Unexplained Pulmonary Infiltrates Research Articles

Diagnostic yield, safety, and impact of transbronchial lung biopsy in mechanically ventilated, critically ill patients: a retrospective study

BackgroundPulmonary infiltrates of variable etiology are one of the main reasons for hypoxemic respiratory failure leading to invasive mechanical ventilation. If pulmonary infiltrates remain unexplained or progress despite treatment, the histopathological result of a lung biopsy could have significant impact on change in therapy. Surgical lung biopsy is the commonly used technique, but due to its considerable morbidity and mortality, less invasive bronchoscopic transbronchial lung biopsy (TBLB) may be a valuable alternative.MethodsRetrospective, monocentric, observational study in mechanically ventilated, critically ill patients, subjected to TBLB due to unexplained pulmonary infiltrates in the period January 2014 to July 2019. Patients’ medical records were reviewed to obtain data on baseline clinical characteristics, modality and adverse events (AE) of the TBLB, and impact of the histopathological results on treatment decisions. A multivariable binary logistic regression analysis was performed to identify predictors of AE and hospital mortality, and survival curves were generated using the Kaplan-Meier method.ResultsForty-two patients with in total 42 TBLB procedures after a median of 12 days of mechanical ventilation were analyzed, of which 16.7% were immunosuppressed, but there was no patient with prior lung transplantation. Diagnostic yield of TBLB was 88.1%, with AE occurring in 11.9% (most common pneumothorax and minor bleeding). 92.9% of the procedures were performed as a forceps biopsy, with organizing pneumonia (OP) as the most common histological diagnosis (54.8%). Variables independently associated with hospital mortality were age (odds ratio 1.070, 95%CI 1.006–1.138; p = 0.031) and the presence of OP (0.182, [0.036–0.926]; p = 0.040), the latter being confirmed in the survival analysis (log-rank p = 0.040). In contrast, a change in therapy based on histopathology alone occurred in 40.5%, and there was no evidence of improved survival in those patients.ConclusionsTransbronchial lung biopsy remains a valuable alternative to surgical lung biopsy in mechanically ventilated critically ill patients. However, the high diagnostic yield must be weighed against potential adverse events and limited consequence of the histopathological result regarding treatment decisions in such patients.

Utility of surgical lung biopsy in critically ill patients with diffuse pulmonary infiltrates: a retrospective review.

There are conflicting reports regarding the role of surgical lung biopsies in patients who present to the intensive care unit (ICU) with unexplained respiratory failure and diffuse pulmonary infiltrates on imaging. To describe the utility of surgical lung biopsies in patients presenting to the ICU with unexplained respiratory failure and diffuse pulmonary infiltrates. A retrospective cohort study was performed. All patients admitted to the ICU who underwent a surgical lung biopsy for the investigation of respiratory failure and unexplained pulmonary infiltrates between 1998 and 2012 were included. The primary outcome measures for this descriptive study were the biopsy histopathology, changes in patient management following biopsy and in-hospital mortality. A total of 30 patients was included in the review. Biopsies in 22 patients (73%) demonstrated diffuse alveolar damage (DAD), with 15 of these biopsies (50%) suggesting a specific underlying aetiology. In 73% of cases (n = 22), the biopsy finding was associated with a change in management, although this generally involved the escalation of an existing therapy rather than initiation of a new treatment. Biopsies were performed at a median 10 days after admission (interquartile range 5-17 days), with the majority of patients being treated empirically prior to the biopsy with systemic steroids and broad-spectrum antimicrobials. Mortality was 53%. In this series, DAD was the most frequent pathology. The biopsy result was associated with a change in management in a majority of the subjects, most frequently an escalation of prior empiric therapy. Mortality was high.

Aggressive Pulmonary Calcification Developed After Living Donor Kidney Transplantation in a Patient With Primary Hyperparathyroidism

Metastatic pulmonary calcification, defined as calcium deposition in the intact lung, is commonly seen in patients with chronic renal failure, and it is known to be a benign clinical condition when detected by chance in an asymptomatic patient. Here we report the case of a 33-year-old woman who developed rapid and aggressive metastatic pulmonary calcification shortly after a living donor kidney transplantation, which induced acute antibody-mediated rejection. The patient's metastatic pulmonary calcification was successfully improved by extensive treatment for graft rejection, the correction of her accompanying primary hyperparathyroidism, and medical treatment with a bisphosphonate and sodium thiosulfate. Aggressive pulmonary calcification is reported as a rare complication seen in patients who have undergone a failed renal transplantation. A failed renal graft and accompanying secondary hyperparathyroidism seem to accelerate metastatic calcification. Most of the patients who develop aggressive pulmonary calcification suffer from the rapid progression of dyspnea and occasionally fever, and they die of respiratory failure. Pulmonary calcification should be considered in a patient developing dyspnea and unexplained pulmonary infiltrate, especially in the context of renal graft rejection; otherwise the prognosis of the patient will be very poor.

Impact of Toxocariasis in Patients with Unexplained Patchy Pulmonary Infiltrate in Korea

Toxocariasis is one of the causes of pulmonary eosinophilic infiltrate that is increasing in Korea. This study was designed to identify the prevalence of toxocara seropositivity in patients with unexplained pulmonary patchy infiltrate and to evaluate associated factors. We evaluated 102 patients with unexplained pulmonary patchy infiltrate on chest computed tomography (CT) scan. As a control set, 116 subjects with normal chest CT were also evaluated. History of allergic disease, drug use, parasitic disease and raw cow liver intake were taken. Blood eosinophil count and total IgE level were measured. Specific serum IgG antibody to Toxocara canis larval antigen and specific IgG antibodies to 4 other parasites were measured by enzyme-linked immunosorbent assay (ELISA). In the infiltrate group, 66.7% subjects were toxocara seropositive whereas 22.4% of the control group were seropositive (p<0.001). In the infiltrate group, patients with a history of eating raw cow liver (odds ratio [OR], 7.8) and patients with eosinophilia (OR, 5.2) had a higher incidence of toxocara seropositivity. Thirty-five percent of toxocara seropositive patients with infiltrate exhibited migrating infiltrate and 48% had decreased infiltrate on the follow-up CT. We recommend that toxocara ELISA should be performed in patients with unexplained pulmonary patchy infiltrate, and that the eating of raw cow liver should be actively discouraged.

Outcome of Hematopoietic Stem Cell Recipients Who Were Mechanically Ventilated and Admitted to Intensive Care Units

To evaluate the ICU mortality rate of mechanically ventilated hematopoietic stem cell transplantation (HSCT) recipients and to identify the factors that were associated with ICU mortality. The impact of surgical lung biopsy (SLB) in patients with unexplained pulmonary infiltrates was also evaluated. Forty-one mechanically ventilated HSCT recipients admitted to the ICU during the study period were enrolled. The medical records were reviewed and data at ICU admission were analyzed. Data were compared between ICU survivors and nonsurvivors. The pathologic findings of SLB and the resulting impact on treatment were analyzed. Eight patients (19.5%) survived the ICU stay, and seven (17%) lived to hospital discharge. The most common etiologies of ICU mortality included bacterial pneumonia, cytomegalovirus pneumonia, diffuse alveolar hemorrhage, sepsis, and aspergillosis. The factors associated with higher mortality were older age when performing HSCT, older age at ICU admission, higher acute physiology and chronic health evaluation (APACHE) II score, shock, higher respiratory rate, and higher heart rate at the time of ICU admission. Ten patients underwent SLB which resulted in treatment changes in five of them. Three patients had complications of SLB and one patient died of complications. The ICU mortality rate of mechanically ventilated HSCT recipients was high. Factors associated with ICU mortality were older age, high APACHE II score, presence of shock, and higher respiratory or heart rate at the time of ICU admission. SLB might provide specific diagnosis in HSCT recipients with unexplained pulmonary infiltrates and aid modification of treatment.

The Findings of Surgical Lung Biopsy in HIV Patients in the Era of Highly Active Antiretroviral Therapy

Surgical lung biopsy (SLB) is rarely necessary in the evaluation of pulmonary infiltrates in patients with human immunodeficiency virus (HIV). The aim of this study is to describe the findings of SLB in a recent cohort of HIV-infected patients with unexplained pulmonary infiltrates, and determine the impact of this procedure on management and outcome of these patients. We used a retrospective review of medical records for this study. Twenty-six patients who underwent SLB where evaluated. The procedure was performed either by video-assisted thoracoscopy, in 42% of the cases, or by thoracotomy in 58%. Eleven patients (42%) had focal infiltrates, and 15 (58%) had diffuse infiltrates. There were 31 diagnoses in the 26 patients; 26 (84%) were specific and 5(16%) were nonspecific. The most common specific diagnoses were infection (58%), malignancy (16%), and inflammatory conditions (10%). Pneumocystis carinii, alone or in combination with other conditions, was the most common diagnosis of all biopsies (34%). Surgical lung biopsy led to a change in management in 17 patients (65%), and was associated with complications in 4 patients (15%). The in-hospital mortality rate was 27%. Surgical lung biopsy is a relatively safe procedure, and provides a specific diagnosis in the majority of patients with HIV infection and unexplained pulmonary infiltrates. Pneumocystis carinii alone or in combination with other conditions is the most common finding.

Surgical lung biopsy in patients with hematological malignancy or hematopoietic stem cell transplantation and unexplained pulmonary infiltrates: Improved Outcome with specific diagnosis

Using a retrospective review of medical records, we sought the findings of surgical lung biopsy (SLB) in patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT) and unexplained pulmonary infiltrates and to determine the impact of this procedure on management and outcome of these patients. Sixty-two patients who underwent SLB were evaluated; 31 patients had underlying hematological malignancy and 31 patients were HSCT recipients; 58% of whom underwent allogeneic HSCT. Thirty-three patients (53%) had focal infiltrates on chest CT scan while 29 (47%) had diffuse infiltrates. Thirteen patients were mechanically ventilated prior to SLB, and 27 (43%) were neutropenic. There were 66 diagnoses in the 62 patients, 44 (67%) were specific and 22 (33%) were nonspecific. The most common specific diagnoses were infection (29%), malignancy (27%), and inflammatory conditions (11%). Aspergillosis was the most common diagnosis of all biopsies (21%). SLB led to a change in therapy in 40% of patients and was associated with complications in 7 patients (11%). Specific diagnosis was more likely to lead to a change in therapy (48% vs. 27%, P = 0.06) and was associated with a lower mortality when compared to a nonspecific finding (30% vs. 59%, P = 0.02). Nonspecific diagnosis, on the other hand, was seen more in patients on mechanical ventilation prior to SLB compared to those off mechanical ventilation (69% vs. 27%, P = 0.02). SLB provides a specific diagnosis in the majority of patients with hematologic malignancy or HSCT recipients and unexplained pulmonary infiltrates. Specific diagnosis is more likely to lead to a change in therapy and is associated with a better outcome.

PULMONARY COMPLICATIONS OF LIVER TRANSPLANTATION

The preoperative pulmonary evaluation of organ transplant candidates involves the diagnosis of unexplained pulmonary infiltrates or symptoms, interpretation of pulmonary function abnormalities, and an assessment of surgical risk. Pretransplant pulmonary considerations in patients with end-stage hepatic diseases relate primarily to hypoxemia from poorly understood intrapulmonary vascular dilatations, mechanical dysfunction, and states of increased extravascular lung water. Except in severe cases, however, these generally do not prohibit liver transplantation, and even are likely to improve after transplant surgery. Early postoperative complications may be categorized as those expected from extensive intra-abdominal surgery that requires significant volume resuscitation, which typically are managed in the usual manner for those clinical situations. As immunosuppression begins to have an effect, the LTx recipient becomes susceptible to the same opportunistic infectious organisms (with their frequent pulmonary involvement) that cause significant morbidity and mortality in recipients of other solid organ transplants. Because many of the immunosuppressive agents also are the same, noninfectious side effects such as pulmonary edema and malignancy also are similar. As with all immunocompromised patients, prophylaxis, when possible, persistent infection surveillance, and an aggressive diagnostic and therapeutic approach help decrease the impact of pulmonary dysfunction in LTx recipients.

Spectrum of Invasive Pulmonary Aspergillosis in Immunocompetent Patients With Chronic Obstructive Pulmonary Disease

Invasive pulmonary aspergillosis is a well-recognized complication in immunocompromised patients, especially those with neutropenia. We report four cases of invasive pulmonary aspergillosis in patients whose main underlying disease was chronic obstructive pulmonary disease (COPD). Two patients had an acute fatal course, one had chronic necrotizing pulmonary aspergillosis ending in an acute fatal course, and the other had a semiacute disease that responded to amphotericin B. Autopsy on three patients showed invasive pulmonary aspergillosis in both lungs, and tissue invasion was documented by transbronchial biopsy in the patient who survived. Retrospective review of all cultures that grew Aspergillus species from bronchoscopic specimens showed no false-positive results, and this procedure proved to be the most useful maneuver in making the diagnosis. Invasive pulmonary aspergillosis should be in the differential diagnosis in patients with COPD and unexplained pulmonary infiltrates.

Diagnostic Significance of Increased Bronchoalveolar Lavage Fluid Eosinophils

We determined the incidence of increased bronchoalveolar lavage (BAL) fluid eosinophil percentages in 1,059 consecutive patients undergoing bronchoscopy with BAL over a 33-month period. Forty-eight (48) patients were found to have 5% or more BAL eosinophils. The most common causes for increased BAL eosinophils were interstitial lung diseases (40% of patients), acquired immunodeficiency syndrome (AIDS)-associated pneumonia (17% of patients), idiopathic eosinophilic pneumonia (15% of patients), and drug-induced lung disease (12% of patients). Together, these four diagnoses accounted for 84% of all patients. In contrast, eosinophils were uncommon in the BAL of patients with the adult respiratory distress syndrome, lung cancer, community-acquired pneumonia, or immunocompromising diseases other than AIDS. The finding of increased BAL eosinophils was most helpful in patients presenting with unexplained pulmonary infiltrates. In these patients, this finding was often an important clue to the final diagnosis. We conclude that although the finding of an increased percentage of BAL eosinophils is uncommon, when present it is relatively specific for a limited number of diseases.

Alveolar cell carcinoma complicating sickle cell anemia: A chance occurrence?

Alveolar cell carcinoma, a neoplasm associated with pre-existing inflammatory lung disease, has not been reported previously in patients with sickle cell disease. We present such a patient and suggest that chronic pulmonary scarring in this setting predisposed to development of his malignancy. As survival increases in individuals with sickle cell disease, alveolar cell carcinoma must be considered in these differential diagnosis of otherwise unexplained chronic pulmonary infiltrates.

Isolation of Exophiala jeanselmei From Light-Green Staining Solution

A 7-year-old boy underwent an open lung biopsy as part of a workup for unexplained pulmonary infiltrates. Gomori's methenamine silver-stained sections revealed fungal hyphae in a background of chronic interstitial pneumonitis, with no evidence of abscess or granuloma formation. To explain this discrepancy, we cultured the light-green solution used as the counterstain. A dematiaceous fungus was isolated and identified as Exophiala jeanselmei. Without cultural identification of this fungus, observation of the hyphal forms in tissue sections could have led to the misdiagnosis of the patient's illness and inappropriate treatment.

Sputum examination for the diagnosis of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

The diagnostic utility of sputum examination in patients with Pneumocystis carinii pneumonia secondary to the acquired immunodeficiency syndrome (AIDS) has so far not been determined. Sputum was induced in 43 patients with AIDS or suspected AIDS just prior to fiberoptic bronchoscopy, scheduled because of an unexplained pulmonary infiltrate on a chest radiograph. Pneumocystis carinii pneumonia was diagnosed by sputum examination and/or by a bronchoscopic procedure in 20 patients. Of these, sputum samples were positive for Pneumocystis organisms in 11 (55%) of 20 patients tested, bronchial washings were positive in 11 (79%) of 14 patients tested, brush biopsies were positive in 9 (53%) of 17 patients tested, and transbronchial lung biopsies were positive in 18 (90%) of 20 patients tested. The presence of P. carinii cysts in sputum did not correlate with the presence of alveolar macrophages in sputum nor with the volume of sputum. Sputum examination for P. carinii organisms, employed as a first diagnostic step in patients with AIDS with pulmonary infiltrates, may frequently obviate the need for bronchoscopy.

Metastatic Carcinoma in Inguinal Hernia Sac

A patient with unexplained low back pain, weight loss, and pulmonary infiltrate underwent an inguinal herniorrhapy. Histologic examination of the grossly normal hernia sac revealed metastatic adenocarcinoma. The patient died of cachexia 10 months later. This case observation suggests the necessity of histologic examination of grossly normal hernia sacs.

Sea-Blue Histiocytes

Sea-blue histiocytes were found scattered throughout Wright-Giemsa-stained smears of a bone marrow aspiration from a 33-year-old man with recently diagnosed chronic myelogenous leukemia. Such cells have been occasionally discovered in bone marrow since the original report by Wewalka 1 in 1950. A genetic syndrome has become recognized having a usual presentation early in the third decade of life with hepatosplenomegaly and thrombocytopenic purpura. Macular abnormalities, unexplained pulmonary infiltrates, and neurological abnormalities have been seen in some patients. Pathologically, infiltration by histiocytes is seen in bone marrow and spleen. The histiocytes are typically 20 to 60 μm in diameter and have a single eccentric nucleus with a prominent nucleolus. Contained in the cytoplasm are numerous large granules that stain brilliantly blue-green or sea-green on Wright-Giemsa-stained preparations. These granules are also stained intensely by Sudan black and other lipid stains, and increased storage of sphingomyelin and glycosphingolipids has been found in the

Unexplained pulmonary infiltrates in the compromised patient. An invasive investigation in a consecutive series.

A series of 51 consecutive unexplained pulmonary infiltrates were reviewed retrospectively, in a group of 48 patients in whom invasive procedures were performed. Fifty-two percent of these patients had leukemia or lymphoma and 40% had solid tumors. All patients had lung tissue obtained premortem either by transbronchial biopsy through the flexible fiberoptic bronchoscope or by open lung biopsy. There was a 27% complication rate in these invasive procedures including bleeding, pneumothorax, and ventilatory support. Infectious agents were found in only 13 cases (25%) with a mortality rate of 62%. The pathologic finding of the underlying malignant disease or organizing pneumonia portended a poor prognosis with 100% and 80% mortality, respectively. Twenty-one patients had biopsy tissue revealing only nonspecific pathologic changes and were associated with the lowest mortality (19%). It was found that 50% of the solid tumor patients with unexplained pulmonary infiltrates had nonspecific pathologic changes. The biopsy findings resulted in a change in the therapy in 29% of the cases and in 19% of the cases the subsequent change in therapy resulted in marked improvement. The lung biopsy is useful to diagnose treatable infectious disease, as well as for prognostic guidance in caring for critically ill compromised patients.