Pulmonary histopathology of interstitial lung disease associated with antisynthetase antibodies.

BACKGROUND: We aimed to determine if antibody type is an indicator of pulmonary histopathology, using antisynthetase antibody positive interstitial lung disease (ILD) cases with lung biopsy or autopsy findings. METHODS: We conducted a comprehensive review of the English language literature in PubMed to identify ILD histopathology results for cases with antibodies against anti-aminoacyl-transfer RNA (tRNA) synthetases (anti-ARS antibodies), including Jo1, PL-12, PL-7, KS, ES, and OJ. We additionally identified patients who had ILD, anti-ARS antibodies, and a lung biopsy between 2015 and 2020 at Beth Israel Deaconess Medical Center. For each case, we documented the specific anti-ARS antibody and major histopathologic patterns identified on biopsy or autopsy, including usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), and acute lung injury (ALI). To determine if histopathology varied by antibody type, we compared the proportion of each of four major patterns by antibody type using the Fisher's Exact test. RESULTS: We identified 310 cases with pathology findings and anti-ARS antibody positivity, including 12 cases from our institution. The proportion of NSIP differed significantly across antibody type, found in 31% of Jo1 (p < 0.01), 67% of EJ (p < 0.01), and 63% of KS (p < 0.01) cases. OP was common in Jo1 (23%, p = 0.07), but rare in EJ (4%, p = 0.04) and KS (4%, p = 0.04). UIP was common in PL-12 alone (36%, p = 0.03). CONCLUSION: The frequency of histopathologic findings in ILD with anti-ARS positivity varies significantly by antibody type, and NSIP occurs in less than half of all cases.

E-Cigarette Use, Small Airway Fibrosis, and Constrictive Bronchiolitis.

BACKGROUND: Vaping, including the use of electronic cigarettes (e-cigarettes), has become increasingly prevalent, yet the associated long-term health risks are largely unknown. Given the prevalence of use, particularly among adolescents early in their lifespan, it is vital to understand the potential chronic pathologic sequelae of vaping. METHODS: We present the cases of four patients with chronic lung disease associated with e-cigarette use characterized by clinical evaluation, with pulmonary function tests (PFTs), chest high-resolution computed tomography (HRCT), endobronchial optical coherence tomography (EB-OCT) imaging, and histopathologic assessment. RESULTS: Each patient presented with shortness of breath and chest pain in association with a 3- to 8-year history of e-cigarette use, with mild progressive airway obstruction on PFTs and/or chest HRCT findings demonstrating evidence of air trapping and bronchial wall thickening. EB-OCT imaging performed in two patients showed small airway-centered fibrosis with bronchiolar narrowing and lumen irregularities. The predominant histopathologic feature on surgical lung biopsy was small airway-centered fibrosis, including constrictive bronchiolitis and MUC5AC overexpression in all patients. Patients who ceased vaping had a partial, but not complete, reversal of disease over 1 to 4 years. CONCLUSIONS: After thorough evaluation for other potential etiologies, vaping was considered to be the most likely common causal etiology for all patients due to the temporal association of symptomatic chronic lung disease with e-cigarette use and partial improvement in symptoms after e-cigarette cessation. In this series, we associate the histopathologic pattern of small airway-centered fibrosis, including constrictive bronchiolitis, with vaping, potentially defining a clinical and pathologic entity associated with e-cigarette use. (Funded in part by the National Institutes of Health.).

Contributions of asthma, rhinitis and IgE to exhaled nitric oxide in adolescents.

Exhaled nitric oxide fraction (F eNO) is an indicator of allergic airway inflammation. However, it is unknown how asthma, allergic rhinitis (AR) and allergic sensitisation relate to F eNO, particularly among adolescents and in overlapping conditions. We sought to determine the associations between asthma, AR, and aeroallergen immunoglobulin (Ig)E and F eNO in adolescents. We measured F eNO among 929 adolescents (aged 11-16 years) in Project Viva, an unselected prebirth cohort in Massachusetts, USA. We defined asthma as ever asthma physician diagnosis plus wheezing in the past year or taking asthma medications in the past month, AR as a physician diagnosis of hay fever or AR, and aeroallergen IgE as any IgE >0.35 IU·mL-1 among 592 participants who provided blood samples. We examined associations of asthma, AR and IgE with percent difference in F eNO in linear regression models adjusted for sex, race/ethnicity, age and height, maternal education and smoking during pregnancy, and household/neighbourhood demographics. Asthma (14%) was associated with 97% higher F eNO (95% CI 70-128%), AR (21%) with 45% higher F eNO (95% CI 28-65%), and aeroallergen IgE (58%) with 102% higher F eNO (95% CI 80-126%) compared to those without each condition, respectively. In the absence of asthma or AR, aeroallergen IgE was associated with 75% higher F eNO (95% CI 52-101), while asthma and AR were not associated with F eNO in the absence of IgE. The link between asthma and AR with F eNO is limited to those with IgE-mediated phenotypes. F eNO may be elevated in those with allergic sensitisation alone, even in the absence of asthma or AR.

Five Questions for Residency Leadership in the Time of COVID-19: Reflections of Chief Medical Residents From an Internal Medicine Program.

The COVID-19 pandemic has drastically affected the traditional methods residency programs use to train their residents. Chief residents serve a unique role as part of the residency leadership to foster the education and development of the residents. Given the rapid shift in demands on physicians in the face of the pandemic, the responsibilities of the chief residents have also shifted to help prepare the residents to meet these demands as frontline providers. There is not a precedent for how residency programs respond to this crisis while maintaining their primary role to develop and train physicians. The authors have identified 5 questions chief residents can ask to guide their program's response to the demands of COVID-19 during this uncertain time in health care.

Obesity, sedentary lifestyle, and exhaled nitric oxide in an early adolescent cohort.

Fractional exhaled nitric oxide (FeNO) is a marker of airway inflammation that is well-characterized in allergic disease states. However, FeNO is also involved in nonallergic inflammatory and pulmonary vascular mechanisms or responses to environmental stimuli. We sought to determine the extent to which obesity or sedentary lifestyle is associated with FeNO in adolescents not selected on the basis of allergic disease. In Project Viva, a prebirth cohort study, we measured body mass index (BMI), skinfold thicknesses, waist circumference, body fat, hours watching television, hours of physical activity, and heart rate after exercise among 929 adolescents (median age, 12.9). We measured FeNO twice and averaged these as a continuous, log-transformed outcome. We performed linear regression models, adjusted for child age, sex, height, and race/ethnicity, maternal education and smoking during pregnancy, household income and smoking, and neighbourhood characteristics. In secondary analysis, we additionally adjusted for asthma. More than 2 hours spent watching TV was associated with 10% lower FeNO (95% confidence interval [CI]: -20, 0%). Higher body fat percentage was also associated with lower FeNO. After additional adjustment for asthma, teens who are underweight (BMI <5th %tile, 3%) had 22% lower FeNO (95%CI: -40, 2%) and teens who are overweight (BMI ≥85th %ile, 28%) had 13% lower FeNO (95%CI: -23, -2%). Each of these associations of lifestyle and body weight with lower FeNO were greater in magnitude after adjusting for asthma. In summary, sedentary lifestyle, high and low BMI were all associated with lower FeNO in this adolescent cohort.

Epigenetic factors and autism spectrum disorders.

Autism is a complex neurodevelopmental disorder that has significant phenotypic overlap with several diseases, many of which fall within the broader category of autism spectrum disorders (ASDs). The etiology of the disorder is unclear and seems to involve a complex interplay of polygenic as well as environmental factors. We discuss evidence that suggests that epigenetic dysregulation is highly implicated as a contributing cause of ASDs and autism. Specifically, we examine neurodevelopmental disorders that share significant phenotypic overlap with ASDs and feature the dysregulation of epigenetically modified genes including UBE3A, GABA receptor genes, and RELN. We then look at the dysregulated expression of implicated epigenetic modifiers, namely MeCP2, that yield complex and varied downstream pleiotropic effects. Finally, we examine epigenetically mediated parent-of-origin effects through which paternal gene expression dominates that of maternal contributing to contrasting phenotypes implicated in ASDs. Such preliminary evidence suggests that elucidating the complex role of epigenetic regulations involved in ASDs could prove vital in furthering our understanding of the complex etiology of autism and ASDs.