Background Neurofibromatosis Type 1 (NF1) is a genetic disorder resulting from mutations in the NF1 tumor suppressor gene. Neurofibromin, the protein product of NF1, functions as a negative regulator of Ras activity in circulating hematopoietic and vascular wall cells, which are critical for maintaining vessel wall homeostasis. NF1 patients have evidence of chronic inflammation resulting in development of premature cardiovascular disease, including arterial aneurysms, which may manifest as sudden death. However, the molecular pathogenesis of NF1 aneurysm formation is unknown. Method and Results Utilizing an angiotensin II-induced aneurysm model, we demonstrate that heterozygous inactivation of Nf1 (Nf1+/−) enhanced aneurysm formation with myeloid cell infiltration and increased oxidative stress in the vessel wall. Using lineage-restricted transgenic mice, we show loss of a single Nf1 allele in myeloid cells is sufficient to recapitulate the Nf1+/− aneurysm phenotype in vivo. Finally, oral administration of simvastatin or the antioxidant apocynin, reduced aneurysm formation in Nf1+/− mice. Conclusion These data provide genetic and pharmacologic evidence that Nf1+/− myeloid cells are the cellular triggers for aneurysm formation in a novel model of NF1 vasculopathy and provide a potential therapeutic target.

Introduction Oral antibiotics are frequently prescribed for outpatient pulmonary exacerbations (PEx) in children with cystic fibrosis (CF). This study aimed to characterize oral antibiotic use for PEx and treatment outcomes at two large US CF centers. Methods Retrospective, descriptive study of oral antibiotic prescribing practices among children with CF ages 6–17 years over 1 year. The care setting for antibiotic initiation (clinic or phone encounter) was determined and outcomes were compared. Results A total of 763 oral antibiotic courses were prescribed to 312 patients aged 6–17 years (77% of 403 eligible patients) with a median of two courses per year (range: 1–10). Fifty‐eight percent of prescriptions were provided over the phone. Penicillin was the most commonly prescribed antibiotic class (36% of prescriptions) but differences in antibiotic class prescriptions were noted between the two centers. Hospitalizations occurred within 3 months following 19% of oral antibiotic courses. Forced expiratory volume in 1 s (FEV1) recovered to within 90% of prior baseline within 6 months in 87% of encounters; the mean (SD) % recovery was 99.6% (12.1%) of baseline. Outcomes did not differ between phone and clinic prescriptions. Conclusions Phone prescriptions, commonly excluded in studies of PEx, made up more than half of all oral antibiotic courses. Heterogeneity in prescribing patterns was observed between the two centers. Most patients had improvement in FEV1 returning to near their prior baseline, but hospitalizations occurred in one‐fifth following oral antibiotic treatment. Efforts to optimize PEx treatment must consider care that occurs over the phone; this is particularly important as the use of telemedicine increases.

Letter to the Editor, Pulmonary eosinophilia represents a group of heterogeneous disorders consisting of lung disease and eosinophilia in the peripheral blood, alveoli, and/or pulmonary interstitium. 1 Subtype classifications include eosinophilic pneumonia (acute and chronic), allergic bronchopulmonary aspergillosis (ABPA), eosinophilic granulomatosis with polyangiitis (EGPA), drug or parasite-induced pulmonary eosinophilia, hypereosinophilic syndromes, and idiopathic pulmonary eosinophilia. 1 These classifications are based on adult populations, and therefore may not always be applicable to pediatric patients. As pulmonary eosinophilia rarely occurs in children and is largely described through case reports, its true incidence in pediatric populations is unknown. We report three cases of pediatric pulmonary eosinophilia identified at a single center within a 5-month period in 2019, all of which posed classification challenges. Benralizumab, an anti-interleukin-5 receptor alpha (IL-5Rα) monoclonal antibody, was used in all three cases under the impression of probable beneficial effect.

Introduction: E-cigarette vaping is a major aspect of nicotine consumption, especially for children and young adults. An acute vaping model has not been demonstrated in the hamster, which has the unique benefit of becoming infected with and transmitting respiratory viruses, including SARS-CoV-2, without genetic alteration. Methods: Using a two-day, whole-body vaping exposure protocol in male hamsters, we evaluated serum cotinine, bronchoalveolar lavage cells, lung and nasal histopathology, and gene expression in the nasopharynx and lung through RT-qPCR. Results: In nasal tissue, RT-qPCR analysis revealed nicotine-dependent increases in genes associated with type 1 inflammation (CCL-5 and CXCL-10), fibrosis (TGF-b), a nicotine-independent increase oxidative stress response (SOD-2), and a nicotine-independent decrease in the vasculogenesis/angiogenesis (VEGF-A). In the lung, nicotine-dependent increases in the expression of genes involved in the renin-angiotensin pathway (ACE, ACE2), coagulation (tissue factor, Serpine-1), extracellular matrix remodeling (MMP-2, MMP-9), type 1 inflammation (IL-1b, TNF-a, and CXCL-10), fibrosis (TGF-b and Serpine-1), oxidative stress response (SOD-2), neutrophil extracellular traps release (ELANE), and vasculogenesis and angiogenesis (VEGF-A) were identified. Conclusion: To our knowledge, this is the first demonstration that the Syrian hamster is a viable model of e-cig vaping. In addition, this is the first report that e-cig vaping with nicotine can increase tissue factor gene expression in the lung. Our results show that even an acute exposure to e-cigarette vaping causes significant upregulation of mRNAs in the respiratory tract from pathways involving the renin-angiotensin system, coagulation, extracellular matrix remodeling, type 1 inflammation, fibrosis, oxidative stress response, NETosis, vasculogenesis, and angiogenesis.

An area of physical chemistry for which it is particularly hard to find appropriate experiments is the kinetic theory of gases. To fill this need the authors have developed a computer-modeled kinetic theory experiment for the physical chemistry laboratory.

E-cigarette, or vaping product, use associated lung injury (EVALI) refers to respiratory illness in patients with recent vaping and no signs of infection or underlying illness. EVALI can cause severe acute respiratory distress syndrome and death. A spectrum of diagnoses can fit the description of EVALI since it

No abstract

No abstract