The correct answers are allergic bronchopulmonary aspergillosis and asthma.

Asthma is a chronic inflammatory disease of the airways characterized by hyperresponsiveness to a

variety of stimuli, with symptoms including episodic wheezing and dyspnea. Approximately 75% of cases
of asthma are diagnosed before the patient is 7 years of age, but asthma may develop at any age.
Allergic bronchopulmonary aspergillosis is an allergic pulmonary disorder caused by a hypersensitivity
reaction to aspergillus species. Recurrent shortness of breath, cough, wheezing, and nocturnal worsening
of symptoms may be consistent with allergic bronchopulmonary aspergillosis or asthma.

Incorrect Answers
Vocal-cord dysfunction involves a structurally normal larynx and abnormal adduction of the vocal cords
during breathing. Typically, symptoms are not ameliorated by albuterol, and stridor can be detected on
physical examination.
COPD is a heterogeneous collection of pulmonary diagnoses characterized by chronic and progressive
airflow obstruction that is not fully reversible. The patient’s young age and symptoms are inconsistent with
COPD, particularly given the absence of a history of smoking.
A cough in conjunction with retrosternal burning may be symptomatic of GERD, but shortness of breath
and wheezing are not.
Idiopathic pulmonary fibrosis is an interstitial lung disease characterized by chronic, progressive fibrosis of
the lung parenchyma and restrictive physiological impairment. Although idiopathic pulmonary fibrosis may
cause substantial respiratory distress, wheezing is uncommon.
The correct answer is obstructive process with bronchodilator response.
Spirometry should be performed routinely when the diagnosis of asthma is suspected. During the test, the
patient inhales to the greatest extent possible and then exhales forcefully, rapidly, and completely into a
spirometer. Measurements obtained during spirometry include FEV1 and FVC. An FEV1:FVC ratio of less
than 0.70, or below the 5th percentile, is consistent with obstruction. Diffuse intrathoracic airflow
obstruction is reflected in concave flow-volume loops. The patient’s results reveal an FEV1:FVC ratio of
0.58, and the “scooped-out” pattern of her flow-volume loop is characteristic of obstruction.
Once obstruction is diagnosed, the response to bronchodilator therapy should be assessed.
Responsiveness is defined as an increase in FEV1 of at least 12% and an increase in FEV1 or FVC of at
least 200 ml after the administration of a quick-acting bronchodilator. The patient’s post-bronchodilator
increase in FEV1 of 22% and 300 ml is consistent with a response to bronchodilator therapy.
Bronchodilator response is tested only in patients who show an obstructive defect.

Incorrect Answers
Restrictive disease is characterized by decreased lung compliance and increased elastic recoil, which
result in a reduction in total lung capacity and vital capacity but a normal or increased FEV1:FVC ratio.
Values for total lung capacity and vital capacity that are below the 5th percentile (or less than
approximately 80% of the predicted value) are consistent with restriction. Lung volumes, which were not
measured in this patient, are necessary to make the diagnosis of a restrictive ventilatory defect.
Restriction is indicated by a flow-volume loop with a convex shape, a reduced peak flow, and a rapid,
steep phase that is independent of patient effort.
The most striking abnormality on the patient’s CT scan is the presence of scattered, subpleural,
consolidative opacities in both lungs.

The differential diagnosis for subpleural opacities includes eosinophilic granulomatosis with polyangiitis,
eosinophilic pneumonia, organizing pneumonia, and pulmonary emboli with resulting parenchymal
infarction. Peripheral air-space opacification, a finding associated with allergic bronchopulmonary
aspergillosis, may have an appearance that is similar to that of subpleural opacities on CT, but other CT
findings associated with allergic bronchopulmonary aspergillosis, such as bronchiectasis, ground-glass
attenuation, mucus plugging, and mucus with areas of high attenuation, are not seen on the patient’s CT.

Incorrect Answers
Bronchiectasis can be either local or diffuse. Findings on CT that are consistent with bronchiectasis
include dilatation of the airway lumen, the absence of tapering in an airway near the periphery of the
lungs, varicose structures along airways, and ballooned cysts at the end of a bronchus.
Ground-glass opacities represent areas of hazy, increased attenuation in the lung parenchyma, with
preservation of the bronchial tree and vascular margins. These opacities can be seen in several
conditions, including atypical infections, hypersensitivity pneumonia, several interstitial lung diseases,
sarcoidosis, pulmonary edema, and pulmonary hemorrhage.
Pneumothorax is an abnormal collection of gas between the visceral and parietal pleura of the lung. Small
amounts of gas in the pleural space can be detected on CT.
Small, peripheral pulmonary emboli can result in pulmonary infarction by occluding subsegmental
branches of the pulmonary artery. On CT, pulmonary infarction can appear as a wedge-shaped subpleural
opacification. The subpleural findings on this patient’s CT images are more consistent with subpleural
opacities than with the wedge-shaped lesions that suggest pulmonary infarction.
The correct answers are chronic eosinophilic pneumonia and eosinophilic granulomatosis
with polyangiitis.
The finding of peripheral eosinophilia, the refractory nature of the patient’s symptoms, the negative results
for aspergillus on skin tests, and the normal levels of aspergillus-specific IgE suggest chronic eosinophilic
pneumonia or eosinophilic granulomatosis with polyangiitis. The initial presentation of patients with
eosinophilic granulomatosis with polyangiitis frequently includes symptoms resembling those of asthma,
allergic rhinitis, or atopic disease. After this prodromal phase, subsequent phases of the syndrome are
characterized by peripheral-blood eosinophilia and eosinophilic infiltration of the organs, followed by
necrotizing vasculitis involving small and medium-sized arteries, with granuloma formation.
Patients with any one of these conditions may present with symptoms similar to those of asthma, but
these conditions can be distinguished from asthma with further testing. Chronic eosinophilic pneumonia is
often characterized by cough, shortness of breath, and wheezing on physical examination, and a
prominent eosinophilia is often seen.

Incorrect Answers
Although there are objective data that support the diagnosis of asthma, such as airflow obstruction that
abates in response to bronchodilator therapy, expiratory wheezing remains on physical examination, and
the patient’s symptoms have progressed despite her adherence to appropriate and maximal medical
therapy for asthma. Asthma alone can cause peripheral eosinophilia, but rarely to the degree observed in
this patient.
The eosinophilia and the patient’s refractory symptoms are consistent with allergic bronchopulmonary
aspergillosis, but the normal results on an aspergillus skin test and the normal levels of aspergillus-
specific IgE make this diagnosis unlikely.
Given her place of birth and elevated serum IgE level, infection with Strongyloides stercoralis must be
considered, but it was ruled out by the normal results on antibody tests. Chronic strongyloidiasis can
cause asthma-like symptoms that usually worsen on treatment with glucocorticoids, which is the treatment
of choice for eosinophilic granulomatosis with polyangiitis.
The correct answer is necrotizing vasculitis.
Biopsy specimens from affected organ tissue in patients with eosinophilic granulomatosis with polyangiitis
typically reveal vasculitis of the small and medium-sized vessels, necrosis, and the extravascular
infiltration of eosinophils. Biopsy specimens from the lungs in patients with chronic eosinophilic
pneumonia typically reveal the accumulation of eosinophils and lymphocytes in alveoli and the interstitium.
Vasculitis can also be seen in patients with chronic eosinophilic pneumonia, but granulomas and necrosis
are absent. Although chronic eosinophilic pneumonia can be associated with atopy, the disease typically
affects patients in their 30s and 40s.
The finding of necrotizing vasculitis supports a diagnosis of eosinophilic granulomatosis with polyangiitis.
At this time, there is no evidence of extrapulmonary vasculitis, which can occur with eosinophilic
granulomatosis with polyangiitis (and which further distinguishes this condition from chronic eosinophilic
pneumonia), but the patient should be monitored for the development of extrapulmonary vasculitis.

Incorrect Answers
Because the patient’s clinical presentation is not consistent with a neoplastic process, malignant cells
would not be expected. If a malignant process were involved, metastatic disease to the lung would be the
most probable diagnosis.
Bacterial and fungal pneumonia are also inconsistent with the patient’s presentation, given the absence of
fever, productive cough, or any of the typical radiographic infiltrates associated with these diagnoses.
The correct answer is prednisone.
Glucocorticoids are the first-line treatment for eosinophilic granulomatosis with polyangiitis. Longitudinal
data have suggested that the majority of patients with eosinophilic granulomatosis with polyangiitis who
were treated with prednisone had remission; however, the majority of patients who had remission also had
relapse within the next few years.

Incorrect Answers
Cyclophosphamide is used as adjuvant therapy in patients who have a relapse during or after
glucocorticoid treatment or who have substantial vasculitic end-organ involvement. Cyclophosphamide is
also used in patients who do not have a response to glucocorticoids.
Azathioprine — and less frequently, methotrexate — is typically used after the induction of remission with
cyclophosphamide or as a glucocorticoid-sparing agent in patients who require long-term treatment with
prednisone at higher doses. Case reports and series have described clinical improvement in patients
treated with plasma exchange or intravenous immune globulin.
A recent randomized, controlled trial reported that the addition of an anti–interleukin-5 monoclonal
antibody (mepolizumab) to a stable regimen of glucocorticoids in patients with relapsing or refractory
eosinophilic granulomatosis with polyangiitis resulted in greater achievement and maintenance of
symptom remission than did the addition of placebo.