📄 asthma
ESSENTIALS OF DIAGNOSIS
Episodic or chronic symptoms of wheezing, dyspnea, or cough Symptoms frequently worse at night or in the early morning Prolonged expiration and diffuse wheezes on physical examination Limitation of airflow on pulmonary function testing or positive bronchoprovocation challenge Reversibility of airflow obstruction, either sponta- neously or following bronchodilator therapy General Considerations
Asthma is a common disease, affecting approximately 8–10% of the population
It is slightly more common in male children (younger than 14 years) and in female adults
There is a genetic predisposition to asthma
Prevalence, hospitalizations, and fatal asthma have all increased in the United States over the past 20 years
Each year, approximately 10 million office visits, 1
8 million emergency department visits, and more than 3500 deaths in the United States are attributed to asthma
Hospitalization rates have been highest among blacks and children, and death rates are consistently highest among blacks aged 15–24 years
Definition & Pathogenesis Asthma is a chronic disorder of the airways characterized by variable airway obstruction, airway hyperresponsiveness, and airway inflammation
No single histopathologic feature is pathognomonic but common findings include airway inflammatory cell infiltration with eosinophils, neutrophils, and lymphocytes (especially T cells); goblet cell hyperplasia, sometimes plugging of small airways with mucus; collagen deposition beneath the basement membrane; hypertrophy of bronchial smooth muscle; airway edema; mast cell activation; and denudation of airway epithelium
IgE plays a central role in the pathogenesis of allergic asthma
IL-5 is important in promoting eosinophilic inflammation
The strongest identifiable predisposing factor for the development of asthma is atopy, but obesity is increasingly recognized as a risk factor
Exposure of sensitive patients to inhaled allergens increases airway inflammation, airway hyper-responsiveness, and symptoms
Symptoms may develop immediately (immediate asthmatic response) or 4–6 hours after allergen exposure (late asthmatic response)
Common allergens include house dust mites (often found in pillows, mattresses, upholstered furniture, carpets, and drapes), cockroaches, cat dander, and seasonal pollens
Substantially reducing exposure reduces pathologic findings and clinical symptoms
Nonspecific precipitants of asthma include exercise, upper respiratory tract infections, rhinosinusitis, postnasal drip, aspiration, gastroesophageal reflux, changes in the weather, and stress
Exposure to products of combustion (eg, from tobacco, crack cocaine, methamphetamines, and other agents) increases asthma symptoms and the need for medications and reduces lung function
Air pollution (increased air levels of respirable particles, ozone, SO2, and NO2) precipitate asthma symptoms and increase emer- gency department visits and hospitalizations
Selected individuals may experience asthma symptoms after exposure to aspirin (aspirin exacerbated respiratory disease), nonsteroidal anti-inflammatory drugs, or tartrazine dyes
Other medications may precipitate asthma symptoms
Occupational asthma is triggered by various agents in the workplace and may occur weeks to years after initial exposure and sensitization
Women may experience catamenial asthma at predictable times during the men- strual cycle
Exercise-induced bronchoconstriction begins during exercise or within 3 minutes after its end, peaks within 10–15 minutes, and then resolves by 60 minutes
This phenomenon is thought to be a consequence of the airways’ attempt to warm and humidify an increased volume of expired air during exercise
“Cardiac asthma” is wheezing precipitated by decompensated heart failure
Cough-variant asthma has cough instead of wheezing as the predominant symptom of bronchial hyperreactivity Clinical Findings
Symptoms and signs vary widely among patients as well as individually over time
Symptoms and Signs
Asthma is characterized by episodic wheezing, difficulty in breathing, chest tightness, and cough
Excess sputum production is common
The frequency of asthma symptoms is highly variable
Some patients have infrequent, brief attacks of asthma while others may suffer nearly continuous symptoms
Asthma symptoms may occur spontaneously or be and consider short course of oral systemic corticosteroids Before step up in therapy:
Review adherence to medication, inhaler
If an alternative treatment option was used in a step, discontinue and use the preferred treatment for that step
Adapted from National Asthma Education and Prevention Program
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma
allergic asthma
Eczema, atopic dermatitis, or other allergic skin disorders may also be present
Wheezing or a prolonged expiratory phase during normal breathing correlates well with the presence of airflow obstruction
(Wheezing during forced expiration does not
) Chest examination may be normal between exacerbations in patients with mild asthma
During severe asthma exacerbations, airflow may be too limited to produce wheezing, and the only diagnostic clue on auscultation may be globally reduced breath sounds with prolonged expiration
Hunched shoulders and use of accessory muscles of respiration suggest an increased work of breathing
Laboratory Findings
Arterial blood gas measurements may be normal during a mild asthma exacerbation, but respiratory alkalosis and an increase in the alveolar-arterial oxygen difference (A–a–Do2) are common
During severe exacerbations, hypoxemia develops and the Paco2 returns to normal
The combination of an increased Paco2 and respiratory acidosis may indicate impending respiratory failure and the need for mechanical ventilation
Pulmonary Function Testing
Clinicians are able to identify airflow obstruction on examination, but they have limited ability to assess its severity or to predict whether it is reversible
The evaluation for asthma should therefore include spirometry (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], FEV1/ FVC) before and after the administration of a short-acting bronchodilator
These measurements help determine the presence and extent of airflow obstruction and whether it is immediately reversible
Airflow obstruction is indicated by a reduced FEV1/FVC ratio
Significant reversibility of airflow obstruction is defined by an increase of 12% or more and 200 mL in FEV1 or FVC after inhaling a short-acting bronchodilator
A positive bronchodilator response strongly confirms the diagnosis of asthma but a lack of responsiveness in the pulmonary function laboratory does not preclude success in a clinical trial of bronchodilator therapy
Severe airflow obstruction results in significant air trapping, with an increase in residual volume and consequent reduction in FVC, resulting in a pattern that may mimic a restrictive ventilatory defect
Bronchial provocation testing with inhaled histamine or methacholine may be useful when asthma is suspected but spirometry is nondiagnostic
Bronchial provocation is not recommended if the FEV1 is less than 65% of predicted
A positive methacholine test is defined as a fall in the FEV1 of 20% or more at exposure to a concentration of less than or equal to 8 mg/mL
A negative test has a negative predictive value for asthma of 95%
Exercise challenge testing may be useful in patients with symptoms of exercise- induced bronchospasm
Peak expiratory flow (PEF) meters are handheld devices designed as personal monitoring tools
PEF monitoring can establish peak flow variability, quantify asthma severity, and provide both patient and clinician with objective measurements on which to base treatment decisions
Complications
Complications of asthma include exhaustion, dehydration, airway infection, and tussive syncope
Pneumothorax occurs but is rare
Acute hypercapnic and hypoxemic respiratory failure occurs in severe disease
Differential Diagnosis
Patients who have atypical symptoms or poor response to therapy may have a condition that mimics asthma
These disorders typically fall into one of five categories: upper airway disorders, lower airway disorders, systemic vasculitides, cardiac disorders, and psychiatric disorders
Upper airway disorders that mimic asthma include vocal fold paralysis, vocal fold dysfunction syndrome, foreign body aspiration, laryngotracheal masses, tracheal narrowing, tracheobronchomalacia, and airway edema (eg, angioedema or inhalation injury)
Lower airway disorders include nonasthmatic chronic obstructive pulmonary disease (COPD) (chronic bronchitis or emphysema), bronchiectasis, allergic bronchopulmonary mycosis, cystic fibrosis, eosinophilic pneumonia, hypersensitivity pneumonitis, sarcoidosis, and bronchiolitis obliterans
Systemic vasculitides with pulmonary involvement may have an asthmatic component, such as eosinophilic granulomatosis with polyangiitis
Cardiac disorders include heart failure and pulmonary hypertension
Psychiatric causes include conversion disorders (“func- tional” asthma), emotional laryngeal wheezing, vocal fold dysfunction, or episodic laryngeal dyskinesis
Rarely, Münchausen syndrome or malingering may explain a patient’s complaints
Treatment
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Pharmacologic Agents Asthma medications can be divided into two categories: (1) quick-relief (reliever) medications that act principally by direct relaxation of bronchial smooth muscle, thereby promoting prompt reversal of acute airflow obstruction to relieve accompanying symptom; and (2) long-term control (controller) medications that act primarily to attenuate airway inflammation and that are taken daily independent of symptoms to achieve and maintain control of persistent asthma
Anti-inflammatory agents, long-acting bronchodilators, and leukotriene modifiers comprise the important long-term control medications
Other classes of agents are mentioned briefly below
Most asthma medications are administered by inhalation or orally
Inhalation of an appropriate agent results in a more rapid onset of pulmonary effects as well as fewer systemic effects compared with oral administration of the same dose
Proper inhaler technique and the use of an inhalation chamber (a “spacer”) with metered-dose inhalers (MDIs) decrease oropharyngeal deposition and improve drug delivery to the lung
Nebulizer therapy is reserved for patients who are acutely ill and those who cannot use inhalers because of difficulties with coordination, understanding, or cooperation
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Beta-adrenergic agonists—Beta-agonists are divided into short-acting beta-agonists (SABAs) and longacting beta-agonists (LABAs)
SABAs, including albuterol, levalbuterol, bitolterol, pirbuterol, and terbutaline ), are the mainstays of reliever or rescue therapy for asthma patients; all asthmatics should have immediate access to a SABA
SABAs are the most effective bronchodilators during exacerbations and provide immediate relief of symptoms
There is no convincing evidence to support the use of one agent over another
Administration before exercise effectively prevents exercise-induced broncho constriction
Inhaled SABA therapy is as effective as oral or paren teral therapy in relaxing airway smooth muscle and improving acute asthma and offers the advantages of rapid onset of action (less than 5 minutes) with fewer systemic side effects
Repetitive administration produces incremental bronchodilation
One or two inhalations of a SABA from an MDI are usually sufficient for mild to moderate symptoms
Severe exacerbations frequently require higher doses: 6–12 puffs every 30–60 minutes of albuterol by MDI with an inhalation chamber or 2
5 mg by nebulizer provide equivalent bronchodilation
Administration by nebulization does not offer more effective delivery than MDIs used correctly but does provide higher doses
With most SABAs, the recommended dose by nebulizer for acute asthma (albuterol, 2
5 mg) is 25–30 times that delivered by a single activation of the MDI (albuterol, 0
09 mg)
This difference suggests that standard dosing of inhalations from an MDI are often insufficient in the setting of an acute exacerbation
Independent of dose, nebulizer therapy may be more effective in patients who are unable to coordinate inhalation of medication from an MDI because of age, agitation, or severity of the exacerbation
Scheduled daily use of SABAs is not recommended
Increased use (more than one canister a month) or lack of expected effect indicates diminished asthma control and the need for additional long-term control therapy
LABAs provide bronchodilation for up to 12 hours after a single dose
Salmeterol and formoterol are the LABAs available for asthma in the United States
They are admin- istered via dry powder delivery devices
They are indicated for long-term prevention of asthma symptoms (including nocturnal symptoms) and for prevention of exercise- induced bronchospasm
When added to low and medium daily doses of inhaled corticosteroids .LABAs provide control equivalent to what is achieved by doubling the inhaled corticosteroid dose
Side effects are minimal at standard doses
LABAs should not be used as monotherapy since they have no anti-inflammatory effect and since monotherapy has been associated with a small but statistically significant increased risk of severe or fatal asthma attacks in two large studies
This increased risk has not been fully explained but may relate to genetic variation in the beta-adrenergic receptor; it remains an area of contro- versy
The efficacy of combined inhaled corticosteroid and LABA therapy has led to the marketing of combination medications that deliver both agents simultaneously (Table 9–3)
Combination inhalers containing formoterol and budesonide have shown efficacy in both rescue (given formoterol’s short time to onset) and maintenance (budesonide)
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Corticosteroids—Corticosteroids are the most potent and consistently effective anti-inflammatory agents currently available
They decrease both acute and chronic inflammation, resulting in reduced symptoms and improved lung function
These agents may also potentiate the action of beta-adrenergic agonists
Inhaled corticosteroids are preferred, first-line agents for all patients with persistent asthma
Patients with per sistent symptoms or asthma exacerbations who are not taking an inhaled corticosteroid should be started on one
