Loma Linda University Medical Center

Asthma

Pathophysiology

• Inflammation of airways causing reduction in airway diameter.

• Smooth muscle contraction, vascular congestion, bronchial wall edema and thick secretions

• Changes are measured in pulmonary function tests, increased work of breathing, abnormal distribution of pulmonary flow

Pathophysiology…

• Large and small airways often contain plugs composed of mucus, serum proteins, inflammatory cells, and cellular debris

• Microscopic level, airways are infiltrated with eosinophils and mononuclear cells

• Microvascular leakage , epithelial disruption, vasodilation

Over time

• Airway smooth muscle hypertrophies and new vessel formation, increased number of goblet cells and deposition of interstitial collagen beneath epithelieum.

• Inflammation can be acute, chronic or subacute

Acute reaction

• Antigens come in contact with mast cells in submucosa and mediators like histamine, leukotrienes, chemokines, tryptase, interleukin-5, interleukin-8, proinflammatory cytokines and interleukin- 4 produce inflammatory reaction, with bronchoconstriction, vascular congestion, edema formation, increased mucus production, impaired mucociliary transport

Activation

• Eosinophils, platelets and polymononuclear cells are activated and recruited to site and IgE response activated

• This process is multicellular, redundant, self-amplifying

Atopy

• Allergic asthma is frequently associated with family or personal hx of allergic dx such as rhinitis, urticaria and eczema

Triggers

• Stimuli for asthma are viral infections, exercise, indoor antigens like mold, dust mites, cockroaches, animal dander, occupational exposures like metal salt, wood veggie dust, pharmaceutical, chemical and plastic, bio enzymes, vapors, gases, aerosols

Stimuli

• Aspirin, B-blockers, NSAIDs, sulfating agents, tartrazine dyes, food additives, preservatives

• Cold air, emotional situations

Epidemiology in U.S.

• Current asthma prevalence is higher among

-children than adults

-boys than girls

-women than men

• Asthma morbidity and mortality is higher among African Americans than caucasians

Clinical Features

• Triad: dyspnea, wheezing, cough

• chest tightness/constriction, prolonged expiration and accessory muscle use

• Respiratory failure: silent chest reflects severe airflow obstruction

Key history

• Onset, duration, frequency

• Present management and medications

• Hx of intubation, ICU admission

• Smoking

• Oral corticosteroids use

• Usual exacerbation pattern and outcome

• Best spirometry

Risk factors for death

• Past hx of sudden severe exacerbation

• Prior intubation

• Prior admission to icu for asthma

• 2 or more hospitalizations in last yr for asthma

• 3 or more ER visits for asthma in 1 yr

• >2 B-agonist canisters 1 month

Other Risk Factors

• Current systemic corticosteroids or recent withdrawl from systemic corticosteroids

• Comorbidity like cardiovascular dz• Serious psychiatric or pyscho-social problem• Low socioeconomic status in urban residents• Illicit drug use • difficulty perceiving airflow obstruction or its

severity

Pulmonary Function Test

• FEV1: volume of air forced expiratory over 1 second and converted to a % and compared to normal based on height, age and gender

• >80% of predicted is Normal

• 60-79% mild obstruction

• 40-59% moderate obstruction

• <40% is severe

PFT

• PEFR: peak expiratory flow rate• Personal device that patient

takes home to measure asthma control usually green means good control, yellow means caution, narrowing of airways, and red is emergency, severe narrowing

Diagnosis

• Bedside spirometry: FEV1 and peak expiratory flow rate PEFR directly measure the degree of large airway obstruction. Serial measurements help us determine severity and response to therapy. Pt have their personal best PEFR or FEV1 or if unknown the % of predicted spirometric values .

• Pulse ox• ABG not needed for mild/mod if Pco2 >42mmhg

indicates severe obstruction• CXR if suspect ptx,pneumomediastinum,pna

Treatment

• Acute: B-agonist, anticholinergics, glucocorticoids. Magnesium, heliox (mix of helium and oxygen) and ketamine may be considered.

• Maintenance mast-cell stabilizers, methlyxanthines, leukotriene modifiers, long-acting B2 agonist ie salmeterol q12 hrs

B-agonists

• B1 vs B2: more B2 specific agents preferred

• Aerosol treatments given Q15-20mins or continuous

• Epi nor terbutaline subcutaneous

• Iv infusions carry no advantage

Corticosteroids

• prednisone 40mg-60mg PO or

• methylprednisolone 60mg-125mg IV bolus, then q4-6hrs

• If Dc home (with PEFR <70% predicted after aggressive tx, but with no distress) then give non-taper 3 -10 day burst oral steroids ex: prednisone 40 to 60mg Qday

• Consider additional inhaled steroids

Anticholinergics

• Synergistic with B-agonists that dilate smaller airways and these affect large, central airways

• Atropine sulfate had systemic effects, replaced by ipratroprium bromide: nebulized or MDI

Others

• Theophylline: mechanism unknown and no longer 1st line agent, when used with B2 agonists, increases toxicity that cause cardiac arrhymias and seizures. Serum levels can be measured, <30ug/ml desired

• Magnesium sulfate for severe: 1-2grams IV over 30mins

Others

• Heliox, shown to lower airway resistance in severe case: 80%He and 20% O2

• Ketamine: derivative of phencyclidine produces dissociative anesthesia and bronchodilation

• Mast cell modifiers: cromolyn and nedocromil block chlorine channels inhibit early and late responses to allergen challenge and exercise

Leukotriene modifiers

• Leukotrienes are potent proinflammtory mediators that contract smooth muscle, increase microvascular permeability, stimulate mucus secretion, decrease mucociliary clearance, and recruit eosinophils into the airway

• Ex: montelukast, zafirlukast, zileuton oral tab. Not used for acute exacerbation

Severity of Asthma Exacerbations based on Sxs, Signs, Functions

• talks in sentences, can lie down, gets breathless when walking

• RR ↑ moderate wheeze HR <100, pulsus paradoxus absent <10mmHg

• Mild PEF 80%predicted or 80% personal best, SaO2% >95% PaO2 NL, PaCo2 <42

Moderate Severity

• talks in phrases, prefers sitting, gets breathless while talking, usually agitated

• RR ↑, accessory muscle use, loud wheeze HR 100-120, pulsus paradoxus 10-25mmHg

• PEF 50-80%predicted or personal best, SaO2% 91-95% PaO2 >60mmHg, PaCo2 <42

Severe Exacerbation

• talks in words, sits upright, breathless at rest

• RR >30, accessory muscle use, wheeze loud inhalation and exhalation, HR >120, pulsus paradoxus >25mmHg

• PEF <50%predicted or personal best, Sao2% <91% Pao2 <60, possible cyanosis, PaCo2 >42, possible resp. failure

Exacerbation turns to Failure

• Drowsy or confused

• Paradoxical thoracoabdominal movement

• No wheeze

• HR bradycardia

• No pulsus paradoxus suggests muscle fatigue

Mechanical Ventilation

• Try non-invasive positive pressure ventilation, but if hypercarbia and acidosis progresses or pt becomes exhausted or confused, intubation and ventilation are necessary for resp failure. MV does not relieve airflow obstruction, it eliminates the work of breathing and enables pt to rest

Disposition

DC if

• Resolution of wheezing

• Normalization FEV1 or PEFR>70% and

• Combination of pt hospitalization record, compliance, how does the pt look?

• Re-exam pt every 1-2 hrs, repeat PEFR

• Admit if pt does not respond well after 4-6 hrs of care, Pco2 >41

Dosages: Acute exacerbation

• Albuterol

-nebulizer solution 5mg/mL

Adult 2.5-5mg Q 20min x 3, then 2.5-10mg q 1-4 hrs prn OR 10-15mg per hr continuously

-MDI (90µg/puff)

4-8 puffs q 20min up to 4 hr, then q 1-4hr prn

Beta agonist

• Epinephrine (1:1000 or 1 mg/mL)

-0.3-0.5mg SC Q20 x 3

• Terbutaline (1mg/mL)

-0.25mg SC q20min x 3

Ipratropium bromide

• Nebulizer solution (0.2mg/mL)

-0.5mg q30min x 3 then 2-4h prn

May be mixed into nebs with albuterol as additive treatment, not 1stline

• MDI (18µg/puff) 4-8 puffs q6-8hrs

Steroids

• Prednisone 120-180mg per 24 hrs divided into 3 or 4 doses done for 48hrs, then 60-80mg per day until FEV1 or PEFR reaches 70% of predicted or PB.

Case

• 40F brought in by ambulance for SOB

• RR 40, shallow, looks distressed, not speaking

• Hx of asthma, never been intubated, but hospitalized multiple times, nonsmoker

• Triggered by cigarette smoker

• What are your next steps?

DDX

• CHF• Upper airway obstruction• Aspiration of FB or gastric acid• Bronchogenic carcinoma with endobronchial

obstruction• Metastatic carcinoma with lymphangitic

metastasis• Sarcoidosis with endobronchial obstruction• Vocal cord dysfunction• Pulmonary Embolus

Reference

• Tintinalli, Judith; Kelen, Gabor; Stapczynski, Stephan. Emergency Medicine: A Comprehensive Study Guide. 6th Edition.Mcgraw-Hill, 2003

• http://www/cdc/gov/asthma/speakit/default.html slide of Epidemiology