Asthma

• Asthma is a chronic inflammatory disorder of airways.

• The expression of asthma results of a complex interrelationship of genetic susceptibility & environmental influences.

• Multiple factors that trigger bronchospasm, include:-allergens-emotions -environment(weather changes, smoke) -exercise-respiratory infections

• Signs & Symptoms :1. Chronic Asthma:

- Shortness of breath/ dyspnea- Wheezing- Cough- Sputum - Chest tightness

**Occur continuously or episodic.

• Treatment recommendation of chronic asthma is based on its classification:* Mild intermittent* Mild persistent* Moderate persistent* Severe Persistent

2. Acute Asthma:• Signs/symptoms are similar to chronic .• Additional S/S may also be present, i.e.:

-Tachypnea-Tachycardia-Retractions-Cyanosis-Hypoxemia

• Sudden onset occurs in :acute, exacerbations, status asthmaticus.

• S/S may progress over hours, days, weeks before reaching functional deterioration.

• Eosinophils in the airways indicates allergic component.

• Typical triggers: * Allergens * Exercise

* Psychological stress

3. Exercise-Induced Bronchospasm: • Transient narrowing of airways after vigorous

exercise.

• Cold-dry air provokes EIB.

• In EIB, a reduction of @ least 15% in FEV1following exercise.

4. Nocturnal Asthma:

• In normal diurnal variation, the lung function reaches its peak @ 4 PM & reaches its minimum @ 4 AM.

• Symptoms of dyspnea & cough may waken the patient requiring a bronchodilator treatment.

• GERD, Obesity, & increased age are associated with nocturnal asthma.

• Evaluation is important for treatment guidelines.

5. PMS Asthma:• Asthma symptoms increase in days before & during menses in asthmatic

patient by an unknown mechanism.

• May be due to usual increase in Beta-2 receptor density during the Luteal phase of the menstrual cycle in non-asthmatic females which is absent in PMS asthma.

• Treatment includes:-Hormones-Leukotriene antagonists-ICS-LABA

• Diagnosis:- Based on : 1.Clinical History

2.PFTs ( Objective Measures )-Recurrent Exacerbations may be provoked by:

*Viral Resp. Infections*Psychological Factors*Allergens*Irritants (Dry powders, Chemicals,…)

*Exercise*Hx of nocturnal Symptoms*Meds. ( ASA, NSAID,…)

-Physical exam maybe normal.

• Other allergic symptoms may be present with allergic (atopic) asthma, include:-Rhinitis-Sinusitis-Eczema-Blood eosinophilia-Sputum eosinophilia

• Allergen exposure leads to:a. Immediate (Early) asthmatic response (IAR): decreased PFT within minutesb. Late asthmatic response (LAR):

2nd decrease in PFT several hours of exposure.

• Spirometry:1. FEV1: - Most commonly used spirometric evaluation of pulm. function.

- Volume of air expelled within 1st second of forced expiration after max.

inhalation.2. PEF: - Max. rate @ which air is exhaled from lungs

with forced expiratory maneuver. - Correlates well with FEV1 - Accurate & obj. self-monitoring of pulm. functions by simple portable inexpensive peak flow-meter.

Disadvantage: Dependent of patient effort.

• Assessment of Allergy:• 60-78% of asthma in adults has allergic

component.• Up to 93% of asthma in children has allergic

component.* Allergen prick skin is the most commonly diagnostic

test for atopy, & patient should takeoral antihistamine before test.

* Tx : Anti IgE Monoclonial Antibody.

• Chest X-Ray:• Normal in mild disease.• Hyperinflation in severe chronic asthma.Therapeutic Plan:Treatment Guidelines:4 Major Components of Asthma Management: 1.Use of objective measures to assess & monitor2.Control factors contributing to severity.3.Use of optimal pharmacological therapy.4.Provide patient education & develop partnership in asthma

care.

• Goals of Asthma Management:1. Maintain normal activity levels.2. Maintain (near) normal PFTs.3. Prevent chronic & troublesome symptoms.4. Prevent recurrent exacerbation of asthma & min.

need for emergency dept. visits or hospitalization.5. Provide optimal pharmacotherapy with min. or no

side effects.6. Meet patients’ & families’ expectations of satisfaction

with asthma care.

• Recommended Use of Spirometry:

1. At the time of diagnosis (for pts. >5 y.o.)for assessing severity & reversibility.

2. Following initiation of treatment after S/Sstabilize (effectiveness & response).

3. At least every 1-2 yrs. to monitor disease progression.

I. Long-Term Treatment:• Recommended treatment is based on :

Persistence & Severity of symptoms.

**Refer to Guidelines of Stepwise approach to Treatment of Chronic Asthma.

• Only Mild intermittent (Step1) does not require long-term treatment.

• All asthma patients should use SABA for acute symptoms.

• Recommendation: All asthma patients should receive action plan for daily long-term meds. & for what to do in acute exacerbation of asthma.

• Anti-inflammatory meds. esp. ICS are the cornerstone of long-term daily therapy for persistent asthma.

• As monotherapy, ICS is > effective than cromoly, leuk. Modifiers, nedocromil, & theophylline.

• Rescuers: SABA & systemic corticosteroids• Controllers: All others & oral corticosteroids

• ICS : the only long-term controller shown to reduce risk of death from asthma.

• Persistent asthma pts. should not use regular administration of SABA or LABA as long-term controller monotherapy.

• ICS + LABA combination is more effective than doubling ICS dose.

• If the pt. has hx of frequent severe exacerbations increase ICS dose + LABA

• 4 times increase in ICS dose may be required to produce significant reduction in asthma exacerbation.

• Adding any one of the alternatives to ICS( if pt. can not tolerate LABA ) is as effective as doubling the ICS dose.

• Many prescribe severe persistent asthma pt. a 3rd long-term controller before starting oral corticosteroid.

• Current Evidence does not support additional benefit from adding 3rd or 4th long-term controllers.

• Patients with severe atopic (allergic) asthma & high IgE conc. could discontinue oral corticosteroid following Omalizomab therapy.

II. Acute Asthma:• All levels of severities are @ risk of acute exacerbation even

if well-controlled on long-term controllers ( if exposed to specific triggers).

• Fig. 34.5 p.889: Home Management of Acute Exacerbation.

• Fig. 34.6 p. 891: Treating Acute Exacerbation of Asthma in E.R. or Hospital.

• Table 35.4 p.894: Recommended Doses for Severe Acute Asthma

• SABAs are the most effective quick relief (rescue) meds. • No advantage of nebulizer over MDI + spacer.• Parenteral SABA should NOT be used due to increased S/Es

without increasing efficacy.

• Short Acting Anticholinergic Ipratropium Br.is used only for those:

1)intolerant to SABA or 2)not completely responding to usual doses of SABA in E.R., adding Ipratropium Br. to SABA reduces the risk of hospitalization.

• Most asthma exacerb. pts. @ E.R. or clinic respond adequately to 1st 3 doses of SABA& can be discharged.

• It is recommended that inadequate response to initial bronchdilators (SABA & Ach) should be started on systemic corticosteroid p.o. or I.V. (No advantage in efficacy of either one).

• ICS is NOT as effective as systemic corticosteroid in severe acute asthma, but adding ICS to the usual short course systemic corticosteroid, prevents relapse following discharge from E.R.

• Nondrug Management of Severe Acute Asthma:

1. Low flow O₂ therapy by nasal canulae to prevent hypoxemia.

2. Pulse oximetry 3. O₂ flow to mainaitn O₂ Saturation≥90%.4. In very severe cases, ABGs are used to

monitor pCO₂ if it is normal to increased after intensive therapy due to risk of resp. failure.

5. All pts. should measure their PEF after initial SABA.

• Pediatric Treatment in Acute Asthma:

• In acute severe asthma, treatment is similar to adults with dose differences.

• As alternatives in pediatric treatment of chronic asthma, leuk.modifiers & cromolyn are safer than theophylline.

• Pharmacotherapy:• Treatment includes providing optimal pharmacotherapy with min.

or no ADRs.• Meds. for asthma: 1. Bronchdilators

&2. Anti-inflammatory*Rescuers/ “Quick- relief agents”:

1. SABA2. Acholinergic3. Short-term systemic corticosteroids

* Controllers / “Long-term control agents”:Inhaled or oral corticosteroids, cromolyn, nedocromil, LABA, theoph., leukot. modifiers.

I. Bronchodilators:1) Beta-2 adrenergic agonists:

-Safest & most effective bronchodilatorsa. SABA: - Albuterol b. LABA: - Salmeterol - Bitolterol - Formoterol

- Metaproterenol - Pirbuterol - Terbutaline

• Increasing the use of SABA can be a marker of poor asthma control, & ICS should be added or increased in dose.

* Guidelines recommend SABA to be used as: 1) prn for intermittent symptoms.

or 2) 1st line therapy for severe acute asthma.

• In severe asthma, SABA is administered as:-MDI + spacer-Intermittent nebulizer-continuous nebulizer

• There is NO difference in efficacy between the 3 methods.

• I.V. SABA is NOT recommended

• No difference was shown in the efficacy between cont. & intermittent SABA delivery for adults, however, ICU asthma children showed greater improvement with cont. nebulizer albuterol.

• SABA : - The treatment of choice to prevent exercise-induced asthma (EIA).

-Provides 4-hr duration when given just before exercise.

• LABA: - Recommended for persistent asthma only in combination with ICS (NOT monotherapy).

- Both LABAs are indicated for preventing EIA when used 15-30 min before long exercise.

- In combination with ICS, LABA controls EIA for up to 12 hrs.

2) Theophylline:-Bronchodilator & now weak anti-inflammatory.-Weak bronchodilator compared with beta2 agonists.-Administered p.o., I.V., or rectally.

-Therapeutic range: 5-15ug/ml.

* Addition of theophylline to optimal inhaled SABA + systemic corticosteroid in E.R. or hospital showed NO added benefit for acute severe asthma over optimal beta2 agonist + systemic corticosteroid alone.

• I.V. theophylline: Reserved for those who fail to respond to high-dose inhaled SABA + systemic corticosteroid in severe acute asthma.

• Role of theophylline in chronic asthma is reduced because: - New agents (LABA)

- Its addition has similar efficacy as increasing the ICS dose.

**Theophylline is reserved as a second line add-on treatment for chronic persistent asthma.

3) Anticholinergics:• Ipratropium Bromide: -Short-Acting (4-8hrs) - Less bronchodilation than beta-2 agonists. • Guidelines recommend the use nebulized

Ipratropium in combination with beta-2 agonists for the treatment of acute severe asthma in those who fail to respond to initial treatment with SABA.

• Guidelines do NOT include anticholinergic therapy in the management of chronic asthma (more effective meds. available).

II. Anti-inflammatory Agents:1) Cromolyn Na/ Nedocromil:• Not used for acute asthma.• Dosed 3 or 4 X daily.• Inhibit IAR & LAR• Prevent EIA (lesser extent than inhaled beta2

agonists) if used 15-30min. before exposure.• Clinical effects are seen within 1 wk. of starting

therapy & 4 wks. are required to determine efficacy.• Guidelines recommend Cromolyn& Nedocromil as

2nd-line therapy only in mild persistent asthma in children & adults.

2) Leukotriene Modifiers: (Newest Class):*(Zileuton:QID, Zafirlukast:BID, Montelukast:QD)*Reduce IAR & LAR.*All administered p.o.• Montelukast: Given @ bedtime to reach highest

serum conc. during the night & early morning hours when symptoms tend to be worse.

*Zafirlukast: Bioavailability sig. reduced w/ food.*Zileuton: Sig.DI profile& liver toxicity.

• Montelukast:• Preferred because:

1) Once daily dosing.2) Lack of drug & food interaction.3) The only one approved for children

as young as 1 y.o.

*Montilukast + ICS has similar efficacy as doubling ICS dose.

• Guidelines currently recommend Leukotriene Modifier :

1) As single drug therapy for mild-persistent asthma (step2) as alternative after therapy with ICS has been considered.

2) As 2nd line therapy in moderate-persistent asthma (step3) after LABA as add-on therapy to ICS.

**Greatest advantage is the ORAL dosage form.

3) Corticosteroids:• Most potent anti-inflammatory used in asthma

treatment.A) ICS:• ICS : The most effective long-term control therapy for

persistent asthma.

• ICS use is assoc. w/ :1. Reduced risk of hospit. & acute exacerbation.2. Offers the only long-term

control therapy assoc. w/ reduced risk of dying from asthma.

• Gargling w/ water & spitting immediately after DPI ICS may reduce the GI.

• Both:1) Gargling & 2) Use of VHC w/MDI

Reduce local ADRs i.e. oropharyngeal thrust & hoarseness.

* More potent ICSs are preferred due to lower doses used.

See table 34.5 for Doses of ICSs

• Most patients are treated w/ low-med. doses.

• High doses have greater potential for systemic S/Es.

• Growth suppression or growth retardation were reported w/ low-med doses ICS w/ only small effect (1-2 cm in 1 yr) w/ final adult height not affected.

• It is recommended for children on ICS to have their heights monitored routinely.

• Only those on high doses ICS must have their bone mineral density & HPA- Axis monitored.

• Dosing ICS is initially based on severity.

• Usual recommendation is for ICS to be adm. BID.

• Many with mild cases may be controlled on QD in late afternoon or evening.

• ICS + LABA can reduce the ICS dose, & can have greater efficacy than doubling the ICS dose.

• LABA can not replace ICS due to lack of anti-inflammatory effect.

B) Systemic Corticosteroids: (Rescuer & Controller)• Rescuers for acute asthma exacerbations.• Oral Prednisone & Prednisolone : Most commonly used w/

min. mineral corticoid activity.• No advantage of I.V. over oral in the onset or efficacy.• Higher doses are assoc. w/ more S/Es & NO greater benefit.

As rescuers, their use is recommended only for those NOT responding to initial 3 doses of inhaled SABA.

• The use of systemic corticosteroids for additional 7-10 days after discharge from E.R. to home may reducethe # of relapses , & the addition of ICS @ this time may produce added benefits.

* Most studies used dosage regimens from 3-10 days. (table 34.4)

• Patients receiving 3-4 “short bursts” prednisone (≤ 10 d) did not show long-term corticosteroid toxicity.

• At least 8 bursts (@ least 10d each) showed similar reduction in mineral density as QD or QOD dosing.

• Those requiring > 3-4 courses prednisone should be replaced on appropriate long-term control therapy w/ ICS.

• Tapering may be unnecessary if started on ICS.

III. Anti-IgE Monoclonal Antibodies:• Omalizumab : The 1st agent approved by FDA

in 2003 for pts. ≥ 12y.o.• Critical role in inflammatory process in allergic asthma.• SQ every 2-4 wks.• Dose calculated based on weight & baseline IgE.• Very expensive.• Effective in:1) Reducing allergic asthma exacerbations.2) Reducing steroid-dose in mod.-sev. allergic asthma.3) Increasing quality of life.

• Potential for rare anaphylaxis, transient thrombocytopenia, urticatia, & risk of malignancy in the label.

** Reserved for patients with severe allergic asthma not adequately controlled with standard therapy.**

***≥ 12% improvement in FEV1 after the administration of SABA is considered significant clinical reversibility.***