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Pulmonary Disease in the Immunocompromised Host (First of Two Parts)

1985; Elsevier BV; Volume: 60; Issue: 7 Linguagem: Inglês

10.1016/s0025-6196(12)60872-6

1942-5546

Edward C. Rosenow, Walter R. Wilson, Franklin R. Cockerill,

Pneumocystis jirovecii pneumonia detection and treatment

With few exceptions, pulmonary complications in the immunocompromised host will proceed to death unless the clinician intercedes. The differential diagnosis of diffuse pulmonary disease in this setting includes (1) infection, most commonly from opportunistic organisms; (2) recurrence or extension of the basic underlying disease process to involve the lungs; (3) adverse pulmonary reaction to drugs; (4) a new, unrelated disease process such as cardiac pulmonary edema or pulmonary emboli; and (5) any combination of these categories. Up to a third of these patients have two or more complications, such as pneumonitis from two different opportunistic organisms or an opportunistic infection and a drug-induced pulmonary complication. An understanding of the host defense that is compromised enables the clinician to narrow the differential diagnosis. The most common types of impairment of defense mechanisms are reductions in the number of granulocytes, B-lymphocytes, or T-lymphocytes, and not uncommonly, two or all three of these types of cells are involved. Impairment of each of these cell types is associated with an increased frequency of infection by a particular group of organisms. Consequently, the clinician can be somewhat selective if empiric therapy is being considered. In the immunocompromised patient, most pulmonary complications, including drug-induced pulmonary disease and pulmonary emboli, are associated with fever that mimics an infection. Up to 25% of the pulmonary complications in these patients are noninfectious. With few exceptions, pulmonary complications in the immunocompromised host will proceed to death unless the clinician intercedes. The differential diagnosis of diffuse pulmonary disease in this setting includes (1) infection, most commonly from opportunistic organisms; (2) recurrence or extension of the basic underlying disease process to involve the lungs; (3) adverse pulmonary reaction to drugs; (4) a new, unrelated disease process such as cardiac pulmonary edema or pulmonary emboli; and (5) any combination of these categories. Up to a third of these patients have two or more complications, such as pneumonitis from two different opportunistic organisms or an opportunistic infection and a drug-induced pulmonary complication. An understanding of the host defense that is compromised enables the clinician to narrow the differential diagnosis. The most common types of impairment of defense mechanisms are reductions in the number of granulocytes, B-lymphocytes, or T-lymphocytes, and not uncommonly, two or all three of these types of cells are involved. Impairment of each of these cell types is associated with an increased frequency of infection by a particular group of organisms. Consequently, the clinician can be somewhat selective if empiric therapy is being considered. In the immunocompromised patient, most pulmonary complications, including drug-induced pulmonary disease and pulmonary emboli, are associated with fever that mimics an infection. Up to 25% of the pulmonary complications in these patients are noninfectious. The immunocompromised host (ICH), a person whose defense mechanisms are impaired, is increasingly a product of progress. A few decades ago, only radiation therapy and a few chemotherapeutic agents such as nitrogen mustard might have affected a patient's immune system. Most patients died of their basic disease before complications related to impairment of their defense mechanisms could develop. Today, almost any physician—not just the infectious disease specialist, pulmonologist, hematologist, and oncologist—might encounter an immunocompromised patient. For example, the surgeon who is asked to perform an emergency biopsy, the anesthesiologist, the pathologist, and the primary-care physician should be aware of the diseases, drugs, and chemotherapeutic agents that might impair function of the immune system. In this review, we will discuss only the acquired forms of immunosuppression (Table 1) and in particular the pulmonary diseases that afflict the ICH.Table 1Defense Mechanism Impairment ("The Compromised Host") and Involved Organisms in Specific Diseases or Conditions*Diseases that may cause no host defense impairment until they are treated:ConditionDefense mechanism impairedOrganism involved Lymphoproliferative disorders Acute and chronic lymphocytic leukemiaNon-Hodgkin's lymphomaMultiple myelomaHypogammaglobulinemia, acquired and congenitalDrug therapy CorticosteroidsAlkylating agentsAntimetabolitesB-lymphocyte disease (impaired antibody formation) Streptococcus pneumoniaePseudomonas aeruginosaOther gram-negative organismsPneumocystis and cytomegalovirus Lymphoma Hodgkin's diseaseNon-Hodgkin's lymphomaCarcinoma and sarcoma (usually widespread or metastatic; unrelated to drug reaction or treatment)Renal insufficiencyAcquired immunodeficiency syndromeDrug therapy CorticosteroidsAlkylating agentsAntimetabolitesIrradiation T-lymphocyte (cell-mediated immunity) Cryptococci and other fungiMycobacterium tuberculosisHerpes group viruses including cytomegalovirusPneumocystisToxoplasmaLegionellaNocardiaCandida speciesListeria Myeloproliferative disorders Acute and chronic myelocytic leukemiaAgnogenic myeloid metaplasiaDrug therapy CorticosteroidsDrugs suppressing granulocytes Impaired or reduced granulocyte functionAltered inflammatory response Escherichia coliPseudomonasKlebsiellaAspergillusStaphylococcus aureusSerratiaCandida speciesNocardiaHaemophilus influenzaeOrgan transplantationDepends on the underlying disease and immunosuppressive drugs used 1.Any of the above-listed conditions when early or localized.2.Connective tissue disorders such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, Wegener's granulomatosis, and Goodpasture's syndrome.3.Acute leukemia.* Diseases that may cause no host defense impairment until they are treated: Open table in a new tab 1.Any of the above-listed conditions when early or localized.2.Connective tissue disorders such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, Wegener's granulomatosis, and Goodpasture's syndrome.3.Acute leukemia. The lungs are involved in most complications in the ICH; if the lung disease is diffuse, the mortality approaches 50%.1Bode FR Paré JA Fraser RG Pulmonary diseases in the compromised host: a review of clinical and roentgenographic manifestations in patients with impaired host defense mechanisms.Medicine (Baltimore). 1974; 53: 255-293Crossref PubMed Google Scholar, 2Pennington JE Feldman NT Pulmonary infiltrates and fever in patients with hematologic malignancy: assessment of transbronchial biopsy.Am J Med. 1977; 62: 581-587Abstract Full Text PDF PubMed Google Scholar, 3Nash G Pathologic features of the lung in the immunocompromised host.Hum Pathol. 1982; 13: 841-858Abstract Full Text PDF PubMed Google Scholar, 4Singer C Armstrong D Rosen PP Walzer PD Yu B Diffuse pulmonary infiltrates in immunosuppressed patients: prospective study of 80 cases.Am J Med. 1979; 66: 110-120Abstract Full Text PDF PubMed Google Scholar Most immunocompromised patients with diffuse pulmonary infiltrates have typical manifestations: fever, nonproductive cough, dyspnea, abnormal chest roentgenographic findings, anemia of various degrees, normal or low leukocyte count, and a low platelet count. Usually the PaO2 is low. The chest roentgenogram is never diagnostic of a single entity. Even at autopsy, however, an exact etiologic diagnosis eludes the pathologist and bacteriologist in 15 to 20% of cases.4Singer C Armstrong D Rosen PP Walzer PD Yu B Diffuse pulmonary infiltrates in immunosuppressed patients: prospective study of 80 cases.Am J Med. 1979; 66: 110-120Abstract Full Text PDF PubMed Google Scholar Consequently, any report of a specific diagnosis in 80 to 100% of cases of transbronchoscopic or open-lung biopsy may be questionable. Furthermore, establishing a precise cause of the pulmonary disease with an invasive procedure does not necessarily alter or improve the overall outcome by more than 10 to 20%. Pulmonary infection occurs in about 75% of the pulmonary complications in the ICH—but in more than 90% if the patient has severe neutropenia (less than 500 neutrophils/mm3) or if the lung process is focal. In Part 1 of this review, the noninfectious pulmonary complications in the ICH will be addressed. Part 2 (to be published in the August issue of the Proceedings) will discuss infections in immunocompromised patients with pulmonary infiltrates and the appropriate diagnostic approaches to such conditions. The few previously published reports on pulmonary problems in the ICH have focused on specific disease entities1Bode FR Paré JA Fraser RG Pulmonary diseases in the compromised host: a review of clinical and roentgenographic manifestations in patients with impaired host defense mechanisms.Medicine (Baltimore). 1974; 53: 255-293Crossref PubMed Google Scholar, 2Pennington JE Feldman NT Pulmonary infiltrates and fever in patients with hematologic malignancy: assessment of transbronchial biopsy.Am J Med. 1977; 62: 581-587Abstract Full Text PDF PubMed Google Scholar, 3Nash G Pathologic features of the lung in the immunocompromised host.Hum Pathol. 1982; 13: 841-858Abstract Full Text PDF PubMed Google Scholar, 4Singer C Armstrong D Rosen PP Walzer PD Yu B Diffuse pulmonary infiltrates in immunosuppressed patients: prospective study of 80 cases.Am J Med. 1979; 66: 110-120Abstract Full Text PDF PubMed Google Scholar, 5Williams DM Krick JA Remington JS Pulmonary infection in the compromised host.Am Rev Respir Dis. 1976; 114 (593-627): 359-394PubMed Google Scholar, 6Matthay RA Greene WH Pulmonary infections in the immunocompromised patient.Med Clin North Am. 1980; 64: 529-551PubMed Google Scholar, 7Krick JA Remington JS Opportunistic invasive fungal infections in patients with leukaemia and lymphoma.Clin Haematol. 1976; 5: 249-310PubMed Google Scholar, 8Valdivieso M Gil-Extremera B Zornoza J Rodriguez V Bodey GP Gram-negative bacillary pneumonia in the compromised host.Medicine (Baltimore). 1977; 56: 241-254Crossref PubMed Google Scholar, 9Greenman RL Goodall PT King D Lung biopsy in immunocompromised hosts.Am J Med. 1975; 59: 488-496Abstract Full Text PDF PubMed Google Scholar, 10Jaffe JP Maki DG Lung biopsy in immunocompromised patients: one institution's experience and an approach to management of pulmonary disease in the compromised host.Cancer. 1981; 48: 1144-1153Crossref PubMed Google Scholar, 11Rossiter SJ Miller DC Churg AM Carrington CB Mark JBD Open lung biopsy in the immunosuppressed patient: is it really beneficial?.J Thorac Cardiovasc Surg. 1979; 77: 338-345PubMed Google Scholar, 12Masur H Shelhamer J Parrillo JE The management of pneumonias in immunocompromised patients.JAMA. 1985; 253: 1769-1773Crossref PubMed Google Scholar rather than on the overall scope of in volvement. Approximately a third of the patients, however, have two or more complications—such as two or three different opportunistic lung infections, a lung infection and drug-induced lung disease, or infection and recurrent lymphoma. Thus, the clinician must be aware of all possible types of complications. Table 2 lists five categories of pulmonary disease in the ICH. Each of these categories should be considered in every immunocompromised patient.Table 2Five Categories of Pulmonary Disease in the Immunocompromised Host Extension of basic underlying disease process to involve the lungsOpportunistic infection (or infections)Pulmonary reaction to drugsA new, unrelated disease processAny combination of the above items Open table in a new tab The systemic host defense mechanisms are listed in Table 1. Impairment of the number or the function of the T cells, B cells, or granulocytes compromises the resistance of the host to infection and to immunosurveillance. Some diseases cause an impairment of one or more of these mechanisms, but in most patients, the impairment is brought about by the effect of drugs on the immune system of the leukocyte. For example, suppression of the immune system is necessary for a successful transplantation; in this setting, secondary infections can occur. Table 1 also shows the host defense mechanisms that are impaired and the most likely organisms that act as opportunists in this setting. This format helps to narrow the differential diagnosis. These patients, however, are also prone to acquire a nosocomial infection superimposed on the preexisting pulmonary complication that prompted hospitalization.13LaForce FM Hospital-acquired gram-negative rod pneumonias: an overview.Am J Med. 1981; 70: 664-669Abstract Full Text PDF PubMed Google Scholar, 14Young LS Nosocomial infections in the immunocompromised adult.Am J Med. 1981; 70: 398-404Abstract Full Text PDF PubMed Google Scholar, 15Johanson Jr, WG Higuchi JH Chaudhuri TR Woods DE Bacterial adherence to epithelial cells in bacillary colonization of the respiratory tract.Am Rev Respir Dis. 1980; 121: 55-63PubMed Google Scholar Other mechanisms that impair host defense are splenectomy (surgical removal or autosplenectomy) and a break in the mucocutaneous barrier such as occurs with prolonged intravascular catheterization or nasogastric intubation. Systemic Candida infection is more common in persons who have a mucocutaneous break than in other patients. Of the conditions listed in Table 1 that could involve the lungs, the most common are malignant lesions (particularly the lymphomas and leukemias), organ and bone marrow transplantation, noninfectious complications of renal insufficiency, connective tissue disorders, and, most recently, acquired immunodeficiency syndrome (AIDS). These conditions will be discussed individually. Metastasis to the lungs occurs in up to a third of the patients who die of cancer. The initial manifestations and the roentgenographic picture of hematogenous or lymphangitic infiltrates are fairly characteristic. Usually, metastatic carcinoma or sarcoma is not associated with fever, and it rarely occurs even subacutely. Rather, it tends to occur insidiously and does not mimic an infection or a drug reaction; the rare exception is some fungal infections that can be indolent and can mimic nodular metastasis. Metastatic lesions can frequently be diagnosed on the basis of results of induced sputum cytology, fiberbronchoscopy and transbronchoscopic lung biopsy, or transthoracic needle aspiration. The diagnostic yield with use of these studies varies from 50 to 90%. The hematologic malignant lesions that occur in the lungs present the greatest challenge, as they are difficult to diagnose unless mediastinoscopy or a thoracotomy is performed. Nonetheless, lymphomas tend to recur in the lungs and mediastinal nodes with enough regularity that recurrent lesions must be considered in every patient with a known lymphoma. They account for almost two thirds of the ICHs in whom pulmonary problems are encountered.1Bode FR Paré JA Fraser RG Pulmonary diseases in the compromised host: a review of clinical and roentgenographic manifestations in patients with impaired host defense mechanisms.Medicine (Baltimore). 1974; 53: 255-293Crossref PubMed Google Scholar, 4Singer C Armstrong D Rosen PP Walzer PD Yu B Diffuse pulmonary infiltrates in immunosuppressed patients: prospective study of 80 cases.Am J Med. 1979; 66: 110-120Abstract Full Text PDF PubMed Google Scholar, 9Greenman RL Goodall PT King D Lung biopsy in immunocompromised hosts.Am J Med. 1975; 59: 488-496Abstract Full Text PDF PubMed Google Scholar Greenman and associates9Greenman RL Goodall PT King D Lung biopsy in immunocompromised hosts.Am J Med. 1975; 59: 488-496Abstract Full Text PDF PubMed Google Scholar further noted that 50% of their patients with lymphoma had biopsy evidence of a lymphomatous infiltrate in the lungs. On a chest roentgenogram, lymphoma can mimic other pulmonary processes such as infection or drug reaction. Radiologically, pulmonary lymphomas can be nodules (most often the lesions are multiple rather than single, and some of them cavitate), a localized infiltrate, a diffuse process, or an infiltrate that extends directly into the lung parenchyma from the mediastinal adenopathy.16Kaplan HS Hodgkin's Disease. Second edition. Harvard University Press, Cambridge1980: 146-235Google Scholar Pleural effusion occurs in almost a third of the patients. Mediastinal and hilar lymphadenopathy is common in ICHs who have intrathoracic lymphomatous disease but is less common if they have had prior mediastinal irradiation. Fever is frequently present. Several facts are useful in determining whether the chest roentgenographic abnormality is a lymphoma or some other process.17Sakula A Primary malignant lymphoma of lung.Postgrad Med J. 1979; 55: 46-49Crossref PubMed Google Scholar Lung involvement occurs initially in 5 to 20% and eventually in 20 to 60% of patients with lymphoma—and more commonly in those who have Hodgkin's disease.18Filly R Blank N Castellino RA Radiographic distribution of intrathoracic disease in previously untreated patients with Hodgkin's disease and non-Hodgkin's lymphoma.Radiology. 1976; 120: 277-281PubMed Google Scholar, 19Whitcomb ME Schwarz MI Keller AR Flannery EP Blom J Hodgkin's disease of the lung.Am Rev Respir Dis. 1972; 106: 79-85PubMed Google Scholar, 20Ultmann JE Cunningham JK Gellhorn A The clinical picture of Hodgkin's disease.Cancer Res. 1966; 26: 1047-1060PubMed Google Scholar, 21Peckham MJ Lung involvement.in: Smithers D Hodgkin's Disease. Churchill Livingstone, New York1973: 118-127Google Scholar, 22Strickland B Intra-thoracic Hodgkin's disease. II. Peripheral manifestations of Hodgkin's disease in the chest.Br J Radiol. 1967; 40: 930-938Crossref PubMed Google Scholar, 23Manoharan A Pitney WR Schonell ME Bader LV Intrathoracic manifestations in non-Hodgkin's lymphoma.Thorax. 1979; 34: 29-32Crossref PubMed Google Scholar, 24Macdonald JB Lung involvement in Hodgkin's disease.Thorax. 1977; 32: 664-667Crossref PubMed Google Scholar, 25Rosenberg SA Diamond HD Jaslowitz B Craver LF Lymphosarcoma: a review of 1269 cases.Medicine (Baltimore). 1961; 40: 31-84Crossref PubMed Google Scholar Nodular sclerosing Hodgkin's disease is the type of lymphoma that most frequently involves the lung parenchyma; if the patient has not received radiation treatment, the mediastinal and hilar nodes will usually be enlarged (Fig. 1). If the cell type is lymphocytic-depleted or non-Hodgkin's lymphoma, however, nodal enlargement is less likely to accompany the lung parenchymal involvement. If the patient has received irradiation to the mediastinum, relapses involving the lungs are infrequently associated with lymph node involvement and lymphadenopathy.26Castellino RA Blank N Cassady JR Kaplan HS Roentgenologic aspects of Hodgkin's disease. II. Role of routine radiographs in detecting initial relapse.Cancer. 1973; 31: 316-323Crossref PubMed Google Scholar, 27Lee CKK Bloomfield CD Levitt SH Results of lung irradiation for Hodgkin's disease patients with large mediastinal masses and/or hilar disease.Cancer Treat Rep. 1982; 66: 819-825PubMed Google Scholar, 28Costello P Mauch P Radiographic features of recurrent intrathoracic Hodgkin's disease following radiation therapy.Am J Roentgenol. 1979; 133: 201-206Crossref PubMed Google Scholar Castellino and associates,26Castellino RA Blank N Cassady JR Kaplan HS Roentgenologic aspects of Hodgkin's disease. II. Role of routine radiographs in detecting initial relapse.Cancer. 1973; 31: 316-323Crossref PubMed Google Scholar however, reported that 21% of recurrent or relapsing lesions can occur within sites of previous treatment or adjacent fields (marginal recurrences); thus, mediastinal adenopathy can occur in previously radiated areas. If low-dose whole-lung irradiation is given along with mantle irradiation, the frequency of intrathoracic recurrence is substantially reduced.26Castellino RA Blank N Cassady JR Kaplan HS Roentgenologic aspects of Hodgkin's disease. II. Role of routine radiographs in detecting initial relapse.Cancer. 1973; 31: 316-323Crossref PubMed Google Scholar, 27Lee CKK Bloomfield CD Levitt SH Results of lung irradiation for Hodgkin's disease patients with large mediastinal masses and/or hilar disease.Cancer Treat Rep. 1982; 66: 819-825PubMed Google Scholar Bronchoscopy and biopsy or transthoracic needle aspiration has a low yield for detection of lymphoma, and open-lung biopsy is frequently necessary for confirmation of the occurrence of lymphoma in the lung.29Harlan JM Fennessy JJ Gross NJ Bronchial brush biopsy in Hodgkin's disease.Chest. 1974; 66: 136-138Crossref PubMed Google Scholar In 60 to 80% of patients with leukemia, a pulmonary infiltrate will develop some time during the course of the disease; in some studies, more than 90% have had a pulmonary infiltrate on a preterminal chest roentgenogram.30Tenholder MF Hooper RG Pulmonary infiltrates in leukemia.Chest. 1980; 78: 468-473Crossref PubMed Google Scholar, 31Maile CW Moore AV Ulreich S Putman CE Chest radiographic-pathologic correlation in adult leukemia patients.Invest Radiol. 1983; 18: 495-499Crossref PubMed Google Scholar, 32Bodey GP Powell Jr, RD Hersh EM Yeterian A Freireich EJ Pulmonary complications of acute leukemia.Cancer. 1966; 19: 781-793Crossref PubMed Google Scholar, 33Wardman AG Milligan DW Child JA Delamore IW Cooke NJ Pulmonary infiltrates and adult acute leukaemia: empirical treatment and survival related to the extent of pulmonary radiological disease.Thorax. 1984; 39: 568-571Crossref PubMed Google Scholar, 34Bedrossian CWM Luna MA Conklin RH Miller WC Alveolar proteinosis as a consequence of immunosuppression: a hypothesis based on clinical and pathologic observations.Hum Pathol. 1980; 11: 527-535PubMed Google Scholar Table 3 lists the potential causes of pulmonary disease in patients with leukemia. Although infection is the most common cause (Balducci and associates35Balducci L Halbrook JC Chapman SW Vance RB Thigpen JT Morrison FS Acute leukemia and infections: perspectives from a general hospital.Am J Hematol. 1983; 15: 57-63Crossref PubMed Google Scholar reported a 71% incidence of infection in patients with acute leukemia, almost half of which were respiratory tract infections), the frequency of occurrence is almost directly proportional to the degree of neutropenia. The untreated patient with leukemia generally has an intact T-cell and B-cell population; thus, opportunistic infections other than from bacteria are uncommon before treatment. Pulmonary infiltrates in the untreated patient with leukemia are caused by bacterial pneumonia, leukemic infiltrates (Fig. 2), or hemorrhage.Table 3Causes of Pulmonary Disease in Patients With Leukemia InfectionLeukemic infiltrationDrug effectHemorrhageLeukostasisLeukemic cell lysis pneumonopathyHyperleukocytic reactionAlveolar proteinosis Open table in a new tab Tenholder and Hooper30Tenholder MF Hooper RG Pulmonary infiltrates in leukemia.Chest. 1980; 78: 468-473Crossref PubMed Google Scholar provided a perspective in their study of 139 patients with leukemia, 63% of whom had one or more episodes of localized or diffuse pulmonary infiltrates. Seventeen episodes occurred before and 81 occurred during treatment. Before treatment, patients with localized disease usually had bacterial pneumonia, whereas those with diffuse disease usually had noninfectious conditions, including leukemic infiltration, hemorrhage, or cardiac edema. Interesting findings were noted during treatment. If the process was local, it was an infection 74% of the time, but only 10% of these cases were opportunistic infections. In contrast, if the diffuse disease was due to an infection (as it was in 35%), then almost all were opportunistic infections. These investigators concluded that a localized pulmonary infiltrate detected before or during treatment in a patient with leukemia should be treated with an antibacterial agent before an invasive diagnostic procedure is attempted. In decreasing order of frequency, the causes of the diffuse disease in the treated patients were infection, hemorrhage, leukemic infiltration, and cardiac pulmonary edema. In an autopsy study of patients who had had leukemia, Maile and associates31Maile CW Moore AV Ulreich S Putman CE Chest radiographic-pathologic correlation in adult leukemia patients.Invest Radiol. 1983; 18: 495-499Crossref PubMed Google Scholar found infectious pulmonary infiltrates in 57%, pleural effusion in 40%, leukemic infiltration in 26%, and lymphadenopathy in 17%. They reported that pulmonary infection was the most common cause of chest roentgenographic opacities. In various published reports of patients who had had leukemia, pulmonary infiltrates were found in 25 to 64% at autopsy, but this involvement was not evident roentgenographically in more than half of these cases.1Bode FR Paré JA Fraser RG Pulmonary diseases in the compromised host: a review of clinical and roentgenographic manifestations in patients with impaired host defense mechanisms.Medicine (Baltimore). 1974; 53: 255-293Crossref PubMed Google Scholar, 3Nash G Pathologic features of the lung in the immunocompromised host.Hum Pathol. 1982; 13: 841-858Abstract Full Text PDF PubMed Google Scholar, 4Singer C Armstrong D Rosen PP Walzer PD Yu B Diffuse pulmonary infiltrates in immunosuppressed patients: prospective study of 80 cases.Am J Med. 1979; 66: 110-120Abstract Full Text PDF PubMed Google Scholar, 5Williams DM Krick JA Remington JS Pulmonary infection in the compromised host.Am Rev Respir Dis. 1976; 114 (593-627): 359-394PubMed Google Scholar, 6Matthay RA Greene WH Pulmonary infections in the immunocompromised patient.Med Clin North Am. 1980; 64: 529-551PubMed Google Scholar, 7Krick JA Remington JS Opportunistic invasive fungal infections in patients with leukaemia and lymphoma.Clin Haematol. 1976; 5: 249-310PubMed Google Scholar, 8Valdivieso M Gil-Extremera B Zornoza J Rodriguez V Bodey GP Gram-negative bacillary pneumonia in the compromised host.Medicine (Baltimore). 1977; 56: 241-254Crossref PubMed Google Scholar, 9Greenman RL Goodall PT King D Lung biopsy in immunocompromised hosts.Am J Med. 1975; 59: 488-496Abstract Full Text PDF PubMed Google Scholar, 10Jaffe JP Maki DG Lung biopsy in immunocompromised patients: one institution's experience and an approach to management of pulmonary disease in the compromised host.Cancer. 1981; 48: 1144-1153Crossref PubMed Google Scholar, 11Rossiter SJ Miller DC Churg AM Carrington CB Mark JBD Open lung biopsy in the immunosuppressed patient: is it really beneficial?.J Thorac Cardiovasc Surg. 1979; 77: 338-345PubMed Google Scholar, 12Masur H Shelhamer J Parrillo JE The management of pneumonias in immunocompromised patients.JAMA. 1985; 253: 1769-1773Crossref PubMed Google Scholar, 13LaForce FM Hospital-acquired gram-negative rod pneumonias: an overview.Am J Med. 1981; 70: 664-669Abstract Full Text PDF PubMed Google Scholar, 14Young LS Nosocomial infections in the immunocompromised adult.Am J Med. 1981; 70: 398-404Abstract Full Text PDF PubMed Google Scholar, 15Johanson Jr, WG Higuchi JH Chaudhuri TR Woods DE Bacterial adherence to epithelial cells in bacillary colonization of the respiratory tract.Am Rev Respir Dis. 1980; 121: 55-63PubMed Google Scholar, 16Kaplan HS Hodgkin's Disease. Second edition. Harvard University Press, Cambridge1980: 146-235Google Scholar, 17Sakula A Primary malignant lymphoma of lung.Postgrad Med J. 1979; 55: 46-49Crossref PubMed Google Scholar, 18Filly R Blank N Castellino RA Radiographic distribution of intrathoracic disease in previously untreated patients with Hodgkin's disease and non-Hodgkin's lymphoma.Radiology. 1976; 120: 277-281PubMed Google Scholar, 19Whitcomb ME Schwarz MI Keller AR Flannery EP Blom J Hodgkin's disease of the lung.Am Rev Respir Dis. 1972; 106: 79-85PubMed Google Scholar, 20Ultmann JE Cunningham JK Gellhorn A The clinical picture of Hodgkin's disease.Cancer Res. 1966; 26: 1047-1060PubMed Google Scholar, 21Peckham MJ Lung involvement.in: Smithers D Hodgkin's Disease. Churchill Livingstone, New York1973: 118-127Google Scholar, 22Strickland B Intra-thoracic Hodgkin's disease. II. Peripheral manifestations of Hodgkin's disease in the chest.Br J Radiol. 1967; 40: 930-938Crossref PubMed Google Scholar, 23Manoharan A Pitney WR Schonell ME Bader LV Intrathoracic manifestations in non-Hodgkin's lymphoma.Thorax. 1979; 34: 29-32Crossref PubMed Google Scholar, 24Macdonald JB Lung involvement in Hodgkin's disease.Thorax. 1977; 32: 664-667Crossref PubMed Google Scholar, 25Rosenberg SA Diamond HD Jaslowitz B Craver LF Lymphosarcoma: a review of 1269 cases.Medicine (Baltimore). 1961; 40: 31-84Crossref PubMed Google Scholar, 26Castellino RA Blank N Cassady JR Kaplan HS Roentgenologic aspects of Hodgkin's disease. II. Role of routine radiographs in detecting initial relapse.Cancer. 1973; 31: 316-323Crossref PubMed Google Scholar, 27Lee CKK Bloomfield CD Levitt SH Results of lung irradiation for Hodgkin's disease patients with large mediastinal masses and/or hilar disease.Cancer Treat Rep. 1982; 66: 819-825PubMed Google Scholar, 28Costello P Mauch P Radiographic features of recurrent intrathoracic Hodgkin's disease following radiation therapy.Am J Roentgenol. 1979; 133: 201-206Crossref PubMed Google Scholar, 29Harlan JM Fennessy JJ Gross NJ Bronchial brush biopsy in Hodgkin's disease.Chest. 1974; 66: 136-138Crossref PubMed Google Scholar, 30Tenholder MF Hooper RG Pulmonary infiltrates in leukemia.Chest. 1980; 78: 468-473Crossref PubMed Google Scholar, 31Maile CW Moore AV Ulreich S Putman CE Chest radiographic-pathologic correlation in adult leukemia patients.Invest Rad