Noninfectious lung complications after allogeneic haematopoietic stem cell transplantation.

Epidemiological data on late-onset noninfectious pulmonary complications (LONIPCs) following allogeneic haematopoietic stem cell transplantation (HSCT) are derived exclusively from retrospective studies and are conflicting. We aimed to evaluate prospectively the incidence, risk factors and outcomes for LONIPCs.All consecutive patients scheduled to receive allogeneic HSCT between 2006 and 2008 at a university teaching hospital in France were screened for inclusion in the study. Eligible patients were those surviving at day 100. Among 243 screened patients, 198 patients were included in the analysis. The median (interquartile range) follow-up was 72.3 (15.2-88.5) months. 55 LONIPCs were diagnosed in 43 patients. Bronchiolitis obliterans syndrome (n=22) and interstitial lung disease (n=12) were the most common LONIPCs. At 36 months after inclusion, the estimated cumulative incidence of LONIPCs was 19.8% (95% CI 14.2-25.3%). The estimated median survival after the diagnosis of LONIPCs was 78.5 months (95% CI 20.0-not reached). Based on a multivariate Cox model, a history of chest irradiation anytime prior to HSCT, a history of pneumonia within 100 days post-HSCT and a low mean forced expiratory flow at 25-75% of forced vital capacity at day 100 were associated with the development of LONIPCs.Our data provide clues to identify patients at high risk of developing LONIPCs. These patients should be targeted for close monitoring to provide earlier LONIPC treatment or prophylactic treatment.

Lung histopathology of non-infectious pulmonary complications after allogeneic haematopoietic stem cell transplantation.

AIMS: Non-infectious pulmonary complications (NIPCs) occur frequently following allogeneic haematopoietic stem cell transplantation (HSCT). As there is no consensus on the description of the related pulmonary pathological lesions, pathologist reports and clinical conclusions are largely inconsistent in routine practice. The aim of our study was to provide an accurate overview of post-allogeneic HSCT NIPCs from a large number of lung biopsies. METHODS AND RESULTS: We reviewed 61 lung biopsies in patients with an NIPC, including 51 surgical lung biopsies, four post-mortem biopsies and six lung explants. We found both bronchiolar (n = 59) and alveolar/interstitial pathologies (n = 27). We describe two types of bronchiolar lesions: bronchiolectasies (n = 37) and fibrous and cellular lesions with luminal narrowing (n = 43). We found a wide spectrum of airway/interstitial pathologies that were labelled using the terminology of the 2013 American Thoracic Society and European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs), including the following: organising pneumonia (OP, n = 8), non-specific interstitial pneumonia (NSIP, n = 9), diffuse alveolar damage (DAD, n = 6), lymphoid interstitial pneumonia (LIP, n = 1) and pleuroparenchymal fibroelastosis (PPFE, n = 2), as well as one instance of associated PPFE and NSIP. CONCLUSIONS: Interstitial pathology was associated with bronchiolar lesions in 41% of the cases reviewed (n = 25). Lung airway and interstitial inflammation was still present in lung explants from patients who underwent lung transplantation for post-allogeneic HSCT end-stage respiratory insufficiency. Herein, we describe a wide spectrum of pathological lung lesions encountered in post-allogeneic HSCT NIPCs.

Budesonide/Formoterol for bronchiolitis obliterans after hematopoietic stem cell transplantation.

RATIONALE: Systemic steroids are the standard treatment for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) despite their poor efficacy and disabling side effects. OBJECTIVES: To evaluate the effectiveness and tolerance of budesonide/formoterol as an alternative treatment for BOS after HSCT. METHODS: In this randomized, double-blind, placebo-controlled study, we randomly assigned 32 HSCT recipients with mild/severe BOS to receive budesonide/formoterol or placebo for 6 months. The primary outcome was the change in the FEV1 after 1 month of treatment (M1) compared with the baseline value. Patients were unblinded at M1 if there was no improvement in the FEV1. Those who had initially received placebo were switched to budesonide/formoterol. Intention-to-treat analysis was performed to assess the primary outcome. Additional analyses took scheduled treatment contamination into account. MEASUREMENTS AND MAIN RESULTS: At M1, the median FEV1 increased by 260 ml in the budesonide/formoterol arm compared with 5 ml in the placebo arm (P = 0.012). The median increases in the FEV1 at M1 relative to the baseline value for the treated and placebo groups were 13 and 0%, respectively (P = 0.019). Twenty-five patients received budesonide/formoterol during the study. The median difference in the FEV1 between the baseline and after 1 month of treatment for these patients was +240 ml (P = 0.0001). The effect of budesonide/formoterol on the FEV1 was maintained in the 13 patients who completed 6 months of treatment. CONCLUSIONS: Budesonide/formoterol administration led to a significant improvement in the FEV1 in patients with mild/severe BOS after allogeneic HSCT. Clinical trial registered with www.clinicaltrials.gov (NCT00624754).

The strategy for the diagnosis of invasive pulmonary aspergillosis should depend on both the underlying condition and the leukocyte count of patients with hematologic malignancies.

The identification of the causative organism in invasive pulmonary aspergillosis (IPA) is recommended. We investigated whether a mycologic diagnostic strategy could be optimized based on patient characteristics. Fifty-five patients were enrolled in a prospective study. The presence of Aspergillus in respiratory samples occurred more frequently in non-acute leukemia (AL) patients than in AL patients (P = .0003), and in patients with leukocyte counts more than 100/mm(3) (P = .002). In a logistic regression model, these 2 factors appeared to be independent, with an adjusted odds ratio of 7.14 (95% confidence interval, 1.40-36.5) for non-AL patients and an adjusted odds ratio of 6.97 (95% confidence interval, 1.33-36.5) for patients with leukocyte counts more than 100/mm(3). A positive mycologic result was also more frequent among patients with lung CT scan signs of airway-invasive disease than among other patients (P = .043). Airway-invasive signs were more frequent among non-AL patients (P = .049), whereas angioinvasive disease was more frequent among both AL patients (P = .01) and patients with leukocyte counts less than 100/mm(3) (P = .001). A concomitant pulmonary infection was identified more frequently among non-AL patients (P = .005 vs allogeneic hematopoietic stem cell transplant and P = .048 vs others). Our results suggest that different strategies for diagnosing IPA should be considered based on the underlying condition.

Prospective evaluation of clinical and biological markers to predict the outcome of invasive pulmonary aspergillosis in hematological patients.

Early evaluation of treatment efficacy in invasive aspergillosis (IA), a leading cause of morbidity and mortality in hematological patients, remains a challenge. We conducted a prospective study to evaluate the performance of different markers in predicting the outcome of patients with IA. Both clinical and biological criteria were assessed 7, 14, 21, and 45 days after inclusion in the study, and mortality was assessed at day 60. The association between baseline data and their evolution and the day 45 response to treatment was analyzed. A total of 57 patients (4 with proven, 44 with probable, and 9 with possible aspergillosis according to the revised EORTC/MSG [European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group] definitions) were included. At day 45, 30 patients (53%) were determined to be responders, 25 (44%) were nonresponders, and 2 were not able to be evaluated. Twenty patients died within the 60 days of follow-up. We found that a poor day 45 outcome was associated with patients who had high baseline serum galactomannan (GM) antigen levels and those receiving steroids at the time of IA. A consistently negative serum GM index was associated with a good outcome, and the day 14 clinical evaluation was predictive of the day 45 outcome. No association was found between Aspergillus antibodies or DNA detection and patients' outcome. We conclude that the GM index value at diagnosis of IA, GM index kinetics, and clinical evaluation at day 14 are good markers for predicting the outcome of patients with IA and should be taken into account for adapting antifungal treatment.

Scoliosis and bronchial obstruction.

Severe scoliosis may have a significant effect on respiratory function. The effect is most often restrictive due to severe anatomical distortion of the chest, leading to reduced lung volumes, limited diaphragmatic excursion and chest wall muscle inefficiency. Bronchial compression by the deformed spine may also occur but is more unusual. Management options include a conservative approach using bracing and physiotherapy in mild cases, as well as surgical correction of the scoliosis in more severe cases. Bronchial stenting has also been used successfully as an alternative to surgical correction, and in cases in which spinal surgery was either unsuccessful or not feasible. The authors present a case involving a 52-year-old woman who exhibited symptomatic compression of the bronchus intermedius by severe residual scoliosis despite previous corrective surgery. She was treated with an indwelling bronchial stent.

A curious lobe.

A case of azygos lobe is presented. An azygos lobe is an accessory lobe of the lung that may occasionally be confused with a pathological process such as a bulla, lung abscess or neoplasm. Its pathogenesis is discussed, as are the characteristic x-ray features that enable an accurate diagnosis.