TITLE: ASTHMA
AUTHORS: GEORGES S. JUVELEKIAN, MD --
Department of Pulmonary and Critical Care Medicine
   JAMES K. STOLLER, MD, MS --
Department of Pulmonary and Critical Care Medicine
   SERPIL C. ERZURUM, MD -- --
Department of Pulmonary and Critical Care Medicine
PUBLISHED: JANUARY 22, 2003
REVISED: FEBRUARY 28, 2005
Table 1:
Stepwise Approach for Managing Asthma in Adults and Children Older Than 5 Years of Age: Treatment
Classify Severity:
Clinical Features Before Treatment or Adequate Control
Medications Required to Maintain Long-Term Control
  
Symptoms/Day
Symptoms/Night
PEF or FEV1
PEF Variability
Daily Medications
Step 4

Severe Persistent
Continual
Frequent
< 60%
> 30%
Preferred Treatment
—High-dose inhaled corticosteroids
AND
—Long-Acting beta2-agonists
AND, if needed,
—Corticosteroid tablets or syrup long term (2 mg/kg/day, generally do not exceed 60 mg per day). (Make repeat attempts to reduce systemic corticosteroids and maintain control with high-dose inhaled corticosteroids.)
Step 3

Moderate Persistent
Daily
> 1 night/week
> 60% - <80%
> 30%
Preferred Treatment
—Low-to-medium dose inhaled corticosteroids and long-acting beta2-agonists.
Alternative Treatment
—Increase inhaled corticosteroids within medium-dose range
OR
—Low-to-medium dose inhaled corticosteroids and either leukotriene modifier or theophylline.

If needed (particularly in patients with recurring severe exacerbations):
Preferred Treatment
—Increase inhaled corticosteroids within medium-dose range and
add long-acting beta2-agonists.
Alternative Treatment
—Increase inhaled corticosteroids within medium-dose range and add either leukotriene modifier or theophylline.
Step 2

Mild Persistent
> 2/week but < 1x/day
> 2 nights/month
> 80%
20 - 30%

Preferred Treatment
—Low-dose inhaled corticosteroids
Alternative Treatment
(listed alphabetically): cromolyn, leukotriene modifier, nedocromil, OR sustained release theophylline to serum concentration of 5-15 µg/mL.
Step 1

Mild Intermittent
< 2 days/week
< 2 nights/month
> 80%
< 20%
 No daily medication needed.

Severe exacerbations may occur, separated by long periods of normal long function and no symptoms. A course of systemic corticosteroids is recommended.
  

 

Table 2:
Usual Dosages for Long-Term-Control Medications
Medication
Dosage Form
Adult Dose
Child Dose*
Inhaled Corticosteroids (See Estimated Comparative Daily Dosages for Inhaled Corticosteroids-Table 3)
Systemic Corticosteroids                                                    (Applies to all three corticosteroids)
Methylprednisone 2,4,8,16, 32 mg tablets
  • 7.5-60 mg daily in a single dose in a.m. or qod as needed for control
  • Short-course "burst" to achieve control: 40-60 mg per day as single or 2 divided doses for 3-10 days
    (with/without taper)
  • 0.25-2 mg/kg daily in single dose in a.m. or qod as needed for control
  • Short-course "burst":
    1-2 mg/kg/day, maximum 60 mg/day for 3-10 days

 
Prednisolone

5 mg tablets, 5 mg/5 mL, 15
mg/5 mL
Prednisone

1, 2.5, 5, 10, 20, 50 mg tablets; 5 mg/mL, 5 mg/mL
Long-acting Inhaled Beta2-Agonists (Should not be used for symptom relief or for exacerbations. Use with inhaled corticosteroids.)
Salmeterol MDI
21 µg/puff
DPI
50 µg/blister		 2 puffs q 12 hours


1 blister q 12 hours		 1-2 puffs q 12 hours


1 blister q 12 hours
Formoterol DPI
12 µg/single-use capsule		 1 capsule q 12 hours 1 capsule q 12 hours
Combined Medication
Fluticasone/Salmeterol DPI
100, 250, or 500 µg/50µg		 1 inhalation bid; dose depends on severity of asthma 1 inhalation bid; dose depends on severity of asthma
Cromolyn and Nedocromil
Cromolyn MDI
1 mg/puff
nebulizer 20 mg/ampule
 2-4 puffs tid-qid

1 ampule tid-qid


 1-2 puffs tid-qid

1 ampule tid-qid
Nedocromil MDI
1.75 mg/puff		 2-4 puffs bid-qid 1-2 puffs bid-qid
Leukotriene Modifiers
Montelukast 4 or 5 mg chewable tablet
10 mg tablet
 10 mg qhs 4 mg qhs (2-5 yrs)
5 mg qhs (6-14 yrs)
10 mg qhs (>14 yrs)
Zafirlukast 10 or 20 mg tablet 40 mg daily (20 mg tablet bid) 20 mg daily (7-11 yrs)(10 mg tablet bid)
Zileuton 300 or 600 mg tablet 2,400 mg daily (give tablets qid)
Methylxanthines (Serum monitoring is important [serum concentration of 5-15 µg/mL at steady state]).
Theophylline Liquids, sustained- release tablets, and capsules Starting dose 10 mg/kg/day up to 300 mg max; usual max 800 mg/day

Starting dose 10 mg/kg/day; usual max:
< 1 year of age: 0.2 (age in weeks)
+ 5 = mg/kg/day
> 1 year of age: 16 mg/kg/day

 
  

 

Table 3:
Estimated Comparative Daily Dosages for Inhaled Corticosteroids
Drug
Low Daily Dose
Medium Daily Dose
High Daily Dose
Adult
Child*
Adult
Child*
Adult
Child*
Beclomethasone CFC
42 or 84µg/puff		 168-504 µg 84-336 µg 504-804 µg 336-672 µg > 840 µg > 672 µg
Beclomethasone HFA
40 or 80 µg/puff
 80-240 µg 80-160 µg 240-480 µg 160-320 µg > 480 µg > 320 µg
Budesonide DPI
200 µg/inhalation		 200-600 µg 200-400 µg 600-1,200 µg 400-800 µg > 1,200 µg > 800 µg
Inhalation suspension for nebulization (child dose)   0.5 mg 1.0 mg   2.0 mg
Flunisolide
250 µg/puff		 500-
1,000 µg		 500-750 µg 1,000-2,000 µg 1,000-1,250 µg > 2,000 µg > 1,250 µg
Fluticasone
MDI: 44, 110, or 220 µg/puff
DPI: 50, 100, or 250 µg/inhalation		 88-264 µg

88-176 µg

 264-660 µg 176-440 µg > 660µg > 440 µg
100-300 µg 100-200 µg 300-600 µg 200-400 µg > 600 µg > 400 µg
Triamcinolone acetonide
100 µg/puff		 400-1,000 µg 400-800 µg 1,000-2,000 µg 800-1,200 µg > 2,000 µg > 1,200 µg
*Children < 12 years of age

 

Table 4:
Inhalant Allergens
Indoor
Outdoor
Dust Mites
Tree
Cockroach
Grass
Pets (cat, dog, etc)
Ragweed/Other weeds
Mold Spores
Mold Spores
  

 

Table 5:
Pharmacologic Agents for the Treatment of Asthma
Generic
Name
Brand Name
(Manufacturer)
Delivery Route/
Device
Suggested Dosage
(Adults)
Comment
Anticholinergics
Atropine
sulfate		 Many Solution
0.2% (1 mg/0.5 mL)
0.5% (2.5 mg/0.5 mL)
(1.25 mg)		 0.025 mg/kg diluted with 3-5 mL NS q 6-8 hr Minimal side effects with ipratropium;
Ipratropium
bromide		 Atrovent
(Boehringer)

MDI (18 g/puff)

Solution 0.02% (500-µ g unit dose vial)

 2-4 puffs qid; max = 12 puffs/day
500 µg/tid, qid		 Approved for COPD only
Tiotropium Spiriva (Boehringer) DPI 8 mg/puff 1 puff per day Approved for COPD only
β2-Adrenergic Agents
Albuterol sulfate Airet (Medeva)
Albuterol (various generic)
 
Proventil (Schering)

Solution (0.83%)
Solution (0.83%, 0.5%)
MDI (90 µg puff)

 

 



Solution for nebulizer

 

Tablets (2,4 mg)

2.5-10 mg q 6-8 hr
2.5-10 mg q 6-8 hr ml
(0.5 mL)
Acute: 2-4 puffs q 4-6 hr; max 16-20 puffs/day
Prophylaxis: 2 puffs 15 min before exercise

2.5-10 mg a 6-8 hr
(0.083%) (3 mL) or (0.5%) (0.5 mL)

2-4 mg q 6-8 hr; max: 32 mg/day
2-4 puffs q 4-6 hr
4 mg q 12 hr

 Inaled agents have fewer systemic side effects;
β-2 selective agents are albuterol, bitolterol, metaproterenol, pirbuterol, almeterol, terbutaline
Proventil-HFA (Schering) MDI (90 µg/puff)
Repetabs (sustained Release tablets), 4 mg		 2-4 puffs q 4-6 hr
4 mg q 12 hr
Ventolin (Glaxo)

MDI (90 µg/puff)

Rotohaler (200 µg/
Rotacap)
Solution for nebulizer
(0.083% µg mL, 0.5% 20 mL)
Tablets (2,4 mg)

 Max: 16-30 puffs/day (200 puffs)
200-400 µg q 6-8 hr; max dose=2.4 mg/day
2.5-10 mg q 6-8 hr
Volmax (Muro) Sustained-release tablets (4, 8 mg) 4-8 mg q 12 hr
Bitolterol mesylate Tornalate (Sanofi Winthrop) MDI (370 µg/puff) 2 puffs q 6 hr
Epinephrine Medihaler-Epi (3M Pharm) Many

MDI (300 µg/puff)

 2 puffs qid
Adrenalin chloride
(Parke-Davis)		 SC inection 1:1000 (1 mg/mL) 0.2-0.5 mg SC (0.2-0.5 mL SC) q 20 min
Formoterol Foradil (Novartis)
(investigational in USA)		 MDI
DPI
Isoetharine HCl Bronkometer
(Sanofi Winthrop)
Many

MDI (340 µg/puff)

Solutions for inhalation

1-2 puffs q 4 hr

0.25-1 mL nebulized with NS
Isoproterenol HCL Medihaler-150 (3M Pharm)
Isuprel Mistometer
(Sanofi Winthrop)

MDI (800 µg/puff)

MDI (131 µg/puff)

Solution (0.5%, 1%, 5%)
Tablets (glossets 10, 15 mg)

1-2 puff qid

1-2 puffs qid
0.5 ml in 2.5 ml NS 1 3-4 hr
10-20 mg q 4 hr
Levalbuterol Xopenex (Sepracor) Solution for nebulizer (0.63 mg) 0.63 mg q 6-8 hr
Metaproterenol Alupent (Boehringer)

MDI (650 µg/puff)


Solution (0.4%, 0.6%)


Tablets (10, 20 mg)

2-3 puffs q 3-4 hr max=12 puff/day

0.3 mL in 2.5 mL NS q 4-6 hr

10 mg q 6-8 hr, 10 mg up to 20 mg
Metaprel (Sandoz)

MDI (650 µg/puff)


Solution (0.5%)


Tablet (10, 20 mg)

2-3 puffs q 3-4 hr; max=12

0.3 mL in 2.5 mL NS q 4-6 hr

10 mg q 6-8 hr, up to 20 mg
Pirbuterol acetate Maxair (3M Pharm)

MDI (200 µg/puff)


AutoHaler

1-2 puffs q 4-6 hr; max=12 puffs/day

2 puffs q 6 hr
Salmeterol Serevent (Glaxo) MDI (46 µg/puff)
Diskus (DPI 50 µg/puff)		 2 puffs q 12 hr
Terbutaline sulfate Brethaire (Geigy)

MDI (200 µg/puff)
Solution for SC
injection or nebulizer (1 mg/mL)


Tablet (2.5, 5 mg)

1-2 puffs q 4-6 hr
0.25 mg SC q 15-30 min; max = 0.50 mg/4 hr, 0.75-2.5 mg nebulized with NS

2.5-5 mg tid; max=15 mg/24 hr
Bricanyl
(Marion Merrell Dow)		 MDI (200 µg/puff)
Tablets (2.5, 5 mg)		 1-2 puffs q 4-6 hr
2.4-5 mg tid max=15 mg/24 hr
Cromoglycates
Cromolyn sodium Intal (Fisons) Spinhaler (20 mg capsules)
MDI (800 µg/puffs)
Solution (20 mg/2 ml ampule)

20 mg qid
 
2 puffs qid
1 ampule qid

 Contraindication in acute asthma
Inhaled corticosteroids
Nedocromil sodium
Beclomethasone dipropionate		 Tilade (Aventis)
Beclovent (Allen & Hanburys)		 MDI (1.75 mg/puff)
MDI (42 µg/puff)		 2 puffs bid, tid, qid
2 puffs tid-qid: max=20 puffs/day		  
Need more than 400 µg/day to maintain off oral steroids, no adrenal suppression if <800-1200 µg/day

HFA-BDP
Qvar (3M)
Vanceril (Schering)

Vanceril DS

MDI (40 or 80 µg/puff)
 
MDI (42 µg/puff)
 
MDI (84 µg/puff)

 2-8 puffs bid
 
2 puffs tid-qid; max=20 puffs/day
2 puffs tid-qid; max=20 puffs/day
Budesonide

Pulmicort
(AstraZeneca)
 
Pulmicort Respules
(AstraZeneca)

Turbuhaler (200 µg/puff)
 
 
Solution (0.25 mg/2ml or 0.50 mg/2ml)

400-1600 µg in divided doses bid-qid
 
0.25 mg to 1 mg qd-bid

 Approved for 12 mos-8 yrs; only approved
Flunisolide AeroBid (Forest) MDI (250 µg/puff) 2 puffs bid; max=8 puffs/day
Fluticasone propionate Flovent (Glaxo) MDI (44, 110, 220, µg/puff)
Diskus powder inhaler
(50, 100, 250 µg/puff)		 100-800 µg/day

Mometasone furoate
(investigational in US)

Triamcinolone acetonide

Asthmanex
(Schering)

Azmacort (Rhone-Poulenc Rorter)

N/A
 

MDI (100 µg/puff)

N/A
 

2-4 puffs qid; max=16 puffs/day

Combination Products

Albuterol/
ipratropium

Salmeterol/flutcasone
 

Fomoterol/budesonide
(investigational)

Combivent
(Boehringer-Ingelheim)

Advair (Glaxo)


Symbicort
(AstraZeneca)

MDI (18 µg/ipratropium/
103 µg/albuterol per puff)

Diskus (DPI)


Turbuhaler

2 puffs qid
 

50/100, 50/250, 50/500
(1 puff bid)

N/A
Antileukotrienes

Montelukast
Zafirlukast

Zileuton

Singulair (Merck)
Accolate (Zeneca)

Zyflo (Abbott)

Tablet (5, 10 mg)
Tablets (20 mg)

Tablets (600 mg)

10 mg qd in the evening
20 mg bid

600 mg qid

Churg-Strauss
Take on empty stomach; drug interactions
Need to follow LFTs, drug interactions
Methylxanthines
Aminophylline Various IV Load: If not on theophylline at home, 5-6 mg/kg over 20 min; if on theophylline, level pending, 3 mg/kg over 20 min; a bolus of 0.5 mg/kg will increase level by 2 in the average adult. Maintenacne 0.5-0.9 mg/kg/hr; 200-400 mg bid Decreased clearance with cirrhosis, CHF, erythromycin, cimetidine, troleadomycin increased clearance with smoking, young age, and phenobarbital. Need to follow serum levels
Anti-IgE
Omalizumab Xolar
(Genentech/Novartis)		 Subcutaneous 0.016 mg X body wt (kg) X IgE level (IU/ml); also see nomogram See text for details; Urticaria 2%-3% anaphylaxis 0.01%-0.1%
HFA=hydrofluroalkaline-134a; DPI=dry powder inhaler; MDI=pressurized metered dose inhaler; BDP=beclomethasone dipropionate; SC=subcutaneous; LFT=liver function tests; CHF=congestive heart failure; N/A=not available.
  

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