Patients with common variable immunodeficiency (CVID) are occasionally recognized to have a concurrent noncaseating granulomatous disease. The granulomatous disease (GD) associated with CVID shares many clinical properties typical of sarcoidosis. Some investigators speculate that the GD-CVID is actually sarcoidosis that is expressed atypically because of the patient's immunodeficiency. Clinical differences, however, have led other investigators to speculate that the GD-CVID is a distinct "sarcoid-like" granulomatous process.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a growing problem worldwide due to the emergence of multi-drug resistant and extensively-drug resistant strains of the bacteria. A key to combatting the spread of these strains lies in the understanding of gene expression occurring in Mtb. This study focuses on the development and optimization of a luciferase-based bioluminescent transcriptional reporter that can be used to monitor gene expression in Mtb. The luminescent signal emitted from the reporter can be measured and correlated with the level of transcription of certain genes. This study focuses specifically on a gene called whiB7 which encodes a transcription factor known to contribute to the drug resistance of Mtb. The drug-inducible whiB7 promoter was cloned into various locations in the luciferase plasmid in order to determine the ideal configuration of the reporter for maximum luminescence. The optimized luciferase reporter was then compared with a fluorescent transcriptional reporter, mCherry, also under control of the whiB7 promoter. Fluorescent reporters present some disadvantages including delayed kinetics and inability to accurately reflect gene downregulation due to long half-life of reporter proteins. It was hypothesized that the luciferase reporter would solve these problems by offering a more sensitive and dynamic tool to monitor gene expression. Quantitative real-time PCR was used to measure whiB7 mRNA present in cultures containing either the luciferase or mCherry reporters. The luminescent and fluorescent signal given from these reporters was then compared to actual mRNA expression. It was observed that the signal from the luciferase reporter more closely matched mRNA expression at each timepoint, indicating that the luciferase reporter is a better gauge of actual gene expression levels than the mCherry reporter.

Pseudomonas aeruginosa (PA) is a gram-negative bacillus well known for colonizing human respiratory airways and causing opportunistic infections. Children with neuromuscular disease (NMD) including cerebral palsy (CP) and severe upper airway obstruction who get infected with PA, their chances of experiencing a severe illness, being admitted to a pediatric intensive care unit, and extended or repeated hospital stays increase dramatically. These patients often need a surgical procedure called tracheostomy which act as a channel for microbes to enter lower respiratory tract and increase infections, despite its well documented impact as an opportunistic pathogen comprehensive investigation into the diversity of PA in such vulnerable populations is limited. To fill this gap in knowledge we perform whole genome sequencing (WGS) and phenotypic analysis of 40 PA isolates from the respiratory tract of this susceptible population with and without tracheotomies. Pangenome analysis showed highly variable genome content with 16,212 total genes of which 2326 are core genes. MLST revealed diverse sequence types (STs) among the studied population with 21 known and 10 new STs. Genotypic analysis revealed moderate variations in the antimicrobial resistance determinants and virulence factors among all isolates. In total 8 serogroups were identified, with serogroups O6 and O11 accounting for 70% of all the isolates. Genotypic diversity was observed in overall population however comparative analysis among tracheostomized and non-tracheostomized patient groups showed significant similarity which aligns with the phenotypic analysis revealing significant similarity with minor differences in biofilm formation, motility, hemolysis production, and pigment production. Last, we explored putative healthcare transmission and identified three potential transmission events. These findings provide insight into how WGS along with phenotypic analysis can help us better understand population dynamics, epidemiology, virulence profile and antibiotic resistance profile of PA contributing to respiratory infections which has valuable therapeutic implications for epidemiology and disease management.

Background: Humanmilk oligosaccharides (HMOs) support and concurrently shape the neonatal immune system through various mechanisms. Thereby, they may contribute to lower incidence of infections in infants. However, there is limited evidence on the role of individual HMOs in the risk of otitis media (OM), as well as lower and upper respiratory tract infections (LRTI and URTI, respectively) in children up to 2 years. Objective: To investigate whether individual HMO concentrations measured at 6 weeks of lactation were associated with risk of OM, LRTI or URTI up to 2 years in breastfed infants. Associations with OM, LRTI and URTI were determined for the most prominent human milk oligosaccharides including 13 neutral, partly isomeric structures (trioses up to hexaoses), two acidic trioses, and lactose. Design: HMO measurements and physician reported data on infections were available from human milk samples collected at 6 weeks postpartum (n = 667). Associations of HMOs with infections were assessed in crude and adjusted models using modified Poisson regression. Results: Absolute concentrations (median [min, max], in g/L) of 2′-fucosyllactose (2′-FL) tended (p = 0.04) to be lower, while lacto-N-tetraose (LNT) was higher in the milk for infants with OM in the 1st year of life (p = 0.0046). In the milk of secretor mothers, LNT was significantly higher in the milk for infants with OM (RR [95% CI]: 0.98 [0.15, 2.60]) compared to infants without OM (RR [95% CI]: 0.76 [0.14, 2.90]) at 1 year (p = 0.0019). No statistically significant milk group differences and associations were observed for OM, LRTI, and URTI (p > 0.0031). Conclusion: Our findings suggest that neither prominent neutral individual HMOs (ranging from 2′-FL to LNDFHs) nor acidic human milk sialyllactoses or lactose are significantly associated with a reduced or increased risk of infections in infants up to 2 years of age. Further research is needed to determine whether specific HMOs could potentially reduce the incidence or alleviate the course of distinct infections in early life.

Introduction: Neutrophils (PMNs) and Macrophages are the first responders recruited consecutively to the site of injury/inflammation. PMNs’ response/fate as well as macrophage reprogramming ultimately determine the course of resolution of inflammation. Physiologic wound healing has a significant inflammatory component. An exaggerated inflammation however is self-defeating leading to delayed healing. Parenteral vitamin C (VitC) attenuated inflammation in murine sepsis models and in patients with sepsis. However information about the mechanisms by which VitC regulates these events is limited. Methods: Humanized mice lacking VitC synthesis capability (Gulo-/-) were used. VitC sufficient and deficient mice were challenged with sterile inflammation, or septic insults. Some VitC deficient mice received parenteral VitC (200mg/kg) following the challenge to give deficient + AscA mice up to 14 days. Using a murine model of excisional wound, two full thickness excisional wounds were created on the back of the different Gulo-/- mice groups. Wound tissues were excised at day 7 and 14 post-wounding for analysis. Cell counts, immunohistochemistry, circulating free DNA, the expression of pro- and anti-inflammatory proteins were investigated. Additional in vitro experiments were carried out using human PMN (huPMNs), THP-1 monocyte/macrophage, and neonatal human dermal fibroblasts (HnDF). Results: VitC deficiency delayed resolution of lung inflammation and led to exaggerated pro-inflammatory responses. PMNs from VitC deficient mice demonstrated increased autophagy, histone citrullination, and NFκB activation, while inhibiting apoptosis. VitC sufficiency/supplementation restored macrophage phenotype, as well as attenuated neutrophil extracellular trap (NET) formation. VitC attenuated pro-inflammatory responses in THP-1 macrophages. In wound healing model, wounds from VitC sufficient/AscA infused mice had lower gene expression of the pro-inflammatory mediators; higher expression of genes promoting wound healing and resolution. Exposure of HnDF to AscA increased their intracellular VitC levels; promoted fibroblast proliferation and induced expression of fibroblast self-renewal genes. Conclusion: Our findings identify VitC as a novel regulator of PMN and macrophage responses. In wound healing, VitC favorably impacted the spatiotemporal expression of transcripts associated with early resolution of inflammation and tissue remodeling. Collectively, these results substantiate the protective notion of parenteral VitC and support its clinical use.

Obesity is recognized as an important risk factor for the development of many chronic diseases such as hypertension, Type 2 diabetes mellitus (T2DM) cardiovascular disease, cancer, renal disease, neurologic dysfunction, metabolic syndrome and asthma (3, 4). Circulating serum adiponectin levels in obese asthmatics have been reported to be low. Therefore, we aimed to investigate the role of adiponectin in a mucus hypersecretion model and hypothesized that adiponectin would decrease IL-13 induced MUC5AC expression from differentiated NHBE cells and that increasing concentrations of IL-13 would cause a decrease in Adipo R1 and Adipo R2 expression. MUC5AC expression with exposure to adiponectin was not significant. However, mRNA expression of Adipo R1 and Adipo R2 was significantly decreased by stimulation of IL-13 for acute (24 hours) and chronic (14 days) exposure. Therefore, the obese state and specifically IL-13 concentration could play a role in Adipo R1 and Adipo R2 expression within NHBE cells.

INTRODUÇÃO: A saúde passou a ser avaliada sob a óptica de qualidade de vida, a partir de 1948, com a definição da Organização Mundial da Saúde, como bem estar físico, mental e social e não mais ausência de doença. A saúde em crianças tem sido definida como um conceito subjetivo e multidimensional que deve incluir a avaliação física, o impacto psicossocial da doença sobre a criança e sua família. Em sociedades desenvolvidas ou em desenvolvimento é grande a importância epidemiológica da doença respiratória. Tal fato decorre do importante impacto exercido sobre seus expressivos índices de morbidade e de mortalidade na população infantil. Fazse necessário então, pela importância epidemiológica da doença respiratória, a incorporação de novas técnicas e processos para o estudo das condições de saúde da população com e sem problemas respiratórios sob a óptica da percepção dos pais ou responsáveis. Com o objetivo de estudar o impacto das doenças respiratórias nas condições de saúde das crianças de 5 a 9 anos de idade residentes no Distrito de Saúde Escola do Butantã foi utilizado, no presente estudo, o instrumento Child Health Questionnaire versão destinada aos pais(CHQ-PF-50), validado no mundo e no Brasil. Avaliou-se também a relação da declaração de doença respiratória segundo a instituição de ensino, instrução dos pais, faixa de renda e etnia MÉTODOS: Avaliaram-se as condições de saúde de 959 crianças na faixa etária de 5 a 9 anos de idade residentes no Distrito do Butantã, na Cidade de São Paulo, com e sem doença respiratória declarada pelos pais ou responsáveis. No período de março a julho de 2004. A pesquisa foi do tipo descritivo, com enfoque retrospectivo através da análise de dados disponibilizado junto a um banco de dados. Para tanto foi utilizado o método de levantamento de informações junto aos elementos amostrais, por meio de instrumento de coleta de dados estruturado e não disfarçado, utilizando o CHQ-PF50. As doenças respiratórias perguntadas e declaradas foram: rinite, sinusite, otite, laringite, faringoamigdalite, pneumonia, asma ou quadro asmatiforme. Os dados apresentados nesse trabalho foram analisados a partir de um conjunto de procedimentos aplicados aos dados originais coletados, conforme orientação metodológica encontrada em Landgraf et al.RESULTADOS:O estudo indicou que as crianças cujos pais referiram doença respiratória apresentaram condições de saúde insatisfatórias, quando comparadas às crianças sem doença respiratória. Pais de crianças que estudam em escolas privadas e com maior grau de escolaridade referiram mais doença respiratória em seus filhos. A renda mensal ou etnia não interferiu na declaração de doença respiratória. CONCLUSÕES: Para melhorar as condições de saúde das crianças com doença respiratória é necessário o entendimento dessas patologias no âmbito global, biopsico e social, além do aprimoramento educacional da população. / BACKGROUND: The health has been evaluated in terms of quality of life, from 1948, with the definition of the World Health Organization, as well the physical, mental and social rather than absence of disease. The health of children has been defined as a subjective and multidimensional concept that includes a physical evaluation, the psychosocial impact of disease on the child and his family. In societies developed or developing is great epidemiological importance of respiratory disease. This fact stems from the important impact on their expressive rates of morbidity and mortality in children. It becomes necessary then, the epidemiological importance of respirator tract disease, the incorporation of new techniques and processes for the study of the health of the population with and without respiratory problems in terms of the perception of parents or guardians. In order to study the impact of respiratory tract diseases in the health conditions of children from 5 to 9 years of age in the District Health School of Butantã was used in this study, the instrument Child Health Questionnaire version aimed at parents (CHQ - PF-50), validated in the world and Brazil. Was also evaluated the relationship of the declaration of respiratory tract disease according to the university, education of parents, track income and ethnicity METHODS: We evaluated the health of 959 children aged from 5 to 9 years of age residing in District of Butantã in the city of Sao Paulo, with and without respiratory tract disease declared by the parents or guardians. From March to July 2004. The research was a descriptive, with a focus through the retrospective analysis of data provided with a database. To that end we used the method of lifting elements of information from the sample by means of data collection instrument structured and not undercover, using the CHQ-PF50. Respiratory tract diseases were asked and declared: rhinitis, sinusitis, ear infections, laryngitis, pharyngitis, pneumonia, asthma or asthma framework. The data presented in this study were analyzed from a set of procedures applied to the original data collected as methodological guidance found in Landgraf et al.RESULTS: The study indicated that children whose parents had reported respiratory tract disease conditions of poor health, compared to children without respiratory tract disease. Parents of children who study in private schools and with a higher degree of education reported more respiratory disease to their children. The monthly income or ethnicity did not interfere in the declaration of respiratory tract disease. CONCLUSIONS: To improve the health conditions of children with respiratory tract disease is necessary to understand such conditions in the global context, and social biopsico, in addition to improving education of the population.

Submitted by VINÍCIUS ATHAYDES CANELLO null (vinaocanello@hotmail.com) on 2017-03-16T11:28:58Z No. of bitstreams: 1 Tese Versão Final.pdf: 4376586 bytes, checksum: 13d4cc1c29f43d7c4deb2102a7b48543 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2017-03-22T16:42:38Z (GMT) No. of bitstreams: 1 canello_va_dr_jabo.pdf: 4376586 bytes, checksum: 13d4cc1c29f43d7c4deb2102a7b48543 (MD5) / Made available in DSpace on 2017-03-22T16:42:38Z (GMT). No. of bitstreams: 1 canello_va_dr_jabo.pdf: 4376586 bytes, checksum: 13d4cc1c29f43d7c4deb2102a7b48543 (MD5) Previous issue date: 2017-02-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O grande desafio do sistema de defesa respiratório é a manutenção dos animais em baias. Pois, devido a diversos fatores, acaba por aumentar as chances do desenvolvimento de afecções respiratórias e a qualidade do material utilizado como cama é fator agravante. Diante disto, três grupos com 5 equinos cada foram submetidos a 45 dias sob o mesmo manejo, sendo dois grupos estabulados com diferentes tipos de cama, um com maravalha esterilizada (ME) e o outro com maravalha não esterilizada (MNE), e o terceiro grupo a pasto (Pasto). Foram realizadas análises do lavado broncoalveolar (LBA) (celularidade e marcadores de estresse oxidativo) e hemograma antes do início do manejo (Basal) e posteriormente a cada 15 dias (M15, M30 e M45). Também foi avaliada a presença de gêneros fúngicos nas amostras de cama, e do feno utilizado na alimentação dos animais. Os hemogramas permaneceram dentro dos valores da normalidade. Os valores obtidos de malondialdeído (MDA) e ácido úrico no LBA não apresentaram diferença entre os momentos e grupos avaliados. A vitamina C no LBA apresentou queda em seus valores em M30. Os três grupos apresentaram queda nas concentrações de glutationa reduzida em M30, tendo havido diferença significativas entre os grupos Pasto e MNE. Os grupos ME e MNE apresentaram queda nos valores de glutationa oxidada em M45, já o grupo Pasto apresentou queda constante a partir de M15, com diferença significativa em relação ao grupo ME em M30. A superóxido dismutase apresentou aumento em M30 no grupo MNE, levando a diferença significativa em relação aos grupos Pasto e ME. A glutationa peroxidase no LBA apresentou queda significativa no grupo ME em M45. Quanto a celularidade do LBA a contagem de células nucleadas totais e eosinófilos não apresentaram diferenças significativas. O grupo ME apresentou elevação nos valores de neutrófilos em M30, levando a diferença significativa em relação aos grupos MNE e Pasto, já o grupo MNE apresentou queda significativa em M45. Os grupos ME e MNE apresentaram queda nos valores de linfócitos no LBA em M30, já o grupo Pasto apresentou queda em M15. O grupo Pasto apresentou aumento dos macrófagos no LBA em M15 e M30. As análises das amostras de cama e feno apresentaram baixas porcentagens de gêneros fúngicos. Grande parte das alterações apresentadas ocorreram em M30, momento em que foram registradas as menores temperaturas e maiores velocidades dos ventos durante todo período experimental, o que possivelmente levou a um desequilíbrio oxidativo pontual, com pequenas variações na celularidade do LBA. Acredita-se que o manejo, as boas condições de higiene e ventilação das baias tenham contribuído para que não houvesse o desenvolvimento de alterações inflamatórias no sistema respiratório dos animais avaliados. Deste modo, podemos concluir que não houve diferenças significativas na manutenção dos animais nos diferentes tipos de cama em relação a resposta inflamatória, estresse oxidativo e desenvolvimento fúngico. / The great challenge of the respiratory defense system is the maintenance of animals in stalls, which due to several factors ends up increasing the chances of development of respiratory diseases. The quality of the material used as bed is an aggravating factor. Three groups of 5 horses were submitted to 45 days under the same management, and two groups were housed with different types of beds, one with sterilized wood shaving (ME) and the other with unsterilized wood shaving (MNE), and the third group was maintened in the pasture. Bronchoalveolar lavage fluid (BALF) and hemoglobin analyzes were performed before baseline and then every 15 days (M15, M30 and M45). It was also evaluated the possible presence of fungal genera in bed samples, and in hay used in animal feeding. The hemograms remained within normal values. The values of malondialdehyde (MDA) and uric acid in BALF showed no difference between the moments and groups evaluated. Vitamin C in BALF showed a decrease in M30 values. The three groups showed a decrease in the concentrations of glutathione reduced in M30, and there were significant differences between the groups pasture and MNE. The ME and MNE groups showed a decrease in the values of oxidized glutathione in M45, whereas the pasture group presented a constant drop from M15, with a significant difference in relation to the ME group in M30. Superoxide dismutase increased in M30 in the MNE group, leading to a significant difference in relation to the pasture and ME groups. Glutathione peroxidase in BALF showed a significant decrease in the ME group in M45. As for the cellularity of BALF, total nucleated and eosinophil counts did not showed significant differences. The ME group presented elevation in neutrophil values in M30, leading to a significant difference in relation to the MNE and pasture groups, whereas the MNE group presented a significant decrease in M45. The ME and MNE groups presented a decrease in lymphocyte values in the BALF in M30, whereas the pasture group presented a decrease in M15. The pasture group presented increase of the macrophages in the BALF in M15 and M30. Bed and hay samples showed low percentages of fungal genera. Most of the alterations presented occurred in M30, at which time the lowest temperatures were recorded throughout the experimental period, possibly leading to a punctual oxidative imbalance, with small variations in BALF cellularity. It is believed that management, good conditions of hygiene and ventilation of the boxes contributed to the no development of inflammatory changes in the respiratory system of the animals evaluated. Thus, we can conclude that there were no significant differences in the maintenance of the animals in the different types of bed in relation to the inflammatory response, oxidative stress and fungal development.

INTRODUÇÃO: A saúde passou a ser avaliada sob a óptica de qualidade de vida, a partir de 1948, com a definição da Organização Mundial da Saúde, como bem estar físico, mental e social e não mais ausência de doença. A saúde em crianças tem sido definida como um conceito subjetivo e multidimensional que deve incluir a avaliação física, o impacto psicossocial da doença sobre a criança e sua família. Em sociedades desenvolvidas ou em desenvolvimento é grande a importância epidemiológica da doença respiratória. Tal fato decorre do importante impacto exercido sobre seus expressivos índices de morbidade e de mortalidade na população infantil. Fazse necessário então, pela importância epidemiológica da doença respiratória, a incorporação de novas técnicas e processos para o estudo das condições de saúde da população com e sem problemas respiratórios sob a óptica da percepção dos pais ou responsáveis. Com o objetivo de estudar o impacto das doenças respiratórias nas condições de saúde das crianças de 5 a 9 anos de idade residentes no Distrito de Saúde Escola do Butantã foi utilizado, no presente estudo, o instrumento Child Health Questionnaire versão destinada aos pais(CHQ-PF-50), validado no mundo e no Brasil. Avaliou-se também a relação da declaração de doença respiratória segundo a instituição de ensino, instrução dos pais, faixa de renda e etnia MÉTODOS: Avaliaram-se as condições de saúde de 959 crianças na faixa etária de 5 a 9 anos de idade residentes no Distrito do Butantã, na Cidade de São Paulo, com e sem doença respiratória declarada pelos pais ou responsáveis. No período de março a julho de 2004. A pesquisa foi do tipo descritivo, com enfoque retrospectivo através da análise de dados disponibilizado junto a um banco de dados. Para tanto foi utilizado o método de levantamento de informações junto aos elementos amostrais, por meio de instrumento de coleta de dados estruturado e não disfarçado, utilizando o CHQ-PF50. As doenças respiratórias perguntadas e declaradas foram: rinite, sinusite, otite, laringite, faringoamigdalite, pneumonia, asma ou quadro asmatiforme. Os dados apresentados nesse trabalho foram analisados a partir de um conjunto de procedimentos aplicados aos dados originais coletados, conforme orientação metodológica encontrada em Landgraf et al.RESULTADOS:O estudo indicou que as crianças cujos pais referiram doença respiratória apresentaram condições de saúde insatisfatórias, quando comparadas às crianças sem doença respiratória. Pais de crianças que estudam em escolas privadas e com maior grau de escolaridade referiram mais doença respiratória em seus filhos. A renda mensal ou etnia não interferiu na declaração de doença respiratória. CONCLUSÕES: Para melhorar as condições de saúde das crianças com doença respiratória é necessário o entendimento dessas patologias no âmbito global, biopsico e social, além do aprimoramento educacional da população. / BACKGROUND: The health has been evaluated in terms of quality of life, from 1948, with the definition of the World Health Organization, as well the physical, mental and social rather than absence of disease. The health of children has been defined as a subjective and multidimensional concept that includes a physical evaluation, the psychosocial impact of disease on the child and his family. In societies developed or developing is great epidemiological importance of respiratory disease. This fact stems from the important impact on their expressive rates of morbidity and mortality in children. It becomes necessary then, the epidemiological importance of respirator tract disease, the incorporation of new techniques and processes for the study of the health of the population with and without respiratory problems in terms of the perception of parents or guardians. In order to study the impact of respiratory tract diseases in the health conditions of children from 5 to 9 years of age in the District Health School of Butantã was used in this study, the instrument Child Health Questionnaire version aimed at parents (CHQ - PF-50), validated in the world and Brazil. Was also evaluated the relationship of the declaration of respiratory tract disease according to the university, education of parents, track income and ethnicity METHODS: We evaluated the health of 959 children aged from 5 to 9 years of age residing in District of Butantã in the city of Sao Paulo, with and without respiratory tract disease declared by the parents or guardians. From March to July 2004. The research was a descriptive, with a focus through the retrospective analysis of data provided with a database. To that end we used the method of lifting elements of information from the sample by means of data collection instrument structured and not undercover, using the CHQ-PF50. Respiratory tract diseases were asked and declared: rhinitis, sinusitis, ear infections, laryngitis, pharyngitis, pneumonia, asthma or asthma framework. The data presented in this study were analyzed from a set of procedures applied to the original data collected as methodological guidance found in Landgraf et al.RESULTS: The study indicated that children whose parents had reported respiratory tract disease conditions of poor health, compared to children without respiratory tract disease. Parents of children who study in private schools and with a higher degree of education reported more respiratory disease to their children. The monthly income or ethnicity did not interfere in the declaration of respiratory tract disease. CONCLUSIONS: To improve the health conditions of children with respiratory tract disease is necessary to understand such conditions in the global context, and social biopsico, in addition to improving education of the population.

Disease mapping is used to identify high risk areas, inform resource allocation and generate hypotheses. The stroke and diabetes belts in the U.S. have encouraged public dialogue and spurred research. Lung cancer is the leading cause of U.S. cancer mortality, accounting for 158135 deaths in 2010 compared to 129180 from cerebrovascular disease and 68905 from diabetes mellitus. If one exists, defining a distinct pattern of high lung cancer mortality could increase public awareness of the disease and facilitate investigation of its determinants. To begin our inquiry, we generated a map and observed an area of high lung cancer mortality, primarily in the Southeast. However, variability in county rates, likely due to small populations, made determining patterns difficult. Spatial smoothing can clarify obscured patterns. We downloaded county lung cancer mortality rates, population sizes and death counts. Concurrent incidence and mortality rates for lung cancer were nearly equivalent, so mortality was used as a proxy for risk. After downloading county population centroids with latitudes and longitudes, we implemented a median-based, weighted, two-dimensional smoothing algorithm to enhance spatial patterns by borrowing strength from neighbor counties. The algorithm selected three proximate centroids, forming a “triple,” anchored by the centroid of the county to be smoothed. The parameter for nearest neighbor (NN) counties was set to NN=10, with the number of triples (NTR) for each county NTR=(2/3)*NN, producing seven collinear triples for each county with a center angle ≥135°. Median rates for the top and bottom 50% of neighbor counties were calculated and weighted by 1/SE, creating a “window,” whereby if the original rate was between the two medians, or if the county population was sufficiently large, it was not smoothed. If the original rate was outside the window, it was adjusted according to the corresponding neighbor median. Ten iterations of this process were conducted for each county. Smoothed rates were imported to ArcGIS and joined to a U.S. counties layer. Congruent counties in or near the Southeast with rates above 64 per 100,000 were defined as one class. We observed clustering of high lung cancer mortality, comprising 724 counties and forming an arc not evident in the unsmoothed data. This area, which we define as the lung cancer belt, included nearly all of Arkansas, Kentucky and Tennessee, and portions of 16 other states. Heavily affected regions include much of the Ohio Valley, Central Appalachia, the Tennessee Valley, the Ozarks, the Mississippi Delta and the northern Gulf Coast. Smoking, a modifiable behavior, causes the majority of lung cancer deaths, and is the single leading cause of mortality in the United States. Lung cancer mortality rates presented at the state level obscure differences within states. The lung cancer belt may provide a tool to identify areas in greatest need of resources. National survey data could be utilized to determine demographic, socioeconomic and behavioral differences between the lung cancer belt and the rest of the nation.