Asthma exacerbations

The dose-response curve for P2-adrenergic agonists is shifted to the right with increased levels of bronchoconstriction. This explains the need for higher and more frequent doses during an acute asthma exacerbation... 

Viral infections are the most common cause of increased asthma symptoms and asthma exacerbations. 

Worsening or acute asthma can be a life-threatening situation, and appropriate outcomes require rapid assessment and appropriate intensification of therapy. Mortality associated with asthma exacerbations is usually related to an inappropriate assessment of the severity of the exacerbation resulting in insufficient treatment or referral for medical care.12 The goals... 

In persistent asthma, inhaled corticosteroids provide the most comprehensive control of the inflammatory process and are the cornerstone of therapy.2 Inhaled corticosteroids are more effective than cromolyn, leukotriene modifiers, nedocromil, and theophylline in reducing markers of inflammation and AHR, improving lung function, and preventing emergency department visits and hospitalizations due to asthma exacerbations.2,25 The primary... 

FIGURE 11-2. Home management of acute asthma exacerbation. Patients at risk for asthma-related death should receive immediate clinical attention after initial treatment. PEF, peak expiratory flow. 

Starting therapy at home allows for rapid initiation and early assessment of response. Patients should follow their written action plan as symptoms intensify or lung function deteriorates. An algorithm for the initial treatment of an asthma exacerbation at home is shown in Fig. 11-2. Based on the initial response to P2-agonist therapy, the severity of the exacerbation can be assessed, and treatment can be appropriately intensified.1... 

FIGURE 11-3. Emergency department and hospital-based management of asthma exacerbation. FEV-, forced expiratory volume in 1 second Pco2, partial arterial pressure of carbon dioxide PEF, peak expiratory flow 02, oxygen. (From Kelly HW, Sorkness CA. Asthma. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 517, with permission.)... 

TABLE 11-5. Dosages of Selected Medications for Asthma Exacerbations in Emergency Medical Care or Hospital... 

Routine antibiotic use is not warranted because the primary infectious agents associated with asthma exacerbations are viruses.2,3 Antibiotics should be reserved for situations when bacterial infection is strongly suspected (e.g., fever and purulent sputum, pneumonia, and suspected sinusitis). 

Patterson suffered the first of many severe asthmatic attacks after collecting acidic gas samples from a Hawaiian volcano in 1983. The steroids he took for the asthma exacerbated his inherited osteoporosis, and his frame shrank nine inches to five foot seven. He applied twice for funds to create a line of lead-free rats to study biological processes in uncontaminated mammals. After both applications were rejected, he frequently became depressed. 

Taylor DR, Drazen JM, Herbison GP, Yandava CN, Hancox RJ, Town GI. Asthma exacerbations during long term beta agonist use influence of beta[2] adrenoceptor polymorphism. Thorax 2000 55[9] 762 767. 

The history and physical examination should be obtained while initial therapy is being provided. A history of previous asthma exacerbations (e.g., hospitalizations, intubations) and complicating illnesses (e.g., cardiac disease, diabetes) should be obtained. The patient should be examined to assess hydration status use of accessory muscles of respiration and the presence of cyanosis, pneumonia, pneumothorax, pneumomediastinum, and upper airway obstruction. A complete blood count may be appropriate for patients with fever or purulent sputum. 

Fig. 80-1 depicts the NAEPP stepwise approach for managing chronic asthma. Fig. 80-2 illustrates the recommended therapies for home treatment of acute asthma exacerbations. 

FIGURE 80-2. Home management of acute asthma exacerbation. Patients at risk of asthma-related death should receive immediate clinical attention after initial treatment. Additional therapy may be required. (MDI, metered-dose inhaler PEF, peak expiratory flow.) (Adapted from NHLBI, National Asthma Education and Prevention Program, Expert Panel Report 2. Guidelines for the Diagnosis and Management of Asthma. NIH Publication No. 97-4051. Bethesda, MD U.S. Department of Health and Human Services, 1997.)... 

Workers afflicted with OA, may suffer multiple hardships including lower wages due to transfer to other jobs, reduction in job responsibility, lost work days, lack of productivity, and long term unemployment. Quality and satisfaction of life can also be affected if there is development and/or worsening of ongoing asthma, exacerbation... 

Working with these rodent models, we have accumulated evidence that indicate local DC (airway mucosal dendritic cells, AMDC) are ideally positioned to drive activation of the aeroallergen-specific Th cells which are responsible for the LPR component of asthma exacerbations (fig. 1). 

Human rhinoviruses (HRV) are members of the Picornaviridae family. The HRVs are classified according to their receptor specificity into members of the major and minor groups. The 87 members of the major-group viruses bind to the intracellular adhesion molecule receptor 1 (ICAM-1), whereas the 12 serotypes of the minor group bind to members of the low-density lipoprotein receptor family (LDLR) [42]. Rhinoviruses cause more than a billion cases of the common cold each year and are also associated with asthma exacerbations [43,44]. Statistically, one encounters one to three infections per year on the average [45]. As a result, rhinoviral infections are responsible for 25 million days of missed work in the USA [46]. 

Improved disease reporting, surveillance, and epidemiologic studies of these diseases are needed. Little information exists about either the chronic effects of acute exposure to these marine toxins or about the long-term effects of chronic exposures, e.g., elderly populations in coastal retirement communities experiencing annual HABs. Little information is available about the environmental health effects, e.g., asthma exacerbations, from exposure to these toxins. 

Resp/rafoAy-Asthma exacerbation, bronchospasm, cough, dyspnea. 

If asthma control is not optimal, conventional advice was to increase the ICS dose. However, it is now apparent, that the dose-response effect of ICS is rather flat, so that there is little improvement in lung function after doubling the dose of inhaled steroid. An alternative strategy is to add some other class of controller drug. Several studies have shown that the combination of ICS and salmeterol or formoterol was more effective than increasing the dose of inhaled corticosteroid in terms of lung function improvement, rescue /32-agonist use, symptom control, and frequency of mild and severe asthma exacerbations. 

Rabe KF, Atienza T, Magyar P, Larsson P, Jorup C, Lal-loo UG. Effect of budesonide in combination with for-moterol for reliever therapy in asthma exacerbations a randomized controlled, double-blind study. Lancet 2006 368 744-53. 

The corticosteroids are effective in most children and adults with asthma. They are beneficial for the treatment of both acute and chronic aspects of the disease. Inhaled corticosteroids, including triamcinolone ace-tonide (Azmflcort),beclomethasone dipropionate (Beclo-vent, Vancerit), flunisolide AeroBid), and fluticasone (Flovent), are indicated for maintenance treatment of asthma as prophylactic therapy. Inhaled corticosteroids are not effective for relief of acute episodes of severe bronchospasm. Systemic corticosteroids, including prednisone and prednisolone, are used for the short-term treatment of asthma exacerbations that do not respond to (32-adrenoceptor agonists and aerosol corticosteroids. Systemic corticosteroids, along with other treatments, are also used to control status asthmaticus. Because of the side effects produced by systemically administered corticosteroids, they should not be used for maintenance therapy unless all other treatment options have been exhausted. 

In clinical studies, a reduction of asthma exacerbations was not observed in oma-lizumab-treated patients who had FEV, >80% at the time of randomization reductions in exacerbations were not seen in patients who required oral steroids as maintenance therapy... 

Pediatric patients with comorbid psychiatric disorders requiring continued treatment for their psychiatric symptomatology (e.g., a schizophrenic patient admitted with an asthma exacerbation)... 

Like mast cell stabilizer, corticosteroids do not relax airway smooth muscle directly but reduce bronchial reactivity, increase airway caliber, suppress inflammatory response to antigen antibody reaction or trigger stimuli and reduce the frequency of asthma exacerbations. They produce more sustained symptomatic relief than any bronchodilator and mast cell stabilizer. 

The causes of airway narrowing in acute asthmatic attacks (or "asthma exacerbations") include contraction of airway smooth muscle inspissation of viscid mucus plugs in the airway lumen and thickening of the bronchial mucosa from edema, cellular infiltration, and hyperplasia of secretory, vascular, and smooth muscle cells. Of these causes of airway obstruction, contraction of smooth muscle is most easily reversed by current therapy reversal of the edema and cellular infiltration requires sustained treatment with antiinflammatory agents. 

Corticosteroids have been used to treat asthma since 1950 and are presumed to act by their broad anti-inflammatory efficacy, mediated in part by inhibition of production of inflammatory cytokines (see Chapter 39). They do not relax airway smooth muscle directly but reduce bronchial reactivity and reduce the frequency of asthma exacerbations if taken regularly. Their effect on airway obstruction may be due in part to their contraction of engorged vessels in the bronchial mucosa and their potentiation of the effects of 13-receptor agonists, but their most important action is inhibition of the infiltration of asthmatic airways by lymphocytes, eosinophils, and mast cells. 

---