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BACKGROUND: Limited data exists suggesting that cumulative exposure to air pollution in the form of fine particulate matter (aerodynamic diameter ≤ 2.5 µm [PM2.5]) may be associated with papillary thyroid carcinoma (PTC), although this relationship has not been widely established. This study aims to evaluate the association between PM2.5 and PTC and determine the subgroups of patients who are at the highest risk of PTC diagnosis. METHODS: Under IRB approval, we conducted a case-control study of adult patients (age ≥ 18) newly diagnosed with PTC between 1/2013-12/2016 across a single health care system were identified using electronic medical records. These patients were compared to a control group of patients without any evidence of thyroid disease. Cumulative PM2.5 exposure was calculated for each patient using a deep learning neural networks model, which incorporated meteorological and satellite-based measurements at the patients' residential zip code. Adjusted multivariate logistic regression was used to quantify the association between cumulative PM2.5 exposure and PTC diagnosis. We tested whether this association differed by gender, race, BMI, smoking history, current alcohol use, and median household income. RESULTS: A cohort of 1990 patients with PTC and a control group of 6919 patients without thyroid disease were identified. Compared to the control group, patients with PTC were more likely to be older (51.2 vs. 48.8 years), female (75.5% vs 46.8%), White (75.2% vs. 61.6%), and never smokers (71.1% vs. 58.4%) (p < 0.001). After adjusting for age, sex, race, BMI, current alcohol use, median household income, current smoking status, hypertension, diabetes, COPD, and asthma, 3-year cumulative PM2.5 exposure was associated with a 1.41-fold increased odds of PTC diagnosis (95%CI: 1.23-1.62). This association varied by median household income (p-interaction =0.03). Compared to those with a median annual household income <$50,000, patients with a median annual household income between $50,000 and < $100,000 had a 43% increased risk of PTC diagnosis (aOR = 1.43, 95%CI: 1.19-1.72), and patients with median household income ≥$100,000 had a 77% increased risk of PTC diagnosis (aOR = 1.77, 95%CI: 1.37-2.29). CONCLUSIONS: Cumulative exposure to PM2.5 over 3 years was significantly associated with the diagnosis of PTC. This association was most pronounced in those with a high median household income, suggesting a difference in access to care among socioeconomic groups.
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Contaminantes Atmosféricos , Contaminación del Aire , Neoplasias de la Tiroides , Adulto , Humanos , Femenino , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Cáncer Papilar Tiroideo/epidemiología , Cáncer Papilar Tiroideo/inducido químicamente , Estudios de Casos y Controles , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Disparidades Socioeconómicas en Salud , Contaminación del Aire/análisis , Neoplasias de la Tiroides/epidemiologíaRESUMEN
PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is a highly prevalent disease with large social and financial burdens. The pathophysiology is multifactorial. Environmental pollutants have been suggested to play a role in the inflammatory component of the disease process. RECENT FINDINGS: Recent work has focused on exposure to various pollutants, primarily particulate matter (PM). Exposure to environmental pollutants leads to upregulation of inflammatory markers and ciliary dysfunction at the cellular level. Mouse models suggest a role for epithelial barrier dysfunction contributing to inflammatory changes after pollutant exposure. Clinical studies support the role of pollutants contributing to disease severity in certain populations, but the role in CRS incidence or prevalence is less clear. Research is limited by the retrospective nature of most studies. This review focuses on recent advancements in our understanding of the impact of environmental pollutants in CRS, limitations of the available data, and potential opportunities for future studies.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Animales , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Humanos , Ratones , Material Particulado/efectos adversos , Estudios RetrospectivosRESUMEN
Air-liquid interface (ALI) cultures are ex vivo models that are used extensively to study the epithelium of patients with chronic respiratory diseases. However, the in vitro conditions impose a milieu different from that encountered in the patient in vivo, and the degree to which this alters gene expression remains unclear. In this study we employed RNA sequencing to compare the transcriptome of fresh brushings of nasal epithelial cells with that of ALI-cultured epithelial cells from the same patients. We observed a strong correlation between cells cultured at the ALI and cells obtained from the brushed nasal epithelia: 96% of expressed genes showed similar expression profiles, although there was greater similarity between the brushed samples. We observed that while the ALI model provides an excellent representation of the in vivo airway epithelial transcriptome for mechanistic studies, several pathways are affected by the change in milieu.
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Mucosa Nasal/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/genética , Mucosa Respiratoria/metabolismo , Transcriptoma , Anciano , Aire , Fumar Cigarrillos/efectos adversos , Medios de Cultivo/química , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Anotación de Secuencia Molecular , Mucosa Nasal/patología , Cultivo Primario de Células , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Mucosa Respiratoria/patología , Análisis de Secuencia de ARN , Cornetes Nasales/metabolismo , Cornetes Nasales/patologíaRESUMEN
A novel N-acyl substituted indole-linked benzimidazoles and naphthoimidazoles were synthesized. Their chemical structures were confirmed using spectroscopic tools including 1H NMR, 13C NMR and CHN-elemental analyses. Anti inflammatory activity for all target compounds was evaluated in-vitro. The synthesized compounds hinder the biofilm formation and control the growth of the pathogen, Staphylococcus epidermis. Anti microbial activity of the compounds was evaluated against both Gram negative and Gram positive bacteria such as Staphylococcus aureus (MTCC 2940), Pseudomonas aeruginosa (MTCC424), Escherchia coli (MTCC 443) and Enterococcus fecalis.
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Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Antiinflamatorios/síntesis química , Antiinflamatorios/farmacología , Bencimidazoles/síntesis química , Bencimidazoles/farmacología , Biopelículas/efectos de los fármacos , Indoles/síntesis química , Indoles/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
Exposure to airborne particulate matter (PM) has been linked to aggravation of respiratory symptoms, increased risk of cardiovascular disease, and all-cause mortality. Although the health effects of PM on the lower pulmonary airway have been extensively studied, little is known regarding the impact of chronic PM exposure on the upper sinonasal airway. We sought to test the impact of chronic airborne PM exposure on the upper respiratory system in vivo. Mice were subjected, by inhalation, to concentrated fine (2.5 µm) PM 6 h/d, 5 d/wk, for 16 weeks. Mean airborne fine PM concentration was 60.92 µm/m3, a concentration of fine PM lower than that reported in some major global cities. Mice were then killed and analyzed for evidence of inflammation and barrier breakdown compared with control mice. Evidence of the destructive effects of chronic airborne PM on sinonasal health in vivo, including proinflammatory cytokine release, and macrophage and neutrophil inflammatory cell accumulation was observed. A significant increase in epithelial barrier dysfunction was observed, as assessed by serum albumin accumulation in nasal airway lavage fluid, as well as decreased expression of adhesion molecules, including claudin-1 and epithelial cadherin. A significant increase in eosinophilic inflammation, including increased IL-13, eotaxin-1, and eosinophil accumulation, was also observed. Collectively, although largely observational, these studies demonstrate the destructive effects of chronic airborne PM exposure on the sinonasal airway barrier disruption and nonallergic eosinophilic inflammation in mice.
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Eosinófilos/patología , Hipersensibilidad/patología , Inflamación/patología , Nariz/patología , Senos Paranasales/patología , Material Particulado/efectos adversos , Animales , Células Epiteliales/metabolismo , Células Epiteliales/patología , Técnica del Anticuerpo Fluorescente , Interleucina-13/metabolismo , Interleucina-1beta/metabolismo , Masculino , Ratones Endogámicos C57BL , Tamaño de la PartículaAsunto(s)
Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Material Particulado/toxicidad , Rinitis/etiología , Sinusitis/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Contaminación del Aire/estadística & datos numéricos , Estudios de Casos y Controles , Enfermedad Crónica , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Femenino , Humanos , Modelos Logísticos , Masculino , Maryland , Persona de Mediana Edad , Material Particulado/análisis , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenAsunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/metabolismo , Trastornos del Olfato/etiología , Mucosa Olfatoria/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/complicaciones , Neumonía Viral/metabolismo , Enzima Convertidora de Angiotensina 2 , COVID-19 , Humanos , Trastornos del Olfato/metabolismo , Pandemias , SARS-CoV-2 , Replicación ViralAsunto(s)
Alérgenos/inmunología , Isotiocianatos/farmacología , Proteína 1 Asociada A ECH Tipo Kelch/deficiencia , Factor 2 Relacionado con NF-E2/metabolismo , Ovalbúmina/inmunología , Sinusitis/etiología , Sinusitis/metabolismo , Animales , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Humanos , Ratones Transgénicos , Sinusitis/patología , SulfóxidosRESUMEN
This review article highlights air pollution as a critical global health concern with emphasis on its effects and role in the development and exacerbation of upper airway and lower airway disease with a focus on allergic rhinitis and asthma. This review underscores the World Health Organization's recognition of air pollution as the biggest environmental threat to human health. It discusses the various components and categories of air pollutants and the evidence-based effects they have on asthma and allergic rhinitis, ranging from pathogenesis to exacerbation of these conditions across various age groups in different geographic locations.
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Contaminantes Atmosféricos , Contaminación del Aire , Asma , Rinitis Alérgica , Humanos , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Asma/epidemiología , Asma/etiología , Rinitis Alérgica/epidemiología , Rinitis Alérgica/etiología , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Nariz/patologíaRESUMEN
OBJECTIVE: To evaluate the contribution of postnasal drip (PND) and chronic cough (CC) to symptoms of patients with chronic rhinitis treated with temperature-controlled radiofrequency (TCRF) neurolysis of the posterior nasal nerve (PNN), and correlate PND and CC scores with components of the reflective total nasal symptom score (rTNSS). METHODS: Pooled data from three prospective studies: two single-arm studies and the index active treatment arm of a randomized controlled trial. Adult patients with baseline rTNSS ≥6 were treated with TCRF neurolysis at nonoverlapping regions of the PNN. PND and CC symptoms were evaluated on a 0 (none) to 3 (severe) scale. RESULTS: Data from 228 patients (57.9% women, 42.1% men) were included. The mean baseline rTNSS was 8.1 (95% confidence interval [CI], 7.8-8.3), which decreased to 3.2 (95% CI, 2.9-3.5) at 6 months. At baseline, 97.4% of patients had PND and 80.3% had CC. Median baseline PND and CC symptom scores were 3 (interquartile range [IQR], 2-3) and 2 (IQR, 1-2), respectively. At 6 months, this decreased to 1 (IQR, 0-2) and 0 (IQR, 0-1), respectively, showing significant improvement from baseline (both p < 0.001). Spearman correlation coefficients with components of rTNSS (rhinorrhea, congestion, itching, sneezing) were 0.16 to 0.22 for CC and 0.19 to 0.46 for PND, indicating only a weak to moderate correlation. CONCLUSION: PND and CC contribute to the symptomatology of chronic rhinitis and are significantly improved after TCRF neurolysis of the PNN. The inclusion of PND and CC symptoms in a chronic rhinitis assessment instrument could provide important additional information for the characterization of the disease state and outcomes after any therapeutic treatment.
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Tos Crónica , Rinitis , Adulto , Femenino , Humanos , Masculino , Tos/terapia , Mucosa Nasal , Estudios Prospectivos , Rinitis/tratamiento farmacológico , Rinorrea , Temperatura , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Obtaining insurance approval is a necessary component of healthcare in the United States and denials of these claims have been estimated to result in a loss of 3% to 5% of revenue. OBJECTIVE: Examine the trends in insurance denials for rhinological procedures. METHODS: A retrospective review of deidentified financial data of patients who were treated by participating physicians across 3 institutions from January 1, 2021, to June 30, 2023. The data was queried for rhinological and non-rhinological procedures via CPT codes. Cumulative insurance denials were calculated and stratified by procedure and insurance type. Write-offs were dollar amounts associated with final denials. RESULTS: A sample of 102,984 procedures and visits revealed a final denial rate between 2.2% and 2.9% across institutions (p = .72). The top three rhinological procedures for final write-offs were: nasal endoscopy (16.24%, $111,836.87), nasal debridement or polypectomy (6.48%, $79,457.51), and destruction of intranasal lesion (2.11%, $56,932.20). The write-off percentage for each procedure was highest among commercial insurance payers as opposed to Medicare or Medicaid. CONCLUSION: Final denial rates of rhinology procedures ranged between 2% and 3%. Common procedures such as nasal endoscopy and nasal debridement are among the highest written-off procedures. Insurance denials can lead to notable revenue loss. Rhinology practices must continue to remain knowledgeable of the changes and effects of insurance reimbursement on their practice.
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Otolaringología , Humanos , Estados Unidos , Estudios Retrospectivos , Otolaringología/economía , Medicare/economía , Endoscopía/economía , Endoscopía/estadística & datos numéricos , Seguro de Salud/economía , Seguro de Salud/estadística & datos numéricos , Medicaid/economíaRESUMEN
INTRODUCTION: Despite effects on quality of life from olfactory and gustatory dysfunction (OD and GD), screening practices are limited, and patients' self-reporting of symptoms remains the only way to understand the burden of chemosensory dysfunction (CSD). Using a large population-based database, we sought to understand factors leading to reduced likelihood of discussing CSD with a provider. METHODS: The 2013â2014 National Health and Nutrition Examination Survey (NHANES) chemosensory protocol was queried for factors influencing discussion of OD/GD with a healthcare provider. Sociodemographic, comorbidity, and objective OD/GD testing results were assessed with a multivariate analysis. RESULTS: Out of 146.1 million US adults, there were an estimated 41.4 million individuals with self-reported OD/GD in the prior 12 months (28.3%). A total of 86.8% of participants did not discuss their problem with a healthcare provider. Men were about half as likely to speak with a healthcare provider (odds ratio [OR] 0.42; 0.26-0.66; p < 0.001) and those with a college education were about nine times more likely to discuss the problem compared to those with less than a ninth-grade educational achievement (OR 8.83; 1.86-41.98; p = 0.02). Those with objective confirmation of CSD were still unlikely to speak with a provider (OR 0.77; 0.44-1.33; p = 0.36). CONCLUSION: Men and those with less education are less likely to discuss OD/GD with a healthcare provider. These populations tend to be at increased risk for CSD, and there are severe downstream health and quality of life implications related to CSD. Dedicated screening and increased public awareness are critical to ensure more equitable care.
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BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent upper respiratory condition that manifests in two primary subtypes: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). While previous studies indicate a correlation between air pollution and CRS, the role of genetic predisposition in this relationship remains largely unexplored. We hypothesized that higher air pollution exposure would lead to the development of CRS, and that genetic susceptibility might modify this association. METHODS: This cohort study involving 367,298 adult participants from the UK Biobank, followed from March 2006 to October 2021. Air pollution metrics were estimated at residential locations using land-use regression models. Cox proportional hazard models were employed to explore the associations between air pollution exposure and CRS, CRSwNP, and CRSsNP. A polygenic risk score (PRS) was constructed to evaluate the joint effect of air pollution and genetic predisposition on the development of CRS. RESULTS: We found that the risk of CRS increased under long-term exposure to PM2.5 [the hazard ratios (HRs) with 95 % CIs: 1.59 (1.26-2.01)], PM10 [1.64 (1.26-2.12)], NO2 [1.11 (1.04-1.17)], and NOx [1.18 (1.12-1.25)], respectively. These effects were more pronounced among participants with CRSwNP, although the differences were not statistically significant. Additionally, we found that the risks for CRS and CRSwNP increased in a graded manner among participants with higher PRS or higher exposure to PM2.5, PM10, or NOx concentrations. However, no multiplicative or additive interactions were observed. CONCLUSIONS: Long-term exposure to air pollution increases the risk of CRS, particularly CRSwNP underscoring the need to prioritize clean air initiatives and environmental regulations.
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Contaminación del Aire , Rinosinusitis , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Contaminación del Aire/efectos adversos , Enfermedad Crónica , Exposición a Riesgos Ambientales/efectos adversos , Predisposición Genética a la Enfermedad , Pólipos Nasales/epidemiología , Pólipos Nasales/genética , Material Particulado , Estudios Prospectivos , Rinosinusitis/epidemiología , Biobanco del Reino Unido , Reino Unido/epidemiologíaRESUMEN
SARS-CoV-2 infection of the upper airway and the subsequent immune response are early, critical factors in COVID-19 pathogenesis. By studying infection of human biopsies in vitro and in a hamster model in vivo, we demonstrated a transition in nasal tropism from olfactory to respiratory epithelium as the virus evolved. Analyzing each variant revealed that SARS-CoV-2 WA1 or Delta infect a proportion of olfactory neurons in addition to the primary target sustentacular cells. The Delta variant possessed broader cellular invasion capacity into the submucosa, while Omicron displayed enhanced nasal respiratory infection and longer retention in the sinonasal epithelium. The olfactory neuronal infection by WA1 and the subsequent olfactory bulb transport via axon were more pronounced in younger hosts. In addition, the observed viral clearance delay and phagocytic dysfunction in aged olfactory mucosa were accompanied by a decline of phagocytosis-related genes. Further, robust basal stem cell activation contributed to neuroepithelial regeneration and restored ACE2 expression postinfection. Together, our study characterized the nasal tropism of SARS-CoV-2 strains, immune clearance, and regeneration after infection. The shifting characteristics of viral infection at the airway portal provide insight into the variability of COVID-19 clinical features, particularly long COVID, and may suggest differing strategies for early local intervention.
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COVID-19 , Resfriado Común , Animales , Cricetinae , Humanos , Anciano , SARS-CoV-2/genética , Síndrome Post Agudo de COVID-19 , COVID-19/genética , AxonesRESUMEN
Mechanisms of tumorigenesis in sinonasal squamous cell carcinoma (SNSCC) remain poorly described due to its rare nature. A subset of SNSCC are associated with the human papillomavirus (HPV); however, it is unknown whether HPV is a driver of HPV-associated SNSCC tumorigenesis or merely a neutral bystander. We hypothesized that performing the first large high-throughput sequencing study of SNSCC would reveal molecular mechanisms of tumorigenesis driving HPV-associated and HPV-independent SNSCC and identify targetable pathways. High-throughput sequencing was performed on 64 patients with HPV-associated and HPV-independent sinonasal carcinomas. Mutation annotation, viral integration, copy number, and pathway-based analyses were performed. Analysis of HPV-associated SNSCC revealed similar mutational patterns observed in HPV-associated cervical and head and neck squamous cell carcinoma, including lack of TP53 mutations and the presence of known hotspot mutations in PI3K and FGFR3. Further similarities included enrichment of APOBEC mutational signature, viral integration at known hotspot locations, and frequent mutations in epigenetic regulators. HPV-associated SNSCC-specific recurrent mutations were also identified including KMT2C , UBXN11 , AP3S1 , MT-ND4 , and MT-ND5 . Mutations in KMT2D and FGFR3 were associated with decreased overall survival. We developed the first known HPV-associated SNSCC cell line and combinatorial small molecule inhibition of YAP/TAZ and PI3K pathways synergistically inhibited tumor cell clonogenicity. In conclusion, HPV-associated SNSCC and HPV-independent SNSCC are driven by molecularly distinct mechanisms of tumorigenesis. Combinatorial blockade of YAP/TAZ and vertical inhibition of the PI3K pathway may be useful in targeting HPV-associated SNSCC whereas targeting MYC and horizontal inhibition of RAS/PI3K pathways for HPV-independent SNSCC. One Sentence Summary: This study solidifies HPV as a driver of HPV-associated SNSCC tumorigenesis, identifies molecular mechanisms distinguishing HPV-associated and HPV-independent SNSCC, and elucidates YAP/TAZ and PI3K blockade as key targets for HPV-associated SNSCC.
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IMPORTANCE: Allergic rhinitis affects up to 40% of the US population. To desensitize allergic individuals, subcutaneous injection immunotherapy or sublingual immunotherapy may be administered. In the United States, sublingual immunotherapy is not approved by the Food and Drug Administration. However, some US physicians use aqueous allergens, off-label, for sublingual desensitization. OBJECTIVE: To systematically review the effectiveness and safety of aqueous sublingual immunotherapy for allergic rhinoconjunctivitis and asthma. EVIDENCE ACQUISITION: The databases of MEDLINE, EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials were searched through December 22, 2012. English-language randomized controlled trials were included if they compared sublingual immunotherapy with placebo, pharmacotherapy, or other sublingual immunotherapy regimens and reported clinical outcomes. Studies of sublingual immunotherapy that are unavailable in the United States and for which a related immunotherapy is unavailable in the United States were excluded. Paired reviewers selected articles and extracted the data. The strength of the evidence for each comparison and outcome was graded based on the risk of bias (scored on allocation, concealment of intervention, incomplete data, sponsor company involvement, and other bias), consistency, magnitude of effect, and the directness of the evidence. RESULTS: Sixty-three studies with 5131 participants met the inclusion criteria. Participants' ages ranged from 4 to 74 years. Twenty studies (n = 1814 patients) enrolled only children. The risk of bias was medium in 43 studies (68%). Strong evidence supports that sublingual immunotherapy improves asthma symptoms, with 8 of 13 studies reporting greater than 40% improvement vs the comparator. Moderate evidence supports that sublingual immunotherapy use decreases rhinitis or rhinoconjunctivitis symptoms, with 9 of 36 studies demonstrating greater than 40% improvement vs the comparator. Medication use for asthma and allergies decreased by more than 40% in 16 of 41 studies of sublingual immunotherapy with moderate grade evidence. Moderate evidence supports that sublingual immunotherapy improves conjunctivitis symptoms (13 studies), combined symptom and medication scores (20 studies), and disease-specific quality of life (8 studies). Local reactions were frequent, but anaphylaxis was not reported. CONCLUSIONS AND RELEVANCE: The overall evidence provides a moderate grade level of evidence to support the effectiveness of sublingual immunotherapy for the treatment of allergic rhinitis and asthma, but high-quality studies are still needed to answer questions regarding optimal dosing strategies. There were limitations in the standardization of adverse events reporting, but no life-threatening adverse events were noted in this review.
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Asma/tratamiento farmacológico , Conjuntivitis Alérgica/tratamiento farmacológico , Desensibilización Inmunológica/métodos , Rinitis Alérgica Perenne/tratamiento farmacológico , Administración Sublingual , Alérgenos/administración & dosificación , Asma/inmunología , Conjuntivitis Alérgica/inmunología , Humanos , Uso Fuera de lo Indicado , Ensayos Clínicos Controlados Aleatorios como Asunto , Rinitis Alérgica , Rinitis Alérgica Perenne/inmunología , Resultado del TratamientoRESUMEN
The unified airway is in constant exposure to environmental factors that promote inflammation and disease. Environmental allergens, including house dust mites, pets, pollens, and molds, are strongly linked with development and exacerbation of upper airway disease with nonlinear dose-dependent relationships. Occupational triggers, including combat exposures and construction workers, are associated with the development of both upper and lower airway disease resulting in a "healthy worker effect" where many people leave jobs due to significant morbidity..
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Inflamación , HumanosRESUMEN
BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial inflammatory condition that remains poorly understood. Over the past decade, we have witnessed impressive scientific advancements that have allowed us to better understand the molecular and cellular mechanisms that underlie the inflammatory processes in mucosal diseases including asthma, allergic rhinitis, and CRSwNP. OBJECTIVE: The present review aims to summarize and highlight the most recent scientific advancements that have enriched our understanding of CRSwNP. METHODS: A comprehensive review of the available literature on the use of new scientific techniques in CRSwNP was performed. We evaluated the most recent evidence from studies using animal models, cell cultures, and genome sequencing techniques and their impact on our understanding of CRSwNP pathophysiology. RESULTS: Our understanding of CRSwNP has rapidly progressed with the development of newer scientific techniques to interrogate various pathways involved in its pathogenesis. Animal models remain powerful tools and have elucidated the mechanisms behind esinophilic inflammation in CRSwNP; however, animal models reproducing polyp formation are relatively sparse. 3D cell cultures have significant potential to better dissect the cellular interactions with the sinonasal epithelium and other cell types in CRS. Additionally, some groups are starting to utilize single-cell RNA sequencing to investigate RNA expression in individual cells with high resolution and on a genomic scale. CONCLUSION: These emerging scientific technologies represent outstanding opportunities to identify and develop more targeted therapeutics for different pathways that lead to CRSwNP. An additional understanding of these mechanisms will be critical for developing future therapies for CRSwNP.
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Asma , Pólipos Nasales , Animales , Epitelio , Inflamación , Modelos AnimalesRESUMEN
BACKGROUND: Meningitis can cause devastating epidemics and is susceptible to climate change. It is unclear how temperature variability, an indicator of climate change, is associated with meningitis incidence. METHODS: We used global meningitis incidence data along with meteorological and demographic data over 1990-2019 to identify the association between temperature variability and meningitis. We also employed future (2020-2100) climate data to predict meningitis incidence under different emission levels (SSPs: Shared Socioeconomic Pathways). RESULTS: We found that the mean temperature variability increased by almost 3 folds in the past 30 years. The largest changes occurred in Australasia, Tropical Latin America, and Central Sub-Saharan Africa. With a logarithmic unit increase in temperature variability, the overall global meningitis risk increases by 4.8 %. Australasia, Central Sub-Saharan Africa, and High-income North America are the most at-risk regions. Higher statistical differences were identified in males, children, and the elderly population. Compared to high-emission (SSP585) scenario, we predicted a median reduction of 85.8 % in meningitis incidence globally under the low-emission (SSP126) climate change scenario by 2100. CONCLUSION: Our study provides evidence for temperature variability being in association with meningitis incidence, which suggests that global actions are urgently needed to address climate change and to prevent meningitis occurrence.
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Epidemias , Meningitis , Anciano , Masculino , Niño , Humanos , Incidencia , Temperatura , Meningitis/epidemiología , África del Sur del Sahara/epidemiología , Cambio ClimáticoRESUMEN
PURPOSE: Cushing Syndrome (CS) is a rare endocrine disorder associated with physical and mental symptoms that can drastically affect quality of life (QoL). This study characterizes QoL in patients with CS, describes their treatment experiences, and identifies patient subsets associated with decreased QoL or shared impressions of treatment. METHODS: A 136-question survey addressing QoL factors and treatment experiences was completed by adult patients with CS from the Cushing Support and Research Foundation. Patient demographics, tumor characteristics, and treatment information were collected. Bivariate analyses were conducted to determine if patients' symptoms or treatment experiences were significantly associated with demographics or other variables. RESULTS: A total of 178 patients, predominantly female (94%) with mean age 53 years, completed the survey. Anxiety and/or depression (n = 163, 94%), loss of physical strength (n = 164, 93%), loneliness (n = 156, 90%), fatigue from treatment (n = 142, 89%), memory loss (n = 153, 88%), insomnia (n = 144, 83%), and pain (n = 141, 83%) were symptoms most commonly experienced by respondents. Patients experiencing delay of diagnosis >10 years were more likely to have suicidal thoughts (p = 0.002). Younger patients were more likely to express concerns about hair loss (p = 0.007), loneliness (p = 0.025), pain (p = 0.004), or the impact of CS on their marriage (p = 0.039) or children (p = 0.024). CONCLUSION: This survey demonstrates CS impacts patients across many dimensions, emphasizing the need for holistic support. We identified patient subsets in which QoL may be improved with additional patient resources or provider attention.