Asthma is classified as atopic or non-atopic. In atopic asthma inflammation and changes in smooth muscle tone in asthma results from the activity of antibodies. Antibodies start the inflammatory response in reaction to antigens to which a person is sensitive or allergic. This is called atopy. Atopic asthmatics react to stuff that most would tolerate: cockroaches, cat dander, and pollen for example. Some people have asthma attacks not based on reactions to antigens. This is non-atopic asthma. These patients can experience asthma attacks resulting from exercise, strong emotional reactions and medicines such as aspirin.(36)

What Triggers an Asthma Attack?

An asthma attack can be caused by a number of different stimuli or trigger:

• Allergic - An allergy is a hypersensitive reaction to intrinsically harmless antigens, most of which are enviromental. (37)
  Inhaled allergens such as pollens, dust mites, animal dander, mold, cockroach droppings
• Inhaled irritants such as tobacco smoke, strong odors, air pollution, solvent fumes
• Weather changes
• Viral or sinus infections
• Exercise
• Reflux disease
• Medications like ACE inhibitors, Beta-blockers, on-steroidal anti-inflammatories
• Foods especially those with sulfites
• Emotional anxiety (36,38,39,40)

How do triggers cause an attack?

The IgE mediated response:
With many asthma attacks, in response to a trigger, bronchial mast cell releases Pro-inflammatory Cytokines, which stimulates T Cells to produce IL-4 which causes B Cells to release IgE which stimulates the bronchial mast cells to repeat the cycle and directly contract airway smooth muscle. The bronchial mast cells also release, Chemokines, Tryptase, other chemicals such as IL-5 and 8 which cause Neutrophils, Eosinophils and Macrophages to cause inflammation in bronchial tubes. Mast cells also play a role in bronchoconstriction by releasing histamines and Leukotrines. (41)

Despite the strong picture of exactly how an asthma attack occurs, the underlying reason why this happens in asthmatics and not all with allergies is not fully understood.(42)

NSAIDss can cause an asthma attack that appears not to be related to the IgE mediated response described above, but involves mediator release from airway cells. (43)

Childhood Asthma
Although the pathogenesis of their disease is similar, Asthma affects children differently than adults. Their smaller lung capacity means they are affected more severely and quickly than their adult counterparts. They breathe harder when their airways become restricted. It is more difficult to test children to determine the severity of their condition. It is also more difficult to give them appropriate rescue medications when they are having an attack.

Furthermore, children can show signs of the disease when they are not having an exacerbation. Asthmatic children not experiencing an asthma attack can show clinical manifestations that are not typically seen in adults: headaches, irritability and depression, allergic shiners, rhinorrhea with yellow or green mucus discharge, sleeping difficulties or congestion with a cough.

Other factors associated with childhood asthma include fatigue, complaints like chest pains or the chest "feeling funny", and the avoidance of activities like sports or sleepovers. An associated symptom in infants might be breathing difficulty and possible grunting during sucking. (41,42,43)

Studies over the past 7 years seem to indicate that when asthma symptoms start during the first 3 years of life there is a decline in lung function growth. However if asthma symptoms start after 3 then there is not this decline in lung function growth. It is thought that these are the children who will develop more severe symptoms later on in life. However most children who wheeze before 3 do not develope asthma.This lead to the development of asthma predictive indexes which are able to pick 66% of children under 3 who were later diagnosed with asthma and 97% of the those who did not have the disease. (44)

Asthma Predictive Index - For children under 3 who have 4 or more wheezing episodes during the past year:
Either 1 Parental history of asthma or 2 A physician diagnosis of atopic dermatitis or evidence of sensitization to aeroallergens
Or two or more of the following
2. Evidence of sensitization to foods
3. Greater than 4% peripheral blood eosinophila
4. Wheezing (apart from colds)(44)

See another closely related Asthma Predictive Index

Asthma Risk Factors

Several factors may place a child at an increased risk for developing asthma. Some risk factors are environmentally-based and preventable; others are non-preventable.

Preventable Risk Factors

Smoking
Around 38% of children today are exposed to tobacco smoke during their first five years. This exposure to second hand smoke can, according to some studies, almost double the prevalence of asthma in children causing an estimated 530 thousand extra doctor visits each year.(45)

Other risk factors:
Presence of allergies
Outdoor or indoor air pollution
Occupational exposure
Obesity
GERD
Low birth weight
CHF
History of PE
Genetics, Ethnic background
History of atopic dermatitis or eczema
Viral infections (46)

Prognosis

Aside from the work on an asthma predictive index there is no clear way to predict the outcome for an individual child that wheezes, but if the child has atopic asthma, if their parents smoke, or if their is a family history of the disease then it is more likely that their condition will continue to adulthood.(47)

There have been studies trying to predict whether an asthmatic will have an attack severe enough to cause death. A near-fatal asthma attack is one where the patient has been intubated, or where the patient has had respiratory failure and altered mental status. These patients tend to be ones with frequent hospitalizations and ER visits. They also tend to have a history of depression, poverty or alcohol abuse. They have a poor perception of being short of breath. There is an increased risk in the African American population, the Hispanic population and in females.(48,49)

Airway Remodeling

In some patients with severe asthma, the constant chronic inflammation of the airways may cause the airway matrix to become distorted (50,51). This is airway remodeling, and it is irreversible. Features of airway remodeling include:

Inflammation
Mucus hypersectretion
Subepithelial fibrosis
Airway smooth muscle hypertrophy
Angiogenesis (50)

Current Approaches to Asthma Treatment

Although the basic treatment of asthmatics has not changed much in 100 years new approaches to the disease are helping those with the disease lead healthier lives.

The three Expert Panel Reports offered a new ways to attack the disease centering on four basic tenants:

1. Accurately measure lung function to determine the severity of the disease and to monitor its course.

2. Eliminate or reduce the environmental factors, either irritants or allergens, which trigger or exacerbate asthma symptoms, including:

• Allergen exposure
• Irritants
• Occupational exposures for asthmatics of working age
• Other factors like:
• Rhinitis/sinusitis
• Gastroesophageal reflux
• Sensitivity to aspirin, other nonsteroidal antiinflammatory drugs, and sulfites
• Topical and systemic beta-blockers
• Viral respiratory infections(52,38)

3. To use medicines to control the inflammation associated with asthma as well as medicines to manage asthma attacks.

4. To educate patients about the nature and management of asthma.(53)

Measurement of lung function

In the first two Expert Panel Reports it was the recommendation of the NAEPP that asthmatics with Moderate Persistent or Severe Persistent asthma use peak flows to monitor the severity of their disease. The 1991 NAEPP report recommended twice daily peak flow monitoring. The 1997 report changed this to once a day. The most recent report further modifies this recommendation to include those who have poor perception of airflow obstruction, worsening asthma or unexplained response to enfirmental or occupational exposures use peak flows. (54)

Those patients with severe asthma are recommended to have pulmonary function studies done at least every one to two years.(55)

Controlling Asthma Triggers

Exposure of asthma patients to irritants or allergens to which they are sensitive has been shown to increase asthma symptoms and cause asthma exacerbations. It therefore stands to reason that limiting asthmatic''s exposure to allergens will improve their disease. (56) The NAECP divided their recommendations on controlling exposure based on the severity of the disease. Patients whose asthma requires them to take daily medications should identify allergen exposure using the patient''''s history to assess sensitivity to seasonal allergens such as pollen. To determine if there is a problem with indoor allergies like warm blooded pets, dust mites, cockroaches and others testing for allergens is recommended. Another reason to use allergy testing for indoor allergens is that the methods used to control indoor allergens can be expensive. (57) One study in 2005 placed the cost at over $1400. (58) Those patients whose asthma is not as severe should avoid exposure to those allergens which appear to cause them trouble. The NAEPP did not support determining the cause of asthma flare-ups in these patients as in more serious cases because of the expense involved. Patients with asthma at any level of severity should avoid irritants such as tobacco smoke, exercising when air pollution is bad, and use of beta-blockers. Patients should be treated for rhinitis, sinusitis, and gastroesophageal reflux, if present.

Patients with asthma should consider an annual influenza vaccine. "However, the vaccine should not be given with the expectation that it will reduce either the frequency or severity of asthma exacerbations during the influenza season."(59)

The Expert Panel could not recommend air cleaners saying "Most studies of air cleaners have failed to demonstrate an effect on asthma symptoms or pulmonary function.  The reason for this is that most particles that an asthmatic will have problems with do not remain airborne." For asthmatics who are sensitive to dust vacuum cleaners should either have a double bag or be fitted with a HEPA filter.  Asthmatics should stay out of rooms that have just been vacuumed.(60)

Asthma Management Guidelines

Written asthma action plans
Asthma self-help or self-management programs have been around for a long time. Among the first formal studies of self-management programs is of a nurse-educator program in the Children''''s Hospital of Pittsburgh in 1981. This plan, although it was mainly concerned with recoginition and avoidance of triggers, still demonstrated that self-management of asthma can be very helpful in decreasing the harmful effects of this disease.(61)

Written asthma action plans now are particullarly recommended "for patients who have moderate or severe persistent asthma, a history of severe exacerbations, or poorly controlled asthma."(62)  Plans have two important elements. Instructions for keeping asthma under control and how to recognize and handle an exacerbation.  See the California RAMP site for an example of asthma action plans (63, 64) 

Stepwise Approach for Managing Asthma
The expert panel with reports in 1991 and 1997 became among the first to develop a protocol for the treatment of asthma. This protocol is known as the Stepwise Approach for Managing Asthma.  The protocol is based on the severity of the patient''''s asthma.  As asthma symptoms increased  the response in terms of increased frequency of treatment and the number of medications given increased. The most recent EPR divided the severity of asthma into imparement and risk.  Imparement deals with frequency and intensity of symptoms. Risk has to do with how likely exacerbations will occur in the future or the likelihood the patient will experience loss of lung function.  These two domains of asthma severity do not correlate with each other.  A person may not be impared much by their asthma, but they are still at risk of having a severe exacerbation. (65)

Asthmatic imparement and the risk of future exacerbations were categorized into four different levels of severity based on symptoms, nighttime awakenings, interference with daily activity, use of SABAs, interference with normal activity, and Lung function.  Lung function did not apply to those patients older than 4 years of age.

1. Intermittent - Symptoms occur less than or equal to two days per week and there are less than two nights per month that the patient is awakened. SABA use is less than 2 days per week.  In intermittent asthma there is no interference with normal activity.  Peak flows  or FEV1s  are greater or equal to 80 percent of normal. FEV1/FVC ratio is normal.

Although it may fluctuate, it is thought that these patients are at risk of at most 1 exacerbation requiring oral systemic corticosteroids per year.

2. Mild Persistent - Symptoms occur more than two days per week but less than once per day and less than two nights per month. Peak flows or FEV1s are greater or equal to 80 percent of normal, and variability is less than 20 to 30%.  SABA use is less than once a day but can be more than twice a week.

A patient with mild persistent asthma is thought to be at risk for 2 or more exacerbation requiring oral systemic corticosteroids per year.

3. Moderate Persistent - Symptoms occur daily or greater than one night per week. Peak flows or FEV1s are greater than 60%, less than 80 percent of normal.  SABA use is daily.

A patient with moderate persistent asthma is thought to be at risk for 2 or more exacerbation requiring oral systemic corticosteroids per year.

44. Severe Persistent - Symptoms occur continually during the day and frequently during the night. Peak flows or FEV1s are less than or equal to 60% of normal. SABA use is several times a day.

A patient with severe persistent asthma is thought to be at risk for 2 or more exacerbation requiring oral systemic corticosteroids per year.

Patients can then be classified based on the lowest of treatment required to maintain control of their disease. Ant intermittent asthmatic would be classified as Step 1 while a patient who uses an albuterol inhaler several times a day and is awakened as much as every night during the week because of their asthma would be classified a step 5 or 6.  Step 6 is the worst an asthmatic can be with this system. (66)

Assessing Asthma Control

The most recent EPR set up a system of monitoring asthma control based on number of symptoms, nighttime awakenings, interference with normal activity and use of SABAs. 

• A patient with well controlled asthma has symptoms less than two days a week, are awakened once a month with asthma symptoms and use their rescue medications two days a week or less .
• A patient is classified as having not well controlled asthma if their symptoms flair more than two days a week if they are awakened more than once a month and if they use SABAs more than two days a week
• A patient is considered to have very poorly controlled asthma if  they have symptoms throughout the day, if they are awakened more than once a week and if they use their SABAs several times a day.

The risk component used to classify asthma severity is used here to help assess the amount of control a patient has when dealing with their asthma.

• Well controlled asthma will have at most one exacerbation a year.
• Not well controlled asthma will have at most 2-3 exacerbations per year.
• Very poorly controlled asthma will have more than 3 exacerbations a year.(67)

Long term management of asthmatics

The steps described above are used to approach the treatment of those with asthma. There are six different steps with the most recent Expert Panel Report with step six being the most intense.  Patients may often move up and down steps as their condition warrents. 

All patients may need two to four puffs of short-acting inhaled beta2-agonists as needed for symptoms. Use of SABA for more than 2 days a week for symptom relief (not prevention of EIB) generally indicates inadequate control according to the Expert Panel and the need to step up to the next level of treatment. 

Step 1 Intermittent - No daily medication needed. If severe exacerbations occur, a course of systemic corticosteroids is recommended.

Step 2 - Preferred treatment is low-dose inhaled corticosteroids. Other treatments include Intal or cromolyn sodium, leukotriene modifiers, nedocromil, or  Theophylline.

Step 3 - Preferred treatment changes depending on the patient''''s age.  If the asthmatic is older than 12 years old than the preferred treatment is is low dose ICS and a or medium-dose inhaled corticosteroids.  Alternatives to this include low dose ICS and a LTRA, theophylline or Zileuton.  If the child is between 5 and 11 then the preffered treatment becomes low-dose ICS and either a LABA or LTRA or Theophylline or a Medium-dose ICS.  If the patient is less than 5 years old then the prefferred medication is a medium-dose ICS.

Step 4 - Preferred treatment for a person over 12 is a medium-dose ICS and a LABA. Alternatives to this is a medium-dose ICS and either a LTRA, Theophylline or Zileuton.  For childeren 5-11 the preferred medications are a medium-dose ICS and LABA.  An alternative to this is a medium-dose ICS and either a LTRA or Theophylline.  For children 0-4 the preferred medications are a medium-dose ICS and either a LABA or Montelukast

Step 5 - Preferred treatment for  a person over 12 is a high-dose ICS and LABA and consider Omalizumab for those with allergies. For children 5-11 preferred treatment is a high-dose ICS and LABA.  An alternative to this is a high-dose ICS and either LTRA or Theophylline.  For children 0-4 the preferred treatment is high-dose ICS and either a LABA or Montelukast.

Step 6 - Preferred treatment for asthmatics over 12 who require this level of treatment is high-dose ICS and LABA and oral corticosteroids and consider Omalizumab for those with allergies.  For those 5-11 preferred treatment is high-dose ICS and LABA and oral systemic corticosteroids.  An alternative is high-dose ICS and either LTRA or Theophylline and oral systemic corticosteroid.  For children 0-4 the preferred treatment for step 6 asthma is high-dose ICS and either LABA or Montelukast and oral systemic corticosteroids.(68)

Medications used in Treating Asthma

Breathing treatments, first used in 1938, have been a mainstay in the treatment of asthma. (69) The medicines given in a breathing treatment can be thought of as performing one of three different functions. The medicine can:

1. Act as an antinflammatory.
2. Act as a bronchodilator
3. Can perform some other function such as decreasing air hunger or delivering an antibiotic.

(For more thorough documentation on these medications, please refer to the documentation that came with the medication.)

Corticosteroids

Physicians first started using corticosteroids for severe asthmatics in the early 1950''''s and their use became the standard of care for severe cases from the 1970''''s. Systemic corticosteroids use can bring severe side effects including Cushing''s Syndrome.  Inhaled versions of the drug were prescribed as early as 1972. Although there was an initial reluctance to prescribe inhaled corticosteroids.  With time that reluctance disapeared. (70,71)

Unlike bronchodilators inhaled anti-inflammatories are now used as a maintenance medicine. But their place in the treatment of asthma has grown, especially with the release of the NAEPP practice guidelines. Anti-inflammatories must be taken at regular intervals in order for them to be fully effective, because asthma control can worsen within a few weeks when an ICS is stopped.(72) Corticosteroids can also be given by an injection by syrup or tablets. By taking a corticosteroid by mouth or by injection the steroid will work much quicker, but side effects are greater. Consult patient information for possible side effects.

The following is a list of corticosteroids given for asthma:

Inhaled corticosteroids

Fluticasone Propionate - Active ingredient of the dry powder inhaler or MDI Advair or as MDI Flovent. (73,75) Fluticasone is a very  potent inhaled corticosteroid(74)

Budesonide inhalation solution - Given via an inhalation suspension, also known as Pulmicort Respules.(76) Also given as turbuhaler(77)

Mometasone inhalation powder - Dried Powder with the brand name of Asmanex Twisthaler(78) Beclomethasone dipropionate - Given via an MDI, it is the active ingredient in QVAR(79)

Flunisolide - It is given via an MDI with the brand name AeroBid (80)

Triamcinolone acetonide - Given via an MDI with the brand name Azmacort(81)

Oral Corticosteroids

Prednisolone Sodium Phosphate -  Given via syrup or tablets.(82)(83)

Prednisone  - Given via syrup, concentrate or tablet  (84)

Methylprednisolone - Given as a liquid, oral tablet or by injection(85)

Others antiinflammatories

Cromolyn Sodium, not a corticosteroid, works by inhibiting the degranulation of sensitized and non-sensitized mast cells which occur after exposure to specific antigens. (86)

Theophylline - Theophylline is a Methylxanthines and is related to caffeine. It is primarily used today as a Long-term control and prevention of symptoms, especially nighttime symptoms.  It has many side-effects especially when blood serum or blood levels are too high. Theophylline may have mild anti-inflammatory effects.(87)

Smooth Muscle Relaxers or Quick Relief Medications

Smooth Muscle Relaxers can work in a couple of different ways. Beta-2 agonists work by stimulating beta2-adrenergic receptors to increase cyclic AMP levels which relax smooth muscles. Atrovent inhibits vagally mediated reflexes.

Alupent - This is the brand name for Metaproterenol Sulfate - Given via an MDI, syrup, tablets, and aerosol. (88)

Albuterol - Given via aerosol, syrup, injection and IV. The preferred way to give albuterol is via aerosol due to decreased side effects. (89)

Ipratropium bromide also known as Atrovent is given via aerosol in moderate to severe exacerbations.(90)  It is the treatment of choice for bronchospasm due to beta-blocker medication. It may be used as an alternative bronchodilator for those who do not tolerate SABA. (91)  It does not yet have FDA approval for the treatment of asthma.(92)

Serevent - A long acting beta-2 agonist. On November 18, 2005 the FDA required the makers of long acting beta2 adrenergic agonists to change their labels to include warnings that even though LABAs decrease the frequency of asthmatic episodes those episodes may become much more severe and may even lead to death (92)

Xopenex, also known as Levalbuterol, is the purified form of Albuterol. It is available as an aerosol and MDI (93)

Immunomodulators - Medications that modify the immune response.  For asthmatics this includes:

• Methotrexate
• Soluble interleukin-4 (IL-4) receptor
• Anti-IL-5, recombinant IL-12
• Cyclosporin A
• Intravenous immunoglobulin (IVIG),
• Clarithromycin
• Omalizumab or Xolair - Omalizumab inhibits IgE from binding to bronchial mast cells.  For patients 12 or older who have moderate to severe persistent asthma this medicine is given via sub cutaneous injection every 2 to 4 weeks. It is for those patients whose asthma isn''''t being controlled by corticosteroids and those patients whose asthma is triggered by year-round allergens in the air. In one study Omalizumab improved quality-of-life scores in severe persistent asthma. It is not for acute bronchospasm or staticus asthmaticus.  Anaphylatic and  urticaria reactions have occured in a small (0.1-0.2%) percent of cases (anti-IgE)(93)

Leukotriene Receptor Antagonists
This relatively new type of medication inhibits leukotrienes when they try to attach to various cellular receptors. Leukotrienes are chemicals released from mast cells and work to contract smooth muscles, increase the ability of small blood vessels to release fluid, increase mucus secretions, and attract various inflammatory cells. It should be noted that these medicines aren''t to be used in place of rescue medications.(94)

Montelukast Sodium or Singulair - Taken as a tablet or chewable tablet or granules is taken once a day. (95)

Zafirlukast or Accolate - Accolate is taken as a tablet twice a day.  (96)

Treating Exacerbations

"Early treatment of asthma exacerbations is the best strategy for management." (98) In the latest EPR exacerbation recommendations include:

• Eduction including a written asthma action plan.
• Recognizing when asthma is getting worse
• Increasing dosage of SABA and maybe adding a systemic corticosteroid
• Removing environmental factors contributing to the disease
• It is no longer recommended to double the dose of ICS for an exacerbation.(99)

If an ER visit is needed then treat with:

• Oxygen
• SABA and add inhaled ipratropium bromide when exacerbations severe
• Systemic corticosteroids
• Possibly magnesium sulfate, heliox
• Use peak flows or fev1 to monitor therapy. This may not be worthwile if the exacerbation is severe(99)

Classifying Asthma Exacerbations
Mild

• Symptoms and Signs -Dyspnea only with activity (assess tachypnea in young children)
• PEF or FEV₁ - PEF =70 percent predicted or personal best
• Clinical Course -
  • Usually cared for at home 
  • Prompt relief with inhaled SABA
  • Possible short course of oral systemic corticosteroids

• Symptoms and Signs - Dyspnea interferes with or limits usual activity
• PEF or FEV₁ - PEF 40-69 percent predicted or personal best
• Clinical Course - 
  
  • Usually requires office or ED visit
  • Relief from frequent inhaled SABA
  • Oral systemic corticosteroids; some symptoms last for 1–2 days after treatment is begun

• Symptoms and Signs - Dyspnea at rest; interferes with conversation
• PEF or FEV₁ - PEF <40 percent predicted or personal best
• Clinical Course -
  
  • Usually requires ED visit and likely hospitalization
  • Partial relief from frequent inhaled SABA
  • Oral systemic corticosteroids; some symptoms last for >3 days after treatment is begun
  • Adjunctive therapies are helpful

• Symptoms and Signs - Too dyspneic to speak; perspiring
• PEF or FEV₁ - PEF <25 percent predicted or personal best
• Clinical Course - 
  
  • Requires ED/hospitalization; possible ICU
  • Minimal or no relief from frequent inhaled SABA
  • Intravenous corticosteroids 
  • Adjunctive therapies are helpful (100)

What remains to be done in asthma treatment

The goals presented by the NAEPP in their reports are daunting for patients. Medications are hard to remember to take on a regular basis. It is hard to take a controller medication routinely if the patient is not feeling symptoms. A study by Shulman, Ronca and Bucuvalas, Inc. demonstrated problems with the care given to asthmatic children. According to the survey 65% did not have a peak flow meter and over half did not have an asthma action plan. A third of asthmatics did not recognize what causes asthma symptoms. (97) Physicians may not be completely compliant with the guidelines set by the NAEPP. Studies highlight some of the differences that physicians may have with the NAEPP report.  Physicians tend not to use peak flow meters as frequently as recommended nor do they use written treatment plans and routine follow up visits.(98)

Next: Read about future treaments for asthma

Sources:

36 . Dr Angela Simpson
Asthma - reducing your exposure to triggers
Last updated 01.08.2005
Available from: http://www.netdoctor.co.uk/diseases/facts/asthma_triggers.htm

37 . Kenneth N. Anderson
Lois E. Anderson
Mosby''s Pocket Dictionary of Medicine, Nursing and Allied Health
The C.V. Mosby Company 1990

38 . Tips to Remember: Asthma triggers and management
Available from:  http://www.aaaai.org/patients/publicedmat/tips/asthmatriggersandmgmt.stm

39 . Adolescent Medicine Avoiding Asthma Triggers
University of Utah Health Sciences Center 2003
Available from: http://healthcare.utah.edu/healthinfo/pediatric/allergy/avdtrig.htm

40 . Pg. 153
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdfanagement

41 . Miriam K Anand, MD
Hypersensitivity Reactions, Immediate
eMedicine.com Article Last Updated: Dec 14, 2007
Available from: http://www.emedicine.com/med/topic1101.htm G

42 . Pg. 37
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdfanagement

43 . Pg. 21
National Asthma Education and Prevention Program
Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/archives/epr-2/index.htm

44 . Pg. 35,48,305
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdfanagement

45 . Secondhand Smoke: A Fact Sheet for Parents
Available from: http://www.fammed.unc.edu/enter/fact_sheets/ParentsFactSheetl.pdf

46 . UPMC
Risk Factors for Asthma
Publisher University of Pittsburgh Medical Center
Available from: http://www.upmc.com/HealthManagement/ManagingYourHealth/PersonalHealth/Children/?chunkiid=19115

47 . Pg. 48
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

48 . Pg. 304
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

49 . David H. Broide, MB, ChB
Researchers Find Clues to Which Asthmatics Are Likely to Experience Near-Fatal or Fatal Attacks
Available from: http://www.medscape.com/viewarticle/445503

50 . Pg. 39 National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

51 . Kathy Conboy-Ellis, RN, PhD, MHA, CPNP, AE-C
AAE National Asthma Educator Certification Review Course Syllabus "Asthma Pathophysiology/Epidemiology, Co-Morbid Conditions"

52 . Pg. 188-194 National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

53 . Pg. 58
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

54 . Pg. 143,144
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

55 . Pg. 81
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

56 . Pg. 191,192
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

57 . pg 192,
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

58 .
Meyer Kattan, MD CM,
a Sally C. Stearns PhD,
b Ellen F. Crain, MD, PhD,
c James W. Stout, MD, MPH,
d Peter J. Gergen, MD,
e Richard Evans III, MD, MPH,
f Cynthia M. Visness, MA, MPH,
g Rebecca S. Gruchalla, MD, PhD,
h Wayne J. Morgan, MD, CM,
i George T. O’Connor, MD, MS,
j J. Patrick Mastin, PhD,
k and Herman E. Mitchell, PhDg
Cost-effectiveness of a home-based environmental intervention for inner-city children with asthma
Boston University Medical Campus
Available from: http://www.bumc.bu.edu/www/busm/pul/PDFs/trans/allergy1.pdf

59 . pg 206
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

60 . pg 153
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

61
Philip Fireman
Gilbert A. Friday
Cathy gira
Wanda A. Viethaler
Lois Michaels
Teaching Self-Management Skills to Asthmatic Children and Their Parents in an Ambulatory Care Setting
Peadiatrics 1981;68;341-348
Available from: http://pediatrics.aappublications.org/cgi/content/abstract/68/3/341

62 . pg 301
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

63 . pg 159-163
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

64
Reagional Asthma Management and Prevention
Asthma Action Plans
Available from: http://www.rampasthma.org/AAP%20page.htm

65 . pg 74
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

66 . pg 97
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

67 . pg 98
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

68 . pg 366, 328, 329
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

69 .Jindal, SK
Asthma control in the first decade of 21st century
Indian Journal of Medical Research
May 2007
Available from: http://findarticles.com/p/articles/mi_qa3867/is_200705/ai_n19435163

70 . Eric K. Chu
JeffreyM.Drazen M.D.
American Journal of Respiratory and Critical Care Medicine
Asthma One Hundred Years of Treatment and Onward
Available from: http://ajrccm.atsjournals.org/cgi/content/full/171/11/1202%20

71 . H. Morrow Brown
G. Storey
Beclomethasone Dipropionate Steroid Aerosol in Treatment of Perennial Allergic Asthma in Children
British Medical Journal July 21, 1973
Available from: http://www.pubmedcentral.nih.gov/pagerender.fcgi?artid=1586362&pageindex=1#page

72. pg 242
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

73. GlaxoSmithKline
PRESCRIBING INFORMATION ADVAIR DISKUS® 100/50 (fluticasone propionate 100 mcg and salmeterol* 50 mcg inhalation powder)
ADVAIR DISKUS® 250/50 (fluticasone propionate 250 mcg and salmeterol* 50 mcg inhalation powder)
ADVAIR DISKUS® 500/50 (fluticasone propionate 500 mcg and salmeterol* 50 mcg inhalation powder)
October 2007
Available from: http://us.gsk.com/products/assets/us_advair.pdf

74Adams N, Lasserson TJ, Cates CJ, Jones PW
Fluticasone versus beclomethasone or budesonide for chronic asthma in adults and children
Date of last subtantive update: August 03. 2007
Available from: http://www.cochrane.org/reviews/en/ab002310.html

75 GlaxoSmithKline.
PRESCRIBING INFORMATION
FLOVENT® HFA 44 mcg (fluticasone propionate 44 mcg) Inhalation Aerosol
FLOVENT® HFA 110 mcg (fluticasone propionate 110 mcg) Inhalation Aerosol
FLOVENT® HFA 220 mcg (fluticasone propionate 220 mcg) Inhalation Aerosol
January 2007
Available from: http://us.gsk.com/products/assets/us_flovent_hfa.pdf

76 AstraZeneca
Product Information Pulmicort Respules® (budesonide inhalation suspension) 0.25 mg, 0.5 mg, and 1mg
Rev. 06/07
http://www.astrazeneca-us.com/pi/pulmicortrespules.pdf

77. AstraZeneca
Product Information PULMICORT TURBUHALER® (budesonide inhalation powder) For Oral Inhalation Only.
Rev. 10/06
Available from: http://www.astrazeneca-us.com/pi/pulmicortturbohaler.pdf

78. Schering Corporation
Product Information ASMANEXTTWISTHALERT220 mcg (mometasone furoate inhalation powder) FOR ORAL INHALATION ONLY
Rev. 7/05
Available from: http://www.spfiles.com/piasmanex.pdf

79. 3M Health Care, Ltd.
Product Information QVAR 40mcg (beclomethasone dipropionate HFA, 40 mcg Inhalation Aerosol) QVAR 80mcg (beclomethasone dipropionate HFA, 80 mcg Inhalation Aerosol)
Rev. 11/05
Available from: http://www.qvar.com/Common/PDF/ProductInformation.pdf

80. Forest Pharmaceuticals, Inc
AEROBID AEROBID-M (flunisolide) Inhaler System
Revised 3/02
Available from: http://www.frx.com/pi/aerobid_pi.pdf

81. Abbott Laboratories
Azmacort (triamcinolone acetonide) Inhalation Aerosol for Oral Inhalation only
Revised September 2007
Available from: http://www.azmacort.com/downloads/Azmacort-PI.pdf

82. CIMA Labs Inc.,
Orapred ODT (Prednisolone sodium phosphate orally disintegrating tablets)
Revised May 2006
 Available from: http://www.orapredsmallpackage.com/educationmaterials/OrapredODTPI.pdf

83.
Prednisolone Dosage Form: Syrup
Drugs.com
Revised: 07/2007
Available from: http://www.drugs.com/pro/prednisolone-syrup.html

84. Prednisone
Medline Plus
Last Revised - 04/01/2006
Available from: http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601102.html

85. Methylprednisolone Oral
Medline Plus
Last Revised - Last Revised - 04/01/2003
Available from: http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682795.html

86. Dey
Cromolyn Sodium Inhalation SolutionUSP Aqueous solution for nebulization
Rev. 1/06
Available from: http://www.dey.com/generics/products/Cromolyn_PI.pdf

87. pg 237
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

88 Boehringer Ingelheim Pharmaceuticals, Inc.,
Alupent® Inhalation Aerosol (metaproterenol sulfate USP)
Revised 2/99
Available from: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Alupent+IA/AlupentIA.pdf

89. DEY®
Albuterol Sulfate Inhalation Solution 0.083%*
Available from: http://www.dey.com/generics/products/albuterol_PI.pdf

90. Nephron pharmaceuticals Corporation
Ipratropium Bromide Inhalation Solution, 0.02%
Rev. 2-11-05
Available from: http://www.nephronpharm.com/pdf/IPB02_Pkg_Insert.pdf

91. Pg. 271
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

92. Pg. 258
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

93. Sepracor Inc.
Xopenex® (levalbuterol HCl) Inhalation Solution, 0.31 mg*, 0.63 mg*, 1.25 mg*
June 2005
Available from: http://www.xopenex.com/xopenexProviders/XopenexUDV400437-R5.pdf

94. Pg. 248
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

95MERCK & CO., INC.
Patient Information SINGULAIR® (SING-u-lair) Tablets, Chewable Tablets, and Oral Granules Generic name: montelukast (mon-te-LOO-kast) sodium
Issued September 2007
Available from: http://www.merck.com/product/usa/pi_circulars/s/singulair/singulair_ppi.pdf

96. AstraZeneca Pharmaceuticals
LP ACCOLATE ZFIRLUKAST TABLETS
Rev 07/04
Available from: http://www.astrazeneca-us.com/pi/accolate.pdf

97. 1997-2007 GlaxoSmithKline.
Children and Asthma in America
Available from: http://www.asthmainamerica.com/children_index.html

98. Jonathan A. Finkelstein, MD,
 MPH Paula Lozano, MD, MPH
Reeva Shulruff, MD
Stephen B. Soumerai, ScD
and Kevin B. Weiss, MD, MPH
Self-Reported Physician Practices for Children With Asthma: Are National Guidelines Followed?
PEDIATRICS Vol. 106 No. 4 Supplement October 2000, pp. 886-896
Available from: http://pediatrics.aappublications.org/cgi/content/full/106/4/S1/886

99. Pg. 396
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

100. Pg. 397,398,399
National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
Available from: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf