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A. Treatment Overview [1,2] navigator

  1. Treatment divided into acute and chronic therapy
    1. Acute therapy focuses on bronchodilation for rapidly improving airflow
    2. Acute therapy of moderate or severe attacks also uses glucocorticoids (steroids) ± additional agents
    3. Chronic asthma therapy should prevent asthma exacerbations
    4. Chronic therapy uses inhaled steroids and/or mast cell stabilizers
    5. Avoid chronic continuous use of short-acting ß-agonists [3]
    6. Chronic low-dose inhaled steroids reduce severe exacerbations [4] and asthma deaths and should be used in any patient with persistent asthma [11]
    7. Moderate persistent asthma responds suboptimally to inhaled steroids alone; long- acting ß-agonists ± LT blockers should be added [29]
    8. Adjusting therapy based on sputum eosinophil counts reduces exacerbations, hospitalizations [6]
  2. Direct Bronchodilators
    1. ß2-agonists inhalants - mainstay of acute and subacute therapy
    2. Ipatropium Bromide (anti-cholinergic) - synergy in acute attacks with ß2-agonists
    3. Theophylline (aminophylline) - usually reserved for severe attacks and nocturnal asthma
    4. Epinephrine - only for severe flares
  3. Anti-Inflammatory Agents
    1. Glucocorticoids (steroids) - inhaled steroids mainstay for chronic control
    2. Oral steroids used for acute exacerbations and in severe asthma
    3. Cromolyn compounds - chronic therapy, mainly in children
    4. Leukotriene (LT) blockers - zafirlukast, montelukast, zileuton
    5. Cyclosporin A - mild steroid sparing activity, may try in very severe patients
    6. Anti-IgE Antibody (Ab) in moderate to severe allergic asthma
    7. Antihistamines and cyclooxygenase inhibitors are generally ineffective
    8. Some antibiotics may have anti-inflammatory activities
  4. Allergy Treatment
    1. Anti-histamines may improve allergy and asthma symptoms
    2. Dust mite immunotherapy may improve asthma symptoms in some patients
    3. Allergen impermeable covers did not reduce asthma [7] or allergic rhinitis [8] in adults, including those with serum IgE to mite antigens
    4. Ragweed immunotherapy did not improve symptoms in allergic patients
  5. Peak Expiratory Flow Monitors
    1. Can be used to evaluate severity and modify treatment
    2. Best used in home setting for patients to chronically monitor bronchospasm level
  6. In patients with esophageal reflux, acid suppression improves asthma symptoms
  7. Telithromycin (Ketek®) for 10 days after acute asthma exacerbation improves symptoms but not FEV1 versus placebo [10]
  8. Asthmatics should receive inactivated influenza vaccine; it is safe and beneficial [9]

B. Acute Asthma Attacksnavigator

  1. Physician and patient must decide if emergency room evaluation is required
  2. Nearly all acute asthma attacks unresponsive to inhaled ß-agonists should be evaluated
  3. Failure to treat acute attacks early and aggressively may lead to severe progression
  4. Recommended Emergency Room Evaluation
    1. Triage for patients with extremely severe disease (see below)
    2. Rapid, initial history, clinical and physical exams
    3. Albuterol nebulizer every 20 minutes x 3
    4. Consider adding ipatroprium [17]
    5. Consider intravenous glucocorticoids with taper in any subject with acute attack
    6. Evaluation at 60 minutes: consider discharge, further outpatient therapy, or hospitalize
    7. Aminophylline + glucocorticoids for 2 hours, with additional nebulizers as needed
    8. If admitted to hospital, consider MICU for frequent observation, nebulization, other
    9. Attempt to determine if initiating factor is present (such as bronchitis, pollution)
  5. In many asthma cases evaluated in emergency room, arterial blood gas is strongly advised
  6. Chest radiography may be useful in patients to evaluate for pneumonia
  7. If patient is discharged, be sure:
    1. Clear instructions for returning to emergency room
    2. Short acting ß2-agonist (± long acting)
    3. Oral glucocorticoid taper for moderate or severe patients
    4. All patients should be discharged on inhaled glucocorticoid (even with oral) [12]
    5. Cromylin compounds generally have no place in acute management
    6. Followup by primary care practitioner ± pulmonary specialist
  8. Nebulized magnesium added to ß-agonists improves FEV1 increase ~25% [13]

C. Treatment of Severe Asthma Attack navigator

  1. Ascertain if history of intubation or use of epinephrine
  2. Immediate oxygen and ß2-agonist
    1. Nebulization with ß2-agonist: albuterol, metoproteranol, salbutamol
    2. Nebulized albuterol 5.0mg q40 minutes may be preferred to 2.5mg q20 minutes
    3. Severe asthma impedes entrance of nebulized drug to small airways
    4. Intravenous salbutamol in children reduced hospital stay and oxygen requirements
    5. Nebulized ipatroprium bromide (Atrovent®), an anticholinergic, added to ß-agonists and steroids reduced hospitalizations by ~30% in children with acute asthma [16]
    6. Ipatroprium + ß-agonists is superior to ß-agonists alone in adults with acute asthma [17]
  3. SC epinephrine 0.3cc of 1:1000 - avoid in heart disease, elderly
  4. Sterdois
    1. Either intravenous (IV; usually preferred) or oral prednisone
    2. IV-methylprednisolone (SoluMedrol®) 80-125mg bolus (1-2mg/kg in children)
    3. Oral prednisone 60mg in adults or 2mg/kg in children can also be used
    4. Systemic glucocorticoids are superior to inhaled fluticasone in acute childhood asthma [18]
    5. Inhaled steroids are not adequate for severe asthma attacks
    6. Doubling dose of inhaled glucocorticoid does not reduce risk of acute attack [19]
  5. Aminophylline
    1. Useful in severe asthma, especially in patients who may require intubation
    2. Bolus (4-6mg/kg IV) then drip (0.6mg/kg/hr)
    3. Close monitoring for tachycardia and drug levels is required
  6. Mechanical ventilation should be used early as needed

D. ß2-Adrenergic Agonist Therapy [2,3] navigator

  1. Use [23]
    1. Short acting ONLY for as needed (PRN) control of mild asthma symptoms
    2. Long acting should always added to inhaled steroids, for persistent asthma
    3. Long acting agents associated with 2-3X increased severe exacerbations, mortality but this meta-analysis did not include combination with steroids [14,24]
    4. Salmeterol (a long acting ß2 agonist) plus inhaled steroids reduced risk for severe exacerbations without effect on asthma-related hospitalizations or death [56]
    5. Long acting agents offer better overall symptom control than short-term agents [27,72]
    6. Long acting agents should NOT be used for acute symptoms
    7. Short acting ß2-agonists must be provided to patients on long acting agents
  2. Short Acting Agents
    1. Usually 2 puffs every 4-6 hours PRN (as needed) only
    2. Useful for rapid symptomatic relief of acute symptoms
    3. Albuterol (Proventil®, Ventolin®, generics)
    4. Levalbuterol (Xopenex®) has no clear advantage over racemic albuterol [20]
    5. Pirbuterol (Maxair®)
    6. Terbutaline (Brethine®)
    7. Bitoterol (Tornalate®)
    8. Oral albuterol 200µg (Proventil®, Vomax®), dose is 200-400µg every q4-6 hours
    9. No particular advantages to any agent in this class
    10. Side effects: tremor, headache, tachycardia, palpitations - especially with oral forms
    11. Side effects generally decline with continued use
    12. Nebulized formulations are available for children and severe cases
  3. Long Acting [24]
    1. Long acting agents for maintenance to control chronic and/or nocturnal symptoms
    2. NOT for acute symptoms and NEVER as first line therapy [23]
    3. Should only be added to inhaled steroids to improve symptoms in persistent asthma [24]; clearly reduce severe exacerbation rates [56]
    4. Salmeterol (Serevent®) - delayed onset of action, bid dosing (qhs for nocturnal only)
    5. Formoterol (Foradil®) - rapid (1-3 minute) onset of action with 12 hour duration [21]
    6. Eformoterol - long acting (bid)
    7. Longer acting agents usually have reduced side effects (slower onset of action)
    8. Salmeterol-Fluticasone (Advair Diskus®) combination [22]
    9. Formoterol-Budesonide (Symbicort®) combination (see below) [72,75]
  4. Efficacy
    1. Patients with asthma should carry short-acting ß-agonists for exacerbations
    2. When long acting agents are prescribed, short acting agents should be used prn as well
    3. In general, long-acting ß-agonists should be used in combination with inhaled steroids [29,56,72]
    4. Solmeterol bid is less effective than triamcinolone 400µg bid for chronic asthma monotherapy [27]
    5. Formoterol added to budesonide highly effective in moderate asthma [72]
    6. Salmeterol effective in exercise induced asthma
  5. Tolerance [3]
    1. Tachyphylaxis due to ß2-receptor down-regulation occured in some controlled studies
    2. Meta-analysis showed repiratory tolerance to regular ß-agonist use [3]
    3. Some link with asthma risk and severity with certain haplotypes, including the glycine-16 ß2-adrenergic receptor polymorphism [67]
    4. Formoterol for 2 weeks maintains bronchodilation but loses its ability to prevent bronchoconstriction after methacholine challenge
    5. Chronic salbutamol (short acting) use for 1 year did not lead to reduced asthma control [30]
    6. Chronic salmeterol use does not reduce efficacy of acute albuterol therapy
    7. Certain mechanisms involved in ß2-agonist mediated bronchodilation may be distinct from those which inhibit bronchoconstrictor effects
    8. May act synergistically with glucocorticoids to reduce inflammation [32]
  6. Severe exacerbations and asthma mortality increased 2-3X with long acting ß-agonists used alone; should always be used with inhaled steroids [14,23,24]

E. Steroids (Glucocorticoids) [2,33] navigator

  1. Most effective anti-asthmatic agents currently available
    1. Stongly recommend daily inhaled steroids for mild-moderate persisent asthma
    2. Intermittent inhaled steroids may be as effective as daily in mild persistent asthma [58]
    3. Severe asthma usually requires oral steroids
  2. Actions [33]
    1. Block late (but not early) bronchoconstriction
    2. Decrease both lymphocyte and eosinophil function
    3. Decrease mast cell infiltration to bronchi
    4. Decrease microvascular leakage
    5. Increase synthesis of annexin-1 (lipocortin), which inhibits arachadonate metabolism
    6. Up regulates pulmonary ß2 adrenergic receptors, synergistic with ß2-agonists [32]
  3. Inhaled Steroids [11]
    1. First line control for ANY persistent asthma and current cornerstone of asthma therapy
    2. Reduces need for systemic steroids, severe exacerbations [4], asthma death
    3. Used in emergency room setting, reduce hospital admission [34]
    4. Should initially be used just after ß2-agonist inhalation
    5. Provide somewhat better control than montelukast (LT inhibitor) [35]
    6. Low dose inhaled steroids control most mild and many moderate asthma patients
    7. Desirable to reduce inhaled steroid dose while maintaining control [26,31]
    8. In patients with good control on inhaled fluticasone100µg bid, salmeterol 50µg qhs + fluticosone 100µg qd provides equivalent control with less steroid [26]
    9. With good control on inhaled fluticasone100µg bid, monelukast 10mg qhs alone provided nearly as good control and substantially reduced steroid use [26]
    10. With good control on inhaled beclomethasone 250µg bid, use of only as needed combination beclomethasone 250µg + albuterol 100µg reduced steroid, provided control [31]
    11. Adding LT receptor blocker to low dose inhaled steroids provides at least as good control and is better tolerated than high dose inhaled steroids [11]
    12. Systemic steroids should be reserved for exacerbations whenever possible (see below)
  4. Inhalers (50-500µg daily)
    1. Beclomethasone diproprionate (Beclovent®, Vanceril®) - 2-4 puffs bid-qid
    2. Triamcinolone acetonide (Azmacort®) - 2-4 puffs po bid to tid
    3. Triamcinolone 4 puffs (800µg) once daily is also very effective
    4. Flunisolide (Aerobid®) - 2-4 puffs bid
    5. Fluticasone propionate (Flovent®) - 2-4 puffs qd-bid (44, 110, and 220µg/puff inhalers)
    6. Fluticasone dry powder (Flovent Rotadisk®) [36]
    7. Fluticasone / Salmeterol - 100, 250 or 500µg fluticasone + 50µg salmeterol [22]
    8. Budesonide (Pulmicort® turbohaler) - 200µg qd-bid; dry powder inhaler available [36]
    9. Budesonide (80, 160µg) / Formoterol (4.5µg) - (Symbicort®) [72,75]
    10. Nebulized budesonide (0.25 bid or 0.5mg qd) available for children [37]
    11. Spacer devise with inhaler is critical for efficient drug delivery
    12. Combination inhaled steroids with long-acting ß-agonists for inadequate control on steroids alone (moderate persistent asthma) [22,29,72]
  5. Utility of Inhaled Steroids [29]
    1. Mainstay of therapy for mild-moderate asthma
    2. Giving ß-2 agonist prior to glucocorticoid inhaler may prevent bronchial irritation
    3. Superior to LT receptor blockade and cromylin compounds [35,38,39,40]
    4. Budesonide added to oral tapered steroids on discharge from emergency department reduced relapses and returns for recurrent acute asthma attacks [12]
    5. Chronic use in asthmatic children did not lead to improved lung function versus placebo [38]
    6. Early chronic inhaled fluticosone in preschool infants with wheezing did not prevent lung function decline or hyper-responsiveness [71]
    7. Doubling dose of inhaled glucocorticoid when peak flow begins to fall does not reduce risk of acute attack [19]
    8. Intermittent inhaled budesonide (400µg/day) did not prevent progression from episodic to persistent wheezing in the first 3 years of life [70]
  6. Side Effects of Inhaled Steroids
    1. Main side effect of inhalers are is oral thrush; very little suppression of adrenal axis
    2. Thorough mouth rinsing after use will help prevent thrush
    3. In children, chronic inhaled budesonide had only transient effects on growth [38,41]
    4. Systemic exposure to inhaled glucocorticoids in patients with moderate to severe asthma is 50-65% that of normal persons [42]
    5. Chronic inhaled glucocorticoids for asthma associated with reduced bone density [43]
    6. Inhaled glucocorticoids increase risk of cataracts in dose-dependent fashion
    7. Several strategies to reduce inhaled steroid dose are available [26,31]
  7. Systemic Steroids
    1. Prednisone - usually given for 3-10 days for exacerbation (40-60mg/d with taper)
    2. Methylprednisolone (SoluMedrol®) - 40-80mg initially; 60-120mg/d in exacerbation
    3. Chronic systemic steroid generally avoided but may be required in severe patients
    4. Side effects with chronic use of >7.5-10mg/d adults, >400µg/d children
    5. Most effective when used as single dose in early morning
    6. Probably no need to taper oral steroids given for <10 days
    7. However, may wish to determine serum ACTH levels prior to stoppping steroids
    8. Reduced ACTH may signal adrenal axis suppression and need for taper
  8. Tapering Oral Steroids
    1. Typical steroid sparing agents are unpredictable in asthma
    2. These include methotrexate and cyclosporine
    3. LT inhibitors may permit reduction in steroid doses
    4. High dose inhaled steroids can improve effective taper of oral agents [12]
    5. Caution when reducing steroids as underlying hypereosinophilia may reappear [45]

F. Leukotriene (LT) Modifiers [2,46]
[Figure] "Leukotriene Synthesis" navigator

  1. Actions
    1. Inhibit various steps in the LT pathway
    2. Cysteinal LTs (LTC4, D4, E4) are >100X more potent bronchoconstrictors than histamine
    3. Main synthetic enzyme is 5-lipoxygenase
    4. Cysteinal LTs all bind to common receptor commonly called LTD4 receptor
    5. Blocking pathways inhibits early allergen responses ~100%, late phase ~50%
    6. May be used as first line, single therapy for mild persistent asthma [47]
    7. Reduces exhaled nitric oxide in asthmatics on inhaled glucocorticoids [48]
    8. May permit reduction in systemic and inhaled glucocorticoid use [45]
    9. Reducing steroids must be done cautiously in this setting or Churg-Strauss Syndrome may be induced [45,49]
  2. Agents [16]
    1. Zariflukast
    2. Montelukast
    3. Pranlukast
    4. Zileuton
  3. Montelukast (Singulair®) [16,53]
    1. LT receptor antagonist
    2. Approved for pediatric (>5 years) and adult prophylactic and chronic use in asthma
    3. Adult dose (>14 years) is 10mg po qpm (once daily dosing only)
    4. Pediatric dose (age 6-14) is one 5mg chewable tablet pm
    5. Reduced nocturnal symptoms and requirements for emergent / urgent asthma treatment
    6. Less effective at increasing FEV1 than beclomethasone 200µg bid over 12 weeks [35]
    7. Good control of moderate asthma though slightly less than beclomethasone [35]
    8. Some synergy with inhaled steroids in patients with persistent symptoms
    9. In chronic persistent asthma on inhaled steroids, adding montelukast provided no additional symptomatic or objective benefit [51]
    10. Efficacy is modestly inferior to fluticasone in patients with persistent asthma [26,40]
    11. Good efficacy in preventing exercise induced asthma, with no reduction over time [55]
    12. Efficacy is superior to salmeterol in preventing exercise induced bronchoconstriction [55]
    13. No hepatic toxicity reported; side effects similar to placebo
  4. Zafirlukast (Accolate®) [50]
    1. Very potent competitive LTD4 (cysteinyl LT Type 1) receptor antagonist
    2. Approved for mild-moderate asthma as adjunctive therapy, chronic asthma control
    3. Dose is 20mg po bid
    4. Generally well tolerated and improves symptoms of asthma
    5. Reduced healthcare contacts and lost work or school and use of ß2 agonists
    6. Mild acute bronchodilatory effects
    7. In asthmatics on inhaled glucocorticoids, as effective as formoterol in controlling asthma symptoms, and also reduced airway inflammation [48]
    8. Increases effects of warfarin [50] and theophylline [51]
    9. Better tolerated and possibly more effective than Zileuton
    10. Routine liver function test monitoring is not required
    11. Incidence of severe liver injury is extremely low [52]
  5. Zileuton (Zyflo®)
    1. Specific 5-Lipoxygenase inhibitor which blocks LT production
    2. Zileuton 800mg bid or 600mg qid: 0.25-0.45L FEV1 increase within 1 hr (15% > baseline)
    3. May prevent asthma exacerbations and reduce oral steroid requirements
    4. Side effects included hepatitis (1-5% significant), nausea and diarrhea
    5. Initial monthly monitoring for transaminase elevations (hepatitis) required
    6. Increases serum levels of theophylline, and increases efficacy of warfarin
  6. Weaning Glucocorticoids while on LT Inhibitors [46,49]
    1. Major issue in patients with severe asthma tapering glucocorticoids
    2. While LT blockers permit tapering of glucocorticoids, unmasking effects have been seen
    3. Pulmonary infiltrates, eosinophilia and cardiomyopathy have been reported [45,49]
    4. This is likely due to unmasking of underlying hypereosinophilic syndrome in patients
    5. This hypereosinophilic syndrome is similar to Churg-Strauss Syndrome

G. Theophylline and Aminophylline [57] navigator

  1. Actions
    1. Methylxanthines that block adenosine receptors at pharmacologic doses
    2. Higher doses are required for cAMP phosphodiesterase (cAMPase) inhibition
    3. Doses below therapeutic range have synergistic efficacy with inhaled steroids
    4. Increases respiratory drive and possibly respiratory muscle strength
  2. Use
    1. Adjunct in severe asthma, particularly in hospitalized patients
    2. Recommended only in moderate to severe acute exacerbations or night attacks
    3. May permit reduction of oral glucocorticoid doses
    4. Aminophylline recommended in patients with severe asthma who are hospitalized
  3. Efficacy
    1. Less effective bronchodilators than the ß2-agonists, with increased side effects
    2. Appears to improve FVC in moderate to severe asthma
    3. May add little to high dose ß-agonist + glucocorticoids in moderate acute asthma
    4. Overall leads to reduced symptoms in children with asthma on inhaled steroids
  4. Dosing (adults and children with no risk factors for decreased clearance)
    1. Subtherapeutic levels (below 10-15µg/mL) have clear efficacy in moderate asthma
    2. Absolutely no benefit but increased side effects with levels >15µg/ml
    3. Initial dose is ~10mg/kg po divided with maximum 300mg/day (eg. 100mg bid-tid)
    4. After 3 days, can increase to 13mg/kg with maximum 450mg/day
    5. Doses over 400-450mg/day are generally not recommended
    6. QD Dosing now available: Slo-bid® Gyrocap, Theo-24®, Theo-Dur®, Uni-Dru®, Uniphyl®
    7. Heart failure, hepatic failure, viral infection, drugs may increase blood levels
    8. Aminophylline is an intravenous form (see above)
  5. Side Effects
    1. Nausea, tachycardia, atrial fibrillation, tremors, headache, polyuria, heartburn
    2. Adenosine antagonism may lead to myocardial ischemia (vasocontriction, tachycardia)
    3. Overall, in correct doses, this is a fairly safe medication
  6. Drug Interactions (incomplete listing)
    1. Cimetidine, erythromycin, other macrolides, ticlopidine, ciprofloxacin increase levels
    2. Methotrexate, tacrine, propranolol, pentoxifylline, fluvoxamine increase levels
    3. Carbamazepine, phenobarbital, phenytoin, rifampin may decrease levels
    4. Use of zafirlukast (Accolate®) may increase theophylline levels to toxic range [51]
    5. Therefore, blood theophylline levels should be monitored when any new drugs added
  7. Phosphodiesterase 4 specific inhibitors cilomilast and roflumilast in development [5]

H. Other Therapeutic Agents [2]navigator

  1. Omalizumab (Xolair®) [28,59,60]
    1. Recombinant humanized monoclonal anti-human IgE antibody (Ab)
    2. Recognizes human IgE specifically at the same part of Fc region as the Fc(E) receptor
    3. Attenutates early- and late-phase reactions to inhaled allergens
    4. Biweekly IV dosing for 20 weeks in patients with allergic asthma on some form of steroids led to improved asthma scores and reduced need for steroids
    5. Some reduction in need for daily ß-adrenergic agonists in treated patients
    6. Serum IgE levels were reduced >95% with high and low dose anti-IgE treatments
    7. Subcutaneous dosing every 2-4 weeks for 16 weeks in children with allergic asthma reduced inhaled glucocorticoid use and number of asthma exacerbations [61]
    8. Clearly improved symptoms and reduced need for steroids in severe asthma [69]
    9. Antibodies to the anti-IgE treatments developed in all patients (no clinical effects)
    10. Dose varies 150-300mg q4 weeks to 225-375mg q2 weeks (effects in 12-16 weeks)
    11. Side effects similar to placebo but ~0.2% anaphylaxis (usually at first dose) [73]
  2. Cromolyn Sodium (Intal®) and Nedocromil (Tilade®)
    1. Appear to block mast cell degranulation
    2. Also blocks late response with bradykinin/sulfer dioxide bronchoconstriction
    3. Preferred over inhaled steroids in children
    4. May be most useful in cold induced and highly allergic asthma
    5. Chronic use in asthmatic children did not lead to improved lung function versus placebo [38]
  3. Ipatropium Bromide (Atrovent®) [62]
    1. Blocks muscarinic M3 acetylcholine receptors in airway; not M3 specific
    2. Very useful in COPD; less effective in asthma
    3. Likely beneficial in emergency cases of acute asthma in adults [62,63]
    4. Meta-anlysis showed 10% improved FEV1 and ~35% reduced hospital visits in adults [63]
    5. In children 2-18 years old, reduced hospitalization rates ~30% [16]
    6. Should only be used as adjunct to ß-agonists in asthma in both adults and children
  4. Antihistamines
    1. Useful with significant allergic component to asthma (atopy)
    2. Combinations with decongestants are commonly used
  5. Immunotherapy
    1. Ragweed immunotherapy in allergic patients did not significantly improve symptoms [64]
    2. Immunotherapy has shown little efficacy for asthma [7,8]
  6. TNFa Blockade [44]
    1. Refractory asthma associated with increased TNFa and its pathway mediators
    2. Etanercept (Enbrel®), a TNFa blocker, 25mg twice weekly for 10 weeks
    3. Improved refractory asthma including quality of life score
    4. Improved FEV1 folowing bronchodilator therapy
  7. Suplatast [66]
    1. Selective Th2 cytokine inhibitor suppresses IL4 and IL5 production
    2. Improved FEV1 and permitted reduction in inhaled glucocorticoids and ß-agonists
    3. Reduced serum levels of eosinophil catioic protein and serum IgE concentrations
    4. Oral agent with potential for add-on utility in asthma
  8. Experimental
    1. IL5 blockade - reduce peripheral and sputum eosinophils, no effect on asthma [65]
    2. IL12 subcutaneously - reduced peripheral eosinophilia; no efficacy in acute asthma
    3. Pitrakinra is an IL4/IL13 receptor antagonist
    4. Pitrakinra 60mg inhalation, but not 25mg subcutaneously, reduced allergen induced bronchoconstriction by 3.7 fold in patients with atopic asthma [8]
  9. Chiropractic manipulation has no benefit in childhood asthma

I. Current Recommendations for Chronic Asthma Control [1,2]navigator

  1. Mild Episodic Asthma
    1. ß-2 adrenergic agonists should be used only prn if possible - Step 1
    2. Cromylin Sodium (especially in children) or Nedocromil - Step 1
    3. Inhaled glucocorticoids in patients who require frequent or regular Step 1 Drug use
    4. Inhaled budesonidereduces severe exaacerbations, improves PFTs in early persistent asthma [4]
    5. LT blockers may be useful for prevention of exacerbations in moderate and mild asthma
  2. Mild Persistent Asthma
    1. Low doses of twice daily inhaled steroids usually sufficient
    2. Breakthrough symptoms treated with prn short acting ß2-agonist
    3. Increase dose of inhaled steroids at onset of exacerbation
    4. LT blockers not as good as inhaled steroids in mild-moderate disease [35]
    5. Inhaled steroids bid may be replaced with steroid/ß2agonist (long acting) once daily
  3. Moderate Asthma (Symptomatic without Therapy) [29]
    1. Inhaled steroids in all adults with moderate persistent asthma [27]
    2. Inhaled steroids are superior to cromylin/nedocromil in children [9]
    3. Inhaled ß2-agonists - long acting perferred over short acting but used in combination with inhaled steroids [29,68,72]
    4. Short acting ß2-agonists are used only on a prn basis
    5. Theophylline - nocturnal asthma attacks, poor respiratory function, Step 3
    6. Oral ß2-agonists are Step 3/4
    7. Strongly consider adding and LT blocker to reduce symptoms
  4. Severe Disease [15]
    1. Oral steroids - rapidly decreases eosinophilia (neutrophil resistant) - Step 3 medication
    2. Treatment daily often required for chronic control (doses >10mg qd prednisone)
    3. Steroid tapering after 10d 40mg/day prednisolone is not required in most patients
    4. Tapering concern arises mainly with disease rebound
    5. Patients also on inhaled steroids and long-acting inhaled ß-agonists for local delivery
    6. Very reasonable to add an LT blocking agent (may reduce symptoms/steroid use)
    7. All patients require short acting ß2-agonists
    8. Main concern is undertreatment and precipitation of severe attack
    9. Thorough evaluation required [15]
  5. Exercise Induced Asthma
    1. ß2-agonists (usually short acting) for difficult to control symptoms
    2. Cromylin compounds are effective also with essentially no side effects
    3. LT inhibitors may show efficacy as prophylactic agents
    4. Patients with frequent need for prophylaxis may benefit from inhaled glucocorticoids
  6. PEF Meters may be useful for moderate and severe asthmatics to guide therapy

References navigator

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  2. Drugs for Asthma. 2000. Med Let. 42(1073):19 abstract
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  5. Lipworth BJ. 2005. Lancet. 365(9454):167 abstract
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  15. Holgate ST and Polosa R. 2006. Lancet. 368(9537):780 abstract
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