Role of integrated computerized tomography-positron emission tomography (CT-PET) in the management of cryptogenic organizing pneumonia
Article Outline
Summary
Cryptogenic organizing pneumonia (COP), also known as bronchiolitis obliterans organizing pneumonia (BOOP) is emerging to be a frequently recognized pulmonary illness. The management and follow-up of the disease progress remains arbitrary. We present a case of COP where integrated computerized tomography-positron emission tomography (CT-PET) along with blood inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to assess the progress of the disease process. Fluorodeoxyglucose (FDG) activity on CT-PET correlated well with blood inflammatory markers during remission and relapse. To the best of our knowledge, this is the first case report to show such correlation. CT-PET may provide valuable information about the disease activity distinguishing active inflammation from residual fibrosis and thus help to tailor the steroid therapy.
Keywords: Cryptogenic organizing pneumonia, Bronchiolitis obliterans organizing pneumonia, Computerized tomography-positron emission tomography
Case history
A 71-years-old female with known history of cardiac arrhythmia, mild bronchial asthma and osteoporosis, was seen in the clinic with 4 weeks history of dry cough, generalized body aches and low grade temperature. Physical examination was normal except bilateral crackles on both lung bases. Blood tests including complete blood count (CBC) with differential, blood urea and creatinine, liver and thyroid functions, collagen vascular disease screening including anti nuclear antibody (ANA), anti-ds-DNA antibody and anti-neutorophilic cytoplasmic antibody (ANCA) were within normal range. Erythrocyte sedimentation rate (ESR) was raised at 140
mm/h and C-reactive protein (CRP) was 130mg/L. Sputum stains and cultures for bacteria, acid fast bacillus (AFB) and fungi did not reveal any organism. Chest X-ray showed bilateral nodular lung infiltrates and airspace disease. Computerized tomography (CT) of chest showed similar findings (Figure 1).
Figure 1.
CT chest on diagnosis.
Patient was treated initially as community acquired pneumonia with combination of second generation cephalosporin and a macrolide, but failed to show any response. Diagnostic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy was non-conclusive. A video-assisted thoracoscopic (VATS) biopsy was obtained which confirmed the histological diagnosis of Cryptogenic organizing pneumonia (COP).
Patient was started on prednisone at a dose of 1mg/kg and azithromycin 250mg three times a week as steroid sparing and anti-inflammatory agent. Patient showed a rapid clinical response to steroid therapy with sharp decline in the inflammatory markers including CRP and ESR. After 4 weeks of therapy, CT-PET was done to assess lung infiltrates and fluorodeoxyglucose (FDG) activity which showed significant decrease in the lung infiltrates and minimal FDG activity in the areas of infiltrates (Figure 2).
Figure 2.
CT and CT-PET after 4 weeks of treatment showing marked resolution of infiltrates and minimal FDG activity on CT-PET.
After 4 weeks, steroid dose was progressively tapered. At 12 weeks, the patient experienced a relapse in the form of clinical symptoms and increase in CRP and ESR. A CT-PET at this time showed markedly increased lung infiltrates and intense FDG activity in these areas (Figure 3).
Figure 3.
CT chest showing relapse after steroid tapering of steroids with intense FDG-uptake on CT-PET.
Steroid dose was increased to her previous high levels, following which she improved clinically and showed marked decline in her blood inflammatory markers and the lung infiltrates on CT-PET with almost minimal FDG pick up (Figure 4).
Figure 4.
CT chest 4 weeks after steroids dose augmentation sowing residual infiltrates with absence of FDG-uptake on CT-PET.
Blood inflammatory markers, CRP and ESR correlated well with CT-PET finding (Figure 5).
Figure 5.
ESR and CRP levels during diagnosis, remission and relapse.
The patient is currently stable under follow up as an out-patient receiving prednisone and azithromycin.
Discussion
COP is emerging to be a significant medical problem since it was first described by Epler et al.1 in the medical literature. Clinical history and physical examination in COP are usually non specific. Chest X-ray and CT chest findings may suggest the diagnosis,2, 3, 4, 5 but histological confirmation of the diagnosis is warranted. Diagnosis could be established by trans-bronchial biopsy,6 percutaneous lung biopsy7 or open lung biopsy8 but video assisted thoracoscopic biopsy9 is the most commonly used procedure for histological diagnosis.
CT-PET has been used to depict increased glucose metabolism in inflammatory and malignant cells. Diseases such as pneumonia10 bronchiolitis11 radiation pneumonitis12 and sarcoidosis13 frequently show increase FDG activity on PET scan.
However, its use in the diagnosis or management COP has never been described to the best of our knowledge. We hypothesize that since COP is an inflammatory process, it should also reflect an increase glucose metabolism on PET scan.
Monitoring the progress of COP by inflammatory markers14, 15 such as white cell count, ESR and CRP has been recommended, but it remains nonspecific and unreliable. There are no specific guidelines for tailoring the steroid therapy for COP, although an arbitrary steroid schedule of 1mg/kg or 60mg/day for 1–3 months, then 40mg/day for 3 months, tapering down to 10–20mg/day for a period of 1 year is usually suggested.16, 17
Based on our hypothesis we decided to follow-up the progress of our patient's disease with CT-PET not only to assess the progress in lung infiltrates, but also to assess actual disease activity by FDG uptake on PET scan, which should distinguish active inflammation from the residual fibrosis. Blood inflammatory markers ESR and CRP were also used to assess the disease activity which correlated well with disease activity as shown on PET scan in our patient. After steroid therapy, she showed a rapid clinical and radiological response which was also evident from sharp decline in her inflammatory markers. Simultaneously, CT-PET showed significant declined in lung infiltrate with minimal FDG activity. After tapering the steroids dose her disease relapsed which became evident by increased inflammatory markers and an intense FDG activity on PET scan. Augmentation of steroid therapy at this stage was followed by decreased levels of inflammatory markers and marked reductions in lung infiltrates with almost absence of FDG activity on PET scan. Although inflammatory markers correlate well with disease activity but CT-PET scan added significantly to assess the inflammatory activity of lung infiltrates and helped us in tailoring the steroid therapy in our patient. We believe that CT-PET can help to indicate whether pulmonary infiltrates represent active inflammation or residual fibrosis, thus allowing to adjust steroid dosage without subjecting the patient to a relapse or the adverse effects of steroids. CT-PET is still not widely available, expensive, and may not be easy to repeat frequently. However, the situation may change in the future. We also suggest that it may be used in the difficult to manage cases.
In conclusion, we propose that CT-PET has the potential to become a valuable monitoring tool in the follow up of COP patients and may help in the adjustment of steroid therapy. Further prospective studies on larger number of patients are needed to verify our observations.
Conflict of interest statement
None of the authors have a conflict of interest to declare in relation to this work.
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PII: S1755-0017(07)00005-X
doi:10.1016/j.rmedc.2007.12.001
© 2007 Elsevier Ltd. All rights reserved.
