A 49-year-old woman presented to urgent care with complaints of worsening dyspnea for the previous two days. She reported that her symptoms had begun gradually; at the time of her presentation, however, she was also experiencing chest tightness, occasional wheezing, and a nonproductive cough. She had experienced similar symptoms in the past and obtained good results by using her albuterol inhaler. During the current episode, however, she had not had the usual response to inhaler treatment.

The patient’s medical history was positive for environmental allergies, asthma, and GERD. Two weeks earlier, she had undergone dilatation and curettage (D&C) for dysfunctional bleeding, with no associated complications.

In the social history, the patient reported drinking four to six caffeine beverages daily and consuming alcohol moderately (two to four glasses of wine per week). She was following no formal dietary regimen. The patient denied current or past history of tobacco use and had not traveled recently. She had no family history of coronary vascular disease.

Her medications included albuterol and desloratadine as needed, pantoprazole 40 mg/d, and drospirenone/ethinyl estradiol. The patient said she used her albuterol inhaler four to six times per month but more often in the summer and fall. Nighttime awakenings due to asthma symptoms occurred no more than twice per month. She denied prior history of acute asthma exacerbations requiring oral systemic corticosteroids. The patient stated that since her D&C, she had been using ibuprofen almost daily for mild abdominal cramping.

A review of systems was positive for mild fatigue since her D&C. The patient denied fever, chills, headache, sore throat, or cough. She did complain of daily nasal congestion but with no unusual drainage. The patient denied orthopnea, chest pain, palpitations, or peripheral edema, as well as nausea, vomiting, diarrhea, constipation, hematochezia, or melena. She admitted to daily heartburn for the previous two weeks that was relieved somewhat with pantoprazole. She had not experienced urinary frequency or urgency, dysuria, or hematuria. She also denied rash, pruritus, weakness, paresthesias, joint pain, or swelling.

Physical examination revealed an alert, oriented female who appeared slightly anxious but was in no acute distress. Specific findings were pulse, 110 beats/min; blood pressure, 138/88 mm Hg; respirations, 24 breaths/min; temperature, 97.7°F; O2 saturation, 92% on room air. Her height measured 5’2” and weight, 150 lb (BMI, 27.43).

Her conjunctiva were slightly injected, and the tympanic membranes were intact bilaterally with a light reflex; the septum was midline. The mucosa was pale, boggy, and moist with clear drainage and no inflammation. The nasopharynx had no erythema, and the tonsils appeared normal, although a cobblestone appearance was noted in the posterior pharynx. The neck was supple with no adenopathy.

The patient’s heart rate, 110 beats/min, was regular with no murmurs, rubs, or gallops. In the lungs, a prolonged expiratory phase was noted, with diffuse wheezing on chest auscultation bilaterally. Neither retractions nor use of accessory muscles with breathing was observed. The abdomen was soft, rounded, and nontender with no organomegaly. Bowel sounds were evident in all four quadrants. The patient’s skin was free of suspicious lesions or rashes. Her extremities were without edema, and no calf tenderness was noted; Homans’ sign was negative. Superficial varicosities were noted bilaterally.

The top differential diagnosis included:

• Acute asthma (risk factors: history of uncontrolled asthma, as evidenced by frequent use of albuterol)

• Acute anemia (risk factors: history of dysfunctional uterine bleeding, recent D&C)

• Pulmonary embolism (risk factors: recent surgery, recent start of oral contraceptive use).

Additional diagnoses to be considered less likely included:

• Acute coronary syndrome/MI (possible causes of chest tightness, dyspnea, dyspepsia; but no chest pain, diaphoresis, or nausea)

• Acute respiratory distress (history of tachycardia, possible dyspnea; but no diaphoresis, cyanosis, retractions, accessory muscle use, or lung crackles)

• Pneumonia (risk factors: recent surgery, possible cause of nonproductive cough; but no evidence of fever, chills, rales, or pleuritic chest pain).

Diagnostic testing included a 12-lead ECG to evaluate the patient for cardiac arrhythmia or injury; on it, tachycardia was noted, with a regular rate of 106 beats/min. The patient’s chest x-ray yielded normal results.

Laboratory testing included a complete blood count to screen for anemia and infection. Results included a white blood cell count of 8,200/mL (normal range, 4,500 to 11,000/mL); hematocrit, 38.2% (normal range for women, 36.1% to 44.3%); hemoglobin, 13.1 g/dL (normal for women, 12.1 to 15.1 g/dL). A comprehensive metabolic panel was performed to assess electrolyte levels and kidney and liver function; findings were normal. Results of a D-dimer assay, which was obtained to exclude pulmonary embolism,¹ were normal at 0.5 mg/L (range, 0.4 to 1.4 mg/L).

In the case of heightened suspicion for MI, the patient would have been transferred to the emergency department (ED) for evaluation, including serial cardiac troponin levels; elevated troponin levels are deemed the standard criterion to define and diagnose MI in a consensus document from the European Society of Cardiology and the American College of Cardiology.² (Troponin-T and troponin-I are more tissue-specific than the MB fraction of creatine kinase [CK-MB] in detecting MI; positive troponin levels are considered virtually diagnostic of MI.² Typically, cardiac troponin levels are measured two to three times over a 12- to 16-hour period.)

Peak expiratory flow (PEF), which was measured to evaluate the patient’s respiratory status, was 150 L/min (compared with personal best for a patient of her height and age, approximately 460 L/min). She was given 2.5 mg/3 mL of inhaled albuterol over 15 minutes. Her PEF increased to 350 L/min. O2 saturation improved to 96% on room air, pulse to 104 beats/min, and respirations 20 breaths/min; her blood pressure reading was now 140/90 mm Hg. A prolonged expiratory phase persisted in the lungs, but diffuse wheezing decreased by 40% on chest auscultation.

A second albuterol treatment was administered 20 minutes later, and the patient’s PEF increased to 380 L/min and O2 saturation to 99%. The lungs presently cleared with no further wheezing noted.

In addition, the patient was given a GI cocktail (ie, liquid antacid combined with an anticholinergic agent and viscous lidocaine). Within 10 minutes, her chest tightness was relieved 100%. Her blood pressure was then measured at 135/84 mm Hg; respirations, 18 breaths/min; and pulse rate, 96 beats/min.

According to the National Asthma Education and Prevention Program (NAEPP) 2007 Guidelines for the Diagnosis and Management of Asthma, Expert Panel Report 3 (EPR-3),³ the patient was classified as having intermittent, not-well-controlled asthma with an acute exacerbation. In addition, she was given a diagnosis of uncontrolled GERD.

DISCUSSION
Asthma Incidence and Risk Factors
Asthma affects approximately 300 million people worldwide and remains a global respiratory concern.⁴ In the United States, this chronic health condition has a prevalence of 8% to 10%. It is estimated that 5% to 10% of asthmatic patients have severe disease that does not respond typically to therapeutic interventions.⁵

Asthma involves bronchial hyperresponsiveness, airflow obstruction, and underlying inflammation. Acute episodes of asthma, arising from bronchospasm, usually manifest with progressively worsening cough, shortness of breath, chest tightness and wheezing (asthma’s hallmark symptoms), or a combination of symptoms.³

Symptoms of asthma or exacerbations of reactive airway disease vary from patient to patient. In addition to the hallmark symptoms noted, subacute or acute episodes of asthma exacerbation are characterized by decreases in expiratory airflow that can be documented by objective measurements of lung function, such as PEF or spirometry; these measures of airflow indicate the severity of an exacerbation more reliably than does perceived symptom severity.³ The EPR-3 panelists recommend determining asthma severity using a combination of objective criteria and clinical symptoms,³ although few clinicians use the objective criteria.⁶

Estimates of the prevalence of GERD among patients with asthma have varied from 34% to 89%.^7-9 Patients with GERD are 1.97 times more likely than patients without GERD to have asthma¹⁰; silent gastroesophageal reflux has been identified in 24% to 62% of patients with asthma, and early studies suggest that treatment for GERD may improve asthma control in patients with severe or difficult-to-control asthma.^8,11,12

The exact link between the two conditions is unclear. However, possible explanations why GERD and asthma coincide are that acid flow causes injury to the lining of the throat, airways, and lungs, making inhalation difficult and often causing a persistent cough; or that when acid enters the esophagus, a nerve reflex is triggered that causes the airways to narrow in order to prevent the acid from entering; this can explain dyspnea.^8,9

Economic Burden
Asthma is costly to treat, and because there is no cure, the expense is ongoing. According to a 2011 report,¹³ the average annual direct cost of care (eg, medications, hospital admissions, nonemergency office visits) for one asthma patient between 2002 and 2007 was $3,259. In 2007, the most current data available, the total cost of asthma in the US was $56 billion, with productivity losses due to mortality accounting for $2.1 billion and morbidity-related losses estimated at $3.8 billion.¹³ The economic consequences of asthma are substantial and can place a considerable burden on affected individuals, their families, the health care system, and society as a whole.³

Current Standard of Care
Based on the scientific literature and the opinions expressed by the NAEPP in the EPR-3,³ clinicians are advised to consider the following general principles and goals for managing asthma: early treatment, special attention to patients at high risk for asthma-related death, and special attention to infants.³ The guidelines emphasize the importance of a clinician/patient partnership to facilitate the asthma patient’s self-management.

Early treatment is a particularly important component for management of asthma exacerbations. Important elements of early treatment include a written asthma action plan, combined with enhanced awareness of the early indicators of an exacerbation (ie, worsening PEF).^3,14 It is believed that if patients are able to monitor their respiratory condition and follow a plan of care based on their PEF and/or signs and symptoms of asthma, they are more likely to achieve optimal management of their disease.¹⁵

Written Asthma Action Plan. The EPR-3³ recommends that health care providers supply all asthmatic patients with a written asthma action plan that will define and support the patient’s efforts at self-management. Written asthma action plans are particularly beneficial for patients with moderate to severe persistent asthma, poorly controlled asthma, or a history of severe exacerbations.^3,14

The written asthma action plan should include instructions for daily management of asthma and ways to recognize and treat worsening asthma, including adjustments to medication dosing. Plans may be based on PEF and/or symptoms. Asthma action plans should be discussed and reevaluated at follow-up visits.³ A sample asthma action plan can be found at www.health.state.ny.us/diseases/asthma/pdf/4850.pdf.¹⁶

Peak Expiratory Flow (PEF). The EPR-3³ recommends PEF monitoring in all asthma patients, regardless of the severity of their exacerbations.¹⁷ PEF-based plans are especially useful for the patient who has difficulty perceiving early signs and symptoms of worsening asthma.^3,18 A PEF-based plan instructs the patient to use quick-relief medications if symptoms occur or if PEF drops below 80% of the patient’s personal or predicted best. (Measured personal best is the patient’s highest PEF in the previous two weeks of good asthma control,^3,19 whereas predicted best is calculated based on findings from a 1983 study by Knudson et al.^3,20)

A PEF between 50% and 79% requires the patient to carefully monitor his or her response to the quick-relief medication and, based on that response, consider whether to contact a health care provider. When PEF falls below 50%, a provider’s immediate intervention is usually recommended.³

In the urgent care or ED setting, according to EPR-3 recommendations,³ the PEF or forced expiratory volume in 1 second (FEV1) is used to indicate the following:

• ≥ 70% predicted PEF or FEV1: goal for discharge

• 40% to 69% predicted PEF or FEV1: incomplete response to treatment, frequent need for treatment in the ED

• 3

Treatment and Management
Asthma management interventions that target the treatment of active disease and predisposing triggers are designed to reduce the severity and/or duration of morbidity associated with asthma—principally, to prevent symptoms and exacerbations (see Table 1³).

When patients are discharged following an asthma exacerbation, their medications should include an oral corticosteroid burst and a short-acting b2-agonist (SABA); the clinician should also consider prescribing an inhaled corticosteroid (ICS).³

It is no longer recommended that ICS dosing be doubled in place of an oral steroid burst.^3,21 The addition of a leukotriene receptor antagonist (LTRA) may also be considered.^3,22

Patients should be given an action plan, and follow-up with a primary care provider should be scheduled within a few days—or even the following day, depending on the severity of the patient’s condition. The importance of follow-up with a primary care provider, a pulmonologist, or an asthma/allergy specialist should be emphasized.^3,23

For patients who have difficulty recognizing their symptoms, a peak flow meter may be useful. This device is also recommended for patients with moderate to severe asthma or a history of numerous severe exacerbations.³ Additionally, spacers should always be used with metered dose inhalers (MDIs), because they make it easier for medication to reach the lungs and reduce the amount deposited in the mouth and throat, where it can lead to irritation. At each office visit, use of the peak flow meter and inhaler technique should be observed, and the action plan reevaluated and changed if necessary.^3,14

Additional components of patient education include instruction in controlling environmental factors: avoiding environmental tobacco smoke, exposure to insect allergens, and molds. It is also important to stress controlling comorbid conditions that influence asthma, such as allergies or GERD. Patients with symptoms of GERD should be advised to take the steps shown in Table 2.^8,24

Clinical Implications
Assessment of the severity of an asthma exacerbation is an essential component of ambulatory asthma care. Underclassification of asthma severity has been associated with increased morbidity and mortality,⁶ and the NAEPP guidelines recommend that clinicians assess and document asthma severity at each clinic visit.^3,25 Patients who receive care based on evidence-based practice guidelines have been shown to experience 28% better outcomes.²⁶

PATIENT OUTCOME
The case patient was discharged on an oral corticosteroid burst and a low-dose ICS. She was instructed how and when to use her SABA and given a prescription for a spacer; use of a peak flow meter was initiated with an estimated personal best goal of 460 L/min. The patient was given a written asthma action plan to help her recognize early signs and symptoms of worsening asthma and was advised to use quick-relief medications if she experienced symptoms or if her PEF dropped below 80% of her predicted best.

The patient’s clinician emphasized the importance of controlling any asthma-triggering environmental factors and reviewed nonpharmacologic interventions to control GERD. The patient was advised to resume desloratadine 5 mg/d and pantoprazole 40 mg/d. She was also instructed to schedule an appointment with her primary care provider within 48 hours and to return to urgent care or the ED with any further exacerbation of respiratory symptoms not controlled by her SABA.

CONCLUSION
Asthma morbidity is a nationally recognized, major public health problem. Given the sharp rise in health care costs and limited resources, health care providers must factor in the comparative effectiveness, comparative cost, and cost-effectiveness of both new and existing health care interventions when making treatment decisions.

Many asthmatic patients face the challenges of health care access and quality. By promoting their self-care and awareness, clinicians can help asthmatic patients achieve better symptom management and use the health care system less often.

REFERENCES
1. Stein PD, Hull RD, Patel KC, et al. D-Dimer for the exclusion of acute venous thrombosis and pulmonary embolism. Ann Intern Med. 2004;140(8):589-602.

2. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined: a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000;36(3):959-969.

3. National Asthma Education and Prevention Program, National Heart, Lung, and Blood Institute. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD: National Heart, Lung, and Blood Institute; 2007. US Department of Health and Human Services publication NIH 07-4051.

4. Lougheed DM. Variability in asthma: symptom perception, care, and outcomes. Can J Physiol Pharmacol. 2007;85(1):149-154.

5. Higgins JC. The ‘crashing asthmatic.’ Am Fam Physician. 2003;67(5):997-1004.

6. Cowen MK, Wakefield DB, Cloutier MM. Classifying asthma severity: objective versus subjective measures. J Asthma. 2007;44(9):711-715.

7. Takenaka R, Matsuno O, Kitajima K, et al. The use of frequency scale for the symptoms of GERD in assessment of gastro-oesophageal reflux symptoms in asthma. Allergol Immunopathol (Madr). 2010;38(1):20-24.

8. Harding SM, Barnes PJ, Hollingsworth H. Gastroesophageal reflux and asthma (2010). www.uptodate.com/contents/gastroesophageal-reflux-and-asthma. Accessed April 5, 2011.

9. Havemann BD, Henderson CA, El-Serag HB. The association between gastro-oesophageal reflux disease and asthma: a systematic review. Gut. 2007;56(12):1654-1664.

10. Tsai MC, Lin HL, Lin CC, et al. Increased risk of concurrent asthma among patients with gastroesophageal reflux disease: a nationwide population-based study. Eur J Gastroenterol Hepatol. 2010;22(10):1169-1173.

11. Harding SM, Richter JE, Guzzo MR, et al. Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome. Am J Med. 1996;100(4):395-405.

12. Gibson PG, Henry RL, Coughlan JL. Gastro-oesophageal reflux treatment for asthma in adults and children. Cochrane Database Syst Rev. 2003;(2):CD001496.

13. Barnett SB, Nurmagambetov TA. Costs of asthma in the United States: 2002-2007. J Allergy Clin Immunol. 2011;127(1):145-152.

14. Walders N, Kercsmar C, Schluchter M, et al. An interdisciplinary intervention for undertreated pediatric asthma. Chest. 2006;129(2):292-299.

15. Morrow R, Fletcher J, Mulvihill M, Park H. The asthma dialogues: a model of interactive education for skills. J Contin Educ Health Prof. 2007;27(1): 49-58.

16. State of New York, Department of Health. Asthma action plan. www.health.state.ny.us/diseases/asthma/pdf/4850.pdf. Accessed April 11, 2011.

17. Picken HA, Greenfield S, Teres D, et al. Effects of local standards on the implementation of national guidelines for asthma: primary care agreement with national asthma guidelines. J Gen Intern Med. 1998;13(10):659-663.

18. Hardie GE, Gold WM, Janson S, et al. Understanding how asthmatics perceive symptom distress during a methacholine challenge. J Asthma. 2002;39(7):611-618.

19. Reddel HK, Marks GB, Jenkins CR. When can personal best peak flow be determined for asthma action plans? Thorax. 2004;59(11):922-924.

20. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis. 1983;127(6):725-734.

21. Ind PW, Dal Negro R, Colman NC, et al. Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma. Respir Med. 2003;97(5):555-562.

22. Price DB, Hernandez D, Magyar P, et al; Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy (COMPACT) International Study Group. Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Thorax. 2003;58(3):211-216.

23. Schatz M, Zeiger RS, Mosen D, et al. Improved asthma outcomes from allergy specialist care: a population-based cross-sectional analysis. J Allergy Clin Immunol. 2005;116(6):1307-1313.

24. Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005;143(3):199-211.

25. Cabana MD, Bruckman D, Meister K, et al. Documentation of asthma severity in pediatric outpatient clinics. Clin Pediatr (Phila). 2003;42(2):121-125.

26. Heater BS, Becker AM, Olson RK. Nursing interventions and patient outcomes: a meta-analysis of studies. Nurs Res. 1988;37(5):303-307.

Woman, 49, With Dyspnea and Chest Tightness