Asthma

From Anvita Health Wiki

Contents 1 More Specific Terms 2 Introduction 3 Classification 4 Etiology 5 Pathology 6 Genetics 7 Clinical-manifestations 8 Laboratory 9 Diagnostic-procedures 10 Radiology 11 Differential-diagnosis 12 Management 13 More General Terms 14 Additional Terms 15 Internet Database 16 References

More Specific Terms

• asthma during pregnancy
• asthma in the elderly
• asthma-related traits
• mild-persistent asthma
• occupational asthma
• reactive airway dysfunction syndrome (RADS)
• status asthmaticus

Introduction

• A chronic illness characterized by airway inflammation* & hyper- responsiveness* of the tracheobronchial tree to diverse stimuli. The clinical course is one of exacerbations & remissions*, but without inevitable progression.
  

• * Triad of asthma

• airway inflammation
• bronchial hyper-responsiveness
• reversibility

Classification

• mild intermittant

• symptoms < 3 times/week
• asymptomatic
• normal peak expiratory flow between exacerbations
• nocturnal symptoms < 3 times/month
• FEV1 >= 80%

• mild persistent

• symptoms > twice weekly, but < daily
• nocturnal symptoms > 2 times/month
• FEV1 >= 80%

• moderate persistent

• daily use of short-acting beta-2 adrenergic agonists
• acute exacerbations > once weekly
• nocturnal symptoms > once weekly
• FEV1 60-80%

• severe persistent

• continual symptoms that limit physical activity
• nocturnal symptoms frequent
• FEV1 < 60%

• exercise-induced asthma
  

• Also see alternative classification of asthma

Etiology

• Exercise-induced asthma (also cold air)
• GERD-induced asthma [26]

• 80% of adult asthma with some reflux
• innervation of lower esophagus ( vagus) is same as innervation of lungs
• theophylline, EtOH & tobacco increase reflux

• sinobronchial-induced asthma

• pollens
• dust & dust mites
• animal dander
• cockroaches

• occupational asthma:

• allergy to Latex
• industrial agents

• pharmaceutical agents

• beta-adrenergic antagonists can worsen asthma
• ACE inhibitors can cause coughing in asthmatics
• aspirin & other NSAIDs can cause acute, severe asthma
• acetaminophen, children & adolescents ? [36]

• nitrogen dioxide exposure [10]
• mycoplasma or chlamydia may be associated with attack, especially 1st attack in children [13]

Pathology

• mucous gland hypertrophy with mucous hypersecretion & mucous plugs
• epithelial desquamation & replacement primarily with proliferating goblet cells
• loss of normal epithelial barriers to respiratory irritants & exposure of nerve endings
• widening of basement membrane
• intraepithelial leukocytes & mast cells
• mast cell degranulation
• eosinophilic infiltration of submucosa

• in asphyxic asthma, neutrophils predominate in airways

• round cell infiltration of bronchial submucosa
• bronchial hyper-responsiveness ( pathognomonic feature)

• asthmatics are 100 times more sensitive to the broncho- constricting effects of LTD4 than normal individuals

• obstruction of airflow by secretions & edema of bronchial mucosa
• disruption of elastic fibers [2]

Genetics

• (also see OMIM )
• G protein-coupled receptor for asthma susceptibility ( GPRA) gene
• asthma-associated alternatively spliced gene 1
• susceptibility to asthma associated with:

• defects in DPP10
• defects in ADAM33
• defects in TBX21

• other implicated genes: MS4A2, PLA2G7

Clinical-manifestations

• symptoms may be intermittent, seasonal, related to workplace or activity
• dyspnea, wheezing, cough, chest tightness
• hyperinflation; use of accessory muscles
• impaired lung expansion
• decreased fremitus
• hyperresonant; low diaphragm to percussion
• prolonged expiration
• nasal polyps

Laboratory

• arterial blood gas ( hospitalized patients)

• a normal pCO2 in severe asthma indicates impending respiratory failure

• sputum cytology: 53% with sputum eosinophilia [38]

Diagnostic-procedures

• pulmonary function testing:

• often a reduction in FEV1 > than any reduction in FVC
• improvement following inhalation of a bronchodilator (> 12%)
• more severe obstruction resulting in air trapping is identified by an increased residual volume
• DLCO is typically normal or elevated in patients with asthma
• every 2 years [24]
• normal spirometry does not rule out asthma

• methacholine challenge: known airway irritant

• a negative test rules out asthma
• a positive test does not establish diagnosis [3]

• peak flow meter (useful at home, emergency department)
• echocardiogram (difficult to control asthma)

Radiology

• chest X-ray (difficult to control asthma)
• bone-density scan: patients on chronic corticosteroids

Differential-diagnosis

• chronic eosinophilic pneumonia
• allergic bronchopulmonary aspergillosis
• Churg-Strauss angiitis
• GERD (may aggravate asthma) [3]
• chronic obstructive pulmonary disease
• vocal cord dysfunction
• heart failure
• bronchiectasis
• mechanical airway obsruction
• cystic fibrosis [2]

Management

• acute asthma

• also see status asthmaticus
• see individual therapeutic classes
• systemic glucococorticoids
• beta-2 adrenergic receptor agonists

• MDI as effective as nebulizer [32]

• epinephrine SQ 0.3-0.5 mL of a 1:1000 solution

• rescue medication for life-threatening asthma

• heliox may be of benefit vs endotracheal intubation for severe asthma

• goals of asthma management:

• reduce chronic airway inflammation
• alleviate symptoms of disease
• prevent exacerbations
• eliminate contributing medications

• beta-blockers (including ophthalmic agents)
• aspirin, NSAIDs if patient is sensitive

• identify precipitating conditions

• the most common cause of corticosteroid-dependent asthma is non-compliance with medications, especially inhaled corticosteroids
• ensure proper technique for using inhalers [3]

• during an acute exacerbation, additional goals include:

• ensure adequate gas exchange
• reduce the work of breathing

• chronic management goals also include:

• avoid side affects of medications
• identify precipitants of exacerbations
• allergen skin testing may be indicated

• stepwise management based on classification

• mild intermittant

• short-acting beta2-agonist (i.e. albuterol MDI PRN)

• mild persistent

• short-acting beta2-agonist + low-dose inhaled corticosteroid

• moderate persistent

• short-acting beta2-agonist +
• inhaled corticosteroid with or without long-acting beta2-agonist or leukotriene inhibitor

• severe persistent

• short-acting beta2-agonist +
• inhaled corticosteroid +
• long-acting beta2-agonist +
• consideration for oral corticosteroids
• consider omalizumab ( Xolair) in patients with allergies [3]

• exercise-induced asthma

• for infrequent symptoms, albuterol MDI, cromylin, or neocromodil 15-30 minutes prior to exercise
• for symptoms > twice weekly, leukotriene inhibitor or treat according to 1-4 (above)

• difficult to control asthma

• life style modifications
• trial of acid suppression with a proton pump inhibitor for potential GERD [3]
• tiotropium added to inhaled glucocorticoid may improve symptoms & pulmonary function [28]

• avoid: long-acting beta2-agonist as single agent
• anti-inflammatory agents

• glucocorticoids

• inhaled glucocorticoids for maintenance

• prophylaxis

• beclomethasone MDI 2 puffs QID
• triamcinolone MDI 2 puffs QID
• flunisolide MDI 2 puffs BID

• high dose (4X prophylactic dose)* for acute exacerbations in combination with beta-adrenergic receptor agonists [5]; 2X dose not effective [14]
• reduce to prophylactic dose after acute exacerbation resolves [9]

• systemic therapy for acute exacerbations

• methylprednisolone IV 60-125 mg every 6 hours (unlike prednisone, does not require hepatic metabolism for glucocorticoid activity)
• prednisone

• initially: 40-60 mg QD (more effective if divided BID)
• 1 mg/kg PO QD in children [11]
• < 2 weeks of therapy does NOT require taper

• methylprednisolone

• Medrol DosePack
• Depo-Medrol 80-160 mg IM, if non-compliance is an issue
• glucocorticoids do not affect course of disease [22]
• high-dose inhaled glucocorticoids do not replace oral glucocorticoids for acute exacerbations [23]
• maintenance glucocorticoids stunt growth in children [30]
• intermittent high-dose inhaled budesonide at the onset of respiratory tract disease as effective as low-dose daily inhaled glucocorticoids in preschool children [35]
• patients with sputum eosinophilia seem to respond better to glucocorticoids than those without [38]

• cromolyn sodium MDI 2 puffs QID (not 1st line)
• nedocromil sodium MDI 2 puffs QID (not 1st line)
• agents for use with poor response to glucocorticoids

• methotrexate
• gold salts
• cyclosporine
• troleamdromycin 250 mg PO QD ( hepatotoxic)

• bronchodilators

• beta-adrenergic receptor agonists (1st line agents)

• inhaled selective beta-2 agonists

• albuterol MDI
• albuterol nebulizer
• MDI with spacer more effective in reducing hospitalization in children [15]
• heliox may be useful [19]

• long-acting beta-2 agonist MDI (NOT for monotherapy)

• salmeterol ( Serevent) or formoterol ( Foradil)
• for use in conjunction with inhaled steroid
• no increase in mortality with use of long-acting beta-2 agonist [17]

• epinephrine SQ 0.3-0.5 mL of a 1:1000 solution

• rescue medication for life-threatening asthma
• 3 doses 15 minutes apart may be given
• maximum dose 1 mg

• isoproterenol ( Isuprel)
• isoetharine ( Bronkosol) nebulizer

• theophylline & aminophylline
• heliox may be useful in conjunction with bronchodilators

• combination therapy:

• Advair salmeterol + fluticasone
• Symbovort formoterol + budesonide [24]
• adding a long-acting beta-2 adrenergic agonist to an inhaled glucocorticoid is more effective than doubling the glucocorticoid dose [3] in adults
• in children, a long-acting beta-2 adrenergic agonist added to an inhaled glucocorticoid is not inferior to doubling the dose of glucocorticoid, but may result in more frequent hospitalizations [29]
• combination rescue with beclomethasone plus albuterol without maintenance glucocorticoids may be an option for children as this approach avoids stunted growth associated with maintenance glucocorticoids [30]

• anticholinergic agents

• tiotropium ( Spiriva) as add-on to inhaled glucocorticoid for uncontrolled asthma [28,34]

• omalizumab ( Xolair) recombinant humanized monoclonal anti- IgE antibody modestly lowers frequency of severe asthma exacerbations in patients inadequately controlled on standard therapy [33]
• magnesium sulfate: 1-2 g IV over 20 min [8]
• leukotriene receptor antagonists ( prophylaxis)

• agents

• montelukast ( Singulair) 5-10 mg PO QD (see MOSAIC trial)
• zafirlukast ( Accolate) 20 mg PO BID

• indications

• aspirin-sensitive asthma
• exercise-induced asthma
• virus-induced wheezing [3]

• addition of leukotriene receptor antagonist to glucocorticoid NOT of benefit [7]
• leukotriene antagonists likely work well in real-world settings because of their ease of use [31]

• zileuton ( Zyflo), a 5- lipoxygenase inhibitor
• theophylline:

• use with caution or not at all
• toxicity may result from drug interactions

• antihistamines are NOT contraindicated
• routine use of proton pump inhibitor not indicated [27]

• proton pump inhibitors do not improve symptoms of asthma [37]

• homeopathic therapy for dust mite allergy not useful [6]
• follow-up

• inhaled corticosteroid may cause thrush, hoarseness & osteopenia
• low threshold for prescribing calcium, vitamin D

• patient education:

• self management skills based on classification
• poor control is often due to improper use of inhalers

• environmental control

• air- conditioning in a tightly closed home is most effective
• only industrial quality masks are capable of excluding pollen particles
• frequent bathing of animals or complete avoidance

• investigational

• bronchial thermoplasty

More General Terms

• obstructive lung disease
• type 1 hypersensitivity; immediate hypersensitivity (allergy)
• chronic lung disease

Additional Terms

• alternative classification of asthma
• assessment of severity of acute asthma
• asthma-related traits
• conditions that may present as refractory asthma
• industrial agents that can cause asthma
• metered dose inhaler (MDI)
• nasal polyps with asthma
• provocation inhalation challenge test; methacholine challenge test
• referral of asthmatic patients

Internet Database

OMIM: 600807
OMIM: 208550
OMIM: 147050
OMIM: 607277
OMIM: 608584
OMIM: 608595
OMIM: 608596

References

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asthma