TOC | Pulm

ASTHMA      See also   Bronchitis | COPD          REF:  ACP Medicine  Best Dx/Best Rx 2006  | asthma2007.pdf | asthma_rx2009.pdf | asthma-Rx2009.htm

Definition/Key Clinical Features  |  Differential Diagnosis  |  Best Tests  |  Best Therapy  | Drugs  |  Best References Medications for Asthma & COPD     Beta-2 Agonist  |  Inhaled corticosteroids  |  Anti-cholinergic  | Leukotriene Inhibitors

Definition/Key Clinical Features Reversible narrowing of airways in response to various stimuli and airway inflammation During periods of normal lung function, no abnormal physical findings Symptoms: always try to quantify—e.g., mild-moderate-severe, scale 1–5 Wheezing Cough (nonproductive or with copious sputum) Shortness of breath Chest tightness (often confused with angina pectoris) Desperate hunger for air with severe attacks

Classification of asthma severity and step-wise therapy     For All Patients - Quick Relief Rx: Short-acting bronchodilator: 2-4 puffs short-acting inhaled beta2-agonists as needed for Sx. Intensity of Rx will depend on severity of exacerbation;  up to 3 Rx at 20-minutes intervals or a single nebulizer Rx as needed.  Course of systemic corticosteroids may be needed. Use of short-acting beta2-agoniss > 2 x/week in intermittent asthma  (daily, or increasing use in peersistent asthma) mah indicate the need to initiate (increase) long-term therapy. Mild intermittent Treat patients with mild intermittent asthma with a quick relief medication (e.g., a short-acting ß-agonist). - Symptoms <=2 per week, Asymptomatic and normal PEF between exacerbations, Exacerbations brief (a few hours to a few days); intensity may vary: nocturnal Sx <=2 per month; - FEV1 or PEF >=80% predicted; PEF variability <20% Long-term control: No daily medication needed Mild persistent Treat patients with mild persistent asthma with one long-term controller medication. - Symptoms >2 per week but <1 per day; Exacerbations may affect activity; Nocturnal Sx >2 per month - FEV1 or PEF >=80% predicted; PEF variability 20%-30%; Long-term control: One daily medication: Anti-inflammatory*: either inhaled corticosteroid (low doses) or cromolyn* or nedocromil* (children usually begin with a trial of cromolyn or nedocromil); Sustained-release theophylline to serum concentration of 5-15 µg/mL is an alternative, but not preferred, therapy. Montelukast, zafirlukast, or zileuton may also be considered for patients age 12 and older, although their position in therapy is not fully established Moderate persistent Treat patients with moderate persistent asthma with one or two long-term controller medications. - Daily symptoms;Daily use of inhaled short-acting Beta2-agonist; Exacerbations may affect activity; Exacerbations >=2 per week; may last days; Nocturnal Sx >1 per week - FEV1 or PEF >60%-<80% predicted; PEF variability >30% Long-term control:   Preferred treatment: Low-to-medium dose inhaled corticosteroids and long-acting inhaled 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 inhaled Beta2-agonists. Alternative treatment: Increase inhaled corticosteroids in medium-dose range, and add either leukotriene modifier or theophylline Severe persistent Recognize that patients with severe persistent asthma may require at least three daily medications to manage their disease. - Continual symptoms; Limited physical activity; Frequent exacerbations; Nocturnal Sx frequent; - FEV1 or PEF <60% predicted; PEF variability >30 %  Long-term control:   Preferred treatment: High-dose inhaled corticosteroids AND Long-acting inhaled ?2-agonists AND, if needed, Corticosteroid tablets or syrup long term (2 mg/kg·d, generally do not exceed 60 mg/d). (Make repeat attempts to reduce systemic corticosteroids and maintain control with high-dose inhaled corticosteroids.)

Differential Diagnosis    Upper airway obstruction Viral tracheobronchitis Chronic obstructive pulmonary disease Congestive heart failure Pulmonary embolism Churg-Strauss syndrome

Medications for Asthma & COPD     Beta-2 Agonist  |  Inhaled corticosteroids  |  Anti-cholinergic  | Leukotriene Inhibitors

Best Tests    No single lab test can establish diagnosis; bronchodilator responsiveness provides supportive evidence Spirometry > 15% increase in airflow (FEV1 or FVC) after bronchodilator inhalation suggests asthma Lacks sensitivity and specificity False negatives occur during asymptomatic periods False positives occur with chronic bronchitis, emphysema, or other diseases with chronic airflow obstruction Bronchoprovocation with methacholine May be helpful if pulmonary function is normal Abnormal response is > 20% decline in FEV1 Other provocative agents are cold, exercise, and histamines CXR may exclude alternative diagnoses; not recommended for screening or diagnosis CBC, sputum exam, IgE measurement, allergy skin test not useful in most cases Red Flags Following factors suggest greater risk: Advanced age Greater airway reactivity Previous use of mechanical ventilation Long-term steroid therapy Previous hospitalizations for asthma Problems with compliance Major psychiatric diagnoses Use of major tranquilizers

Assess peak flow and patient respiratory symptoms to determine need for hospitalization. * Hospitalize patients with: An incomplete response to therapy during an exacerbation (PEFR >=50%, but <70% of predicted) Mild-to-moderate symptoms * Admit to intensive care unit any patients with: A worse response to therapy (FEV1 or PEFR <50% of predicted) An elevated partial pressure of carbon dioxide (PaCO2) Severe symptoms Recognize that certain historical factors reflect risk for near-fatal and fatal events and lower the threshold for hospital admission for a person with an acute exacerbation.  Lower the threshold for admission for patients having: o An asthma exacerbation with a history of: Prior intubation Multiple asthma-related hospitalizations Emergency department visits during the previous 12 months Low adherence to inhaled corticosteroids o Acute asthma exacerbations with a history of: Depression Substance abuse Personality disorders Unemployment Recent bereavement

Best Therapy     Emergency Assess oxygenation by pulse oximetry Increase O2 sat to >90% Measure ABGs Rapidly evaluate for hypercapnia, pneumothorax, atelectasis, or pneumonia Administer shorter-acting beta-adrenergic agonist by inhalation 1. Remove underlying precipitating causes, as infection, chemical irritation, anxiety, etc. 2. O2 supplement, hydration, antibiotics, & sedatives cautiously 3. Bronchodilators 4. Anti-inflammatory Meds 5. Bronchoscopic removal of mucus plugs, etc. 6. Mechanical ventilator 7. Misc: Magnesium 1.2 g in 150ml NS IV over 20 min after albuterol nebulizer Rx. 8.  Lung Volume Reduction Surgery (LVRS) in selected patients with symptomatic upper lobe emphysema.

Medications for Asthma & COPD     Beta-2 Agonist  |  Inhaled corticosteroids  |  Anti-cholinergic  | Leukotriene Inhibitors

Medications for Asthma & COPD     Beta-2 Agonist  |  Inhaled corticosteroids  |  Anti-cholinergic  | Leukotriene Inhibitors

Beta-2 Agonist   * * Aerochamber - better delivery.   Spacer device Inhaled short-acting beta2 agonists: first-line p.r.n. therapy; no significant differences in efficacy among inhaled short-acting beta2 agonists; dilute aerosols to minimum of 4 ml at gas flow of 6-8 L/min Albuterol (Ventolin, Proventil) Nebulizer, 5 mg/ml   0.5 ml in 2.5 ml NS(2.5 mg) Dose: maintenance, 1.25–5.0 mg q. 4–8 hr p.r.n; exacerbation, 5 mg q. 2 hr MDI, 84 ¼g/puff: MDI as effective as nebulizer when used with spacer Dose: maintenance, 2–4 puffs q. 6 hr p.r.n; exacerbation, 3–8 puffs q. 2 hr Pirbuterol (Maxair) MDI, 200 ¼g/puff Dose: maintenance, 2–4 puffs q. 6 hr p.r.n.; exacerbation, not studied Alupent (Metaproterenol) 0.3 ml in 2.5 ml NS (15 mg) Levalbuterol (Xopenex) Dosage forms: 0.31,0.63,1.25/3 mL neb MDI 45 ug/puff Dose tid   Combined short-acting beta2 agonist and anticholinergic: use when both are indicated MDI Combivent albuterol (90 ¼g/puff) + ipratropium bromide (18 ¼g/puff) Dose: maintenance, not recommended; exacerbation, 3–8 puffs q. 2 hr Inhaled long-acting beta2 agonists: first-line scheduled bronchodilator therapy Arformotero (Brovana) 15 mcg twice daily dosing by jet nebulizer - Median time to onset was 6.7 min & 20 min after the first dose.  Peak bronchodilator effect was generally seen within 1-3 hours of dosing - It is not indicated for the Rx of acute episodes of bronchospasm Salmeterol (Serevent Diskus): Slower onset of action; not used as a rescue bronchodilator MDI, 21 ¼g/puff Dose: maintenance, 2 puffs q. 12 hr; exacerbation, not recommended Cost/mo: $50.00–69.99 DPI, 50 ¼g/blister Dose: maintenance, 1 blister q. 12 hr Formoterol (Foradil) : faster onset of action than salmeterol; may be used as a rescue bronchodilator DPI, 12 ¼g/capsule Dose: maintenance, 1 capsule q. 12 hr; exacerbation, not recommended Combined long-acting beta2 agonit and corticosteroid: Advair (fluticasone/Flovent + salmeterol/Serevent) DPI 100/50, 250/50, 500/50) 1 inhalation bid   ; MDI 45, 115, or 230 2 puffs bid Symbicort (Budesonide with formoterol) MDI 80 or 160 2 puffs twice daily. Medications for Asthma & COPD     Beta-2 Agonist  |  Inhaled corticosteroids  |  Anti-cholinergic  | Leukotriene Inhibitors

Inhaled Corticosteroids: first choice of anti-inflammatory agents; various inhaled corticosteroid agents differ in potency Fluticasone (Flovent): highest potency; also formulated in combination with salmeterol in DPI Dose: low, 83-264 µg; medium, 264-660 µg; high, > 660 µg 44 µg/puff: low, 2-4 puffs/day 110 µg/puff: low, 2 puffs/day; medium, 2-6 puffs/day; high, > 6 puffs/day 220 µg/puff: medium, 1-2 puffs/day; high, > 3 puffs/day Budesonide (Pulmicort): second-highest potency; DPI inhaler Dose: low, 200-400 µg; medium, 400-600 µg; high, > 600 µg 220 µg/puff: low, 1-2 puffs/day; medium, 2-3 puffs/day; high, > 3 puffs/day Beclomethasone (QVAR): third-highest potency; available in HFA MDI, possibly improving effectiveness Dose: low, 168-504 µg; medium, 504-840 µg; high, > 840 µg 42 µg/puff: low, 4-12 puffs/day; medium, 12-20 puffs/day; high, > 20 puffs/day 40-80 mcg 1-2 puffs bid Flunisolide (Aerobid): lowest potency Dose: low, 500-1,000 µg; medium, 1,000-2,000 µg; high, > 2000 µg 42 µg/puff: low, 4-12 puffs/day; medium, 12-20 puffs/day; high, > 20 puffs/day Mometasone (Asmenex) 110 or 220 ug/puff once daily dose Triamcinolone (Azmacort): lowest potency; provided with spacer Dose: low, 400-1,000 µg; medium, 1,000-2,000 µg; high, > 2,000 µg 100 µg/puff: low, 4-10 puffs/day; medium, 10-20 puffs/day; high, > 20 puffs/day Systemic Corticosteroids Prednisone: usual oral agent; q.d. initially, then wean off, if possible, or switch to q.o.d. Dose: initial, 0.5-1.0 mg/kg/day; maintenance, none or minimal Methylprednisolone, oral: less commonly used oral agent; q.d. initially, then wean off, if possible, or switch to q.o.d. Dose: initial, 24-48 mg/day; maintenance, none or minimal Methylprednisolone, I.V.: usual I.V. agent; oral therapy is as effective Dose: initial, 60-125 mg IV q. 6-8 hr; maintenance, none Medications for Asthma & COPD     Beta-2 Agonist  |  Inhaled corticosteroids  |  Anti-cholinergic  | Leukotriene Inhibitors

Anticholinergic drugs: Atrovent (Ipratropium)  inhaler 2-4 puffs q6h Atrovent 0.5mg (1 unit dose) nebulizer soln in 2.5 mL NS 3-4x/d Atropin 0.5 mg in 2.5 ml NS q6-8h Spiriva HandiHaler (tiotropium) 18 mcg/cap  DOSE: 1 cap inhaled qd Info: dry pwdr caps for use w/ HandiHaler device only   Mechanism Of Action: antagonizes acetylcholine receptors, producing bronchodilation (anticholinergic) Medications for Asthma & COPD     Beta-2 Agonist  |  Inhaled corticosteroids  |  Anti-cholinergic  | Leukotriene Inhibitors

Leukotriene Inhibitors: less effective than inhaled corticosteroids; help with associated allergic rhinitis; use for aspirin-sensitive patients Montelukast (Singulair): first choice of leukotriene inhibitors; note q.h.s. dosing; no lab monitoring or restrictions related to meals Dose: 10 mg q.h.s. Cost/mo: $60.00-69.99 Zafirlukast (Accolate): should be taken at least 1 hr before or 2 hr after meals Dose: 20 mg b.i.d. Cost/mo: $50.00-59.00 Zileuton  (Zyflo): must monitor LFTs Dose: 600 mg q.i.d. Cost/mo: $79.00-89.99 Methotrexate (Rheumatrex, Trxall): efficacy controversial; toxic drug, must monitor blood counts and LFTs closely; should be given only by asthma expert Dose: 7.5 mg/wk (adjust to effect; maximum 25 mg/wk) Cost/mo: $10.00-19.99

Medications for Asthma & COPD     Beta-2 Agonist  |  Inhaled corticosteroids  |  Anti-cholinergic  | Leukotriene Inhibitors    OTHERS RX: Cromolyn Sodium (Intal): much less potent than inhaled steroids; used more often in children; no steroid side effects Dose: initial, 2-4 puffs q.i.d.; maintenance, 2 puffs q.i.d. Cost/mo: $30.00-39.99/canister Nedocromil: much less potent than inhaled steroids; no steroid side effects Dose: initial, 2 puffs q.i.d.; maintenance, 2 puffs q.i.d. Cost/mo: $50.00-59.99 Nonselective beta-2 agonists * Patients whose bronchoconstriction is resistant to continuous handheld nebulizer treatments with traditional beta-2 agonists may be candidates for nonselective beta-2 agonists (eg, epinephrine 0.3-0.5 mg  SC  q 30 min x 3; or terbutaline 0.25 mg SC) administered subcutaneously. However, systemic therapy has no proven advantage over aerosol therapy with selective beta-2 agents. Susphrine 0.1-0.3 ml 1:200 SQ *Avoid or use cautiously in heart or HBP pts. * Aminophylline The loading dose is usually 5-6 mg/kg, followed by a continuous infusion of 0.5-0.9 mg/kg/h o Conflicting reports on the efficacy of aminophylline therapy have made it controversial. o Starting intravenous aminophylline may be reasonable in patients who do not respond to medical treatment with bronchodilators, oxygen, corticosteroids, and intravenous fluids within 24 hours. o Recent data suggest that aminophylline may have an anti-inflammatory effect in addition to its bronchodilator properties. o The loading dose is usually 5-6 mg/kg, followed by a continuous infusion of 0.5-0.9 mg/kg/h. o Physicians must monitor a patient's theophylline level. Traditionally, the level was targeted to the higher end of the local therapeutic range; however, many authorities suggest that the lower portion of the range (ie, >5 but <10) may be preferable if the patient can obtain the benefits of the drug in the lower range. o Adverse effects can include tachyarrhythmia, nausea, seizures, and anxiety. Theophylline: third choice; relatively weak bronchodilator; used only when all other agents optimized; significant toxicity; must monitor levels Dose: maintenance, 100–200 mg b.i.d.; exacerbation, adjust to serum level 10–20 µg/ml  Proventil (Albuterol) 2-4mg tablet qid PO REF:  http://www.emedicine.com/MED/topic2169.htm   2004

Medications for Asthma & COPD     Beta-2 Agonist  |  Inhaled corticosteroids  |  Anti-cholinergic  | Leukotriene Inhibitors

* [DPI—dry-powder inhaler; MDI--metered-dose inhaler]

Nonselective beta-2 agonists * Patients whose bronchoconstriction is resistant to continuous handheld nebulizer treatments with traditional beta-2 agonists may be candidates for nonselective beta-2 agonists (eg, epinephrine [0.3-0.5 mg]  SC or terbutaline [0.25 mg] SC) administered subcutaneously. However, systemic therapy has no proven advantage over aerosol therapy with selective beta-2 agents. * Aminophylline The loading dose is usually 5-6 mg/kg, followed by a continuous infusion of 0.5-0.9 mg/kg/h o Conflicting reports on the efficacy of aminophylline therapy have made it controversial. o Starting intravenous aminophylline may be reasonable in patients who do not respond to medical treatment with bronchodilators, oxygen, corticosteroids, and intravenous fluids within 24 hours. o Recent data suggest that aminophylline may have an anti-inflammatory effect in addition to its bronchodilator properties. o The loading dose is usually 5-6 mg/kg, followed by a continuous infusion of 0.5-0.9 mg/kg/h. o Physicians must monitor a patient's theophylline level. Traditionally, the level was targeted to the higher end of the local therapeutic range; however, many authorities suggest that the lower portion of the range (ie, >5 but <10) may be preferable if the patient can obtain the benefits of the drug in the lower range. o Adverse effects can include tachyarrhythmia, nausea, seizures, and anxiety. REF:  http://www.emedicine.com/MED/topic2169.htm   2004

Best References

• Busse W, Raphael GD, Galant S, et al: Low-dose fluticasone propionate compared with montelukast for first-line treatment of persistent asthma: a randomized clinical trial. J Allergy Clin Immunol 107:461, 2001

• Busse WW, Lemanske RF Jr: Asthma. N Engl J Med 344:350, 2001

• Busse, et al: J Allergy Clin Immunol 107:461, 2001

• Busse, et al: N Engl J Med 344:350, 2001

• Cochrane, et al: Chest 117:542, 2000

• NIH Guidelines (NIH Publication No 97-4051), Bethesda, Maryland, 1997 (www.nhlbi.nih.gov/health/prof/lung/asthma/practgde.htm)

• Shrewsbury, et al: BMJ 320:1368, 2000
• Suissa, et al: J Allergy Clin Immunol 107:937, 2001
• Taylor, et al: Thorax 55:595, 2000
• Virchow, et al: Am J Respir Crit Care Med 162:578, 2000

Medications for Asthma & COPD     Beta-2 Agonist  |  Inhaled corticosteroids  |  Anti-cholinergic  | Leukotriene Inhibitors   

Treatment of Status Asthmaticus in Children

Definition of Status Asthmaticus:
A sudden intense and continuous aggravation of a state of asthma, marked by dyspnea to the point of exhaustion and collapse and not responding to the usual therapeutic efforts.

REF:  E-Medicine  January 17, 2006 Adam Schwarz, MD, http://www.emedicine.com/ped/topic2150.htm

Overall care for a child with asthma includes intensive outpatient treatment with medications and alteration of the environment.
Admission to the hospital represents a failure of outpatient management. This discussion is limited to inpatient treatment for status asthmaticus.

* Oxygen

• Oxygen is the primary therapeutic modality. Supplemental oxygen must be provided in any patient who presents with status asthmaticus. Oxygen helps to correct V/Q mismatch. Oxygen can be provided via nasal cannula or face masks.
• In the event of significant hypoxemia, nonrebreathing masks may be used to deliver as much as 98% oxygen. The goal in supplemental oxygen therapy is to maintain oxygen saturation above 90%.

* Inhaled beta-agonists

• Beta-agonist agents, typically albuterol or salbutamol, and terbutaline, are the mainstays of acute therapy in asthma. They act via stimulation of cyclic adenosine monophosphate (AMP)–mediated bronchodilation. The airway is rich in beta-receptors; the stimulation of these receptors relaxes airway smooth muscles, increases mucociliary clearance, and decreases mucous production.
• The nebulized inhaled route of administration is generally the most effective route of delivery, though some patients with severe refractory status asthmaticus may benefit by the addition of beta-agonists delivered intravenously. Beta-agonists are generally most effective in the early asthma reaction phase. However, patients who present with status asthmaticus despite frequent use of beta-agonists at home may have tachyphylaxis and resistance to these agents. Therefore, these patients may not respond as well when these agents are given in the hospital. Inhaled beta-agonists can be administered intermittently or as continuous nebulized aerosol in a monitored setting.

* Corticosteroids

• Corticosteroids, such as methylprednisolone or prednisone, are critical in the therapy of status asthmaticus and are used to decrease the intense airway inflammation and swelling in asthma. In addition, corticosteroids potentiate the effects of beta-agonist agents and improve capillary leak. Therefore, corticosteroids affect the late asthma reaction phase.
• Corticosteroids may be administered intravenously or orally. Although most practitioners administer corticosteroids intravenously during status asthmaticus, some studies indicate that early administration of oral corticosteroids may be just as effective.

* Anticholinergics

• Anticholinergic agents act via inhibition of cyclic guanosine monophosphate (GMP)–mediated bronchoconstriction. They may also decrease mucus production and improve mucociliary clearance
• Ipratropium bromide (Atrovent), a quaternary amine that does not cross the blood-brain barrier, is the recommended sympathomimetic agent of choice. Atropine, a tertiary amine, may also be used and nebulized but may cause CNS effects because it may enter the CNS. In patients with severe airflow obstruction, the combination of ipratropium and albuterol can provide better bronchodilatation than albuterol alone.

* Further therapy: Although not as well investigated in large-scale, randomized, controlled trials, other therapies may be helpful when the standard combination of oxygen and intermittent or continuous beta-agonists (ie, albuterol), intermittent inhaled anticholinergics (ie, ipratropium bromide), and corticosteroids are insufficient in relieving significant respiratory distress in severe acute asthma. These include the following:

o Magnesium sulfate

• Magnesium can relax smooth muscle and hence cause bronchodilation by competing with calcium at calcium-mediated smooth muscle binding sites. The published doses used range from 25-75 mg/kg infused over 20 minutes, with a maximum of 2-2.5 g/dose. One double-blind placebo-controlled study reported a significant increase in peak expiratory flow, FEV1, and forced vital capacity in children who had asthma and were treated with a single 40-mg/kg dose of magnesium sulfate (MgSO4) infused over 20 minutes, along with steroids and inhaled bronchodilators, compared with control subjects who received saline placebo. In addition, patients who received intravenous magnesium were significantly more likely to be discharged home from the presenting ED than control subjects (8/18 vs 0/14; P = .002).
• No data currently exist regarding duration of effect or efficacy with repeated doses, and no guidelines describe the monitoring of serum magnesium levels if more than an initial magnesium dose is administered. In one small study of 4 children who received 40-50 mg/kg MgSO4, serum magnesium levels were all less than 4 mg/dL, whereas ECG changes are generally not seen until levels exceed greater than 4-7 mg/dL. Adverse effects may include facial warmth, flushing, tingling, nausea, and hypotension.

o Intravenous beta-agonists

• Some patients with refractory status asthmaticus may respond to intravenous administration of beta-agonists. Intravenous albuterol and salbutamol may be administered where available but are not available in the United States. Intravenous terbutaline is most commonly used in the United States. Reported doses for intravenous terbutaline have ranged from 0.4-10 mcg/kg/min in children. Historically, isoproterenol has been used, but its potent beta1 stimulation may lead to significant tachycardia and inotropy, which has caused myocardial infarction in adults.
• The dose administered should be titrated to effect and adverse cardiac effects (tachycardia, arrhythmias, ECG changes). Some practitioners advocate monitoring cardiac enzyme levels in patients who receive prolonged significant infusions of intravenous beta-agonists.

o Ketamine

• Ketamine is a short-acting pentachlorophenol (PCP) derivative that exerts bronchodilatory effects because it leads to an increase in endogenous catecholamine levels, which may bind to beta-receptors and cause smooth muscle relaxation and bronchodilation.
• Case reports have also described the use of ketamine as a sedative to reduce anxiety and agitation that can exacerbate tachypnea and work of breathing and potentially obviate further respiratory failure in small children with status asthmaticus.

o Methylxanthines

• The role of methylxanthines, such as theophylline or aminophylline, in the treatment of severe acute asthma has been seriously challenged since the advent of potent selective beta-agonists and their use at higher doses. At therapeutic doses, methylxanthines are weaker bronchodilators than beta-agonists and have many undesirable adverse effects, such as frequent induction of nausea and vomiting. Furthermore, most studies have failed to show additional benefit when methylxanthines are administered to patients who are already receiving frequent beta-agonists and steroids.
• Nevertheless, several recent prospective, randomized, controlled studies in children with refractory status asthmaticus have reexamined the role of the methylxanthines theophylline and aminophylline and demonstrated improvement in the clinical asthma scores when compared with placebo control. One study compared intravenous theophylline with intravenous terbutaline in critically ill children with refractory asthma and demonstrated equal therapeutic efficacy but significantly lower costs associated with theophylline use. Among the theophylline effects that are important in managing asthma are bronchodilatation, increased diaphragmatic function, and central stimulation of breathing.

PEFR - Peak Flow Rate L/min  

For Normal Male  (50-70% of expected)                          REF:  Assess Peak Flow Meter Info

Age	5'0" Normal Predicted	5'0"	5'5" Normal Predicted	5'5"	5'10" Normal Predicted	5'10"	6'3" Normal Predicted	6'3"	6'8" Normal Predicted	6'8"
20	554	277 - 388	575	288 - 403	594	297 - 416	611	306 - 428	626	313 - 438
25	580	290 - 406	603	302 - 422	622	311 - 435	640	320 - 448	656	328 - 459
30	594	297 - 416	617	309 - 432	637	319 - 446	655	328 - 459	672	336 - 470
35	599	300 - 419	622	311 - 435	643	322 - 450	661	331 - 463	677	339 - 474
40	597	299 - 418	620	310 - 434	641	321 - 449	659	330 - 461	675	338 - 473
45	591	296 - 414	613	307 - 429	633	317 - 443	651	326 - 456	668	334 - 468
50	580	290 - 406	602	301 - 421	622	311 - 435	640	320 - 448	656	328 - 459
55	566	283 - 396	588	294 - 412	608	304 - 426	625	313 - 438	640	320 - 448
60	551	276 - 386	572	286 - 400	591	296 - 414	607	304 - 425	622	311 - 435
65	533	267 - 373	554	277 - 388	572	286 - 400	588	294 - 412	603	302 - 422
70	515	258 - 361	535	268 - 375	552	276 - 386	568	284 - 398	582	291 - 407
75	496	248 - 347	515	258 - 361	532	266 - 372	547	274 - 383	560	280 - 392

PEFR For Normal Female  (50-70% of expected)

Age	4'7" Normal Predicted	4'7"	5'0" Normal Predicted	5'0"	5'5" Normal Predicted	5'5"	5'10" Normal Predicted	5'10"	6'3" Normal Predicted	6'3"
20	444	222 - 311	460	230 - 322	474	237 - 332	486	243 - 340	497	249 - 348
25	455	228 - 319	471	236 - 330	485	243 - 340	497	249 - 348	509	255 - 356
30	458	229 - 321	475	238 - 333	489	245 - 342	502	251 - 351	513	257 - 359
35	458	229 - 321	474	237 - 332	488	244 - 342	501	251 - 351	512	256 - 358
40	453	227 - 317	469	235 - 328	483	242 - 338	496	248 - 347	507	254 - 355
45	446	223 - 312	462	231 - 323	476	238 - 333	488	244 - 342	499	250 - 349
50	437	219 - 306	453	227 - 317	466	233 - 326	478	239 - 335	489	245 - 342
55	427	214 - 299	442	221 - 309	455	228 - 319	467	234 - 327	477	239 - 334
60	415	208 - 291	430	215 - 301	443	222 - 310	454	227 - 318	464	232 - 325
65	403	202 - 282	417	209 - 292	430	215 - 301	441	221 - 309	451	226 - 316
70	390	195 - 273	404	202 - 283	416	208 - 291	427	214 - 299	436	218 - 305
75	377	189 - 264	391	196 - 274	402	201 - 281	413	207 - 289	422	211 - 295

On the basis of careful serial studies of sputum specimens from patients with chronic obstructive pulmonary disease, obtained during both stable periods and exacerbations, the authors found that the appearance of Streptococcus pneumoniae or Moraxella catarrhalis in sputum cultures was significantly associated with symptoms of exacerbation.  Furthermore, they subjected the sputum isolates to molecular typing in order to identify different bacterial strains.  Exacerbations were more strongly associated with changes in the bacterial strain than with the simple presence or absence of a pathogen in cultured sputum.  Most striking was the case of Haemophilus influenzae; the presence or absence of this pathogen in sputum was not related to the risk of an exacerbation, but the presence of a new strain of the organism was.

Finally, should the results of the study by Sethi et al. change clinical practice?
Probably not, since the findings support the current empirical use of antibiotics to treat exacerbations of chronic obstructive pulmonary disease and illustrate the difficulties in interpreting the results of routine sputum cultures. The study does, however, point to a major gap in our knowledge — namely, which antibiotics should be used. The studies demonstrating the efficacy of antibiotics are old and involved the use of inexpensive agents with a relatively narrow spectrum. Bacterial resistance to these antibiotics has increased, and expensive, broad-spectrum agents are often used now, though there is little evidence that they have superior benefits.

Sethi S, Evans N, Grant BJB, Murphy TF. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease.
N Engl J Med August 15, 2002;347:465-471.

       2009

Medications for Asthma & COPD     Beta-2 Agonist  |  Inhaled corticosteroids  |  Anti-cholinergic  | Leukotriene Inhibitors