Pulmonary complications in cancer patients

The respiratory system is a common site for complications due to cancer and cancer therapy. Several factors can lead to pulmonary complications. Immunosuppression caused by the underlying disease or the cancer therapy can lead to infectious disease. In addition, the lungs contain an enormous capillary bed through which flows the entire venous circulation, making it a frequent site of metastasis and pulmonary emboli. Finally, the pulmonary capillary bed is uniquely sensitive to side effects of chemotherapy and radiation therapy, which often lead to respiratory symptoms. This article reviews the presentation, diagnosis, and therapy of common infectious and noninfectious disorders of the pulmonary system that occur in cancer patients. Immunosuppression is defined as a relative or absolute defect in antigen processing or effector cell function. Clinically, it is defined by the susceptibility of certain populations to specific types of infections. Immunosuppression caused by the disease or by the treatment can cause qualitative and quantitative immunologic defects. Certain general immunologic defects are associated with specific infectious organisms, and recognition of an immunologic defect can help in the prediction of the infectious agent (Table Besides immunologic defects, other factors, such as environmental exposure, travel history, iatrogenic procedures, recent hospitalization, and/or antibiotic therapy, must be taken into account in determining the infectious agent. Review of the radiologic pattern of infiltration also helps focus the differential diagnosis on a subset of likely etiologic agents. A distinction is often made between processes involving a single lobe or segment (localized) and those involving multiple lobes bilaterally (diffuse). The presence of a localized infiltrate with an appropriate clinical history suggests the diagnosis of a bacterial pneumonia. Diffuse infiltrates suggest either infection, especially Pneumocystis and cytomegalovirus (CMV) pneumonia, or noninfectious etiologies, such as drug toxicity and lymphangitic spread of tumor.2 The presence of infiltrates, cavitation, nodules, adenopathy, or pleural effusions can help focus attention on certain disorders (Table 2). Pulmonary symptoms in cancer patients with normal chest radiographs also need further evaluation. Tests that are more sensitive than the chest radiograph to detect pulmonary disease include measurement of the diffusing capacity, rest and exercise blood-gas determination or oximetry, gallium chest scanning, and computed tomography of the chest. The seriousness and tempo of an illness are also helpful in determining whether there is time to wait for a response to empiric therapy or whether an invasive procedure should be performed immediately. For the very ill cancer patient with pulmonary disease, often the goal is to achieve a specific etiologic diagnosis quickly and safely. Adequate samples of lower respiratory tract secretions and/or lung tissue are usually required for pathologic examination, microbial stains, and cultures. Table 3 lists the invasive procedures available for diagnosing pulmonary infiltrates in cancer patients along with an outline of specific etiologic yields and complication rates. Most procedures have a significant false-negative rate, further complicating the decision making, and in some cases even at autopsy a specific etiologic diagnosis cannot be made. It is important to note that survival is often not affected by making a specific pulmonary diagnosis. Studies do show, however, that morbidity is lessened by making a definitive diagnosis. Thus, bron-choscopy with bronchoalveolar lavage and transbronchial biopsy (if safe) is usually performed as the initial invasive procedure.3, 4 In general video-assisted thoracoscopic surgery has been shown to be a safe and effective method of obtaining lung tissue with less morbidity when compared with conventional thoracotomy, although no studies have been restricted exclusively to immunocompromised hosts (Table 3). Although sputum and serologic examinations are neither sensitive nor specific for most pulmonary diseases, occasionally a definitive diagnosis can be made by these methods. The presence of malignant cells, Legionella antigen, or Pneumocystis carinii in the sputum is specific but not sensitive for these disorders. The indications for sputum induction for diagnosis of pulmonary disorders in non-HIV immunocompromised patients have not been defined, but sputum induction may have a role in diagnosing P. carinii pneumonia and tuberculosis (TB). The presence of Cryptococcus antigen in the serum is highly sensitive and specific for disseminated cryptococcosis but may not be sensitive for pulmonary Cryptococcus infection alone. Serologic tests that demonstrate antibodies for Aspergillus, Blastomyces, and Histoplasma are suggestive of active infection, but the sensitivity of these studies is quite low. More recently, radioimmunoassay for Histoplasma capsulatum antigen has been shown to provide a rapid method for diagnosing disseminated histoplasmosis. The antigen can be detected in 50 percent of blood and 90 percent of urine samples from patients with disseminated histoplasmosis.5 Most of these data come from patients with acquired immunodeficiency syndrome (AIDS). Whether the sensitivity is this high in non-AIDS immunocompromised patients remains unknown. The diagnosis of invasive aspergillo-sis usually requires a biopsy of the infected tissue because the organism is ubiquitous and cultures are nonspecific for invasive disease. However, in neutropenic patients (especially with leukemia) who remain febrile on broad-spectrum antibiotics, the presence of the organism in sputum or bronchoscopic specimens may be a reliable guide to make a diagnosis of pulmonary Aspergillus infection because these patients are at greatest risk to develop invasive disease.6 The type of bacterial pneumonia that develops in a cancer patient depends on several factors, including the underlying immunologic defect, the duration of the immunocompromised state, and whether the infection is community acquired or nosocomial. Streptococcus pneumoniae and Haemophilus influenzae are seen in cancer patients with B-cell defects. Gramnegative organisms including Pseudomonas aeruginosa, Escherichia coli, and Klebsiella species are common in neutropenic patients, but the widespread use of effective gram-negative antibiotic regimens has led to a decrease in the incidence of P. aeruginosa infections and to an increase in gram-positive infections in this patient population. The major risk factors for the occurrence of bacterial pneumonia in cancer patients besides neutropenia include corticosteroid administration, inadequate pulmonary drainage from obstructing tumor, and decreased cough. The clinical signs and symptoms of pneumonia may be typical ones, including acute onset of shaking chills, fever, and productive cough, but in the setting of granulocytopenia, patients may present with atypical or absent findings. Sputum production is seen in fewer than 60 percent of neutropenic patients, and when the absolute neutrophil count is less than 1,000 cells/mm3, purulent sputum is seen in less than eight percent of patients. In cancer patients the most sensitive sign of bacterial pneumonia is fever, which occurs in virtually all patients who have bacterial pneumonia. Although rales and signs of consolidation occur inconsistently, the chest radiograph is abnormal in 93 percent to 97 percent of patients, usually showing localized infiltrates. The usefulness of sputum examination in the immunocompromised patient with pneumonia is controversial. If the patient has sputum and a suspected bacterial pneumonia, we usually send it for gram stain and routine culture. The results are used as a guide to antibiotic therapy if the patient is not improving on the initially prescribed regimen. Bacterial pneumonia in cancer patients can and the incidence of and is in patients with absolute neutrophil of less than 1,000 broad-spectrum antibiotic should be when the diagnosis of bacterial pneumonia is suspected or more when the neutropenic patient with and no with a or an are in neutropenic patients. In some studies has been shown to be as effective and less than antibiotic However, the of organisms with drug therapy Although the duration of antibiotic therapy for neutropenic patients is a is usually if there is rapid clinical and blood cell neutropenia is be even if the patient is If the neutropenic patient remains febrile or not on broad-spectrum antibiotics, that must be include of antibiotic therapy, therapy to infections (especially and of an invasive procedure to make a specific diagnosis. a cancer patient who is not neutropenic with suspected bacterial pneumonia and is the for treatment are used as for the Although most bacterial in immunocompromised patients are to be acquired by the respiratory or the some are caused by patients at risk for pneumonia include those with and and those with due to infection, and/or radiation therapy. common of bacterial pneumonia in cancer patients include Legionella and and disease in the immunocompromised is often acquired from a and a productive are the presence of infiltrates and is of the organism from respiratory or pleural is the for diagnosis. tests are but have of Legionella requires the use of that can Although is the antibiotic of some for the duration of therapy, which should be at infection occurs in patients with of and presence in respiratory secretions should be of to of therapy is and therapy should be for at to eight are the of therapy. However, if patients cannot or or in with has been Although bacterial pneumonia by has not been in the immunocompromised is and influenzae should be in patients at risk for this infection patients, patients with defects, in cancer patients with quantitative or qualitative such as patients with or has decreased the of of pneumonia and other infections in these patients. The of factors to cancer patients who are at risk for morbidity from febrile neutropenia to be of greatest if neutropenia The of is in some immunocompromised patients, those with lung and and but incidence in cancer patients remains low. In patients with lung and and develops in the of the disease, in patients with the infection develops when the underlying is In most cancer patients with the disease results from of a However, the and that cancer increase the susceptibility to active infection from as of is often because and symptoms are to the underlying radiographs can typical lobe but lower lobe infiltrates, nodules, and a pattern occur more in patients. Sputum examination should be although it is less often in these sputum are for the should be for sensitive is and as effective in immunocompromised patients as it is in the general population. of the incidence of initially a is and the of If the organism is sensitive to and the can be and therapy should be for an to If there is microbial to or treatment with the sensitive drug or and should be to at including sputum as are no studies on of for or to which the organism is sensitive should be The appropriate duration of treatment is but should be for or Whether of localized disease has is unknown. patients with should of with increase the sensitivity of the in cancer patients, it should be performed therapy is and a of of is used to a an of that is as a is not for because disseminated disease and have been in immunocompromised patients. Pulmonary infections with which are in and often are from but are not and are the most organisms and occur in patients with lung and and cell A has been as a in immunocompromised The organism pulmonary and disease (especially in the and and has been in patients and the of atypical is often and usually requires to to which the organism is sensitive for or A to pulmonary infections in the immunocompromised patient is to on the of the underlying immunologic defects. with neutropenia more develop infections with Aspergillus, and organisms are because usually patients with abnormal with defects more often develop infections with Cryptococcus Histoplasma and organisms are because also normal Aspergillus and Cryptococcus are major of pneumonia in patients with be patients at risk for invasive pulmonary include those with those antibiotic therapy, and/or and those with a history of Aspergillus pneumonia. The clinical of pulmonary include fever, cough, and chest with or more a the of Aspergillus pneumonia is with pulmonary infiltrates that do not to is a complication and to occur the of and is of pulmonary Aspergillus infection that occurs in immunocompromised patients. present with and/or and the chest radiograph can be normal or Aspergillus pneumonia may or may not the disease. in the of Aspergillus infection, the chest radiograph may be or it may a single multiple or a that pulmonary A computed of the chest can the chest radiograph Aspergillus infections are to and because are an important cause of in neutropenic patients, empiric therapy for in the setting has is the drug of for invasive should be in patients and therapy, have disease especially with which can of drug with and to be for the treatment of Aspergillus infection in immunocompromised for treatment of include antibodies to to increase the of drug and drug to most likely to be infected to the The with survival in patients with invasive is of the underlying and of The role of factors remains cryptococcosis is by the occurrence of and pulmonary which occurs in to 50 percent of patients with disseminated pneumonia is less pneumonia usually as a that from to in and lung adenopathy, and pleural effusions are in cancer patients. However, are common in patients. the disease is disseminated when it and urine cultures provide for diagnosis. when the organism is from respiratory the patient should be for disseminated infection, including a The for antigen is for diagnosis and should be to the of is the therapy for infection, and is This should be in patients with In patients with pulmonary cryptococcosis may be but there is no as to the and duration of therapy. Although role in the non-AIDS immunocompromised patient is is a for the treatment of pulmonary In patients who are with of morbidity and can occur infection or of certain (CMV) is a major cause of morbidity and in in of and other cancer patients, it active disease. The clinical and of pneumonia are nonspecific and often from other common If the organism is from bronchoalveolar or urine in even if treatment for is usually The of and has been shown in studies of patients to decrease the from this disease. In with this the from pneumonia has decreased from 90 percent to Although to pneumonia in studies have shown a survival associated with respiratory and can occasionally cause pneumonia in patients with of A and the use of an and although the response in immunocompromised patients is it is that such patients P. carinii pneumonia if occurs in patients who have normal function. In cancer patients, occurs most in patients who have underlying associated with defects in who have or who are especially or A at that of the cases percent in patients with percent in patients with and percent in is the drug of for invasive cough, of and are the typical symptoms of Pneumocystis pneumonia. The history of is a of the lungs in The typical of is of and infiltrates. or infiltrates, and multiple nodules, a lobe infiltrates, and normal chest radiographs have also been The diagnosis of is made by the organism in respiratory secretions or Although sputum has a high in patients, sensitivity in cancer patients with to be low. most bron-choscopy is the procedure of to provide the diagnosis in cancer patients. are that are highly effective in the treatment of and If a patient not to initial therapy, there are no studies the However, most from to and such as and have some Pneumocystis pneumonia, but major especially usefulness in cancer patients. some in the treatment of with less toxicity but when compared with conventional agents. Pulmonary is a frequent complication of cancer treatment and may be of or in patients have shown that the of to conventional in patients with to as an of or an to of on is are no in cancer patients, and there are no specific for therapy or for It has been that or the in cancer patients therapy may be in patients with to can be by of of a for a has a high of in has a of to 50 percent in cancer patients, the need for patients who include those with defects in and those of for cancer patients should also be Although is the drug of for the use of is an effective in cancer patients who are to include to or of these has been shown in patients, it is are effective in other immunocompromised patients as other can cause pulmonary disease in cancer patients. should be in patients who have been to infection time in and develop illness or treatment that The diagnosis should be in patient who from an and develops symptoms of or and develops pneumonia. Although blood cultures may be for or more from the the diagnosis is made by the in sputum or other respiratory tract especially bronchoalveolar lavage The may also be in or in if therapy for is The duration of therapy is usually between and However, the treatment time is unknown. If or active infection with is or highly treatment with should be and active disease is an cause of pulmonary infiltrates in immunocompromised patients. The setting of is with pulmonary disease it is usually in patients with infection or treatment for cancer are at risk for a of pulmonary complications. The is on to in this The differential diagnosis is Besides pulmonary infection the most frequent are of disease, cancer in the from or pulmonary of or pleural pulmonary and and pulmonary and are less lung diseases, such as pulmonary must also be from acute Review of radiographs in this setting is for a of the diseases, such as can occur in cancer patients as as other who have due to cancer or the effects of chemotherapy of as the initial In some therapy can be highly effective in these symptoms. for noninfectious pulmonary often as a of the of in the chest in several disease most often as single or multiple nodules, in a lymphangitic and/or as a pleural Certain types of cancer can and present with or on the chest and cancer most these cell cancer and can also can cause and with or infiltrates. usually present in the chest as but nodules, infiltrates often with and/or pleural effusions may also be can be associated with or other such as cell and can these for cell to the lungs often can also cause in the pulmonary symptoms and infiltrates. are to between lung and lung cancer can present as a with or or of from an may lead to cough, localized or an The bronchoalveolar usually as a which a often showing It is that for certain as and cell and of single or a of pulmonary due to disease is associated with a survival in highly patients who have no other site of with and cancer who present with a have a high of a such as lung Pulmonary is a frequent complication of cancer treatment and may be of or from or radiation therapy may not for chemotherapy is or may also present in a more with onset of pulmonary can be associated with specific such as therapy, or an acute to as treatment for cancer are to a of infections that can lead to respiratory with are at risk for a capillary syndrome with infiltrates that may lead to respiratory those with acute who develop this complication from therapy, may to with a history of radiation therapy to the chest have an incidence of disease. may also be at risk for the of disease. pleural effusions due to cancer are usually but can be are seen most with lung and and but can also be seen with a of other including cancer and A pleural associated with lung cancer not in make the patient malignant pleural disease must be although most patients to be for The of a malignant pleural due to lung cancer has as with a malignant pleural of a a survival of chest drainage and are often for effective of malignant chest drainage and are often for effective of in normal is the agent of for due to However, side effects such as are and pulmonary infiltrates can can also be video-assisted with a high of in with cancer are at risk of disease due to several factors, including of factors from in the and due to complicating and treatment side and of pulmonary and venous are the as in patients, that may have to be for a of time in some patients be patients with disease are often and may with and/or Pulmonary drug toxicity from can be to because there are no findings. requires the history, and and with the results of studies such as which is often to computed are helpful in disease or nodules, when signs and symptoms are may in the even when chest radiographs are is sensitive for active but is not Although is helpful in lung biopsy is to make specific Pulmonary diffusing and rest and exercise blood or oximetry, can be for and toxicity from of underlying disease. is the of a agent that can cause pulmonary The toxicity is a of to of lower toxicity at a of often present with fever, cough, and infiltrates, which can to infiltrates. However, not patient with toxicity these findings. effusions are and should be for other if can also uniquely cause an acute chest toxicity has been in and and the are an to pulmonary capillary and type that is associated with of and an response that further tissue and also and the of for such as with this radiation therapy and toxicity are with the effects on the It is not whether there is safe or duration of therapy Thus, must be made to is to of cause in patients with with toxicity should not further of the patients often to in an initial of a response is the must be very pulmonary toxicity also can in regimens with and when used as therapy for cell lung present with acute or of the and this may be by and/or pulmonary other patients a onset of The is often by infiltrates, with and a in the diffusing The of is not as as with although to the pulmonary to be the are less data available with and radiation it to to in these patients as due to the clinical that some of these patients have a significant of pulmonary general for and to high Most patients with toxicity some treatment with is to for a of several including through patients have from are a of for and treatment of including tissue in the for pulmonary toxicity with is Pulmonary toxicity from is but it may to the that occurs in with other agents. in the high used in the treatment of pulmonary that may to The has a pattern with lung Most studies risk of pulmonary the pulmonary response to is A more recent and widespread use of is in the treatment of cancer or with chemotherapy and or cell in this setting is common and is usually to although patients with for may be more sensitive to lower have a Most patients with toxicity some treatment with toxicity may present as acute with or as pulmonary The pulmonary can occur in patients drug The chest usually infiltrates, but or an may be The a response in the response to is usually is less with but the toxicity is and can acute which is an response to the The symptoms usually to with and is usually also a state, which can be associated with pleural It is that cancer patients with high of for pulmonary toxicity are at risk for and we should Pneumocystis with a if the patient not have a history of radiation used in the treatment of lung and cancer can cause if a is Most of lung are to an incidence of less than percent for radiation radiation to the of The symptoms are cough, fever, and onset of radiographs infiltrates, which may have a to the of the radiation However, infiltrates the radiation or in the lung can be effusions if present are usually and are with the acute patients to acute respiratory which may be or which to The is to be by to the pulmonary capillary by an that to and may be in this is to patients with and to to drug has noninfectious pulmonary including pulmonary the pneumonia and disease. pulmonary occurs in the in patients who treatment with and/or chest respiratory syndrome can infection in this setting as respiratory syndrome may also be in to the effects of the on the pulmonary and to the of due to acute disease. pulmonary may also be associated with disease, important complication of with acute are at risk for disseminated which may lead to pulmonary Pulmonary is most often seen in those with radiation therapy for disease in the usually or infiltrates. lavage in this has a of in can be shown to contain if is with pulmonary bron-choscopy is usually to make the diagnosis and to help infection as the underlying cause of the The is but by treatment and for may a patients develop respiratory on this is although to have been The pneumonia which usually with and pulmonary infiltrates, must be from in the A recent defined this syndrome as of widespread with signs and symptoms of pneumonia, infiltrates, and of abnormal pulmonary In addition, active pulmonary infection must be by bronchoalveolar lavage and/or lung The is also and the of active is that lung from regimens for may be by the effects of or other A subset of patients with this diagnosis to but the is For that are disease develops Most of these patients have pulmonary including in and diffusing which to remain A of patients develop more that may be by cough, and/or of these patients demonstrate This may be to disease in the may and be to therapy, in and However, and the presence of pulmonary infiltrates should suggest infectious of which may be if patients may have with also as pneumonia, a than the with pneumonia may also occur in cancer patients who have not with pneumonia a if with a high of should be in patients with infiltrates and no infectious diagnosis. The of with pneumonia is disease, but disease often demonstrate a pattern with a pneumonia is patients may have an pattern of disease. lung biopsy is usually to make the diagnosis, although at with transbronchial biopsy is In patients who develop lung disease as a complication of cancer lung may be an should also be that the use of or can be very effective in the by patients with cancer in the Pulmonary complications of cancer and cancer therapy a of disease. diagnosis and treatment are to achieve an