C T Deshmukh
Asthma Management Guidelines
Various expert committees and global expert panels have reviewed scientific literature over the past many years and have recommended the stepwise management of asthma according to asthma severity. Nearly all the national asthma programs have been following these guidelines. This definite and practical approach has been used world wide with both the patient and doctor satisfaction.
Among the few recommendations are:
- Stepwise approach to using medications and early use of anti-inflammatory medication especially in persistent asthma to gain and maintain control of asthma.
- Classifications of asthma severity linked to treatment alternatives.
- Prevention of asthma and its risk factors by reducing exposures to environmental allergens and secondhand tobacco smoke helps in optimal asthma control and reducing the dose of medications.
- Identifying specific allergens for each patient by detail history and allergy testing, and recommendations for reducing exposures to these allergens
- Emphasis on teaching asthma self-management and prevention risk factors to patients
- Treatment according to patient’s cultural, ethnic and economic factors
- Objective measurement to be recommended wherever possible (PEFR meter)

First step in the patients stepwise therapy is assess the patients disease severity. This is done by evaluating the symptoms, history including financial history, current treatment/medications and the response, clinical examination and when possible objective measurement of lung function to establish base line and assess severity. It is recommended that spirometry, which measures lung function, be used in an initial diagnostic work-up.

Classification of Asthma severity:
Severe persistent asthma - Step 4
• Continuous complaints. Frequents acute attacks. Limited physical activity.
• Frequent or daily night symptoms.
• FEV1/PEFR < 60% PEFR variability > 30%

Moderate persistent asthma - Step 3
• Daily complaints. Needs daily-inhaled beta 2agonist. Gets acute attacks twice a week.
• Nocturnal symptoms more than once a week.
• FEV1/PEFR 60 - 80% PEFR variability > 30%

Mild persistent asthma - Step 2
• Complaints more than twice a week but less than once a day. Acute attacks affect daily activity.
• Nocturnal symptoms more than twice a month.
• FEV1/PEFR 80%, PEFR variability 20-30%

Mild intermittent asthma - Step 1
• Complaints twice a week.
• No complaints in the night. PEFR normal between attacks. Attacks short duration and less than twice a month.
• FEV1/PEFR 80 % PEFR variability < 30 %

Individual is assigned to the most severe grade in which any of the above parameter occurs. Individual’s classification may change over time. At any level patient can have mild, moderate or severe exacerbation of asthma.
For patient management in the stepwise plan the asthma drugs are divided into two groups. This classification reflects how we use the medication, not what the mechanism of action is.

1. Long term therapy or controller drugs (maintenance)
i.    Inhaled and oral steroids
ii.    Cromolyn sodium and Nedocromil sodium
iii.    Leukotriene antagonist
iv.    Long acting beta2 agonist (inhaled Salmeterol or sustained release salbutamol)
v.    Methylxanthines sustained released
2. Quick relief therapy or short acting bronchodilators
i.    Inhaled short acting beta2 agonist (salbutamol, terbutaline)
ii.    Inhaled anticholinergics (ipratopium bromide)
iii.    Oral steroids

Depending on asthma severity the above medications are recommended alone or in combinations and varying dosages.

Stepwise therapy summary:
Step 1:
•    First intervention should be a ß2 agonist delivered promptly by an age-appropriate inhalation device. This is given repeatedly when needed. It is also the treatment of choice for prophylaxis of exercise-induced asthma.
•    An oral ß2 agonist syrup may be appropriate for infants and toddlers with trivial symptoms who have never required emergency care, in order to avoid the expense and bother of a nebulizer.
•    If sub responsiveness to beta-2 agonists is present, then high dose oral corticosteroids should be given and continued until the patient is symptom-free for 24 hours. This usually requires 5 to 10 days of therapy.

Step 2:
•    If poor response or needs daily use of short acting brochodilators, one of these drugs given twice a day, can be started to prevent asthma exacerbations, depending on preference for inhaled or oral medication.
1)    Inhaled low dose corticosteroids.
2)    Slow-release Theophylline
3)    Inhaled cromolyn or Nedocromil sodium.
4)    Consider Leukotriene antagonists for older patients.
•    Most prefer low dose inhaled steroids. Cromolyn administered by nebulizer solution may be an alternative for young children who cannot use a metered dose inhaler, even with an assist device. However, this modality is more costly and time consuming, requiring multiple daily treatments.

Step 3:
•    If symptoms are not controlled or daily short acting brochodilators are needed then two drugs may be required for proper control.
•    Try with moderate dose of inhaled steroids first.
•    Add slow release Theophylline or inhaled Salmeterol if no response.
•    Alternate-morning administration of shorter-acting oral corticosteroids such as prednisone, prednisolone, or Methylprednisolone can be given as an alternative to inhaled corticosteroids for most patients who cannot or will not comply with inhaled corticosteroids.
•    One or two maintenance medications at a twice-daily schedule with judicious use of a pre-exercise beta-2 agonist and appropriate measures of intervention, is generally sufficient for control of asthma.

Step 4:
•    Patients who are still not free from symptoms and need more than once a day short acting bronchodilators need at least two drugs for prevention of asthma.
•    High dose inhaled steroids are given.
•    And long acting bronchodilator (inhaled or oral  beta 2 agonist or theophylline)
•    And/or oral steroids

All patients requiring maintenance medication should, in general be evaluated to determine the role of environmental factors involved in their symptoms. This evaluation involves careful history and skin testing for specific IgE. This would be particularly relevant for patients requiring more than either Theophylline or low-dose inhaled steroids for maintenance. Specific immunotherapy may be tried in severe asthma who need two drugs for control. Each visit special attention is taken to evaluate the compliance and method of delivery of drugs.

Initiation of therapy:
•    Better to start at higher step than patient’s severity and then step down.
•    Achieve rapid control of symptoms by short oral course of steroids.
•    Alternately one can start at a step consistent with patient’s severity and step up if needed.

Maintenance therapy:
•    Start and maintain therapy as mentioned above with either single or combination therapy.
•     Regular patient follow up every 1 – 6 months to decide if changes are needed in stepwise therapy.
•    Before making any changes in step wise therapy check patient’s compliance and environmental control measures.

Intervention alone is sufficient for treatment of those with intermittent asthma. However, patients with chronic disease need maintenance medication in addition, to prevent their daily symptoms. Patients with seasonal allergic disease may require maintenance medication, but only seasonally, and patients with chronic disease may require seasonal increases in their maintenance medication during seasonal allergic exacerbations. Adding or increasing maintenance medication at the times when increased symptoms are anticipated avoids morbidity and decreases the likelihood that urgent care will be needed.

Treatment goals:
Although there is no cure for asthma at present, asthma stepwise treatment along with environmental control measures is designed to provide optimal control of asthma and simultaneously limiting side effects of drugs. The following goals should be aimed for:
1.    Prevent symptoms including nocturnal symptoms and exercise-induced symptoms.
2.    Near normal pulmonary functions.
3.    Maintaining normal physical activity and sleep patterns.
4.    Try to eliminate exposure to allergens and triggers and hence reduce exacerbations.
5.    Reduce need for emergency visits for acute exacerbations and hospitalization.
6.    Reduce dosage and side effects of drugs.
7.    Use of inhaled beta-2 agonist < twice-daily.
8.    Use of short courses of high dose daily oral corticosteroids < 4 times yearly.
9.     Satisfaction of patients and relatives.

Maintenance drugs:
  • Recognition of importance of inflammation in the pathogenesis has led to early use of inhaled steroids and is considered the first line of therapy by most in persistent asthma.
  • Steroids exert multiple effects on the pathogenesis of inflammation which includes interference with arachidonic acid metabolism, synthesis of leukotrienes and prostaglandins, prevention of activation of inflammatory cells and increased responsiveness of  b2 receptors.
  • Systemic corticosteroids should be considered in the management of acute asthma when the patient does not respond readily to bronchodilators.
  • Early use of corticosteroids shortens the course of asthma, prevents relapses, and reduces the need for hospitalization. The early use of corticosteroids is of particular importance in patients who have a history consistent with fatality-prone asthma.
  • Intravenous corticosteroids may be lifesaving in the treatment of severe intractable asthma.
  • After episodes of severe intractable asthma, complete restoration of pulmonary function may require weeks of treatment. Therefore after such events, corticosteroids should be continued at least until symptoms are controlled and pulmonary function is restored.
  • Inhaled steroids are the primary drugs of choice for persistent asthma. Currently available inhaled preparations include Beclamethasone diproprionate, Budesonide, Fluticasone, Flunisolide and triamcinolone.
  • Benefits of inhaled steroids are seen after 2 – 4 weeks of therapy. Aim is to get a daily dose that controls asthma and then step down to minimum dose, which can maintain that control.
  • Moderate to severe asthmatic require high doses inhaled steroids along with inhaled long acting bronchodilators or theophylline.
  • Because of the potential for significant side effects from the prolonged use of systemic corticosteroids (and possibly high-dose inhaled corticosteroids), the need for oral corticosteroids should be monitored by pulmonary function tests, and inadequate control with maximal use of other treatment approaches should be a prerequisite for the long-term administration of systemic corticosteroids.
  • Adverse effects on linear growth from inhaled steroids are dose dependent. There is no evidence growth retardation occurs with the dose of inhaled steroids being less than 400 mg / day.
  • Use of spacers can reduce the dose and side effects and should be used in any patient taking moderate to high doses of steroids.
  • For interventional therapy predinisolone or such equivalent can be given in the dose between 1 - 2 mg/kg per day in 2 - 3 divided doses. Dosage should be continued until the patient is free from symptoms and signs of asthma. The average duration of therapy is 7 days. Dosage should be discontinued without tapering. Oral corticosteroids are as effective as parenteral unless they are not retained.

Doses of inhaled steroids

Drug Low dose (mcg/day) Medium dose (mcg/day) High dose (mcg g/day)
Beclamethasone dipropionate 200 – 400 400 - 600 600 – 800
Budesonide 200 – 400 400 - 600 600 – 800
Fluticasone 125 – 250 250 - 500 500 – 750

Cromolyn sodium and Nedocromil sodium
  • Cromolyn remains the safest drug in asthma.
  • It modulates mast cell mediator release and eosinophil recruitment. Cromolyn has the ability to attenuate both early and late-phase IgE-mediated reactions.
  • It is not effective in acute episodes and may not be useful below 1 year of age.
  • In mild persistent asthma under 5 years of age it can be tried before low dose steroid therapy. Cromolyn can be effective in many patients, alone or in conjunction with bronchodilators, in preventing the symptoms of mild-to-moderate asthma.
  • Two inhalations of the standard metered dose inhaler 4 times daily is the recommended dose.
  • Maximum effect may take 1 – 2 months.
  • Cromolyn can be effective in preventing or diminishing exercise-induced asthma when given 15 to 30 minutes before exercise.
  • Available as inhalers, spinhaler capsules and nebulizer solution.
  • For the treatment of acute severe asthma, Theophylline is less effective than inhaled or injected B2-selective agonists.
  • Bronchodilator effect by: phosphodiesterase inhibition, intracellular calcium modulation and prostaglandin antagonism.
  • Maintenance therapy with Theophylline is effective in reducing the frequency and severity of the symptoms of chronic asthma. It may be similar in effectiveness to cromolyn or b2-agonists. It is generally used along with low dose steroids or cromolyn sodium.
  • Sustained release preparations allow for effective control of nocturnal symptoms.
  • Dose varies with age and other factors, begin dose at 10 mg/kg per day in two divided doses. Final dosage is usually based on the peak serum concentration measurement obtained at steady state.
  • Patients with mild chronic asthma may be controlled at steady-state Theophylline serum concentrations less than 10 ug/ml; patients with more severe disease may require concentrations greater than 10 ug/ml for effective control of symptoms.
  • The rate of Theophylline metabolism varies greatly among patients and is influenced by numerous medical conditions and other drugs. The rate of Theophylline metabolism is reduced, leading to increased serum levels, in such conditions as cardiac decompensation, respiratory failure, hepatic cirrhosis, sustained high fever, viral infections, hypothyroidism, and after administration of cimetidine, oral contraceptives, erythromycin, ciprofloxacin, and disulfiram. In contrast, factors such as cigarette or marijuana smoking, hyperthyroidism, rifampin, phenytoin, carbamazipine, and Phenobarbital increase the rate of metabolism.
  • Oral slow-release formulations provide stable serum concentrations and increases patient compliance. However, the rate and extent of absorption vary between formulations, between individuals, and possibly in the same individual from time to time. Food ingestion may also affect the rate of absorption in different ways depending on the specific formulation.
Do not –    
1) Increase the dose if it is already at lower end of range.
2) Maintain any dose that is not tolerated 
3) Allow generic substitution
Leukotriene antagonists and inhibitors
  • First new class of anti asthma drugs in more than 25 years.
  • They can either block leukotriene receptors (Zafirlukast, Montelukast) or inhibit enzyme 5 lipoxygenase ( Zileuton).
  • They produce long-term bronchodilatation.
  • Main advantage is that they can be taken orally once or twice a day.
  • They may be used instead of steroids in children more than 5 years of age who have mild persistent asthma. They can also be used along with steroids to reduce the doses of steroids. Exact role in management is still evolving.
Long acting Inhaled beta 2 agonist
  • They are used as adjunct to inhaled steroids and other anti-inflammatory agents. Never to be used as single drug therapy.
  • Can be used in nocturnal symptoms.
  • Not to be used for acute attacks.
  • Available as Rotacaps, Inhaler or diskhaler.
  • Given as 25 mg per dose twice a day.

Intervention drugs
Short acting beta2 agonist
  • Beta-agonist bronchodilators vary in their degree of selectivity from non-selective (e.g., isoproterenol) to relatively beta-selective agonists (beta 2-agonists) (e-g., Salbutamol or albuterol, terbutaline). It is preferable to use a selective beta 2-agonist because they have a longer duration of action and are less likely to produce cardiovascular side effects.
  • Inhaled beta 2-agonists are preferable to oral drugs the treatment of chronic asthma because rapid onset of action, are generally more effective than other routes of administration, and infrequently produce adverse reactions. Inhaled beta 2-agonists are generally the safest and most effective treatment for acute asthma. In general, oral 2-agonists should not be administered for the treatment of acute severe asthma. They are available in inhaler, nebulized solution and oral forms.
  • Inhaled beta 2-agonists may be more effective when administered on an as needed basis rather than on a regular basis in the treatment of chronic asthma. If greater than eight inhalations per day (or approximately one canister per month) are needed, the addition of cromolyn, nedocromil, or inhaled cortosteroids should be considered.
  • The administration of beta 2-agonists in the treatment of acute or chronic asthma is not a substitute for the early use of anti-inflammatory drugs.
  • Spacers attached to inhaled b2-agonists improve drug delivery in patients who do not correctly use inhalers. Patients must be carefully instructed, often more than once, in the use of inhaled B2-agonists because a large percentage of patients fail to use inhaler devices correctly.
  • Inhaled Beta 2-agonists are generally considered the agent of choice for prevention of exercise induced asthma. It should be taken 15 to 30 minutes before exercise.
  • Tolerance to B2-agonists may develop after continued use of these drugs and can be associated with an unrecognized decrease in efficacy and delay in seeking medical attention. This may be reversible after the administration of corticosteroids,
  • Tremor and central nervous system effects are minimized by inhalation of B2-agonists, although hypokalemia and significant cardiovascular effects can occur when these drugs are administered by this route. Serious adverse effects from the administration of B2-agonists, when administered in recommended doses, are uncommon when given orally and extremely uncommon when administered by inhalation.
  • B2-agonists when administered by inhalation, can produce a sudden paradoxical increase in bronchospasm, which may be life-threatening in some asthmatic patients.
Inhaled anticholinergic agents
  • Drugs such as ipratropium, appear to be more effective when used to treat patients with chronic mild to moderate asthma.
  • Ipratropium, may be indicated in whom alternative agents have not been sufficiently effective, are inappropriate because of other medical conditions, or have produced unacceptable side effects.
  • Inhaled anticholinergic medication is not sufficiently effective to be used as a single agent in the treatment of acute severe asthma but may benefit when combined with a B-agonist or other primary therapeutic agent.
 Other drugs:
  • Antihistamines can be safely used in most patients with asthma.
  • Based on their ability to block late-phase responses to allergen exposure, newer antihistamines may play a greater role in the future treatment of asthma.
  • There is a strong clinical impression that improvement of upper respiratory tract symptoms by antihistamines in patients who have concomitant allergic rhinitis and asthma may facilitate the treatment of lower respiratory tract symptoms.
Hydration and pharmacomucolytic agents
  • Adequate hydration is recommended for patients with asthma, but careful monitoring of fluid and electrolyte balance should prevent overhydration. Dehydration may occur with severe asthma and should be corrected. However, fluid overload may have adverse pulmonary and circulatory effects and must be prevented by careful monitoring of fluid and electrolyte balance.
  • Guaifenesin and Potassium Iodide may be worth a trial in some asthmatic patients, although the mechanisms of action are unclear.
  • Infections associated with asthma exacerbations are almost always viral in origin and do not require antibiotic therapy.
  • Bacterial infections, such as acute and chronic sinusitis, should be treated appropriately, including the prompt and adequate use of antibiotics.
  • Influenza can be associated with increased asthma. Therefore appropriate immunization is essential in patients with moderately severe or severe asthma.
  • Routine vaccinations are not contra-indicated in patients with asthma or other allergic conditions. Patients who have a history of egg sensitivity should be skin tested with the vaccination material.
  • Short-term, low-to-moderate dose systemic corticosteroids, alternate-day corticosteroids, or topical corticosteroids are not immunosuppressive and are not a contraindication for immunization.
  • Influenza vaccine and pneumococcal vaccine are recommended for patients with chronic pulmonary disease including asthma.
Drug delivery:
  • Where ever possible inhaled route of drug delivery is the preferred route in asthma except for theophylline.
  • Metered dose inhaler (MDI) can be used for a child who is about 6 – 7 years and is trained properly with the technique. It is better to use an assist device or spacer when using MDI for children.
  • Inhaled therapy with the metered dose inhaler (MDI) has been effectively used for smaller children with the aid of a mask.
  • MDI with spacer should be the device of choice in children as it is simple and convenient form of therapy and can be used in an acute exacerbation.
  • Children who are unable to take medication with MDI or cannot tolerate it can be given the medication via the nebulizer.
  • Dry powder inhalers are other simple devices for use in children over 4 – 5 years of age.
Physicians and patients have several options to use the inhalation drugs in asthma and the device selected will depend on age, cost and convenience of the patient.

  • There is a strong link between inhaled allergens and asthma. Exposure to irritants or allergens, which the patient is sensitive to, increases the symptoms and precipitates asthma exacerbations.
  •  It is very important to take a careful history to identify such factors. History is usually adequate for seasonal allergies.
  • If available, skin testing and in vitro testing for specific IgE antibodies may be useful to identify perennial indoor allergens.
  •  Once asthma triggers have been identified the next step is to reduce the exposure to those triggers. Avoidance of triggers requires a high level of commitment on part of the patient and family.
  • Avoidance is most important in moderate to severe asthmatics and may help in reducing the dosage or need for medication. Aspects of responsibility for treatment may apply to all environments in which the child spends a significant amount of time, such as preschool, school, or day care. The greatest effort is spent in relation to the bedroom, where children spend a major part of their time.
Recommendations (where ever possible):
  • Annual influenza vaccine for patients with persistent asthma.
  • Skin testing / invitro testing for at least in persistent asthma.
  • Not to use chemicals to kill house dust mites / cockroaches.
  • Aspirin not to be used in persons sensitive to it.
  • Avoid exposure to all tobacco smoke limiting exposure to allergens they are sensitive to, other irritants, as well as to house dust mite, cockroach, mold, animal, and pollen allergens..
  • Avoid exertion when air pollution levels are high.
  • Exercise-induced bronchospasm is common in children. Pretreatment with B2-agonists and/or Cromolyn Sodium can prevent symptoms. Optimal control of chronic asthma by anti-inflammatory therapy also can decrease the frequency and intensity of exercise induced asthma.
  • Avoid taking nonselective b-adrenergic antagonists (blockers for migraine, stage fright)
  • Consider allergen immunotherapy when connection between symptom and exposure to unavoidable allergen is clear and symptoms occur during most of the year.
  • The use of Acyclovir and/or varicella immune globulin should be considered in children who have a negative varicella history and/or antibody titer and who receive or recently have received systemic steroids and have been exposed to varicella.
Managing coexisting disease:
Asthma is better managed and drug therapy may be drastically reduced if coexisting diseases are managed. Examples of such diseases include rhinitis, sinusitis, Gastroesophageal reflux disease.

Assessment, monitoring, follow-up:
  • The condition of a patient's asthma will change depending on the environment, patient activities, management practices, and other factors. Thus, even when patients have their asthma under control, monitoring and treatment are needed to maintain control.
  • Consider signs, symptoms, pulmonary functions, quality of life, functional status, and history of asthma exacerbations, current drug therapy patient education, drug delivery techniques and patient satisfaction. Home monitoring of PEFR is an important aspect of asthma treatment.
  • Patients should receive routine follow-up at scheduled intervals to assess control and assure safety of treatment.
  • Measurement of pre- and post-bronchodilator pulmonary function with office spirometry should be performed at each visit.
  • Growth and weight gain should be monitored, because both asthma and treatment with maintenance inhaled or alternate-morning oral corticosteroids have the potential to slow growth.
  • Blood pressure measurement and eye exam for cataracts should be performed on all patients receiving maintenance corticosteroids. In susceptible patients, increased blood pressure may be a systemic effect of corticosteroids. Also, an increased risk of cataracts has been demonstrated even from inhaled corticosteroids.
  • Frequency of follow-up. Patients with an intermittent pattern of asthma can be followed with annual checkups if they meet criteria for control. However, more frequent visits may be required to reinforce instructions.
  • Patients with a chronic pattern of asthma should be followed closely until criteria for control are met. Once disease control is achieved moderate to severe asthmatics should follow up every 3 months. Patients on low doses of inhaled corticosteroid or other single-maintenance medication may be followed once every 6 months.

Asthma Asthma 12/21/2000
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