A Case of "Refractory Asthma"

A 43-year-old African American woman presented to the emergency department with severe dyspnea, wheeze, and cough productive of white sputum. Three years earlier, she had been given a diagnosis of asthma based on symptoms of wheeze and cough; her treatment regimen included intermittent use of albuterol.

The patient’s present symptoms began approximately 2 weeks ago and progressively worsened over the preceding 4 days. She denied chest pain, fever, and chills but noted extreme fatigue when attempting her daily activities. In addition to asthma, she has a 30-pack-year smoking history. Two primary care visits in the preceding 2 weeks resulted in empiric treatment for an infectious asthma flare with oral prednisone(Drug information on prednisone) (30 mg once daily), azithromycin(Drug information on azithromycin) (7-day course), inhaled fluticasone(Drug information on fluticasone), and as-needed albuterol inhaler. Her albuterol use had escalated to at least 6 times a day, with only modest symptom relief.

On initial examination, the patient was in extremis, sitting upright in bed, using accessory respiratory muscles, and unable to complete sentences because of severe dyspnea. Vital signs were as follows: temperature, 37°C (98.6°F); respiratory rate, 28 breaths per minute; heart rate, 120 beats per minute; and oxygen saturation on room air, 85%. Chest auscultation revealed bilateral diffuse coarse crackles and wheeze. A chest radiograph demonstrated prominence of the interstitial markings (Figure 1).

The patient was admitted with a tentative diagnosis of infectious exacerbation of asthma and pneumonia. She was treated with oxygen via nasal cannula (4 L/min); intravenous hydrocortisone(Drug information on hydrocortisone), levofloxacin, and metronidazole(Drug information on metronidazole); nebulized albuterol every 4 hours; and smoking cessation counseling. A pulmonary consultation was requested on day 5 because the patient did not have an appreciable clinical response to therapy. A CT scan of the chest revealed bilateral, diffuse, ground-glass opacities without significant air trapping (Figure 2).

Bronchoscopy was subsequently performed. Findings included clear secretions and thick mucous plugs. Bronchoalveolar lavage (BAL) and transbronchial biopsy specimens were obtained from the right upper and lower lobes. The BAL fluid was negative for fungi, Mycobacterium tuberculosis, and viruses; cytological examination of the specimens yielded negative results. Bacterial culture revealed rare Klebsiella pneumoniae that was sensitive to levofloxacin(Drug information on levofloxacin). The presumed diagnoses at this time remained asthma flare with diffuse mucous plugging and pneumonia caused by K pneumoniae.

The patient’s symptoms, exercise tolerance, and oxygen requirement improved gradually, and she was discharged 5 days later with portable oxygen, a 10-day oral prednisone taper, inhaled fluticasone, and nebulized albuterol. Outpatient pulmonary and smoking cessation follow-up appointments 1 week later were missed, and the patient did not return until 8 weeks later, when she reported that her respiratory status remained unchanged. Pulmonary function test results are shown in the Table.

A repeated CT scan revealed persistent ground-glass infiltrates. The patient underwent a thoracoscopic biopsy. A low-power view of the specimen is shown in Figure 3.

What is causing this young woman’s asthma exacerbation and ground-glass infiltrates? How would you proceed?

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