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Many vulnerable people lose their health or lives each year as a result of unhealthy environmental conditions that perpetuate medical conditions within the scope of allergy and immunology specialists' expertise. While detrimental environmental factors impact all humans globally, the effect is disproportionately more profound in impoverished neighborhoods. Environmental injustice is the inequitable exposure of disadvantaged populations to environmental hazards. Professional medical organizations such as the American Academy of Allergy, Asthma & Immunology (AAAAI) are well positioned to engage and encourage community outreach volunteer programs to combat environmental justice. Here we discuss how environmental injustices and climate change impacts allergic diseases among vulnerable populations. We discuss pathways allergists/immunologists can use to contribute to addressing environmental determinants by providing volunteer clinical service, education, and advocacy. Furthermore, allergists/immunologists can play a role in building trust within these communities, partnering with other patient advocacy nonprofit stakeholders, and engaging with local, state, national, and international nongovernmental organizations, faith-based organizations, and governments. The AAAAI's Volunteerism Addressing Environmental Disparities in Allergy (VAEDIA) is the presidential task force aiming to promote volunteer initiatives by creating platforms for discussion and collaboration and by funding community-based projects to address environmental injustice.
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Alergia e Inmunología , Hipersensibilidad , Voluntarios , Humanos , Comités Consultivos , Alergia e Inmunología/educación , Cambio Climático , Exposición a Riesgos Ambientales/efectos adversos , Hipersensibilidad/inmunología , Justicia Social , Estados UnidosRESUMEN
Respiratory-related diseases are a leading cause of death in rheumatoid arthritis (RA) and are disproportionately higher in men, which may be attributable to environmental risk factors. Animal studies have demonstrated potentiated autoimmunity, arthritis, and profibrotic/inflammatory lung disease with a combination of airborne exposures and collagen-induced arthritis (CIA). This study aimed to determine whether hormone-dependent differences explained these observations. Arthritis-prone male intact and castrated DBA/1J mice received intranasal inhalation of lipopolysaccharide (LPS) daily for 5 wk and CIA induction. Arthritis scores and serum pentraxin-2 levels were increased in castrated versus intact mice. In contrast, airway cell influx, lung tissue infiltrates, and lung levels of proinflammatory and profibrotic markers (C5a, IL-33, and matrix metalloproteinases) were reduced in castrated versus intact mice. CIA + LPS-induced lung histopathology changes and the expression of lung autoantigens including malondialdehyde acetaldehyde (MAA)- and citrulline (CIT)-modified proteins and vimentin were reduced in castrated animals. There were no differences in serum anti-MAA or anti-CIT protein antibody (ACPA) levels or serum pentraxin levels between groups. Testosterone replacement led to a reversal of several lung inflammatory/profibrotic endpoints noted earlier in castrated male CIA + LPS-treated mice with testosterone supplementation promoting neutrophil influx, MAA expression, and TNF-α, IL-6, and MMP-9. These findings imply that testosterone contributes to lung and arthritis inflammatory responses following CIA + LPS coexposure, but not to systemic autoantibody responses. The CIA + LPS model provides a paradigm for investigations focused on the mechanistic underpinnings for epidemiologic and phenotypic sex differences in RA-related lung disease.NEW & NOTEWORTHY Our study shows that testosterone acts as a key immunomodulatory hormone contributing to critical features of rheumatoid arthritis (RA)-associated lung disease in the setting of airborne endotoxin (lipopolysaccharide; LPS) exposures and concomitant arthritis induction in mice. The exaggerated airway inflammation observed following combined exposures in male mice was accompanied by increases in profibrotic mediators, netosis, and increased expression of lung autoantigens, all relevant to the pathogenesis of lung disease in arthritis.
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Artritis Experimental , Artritis Reumatoide , Enfermedades Pulmonares , Humanos , Masculino , Femenino , Animales , Ratones , Lipopolisacáridos/farmacología , Endotoxinas , Testosterona/farmacología , Ratones Endogámicos DBA , AutoantígenosRESUMEN
OBJECTIVE: Although clinical and genetic risk factors have been identified for rheumatoid arthritis-associated interstitial lung disease (RA-ILD), there are no current tools allowing for risk stratification. We sought to develop and validate an ILD risk model in a large, multicentre, prospective RA cohort. METHODS: Participants in the Veterans Affairs RA (VARA) registry were genotyped for 12 single nucleotide polymorphisms (SNPs) associated with idiopathic pulmonary fibrosis. ILD was validated through systematic record review. A genetic risk score (GRS) was computed from minor alleles weighted by effect size with ILD, using backward selection. The GRS was combined with clinical risk factors within a logistic regression model. Internal validation was completed using bootstrapping, and model performance was assessed by the area under the receiver operating curve (AUC). RESULTS: Of 2,386 participants (89% male, mean age 69.5 years), 9.4% had ILD. Following backward selection, five SNPs contributed to the GRS. The GRS and clinical factors outperformed clinical factors alone in discriminating ILD (AUC 0.675 vs 0.635, p< 0.001). The shrinkage-corrected performance for combined and clinical-only models was 0.667 (95% CI 0.628, 0.712) and 0.623 (95% CI 0.584, 0.651), respectively. Twenty percent of the cohort had a combined risk score below a cut-point with >90% sensitivity. CONCLUSION: A clinical and genetic risk model discriminated ILD in a large, multicentre RA cohort better than a clinical-only model, excluding 20% of the cohort from low-yield testing. These results demonstrate the potential utility of a GRS in RA-ILD and support further investigation into individualized risk stratification and screening.
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BACKGROUND: Environmental/occupational exposures cause significant lung diseases. Agricultural organic dust extracts (ODE) and bacterial component lipopolysaccharide (LPS) induce recruited, transitioning murine lung monocytes/macrophages, yet their cellular role remains unclear. METHODS: CCR2 RFP+ mice were intratracheally instilled with high concentration ODE (25%), LPS (10 µg), or gram-positive peptidoglycan (PGN, 100 µg) for monocyte/macrophage cell-trafficking studies. CCR2 knockout (KO) mice and administration of intravenous clodronate liposomes strategies were employed to reduce circulating monocytes available for lung recruitment following LPS exposure. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected. Pro-inflammatory and/or pro-fibrotic cytokines, chemokines, and lung extracellular matrix mediators were quantitated by ELISA. Infiltrating lung cells including monocyte/macrophage subpopulations, neutrophils, and lymphocytes were characterized by flow cytometry. Lung histopathology, collagen content, vimentin, and post-translational protein citrullination and malondialdehyde acetaldehyde (MAA) modification were quantitated. Parametric statistical tests (one-way ANOVA, Tukey'smultiple comparison) and nonparametric statistical (Kruskal-Wallis, Dunn's multiple comparison) tests were used following Shapiro-Wilk testing for normality. RESULTS: Intratracheal instillation of ODE, LPS, or PGN robustly induced the recruitment of inflammatory CCR2+ CD11cintCD11bhi monocytes/macrophages and both CCR2+ and CCR2- CD11c-CD11bhi monocytes at 48 h. There were also increases in CCR2+ CD4+ and CD8+ T cells and NK cells. Despite reductions in LPS-induced lung infiltrating CD11cintCD11bhi cells (54% reduction), CCR2 knockout (KO) mice were not protected against LPS-induced inflammatory and pro-fibrotic consequences. Instead, compensatory increases in lung neutrophils and CCL2 and CCL7 release occurred. In contrast, the depletion of circulating monocytes through the administration of intravenous clodronate (vs. vehicle) liposomes 24 h prior to LPS exposure reduced LPS-induced infiltrating CD11cintCD11bhi monocyte-macrophage subpopulation by 59% without compensatory changes in other cell populations. Clodronate liposome pre-treatment significantly reduced LPS-induced IL-6 (66% reduction), matrix metalloproteinases (MMP)-3 (36%), MMP-8 (57%), tissue inhibitor of metalloproteinases (61%), fibronectin (38%), collagen content (22%), and vimentin (40%). LPS-induced lung protein citrullination and MAA modification, post-translational modifications implicated in lung disease, were reduced (39% and 48%) with clodronate vs. vehicle liposome. CONCLUSION: Highly concentrated environmental/occupational exposures induced the recruitment of CCR2+ and CCR2- transitioning monocyte-macrophage and monocyte subpopulations and targeting peripheral monocytes may reduce the adverse lung consequences resulting from exposures to LPS-enriched inhalants.
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Enfermedades Pulmonares , Monocitos , Ratones , Animales , Monocitos/metabolismo , Liposomas/metabolismo , Vimentina/metabolismo , Lipopolisacáridos/farmacología , Ácido Clodrónico/farmacología , Ácido Clodrónico/metabolismo , Linfocitos T CD8-positivos , Pulmón , Macrófagos/metabolismo , Enfermedades Pulmonares/metabolismo , Exposición a Riesgos Ambientales , Colágeno/metabolismo , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Whereas differences in inducible laryngeal obstruction (ILO) presentation based on age have been demonstrated within pediatric populations, age-based differences in adult populations is lacking. OBJECTIVE: The purpose of this study was to describe differences in ILO based on age in adults. METHODS: Subjects age >16 years with confirmed ILO (vocal cord adduction >50% during inspiration) via provocation-challenge rhinolaryngoscopy by their treating allergist were included. An investigator designed questionnaire was administered using REDCap with corresponding medical data collection. Chi-square tests, Student's t-tests, ANOVA, Cochran-Armitage test for trend, and Fisher's exact test were utilized. RESULTS: The median age of the 67 subjects was 50 years. P-values <0.05 were considered significant. Those age <50 years (N=31; mean age 35.6 years) reported more symptoms vs age ≥50 years (N=36; mean age 61.8 years), including shortness of breath at rest and exertion (84% vs 39%, 94% vs 72%), throat tightness (81% vs 50%), chest tightness (81% vs 47%), and difficulty getting air in (81% vs 56%). Those age <50 years had increased history of anxiety (68% vs 33%), asthma (55% vs 31%), positive methacholine challenge (52% vs 22%), increasing triggers with time (87% vs 43%), higher Pittsburgh Vocal Cord Dysfunction Index Scores (6.9 vs 5.5), and inspiratory curve flattening (48% vs 24%). Additional age-based subdivisions confirmed significant trends with lowest reported ILO characteristics and symptoms in those age ≥65 years. CONCLUSION: A high index of suspicion for ILO should be maintained in older adults as they may report less typical ILO symptoms and anxiety associations that prompt ILO evaluation.
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Environmental justice is the concept that all people have the right to live in a healthy environment, to be protected against environmental hazards, and to participate in decisions affecting their communities. Communities of color and low-income populations live, work, and play in environments with disproportionate exposure to hazards associated with allergic disease. This unequal distribution of hazards has contributed to health disparities and is largely the result of systemic racism that promotes segregation of neighborhoods, disinvestment in predominantly racial/ethnic minority neighborhoods, and discriminatory housing, employment, and lending practices. The AAAAI Environmental Exposure and Respiratory Health Committee and Diversity, Equity and Inclusion Committee jointly developed this report to improve allergy/immunology specialists' awareness of environmental injustice, its roots in systemic racism, and its impact on health disparities in allergic disease. We present evidence supporting the relationship between exposure to environmental hazards, particularly at the neighborhood level, and the disproportionately high incidence and poor outcomes from allergic diseases in marginalized populations. Achieving environmental justice requires investment in at-risk communities to increase access to safe housing, clean air and water, employment opportunities, education, nutrition, and health care. Through policies that promote environmental justice, we can achieve greater health equity in allergic disease.
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Justicia Ambiental , Hipersensibilidad , Humanos , Etnicidad , Diversidad, Equidad e Inclusión , Grupos Minoritarios , Exposición a Riesgos AmbientalesRESUMEN
OBJECTIVES: To quantify associations of serum alarmins with risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: Using serum collected at enrolment, three alarmins (interleukin [IL]-33, thymic stromal lymphopoietin [TSLP], and IL-25) were measured in a multicentre prospective RA cohort. ILD was classified using systematic medical record review. Cross-sectional associations of log-transformed (IL-33, TSLP) or quartile (IL-25) values with RA-ILD at enrolment (prevalent RA-ILD) were examined using logistic regression, while associations with incident RA-ILD developing after enrolment were examined using Cox proportional hazards. Covariates in multivariate models included age, sex, race, smoking status, RA disease activity score, and anti-cyclic citrullinated antibody positivity. RESULTS: Of 2,835 study participants, 115 participants (4.1%) had prevalent RA-ILD at baseline and an additional 146 (5.1%) developed incident ILD. There were no associations between serum alarmin concentrations and prevalent ILD in unadjusted or adjusted logistic regression models. In contrast, there was a significant inverse association between IL-33 concentration and the risk of developing incident RA-ILD in unadjusted (HR 0.73 per log-fold increase; 95% CI 0.57-0.95; p= 0.018) and adjusted (HR 0.77; 95% CI 0.59-1.00, p= 0.047) models. No significant associations of TSLP or IL-25 with incident ILD were observed. CONCLUSIONS: In this study, we observed a significant inverse association between serum IL-33 concentration and the risk of developing incident RA-ILD, but no associations with prevalent ILD. Additional investigation is required to better understand the mechanisms driving this relationship and how serum alarmin IL-33 assessment might contribute to clinical risk stratification in patients with RA.
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PURPOSE OF REVIEW: Occupational rhinitis is an underdiagnosed disease with significant morbidity and implications in the workplace. Multiple factors associated with this disease continue to pose a challenge to investigators. This review aims to summarize recent literature in occupational rhinitis, including classifications, pathogenesis, diagnosis, and treatment, as well as the impact of occupational rhinitis on individuals. Additionally, it identifies areas in need of further research and investigation. RECENT FINDINGS: We highlight current research on the association between occupational rhinitis and occupational asthma and the role of immunotherapy in this disease. Discussion includes the impact of social trends on workers and the wider consequences of occupational rhinitis including decreased work productivity, absenteeism, and socioeconomic burden. Occupational rhinitis remains a challenging disease entity due to the numerous potential causative factors, reduced recognition, morbidity in asthma, and therapeutic limitations. Additional research is needed to better identify disease predictors and develop effective management strategies.
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Asma Ocupacional , Enfermedades Profesionales , Exposición Profesional , Rinitis , Humanos , Rinitis/diagnóstico , Rinitis/epidemiología , Rinitis/terapia , Enfermedades Profesionales/diagnóstico , Exposición Profesional/efectos adversos , Lugar de TrabajoRESUMEN
PURPOSE OF REVIEW: Occupational lung disease, including asthma, is a significant cause of disability worldwide. The dose, exposure frequency, and nature of the causal agent influence the inflammatory pathomechanisms that inform asthma disease phenotype and progression. While surveillance, systems engineering, and exposure mitigation strategies are essential preventative considerations, no targeted medical therapies are currently available to ameliorate lung injury post-exposure and prevent chronic airway disease development. RECENT FINDINGS: This article reviews contemporary understanding of allergic and non-allergic occupational asthma mechanisms. In addition, we discuss the available therapeutic options, patient-specific susceptibility and prevention measures, and recent scientific advances in post-exposure treatment conception. The course of occupational lung disease that follows exposure is informed by individual predisposition, immunobiologic response, agent identity, overall environmental risk, and preventative workplace practices. When protective strategies fail, knowledge of underlying disease mechanisms is necessary to inform targeted therapy development to lessen occupational asthma disease severity and occurrence.
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Asma Ocupacional , Hipersensibilidad , Enfermedades Profesionales , Exposición Profesional , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Asma Ocupacional/etiología , Asma Ocupacional/prevención & control , Exposición Profesional/efectos adversosRESUMEN
BACKGROUND: Attributes defining the Social Determinants of Health (SDoH) are associated with disproportionate exposures to environmental hazards and differential health outcomes among communities. The dynamics between SDoH, disproportionate environmental exposures, and differential health outcomes are often specific to micro-geographic areas. METHODS: This study focused on children less than 20 years of age who lived in Douglas County, Nebraska, during 2016-2019. To assess the role of SDoH in differential exposures, we evaluated the association between SDoH metrics and criteria pollutant concentrations and the association between SDoH and pediatric asthma exacerbations to quantify the role of SDoH in differential pediatric asthma outcomes. The Bayesian Poisson regression model with spatial random effects was used to evaluate associations. RESULTS: We identified significant positive associations between the annual mean concentration of criteria pollutants (carbon monoxide, particulate matter2.5, nitrogen dioxide, sulfur dioxide) with race (Non-Hispanic Black and Hispanic/Latino), financial stability, and literacy. Additionally, there were significant positive associations between higher rates of pediatric asthma emergency department visits and neighborhoods with more Non-Hispanic Black children, children without health insurance coverage, and households without access to a vehicle. CONCLUSIONS: Non-Hispanic Black and Hispanic/Latino children living in Douglas County, NE experience disproportionately higher exposure to criteria pollutant concentrations. Additionally, higher rates of asthma exacerbations among Non-Hispanic Black children could be due to reduced access to respiratory care that is potentially the result of financial instability and vehicle access. These results could inform city planners and health care providers to mitigate respiratory risks among these higher at-risk populations.
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Asma , Contaminantes Ambientales , Niño , Humanos , Determinantes Sociales de la Salud , Teorema de Bayes , Asma/epidemiología , Evaluación de Resultado en la Atención de SaludRESUMEN
Livestock workers experience an increased burden of bioaerosol-induced respiratory disease including a high prevalence of rhinosinusitis. Dairy operations generate bioaerosols spanning the inhalable size fraction (0-100 µm) containing bacterial constituents such as endotoxin. Particles with an aerodynamic diameter between 10 and 100 µm are known to deposit in the nasopharyngeal region and likely affect the upper respiratory tract. We evaluated the effectiveness of a hypertonic saline nasal lavage in reducing inflammatory responses in dairy workers from a high-volume dairy operation. Inhalable personal breathing zone samples and pre-/post-shift nasal lavage samples from each participant over five consecutive days were collected. The treatment group (n = 5) received hypertonic saline while the control group (n = 5) received normotonic saline. Personal breathing zone samples were analyzed for particulate concentrations and endotoxin using gravimetric and enzymatic methods, respectively. Pro- and anti-inflammatory cytokines (i.e., IL-8, IL-10, and TNF-α) were measured from nasal lavage samples using a multiplex assay. Inhalable dust concentrations ranged from 0.15 to 1.9 mg/m3. Concentrations of both pro- and anti-inflammatory cytokines, specifically IL-6, IL-8, and IL-10, were significantly higher in the treatment group compared to the control group (p < 0.02, p < 0.04, and p < 0.01, respectively). Further analysis of IL-10 anti-inflammatory indicates a positive association between hypertonic saline administration and IL-10 production. This pilot study demonstrates that hypertonic saline nasal lavages were successful in upregulating anti-inflammatory cytokines to support larger interventional studies.
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Interleucina-10 , Interleucina-8 , Humanos , Proyectos Piloto , Solución Salina Hipertónica , Citocinas , Polvo/prevención & control , Polvo/análisis , Endotoxinas/análisis , AntiinflamatoriosRESUMEN
OBJECTIVES: To determine whether RA and interstitial lung disease (ILD) severity measures are associated with survival in patients with RA-ILD. METHODS: We studied US veterans with RA-ILD participating in a multicentre, prospective RA cohort study. RA disease activity (28-joint DAS [DAS28-ESR]) and functional status (multidimensional HAQ [MDHAQ]) were collected longitudinally while pulmonary function tests (forced vital capacity [FVC], diffusing capacity for carbon monoxide) were obtained from medical records. Vital status and cause of death were determined from the National Death Index and administrative data. Predictors of death were assessed using multivariable Cox regression models adjusting for age, sex, smoking status, ILD duration, comorbidity burden and medications. RESULTS: We followed 227 RA-ILD participants (93% male and mean age of 69 years) over 1073 person-years. Median survival after RA-ILD diagnosis was 8.5 years. Respiratory diseases (28%) were the leading cause of death, with ILD accounting for 58% of respiratory deaths. Time-varying DAS28-ESR (adjusted hazard ratio [aHR] 1.21; 95% CI: 1.03, 1.41) and MDHAQ (aHR 1.85; 95% CI: 1.29, 2.65) were separately associated with mortality independent of FVC and other confounders. Modelled together, the presence of either uncontrolled disease activity (moderate/high DAS28-ESR) or FVC impairment (<80% predicted) was significantly associated with mortality risk. Those with a combination of moderate/high disease activity and FVC <80% predicted had the highest risk of death (aHR 4.43; 95% CI: 1.70, 11.55). CONCLUSION: Both RA and ILD disease severity measures are independent predictors of survival in RA-ILD. These findings demonstrate the prognostic value of monitoring the systemic features of RA-ILD.
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Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Veteranos , Humanos , Masculino , Anciano , Femenino , Estudios de Cohortes , Estudios Prospectivos , Artritis Reumatoide/tratamiento farmacológico , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown. METHODS: Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV1/FVC ratio < 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation. RESULTS: The study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on FEV1/FVC ratio was demonstrated among subjects with COPD (N = 245, p = 0.01). There was a positive correlation among former smokers and negative correlation among current or never smokers with COPD. Among former smokers with COPD, CC16 levels were also positively correlated with years since smoking cessation, and inversely related with pack-years smoked. Increasing CC16 levels were associated with lower odds of COPD (ORadj = 0.36, 95% CI 0.22-0.57, Padj < 0.0001). CONCLUSIONS: Smoking status is an important effect modifier of CC16 relationships with lung function. Increasing serum CC16 corresponded to increases in FEV1/FVC ratio in former smokers with COPD versus opposite relationships in current or never smokers. Additional longitudinal studies may be warranted to assess relationship of CC16 with smoking cessation on lung function among subjects with COPD.
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Enfermedad Pulmonar Obstructiva Crónica , Uteroglobina , Antiinflamatorios/metabolismo , Antioxidantes/metabolismo , Broncodilatadores/metabolismo , Estudios Transversales , Femenino , Humanos , Pulmón/metabolismo , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Humo , Fumar/efectos adversos , Fumar/epidemiología , Nicotiana , Uteroglobina/metabolismoRESUMEN
Immunogenetic as well as environmental and occupational exposures have been linked to the development of rheumatoid arthritis (RA), RA-associated lung disease, and other primary lung disorders. Importantly, various inhalants can trigger post-translational protein modifications, resulting in lung autoantigen expression capable of stimulating pro-inflammatory and/or pro-fibrotic immune responses. To further elucidate gene-environment interactions contributing to pathologic lung inflammation, we exploited an established model of organic dust extract (ODE) exposure with and without collagen-induced arthritis (CIA) in C57BL/6 wild type (WT) versus HLA-DR4 transgenic mice. ODE-induced airway infiltration driven by neutrophils was significantly increased in DR4 versus WT mice, with corresponding increases in bronchoalveolar lavage fluid (BALF) levels of TNF-âº, IL-6, and IL-33. Lung histopathology demonstrated increased number of ectopic lymphoid aggregates comprised of T and B cells following ODE exposure in DR4 mice. ODE also induced citrullination, malondialdehyde acetaldehyde (MAA) modification, and vimentin expression that co-localized with MAA and was enhanced in DR4 mice. Serum and BALF anti-MAA antibodies were strikingly increased in ODE-treated DR4 mice. Coupling ODE exposure with Type II collagen immunization (CIA) resulted in similarly augmented pro-inflammatory lung profiles in DR4 mice (relative to WT mice) that was accompanied by a profound increase in infiltrating lung CD4+ and CD8+ T cells as well as CD19+CD11b+ autoimmune B cells. Neither modeling strategy induced significant arthritis. These findings support a model in which environmental insults trigger enhanced post-translational protein modification and lung inflammation sharing immunopathological features with RA-associated lung disease in the selected immunogenetic background of HLA-DR4 mice.
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Artritis Reumatoide , Enfermedades Pulmonares , Neumoconiosis , Neumonía , Animales , Autoantígenos , Linfocitos T CD8-positivos/metabolismo , Polvo , Antígeno HLA-DR4/metabolismo , Pulmón/metabolismo , Enfermedades Pulmonares/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neumoconiosis/metabolismo , Neumonía/metabolismoRESUMEN
Cannabis is the most widely used recreational drug in the world. Cannabis sativa and Cannabis indica have been selectively bred to develop their psychoactive properties. The increasing use in many countries has been accelerated by the COVID-19 pandemic. Cannabis can provoke both type 1 and type 4 allergic reactions. Officially recognized allergens include a pathogenesis-related class 10 allergen, profilin, and a nonspecific lipid transfer protein. Other allergens may also be relevant, and recognition of allergens may vary between countries and continents. Cannabis also has the potential to provoke allergic cross-reactions to plant foods. Since cannabis is an illegal substance in many countries, research has been hampered, leading to challenges in diagnosis since no commercial extracts are available for testing. Even in countries such as Canada, where cannabis is legalized, diagnosis may rely solely on the purchase of cannabis for prick-to-prick skin tests. Management consists of avoidance, with legal issues hindering the development of other treatments such as immunotherapy. Education of healthcare professionals is similarly lacking. This review aimed to summarize the current status of cannabis allergy and proposes recommendations for the future management of this global issue.
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COVID-19 , Cannabis , Hipersensibilidad a los Alimentos , Hipersensibilidad , Alérgenos , Antígenos de Plantas , Cannabis/efectos adversos , Consenso , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/etiología , Humanos , Hipersensibilidad/diagnóstico , Inmunoglobulina E , Pandemias , Pruebas CutáneasRESUMEN
PURPOSE OF REVIEW: Adverse occupational and environmental exposures are common causes of respiratory disease and health consequences requiring medical care. Understanding how these various exposures affect patients and how to elicit an adequate history is critical for any clinician. Military personnel are often overlooked when discussing groups at risk for environmental exposure-associated airway disease. There are close to 20 million active duty and veterans in the USA, and nearly all clinicians will at some point care for a patient that has served in the military. RECENT FINDINGS: Exposures related to military work include burn pits, chemicals/toxins, sandstorms, and living conditions. Burn pits and military waste are increasingly recognized as potential hazards attributed to the ongoing conflicts in the Middle East. The link between these various military exposures and acute or chronic airway diseases remains difficult. Epidemiological studies are emerging to demonstrate correlations with chronic lung disease and prolonged burn pit exposure. This review provides an overview of potential occupational and environmental exposures that may affect current and/or former military service men and women.
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Personal Militar , Exposición Profesional , Humanos , Exposición Profesional/análisis , VeteranosRESUMEN
OBJECTIVE: Identify key features of IL-33 immunobiology important in allergic and nonallergic airway inflammatory diseases and potential therapeutic strategies to reduce disease burden. DATA SOURCES: PubMed, clinicaltrials.gov. STUDY SELECTIONS: A systematic and focused literature search was conducted of PubMed from March 2021 to December 2021 using keywords to either PubMed or BioMed Explorer including IL-33/ST2, genetic polymorphisms, transcription, translation, post-translation modification, nuclear protein, allergy, asthma, and lung disease. Clinical trial information on IL-33 was extracted from clinicaltrials.gov in August 2021. RESULTS: In total, 72 publications with relevance to IL-33 immunobiology and/or clinical lung disease were identified (allergic airway inflammation/allergic asthma n = 26, non-allergic airway inflammation n = 9, COPD n = 8, lung fibrosis n = 10). IL-33 levels were higher in serum, BALF and/or lungs across inflammatory lung diseases. Eight studies described viral infections and IL-33 and 4 studies related to COVID-19. Mechanistic studies (n = 39) including transcript variants and post-translational modifications related to the immunobiology of IL-33. Single nucleotide polymorphism in IL-33 or ST2 were described in 9 studies (asthma n = 5, inflammatory bowel disease n = 1, mycosis fungoides n = 1, ankylosing spondylitis n = 1, coronary artery disease n = 1). Clinicaltrials.gov search yielded 84 studies of which 17 were related to therapeutic or biomarker relevance in lung disease. CONCLUSION: An integral role of IL-33 in the pathogenesis of allergic and nonallergic airway inflammatory disease is evident with several emerging clinical trials investigating therapeutic approaches. Current data support a critical role of IL-33 in damage signaling, repair and regeneration of lungs.
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Asma , COVID-19 , Hipersensibilidad , Humanos , Asma/tratamiento farmacológico , Interleucina-33/genética , Interleucina-33/metabolismo , Proteína 1 Similar al Receptor de Interleucina-1/metabolismo , Pulmón/patología , Inflamación/patologíaRESUMEN
BACKGROUND: Respiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation. METHODS: Sensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included lung mRNA and protein markers of allergic inflammation, histology for mucus cell metaplasia and lung immune cell influx by cytospin and flow cytometry. RESULTS: While thymic stromal lymphopoietin (TSLP) and IL-33 were detected 6 h after RSV infection in the OVA-RSV mice, IL-23 protein was uniquely upregulated in RSV-infected mice alone. OVA-RSV animals varied from RSV- or OVA-treated mice as they had increased lung eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) detectable as early as 6 h after RSV infection. Neutralized IL-33 significantly reduced ILC2 and eosinophils, and the prototypical allergic proteins, IL-5, IL-13, CCL17 and CCL22 in OVA-RSV mice. Numbers of neutrophils and ILC3 were also reduced with anti-IL-33 treatment in both RSV and OVA-RSV treated animals as well. CONCLUSIONS: Taken together, our findings indicate a broad reduction in allergic-proinflammatory events mediated by IL-33 neutralization in RSV-induced asthma exacerbation.
Asunto(s)
Asma/metabolismo , Asma/virología , Interleucina-33/metabolismo , Infecciones por Virus Sincitial Respiratorio/metabolismo , Virus Sincitiales Respiratorios , Animales , Asma/inducido químicamente , Asma/inmunología , Femenino , Interleucina-33/inmunología , Linfocitos/inmunología , Linfocitos/metabolismo , Linfocitos/virología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/toxicidad , Infecciones por Virus Sincitial Respiratorio/inmunologíaRESUMEN
Exposure to agricultural bioaerosols can lead to chronic inflammatory lung diseases. Amphiregulin (AREG) can promote the lung repair process but can also lead to fibrotic remodeling. The objective of this study was to determine the role of AREG in altering recovery from environmental dust exposure in a murine in vivo model and in vitro using cultured human and murine lung fibroblasts. C57BL/6 mice were intranasally exposed to swine confinement facility dust extract (DE) or saline daily for 1 wk or allowed to recover for 3-7 days while being treated with an AREG-neutralizing antibody or recombinant AREG. Treatment with the anti-AREG antibody prevented resolution of DE exposure-induced airway influx of total cells, neutrophils, and macrophages and increased levels of TNF-α, IL-6, and CXCL1. Neutrophils and activated macrophages (CD11c+CD11bhi) persisted after recovery in lung tissues of anti-AREG-treated mice. In murine and human lung fibroblasts, DE induced the release of AREG and inflammatory cytokines. Fibroblast recellularization of primary human lung mesenchymal matrix scaffolds and wound closure was inhibited by DE and enhanced with recombinant AREG alone. AREG treatment rescued the DE-induced inhibitory fibroblast effects. AREG intranasal treatment for 3 days during recovery phase reduced repetitive DE-induced airway inflammatory cell influx and cytokine release. Collectively, these studies demonstrate that inhibition of AREG reduced, whereas AREG supplementation promoted, the airway inflammatory recovery response following environmental bioaerosol exposure, and AREG enhanced fibroblast function, suggesting that AREG could be targeted in agricultural workers repetitively exposed to organic dust environments to potentially prevent and/or reduce disease.
Asunto(s)
Anfirregulina/farmacología , Polvo/prevención & control , Exposición a Riesgos Ambientales/efectos adversos , Fibroblastos/efectos de los fármacos , Exposición por Inhalación/efectos adversos , Pulmón/efectos de los fármacos , Agricultura/métodos , Animales , Células Cultivadas , Quimiocina CXCL1/metabolismo , Citocinas/metabolismo , Femenino , Fibroblastos/metabolismo , Humanos , Interleucina-6/metabolismo , Pulmón/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Environmental organic dust exposures enriched in Toll-like receptor (TLR) agonists can reduce allergic asthma development but are associated with occupational asthma and chronic bronchitis. The TLR adaptor protein myeloid differentiation factor88 (MyD88) is fundamental in regulating acute inflammatory responses to organic dust extract (ODE), yet its role in repetitive exposures is unknown and could inform future strategies. METHODS: Wild-type (WT) and MyD88 knockout (KO) mice were exposed intranasally to ODE or saline daily for 3 weeks (repetitive exposure). Repetitively exposed animals were also subsequently rested with no treatments for 4 weeks followed by single rechallenge with saline/ODE. RESULTS: Repetitive ODE exposure induced neutrophil influx and release of pro-inflammatory cytokines and chemokines were profoundly reduced in MyD88 KO mice. In comparison, ODE-induced cellular aggregates, B cells, mast cell infiltrates and serum IgE levels remained elevated in KO mice and mucous cell metaplasia was increased. Expression of ODE-induced tight junction protein(s) was also MyD88-dependent. Following recovery and then rechallenge with ODE, inflammatory mediators, but not neutrophil influx, was reduced in WT mice pretreated with ODE coincident with increased expression of IL-33 and IL-10, suggesting an adaptation response. Repetitively exposed MyD88 KO mice lacked inflammatory responsiveness upon ODE rechallenge. CONCLUSIONS: MyD88 is essential in mediating the classic airway inflammatory response to repetitive ODE, but targeting MyD88 does not reduce mucous cell metaplasia, lymphocyte influx, or IgE responsiveness. TLR-enriched dust exposures induce a prolonged adaptation response that is largely MyD88-independent. These findings demonstrate the complex role of MyD88-dependent signaling during acute vs. chronic organic dust exposures.