1. 
   

   Which patients with asthma require hospital admission?

   
   
2. 
   

   What are the evidence-based guidelines for treatment of asthma in the hospital?

   
   
3. 
   

   What is the optimal dosing of systemic corticosteroids in the treatment of an acute asthma exacerbation?

   
   
4. 
   

   Which asthma patients require admission to the intensive care unit?

   
   
5. 
   

   When is intubation indicated in the case of severe asthma?

   
   
6. 
   

   What conditions need to be met before discharging a patient from the hospital?

Asthma is a chronic respiratory disease associated with reversible airflow obstruction, bronchial hyperresponsiveness (BHR), and airway inflammation that can be triggered by various stimuli including viral upper respiratory infection, environmental allergens, and occupational exposures, and can lead to recurrent episodes of wheezing, cough, and dyspnea.

In the United States in 2009, the prevalence of asthma was 8.2% affecting 24.6 million people (17.5 million adults and 7.1 million children). Thus, asthma stands as one of the leading chronic diseases in the United States.

The prevalence of current asthma is higher in children (9.6%) compared to adults (7.7%), and in females (9.3%) compared to males (7.0%). There is considerable variation in asthma prevalence estimates across racial and ethnic groups, with African Americans having higher prevalence than Caucasians and Hispanics. However, within Hispanics, there is marked variation among different ethnic groups; for example, Puerto Ricans have the highest asthma prevalence in the U.S. population in contrast to Mexican Americans, who have the lowest prevalence rates. The reasons why there are large differences in asthma prevalence rates across races and ethnicities are poorly understood and are likely explained by multiple factors including genetic susceptibility, health care access, environmental exposures, and nutritional factors.

History and physical examination of the asthmatic patient reveal recurrent respiratory symptoms characterized by wheezing, cough, and chest tightness. Trigger exposures may exacerbate respiratory symptoms and may include exposure to airway irritants (smoke, strong fumes, air pollution, etc.), aeroallergens, respiratory infections, and cold air. Psychological stress and physical exercise are also known to trigger respiratory symptoms in the absence of any other concomitant exposures; however, in many instances trigger factors are not identified.

Respiratory symptoms may have a nocturnal predominance and are frequently more severe in the morning after waking up, when airflows are usually lower. The frequency and severity of respiratory symptoms is highly variable and may stem from sporadic to constant and from barely noticeable to life threatening.

Although asthma is generally regarded as a single disease entity, it is likely a syndrome composed of a heterogeneous group of pathophysiologic mechanisms (different triggers, risk factors, patterns of inflammation, and response to treatment, etc.) that cause airway obstruction and common respiratory symptoms. Persistent adult asthma phenotypes have been broadly divided into the following categories: clinical or physiologic phenotypes (severity defined, exacerbation prone, treatment resistant, and adult versus child onset); phenotypes related to triggers (aspirin sensitivity, environmental and occupational exposures, menses, and exercise); and inflammatory phenotypes (eosinophilic, neutrophilic, and pauci-inflammatory). Many nonallergic phenotypes and phenotypes that begin in adulthood likely have very different pathophysiologies than allergic asthma. Although this classification scheme is useful to describe the pathophysiology of asthma, considerable overlap among categories exists.

In allergic asthma, an allergen is initially exposed to dendritic cells functioning as antigen-presenting cells. These cells interact with B lymphocytes to produce immunoglobulin E (IgE) in the context of appropriate cytokine and T lymphocyte interactions. Circulating IgE binds high-affinity receptors in blood and tissue mast cells and low-affinity receptors on the surface of lymphocytes, eosinophils, neutrophils, platelets, and macrophages, thus recruiting these cells to the airways. Subsequent exposures to the same antigen will crossbridge IgE bound to mast cell receptors, facilitating mast cell degranulation and release of various cytokines and chemokines, which recruit additional inflammatory cells to the lungs.

The initial release of histamine and leukotrienes from mast cells leads to constriction of airway smooth muscle and can lead to airway obstruction. The early phase of inflammation encompasses the response in the first hour and is followed by a later phase within four to six hours, in which prolonged airway obstruction develops due to cytokine release from resident epithelial cells and inflammatory cells, as well as recruited inflammatory cells. In addition to airway obstruction, this inflammatory response leads to airway edema, mucous hypersecretion, and bronchial hyperresponsivness (BHR). Over time and in relation to the degree of underlying inflammation and disease severity, BHR becomes nonspecific; that is, BHR can be elicited through a variety of nonallergen factors such as strong fumes, air pollution, cold air, exercise, and psychological stress.

Many diseases present with similar respiratory symptoms to asthma, and clinicians should maintain a high index of suspicion for alternate respiratory diagnoses (Table 238-1). Wheezing and cough can occur with congestive heart failure, which may be associated with airway vascular congestion and peribronchial cuffing secondary to pulmonary edema, bibasilar inspiratory crackles on auscultation, and an elevated serum brain natriuretic peptide (BNP). Airway obstruction (eg, foreign body, tumor, laryngeal edema, anaphylaxis, and other) could lead to stridor, which can be mistaken for wheezing.

Paradoxical vocal fold motion disorder (PVFMD), a poorly understood disease that can mimic asthma, is characterized by abnormal adduction of the vocal cord folds during inhalation and occasionally during exhalation, which can lead to complete or partial transient laryngeal occlusion. During these paradoxical vocal cord motion events, patients experience significant respiratory distress characterized by cough, dyspnea, a choking sensation, and wheezing or stridor. Relief with short acting beta-agonists or other medications used for asthma control is minimal to none. The severity and repetitive nature of symptoms caused by PVFMD lead to high health care utilization.

PVFMD is commonly encountered among patients referred for difficult or refractory asthma and chronic cough evaluation. However, among patients referred to tertiary centers for refractory asthma or cough, the prevalence of PVFMD can be as high as 40% to 50%. Many PVFMD patients inappropriately receive chronic systemic steroids. Patients with PVFMD commonly have frequent emergency department visits and may be intubated for respiratory distress.

Differentiating asthma and chronic obstructive lung disease (COPD) can be very difficult, and at times impossible. (See Chapter 239 for a comprehensive review of COPD). Although asthmatics would be expected to have a more reversible airway obstructive process than patients with COPD, this characteristic occurs with high variability in COPD patients, as up to one-third or more of patients with COPD will have a reversible component to their obstruction. Both disorders can coexist in the same patient as a result of chronic smoking and/or airway remodeling. Emphysematous changes on chest computed tomography (CT) and/or severe airway obstruction with hyperinflation in the absence of an acute exacerbation would favor the diagnosis of COPD over asthma.

Bronchiectasis can also present with airway obstruction and symptoms compatible with asthma. However, clinical features that reduce the likelihood of asthma diagnosis include chronic sputum production at baseline, recurrent lower-tract respiratory infections, hemoptysis, and inspiratory crackles on auscultation. Chest CT should detect bronchiectasis. In approximately 1% to 2% of patients, bronchiectasis and asthma coexist with bronchopulmonary aspergillosis (ABPA). In this case, bronchiectasis occurs predominantly centrally, with areas of mucoid impaction. Patients with ABPA usually have IgE levels greater than 1000 ng/ml with peripheral blood eosinophilia more than 10% specific Aspergillous IgG or IgE antibodies. A negative intradermal test for Aspergillus antigen adequately rules out this condition.

Asthma diagnosis must be confirmed by pulmonary function testing that shows evidence of airway obstruction with a bronchodilator response greater than or equal to 12% (or 200 mL) improvement of the forced expiratory volume in one second (FEV1) after short-acting bronchodilators. Bronchodilation should only be assessed after witholding asthma medications at least 4 hours for short-acting β2-receptor agonists (SABA) and 24 hours for long-acting β2-receptor agonists (LABA).

In cases where there is no evidence of airway obstruction or bronchodilation on initial pulmonary function testing, patients should undergo testing with methacholine (a cholinergic agent used to elicit bronchial constriction) to exclude asthma. A positive test occurs when there is a reduction in FEV1 greater than or equal to 20% (percent change 20 or PC20) from the baseline postmethacholine level. The methacholine test is very sensitive (ie, it would be unusual to have asthma with a negative test) but lacks specificity, such that a positive test can be seen in the setting of other airway diseases or allergies. Diligent assessment for presence or absence of asthma through testing and evaluation of treatment response will help eliminate the approximately 30% of patients who are incorrectly diagnosed with this disease clinically (false positive) and are unnecessarily treated with corticosteroids.

When patients with severe asthma exacerbations do not adequately respond to outpatient therapy, clinical assessment should include a brief history, physical examination (assess respiratory rate and heart rate, use of accessory respiratory muscles, chest retraction, neck and pulmonary auscultation, oxygen saturation), and pulmonary function testing (FEV1 or peak expiratory flow [PEF] measurement) to help triage for possible hospital admission.

Several published guidelines aid clinicians in admission decision making. A triage system based on the history of symptoms and spirometric measurement (PEF or FEV1) can aid triage decision making (Table 238-2).

Patients admitted with high risk of asthma-related death (Table 238-3) should receive very close inpatient monitoring, possibly in the intensive care unit (ICU), based on response to initial therapy.