Ready Reckoner for Treatment in Pediatrics Sumitha Nayak
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Asthma in Children1

 
ASTHMA
 
Definition
Asthma is a chronic inflammatory condition of the lung airways resulting in episodic airflow obstruction. This chronic inflammation results in airway hyper-responsiveness (AHR) to allergens or other inhaled substances. In case of recurrent and long-standing episodes, there is resultant airway remodeling, which could result in compromised airways.
By using the predictive test for asthma, it may be possible to predict the occurrence of asthma in a child with wheezing. The criteria can be divided into major and minor.
 
Major Criteria
  1. History of asthma in parents
  2. Eczema associated with wheezing
  3. Inhaled allergen sensitivity.
 
Minor Criteria
  1. Allergic rhinitis, especially recurrent
  2. Wheezing other than with cold symptoms
  3. Food allergen sensitivity
  4. Increased eosinophils in blood (>/=4%).
The occurrence of one major criteria or two minor criteria provides a 77 percent chance of the persistence of wheezing into adulthood.2
 
Etiology
Genetic predisposition: Familial disposition to hyper-reactive airways
Environmental factors: Asthma can be triggered by some environmental allergens like pollen, nuts, foods, chocolate
  • Recurrent respiratory infection
  • Smoke inhalation
  • Environmental tobacco smoke.
All these factors (Fig. 1.1) trigger airway hyper-reactivity, which eventually results in airway remodeling. This is a single important factor in the progress to asthma in adulthood.
 
Risk Factors
Risk factors in childhood which could be predictive of asthma; are the following:
  1. Recurrent wheezing episodes
  2. Allergic rhinitis
  3. Allergic dermatitis
  4. Allergy
  5. Food sensitization
  6. Inhaled allergen sensitization
    zoom view
    Fig. 1.1: Etiopathogenesis of bronchial asthma with treatment modalities
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  7. Familial history of asthma in parents
  8. Recurrent lower respiratory infection
  9. Bronchiolitis
  10. Environmental tobacco smoke inhalation (Fig. 1.2).
 
Symptoms
  • Recurrent cough with expectoration of mucoid sputum
  • Preceded by cold, runny nose or non-specific viral infection
  • Difficulty in breathing not relieved by usual cough medications
  • Recurrent cough
  • Cough increases during the late night and early morning
  • Cough increases on exposure to aeroallergens
  • Cough increases with exercise
  • Chest pain—non-focal
  • Skin rash and itching associated with cough
  • Flexural eczematous skin patches, more on elbows and knees.
 
Signs
  • Dyspnea
  • Respiratory distress
  • Expiratory wheeze on auscultation
  • Eczematous skin lesions
  • Reduced breath sounds may indicate airway obstruction
  • SPO2 may be reduced on auscultation.
In case of absent breath sounds, it indicates severe airway obstruction and needs urgent treatment.
zoom view
Fig. 1.2: Narrowed bronchial lumen due to edema, as seen in bronchial asthma
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Investigations
No definitive investigation is available. However, when a strong background history of allergy is present, the following tests may aid in the diagnosis:
  1. *CBC, ESR, Absolute eosinophil count (AEC)
  2. Sputum test for eosinophils
  3. Chest X-ray—to rule out any superadded/underlying infections. In asthma, the X-ray shows increased airway markings.
  4. Therapeutic test—response to inhaled short-acting beta-agonists (SABA)—instant improvement is seen in case of hyper-reactive airway disease.
  5. Pulmonary function tests aid in the diagnosis, by showing the extent of airway obstruction and residual airway function. Spirometry is essential to outline the patient's lung function. At times of distress, the peak flow meter reading gives an indication of the airway obstruction.
  6. Lung function tests
  7. Spirometry tests—shows airflow obstruction
    Low FEV1
    FEV1/FVC less than 0.8.
    After broncodilator (SABA) inhalation, improvement is noted.
    FEV1 greater than or equal to 12 percent
    Exercise challenge shows worsened functions:
    FEV1 shows lowered levels, over 15 percent of pretest level
    Diurnal variation in FEV1 noted.
    *CBC-complete blood count
    ESR-Erythrocyte sedimentation rate
    FVC-Forced vital capacity
    FEV-Forced expectorant volume
 
Classification of Asthma
Depending on the degree of control of the asthma, it can be divided into four:
  1. Well controlled
  2. Partly controlled
  3. Uncontrolled
  4. Exacerbation
 
Well-controlled Asthma
  • No day/night time symptoms.
  • No exacerbations
    5
    zoom view
    Fig. 1.3: Inflammation in asthma
  • No need for reliever medication
  • Normal lung functions—peak expiratory flow (PEF) and FEV1.
 
Partly Controlled Asthma
  • Symptoms more than two times/week
  • Limitation of activities present
  • Nocturnal symptoms present
  • Need for reliever medications, more than two times/week
  • Impaired lung functions as measured by FEV1 of best less than 80 percent
  • Exacerbations one or more per year.
 
Uncontrolled Asthma
  • Over three features of the above mentioned, in any one week
  • Impaired lung function measured by less than 60 to 80 percent of personal best
  • Exacerbations—one in any one week.
 
Exacerbation
  • Continuous symptoms, requiring frequent reliever medications
  • May need hospitalization and oxygen therapy
  • Lung functions poor.
As can be observed from Figure 1.3, inflammation in the airways play a major role in the pathogenesis of asthma. Hence an antiinflammatory drug is essential in the management. However, for quick relief, most children need a short-acting bronchodilator (SABD).6

BOX 1.1 :  Asthma Management

  • Regular assessment and monitoring
  • Control of factors contributng to severity
  • Asthma pharmacotheraphy
  • Patient education
 
Management of Asthma
Management of asthma, includes all the four aspects, as mentioned in Box 1.1.
  1. The child needs to be assessed regularly, at least every 3 to 4 weeks, to check for control of symptoms, compliance with medication, avoidance of allergens, etc.
  2. Control of aggravating factors include avoidance of allergens and precipitating factors and prevention of viral infections.
  3. Asthma pharmacotherapy is extremely important to keep the symptoms under control.
  4. Patient education must be an ongoing process to educate and sensitise the parents to the child's condition, what they must do in an exacerbation and how they can help to prevent exacerbations.
  5. The treatment modalities can be broadly divided into:
    1. Reliever medication
    2. Controller medication.
Inhaler therapy is the mainstay of treatment in case of childhood asthma.
 
Types of Inhalation Devices Available
 
Nebulizer
Nebulizer is power driven, hence it does not require patient effort to take the medication. Useful when child is severely dyspneic, and also in infants and young children who are unable to coordinate the respiratory effort.
 
MDI (metered-dose inhaler)
MDI (metered-dose inhaler) with or without spacer has the same effect and rapidity of action as the nebulizer. However, patient effort is required, hence may not be useful when child is severely dyspneic usually recommended for those above the age of 6 years, as patient compliance without the spacer can be assured.7
 
Dry Powder Inhaler
Dry powder inhaler (DPI) is recommended for children above 3 to 4 years, as they can be trained to blow as in blowing candles or a whistle. Inhalation devices are available as rotahaler, diskhaler, turbuhaler. Type of device selected depends on the child's acceptance and age.
Optimal inhalation technique for each puff of MDI-delivered medication is a slow (5 sec) inhalation, then a 5 to 10 sec breath hold. No waiting time between puffs of medication is needed. Young pre-school-age children cannot perform this inhalation technique; MDI medications can then be delivered with a spacer and mask, using a different technique: Each puff administered with regular breathing for about 30 sec or 5 to 10 breaths, a tight seal must be maintained, and talking, coughing, or crying will blow the medication out of the spacer. This technique will not deliver as much medication per puff when compared with the optimal MDI technique used by older children and adults.
 
Reliever Medications
The reliver medications are short-acting and gives immediate relief of symptoms (Box 1.2).
 
Recommended use
  1. During exacerbations of asthma
  2. In case of persistent cough
  3. To give rapid relief of symptoms

BOX 1.2 :  Reliever Medications

  • Rapid-acting inhaled β2-agonists
  • Systemic glucocorticosteroids
  • Anticholinergics
  • Methylxanthines
  • Short-acting oral β2-agonists
 
Rapid-acting beta-2-agonists
Salbutamol/Albuterol—Dose: 0.15 mg/kg/dose.
In case of use in the nebulizer, it should be diluted with normal saline to give a total volume of 3 ml.
Can be repeated every 20 minutes for maximum of three doses in case of severe bronchospasm.
SPO2 to be maintained above 92 percent.
8Oxygen inhalaton may be needed to avoid ventilation: perfusion mismatch.
 
Anticholinergics
Ipratropium bromide may be added to the salbutamol. It provides both mucolytic and bronchodilator functions. It must not be used without salbutamol.
Dose: 0.5 mg/dose every 6 to 8 hourly as needed. Can be mixed in the nebulizer with salbutamol and ICS.
 
Methylxanthines
Methylxanthines like theophylline have been used as reliever medication. However, the therapeutic levels of the drug need to be monitored, as the therapeutic window is very narrow. It is not recommended for use as monotherapy in children for this reason. The absorption of the drug varies with different preparations.
 
Oral Corticosteroids
These corticosteroids have an anti-inflammatory effect. Its use is indicated in severe asthma or in exacerbations not responding to inhaled medications.
Prednisolone dose: 0.5 to 1 mg/kg every 6 to 12 hourly for 48 hours, then 1 to 2 mg/kg every 12 hourly till symptoms subside. Dosing preferred at 8 am to reduce the effect of adrenal suppression. Prednisolone is available as 5 mg tablets.
 
Oral beta-2-agonists
Not routinely recommended as the dose is difficult to adjust and the risk of side effects is high due to the narrow therapeutic range.
 
Controller Medications
These are the mainstay of asthma control.
 
Inhaled Corticosteroids (ICS)
Inhaled corticosteroids are the most potent and effective medications for the treatment of asthma in children.
Dose: depends and varies with the type of ICS.
Beclomethasone: 100 to 200 microgram every 6 to 8 hourly. Maximum 600 microgram per day.
9Budesonide: 200 to 400 microgram every 6 to 8 hourly. Maximum 800 microgram per day.
Fluticasone: 100 to 200 microgram per day every 8 to 12 hourly.
 
Long-acting Beta Agonists
Not to be used without ICS. It can be combined with ICS for inhalation therapy.
Salmeterol MDI: 1 to 2 puffs every 12 to 24 hourly
Formoterol DPI: 1 capsule every 12 to 24 hourly
Salmeterol and Fluticasone combined MDI available. To be used 1 to 2 puffs every 12 hourly.
Daily ICS therapy is the treatment of choice for all patients with persistent asthma. ICS therapy has been shown to improve lung function and reduce AHR, ‘rescue’ medication use asthma symptoms and, most importantly, reduce urgent care visits, hospitalizations, and prednisone use for asthma exacerbations by about 50 percent. ICS therapy may lower the risk of death due to asthma.
 
Leukotriene Inhibitors
Leukotrienes are known to aggravate bronchospasm, induce mucus secretion and have inflammatory effects on the airways. Hence, leukotriene inhibitors can reverse these effects and have been known to help in asthma control in children.
Two-types of leukotriene inhibitors are currently available:
 
Zafirlukast and Montelukast
Zafirlukast and Montelukast of the two, montelukast has found widespread acceptance and use in children. It is recommended to be used as a first-line drug along with ICS in those children who have mild to moderate symptoms. For those with severe disease, it needs to be combined with LABA + ICS to give optimal benefits.
As the leukotrine receptor antagonists (LTRAs) have specific actions on the leukotrienes produced in the system, the side effects of the drug are practically non-existent.
LTRAs are useful in viral-induced as well as exercise-induced asthma and also in intrinsic asthma.
Dose: 0–1 year: 4 mg sachets/4 mg tablets
1–6 year: 4 mg tablets
6–12 year: 5 mg tablets
> 12 year: 10 mg tablets
10All tablets are chewable, hence acceptance is easy. Alternatively, it may be crushed or the sachets may be mixed with the foods that are consumed by the child. Treatment duration of 3 to 6 months is recommended.
Sometimes, the child who has recurrent attacks of wheezing, may need the leukotriene inhibitor to be administered for slightly longer duration of time. This has practical implications, as the frequency of use of rescue medications are definitely reduced.
Some children may need repeated courses of administration of leukotriene inhibitors. Hence, on a seasonal requirement, the drug may be administered every year for durations of 3 to 6 months, to keep the child symptom free.
 
Suggested Treatment Protocol
A suggested protocol for treatment of asthma is schematically shown in Figure 1.4.
 
Follow-up
All asthma patients must be followed up regularly to ensure drug compliance and to stabilize the treatment. As it is a chronic disease, the child needs long-term treatment. As such, once the child becomes symptom free, the dose of inhaled medication is reduced to the lowest level which keeps the child comfortable and symptom free.
Step-down treatment: This implies that once control has been achieved, the drug is gradually reduced to the lowest recommended dose that can keep the child asymptomatic.
Step-up treatment: This indicates that in case a child who had been maintained on the lowest recommended dose, develops a breakthrough exacerbation, the dose of the inhaled medication needs to be increased to the level at which symptom control can be achieved.
zoom view
Fig. 1.4: Suggested treatment protocol
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It is better to go for an aggressive approach to obtain symptom control faster and then step-down the therapy.
 
Avoidance of Triggers
  • Regular follow-up and counseling is needed to avoid contact with triggers—environmental smoke, tobacco smoke, pollens, dust, etc.
  • Regular follow-up is essential to check drug compliance and appropriate use of MDI.
  • Regular follow-up is needed to maintain adequate drug dosage and maintain the child symptom free.
  • Recommend vaccination with seasonal influenza vaccine. This is particularly helpful in viral-induced asthma, by reducing the number of viral infections.
 
Prognosis
Thirty to thirty-five percent of children suffer from recurrent cough and wheezing in childhood. Of these, one-third go on to become persistent wheezers in adulthood, while two-third recover.
The extent and severity of wheezing and the lung functions are a guide to predict if the child will go on to become a wheezer in adulthood. Spontaneous improvement is known to occur at the age of 5 to 6 years and again by 12 to 13 years of age.
 
STATUS ASTHMATICUS
Status asthmaticus is defined as an exacerbation of asthma, not responding to regular antiasthmatic medication. The patient needs to be attended to immediately and the airway obstruction reversed at the earliest.
 
Treatment
  1. Monitor SPO2. If it is below 92 percent, administer O2. In case of hypoxemia, oxygen inhalation is required and may be given at levels of 5 to 6 litres/min. While ongoing SABA treatments, it is essential to administer oxygen to avoid ventilation/perfusion (V:Q) mismatch which may occur during recovery.
  2. Short-acting beta-agonist (SABA) by nebulization. Repeated doses (salbutamol/albuterol) may be given every 15 to 20 minutes, for a maximum of three times, until the airway obstruction improves. Then it may be recommended every 4 to 6 hourly. Dose 0.15 mg/kg.
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  3. Ipratropium may be added to the SABA. This helps in relieving the bronchoconstriction. It reduces mucus secretion and undergo synergistic interactions with the SABA.
  4. ICS to be administered. In severe cases, budesonide is recommended. Dose—200 microgram per kg to be given every 4 to 6 hourly, depending on the severity.
  5. In case of suspected underlying lung pathology, IV antibiotic is recommended, preferably a broad-spectrum drug.
  6. IV corticosteroid as a short course is recommended to hasten recovery and to reduce the airway inflammation. Hydrocortisone IV is fast acting. Once the child is better, it may be changed to oral steroid for three days.
  7. IV maintenance fluids to be given as the child would be dyspneic and unable to eat/drink sufficiently.
Once a patient has developed status asthmaticus, the patient needs to be closely monitored with regard to compliance with drugs. The child needs careful titration of the administered drugs to ensure that the symptoms are adequately controlled and no breakthrough symptoms develop.
Patient counseling needs to be done on a regular basis and a written protocol must be given for action to be taken during worsening of symptoms.
FURTHER READINGS
  1. Bacherior LB, Boner A, Corlsen KH, et al. Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. European Pediatric Asthma Group. Department of Pediatrics, Washington University,  St Louis,  MO, USA. Allergy. 2008;63(1):5–34.
  1. Becker A, Gie RP, Chan-yeeing M. Management of childhood asthma. Int J Tuberc Lung Dis. 2006;10(6):592–99.
  1. Berger WE. New approaches to managing asthma: a US perspective. Ther Clin Risk Manag. 2008;4(2):363–79.
  1. Bousquet J, Demoly P, Godard P. Recommendations for the management of asthma: Rev Prat. 2001 15;51(5):533–7. [Article in French]. Service des maladies respiratoires, CHU Monptellier, INSERM U454, Hôpital Arnaud-de-Villeneuve 34 295 Montpellier.
  1. Centers for Disease Control and Prevention. National Center for Health Statistics. Asthma Prevalence, Health Care Use and Mortality: United States, 2003–05. January 2007.
  1. Centers for Disease Control and Prevention. National Center for Health Statistics, National Health Interview Survey, 2005. Analysis by the American Lung Association, Research and Program Services Division using SPSS and SUDAAN.
  1. 13 Expert Panel Report 3 (EPR-3): Guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol. 2007;120 (5 Suppl):S94–138.
  1. Fuhlbrigge AL, Guilbert T, Spahn J, et al. The influence of variation in type and pattern of symptoms on assessment in pediatric asthma. Pediatrics. 2006;118:619–25.
  1. Galant SP, Morphew T, Amaro S, et al. Current asthma guidelines may not identify young children who have experienced significant morbidity. Pediatrics. 2006;117:1038–45.
  1. Janson S. National Asthma Education and Prevention Program, Expert Panel Report. II: Overview and application to primary care. School of Nursing, University of California,  San Francisco,  USA. Lippincotts Prim Care Pract. 1998;2(6):578–88.
  1. Morgan WJ, Stern DA, Sherrill DL, et al. Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence. Am J Respir Crit Care Med. 2005;172:1253–58.
  1. National Asthma Education and Prevention Program. Expert panel report: Guidelines for the diagnosis and management of asthma. Update on selected topics-2002. J Allergy Clin Immunol. 2002;110(5 Suppl):S141–S219.
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  1. Thomas M. Breaking new ground: challenging existing asthma guidelines. Department of General Practice and Primary Care, University of Aberdeen, Foresterhill Health Centre,  Westburn Road, Aberdeen AB25 2AY, UK. BMC Pulm Med. 2006 30;6 Suppl 1:S.
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