Pulmonary Infiltrates In Patients Research Articles

DIFFUSE ALVEOLAR HEMORRHAGE: A RARE COMPLICATION OF ACUTE MYELOID LEUKEMIA

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary syndrome affecting individuals with hematologic malignancies with increased incidence post bone marrow transplant. We present a rare case of DAH presumably related to pulmonary leukemic infiltration (PLI) in a newly diagnosed Acute Myelogenous Leukemia (AML) patient. CASE PRESENTATION: A 55-year-old female, previously healthy, presented to the emergency room with a 1-week history of dyspnea, cough, and epistaxis. Laboratory data were relevant for leukocytosis (WBC 150,000/mm3) with 84% blasts, thrombocytopenia (platelets 15,000/mm3), and anemia (Hb 8.9 g/dL). CT angiography of the chest was negative for pulmonary embolism but showed scattered bilateral ground-glass opacities (GGO). Peripheral blood flow cytometry revealed AML. She underwent leukapheresis with an appropriate response. On day 5 of admission, she was transferred to the intensive care unit for increased oxygen requirement and required endotracheal intubation the day after. Chest CT showed significant worsening in bilateral GGO and septal thickening. WBC 27,000/mm3, Hb 7.7 g/dL, and platelets 50,000/mm3. Bronchoscopy with serial bronchoalveolar lavages (BAL) showed an increasingly bloody return. BAL cell differential was significant for 75% blasts. She was treated with platelet transfusion, nebulized tranexamic acid, high dose corticosteroids, and empiric antibiotic therapy. Emergent induction chemotherapy (daunorubicin + cytarabine) was started. Repeat bronchoscopy in 48h showed resolution of DAH and undetectable blasts in BAL. She was extubated on day 7 post-intubation, and her respiratory status improved back to baseline. DISCUSSION: Pulmonary opacities in leukemia may be the result of an infectious process, pulmonary edema, drug toxicity, diffuse alveolar hemorrhage, intravascular leukostasis, or pulmonary leukemic infiltrates. Though the timing of pulmonary complications, clinical presentation, and chest CT findings may help identify the etiology, diagnosis is frequently challenging, and early BAL may be of benefit. In this patient, worsening respiratory status and pulmonary infiltrates despite leukapheresis excluded leukostasis and suggested PLI. Hemoptysis is absent in more than one-third of patients with DAH. She had no hemoptysis, and DAH was subsequently diagnosed with bronchoscopy. We believe that early diagnosis of PLI, excellent response to induction chemotherapy, along with other supportive measures led to a favorable outcome. CONCLUSIONS: Early recognition of acute respiratory failure etiology in patients with leukemia and pulmonary infiltrates is essential. Albeit rare, DAH should always be on the differential as early identification and treatment can likely improve outcomes. REFERENCE #1: Nanjappa S, Jeong DK, Muddaraju M, Jeong K, Hill ED, Greene JN. Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia. Cancer Control. 2016 Jul;23(3):272-7 REFERENCE #2: Nucci M, Nouér SA, Anaissie E. Distinguishing the Causes of Pulmonary Infiltrates in Patients with Acute Leukemia. Clin Lymphoma Myeloma Leuk. 2015 Jun;15 Suppl: S98-103. DISCLOSURES: No relevant relationships by Tony Abdo, source=Web Response No relevant relationships by Samiksha Gupta, source=Web Response No relevant relationships by SYED HUSSAIN, source=Web Response No relevant relationships by Miloni Parmar, source=Web Response

Clinical Usefulness of Bronchoalveolar Lavage in the Management of Pulmonary Infiltrates in Adults with Hematological Malignancies and Stem Cell Transplantation.

IntroductionPulmonary complications are frequent in patients with hematologic malignancies and stem cell transplantation. Regardless of the microbiological usefulness of bronchoalveolar lavage (BAL), little information exists on both its benefits as a guide for therapeutic decisions and its impact on patients’ clinical outcome.MethodsA prospective observational single-center study was performed between July 2011 and July 2016. Consecutive episodes of pulmonary infiltrates were analyzed in subjects over 18 years of age who presented hematologic malignancies and underwent chemotherapy or stem cell transplantation.ResultsNinety-six episodes of pulmonary infiltrates were analyzed. Acute leukemia was the most frequent underlying condition. Thirty-seven patients (38.5%) received a stem cell transplant. Sixty-one (62.9%) were neutropenic at the moment of inclusion in the study. A definitive etiologic diagnosis was obtained in 41 cases (42.7%), where infection accounted for the vast majority of cases (33 cases, 80.5%). Definitive diagnosis was reached by non-invasive methods in 13 cases (13.5%). BAL was performed in 47 cases and led to a diagnosis in 40.4% of the cases. BAL results led to therapeutic changes in 27 cases (57.4%), including the addition of new antimicrobials to empiric treatments in 10. Regarding BAL’s safety, two patients experienced minor adverse events and one a severe adverse event; no procedure-related deaths were observed.ConclusionsInfection was the leading cause of pulmonary infiltrates in patients with hematologic malignancies and stem cell transplantation. BAL was a useful decision-making diagnostic tool, with minor adverse events.

EP1.16-38 Pulmonary Infiltrates in Patients Treated with Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy

Interstitial lung disease (ILD) is one of the fatal toxicities of anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Some possible risk factors are indicated like male, smoker, and previous history of interstitial pneumonia, but clinical, and radiologic features are not well known. Patients who received anti-PD-1/PD-L1 monotherapy were identified at our hospital from March 2016 to October 2018. We identified the patients who developed pulmonary infiltrates after PD-1/PD-L1 therapy, cases with confirmed malignant lung infiltration were excluded. We retrospectively analyzed their clinical and radiological features. Of 77 patients who received anti-PD-1/PD-L1 mAbs, pulmonary infiltrates developed in 10. The clinical and radiologic features are shown in Table1,2.Table.1Baseline characteristics of 10 patients with pulmonary infiltrates related to immune checkpoint inhibitors.PtSexAgeHistologySmoking statusSmoking (pack-years)StagePrimary sitePerformance statusPrior chemotherapyRadiation history to the ChestTPS (22c3)Agents1M73AdenoFormer45ⅣRight upper lobe0NoneNone100Pembrolizumab2M74AdenoFormer80ReccurentRight lower lobe1NoneNone95Pembrolizumab3M71SquamousCurrent85.5ⅣRight lower lobe1NoneNone70Pembrolizumab4M84AdenoCurrent48ⅢCLeft lower lobe1NoneNone65Pembrolizumab5M71SquamousFormer46ⅣRight upper lobe1Carboplatin/nab-PaclitaxelDocetaxelNone30Pembrolizumab6M70SquamousFormer80ⅣLeft upper lobe0Carboplatin/nab-PaclitaxelCarboplatin/S1NoneNANivolumab7M61AdenoFormer28ⅢBLeft upper lobe1Carboplatin/PaclitaxelDocetaxelCarboplatin/PemetrexedCarboplatin/nab-Paclitaxel60GyNANivolumab8M61AdenoFormer37ⅣRight pleural0Carboplatin/PaclitaxelCarboplatin/PemetrexedDocetaxelCarboplatin/S-1NoneNANivolumab9M58SquamousFormer54ⅣLeft upper lobe2Carboplatin/Paclitaxel70GyNANivolumab10M81SquamousFormer59ⅣRight upper lobe2DocetaxelCarboplatin/S-1 nab-PaclitaxelNoneNANivolumab Open table in a new tab Table.2Occurrence with pulmonary infiltrates related to immune checkpoint inhibitors.PtRadiographic pattermGradeDistributionTime to event onset, daysKL-6, U/mlCRP at onset, mg/dlTreatmentTime from treatment to resolution/ resolving, daysOutcomeat Baselineat Event onset1DAD4Bilateral/Diffuse151493434825.2Steroid pulse therapyAntibiotics64Resolving2OP5Bilateral/Diffuse936894825.2Steroid pulse therapyAntibioticsNot resolvedNot resolved3OP2Bilateral/Focal6334015911.1Oral steroidsAntibiotics9Resolved4NSIP2Bilateral/Diffuse7140748912.2Antibiotics→Oral steroids60Resolved5NSIP3Bilateral/Diffuse1772412669.9Steroid pulse therapy7Resolved6OP3Bilateral/Diffuse29125411820.3Steroid pulse therapyNot resolvedNot resolved7NSIP1Unilateral/Focal2512561890.2None24Resolved8OP2Unilateral/Diffuse70N/A3002.3Steroid pulse therapy69Resolved9NSIP3Bilateral/Diffuse402N/AN/A7.3Steroid pulse therapyOxygen therapyAntibiotics18Resolving10OP1Unilateral/Focal56107812571.0None31Resolved Open table in a new tab Pulmonary infiltrates associated with anti-PD-1/PD-L1 mAbs showed variable onset and clinical, and radiologic appearances. Sometimes it is difficult to identify whether it is ILD or infection. Most ILD cases were successfully treated with corticosteroids, but rarely, ILD worsened despite treatment. Thus, careful monitoring including imaging examinations is important to preventing the worsening of ILD.

Tuberculosis Infection in a Patient Treated With Nivolumab for Non-small Cell Lung Cancer: Case Report and Literature Review

Nivolumab (PD-1 inhibitor) and other immune checkpoint inhibitors are used primarily to promote reactivation of anti-tumor immunity. However, due to their generalized immunorestorative properties, these agents may also trigger an unusual spectrum of side-effects termed immune-related adverse events. In the case of the lung, pulmonary infiltrates in patients treated with the anti-PD-1 inhibitors, nivolumab, or pembrolizumab, especially patients with non-small cell lung cancer, can result from immune-related pneumonitis, which, until fairly recently was believed to be of non-infective origin. This, in turn, may result in progression and pseudo-progression of disease. An increasing body of evidence has, however, identified pulmonary tuberculosis as an additional type of anti-PD-1 therapy-associated, immune-related adverse event, seemingly as a consequence of excessive reactivation of immune responsiveness to latent Mycobacterium tuberculosis infection. The current case report describes a 56-year old Caucasian female who presented with microbiologically-confirmed tuberculosis infection while on nivolumab therapy for non-small cell lung cancer. Notably, the patient, seemingly the first described from the African Continent, had not received immunosuppressive therapy prior to the diagnosis of tuberculosis.

Role of fiberoptic bronchoscopy in the diagnosis of pulmonary infiltrates in patients with hematological malignancies

RationalePatients with hematological malignancies are a special challenge to health care providers as they undergo a wide variety of immune-suppressive therapies. Both disease and therapy can cause complications. The lungs may be directly injured through infectious or toxic insults. Early identification of the nature of infiltrates will result in better outcome in the management of these patients. Fiberoptic bronchoscopy (FOB) may be a good tool for indentifying the infiltrate nature by using different diagnostic techniques like transbronchial lung biopsy (TBLB) and bronchoalveolar lavage (BAL).Patients and methodsThis study was performed over 6 months, in Kasr Al-Aini Hospital, Cairo University. It included 30 patients with hematological malignancies presenting with pulmonary infiltrates confirmed by computed tomography of the chest. All patients underwent history taking, clinical examination, and investigations included complete blood count and coagulation profile, BAL for culture and sensitivity, cytology examination, and TBLB.ResultsOverall diagnostic yield of FOB was 73.3% in this study. The diagnostic yield of FOB was higher for infectious (43.3%) than both noninfectious (20%) and mixed (10%) etiologies. The combined diagnostic yield of BAL for bacteriological examination and TBLB was higher than that of BAL for cytology examination. Bacteriological examination revealed a predominance for gram-negative bacteria in 62.5% of total culture and sensitivity.ConclusionThis study supports the role of FOB as the initial procedure of choice for identifying the nature of pulmonary infiltrates in patients with hematological malignancies. Because our results suggest that BAL and TBLB are complementary, we recommend performing TBLB whenever it is deemed safe. On the contrary, cytological examination of BAL fluids was not helpful in reaching a final diagnosis.

Distinguishing the Causes of Pulmonary Infiltrates in Patients With Acute Leukemia.

Pulmonary infiltrates are commonly observed in patients with acute leukemia (AL), particularly acute myeloid leukemia, who undergo remission induction therapy. The mortality rate is unacceptably high and depends on 3 factors: the host (performance status, comorbidities, and frailty), the etiology of the infiltrates and the type of response to antileukemic therapy. The approach to the diagnosis of pulmonary infiltrates in patients with AL includes a medical history, thorough physical examination, radiologic pattern of the infiltrates (focal vs. diffuse), and timing of their appearance in relation to the start of antileukemic therapy (early, ie, within the first 2 weeks or late). Localized infiltrates are most commonly caused by bacterial (early) and fungal infections (late). Diffuse early infiltrates might be caused by leukemic infiltration of the lungs, pulmonary hemorrhage and/or edema, diffuse alveolar damage, viral pneumonia, and rarely transfusion-related acute lung injury (TRALI) or the differentiation syndrome. Similar to the early phase, pulmonary edema, viral pneumonia, and rarely TRALI might cause diffuse infiltrates during the late phase, in addition to immune reconstitution and pneumocystosis, particularly among patients with acute lymphoblastic leukemia. Diagnostic tests, invasive and noninvasive, can be particularly useful to establish the diagnosis. Early intervention is critical and is based on the most likely diagnosis with modification when the etiology is confirmed.

Significance of Diffuse Pulmonary Infiltrates in Patients With Lung Cancer

Significance of Diffuse Pulmonary Infiltrates in Patients With Lung Cancer

Pneumocystis jirovecii pneumonia following everolimus treatment of metastatic breast cancer

Everolimus is an inhibitor of mammalian target of rapamycin with anti-tumour activity. While everolimus is known to cause drug-induced pneumonitis, it is rarely associated with Pneumocystis jirovecii pneumonia (PJP). We report a patient on everolimus therapy for metastatic breast cancer that developed PJP. Diagnosis was based on clinical features and a quantitative polymerase chain reaction for P. jirovecii DNA. Clinicians should consider PJP as a potential cause of pulmonary infiltrates in patients treated with everolimus.

Progression To Lower Respiratory Tract Disease In Parainfluenza Virus Infection After Hematopoietic Cell Transplantation Based On a New Classification

BackgroundParainfluenza virus (PIV) is a respiratory virus that infects approximately 10% of hematopoietic cell transplantation (HCT) recipients. A substantial proportion of patients with lower respiratory tract disease (LRD) present without prior upper respiratory tract infection (URI), but reasons for the lack of early detection are poorly understood. Since the definition of LRD differs among studies, we previously proposed a classification of LRD (possible, probable, and proven) that correlates with clinical outcomes (54thASH meeting; abstract #458). The classification demonstrated that patients with PIV detection in lungs (probable and proven LRD) had significantly worse survival than those with PIV detection in a nasopharyngeal (NP) sample alone (possible LRD and URI), with day 90 overall survival 50% vs. 90%, respectively. The purpose of the study was (1) to evaluate risk factors for progression to proven and probable LRD and (2) to determine factors associated with LRD without preceding URI. Patients and methodsThis retrospective cohort study included 391 HCT recipients with PIV infection transplanted between 1990 and 2011 at FHCRC. PIV detection was performed by conventional culture, direct fluorescent antibody testing, and/or polymerase chain reaction. Categories of PIV infection were defined according to site of PIV detection and radiography: URI: PIV detection in NP sample without new pulmonary infiltrates; possible LRD: detection in NP sample with new pulmonary infiltrates; probable LRD: detection in lung (BAL or biopsy) sample without new pulmonary infiltrates; and proven LRD: detection in lung sample with new pulmonary infiltrates. Patients diagnosed with LRD ≥ 2 days after URI diagnosis were considered to have progression to LRD. Risk factors for progression to proven/probable LRD were analyzed using Cox proportional hazards models, and comparisons between LRD cases with or without prior URI were performed by logistic regression models. ResultsAmong 391 patients, 344 had a positive NP sample at diagnosis of PIV infection and 47 were diagnosed with a positive lung sample alone. Among 344 patients, 61 progressed to LRD and median time to progression was 7 days (range, 2–40). The cumulative incidence of progression by 30-days among patients who presented with URI was 19%; 5%, 4% and 11% of patients progressed to possible, probable and proven LRD, respectively, and 28% of patients with possible LRD further progressed to proven LRD. In a multivariate model among the 344 patients, bone marrow (BM) or cord blood (CB) as cell source (aHR, 3.1; 95% CI, 1.6-5.9, p < 0.001), lymphocyte count less than 100/µL at time of PIV infection (aHR, 2.7; 95% CI, 1.5-4.8, p = 0.001), steroid use greater than 1mg/kg/day before PIV infection (aHR, 2.1; 95% CI, 1.1-4.1, p = 0.035), and PIV type 3 (aHR, 10.0; 95% CI, 1.4-100, p = 0.021) were significantly associated with progression to proven/probable LRD. New pulmonary infiltrates in patients with upper respiratory viral detection (possible LRD) was also associated with progression to proven/probable LRD (aHR, 5.2; 95% CI, 2.8-9.5, p < 0.001). Among 56 patients with possible LRD, all patients who had BM or CB as cell source and high-dose steroids progressed to proven/probable LRD while patients receiving peripheral blood stem cells (PBSCs) with low or no steroid exposure rarely progressed. Among 94 proven/probable LRD cases, 47 presented with LRD without prior URI. PBSCs as cell source (aOR, 4.20; 95% CI, 1.7-10, p = 0.002) and inpatient status at diagnosis (aOR, 3.86; 95% CI, 1.5-9.7, p = 0.004) were significantly associated with progression to LRD without prior URI. Overall, 9 / 47 patients (19%) without virologically proven prior URI had NP tests that were negative or non-interpretable. ConclusionProgression from URI to proven/probable LRD occurs in 21% of PIV-infected patients. Risk factors for progression include PIV-3 subtype, high-dose steroids, BM or CB as cell source and lymphopenia. Progression rates are also high in patients with possible LRD. These data provide important information for clinical trial design as new antivirals are being developed. Strategies are needed to improve detection of PIV prior to progression. Disclosures:Seo:Ansun BioPharma: Research Funding. Boeckh:Ansun BioPharma: Research Funding.

Pulmonary involvement by chronic lymphocytic leukemia/small lymphocytic lymphoma is a specific pathologic finding independent of inflammatory infiltration

Pulmonary infiltrates in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are usually secondary to infection, but a subset is due to pathologic infiltration of malignant lymphocytes into the lung parenchyma. In cases with both CLL/SLL and inflammatory infiltrates, it is unknown whether the CLL infiltrate represents a nonspecific “passenger effect” secondary to ongoing inflammation or pathologic leukemic pulmonary infiltration (LPI). We reviewed 49 lung biopsies taken from 38 patients with CLL/SLL. LPI was found in 2 of 21 cases (9.5%) with acute inflammation, 0 of 10 cases of chronic inflammation and in 7 of 18 cases (38.8%) without any pathologic findings of acute or chronic inflammation (p = 0.01). These results demonstrate that LPI identified in biopsies with concurrent inflammation is uncommon, and that most inflammatory infiltrates in patients with CLL do not cause “passenger effect” CLL infiltration. Therefore, LPI usually represents a specific pathologic process. We conclude that bronchoscopy with transbronchial biopsy is an effective tool for guiding treatment decisions for symptomatic patients with CLL with pulmonary infiltrates. Moreover, LPI by CLL is not a bystander effect secondary to acute inflammation, but instead represents a distinct pathologic process in a subset of patients.

Genome wide association identifies PPFIA1 as a candidate gene for acute lung injury risk following major trauma.

Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research.

Pulmonary Infiltration by CLL/SLL in the Presence of Inflammation: Significant or Incidental Finding?.

Abstract 2352Poster Board II-329Radiographically identified pulmonary infiltrates in patients with CLL are usually secondary to infectious causes. However, a subset of patients develop pathologic leukemic infiltrates. Lung biopsies containing both inflammation and CLL infiltrates are particularly problematic. It is unclear in such cases whether the CLL infiltrate represents a nonspecific “passenger effect” secondary to ongoing inflammation versus a pathologic leukemic infiltrate. Furthermore, it is unknown whether there are clinical factors that would help predict who is at higher risk for pulmonary infiltration by CLL. We retrospectively analyzed 45 transbronchial lung biopsies taken from 37 patients at the Cleveland Clinic between 1999 and 2008. We reviewed the biopsies for evidence of acute or chronic inflammation and involvment by CLL. Acute inflammation in our biopsies consisted of acute pneumonias. Cases displaying a lymphocytic infiltrate suspicious for CLL on routine H&E sections were further investigated by immunohistochemistry. The patients studied were 67.5% male with a median age of 67 (45-83) and a median absolute lymphocyte count of 2.75 (0.12 – 86.08). All patients at the time of diagnosis with CLL had flow cytometery of blood and/or bone marrow demonstrating CD5, CD19 positive B cells consistent with CLL. 72% of all patients were previously treated and 52% of patients had a RAI stage > 2 at the time of their diagnosis with CLL. CLL was identified in 20% of the biopsies. Of the 31.1% of biopsies showing acute inflammation, none had leukemia. CLL infiltration was found in association with and without chronic inflammation in 25% and 30.4% of the biopsies respectively. The median peripheral blood absolute lymphocyte count was 3.64 (1.33 – 86.08) in those with leukemic biopsies and 8.31 (0.12 – 79.12) in those without leukemic biopsies. Furthermore, only 33% of the patients with CLL positive biopsies had a RAI stage ≥ 3. At the time of biopsy, 7 previously treated patients were in remission; none of these cases displayed evidence of CLL in lung tissue. We found that the incidence of leukemic infiltration of lung biopsies did not increase in the presence of inflammation. In fact, the incidence of infiltration of biopsies with inflammation was lower than those without inflammation. These results demonstrate that leukemic infiltration on biopsies with inflammation is uncommon, and suggests that this phenomenon represents true, pathologic infiltration of the tissue by CLL and not a “passenger effect”. To the authors knowledge this is the largest study evaluating the association of inflammation and pathologic infiltration of pulmonary tissue by CLL. Disclosures:No relevant conflicts of interest to declare.

Investigation and management of a child who is immunocompromised and neutropoenic with pulmonary infiltrates

Paediatric neutropoenia encompasses a vast range of congenital and acquired causes. Postinfectious neutropoenia represents the most common cause of acquired isolated neutropoenia.1 Neutropoenia following viral infections tend to be brief...

Cetuximab-Associated Pulmonary Toxicity

There is increasing evidence for the use of epidermal growth factor receptor (EGFR) inhibitors in head and neck, non-small-cell lung, and colorectal cancers. We report the case of a 78-year-old man with metastatic colorectal cancer (CRC) involving liver and lung who received cetuximab plus irinotecan as third-line treatment. Two months later, he presented with signs and symptoms consistent with bronchiolotis obliterans organizing pneumonia secondary to cetuximab. Reports of cetuximab-associated pulmonary toxicity are rare, although there have been extensive reports of interstitial fibrosis with the use of other EGFR inhibitors such as gefitinib and erlotinib. There are many causes of pulmonary infiltrates in patients treated for advanced CRC, and this case highlights the importance of considering drug toxicity.

The Impact of Open Lung Biopsy on Diffuse Pulmonary Infiltrates in Patients with AIDS

The evidence concerning open lung biopsy (OLB) for diffuse pulmonary infiltrates in patients with AIDS is limited. This study retrospectively evaluated the diagnostic and therapeutic yields of OLB compared with bronchoscopy for patients with AIDS with diffuse pulmonary infiltrate treated in the National Taiwan University Hospital from 1997 to 2004. There were 15 and 46 patients enrolled in the OLB and bronchoscopic groups in this study, respectively. As compared with the bronchoscopic group, patients from the OLB group had a higher chance of acquiring a specific diagnosis and possible change of therapy (73 vs 32.6% and 60 vs 21.7%, respectively; P < 0.05). There were two (13.3%) patients with prolonged air leak (greater than 7 days) in the OLB group, whereas four patients (8.7%) had procedure-related complications in the bronchoscopic group. There was no procedure-related mortality in the OLB group. This study demonstrated that OLB can be safely performed in select patients and provide a superior diagnostic and therapeutic benefit compared with bronchoscopy for diffuse pulmonary infiltrates in patients with AIDS. This procedure should be performed early in the clinical course to avoid irreversible clinical deterioration of the patients with severe illness.

Implications of Early Versus Late Bilateral Pulmonary Infiltrates in Patients with Aneurysmal Subarachnoid Hemorrhage

Bilateral pulmonary infiltrates occur frequently following aneurysmal subarachnoid hemorrhage (SAH), and may be associated with worse outcomes. The etiology, natural history, and prognosis of infiltrates occurring soon after SAH may differ from the characteristics of infiltrates developing at a later time. We performed a retrospective cohort study involving 245 consecutive patients with a ruptured cerebral aneurysm to assess the association between "early" (< or = 72 h) or "late" (>72 h) bilateral pulmonary infiltrates and subsequent death or neurologic impairment. We used logistic regression models to adjust for baseline differences in age, level of consciousness, amount of blood on computed tomography, and the presence or absence of clinical vasospasm. Sixty-seven patients (27%) developed bilateral pulmonary infiltrates. Of these, 36 (54%) had early infiltrates, 24 (36%) had late infiltrates, and 7 (10%) had both. Twenty-eight patients (11% of entire cohort) met criteria for acute respiratory distress syndrome (ARDS). Patients with early infiltrates were more likely to have presented with stupor or coma than patients who developed infiltrates later (64% vs. 29%, P < 0.01). In multivariable analysis, late pulmonary infiltrates were strongly predictive of poor outcome (OR 5.0, 95% CI 1.9-13.6, P < 0.01), while early infiltrates were not (OR 1.2, 95% CI 0.5-3.0, P = 0.66). Bilateral pulmonary infiltrates after SAH most often occur within three days of aneurysm rupture. However, only infiltrates occurring beyond this time are independently associated with poor outcome. Increased emphasis on the prevention of late pulmonary complications has the potential to improve outcomes in SAH.

The development of sarcoidosis with the use of alemtuzumab – clues to T‐cell immune reconstitution

The development of sarcoidosis with the use of alemtuzumab – clues to T‐cell immune reconstitution

Organizing Pneumonia and Pulmonary Eosinophilic Infiltration Associated with Daptomycin

To report a case of organizing pneumonia with pulmonary eosinophilic infiltrates in a patient receiving daptomycin. An 84-year-old man developed bilateral, irregularly shaped nodules and infiltrates in the mid and peripheral lung and multiple mediastinal lymph nodes following treatment with intravenous daptomycin for infection of his left knee prosthesis. His other symptoms included decreased appetite, weight loss (6.8 kg over 4-6 wk), malaise, and generalized weakness after 4 weeks of daptomycin therapy. Transthoracic needle biopsy revealed organizing pneumonia with scattered eosinophils. His symptoms and results of computed tomography (CT) scan improved in the month following discontinuation of daptomycin. The Naranjo probability scale indicated a probable reaction to daptomycin. Pulmonary reactions have been reported with numerous drugs and have a wide range of clinical and radiographic presentations. Clinical trials have shown that daptomycin is well tolerated and has an adverse effect profile similar to that of vancomycin and the semisynthetic penicillins. This case report suggests that chronic use of daptomycin caused organizing pneumonia with eosinophilic infiltrates in a patient treated for an infected knee prosthesis. A definite mechanism for this reaction is not known. We speculate that the chronic administration of daptomycin allowed drug accumulation in surfactant in the alveolar spaces. This may result in higher concentrations of drug near the alveolar epithelial surface, which could injure the epithelium, resulting in organizing pneumonia. Development of new pulmonary infiltrates in patients treated with chronic daptomycin therapy should alert healthcare workers to this potential association.

Fatal case of amiodarone-induced acute respiratory distress syndrome in a patient with severe left ventricular dysfunction due to extensive anterior acute myocardial infarction.

We here report a case of 71-year-old man with acute extensive anterior myocardial infarction, who was complicated with ventricular tachycardia (VT) even after successful percutaneous coronary intervention. As intravenous administration of nifekalant terminated VT, we started oral administration of amiodarone (day 1). We gave 400 mg of amiodarone a day for the first week and 200 mg a day from the second week. The patient was stable with normoxia by day 20, in spite of pulmonary congestion-like infiltrates on chest X-ray. On day 21, he was complicated with acute respiratory distress syndrome. Immediate discontinuance of amiodarone and high-dose pulse glucocorticoid therapy with intubation slightly improved the infiltrations on chest X-ray. However, glucocorticoid therapy induced hyperglycemia with an increase in plasma osmolality, complicated with hypoalbuminemia, and gastrointestinal bleeding. Despite treatment with a large amount of saline, high-doses of catecholamines, and blood transfusion, the patient died on day 28. It is sometimes difficult to diagnose congestive heart failure or amiodarone-induced pulmonary infiltrates in patients with severe left ventricular dysfunction.

Diagnostic value of C-reactive protein in discriminating fungal from nonfungal pulmonary infiltrates in patients with hematologic malignancies

The objective of this study was to assess the utility of C-reactive protein (CRP) on differential diagnosis of pulmonary infiltrates occurring in 143 febrile patients with hematologic malignancies. Serum CRP level, measured on the first day of pneumonia, was significantly higher in patients with fungal lung infiltrates than in those with nonfungal pneumonia (22.3 mg/dl vs 7.3 mg/dl; p<0.0001). Predictive factors for fungal pneumonia were CRP level higher than 10 mg/dl, neutropenia longer than 10 days, and active underlying disease.