treatment must be referred to a pulmonologist.

There is little scientific evidence that ionisers, oxygen therapy, acupuncture, homeopathy and exclusion diets are useful in the treatment of asthma.

Immunotherapy in the form of desensitisation is not routinely recommended for asthma.

Nebuliser use in chronic persistent asthma is limited. They are generally over prescribed. The guidelines for nebulised bronchodilator treatment in chronic persistent asthma are summarised in Table No 8

Table No 8: Guidelines for prescribing nebulised bronchodilator for chronic persistent asthma

1. Before prescribing nebulised bronchodilators:

 Optimise other steps in asthma management – it is not a substitute for adequate preventor and controller medication

 Stabilise asthma with a short course of oral prednisone

 Refer to pulmonologist for review

2. Supervision:

 Verbal and written instruction on method and frequency of use

 Action to be taken in the event of worsening asthma

 Emphasise need to attend for follow-up visits

 Regular PEF monitoring

 Regular servicing of nebuliser

3. Follow-up:

 Review within 2 weeks

 Attempt to withdraw regular nebuliser use

 If nebulisation needed more than 3 times a day refer to a pulmonologist or admit to hospital for stabilisation

® SELF-MANAGEMENT PLAN FOR ASTHMA
^{8, 13}

Optimal management of a chronic disease like asthma requires the active participation of patients. To achieve this, patients require education about asthma and a detailed management plan. A systematic approach is necessary to ensure that all relevant details are included and education should be staged over several visits. The use of nurse educators and other specially trained healthcare professionals is cost-effective in this regard.

Goals of asthma education include:

 An explanation of the nature of asthma and its allergic basis

 A description of the different classes of drugs and their purpose in treatment

 Advice on prevention strategies (allergens and tobacco smoke avoidance)

 The correct use of inhalers and the opportunity to practice under supervision

 How to recognize worsening asthma

 In some patients, particularly those requiring stabilization or patients who have had a recent exacerbation or deterioration, the use of a PEF meter and chart

Instructions to patients about self-management:

 Instructions must be written and should include the class, name, strength, dose and frequency of each of the asthma medications prescribed, including the correct use of inhaler devices

 Realistic goals of treatment in terms of symptom relief and PEF

 Potential side-effects of drugs

 Instruct patients who may require short courses of oral prednisone on when and how to initiate a course

 Details on when and how to obtain access to medical care in emergencies

 Arrangements for a Medic-Alert badge for patients with severe steroid-dependent asthma, known drug hypersensitivities (like aspirin and penicillin) and brittle asthma

 Advice on how to recognize changes in the asthma and when to make adjustments to treatment according to a predetermined schedule

 Emphasise the importance of regular follow-up and when to request earlier review.⁸

® SPECIAL CLINICAL CIRCUMSTANCES ¹³

There are several special clinical circumstances where special precautions and adjustments to asthma management and treatment may be required. These are summarized as follows:

 Pregnancy: Ideally pregnancy should be planned and optimal control achieved prior to conception. The effect of pregnancy is unpredictable: it may remain the same, deteriorate or improve during pregnancy and may vary in different trimesters in successive pregnancies. Current evidence suggests that corticosteroids, b₂ agonists and theophyllines are safe in pregnancy. New drugs for which safety data in pregnancy are not available should be avoided. It is essential that asthma should be optimally controlled during pregnancy through the use of appropriate doses of inhaled corticosteroids.

 Menstruation: Pre-menstrual exacerbations of asthma are common. The mechanism is not well understood. When severe, an increase in the dose of inhaled corticosteroids or a low dose of oral prednisone for 2 – 3 days commencing 1 – 2 days before menstruation begins is often effective.

 Exercise: Exercise induced asthma (EIA) may occur, as an isolated symptom but is usually an indication of sub-optimal asthma control. The preferred treatment is the use of short acting inhaled b₂ agonists 15-20min before exercise. Long-acting b₂ agonists and SR theophyllines may protect against EIA for several hours after dosing. Leukotriene antagonists and the cromones also provide protection against EIA, but are not effective in all patients.

 Elderly patients: Asthma occurs in the elderly and is frequently overlooked or misdiagnosed. The elderly are more susceptible to adverse effects of drugs. SR theophyllines should be used with care because of their narrow therapeutic range. The elderly are also especially prone to the side effects of corticosteroids like osteoporosis, cataracts, glucose intolerance, hypertension and fluid retention.

 Nocturnal asthma: Nocturnal symptoms of asthma are an important indicator of poor control and may signal the onset of impending severe deterioration. Occasionally it is the only symptom of asthma and may be associated with marked falls in the PEF (50% or more). Increased preventor medication, addition of a controller or a short course of oral prednisone must be considered in patients with nocturnal symptoms. Long-acting b₂ agonists and SR theophylline provide an additional benefit to that of anti-inflammatory therapy in controlling nocturnal symptoms.

 Cardiac disease and hypertension: Fluid retention and hypokalaemia induced by corticosteroids and high doses of b₂ agonists may occasionally be a problem in asthma with associated cardiac disease. Pulmonary congestion may manifest with wheezing and may be misdiagnosed as asthma particularly in patients with mitral stenosis and in the elderly. b-blockers, including b-blocker eye drops may be hazardous in asthma.

 Diabetes mellitus: Particular caution is required when prescribing oral corticosteroids. Inhaled corticosteroids are safe and have little effect on glycaemic control.

 Pulmonary tuberculosis: In patients who have had tuberculosis or evidence of healed tuberculosis on chest radiographs, chemoprophylaxis with Isoniazid is not recommended whilst on inhaled corticosteroids and when a short course of oral prednisone is prescribed, as the risk of reactivation has not been shown to be increased.

 Gastro-oesophageal acid reflux: Acid reflux may aggravate asthma and should be considered in patients with difficult asthma and in those with symptoms of acid reflux. The acid reflux may be asymptomatic.

 Sinus disease including postnasal drip: This is frequently associated with atopic asthma and allergic rhinitis. This may aggravate asthma and should be considered in patients with difficult asthma even in the absence of specific symptoms as the patient may be unaware of the postnasal drip.⁸

® REFERRAL TO A PULMONOLOGIST

The majority of asthmatics can be managed optimally in a primary health care facility provided the elements of the asthma guidelines are accommodated. Some patients may require referral to a pulmonologist or a physician with a special interest in asthma where the services of a pulmonologist are not available. The guidelines for referral are presented in Table No 10

Table No 10: When to refer patients to a pulmonologist

A. DIFFICULTY WITH DIAGNOSIS

 persistent cough

 patients receiving multiple courses of antibiotics (>3 in 3 months)

 possibility of COPD

 asthma for the first time after the age of 60 years

 productive cough

 suspected vocal cord dysfunction

B. OCCUPATIONAL ASTHMA

C. MANAGEMENT PROBLEMS

 brittle asthma

 recurrent exacerbations - > 2 per month

 recent discharge following admission for severe exacerbation

 oral corticosteroid dependence

 persistent symptoms despite intensive treatment

 pregnancy

 co-existing significant medical illnesses like thyroid disease, collagen vascular disease, peptic ulcer, cardiac failure

 frequent school or work absenteeism

 significant corticosteroid side-effects

 consideration for immunosuppressive treatment or desensitisation

 consideration for disability grant or medical boarding for asthma

BST PRACTICE

EVIDENE-BASED

GUIDELINE

SUMMARY

NO

YES

NO

NO

NO

YES

YES

YES

► MANAGEMENT IN CHILDREN ^13,17,19

The method of assessment presented conforms to international assessment criteria.

The following points should be noted:

· The assessment of severity is outlined in Fig No 7., which is used to

assign a child to a particular treatment group.

· The assessment of severity refers to a child's symptoms between acute attacks. The assessment and management of the acute attack are dealt with in a separate document.

· Asthma presents as a spectrum of severity rather than in discrete severity groups. Practitioners should attempt to grade each patient accurately but must regard this only as a starting point.

· If unsure of grading, place the child on therapy appropriate to the severity group, which is judged to be the most likely, and monitor control by means of a diary card (for symptoms and/or PEF). Reassess after 4 weeks.

· One or more features may be present to assign a grade of severity; a patient must be assigned to the most severe grade in which any feature occurs.

· Asthma severity can vary with time. Regular reassessment is necessary with a view to stepping therapy up or down.

· The PEF is assessed at times other than during acute exacerbations. The predicted or the best PEF, whichever is higher, should be utilised.

· In practice about 70% of childhood asthmatics will fall into the intermittent or
mild persistent', 25% into the 'moderate persistent' and 5% into the 'severe persistent' categories.

Fig No 7: Management of asthma in children

· MANAGEMENT GOALS

The goal is effective control of asthma, which strives to ensure that the asthmatic is able to lead a normal and physically active life. For a 'normal life' the aim is to:

 Be completely free from any symptoms, i.e. cough, wheeze and breathlessness.

 Attend school regularly and participate fully in all school activities, including sporting activities.

 Have restful sleep, free from nighttime cough and/or wheeze.

 Grow and develop normally.

 Minimise the number of attacks of acute asthma and avoid hospitalisation.

 Avoid medication-related side-effects.

·
PRINCIPLES

A comprehensive therapeutic approach is required to meet the above objectives. This includes the following:

 Early diagnosis and objective assessment of severity.

 Control of the environment to exclude cigarette smoke and reduce exposure to triggers such as viral infection and allergens.

 Optimal use of medications to limit side effects and cost, using the most appropriate delivery system.

 Follow-up and regular re-evaluation (clinical evaluation and quality of life).

 Patient and parent education.

Optimal management of asthma includes avoidance of triggers / environmental control, pharmacotherapy and education .

®
Environmental control

1. Indoors

¨
Cigarette smoking is harmful.

Smoking should not be allowed in the home of any asthmatic and active steps should be taken to inform the parents of the problem,encouraging smokers to quit.

¨ Indoor allergens

A detailed history should identify which allergens are likely to be significant. If there is uncertainty after taking a history,and the child has persistent asthma,then specific allergen testing by Skin Prick Test or RAST is indicated.

a. House dust mites:

Mattress, pillow and duvet covers with mite impermeable characteristics are recommended. Bedding should be washed regularly at temperatures greater than 60^oC. Rooms should be well ventilated. Carpets should be removed from the living areas and especially the bedrooms. Acaricides are ineffective. Other sources of house dust mite should also be considered, e.g., fluffy toys and feather pillows.

b.
Cockroaches:

Cockroach allergy is widespread. They may be a cause of ongoing airway inflammation and sensitivity to cockroaches is a risk factor for more severe asthma. Obsessive cleaning, "bait stations" and/or boric acid indoors can reduce cockroach numbers.

c. Pets:

Asthmatics known to be allergic to dogs or cats should avoid contact with them. Cat allergens are notoriously difficult to eliminate and may persist for several months after the cat has been removed from the home.

Mould:

Obvious sources of indoors mould in bathrooms, kitchen and damp parts of the home should be treated with proper plumbing, damp proofing, mould repellent paint and Lysol sprays.

2. Outdoors

Outdoor allergens

Moulds are important sources of outdoor allergen and sensitive children are advised to avoid exposure to mouldy places, e.g. farms, forests, compost heaps or parks, particularly in autumn, winter and in spring. Grasses may be implicated in perennial asthma.

Exercise

Exercise induced asthma can be prevented by the use of a short-acting b₂ agonist. LABA are preferred for children who engage in repetitive exercise because of their prolonged duration of action. Leukotriene antagonists are also an option for preventive treatment of exercise induced asthma.

Dietary factors

These may be divided into additives, e.g. Preservatives and allergens. Children with asthma should avoid exposure to cooldrinks containing sulphur dioxide (SO₂) and sodium benzoate. Food allergens are a rare cause of asthma as an isolated manifestation. Milk allergy may play a role in the child below the age of 2 years, especially with concomitant eczema.

® Pharmacotherapy

Pharmacotherapy is the cornerstone of asthma management. Initial treatment is based upon the clinical assessment of severity, according to the classification.

· Principles of medication

When selecting medication for an asthmatic patient, the following principles apply:

 Asthma is an inflammatory disease of the airways.

 Regular anti-inflammatory medication is indicated for persistent asthma.

 Inhaled therapy is preferable.

 Inhaled b₂ agonists are cheaper per dose than syrups and tablets.

The drugs are conveniently classified as:

·
Relievers – acute relief from symptoms

 Preventers
– anti-inflammatory

·
Controllers – drugs, which have a sustained bronchodilatory action, but unproven anti- inflammatory action

A. RELIVERS

· Short-acting ß₂agonists

Short-acting ß₂agonists are generally used on an as needed (prn) basis. Their use can be minimised by the optimal use of anti-inflammatory agents and controllers. Oral preparations of short acting ß₂agonists are appropriate for use in patients unable to use inhaled medication. Short-acting ß₂ agonist inhalers provide relief from acute symptoms of asthma.

· Anticholinergics (Ipratropium bromide)

These drugs work by inhibiting vagally mediated bronchoconstriction. They are less potent bronchodilators than inhaled ß₂agonists and in general have a slower onset of action (30 to 60 minutes to maximum effect). They may be used in patients who cannot tolerate ß₂agonists or as adjunctive bronchodilator treatment in patients who do not obtain adequate symptom relief during acute asthma. Ipratropium bromide benefits in long-term management of asthma have not been established.

B. PREVENTERS

Anti-inflammatory treatment is recommended for all patients with persistent asthma. These drugs modify the airway inflammation that is characteristic of asthma. Inhaled corticosteroids are the most widely studied and recommended drugs in this class for asthma. Other drugs with weak to mild anti-inflammatory effects include the cromones, (sodium cromoglycate and nedocromil sodium), the sustained release theophyllines and the most recently developed leukotriene antagonists.

· Inhaled
corticosteroids

Studies in adults suggest that early use of ICS may prevent remodelling of the airway by inflammation, which eventually results in fixed airway obstruction, although this has not been conclusively proven in children. Early treatment with ICS is claimed to minimise lung function decline in children. There are no comparable data for children younger than 5 years.

¨ Indications

International and local guidelines recommend the use of anti-inflammatory therapy when asthma is persistent. ICS should be used as first line treatment in moderate to severe persistent asthma. This agent may also be used in mild persistent asthma, but currently concerns about the safety of ICS in mild asthma remain a source for debate. For this reason, the benefits must be weighed up against the risks and side-effects in the milder forms of asthma

¨Dose

The optimal dose of ICS should be the lowest dose that is needed for good disease control. There is evidence that low doses (100-200 µg/day) of ICS are highly effective in childhood asthma. The dose for each child should be individualised and continuously titrated. Increasing doses do not necessarily increase effectiveness but do result in systemic bioavailability with potential side effectsts. For inhaled beclomethasone or equivalent (Fig.), doses >400 mg/day may be associated with a risk of systemic side effects. The recommended approach is to start at a dose of ICS appropriate to the child's symptoms and lung function (Fig.), and gradually decrease the dose as symptoms and lung function improve. The efficacy and safety of inhaled steroids are increased by the use of spacer devices. Certain dry powder devices such as the turbuhaler and accuhaler increase the drug delivery to the lung, and therefore lower doses may be used. ICS are usually administered twice daily. It is reasonable to use generic preparations where they have demonstrated bioequivalence and offer cost advantage.

· Cromones

Sodium cromoglycate and nedocromil have weak anti-inflammatory effects. They are mainly of value in young atopic patients with mild asthma. Their disadvantages include higher cost, frequent dosing interval and poor efficacy in comparison with inhaled corticosteroids. Monitoring of symptoms and lung function is recommended and inhaled corticosteroids should be substituted if control is inadequate after 6-12 weeks treatment. Cromones may be tried in asthmatics with a persistent cough despite optimal treatment with corticosteroids. They are also effective for the prevention of exercise induced asthma. Their main advantage is a good safety profile.

C. CONTROLLERS

These are agents that have prolonged bronchodilatory action, but weak anti-inflammatory effects. They include the long-acting ß₂agonists and the slow release xanthines (theophyllines). Leukotriene antagonists may be also classified as controllers.

· Long-acting ß₂agonist (LABA) inhalers

Salmeterol and formoterol are LABA inhaler therapy, administered twice daily because of their greater than 12 hour duration of action. This sustained action is useful for control of nocturnal symptoms and to prevent exercise induced asthma (as they may provide longer protection than the short-acting beta₂ agonists).

LABA are not suitable for relief of asthma exacerbations although formoterol has an acute onset of bronchodilation (within 10-15 mins of administration). Side-effects of these drugs include palpitations and tremors.

Adult studies have shown that combining moderate doses of inhaled corticosteroids with LABA provides better asthma control compared to doubling the dose of steroids (Facet study). There is a paucity of data on the combined use of inhaled steroids and LABA in paediatric asthma. The two studies which evaluated LABA as add on treatment have shown conflicting results^.

· Slow-release xanthines (SR theophyllines)

SR theophyllines can be used in combination with inhaled steroids as an add on treatment and for control of nocturnal asthma.These agents may be used as an alternative to inhaled corticosteroids for mild persistent asthma in certain situations,(e.g. If inhaled corticosteroids unavailable or patients prefer oral medication).

· Leukotriene receptor antagonists

Leukotriene receptor antagonists inhibit the effect of the cysteinyl leukotrienes, products of arachidonic acid metabolism. They have been shown to:

^improve asthma control, in persistent asthma (mild, moderate and severe)

^{}attenuate exercise induced asthma

^{}be of value in aspirin induced asthma

^{}have a rapid onset of action (within 1-3 hours)

Current recommendation is to classify them as controllers but evidence is accumulating that they have anti-inflammatory effects. LRAs have a role in moderate and severe persistent asthma as a steroid-sparing agent. The role of these agents as monotherapy in mild persistent asthma still needs to be determined. A trial of treatment is acceptable in this situation (maximum duration for 30 days). If asthma is not controlled on LRAs, switch to inhaled steroids. Churg-Strauss syndrome, a form of systemic vasculitis, in association with the administration of leukotriene antagonists in adults has been reported. To date, there are no reports of this condition in children.

OTHER DRUGS

· Oral corticosteroids

Oral corticosteroids such as prednisone may be considered in patients with poorly controlled severe asthma on optimal doses of inhaled corticosteroids and controller medications. These patients should be referred to a specialist for review. Long term oral corticosteroids whilst relatively inexpensive are associated with serious systemic corticosteroids side effects.

Short courses (7-14 days) of oral steroids (prednisone 1-2 mg/kg/day with an upper limit of 60 mg/day) are generally necessary in the treatment of acute exacerbations of asthma. It is not necessary to taper oral steroids if used as a short course. Maintenance treatment with daily or alternate-day oral steroids is indicated only in those patients not controlled by high dose inhaled steroids. In children on oral steroids extra care should be taken during episodes of increased stress, e.g. surgery.

· Antihistamines

Ketotifen and cetrizine have no proven benefit in young children (< 3 years) with established asthma, but may be used in young children with multiple allergies. The clinical benefits of ketotifen may only be evident after more than two months of treatment.

DEVICES FOR DELIVERING INHALED THERAPY IN CHILDREN

All delivery systems must be assessed on an individual basis taking the limitations of the patient as well as the delivery system into account.

Spacer devices

 Steroids inhaled from a MDI must always be prescribed with an appropriate spacer to improve drug delivery and diminish side-effects.

 Smaller volume spacers (250-300 ml) are suitable for children younger than 5 years and larger volume spacers (> 500 ml) for older children. Static electricity diminishes the amount of drug delivered and can be minimised by using a stainless steel spacer, a low static spacer or by priming a spacer with multiple actuations from a MDI before use.

 Spacers should be washed weekly. To reduce the static electricity in plastic spacers the spacer should be washed with a liquid detergent, not rinsed in water, and left to drip-dry overnight.

 If commercially available spacers are not available a 500 ml plastic bottle can be used as a spacer. A hole to fit the MDI is cut or melted into the bottom of the bottle using the hot wire technique²³. Polystyrene cups are not efficient spacers.

 One puff at a time should be actuated into the spacer and the child should breathe 4-5 times before the next actuation. After inhalation of ICS, the mouth should be rinsed. If a spacer with a facemask is used it should be applied tightly to the face. The face should be washed after corticosteroid inhalation to prevent skin changes, (spider naevi, atrophy).

§
Children under 3 years of age:

The delivery system of choice is a MDI with a spacer. The spacer should be fitted with a facemask.

Nebulisers are an alternative, but should only be prescribed if the child is not able to use a MDI and a spacer.

Dry powder devices and breath-actuated MDI should not be used.

§ Children between 3 and 5 years of age:

The delivery system of choice is a MDI with a spacer. The spacer should be used with a mouthpiece. Should the child be unable to manage a mouthpiece, then a facemask may be used.

Breath-actuated systems are not indicated. Dry powder devices are generally not indicated, but some have successfully been used in children as young as 3-4 years; this must be evaluated on an individual basis. Nebulisers are very seldom indicated in this age group and should only be used if children refuse to use spacers.

§ Children older than 5 years of age:

The delivery system of choice is a MDI with a spacer. The spacer should be used with a mouthpiece. Dry powder devices and breath-actuated devices can be used successfully. Nebulisers should only be used in this age group in exceptional circumstances.

LUNG FUNCTION TESTING

Cheap hand-held devices (Assess, Mini-Wright, Pocket peak flow, Vitalograph) can measure peak Expiratory Flow (PEF). They indicate the trend in airway obstruction and improvement on therapy, and can be used to measure bronchial variability (the difference between the early morning and late afternoon peak flow readings). All children >5 years should have their peak flow measured during the initial evaluation and at follow-up. Peak flow meters should be considered for short-term home monitoring in moderate and severe asthmatics. Other measures of lung function (FEV, MMEF and FVC) can be measured by spirometry (preferably performed by a specialist).

IMMUNOTHERAPY

Allergen immunotherapy with specific allergens modulates the immune response in the direction of a protective, non-allergic response. There is new evidence that in young children whose rhinitis is treated with immunotherapy, the risk of developing asthma may be reduced. At present, however there is insufficient data to recommend routine treatment with immunotherapy for allergic asthmatics. There is a risk of the induction of severe bronchospasm and ideal protocols are still under investigation. At present, immunotherapy for asthma should only be conducted in the context of research studies.

SPECIAL CONSIDERATION IN CHILDHOOD ASTHMA

· Pharmacotherapy for asthma in children younger than 5 years of age

For children under the age of 5 years the same basic steps must be taken as in older children. Note that the assessment and monitoring of severity with measurements of lung function, including PEF, are not feasible in this subgroup of patients. Therefore, classifying asthma severity must be based on clinical criteria. The history is fundamental and the symptoms must be described as wheezing and/or cough and/or dyspnoea. Essential elements in decision making are evaluation of the child's quality of life and physical examination.

® Relievers:

The same doses of ß₂ agonists are recommended for young children as for adults due to the inefficiency of the delivery systems. Oral ß₂ gonists and short acting theophyllines are not recommended because of the side-effect profile.

®Preventers:

In Children with moderate or severe persistent asthma inhaled corticosteroids are the drug of choice. The safe dose is still 400 µg of beclomethasone or equivalent per day. Cromones may be used as preventer therapy on a trial basis (6-8 week duration), in children with mild to moderate persistent asthma. If there is no or poor response, patients should be switched to ICS.

® Controllers:

The use of long-acting ß₂ agonists or slow release theophylline preparations would be similar to the older child although there are no trials showing efficacy. Leukotriene receptor antagonists have recently been approved (by the FDA in the USA) for use in children aged 2 - 5 years.

Tapering and terminating therapy

Children on anti-asthma therapy should be reviewed at least every 3 months. If their asthma is well controlled (on clinical assessment and lung function) for a period of 3-6 months, treatment should be reduced. Stepping down is done as follows: first aim to discontinue oral steroids; next reduce dosage of inhaled steroids to a medium dose (if on high doses); thereafter aim to reduce or stop controller treatment; finally aim to further reduce inhaled steroids to lowest effective dose.

SELF-MANAGEMENT PLAN FOR ASTHMA

Patients and parents must be encouraged to participate actively in their own management. Wherever possible the patients and parents should be given a written plan. The elements of a self-management plan are summarised as follows:

 Instructions on avoidance measures including allergens and tobacco smoke.

 Training patients and parents to recognize alterations in their asthma and to know when to make adjustments to their treatment.

 Educating patients and parents about asthma and its treatment (e.g. correct use of inhalers; correct use of peak flow meter; recognition of symptoms and signs of worsening asthma).

 A crisis plan for management of acute exacerbations of asthma and access to health care in emergencies.

 Arrangements for a "Medic-Alert" badge for patients with severe steroid dependent asthma, known drug hypersensitivity like aspirin sensitivity and brittle asthma.

® INHALATION DEVICES USED IN ASTHMA MANAGEMENT:

1. INHALERS:

The choice of suitable inhalation device is vital in asthma management. The incorrect use of inhalers will lead to suboptimal treatment.

The different types of inhalers and the method to use them are given below

2. NEBULIZERS ¹⁷:

A nebulizer produces an aerosol by blowing air of oxygen through a solution to produce droplets of 5mm or less in size.These are useful in patients who are unable to use conventional inhalers.

Overview of Selected Drugs Used to treat Asthma ⁶

TABLE NO 10: Daily Dosing Guidelines for Inhaled Anti-inflammatory Agent
	Dosage
Agent*	Low dose (per day)	Medium dose (per day)	High dose (per day)
Corticosteroids
Beclomethasone (Beclovent, Vanceril): 42 and 84 µg per puff	Adults: 4 to 12 puffs at 42 µg per puff or 2 to 6 puffs at 84 µg per puff	Adults: 12 to 20 puffs at 42 µg per puff or 6 to 10 puffs at 84 µg per puff	Adults: more than 20 puffs at 42 µg per puff or more than 10 puffs at 84 µg per puff
	Children: 2 to 8 puffs at 42 µg per puff	Children: 8 to 16 puffs at 42 µg per puff	Children: more than 16 puffs at 42 µg per puff
Budesonide (Pulmicort): 200 µg per puff	Adults: 1 or 2 puffs Children: 1 puff	Adults: 2 or 3 puffs Children: 1 or 2 puffs	Adults: more than 3 puffs Children: more than 2 puffs
Flunisolide (AeroBid): 250 µg per puff	Adults: 2 to 4 puffs Children: 2 or 3 puffs	Adults: 4 to 8 puffs Children: 4 or 5 puffs	Adults: more than 8 puffs Children: more than 5 puffs
Fluticasone (Flovent): 44 µg, 110 µg and 220 µg per puff	Adults: 2 to 6 puffs at 44 µg per puff or 2 puffs at 110 µg per puff	Adults: 2 to 6 puffs at 110 µg per puff	Adults: more than 6 puffs at 110 µg per puff or more than 3 puffs at 220 µg per puff
	Children: 2 to 4 puffs at 44 µg per puff	Children: 4 to 10 puffs at 44 µg per puff or 2 to 4 puffs at 110 µg per puff	Children: more than 4 puffs at 110 µg per puff
Triamcinolone acetonide (Azmacort): 100 µg per puff	Adults: 4 to 10 puffs Children: 4 to 8 puffs	Adults: 10 to 20 puffs Children: 8 to 12 puffs	Adults: more than 20 puffs Children: more than 12 puffs
Mast cell stabilizers
Cromolyn sodium MDI (Intal), 800 mg per puff; nebulizer, 20 mg per 2-mL ampule	Adults: 6 puffs or 3 ampules in three divided doses	Adults: 9 to 12 puffs in three divided doses	Adults: 16 puffs in three divided doses or 4 ampules in four divided doses
	Children: 3 puffs or 3 ampules in three divided doses	Children: 6 puffs in three divided doses	Children: 8 puffs or 4 ampules in four divided doses
Nedocromil (Tilade), 1.75 mg per puff	Adults: 4 to 6 puffs in two to three divided doses	Adults: 9 to 12 puffs in two to three divided doses	Adults: 16 puffs in four divided doses
	Children: 2 to 3 puffs in two to three divided doses	Children: 4 to 6 puffs in two to three divided doses	Children: 8 puffs in four divided doses
*--Dosage equivalency is difficult to define because of the differences in potency, administration devices, bioavailability and clinical outcomes with various doses. Adapted from National Asthma Education and Prevention Program (National Heart, Lung, and Blood Institute) Second Expert Panel on the Management of Asthma. Expert panel report 2: guidelines for the diagnosis and management of asthma. Bethesda, Md.: National Institutes of Health, 1997; publication no. 97-4051.

Table No 11:

*Fig No 8: Step Therapy for Long-Term Control and Quick Relief of Asthma in Adults and Children Older Than Five Years⁶**
Long-term control
Step 1: mild intermittent asthma	No daily medication needed
Step 2: mild persistent asthma	One daily medication: Anti-inflammatory drug Low-dose inhaled corticosteroid or cromolyn (Intal) or nedocromil (Tilade)† Children usually begin with a trial of cromolyn or nedocromil Zafirlukast (Accolate) or zileuton (Zyflo) may also be considered in patients 12 years or older or Sustained-release theophylline to serum concentration of 5 to 15 µg per mL is an alternative but not preferred therapy
Step 3: moderate persistent asthma	One daily medication: Medium-dose inhaled corticosteroid† or Two daily medications: Low- to medium-dose inhaled corticosteroid and long-acting bronchodilator, especially for nighttime symptoms (either salmeterol [Serevent],† sustained-release theophylline or long-acting beta₂ agonist tablets)
Step 4: severe persistent asthma	Daily medications: High-dose inhaled corticosteroid and Long-acting bronchodilator (salmeterol,† sustained-release theophylline or long-acting beta₂ agonist tablets) and Oral corticosteroid in a dosage of 2 mg per kg per day with the daily dose generally not exceeding 60 mg

®ROLE OF PHARMACIST IN ASTHMA MANAGEMENT¹⁵

Whether they work in community pharmacies, hospitals, or clinics, pharmacists are in a pivotal position to contribute to the overall management of asthma. Every year, pharmacists fill more than7 million prescriptions for asthma medications, which remain the principal treatment for the disease. Pharmacists have many other opportunities to assisting he management of asthma.

Pharmacists can educate patients by providing information on the types and purposes of asthma medications and by demonstrating how to use inhaled medications and peak flow meters. They can reinforce and clarify the instructions contained in a patient's individual asthma management plan. In addition, pharmacists can refer patients who use over-the-counter medications to physicians for medical care Pharmacists can be valuable source of important information for other members of the health care team. They can monitor medication use and refill intervals and use this information to alert prescribers and help identify patients with poorly controlled asthma. Pharmacists also can share information about asthma medications and the National Asthma Education and Prevention Program guidelines on the diagnosis and management of asthma with members of the health care team.

Action Plan for Pharmacists

1. Educate patients about asthma medications.

2. Instruct patients about the proper techniques for inhaling medications.

3. Monitor medication use and refill intervals to help Identify patients with poorly 
    controlled asthma.

4. Encourage patients purchasing OTC asthma inhalers or tablets to seek medical care.

5. Help patients use peak flow meters appropriately.

6. Help patients discharged from the hospital understand their asthma management plan.

ACTION PLAN FOR PHARMACISTS

There are numerous areas where pharmacists can contribute to improving health outcomes in patients with asthma.

Pharmacists can:

1. Educate patients about the role of each medication.

Pharmacists can help patients understand that, with appropriate therapy, most patients can lead normal, productive, and physically active lives. Pharmacist's can educate patients about the two broad categories of asthma medications:

Medications used to prevent and/or decrease the frequency of symptoms.

Preventive medication should be taken on a regular basis even when the patient is free of symptoms. This type of long-term medication includes inhaled anti-inflammatory agents such ascorticosteroids, cromolyn, and nedocromil,which are preferred therapy.   It may include extended-release formulations of theophylline. Also included as long-term medication are extended-release oral and long-acting inhaledbeta2-agonists, which are added to inhaled corticosteroidswhen the recommended doses of inhaled corticosteroids are not sufficient to control chronic symptoms, especially nighttime symptoms. Preventive long-term medication also may include, for severe asthma, alternate day oralcorticosteroid therapy. In addition, the use of a short- or long-acting inhaled beta2-agonists or cromolyn beforeexercise to prevent exercise-induced bronchospasm falls into the "prevention" category.

Medications taken to relieve asthma symptoms.

Medications in this category are designed to relieve symptoms and generally are prescribed to be taken only as needed (PRN). This therapy includes primarily short-acting inhaled beta2-agonists (albuterol, bitolterol, pirbuterol,or terbutaline). In addition, a short course of oralcorticosteroids for patients who are not fully responsive to inhaled bronchodilators may be used to treat acute exacerbations of asthma.

An effective asthma management plan should ensure that the patient is given written and verbal instructions that describe when and how a medication should be taken, how much to take, how to evaluate the response to therapy, when to seek medical care, and what to do when the desired effect isn't achieved or side effects are encountered. Pharmacists can reinforce these instructions by reminding patients, for example, to contact their physician when acute symptoms are not relieved by using their short-acting beta2-agonists inhaler as directed or when their peak expiratory flow rate (PEFR) drops below a predetermined value.

Signs of Poorly Controlled Asthma

Any one of the following criteria may indicate the need for medication adjustment, improved medication administration technique, or patient education concerning asthma and its management:

```
Adverse effects from medications.
```

Waking up at night from symptoms of asthma more than twice a month.

Increased use of inhaled, short-acting beta2-agonists

    (E.g., more than three to four times in 1 day).

Long-term overuse of inhaled, short-acting beta2-agonists (e.g., refilling the prescription more often than one canister/month or more than one canister/2 months of a short-acting agent when it is used in addition to a long-acting agent).

Overuse or misuse of inhaled long-acting beta2-agonists.

No adherence to anti-inflammatory medications (e.g., refilling the prescription less than half as often as would be required if the directions on the prescription were followed).

Failure to achieve quick and sustained response (i.e., beginning within 10 to 20 minutes and lasting longer than 3 to 4 hours) to short-acting beta2-agonists during an acute asthma episode (as measured by a decrease in symptoms or an increase in peak expiratory flow rate).

Poor tolerance to physical activity (i.e., the patient experiences symptoms of exercise-induced asthma).

Missing school or work because of asthma symptoms.

An emergency department visit or hospitalization for asthma.

2. Instruct patients about the proper techniques for inhaling medications

Inhaled medications are preferred over oral therapies. However, a major limitation in their effectiveness is the patient's ability to use the device appropriately. Studies suggest that members of the health care team (e.g., physicians, nurses, and pharmacists) may not adequately instruct patients on how to use a metered-dose inhaler (MDI).  Improper MDI technique can be one cause of a poor response to therapy. Pharmacists can play an important role on the health care team by teaching patients with asthma about proper medication technique. Other devices, such as dry powder inhalers, breath-actuated inhalers, and nebulize, are also available, and they require different techniques for administration. A placebo inhaler, which can be obtained from pharmaceutical manufacturers, and instructional videos, may be useful in demonstrating proper

technique.

3. Monitor medication use and refill intervals to help identify patients with poorly

    Controlled asthma.

During symptomatic periods, selective short-acting inhaledbeta2-agonists may be sufficient to relieve asthma symptoms. When asthma is stable, it is preferable to use these agents on an as-needed basis. Overuse and over reliance on short-acting inhaled beta2-agonists can be signs that asthma is poorly controlled. During an exacerbation, patients may increase the dose and/or frequency of use, which may lead toa delay in seeking appropriate medical care.

Pharmacists may find indications of chronic overuse of medical history and the frequency of refills.  Overuse can be defined as using more than one canister per month of short- or long-acting beta2-agonists or more than one canister of  a short-acting beta2-agonists in 2 months when used in conjunction with a long-acting agent. Pharmacists should also monitor for overuse of a long-acting beta2-agonists (e.g., salmeterol). In general, these agents should not be used more than twice a day and are not appropriate to relieve acute symptoms.

If overuse is noted, pharmacists should alert the physician, who can assess the need for reevaluation of the patient and consider whether the patient needs to initiate or intensifyAnti-inflammatory therapy. Before contacting the physician, pharmacists should have the patient demonstrate his or herMDI technique. Poor technique may be one of the causes of Overuse of an MDI. The physician will find this information useful in making a decision on how to respond to the situation. Physicians also may want to evaluate recent trends in peak flow meter readings.

Physicians will consider several factors when deciding whether to initiate or increase anti-inflammatory therapy. In general, a short course of oral corticosteroids may be indicated if the excessive use of an MDI is short term; due to an acute, severe episode; or the result of an isolated exacerbation caused by a common cold or other upper respiratory tract infections. The initiation or dose increase of an inhaled anti-inflammatory agent (corticosteroids, cromolyn, or nedocromil) as long-term therapy may be indicated if the patient relies on short-acting inhaled beta2-agonists daily to relieve symptoms, has frequent fluctuations in the peak expiratory flow rate, or has other signs of poorly controlled asthma

Patients on preventive therapy for asthma also should be monitored for signs of no adherence to anti-inflammatory therapy. In some cases, patients do not adhere toanti-inflammatory therapy because they do not understand the purpose of or perceive any immediate benefit from this Therapy. Some patients may be discouraged about following their prescribed regimen because they fear adverse reactions longer than indicated by the directions for use on the Prescription may indicate no adherence. For example, if an inhaled anti-inflammatory agent contains 100 puffs and the directions are to take 2 puffs twice a day, a patient refilling the prescription once every 60 days is underusingthe medication. In this example, the canister should be depleted in 25 days (100 puffs divided by 4 puffs per day =25 days).

4. Encourage patients purchasing OTC asthma inhalers or tablets to seek medical care.

Asthma is one of the very few potentially fatal diseases for which OTC products are available for self-treatment. Use ofOTC inhalers may lead to a delay in seeking appropriate medical care. Pharmacists should refer anyone using an OTC product for respiratory symptoms to a physician for diagnosis, regular monitoring, and proper treatment. The physician can then determine the need for other therapies, such as an inhaled anti-inflammatory agent to prevent

Over-the-counter inhalers contain epinephrine, which is anon selective, weak, and extremely short-actingbronchodilator. Thus, if physicians determine that the PRNuse of an inhaled bronchodilator is indicated, they can that will provide greater efficacy and a longer duration of Combination of ephedrine and theophylline. Generally, bronchodilators are less effective and cause more side effects when administered by the oral route; and combinations of theophylline and ephedrine have the potential to cause synergistic toxicity.

5. Help patients use peak flow meters appropriately.

It is recommended that clinicians consider peak expiratory flow rate monitoring for patients over 5 years of age with moderate or severe asthma. Regular home monitoring may detect decreased lung function and signs of an impending asthma episode before it become more severe. The PEFR is the greatest flow velocity that can be obtained during a forced expiration starting with fully inflated lungs. It provides a simple, quantitative, and reproducible measure of airway obstruction with a relatively inexpensive device that is available without a prescription.

Measuring PEFR in a patient with asthma is analogous to measuring blood pressure with sphygmomanometer or blood glucose to guide insulin dosage. The PEFR is used by the Physician to assess the severity of asthma as a basis for adding medication, monitoring response to chronic therapy, and detecting deterioration in lung function before symptoms develop. The physician may consider more aggressive therapy if the patient's highest value is less than 80 percent of predicted value and/or daily variability is more than 20

Pharmacists should discuss the following items with patients:

The intended purpose of a peak flow meter

(2) How to use it and record the values. The patient's physician should develop an individualized plan for the use of the peak flow meter. The plan should include a threshold value and instructions on what the patient should do if the PEFR drops below this value (e.g., increase medication, call the physician, or seek emergency medical care).

6. Help patients discharged from the hospital after an asthma exacerbation understand their asthma management plan

Every patient being discharged from the hospital for the treatment of acute asthma should receive and understand an individualized asthma management plan. An asthma management plan should include specific written instructions for patients and families. Hospital pharmacists can discuss such a plan with a patient before discharge, reinforcing and clarifying instructions that have been designed to prevent subsequent hospitalizations or emergency department visits. Pharmacists also can review the patient's inhaler and peak flow meter technique and provide instruction, if needed.

Written Guidelines for Patients and Families ¹⁵

Written guidelines should include the following points:

Specific instructions about use of medications, including dose, frequency of administration, guidelines for changing dose or adding medications if appropriate, and adverse effects to report to the clinician.

The importance of long-term preventive medications.

How to monitor body signs or symptoms and/or PEFR to detect increasing airflow obstruction as early as possible; early signs of airflow obstruction vary according to the individual and should be identified for each patient.

Criteria for initiating or modifying treatment: a drop in PEFR or early signs or symptoms.

List of steps to take in managing an acute asthma episode i.e., remove the precipitating trigger, give medication, avoid strenuous physical activity, and keep patient and family calm

Specific criteria for seeking emergency medical care, including a pattern of declining PEFR; failure of medications at home to control worsening symptoms; difficulty in breathing (wheeze may be absent), walking, or talking; intercostal retractions; blue fingernails or lips.

Observable signs that long-term therapy is less than optimal, such as asthma symptoms that cause sleep interruption, consistently low or highly variable PEFR,and/or too frequent use of short-acting inhaled beta2-agonists.  Such signs should be promptly discussed with the clinician.

CONCLUSION:

Asthma is a complicated disease with a multitude of clinical presentations. The exact defect in asthma has not been defined, and it may be that asthma is a common presentation of heterogenous group of diseases. Asthma is defined and characterized by excessive reactivity of the bronchial tree to a wide variety of noxious stimuli. The reaction is characterized by bronchospasm, excessive mucus production, and inflammation. The central role of inflammation in inducing and maintaining BHR is now becoming widely appreciated and studied. The goal of asthma therapy is to normalize, ass much as possible, the patient's life and prevent chronic irreversible lung changes. Drugs are the mainstay of asthma therapy. The goal of drug therapy is to use the minimum amount possible to completely control the disease. In chronic asthma, therapy should be aimed at both bronchospasm and inflammation in order to produce the best results. Patients should be followed and nonitored diligently for toxicities. Although death from asthma is an uncommon event, the most common cause of death is underassessment of the severity of obstruction either by the patient or by the clinician; the next common cause is undertreatment. A corner stone of any therapy is education and the realization that most asthma deaths are avoidable.¹⁶

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URL://http//www.cleveland clinicmeded.com. Accessed on August 16, 2006

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Accessed on August 30, 2006.

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Joseph T. Dipiro, Robert L. Talbert, Gury. C. Yee, Gary R Matzke, Barbara G. Wells, L. Michael Posey, editors. Pharmacotherapy a pathophysiologic approach. 5^th ed. Mcgraw-hill; 2002. p 475-508.

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Cite this: Abey T Thomas, R. Raj, "Asthma, a comprehensive outlook", B. Pharm Projects and Review Articles, Vol. 1, pp. 43-79, 2006. (http://farmacists.blogspot.in/)

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Tuesday, April 21, 2009

ASTHMA, A COMPREHENSIVE OUTLOOK

ASTHMA, A COMPREHENSIVE OUTLOOK

· MANAGEMENT GOALS

·
PRINCIPLES

® Pharmacotherapy

· Principles of medication

¨Dose

C. CONTROLLERS

· Long-acting ß₂agonist (LABA) inhalers

· Leukotriene receptor antagonists

OTHER DRUGS

DEVICES FOR DELIVERING INHALED THERAPY IN CHILDREN

LUNG FUNCTION TESTING

IMMUNOTHERAPY

SPECIAL CONSIDERATION IN CHILDHOOD ASTHMA

· Pharmacotherapy for asthma in children younger than 5 years of age

Tapering and terminating therapy

32 comments:

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Join Here to Get Full Text "B. Pharmacy Projects"

Tuesday, April 21, 2009

ASTHMA, A COMPREHENSIVE OUTLOOK

ASTHMA, A COMPREHENSIVE OUTLOOK

· MANAGEMENT GOALS

· PRINCIPLES

® Pharmacotherapy

· Principles of medication

¨Dose

C. CONTROLLERS

· Long-acting ß2 agonist (LABA) inhalers

· Leukotriene receptor antagonists

OTHER DRUGS

DEVICES FOR DELIVERING INHALED THERAPY IN CHILDREN

LUNG FUNCTION TESTING

IMMUNOTHERAPY

SPECIAL CONSIDERATION IN CHILDHOOD ASTHMA

· Pharmacotherapy for asthma in children younger than 5 years of age

Tapering and terminating therapy

32 comments:

Total Pageviews

Visit us on Facebook

Welcomes You

Search This Blog

·
PRINCIPLES

· Long-acting ß₂agonist (LABA) inhalers