Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation.

RATIONALE: Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown. OBJECTIVES: To investigate whether changes in gut microbiota are associated with PCs after HCT. METHODS: A single-center observational study was performed on 94 patients who underwent HCT from 2009 to 2011 and who were previously enrolled in a protocol for 16S ribosomal RNA sequencing of fecal microbiota. The primary endpoint, PC, was defined by new abnormal parenchymal findings on chest imaging in the setting of respiratory signs and/or symptoms. Outcomes were collected up to 40 months after transplant. Clinical and microbiota risk factors for PCs and mortality were evaluated using survival analysis. MEASUREMENTS AND MAIN RESULTS: One hundred twelve PCs occurred in 66 (70.2%) subjects. A high comorbidity index (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.30-4.00; P = 0.004), fluoroquinolones (HR, 2.29, 95% CI, 1.32-3.98; P = 0.003), low baseline diversity (HR, 2.63; 95% CI, 1.22-5.32; P = 0.015), and γ-proteobacteria domination of fecal microbiota (HR, 2.64; 95% CI, 1.10-5.65; P = 0.031), which included common respiratory pathogens, predicted PCs. In separate analyses, low baseline diversity was associated with PCs that occurred preengraftment (HR, 6.30; 95% CI, 1.42-31.80; P = 0.016), whereas γ-proteobacteria domination predicted PCs postengraftment (HR, 3.68; 95% CI, 1.49-8.21; P = 0.006) and overall mortality (HR, 3.52; 95% CI, 1.28-9.21; P = 0.016). Postengraftment PCs were also independent predictors of death (HR, 2.50; 95% CI, 1.25-5.22; P = 0.009). CONCLUSIONS: This is the first study to demonstrate prospective changes in gut microbiota associated with PCs after HCT. Postengraftment PCs and γ-proteobacteria domination were predictive of mortality. This suggests an adverse relationship between the graft and lung, which is perhaps mediated by bacterial composition in the gut. Further study is warranted.

Addressing Maternal Health Disparities: Building a Novel Two-Generation Approach to Comprehensive Postpartum Care.

The United States is facing a maternal health crisis with increasing rates of severe maternal morbidity and mortality. To improve maternal health and promote health equity, the authors developed a novel 2-generation model of postpartum and pediatric care. This article describes the Two-Generation Clinic (Two-Gen) and model of care. The model combines a dyadic strategy for simultaneous maternal and pediatric care with the collaborative care model in which seamless primary and behavioral health care are delivered to address the physical health, behavioral health, and social service needs of families. The transdisciplinary team includes primary care physicians, nurse practitioners, psychiatrists, obstetrician-gynecologists, social workers, care navigators, and lactation specialists. Dyad clinic visits are coscheduled (at the same time) and colocated (in the same examination room) with the same primary care provider. In the Two-Gen, the majority (89%) of the mothers self-identify as racial and ethnic minorities. More than 40% have a mental health diagnosis. Almost all mothers (97.8%) completed mental health screenings, >50.0% have received counseling from a social worker, 17.2% had a visit with a psychiatrist, and 50.0% received lactation counseling. Over 80% of the children were up to date with their well-child visits and immunizations. The Two-Gen is a promising model of care that has the potential to inform the design of postpartum care models and promote health equity in communities with the highest maternal health disparities.

Diagnostic Evaluation of Pulmonary Abnormalities in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation.

Pulmonary complications (PC) of hematologic malignancies and their treatments are common causes of morbidity and mortality. Early diagnosis is challenging due to host risk factors, clinical instability, and provider preference. Delayed diagnosis impairs targeted treatment and may contribute to poor outcomes. An integrated understanding of clinical risk and radiographic patterns informs a timely approach to diagnosis and treatment. There is little prospective evidence guiding optimal modality and timing of minimally invasive lung sampling; however, a low threshold for diagnostic bronchoscopy during the first 24 to 72 hours after presentation should be a guiding principle in high-risk patients.

Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy.

Purpose Pneumonitis is an uncommon but potentially fatal toxicity of anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Clinical, radiologic, and pathologic features are poorly described. Methods Patients who received anti-PD-1/PD-L1 monotherapy or in combination with anti-cytotoxic T-cell lymphocyte-4 mAb were identified at two institutions (Memorial Sloan Kettering Cancer Center: advanced solid cancers, 2009 to 2014, and Melanoma Institute of Australia: melanomas only, 2013 to 2015). Pneumonitis was diagnosed by the treating investigator; cases with confirmed malignant lung infiltration or infection were excluded. Clinical, radiologic, and pathologic features of pneumonitis were collected. Associations among pneumonitis incidence, therapy received, and underlying malignancy were examined with Fisher's exact test as were associations between pneumonitis features and outcomes. Results Of 915 patients who received anti-PD-1/PD-L1 mAbs, pneumonitis developed in 43 (5%; 95% CI, 3% to 6%; Memorial Sloan Kettering Cancer Center, 27 of 578 [5%]; Melanoma Institute of Australia, 16 of 337 [5%]). Time to onset of pneumonitis ranged from 9 days to 19.2 months. The incidence of pneumonitis was higher with combination immunotherapy versus monotherapy (19 of 199 [10%] v 24 of 716 [3%]; P < .01). Incidence was similar in patients with melanoma and non-small-cell lung cancer (overall, 26 of 532 [5%] v nine of 209 [4%]; monotherapy, 15 of 417 v five of 152 [ P = 1.0]; combination, 11 of 115 v four of 57 [ P = .78]). Seventy-two percent (31 of 43) of cases were grade 1 to 2, and 86% (37 of 43) improved/resolved with drug holding/immunosuppression. Five patients worsened clinically and died during the course of pneumonitis treatment; proximal cause of death was pneumonitis (n = 1), infection related to immunosuppression (n = 3), or progressive cancer (n = 1). Radiologic and pathologic features of pneumonitis were diverse. Conclusion Pneumonitis associated with anti-PD-1/PD-L1 mAbs is a toxicity of variable onset and clinical, radiologic, and pathologic appearances. It is more common when anti-PD-1/PD-L1 mAbs are combined with anti-cytotoxic T-cell lymphocyte-4 mAb. Most events are low grade and improve/resolve with drug holding/immunosuppression. Rarely, pneumonitis worsens despite immunosuppression, and may result in infection and/or death.

Diagnostic bronchoscopy in solid-organ and hematopoietic stem cell transplantation.

Fiberoptic bronchoscopy is a valuable diagnostic tool in solid-organ and hematopoietic stem cell transplant recipients presenting with a range of pulmonary complications. This article provides a comprehensive overview of the utility and potential adverse effects of diagnostic bronchoscopy for transplant recipients. Recommendations are offered on the selection of patients, the timing of bronchoscopy, and the samples to be obtained across the spectrum of suspected pulmonary complications of transplantation. Based on review of the literature, the authors recommend early diagnostic bronchoscopy over empiric treatment in transplant recipients with evidence of certain acute, subacute, or chronic pulmonary processes. This approach may be most critical when an underlying infectious etiology is suspected. In the absence of prompt diagnostic information on which to base effective treatment, the risks associated with empiric antimicrobial therapy, including medication side effects and the development of antibiotic resistance, compound the potential harm of delaying targeted management.

The association of systemic microvascular changes with lung function and lung density: a cross-sectional study.

Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45-84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA) were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV(1)) (P<0.001) and FEV(1)/forced vital capacity (FVC) ratio (P = 0.04). Albumin-to-creatinine ratio was inversely associated with FEV(1) (P = 0.002) but not FEV(1)/FVC. Myocardial blood flow (n = 126) was associated with lower FEV(1) (P = 0.02), lower FEV(1)/FVC (P = 0.001) and greater percentage LAA (P = 0.04). Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition.