Theme Symposium CURRENT MANAGEMENT : ASTHMA Swati Bhave* and Harish K. Pemde** From the: *Visiting Consultant in Pediatrics, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India. ** Associate Professor of Pediatrics, Department of Pediatrics, Kalawati Saran Children’s Hospital, Lady Hardinge Medical College, New Delhi 110 001, India. Correspondence to: Dr.Swati Bhave, C-II/44, Shahjahan Road, New Delhi, India. E-mail: sbhave@vsnl.com Prevalence of asthma is increasing and a lot of developments have occurred in its management. Most of the patients can be very well managed in office practice and only a minority of patients requires emergency care or hospitalization. Clinical staging of asthma has made the decisions for drug therapy easy and objective. Inhaled drugs have made management of asthma easier and effective with minimal side effects. Availability of newer drugs and inhaler devices has further simplified the management. Partnership with family for reduction of risk factors and control of environmental factors is important. The patient/parent education improves the management of asthma at home and early and timely referral to emergency department. Well managed asthma in children will help the patients in leading a near normal life including participation in sports and other physical activities. This article describes the management of asthma in children in office practice. INTRODUCTION DIAGNOSING ASTHMA THE prevalence and severity of childhood asthma have increased substantially in recent years. Despite continued research and the development of new pharmacological agents, it is one of the leading causes for emergency care requirements, cause for considerable morbidity, and occasional mortality at all ages. A good history and clinical examination usually suffice to diagnose masthma in most patients. A diagnosis of asthma should be considered if the following features are present: The most important point is that this can be very well managed from clinic or office of a physician. This article describes the essential components of management of asthma in children in office practice. • • • Unexplained cough, especially during night or after exercise; Recurrent episodes of wheezing, with or without respiratory distress; Tightness of chest or discomfort after exercise or exposure to any irritant. DEFINITION There are several definitions available but based on the functional consequences of airway inflammation, an operational description of asthma is has been given by Global Initiative for Asthma (GINA) 2002 as follows. Asthma is chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation causes an associated increase in airway hyper responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, coughing, particularly in night or in the morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. Apollo Medicine, Vol. 2, No. 4, December 2005 334 Table 1: Parents of the children suspected to be asthmatic should be asked the following key questions when considering asthma. (a) Troublesome cough which is particularly worse at night? (b) Awakened by coughing or difficulty in breathing? (c) Does their child experience breathing problems during change of a particular season? (d) Does the child have had an attack or recurrent episodes of wheezing (high pitched whistling sounds when breathing out)? (e) Does the child cough, wheeze or develop chest tightness after exposure to airborne allergens or irritant, e.g., smoke, dust etc? Theme Symposium Differential diagnosis Diagnosing asthma and labeling a child as asthmatic are at times difficult. The younger the child, the greater the likelihood is that the recurrent wheezing can be explained by some mechanism or alternative diagnosis. Recurrent wheezing in infancy can be caused by a large number of diseases. All that wheezes is not asthma. Alternative or additional diagnosis should be considered when the history is atypical or the response to proper medical treatment is poor. It is important to realize that asthma may often coexist with other conditions. A large number of conditions can result in symptoms suggestive of asthma. Common conditions to be considered in atypical cases are given in Table 2. A trial of treatment is probably the most confident way of diagnosing asthma in children. Any child who has recurrent episodes of wheezing after ruling out the alternative diagnosis may be treated as asthma in order to benefit the child with medicines which will reduce the severity of symptoms and will prevent the life threatening episodes. These aspects should be discussed with the family and appropriate treatment should be given. Laboratory investigations Asthma is mainly a clinical diagnosis. Although some investigations may be done to rule out alternative diagnosis. Chest X-ray and eosinophil count are useful. Pulmonary function test (PFT) In children younger than 5 years it becomes important to distinguish between early onset asthma versus wheeze associated lover respiratory infection (WALRI) .This is because early onset asthma requires intensive therapy where as WALRI requires treatment only for each episode and most children will not have symptoms after the age of five and the parents can be given a good prognosis PFT is not available easily in many centres especially rural setups. Is very important but not essential for diagnosis. However, it plays an important role in doubtful cases and in monitoring of response of treatment. Peak Expiratory flow rate (PEFR) can be done in children as young as 3-4 yrs (Tables 3 & 4) but full Spirometry is generally possible only by age 6 or 7 years. In WALRI, infants have recurrent wheezing episodes triggered by viral upper respiratory infections. They generally have no atopic features like seborrhea, dermatitis, or family history of asthma or atopy. They may respond less optimally to bronchodilators Treating a child with asthma Early onset asthma infants may have atopic background and may continue to have recurrent episodes of wheezing often severe enough to warrant hospitalization. They have a strong family history and respond well to bronchodilators 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. This definite and practical approach has been used world wide with satisfying results for both the patient and the doctor. Treatment goals The treatment plan should be aimed for: Table 2: Differential diagnosis of asthma in children. • • • • • • • • • • • • • • • • Laryngotracheomalacia Foreign bodies in airway or esophagus Chronic viral infections (including HIV related infections of the lungs) Bronchiolitis Endobronchial tuberculosis Pertussis Croup Gastroesophageal reflux Aspiration syndromes Bronchiectasis Immunodeficiency diseases Cystic fibrosis Tropical eosinophilia Congenital anomalies of respiratory, gastrointestinal or cardiovascular systems Primary immune deficiency Primary ciliary dyskinesia syndrome 1. Freedom from 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. Satisfaction of patients and relatives. 8. Improve quality of life. For achieving these goals 6 components should be followed. 1. Develop a partnership with family. 2. Assessment and monitoring of asthma severity. 3. Avoid exposure to risk factors. 335 Apollo Medicine, Vol. 2, No. 4, December 2005 Theme Symposium Table 3: Peak expiratory flow rate (PEFR). • Peak expiratory flow rate (PEFR) is the fastest rate at which air can move through the airways during a forced expiration. • PEFR can be easily measured by a simple device the peak flow meter, which is a small, portable and inexpensive device. • The peak flow during forced exhalation occurs after about 25 % of the vital capacity has been exhaled .It does not require a complete exhalation like a spirometer; even a dyspneic patient is able to perform the test. • PEFR provides simple, quantitative measure of airflow obstruction, which can be performed in home, school, and work place for a quick measure of lung function. • PEFR should be done at least once a day in all individuals who have more than mild asthma severity. PEFR can provide direct assessment of airflow limitations, diurnal variation and reversibility. The test should be done in the morning and compared with the patient's best effort. • Patient's best effort is taken as the average reading taken when the patient is a symptomatic over a period of 2 - 3 weeks. PEFR measurements instructions: 1. Place indicator at the base of the scale 2. Stand up and take deep breath 3. Place meter in mouth and close lips around the mouth piece 4. Blow out as hard as possible (same as blowing a balloon) 5. Write down achieved measurement 6. Repeat process two more times 7. Record the highest of the values achieved Reinforcement of proper technique at every visit is important. Same PEFR meter to be used by the patient at all times. Good control is maintaining PEFR at above 80 - 90 % of normal. A drop in more than 50 - 60 % is indication that the attack is severe and medical help may be needed. Daily monitoring can also help in monitoring environmental triggers. Peak flow reading taken regularly can give a warning of an impending attack of broncho-spasm before it starts. One can thus prevent it by stepping up the 'Controller' therapy.The diurnal peak flow variation of a patient with asthma is often more than 20%. An asthmatic's peak flow graph shows wide fluctuations giving a 'saw-toothed' appearance. The more wide the fluctuations, the more severe the asthma. Diurnal variability <20% indicates good control of asthma or asthma in remission. Table 4: Spirometry. The findings in asthma are: • Increased total lung capacity, Functional residual capacity and residual volume. • Decrease in vital capacity • Decreased dynamic tests of air flow i.e. FEV1, FVC, Maximum expiratory flow between 25 - 75 % of vital capacity FEV1 is considered single best measure of lung function to assess asthma severity. FEV25-75 is used to assess function of smaller airways in children. Indications for spirometry: 1. At the time of initial diagnosis 2. After patient has stabilized on treatment 3. At least 1 - 2 yearly for periodic check on PEFR in moderate to severe asthmatics 4. When reducing the dosage of medications Spirometry results only reflect the lung function at the time of testing and thus can be normal since asthma is a dynamic condition. The procedure is expensive and the equipment is not widely available. Hence it has a restricted role in the diagnosis of asthma in Indian setting. Apollo Medicine, Vol. 2, No. 4, December 2005 336 Theme Symposium Medications in Asthma 4. Define long term management plan. 5. Establish plans for management of exacerbations. 6. Ensure regular follow up care. These are classified as relievers used for relief of acute attacks and controllers used for long term management as prophylactic (Tables 5 & 6). Develop a partnership with family It is important to educate family and if child is old enough then the child too, about the nature of the illness and the likely course of the illness. They should be clearly told the steps child and family has to observe about the other parts of asthma management. Avoid exposure to risk factors In several patients some allergen might be found in the environment. An attempt should be made to find any precipitant of acute exacerbations. Most of the times, it is not possible to pin point the precipitant. However, following measures improve control of asthma symptoms. • • • • • • • • • Encase mattress, pillow, and quilt in impermeable covers. Wash all bedding in the hot cycles (55-60ºC) weekly. Replace carpets with linoleum or wood flooring. Minimize upholstered furniture/replace with leather furniture. Replace curtains with blinds or easily washable curtains. Hot wash/freeze soft toys. Keep the pets out of the main living areas and the bedroom. Avoidance of indoor air pollutants like active and passive smoking. Avoid foods containing preservatives. Classification of asthma severity and treatment protocol Assessing asthma severity First step in the patients stepwise therapy is assess the patients’ disease severity. This is done by evaluating the symptoms, history, current treatment/medications and the response, clinical examination and when possible objective measurement of lung functions to establish base line and to assess and monitor severity. It is recommended that spirometry (whenever possible) be used in an initial diagnostic work-up. Asthma treatment is given in step up and step down manner depending upon the severity of the disease Hence, the first step in management is to assess and grade the degree of severity as severe persistent, moderate persistent, mild persistent and mild intermittent, to decide which step in the treatment protocol to put the patient on (Tables 7 & 8). An individual child is assigned to the most severe grade in which any of the above parameter occurs. Individual’s classification may change over time. Further, if the patient is already on treatment for asthma, severity classification should be interpreted in context of both, the step of treatment as well as the current clinical features. Thus, a patient may be reclassified as moderate persistent, if Table 5: Asthma medications. 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 (i) (ii) (iii) (iv) (v) Inhaled and oral steroids Long acting beta-2 agonist (inhaled salmeterol or sustained release salbutamol) Leukotriene antagonist Cromolyn sodium Methylxanthines sustained released 2. Quick relief therapy or short acting bronchodilators (i) Inhaled short acting beta-2 agonist (salbutamol, terbutaline) (ii) Inhaled anticholinergics (ipratopium bromide) (iii) Oral steroids (iv) Rescue steroids are oral prednisone at 1-2 mg/kg for a short duration of 1-5 days to be used in an acute attack. Short course of less than five days does not need tapering. All patients requiring controller medication should, in general be evaluated to determine the role of environmental factors involved in their symptoms. 337 Apollo Medicine, Vol. 2, No. 4, December 2005 Theme Symposium Table 6: 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. • Dry powder inhalers are other simple devices for use in children over 4-5 years of age. Table 7: Clinical classification of asthma. Degree Symptoms Acute attacks Physical activity Night symptoms FEV1/PEFR Need of medications Severe persistent asthma Daily Very frequent Limited Frequent or daily 60 % of predicted PEFR variability >30 % Needs chronic treatment Moderate Persistent Asthma Daily Twice a week Affected more than once a week 60-80%, of predicated PEFR variability >30 % Needs dailyinhaled short acting beta-2 agonist Mild persistent asthma < once a day But > once a week Affected daily activity More than twice a month 80% of predicated PEFR Variability 20-30% Needs beta agonist for attacks Nil PEFR 80 % PEFR variability <20 % PEFR normal in between attacks Needs beta agonist for attacks Mild intermittent asthma <once a week <twice a month Table 8: Severity of asthma when patient is on controller drugs. Current Treatment Asthma symptoms over last several weeks similar to those Step Mild intermittent Mild persistent Moderate persistent C ur r e n t L e v e l s o f a s t h m a s e v e r i t y* Step-1 1 2 3 Step-2 2 3 4 Step-3 3 4 4 Step-4 4 4 4 *1-Mild intermittent, 2-Mild persistent, 3-Moderate persistent, and 4-Severe persistent. despite being on step 2, clinical features of mild persistent are still present. Define long term management plan The gold standard for long term management is inhaled steroids. The molecule that has been the longest in the market is Beclamethasone Dipropionate. It is very effective and the cheapest. However, in higher doses it does have Apollo Medicine, Vol. 2, No. 4, December 2005 systemic absorption and affection of the HP Axis. Budesonide is costlier than Beclamethasone, but being more potent is required in a lesser dose and has much lesser effect on the HPA axis. Fluticasone has the least systemic absorption and being lipophilic has better action on the target cells however it is the costliest. Which one to select will depend on the physician’s clinical experience, the patient’s choice and economic condition of family. If 338 Theme Symposium higher doses are required it is better to chose budesonide or fluticasone for lesser toxicity. Fluticasone was marketed initially for children above 4 yrs but now some research trials are showing that it can be used as early as eighteen months (Table 9). Step 3 (Moderate persistent asthma) Depending on asthma severity the medications are recommended alone or in combinations and varying doses. • • Stepwise drug therapy Step 1 (Mild intermittent asthma) • • No long term controller therapy is needed. • Beta-2 agonists (salbutamol, levo-salbutamol, terbutaline) are used as and when necessary including before exercise, in case child develops symptoms with exercise. • Step 4 (Severe persistent asthma) • Oral beta-2 agonist syrup may be appropriate for infants and toddlers when inhalation therapy is not available or feasible. Step 2 (Mild persistent asthma) • Inhaled low dose glucocorticosteroid (beclomethasone, budesonide, fluticasone) (100-400 microgram budesonide or equivalent) is the drug of choice. • Sustained-release theophylline is an alternative and has mild anit-inflammatroy action • Leukotriene modifiers are best used as add on therapy with inhaled steroids when the steroids are needed in high doses .They have the advantage of single oral dose specially in younger children They can reduce the requirement of steroids in patients with moderate to severe asthma and may improve asthma control as an additive effect.They also are useful as add on therapy when tapering down high doses of steroid. However, most studies show that they are less effective than long acting inhaled beta-2 agonists as add on therapy. There are some studies showing benefits of using Leukotriene antagonists alone as a controller drug. However, it is still not recommended as a mono therapy for severe and moderatively severe persistent asthma. A combination of moderate dose of inhaled steroids and inhaled long acting beta-2 agonist (salmeterol, or formoterol) is preferred. They have best synergistic action. Other options are use moderate dose of inhaled steroids (400-800 microgram budesonide or equivalent), and add or leukotriene modifiers (monteleukast, zafirleukast) or sustained release theophylline. Inhaled glucocrticosteroid in higher doses (>800 microgram budesonide or equivalent) may also be given as a single drug. But one has to monitor for side effects with such high doses High dose inhaled steroids (>800 microgram budesonide or equivalent) and long acting bronchodilator (inhaled beta-2 agonist or theophylline) or leukotriene modifier are given. Oral steroids in once daily dose added may be useful. For brittle asthma one has to give drugs like immunosuppressant therapy Initiation of therapy Is it advisable to start at higher step than patient's severity and then step down?. 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 3-6 months or earlier if symptoms recur 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. Stepping up or down the treatment plan Low dose Medium dose High dose The patient should be followed at least every 3 months and every time severity should be assessed using the criteria given above. Whenever, patient moves up or down in the severity then tmreatment should also be changed accordingly. Treatment can therefore be stepped “up” or titrated against the symptomatic class. Stepping “down” should be attempted once the patient achieves control and is able to maintain it for a practically sufficient length of time (5-6 months). Beclomethasone Dipropionate 100-400 400-800 >800 Seasonal variability Budesonide 100-200 200-400 >400 Fluticasone 100-200 200-500 >500 Patients with seasonal allergic disease may require maintenance medication, but only just before season continuing till the risk persists. Other patients with chronic Table 9: Comparative doses of inhaled steroids (microgram/day). Drug 339 Apollo Medicine, Vol. 2, No. 4, December 2005 Theme Symposium 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. 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. Management of exacerbation beta-2 agonists then give one dose of oral steroid (prednisolone) and contact physician. The patient should be taken to emergency room if: • • • • Asthma exacerbations are acute episodes of progressive worsening of breathing, cough, wheeze and chest tightness. These exacerbations are characterized by decrease in PEFR whish in turn can be easily quantified by PEFR meter or spirometer. These objective measurements indicate severity more accurately than symptoms. Management of exacerbations in clinic/office Mild to moderate exacerbations can be treated at clinic. Following steps can be taken. Assess the severity of exacerbation by PEFR • Acute asthma The aim in management of acute asthma is: • • • Correct significant hypoxemia (O2, mechanical ventilation rarely needed). Reverse airflow obstruction as rapidly as possible. Reduce inflammation and risk of recurrence by intensifying therapy. Early treatment is important to prevent hospitalization and/or the attack from becoming severe. The following points are important for the same: 1. Provide written instruction to patient for home treatment. 2. Early diagnosis of worsening by PEFR meter 3. Early contact with doctor regarding clinical or PEFR changes. 4. Early increase in therapy (beta-2 agonist, oral steroids). 5 Remove precipitating factors, if any. • • • • If available PEFR can be measured. This may be decreased by 20 % from the baseline. Start with short acting B2 agonist with Mask/Spacer every 20 minutes for 3 times. If patient improves with this, give it every 4-6 hourly and report to the physician. If patient does not improve after 3 doses of short acting Apollo Medicine, Vol. 2, No. 4, December 2005 PEFR <50 % of expected, requires immediate treatment but start process of indoor admission for further management If PEFR is between 60 -80 % of expected • • • • • • Home management Asthma exacerbations can be identified by increase in cough, wheeze and breathlessness. Following steps can be taken at home. All parents of children with asthma should be explained this and preferably a written treatment plan should be given to them for managing exacerbations. The patient is a high risk for asthma-related death. The exacerbation is severe (PEF remains less than 60 percent of predicted or personal best after B2 agonist therapy) There is no improvement after 3 doses of bronchodilator There is further deterioration • • • Begin nebulization with salbutamol (0.15 mg/kg/dose). Give three dose at the interval of 20 minutes. Levosalbutamol and ipratropium bromide can also be used in place of salbutamol. Oxygen if available in the office/clinic should be also started. If patient does not improve then try intradermal terbutaline. This will open up the airways and then the nebulizer will be more effective. Ipratropium is used mainly in small children specially with spasmodic cough and when there is tachycardia with salbutamol. Give one dose of steroid (prednisolone). Rescue steroids should be given for 3-5 days. Assess the severity and whether improvement is present. Even after this, if the patient does not improve then this child should be referred to emergency department for further management. If patient improves, observe for an hour and send home. Patient should be given a proper medication plan and advised emergency admission if no improvement or any deterioration. Follow-up care • • 340 Asthma is a chronic illness and patients require a regular follow up to assess control and to assure safety of treatment. Patients should receive routine follow-up at scheduled Theme Symposium • • • • intervals. Measurement of pre- and post-bronchodilator pulmonary function 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 at least once every year. In susceptible patients, increased blood pressure may be a systemic effect of 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 singlemaintenance medication may be followed once every 6 months. to know how to recognize symptom patterns indicating that their asthma is getting out of control. This can prevent emergency room visits and hospitalizations 2. Roles of medications–difference between quick relief and long term controller drugs should be well explained. 3. Explain and monitor at each visit the skills needed for inhaler and spacer use and self monitoring with PEFR meter. 4. Environmental control measures and avoidance measures should be discussed. 5. When and how to take rescue steps, according to the given written treatment plans. Acknowledgments The authors wish to acknowledge the contribution of Dr.Kush Jhunjhunwala, Senior Resident, and Dr. Vipul Shandilya, Research Officer, Kalawati Saran Children's Hospital, New Delhi in preparation of the manuscript of this article. REFERENCES Patient education Education of patient and active partnership of patient and doctor is the cornerstone of asthma management. Starting patient and family education at the time of diagnosis, integrating it into every step of clinical asthma care, and tailoring it specifically to the needs of each patient, with sensitivity to cultural beliefs and practices are important. 1. British Thoracic Society (BTS) Guidelines for the management of asthma-2003, Thorax 2003; 58 (Suppl); i-i 94. 2. Keeley D, Rees J. New guidelines on asthma management. Br Med J 1997 Feb 1; 314: 315-316. 3. Meenu Singh. Newer drugs for asthma. Indian J Pediatrics 2004 Aug; 721-727. 4. Global initiative for asthma (GINA)–Update 2003. 5. Asthma by consensus-IAP Respiratory Chapter, 2003. Patient education should cover 6. Ghai OP, Essential Pediatrics, 6th edn, pp. 354-365. 1. Basic asthma facts should be told to parents and children (if older) for them to understand their asthma; 7. Kabra SK, Lodha R. Long term management of asthma. Indian J Pediatr 2003; 70: 63-72. 341 Apollo Medicine, Vol. 2, No. 4, December 2005