Diffuse pulmonary infiltrates after bone marrow transplantation: the role of open lung biopsy

doi:10.1016/j.athoracsur.2004.03.002

The Annals of Thoracic Surgery

Volume 78, Issue 1, July 2004, Pages 267-272

https://doi.org/10.1016/j.athoracsur.2004.03.002 Get rights and content

Abstract

Background

Diffuse pulmonary infiltrates is the major complication and cause of mortality after bone marrow transplantation. We analyzed the etiologies and prognostic factors in bone marrow recipients with diffuse pulmonary infiltrates and assessed the role of open lung biopsy in managing this complication.

Methods

Medical records of patients with diffuse pulmonary infiltrates after bone marrow transplantation were reviewed. Possible prognostic factors were analyzed by multivariate logistic regression.

Results

Sixty-eight (20%) of 341 bone marrow recipients had diffuse pulmonary infiltrates and 34 died. Thirty-five underwent open lung biopsy, resulting in therapeutic changes in 22 (63%) and clinical improvement in 16 (46%). The leading diagnoses were idiopathic interstitial pneumonitis (40%) and cytomegalovirus pneumonitis (20%). Cytomegalovirus pneumonitis caused radiographically observable interstitial infiltrates exclusively and was frequently associated with hepatitis. Idiopathic interstitial pneumonitis resulted in either diffuse ground-glass opacity or interstitial infiltrates. Three (9%) patients had miliary tuberculosis. Respiratory failure (p < 0.001) and acute graft-versus-host disease (p = 0.016) were the poor prognostic factors.

Conclusions

Among bone marrow recipients, we found diffuse pulmonary infiltrates in 20% and a mortality rate of 50%. Idiopathic interstitial pneumonitis and cytomegalovirus pneumonitis were the most common causes and should be suspected in patients with diffuse interstitial infiltrates. In endemic areas, miliary tuberculosis should be suspected in bone marrow recipients with diffuse reticulonodular lesions. Respiratory failure and acute graft-versus-host disease were poor prognostic factors. By establishing a correct diagnosis, open lung biopsy led to treatment changes in about two-thirds of these patients.

Section snippets

Patients and methods

This study was conducted in the National Taiwan University Hospital, a tertiary-care referral center with 2,000 beds, by review of the medical records and chest images of 341 patients with hematologic diseases who underwent BMT between July 1995 and June 2001. Patients in whom DPI developed were included, with DPI defined as the presence of infiltrates over all four quadrants of the lung fields as seen on chest radiograph. The date of onset was defined as the earliest date when image study

Results

From July 1995 through June 2001, pulmonary infiltrates after BMT occurred in 188 (55.1%) of 341 patients. Diffuse pulmonary infiltrates developed in 68 (19.9%) of the 341 patients, including 63 (23.7%) of 266 allogeneic recipients and 5 (6.67%) of 75 autologous recipients. The clinical characteristics of the 68 patients are listed in Table 1. Relapse of underlying disease before the onset of DPI was proved in 5 (7.4%) of the 68 patients. Sputum collected during the course of DPI was

Comment

Consistent with previous reports 2, 3, our incidence of pulmonary infiltrates after BMT was 55.1% (188 of 341 patients). About one-third of these patients had DPI (68 of 188 patients; 36.2%), with a high mortality rate (50%). The results of open lung biopsy caused major therapeutic change in two-thirds and were associated with clinical improvement in nearly half of the biopsy patients. Patients who underwent open lung biopsy had a much shorter length of mechanical ventilation than patients who

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Non-invasive diagnostic tests, such as sputum cultures, blood cultures, and serological tests, have limited diagnostic value in this setting. While open lung biopsy has the highest yield, the complication rate limits its use.7,8 Fiberoptic bronchoscopy with bronchoalveolar lavage (FOB-BAL) enables the selective collection of lung fluid so that a specific diagnosis of infectious, malignant, or hemorrhagic disorders can be achieved with relative ease.
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All consecutive patients with HM and pulmonary infiltrates, who underwent FOB-BAL between January 2008 and January 2013, were included in the analysis. Clinical characteristics, FOB-BAL results, and treatment adjustments were recorded, and factors predicting a positive BAL were assessed.
Four hundred and twenty-five FOB-BAL procedures were analyzed. BAL revealed a specific diagnosis in 219 (51.5%) patients, 208 of them with a pulmonary infection. Infectious etiological agents found were mainly Aspergillus spp (n = 142), bacterial species (n = 44), and Pneumocystis jirovecii (n = 34). Multivariate analysis showed that a lymphoproliferative disease, ≥2 symptoms (dyspnea/cough/hemoptysis/pleuritic pain), and less than 4 days between symptom appearance and FOB-BAL, predicted a positive FOB-BAL result. BAL results prompted a treatment modification in 48% of subjects.
FOB-BAL in conjunction with molecular assays is efficient in the rapid detection of life-threatening infections, allowing for adjustment of anti-infective therapy, which may result in better outcomes and reduce treatment-related toxicity.
Breathing difficulties in children subjected to bone marrow transplantation
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Hasta el 60% de los niños que reciben trasplante de médula ósea (TMO) presentan dificultad respiratoria. Supone una complicación cada vez más frecuente debido al aumento en el número de aplicaciones terapéuticas del TMO y al mejor abordaje terapéutico de los problemas asociados al mismo. Se describen las diferentes causas de dificultad respiratoria tras TMO en función de su instauración (precoz o tardía) o la presencia de infección en el origen de la misma. Se revisa a su vez el diagnóstico y tratamiento de cada una de ellas.
Up to 60% of all children that receive to bone marrow transplantation (BMT) develop respiratory distress. It constitutes a common complication in this kind of patients, due to the increasing number of therapeutic applications of BMT and to improvement in the therapeutic approach to the problems associated with this procedure. We describe the different causes of respiratory distress after BMT in relation to its initiation or the presence of infection in its origin. The diagnosis and treatment are also reviewed.
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La prise en charge d’une complication respiratoire chez un patient d’immunohématologie (IH) peut nécessiter, après diverses investigations, une intervention chirurgicale pulmonaire à visée diagnostique ou thérapeutique. Les complications postopératoires sont, dans ce contexte, mal connues. Entre octobre 2001 et janvier 2009, parmi 400 patients d’IH hospitalisés à l’hôpital Foch pour une complication respiratoire, 17 d’entre eux (13 hommes, d’âge moyen 46 ± 15 ans) ont eu besoin d’un acte chirurgical pulmonaire. Leur maladie hématologique était une leucémie, aiguë (n = 7), ou chronique (n = 5), un lymphome (n = 4) et huit étaient allogreffés de cellules souches hématopoïétiques. Treize patients avaient reçu au préalable un traitement potentiellement pneumotoxique. Les signes respiratoires évoluaient depuis 112 jours en moyenne (10–663 jours), et 14 recevaient un traitement antibiotique et/ou antifongique. Trois patients étaient thrombopéniques (transfusion plaquettaires, n = 2), et un patient présentait une leucopénie (leucocytose inférieure à 500/mm³). La chirurgie a consisté en l’exérèse d’un foyer mycotique résiduel (n = 5), ou en des biopsies pulmonaires à visée diagnostique (n = 12) : pneumopathie infiltrative non spécifique (n = 4), réaction de greffon contre l’hôte pulmonaire (n = 3), pneumocystose granulomateuse (n = 1), aspergillose invasive (n = 1), carcinome bronchique (n = 1), tuberculose pulmonaire (n = 1) et lymphoprolifération EBV-induite (n = 1). Le geste chirurgical a conduit à des modifications thérapeutiques dans dix cas (84 %). Tous les patients ont été extubés dans les 24 heures après l’intervention. Les complications postopératoires ont été un syndrome coronarien aigu d’évolution favorable (n = 1), une pneumonie (n = 3), un hématome intrapulmonaire (n = 1) et un bullage persistant plus de trois jours (n = 3). Sept patients ont été admis en unité de soins intensifs (USI) et cinq ont eu recours à de la ventilation non invasive. Chez trois patients, l’évolution a été secondairement défavorable, par aggravation de la pathologie respiratoire : pneumopathie interstitielle (n = 2) et pneumocystose (n = 1). La chirurgie pulmonaire ne doit pas être récusée chez des malades d’IH chez lesquels elle a deux indications : (1) thérapeutique, pour l’exérèse de nodules mycotiques persistant après traitement médical antifungique ; (2) diagnostique, permettant de fréquentes adaptations thérapeutiques au prix de complications modestes chez des malades sélectionnés au cas par cas selon leur état général, respiratoire et surtout leur pronostic hématologique.
Respiratory complications are frequent in haematological patients. Lung surgery, either for diagnosis or treatment, is considered useful but hazardous in these patients. We performed a reappraisal study of this purpose; retrospective study in a university centre, located in the Paris area, France. We analysed the entire records of all the haematological patients admitted in the Thoracic Surgery department from October 2001 to January 2009, among 400 haematological patients with pulmonary complications admitted to the Respiratory Diseases department. Seventeen patients (male: n = 13, mean age 47 ± 15 years) underwent lung surgery. Underlying haematological disease was acute (n = 7) or chronic (n = 5) leukaemia, lymphoma (n = 4), and eight have had stem cell transplantation. Thirteen patients had been exposed to a cytotoxic chemotherapy with known pulmonary toxicity. Respiratory diseases have been evolving for 112 days (10–663 days), and 14 patients received previously antibiotic and/or antifungal therapy. One patient was neutropenic and three had thrombopenia. Five patients underwent curative surgery for a residual pulmonary nodule after medical treatment of invasive aspergillosis, and 12 had a diagnostic procedure (open lung biopsy by video-assisted thoracoscopy [n = 2]; thoracotomy [n = 8]). Surgery permitted a final diagnosis in all 12 cases: non-specific infiltrative pneumonia (n = 4), pulmonary graft versus host disease (n = 3), granulomatous pneumocystosis (n = 1), invasive aspergillosis (n = 1), bronchial carcinoma (n = 1), EBV-related lymphoproliferation (n = 1), and tuberculosis (n = 1). Therapeutic regimens were modified according to the surgical results in ten cases (84%). All patients were extubated at the end of surgery. Post-operative complications were: prolonged air leaks (n = 3), pneumonia (n = 1), parenchymal hematoma (n = 1), acute coronary syndrome (n = 1). Seven patients were admitted in the Intensive Care Unit, and five had non-invasive ventilation. Three patients died from respiratory failure: NSIP (n = 2), pneumocystosis (n = 1). Lung surgery for selected haematological patients has two indications: (1) curative surgery, for a residual pulmonary nodule after medical treatment of invasive aspergillosis; (2) diagnostic procedure, leading frequently to modifications of therapeutic regimens, with low rate of complications, in highly selected patients.
Critical Illness Involving Children Undergoing Hematopoietic Progenitor Cell Transplantation
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Original article: general thoracicDiffuse pulmonary infiltrates after bone marrow transplantation: the role of open lung biopsy

Abstract

Background

Methods

Results

Conclusions

Section snippets

Patients and methods

Results

Comment

Chest

Chest

Chest

Chest

Chest

Chest

J Pediatr Surg

Chest

Chest

Am J Med

Crit Care Clin

Blood

Allogeneic bone marrow transplantationcurrent status and future directions

Blood

Open lung biopsy in immunocompromised children with pulmonary infiltrates

Am J Dis Child

Diagnosis of pneumonitis in immunocompromised patients by open lung biopsy

Cancer

Predictors of mortality in the immunocompromised patient with pulmonary infiltrates

Arch Intern Med

Risk-adapted pre-emptive therapy for cytomegalovirus disease in patients undergoing allogeneic bone marrow transplantation

Bone Marrow Transplant

Extended antigenemia surveillance and late cytomegalovirus infection after allogeneic BMT

Bone Marrow Transplant

CMV antigenemia assay using indirect ALP-immunostaining in bone marrow transplant recipients

Transplant Proc

Original article: general thoracic
Diffuse pulmonary infiltrates after bone marrow transplantation: the role of open lung biopsy