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1.
Am J Respir Crit Care Med ; 209(1): 48-58, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37934672

RESUMO

Rationale: Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component. Objectives: To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and patients with COPD with varying degrees of emphysema. Methods: Lung sections from 40 patients with COPD and ever-smokers were used for LF proteomic and transcriptomic spatial profiling. Formalin- and O.C.T.-fixed lung samples obtained from biopsies or lung explants were assessed for LF presence. Emphysema measurements were obtained from clinical chest computed tomographic scans. High-confidence transcriptional target intersection analyses were conducted to resolve emphysema-induced transcriptional networks. Measurements and Main Results: Overall, 115 LFs from ever-smokers and Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-2 and GOLD 3-4 patients were analyzed. No LFs were found in never-smokers. Differential gene expression analysis revealed significantly increased expression of LF assembly and B cell marker genes in subjects with severe emphysema. High-confidence transcriptional analysis revealed activation of an abnormal B cell activity signature in LFs (q-value = 2.56E-111). LFs from patients with GOLD 1-2 COPD with emphysema showed significantly increased expression of genes associated with antigen presentation, inflammation, and B cell activation and proliferation. LFs from patients with GOLD 1-2 COPD without emphysema showed an antiinflammatory profile. The extent of centrilobular emphysema was significantly associated with genes involved in B cell maturation and antibody production. Protein-RNA network analysis showed that LFs in emphysema have a unique signature skewed toward chronic B cell activation. Conclusions: An off-targeted B cell activation within LFs is associated with autoimmune-mediated emphysema pathogenesis.


Assuntos
Enfisema , Linfadenopatia , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/genética , Proteômica , Perfilação da Expressão Gênica
2.
Artigo em Inglês | MEDLINE | ID: mdl-38064378

RESUMO

RATIONALE: Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component. OBJECTIVE: To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and COPD patients with varying degrees of emphysema. METHODS: Lung sections from 40 COPD patients and ever-smokers were used for LF proteomic and transcriptomic spatial profiling. Formalin and OCT-fixed lung samples obtained from biopsies or lung explants, were assessed for LF presence. Emphysema measurements were obtained from clinical chest CT scans. High confidence transcriptional (HCT) target intersection analyses were conducted to resolve emphysema-induced transcriptional networks. MEASUREMENTS AND MAIN RESULTS: Overall, 115 LFs from ever-smokers and GOLD 1-2 and GOLD 3-4 patients were analyzed. No LFs were found in never-smokers. Differential gene expression analysis revealed significantly increased expression of LF assembly and B cell markers genes in subjects with severe emphysema. HCT analysis revealed activation of abnormal B cell activity signature in LFs (q-value: 2.56E-111). LFs from GOLD 1-2 COPD patients with emphysema showed significantly increased expression of genes associated with antigen presentation, inflammation, and B cell activation and proliferation. LFs from GOLD 1-2 COPD patients without emphysema showed an anti-inflammatory profile. The extent of centrilobular emphysema was significantly associated with genes involved in B cell maturation and antibody production. Protein-RNA network analysis showed that LFs in emphysema have a unique signature skewed towards chronic B cell activation. CONCLUSIONS: An off-targeted B cell activation within LFs is associated with autoimmune-mediated emphysema pathogenesis.

3.
Eur Respir J ; 59(3)2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34385268

RESUMO

BACKGROUND: Obese children with asthma are more vulnerable to air pollution, especially fine particulate matter (PM2.5), but reasons are poorly understood. We hypothesised that differences in breathing patterns (tidal volume, respiratory rate and minute ventilation) due to elevated body mass index (BMI) may contribute to this finding. OBJECTIVE: To investigate the association of BMI with breathing patterns and deposition of inhaled PM2.5. METHODS: Baseline data from a prospective study of children with asthma were analysed (n=174). Tidal breathing was measured by a pitot-tube flowmeter, from which tidal volume, respiratory rate and minute ventilation were obtained. The association of BMI z-score with breathing patterns was estimated in a multivariable model adjusted for age, height, race, sex and asthma severity. A particle dosimetry model simulated PM2.5 lung deposition based on BMI-associated changes in breathing patterns. RESULTS: Higher BMI was associated with higher tidal volume (adjusted mean difference (aMD) between obese and normal-range BMI of 25 mL, 95% CI 5-45 mL) and minute ventilation (aMD 453 mL·min-1, 95% CI 123-784 mL·min-1). Higher tidal volumes caused higher fractional deposition of PM2.5 in the lung, driven by greater alveolar deposition. This translated into obese participants having greater per-breath retention of inhaled PM2.5 (aMD in alveolar deposition fraction of 3.4%, 95% CI 1.3-5.5%), leading to worse PM2.5 deposition rates. CONCLUSIONS: Obese children with asthma breathe at higher tidal volumes that may increase the efficiency of PM2.5 deposition in the lung. This finding may partially explain why obese children with asthma exhibit greater sensitivity to air pollution.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Obesidade Infantil , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Asma/complicações , Criança , Exposição Ambiental , Humanos , Pulmão , Material Particulado/análise , Obesidade Infantil/complicações , Estudos Prospectivos , Volume de Ventilação Pulmonar
4.
Respir Res ; 23(1): 153, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35689238

RESUMO

BACKGROUND: Service member exposure to explosive blast overpressure waves is common with considerable attention to traumatic brain injury (TBI) and neuropsychological sequalae. Less is known about the impacts on the respiratory system, particularly long-term effects, despite vulnerability to overpressure. Using a national registry, we previously observed an independent relationship between self-reported blast exposure and respiratory symptoms; however, the impact on objective measures of pulmonary function is poorly understood. METHODS: 307 Veterans referred to our national specialty center for post-deployment health concerns underwent a comprehensive multi-day evaluation that included complete pulmonary function testing (PFT), occupational and environmental medicine history, neuropsychological or psychological evaluation. We developed an a priori chart abstraction process and template to classify Veterans into blast exposure groups: (1) none, (2) single-mild, or (3) multiple-mild. This template focused primarily on clinician documented notes of blast related TBI that were used as proxy for blast overpressure injury to thorax. PFT variables characterizing flow (FEV1%; %∆FEV1), volume (TLC%), diffusion (DLCO%) and respiratory mechanics (forced oscillometry) were selected for analysis. RESULTS: Veterans (40.5 ± 9.7 years; 16.3% female) were referred 8.6 ± 3.6 years after their last deployment and presented with considerable comorbid conditions and health problems (e.g., 62% post-traumatic stress, 55% dyspnea). After chart abstraction, Veterans were assigned to none (n = 208), single mild (n = 52) and multiple mild (n = 47) blast exposure groups. Among the blast exposed, clinicians documented 73.7% were < 50 m from the blast and 40.4% were physically moved by blast. PFT outcome measures were similar across all groups (p value range: 0.10-0.99). CONCLUSIONS: In this referred sample of deployed Veterans, PFT measures of flow, volume, diffusion, and respiratory mechanics were not associated with clinician documented blast exposure per the retrospective chart abstraction methodology applied. Yet, these clinical findings suggest future research should determine and assess distinction between Veteran recollections of perceived blast experiences versus overpressure wave exposure to the respiratory system.


Assuntos
Traumatismos por Explosões , Transtornos de Estresse Pós-Traumáticos , Veteranos , Traumatismos por Explosões/complicações , Traumatismos por Explosões/diagnóstico , Traumatismos por Explosões/epidemiologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Estudos Retrospectivos , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Veteranos/psicologia
5.
Am J Respir Crit Care Med ; 204(6): 651-666, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34033525

RESUMO

Rationale: Cigarette smoke (CS) inhalation triggers oxidative stress and inflammation, leading to accelerated lung aging, apoptosis, and emphysema, as well as systemic pathologies. Metformin is beneficial for protecting against aging-related diseases. Objectives: We sought to investigate whether metformin may ameliorate CS-induced pathologies of emphysematous chronic obstructive pulmonary disease (COPD). Methods: Mice were exposed chronically to CS and fed metformin-enriched chow for the second half of exposure. Lung, kidney, and muscle pathologies, lung proteostasis, endoplasmic reticulum (ER) stress, mitochondrial function, and mediators of metformin effects in vivo and/or in vitro were studied. We evaluated the association of metformin use with indices of emphysema progression over 5 years of follow-up among the COPDGene (Genetic Epidemiology of COPD) study participants. The association of metformin use with the percentage of emphysema and adjusted lung density was estimated by using a linear mixed model. Measurements and Main Results: Metformin protected against CS-induced pulmonary inflammation and airspace enlargement; small airway remodeling, glomerular shrinkage, oxidative stress, apoptosis, telomere damage, aging, dysmetabolism in vivo and in vitro; and ER stress. The AMPK (AMP-activated protein kinase) pathway was central to metformin's protective action. Within COPDGene, participants receiving metformin compared with those not receiving it had a slower progression of emphysema (-0.92%; 95% confidence interval [CI], -1.7% to -0.14%; P = 0.02) and a slower adjusted lung density decrease (2.2 g/L; 95% CI, 0.43 to 4.0 g/L; P = 0.01). Conclusions: Metformin protected against CS-induced lung, renal, and muscle injury; mitochondrial dysfunction; and unfolded protein responses and ER stress in mice. In humans, metformin use was associated with lesser emphysema progression over time. Our results provide a rationale for clinical trials testing the efficacy of metformin in limiting emphysema progression and its systemic consequences.


Assuntos
Metformina/uso terapêutico , Substâncias Protetoras/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Enfisema Pulmonar/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores/metabolismo , Fumar Cigarros/efeitos adversos , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/metabolismo , Resultado do Tratamento
6.
Respir Res ; 22(1): 70, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637087

RESUMO

BACKGROUND: Metformin is associated with improved respiratory outcomes in asthma; however, metformin in COPD and asthma-COPD overlap (ACO) remains unexplored. OBJECTIVE: To determine the association between metformin use and respiratory outcomes in COPD and ACO. STUDY DESIGN AND METHODS: Participants with COPD (FEV1/FVC < 0.70) in the Genetic Epidemiology of COPD study (COPDGene®) were categorized as ACO (n = 510), defined as concurrent physician-diagnosed asthma before age 40 years, or COPD alone (n = 3459). We estimated the association of baseline metformin use with (1) rate of total and severe respiratory exacerbations during follow-up, (2) cross-sectional St. George's Respiratory Questionnaire (SGRQ) score, six-minute walk distance (6MWD), and post-bronchodilator FEV1 percent predicted (FEV1pp), and (3) 5-year change in SGRQ, 6MWD, and FEV1pp. We also examined change in SGRQ, 6MWD and FEV1pp among participants who initiated metformin during follow-up (n = 108) compared to persistent metformin non-users (n = 2080). Analyses were adjusted for sociodemographic factors, medications, and comorbidities. RESULTS: Among participants with ACO, metformin use was associated with lower rate of total (adjusted incidence rate ratio [aIRR] 0.3; 95% confidence interval [95%CI] 0.11, 0.77) and severe exacerbations (aIRR 0.29; 95%CI 0.10, 0.89). Among participants with COPD alone, there was no association between metformin use with total (aIRR 0.98; 95%CI 0.62, 1.5) or severe exacerbations (aIRR 1.3; 95% CI 0.68, 2.4) (p-interaction < 0.05). Metformin use was associated with lower baseline SGRQ score (adjusted mean difference [aMD] - 2.7; 95%CI - 5.3, - 0.2) overall. Metformin initiation was associated with improved SGRQ score (aMD -10.0; 95% CI - 18.7, - 1.2) among participants with ACO but not COPD alone (p-interaction < 0.05). There was no association between metformin use and 6MWD or FEV1pp in any comparison. CONCLUSIONS: Metformin use was associated with fewer respiratory exacerbations and improved quality of life among individuals with ACO but not COPD alone. Results suggest a potential role for metformin in ACO which requires further prospective study. TRIAL REGISTRY: NCT00608764.


Assuntos
Asma/tratamento farmacológico , Asma/epidemiologia , Volume Expiratório Forçado/efeitos dos fármacos , Metformina/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Adulto , Idoso , Asma/fisiopatologia , Estudos de Coortes , Comorbidade , Estudos Transversais , Feminino , Seguimentos , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Metformina/farmacologia , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória/métodos , Estudos Retrospectivos , Resultado do Tratamento
7.
Curr Opin Pulm Med ; 27(1): 29-36, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002990

RESUMO

PURPOSE OF REVIEW: Disorders of glucose metabolism, including insulin resistance, prediabetes, and diabetes, have been identified as risk factors for worsened asthma. This review summarizes emerging evidence for their role as modifiable risk factors in asthma, including the potential benefit of diabetes medications on asthma outcomes. RECENT FINDINGS: Experimental studies show that hyperinsulinemia associated with insulin resistance is associated with airway smooth muscle proliferation and promotes contractility. Epidemiologic studies have identified a higher prevalence of glycemic dysfunction among those with severe and uncontrolled asthma, and longitudinal studies have associated prediabetes and diabetes with higher risk of asthma exacerbations. The potential benefits of thiazolidinediones (TZDs), glucagon-like peptide-1 agonists, and metformin being investigated in asthma, but thus far interventional studies of TZDs have reported null results. On the contrary, observational studies have inconsistently controlled for relevant confounders which leaves conclusions vulnerable to misattribution of relationships due to corelated metabolic disorders, including dyslipidemia. SUMMARY: Developing evidence suggests that disorders of glucose metabolism may be associated with worsening asthma. However, these conditions arise within a network of obesity-related metabolic diseases that may themselves worsen asthma. Few interventional trials have not identified a benefit, but data have been limited. Additional research is needed to define the potential independent impact of disorders of glucose metabolism in asthma.


Assuntos
Asma/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Resistência à Insulina/fisiologia , Obesidade/fisiopatologia , Asma/complicações , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Humanos , Obesidade/complicações , Fatores de Risco
9.
Am J Epidemiol ; 188(11): 1977-1983, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504124

RESUMO

An obesity paradox in chronic obstructive pulmonary disease (COPD), whereby overweight/obese individuals have improved survival, has been well-described. These studies have generally included smokers. It is unknown whether the paradox exists in individuals with COPD arising from factors other than smoking. Nonsmoking COPD is understudied yet represents some 25%-45% of the disease worldwide. To determine whether the obesity paradox differs between ever- and never-smokers with COPD, 1,723 adult participants with this condition were examined from 2 iterations of the National Health and Nutrition Examination Survey (1988-1994, 2007-2010), with mortality outcomes followed through December 2011. Using Cox proportional hazards models, adjusted for sociodemographic factors, lung function, and survey cycle, ever/never-smoking was found to modify the association between body mass index and hazard of death. Compared with normal-weight participants, overweight/obese participants had lower hazard of death among ever-smokers (for overweight, adjusted hazard ratio (aHR) = 0.56, 95% confidence interval (CI): 0.43, 0.74; for obesity, aHR = 0.66, 95% CI: 0.48, 0.92), but never-smokers did not (overweight, aHR = 1.41, 95% CI: 0.66, 3.03; obesity, aHR = 1.29, 95% CI: 0.48, 3.48). An obesity paradox appeared to be absent among never-smokers with COPD. This, to our knowledge, novel finding might be explained by pathophysiological differences between smoking-related and nonsmoking COPD or by smoking-associated methodological biases.


Assuntos
Obesidade/complicações , Doença Pulmonar Obstrutiva Crônica/mortalidade , Fumar/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Doença Pulmonar Obstrutiva Crônica/complicações , Estados Unidos/epidemiologia
10.
J Public Health Manag Pract ; 25(2): E7-E16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29883368

RESUMO

CONTEXT: Secondhand smoke exposure (SHSe) affects up to half of all children in the United States. Many studies have identified factors associated with in-home SHSe, but few have contrasted these factors between households with and without residential smokers. In the latter case, exposure occurs from only external sources that enter the home, such as visitors or environmental incursion. OBJECTIVE: Among children with SHSe at home, to examine demographic and psychosocial differences between households with and without residential smokers. DESIGN: Baseline analysis of an observational cohort. SETTING: Baltimore City, Maryland. PARTICIPANTS: A total of 157 children with asthma, aged 5 to 12 years. MEASURES: At-home airborne nicotine, caregiver-reported depression, asthma-related quality of life, functional social support, and demographics. Univariable comparisons were performed between SHS-exposed households with and without residential smokers. Multivariable logistic regression models were fit to examine associations between measured factors and absence of residential smokers. RESULTS: Children (78.3%) had at-home SHSe. Of these, 40.7% lived in households without residential smokers. Compared with households with residential smokers, these caregivers endorsed stronger beliefs in SHS harms and also worse functional social support and asthma-related stress, despite no differences in asthma morbidity. In adjusted models, SHS-exposed children with caregivers in the lowest tertile of functional social support (adjusted odds ratio, 3.50; 95% confidence interval, 1.12-10.99), asthma-related quality of life (2.90; 1.06-7.95), and those living alone (5.28; 1.26-22.15) had at least twice higher odds of having exclusively external SHSe than the highest tertile (P trends < .05). CONCLUSIONS: In-home SHS exposure remains alarmingly high in urban environments. However, a substantial proportion of this exposure appears to be occurring only from external sources that enter the home. Caregivers in these homes had higher desire but lower agency to avoid SHSe, driven by lack of functional support and physical isolation. Public policies targeting these factors may help remediate exposure in this especially vulnerable population.


Assuntos
Asma/fisiopatologia , Exposição Ambiental/efeitos adversos , Características da Família , Fumantes/estatística & dados numéricos , Poluição por Fumaça de Tabaco/efeitos adversos , Asma/epidemiologia , Baltimore/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Masculino , Poluição por Fumaça de Tabaco/estatística & dados numéricos , População Urbana/estatística & dados numéricos
13.
Chest ; 165(5): 1049-1057, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38365175

RESUMO

TOPIC IMPORTANCE: Patient-reported outcomes (PROs) are information provided by patients on their condition, function, well-being, or experience. Instruments to quantify PROs, called patient-reported outcome measures (PROMs), allow standardized assessment of a unique dimension of health that cannot be measured physically. Herein, we discuss how to appraise PROMs critically and provide an update on their use in asthma clinical practice and research. REVIEW FINDINGS: Asthma-specific PROMs have been developed to measure a wide array of disease characteristics, including symptoms, medication use, exacerbations, and impairments to emotional and physical function. Some PROMs also include spirometry or expand questions to overlap with rhinitis symptoms. Use of PROMs to understand asthma control is included in management guidelines, yet real-world evidence of their effectiveness in improving asthma care remains limited. These instruments may be less accurate in characterizing patients with poorly controlled asthma and have modest correlation with exacerbation risk. Two new PROMs are highlighted, the Asthma Impairment and Risk Questionnaire as an instrument to assess asthma control that incorporates domains related to exacerbation risk and impairment, and the CompEx as a composite of daily diary reporting combined with exacerbation events as an early efficacy signal for interventional trials. SUMMARY: PROMs are fundamental to asthma assessment. Novel instruments may improve the detection of patients at risk for poor outcomes and shorten the drug discovery pipeline. However, urgent research is needed to understand their practical utility in clinical settings.


Assuntos
Asma , Medidas de Resultados Relatados pelo Paciente , Humanos , Asma/terapia , Asma/fisiopatologia , Qualidade de Vida
14.
J Allergy Clin Immunol Pract ; 11(12): 3700-3705.e2, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37716524

RESUMO

BACKGROUND: Metabolic conditions may worsen asthma. There is a need to define a composite biomarker of metabolic dysfunction that has relevance to asthma outcomes. OBJECTIVE: To determine the association of the triglyceride-glucose index (TyG), a biomarker of metabolic syndrome and insulin resistance, with risk of severe asthma exacerbation. METHODS: A 5-year retrospective cohort of patients with asthma receiving health care from the US Veterans Health Administration from January 1, 2015, to December 31, 2019, was constructed. Fasting TyG values were extracted. Patients were followed for a severe asthma exacerbation, defined as an asthma-related corticosteroid prescription fill or an emergency encounter or hospitalization for asthma. Adjusted models estimated the relative hazard of exacerbation associated with elevated TyG, accounting for known exacerbation risk factors. RESULTS: A total of 108,219 patients fulfilled study criteria. Over 286,343 person-years of follow-up, 21,467 exacerbations were identified, corresponding to a crude rate of 7.5 exacerbations/100 person-years. In exploratory analysis, we found a threshold effect at a TyG of 8.3, which was defined as elevated. In a fully adjusted model, patients with an elevated TyG had a 6% (95% CI, 3%-10%) higher hazard for severe asthma exacerbation, independent of eosinophil count, smoking, obesity, and asthma treatment intensity. CONCLUSIONS: Elevated TyG is a risk factor for severe asthma exacerbation independent of conventional predictors. Elevated TyG may identify patients who warrant more intensive asthma treatment and who are candidates for future clinical trials of metabolic intervention for purposes of improving asthma morbidity.


Assuntos
Asma , Glucose , Humanos , Glucose/uso terapêutico , Estudos Retrospectivos , Triglicerídeos/uso terapêutico , Asma/tratamento farmacológico , Fatores de Risco , Biomarcadores
15.
Pediatr Pulmonol ; 58(6): 1683-1690, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36852547

RESUMO

RATIONALE: Obstructive sleep apnea is highly prevalent in children with asthma, particularly in obese children. The sleep-related breathing disorder screening questionnaire has low screening accuracy for obstructive sleep apnea in children with asthma. Our goal was to identify the questions on the sleep-related breathing disorder survey associated with obstructive sleep apnea in children with asthma. METHODS: Participants completed the survey, underwent polysomnography and their body mass index z-score was measured. Participants with survey scores above 0.33 were considered high risk for obstructive sleep apnea and those with an apnea-hypopnea index ≥ 2 events/h classified as having obstructive sleep apnea. Logistic regression was used to examine the association of each survey question and obstructive sleep apnea. Positive and negative predictive values were calculated to estimate screening accuracy. RESULTS: The prevalence of obstructive sleep apnea was 40% in our sample (n = 136). Loud snoring, morning dry mouth, and being overweight were the survey questions associated with obstructive sleep apnea. The composite survey score obtained from all 22 questions had positive and negative predictive values of 51.0% and 65.5%, while the combined model of loud snoring, morning dry mouth, and being overweight had positive and negative predictive values of 60.3% and 77.6%. On the other hand, the body mass index z-score alone had positive and negative predictive values of 76.3% and 72.2%. CONCLUSIONS: The body mass index z-score is useful for obstructive sleep apnea screening in children with asthma and should be applied routinely given its simplicity and concerns that obstructive sleep apnea may contribute to asthma morbidity.


Assuntos
Asma , Obesidade Infantil , Apneia Obstrutiva do Sono , Humanos , Criança , Ronco/epidemiologia , Sobrepeso , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Asma/complicações , Asma/diagnóstico , Asma/epidemiologia
16.
JAMA Netw Open ; 6(8): e2330856, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37615985

RESUMO

Importance: Many pulse oximeters have been shown to overestimate oxygen saturation in persons of color, and this phenomenon has potential clinical implications. The relationship between overestimation of oxygen saturation with timing of COVID-19 medication delivery and clinical outcomes remains unknown. Objective: To investigate the association between overestimation of oxygen saturation by pulse oximetry and delay in administration of COVID-19 therapy, hospital length of stay, risk of hospital readmission, and in-hospital mortality. Design, Setting, and Participants: This cohort study included patients hospitalized for COVID-19 at 186 acute care facilities in the US with at least 1 functional arterial oxygen saturation (SaO2) measurement between March 2020 and October 2021. A subset of patients were admitted after July 1, 2020, without immediate need for COVID-19 therapy based on pulse oximeter saturation (SpO2 levels of 94% or higher without supplemental oxygen). Exposures: Self-reported race and ethnicity, difference between concurrent SaO2 and pulse oximeter saturation (SpO2) within 10 minutes, and initially unrecognized need for COVID-19 therapy (first SaO2 reading below 94% despite SpO2 levels of 94% or above). Main Outcome and Measures: The association of race and ethnicity with degree of pulse oximeter measurement error (SpO2 - SaO2) and odds of unrecognized need for COVID-19 therapy were determined using linear mixed-effects models. Associations of initially unrecognized need for treatment with time to receipt of therapy (remdesivir or dexamethasone), in-hospital mortality, 30-day hospital readmission, and length of stay were evaluated using mixed-effects models. All models accounted for demographics, clinical characteristics, and hospital site. Effect modification by race and ethnicity was evaluated using interaction terms. Results: Among 24 504 patients with concurrent SpO2 and SaO2 measurements (mean [SD] age, 63.9 [15.8] years; 10 263 female [41.9%]; 3922 Black [16.0%], 7895 Hispanic [32.2%], 2554 Asian, Native American or Alaskan Native, Hawaiian or Pacific Islander, or another race or ethnicity [10.4%], and 10 133 White [41.4%]), pulse oximetry overestimated SaO2 for Black (adjusted mean difference, 0.93 [95% CI, 0.74-1.12] percentage points), Hispanic (0.49 [95% CI, 0.34-0.63] percentage points), and other (0.53 [95% CI, 0.35-0.72] percentage points) patients compared with White patients. In a subset of 8635 patients with a concurrent SpO2 - SaO2 pair without immediate need for COVID-19 therapy, Black patients were significantly more likely to have pulse oximetry values that masked an indication for COVID-19 therapy compared with White patients (adjusted odds ratio [aOR], 1.65; 95% CI, 1.33-2.03). Patients with an unrecognized need for COVID-19 therapy were 10% less likely to receive COVID-19 therapy (adjusted hazard ratio, 0.90; 95% CI, 0.83-0.97) and higher odds of readmission (aOR, 2.41; 95% CI, 1.39-4.18) regardless of race (P for interaction = .45 and P = .14, respectively). There was no association of unrecognized need for COVID-19 therapy with in-hospital mortality (aOR, 0.84; 95% CI, 0.71-1.01) or length of stay (mean difference, -1.4 days; 95% CI, -3.1 to 0.2 days). Conclusions and Relevance: In this cohort study, overestimation of oxygen saturation by pulse oximetry led to delayed delivery of COVID-19 therapy and higher probability of readmission regardless of race. Black patients were more likely to have unrecognized need for therapy with potential implications for population-level health disparities.


Assuntos
COVID-19 , Saturação de Oxigênio , Humanos , Feminino , Pessoa de Meia-Idade , Estudos de Coortes , COVID-19/terapia , Oximetria , Etnicidade
17.
Acad Pediatr ; 23(4): 814-820, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36272721

RESUMO

OBJECTIVE: To determine whether school infrastructure is associated with health and academic outcomes among elementary school children with asthma. METHODS: We conducted a retrospective cohort study of linked medical, academic, and facilities data from a large mid-Atlantic school district of the United States. All K-5 students with asthma who were enrolled under the state's Children's Health Insurance Program were included. We estimated associations of the infrastructure quality of the student's school, as assessed by an engineering firm in Summer 2011 and represented by the Facility Condition Index (FCI), with asthma health outcomes, absenteeism, and standardized test scores in math and reading in the 2 academic years thereafter. RESULTS: A total of 6558 students were identified, the majority non-Hispanic Black, across 130 schools. Most schools (97/130, 75%) were in very poor or worse condition. In cluster-adjusted models accounting for demographics, grade, school-specific area deprivation, and inhaled corticosteroid use, a one standard deviation increase in FCI, corresponding to greater infrastructure deficiency, was associated with higher rates of asthma-related hospitalizations (incidence rate ratio [IRR] 1.16; 95% confidence interval [CI] 1.03, 1.32), more absenteeism (IRR 1.05; 95% CI 1.01, 1.08), and lower scores in math (mean difference [MD] -3.3; 95% CI -5.5, -1.2) and reading (MD -3.0; 95% CI -5.1, -0.9). There were no differences in rates of asthma-related emergency visits or steroid prescriptions. CONCLUSIONS: Children with asthma attending schools with poorer infrastructure had worse health and academic outcomes. Public policy emphasizing reinvestment in school infrastructure may be a potential means of addressing asthma disparities.


Assuntos
Asma , Instituições Acadêmicas , Humanos , Criança , Estados Unidos/epidemiologia , Estudos Retrospectivos , Asma/epidemiologia , Logro , Estudantes
18.
Front Public Health ; 10: 994443, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466537

RESUMO

Burnout is an epidemic, with deleterious effects on individuals, patient care, and healthcare systems. The Coronavirus Disease 2019 (COVID-19) pandemic may be exacerbating this problem. We aimed to explore socio-cultural and gender norms that modulate burnout development in physicians during the pandemic and analyze any disparities associated with gender, marital and immigration status and work-life balance. We conducted an online cross-sectional survey of physicians (August-November, 2021): The Maslach Burnout Inventory-Human Services Survey (MBI-HSS) was used to measure burnout, combined with a validated survey assessing work-life balance. Demographic data was obtained for each participant. MBI-HSS subscales were measured, along with work and home related changes due to COVID-19. The association between life changes due to COVID-19 and odds of burnout was estimated by logistic regression. Complementary analysis was performed to determine factors most associated with burnout. 352 respondents were analyzed. There was a high prevalence of burnout. Over half of individuals reported a high degree of emotional exhaustion (EE) (56%). 83% of individuals reported at least one life factor changed due to COVID-19. Home-related life changes due to COVID-19 were associated with 143% higher odds of emotional burnout [adjusted odds ratio (aOR) 2.43; 95% confidence interval (CI) 1.49, 3.98] after covariate adjusted analysis. High EE was most evident when there were three or more life changes, suggesting a cumulative effect. First-generation immigrants, older physicians, and trainees were identified as protective factors. Although female gender was identified as a factor related to EE through forward selection, this was not statistically significant (aOR 1.34; 95% CI 0.80, 2.24). Burnout remains pervasive among physicians. We highlight new risk factors for EE (home-life changes due to COVID-19), and protective factors (first-generation immigrants) not previously explored. Understanding burnout and its disparities allows for improved mitigation strategies, decreasing its deleterious effects.


Assuntos
COVID-19 , Emigrantes e Imigrantes , Humanos , Feminino , Pandemias , COVID-19/epidemiologia , Estudos Transversais , Esgotamento Psicológico
19.
JAMA Intern Med ; 182(7): 730-738, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35639368

RESUMO

Importance: Pulse oximetry guides triage and therapy decisions for COVID-19. Whether reported racial inaccuracies in oxygen saturation measured by pulse oximetry are present in patients with COVID-19 and associated with treatment decisions is unknown. Objective: To determine whether there is differential inaccuracy of pulse oximetry by race or ethnicity among patients with COVID-19 and estimate the association of such inaccuracies with time to recognition of eligibility for oxygen threshold-specific COVID-19 therapies. Design, Setting, and Participants: This retrospective cohort study of clinical data from 5 referral centers and community hospitals in the Johns Hopkins Health System included patients with COVID-19 who self-identified as Asian, Black, Hispanic, or White. Exposures: Concurrent measurements (within 10 minutes) of oxygen saturation levels in arterial blood (SaO2) and by pulse oximetry (SpO2). Main Outcomes and Measures: For patients with concurrent SpO2 and SaO2 measurements, the proportion with occult hypoxemia (SaO2<88% with concurrent SpO2 of 92%-96%) was compared by race and ethnicity, and a covariate-adjusted linear mixed-effects model was produced to estimate the association of race and ethnicity with SpO2 and SaO2 difference. This model was applied to identify a separate sample of patients with predicted SaO2 levels of 94% or less before an SpO2 level of 94% or less or oxygen treatment initiation. Cox proportional hazards models were used to estimate differences by race and ethnicity in time to recognition of eligibility for guideline-recommended COVID-19 therapies, defined as an SpO2 level of 94% or less or oxygen treatment initiation. The median delay among individuals who ultimately had recognition of eligibility was then compared. Results: Of 7126 patients with COVID-19, 1216 patients (63 Asian [5.2%], 478 Black [39.3%], 215 Hispanic [17.7%], and 460 White [37.8%] individuals; 507 women [41.7%]) had 32 282 concurrently measured SpO2 and SaO2. Occult hypoxemia occurred in 19 Asian (30.2%), 136 Black (28.5%), and 64 non-Black Hispanic (29.8%) patients compared with 79 White patients (17.2%). Compared with White patients, SpO2 overestimated SaO2 by an average of 1.7% among Asian (95% CI, 0.5%-3.0%), 1.2% among Black (95% CI, 0.6%-1.9%), and 1.1% among non-Black Hispanic patients (95% CI, 0.3%-1.9%). Separately, among 1903 patients with predicted SaO2 levels of 94% or less before an SpO2 level of 94% or less or oxygen treatment initiation, compared with White patients, Black patients had a 29% lower hazard (hazard ratio, 0.71; 95% CI, 0.63-0.80), and non-Black Hispanic patients had a 23% lower hazard (hazard ratio, 0.77; 95% CI, 0.66-0.89) of treatment eligibility recognition. A total of 451 patients (23.7%) never had their treatment eligibility recognized, most of whom (247 [54.8%]) were Black. Among the remaining 1452 (76.3%) who had eventual recognition of treatment eligibility, Black patients had a median delay of 1.0 hour (95% CI, 0.23-1.9 hours; P = .01) longer than White patients. There was no significant median difference in delay between individuals of other racial and ethnic minority groups and White patients. Conclusions and Relevance: The results of this cohort study suggest that racial and ethnic biases in pulse oximetry accuracy were associated with greater occult hypoxemia in Asian, Black, and non-Black Hispanic patients with COVID-19, which was associated with significantly delayed or unrecognized eligibility for COVID-19 therapies among Black and Hispanic patients. This disparity may contribute to worse outcomes among Black and Hispanic patients with COVID-19.


Assuntos
COVID-19 , Etnicidade , COVID-19/terapia , Estudos de Coortes , Feminino , Humanos , Hipóxia , Grupos Minoritários , Oximetria/métodos , Oxigênio , Estudos Retrospectivos
20.
Front Physiol ; 13: 883275, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574481

RESUMO

Obese asthma is a unique phenotype of asthma characterized by non-allergic airway hyperresponsiveness (AHR) and inflammation which responds poorly to standard asthma therapy. Metformin is an oral hypoglycemic drug with insulin-sensitizing and anti-inflammatory properties. The objective of the current study was to test the effect of metformin on AHR in a mouse model of diet-induced obesity (DIO). We fed 12-week-old C57BL/6J DIO mice with a high fat diet for 8 weeks and treated them with either placebo (control, n = 10) or metformin (n = 10) added in drinking water (300 mg/kg/day) during the last 2 weeks of the experiment. We assessed AHR, metabolic profiles, and inflammatory markers after treatments. Metformin did not affect body weight or fasting blood glucose, but significantly reduced serum insulin (p = 0.0117). Metformin reduced AHR at 30 mg/ml of methacholine challenge (p = 0.0052) without affecting baseline airway resistance. Metformin did not affect circulating white blood cell counts or lung cytokine mRNA expression, but modestly decreased circulating platelet count. We conclude that metformin alleviated AHR in DIO mice. This finding suggests metformin has the potential to become an adjuvant pharmacological therapy in obese asthma.

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