Asthma.

Abstract: This article is a comprehensive review of asthma that discusses risk factors, diagnosis, and management. Guidelines for choosing appropriate asthma therapy are discussed. Key aspects of patient education are described. Reasons for the failure of asthma therapy with potential remedies are presented. Regular follow-up for good asthma care is emphasized.

Key Words: asthma, [beta]-agonists, corticosteroids 

**********

There is an epidemic of asthma affecting approximately 20.1 million individuals in the United States, 6.3 million of whom are children. Although the cause of the 300% increase in asthma prevalence during the past several decades is not clear, increases have occurred in both children and adults. Cleaner ways of living, excessive antibiotic use, smaller families with fewer siblings, and an overall lack of exposure to microbes early in life are postulated to be linked to allergies and asthma. (1), (2) The asthma epidemic is likely to be multifactorial, just like the disease itself.

Asthma is a chronic disease with reversible airflow obstruction manifesting clinically as cough, wheeze, shortness of breath, and chest tightness. Associated bronchial hyperresponsiveness, a condition reflecting small airway inflammation, causes chest tightness and cough with exposure to dust, smoke, weather changes, cold air, and exercise. This inflammation seems to be induced by the products of eosinophils, mast cells, neutrophils, lymphocytes, epithelial lining of the airways, endothelial lining of the vasculature, and airway smooth muscle. A variety of mediators including histamine, leukotrienes, prostaglandins, toxic proteins, and growth factors have been implicated. This complex inflammatory cascade is orchestrated by an intricate network of cytokines and chemokines, as discussed elsewhere. (3) This chronic inflammation, the true marker of asthma, can incite "airway remodeling," structural changes in the lung that are less reversible and perhaps associated with accelerated decline in lung function.

The major risk factor for persistent asthma in all age groups is atopy (ie, the predisposition to mount immunoglobulin E-mediated allergic responses to ubiquitous glycoproteins in the environment). Indeed, in one large study of more than 1,000 children with asthma, almost 90% had allergic sensitization to at least one aeroallergen. (4) Some of the other risk factors for persistent asthma in children and adults are listed in Table 1. Chronic rhinitis, both allergic and nonallergic, is a risk factor for asthma in all age groups.

Diagnosing Asthma

The standard approach to the diagnosis of any medical condition includes taking a good medical history, performing a focused physical examination, and conducting appropriate diagnostic tests.

History

Various aspects of a focused present, past, and family history can raise suspicion of and give clues to the diagnosis of asthma. Some of these are listed in Table 2.

Physical Examination

Physical examination during an office visit may be completely normal because of the episodic nature of the airflow obstruction seen in asthma. The presence of diffuse, polyphonic wheezing is an obvious "red flag." More subtle findings of a prolonged expiratory phase or end-expiratory wheeze may be missed on tidal breathing but can be uncovered with deep breathing. Hyperinflation of the chest noted as an increased anteroposterior diameter of the chest might be seen as a consequence of air trapping in asthma but also might be present in other conditions, such as emphysema. Upper airway inflammation with nasal pallor or erythema, nasal secretions, mucosal edema, turbinate hypertrophy, and/or nasal polyps as well as allergic shiners may be noted on examination. The presence of atopic dermatitis/eczema will increase the likelihood of finding concomitant asthma.

Pulmonary Function Testing

Diagnostic testing in asthma initially involves both clinic-based spirometry and home-based peak flow (PF) monitoring. Clinic-based spirometry is the "gold standard" for the diagnosis of airflow obstruction. Reasonably priced, hand-held spirometers are now widely available for office-based practices. Pre- and postbronchodilator spirometry (using a short-acting [[beta].sub.2]-agonist such as albuterol) is a critical tool in the diagnosis of asthma. The measurements generated by spirometry include forced vital capacity (FVC), forced expiratory volume in 1 second (FE[V.sub.1]), and FE[V.sub.1]-FVC ratio. Typically, FVC may be normal or slightly reduced from predicted values (on the basis of patient age, height, sex, and race) in most patients with asthma. FE[V.sub.1] is often decreased below the predicted level and is used in classifying asthma severity. The most sensitive indicator of airflow obstruction is FE[V.sub.1]-FVC ratio and is usually less than 0.8. An increase in FE[V.sub.1] of greater than 12% and 200 ml from baseline is defined as significant reversibility of airflow obstruction. Sometimes, a 2-week course of oral corticosteroids at 2 mg/kg (maximum, 60 mg/d) is required to demonstrate this reversibility. More specialized laboratory testing, such as full-body plethysmography and methacholine or exercise bronchoprovocation challenges, may be undertaken by asthma specialists to rule out or to confirm the diagnosis of asthma. Monitoring and documenting the best of at least three PF readings twice daily--once first thing in the morning and then again in the midafternoon (ie, AM/PM)--can provide valuable data. More than 20% variability in the AM/PM PFs, with AM PF readings often being lower than PM PF, is a diagnostic feature of asthma.

Other Tests

A chest x-ray is often indicated in newly diagnosed asthma patients to exclude other possible diagnoses. Allergy skin testing can be very informative in controlling potential environmental triggers of asthma and considering allergen immunotherapy that may be very helpful in certain patients. Current guidelines recommend allergy testing for all asthmatics with allergic triggers by history. Evaluation for comorbid conditions such as chronic sinusitis and gastroesophageal reflux disease is often important for optimal asthma control. Many asthmatic patients have chronic sinusitis with few symptoms.

Differential Diagnosis

The list of conditions that may present with wheeze and cough is quite extensive, but some of the more common ones are listed in Table 3.

Classifying Asthma Severity

Once an asthma diagnosis has been established, it is essential to classify the asthma severity level to determine the most effective pharmacologic therapy for a patient. The National Asthma Education and Prevention Program Expert Panel Report from the National Institutes of Health, National Heart, Lung, and Blood Institute contains guidelines for the diagnosis and management of asthma. (5) An update to the most recent Expert Panel Report was released in July 2002. (6) The subjective symptom-based and objective PF- or FE[V.sub.1]-based criteria are presented in Table 4. A patient needs to have only one criterion to be placed in the highest applicable category. For example, if a patient has asthma symptoms only 2 d/wk and has peak expiratory flow of >80% but wakes up more than 1 night per week, he or she is classified as having moderate persistent asthma, not mild persistent asthma.

Management of Asthma

Goals of asthma therapy are minimal or no day and nighttime symptoms; minimal exacerbations; no limitation in activities of school, work, or play; maintenance of normal lung function; minimal use of [beta]-agonist rescue ([less than or equal to]3 d/wk); and minimal or no adverse medication effects. Good asthma management involves the following:

* Control of factors that contribute to asthma severity

* Pharmacologic therapy

* Patient education and regular reassessment

Control of Factors that Contribute to Asthma Severity. The "one-airway" hypothesis emphasizes the close connection between upper and lower airway inflammation in the control of asthma. (7) Appropriate treatment of rhinosinusitis can greatly improve asthma control. A careful environmental history should help identify potential irritants to which a patient with asthma is exposed. Careful avoidance of these irritants can make asthma more manageable. Strict avoidance of environmental tobacco smoke exposure in the house and the car is of utmost importance. Asthmatics who smoke must be counseled to quit. Skin testing to identify specific allergen sensitivities is recommended for most patients with persistent asthma. Once identified, adherence to allergen avoidance measures for those specific allergens is recommended. Avoidance of irritants such as outdoor pollutants, indoor smoke from fireplaces or stoves, and occupational and/or household chemicals reduces acute attacks of asthma. Avoidance of aspirin and other nonsteroidal anti-inflammatory drugs in sensitive patients or desensitization of those who need to use such drugs regularly is important in some cases. Treatment of other comorbid conditions such as gastroesophageal reflux disease and vocal cord dysfunction can have a huge impact on asthma control. (8)

Pharmacologic Therapy of Asthma

Currently available medications for asthma therapy are best categorized into long-term control medications taken regularly to treat inflammation in persistent asthma (ie, daily controllers) and quick-relief medications for prompt reversal of acute airflow obstruction (ie, rescue medications). The various drugs currently available in these two categories for the treatment of asthma in the United States are listed in Table 5. Every asthmatic with intermittent or persistent asthma should be prescribed a short-acting [[beta].sub.2]-agonist (eg, albuterol) for use during acute asthma attacks. All patients with persistent asthma should use a daily control anti-inflammatory medication.

Choice of Medications

Inhaled cortices are the preferred, most effective, and most potent anti-inflammatory class of medications available for the treatment of all levels of persistent asthma. At the recommended low to moderate doses, they are safe, with no significant side effects on growth, development, and bone density noted in a large, prospective study of more than 1,000 children. (4) The inhaled cortices available have certain differences in their characteristics. Fluticasone, Budesonide, and beclomethasone are more potent than flunisolide and triamcinolone. This reduces the number of puffs needed to achieve the same effect. Fluticasone and Budesonide have lower systemic bioavailability, inactive metabolites, and greater first-pass hepatic metabolism than beclomethasone, which improves their topical-systemic therapeutic ratio and decreases systemic side effects.

The brief discussion that follows reviews the various options in treating patients with persistent asthma. Every effort should be made to take patient preferences into account when making a choice between these options. A 5- to 7-day burst of oral cortices (2 mg/kg; maximum, 60 mg/d) might be administered at any of these levels to jump-start the anti-inflammatory therapy and gain rapid control of the disease. Once the patient's asthma is controlled, remember to step down gradually to the least effective dose needed to maintain control of this chronic disease.

Rescue Medications. Albuterol delivered through a metered dose inhaler or nebulizer is the most commonly used rescue medication. Pirbuterol acetate administered through a breath-actuated inhaler is an attractive rescue option for patients older than 7 years of age who do not want to use a spacer device. Adolescents may find this device appealing for use 15 to 20 minutes before exercise to prevent exercise-induced bronchospasm. A new option for nebulized rescue therapy is levalbuterol, the active R-isomer of albuterol (50:50 R-isomer + S-isomer). Although, levalbuterol causes no fewer side effects than albuterol at equivalent doses (ie, 1.25 mg levalbuterol = 2.5 mg albuterol), in acute asthma therapy, when frequent treatments are needed, lack of accumulation of the inactive S-isomer present in albuterol but not in levalbuterol might prevent in vitro toxicity. (9) Low-dose albuterol (0.63, 1.25 mg/vial) is now available for use in younger children as rescue therapy and causes less tachycardia, tremors, and nausea than does premixed albuterol (2.5 mg/vial).

Mild Persistent Asthma. For patients who refuse to take inhaled cortices or are unable to take them, nonsteroidal anti-inflammatory agents (nedocromil sodium or sodium cromoglycate) might be options. These agents have excellent safety profiles but are maximally efficacious only if administered three to four times per day. Adherence to such therapy is often poor. These agents are less effective than inhaled cortices in preventing asthma exacerbations.

The leukotriene-receptor antagonists montelukast and zafirlukast are also alternatives for treatment of mild persistent asthma. These oral agents are less potent than inhaled cortices but are good options for steroid-phobic patients, patients unable to take inhaled cortices, and those without severe or frequent flares. They also have the advantage of providing some symptom relief for coexistent allergic rhinitis symptoms. They provide partial protection against exercise-induced bronchospasm. The other leukotriene-modifier zileuton, a 5-lipoxygenase inhibitor, must be administered four times per day and has the potential for hepatic toxicity.

Theophylline is a phosphodiesterase inhibitor with bronchodilatory and anti-inflammatory properties. It can be administered orally once daily in sustained-release forms or as many as three times per day in regular preparations. It has a narrow therapeutic index (recommended serum level, 5-15 [micro]g/ml), with toxicity (nausea, vomiting, tachycardia, headache, and even seizures) manifested when serum levels exceed 20 to 25 [micro]g/ml. Mandatory serum level monitoring, first at monthly and then at quarterly intervals, makes this drug a less attractive option for treatment. Drug interactions causing increased serum levels when coadministered with ciprofloxacin, erythromycin, oral contraceptives, and carbamazepine, are additional deterrents to the routine use of theophylline in mild asthma. Finally, theophylline may aggravate gastroesophageal reflux, which is a common comorbidity with asthma. Low doses of inhaled cortices should be prescribed for the majority of patients with mild persistent asthma.

Moderate Persistent Asthma. Asthma in some patients can be controlled with medium doses of inhaled cortices and others need combination therapy. The most effective combination therapy uses low to medium doses of inhaled cortices with a long-acting [beta]-agonist (LABA) such as salmeterol and formoterol. The LABA in this combination provides 12-hour bronchodilation, which is specifically helpful in reducing nighttime asthma symptoms and can also prevent exercise-induced bronchospasm. In vitro studies suggest synergistic anti-inflammatory effects of inhaled cortices and LABA. The other option available is to combine low to medium doses of inhaled cortices with a leukotriene-receptor antagonist such as montelukast or zafirlukast. The ease of administration of these add-on agents orally can improve adherence to therapy while providing additional anti-inflammatory control. Finally, low- to medium-dose inhaled cortices can be combined with theophylline or zileuton, but these remain less attractive options for reasons discussed above.

Severe Persistent Asthma. The preferred combination therapy at this level of severity is high doses of potent inhaled cortices such as fluticasone, Budesonide, or beclomethasone with a LABA (salmeterol or formoterol). Some patients will need oral cortices in addition to maintain control. Beginning with a daily dose of oral cortices to achieve control of disease, attempts are made to gradually taper this to an alternate-day dosing of less than 12 mg (prednisone or prednisolone) every other day, because the least adrenal suppression in adults may be seen at such doses. Every effort to maximize inhaled cortices dosing (four times per day instead of twice daily) and reduce oral corticosteroid dosing must be made. Treatment of gastroesophageal reflux, chronic rhinosinusitis, and depression that interferes with adherence to therapy is important in these patients. Regular monitoring for steroid side effects such as osteopenia or osteoporosis by bone mineral densitometry studies, cataracts by annual ophthalmologic examination, hypertension, and diabetes must be conducted in these patients. Supplemental calcium, vitamin D and, in selected cases, bisphosphonates are indicated to prevent or treat osteoporosis in severe asthmatic adults on chronic high-dose inhaled and oral cortices.

Special Considerations in Infants and Young Children. The youngest wheezers with more than four wheezing episodes or severe episodes of wheezing less than 6 weeks apart can greatly benefit from preventive asthma therapy. Inhaled cortices are the preferred first-line therapy in this age group according to updated National Asthma Education and Prevention Program guidelines. (6) The inhaled corticosteroid Budesonide is available as respules for nebulized therapy for children over 12 months of age. Dosed twice daily to achieve control and once daily for maintenance therapy, this drug is a safe option for treating young wheezers. Fluticasone administered through a pressurized metered-dose inhaler (pMDI) used with a spacer is approved for those as young as 4 years of age. Other options include montelukast and nebulized cromolyn sodium, which have been approved for children 2 years and older. The low-dose nebulized short-acting [[beta].sub.2]-agonists albuterol and levalbuterol are appropriate rescue therapy in these young children, with similar efficacy being noted when albuterol is administered using a pMDI and spacer with a well-fitted facemask.

Choice of Delivery Devices

The pMDIs remain the most commonly prescribed aerosol delivery devices, especially for [[beta].sub.2]-agonists, anticholinergics, and nedocromil. These devices need a certain degree of coordination with slow, deep inhalation begun with actuation of the device followed by 10 seconds of breath holding. Young children and older adults often have difficulty coordinating the actuation and inhalation. Even with good technique, 85 to 90% of the medicine deposits on the oropharynx reduce efficacy. Use of a volume-holding chamber or spacer device can enhance the delivery of the drug to the lungs and is strongly recommended in all children and adults. Several recent studies have found that an average of six to eight puffs (540-720 [micro]g) of albuterol administered through a pMDI with a spacer is just as effective as 2.5 mg (2,500 [micro]g) of albuterol administered through a nebulizer/compressor device in children and adults. Use of a facemask with a spacer in children younger than 4 years of age and a spacer with a mouthpiece for those older than 4 years of age would be recommended. A few commonly prescribed spacers on the U.S. market are E-Z Spacer (WE Pharmaceuticals, Inc., Ramona, CA), AeroChamber (Monaghan Medical Corp., Plattsburgh, NY), Easivent (Dey Laboratories, Napa, CA), and InspirEase (Key Pharmaceuticals, a division of Schering-Plough Corp., Kenilworth, NJ). The E-Z spacer is a compact, collapsible device that can be used with a facemask in small children and with a mouth-piece in older children. All spacers need to be regularly cleaned once a week for optimal drug delivery.

With the gradual phasing out of old chlorofluorocarbon-driven pMDIs and the introduction of new hydrofluoroalkane-driven pMDIs, some studies have found better lung deposition of drugs with the new devices. Smaller aerosol particle size (<5 [mirco]m) improves deposition in distal airways where inflammation is often present. Washing the mouth after using medications from a pMDI reduces systemic absorption of those medications. Short-acting [[beta].sub.2]-agonist (ie, pirbuterol acetate) is available as a breath-actuated MDI that does not require a spacer to be used with it. Because no coordination of actuation and inhalation is needed for these devices, they may be ideal for children older than 7 years of age, adolescents, and the elderly.

Dry powder inhaler devices are available for LABA and inhaled corticosteroid preparations. These devices have better lung deposition of drugs than pMDIs and do not need a spacer. Most 5-year-olds and some 4-year-olds can generate the 40 to 60 L/min inspiratory flow rate required to extract a dose of the drug out of the device. Mouth washing after use is recommended.

Nebulizers can be used to deliver [[beta].sub.2]-agonists, cromolyn, anticholinergics, and Budesonide. Different ultrasonic and jet nebulizer devices can generate a variety of particle sizes and output rates. For acute asthmatic exacerbations, nebulizer use is commonplace but may be gradually replaced by pMDI with spacer use in many settings. Blow-by nebulizer therapy leads to significant wastage of medication and poor efficacy and thus must be strongly discouraged. Use of a well-fitted face-mask in young children and a mouthpiece in all older patients must be the standard of care with nebulizer therapy. Newer breath-actuated nebulizer devices markedly reduce wastage by eliminating continuous nebulization of drugs even when the patient is not inspiring. Portable compressor devices have made nebulization therapy easily accessible when needed.

Patient Education

Patient education is critical to ensure successful and continued adherence to therapy. The key points of patient education are listed in Table 6. We must give the patient and/or the patient's parent a chance to ask questions and voice concerns.

Management of Outpatient Asthma Exacerbation

The keys to successful management of outpatient exacerbations are early recognition, prompt reversal of airflow obstruction, and close follow-up with added anti-inflammatory therapy. Short-acting [[beta].sub.2]-agonists, oxygen, and oral or parenteral cortices form the cornerstone of acute asthma management in the office. Antibiotics are not appropriately prescribed for most asthma exacerbations. For further details, the reader is directed to a recently published review of this topic. (10)

Follow-up Care

After initial diagnosis of persistent asthma has been made and anti-inflammatory therapy initiated, follow-up should be in 2 weeks and every 2 to 4 weeks thereafter until adequate control is achieved. If marked improvement is noted, anti-inflammatory therapy may be tapered but should not be discontinued. If asthma is not well controlled, adherence to therapy, technique with delivery devices, home PF monitoring, and environmental control measures must be reviewed and errors remedied. Therapy may need to be escalated if symptoms persist despite excellent compliance. Once asthma is well controlled, mild patients may be seen every 6 months, moderate patients may be seen every 3 to 4 months, and severe patients need individualized closer follow-up. Interval events of acute exacerbations, prednisone bursts, hospitalizations or urgent care visits, or increased symptoms may prompt added interventions or escalation of therapy. Spirometry must be repeated when adequate control is achieved, then annually for most, and more often in some patients. Referral to an allergy/asthma specialist should be considered for most moderate, all severe, and a few mild asthmatics with frequent or severe exacerbation history. Reasons for failure of therapy and potential remedies are listed in Table 7.

Conclusion

Asthma is a dynamic, multifactorial, inflammatory disease that can be effectively managed in most patients with currently available therapy. Every effort must be made to identify this often underdiagnosed and definitely undertreated chronic illness. Daily controller anti-inflammatory therapy can improve quality of life significantly. Partnering with the patient or parent to achieve best adherence to therapy is critical for good outcomes. Almost every patient with asthma must be able to work, play, sleep, and lead a normal life with good therapy and close follow-up.

To maintain a well-balanced perspective, The person who has a dog to worship him Should also have a cat to ignore him.

--Author unknown

Key Points

* Asthma is an immunologically mediated disease of airway inflammation.

* Persistent asthma is often associated with chronic rhinosinusitis.

* Use of present asthma guidelines tends to improve outcomes in the treatment of asthma.

Appendix: Patient and Physician Asthma Resources

1. National Asthma Education and Prevention Program: http://www.nhlbi.nih.gov/about/naepp/index.htm

2. National Heart, Lung and Blood Institute. Asthma Information: http://www.nhlbi.nih.gov/health/public/lung/index.htm

3. Global Initiative for Asthma: http://www.ginasthma.com

4. Medfacts: National Jewish Medical and Research Center: http://www.njc.org.medfacts.htm#AsthmaMedFacts

5. Allergy and Asthma Network Mothers of Asthmatics. Breatherville USA: http://www.aanma.org/breatherville.htm

6. American Academy of Allergy Asthma and Immunology: http://www.aaaai.org/patients/allergic_conditions/asthma.stm

7. Allergy, Asthma and Immunology Online: http://www.allergy.mcg.edu/

8. American Lung Association: http://www.lungusa.org/asthma/

Table 1. Risk factors for persistent asthma in children and adults

Risk factors in children              Risk factors in adults

Atopy                                 Atopy

Parental history of asthma            Cigarette smoking

Severe lower respiratory tract        Rhinitis, allergic and nonallergic
infections

Atopic dermatitis                     Childhood asthma history

Allergic rhinitis                     Family history of asthma

Food allergies                        Female sex

Wheezing apart from colds

Elevated serum immunoglobulin E in
  infancy

Peripheral blood eosinophilia (>4%)

Obesity

Male sex

Table 3. A few differential diagnoses of cough and wheeze in children
and adults

Children                                 Adults

Viral bronchiolitis        Chronic obstructive pulmonary disease

Chronic rhinosinusitis     Chronic rhinosinusitis

Cystic fibrosis            Gastroesophageal reflux

Laryngomalacia             Congestive heart failure

Tracheobronchomalacia      Tumors/masses compressing the airways

Foreign body               Drug-induced cough (eg, angiotensin-

Chronic aspiration           converting enzyme inhibitors)

Gastroesophageal reflux    Interstitial lung diseases

Vascular rings             Hypersensitivity pneumonitis

Tumors/masses compressing  Vocal cord paralysis

  the airways              Vocal cord dysfunction

Congestive heart failure

Vocal cord dysfunction

Table 4. Asthma severity classification before initiation of therapy
(a), (b)

                              Days with symptoms
Severity           (exacerbations)

Severe persistent           Continuous (frequent)

Moderate persistent         Daily ([greater than or equal to]2 times/wk)

Mild persistent             3-6 times/wk (affect activity)

Mild intermittent           [less than or equal to]2 times/wk (brief
                            and of varying intensity)

Severity                    Nights with
        symptoms

Severe persistent           Frequent

Moderate persistent         5/mo

Mild persistent             3-4/mo

Mild intermittent    [less than or equal to]2/mo

                        PEFR or FE[V.sub.1]
                           (% predicted)
                        PEFR variability
Severity                    (AM VS. PM)

Severe persistent      [less than or equal to]60%

                                  >30%

Moderate persistent             60-80%

                                  >30%

Mild persistent        [greater than or equal to]80%

                                20-30%

Mild intermittent      [greater than or equal to]80%

                                  <20%

Severity                    Controller therapy options

Severe persistent    High-dose iGC plus LABA or LTRA or
                       sustained-release theophylline and/or
                       LABA tablet

                     Oral GC as needed

Moderate persistent  Medium dose iGC or low dose iGC plus
                      LABA or LTRA or sustained-release
                      theophylline or LABA tablets

Mild persistent      Low-dose iGC or nedocromil or cromolyn or
                      LTRA (sustained-release theophylline is an
                      alternative)

Mild intermittent    No daily medication is needed

(a) iGC, inhaled glucocorticoid; LABA, long-acting [beta]-agonist
(inhaled); LTRA, leukotriene-receptor antagonist; PEFR, peak expiratory
flow rate; FE[V.sub.1], forced expiratory volume in 1 second.
(b) Any one feature of severity is sufficient to place patient in that
category. Any individuals classification may change over time (dynamic
disease). Severe life-threatening exacerbations can occur even in
mild intermittent patients. Patients of all severity
levels must have a short-acting [[beta].sub.2]-agonist (rescue)
prescription.

Table 5. Pharmacologic agents currently available for asthma management
in the United States (a)

Quick-relief medications         Long-term control
(rescue medications)             medications(daily
        controllers)

Short-acting inhaled            Nonsteroidal anti-inflammatory
[[beta].sub.2]-agonists

  Pressurized metered-dose        Cromolyn (Intal) pMDI and

    inhalers                        nebulizer

    Albuterol (Proventil,         Nedocromil (Tilade) pMDI

      Ventolin)                 Inhaled glucocorticoids

    Pirbuterol (Maxair)            Flunisolide (Aerobid) pMDI

    Terbutaline (Brethaire)        Tramcinolone (Azmacort) pMDI

    Metproterenol (Alupent)        Beclomethasone (Beclovent,

  Nebulization solutions             Vanceril, Qvar) pMDI

    Albuterol (Proventil,           Fluticasone (Flovent) pMDI

      Ventolin, Acuneb)             Budesonide (Pulmicort) DPI,

    Levalbuterol (Xopenex)            nebulizer solution

Inhaled anticholinergics       Long-acting inhaled [beta]-agonists

  Ipratropium (Atrovent)         Salmeterol (Serevent) DPI

Systemic glucocorticoid burst    Formoterol (Foradil) DPI

  Prednisone (eg, Deltasone),  Leukotriene modifiers

  Prednisolone (eg, Orapred)     Montelukast (Singulair)

  Methylprednisolone (Medrol)    Zafirlukast (Accolate)

  Methylprednisolone sodium      Zileuton (Zyflo)

   succinate (Solumedrol)      Theophylline (eg, generic, Uniphyl,

                                  Slobid, Theodur)

                                  Tablet or capsule

                               Oral glucocorticoids

                                 Prednisone

                                 Methylprednisolone

(a) pMDI, pressurized metered-dose inhaler; DPI, dry powder inhaler.

Table 7. A few reasons for failure of therapy, and potential remedies

Reasons for failure of               Potential remedy
therapy

Nonadherence

  Treatment-related barriers

    Prolonged therapy with     Prepare patient and set realistic goals

      slow effects

    Expense                    Social worker support, generic drugs

    Adverse drug effects       Monitor therapy and counsel in

                                advance

    Complex medical regimens   Simplify therapy, once daily, pillboxes

  Physician-related barriers

    Scheduling difficulties    Avoid lapses in follow-up, increase

                                appointment times and availability

    Uninterested clinician

    Rotating caregivers

  Patient-related barriers

    Lack of understanding of   Educate patient on various aspects of

      disease and therapy       asthma, inflammation, and therapy

    Insufficient faith in      Be nonjudgmental, nonthreatening

      caregiver

    Psychological barriers     Psychological evaluation and therapy

    Lack of motivation

Poor technique with devices    Demonstrate and reassess at each visit

Incorrect use of medications   Written instructions for medications

Discontinuation of therapy     Regular follow-up

Lack of environmental control  Educate and provide resources

From the Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS.

Reprint requests to Sitesh R. Roy, MD, Department of Pediatrics, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216. Email: [e-mail]

Accepted August 19, 2003.

Copyright [c] 2003 by The Southern Medical Association 0038-4348/03/9611-1061

References

1. Liu AH, Szefler SJ. Advances in childhood asthma: hygiene hypothesis, natural history, and management. J Allergy Clin Immunol 2003;111(3 Suppl):S785-S792.

2. Martinez FD. Links between pediatric and adult asthma. J Allergy Clin Immunol 2001;107(5 Suppl):S449-S455.

3. Busse WW, Lemanske RF Jr. Asthma. N Engl J Med 2001;344:350-362.

4. The Childhood Asthma Management Program Research Group. Long-term effects of Budesonide or nedocromil in children with asthma. N Engl J Med 2000;343:1054-1063.

5. National Asthma Education and Prevention Program. Clinical Practice Guidelines: Expert Panel Report 2--Guidelines for the Diagnosis and Management of Asthma (NIH Publication No. 97-4051). Bethesda, MD, National Institutes of Health, National Heart, Lung, and Blood Institute, 1997. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. Accessed September 17, 2003.

6. National Asthma Education and Prevention Program. Clinical Practice Guidelines: Expert Panel Report 2--Guidelines for the Diagnosis and Management of Asthma: Update on Selected Topics 2002 (NIH Publication No. 02-5075). Bethesda, MD, National Institutes of Health, National Heart, Lung, and Blood Institute, 1997. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/execsumm.pdf. Accessed September 17, 2003.

7. Bachert C, van Cauwenberge P, Khaltaev N, et al; World Health Organization. Allergic rhinitis and its impact on asthma: Executive summary of the workshop report 7-10 December 1999, Geneva, Switzerland. Allergy 2002;57:841-855.

8. Wood RP II, Milgrom H. Vocal cord dysfunction. J Allergy Clin Immunol 1996;98:481-485.

9. Ahrens R, Weinberger M. Levalbuterol and racemic albuterol: Are there therapeutic differences? J Allergy Clin Immunol 2001;108:681-684 (editorial).

10. Roy SR, Milgrom H. Managing outpatient asthma exacerbations. Curr Allergy Asthma Rep 2003;3:179-189.

RELATED ARTICLE: Table 2. Historical clues raising suspicion of and giving clues to the diagnosis of asthma

Repeated physician-diagnosed wheezing

Clinical and subjective improvement of symptoms with bronchodilator use

Repeated diagnosis of "bronchitis," "bronchiolitis," and "touch of pneumonia"

Wheeze or cough worse at night or early in the morning

Common triggers, including viral infections, exercise, dust, smoke, allergens, cold air, strong emotions, strong odors or chemicals, changes in weather, and menses 

Aspirin/nonsteroidal anti-inflammatory drug sensitivity and nasal polyps

Personal history of other atopic diseases (ie, atopic eczema, rhinitis, food allergy)

Family history of asthma or other atopic diseases

RELATED ARTICLE: Table 6. Key points in patient education for asthma

Relevant environmental control (tobacco elimination, allergen avoidance)

Contrast normal and inflamed asthmatic airways and relate to symptoms

Explain role of daily controller therapy to reduce inflammation and as-needed rescue therapy to relieve symptoms of asthma

Teach and assess correct technique with inhaler and nebulizer use and care

Provide peak flow meter, show when and how to use it

How to recognize early warning signs of an asthma attack

Asthma action plan for day-to-day care and treatment of an asthma attack

Provide 24-h telephone access to medical advice

Develop a partnership with patient/parent for open communication

Sitesh R. Roy, MD