Diagnosis of Asthma

Establishing the diagnosis is critical, although historically asthma has often been
misdiagnosed. Particularly in the young child, the symptoms resulting from airway
inflammation associated with asthma have been misdiagnosed as pneumonia and bronchitis,
leading to ineffective and unnecessary use of antibiotics (Figure 1). If there is not a firmly
established alternative diagnosis, asthma should be considered when patients present with the
following symptoms:

recurrent or chronic lower respiratory wheezing most prominent on expiration

recurrent or chronic coughing
repeated diagnoses of bronchitis
repeated diagnoses of pneumonia not clinically consistent with pyogenic infection

The diagnosis of asthma is most efficiently confirmed by demonstrating the complete

response of symptoms, or spirometric measurement of airway obstruction, to an inhaled 2
agonist and/or a 5 to 10 day course of high dose oral corticosteroids. Patients not clearly
made asymptomatic with these measures should be referred to an appropriate subspecialist
for further investigation of other inflammatory or occasionally functional disorders that can
cause similar symptoms. These can include such varied disorders as cystic fibrosis, cigarette
smoking induced chronic obstructive pulmonary disease, primary ciliary dyskinesia, tracheal
or bronchial malacia, foreign body aspiration, vocal cord dysfunction, or habit cough
syndrome.

Classification by Clinical Pattern

Planning effective and efficient strategies for managing asthma requires identification of the
clinical pattern of disease in the patient to be treated. These clinical patterns include:

Intermittent

Patients with episodic illness interspersed with extended symptom-free periods. Episodes are
most commonly triggered by viral respiratory infections or transient exposure to an
environmental allergen or irritant.

Chronic

Patients experience virtually daily symptoms and, in the absence of continuous therapy, do
not have extended symptom-free periods.

Seasonal allergic

Patients experience virtually daily symptoms during an inhalant allergy season. In the North
Central United States, this is most commonly from outdoor molds that grow on decaying
vegetation from early spring through late fall, with peaks particularly in the spring and fall.
Allergens and seasonal patterns will vary with the geographic region. In other parts of the
world, seasonal symptoms may be in reaction to molds, pollens, or a combination of both.
There is potential overlap among these clinical patterns. For example, patients with chronic
disease often have intermittent exacerbations from viral respiratory illness and may have
seasonal allergic exacerbations. Nonetheless, identification of the clinical pattern contributes
to the determination of a therapeutic strategy.

Severity, as assessed by degree of morbidity, is independent of the clinical pattern. Both

intermittent and chronic disease may range from relatively benign to life-threatening.
Severity should be judged by the frequency and intensity of urgent care requirements, missed
school or work, and interference with activity or sleep.

Therapeutic Strategies
Therapeutic strategies fall into two categories: intervention, defined as measures to stop acute
symptoms, and maintenance, defined as measures to prevent symptoms from occurring.

All patients require availability of efficient and effective intervention measures. Effective
intervention requires anticipating symptom progression so that anti-inflammatory
corticosteroids, which act slowly, may be started before urgent care is needed. Therefore, 2
agonists and corticosteroids should be available at home, and patients and their families
should be taught when and how to apply them, as outlined below.

Intervention alone is sufficient for treatment of those with intermittent asthma. However,
patients with chronic disease need maintenance medication in addition, to prevent their daily
symptoms. Patients with seasonal allergic disease may require maintenance medication, but
only seasonally, and patients with chronic disease may require seasonal increases in their
maintenance medication during seasonal allergic exacerbations. Adding or increasing
maintenance medication at the times when increased symptoms are anticipated avoids
morbidity and decreases the likelihood that urgent care will be needed.

Pharmacologic therapy must meet several criteria to be considered successful in controlling

asthma (Table 1). First, the treatment plan should eliminate the need for hospitalization and
unscheduled medical care due to asthma, and should prevent asthma from interfering with
sleep or any activities, including competitive athletics. Maintenance therapy, when needed,
should minimize the need for intervention with inhaled 2 agonist to a maximum of twice
daily, not counting pre-exercise prophylaxis, and reduce the need for intervention with short
courses of high dose daily oral corticosteroids ideally to no more than four times yearly.
Long-term use of daily oral corticosteroids is not safe in any dose and is not indicated for
acceptable control of asthma. Patients on maintenance therapy should be capable of normal
post-bronchodilator pulmonary function by office spirometry. Finally, patients should suffer
no adverse medication effects or adverse effects of treatment on their quality of life.

Low-intensity High-yield Early Intervention Measures

The first intervention should be a 2 agonist delivered promptly by age-appropriate
inhalational device (Figure 2). This should be applied repeatedly when needed. An inhaled 2
agonist is also the most effective means of prophylaxis for exercise-induced bronchospasm.
Careful instruction regarding appropriate use of the prescribed device is essential.
In the case of subresponsiveness to 2 agonists, identified by incomplete clearing of
symptoms or need for repeated use, high dose oral corticosteroids should be initiated
immediately and continued until the patient is symptom-free for 24 hours. This usually
requires 5 to 10 days of therapy (Figure 3). Patients must be educated on the criteria for
subresponsiveness to 2 agonists, which include failure to experience complete relief of
symptoms, failure of the 2 agonist effect to last 4 hours, and repeated use (for example,
symptoms requiring a third use within any eight-hour period). This algorithm should be
clearly communicated to the patient. Patients who have had previous urgent care
requirements or hospitalizations require a low threshold for progression to corticosteroid
therapy (Table II).

Early and vigorous intervention with these measures efficiently and effectively prevents at
least 90% of acute exacerbations of asthma from requiring emergency medical care or
hospitalization. There are no absolute contraindications to either of these measures. It should
be noted, however, that corticosteroids will increase hyperglycemia in diabetics. Also, the
onset of chickenpox in children receiving corticosteroids during the incubation period
justifies institution of acyclovir in full recommended doses.

Low-intensity High-yield Maintenance Measures

Low dose inhaled corticosteroids should be administered as the first-line of treatment in
preventing asthma exacerbations.

Inhaled corticosteroids

If the inhaled corticosteroid at low to usual doses does not result in criteria for control (table
1), a long acting 2 agonist is generally the most effective additive agent. The combination of
an inhaled steroid and a long acting 2 agonist is available as Advair (fluticasone and
salmeterol) and as Symbicort (budesonide and formoterol), both of which are dry powder
inhalers. However, there is an occasional patient who has worsening of their asthma control
with the addition of a long acting 2 agonist. This is observed particularly when the response
to a rescue bronchodilator such as albuterol becomes lessened after beginning a long acting
2 agonist. Theophylline also has substantial additive effect with an inhaled steroid but
requires careful dosing and monitoring of serum theophylline concentrations. Both a long
acting 2 agonist and theophylline added to a usual dose of inhaled corticosteroid results in
greater effectiveness than a higher does of inhaled corticosteroid. Montelukast (Singulair)
also has additive effect with an inhaled steroid but that effect appears to be less than that for a
long acting 2 agonist or theophylline.

A maximum of two maintenance medications at a twice-daily schedule with judicious use of

a pre-exercise 2 agonist and appropriate measures of intervention, is generally sufficient for
control of asthma. Patients requiring maintenance medication should, in general be evaluated
to determine the role of environmental factors involved in their symptoms. This evaluation
involves careful history and skin testing for specific IgE. This would be particularly relevant
for patients requiring more than low-dose inhaled steroids for maintenance.

If asthma is resistant to control by the regimens listed above, the patient should be referred to
subspecialty clinical care for more intensive evaluation and treatment.
Follow-up Guidelines
Patients whose disease meets criteria for control should receive routine follow-up at
scheduled intervals to assess control and assure safety of treatment (Table IV). Measurement
of pre- and post-bronchodilator pulmonary function with office spirometry should be
performed at each visit. Growth and weight gain should be monitored, because both asthma
and treatment with maintenance inhaled have the potential to slow growth. Blood pressure
measurement and eye exam for cataracts should be performed on all patients receiving
maintenance corticosteroids. In susceptible patients, increased blood pressure may be a
systemic effect of corticosteroids. Also, a small increased risk of cataracts has been
demonstrated even from inhaled corticosteroids.

Frequency of follow-up

Patients with an intermittent pattern of asthma can be followed with annual checkups if they
meet criteria for control. However, more frequent visits may be required to reinforce
instructions. Patients with a chronic pattern of asthma should be followed closely until
criteria for control are met. Once disease control on stable doses of medication has been
achieved, appropriate follow-up depends on the maintenance regimen. Patients requiring
more than low doses of inhaled corticosteroids, alternate morning prednisone, or more than
one maintenance medication should be seen every three months. Patients on low doses of
inhaled corticosteroid or other single-maintenance medication may be followed once every 6
months.

Guidelines For Urgent Physician Care of Acute Symptoms

Patients should be treated immediately with oxygen if they are in respiratory distress (Figure
4). They should also be given a 2 agonist immediately, by inhalation if they are capable of
effective inhalation, and by injection if they are severely dyspneic. High dose systemic
corticosteroids should be administered promptly by mouth if there is no concern regarding
retention, and parenterally if the patient is obtunded or vomiting. The patient should be
monitored with pulse oximetry. Blood gases should be drawn (venous or capillary gases are
adequate when pulse oximeter is used) if O2 saturation is less than 94 percent on room air and
patient is dyspneic or retracting, or if O2 saturation is less than 90 percent regardless of signs
or symptoms (Table V).

Patients may be discharged if they are comfortable at rest without retractions or use of
accessory muscles of respiration, and if O2 saturation is greater than 90% on room air. Early
follow-up is important. Patients should be admitted to the hospital if respirations continue to
be labored or their O2 saturation is less than or equal to 90%. They should also be admitted if
they are sufficiently dehydrated to require IV hydration, or if they have a history of rapid
deterioration and distant access to an appropriately staffed ICU (Table VI). Dehydration is
particularly likely to occur in small children because of decreased intake during an extended
period of respiratory distress, combined with increased insensible losses.

Once admitted, patients may be discharged when they are comfortable at rest without
retractions or use of accessory muscles of respiration, and their O2 saturation greater than
90%. Discharge should be delayed if labored respirations continue or O2 saturation remains
below 90%, the patient is sufficiently dehydrated to require IV hydration, there is a history of
rapid deterioration and distant access to an appropriately staffed ICU, or social concerns
regarding home care.

The considerations for decision-making regarding admission or discharge for asthma are
based on three related principles. First, there are no medications for asthma that are inherently
more effective parenterally than orally or by inhalation. Second, there is therefore nothing
that can routinely be done in the hospital that can not be done at home, except providing
oxygen, close monitoring, and assisted ventilation, if needed. And third, admission and
discharge decisions are based on the level of concern for the possibility of respiratory failure.

Formulary of Commonly Used Anti-asthmatic Medication

Inhaled2 agonists

Albuterol, pirbuterol (Maxair Autohaler) or levalbuterol. Two to six inhalations of the

metered dose inhaler can be used when needed for acute symptoms or pre-exercise to block
exercise induced bronchospasm. Use an assist device such as the Maxair Autohaler (3M) or a
valved holding chamber (AeroChamber Max or Pari Vortex) for patients with difficulty
coordinating inspiration with activation. Albuterol nebulizer solution, 2.5 mg can be used via
a compressed air driven nebulizer, but generally provides no more benefit than 6 inhalations,
one at a time, from the MDI through a valved holding chamber (with face mask if needed).
Levalbuterol (Xopenex) is the active component of racemic albuterol and has no therapeutic
advantage over racemic albuterol when used in equivalent doses; bronchodilation and side
effects do not differ significantly.

Systemic corticosteroids

For interventional therapy, a sufficiently high dose of prednisone or equivalent should be

used such that more is unlikely to be beneficial. For prednisone, we use the following doses:
less than 1 year old, 15 mg bid; 1 to 3 years old, 20 mg bid; 3 to 13 years old, 30 mg b.i.d.;
>13 years old, 40 mg bid. Higher doses may be justified for impending or actual respiratory
failure. For ambulatory use, patients should be instructed to discontinue the evening dose if
any side effects develop during the course of therapy. These may include insomnia, mood or
behavior changes, musculoskeletal pains, or bloating. Methylprednisolone may be used as a
substitute for prednisone at 80% of the prednisone dose if side effects from short courses of
prednisone remain troublesome. Dosage should be continued until the patient is free from
symptoms and signs of asthma. The mean duration of therapy is 7 days, with a usual range of
5 to 10 days. Dosage should be discontinued without tapering. Oral corticosteroids are as
effective as parenteral unless they are not retained.

Inhaled corticosteroids

Beclomethasone dipropionate is available at 40 and 80 micrograms per metered inhalation

(QVAR 40 or 80) with 100 metered inhalations per canister. This HFA microaerosal
formulation provides considerably improved delivery over older formulations of this drug.
Fluticasone is available at 3 concentrations, each with 120 metered inhalations per canister -
44, 110, and 220 mcg per metered inhalation (Flovent 44, Flovent 110, Flovent 220);
budesonide (Pulmicort Flexhaler ) is available as a 120 dose dry powder inhaler at 180 and 90
mcg per inhalation and as Pulmicort respules for delivery by compressed air driven nebulizer
with face mask (250 mcg or 500 mcg/dose). Mometasone is available as a dry powder inhaled
(Asmanex Twisthaler) with 30, 60, or 120 inhalations for the 220 (that delivers 200
mcg/inhalation) and with 30 inhalations of the 110 (that delivers 100 mcg per inhalation).
However, metered dose inhalers, propellent driven or dry powder, are much more convenient
and cost effective than the nebulizer preparation. Even for infants and toddlers, an assist
device, such as the AeroChamber or Pari Vortex with soft flexible face mask permits
effective delivery from an MDI.(Figure 2) For all inhaled corticosteroids, the lower end of the
dose recommendations is generally adequate since inhaled corticosteroids have a shallow
dose-response relationship. Adding salmeterol, formaoterol, or theophylline is usually more
effective than increasing the dose of inhaled corticosteroid. None of the inhaled
corticosteroids are of value for the prevention of urgent medical care or hospitalization
resulting from viral respiratory infection induced asthmatic exacerbations, even when given
in high doses.

Salmeterol and formoterol

Long acting 2 agonists (LABAs) include both salmeterol and formoterol and are available as
the dry powder inhalers, Serevent and Foradil. However, they are more typically and
preferable used in combination products with an inhaled corticosteroid, Advair (fluticasone
and salmeterol) and Symbicort (budesonide and formoterol). These are maintenance
medications and not meant to be for acute symptoms. The "black box" warnings that the FDA
now requires to be associated with these products are the consequence of a small number of
acute life-threatening events and fatalities associated with their use in an uncontrolled
manner. Since there appears to be occasional patients who experience less good control with
these medications, they are best added to an inhaled corticosteroid as one of the combination
products (Advair or Symbicort) with the patient then observed to see if they experience the
usual increased benefit from the combination or if they are the very occasional exception who
experience less good control of asthma, especially manifested by increasing requirement for
acute bronchodilator use with less benefit from that standard initial intervention measure for
acute asthma

Theophylline

Theophylline is less frequently used currently than it was in the past. Although an effective
maintenance medication, whether used alone or when added to an inhaled steroid, it requires
careful dosing and monitoring of serum theophylline concentration to be used with maximal
safety and effectiveness.

Montelukast (Singulair)

Montelukast is marketed as a once daily evening dosage preparation, 10 mg plain tablets with
5 and 4 mg chewable tablets for younger children, and 4 mg packets of a granular preparation
for infants and toddlers. Its efficacy is modest but often adequate for those with mild chronic
disease. There is at least some additive effect with inhaled corticosteroids. No toxicity or drug
interactions has been described.

Table I - Criteria for Control of Asthma

 Absence of hospitalization
Absence of unscheduled medical care
Absence of interference with sleep or activities (including competitive athletics)
Infrequent intervention with inhaled Theophylline is less frequently used currently
than it was in the past. Although an effective maintenance medication, whether used
alone or when added to an inhaled steroid, it requires careful dosing and monitoring
of serum theophylline concentration to be used with maximal safety and effectiveness.
agonist (not counting pre-exercise prophylaxis) < twice-daily
Infrequent intervention with short courses of high dose daily oral corticosteroids (< 4
times yearly ideally, but some young children may have viral respiratory induced
exacerbations more frequently for an occasional year for which, there is no good
alternative to an oral corticosteroid)
Normal or best attainable post-bronchodilator pulmonary function by office
spirometry
Absence of adverse medication effects
Absence of effects of asthma or its treatment on quality of life

Table II - Algorithm for Effective Intervention

Start with
Inhaled 2 agonist
(albuterol or pirbuterol)

if incomplete response, then...

Short course high-dose systemic corticosteroids

until clear (~5 to 10 days).

Table III - Algorithm for Maintenance Therapy

Start with
Low-dose Inhaled Corticosteroid
(montelukast may be given a trial for mild chronic asthma)

then...

Inhaled corticosteroid and long acting 2 (salmeterol of formeterol), theophylline or

montelukast are alternatives
(or montelukast if great effect not needed)

Table IV- Follow-up Guidelines for Asthma

 Intermittent - Reassess at 6- to 12-month intervals once controlled, however:
o Reinforce intervention measures with telephone contact during acute
exacerbations
o Monitor frequency of intervention
o Reassess if 2 used multiple times weekly

Chronic
o Reassess at least monthly until controlled
o Once controlled, reassess at 6- to 12-month intervals for patients on stable
low-dose inhaled corticosteroids or theophylline
o Reassess others at no greater than three month intervals

Table V - Guidelines for Urgent Physician Care of Acute

Symptoms
Immediate oxygen for patients in respiratory distress
Immediate 2 agonist by inhalation if patient can inhale effectively
Initial bronchodilator dose by injection of epinephrine or tertbutaline if patient is
severely dyspneic
Prompt administration of high dose systemic corticosteroid
Monitor with pulse oximeter
Blood gases if O2 saturation <94 percent at room air and patient is dyspneic or
retracting, or if O2 saturation <90 percent regardless of signs or symptoms

Table VI - Guidelines for Admission to Hospital

Admission not generally needed if:
o Comfortable at rest without retractions or use of accessory muscles of
respiration
o O2 saturation >90 percent at room air*

Admit to hospital if:

o Labored respirations continue
o O2 saturation less than or equal to 90 percent
o Dehydrated sufficient to require IV hydration
o History of rapid deterioration and distant access to appropriately staffed ICU
*Early follow-up is important.

Recommendations for Further Reading

1. Weinberger M: Proceedings of consensus conference on treatment of viral respiratory
infection induced asthma in young children. J Pediatr, 142; Suppl, Feb 2003:S1 and
S45-46
2. Weinberger M: Epidemiology and natural history of asthma. J Pediatr 142; Suppl, Feb
2003:S15-20
3. Weinberger M: Treatment strategies for viral respiratory infection induced asthma. J
Pediatr 142; Suppl, Feb 2003:S34-39
4. Weinberger M, Abu-Hasan M. Pseudo-asthma: when cough, wheezing, and dyspnea
are not asthma. Pediatrics 2007;120:855-864.
5. Weinberger M. Pediatric asthma and related allergic and nonallergic diseases:patient-
oriented evidence-based essentials that matter. Pediatric HealthOctober 2008, Vol. 2,
No. 5, Pages 631-650
http://www.futuremedicine.com/doi/abs/10.2217/17455111.2.5.631
6. Weinberger M. Childhood Asthma: Why is there controversy regarding this
commondisorder. In Treatment Strategies Pediatrics, December 2011, Volume 2,
Issue http://viewer.zmags.com/publication/07bdda69#/07bdda69/46
7. Weinberger M. Editorial. What IS the problem with asthma care for children? Arch
Pediatr Adolesc Med. 2011;165:473-475.
8. Weinberger M, Abu-Hasan M. Chapter 46: Asthma in the pre-school child. In
Kendigs Disordres of the Respiratory Tract in Children, 8th edition. Edited by RW
ilmott, TF Boat, A Bush, V Chernick, RR Deterding, F Ratjen. 2012, Elsevier
Saunders, pp 686-699.