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1.
Sleep ; 45(8)2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35665826

RESUMO

STUDY OBJECTIVES: Sleep is an important dimension in the care of chronic obstructive pulmonary disease (COPD), but its relevance to exacerbations is unclear. We wanted to assess whether sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI) is associated with an increased risk of COPD exacerbations and does this differ by socio-environmental exposures. METHODS: We included 1647 current and former smokers with spirometrically confirmed COPD from the SPIROMICS cohort. We assessed incidence rate ratios for exacerbation using zero-inflated negative binomial regression adjusting for demographics, medical comorbidities, and multiple metrics of disease severity, including respiratory medications, airflow obstruction, and symptom burden. Our final model adjusted for socio-environmental exposures using the Area Deprivation Index, a composite measure of contemporary neighborhood quality, and Adversity-Opportunity Index, a composite measure of individual-level historic and current socioeconomic indicators. We used a pre-determined threshold of 20% missingness to undertake multiple imputation by chained equations. As sensitivity analyses, we repeated models in those with complete data and after controlling for prior exacerbations. As an exploratory analysis, we considered an interaction between socio-environmental condition and sleep quality. RESULTS: After adjustment for all co-variates, increasing PSQI scores (range 0-21) were associated with a 5% increased risk for exacerbation per point (p = .001) in the imputed dataset. Sensitivity analyses using complete cases and after controlling for prior exacerbation history were similar. Exploratory analysis suggested less effect among those who lived in poor-quality neighborhoods (p-for-interaction = .035). CONCLUSIONS: Poor sleep quality may contribute to future exacerbations among patients with COPD. This represents one target for improving disease control. CLINICAL TRIAL REGISTRATION: Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). ClinicalTrials.gov Identifier# NCT01969344. Registry URL: https://clinicaltrials.gov/ct2/show/.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Transtornos do Sono-Vigília , Progressão da Doença , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Índice de Gravidade de Doença , Qualidade do Sono , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia
2.
Chronic Obstr Pulm Dis ; 9(3): 366-376, 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35731929

RESUMO

Rational: Poor indoor air quality has been associated with worse chronic obstructive pulmonary disease (COPD) morbidity. In-home portable air cleaners reduce indoor pollutants and could improve respiratory health. Factors associated with air cleaner adherence among adults with COPD remains unknown. Methods: In a 6-month trial of former smokers with COPD, participants (n=116) received active or sham portable air cleaners. Air cleaner adherence was measured by electronic monitors. Potential baseline predictors of adherence included individual factors (demographics, socioeconomic status, smoking history, psychological well-being), COPD disease severity, and housing characteristics. Time and season were also considered. Stepwise logistic regression and longitudinal fixed effect analysis were performed to assess independent predictors of adherence. Results: A total of 109 participants had an objective measure of adherence, and 76.1% used at least 1 air cleaner 80% of the time (defined a priori as adherent). Higher annual household income ≥$35,000 (odds ratio [OR]=4.4, 95% confidence interval [CI], 1.1-18.0) and use of heat pump/electricity (versus gas) for heating (OR=6.1, 95%CI, 1.7-22.4) were associated with higher odds of adherence. Further, poor quality of life (St George's Respiratory Questionnaire, per 10-point increase) and prior year exacerbations were associated with lower odds of adherence (OR=0.65, 95%CI, 0.4-1.0) and (OR=0.26, 95%CI, 0.1-0.9), respectively. Adherence was highest during the first month and lower during winter compared to other seasons. Conclusion: These findings suggest that cold weather season, use of gas for home heating, and lower annual income negatively impact adherence. Poor quality of life and worse disease control may also decrease adherence. Addressing factors associated with air cleaner adherence should be considered when designing future environmental studies.

4.
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.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35549640

RESUMO

RATIONALE: Chronic obstructive pulmonary disease (COPD) is defined by fixed spirometric ratio FEV1/FVC < 0.70 following inhaled bronchodilators. However, the implications of variable obstruction (VO), in which the pre-bronchodilator FEV1/FVC ratio is <0.70 but increases to ≥0.70 following inhaled bronchodilators, have not been determined. OBJECTIVES: We explored differences in physiology, exacerbations, and health status in participants with VO compared to reference participants without obstruction. METHODS: Data from the Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) cohort was obtained. Participants with variable obstruction (VO) were compared to reference participants without obstruction. MEASUREMENTS: We assessed differences in baseline radiographic emphysema and small airways disease at study entry, baseline and change in lung function by spirometry, functional capacity by 6-minute walk, health status using standard questionnaires, exacerbation rates, and progression to COPD between the two groups. All models were adjusted for participant characteristics, asthma history, and tobacco exposure. MAIN RESULTS: We assessed 175 participants with VO and 603 reference participants without obstruction. Participants with VO had 6.2 times the hazard of future development of COPD controlling for other factors (95% CI 4.6-8.3, P<0.001). Compared to reference participants, the VO group had significantly lower baseline pre- and post-BD FEV1, and greater decline over time in post-BD FEV1, and pre- and post-bronchodilator FVC. There were no significant differences in exacerbations between groups. CONCLUSIONS: Significant risk for future COPD development exists for those with pre- but not post-bronchodilator airflow obstruction. These findings support consideration of expanding spirometric criteria defining COPD to include pre-BD obstruction.

6.
Chronic Obstr Pulm Dis ; 9(2): 195-208, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35403414

RESUMO

Rationale: It has been suggested that patients with chronic obstructive pulmonary disease (COPD) experience considerable daily respiratory symptom fluctuation. A standardized measure is needed to quantify and understand the implications of day-to-day symptom variability. Objectives: To compare standard deviation with other statistical measures of symptom variability and identify characteristics of individuals with higher symptom variability. Methods: Individuals in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Exacerbations sub-study completed an Evaluating Respiratory Symptoms in COPD (E-RS) daily questionnaire. We calculated within-subject standard deviation (WS-SD) for each patient at week 0 and correlated this with measurements obtained 4 weeks later using Pearson's r and Bland Altman plots. Median WS-SD value dichotomized participants into higher versus lower variability groups. Association between WS-SD and exacerbation risk during 4 follow-up weeks was explored. Measurements and Main Results: Diary completion rates were sufficient in 140 (68%) of 205 sub-study participants. Reproducibility (r) of the WS-SD metric from baseline to week 4 was 0.32. Higher variability participants had higher St George's Respiratory Questionnaire (SGRQ) scores (47.3 ± 20.3 versus 39.6 ± 21.5, p=.04) than lower variability participants. Exploratory analyses found no relationship between symptom variability and health care resource utilization-defined exacerbations. Conclusions: WS-SD of the E-RS can be used as a measure of symptom variability in studies of patients with COPD. Patients with higher variability have worse health-related quality of life. WS-SD should be further validated as a measure to understand the implications of symptom variability.

7.
Environ Res ; 212(Pt A): 113192, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35346652

RESUMO

Organophosphate esters (OPE) are flame retardants and plasticizers used in a wide range of consumer products. Despite their widespread use, few studies have characterized pediatric exposures. We assessed variability and predictors of OPE exposures in a cohort panel study of 179 predominantly Black school-aged children with asthma in Baltimore City, MD. The study design included up to four seasonal week-long in-home study visits with urine sample collection on days 4 and 7 of each visit (nsamples = 618). We quantified concentrations of 9 urinary OPE biomarkers: bis(2-chloroethyl) phosphate (BCEtp), bis(1-chloro-2-propyl) phosphate, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-benzyl phosphate (DBuP), di-benzyl phosphate, di-o-cresylphosphate, di-p-cresylphosphate (DPCP), di-(2-propylheptyl) phthalate (DPHP), 2,3,4,5-tetrabromo benzoic acid. We assessed potential predictors of exposure, including demographic factors, household characteristics, and cleaning behaviors. We calculated Spearman/tetrachoric correlations and intraclass correlation coefficients (ICCs) to examine within-week and seasonal intra-individual variability, respectively. We assessed OPE predictors using linear models for continuous log2 concentrations (BDCPP and DPHP) and logistic models for odds of detection (BCEtP, DBuP, DPCP), with generalized estimating equations to account for repeated measures. For all OPEs, we observed moderate within-week correlations (rs: 0.31-0.63) and weak to moderate seasonal reliability (ICC: 0.18-0.38). BDCPP and DPHP concentrations were higher in the summer compared to other seasons. DPHP concentrations were lower among males than females (%diff: -53.5%; 95% CI: -62.7, -42.0) and among participants spending >12 h/day indoors compared to ≤12 h (%diff: -20.7%; 95% CI: -32.2, -7.3). BDCPP concentrations were lower among children aged 8-10 years compared to 5-7 years (%diff: -39.1%; 95% CI: -55.9, -15.9) and higher among children riding in a vehicle on the day of sample collection compared to those who had not (%diff: 28.5%; 95% CI: 3.4, 59.8). This study is the first to characterize within-week and seasonal variability and identify predictors of OPE biomarkers among Black school-aged children, a historically understudied population.


Assuntos
Retardadores de Chama , Organofosfatos , Biomarcadores , Criança , Ésteres , Feminino , Humanos , Masculino , Organofosfatos/urina , Fosfatos , Reprodutibilidade dos Testes
8.
Sci Total Environ ; 829: 154694, 2022 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-35318050

RESUMO

BACKGROUND: Neighborhood poverty has been associated with poor health outcomes. Previous studies have also identified adverse respiratory effects of long-term ambient ozone. Factors associated with neighborhood poverty may accentuate the adverse impact of ozone on respiratory health. OBJECTIVES: To evaluate whether neighborhood poverty modifies the association between ambient ozone exposure and respiratory morbidity including symptoms, exacerbation risk, and radiologic parameters, among participants of the SPIROMICS AIR cohort study. METHODS: Spatiotemporal models incorporating cohort-specific monitoring estimated 10-year average outdoor ozone concentrations at participants' homes. Adjusted regression models were used to determine the association of ozone exposure with respiratory outcomes, accounting for demographic factors, education, individual income, body mass index (BMI), and study site. Neighborhood poverty rate was defined by percentage of families living below federal poverty level per census tract. Interaction terms for neighborhood poverty rate with ozone were included in covariate-adjusted models to evaluate for effect modification. RESULTS: 1874 participants were included in the analysis, with mean (± SD) age 64 (± 8.8) years and FEV1 (forced expiratory volume in one second) 74.7% (±25.8) predicted. Participants resided in neighborhoods with mean poverty rate of 9.9% (±10.3) of families below the federal poverty level and mean 10-year ambient ozone concentration of 24.7 (±5.2) ppb. There was an interaction between neighborhood poverty rate and ozone concentration for numerous respiratory outcomes, including COPD Assessment Test score, modified Medical Research Council Dyspnea Scale, six-minute walk test, and odds of COPD exacerbation in the year prior to enrollment, such that adverse effects of ozone were greater among participants in higher poverty neighborhoods. CONCLUSION: Individuals with COPD in high poverty neighborhoods have higher susceptibility to adverse respiratory effects of ambient ozone exposure, after adjusting for individual factors. These findings highlight the interaction between exposures associated with poverty and their effect on respiratory health.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Doença Pulmonar Obstrutiva Crônica , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estudos de Coortes , Exposição Ambiental/análise , Humanos , Pessoa de Meia-Idade , Ozônio/análise , Pobreza , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Fumantes
9.
Chronic Obstr Pulm Dis ; 9(2): 111-121, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35114743

RESUMO

BACKGROUND: Forced expiratory volume in 1 second (FEV1) is central to the diagnosis of chronic obstructive pulmonary disease (COPD) but is imprecise in classifying disease burden. We examined the potential of the maximal mid-expiratory flow rate (forced expiratory flow rate between 25% and 75% [FEF25%-75%]) as an additional tool for characterizing pathophysiology in COPD. OBJECTIVE: To determine whether FEF25%-75% helps predict clinical and radiographic abnormalities in COPD. STUDY DESIGN AND METHODS: The SubPopulations and InteRediate Outcome Measures In COPD Study (SPIROMICS) enrolled a prospective cohort of 2978 nonsmokers and ever-smokers, with and without COPD, to identify phenotypes and intermediate markers of disease progression. We used baseline data from 2771 ever-smokers from the SPIROMICS cohort to identify associations between percent predicted FEF25%-75% (%predFEF25%-75%) and both clinical markers and computed tomography (CT) findings of smoking-related lung disease. RESULTS: Lower %predFEF25-75% was associated with more severe disease, manifested radiographically by increased functional small airways disease, emphysema (most notably with homogeneous distribution), CT-measured residual volume, total lung capacity (TLC), and airway wall thickness, and clinically by increased symptoms, decreased 6-minute walk distance, and increased bronchodilator responsiveness (BDR). A lower %predFEF25-75% remained significantly associated with increased emphysema, functional small airways disease, TLC, and BDR after adjustment for FEV1 or forced vital capacity (FVC). INTERPRETATION: The %predFEF25-75% provides additional information about disease manifestation beyond FEV1. These associations may reflect loss of elastic recoil and air trapping from emphysema and intrinsic small airways disease. Thus, %predFEF25-75% helps link the anatomic pathology and deranged physiology of COPD.

10.
Am J Respir Crit Care Med ; 205(4): 421-430, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34449285

RESUMO

Rationale: Indoor particulate matter is associated with worse chronic obstructive pulmonary disease (COPD) outcomes. It remains unknown whether reductions of indoor pollutants improve respiratory morbidity. Objectives: To determine whether placement of active portable high-efficiency particulate air cleaners can improve respiratory morbidity in former smokers. Methods: Eligible former smokers with moderate-to-severe COPD received active or sham portable high-efficiency particulate absolute air cleaners and were followed for 6 months in this blinded randomized controlled trial. The primary outcome was 6-month change in St. George's Respiratory Questionnaire (SGRQ). Secondary outcomes were exacerbation risk, respiratory symptoms, rescue medication use, and 6-minute-walk distance (6MWD). Intention-to-treat analysis included all subjects, and per-protocol analysis included adherent participants (greater than 80% use of air cleaner). Measurements and Main Results: A total of 116 participants were randomized, of which 84.5% completed the study. There was no statistically significant difference in total SGRQ score, but the active filter group had greater reduction in SGRQ symptom subscale (ß, -7.7 [95% confidence interval (CI), -15.0 to -0.37]) and respiratory symptoms (Breathlessness, Cough, and Sputum Scale, ß, -0.8 [95% CI, -1.5 to -0.1]); and lower rate of moderate exacerbations (incidence rate ratio, 0.32 [95% CI, 0.12-0.91]) and rescue medication use (incidence rate ratio, 0.54 [95% CI, 0.33-0.86]) compared with sham group (all P < 0.05). In per-protocol analysis, there was a statistically significant difference in primary outcome between the active filter versus sham group (SGRQ, ß -4.76 [95% CI, -9.2 to -0.34]) and in moderate exacerbation risk, Breathlessness, Cough, and Sputum Scale, and 6MWD. Participants spending more time indoors were more likely to have treatment benefit. Conclusions: This is the first environmental intervention study conducted among former smokers with COPD showing potential health benefits of portable high-efficiency particulate absolute air cleaners, particularly among those with greater adherence and spending a greater time indoors.


Assuntos
Filtros de Ar , Poluição do Ar em Ambientes Fechados/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/reabilitação , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do Tratamento , Teste de Caminhada
11.
Am J Respir Crit Care Med ; 205(4): 412-420, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34752729

RESUMO

Rationale: Environmental exposures have been associated with adverse outcomes in chronic obstructive pulmonary disease (COPD). Approximately one-third of individuals with COPD have allergic sensitization, but it is unknown whether exposure to allergens in the home is associated with outcomes. Objectives: To determine the prevalence and associations of allergen sensitization with exposure to common indoor allergens with symptoms and exacerbation risk in COPD. Methods: Allergen sensitization to five common indoor allergens was assessed in former smokers with COPD. Home settled dust was assessed for presence of corresponding allergens. Sensitization and exposure status was determined and associations evaluated in adjusted models with longitudinal outcomes including symptoms, lung function, and exacerbations. Interactions were assessed between sensitization/exposure status and lung function. Measurements and Main Results: One hundred eighty-three individuals studied were on average 67.3 years of age (SD, 8.22) with average FEV1 of 53.2% (SD, 17.6%). Seventy-seven percent of participants were exposed to at least one tested allergen, and 17% had sensitization with corresponding allergen exposure. After adjustment, sensitization with exposure was associated with lower lung function (ß, -8.29; 95% confidence interval [CI], -14.80 to -1.77), higher St. George's Respiratory Questionnaire Total Score (ß, 6.71; 95% CI, 0.17 to 13.25), and higher exacerbation risk (odds ratio, 2.31; 95% CI, 1.11 to 4.79). Associations appeared to be more pronounced among individuals with lower lung function. Conclusions: Allergen exposures are common in COPD and associated with adverse outcomes among those with concomitant allergen sensitization. This study establishes allergens as an important home exposure that potentially could be addressed with comprehensive home environmental modification strategies to improve COPD outcomes.


Assuntos
Alérgenos/efeitos adversos , Poeira/imunologia , Exposição Ambiental/efeitos adversos , Hipersensibilidade/etiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos/imunologia , Progressão da Doença , Feminino , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/epidemiologia , Hipersensibilidade/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/imunologia , Índice de Gravidade de Doença
12.
J Asthma ; 59(5): 946-955, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33625291

RESUMO

OBJECTIVE: Black children and children from low-income communities are disproportionately affected by asthma, attributed partly to pollution exposure. Air purifiers reduce indoor air pollution and improve asthma symptoms in children. In order to implement air purifier interventions, an understanding of patterns of use and potential barriers is necessary. METHODS: In a home intervention study, 127 children with asthma living in Baltimore were randomized to receive two active or two placebo air purifiers. The 16-week study period included: baseline clinic visit, home visit for air purifier installation (active or placebo) with instruction to use the high or turbo settings, and electronic adherence monitoring of air purifiers. Determinants of adherence were identified using linear regression models. RESULTS: Air purifiers were used 80% of the time, and participants demonstrated adherence to high or turbo settings for 60% of the time. In an adjusted model, season was the major determinant of air purifier adherence, with 21% lower use in the winter (p = 0.025) attributed to the cold draft generated by the machine. CONCLUSION: In a clinical trial with electronic adherence monitoring, air purifier use was high and participants were adherent to use of high or turbo settings the majority of the time. Addressing practical barriers to consistent use, such as draft during the winter, in addition to financial barriers may improve air purifier adherence among children with asthma living in low-income, urban households. CLINICAL TRIALS REGISTRY NUMBER: NCT02763917.


Assuntos
Filtros de Ar , Poluição do Ar em Ambientes Fechados , Asma , Poluição do Ar em Ambientes Fechados/análise , Asma/tratamento farmacológico , Criança , Humanos , Pobreza , Estações do Ano
13.
Ann Am Thorac Soc ; 19(2): 171-178, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34410883

RESUMO

Rationale: Individuals with chronic obstructive pulmonary disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. Objectives: Examine the impact of depressive symptoms compared with FEV1% on COPD morbidity. Methods: Using longitudinal data from individuals with COPD in the Subpopulations and Intermediate Outcome Measures in COPD Study, longitudinal growth analysis was performed to assess COPD morbidity by assessing differences in baseline 6-minute walk distance and patient reported outcomes (PROs) and their rate of change over time explained by depressive symptoms or lung function, as measured by Hospital Anxiety and Depression Scale or FEV1% respectively. PROs consisted of in-person completion of St. George's Respiratory Questionnaire, COPD Assessment Test, Functional Assessment of Chronic Illness Therapy Fatigue, and Modified Medical Research Council Dyspnea Scale measures. Results: Of the individuals analyzed (n = 1,830), 43% were female, 81% Caucasian with mean ± SD age of 65.1 ± 8.1, and 52.7 ± 27.5 pack-years smoking. Mean ± SD FEV1% was 60.9 ± 23.0% and 20% had clinically significant depressive symptoms. Adjusted models showed higher Hospital Anxiety and Depression Scale scores and lower FEV1% each were associated with worse PROs at baseline (P ⩽ 0.001). Depression accounted for more baseline variance in St. George's Respiratory Questionnaire, COPD Assessment Test, and Functional Assessment of Chronic Illness Therapy Fatigue than FEV1%, explaining 30-67% of heterogeneity. FEV1% accounted for more baseline variance in Modified Medical Research Council Dyspnea Scale and 6-minute walk distance than depression, explaining 16-32% of heterogeneity. Depressive symptoms accounted for 3-17% variance in change over time in PROs. In contrast, FEV1% accounted for 1-4% variance over time in PROs. Conclusions: Depression is more strongly associated with many PROs at baseline and their change over time compared with FEV1%. Recognizing and incorporating the impact of depressive symptoms into individualized care may improve COPD outcomes.


Assuntos
Depressão , Doença Pulmonar Obstrutiva Crônica , Depressão/epidemiologia , Feminino , Volume Expiratório Forçado , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Qualidade de Vida , Testes de Função Respiratória , Fumar , Inquéritos e Questionários
14.
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 Pediátrica , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Asma/complicações , Criança , Exposição Ambiental , Humanos , Pulmão , Material Particulado/análise , Obesidade Pediátrica/complicações , Estudos Prospectivos , Volume de Ventilação Pulmonar
15.
J Cyst Fibros ; 21(2): e129-e135, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34531156

RESUMO

BACKGROUND: Exposure to higher levels of outdoor air pollution is associated with increased morbidity in individuals with cystic fibrosis. Limited information exist regarding the potential adverse effects of indoor air pollution on those with cystic fibrosis. METHODS: Individuals with cystic fibrosis who were enrolled in the Twin and Sibling Study from 2000-2013, self-reported exposure to four known sources of indoor air pollution (secondhand smoke, forced hot air, wood stove and fireplace). Change in lung function, rates of hospitalizations and pulmonary exacerbations were followed over 4 years to compare outcomes in those who were exposed to those who were not exposed. RESULTS: Of 1432 participants with data on secondhand smoke exposure, 362 (25.3%) were exposed. Of 765 individuals with data on forced hot air exposure, 491 (64.2%) were exposed. Of 1247 participants with data on wood stove exposure and 830 with data on fireplace exposure, 182 (14.6%) and 373 (44.9%) were exposed, respectively. In longitudinal analysis, pediatric individuals either exposed to secondhand smoke or to forced hot air had a 0.60% predicted/year decrease in FEV1% predicted (P=0.002) or a 0.46% predicted/year decrease in FEV1% predicted (P=0.048), respectively compared to individuals who were not exposed. Adults exposed to secondhand smoke had a 42% increased yearly risk of hospitalization compared to those who were not exposed (P=0.045). CONCLUSIONS: Our questionnaire-based data suggest that exposure to sources of indoor air pollution increase morbidity in both the pediatric and adult cystic fibrosis populations. Future studies with quantitative indoor air quality assessments are needed.


Assuntos
Poluição do Ar em Ambientes Fechados , Fibrose Cística , Poluição por Fumaça de Tabaco , Adulto , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise , Criança , Fibrose Cística/epidemiologia , Humanos , Pulmão , Morbidade
16.
Am J Respir Crit Care Med ; 205(7): 819-829, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34913855

RESUMO

Rationale: African American individuals have worse outcomes in chronic obstructive pulmonary disease (COPD). Objectives: To assess whether race-specific approaches for estimating lung function contribute to racial inequities by failing to recognize pathological decrements and considering them normal. Methods: In a cohort with and at risk for COPD, we assessed whether lung function prediction equations applied in a race-specific versus universal manner better modeled the relationship between FEV1, FVC, and other COPD outcomes, including the COPD Assessment Test, St. George's Respiratory Questionnaire, computed tomography percent emphysema, airway wall thickness, and 6-minute-walk test. We related these outcomes to differences in FEV1 using multiple linear regression and compared predictive performance between fitted models using root mean squared error and Alpaydin's paired F test. Measurements and Main Results: Using race-specific equations, African American individuals were calculated to have better lung function than non-Hispanic White individuals (FEV1, 76.8% vs. 71.8% predicted; P = 0.02). Using universally applied equations, African American individuals were calculated to have worse lung function. Using Hankinson's Non-Hispanic White equation, FEV1 was 64.7% versus 71.8% (P < 0.001). Using the Global Lung Initiative's Other race equation, FEV1 was 70.0% versus 77.9% (P < 0.001). Prediction errors from linear regression were less for universally applied equations compared with race-specific equations when examining FEV1% predicted with the COPD Assessment Test (P < 0.01), St. George's Respiratory Questionnaire (P < 0.01), and airway wall thickness (P < 0.01). Although African American participants had greater adversity (P < 0.001), less adversity was only associated with better FEV1 in non-Hispanic White participants (P for interaction = 0.041). Conclusions: Race-specific equations may underestimate COPD severity in African American individuals.Clinical trial registered with www.clinicaltrials.gov (NCT01969344).


Assuntos
Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Volume Expiratório Forçado , Humanos , Pulmão/diagnóstico por imagem , Testes de Função Respiratória , Capacidade Vital
17.
Front Immunol ; 12: 744782, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721414

RESUMO

Introduction: There is evidence that obesity, a risk factor for asthma severity and morbidity, has a unique asthma phenotype which is less atopic and less responsive to inhaled corticosteroids (ICS). Peripheral blood mononuclear cells (PBMC) are important to the immunologic pathways of obese asthma and steroid resistance. However, the cellular source associated with steroid resistance has remained elusive. We compared the lymphocyte landscape among obese children with asthma to matched normal weight children with asthma and assessed relationship to asthma control. Methods: High-dimensional flow cytometry of PBMC at baseline and after dexamethasone stimulation was performed to characterize lymphocyte subpopulations, T-lymphocyte polarization, proliferation (Ki-67+), and expression of the steroid-responsive protein FK506-binding protein 51 (FKBP51). T-lymphocyte populations were compared between obese and normal-weight participants, and an unbiased, unsupervised clustering analysis was performed. Differentially expressed clusters were compared with asthma control, adjusted for ICS and exhaled nitric oxide. Results: In the obese population, there was an increased cluster of CD4+ T-lymphocytes expressing Ki-67 and FKBP51 at baseline and CD4+ T-lymphocytes expressing FKBP51 after dexamethasone stimulation. CD4+ Ki-67 and FKBP51 expression at baseline showed no association with asthma control. Dexamethasone-induced CD4+ FKBP51 expression was associated with worse asthma control in obese participants with asthma. FKBP51 expression in CD8+ T cells and CD19+ B cells did not differ among groups, nor did polarization profiles for Th1, Th2, Th9, or Th17 percentage. Discussion: Dexamethasone-induced CD4+ FKBP51 expression is uniquely associated with worse asthma control in obese children with asthma and may underlie the corticosteroid resistance observed in this population.


Assuntos
Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Linfócitos T CD4-Positivos/imunologia , Dexametasona/uso terapêutico , Obesidade Pediátrica/complicações , Proteínas de Ligação a Tacrolimo/biossíntese , Filtros de Ar , Asma/complicações , Asma/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Criança , Resistência a Medicamentos/imunologia , Feminino , Humanos , Masculino , Material Particulado/efeitos adversos , Obesidade Pediátrica/imunologia
18.
J Allergy Clin Immunol ; 148(6): 1589-1595, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34536413

RESUMO

BACKGROUND: Total serum IgE (tIgE) is an important intermediate phenotype of allergic disease. Whole genome genetic association studies across ancestries may identify important determinants of IgE. OBJECTIVE: We aimed to increase understanding of genetic variants affecting tIgE production across the ancestry and allergic disease spectrum by leveraging data from the National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine program; the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA); and the Atopic Dermatitis Research Network (N = 21,901). METHODS: We performed genome-wide association within strata of study, disease, and ancestry groups, and we combined results via a meta-regression approach that models heterogeneity attributable to ancestry. We also tested for association between HLA alleles called from whole genome sequence data and tIgE, assessing replication of associations in HLA alleles called from genotype array data. RESULTS: We identified 6 loci at genome-wide significance (P < 5 × 10-9), including 4 loci previously reported as genome-wide significant for tIgE, as well as new regions in chr11q13.5 and chr15q22.2, which were also identified in prior genome-wide association studies of atopic dermatitis and asthma. In the HLA allele association study, HLA-A∗02:01 was associated with decreased tIgE level (Pdiscovery = 2 × 10-4; Preplication = 5 × 10-4; Pdiscovery+replication = 4 × 10-7), and HLA-DQB1∗03:02 was strongly associated with decreased tIgE level in Hispanic/Latino ancestry populations (PHispanic/Latino discovery+replication = 8 × 10-8). CONCLUSION: We performed the largest genome-wide association study and HLA association study of tIgE focused on ancestrally diverse populations and found several known tIgE and allergic disease loci that are relevant in non-European ancestry populations.


Assuntos
Asma/genética , Dermatite Atópica/genética , Genótipo , Antígeno HLA-A2/genética , Cadeias beta de HLA-DQ/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , National Heart, Lung, and Blood Institute (U.S.) , Estados Unidos , Sequenciamento Completo do Genoma , Adulto Jovem
19.
J Immunol ; 207(2): 398-407, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34193598

RESUMO

Alterations in gut microbiota in early life have been associated with the development of asthma; however, the role of gut bacteria or the IgA response to gut bacteria in school-aged children with asthma is unclear. To address this question, we profiled the microbial populations in fecal and nasal swab samples by 16S rRNA sequencing from 40 asthma and 40 control children aged 9-17 y from Peru. Clinical history and laboratory evaluation of asthma and allergy were obtained. Fecal samples were analyzed by flow cytometry and sorted into IgA+ and IgA- subsets for 16S rRNA sequencing. We found that the fecal or nasal microbial 16S rRNA diversity and frequency of IgA+ fecal bacteria did not differ between children with or without asthma. However, the α diversity of fecal IgA+ bacteria was decreased in asthma compared with control. Machine learning analysis of fecal bacterial IgA-enrichment data revealed loss of IgA binding to the Blautia, Ruminococcus, and Lachnospiraceae taxa in children with asthma compared with controls. In addition, this loss of IgA binding was associated with worse asthma control (Asthma Control Test) and increased odds of severe as opposed to mild to moderate asthma. Thus, despite little to no change in the microbiota, children with asthma exhibit an altered host IgA response to gut bacteria compared with control participants. Notably, the signature of altered IgA responses is loss of IgA binding, in particular to members of Clostridia spp., which is associated with greater severity of asthma.


Assuntos
Asma/imunologia , Microbioma Gastrointestinal/imunologia , Imunoglobulina A/imunologia , Adolescente , Bactérias/genética , Bactérias/imunologia , Estudos de Casos e Controles , Criança , Fezes/microbiologia , Feminino , Humanos , Hipersensibilidade/imunologia , Masculino , Microbiota/genética , Microbiota/imunologia , Peru , RNA Ribossômico 16S/genética , Adulto Jovem
20.
J Allergy Clin Immunol Pract ; 9(11): 4014-4020.e4, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34293503

RESUMO

BACKGROUND: Diabetes is associated with worse asthma morbidity. Metformin, which treats diabetes, may have a role among patients with asthma and glycemic dysfunction. OBJECTIVE: To determine the association between metformin use and asthma exacerbations among patients with diabetes. METHODS: We queried the Johns Hopkins electronic health record from April 1, 2013, to May 31, 2018. Adults with asthma and diabetes were followed from first hemoglobin A1c (HbA1c) test to an asthma-related systemic corticosteroid prescription, emergency department (ED) visit, or hospitalization. Multivariable Cox models estimated time to each outcome associated with metformin use, modeled as either time-invariant (status at HbA1c testing) or time-dependent (based on fill data). Mediation of results by HbA1c was assessed. Sensitivity analysis was performed by propensity score matching. RESULTS: The cohort comprised 1749 adults with asthma and diabetes. Metformin use at entry was associated with a lower hazard of asthma-related ED visits (adjusted hazard ratio [aHR], 0.40; 95% CI, 0.22-0.75) but not steroid prescription (aHR, 0.89; 95% CI, 0.70-1.13) or hospitalization (aHR, 0.38; 95% CI, 0.13-1.12). HbA1c did not mediate the association with ED visits. With metformin exposure modeled as time-dependent, metformin use was additionally associated with lower hazard of asthma-related hospitalization (aHR, 0.30; 95% CI, 0.09-0.93). Results were consistent within a subcohort of 698 metformin users matched 1:1 to nonusers by propensity score. CONCLUSIONS: Metformin use, independent of glycemic control and obesity, was associated with lower hazard of asthma-related ED visits and hospitalizations. Metformin may have benefit in patients with asthma and glycemic dysfunction.


Assuntos
Asma , Diabetes Mellitus Tipo 2 , Metformina , Adulto , Asma/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobina A Glicada/análise , Hospitalização , Humanos , Metformina/uso terapêutico , Estudos Retrospectivos
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