of bronchiolitis obliterans syndrome, although additional studies are needed [47]. Other potential approaches include photopheresis, total lymphoid irradiation, long-term azithromycin, plasmapheresis, and inhaled cyclosporine [47].

Difuse Panbronchiolitis

The optimal therapy is still unknown. Low doses of oral erythromycin (200–600 mg/day) or clarithromycin (250 or 500 mg/ day) or azithromycin have been used for most patients [55]. Erythromycin impairs neutrophil chemotaxis, neutrophil superoxide production, and neutrophil-derived elastolytic activity and decreases the number of neutrophils in BAL uid, following challenge with Gram-negative bacteria [2, 3]. Erythromycin has also been shown to reduce the circulating pool of T lymphocytes bearing HLA-DR, a marker of cellular activation. Azithromycin appears to work by targeting cytokine production, proliferation, apoptosis, and autophagy of T cells [56].

Follicular Bronchiolitis

Follicular bronchiolitis is usually treated as part of the underlying disease, whether it is a connective tissue or associated with immunodefciency [3]. Successful treatment of RA-related follicular bronchiolitis with macrolides has been reported [57]. Corticosteroids have been used, with relapses occurring when steroids are tapered [58].

Airway-Centered Interstitial Fibrosis

The optimal treatment for airway-centered interstitial fbrosis is not known. Glucocorticoid therapy has been tried with limited success.

Proliferative Bronchiolitis

Glucocorticoids are commonly employed and are quite effective in cases of proliferative bronchiolitis, particularly when it is associated with organizing pneumonia (e.g., cryptogenic organizing pneumonia). A common approach is to start with prednisone 0.5–1 mg/kg lean body weight per day to a maximum of 60 mg per day, administered as a single oral dose in the morning. Prednisone is gradually tapered over 3–6 months. Relapses have been reported with the premature cessation of glucocorticoid therapy in some of these patients.

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Clinical Vignette

A 30-year-old man with a history of severe persistent asthma since childhood was referred for consultation for presumed chronic Aspergillus infection that was being treated with voriconazole therapy.

He was a lifelong nonsmoker. His lifelong asthma was associated with atopic dermatitis and chronic allergic rhinosinusitis. He was treated with an inhaled corticosteroid and a long-acting beta-agonist. Two years prior to the current presentation, he was diagnosed at an outside hospital with “semi-invasive” Aspergillus pulmonary infection after presenting with chills, cough productive of sputum, and shortness of breath. Chest CT imaging showed a right middle lobe pulmonary opacity. Sputum culture and CT-guided lung biopsy grew Aspergillus fumigatus. He was treated with oral itraconazole for 6 months with clinical and radiographic improvement.

Two years later, he noted fever, cough productive of brown sputum, dyspnea, and wheezing. Repeat chest CT imaging showed a large right lung opacity and smaller left lung opacities, and the sputum culture grew Aspergillus fumigatus for which he was begun on voriconazole 200 mg twice a day (BID) for presumptive recurrent Aspergillus infection. Our evaluation revealed a thin man with no distress. On auscultation, he had no wheezing. There was no clubbing. White

D. Stahlbaum (*) · M. E. Strek

Pulmonary and Critical Care, University of Chicago, Chicago, IL, USA

e-mail: danielle.stahlbaum@uchospitals.edu; mstrek@medicine.bsd.uchicago.edu

K. Patterson

Respiratory Medicine, Brighton and Sussex Medical School, Brighton, UK

e-mail: k.patterson@bsms.ac.uk

blood cell count was 13.4 k/μL with 8.3% eosinophils. Serum immunoglobulin E was 5355 IU/mL. Spirometry showed moderately severe air ow obstruction with a forced vital capacity (FVC) of 4.30 L (78% predicted) and a forced expiratory volume in the frst second (FEV1) of 2.28 L (53% predicted) with 32% improvement after the use of the inhaled bronchodilator. Reviews of prior and current chest radiographs (Fig. 4.1) and CT chest imaging (Fig. 4.2) by thoracic radiology revealed additional fndings of central bronchiectasis, hyperdense mucus plugging, and eeting parenchymal opacities.

The constellation of severe persistent asthma, bronchiectasis, eosinophilia, elevated IgE level with Aspergillus in the sputum, and CT scans showing hyperdense mucus plugging with eeting pulmonary parenchymal opacities was highly suggestive of allergic bronchopulmonary aspergillosis (ABPA). The diagnosis was further solidifed by a high-titer positive serum IgE to A. fumigatus. The patient declined oral corticosteroids but preferred to continue on voriconazole with resolution of the cough, sputum, dyspnea and wheezing, a decline in the absolute eosinophil count to 500 and serum IgE to 2425 IU/mL, and improvement in the parenchymal opacities. After 6 months of therapy, he required dose reduction of the voriconazole to 200 mg daily for elevated levels of hepatic function tests. After a total of 12 months of therapy, at which time the serum IgE was 1000 IU/mL, voriconazole was discontinued. Two months later, he noted fatigue, cough with brown mucus plugs, and wheezing. His serum IgE was increased to 3814 IU/ mL. He was restarted on voriconazole 200 mg daily, but, despite therapeutic levels, he did not improve. What therapies should be prescribed?