RESUMO
INTRODUCTION: Chronic lung allograft dysfunction (CLAD) is a lung transplant complication for which four phenotypes are recognized: Bronchiolitis obliterans syndrome (BOS), Restrictive allograft syndrome (RAS), mixed and undefined phenotypes. Weight gain is common after transplant and may negatively impact lung function. Study objectives were to describe post-transplant weight trajectories of patients who developed (or did not) CLAD phenotypes and examine the associations between BMI at transplant, post-transplant changes in weight and BMI, and the risk of developing these phenotypes. METHODS: Adults who underwent a bilateral lung transplant between 2000 and 2020 at our institution were categorized as having (or not) one of the four CLAD phenotypes based on the proposed classification system. Demographic, anthropometric, and clinical data were retrospectively collected from medical records and analyzed. RESULTS: Study population included 579 recipients (412 [71.1%] CLAD-free, 81 [14.0%] BOS, 20 [3.5%] RAS, 59 [10.2%] mixed, and 7 [1.2%] undefined phenotype). Weight gains of greater amplitude were seen in recipients with restrictive phenotypes than CLAD-free and BOS patients within the first five years post-transplant. While the BMI category at transplant was not statistically associated with the risk of developing CLAD phenotypes, an increase in weight (Hazard ratio [HR]: 1.04, 95% CI [1.01-1.08]; P = .008) and BMI (HR: 1.13, 95% CI [1.03-1.23]; P = .008) over the post-transplant period was associated with a greater risk of RAS. CONCLUSION: Post-LTx gain in weight and BMI modestly increased the risk of RAS, adding to the list of unfavorable outcomes associated with weight gain following transplant.
RESUMO
Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots (DBSs) to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels. Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than 6 months earlier, spike levels fell notably and continuously for the 9-month post-vaccination. In contrast, among adults infected within 6 months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than 6 months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% confidence interval 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the coronavirus disease 2019 (COVID-19) weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity. Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected DBSs are a practicable biological surveillance platform. Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinação , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Canadá/epidemiologia , SARS-CoV-2/imunologia , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Estudos de Coortes , Idoso , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto JovemRESUMO
Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. Our study on 68 PWH and 23 HIV-negative participants aged 55 and older post-three vaccine doses showed equally strong anti-spike IgG responses in serum and saliva through week 48 from baseline, while PWH salivary IgA responses were low. PWH had diminished live-virus neutralization responses after two vaccine doses, which were 'rescued' post-booster. Spike-specific T cell immunity was enhanced in PWH with normal CD4+ T cell count, suggesting Th1 imprinting. The frequency of detectable HIV viremia increased post-vaccination, but vaccines did not affect the size of the HIV reservoir in most PWH, except those with low-level viremia. Thus, older PWH require three doses of COVID-19 vaccine for maximum protection, while individuals with unsuppressed viremia should be monitored for adverse reactions from HIV reservoirs.
RESUMO
Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. We followed 68 PWH aged 55 and older and 23 age-matched HIV-negative individuals for 48 weeks from the first vaccine dose, after the total of three doses. All PWH were on antiretroviral therapy (cART) and had different immune status, including immune responders (IR), immune non-responders (INR), and PWH with low-level viremia (LLV). We measured total and neutralizing Ab responses to SARS-CoV-2 spike and RBD in sera, total anti-spike Abs in saliva, frequency of anti-RBD/NTD B cells, changes in frequency of anti-spike, HIV gag/nef-specific T cells, and HIV reservoirs in peripheral CD4 + T cells. The resulting datasets were used to create a mathematical model for within-host immunization. Various regimens of BNT162b2, mRNA-1273, and ChAdOx1 vaccines elicited equally strong anti-spike IgG responses in PWH and HIV - participants in serum and saliva at all timepoints. These responses had similar kinetics in both cohorts and peaked at 4 weeks post-booster (third dose), while half-lives of plasma IgG also dramatically increased post-booster in both groups. Salivary spike IgA responses were low, especially in INRs. PWH had diminished live virus neutralizing titers after two vaccine doses which were 'rescued' after a booster. Anti-spike T cell immunity was enhanced in IRs even in comparison to HIV - participants, suggesting Th1 imprinting from HIV, while in INRs it was the lowest. Increased frequency of viral 'blips' in PWH were seen post-vaccination, but vaccines did not affect the size of the intact HIV reservoir in CD4 + T cells in most PWH, except in LLVs. Thus, older PWH require three doses of COVID-19 vaccine to maximize neutralizing responses against SARS-CoV-2, although vaccines may increase HIV reservoirs in PWH with persistent viremia.
RESUMO
Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding for the ion channel cystic fibrosis transmembrane conductance regulator (CFTR). The management of CF disease has evolved in recent decades from treating downstream disease manifestations affecting the airways, the lungs and the gastrointestinal system to addressing the CFTR gene defect. The advent of CFTR modulators, which correct the functionality of the defective CFTR, contributes to reshaping the landscape of CF demographics, prognosis and therapies, including nutritional management. A spectrum of clinical manifestations is emerging within the same patient population where undernutrition and nutritional deficiencies coexist with excessive weight gain and metabolic derangements. Such contrasting presentations challenge current practices, require adjustments to traditional approaches, and involve more individualised interventions. This narrative review examines the current state of knowledge on the nutritional management of people living with cystic fibrosis from early life to adulthood in the era of CFTR modulation.
Assuntos
Fibrose Cística , Humanos , Fibrose Cística/complicações , Fibrose Cística/genética , Fibrose Cística/terapia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/uso terapêutico , Prognóstico , Pulmão , Medicina de PrecisãoRESUMO
Previous studies have reported impaired humoral responses after SARS-CoV-2 mRNA vaccination in patients with immune-mediated inflammatory diseases (IMIDs), particularly those treated with anti-TNF biologics. We previously reported that IMID patients diagnosed with inflammatory bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, or rheumatoid arthritis exhibited greater waning of Ab and T cell responses than healthy control subjects after SARS-CoV-2 vaccine dose 2. Fewer data are available on the effects of third and fourth doses. This observational cohort study collected plasma and PBMCs from healthy control subjects and untreated or treated patients with IMIDs prevaccination and after one to four doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). SARS-CoV-2-specific Ab levels, neutralization, and T cell cytokine release were measured against wild-type and Omicron BA.1 and BA.5 variants of concern. Third vaccine doses substantially restored and prolonged Ab and T cell responses in patients with IMIDs and broadened responses against variants of concern. Fourth-dose effects were subtle but also prolonged Ab responses. However, patients with IMIDs treated with anti-TNF, especially patients with inflammatory bowel disease, exhibited lower Ab responses even after the fourth dose. Although T cell IFN-γ responses were maximal after one dose, IL-2 and IL-4 production increased with successive doses, and early production of these cytokines was predictive of neutralization responses at 3-4 mo postvaccination. Our study demonstrates that third and fourth doses of the SARS-CoV-2 mRNA vaccines sustain and broaden immune responses to SARS-CoV-2, supporting the recommendation for three- and four-dose vaccination regimens in patients with IMIDs.
Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Vacinas , Humanos , Adulto , Vacinas contra COVID-19 , SARS-CoV-2 , Vacina BNT162 , Agentes de Imunomodulação , Inibidores do Fator de Necrose Tumoral , COVID-19/prevenção & controle , Vacinação , Citocinas , Anticorpos AntiviraisRESUMO
OBJECTIVES: The classical glycosylated hemoglobin A1c threshold of 6.5% is an insensitive screening test for cystic fibrosis-related diabetes (CFRD). We sought to identify CF-specific A1C thresholds associated with 1) risk of progression to CFRD and 2) changes in body mass index (BMI) and forced expiratory volume (FEV1). METHODS: We studied the cross sectional and longitudinal associations between A1c, BMI, and FEV1 in 2 cohorts of 223 children (followed for up to 8 years) and 289 adults (followed for a mean of 7.5 ± 4.3 years) with CF but without diabetes at baseline and undergoing regular assessments including Oral Glucose Tolerance Test (OGTT). RESULTS: For the onset of OGTT-defined CFRD optimal A1c threshold was 5.9% in adults (sensitivity: 67% and specificity: 71%) and 5.7% for children (sensitivity: 60% and specificity: 47%). Kaplan-Meier analysis of progression to CFRD according to baseline A1C showed increased the risk of developing CFRD for A1c ≥ 6.0% in adults (P = 0.002) and ≥ 5.5% in children (p = 0.012). Temporal changes in BMI and FEV1 according to baseline A1C in adults were assessed with a linear mixed-effect model, BMI significantly increased over time in subjects with a baseline A1c < 6%, but those with a A1C ≥ 6.0% gained significantly less weight over time (P = 0.05). There was no difference in FEV1 according to baseline A1c category. CONCLUSION: An A1C above 6% may be associated with a high risk of developing CFRD and a lower probability of weight gain in both adults and children with CF.
Assuntos
Fibrose Cística , Diabetes Mellitus , Intolerância à Glucose , Humanos , Adulto , Criança , Hemoglobinas Glicadas , Fibrose Cística/complicações , Fibrose Cística/epidemiologia , Fibrose Cística/diagnóstico , Glicemia , Estudos Transversais , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/diagnóstico , Aumento de Peso , Intolerância à Glucose/complicaçõesRESUMO
In January 2022, a group of experts came together to discuss current perspectives and future directions in nutritional immunology as part of a symposium organized by the Canadian Nutrition Society. Objectives included (1) creating an understanding of the complex interplay between diet and the immune system from infants through to older adults, (2) illustrating the role of micronutrients that are vital to the immune system, (3) learning about current research comparing the impact of various dietary patterns and novel approaches to reduce inflammation, autoimmune conditions, allergies, and infections, and (4) discussing select dietary recommendations aimed at improving disease-specific immune function. The aims of this review are to summarize the symposium and to identify key areas of research that require additional exploration to better understand the dynamic relationship between nutrition and immune function.
Assuntos
Dieta , Estado Nutricional , Lactente , Humanos , Idoso , Canadá , Micronutrientes , Vitamina DRESUMO
BACKGROUND: Lung transplant (LTx) recipients who gain weight after transplantation may experience an upward shift in body mass index (BMI) that places them in the obese category. The incidence, risk factors, and impact on metabolic health and mortality of new-onset obesity have not been documented in the LTx setting. METHODS: This single-center retrospective study included 564 LTx recipients. Individuals were stratified according to their BMI trajectories from pretransplant evaluation up to 10 y posttransplant. New-onset obesity was defined as a pretransplant BMI <30 kg/m 2 and posttransplant BMI >30 kg/m 2 . The incidence, risk factors, and posttransplant diabetes mellitus, metabolic syndrome, and mortality of recipients with new-onset obesity were compared with those of nonobese (BMI <30 kg/m 2 , pre/post-LTx), consistently obese (BMI >30 kg/m 2 , pre/post-LTx), and obese recipients with weight loss (BMI >30 kg/m 2 pre-LTx, BMI <30 kg/m 2 post-LTx). RESULTS: We found that 14% of recipients developed obesity after transplantation. Overweight individuals (odds ratio [OR]: 9.01; 95% confidence interval [CI] [4.86-16.69]; P < 0.001) and candidates with chronic obstructive pulmonary disease (OR: 6.93; 95% CI [2.30-20.85]; P = 0.001) and other diagnoses (OR: 4.28; 95% CI [1.22-14.98]; P = 0.023) were at greater risk. Multivariable regression analysis showed that new-onset obesity was associated with a greater risk of metabolic syndrome (hazard ratio: 1.70; 95% CI [1.17-2.46]; P = 0.005), but not of posttransplant diabetes mellitus, than nonobesity. Recipients with new-onset obesity had a survival comparable to that of consistently obese individuals. CONCLUSIONS: A greater understanding of the multifaceted nature of post-LTx obesity may lead to interventions that are better tailored to the characteristics of these individuals.
Assuntos
Diabetes Mellitus , Transplante de Pulmão , Síndrome Metabólica , Humanos , Incidência , Estudos Retrospectivos , Síndrome Metabólica/complicações , Obesidade/complicações , Obesidade/epidemiologia , Índice de Massa Corporal , Transplante de Pulmão/efeitos adversos , Fatores de Risco , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologiaAssuntos
Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Cobertura Vacinal , Adulto , Anticorpos Antivirais , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/uso terapêutico , Canadá/epidemiologia , Ensaio de Imunoadsorção Enzimática , Humanos , Cobertura Vacinal/estatística & dados numéricosRESUMO
BACKGROUND: Indeterminate glycemia (INDET) and impaired glucose tolerance (IGT) are independently associated with cystic fibrosis-related diabetes (CFRD) risk. We determined whether patients meeting both criteria have increased risk of diabetes in 2 separate adult cohorts. METHODS: The Montreal Cystic Fibrosis Cohort (MCFC; nâ =â 293 baseline and 198 for prospective analysis excluding subjects identified with incident CFRD at baseline) and the Lyon cystic fibrosis cohort [Determination of the Predictive Factors in the Reversibility or the Aggravation in the Disorders of the Glucose Metabolism in Cystic Fibrosis Patients (DIAMUCO); nâ =â 144/105] are prospective observational cohorts. RESULTS: In the MCFC and DIAMUCO cohorts, mean age was 25.5â ±â 7.7 and 25.0â ±â 8.6 years; body mass index, 21.7â ±â 3.0 and 20.2â ±â 2.2 kg/m2; percentage of forced expiratory volume expired in 1 sec, 73.2â ±â 22.1 and 62.5â ±â 21.9; and follow-up, 6.9â ±â 3.8 and 2.4â ±â 1.2 years, respectively. In the MCFC cohort, the IGT only and combined INDET and IGT (INDETâ +â IGT) groups had greater risk of CFRD (Pâ =â 0.0109). In the DIAMUCO cohort, there was lower diabetes-free survival in the INDETâ +â IGT group (Pâ =â 0.0105). In both cohorts, CFRD risk ranged from 17% in normal glucose tolerance patients up to 42% to 56% in patients with INDETâ +â IGT. CONCLUSION: Patients who meet combined criteria have a higher risk of developing diabetes probably justifying closer follow-up.
Assuntos
Fibrose Cística , Diabetes Mellitus , Intolerância à Glucose/epidemiologia , Adolescente , Adulto , Doenças Assintomáticas , Estudos de Coortes , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Feminino , Seguimentos , França/epidemiologia , Intolerância à Glucose/complicações , Intolerância à Glucose/diagnóstico , Intolerância à Glucose/patologia , Humanos , Masculino , Quebeque/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Little is known about long-term bone mineral density (BMD) changes and fractures in lung transplant recipients with cystic fibrosis (CF). We examined femur and lumbar spine (LS) BMD changes in men and women with CF up to 10 years post-transplant and documented post-transplant fracture prevalence. METHODS: Retrospective study of individuals who had undergone a lung transplant (2000-2015) and had a pre-transplant and at least one BMD measurement after transplant. Vertebral fractures were assessed on chest computed tomography scans and other fractures abstracted from medical records. RESULTS: The cohort consisted of 131 individuals; 53% males, median age: 28 years [interquartile range: 24-35] and 31% having pre-transplant low bone mass. Most recipients were given bisphosphonates after transplant with proportion reaching 94% at 10 years. Up to 10 years post-transplant, men experienced positive or little change in LS BMD, indicating minimal loss from pre-transplant values. In contrast, women displayed negative changes in BMD up to 5 years post-transplant before recovering pre-transplant BMD values by 10 years. Similar patterns were observed at the femur BMD where men demonstrated a lower bone loss and faster recovery towards pre-transplant values than women. After transplant, 88% of recipients maintained their pre-transplant bone status, 3% experienced an improvement, mostly progressing from low bone mass to normal status whereas 9% had a deterioration of their pre-transplant bone status. Twenty-seven recipients suffered fractures in the post-transplant period. CONCLUSIONS: These findings underline that lung recipients with CF remain at risk of skeletal fragility despite prompt initiation of post-transplant anti-osteoporosis therapy.
Assuntos
Densidade Óssea , Fibrose Cística/cirurgia , Transplante de Pulmão , Fraturas por Osteoporose/epidemiologia , Transplantados , Adulto , Feminino , Humanos , Masculino , Prevalência , Estudos Retrospectivos , Fatores SexuaisRESUMO
OBJECTIVES: Our aims in this study were to document the screening rate for cystic fibrosisârelated diabetes (CFRD) in children followed at a cystic fibrosis (CF) clinic in Canada and to evaluate the accuracy of various glycated hemoglobin (A1C) cutoffs to screen for CFRD and impaired glucose tolerance (IGT) in a pediatric CF population. METHODS: The CFRD screening rate was calculated over a follow-up period of up to 8 years among children who attended the CF clinic between 1993 and 2018. Test performance of A1C at various thresholds ranging from 5.5% to 6.2% was compared with the oral glucose tolerance test (OGTT) as the reference method. Children with CF aged ≥10 years with an OGTT performed within 120 days of A1C measurement were included in the analysis. RESULTS: The overall CFRD screening rate was 53.0%. A total of 256 children were included for the A1C performance analysis, of whom 8.6% had an OGTT-confirmed CFRD diagnosis. An A1C threshold of 5.8% demonstrated an optimal balance between sensitivity (90.9%) and specificity (60.7%) for CFRD screening, leading to a potential reduction of 56.3% of the annual required OGTTs. A1C demonstrated poor accuracy for identifying children with IGT. CONCLUSIONS: An A1C threshold ≥5.8% allows for identification of children requiring further CFRD investigations, which may reduce the clinical burden of children with CF without compromising the ability of early CFRD diagnosis.
Assuntos
Fibrose Cística , Diabetes Mellitus , Intolerância à Glucose , Glicemia , Criança , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Intolerância à Glucose/diagnóstico , Intolerância à Glucose/epidemiologia , Hemoglobinas Glicadas/análise , HumanosRESUMO
BACKGROUND AND AIMS: Deterioration of anthropometric and lung function parameters was shown to precede the onset of cystic fibrosis-related diabetes (CFRD) in adults. In children, studies have been conducted in small cohorts with relatively short observation period. Study objectives were to document the longitudinal trends of anthropometric, pulmonary, nutritional and metabolic parameters from cystic fibrosis (CF) diagnosis to the ascertainment of abnormal glucose tolerance and identify parameters associated with the incidence of such abnormalities in a pediatric CF cohort. METHODS AND RESULTS: Retrospective cohort study of 281 children with CF. Longitudinal trends of anthropometric, lung function, nutritional and metabolic data were generated from CF diagnosis to the ascertainment of abnormal glucose tolerance defined as the presence of either impaired glucose tolerance (IGT), unconfirmed CFRD or CFRD. Cox models and Kaplan-Meier curves were used to identify factors associated with developing abnormal glucose tolerance. Forty-five percent of cohort had normal glucose tolerance (NGT), 27% IGT, 10% unconfirmed CFRD and 18% CFRD. Children who developed CFRD displayed lower height z-scores from a very early age. Conversely, HbA1c levels began to rise closer to CFRD ascertainment. Height z-scores (HR: 0.45; CI 95% [0.29-0.69]) and HbA1c (HR: 2.43; CI 95% [1.86-3.18]) in years preceding ascertainment were associated with the risk of developing CFRD. CONCLUSION: Children who developed CFRD display distinctive trends for height z-scores from a very early age, whereas HbA1c appears as a marker of established glucose metabolism derangements.
Assuntos
Glicemia/metabolismo , Fibrose Cística/complicações , Intolerância à Glucose/etiologia , Adolescente , Fatores Etários , Biomarcadores/sangue , Criança , Fibrose Cística/diagnóstico , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/diagnóstico , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
Previously, we showed that nearly 70% of children followed in our sickle cell disease (SCD) clinic were vitamin D- deficient and had low vitamin intake with poor use of supplements. We compared the change in serum 25-hydroxyvitamin D [25(OH)D], safety and clinical impact of two vitamin D supplementation regimens in children with SCD. Children (5-17 years, all genotypes) were randomized to a single bolus of vitamin D3 (300 000 IU; n = 18) or placebo (n = 20). All children received a prescription for daily 1 000 IU vitamin D3 . Serum 25(OH)D and calcium, urinary calcium/creatinine ratio, musculoskeletal pain, quality of life, haematology and bone markers were assessed at baseline and three months post intervention. Bolus administration led to a greater rise in 25(OH)D levels from baseline compared to placebo (20 ± 16 nmol/l vs. 2 ± 19 nmol/l; P = 0·003) and correction of vitamin D deficiency. No hypercalcaemia nor hypercalciuria occurred during the study, but more children in the bolus group experienced gastrointestinal symptoms within the first month (P = 0·04). There were no differences between groups for other outcomes. The use of a high-dose vitamin D bolus combined with daily 1 000 IU vitamin D3 was more efficient in raising 25(OH)D levels than daily supplementation alone in children with SCD.
Assuntos
Anemia Falciforme/tratamento farmacológico , Colecalciferol/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Cálcio/sangue , Criança , Pré-Escolar , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Feminino , Humanos , Masculino , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Vitaminas/administração & dosagemRESUMO
The last couple of decades have seen an explosion in our interest and understanding of the role of vitamin D in the regulation of immunity. At the molecular level, the hormonal form of vitamin D signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. The VDR and vitamin D metabolic enzymes are expressed throughout the innate and adaptive arms of the immune system. The advent of genome-wide approaches to gene expression profiling have led to the identification of numerous VDR-regulated genes implicated in the regulation of innate and adaptive immunity. The molecular data infer that vitamin D signaling should boost innate immunity against pathogens of bacterial or viral origin. Vitamin D signaling also suppresses inflammatory immune responses that underlie autoimmunity and regulate allergic responses. These findings have been bolstered by clinical studies linking vitamin D deficiency to increased rates of infections, autoimmunity, and allergies. Our goals here are to provide an overview of the molecular basis for immune system regulation and to survey the clinical data from pediatric populations, using randomized placebo-controlled trials and meta-analyses where possible, linking vitamin D deficiency to increased rates of infections, autoimmune conditions, and allergies, and addressing the impact of supplementation on these conditions.
Assuntos
Imunidade Adaptativa , Autoimunidade , Fenômenos Fisiológicos da Nutrição Infantil/imunologia , Suplementos Nutricionais , Imunidade Inata , Fatores Imunológicos , Vitamina D/farmacologia , Vitamina D/fisiologia , Fatores Etários , Doenças Autoimunes/etiologia , Criança , Pré-Escolar , Doenças Transmissíveis/etiologia , Feminino , Humanos , Hipersensibilidade/etiologia , Lactente , Masculino , Receptores de Calcitriol/metabolismo , Receptores de Calcitriol/fisiologia , Transdução de Sinais/fisiologia , Vitamina D/metabolismo , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/imunologiaRESUMO
Advancements in research and care have contributed to increase life expectancy of individuals with cystic fibrosis (CF). With increasing age comes a greater likelihood of developing CF bone disease, a comorbidity characterized by a low bone mass and impaired bone quality, which displays gender differences in severity. However, pathophysiological mechanisms underlying this gender difference have never been thoroughly investigated. We used bone marrow-derived osteoblasts and osteoclasts from Cftr+/+ and Cftr-/- mice to examine whether the impact of CF transmembrane conductance regulator (CFTR) deletion on cellular differentiation and functions differed between genders. To determine whether in vitro findings translated into in vivo observations, we used imaging techniques and three-point bending testing. In vitro studies revealed no osteoclast-autonomous defect but impairment of osteoblast differentiation and functions and aberrant responses to various stimuli in cells isolated from Cftr-/- females only. Compared with wild-type controls, knockout mice exhibited a trabecular osteopenic phenotype that was more pronounced in Cftr-/- males than Cftr-/- females. Bone strength was reduced to a similar extent in knockout mice of both genders. In conclusion, we find a trabecular bone phenotype in Cftr-/- mice that was slightly more pronounced in males than females, which is reminiscent of the situation found in patients. However, at the osteoblast level, the pathophysiological mechanisms underlying this phenotype differ between males and females, which may underlie gender differences in the way bone marrow-derived osteoblasts behave in absence of CFTR.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Osteoblastos/metabolismo , Animais , Osso e Ossos/metabolismo , Osso e Ossos/fisiologia , Diferenciação Celular/fisiologia , Fibrose Cística/metabolismo , Fibrose Cística/patologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Osteoblastos/fisiologia , Osteoclastos/metabolismo , Osteoclastos/fisiologia , Osteogênese/fisiologia , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: Weight gain is commonly seen in lung transplant (LTx) recipients. Although previous studies have focused on weight changes at fixed time periods and relatively early after transplant, trends over time and long-term weight evolution have not been described in this population. The study objectives were to document weight changes up to 15 years post-LTx and assess the predictors of post-LTx weight changes and their associations with mortality. METHODS: Retrospective cohort study of LTx recipients between January 1, 2000, and November 30, 2016 (n = 502). Absolute weight changes from transplant were calculated at fixed time periods (6 mo, 1, 2, 5, 10, and 15 y), and continuous trends over time were generated. Predictors of weight changes and their association with mortality were assessed using linear and Cox regression analysis. RESULTS: LTx recipients experienced a gradual increase in weight, resulting from the combination of multiple weight trajectories. Interstitial lung disease diagnosis negatively predicted post-LTx weight changes at all time points, whereas transplant body mass index categories were significant predictors at earlier time points. Patients with a weight gain of >10% at 5 years had a better survival (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.20-0.66), whereas a 10% weight loss at earlier time points was associated with worse survival (1 y: HR, 2.04; 95% CI, 1.22-3.41 and 2 y: HR, 2.37; 95% CI, 1.22-4.58). CONCLUSIONS: Post-LTx weight changes display various trajectories, are predicted to some extent by individual and LTx-related factors, and have a negative or positive impact on survival depending on the time post-LTx. These results may lead to a better individualization of weight management after transplant.
Assuntos
Índice de Massa Corporal , Previsões , Transplante de Pulmão/mortalidade , Transplantados , Aumento de Peso/fisiologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Quebeque/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendênciasRESUMO
Nutritional deficiencies often precede the diagnosis of cystic fibrosis (CF) in infants, and occur at a stage where the rapidly developing brain is more vulnerable to insult. We aim to compare fat-soluble nutrient status of newly diagnosed non-screened infants with CF to that of healthy infants, and explore the association with neurodevelopment evaluated by electroencephalography (EEG). Our results show that CF infants had lower levels of all fat-soluble vitamins and docosahexaenoic acid (DHA) compared to controls. The auditory evoked potential responses were higher in CF compared to controls whereas the visual components did not differ between groups. DHA levels were correlated with auditory evoked potential responses. Although resting state frequency power was similar between groups, we observed a negative correlation between DHA levels and low frequencies. This study emphasizes the need for long-term neurodevelopmental follow-up of CF infants and pursuing intervention strategies in the future.