The Role of Chest CT in Evaluation of the Febrile Bone Marrow Transplant Recipient

airway obstruction due to emphysema. N Eng)

J Med 1984;

311:421-25

6 Lefcoe NM, Toogood JH, Blennerhassett G, Baskerville J, Paterson NAM. The addition of an aerosol anticholinergic to an oral beta agonist plus theophylline in asthma and bronchitis. Chest 198; 82:300-()5 7 Light Rw, Conrad SA, George RB. The one best test for evaluating the effects of bronchodilator therapy. Chest 1977; 72:512-16 8 Berger R, Smith D. Acute postbronchodilator changes in pulmonary function parameters in patients with chronic airways obstruction. Chest 1988; 93:541-46

The Role of Chest CT In Evaluation of the Febrile Bone Marrow lhlnsplant Recipient Bone marrow transplantation is used as treatment for a growing number ofdisorders including acute and chronic leukemia, aplastic anemia, lymphoma, and breast cancer. Many factors determine the survival of patients undergoing bone marrow transplantation. In the immediate post-transplantation period prior to successful marrow engraftment, infection remains one of the major causes of morbidity and mortality. 1_. Most infections during this period of profound bone marrow aplasia are due to bacteria and fungi, with the risk of invasive fungal disease increasing proportionally to the depth and duration of granulocytopenia.5 After successful marrow engraftment, viral infections, particularly those due to cytomegalovirus, become an increasing problem.5 Improved survival of patients undergoing bone marrow transplantation depends critically on early detection and appropriate treatment of opportunistic infections that occur during the aplastic period. Unfortunately, early recognition and definitive diagnosis of such infections, including pulmonary infections, are difficult and often elusive.3.6·7 The most common clinical problem is the profoundly neutropenic patient with persistent fever despite broad spectrum antibiotics. Localizing pulmonary symptoms such as cough or pleuritic chest pain may or may not be present. Many of the plain film findings of early lung infection are subtle and nonspecific. Opportunistic fungal and viral organisms are fastidious and difficult to isolate. Sputum cultures are frequently negative early in the course of infection and may not become positive until long after the culture was obtained. The significance of positive cultures obtained noninvasively from the upper respiratory tract is also controversial as to whether isolated organisms represent true infection or merely colonization. Invasive biopsy procedures which might otherwise provide a definitive diagnosis are often prohibited in such patients because of their compromised respiratory status and severe thrombocytopenia. Yields on attempted biopsies are often 7M

disappointingly low. Although the routine use ofbroadspectrum antibiotics has decreased mortality from bacterial infections, empiric treatment of invasive fungal disease with amphotericin B is not without complications, particularly nephrotoxicity. Thus, substantiating evidence to support a clinical suspicion of invasive fungal infection is often desired before an aggressive course of high-dose antifungal therapy is begun. A rapid, noninvasive technique which could facilitate early detection and characterization of pulmonary infection in the bone marrow transplant recipient might be expected to improve survival from opportunistic pulmonary infection. The article by Barloon et al appearing this month (see page 928) adds to a growing body of evidence to suggest that computed tomography (Cf) has become an important noninvasive tool for the evaluation of the febrile patient following bone marrow transplantation. Their work, along with others, underscores the potential role of cr in the aggressive management of opportunistic lung infection through early detection, characterization of pulmonary infiltrates, and determination of disease extent and response to therapy.s- 10 Many questions still remain. Is Cf more sensitive than conventional chest films in detecting early infec-tion in the patient undergoing bone marrow transplantation? In the study by Barloon et al, Cf failed to provide statistically significant additional information in patients with normal chest radiographs, but the study was not designed as a prospective comparison of serial chest films and serial Cf examinations in their respective abilities to detect early lung infection. Circumstantial evidence provided from work on other pulmonary diseases would suggest that cr might be more sensitive in detecting at least certain types of lung infection in this patient population. cr has clearly been shown to be more sensitive than conventional radiographs in the detection of pulmonary nodules and metastases. 11• 1• It would not be surprising, therefore, if cr were found to be more sensitive than conventional plain films in detecting early invasive pulmonary aspergillosis, since the earliest pulmonary lesions in this infection are small inftammatory nodules.15 In addition, conventional radiographs of the chest are often limited in the acutely ill patient by poor inspiratory effort, portable technique, and respiratory motion. Advances in Cf technology and decreases in scan acquisition times have contributed greatly to both the speed and quality of cr examinations, particularly in the immunocompromised host with pulmonary infection. One second and subsecond Cf scan times are now available on many state-of-theart Cf scanners, eliminating many of the earlier problems of respiratory artifacts in the acutely ill patient and allowing diagnostic examinations of the chest to be performed in 10 minutes or less. High-

resolution cr allows visualization of additional detail of the lung parenchyma that further helps to identify and characterize the pulmonary process. Are the cr appearances of pulmonary infections more specific than plain film findings? The purpose of the study by Barloon et al was to determine if Cf provided additional, clinically useful information regarding the presence of pulmonary infection. Although many of the cr findings of pulmonary diseases are nonspecific, the cr findings of invasive fungal disease, particularly invasive pulmonary aspergillosis in this clinical setting, are often distinguishable from other bacterial or viral infections. 10 As Barloon et al point out in their article, being able to identify cr findings of fungal infection in cases where the conventional radiographs remained nonspecific added confidence in the diagnosis of fungal infection and in the appropriateness of aggressive antifungal therapy. Finally, do early detection and characterization of lung infection by cr improve survival and ultimate outcome? Barloon et al concluded from their study that cr does provide significant information in the febrile bone marrow transplant patient with nonspecific chest film findings, but that the mortality is quite high in this group and that it may be difficult to prove definitively that Cf affects outcome. In order to test the ability of cr to affect outcome, one would need to screen all febrile aplastic patients and compare serial chest films to serial cr scans in their ability to detect and characterize early infection, at a time when intervention could affect outcome . Patients in the present study may have had fairly well-established pulmonary infection by the time the cr was performed, since those included in the study were symptomatic patients that the clinical staff suspected of having pulmonary disease, but whose serial chest radipgraphs failed to provide sufficient information to initiate or to continue treatment. It remains to be seen whether serial cr examinations, used as a primary screening modality, may indeed have a significant impact on mortality, particularly from fungal infection. Some clinical evidence does exist to suggest that early presumptive diagnosis of fungal infection with the aid of cr surveillance and rapid institution of aggressive antifungal therapy leads to improved survival.8 cr surveillance has also been used effectively to monitor disease activity, document progression or resolution of fungal infection in response to therapy, and detect reactivation offungal disease during subsequent treatment cycles.9 Whether an improvement in survival from bacterial and viral infections can be demonstrated with the aid of early cr detection has yet to be demonstrated. janet E. Kuhlman, M.D., F.C.C.P. Baltimore The RusseU H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions.

REFERENC ES 1 Hamilton PJ, Pearson ADJ. Bone marrow transplantation and the lung. Thorax 1986; 41:497-502 2 Paulin T, Ringden 0, Nilsson B, Lonnqvist B, Gahrton G . Variables predicting bacterial and fungal infections after allogeneic marrow engraftment. Transplantation 1987; 43:393-98 3 Meyers JD, Flournoy N, Thomas ED. Nonbacterial pneumonia after allogeneic marrow transplantation: a review of ten years' experience. Rev Infect Dis 1982; 4:1119-32 4 Watson JG. Problems of infection after bone marrow transplantation. J Clin Pathol 1983; 36:683-92 5 Winston DJ, Ho WG, Champlin RE , Gale RP. Infectious complications of bone marrow transplantation. Exp Hematol 1984; 12:205-15 6 Meyers RD, Young LS, Armstrong D , Yu D. Aspergillosis complicating neoplastic disease. Am J Med 1973; 54:&-15 7 Aisner J, Schimpf£ JC , Wiernik DH. Treatment of invas.ive aspergiUosis: relation of early diagnosis and treatment to response. Ann Intern Med 1977; 86:539-43 8 Burch PA, Karp JE, Men: WG, Dick JD, Kuhlman JE, Fishman EK. Favorable outcome of invasive aspergiUosis in patients with adult acute leukemia. JClin Oncol I987; 5:1985-93 9 Karp JE, Burch PA, Men: WG. An approach to intensive antileukemia therapy in patients with previous invasive aspergillosis. Am J Med 1988; 85:~ 10 Kuhlman JE, Fishman EK, Siegelman SS. Invasive pulmonary aspergillosis in acute leukemia: Characteristic 6ndings on CT, the CT halo sign, and the role of CT in early diagnosis. Radiology 1985; 157:611-14 11 Schaner EG, Chang AE, Doppman JL, Conkle DM, Flye MW, Rosenberg SA. Comparison ofcomputed and conventional whole lung tomography in detecting pulmonary nodules: a prospective radiologic-pathologic study. AJR 1978; 131:51-4 12 Zerhouni EA, Stitik FP. Siegelman SS, Naidich DP. Sagel SS, Proto AV. et al. CT of the pulmonary nodule: a cooperative study. Radiology 1986; 160:31~27 13 Muhm JR. Brown LR, Crowe JK, Sheedy PF, Hattery RR, Stephen DH. Comparison of whole lung tomography and computed tomography for detecting pulmonary nodules. AJR 1978; 181:981-84 14 McLoud TC, Wittenberg J, Ferrucci JT. Computed tomography of the thorax and standard radiographic evaluation of the chest: a comparative study. JComput Assist Tomogr 1979; 3:17(}.8() 15 Orr DP. Myerowitz RL, Dubois PJ. Pathoradiologic correlation of invasive pulmonary aspergillosis in the compromised host. Cancer 1978; 41:2028-39

Clinical Applications of Forced Oscillation Technique Dubois et al• introduced the forced oscillation technique (FOT) in 1956 as a method to characterize the mechanical properties of the respiratory system over a wide range of frequencies. However, only in the 1970s, when microprocessor techniques became available, allowing the analysis of complex signals by means of the Fourier transform, were more in-depth investigations possible of frequency characteristics of the impedance of the respiratory system and of its two components-the real part or resistance (Rrs), and the imaginary part or reactance (Xrs, which CHEST I 99 I 4 I APRIL, 1991

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