OVERVIEW ã…¡ Chronic inflammatory disorder of airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. Causes may be due to genetic factors or environmental exposures (see Risk Factors).
| Table (1). Pathophysiology and risk factors of asthma | |
|---|---|
| ASTHMA | COMMENT |
| Pathophysiology |
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| Risk factors |
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SIGNS AND SYMPTOMS
FOR CHRONIC ASTHMA Chronic asthma, symptoms include episodic dyspnea with wheezing, chest tightness, and coughing that may occur spontaneously, with exercise, or after exposure to known allergens. Signs include Expiratory wheezing; dry, hacking cough; atopy (eg, allergic rhinitis, eczema) and can vary in frequency from intermittent to chronic daily symptoms. Severity determined by lung function, symptoms, nighttime awakenings, and interference with normal activity.
FOR ACUTE SEVERE ASTHMA, symptoms include anxiousness with acute distress and complaints of severe dyspnea, shortness of breath, and chest tightness unresponsive to usual measures. Signs include expiratory and inspiratory wheezing; dry, hacking cough; tachypnea; tachycardia; pallor or cyanosis; hyperinflated chest with intercostal and supraclavicular retractions.
DIAGNOSIS
MEANS OF CONFIRMATION AND DIAGNOSIS ã…¡ For Chronic asthma, history of recurrent episodes of coughing, wheezing, chest tightness, or shortness of breath and confirmatory spirometry.It may be family history of allergy or asthma, or patient symptoms of allergic rhinitis. History of exercise or cold air precipitating symptoms during specific allergen seasons. For acute severe asthma, history of previous asthma exacerbations (e.g, hospitalizations, intubations) and complicating illnesses (e.g, cardiac disease, diabetes). Assess hydration status; use of accessory muscles of respiration; and presence of cyanosis, pneumonia, pneumothorax, pneumomediastinum, and upper airway obstruction.
LABORATORY TESTS ã…¡ Obtain complete blood count (CBC) when fever or purulent sputum present. In acute severe asthma, arterial blood gases may reveal metabolic acidosis and low partial pressure of oxygen (PaO2).
IMAGING ã…¡ Chest radiography in patients with fever to rule out pneumonia. High-resolution chest computed tomography (CT) in patients with chronic or recurring symptoms or possible complications.
DIAGNOSTIC PROCEDURES ㅡ For chronic asthma, spirometry demonstrates obstruction (forced expiratory volume in 1 s [FEV1]/forced vital capacity [FVC] <80%) with reversibility after inhaled β2-agonist administration (at least 12% improvement in FEV1). If baseline spirometry normal, perform challenge testing with exercise, histamine, or methacholine to elicit BHR. For acute severe asthma, peak expiratory flow (PEF) and FEV1 are <40% of normal predicted values. Pulse oximetry reveals decreased arterial oxygen and O2 saturations.
TREATMENT
GENERAL APPROACH ã…¡ Assess documentation of symptom control and risk factors, and if these are uncontrolled, check inhaler technique and adherence, and consider whether symptoms are due to co-morbid condition such as allergic rhinitis, GERD, or obesity rather than asthma. Adjust therapy (up or down), both drug therapy and non pharmacological strategies; treat modifiable risk factors. Review response, assess and optimize asthma control about every 3 months. See Figure 1, self-management of worsening asthma in adults and adolescents with a written asthma action plan. (From National Heart Lung Blood Institute, National Asthma Education and Prevention Program . Expert panel report 3: guidelines for the diagnosis and management of asthma. Summary report 2007, NIH Publication No. 08-5846, Bethesda, MD, 2007, U.S. Department of Health and Human Services, 45, http://www.nhlbi.nih.gov/guidelines/asthma/asthsumm.pdf)
Non-pharmacological Therapy include patient education and teaching of self-management skills, avoidance of known environmental triggers, indoor allergens, and medications in sensitive patients, smoking cessation, supplemental oxygen for patients with acute severe asthma to maintain arterial oxygen saturation 90% and Hydration as indicated.
FIRST LINE PHARMACOLOGICAL THERAPY
SHORT-ACTING BRONCHODILATORS ã…¡ Quick-relief medications used on an as-needed basis for long-term management of all severities of asthma as well as for rapid treatment of exacerbations given via either MDI or nebulization. For long-term management, a SABA used on an as-needed basis (e.g., albuterol, two puffs q6h) is appropriate. SABA is considered the drug of choice for preventing exercise-induced bronchoconstriction. During an exacerbation, reversal of airflow obstruction is achieved most effectively by frequent administration of an inhaled SABA.
For a mild to moderate exacerbation, initial treatment starts with two to six puffs of albuterol via MDI with a spacer or 2.5 mg via nebulizer and is repeated q20min until improvement is obtained or toxicity is noted. For a severe exacerbation, albuterol 2.5-5 mg q20min with ipratropium bromide 0.5 mg q20min should be administered via nebulizer. Alternatively, albuterol 10-15 mg, administered continuously over an hour, may be more effective in severely obstructed adults. If used, telemetry monitoring is necessary.
Levalbuterol four to eight puffs or nebulized 1.25-2.5 mg q20min can be substituted for albuterol but has not been associated with fewer side effects in adults. The subsequent dosing schedule is adjusted according to the patient's symptoms and clinical presentation. Often, patients require a SABA q2-4h during an acute attack. The use of an MDI with a spacer device under supervision of trained personnel is as effective as aerosolized solution by nebulizer. Cooperation may not be possible in the patient with severe airflow obstruction. In rare circumstances, SC administration of a β2-adrenergic agonist in the form of aqueous epinephrine (0.3-0.5 mL of a 1:1000 solution SC q20min) or terbutaline (0.25 mg SC q20min) for up to three doses can be used. Inhaled medications remain the preferred approach and SC therapy should only be provided in the absence of an effective inhaled option. Importantly, recent myocardial infarction or active angina are contraindications to SC therapy. All SABAs now use hydrofluoroalkane (HFA) as a propellant. They should be primed with four puffs when first used and again if not used over 2 weeks.
ICSs ã…¡ ICSs are safe and effective for the treatment of persistent asthma. They are generally administered via a dry powder inhaler, MDI with a spacing device, or nebulized. Dosing depends on assessment of severity and control. Once-daily dosing of ICS may be as effective as twice-daily dosing. Systemic corticosteroid absorption can occur in patients who use high doses of ICS. Consequently, prolonged therapy with high-dose ICS should be reserved for patients with severe disease or for those who otherwise require oral corticosteroids. Pharmacological inhibitors of cytochrome P450 may reduce steroid elimination in patients on ICS, thus increasing steroid side effects. Attempts should be made to decrease the dose of ICS every 2-3 months to the lowest possible dose to maintain control.
| Table (2). Comparative Daily Adult Dosages for Inhaled Corticosteroids | |||
|---|---|---|---|
| Drug | Low Dose | Medium Dose | High Dose |
| Beclomethasone HFA (40 or 80 μg/puff) | 80-240 μg | >240-480 μg | >480 μg |
| Budesonide DPI (90, 180, or 200 μg/dose) | 180-600 μg | >600-1200 μg | >1200 μg |
| Budesonide nebulized respules (250, 500, or 1000 μg/respules) | 250-500 μg | >500-1000 μg | >1000 μg |
| Ciclesonide HFA (80 or 160 μg/puff) | 160-320 μg | >320-640 μg | >640 μg |
| Fluticasone propionate HFA (44, 110, or 220 μg/puff) | 88-264 μg | >264-440 μg | >440 μg |
| Fluticasone furoate (100, 220 μg/puff) | 100-300 μg | >300-500 μg | >500 μg |
| Mometasone furoate DPI (110 or 220 μg/puff) | 220 μg | 440 μg | >440 μg |
| Combination Agents | |||
| Budesonide/formoterol (MDI: 80/4.5 or 160/4.5 μg/puff) | Two puffs bid: 80/4.5 μg/puff | Two puffs bid: 80/4.5 to 160/4.5 μg/puff | Two puffs bid: 160/4.5 μg/puff |
| Fluticasone/salmeterol (MDI: 45/21, 115/21, or 230/21 μg/puff) (DPI: 100/50, 250/50, or 500/50 μg/dose) | One inhalation bid: 100/50 μg | One inhalation bid: 250/50 μg | One inhalation bid: 500/50 μg |
| Fluticasone/vilanterol (DPI: 100/25, 200/25 μg/puff) | One inhalation daily: 100/25 μg | One inhalation daily: 200/25 μg | One inhalation daily: 200/25 μg |
| Mometasone/formoterol (MDI: 100/5 or 200/5 μg/puff) | Two inhalations bid: 100/5 μg/puff | Two inhalations bid: 100/5 μg/puff to 200/5 μg/puff | Two inhalations bid: 200/5 μg/puff |
| Data from the 2018 GINA Report: Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma - GINA. https://ginasthma.org/2018-gina-re-port-global-strategy-for-asthma-management-and-prevention/. Updated 2018. Accessed September 13, 2018 and Asthma NAE and PP Third Expert Panel on the Diagnosis and Management of Asthma. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. National Heart, Lung, and Blood Institute (US); 2007. DPI, dry powder inhaler; MDI, metered-dose inhaler. |
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LABAs ã…¡ Recommended for moderate and severe persistent asthma in patients not adequately controlled with ICS. Salmeterol or the faster-acting formoterol added to ICS has consistently been shown to improve lung function, improve both day and nighttime symptoms, reduce exacerbations, and minimize the required dose of ICS. LABAs should only be used in combination with ICS in patients with asthma (salmeterol/fluticasone, budesonide/formoterol, or mometasone/formoterol). The benefits of adding LABAs are more substantial than those achieved by leukotriene modifiers (LTMs), theophylline, or increased doses of ICS.
SYSTEMIC CORTICOSTEROIDS ã…¡ It may be necessary to gain control of disease quickly via either oral or IV route. If chronic symptoms are severe and accompanied by nighttime awakening or PEF is <70% of predicted values, a short course of oral corticosteroid (prednisone 40-60 mg/d for 5-7 days) might be necessary. Long-term therapy is occasionally necessary and should be started at low dose (≤10 mg/d prednisone or equivalent), and repeated attempts should be made to reduce the dose while patients are receiving high-dose ICS. Side effects associated with long-term therapy should be closely monitored. Osteoporosis prophylaxis may be necessary.
During an exacerbation, systemic corticosteroids speed the resolution of exacerbations of asthma and should be administered promptly to all patients. The ideal dose of corticosteroid needed to speed recovery and limit symptoms is not well defined. A single or divided daily dose equivalent to prednisone 40-60 mg is usually adequate. Oral corticosteroid administration seems to be as effective as IV administration if given in equivalent doses. IV methylprednisolone, 125 mg, given on initial presentation, decreases the rate of return to the emergency department (ED) for patients who are discharged. For maximal therapeutic response, tapering of high-dose corticosteroids should not take place until objective evidence of clinical improvement is observed (usually 36-48 hours or when PEF >70%). Initially, patients are given a daily dose of oral prednisone, which is then reduced slowly. A 7- to 14-day tapering dose of prednisone is usually successful in combination with an ICS instituted at the beginning of the tapering schedule. In patients with severe disease or with a history of respiratory failure, a slower dose reduction is appropriate. Patients discharged from the ED should receive oral corticosteroids. A dose of prednisone, 40 mg/d for 5-7 days, can be substituted for a tapering schedule in selected patients. Either regimen should be accompanied by the initiation of an ICS or an increase in the previous dose of ICS.
SECOND LINE PHARMACOLOGICAL THERAPY
LEUKOTRIENE MODIFIERS (LTM) ã…¡ Montelukast (10 mg PO daily) and zafirlukast (20 mg PO bid) are oral leukotriene receptor antagonists (LTRAs), and zileuton (extended-release 1200 mg bid) is an oral 5-Lipoxygenase inhibitor. The LTRAs are recommended as an alternative first-line medication for mild persistent asthma and as an add-on to ICS for more severe forms of asthma.
As add-on therapy to ICS, these agents have been shown to improve lung function, lead to improved quality of life, and lead to fewer exacerbations. However, compared with ICS plus LABA, they are not as effective in improving asthma outcomes. A LTM should be considered for patients with aspirin-sensitive asthma, exercise-induced bronchoconstriction, or concurrent allergic rhinitis, or individuals who cannot master the use of an inhaler.
OMALIZUMAB (Xolair) ã…¡ For treatment of allergic asthma not well controlled by oral or ICS. Dose determined by baseline total serum IgE level (IU/mL) and body weight (kg) ranges from 150 to 375 mg given subcutaneously at 2- or 4-week intervals. High cost limits use as step 5 or 6 for patients with allergies and severe persistent asthma inadequately controlled with combined high-dose ICS and LABA and at risk for severe exacerbations. Side effects: 0.2% incidence of anaphylaxis; observe patients for reasonable period after injection.
REFERENCES
- National Institutes of Health, National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3). Guidelines for the Diagnosis and Management of Asthma—Summary Report 2007. http://www.nhlbi.nih.gov/guidelines/asthma/asthsumm.pdf
2018 GINA Report: Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma - GINA. https://ginasthma.org/2018-gina-report-global-strategy-for-asthma-management-and-prevention
Asthma NAE and PP Third Expert Panel on the Diagnosis and Management of Asthma. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. National Heart, Lung, and Blood Institute (US); 2007.CDC - Asthma - Most Recent Asthma Data. https://www.cdc.gov/asthma/most_recent_data.htm