ASTHMA: ASTHMA Rochelle M. Nolte, MD CDR USPHS Family Medicine


Objectives: Objectives At the conclusion of the presentation, participants should be able to: ID signs and symptoms consistent with asthma and allergic rhinitis Differentiate the various severities of asthma Summarize an appropriate treatment regimen for asthma of various severities


Allergic Rhinitis: Allergic Rhinitis Symptoms: sneezing, itching, rhinorrhea, and congestion Nasal smear with >10% eosinophils suggestive Dx can be confirmed by allergen-specific Ig-E Classification Persistant or intermediate Graded relative to severity


Allergic Rhinitis: Allergic Rhinitis Affects 15%-50% of world-wide population Affects 40 million people in the US Prevalence increasing (increasing airborne pollutants, rising dust mite populations, poor ventilation in buildings, increased time indoors by people and pets, dietary factors, changes in gut indigenous microflora, increased abx use, increasingly sedentary lifestyle????????)


Allergic Rhinitis: Allergic Rhinitis Associated with asthma 95% of people with allergic asthma have rhinitis 30% of people with allergic rhinitis have asthma (compared to 3-5% of general population) Family history of atopy seems associated with progression of either allergic rhinitis or asthma to allergic rhinitis + asthma Treatment of allergic rhinitis reduces ER visits for asthma


Management of Allergic Rhinitis: Management of Allergic Rhinitis Identification of allergens Pollen Molds/fungi Dust mites Animal dander Cockroaches Avoid or minimize exposure to allergens Patient education


Management of Allergic Rhinitis: Management of Allergic Rhinitis Pharmacotherapy Intra-nasal corticosteroids Antihistamines (non-sedating preferred) Not recommended to use sedating qhs and non-sedating qAM Decongestants Antihistamine/decongestant combinations Mast cell stabilizers Leukotriene antagonists


Management of Allergic Rhinitis: Management of Allergic Rhinitis Allergen Immunotherapy Repeated, controlled administration of specific allergens to patients with IgE-mediated conditions May impede progression of allergic rhinitis to asthma May prevent multiple sensitizations and the need for prolonged/excessive use of pharmacotherapies Consider when sx not controlled on medications


Definition of Asthma: Definition of Asthma Chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are associated with widespread but variable airflow obstruction that is reversible either spontaneously, or with treatment.


Asthma: Asthma Most common chronic condition in children #1 cause of school absenteeism Death rate up 50% from 1980 to 2000 Death rate up 80% in people under 19 Morbidity and mortality highly correlated with Poverty, urban air quality, indoor allergens, lack of patient education, and inadequate medical care About 5000 deaths annually


Asthma: Asthma Every day in the US, because of asthma: 40,000 people miss school or work 30,000 people have an asthma attack 5,000 people visit the emergency room 1,000 people are admitted to the hospital 14 people die (Asthma and Allergy Foundation of America)


Asthma: Asthma In 2000, 11 million reported having asthma attacks >5% of kids <18 reported an asthma attack In 1999, 2 million ER and 478,000 hospitalizations with asthma as the primary dx Mortality in Black males 3X that of white Mortality in Black females 2.5X that of white


Asthma: Asthma Usually associated with airflow obstruction of variable severity. Airflow obstruction is usually reversible, either spontaneously, or with treatment The inflammation associated with asthma causes an increase in the baseline bronchial hyperresponsiveness to a variety of stimuli Clinical Diagnosis


Asthma Triggers: Asthma Triggers Allergens Dust mites, mold spores, animal dander, cockroaches, pollen, indoor and outdoor pollutants, irritants (smoke, perfumes, cleaning agents) Pharmacologic agents (ASA, beta-blockers) Physical triggers (exercise, cold air) Physiologic factors Stress, GERD, viral and bacterial URI, rhinitis


Diagnostic Testing: Diagnostic Testing Peak expiratory flow (PEF) Inexpensive Patients can use at home May be helpful for patients with severe disease to monitor their change from baseline every day Not recommended for all patients with mild or moderate disease to use every day at home Effort and technique dependent Should not be used to make diagnosis of asthma


Diagnostic Testing: Diagnostic Testing Spirometry Recommended to do spirometry pre- and post- use of an albuterol MDI to establish reversibility of airflow obstruction > 12% reversibility or an increase in FEV1 of 200cc is considered significant Obstructive pattern: reduced FEV1/FVC ratio Restrictive pattern: reduced FVC with a normal FEV1/FVC ratio


Diagnostic Testing: Diagnostic Testing Spirometry Can be used to identify reversible airway obstruction due to triggers Can diagnose Exercise-induced asthma (EIA) or Exercise-induced bronchospasm (EIB) by measuring FEV1/FVC before exercise and immediately following exercise, then for 5-10 minute intervals over the next 20-30 minutes looking for post-exercise bronchoconstriction


Diagnostic Testing: Diagnostic Testing Spirometry National Asthma Education and Prevention Program (NAEPP) recommends spirometry: For initial assessment Evaluation of response to treatment Assessment of airway function at least every 1-2 years


Diagnostic Testing: Diagnostic Testing Methacholine challenge Most common bronchoprovocative test in US Patients breathe in increasing amounts of methacholine and perform spirometry after each dose Increased airway hyperresponsiveness is established with a 20% or more decrease in FEV1 from baseline at a concentration < 8mg/dl May miss some cases of exercise-induced asthma


Diagnostic testing: Diagnostic testing Diagnostic trial of anti-inflammatory medication (preferably corticosteroids) or an inhaled bronchodilator Especially helpful in very young children unable to cooperate with other diagnostic testing There is no one single test or measure that can definitively be used to diagnose asthma in every patient


Goals of Asthma Treatment: Goals of Asthma Treatment Control chronic and nocturnal symptoms Maintain normal activity, including exercise Prevent acute episodes of asthma Minimize ER visits and hospitalizations Minimize need for reliever medications Maintain near-normal pulmonary function Avoid adverse effects of asthma medications


Treatment of Asthma: Treatment of Asthma Global Initiative for Asthma (GINA) 6-point plan Educate patients to develop a partnership in asthma management Assess and monitor asthma severity with symptom reports and measures of lung function as much as possible Avoid exposure to risk factors Establish medication plans for chronic management in children and adults Establish individual plans for managing exacerbations Provide regular follow-up care


Written Action Plans: Written Action Plans Written action plans for patients to follow during exacerbations have been shown to: (Cochrane review of 25 studies) Decrease emergency department visits Decrease hospitalizations Improve lung function Decrease mortality in patients presenting with an acute asthma exacerbation NAEPP recommends a written action plan*


Pharmacotherapy: Pharmacotherapy Long-acting beta2-agonists (LABA) Beta2-receptors are the predominant receptors in bronchial smooth muscle Stimulate ATP-cAMP which leads to relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity Inhibits release of mast cell mediators such as histamine, leukotrienes, and prostaglandin-D2 Beta1-receptors are predominant receptors in heart, but up to 10-50% can be beta2-receptors


Pharmacotherapy: Pharmacotherapy Long-acting beta2-agonists (LABA) Salmeterol (Serevent) Salmeterol with fluticasone (Advair) Should only be used as an additional treatment when patients are not adequately controlled with inhaled corticosteroids Should not be used as rescue medication Can be used age 4 and above with a DPI Deaths associated with inappropriate use as only medication for asthma


Pharmacotherapy: Pharmacotherapy Albuterol Short-acting beta2-agonist ATP to cAMP leads to relaxation of bronchial smooth muscle, inhibition of release of mediators of immediate hypersensitivity from cells, especially mast cells Should be used prn not on a regular schedule Prior to exercise or known exposure to triggers Up to every 4 hours during acute exacerbation as part of a written action plan


Pharmacotherapy: Pharmacotherapy Inhaled Corticosteroids Anti-inflammatory (but precise MOA not known) Act locally in lungs Some systemic absorption Risks of possible growth retardation thought to be outweighed by benefits of controlling asthma Not intended to be used as rescue medication Benefits may not be fully realized for 1-2 weeks Preferred treatment in persistent asthma


Pharmacotherapy: Pharmacotherapy Mast cell stabilizers (cromolyn/nedocromil) Inhibits release of mediators from mast cells (degranulation) after exposure to specific antigens Blocks Ca2+ ions from entering the mast cell Safe for pediatrics (including infants) Should be started 2-4 weeks before allergy season when symptoms are expected to be effective Can be used before exercise (not as good as ICS) Alternate med for persistent asthma


Pharmacotherapy: Pharmacotherapy Leukotriene receptor antagonists Leukotriene-mediated effects include: Airway edema Smooth muscle contraction Altered cellular activity associated with the inflammatory process Receptors have been found in airway smooth muscle cells and macrophages and on other pro-inflammatory cells (including eosinophils and certain myeloid stem cells) and nasal mucosa


Pharmacotherapy: Pharmacotherapy Leukotriene receptor antagonists No good long-term studies in pediatrics Montelukast as young as 2; zarfirlukast age 7 Alternate, but not preferred medication in persistent asthma and as addition to ICS Showed a statistically significant, but modest improvement when used as primary medication


Pharmacotherapy: Pharmacotherapy Theophylline Narrow therapeutic index/Maintain 5-20 mcg/mL Variability in clearance leads to a range of doses that vary 4-fold in order to reach a therapeutic dose Mechanism of action Smooth muscle relaxation (bronchodilation) Suppression of the response of the airways to stimuli Increase force of contraction of diaphragmatic muscles Interacts with many other drugs


Various severities of asthma: Various severities of asthma Step-wise pharmacotherapy treatment program for varying severities of asthma Mild Intermittent (Step 1) Mild Persistent (Step 2) Moderate Persistent (Step 3) Severe Persistent (Step 4) Patient fits into the highest category that they meet one of the criteria for


Mild Intermittent Asthma: Mild Intermittent Asthma Day time symptoms 80% of predicted PEF variability < 20% PEF and FEV1 values are only for adults and for children over the age of 5


Mild Persistent Asthma: Mild Persistent Asthma Day time symptoms > 2/week, but 80% of predicted PEF variability 20%-30%


Moderate Persistent Asthma: Moderate Persistent Asthma Day time symptoms q day Night time symptoms > 1 night q week PEF or FEV1 60%-80% of predicted PEF variability >30%


Severe Persistent Asthma: Severe Persistent Asthma Day time symptoms: continual Night time symptoms: frequent PEF or FEV1 30%


Pharmacotherapy for Adults and Children Over the Age of 5 Years : Pharmacotherapy for Adults and Children Over the Age of 5 Years Step 1 (Mild intermittent asthma) No daily medication needed PRN short-acting bronchodilator (albuterol) MDI Severe exacerbations may require systemic corticosteroids Although the overall diagnosis is “mild intermittent” the exacerbations themselves can still be severe


Pharmacotherapy for Adults and Children Over the Age of 5 Years: Pharmacotherapy for Adults and Children Over the Age of 5 Years Step 2 (Mild persistent) Preferred Treatment Low-dose inhaled corticosteroid daily Alternative Treatment (no particular order) Cromolyn Leukotriene receptor antagonist Nedocromil Sustained release theophylline to maintain a blood level of 5-15 mcg/mL


Pharmacotherapy for Adults and Children Over the Age of 5 Years: Pharmacotherapy for Adults and Children Over the Age of 5 Years Step 3 (Moderate persistent) Preferred Treatment Low-to-medium dose inhaled corticosteroids WITH long-acting inhaled beta2-agonist Alternative Treatment Increase inhaled corticosteroids within the medium dose range Add leukotriene receptor antagonist or theophylline to the inhaled corticosteroid


Pharmacotherapy for Adults and Children Over the Age of 5 Years: Pharmacotherapy for Adults and Children Over the Age of 5 Years Step 4 (Severe persistent) Preferred Treatment High-dose inhaled corticosteroids AND long-acting inhaled beta2-agonists AND (if needed) oral corticosteroids


Pharmacotherapy for Infants and Young Children (<5 years): Pharmacotherapy for Infants and Young Children (<5 years) Step 1(mild intermittent) No daily medication needed


Pharmacotherapy for Infants and Young Children (<5 years): Pharmacotherapy for Infants and Young Children (<5 years) Step 2 (mild persistent) Preferred treatment Low-dose inhaled corticosteroids Alternative treatment Cromolyn (nebulizer preferred) OR leukotriene receptor antagonist


Pharmacotherapy for Infants and Young Children (<5 years): Pharmacotherapy for Infants and Young Children (<5 years) Step 3 (moderate persistent) Preferred treatment Low-dose inhaled corticosteroids and long-acting beta2-agonist OR Medium-dose inhaled corticosteroids Alternative treatment Low-dose inhaled corticosteroids with either: Leukotriene receptor antagonist OR theophylline


Pharmacotherapy for Infants and Young Children (<5 years): Pharmacotherapy for Infants and Young Children (<5 years) Step 4 (severe persistent) Preferred treatment High-dose inhaled corticosteroids AND long-acting inhaled beta2-agonist AND (if needed) Oral corticosteroids For young children, inhaled medications should be given by nebulizer, dry powder inhaler (DPI), or MDI with a chamber/spacer


Acute Exacerbations: Acute Exacerbations Inhaled albuterol is the treatment of choice in absence of impending respiratory failure MDI with spacer as effective as nebulizer with equivalent doses Adding an antibiotic during an acute exacerbation is not recommended in the absence of evidence of an acute bacterial infection


Acute Exacerbations: Acute Exacerbations Beneficial Inhaled atrovent added to beta2-agonists High-dose inhaled corticosteroids MDI with spacer as effective as nebulizer Oxygen Systemic steroids Likely to be beneficial IV theophylline


Exercise-induced Bronchospasm: Exercise-induced Bronchospasm Evaluate for underlying asthma and treat SABA are best pre-treatment Mast cell stabilizers less effective than SABA Anticholinergics less effective than mast cell stabilizers SABA + mast cell stabilizer not better than SABA alone


Question: Question Which one of the following is true concerning control of mild persistent asthma in the pediatric population? Cromolyn should not be used under age 5 Atrovent should be added if beta-agonists do not maintain control of asthma LABA should be added if SABA is ineffective SABA may be used q2h to maintain control Initial treatment should be an inhaled anti-inflammatory such as ICS or cromolyn


Answer E: Answer E Initial medications for chronic asthma should include an anti-inflammatory such as ICS or cromolyn. Cromolyn is safe for all pediatric age groups. Atrovent is useful in COPD, but very limited use in asthma. Albuterol should be used up to every 4 hours prn. Overuse of inhaled beta-agonists has been associated with an increased mortality rate.


Question: Question It is estimated allergic rhinitis affects how may people in the US? 20 million 40 million 50 million 100 million Answer: B 40 million


Question: Question Which one of the following statements concerning the association between allergic rhinitis and asthma is false? Almost all patients with allergic asthma also have symptoms of rhinitis About 1/3 of patients with allergic rhinitis also have asthma Pharmacologic treatment for allergic rhinitis will not improve the symptoms of asthma Patients with allergic rhinitis and patients with asthma exhibit peripheral eosinophilia and basophilia.


Answer: C: Answer: C Patients with asthma should have their allergic rhinitis treated People with asthma and allergic rhinitis who are treated for their allergic rhinitis have a significantly lower risk of subsequent asthma-related events than those not treated for allergic rhinitis.


Question: Question Which one of the following findings on a nasal smear suggests a diagnosis of allergic rhinitis? > 10% neutrophils > 10% eosinophils 10% erythrocytes Answer: B >10% eosinophils


Question: Question Which of the following statements is true? An acceptable strategy for eliminating sedating effects of 1st-generation antihistamines and containing the cost of 2nd-generation is to use 2nd-generation in the AM and 1st-generation in the PM In most states, patients taking 1st-generation are considered “under the influence of drugs.” Mast cell stabilizers are becoming an excellent choice for children because of their ability to treat symptoms after they have started and their safety


Answer: B: Answer: B Patients taking 1st-generation antihistamines are considered “under the influence of drugs.” The sedating effects have been shown to carry over to the next day even when taken only at night and this type of chronic use is not recommended. Mast cell stabilizers should be started before symptoms develop, not after.


Questions?: Questions?