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1.
J Asthma ; : 1-3, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573361

RESUMO

Introduction: Asthma is one of the most common airway diseases that nearly all pediatricians will encounter in their clinical practice. Using spirometry to compare a patient's forced expiratory volume in one second (FEV1) both pre- and post-bronchodilator administration is the ideal way to document a paradoxical bronchodilator response. Case Study: Here, we present a patient who experienced paradoxical responses to short acting beta-2 agonists (SABAs; albuterol and levalbuterol). Results: This patient responded to an anti-cholinergic agent (ipratropium bromide) with both subjective as well as objective response. Conclusion: This case highlights the need to include paradoxical response to SABAs in the differential of a patient with poorly controlled asthma. It also provides an example of successful treatment of a pediatric patient with a class of medications previously reserved for adults with chronic obstructive pulmonary disease.

2.
J Allergy Clin Immunol Pract ; 7(6): 1970-1985.e4, 2019 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30877075

RESUMO

BACKGROUND: Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. OBJECTIVE: Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. METHODS: In reviewing the literature and our own database, we identified 85 patients with RAG deficiency, reported between 2001 and 2016, and compiled the largest case series to date of 63 patients with prominent autoimmune and/or hyperinflammatory pathology. RESULTS: Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. Most patients (55.6%) presented with more than 1 autoimmune or hyperinflammatory complication, with the most common etiologies being cytopenias (84.1%), granulomas (23.8%), and inflammatory skin disorders (19.0%). Infections, including live viral vaccinations, closely preceded the onset of autoimmunity in 28.6% of cases. Autoimmune cytopenias had early onset (median, 1.9, 2.1, and 2.6 years for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively). Evans syndrome specifically was associated with lack of response to first-line therapy. Treatment-refractory autoimmunity/hyperinflammation prompted hematopoietic stem cell transplantation in 20 patients. CONCLUSIONS: Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management.

3.
J Allergy Clin Immunol ; 144(1): 236-253, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30738173

RESUMO

BACKGROUND: Gain-of-function (GOF) mutations in PIK3CD cause a primary immunodeficiency characterized by recurrent respiratory tract infections, susceptibility to herpesvirus infections, and impaired antibody responses. Previous work revealed defects in CD8+ T and B cells that contribute to this clinical phenotype, but less is understood about the role of CD4+ T cells in disease pathogenesis. OBJECTIVE: We sought to dissect the effects of increased phosphoinositide 3-kinase (PI3K) signaling on CD4+ T-cell function. METHODS: We performed detailed ex vivo, in vivo, and in vitro phenotypic and functional analyses of patients' CD4+ T cells and a novel murine disease model caused by overactive PI3K signaling. RESULTS: PI3K overactivation caused substantial increases in numbers of memory and follicular helper T (TFH) cells and dramatic changes in cytokine production in both patients and mice. Furthermore, PIK3CD GOF human TFH cells had dysregulated phenotype and function characterized by increased programmed cell death protein 1, CXCR3, and IFN-γ expression, the phenotype of a TFH cell subset with impaired B-helper function. This was confirmed in vivo in which Pik3cd GOF CD4+ T cells also acquired an aberrant TFH phenotype and provided poor help to support germinal center reactions and humoral immune responses by antigen-specific wild-type B cells. The increase in numbers of both memory and TFH cells was largely CD4+ T-cell extrinsic, whereas changes in cytokine production and TFH cell function were cell intrinsic. CONCLUSION: Our studies reveal that CD4+ T cells with overactive PI3K have aberrant activation and differentiation, thereby providing mechanistic insight into dysfunctional antibody responses in patients with PIK3CD GOF mutations.

4.
Clin Immunol ; 197: 219-223, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30368009

RESUMO

Early onset multisystem autoimmunity is commonly the defining feature of IPEX. Recurrent sinopulmonary infections and CVID-like phenotype were not previously recognized as a presentation in IPEX. Herein, we describe three extended family members with IPEX. In addition to autoimmunity, all three had a CVID-like presentation consisting of recurrent sinopulmonary infections, hypogammaglobulinemia and B-cell class switching defect. In vitro studies have shown that the B cell class switching defect is not B cell intrinsic. Additionally, a marked increase in circulating T follicular helper (cTFH) cells with high IFN-γ and IL-17 secretion on stimulation was noted in our patients. The dysregulated cTFH cells could contribute to a decreased B cell class switching. However, the exact mechanism of how expanded and dysregulated cTFH lead to B cell class switching defect and hypogammaglobulinemia in our patients is not clear. Our study could extend the clinical spectrum of IPEX to include a CVID-like presentation.

5.
Mayo Clin Proc ; 93(10): 1423-1430, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30286830

RESUMO

OBJECTIVE: To determine the incidence and temporal trends of food allergies. PATIENTS AND METHODS: We performed a historical cohort study to describe the epidemiology of food allergies among residents of all ages in Olmsted County, Minnesota, during a 10-year period from January 2, 2002, through December 31, 2011, using the Rochester Epidemiology Project database. Overall incidence and trends in biannual incidence rates over time were evaluated. RESULTS: During the 10-year study period, 578 new cases of food allergies were diagnosed. The average annual incidence rate was significantly higher among males compared with females (4.1 [95% CI, 3.6-4.5] vs 3.0 [95% CI, 2.7-3.4]; P<.001; per 10,000 person-years; 3.6 per 10,000 person-years overall). The pediatric incidence rate of food allergy increased from 7.0 (95% CI, 6.2-8.9) to 13.3 (95% CI, 10.9-15.7) per 10,000 person-years between the 2002-2003 and 2006-2007 calendar periods and then stabilized at 12.5 and 12.1 per 10,000 person-years in the last 2 calendar periods. Milk, peanut, and seafood were the most common allergen in infancy, in children between ages 1 and 4 years, and in the adult population, respectively. CONCLUSION: This is one of the first population-based studies to examine the temporal trends of food allergies. The incidence of food allergies increased markedly between 2002 and 2009, with stabilization afterward. Additional longitudinal studies are warranted to assess for epidemiological evidence of changes in food allergy incidence with changing recommendations for allergenic food introduction.

7.
J Clin Immunol ; 38(3): 307-319, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29671115

RESUMO

PURPOSE: We report a female infant identified by newborn screening for severe combined immunodeficiencies (NBS SCID) with T cell lymphopenia (TCL). The patient had persistently elevated alpha-fetoprotein (AFP) with IgA deficiency, and elevated IgM. Gene sequencing for a SCID panel was uninformative. We sought to determine the cause of the immunodeficiency in this infant. METHODS: We performed whole-exome sequencing (WES) on the patient and parents to identify a genetic diagnosis. Based on the WES result, we developed a novel flow cytometric panel for rapid assessment of DNA repair defects using blood samples. We also performed whole transcriptome sequencing (WTS) on fibroblast RNA from the patient and father for abnormal transcript analysis. RESULTS: WES revealed a pathogenic paternally inherited indel in ATM. We used the flow panel to assess several proteins in the DNA repair pathway in lymphocyte subsets. The patient had absent phosphorylation of ATM, resulting in absent or aberrant phosphorylation of downstream proteins, including γH2AX. However, ataxia-telangiectasia (AT) is an autosomal recessive condition, and the abnormal functional data did not correspond with a single ATM variant. WTS revealed in-frame reciprocal fusion transcripts involving ATM and SLC35F2 indicating a chromosome 11 inversion within 11q22.3, of maternal origin. Inversion breakpoints were identified within ATM intron 16 and SLC35F2 intron 7. CONCLUSIONS: We identified a novel ATM-breaking chromosome 11 inversion in trans with a pathogenic indel (compound heterozygote) resulting in non-functional ATM protein, consistent with a diagnosis of AT. Utilization of several molecular and functional assays allowed successful resolution of this case.

8.
Diagn Microbiol Infect Dis ; 90(4): 300-306, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29398461

RESUMO

Norovirus is an emerging pathogen causing gastroenteritis. We sought to identify factors associated with clinical outcomes in a cohort of patients with laboratory-confirmed norovirus infection. We performed a retrospective chart review of patients with positive norovirus polymerase chain reaction in stool between October 1, 2015, and May 31, 2016. 128 unique patients were identified during the study period, 64 of whom had immune deficiency, of which only 3 patients had a primary immune deficiency (common variable immune deficiency), while 61 patients had a secondary immune deficiency. 50% of patients with immune deficiency were hospitalized as compared to only 30% of the non-immune-deficient cohort (odds ratio: 2.1 (1.1-4.18, P=0.04). One-third (32.8%) of the patients had a polymicrobial stool infection, and 21.1% had concurrent Clostridium difficile infection. Initial mean total leukocyte count was higher in the hospitalized group at 8.40×109/L versus 6.31×109/L in the nonhospitalized group (P=0.049). All 13 patients presenting with fever had symptomatic resolution (P=0.002). The presence of C. difficile infection was correlated with persistent symptoms (OR 2.30 [0.95-5.58], P=0.067). The overall mortality rate among our cohort was 3.13% (4 patients). All deceased patients had secondary immune deficiency, and none had C. difficile coinfection. Presence of an immune deficiency increases the risk of hospitalization with norovirus infection. Absence of fever is associated with lower resolution and possibly may contribute to a persistent infectious state. Presence of concomitant C. difficile infection is correlated with a lower overall mortality rate.


Assuntos
Infecções por Caliciviridae/complicações , Infecções por Caliciviridae/patologia , Hospitalização , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Infecções por Clostridium/epidemiologia , Coinfecção/epidemiologia , Fezes/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Norovirus/isolamento & purificação , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
10.
Allergy Asthma Proc ; 38(3): 21-28, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28441981

RESUMO

BACKGROUND: Vitamin D insufficiency has been associated with immune dysfunction and linked to the epidemic of atopic diseases in the Western hemisphere, yet there are studies with conflicting results, and the risk has not been quantified uniformly across studies. OBJECTIVE: To perform a systematic review and meta-analysis to evaluate and quantify if vitamin D deficiency is associated with the presence and persistence of food allergy. METHODS: A systematic review was undertaken to assess for the association between food allergy and vitamin D status in children. RESULTS: A total of 368 citations relevant to this systematic review were identified. In the whole review, 5105 children were included. We did not find a significant association between 25 hydroxy vitamin D (25(OH)D) status and risk of food allergy in children (odds ratio [OR] 1.35 [95% confidence interval {CI}, 0.79-2.29]; p = 0.27, I2 = 58.3%). We conducted subgroup analyses based on different cutoffs of the 25(OH)D status (20 versus 30 ng/mL). Only one study used 30 ng/mL and found that children with <30 ng/mL were more likely to report food allergy than children with a 25(OH)D status of ≥30 ng/mL (OR 2.04 [95% CI, 1.02-4.04]; p = 0.04). Four studies compared children with a 25(OH)D status of <20 ng/mL to children with a 25(OH)D status of ≥20 ng/mL and found no significant differences (OR 1.18 [95% CI, 0.62-2.27]; p = 0.62, I2 = 62.7%). CONCLUSION: Based on the studies analyzed, this systematic review did not identify a significant association between vitamin D status and food allergy. Interpretation of the included studies was limited by a lack of a standard definition for vitamin D deficiency and insufficient knowledge regarding the optimal vitamin D status needed to impact immune function. Longitudinal studies are warranted to assess if vitamin D might contribute to the development of food allergy.


Assuntos
Hipersensibilidade Alimentar/etiologia , Deficiência de Vitamina D/complicações , Vitamina D/normas , Criança , Humanos , Razão de Chances , Vitamina D/imunologia
11.
Ann Allergy Asthma Immunol ; 118(5): 614-620, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28254202

RESUMO

BACKGROUND: A subset of patients with common variable immunodeficiency (CVID) develop granulomatous lymphocytic interstitial lung disease (GLILD), which is associated with early mortality. OBJECTIVE: To determine a set of clinical and/or laboratory parameters that correlate with GLILD. METHODS: A retrospective, nested case-control (patients with CVID diagnosed with GLILD compared with patients with CVID without a diagnosis of GLILD) medical record review was undertaken at Mayo Clinic, Rochester, MN. Network and univariate analysis was used to identify clinical and laboratory parameters at the time of diagnosis that are associated with GLILD. RESULTS: Twenty-six cases with radiologic evidence of GLILD were included in this study. Eighteen cases (69%) cases had coexistent splenomegaly with lower IgA levels (P = .04) compared with the controls. Patients with low IgA levels (<13 mg/dL) also had percentage expansion of low CD21 B cells (CD21low >5%) (P = .007). Univariate analysis revealed that splenomegaly (odds ratio [OR], 17.3; 95% confidence interval [CI], 3.9-74.5), history of immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA) (OR, 4.8; 95% CI, 1.1-20.2), low IgA level (OR, 3.6; 95% CI, 1.2-11.9), and percentage expansion of CD21low (OR, 5.8; 95% CI, 1.6-24.7) were independently associated with GLILD. Logistic regression analysis revealed that splenomegaly, history of ITP or AIHA, low IgA level, and percentage expansion of CD21low B cells are highly sensitive in predicting presence of GLILD (area under the receiver operating curve of 0.86). CONCLUSION: Presence of splenomegaly, history of ITP or AIHA, low serum IgA level, and percentage expansion of CD21low B cells may be useful to identify a group of patients at high risk for development of GLILD.


Assuntos
Imunodeficiência de Variável Comum/complicações , Granuloma/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Algoritmos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Contagem de Leucócitos , Masculino , Fenótipo , Curva ROC , Testes de Função Respiratória , Estudos Retrospectivos
13.
Curr Opin Allergy Clin Immunol ; 16(6): 557-564, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27755184

RESUMO

PURPOSE OF REVIEW: Norovirus infection is an emerging chronic infection in immunocompromised hosts. The aim of this review is to discuss the pathophysiology of Norovirus infection and explore mechanistic models for chronic infection/shedder state, especially in patients with immune deficiency diseases. RECENT FINDINGS: Chronic Norovirus infection is increasingly associated with enteropathy associated with both primary and secondary immune deficiency diseases. There is an ongoing debate in the immune deficiency community whether it is truly a causative agent for the enteropathy or it is an innocent bystander.We describe the historic aspects of Norovirus infection, its immunology and viral structure and the basis for preventive and vaccination strategies.We also postulate in this review a disease model in immune deficiency subjects which creates a milieu for it to become a chronic and explore newer frontiers for disease modification and prevention. SUMMARY: Norovirus is the most common cause of acute gastroenteritis in general population but the factors that lead to its persistence in patients with immune deficiency need further holistic studies. This should include host assessment, microbiome signatures, and viral pathogenic factors assessment.


Assuntos
Infecções por Caliciviridae/imunologia , Gastroenterite/imunologia , Síndromes de Imunodeficiência/imunologia , Norovirus/fisiologia , Vacinas Virais/imunologia , Animais , Doença Crônica , Microbioma Gastrointestinal , Humanos , Hospedeiro Imunocomprometido , Virulência
14.
Case Reports Immunol ; 2016: 7945953, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27579193

RESUMO

The term disappearing HDL syndrome refers to development of severe high density lipoprotein cholesterol (HDL-C) deficiency in noncritically ill patients with previously normal HDL-C and triglyceride levels. Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of the immune system due to an inability to regulate lymphocyte homeostasis resulting in lymphadenopathy and hepatosplenomegaly. We describe a 17-year-old boy who was evaluated in the lipid clinic for history of undetectable or low HDL-C and low density lipoprotein cholesterol (LDL-C) levels. Past medical history was significant for ALPS IA diagnosed at 10 years of age when he presented with bilateral cervical adenopathy. He was known to have a missense mutation in one allele of the FAS protein extracellular domain consistent with ALPS type 1A. HDL-C and LDL-C levels had been undetectable on multiple occasions, though lipids had not been measured prior to the diagnosis of ALPS. He had been receiving sirolimus for immunosuppression. The HDL-C and LDL-C levels correlated with disease activity and improved to normal levels during times when the activity of ALPS was controlled. This case highlights the importance of considering ALPS as a cause of low HDL-C and LDL-C levels in a child with evidence of lymphoproliferation.

15.
J Clin Immunol ; 36(7): 725-32, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27539235

RESUMO

The use of HLA-identical hematopoietic stem cell transplantation (HSCT) demonstrates overall survival rates greater than 75 % for T-B-NK+ severe combined immunodeficiency secondary to pathogenic mutation of recombinase activating genes 1 and 2 (RAG1/2). Limited data exist regarding the use of HSCT in patients with hypomorphic RAG variants marked by greater preservation of RAG activity and associated phenotypes such as granulomatous disease in combination with autoimmunity. We describe a 17-year-old with combined immunodeficiency and immune dysregulation characterized by granulomatous lung disease and autoimmunity secondary to compound heterozygous RAG mutations. A myeloablative reduced toxicity HSCT was completed using an unrelated bone marrow donor. With the increasing cases of immune dysregulation being discovered with hypomorphic RAG variants, the use of HSCT may advance to the forefront of treatment. This case serves to discuss indications of HSCT, approaches to preparative therapy, and the potential complications in this growing cohort of patients with immune dysregulation and RAG deficiency.


Assuntos
Doenças Autoimunes/complicações , Doenças Autoimunes/genética , Doença Granulomatosa Crônica/complicações , Transplante de Células-Tronco Hematopoéticas , Proteínas de Homeodomínio/genética , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/terapia , Adolescente , Alelos , Doenças Autoimunes/diagnóstico , Biomarcadores , Doença Granulomatosa Crônica/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunofenotipagem , Infecção/diagnóstico , Infecção/etiologia , Infecção/terapia , Contagem de Linfócitos , Mutação , Imunodeficiência Combinada Severa/diagnóstico , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transplante Homólogo , Resultado do Tratamento
16.
Ann Allergy Asthma Immunol ; 116(2): 134-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26815706

RESUMO

BACKGROUND: Group B Streptococcus (GBS) is the leading infectious cause of neonatal morbidity and mortality in the United States. Intrapartum administration of antibiotics to mothers with positivity to GBS is performed for prevention, with penicillin being the drug of choice. Previous studies have noted an increase in atopic diseases other than drug allergy associated with intrapartum antibiotic exposure. OBJECTIVE: To determine whether intrapartum exposure to penicillin for GBS increases the likelihood of penicillin allergy in children. METHODS: Retrospective chart review was performed for patients from a birth cohort. The birth cohort included children born in 2007 at a tertiary care hospital and had local addresses. Information on GBS status of the mother, intrapartum antibiotic exposure, delivery mode, and birth order was collected and analyzed. RESULTS: Of 927 children identified, 804 were included in the cohort. Eighty children (10%) had a reported penicillin allergy; most were white (79%) and boys (61%). Intrapartum exposure to penicillin (odds ratio 0.84, 95% confidence interval 0.45-1.57, P = .59) or to amoxicillin or ampicillin (odds ratio 0.22, 95% confidence interval 0.01-3.71, P = .29) did not increase the risk of penicillin allergy in children. In addition, all other factors evaluated did not affect the risk of penicillin allergy in children. CONCLUSION: To the authors' knowledge, this is the first study to evaluate intrapartum exposure to penicillin for GBS treatment and subsequent development of penicillin allergy in the child. In contrast to other atopic diseases, intrapartum antibiotic exposure does not alter the risk of penicillin allergy. Parents and obstetricians should be reassured when using penicillin for prevention of neonatal GBS.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Hipersensibilidade a Drogas/epidemiologia , Penicilinas/efeitos adversos , Penicilinas/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Criança , Feminino , Humanos , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Masculino , Troca Materno-Fetal , Minnesota/epidemiologia , Gravidez , Estudos Retrospectivos , Infecções Estreptocócicas/prevenção & controle , Infecções Estreptocócicas/transmissão , Streptococcus agalactiae
17.
J Clin Invest ; 125(11): 4135-48, 2015 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-26457731

RESUMO

Patients with mutations of the recombination-activating genes (RAG) present with diverse clinical phenotypes, including severe combined immune deficiency (SCID), autoimmunity, and inflammation. However, the incidence and extent of immune dysregulation in RAG-dependent immunodeficiency have not been studied in detail. Here, we have demonstrated that patients with hypomorphic RAG mutations, especially those with delayed-onset combined immune deficiency and granulomatous/autoimmune manifestations (CID-G/AI), produce a broad spectrum of autoantibodies. Neutralizing anti-IFN-α or anti-IFN-ω antibodies were present at detectable levels in patients with CID-G/AI who had a history of severe viral infections. As this autoantibody profile is not observed in a wide range of other primary immunodeficiencies, we hypothesized that recurrent or chronic viral infections may precipitate or aggravate immune dysregulation in RAG-deficient hosts. We repeatedly challenged Rag1S723C/S723C mice, which serve as a model of leaky SCID, with agonists of the virus-recognizing receptors TLR3/MDA5, TLR7/-8, and TLR9 and found that this treatment elicits autoantibody production. Altogether, our data demonstrate that immune dysregulation is an integral aspect of RAG-associated immunodeficiency and indicate that environmental triggers may modulate the phenotypic expression of autoimmune manifestations.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Citocinas/imunologia , Proteínas de Ligação a DNA/deficiência , Doença Granulomatosa Crônica/imunologia , Proteínas de Homeodomínio/imunologia , Proteínas Nucleares/deficiência , Imunodeficiência Combinada Severa/imunologia , Adolescente , Adulto , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Especificidade de Anticorpos , Autoanticorpos/sangue , Doenças Autoimunes/genética , Criança , Pré-Escolar , RNA Helicases DEAD-box/imunologia , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Feminino , Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/terapia , Proteínas de Homeodomínio/genética , Humanos , Lactente , Helicase IFIH1 Induzida por Interferon , Masculino , Camundongos , Camundongos Endogâmicos , Proteínas Nucleares/genética , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/terapia , Receptores Toll-Like/agonistas , Receptores Toll-Like/imunologia , Viroses/imunologia , Adulto Jovem
18.
Ann Allergy Asthma Immunol ; 115(5): 396-401.e2, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26411971

RESUMO

BACKGROUND: Secondhand smoke (SHS) exposure can trigger asthma exacerbations in children. Different studies have linked increased asthma symptoms, health care use, and deaths in children exposed to SHS, but the risk has not been quantified uniformly across studies. OBJECTIVE: To perform a systematic review and meta-analysis to evaluate and quantify asthma severity and health care use from SHS exposure in children. METHODS: A systematic review was undertaken to assess the association between asthma severity and SHS in children. Inclusion criteria included studies that evaluated children with SHS exposure and reported outcomes of interest with asthma severity including exacerbations. Random effect models were used to combine the outcomes of interest (hospitalization, emergency department or urgent care visits, severe asthma symptoms, wheeze symptoms, and pulmonary function test results) from the included studies. RESULTS: A total of 1,945 studies were identified and 25 studies met the inclusion criteria. Children with asthma and SHS exposure were twice as likely to be hospitalized for asthma (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.20-2.86, P = .01) than children with asthma but without SHS exposure. SHS exposure also was significantly associated with emergency department or urgent care visits (OR 1.66, 95% CI 1.02-2.69, P = 0.04), wheeze symptoms (OR 1.32, 95% CI 1.24, 1.41, P < .001), and lower ratio of forced expiratory volume in 1 second to forced vital capacity (OR -3.34, 95% CI -5.35 to -1.33, P = .001). CONCLUSION: Children with asthma and SHS exposure are nearly twice as likely to be hospitalized with asthma exacerbation and are more likely to have lower pulmonary function test results.


Assuntos
Asma/epidemiologia , Asma/etiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adolescente , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Feminino , Volume Expiratório Forçado/fisiologia , Hospitalização , Humanos , Lactente , Masculino , Morbidade , Aceitação pelo Paciente de Cuidados de Saúde , Fatores de Risco , Índice de Gravidade de Doença
19.
Ann Allergy Asthma Immunol ; 115(3): 205-10, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26208757

RESUMO

BACKGROUND: Secondhand smoke (SHS) exposure is known to trigger asthma, but asthma disease severity and comorbidities in children exposed to SHS are not very well quantified. OBJECTIVE: To identify comorbidities and understand health care usage in children with asthma exposed to SHS (cases) compared with children with asthma but without SHS exposure (controls). METHODS: A retrospective nested matched case-and-control study was conducted with children 5 to 18 years old who were enrolled in the Pediatric Asthma Management Program. Pulmonary function testing (spirometry, methacholine challenges, and exhaled nitric oxide) and body mass index were reviewed. Influenza vaccination rates, oral steroid usage, emergency department visits, and hospitalizations were assessed. Network analysis of the 2 groups also was conducted to evaluate for any associations between the variables. RESULTS: Cases had significantly higher body mass index percentiles (>75%, odds ratio [OR] 1.64, 95% confidence interval [CI] 1.22-2.2, P = .001). Cases were less likely to have had a methacholine challenge (OR 0.49, 95% CI 0.36-0.68, P < .001) and an exhaled nitric oxide (OR 0.6, 95% CI 0.37-0.97, P = .04) performed than controls. The ratio of forced expiration volume in 1 second to forced vital capacity and forced expiration volume in 1 second were lower in cases than in controls (P < .05). Cases were less likely to have received an influenza vaccination (OR 0.61, 95% CI 0.45-0.82, P = .001) than controls. Unsupervised multivariable network analysis suggested a lack of discrete and unique subgroups between cases and controls. CONCLUSION: Children with asthma exposed to SHS are more likely to have comorbid conditions such as obesity, more severe asthma, and less health care usage than those not exposed to SHS. Smoking cessation interventions and addressing health disparities could be crucial in this vulnerable population.


Assuntos
Asma/epidemiologia , Exposição por Inalação , Poluição por Fumaça de Tabaco , Adolescente , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Expiração , Feminino , Volume Expiratório Forçado , Hospitalização/estatística & dados numéricos , Humanos , Vacinas contra Influenza , Masculino , Cloreto de Metacolina , Óxido Nítrico/metabolismo , Obesidade/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Espirometria , Vacinação/estatística & dados numéricos
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