ABSTRACT
Rationale: Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives: To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods: Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results: In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM (P < 0.05). Conclusions: Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM.
Subject(s)
Bronchiectasis , Mycobacterium Infections, Nontuberculous , Registries , Humans , Bronchiectasis/mortality , Bronchiectasis/physiopathology , Bronchiectasis/epidemiology , Male , Female , Middle Aged , Aged , Mycobacterium Infections, Nontuberculous/mortality , Mycobacterium Infections, Nontuberculous/epidemiology , United States/epidemiology , Hospitalization/statistics & numerical data , Proportional Hazards Models , Nontuberculous Mycobacteria , Disease ProgressionABSTRACT
Background Chronic obstructive pulmonary disease (COPD) and bronchiectasis can overlap and share pathologic features, such as small airway disease (SAD). Whether the presence of SAD and emphysema in smokers with CT-derived bronchiectasis is associated with exacerbations is unknown. Purpose To assess whether SAD and emphysema in smokers with CT-derived bronchiectasis are associated with future exacerbations. Materials and Methods SAD and emphysema were quantified using the parametric response map method in former and current heavy smokers with and without bronchiectasis at CT from the COPDGene Study (from July 2009 to July 2018). Exacerbations were prospectively assessed through biannual follow-up. An exacerbation was defined as an increase in or new onset of respiratory symptoms treated with antibiotics and/or corticosteroids. Severe exacerbations were defined as those that required hospitalization. The association of a high burden of SAD (≥15.6%) and high burden of emphysema (≥5%) at CT with exacerbations was assessed with generalized linear mixed models. Results Of 737 participants, 387 (median age, 64 years [interquartile range, 58-71 years]; 223 women) had CT-derived bronchiectasis. During a 9-year follow-up, after adjustment for age, sex, race, body mass index, current smoking status, pack-years, exacerbations before study entry, forced expiratory volume in 1 second, or FEV1, and bronchiectasis severity CT score, high burden of SAD and high burden of emphysema were associated with a higher number of exacerbations per year (relative risk [RR], 1.89 [95% CI: 1.54, 2.33] and 1.37 [95% CI: 1.13, 1.66], respectively; P ≤ .001 for both). Results were comparable among participants with bronchiectasis meeting criteria for COPD (n = 197) (RR, 1.67 [95% CI: 1.23, 2.27] for high burden of SAD and 1.51 [95% CI: 1.20, 1.91] for high burden of emphysema; P ≤ .001 for both). Conclusion In smokers with CT-derived bronchiectasis and chronic obstructive pulmonary disease, structural damage to lung parenchyma and small airways was associated with a higher number of exacerbations per year. Clinical trial registration no. NCT00608764 © RSNA, 2021.
Subject(s)
Bronchiectasis/diagnostic imaging , Bronchiectasis/physiopathology , Pulmonary Disease, Chronic Obstructive/physiopathology , Symptom Flare Up , Tomography, X-Ray Computed , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , SmokersABSTRACT
Aspiration is associated with nontuberculous mycobacterial (NTM) pulmonary disease and airway dysbiosis is associated with increased inflammation. We examined whether NTM disease was associated with a distinct airway microbiota and immune profile.297 oral wash and induced sputum samples were collected from 106 participants with respiratory symptoms and imaging abnormalities compatible with NTM. Lower airway samples were obtained in 20 participants undergoing bronchoscopy. 16S rRNA gene and nested mycobacteriome sequencing approaches characterised microbiota composition. In addition, inflammatory profiles of lower airway samples were examined.The prevalence of NTM+ cultures was 58%. Few changes were noted in microbiota characteristics or composition in oral wash and sputum samples among groups. Among NTM+ samples, 27% of the lower airway samples were enriched with Mycobacterium A mycobacteriome approach identified Mycobacterium in a greater percentage of samples, including some nonpathogenic strains. In NTM+ lower airway samples, taxa identified as oral commensals were associated with increased inflammatory biomarkers.The 16S rRNA gene sequencing approach is not sensitive in identifying NTM among airway samples that are culture-positive. However, associations between lower airway inflammation and microbiota signatures suggest a potential role for these microbes in the inflammatory process in NTM disease.
Subject(s)
Microbiota , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/isolation & purification , Respiratory System/microbiology , Aged , Bronchoalveolar Lavage Fluid/microbiology , Female , Humans , Male , Middle Aged , Nontuberculous Mycobacteria/genetics , Prospective Studies , RNA, Ribosomal, 16S/genetics , Sputum/microbiologyABSTRACT
BACKGROUND: High frequency chest wall oscillation (HFCWO) is a form of airway clearance therapy that has been available since the mid-1990s and is routinely used by patients suffering from retained pulmonary secretions. Patients with cystic fibrosis (CF), neuromuscular disease (NMD), and other disorders, including bronchiectasis (BE) and COPD (without BE), are commonly prescribed this therapy. Limited evidence exists describing HFCWO use in the BE population, its impact on long-term management of disease, and the specific patient populations most likely to benefit from this therapy. This study sought to characterize the clinical characteristics of patients with BE who have documented use of HFCWO at baseline and 1-year follow-up. METHODS: An analysis from a large national database registry of patients with BE was performed. Demographic and clinical characteristics of all patients receiving HFCWO therapy at baseline are reported. Patients were stratified into two groups based on continued or discontinued use of HFCWO therapy at 1-year follow-up. RESULTS: Over half (54.8 %) of patients who reported using HFCWO therapy had a Modified Bronchiectasis Severity Index (m-BSI) classified as severe, and the majority (81.4 %) experienced an exacerbation in the prior two years. Of patients with 1-year follow-up data, 73 % reported continued use of HFCWO. Compared to patients who discontinued therapy, these patients were more severe at baseline and at follow-up suggesting that patients with more severe disease are more likely to continue HFCWO therapy. CONCLUSIONS: Patients who have more severe disease and continue to experience exacerbations and hospitalizations are more likely to continue HFCWO therapy. CLINICAL TRIAL REGISTRATION: NA.
Subject(s)
Bronchiectasis , Chest Wall Oscillation , Cystic Fibrosis , Humans , Bronchiectasis/therapy , Cystic Fibrosis/complications , Cystic Fibrosis/therapy , Databases, Factual , RegistriesABSTRACT
BACKGROUND: Nebulized Hypertonic saline (HS) and positive expiratory pressure device (PEP) are often used in patients with bronchiectasis. We sought to describe the clinical characteristics in patients using HS and PEP, utilizing a large national database registry. METHODS: Data from the US Bronchiectasis and NTM Research Registry were used in this study. Patients with a diagnosis of bronchiectasis were included. Eligible patients were assigned to one of four mutually exclusive groups: HS only, PEP only, HS & PEP, or no airway clearance or mucoactive agent. Descriptive statistics were computed for the overall study population and stratified by the four groups. One-way ANOVA and chi-square tests were used to test the difference in the means in continuous variables and the association between categorical variables (respectively) across the four groups. RESULTS: A total of 2195 patients were included. Of those with bronchiectasis and a productive cough, a greater number of patients utilized HS only vs PEP only (17.5 % vs 9.1 %, p < 0.001). Similar association was found in those with Pseudomonas aeruginosa (22.3 % HS only vs 6.5 % PEP only, p < 0.001). There was a higher number of patients who used HS and PEP therapy in combination vs PEP therapy alone (25.0 % vs 9.1 %, p = 0.002), in those with a productive cough. CONCLUSIONS: In patients with bronchiectasis and a productive cough or Pseudomonas aeruginosa, HS is used more often than PEP alone. There is a need for further analysis to compare these two modalities and explore the factors influencing their utilization.
ABSTRACT
Bronchiectasis (BE) is a chronic condition characterized by airway dilation as a consequence of a variety of pathogenic processes. It is often associated with persistent airway infection and an inflammatory response resulting in cough productive of purulent sputum, which has an adverse impact on quality of life. The prevalence of BE is increasing worldwide. Treatment guidelines exist for managing BE, but they are generally informed by a paucity of high-quality evidence. This review presents the findings of a scientific advisory board of experts held in the United States in November 2020. The main focus of the meeting was to identify unmet needs in BE and propose ways to identify research priorities for the management of BE, with a view to developing evidence-based treatment recommendations. Key issues identified include diagnosis, patient evaluation, promoting airway clearance and appropriate use of antimicrobials. Unmet needs include effective pharmacological agents to promote airway clearance and reduce inflammation, control of chronic infection, clinical endpoints to be used in the design of BE clinical trials, and more accurate classification of patients using phenotypes and endotypes to better guide treatment decisions and improve outcomes.
Subject(s)
Bronchiectasis , Quality of Life , Humans , Bronchiectasis/diagnosis , Bronchiectasis/therapy , Bronchiectasis/complications , Cough/complications , Chronic DiseaseABSTRACT
BACKGROUND AND OBJECTIVE: Patients with idiopathic pulmonary fibrosis (IPF) have a higher prevalence of coronary artery disease and this could have an impact on their outcomes. We investigated the predictive ability of coronary artery calcification, assessed by routine CT, which may predict the presence of coronary artery disease. METHODS: The study cohort consisted of patients with IPF and with left heart catheterization data plus CT scans from July 2003 to July 2008. Grades of coronary calcification on CT were compared with left heart catheterization determination of coronary artery disease. RESULTS: There were 57 patients in whom left heart catheterization review demonstrated significant coronary artery disease in 28.1% (16/57), mild disease in 40.3% (23/57) and none in 31.6% (18/57). The median time interval between the catheterization and the reviewed CT scan was 39 days. The sensitivity of moderate to severe calcification for significant coronary artery disease was 81%, while the specificity was 85%, with an associated odds ratio of 25.2 (4.64-166, P < 0.005). There was excellent agreement among three radiologists in the grading of coronary calcification. CONCLUSIONS: Coronary calcification, as assessed by routine CT of the chest, has very good performance characteristics in predicting underlying significant coronary artery disease in patients with IPF. The routine availability of this study enables the ready screening for coronary artery disease in IPF patients.
Subject(s)
Calcinosis/diagnostic imaging , Coronary Artery Disease/diagnostic imaging , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Tomography, X-Ray Computed , Calcinosis/epidemiology , Cardiac Catheterization , Cohort Studies , Coronary Angiography , Coronary Artery Disease/epidemiology , Female , Humans , Idiopathic Pulmonary Fibrosis/epidemiology , Male , Middle Aged , Prevalence , Retrospective Studies , Sensitivity and Specificity , Severity of Illness IndexABSTRACT
RATIONALE: Non-cystic fibrosis bronchiectasis (NCFB) is characterized by dilated bronchi, poor mucus clearance and susceptibility to bacterial infection. Pseudomonas aeruginosa (PA) is one of the most frequently isolated pathogens in patients with NCFB. The purpose of this study was to evaluate the association between presence of PA and disease severity in patients within the US Bronchiectasis and Nontuberculous mycobacteria (NTM) Research Registry (BRR). METHODS: Baseline US BRR data from adult patients with NCFB collected between 2008 and 2018 was used for this study. The presence of PA was defined as one or more positive PA cultures within two years prior to enrollment. Modified Bronchiectasis Severity Index (m-BSI) and modified FACED (m-FACED) were computed to evaluate severity of bronchiectasis. Unadjusted and multivariable multinomial regression models were used to assess the association between presence of PA and severity of bronchiectasis. RESULTS: Average age of the study participants (n = 1831) was 63.7 years (SD = 14.1), 91.5% white, and 78.8% female. Presence of PA was identified in 25.4% of the patients. Patients with presence of PA had significantly lower mean pre-bronchodilator FEV1% predicted compared to those without PA (62.8% vs. 73.7%, p < .0001). In multivariate analyses, patients with presence of PA had significantly greater odds for having high (ORadj = 6.15 (95%CI:3.98-9.50) and intermediate (ORadj = 2.06 (95%CI:1.37-3.09) severity vs. low severity on m-BSI. CONCLUSION: The presence of PA is common in patients with NCFB within the Bronchiectasis and NTM Research Registry. Severity of bronchiectasis is significantly greater in patients with PA which emphasizes high burden of the disease.
ABSTRACT
BACKGROUND: In patients with bronchiectasis, airway clearance techniques (ACTs) are important management strategies. RESEARCH QUESTION: What are the differences in patients with bronchiectasis and a productive cough who used ACTs and those who did not? What was the assessment of bronchiectasis exacerbation frequency and change in pulmonary function at 1-year follow up? STUDY DESIGN AND METHODS: Adult patients with bronchiectasis and a productive cough in the United States Bronchiectasis and NTM Research Registry were included in the analyses. ACTs included the use of instrumental devices and manual techniques. Stratified analyses of demographic and clinical characteristics were performed by use of ACTs at baseline and follow up. The association between ACT use and clinical outcomes was assessed with the use of unadjusted and adjusted multinomial logistic regression models. RESULTS: Of the overall study population (n = 905), 59% used ACTs at baseline. A greater proportion of patients who used ACTs at baseline and follow up continuously had Pseudomonas aeruginosa (47% vs 36%; P = .021) and experienced an exacerbation (81% vs 59%; P < .0001) or hospitalization for pulmonary illness (32% vs 22%; P = .001) in the prior two years, compared with those patients who did not use ACTs. Fifty-eight percent of patients who used ACTs at baseline did not use ACTs at 1-year follow up. There was no significant change in pulmonary function for those who used ACTs at follow up, compared with baseline. Patients who used ACTs at baseline and follow up had greater odds for experiencing exacerbations at follow up compared with those patients who did not use ACTs. INTERPRETATION: In patients with bronchiectasis and a productive cough, ACTs are used more often if the patients have experienced a prior exacerbation, hospitalization for pulmonary illness, or had P aeruginosa. There is a significant reduction in the use of ACTs at 1-year follow up. The odds of the development of a bronchiectasis exacerbation are higher in those patients who use ACTs continuously, which suggests more frequent use in an ill bronchiectasis population.
Subject(s)
Bronchiectasis/therapy , Respiratory Therapy , Aged , Biomedical Research , Bronchiectasis/microbiology , Cohort Studies , Cough , Female , Humans , Male , Middle Aged , Nontuberculous Mycobacteria , Registries , United StatesABSTRACT
To explore demographics, comorbidities, transfers, and mortality in critically ill patients with confirmed severe acute respiratory syndrome coronavirus 2. DESIGN: Retrospective cohort study. SETTING: Data were collected from a large tertiary care public hospital ICU that is part of the largest public healthcare network in the United States. PATIENTS: One-hundred thirty-seven adult (≥ 18 yr old) ICU patients admitted between March 10, 2020, and April 7, 2020, with follow-up collected through May 18, 2020. INTERVENTIONS: None. MEASUREMENTS: Demographic, clinical, laboratory, treatment, and outcome data extracted from electronic medical records. MAIN RESULTS: The majority of patients were male (99/137; 72.3%) and older than 50 years old (108/137; 78.9%). The most reported ethnicity and race were Hispanic (61/137; 44.5%) and Black (23/137; 16.7%). One-hundred six of 137 patients had at least one comorbidity (77.4%). One-hundred twenty-one of 137 (78.1%) required mechanical ventilation of whom 30 (24.8%) moved to tracheostomy and 46 of 137 (33.6%) required new onset renal replacement therapy. Eighty-two of 137 patients (59.9%) died after a median of 8 days (interquartile range 5-15 d) in the ICU. Male sex had a trend toward a higher hazard of death (hazard ratio, 2.1 [1.1-4.0]) in the multivariable Cox model. CONCLUSIONS: We report a mortality rate of 59.9% in a predominantly Hispanic and Black patient population. A significant association between comorbidities and mortality was not found in multivariable regression, and further research is needed to study factors that impact mortality in critical coronavirus disease 2019 patients. We also describe how a public hospital developed innovative approaches to safely manage a large volume of interhospital transfers and admitted patients.
ABSTRACT
BACKGROUND: Increasing numbers of patients are being diagnosed with bronchiectasis, yet much remains to be elucidated about this heterogeneous patient population. We sought to determine the relationship between nutrition and health outcomes in non-cystic fibrosis (non-CF) bronchiectasis, using data from the U.S. Bronchiectasis Nontuberculous Mycobacterial Research Registry (U.S. BRR). METHODS: This was a retrospective, observational, longitudinal study using 5-year follow-up data from the BRR. Bronchiectasis was confirmed on computed tomography (CT). We stratified patients into nutrition categories using body mass index (BMI), and correlated BMI to markers of disease severity. RESULTS: Overall, n = 496 patients (mean age 64.6- ± 13 years; 83.3% female) were included. At baseline 12.3% (n = 61) were underweight (BMI < 18.5kg/m2), 63.9% (n = 317) had normal weight (BMI ≥ 18.5kg/m2 and <25.0kg/m2), 17.3% (n = 86) were overweight (BMI ≥ 25.0kg/m2 and < 30.0kg/m2), and 6.5% (n= 32) were obese (BMI ≥ 30kg/m2). Men were overrepresented in the overweight and obese groups (25.6% and 43.8% respectively, p < 0.0001). Underweight patients had lower lung function (forced expiratory volume in 1 second [FEV1] % predicted) than the other weight groups (64.5 ± 22, versus 73.5 ± 21, 68.5 ± 20, and 76.5 ± 21 in normal, overweight, and obese groups respectively, p = 0.02). No significant differences were noted between BMI groups for other markers of disease severity at baseline, including exacerbation frequency or hospitalization rates. No significant differences were noted in BMI distribution between patients with and without Pseudomonas, non-tuberculous mycobacteria, or by cause of bronchiectasis. The majority of patients demonstrated stable BMI over 5 years. CONCLUSIONS: Although underweight patients with bronchiectasis have lower lung function, lower BMI does not appear to relate to other markers of disease severity in this patient population.
ABSTRACT
Antibiotic therapy against non-tuberculous mycobacteria (NTM) is prolonged and can be associated with toxicity. We sought to evaluate whether chest physical therapy (PT) was associated with clinical improvement in patients with NTM not receiving anti-mycobacterial pharmacotherapy. A retrospective review of 77 subjects that were followed from June 2006 to September 2014 was performed. Baseline time point was defined as the first positive sputum culture for NTM; symptoms, pulmonary function, and radiology reports were studied. Subjects were followed for up to 24 months and results analyzed at specified time points. Half of the subjects received chest PT at baseline. Cough improved at 12 (p = 0.001) and 24 months (p = 0.003) in the overall cohort when compared with baseline, despite lack of NTM antibiotic treatment. Cough decreased at 6 (p = 0.01), 9 (p = 0.02), 12 (p = 0.02) and 24 months (p = 0.002) in subjects that received chest PT. Sputum production also improved at 24 months in the overall cohort (p = 0.01). There was an increase in the percent change of total lung capacity in subjects that received chest PT (p = 0.005). Select patients with NTM may have clinical improvement with chest PT, without being subjected to prolonged antibiotic therapy. Future studies are warranted to prospectively evaluate outcomes in the setting of non-pharmacologic treatment and aid with the decision of antibiotic initiation.
Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Critical Care/organization & administration , Hospitals, Public/organization & administration , Pandemics , Pneumonia, Viral/therapy , Workforce/organization & administration , COVID-19 , Coronavirus Infections/epidemiology , Humans , New York City/epidemiology , Pneumonia, Viral/epidemiology , SARS-CoV-2ABSTRACT
INTRODUCTION: Idiopathic Pulmonary Fibrosis (IPF) is a progressive disease with a poor prognosis for which there is no effective medical therapy. An awareness of comorbidities that are treatable and might impact outcomes in these patients is therefore very important. We sought to determine the prevalence of coronary artery disease (CAD) in IPF patients in comparison to a control group of patients with chronic obstructive pulmonary disease (COPD). We also sought to assess the impact of CAD on IPF patient outcomes. PATIENTS AND METHODS: IPF and COPD transplant candidates whose work-up included left heart catheterization were categorized as having significant CAD, non-significant CAD or no disease. The risk factor profile and prevalence of CAD in both groups was compared. RESULTS: There were 73 IPF and 56 COPD patients. The prevalence of CAD was 65.8% in the IPF group compared to 46.1% in the COPD patients (p<0.028). Significant disease was present in 28.8% of IPF patients vs.16.1% of the COPD patients (p<0.081). Unsuspected significant CAD was found in 18% of IPF patients versus 10.9% of COPD patients (p<0.004). Outcomes of IPF patients with significant CAD was worse than those with no or non-significant disease (p<0.003) with a median survival of 572 days from the time of left heart catheterization. CONCLUSION: There is a higher prevalence of CAD in IPF patients compared to a similarly matched COPD group. This increased association appeared to be independent of common coronary artery risk factors. IPF patients with significant CAD appear to have worse outcomes.
Subject(s)
Coronary Artery Disease/etiology , Idiopathic Pulmonary Fibrosis/complications , Cardiac Catheterization , Coronary Artery Disease/epidemiology , Coronary Artery Disease/physiopathology , Female , Humans , Idiopathic Pulmonary Fibrosis/epidemiology , Idiopathic Pulmonary Fibrosis/physiopathology , Male , Middle Aged , Prevalence , Prospective Studies , Risk Factors , Spirometry , Survival Analysis , United States/epidemiologyABSTRACT
Polycomb group protein Ezh2, one of the key regulators of development in organisms from flies to mice, exerts its epigenetic function through regulation of histone methylation. Here, we report the existence of the cytosolic Ezh2-containing methyltransferase complex and tie the function of this complex to regulation of actin polymerization in various cell types. Genetic evidence supports the essential role of cytosolic Ezh2 in actin polymerization-dependent processes such as antigen receptor signaling in T cells and PDGF-induced dorsal circular ruffle formation in fibroblasts. Revealed function of Ezh2 points to a broader usage of lysine methylation in regulation of both nuclear and extra-nuclear signaling processes.
Subject(s)
Actins/metabolism , Protein Methyltransferases/metabolism , Proteins/physiology , Signal Transduction/physiology , Animals , Antigen Presentation/physiology , Carrier Proteins/metabolism , Cell Cycle Proteins/metabolism , Cell Differentiation/immunology , Cell Differentiation/physiology , Cell Proliferation , Cytoplasm/metabolism , DNA-Binding Proteins , Enhancer of Zeste Homolog 2 Protein , Fibroblasts/drug effects , Fibroblasts/metabolism , Histone-Lysine N-Methyltransferase , Humans , Jurkat Cells , Lymphocyte Activation , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neoplasm Proteins , Nuclear Proteins , Platelet-Derived Growth Factor/pharmacology , Polycomb Repressive Complex 2 , Proteins/genetics , Proteins/metabolism , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-vav , Receptors, Antigen, T-Cell/agonists , Repressor Proteins/metabolism , T-Lymphocytes/metabolism , Thymus Gland/immunology , Thymus Gland/physiology , Transcription Factors , cdc42 GTP-Binding Protein/metabolismABSTRACT
Polycomb group protein Ezh2 is an essential epigenetic regulator of embryonic development in mice, but its role in the adult organism is unknown. High expression of Ezh2 in developing murine lymphocytes suggests Ezh2 involvement in lymphopoiesis. Using Cre-mediated conditional mutagenesis, we demonstrated a critical role for Ezh2 in early B cell development and rearrangement of the immunoglobulin heavy chain gene (Igh). We also revealed Ezh2 as a key regulator of histone H3 methylation in early B cell progenitors. Our data suggest Ezh2-dependent histone H3 methylation as a novel regulatory mechanism controlling Igh rearrangement during early murine B cell development.