A three year old comes in with a complaint of coughing for 2 weeks. Coughing is present every night. He has also had a mild fever, but his temperature has not been 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 minimal distress if any. 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 corticosteroids for bronchospasm and bronchial inflammation. He is also treated with an antihistamine at night to reduce his morning allergy symptoms. In follow-up, his cough does not improve and he is still having fever (T 38.2C, 101.0F). 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.
His chest now sounds clear in the office. After one week of no night cough, his nebulized albuterol+corticosteroid is reduced to 2 times a day. His exercise induced cough gradually resolves. His nebulized corticosteroid is replaced with nebulized cromolyn twice a day and oral montelukast (a leukotriene inhibitor) is added. He enrolls in a soccer league and plays with minimal coughing. His routine nebulized albuterol+cromolyn is stopped and is used only pre-exercise to prevent exercise induced bronchospasm. No cough is observed at night or with exercise. He is continued on nightly antihistamines, pre-exercise albuterol+cromolyn nebs, 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 by far, the most frequent respiratory diagnosis for children admitted to hospitals. It causes 5000 deaths annually in the United States despite the availability of excellent medications. Historically, asthma was characterized as a psychological illness, a surgical illness treated by removal of the carotid body, an environmental illness aggravated by air pollution, and an allergic illness or infectious illness. An allergy role in asthma, was legitimized by the discovery of IgE in 1965. Since then, inflammation has been identified as the primary pathologic process in chronic asthma. Because of the variety of asthma triggers, such as exercise, exposure to smoke, weather changes, and allergies, asthma is now considered to be a syndrome consisting of bronchospasm, airway hyperirritability, and inflammation. The popular term ROAD (reversible obstructed airways 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 decreasing the caliber of the airways, in which case, beta-2 bronchodilators are ineffective.
Currently the NIH Guidelines (1) have served as a standard for diagnosing and treating asthma. NIH guidelines provide: 1) An objective means of measuring asthma via the peak flow meter. 2) A way of objectively categorizing severity classes of patients based on symptoms and/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) For 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.
The realization that IgE existed and could be found in allergic individuals propelled the field of allergy and understanding of asthma into a renaissance of elucidating the actual pathophysiology of allergic diseases. Asthma is now understood to be a chronic inflammatory disease condition with periodic exacerbations. 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 it was ablated by cromolyn and corticosteroids. However, 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.
In the early phase of allergic inflammation, preformed mediators such as histamine and rapidly formed mediators such as leukotrienes are released and cause bronchospasm. Other mediators signal the late phase inflammatory cells. 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 restructuring of the normal histology of the airways. This damage is not restored by beta-2 bronchodilators. An important immunologic occurrence is the activation of the Th2 helper cell, which is pivotal in the progression of the allergic immunologic process. The other helper designated Th1 cell does not enhance the allergic inflammatory process.
Asthma, whatever the severity, is a chronic inflammatory disorder of the airways. The characteristic features of asthmatic inflammation are: mast cell activation, inflammatory cell infiltration, eosinophils, macrophages, neutrophils (particularly in sudden-onset, fatal exacerbations), lymphocytes (TH2-like cells), edema, denudation and disruption of the bronchiolar epithelium, collagen deposition beneath the basement membrane (this is an irreversible process), goblet cell hyperplasia, mucous hypersecretion, and smooth muscle thickening. The primary clinical components of asthma include: bronchospasm, inflammation, airway hyper-reactivity, increased mucous production, and end expiratory hyperinflation ("air trapping").
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. Hence, paying attention to signs of "silent asthma" (asthma not in an acute phase), can prevent costly and life threatening 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. If the asthmatic is already unstable because of a poor maintenance regimen of the existing chronic asthma, the acute phase will begin simultaneously with the first signs of a "cold". If the asthma is managed well, then the cough and wheezing may occur several days after cold symptoms. Hence, early recognition of "asthma in transition" is a major point of cooperation involving the physician and patient. An asthma management plan should include a maintenance plan and provisions for acute onset 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 diagnosis and treatment.
The type of medication used to treat asthma reflects the mechanism of airway obstruction: bronchospasm versus inflammation. This is an extremely simplified version of what really goes on and new pieces of the intricate mechanism are being uncovered. However from a pragmatic standpoint, the logic for appropriate use of individual medications for asthma can be understood by recalling the biphasic reaction.
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
. . . . . 1. Diagnose asthma and classify severity. Identify aggravating and triggering conditions.
. . . . . 2. Prepare an initial treatment plan to stabilize the acute condition. Instruct patient and parents on 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.
. . . . . 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 PRN use of bronchodilators, or pre-exercise use of preventive medications, or pulsing of medications for cold symptoms 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 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 life style.
Asthma is more than an acute process. A large part of treating asthma successfully is to be able to recognize asthma in its early stages and to formulate an appropriate treatment plan before the asthma advances to a critical stage. It is simple to diagnose asthma when the patient is wheezing, displaying intercostal retractions and turning pale or blue. Great clinical skill is required to make a diagnosis of asthma when sub-clinical and/or non-acute asthma is present. A careful detailed history and physical exam are crucial to this end. Asthma is not the acute episode of wheezing as popularly described in lay journals and magazines, but a chronic condition of the airways of the lungs which exhibits recurrent bronchospasm. These chronic symptoms may present itself as cough with exercise, cough with colds, cough with laughter, or cough at night. A peak flow meter can consistently record airflow readings compared against normal values for sex and age.
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, feeling of "tight chest" or difficulty breathing.
The peak flow measurement and FEV1 (forced expiratory volume over one second) are effort dependent measures. 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 conclusions. 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, patient who had exposure to known trigger, persistent cough following bronchitis or pneumonia.
The National Institutes of Health (NIH) guidelines, list as one of several key objectives, forming a partnership with the patient to facilitate treatment of asthma. Good communication and availability to answer questions and concerns are basic to the partnership. Part of your efforts as the treating physician should be focused on getting the patient to respond in a logical manner to cope with changes in his/her clinical state. This is based on the patient understanding the principles of: triggers and aggravators, bronchodilation, inflammation, airway hyper-reactivity and healing. Patients must also understand mucous mobilization and signs and symptoms of asthma out of control which may lead to an acute asthma attack. For example, should the peak flow fall or cough increase, the patient is instructed to upgrade their medications according to a prearranged plan. As the acuteness of the situation resolves, the patient is advised to downgrade their medications back to their maintenance program. 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 maneuvers, are all that is normally required. Obviously, 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 prophylactic medications such as leukotriene inhibitors and inhaled corticosteroids. The NIH guidelines categorizes severity levels into "steps" as follows:
Step 1 (mild intermittent): Day symptoms two days per week or less and night symptoms two nights per month or less. Chronic peak flow is 80% of expected or higher.
Step 2 (mild persistent): Day symptoms greater than two times per week, but less than once per day or night symptoms greater than nights per month. Chronic peak flow is still 80% of expected or higher.
Step 3 (moderate persistent): Day symptoms occur daily or night symptoms occur more than once per week. 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.
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.
In 1896 Solis-Cohen published, "The use of adrenal substances in the treatment of asthma" (adrenalin or epinephrine is a fast and potent bronchodilator). 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 USA. Ephedrine in combination with theophylline, as products called Marax and Tedral, 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 theobromine, a methylxanthine. Although methylxanthines such as theophylline 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 acutely benefit 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, as bronchodilation was the only target of treatment. Bronchodilators can be administered via several inhaled routes: metered dose inhaler (MDI), dry powder inhaler (DPI), nebulizer (Neb, also known as 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.
Bronchodilators Used in Asthma
A. Beta-2 Agonists:
. . . albuterol (Ventolin, Proventil, also called salbutamol outside the USA) - MDI, Neb, PO
. . . L-albuterol (Xopenex - active isomer only) - Neb
. . . terbutaline - MDI, Neb, PO, SC
. . . formoterol (Foradil - very long acting) - DPI
. . . salmeterol (Serevent - used for maintenance therapy) - DPI, MDI
. . . epinephrine (alpha and beta) - MDI, Neb, SC
. . . ipratropium bromide (Atrovent) -MDI, Neb
. . . oxitropium bromide (Oxivent) - MDI
. . . atropine -Neb
. . . aminophylline - PO, IV
. . . theophylline - PO, IV
. . . oxytriphylline - PO
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.
Based on the biphasic mechanism, an anti-inflammatory drug (i.e., corticosteroids) is necessary for the complete treatment of asthma. Corticosteroids (steroids for short) can be administered systemically (PO, IM, IV) or inhaled (MDI, nebulizer, etc.). For asthma of a chronic nature, such as allergic asthma to house dust, a daily regimen of a long acting bronchodilator coupled with a steroid by inhalation would be effective. Steroids take hours to become engaged in its active phase. Their action does not take place directly on the inflammatory tissue but by modulating DNA production of pro-inflammatory cytokines. Their effects are very broad and nonspecific. Steroids 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 steroids is subject to weighing the desired effects against the undesirable effects (benefit vs. risk). If the positive effects of using steroids have an overwhelming advantage over not using the drug, then it is justified to be used on a regular basis. This especially applies to children where growth suppression (in the order of 0.5 to 1.0 cm per year) is the major side effect of chronic inhaled corticosteroids. Catch-up growth occurs in most instances, if the child's condition improves to the point at which inhaled corticosteroids are no longer needed. Many patients require more medications during the fall/winter/spring, and fewer medications during the summer. Occasional bursts of systemic corticosteroids have no significant long term side effects, but chronic or long term use of systemic steroids have major side effects (refer to the chapter on corticosteroids).
Corticosteroids used in Asthma
. . . beclomethasone (Beclovent, Vanceril) - inhaled
. . . triamcinolone (Azmacort) - inhaled, IM
. . . budesonide (Pulmicort) - inhaled
. . . fluticasone (Flovent) - inhaled
. . . flunisolide (AeroBid) - inhaled
. . . mometasone (Asmanex) - inhaled
. . . prednisone - PO
. . . prednisolone (Pediapred, Prelone, Orapred) - PO
. . . methylprednisolone (Medrol, Solumedrol) - PO, IV
. . . dexamethasone (Decadron) - PO, IV
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. These are all given orally.
Leukotriene receptor antagonists (LTRA)
. . . montelukast* (Singulair)
. . . zafirlukast* (Accolate)
. . . pranlukast
. . . zileuton (Zyflo)
*(Some sources spell the suffix as "leukast" instead of "lukast". Roche and Astra Zeneca spell it as "lukast".)
Cromolyn type drugs 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 MDI. Nedocromil (Tilade) is available via MDI.
Goals of Asthma Treatment
. . . 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. Step 1 (mild intermittent) requires no daily medications. ALL of the other categories (i.e., any category with the word "persistent"), requires a chronic controller anti-inflammatory medication.
Step 2 (mild persistent) recommends a low dose inhaled corticosteroid. Alternatively, a cromolyn medication or a leukotriene receptor antagonist may be used. Theophylline is another option, but only in children older than 5 years.
Step 3 (moderate persistent) recommends a low dose inhaled corticosteroid plus a long acting beta-2 agonist (salmeterol or formoterol). Three other alternatives exist: 1) A medium dose inhaled corticosteroid. 2) A low dose inhaled corticosteroid plus an LTRA. 3) A low dose inhaled corticosteroid plus theophylline.
Step 4 (severe persistent) recommends a high dose inhaled corticosteroid, plus a long acting beta-2 agonist.
In addition to the above chronic (long-term) recommendations, acute exacerbations are treated with quick relief (or rescue) medications, which is most commonly prn albuterol and optional short bursts of systemic corticosteroids. Albuterol can be given: 1) Orally at 0.1 mg/kg per dose every 6 to 8 hours. 2) Via nebulizer 2.5 mg unit dose every 4-6 hours. 3) Via metered dose inhaler (MDI) 2-4 puffs every 4-6 hours (however, most studies suggest that 5 to 10 puffs is more equivalent to the 2.5 mg nebulizer treatment).
Systemic corticosteroids are commonly administered as: 1) Oral prednisolone at 2 mg/kg/day given once daily or divided BID. 2) IV methylprednisolone 2 mg/kg, then 1 mg/kg every 6 hours. Systemic corticosteroids are usually given for 4 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 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 >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 prednisolone. 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 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: no coughing, no shortness of breath or rapid breathing, no wheezing or chest tightness, no waking up at night because of asthma symptoms, normal activities including play, sports, and exercise, no episodes of asthma that require a doctor visit, emergency room visit, or urgent care, no absences from school or activities, no missed time from work for the parent or caregiver, normal or near normal lung function, and a healthy self image (i.e., "nothing can stop me attitude").
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, emergency technicians, and respiratory therapists 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:
. . . Past history of sudden severe exacerbations.
. . . Prior intubation for asthma.
. . . Prior admission to intensive care unit for asthma.
. . . Greater than 2 hospitalizations for asthma in the past 12 months.
. . . Greater than 3 emergency room visits for asthma in past 12 months.
. . . Hospitalization or emergency care visit for asthma in the past month.
. . . Use of more than 1 canister per month of inhaled short-acting beta 2 agonist.
. . . Current chronic use of oral corticosteroids.
. . . Difficulty perceiving airflow obstruction or its severity.
. . . 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) A pCO2 of 40 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. In severe patients, aeration is poor, so inhaling albuterol by itself is usually insufficient. Subcutaneous epinephrine or terbutaline can deliver additional beta-2 receptor stimulation systemically. Other therapeutic options include: inhaled 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 (almost impossible). Although such patients have very high pCO2s 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 likelihood 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.
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, etc. Thus, the CXR may be necessary in the process of evaluating some 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.
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 clinical findings signifying the severity of an acute asthma exacerbation.
5. Discuss the approach to an asthmatic in relationship to formulating an acute asthma treatment plan. 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 use medications when their children are not openly symptomatic?
1. National Institutes of Health. NAEPP Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma-Update on Selected Topics 2002.
2. Busse WW, Lemamske RF. Advances in Immunology Asthma. New Engl J Med 2001;344(5):350-363.
3. Kay AB. Advances in Immunology Allergy and Allergic Diseases Part 1. New Engl J Med 2001;344(1): 30-37.
4. Kay AB. Advances in Immunology Allergy and Allergic Diseases Part 2. New Engl J Med 2001;344(2):109-114.
5. Marone G, Austen KF, Holgate ST, Kay BA, Lichtenstein LM (eds). Asthma and Allergic Diseases: Physiology, Immunopharmacology, and Treatment. 1998, San Diego: Academic Press.
6. Barnes PJ, Grunstein MM, Leff AR, Woolcock AJ (eds). Asthma. 1997, Philadelphia: Lippincott Raven.
7. Pearce N, Beasley R, Burgess C, Crane J. Asthma Epidemiology, Principles and Methods. 1998, New York: Oxford University Press.
8. Brenner, BE (ed). Emergency Asthma. 1999, New York: Marcel Dekker.
9. Murphy S, Kelly HW (eds). Pediatric Asthma. 1999, New York: Marcel Dekker.
10. Kotses H, Harver A (eds). Self Management of Asthma. 1998, New York: Marcel Dekker.
11. Szefler SL, Leung DYM (eds). Severe Asthma: Pathogenesis and Clinical Management. 2001, New York: Marcel Dekker.
12. Sheffer A (ed). Fatal Asthma. 1998, New York: Marcel Dekker.
Answers to questions
1. Asthma is best thought of as a chronic inflammatory condition consisting of obstruction of the airways of the lung caused by spasms of the smooth muscle surrounding the airways which, in some cases, can be easily reversed by beta adrenergic 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 muscles (relievers) and reversing the inflammation (controllers).
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, ability to move air through a peak flow meter or spirometer, and oxygen and carbon dioxide concentration in the arterial blood. The second parameter involves the sensitivity of the airways (i.e., the chronic severity classification described in the chapter). Day symptoms, night coughing episodes, peak flow, coughing with exercise, prolonged coughing after upper respiratory infections, and coughing with drinking ice-cold beverages help to categorize the severity of asthma.
4. Wheezing may be heard but if the attack is very severe there may be 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.
6. The asthma maintenance plans are dependent on the patient's severity class (step 1, 2, 3, or 4). For all "persistent" levels, a daily plan will usually involve a long-acting bronchodilator and corticosteroid, LTRA, cromolyn and/or theophylline two to three times a day. 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 short acting bronchodilators 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 air ways 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 steroids in children is that of linear growth. It is now well established that the use of inhaled steroids has significantly less effect on growth than systemic corticosteroids. The length of steroid use (inhaled or systemic), may have some effect on growth but its effect is temporary and in many studies final growth of asthmatics is generally no different than in non asthmatics (i.e., catch up growth occurs if the corticosteroids can be stopped for a period of time long enough for this to occur). 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.