This is the current release of the guideline.

This guideline updates a previous version: Haramati LB, Little BP, Khan A, Mohammed TL, Batra PV, Gurney JW, Jeudy J, MacMahon H, Rozenshtein A, Vydareny KH, Washington L, Kaiser L, Raoof S, Expert Panel on Thoracic Imaging. ACR Appropriateness Criteria® acute respiratory illness in HIV-positive patient. [online publication]. Reston (VA): American College of Radiology (ACR); 2008. 6 p.

The appropriateness criteria are reviewed biennially and updated by the panels as needed, depending on introduction of new and highly significant scientific evidence.

To evaluate the appropriateness of initial radiologic examinations of acute respiratory illness in immunocompromised patients

Immunocompromised patients with acute respiratory illness

Utility of radiologic examination procedures in differential diagnosis

Literature Search Procedure

The Medline literature search is based on keywords provided by the topic author. The two general classes of keywords are those related to the condition (e.g., ankle pain, fever) and those that describe the diagnostic or therapeutic intervention of interest (e.g., mammography, MRI).

The search terms and parameters are manipulated to produce the most relevant, current evidence to address the American College of Radiology Appropriateness Criteria (ACR AC) topic being reviewed or developed. Combining the clinical conditions and diagnostic modalities or therapeutic procedures narrows the search to be relevant to the topic. Exploding the term "diagnostic imaging" captures relevant results for diagnostic topics.

The following criteria/limits are used in the searches.

1. Articles that have abstracts available and are concerned with humans.
2. Restrict the search to the year prior to the last topic update or in some cases the author of the topic may specify which year range to use in the search. For new topics, the year range is restricted to the last 5 years unless the topic author provides other instructions.
3. May restrict the search to Adults only or Pediatrics only.
4. Articles consisting of only summaries or case reports are often excluded from final results.

The search strategy may be revised to improve the output as needed.

The total number of source documents identified as the result of the literature search is not known.

Strength of Evidence Key

Category 1 - The conclusions of the study are valid and strongly supported by study design, analysis and results.

Category 2 - The conclusions of the study are likely valid, but study design does not permit certainty.

Category 3 - The conclusions of the study may be valid but the evidence supporting the conclusions is inconclusive or equivocal.

Category 4 - The conclusions of the study may not be valid because the evidence may not be reliable given the study design or analysis.

The topic author drafts or revises the narrative text summarizing the evidence found in the literature. American College of Radiology (ACR) staff draft an evidence table based on the analysis of the selected literature. These tables rate the strength of the evidence for all articles included in the narrative text.

The expert panel reviews the narrative text, evidence table, and the supporting literature for each of the topic-variant combinations and assigns an appropriateness rating for each procedure listed in the table. Each individual panel member forms his/her own opinion based on his/her interpretation of the available evidence.

More information about the evidence table development process can be found in the ACR Appropriateness Criteria® Evidence Table Development document (see the "Availability of Companion Documents" field).

Modified Delphi Technique

The appropriateness ratings for each of the procedures included in the Appropriateness Criteria topics are determined using a modified Delphi methodology. A series of surveys are conducted to elicit each panelist's expert interpretation of the evidence, based on the available data, regarding the appropriateness of an imaging or therapeutic procedure for a specific clinical scenario. American College of Radiology (ACR) staff distributes surveys to the panelists along with the evidence table and narrative. Each panelist interprets the available evidence and rates each procedure. The surveys are completed by panelists without consulting other panelists. The ratings are a scale between 1 and 9, which is further divided into three categories: 1, 2, or 3 is defined as "usually not appropriate"; 4, 5, or 6 is defined as "may be appropriate'; and 7, 8, or 9 is defined as "usually appropriate." Each panel member assigns one rating for each procedure per survey round. The surveys are collected and the results are tabulated, de-identified and redistributed after each round. A maximum of three rounds are conducted. The modified Delphi technique enables each panelist to express individual interpretations of the evidence and his or her expert opinion without excessive bias from fellow panelists in a simple, standardized and economical process.

Consensus among the panel members must be achieved to determine the final rating for each procedure. Consensus is defined as eighty percent (80%) agreement within a rating category. The final rating is determined by the median of all the ratings once consensus has been reached. Up to three rating rounds are conducted to achieve consensus.

If consensus is not reached, the panel is convened by conference call. The strengths and weaknesses of each imaging procedure that has not reached consensus are discussed and a final rating is proposed. If the panelists on the call agree, the rating is accepted as the panel's consensus. The document is circulated to all the panelists to make the final determination. If consensus cannot be reached on the call or when the document is circulated, "No consensus" appears in the rating column and the reasons for this decision are added to the comment sections.

Not applicable

A formal cost analysis was not performed and published cost analyses were not reviewed.

Criteria developed by the Expert Panels are reviewed by the American College of Radiology (ACR) Committee on Appropriateness Criteria.

ACR Appropriateness Criteria®

Clinical Condition: Acute Respiratory Illness in Immunocompromised Patients

Variant 1: Cough, dyspnea, chest pain, fever.

Radiologic Procedure	Rating	Comments	RRL*
X-ray chest	9
Rating Scale: 1,2,3 Usually not appropriate; 4,5,6 May be appropriate; 7,8,9 Usually appropriate			*Relative Radiation Level

Variant 2: Negative, equivocal, or nonspecific chest radiograph.

Radiologic Procedure	Rating	Comments	RRL*
CT chest without contrast	9
CT chest with contrast	3
CT chest without and with contrast	1
Ga-67 scan lung	1	If PCP is suspected.
Tc-99m DTPA scan lung	1	If PCP is suspected.
Rating Scale: 1,2,3 Usually not appropriate; 4,5,6 May be appropriate; 7,8,9 Usually appropriate			*Relative Radiation Level

Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.

Variant 3: Positive chest radiograph, multiple, diffuse or confluent opacities.

Radiologic Procedure	Rating	Comments	RRL*
CT chest without contrast	7
Transthoracic needle biopsy	5	If serious opportunistic infection is suspected.	NS
CT chest with contrast	3
CT chest without and with contrast	1
Ga-67 scan lung	1	If PCP is suspected.
Tc-99m DTPA scan lung	1	If PCP is suspected.
Rating Scale: 1,2,3 Usually not appropriate; 4,5,6 May be appropriate; 7,8,9 Usually appropriate			*Relative Radiation Level

Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.

Variant 4: Positive chest radiograph, noninfectious disease suspected.

Radiologic Procedure	Rating	Comments	RRL*
CT chest without contrast	8
CT chest with contrast	5	If neoplasm or pulmonary embolus is suspected.
Transthoracic needle biopsy	5	If thoracic malignancy suspected.	NS
CT chest without and with contrast	1
Rating Scale: 1,2,3 Usually not appropriate; 4,5,6 May be appropriate; 7,8,9 Usually appropriate			*Relative Radiation Level

Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.

Summary of Literature Review

There are many causes of immunodeficiency likely to be encountered by today's physician. In recent decades, with advances in medical techniques such as solid organ and stem cell transplantation, cancer therapy, and immunosuppressive therapy, along with the spread of the human immunodeficiency virus (HIV), the number of immunocompromised patients in our health care system has greatly increased. Other causes of immunosuppression seen in medicine today include hematologic malignancies, congenital immunodeficiency syndromes, and the mildly impaired host states, such as diabetes mellitus, advanced age, malnutrition, alcoholism, chronic debilitating illness, and chronic obstructive lung disease. Given the diverse causes of immunosuppression, it is most helpful to diagnose potential infections by thinking in terms of defects in the basic types of immune processes (phagocytosis, humoral or B-cell, complement system, cell-mediated or T-cell, and postsplenectomy), and then determining which has occurred, given the clinical situation at hand. By understanding the immune defect caused by the immunosuppression, the list of likely infecting organisms becomes much shorter.

Acute respiratory illness (ARI) constitutes a group of signs and symptoms that develop over a brief interval (hours to weeks), some of which are constitutional (such as fever, chills, and weight loss) and some of which are organ specific (such as cough, shortness of breath, and chest pain). In immunocompromised individuals, the respiratory system is one of the most frequently involved organ systems that results in complications, often initially manifesting as ARI. Of all pulmonary complications in patients with immunodeficiency, pulmonary infections comprise nearly 75%, many of which progress along a rapid and potentially fatal course. Noninfectious causes of ARI in immunocompromised hosts include pulmonary edema, drug-induced lung disease, atelectasis, malignancy, radiation-induced lung disease, diffuse alveolar hemorrhage, and pulmonary embolus.

Overview of Imaging Modalities

Despite modern advances in computed tomography (CT) technology, the chest radiograph remains first-line in the diagnostic evaluation of immunocompromised patients presenting with ARI. The morphology and distribution of abnormalities on the chest radiograph, along with changes on serial radiographic examinations, can aid in arriving at a differential diagnosis. Chest radiographs also demonstrate the presence of complicating features of pneumonia, such as empyema or abscess. The well-known shortcomings of the chest radiograph, however, are its lack of specificity with regard to actual pathogens, and its overall low sensitivity for detectable abnormalities in immunosuppressed patients with symptomatic disease.

CT is more sensitive and specific than chest radiography for detecting subtle pulmonary findings. Although not recommended for the initial imaging evaluation of patients with ARI, the use of CT has been described in several scenarios regarding the immunocompromised host: to evaluate patients who are clinically symptomatic for ARI, but who have equivocal or normal chest radiographic findings; to better characterize abnormal but nonspecific chest radiograph findings, and to provide essential information for determining the appropriate method and site of lung biopsy. Because the appearance and distribution of airspace abnormalities are better characterized with the high spatial resolution provided by CT, certain diseases such as Pneumocystis jiroveci pneumonia (PCP), invasive pulmonary aspergillosis and cytomegalovirus (CMV) can be identified on CT with a higher degree of confidence than they can on radiography. Recognizing the CT patterns associated with these infections allows for the critical initiation of early empiric therapy, often based on a presumptive radiologic diagnosis, all the while waiting for more definitive microbiologic data which may not be available for days or weeks.

Chest radiography and chest CT are the mainstay imaging modalities in evaluating the immunocompromised host with ARI, although nuclear scintigraphy using gallium-67 (Ga-67) or diethylenetriamine pentaacetic acid-technetium (DTPA-Tc) tracer can also be performed. In this clinical setting, Ga-67 can be used to help diagnose Mycobacterium avium intracellulare, Mycobacterium tuberculosis, and lymphoma based on increased radiotracer activity in hilar and mediastinal lymph nodes. Additionally, Ga-67 can be used to evaluate for the presence of PCP within the lungs in cases where conventional imaging has turned up normal or equivocal findings. Some studies have shown gallium scintigraphy to be more sensitive and specific for the presence of PCP than both chest radiograph and chest CT in acquired immune deficiency syndrome (AIDS) patients.

Discussion of Imaging Modalities by Variant

Variant 1: Cough, Dyspnea, Chest Pain, Fever

When immunocompromised patients present with symptoms of acute onset fever, cough, and shortness of breath, chest radiography should be the first radiologic examination performed. The chest radiograph typically identifies abnormalities if present, although it can be normal in up to 10% of symptomatic patients with proven disease and up to 25% of AIDS patients with PCP. Despite its shortcomings, it remains useful as a screening test for chest disease, as a tool to begin formulating a differential diagnosis, and as a triaging examination to consider additional imaging with chest CT. For patients with acute onset cough and fever, a single focal, segmental, or lobar airspace opacity on chest radiography suggests bacterial pneumonia as the most likely etiology of pulmonary infection.

Fungal pneumonias, PCP, tuberculosis (TB), and noninfectious causes of ARI such as atelectasis and edema are also in the differential diagnosis, although their clinical presentations often differ. If the initial chest radiograph is suggestive of edema, serial chest radiography with concomitant diuresis, for example, would be helpful in confirming cardiogenic pulmonary edema and differentiating it from infectious causes of ARI. Clearly there are many clinical scenarios, such as a focal lobar pneumonia or presumed pulmonary edema, where further radiologic imaging with CT may not be needed unless the patient's clinical picture worsens or fails to improve with therapy.

Variant 2: Negative, Equivocal, or Nonspecific Chest Radiograph

The main limitation of the chest radiograph is its low sensitivity in detecting pulmonary infection, a particular problem in patients with weakened and delayed immune systems. Indeed, the chest radiograph in patients with cough, dyspnea, chest pain, and fever may be equivocal or even negative despite a high suspicion for pulmonary disease. In this setting, chest CT has been shown to offer a distinct advantage in sensitivity for subtle parenchymal abnormalities. In one study, CT performed in febrile neutropenic patients with normal chest radiographs showed pneumonia in 60% of cases at least 5 days before the abnormalities became visible on chest radiographs. The advantage likely lies in its ability to provide cross-sectional imaging and volumetric data, as opposed to the low-resolution two-dimensional data provided by plain radiography. With the high spatial resolution of CT, even subtle parenchymal abnormalities that would escape detection on the chest radiograph are typically quite apparent. The appearance and distribution of lung abnormalities on CT, coupled with information of the patient's clinical presentation, are often quite helpful in formulating a differential diagnosis.

In patients whose primary immune defect is HIV infection, a normal or only subtly abnormal chest radiograph can occasionally occur when they are infected with tuberculosis (TB), CMV pneumonia, or PCP, among other processes. If there is a high clinical suspicion of a pulmonary infection in the setting of a normal chest radiograph, a CT may be warranted to assess for subtle pulmonary parenchymal disease. Miliary or disseminated TB or nodal disease can be readily evident on CT in the face of a normal or near-normal chest radiograph. In one series, 7.2% of patients with HIV and TB had normal chest radiographs. Among patients with culture-positive TB and normal chest radiographs in this series, 90% had negative smears for acid-fast bacilli. Small airways disease with mild bronchiectasis, peribronchial thickening, foci of mucoid impaction, and air trapping may be evident only on CT. Patients who have a normal chest radiograph and PCP will usually have focal areas of ground-glass opacity evident on CT. Cysts, reticular opacities, nodules, or cavities are common additional findings in patients with PCP.

Although one study found CT to be more sensitive and specific than nuclear medicine studies for diagnosing PCP, as well as being cheaper and faster to perform, there is some literature supporting the utility of performing DTPA-Tc and Ga-67 lung scans when PCP is suspected. A classic study involving AIDS patients showed that Ga-67 lung scans have an overall sensitivity of 94% and specificity of 74% for PCP, and when the chest radiograph is negative or equivocal at the time of admission, the sensitivity is 86% and the specificity is 85%. Another study noninvasively detected 34 of 36 patients with PCP using DTPA-Tc lung scanning while inducing sputum, and thus reduced the need for bronchoscopy.

Variant 3: Positive Chest Radiograph, Multiple, Diffuse or Confluent Opacities

Chest CT also is indicated in the immunocompromised patient when the radiograph is positive and shows multiple, confluent or diffuse airspace opacities. In these situations with widespread parenchymal disease, the chest radiograph may serve as an effective screening or triaging modality, but its inherent low resolution makes it a suboptimal examination to determine the actual pattern and distribution of disease, thereby making it an unsuitable standalone study. For example, in febrile patients having undergone stem cell transplantation, the ability of CT to detect halos of ground glass-opacity surrounding bilateral pulmonary nodules is essential in making the early presumptive diagnosis of invasive aspergillosis.

Common patterns of disease found on chest CT include pulmonary nodules, tree-in-bud nodules, parenchymal consolidation, and ground-glass opacities. These patterns are used in the literature to describe the characteristic CT appearances of many pulmonary infections in the immunocompromised host, including PCP, invasive pulmonary aspergillosis, mucormycosis, candidiasis, CMV pneumonia, nocardiosis, and mycobacterial pneumonias. Some researchers even advocate the use of high-resolution chest CT (HRCT) so that lung parenchymal abnormalities can be characterized better in terms of these descriptive patterns of disease; this way, the underlying etiologic agents may be better predicted.

Knowledge of the common organisms that infect the lung, their characteristic appearances on chest CT, their associations with specific immunosuppressive states (for example, solid organ transplantation vs stem cell transplantation vs chronic steroid use), and their usual time ranges of infection is essential when considering a differential diagnosis. The well-recognized patterns of disease that CT is able to detect, taken together with the appropriate clinical and laboratory data, go a long way in piecing together the diagnostic puzzle. Also, when a biopsy is required, CT allows for optimal characterization of the potential target lesions and determination of the safest route and equipment to be used.

Variant 4: Positive Chest Radiograph, Noninfectious Disease Suspected

The high spatial resolution provided by chest CT provides a much more definitive assessment of nonspecific radiographic opacities suspected to be noninfectious. Common noninfectious causes of ARI in immunocompromised hosts include pulmonary edema, drug-induced lung disease, atelectasis, malignancy, radiation-induced lung disease, diffuse alveolar hemorrhage, and thromboembolic disease.

The cross-sectional imaging provided by CT allows for optimal characterization of abnormalities discovered on chest radiography. In patients with a history of prior lung malignancy, recurrence of the primary cancer or development of a secondary lung tumor should always remain a suspicion when the chest radiograph is abnormal. In a similar fashion, metastatic disease to the lungs can occur from nonthoracic primary sites. HIV-associated malignancies include non-Hodgkin's lymphoma, Kaposi's sarcoma, and lung cancer. Kaposi's sarcoma, which occurs 20,000 times more frequently in AIDS patients than in the general population, can involve the lung parenchyma, airways, thoracic lymph nodes, and pleura. Although lung involvement with both Hodgkin's and non-Hodgkin's lymphoma is relatively low at the time of initial presentation, 20% to 25% of patients eventually demonstrate parenchymal involvement.

Studies have shown CT to be more sensitive than radiography in detecting drug-induced lung injury from such agents as bleomycin, busulfan, carmustine, and methotrexate. Chest CT has been shown for years now to be the most efficient and effective means to evaluate for suspected acute pulmonary embolism.

Summary

• Chest radiography is indicated early in the evaluation of the immunocompromised patients with ARI. If the radiograph demonstrates a single, focal airspace abnormality and the patient presents with symptoms of an acute bacterial pneumonia, further imaging with CT may not be needed.
• If the radiograph is normal, equivocal, or nonspecific, but clinical suspicion for disease is high, CT can be performed to evaluate for subtle pulmonary abnormalities or to better characterize nonspecific radiographic disease.
• The ability to recognize patterns of airspace disease on chest CT plays an essential role in refining a differential diagnosis — a particular advantage over the nonspecific chest radiograph.
• CT is also indicated for the planning of image-guided biopsy and/or therapy of intrathoracic abnormalities noted on chest radiographs.
• Nuclear scintigraphy likely has a limited role in the evaluation of immunocompromised patients with ARI.

Abbreviations

• CT, computed tomography
• DTPA, diethylenetriamine pentaacetic acid
• Ga, gallium
• NS, not specified
• PCP, Pneumocystis jiroveci (carinii) pneumonia
• Tc, technetium

Relative Radiation Level Designations

Relative Radiation Level*	Adult Effective Dose Estimate Range	Pediatric Effective Dose Estimate Range
O	0 mSv	0 mSv
	<0.1 mSv	<0.03 mSv
	0.1-1 mSv	0.03-0.3 mSv
	1-10 mSv	0.3-3 mSv
	10-30 mSv	3-10 mSv
	30-100 mSv	10-30 mSv
*RRL assignments for some of the examinations cannot be made, because the actual patient doses in these procedures vary as a function of a number of factors (e.g., region of the body exposed to ionizing radiation, the imaging guidance that is used). The RRLs for these examinations are designated as NS (not specified).

Algorithms were not developed from criteria guidelines.

The recommendations are based on analysis of the current literature and expert panel consensus.

Selection of appropriate radiographic imaging procedures for evaluation of acute respiratory illness in immunocompromised patients

Relative Radiation Level (RRL)

Potential adverse health effects associated with radiation exposure are an important factor to consider when selecting the appropriate imaging procedure. Because there is a wide range of radiation exposures associated with different diagnostic procedures, a relative radiation level indication has been included for each imaging examination. The RRLs are based on effective dose, which is a radiation dose quantity that is used to estimate population total radiation risk associated with an imaging procedure. Patients in the pediatric age group are at inherently higher risk from exposure, both because of organ sensitivity and longer life expectancy (relevant to the long latency that appears to accompany radiation exposure). For these reasons, the RRL dose estimate ranges for pediatric examinations are lower as compared to those specified for adults. Additional information regarding radiation dose assessment for imaging examinations can be found in the American College of Radiology (ACR) Appropriateness Criteria® Radiation Dose Assessment Introduction document (see the "Availability of Companion Documents" field).

The American College of Radiology (ACR) Committee on Appropriateness Criteria and its expert panels have developed criteria for determining appropriate imaging examinations for diagnosis and treatment of specified medical condition(s). These criteria are intended to guide radiologists, radiation oncologists, and referring physicians in making decisions regarding radiologic imaging and treatment. Generally, the complexity and severity of a patient's clinical condition should dictate the selection of appropriate imaging procedures or treatments. Only those examinations generally used for evaluation of the patient's condition are ranked. Other imaging studies necessary to evaluate other co-existent diseases or other medical consequences of this condition are not considered in this document. The availability of equipment or personnel may influence the selection of appropriate imaging procedures or treatments. Imaging techniques classified as investigational by the U.S. Food and Drug Administration (FDA) have not been considered in developing these criteria; however, study of new equipment and applications should be encouraged. The ultimate decision regarding the appropriateness of any specific radiologic examination or treatment must be made by the referring physician and radiologist in light of all the circumstances presented in an individual examination.

An implementation strategy was not provided.

Not applicable: The guideline was not adapted from another source.

The American College of Radiology (ACR) provided the funding and the resources for these ACR Appropriateness Criteria®.

Committee on Appropriateness Criteria, Expert Panel on Thoracic Imaging

Panel Members: Darel E. Heitkamp, MD (Principal Author); Tan-Lucien H. Mohammed, MD (Panel Chair); Jacobo Kirsch, MD (Panel Vice-chair); Judith K. Amorosa, MD; Kathleen Brown, MD; Jonathan H. Chung, MD; Debra Sue Dyer, MD; Mark E. Ginsburg, MD; Jeffrey P. Kanne, MD; Ella A. Kazerooni, MD; Loren H. Ketai, MD; J. Anthony Parker, MD, PhD; James G. Ravenel, MD; Anthony G. Saleh, MD; Rakesh D. Shah, MD

Not stated

This is the current release of the guideline.

This guideline updates a previous version: Haramati LB, Little BP, Khan A, Mohammed TL, Batra PV, Gurney JW, Jeudy J, MacMahon H, Rozenshtein A, Vydareny KH, Washington L, Kaiser L, Raoof S, Expert Panel on Thoracic Imaging. ACR Appropriateness Criteria® acute respiratory illness in HIV-positive patient. [online publication]. Reston (VA): American College of Radiology (ACR); 2008. 6 p.

The appropriateness criteria are reviewed biennially and updated by the panels as needed, depending on introduction of new and highly significant scientific evidence.

Electronic copies: Available in Portable Document Format (PDF) from the American College of Radiology (ACR) Web site.

Print copies: Available from the American College of Radiology, 1891 Preston White Drive, Reston, VA 20191. Telephone: (703) 648-8900.

The following are available:

• ACR Appropriateness Criteria®. Overview. Reston (VA): American College of Radiology; 2 p. Electronic copies: Available in Portable Document Format (PDF) from the American College of Radiology (ACR) Web site.
• ACR Appropriateness Criteria®. Literature search process. Reston (VA): American College of Radiology; 1 p. Electronic copies: Available in Portable Document Format (PDF) from the ACR Web site.
• ACR Appropriateness Criteria®. Evidence table development. Reston (VA): American College of Radiology; 4 p. Electronic copies: Available in Portable Document Format (PDF) from the ACR Web site.
• ACR Appropriateness Criteria®. Radiation dose assessment introduction. Reston (VA): American College of Radiology; 2 p. Electronic copies: Available in Portable Document Format (PDF) from the ACR Web site.

None available

This NGC summary was completed by ECRI on November 12, 2004. The information was verified by the guideline developer on December 21, 2004. This NGC summary was updated by ECRI on March 22, 2006. This NGC summary was updated by ECRI Institute on July 23, 2009. This NGC summary was updated by ECRI Institute on February 29, 2012.

Instructions for downloading, use, and reproduction of the American College of Radiology (ACR) Appropriateness Criteria® may be found on the ACR Web site .