Professional Documents
Culture Documents
Bronchial Asthma
Khaled O Hadeli MD, FCCP
19 98
he defi inition of bronchial b a asthma has s been revi ised since i t was first described by Sir Wi lliam Osler r in ing the last t century, the t definiti on focused d on 1892. Duri clinical and d physiolog gical featur es of rever sible bronc chospasm and bronchial hyper resp onsiveness . This resul lted in confusio on because the two fe eatures may y be shared d by other chro onic airway y disorders such as chronic c airw way pulmonary y disease (C COPD). The lat est definiti ion was rep ported by t he Global Initiative for Asthma (G GINA) prog gram in 20 004; a chro onic inflammato ory disorde er of the airways in n which many m cells and cellular el lements pl lay a role. . The chro onic inflammati ion causes an associ iated incre ase in airw way hyper-resp ponsiveness s that leads s to recurre ent episode s of wheezing, breathlessn b ness, chest tightness, and coughi ing, particularly y at night t or in th e early m orning. Th hese episodes are a usually y associate ed with wi idespread but variable airflow a obs struction that t is oft ten revers ible either spon ntaneously or with tre atment.
Asthma A
199
Asthma
Epidemiology
According to WHO statistics, bronchial asthma affects 300 million people; and 255,000 people died of asthma in 2005. Asthma prevalence increases globally by 50% every decade. The most striking increase in asthma prevalence is seen among children. 80% of asthma deaths occurred in low and lower-income countries, and asthma deaths are projected to increase by 20% if appropriate actions are not taken. The prevalence of asthma in the developed countries ranges from 10.9% in the United States, to more than 15% in the United Kingdom. In developing countries the prevalence of asthma is less. The highest prevalence in Africa (8%) is seen in South Africa, but is increasing at a higher rate in developing countries as they urbanize and westernize. Worldwide, the burden of asthma on the economy exceeds that of tuberculosis and HIV combined. In the United States, asthma-related treatment cost, cost related to loss of work, loss of productivity, and early retirement was estimated to be $12 billion in 2004. These costs are directly related to the severity of the disease. Even though patients with severe asthma constitute only 20% of the total asthma population, they are responsible for 50% of the cost of the disease.
Industrialized countries have a higher prevalence of asthma Developing countries have a higher incidence of asthma Asthma mortality is higher in poor countries The cost of asthma treatment is high
200
Pathophysiology of Asthma
Asthma is a chronic disease with a complex interaction of cells, mediators, and cytokines that result in inflammation. This interaction causes smooth muscle contraction, smooth muscle hypertrophy, micro vascular leakage, bronchial wall oedema, activation of airway neurons, increase in airway responsiveness, stimulation of mucus-secreting cells, mucus plugging of the airways, disruption of the airway epithelium, and ultimately causes widespread airflow limitation. The inflammatory cells involved in the path physiology of asthma include mast cells, macrophages, eosinophils, lymphocytes, neutrophils, basophils, and platelets. These cells are capable of generating mediators that can induce bronchospasm early phase response, or guide the activation and migration of the eosinophils and neutrophils, and cause a late phase response that results in epithelial damage, capillary leak, and mucus hyper secretion. These mediators include histamine, platelet activating factors, leukotrienes LTC4, LTD4, LTE4, prostaglandin D2 and other derivatives of the arachidonic acid cascade.
Complex interaction of cells, mediators, and cytokines. Early or Late phase response Widespread airflow limitation is the ultimate result
201
Asthma
202
203
Asthma
such patients bronchoprovocation testing may be needed to diagnose the disease. A constellation of signs can be seen with bronchial asthma. Most common are tachypnea, prolonged exhalation phase, wheeze, use of accessory muscles, and pulsus paradoxus. The degree of wheezing does not predict the severity of the disease; a quiet chest may actually be a late sign of an acute severe attack. Early in the attack, hyperventilation leads to decrease in CO2. Later on, in advanced and severe cases when FEV1 is less than 15%, VQ mismatch leads to dead space ventilation, combined with increased work of breathing and increased production of CO2 and O2 consumption. Blood levels of CO2 may normalize or even rise to high levels, O2 levels continue to drop.
Wheeze, breathlessness, and cough are the most common asthma symptoms Perception of asthma symptom is variable, depending on the person and the speed of FEV1 declin. Tachypnea and prolonged exhalation phase are the most common physical signs in asthma Hypercarbia, dead space ventilation, and quiet chest in physical examination are advanced findings suggesting a severe attack
204
Classification of Asthma
Class Frequency of Attacks Mild Intermittent < 2 attacks weekly Night time attacks < Two times per month FEV1 or PERF>80%predicted, but PERF variability <20% Mild Persistent > 2 attacks per week, but < 1 attack daily Moderate Persistent Daily attacks > One time per week Severe Persistent Continuous attacks Frequent/ Daily FEV1 or PERF >60%<80%, >30% PERF variability FEV1 or PERF <60%, >30% PERF variability > Two times per month FEV1 or PERF >80% predicted, but PERF variability 20-30% Lung Function
205
Asthma
matics. After establishing an individuals normal range, the peak flow rates can then be followed to monitor the progression of the disease. The National Institute of Health (NIH) has developed guidelines to help patients monitor disease severity and control (zones of airflow limitation).
Green zone (80% and 100% of persons best) indicates good control Yellow (50%-80% of persons best) indicates poor control and warrants patient attention, and possibly a need to increase treatment Red (less than 50%) indicates very poor control and warrants physician involvement
Arterial Blood Gas (ABG): The most common finding in an asthma attack is hypoxemia due to ventilation perfusion (VQ) mismatch. In mild to moderate attacks, hyperventilation leads to hypocarbia and respiratory alkalosis. As previously described, severe asthma exacerbations may lead to normalization or hypercarbia and worsening hypoxemia, heralding respiratory failure. Bronchoprovocation testing: In patients with typical features of asthma, but without spirometric or peak flow confirmation, an inhalation challenge test may be helpful. After giving the patient a dose of short-acting bronchodilators to ensure normal airway at the start of the test, standardized escalating doses of inhaled methacholine or histamine are given. A 20% decline in FEV1 is diagnostic of asthma. Radiological Features: Most commonly, the chest x-ray of an asthmatic will be normal . The main findings
20 06
with severe e airway ob bstruction are hyperin nflation of the chest (figur re 2) and a flat diaphr ragm.
207
Asthma
Coug gh varian nt asthma : Cough is the main symps tom, and d diagnosis s can be made m with bronchopro b ovocation tes sting. The cough usually u res sponds we ell to treatmen nt with bron nchodilator rs and stero oids. Drug g induced d asthma: Main culpr rit drugs in nclude aspirin and a beta-blo ockers. ABPA A (allergic c bronchop pulmonary aspergillos sis or allergic bronchopu ulmonary mycosis): m A form of as sthma t hypersen nsitivity to o fungi u sually thought to reflect Aspergill lus fumigat tus. This fo orm is char racterized by b the formatio on of thick respiratory r secretions and mucus s plug (figure 3), 3 presenc ce of eosi nophilia, high h IgE levels, l antibodie es to asper rgillus, and d recurrent lung infilt trates. If untrea ated this may m lead to bronchiec tasis. Treat tment includes the use of o steroids s. The role e of anti-f fungal medicati ions is less defined.
208
Churg-Strauss syndrome: Is a multisystem disease characterized by allergic rhinitis, asthma, and blood eosinophilia. Involvement of other systems could be seen. The gold standard diagnostic procedure is open lung biopsy with findings including eosinophilic infiltrates, giant cell vasculitis, interstitial granulomas, and eosinophilic lymphadenopathy. Leukotriene modifying agents were implicated in the development of the disease, however, it is believed that the tapering off of the steroids in these patients unmasked the disease rather than the other way around. Treatment is usually with high dose steroids. Fatal or near-fatal asthma: is an important variant of asthma presentation. Despite better understanding of the pathophysiology of asthma and the availability of effective medications, acute attacks with significant mortality rates still occur. According to the British Thoracic Society, risks of developing near fatal attacks are: Previous history of near fatal asthma Previous history of hospitalization due to asthma Previous history of mechanical ventilation due to respiratory failure from asthma Patient on 3 or more classes of asthma medication Heavy use of B-agonist Behavioral problems (non-compliance, alcohol abuse, drug abuseetc.) Social problems (poverty, social isolation, child abuseetc.) Other risk factors include:
Marked fluctuations of PERF am/pm readings People with blunt response to hypoxemia Lack of prophylactic anti-inflammatory treatment
Death is usually due to hypercarbic respiratory failure. Despite severe hypercarbia and very low pH, severe attacks can be reversed with appropriate management.
209
Asthma
When an asthma attack is sudden and respiratory failure occurs fast, the recovery can be quick and complete, compared to attacks that are slow to progress. Patients who require mechanical ventilation pose a significant challenge to the physician. Severe bronchospasm and limitation of airflow make ventilation very difficult; and old strategies aimed at quick correction of blood gas derangement may lead to increased mortality from barotrauma and decreased cardiac output due to increased intrathoracic pressure and decreased venus return. The use of mechanical ventilation strategies leading to permissive hypercarbia has improved the outcomes. Proper asthma control can significantly reduce near fatal attacks and asthma mortality. Measures like the regular use of peak flow meters, written action plans, better patient-physician communication, better patient compliance, and the use of corticosteroids can help in this regard.
Management of Asthma
Environmental control of asthma
Once a patient is diagnosed with asthma, a detailed environmental and occupational history is essential. General or specific advice about environmental changes is the cornerstone of asthma management and control. Patients need to appreciate that asthma is a clinical syndrome, where the clinical manifestation can be controlled but the condition is likely to be lifelong. Environmental education is important for the patient for the rest of his/her life. Occupational exposures and type of home furnishings, that may influence the disease, may be difficult to change at the time of diagnosis, but may be necessary to improve control of the disease.
210
Moderate persistent
SABA
LABA or
and
ICS
vs.
Higher dose ICS with without LMA/Theo Severe Persistent SABA All the above and
oral steroids
Short acting beta-agonist (SABA), Long Acting beta-agonist (LABA), Inhaled corticosteroids (ICS), Leukotrienemodifying agent (LMAs), Cromolyn sodium (Cs), Theophylline (Theo) *If uncontrolled at any severity level, consider pulse
211
Asthma
Medications
Anti-inflammatory Agents Corticosteroid Mode of action: Prevent migration and activation of inflammatory cells, interfere with the production of prostaglandins and leukotrienes, and reduce capillary leak. Use: All forms of asthma with severity higher than mild intermittent. Preparations: Oral and inhaled. Side effects: Long-term use of inhaled corticosteroids is associated with a good safety profile; nonetheless local effects such as hoarseness of voice, dysphonia, cough, and oral candidiasis can be expected. Hypophyseal-pituitary-adrenal suppression, osteoporosis, cataract, hypertension, diabetes mellitus, and immune suppression can be seen, especially with long-term use of oral preparations. Mode of action: Mast cell stabilization Use: Allergen-induced asthma Preparation: Inhalation. Very good safety profile Mode of action: Inhibit the cysteinyl leukotrienes and Leukotriene C4, D4, and E4. Use: particularly useful in allergen-induced asthma, exercise- induced asthma, and aspirin- induced asthma. Preparation: Oral Side effects: Generally very safe with reports of rare cases of Churge-strauss vasculitis in patients with
Cromolyn Sodium
212
Bronchodilators
Short Acting Beta Agonist (SABA) Mode of action: Airway dilation by producing cAMP, also reduce the release of inflammatory mediators and improve mucocilliary transport. Used as rescue medication and prophylactic in exerciseinduced asthma. Use: All levels of severity, preferably on as needed basis. Preparation: Oral and inhaled. Side effects: Despite selectivity, may have systemic adrenergic effects like tremors, arrhythmias, palpitation, and paradoxical bronchospasm. Regular use of Beta 2 agonists is thought to be associated with increased mortality. So, these medications are better used as an as needed rescue medication. Mode of action: Similar to that of short acting bronchodilators, but due to lipophilicity the duration of action is much longer. Use: Moderate persistent severity or higher. Preparation: Inhaler. Side effects: the safety profile of long acting beta agonists is controversial. The weight of evidence favors their use in moderate persistent severity or higher in combination with corticosteroids. Mode of action: Not defined. Methylxanthines are effective bronchodilators with anti-inflammatory properties. Use: Moderate persistent asthma or higher.
Methylxanthines
213
Asthma
Preparation: Oral. Side effects: Narrow therapeutic margin, requires monitoring of therapeutic levels especially in the elderly. Side effects include GI upset in mild toxicity and serious cardiac arrhythmias seen in high blood levels. Mode of action: Inhibits calcium channel smooth muscle and reduce acetylcholine release. Use: Acute severe attack. Preparation: Intravenous. Side effects: circulatory collapse. Mode of action: Reduce vagal tone, synergistically when used with Beta agonists. Use: mainly used in COPD, or as a substitute to beta agonists and methylxanthines in patients with cardiac arrhythmias. Preparation: inhaler. Side effect: slow-acting. Caution in patients with glaucoma or urinary retention.
Magnesium Sulfate
214
may lead to loss of effective communication with the patient, and ultimately poor adherence and outcome.
Further Reading
1. Bethesda MD. Expert panel 2: guidelines for the diagnosis and management of asthma. NIH publication 1997; No. 97-4051. Braman SS. Decreasing the global burden of asthma. Chest 2006; 130(suppl):S4-S12. Masoli M, Fabian D, Holt S, Beasley R, von Hertzen L. GINA program: The global burden of asthma. Allergy 2004;59:469-478. Canonica GW. Treating asthma as inflammory disease. Chest 2006;130(suppl):S21-S28. Hall IP. Genetics and Thorax 1999;54:65-69. pulmonary medicine: asthma.
2. 3.
4. 5. 6. 7. 8.
Kay AB. Pathology of mild, severe, and fatal asthma. Am J Respir Crit Care Med 1996;154(suppl):S66-S69. Graham LM. Classifying 130(suppl):S13-S20. asthma. Chest 2006;
Palma-Carlos AG. Correlation between clinical classification, PEF and FEV1: guidelines and reality. Allergy Immunol (Paris) 2003;35:130-132.
215
Asthma
9.
Corbridge TC, Hall JB. The assessment and management of patient with status asthmaticus. Am J respire Crit Care Med 1995;151:1296-1316.
10. Cockrill BA. ABPA. Annual Rev Med 1999;50:303-316. 11. Jimenez-Friedman G, Beckett W, Szeinuk J, Petsonk E. Clinical evaluation, management, and prevention of workrelated asthma. Am J Ind Med 2000;37:121-141. 12. Greening AP, Ind PW, Northfield M, Shaw G. Added salmeterol versus high-dose corticosteroids in asthma patients. Lancet 1994;344:219-224. 13. Salvi SS, Krishna MT, Sampson AP, Holgate ST. The antiinflammatory effects of Leukotriene-modifying drugs and their use in asthma. Chest 2001; 119:1533-1546. 14. Irwin R. Patient-Focused 130(suppl):S73-S82. Care. Chest 2006;
Websites
1. 2. http://www.ginasthma.com/ Global Initiative for asthma (GINA). www.who.int/respiratory/gard/en/ Global Alliance against Chronic Respiratory Diseases (GARD). 3. www.who.int/topics/asthma/en/ World Health Organization: Asthma, Fact Sheet.