The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition Dr. Franklin Y. Yamamoto. This current third edition chapter is a revision and update of the original author�s work.
A 3 year old boy comes to the office with a complaint of coughing for 2 weeks. Coughing is present every night. He has also had a mild fever, but his temperature was not measured at home. His parents have been using a decongestant/antihistamine syrup and albuterol syrup which were left over from a sibling. Initially the cough improved but it worsened over the next 2 days. He is noted to have morning sneezing and nasal congestion. There are colds going around the pre-school. He has had similar episodes in the past, but this episode is worse. He has no known allergies to foods or medications.
His past history is notable for eczema and dry skin since infancy. He is otherwise healthy and he is fully immunized. His family history is notable for a brother who has asthma. In his home environment, there are no smokers or pets.
Exam: VS T 38.1, P 100, RR 24, BP 85/65, oxygen saturation 99% in room air. He is alert and cooperative in no distress. His eyes are clear, nasal mucosa is boggy with clear discharge, and his pharynx has moderate lymphoid hypertrophy. He has multiple small lymph nodes palpable in his upper neck. His chest has an increased AP diameter and it is tympanitic (hyperresonant) to percussion. Rhonchi and occasional wheezes are heard on auscultation, but there are no retractions. Heart is in a regular rhythm and no murmurs are heard. His skin is dry, but not flaky, inflamed or thickened.
He is initially felt to have moderately persistent asthma and possible asthmatic bronchitis. He is initially treated with nebulized albuterol and nebulized budesonide for bronchospasm and bronchial inflammation. He is also treated with an antihistamine at night to reduce his morning allergy symptoms.
One week later in follow-up, his cough has not improved and he is still having fever (T 38.2). A chest X-ray is obtained, but no radiographic evidence of pneumonia is present. His cough persists, but only with exercise and drinking cold juice. He is scheduled for another follow-up visit next week.
His chest now sounds clear in the office. After one week of no night cough, his nebulized albuterol+budesonide is reduced to 2 times a day. His exercise induced cough gradually resolves. He enrolls in a soccer league and plays with minimal coughing. His parents are concerned about long term corticosteroid use. Since his chronic symptoms have improved, his daily albuterol+budesonide nebulizer treatments are discontinued. He is started on daily oral montelukast syrup and pre-exercise albuterol via inhaler is recommended to prevent exercise induced bronchospasm. No cough is observed at night or with exercise. He is continued on nightly antihistamines, pre-exercise albuterol inhalation, and once daily montelukast. He is given an asthma treatment plan which gives his parents clear instructions on which medications to start based on his symptoms and severity.
Asthma is a frequent respiratory diagnosis for children admitted to hospitals (1,2). It causes about 200 pediatric deaths annually (1) in the United States despite the availability of excellent medications. 50% to 80% percent of children with asthma develop symptoms before 5 years of age with a peak age of 3 years. Inflammation is the primary pathologic process in chronic asthma. Because of the variety of asthma triggers, such as exercise, exposure to smoke, weather changes, allergies, and infections, asthma is now considered to be a syndrome of various environmental and genetic factors consisting of bronchospasm, airway hyperirritability, and inflammation. The popular term ROAD (reversible obstructive airway disease) or RAD (reversible airway disease) is not entirely accurate since this is only part of the disease process and reversibility may not always be evident. This is because obstruction of the airways may be secondary to mucous plugging or inflammatory changes reducing the caliber of the airways, in which case, beta-2 bronchodilators are often ineffective.
Currently the NIH (National Institutes of Health) Guidelines (3) have served as a standard for diagnosing and treating asthma. NIH guidelines provide: 1) An objective means of assessing severity. 2) A way of objectively categorizing severity classes of patients based on symptoms and/or spirometry or peak flow measurements. 3) A comprehensive pharmacologic plan primarily designed to treat inflammation, inclusive of provisions for acute and maintenance care, for each severity level. 4) The identification and removal of (or control of exposure to) known triggers. 5) The direction for forming a partnership with the physician who uses education as a primary basis of this relationship.
Asthma is a chronic inflammatory disease condition with periodic exacerbations. The inflammation is largely due to numerous elements such as mast cells, neutrophils, eosinophils, T-lymphocytes, macrophages, and epithelial cells (2). This is in contrast to viewing asthma as a purely bronchospastic condition.
An acute asthma exacerbation is a biphasic process. Understanding the inflammatory process of asthma came about when it was observed that 4 to 8 hours following allergen exposure, wheezing would occur that was not responsive (or less responsive) to beta agonists but improvement was accelerated by corticosteroids. Since beta agonists could easily neutralize the immediate reaction, occurring within minutes of the allergen exposure, this created a picture of a biphasic reaction to allergen (or infection) induced wheezing. The first phase was described as the immediate (bronchospastic) phase and the second phase as the late phase inflammatory response.
The characteristic features of asthmatic inflammation are mediated by preformed mediators such as histamine, prostaglandin D2 and rapidly formed mediators such as leukotrienes (LTC4, LTD4, and LTE4) are released and cause contraction of airway smooth muscle (bronchospasm). Other mediators upregulate proinflammatory cytokines (interleukins IL-4, IL-5, IL-13), causing recurrent bronchoconstriction a few hours later (4). These cells (e.g., eosinophils) recruit other cells such as epithelial cells to participate in the resultant inflammatory damage of the airways and subepithelial structures. These events eventually result in extensive, often irreversible restructuring of the normal histology of the airways through inflammation, edema, thickening of the basement membrane, subepithelial deposition of collagen, and hypertrophy of mucous glands and smooth muscle (4). This leads to the primary clinical components of asthma: bronchospasm, airway hyperreactivity, increased mucus production, and end expiratory hyperinflation (air trapping). An important immunologic occurrence is the activation of the T-helper 2 (Th2) cells, which is pivotal in the progression of the allergic immunologic process. The other T-helper designated Th2 cell does not enhance the allergic inflammatory process.
There are many presentations of asthma. Asthma is present 24 hours a day, 7 days a week. It may not be in an easily identified form (i.e., there may be no obvious symptoms present). The most recognizable form is the acute episode in which the patient presents with acute shortness of breath. Depending on the underlying degree of inflammatory damage of the airways, the episode may have been festering with persistent cough and occasional bouts of shortness of breath for weeks. Failure to attend to these soft signs of asthma in transition may lead to an acute case of status asthmaticus (severe, refractory asthma that does not respond to standard therapy) (5). Hence, paying attention to the more silent signs of asthma (asthma not in an acute phase), can prevent later consequences. Asthma may appear solely as an event associated with work or exercise. Most asthma in childhood occurs as a result of encounters with respiratory viruses (e.g., respiratory syncytial virus, influenza virus, and rhinovirus). If the asthmatic is already unstable because of a poor maintenance regimen of the existing chronic asthma, the acute phase will begin simultaneously with or soon after the first signs of a cold. If the asthma is managed well, then the cough and wheezing may occur several days after cold symptoms. An asthma management plan should include a maintenance plan and provisions for acute onset of wheezing. Asthma in its most manageable state is outpatient asthma, as opposed to hospital status asthmaticus.
For most medical professionals, the first and everlasting impression of asthma is in hospital status asthmaticus. By far, the more common situation is asthma outside the hospital, in its non-acute form. Therefore, it is highly desirable that medical professionals familiarize themselves with the other faces of asthma to facilitate its diagnosis and treatment. The type of medication used to treat asthma reflects the mechanism of airway obstruction: bronchospasm versus inflammation.
Based on this brief description of the mechanism of asthma, it is now possible to create an asthma treatment program. Genetics aside, elimination of triggers and aggravators of asthma such as allergens, cigarette smoke, and environmental and industrial pollutants, can prevent acute exacerbations of asthma and serve as the first line of defense. Conditions such as weather changes and respiratory infections fall outside of the readily controllable factors.
Approach to Asthma (6)
1. Diagnose asthma and classify its severity. Identify aggravating and triggering conditions.
2. Prepare an initial treatment plan to stabilize the acute condition. Instruct the patient and parents on the signs and symptoms which help to monitor the effectiveness of treatment. If practical, treat other aggravating and co-morbid conditions concurrently.
3. When asthma is stable, proceed to a maintenance plan to allow healing of the damaged airways. This may take weeks to months. Prepare an asthma action plan for up-regulation of medications for unexpected exacerbations. Action plan examples: 1) //www.cdc.gov/asthma/actionplan.html (6), which shows a more open document which must be filled-in by the physician and reviewed with the patient. 2) //www.hawaii.edu/medicine/pediatrics/KapiolaniEDAsthmaActionPlan.pdf which is a more fixed option in which medication options are more standardized so that it can be pre-printed for distribution.
4. When there are no signs of breakthrough cough or wheezing, indicating that the airway hyper-reactivity has subsided and is controlled, switch to a long term maintenance plan. This might be as needed use of bronchodilators, or pre-exercise use of preventive medications, or pulsing of medications for cold symptoms due to respiratory infections in short bursts.
5. Monitor asthma with periodic evaluations and reminder messages of avoidance and check on patients' inhalation technique of medication administration.
Inflammation in asthma contributes to: airway hyperresponsiveness, airflow limitation, respiratory symptoms, coughing, wheezing, shortness of breath, rapid breathing, chest tightness, persistent symptoms, and pathologic damage, even when symptoms are not present. It is often thought that periodic control of acute symptoms is sufficient, but this is suboptimal. Utilization of chronic anti-inflammatory agents result in better long term outcomes for all but the mildest asthmatics.
Co-morbid conditions such as allergic rhinitis, sinusitis, eczema, and gastroesophageal reflux have a profound influence on asthma. Their presence makes asthma extremely difficult to control. The main goal is to keep the patient functional and free of side effects from medications. With this approach, asthmatics have been able to participate in a normal lifestyle.
Signs of "silent asthma" (when no wheezing is heard) include: persistent cough at night, cough with exercise, cough with laughter, cough when consuming cold foods or drinks, prolonged cough following or accompanying a cold, chest tightness, and/or difficulty breathing.
The peak flow measurement and FEV1 (forced expiratory volume over one second) are effort dependent measures. Variation in lung function greater than what would be expected in healthy people is consistent with the diagnosis of asthma (4). Full pulmonary function testing is desirable; however, the equipment is expensive compared to an inexpensive peak flow meter. The ultimate objective measurement for asthma is by body plethysmography (body box), which can measure the end expiratory residual lung volume as well as resistance to airflow. For those patients unable to perform peak flow measurements, clinical history is all you may have to base your assessments. This includes a major group of younger asthmatics from infancy to 4 or 5 years old. Many children in this age group are unable to reliably perform peak flow measurements.
Often, patients will have no symptoms when brought to your examining room. The identification of the role of allergic diseases in asthma relies heavily on patient history. Physicians trained to respond to record what they feel, see, and hear may have a problem forming conclusions based on history alone. Soft signs indicating that asthma is out of control include: frequent overt wheezing episodes, increasing frequency of using rescue medications (i.e., acute use of albuterol), a previously stable asthmatic now having signs of silent asthma, reduction or termination of activities, and/or persistent cough following respiratory infections.
The National Institutes of Health (NIH) guidelines recommend forming a partnership with the pediatric patient as one of several key objectives (3). Good communication and availability to answer questions and concerns are basic to the partnership. Part of your efforts as the treating physician should focus on getting the patient to respond in a logical manner to cope with changes in his/her clinical state. This is based on getting the patient understanding the principles of: triggers and aggravators, bronchodilation, inflammation, airway hyper-reactivity and healing. For example, should the peak flow decline or cough increase, the patient is instructed to upgrade their medications according to a prearranged step-up plan. Before stepping up, observe inhaler technique, and assess adherence and environmental factors (5). As the acuteness of the situation resolves and the asthma is well-controlled for at least 3 consecutive months, the patient is advised to step down (downgrade) their medications back to their maintenance program (7) . Should there be an unanticipated episode of wheezing, immediate activation of the action plan and consultation with the physician for additional treatment schemes is the next step. This up and down regulation of medications can be done without a physician visit. Phone calls, informing the physician's office of these changes, are all that is normally required. Recurrent wheezing episodes, even if reversed easily, might indicate the presence of an unstable condition requiring an adjustment in the basic asthma management plan. Hence, the physician should be apprised of these changing conditions regularly. All asthma management plans should have common goals.
Asthma management plans depend on the severity of the asthmatic. Higher severity levels warrant greater use of corticosteroids and controller medications such as leukotriene inhibitors and inhaled corticosteroids. Controller medications are those that are used every day to reduce baseline inflammation and hyperreactivity in the lungs, while rescue or reliever medications are used to treat acute symptoms such as wheezing, respiratory distress, and cough. The NIH guidelines (3) categorize severity levels into severity steps as follows (5):
Step 1 (intermittent): Day symptoms two days per week or less and night symptoms two nights per month or less. Chronic peak flow is higher than 80%.
Step 2 (mild persistent): Day symptoms greater than two times per week, but less than once per day or night symptoms greater than two nights per month. Chronic peak flow is 80% of expected or higher.
Step 3 (moderate persistent): Day symptoms occur daily or night symptoms occur once a week or more. Chronic peak flow is 60% to 80% of expected value.
Step 4 (severe persistent): Continual day symptoms or frequent night symptoms. Chronic peak flow is less than or equal to 60% of expected value.
Note that steps 2, 3, and 4 are all persistent asthma with mild, moderate, and severe levels of severity. Thus all persistent step categories benefit from chronic controller medications. Step 5 (and sometimes 6) are more severe and beyond the scope of this chapter.
The use of peak flow in the above classification is not required in children 5 years and under. Peak flow data is useful but not required for classification in older age groups, but most children in this age range are capable of performing peak flows.
The major goal is to allow the child to express and achieve his or her maximum natural potential by not allowing the asthma to control him or her. This is a good way to view the end point in asthma management. Along the way, it is crucial to cradle the impressionable self-image so that the child does not have a negative view of himself or herself. The very impressionable years are from about 3 to 10 years of age, when children form their life-long mental image of themselves. Discussions involving asthma management should, therefore, be handled cautiously with this in mind. Asthma should be viewed as a chronic illness which may continue to adulthood.
Bronchodilators
In 1896 Solis-Cohen published, "The use of adrenal substances in the treatment of asthma" (adrenaline or epinephrine is a fast and potent bronchodilator) (8). Epinephrine (most commonly administered subcutaneously, but it could be inhaled as well) was the first line of treatment for acute asthma from the 1950s through the 1970s and early 1980s.
In 1924 ephedrine was isolated from Ma Huang (a Chinese root extract). For the next forty years, ephedrine would be the mainstay for asthma treatment in the U.S. Ephedrine in combination with theophylline, were used extensively in the same period. Interestingly, the ancient Chinese boiled the ephedra root in strong tea for their concoction to treat asthma. The tea contained methylxanthines similar to theophylline. Although methylxanthines are effective bronchodilators, they have been largely replaced by beta-2 agents (e.g., albuterol) which have a faster onset and less toxicity. Adding theophylline does not appear to provide additional benefit to most patients who are receiving high therapeutic doses of albuterol. Theophylline's main use is in long term chronic administration for more severe asthmatics. This change in therapeutic approach from methylxanthines to beta-2 agents did not further our understanding of the true pathophysiology of asthma, since bronchodilation was the only target of early treatments. Bronchodilators can be administered via several inhaled routes: inhaler, dry powder inhaler (DPI), nebulizer (also known as neb, aerosol, updraft, and wet nebulizer), parenteral IV, parenteral subcutaneous injection (SC), and orally (PO). In general, inhaled medications have a faster onset, greater potency and less side effects. In the past, an inhaler used to be called an MDI (metered dose inhaler); however, this terminology has been replaced by HFA (hydrofluoroalkane) inhaler or just plain "inhaler". Inhalers require a propellant which was initially CFC (chlorofluorocarbons). These were banned in the 1980s and replaced by hydrofluoroalkane (HFA) at which point the term MDI was replaced with HFA inhaler to signify that it was free of CFC. While the term MDI is still technically correct, some do not like this term so it appears to be best to use the term" inhaler" by itself. Bronchodilators used in asthma are summarized in table 1 below.
Table 1. Bronchodilators
| Beta-2 agonists - albuterol (Ventolin, Proventil, Proair, also generically called salbutamol in other countries) � Available as nebulizer, inhaler, tablets, syrup - L-albuterol (Xopenex, active isomer only) � nebulizer, inhaler - terbutaline � nebulizer, inhaler, tablets, parenteral (IV, IM, SC) - formoterol (Foradil, LABA) � inhaler, DPI - salmeterol (Seravent, LABA) � inhaler, DPI |
| Non-selective beta agonists - epinephrine (alpha and beta) � nebulizer, inhaler, parenteral - isoproterenol (beta) � parenteral |
| Anticholinergics - ipratropium bromide (Atrovent) � nebulizer, inhaler - atropine � nebulizer |
| Methylxanthines � narrow therapeutic index and require drug level monitoring - theophylline � PO, IV - aminophylline � PO, IV |
| Other drugs with bronchodilator effects include ketamine, calcium channel blockers (e.g., nifedipine), and diuretics; however these drugs are not used routinely in acute asthma (9). |
Anti-Inflammatory Drugs
Based on the biphasic mechanism, an anti-inflammatory drug (i.e., corticosteroids) is necessary for the complete treatment of asthma (2). Corticosteroids can be administered systemically (PO, IM, IV) or inhaled (inhaler, DPI, nebulizer, etc.). For asthma of a chronic nature, such as allergic asthma (e.g., house dust allergy), a daily regimen of a long acting bronchodilator coupled with a corticosteroid by inhalation would be effective. Corticosteroids take hours to become engaged in its active phase. Their effects are very broad and nonspecific. Corticosteroids affect virtually every phase of the inflammatory process. They have an array of impressive and undesirable side-effects, which cause hesitation in their use by physicians as well as patients. As in the use of any medication or therapeutic agent, the employment of corticosteroids is subject to weighing the desired effects against the undesirable effects (benefit vs. harm). If the positive effects of using corticosteroids have an overwhelming advantage over not using the drug, then it is justified to be used. This especially applies to children where growth suppression (in the order of 1 cm) is the side effect of concern for chronic inhaled corticosteroids (4). This must be weighed against the risk of poorly controlled asthma which may delay growth as well. Many patients require more medications during the fall/winter/spring, and fewer medications during the summer. Pediatricians will often modify controller medication use during lower risk months to minimize corticosteroid administration. Occasional bursts of systemic corticosteroids have no significant long term side effects, but chronic or long term use of systemic corticosteroids have major side effects (refer to the chapter on corticosteroids).
Table 2. Corticosteroids used in Asthma
- fluticasone (Flovent) � inhaler
- budesonide (Pulmicort) � inhaler
- beclomethasone
(QVAR, Beclovent, Vanceril) � inhaler
- triamcinolone (Azmacort) � inhaler, IM
- flunisolide (AeroBid) � inhaled
- mometasone (Asmanex) � inhaled
- prednisone � oral
- prednisolone (Pediapred, Prelone, Orapred) � oral
- methylprednisolone (Medrol, Solumedrol) � oral, parenteral
- dexamethasone (Decadron) � oral, parenteral
In addition, one might consider adding a leukotriene inhibitor, also called leukotriene receptor antagonists (LTRA). These leukotriene inhibitors were developed to counteract the all important late phase inflammatory reaction caused by SRS-A (slow reacting substance of anaphylaxis), a compound which was eventually identified as leukotrienes. Their side effects are minimal and are given orally. Montelukast (Singulair) is more commonly used in pediatrics because it is available in syrup and pill forms. Zafirlukast (Accolate) is available as a pill only and indicated for patients 7 years old and above.
Cromolyn and nedocromil stabilize mast cells (inhibit mast cell degranulation). They have less potent anti-inflammatory properties, but they have minimal side effects. Cromolyn (Intal) is available via nebulizer and inhaler, but the use of this class of drug is declining.
Goals of asthma treatment (5) include: 1) Prevent chronic and troublesome symptoms (e.g., cough or breathlessness in the night, in the early morning, or after exertion). 2) Maintain (near) normal pulmonary function. 3) Maintain normal activity levels (including exercise and other physical activity). 4) Prevent recurrent exacerbations of asthma and minimize the need for emergency department visits or hospitalizations. 5) Provide optimal pharmacotherapy with minimal or no adverse effects. 6) Meet patients' and families' expectations of and satisfaction with asthma care.
Specific asthma therapy measures to achieve these goals are based on the NIH severity categories that are summarized in table 3. Step 1 (intermittent) requires no daily medications. Step 1 is managed by a short-acting beta-2 agonist as needed. ALL of the other categories (i.e., any category with the word "persistent"), requires chronic controller anti-inflammatory medication(s) as described in table 3. Children should be regularly assessed to monitor asthma control.
Table 3: Controller medication treatments by steps in pediatric asthma (4,5). All steps include SABA prn for rescue. Reference recommendations vary. Alternative options exist that are not described in the table below. Abbreviations: SABA-short acting beta agonist (i.e., albuterol), prn-as needed, ICS-inhaled corticosteroid, LABA-long acting beta agonist (formoterol, salmeterol), LTRA-leukotriene receptor antagonist
| No controller | Daily low dose ICS or daily LTRA | Daily medium dose ICS or low dose ICS+LTRA | Daily medium dose ICS plus [LABA or LTRA] |
| Low dose ICS whenever prn SABA is used | Daily low dose ICS or daily LTRA or prn low dose ICS whenever prn SABA is used | Daily medium dose ICS or low dose ICS plus [LABA or LTRA] | Daily medium dose ICS plus [LABA or LTRA] |
| prn low dose ICS+formoterol or low dose ICS whenever prn SABA is used | Daily low dose ICS or prn low dose ICS+formoterol | Daily low dose ICS+LABA | Daily medium dose ICS+formoterol or medium/high dose ICS+LABA |
Inhaled medications can be given via nebulizer or inhaler. Inhalers are more portable than air pump type nebulizers which commonly require an electrical outlet. Hand-held battery run ultrasonic nebulizers are available if a portable nebulizer option is required. Delivering albuterol nebulizer versus inhaler with a spacing chamber results in similar effects, but there can be individual factors such a child resistant to treatment and personal preferences that drive patient/parent preferences on nebulizer versus inhaler. However, nebulizers are wet and they require cleaning and storage of wet parts. While this factor might be minimal for prn use, it is much easier to use an inhaler with spacer for chronic daily controller treatment. Plugging in an inhaler, connecting the tubing, placing the meds in the nebulizer, administering the nebulized medication, then cleaning up the wet parts of the nebulizer, all on a daily basis results in significantly more work compared to the use of an inhaler with a spacer.
Note that the daily controller treatment recommendations can be very difficult for patients in the step 3 and 4 categories. Combination products are available Just as an abbreviated set of examples: Advair (DPI with fluticasone and salmeterol), Symbicort (inhaler with budesonide and formoterol).
Omalizumab (Xolair) is a monoclonal anti-IgE antibody pharmaceutical that can be employed for patients who have allergies and severe persistent asthma that is inadequately controlled with standard controller medications. It is administered subcutaneously every 2 or 4 weeks.
In addition to the above chronic (long-term) recommendations, acute exacerbations are treated with quick relief (rescue) medications, which is most commonly prn albuterol and optional short bursts of systemic corticosteroids. Albuterol can be given: 1) Via nebulizer 2.5 mg unit dose every 4-6 hours (at home or more frequently under a physician�s supervision such as in an emergency department). 2) Via metered dose inhaler (MDI) 2-4 puffs every 4-6 hours (while this is a common recommendation, this dose is low compared to the 2.5 mg nebulizer treatment). 3) Orally at 0.1 mg/kg per dose every 6 to 8 hours, but this option is uncommonly used since inhaled routes are superior.
Systemic corticosteroids are commonly administered as: 1) Oral prednisolone at 1 to 2 mg/kg/day in divided doses 1 to 2 times daily for 3 to 5 days. 2) IV methylprednisolone 1 to 2 mg/kg/day in two divided doses (this same dose applies to oral methylprednisolone for acute management) (3,5). 3) Oral dexamethasone (0.3 to 0.6 mg/kg) is a commonly used single or 2-dose strategy. Systemic corticosteroids are usually given for 3 to 5 days and then discontinued if the patient improves. Systemic corticosteroids administered for longer than 7 days require a gradual taper of the medication. If the patient is on inhaled corticosteroids, these should be resumed once systemic corticosteroids are stopped or tapered. Some physicians continue inhaled corticosteroids during systemic corticosteroid bursts to avoid the confusion caused by modifying their chronic medications.
All patients should have a written asthma management/action plan that describes their chronic medications and a plan for the initiation of a rescue plan based on their symptoms and peak flow (if age greater than 5 years). More detailed plans can include recommendations to step up or step down their chronic medications as their chronic symptoms worsen or improve.
If dyspnea still persists, despite rescue medications, then the asthma management plan should refer the patient to a source of immediate medical care (doctor's office during office hours, or emergency room after hours). Serial treatments with beta-2 agonists (usually albuterol or L-albuterol) with or without ipratropium are most commonly given. Inhaled beta-2 agonists can be given continuously for severely ill patients, or serially based on severity. Systemic corticosteroids can be started. Parenteral corticosteroids do not have an onset time advantage over oral corticosteroids; however, very ill children have a higher likelihood of vomiting oral corticosteroids. Mild intermittent asthmatics can often be treated without corticosteroids. The decision to start systemic corticosteroids is based on their response to beta-2 agonists and their previous history which indicates their severity step level. Those who do not respond well to beta-2 agonists should be started on systemic corticosteroids because poor response indicates the presence of significant bronchial inflammation. Those who have required systemic corticosteroids in the past or who have other markers of more severe asthma should also be started on systemic corticosteroids.
Characteristics of good asthma control in children include the following (3,5,10):
- Daytime symptoms (coughing, shortness of breath or
rapid breathing, and wheezing or chest tightness) no more than twice per week.
- Waking up at night because of asthma symptoms no more than twice per month. No interference with normal activities including play, sports, and exercise.
- Few (0-1 per year) exacerbations requiring oral systemic corticosteroids.
- Episodes of asthma that require an acute doctor visit, urgent care, or emergency room visit, needed no more than once per year.
- No absences from school or activities,
no missed time from work for the parent or caregiver.
- Normal or near normal lung function (from baseline).
- Healthy self-image.
Unfortunately, the death rate from asthma is not yielding to the introduction of many excellent and powerful treatments. This condition remains a challenge to the medical care team at all levels from physicians, nurses, respiratory therapists, pre-hospital care personnel, to psychiatrists and social workers. Family, school personnel, coaches, club leaders, and after hours activity supervisors, are all involved in delivering care to the asthmatic.
Risk factors for death from asthma include (3,5):
- Past history of sudden severe exacerbations.
- Prior intubation or mechanical ventilation for asthma.
- Prior emergency care visit and/or admission to intensive care unit for asthma in the past year.
- Hospitalization or emergency care visit for asthma in the past month.
- Use of more than 1 inhaler canister per
month of inhaled short-acting beta 2 agonist.
- Prior or current chronic use of oral corticosteroids.
- Difficulty perceiving airflow obstruction or its severity.
- Poor adherence to asthma medication or lack of an action plan.
- Concurrent food allergy.
- Low socioeconomic status and urban residence.
- Illicit (illegal) drug use.
- Serious psychosocial problems.
Acute signs of severe asthma and potential impending respiratory failure, warranting admission to an intensive care unit include: 1) Oxygen saturation less than 100% despite the administration of supplemental oxygen. 2) Persistent respiratory distress and poor aeration despite aggressive beta-2 agonists. 3) Poor aeration (air exchange) on auscultation, which causes poor air flow and hence, less wheezing. 4) Pallor, cyanosis, or hypoxia by pulse oximetry despite high flow oxygen administration. 5) Fatigue and somnolence. 6) A pCO2 of 40 mmHg or greater on a blood gas. The treatment of severe status asthmaticus bordering on respiratory failure is controversial. It is reasonable to begin with high dose beta-2 agonists; such as a nebulizer treatment with concentrated albuterol, or continuous albuterol (e.g., 20 mg per hour). In severe patients, aeration is poor, so inhaling albuterol by itself is often insufficient. Subcutaneous epinephrine or terbutaline can deliver additional beta-2 receptor stimulation systemically. Other therapeutic options include: IV isoproterenol, IV or inhaled magnesium, IV ketamine, inhaled heliox or anesthetic agents. Such patients should be treated aggressively from the onset to prevent respiratory failure. If the patient fails to improve and respiratory failure ensues, positive pressure ventilation should be directed at maintaining oxygenation above 90% saturation if possible. Severe status asthmaticus results in air trapping, therefore ventilation (air exchange) is difficult. Although such patients can have a very high pCO2 because of air trapping and poor ventilation, the priority should focus on maintaining oxygenation. Attempting to normalize the pCO2 with aggressive positive pressure ventilation will increase the possibility of a pneumothorax which will worsen the hypoxia. This strategy is known as "permissive hypercapnia" because hypercapnia is not as deadly as hypoxemia. Permissive hypercapnia is more likely to avoid a pneumothorax and thus, oxygenation is preserved, improving the overall outcome.
The physiologic mechanism of hypoxia in asthma is ventilation perfusion mismatch (VQ mismatch) due to pulmonary branch blood flow perfusing alveoli that are poorly aerated. Hypoxemia at presentation correlates with the degree of VQ mismatch and is a known predictor of the need for hospitalization.
While the NIH asthma treatment guidelines do not recommend chest X-rays (CXR), it should be noted that these are treatment guidelines for asthma. These are not guidelines for pneumonia, tracheal anomalies, bronchial foreign bodies, mediastinal masses, etc., which can present with wheezing. Thus, the CXR may be necessary in the process of evaluating some wheezing patients to be certain that the patient has asthma and not some other condition which can only be identified on CXR (i.e., to rule out other conditions).
Environmental measures to reduce asthma severity focuses on elimination of household smoking and the reduction of exposure to dust mite and cockroach microantigens in the environment. Wrapping mattresses with plastic casings, conversion of carpeted floors to tile floors, replacing drapes with blinds, and selecting home furnishings which avoid antigen accumulation, may result in improvement. Allergy testing and subsequent immunotherapy to desensitize a patient may be beneficial in some asthmatics.
In summary, asthma is a condition of multiple factors. It can be looked upon as a syndrome of multiple but related elements. It is basically a chronic condition with biphasic components which both result in airflow obstruction by different means. The treatment should take into account the various triggering factors, occupation, age, psychosocial, and economic factors.
Questions
1. How can you best describe asthma?
2. Can you describe the various medications to treat asthma?
3. Can you describe the parameters that are used to classify severity of asthma?
4. Describe the clinical
findings signifying the severity of an acute asthma exacerbation.
5. Discuss the approach to an asthmatic in formulating a plan of anticipated actions for an acute asthma event. What questions do you ask, what physical findings do you look for, and what laboratory parameters are measured?
6. Formulate an asthma maintenance plan.
7. Describe various triggering factors and mechanisms by which they might exert their action.
8. Describe the immunologic chain of events that ultimately
leads to bronchospasm and inflammation.
9. Discuss the pros and cons of corticosteroid use in children and compare them with use in adults.
10. How would you convince parents of asthmatics to administer medications every day, even when their children are not openly symptomatic?
References
1. Centers For Disease Control and Prevention. Most Recent National Asthma Data. April 7, 2021. //www.cdc.gov/asthma/most_recent_national_asthma_data.htm. Accessed April 16, 2022.
2. Tan L. Asthma. In: Ferri FF (ed). 2023 Ferri's Clinical Advisor. 2023. Elsevier, Philadelphia. pp: 188-199.e1.
3. National Institutes of Health. NAEPP Expert Panel Report: 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. December 2020. //www.nhlbi.nih.gov/resources/2020-focused-updates-asthma-management-guidelines. Accessed April 18, 2022.
4. Liu AH,
Spahn JD, Sicherer SH. Chapter 169. Childhood Asthma. In: Kliegman RM, St. Geme JW, Blum NJ, et al (eds). Nelson Textbook of Pediatrics, 21st edition. 2020. Elsevier, Philadelphia. pp: 1095-1115.
5. Global Initiative for Asthma. 2021 GINA Report, Global Strategy for Asthma Management and Prevention.2021.//ginasthma.org/wp-content/uploads/2021/05/Whats-new-in-GINA-2021_final_V2.pdf . Accessed March 2, 2022.
6. Centers For Disease Control and Prevention. Do you have an Asthma Action
Plan? Centers for Disease Control and Prevention. December 4, 2020. //www.cdc.gov/asthma/actionplan.html. Accessed March 2, 2022.
7. Rogers L, Sugar EA, Blake K, et al. American Lung Association Airways Clinical Research Centers. Step-Down Therapy for Asthma Well Controlled on Inhaled Corticosteroid and Long-Acting Beta-Agonist: A Randomized Clinical Trial. J Allergy Clin Immunol Pract. 2018;6(2):633-643.
8. Solis-Cohen S. The use of adrenal substance in the treatment of asthma. J
Asthma. 1900;27(6):401-406.
9. Chu R, Bajaj P. Asthma Medication in Children. Statpearls [Internet]. StatPearls Publishing, Treasure Island, FL, 2022.
10. Azmeh R, Greydanus DE, Agana MG, et al. Update in Pediatric Asthma: Selected Issues. Disease-a-Month. 2020;66(4):100886
Answers to questions
1. Asthma is best thought of as a chronic inflammatory condition and obstruction of the airways of the lung caused by spasms of the smooth muscle surrounding the airways which
present as recurrent wheezing, coughing, chest tightness, and shortness of breath. In some cases, it can be easily reversed by beta-2 bronchodilators. In other cases, corticosteroids may be necessary to reverse the airway obstruction by reducing the inflammatory changes responsible for the airway narrowing. These changes may be caused by a variety of different stimuli.
2. Medications are divided into groups directed towards relaxing bronchial smooth muscle (relievers, rescue medications) and
reversing the chronic inflammation (controllers). Systemic corticosteroids are typically initiated to reverse acute inflammation.
3. This answer can be divided into two parts. The first is used to describe the degree of severity of the acute asthmatic episode. These would include rate and effort of respirations (e.g., retractions), aeration (assessed by auscultation), ventilation perfusion mismatch (assed by oxygen saturation), degree of fatigue/somnolence, and carbon dioxide concentration
on a blood gas. The second parameter involves the chronic severity which is a measure of the sensitivity of the airways. These are classified into the four steps described in the chapter which are based on many factors that include day symptoms, night coughing episodes, peak flow values, coughing with exercise, prolonged coughing after upper respiratory infections, coughing with drinking ice-cold beverages, frequency and level of acute care episodes (e.g., doctor�s office, urgent care, emergency
department, hospitalization, intensive care unit).
4. Wheezing may be heard but if the attack is very severe there may be minimal or no wheezing at all (due to poor air exchange). Aeration is a good indicator of acute severity. Evidence of respiratory distress (retractions, tachypnea) indicates increasing severity until respiratory failure occurs (at which point, the patient may tire and exhibit seemingly less respiratory distress). Hypoxemia is also indicative of severity. Peak flow is
typically low for acute exacerbations. For mild cases, cough may be present at any phase of an asthmatic episode and may be the only sign that bronchospasm is occurring. A peak flow meter reading before and after a challenge of inhaled bronchodilator may reveal an increase in the airflow indicating the presence of bronchospasm.
5. Always consider the triggering event in formulating the treatment plan. Avoidance of the trigger can be very cost effective. Preventive use of medications can be
very useful such as preemptive use of medication with first sign of a cold. Analysis of the symptom's response to initial treatment can guide you in up regulating or down regulating medications. Use of the peak flow meter can serve as an objective means of adjusting medications. If cough and wheezing occur often and there are signs/symptoms of chronic asthma, a maintenance plan of daily medication should be initiated. Efforts should be made to approximate the degree of inflammation in the
airways. This estimation can serve to guide you in the type and dosage of anti-inflammatory medications to use. A contingency plan of what medications to use during an acute episode can be helpful and may help to avoid an unnecessary emergency visit to the hospital. Clinical symptoms are generally more useful than laboratory measurements.
6. The asthma maintenance plans are dependent on the patient's severity class (steps 1-4). For all persistent levels (steps 2, 3, 4), a daily plan will
usually involve an inhaled corticosteroid, long acting beta agonists, and/or a LTRA. Regular monitoring with peak flow meter readings can help to determine if the treatment is helping to return the lungs to normal function. A rescue plan using albuterol with optional systemic corticosteroids may be needed for breakthrough wheezing.
7. Allergen exposure is mediated through IgE with resultant immediate and late phase reactions. A variety of mediators are released and cause a cascade of
immunologic events culminating in tissue edema, increased mucous production, and sloughing of the epithelial layer of the inner lining of the airways. This affects the free and easy movement of air to the alveoli, which affects air exchange and causes atelectasis as the smaller airways are completely plugged by the thickened mucous.
8. Triggering mast cells cause release of mediators, which can cause immediate effects on the lung tissue and smooth muscles. Other mediators are formed and
released later and serve primarily to attract inflammatory cells. Some of these late mediators help to capture the incoming cells. Other mediators recruit epithelial cells and transform then into participants of the reaction causing them to release more mediators (biologic amplification).
9. The critical issue of corticosteroids in children is that of linear growth. It is now well established that the use of inhaled corticosteroids has significantly less effect on growth than long term
systemic corticosteroids. The length of corticosteroid use (inhaled or systemic), may have some effect on growth but its effect is small (in the range of 1 cm of growth). Chronic inflammatory suppression (long term use of inhaled corticosteroids) improves the long term outcome of asthma (i.e., less severity in the future).
10. This is where your ability to practice medicine is tested. You need to educate and persuade the parents that your recommendations are in the best interest of the child
and that it is based on considering the risks against the benefits. This is ideally done without making the parents feel guilty or intimidated by the potential for fatal outcomes. While our goal may be to maintain the patient's lifestyle and lung function, patients may see their goal as getting off medications as soon as possible. For persistent asthmatics, they should be convinced that this is a chronic disease and long term medications will be required. Long term use of medications is
generally very safe and not addictive.
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