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1.
BMC Pulm Med ; 21(1): 275, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425811

RESUMO

BACKGROUND: How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial. We investigated the effects of COPD and CS on the expression of SARS-CoV-2 entry receptor ACE2 in vivo in COPD patients and controls and in CS-exposed mice, and the effects of CS on SARS-CoV-2 infection in human bronchial epithelial cells in vitro. METHODS: We quantified: (1) pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and/or TMPRSS2 mRNA levels by RT-qPCR in two independent human cohorts; and (2) pulmonary ACE2 protein levels by immunostaining and ELISA in C57BL/6 WT mice exposed to air or CS for up to 6 months. The effects of CS exposure on SARS-CoV-2 infection were evaluated after in vitro infection of Calu-3 cells and differentiated human bronchial epithelial cells (HBECs), respectively. RESULTS: ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus controls but similar in central airways. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice. CS treatment decreased viral replication in Calu-3 cells, as determined by immunofluorescence staining for replicative double-stranded RNA (dsRNA) and western blot for viral N protein. Acute CS exposure decreased in vitro SARS-CoV-2 replication in HBECs, as determined by plaque assay and RT-qPCR. CONCLUSIONS: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/enzimologia , Fumar Cigarros/metabolismo , Doença Pulmonar Obstrutiva Crônica/enzimologia , SARS-CoV-2/fisiologia , Fumaça , Idoso , Idoso de 80 Anos ou mais , Enzima de Conversão de Angiotensina 2/genética , Animais , Brônquios , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Gravidade do Paciente , Alvéolos Pulmonares , RNA Mensageiro/metabolismo , Mucosa Respiratória/metabolismo , Serina Endopeptidases/genética , Nicotiana , Replicação Viral
2.
Pharmacogenomics J ; 14(1): 41-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23508266

RESUMO

Reversibility of airway obstruction in response to ß2-agonists is highly variable among asthmatics, which is partially attributed to genetic factors. In a genome-wide association study of acute bronchodilator response (BDR) to inhaled albuterol, 534 290 single-nucleotide polymorphisms (SNPs) were tested in 403 white trios from the Childhood Asthma Management Program using five statistical models to determine the most robust genetic associations. The primary replication phase included 1397 polymorphisms in three asthma trials (pooled n=764). The second replication phase tested 13 SNPs in three additional asthma populations (n=241, n=215 and n=592). An intergenic SNP on chromosome 10, rs11252394, proximal to several excellent biological candidates, significantly replicated (P=1.98 × 10(-7)) in the primary replication trials. An intronic SNP (rs6988229) in the collagen (COL22A1) locus also provided strong replication signals (P=8.51 × 10(-6)). This study applied a robust approach for testing the genetic basis of BDR and identified novel loci associated with this drug response in asthmatics.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Adolescente , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/genética , Broncodilatadores/administração & dosagem , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
3.
Clin Exp Allergy ; 43(3): 304-11, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23414538

RESUMO

BACKGROUND: Epigenetic modifications may have a role in asthma susceptibility. OBJECTIVE: To investigate whether epigenetic modification at birth of a CpG site necessary for the regulation of IL-2 transcription (IL-2 Site1) is associated with the development of asthma during childhood. METHODS: Methylation of IL-2 Site1 was assessed in cord blood from 303 children (225 with atopic mothers); as controls, we measured methylation of a site not important in the transcription of IL-2 (IL-2 Site7) and methylation of the LINE-1 repetitive element. Children were followed to the age of 8 years. Information on severe asthma exacerbations and hospital admissions was collected from child's primary care medical record. To account for potential confounding by bronchiolitis, we used exacerbations/hospitalizations after age 1 year as primary outcomes. RESULTS: There were 49 severe exacerbations amongst 33 children, and 22 hospital admissions amongst 11 children. The risk of asthma exacerbation increased 1.07-fold (95% CI 1.01-1.14, P = 0.03) and the risk of hospital admission increased 1.12-fold (95% CI 1.04-1.20, P = 0.002) for each one per cent increase in IL-2 Site1 methylation. Children who were admitted to hospital at any time-point had significantly higher IL-2 Site1 methylation than children not admitted to hospital (P = 0.007). There was a significant interaction between age at exacerbation (P = 0.03) or hospital admission (P = 0.02) and methylation, with the effect of methylation increasing with increasing age. Methylation of the control IL-2 Site7 or LINE-1 was not a significant predictor of asthma exacerbations/hospital admission, and we found no association between IL-2 Site1 methylation and hospital admissions for other reasons (0.99 [0.92-1.06]). Cord blood mononuclear cell phytohemagglutinin-stimulated lymphoproliferative responses decreased significantly with increasing IL-2 Site1 methylation (P < 0.001). CONCLUSIONS: Increasing methylation in cord blood of a functional CpG site in the IL-2 promoter is associated with increased likelihood of severe asthma exacerbations and hospital admissions for asthma/wheeze between ages of 2 and 8 years.


Assuntos
Asma/genética , Metilação de DNA , Interleucina-2/genética , Regiões Promotoras Genéticas , Criança , Pré-Escolar , Ilhas de CpG , Epigênese Genética , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Elementos Nucleotídeos Longos e Dispersos , Ativação Linfocitária/imunologia , Linfócitos/imunologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Risco , Fatores de Risco
4.
Clin Exp Allergy ; 42(12): 1724-33, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23181788

RESUMO

BACKGROUND: Asthma is a common chronic respiratory disease in children and adults. An important genetic component to asthma susceptibility has long been recognized, most recently through the identification of several genes (e.g., ORMDL3, PDE4D, HLA-DQ, and TLE4) via genome-wide association studies. OBJECTIVE: To identify genetic variants associated with asthma affection status using genome-wide association data. METHODS: We describe results from a genome-wide association study on asthma performed in 3855 subjects using a panel of 455 089 single nucleotide polymorphisms (SNPs). RESULT: The genome-wide association study resulted in the prioritization of 33 variants for immediate follow-up in a multi-staged replication effort. Of these, a common polymorphism (rs9272346) localizing to within 1 Kb of HLA-DQA1 (chromosome 6p21.3) was associated with asthma in adults (P-value = 2.2E-08) with consistent evidence in the more heterogeneous group of adults and children (P-value = 1.0E-04). Moreover, some genes identified in prior asthma GWAS were nominally associated with asthma in our populations. CONCLUSION: Overall, our findings further replicate the HLA-DQ region in the pathogenesis of asthma. HLA-DQA1 is the fourth member of the HLA family found to be associated with asthma, in addition to the previously identified HLA-DRA, HLA-DQB1 and HLA-DQA2.


Assuntos
Asma/genética , Predisposição Genética para Doença , Antígenos HLA-DQ/genética , Cadeias alfa de HLA-DQ/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Asma/epidemiologia , Asma/fisiopatologia , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Allergy ; 66(5): 596-604, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21261657

RESUMO

The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy. A novel phenotype definition and an integrative translational approach are needed to understand how a network of molecular and environmental factors can lead to complex allergic diseases. A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts; (ii) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases; and (iv) Translational integration of systems biology outcomes into health care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes, thus expanding current knowledge of the genomic and environmental determinants of allergic diseases in an integrative way; (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the development of novel treatment modalities, and prevention of allergic diseases; (iii) Improving the health of European citizens as well as increasing the competitiveness and boosting the innovative capacity of Europe, while addressing global health issues and ethical issues.


Assuntos
Hipersensibilidade/etiologia , Comportamento Cooperativo , União Europeia , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/prevenção & controle , Sistemas de Medicação , Fenótipo , Biologia de Sistemas
6.
Clin Exp Allergy ; 40(2): 209-23, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19968655

RESUMO

Atopy is a highly prevalent condition and remains the single biggest risk factor for asthma. Although atopy has a heritable component, the time frame of the increase in the prevalence indicates that it is not due to genetic factors alone. The relationship between allergen exposure and sensitization is complex. Lipopolysaccharide (LPS) and its bioactive moiety endotoxin are common to all gram-negative bacteria, and have been used as a surrogate of microbial load. Endotoxin can be readily measured in dust collected from homes. Some studies have demonstrated a clear inverse dose-response relationship between exposure to endotoxin and the risk of atopy but this finding has not been reproduced in all studies. Our innate immune system recognizes LPS readily via the LPS signal transduction pathway, which has the trimolecular complex of CD14/TLR4/MD2 at the core. A common single-nucleotide polymorphism in the promoter region of CD14 rs2569190 C to T (CD14/-260 or CD14/-159) has been associated with elevated sCD14. Although early studies suggested that this variant was associated with more severe atopy, this finding was not uniformly replicated. It has now been demonstrated in four independent populations that high exposure to endotoxin in the domestic environment is protective against the development of atopy, but only among carriers of the C allele, that is, the environmental exposure is only relevant when taken in the context of the genotype. Furthermore, this interaction is biologically plausible. We propose that neither the environmental exposure nor the genotype in isolation is sufficient to cause complex diseases like asthma and atopy, but disease results from the one acting in the context of the other, of which CD14 and endotoxin is one example contributing to the risk for atopy.


Assuntos
Hipersensibilidade/imunologia , Lipopolissacarídeos/imunologia , Asma/genética , Asma/imunologia , Humanos , Hipersensibilidade/genética , Receptores de Lipopolissacarídeos/genética , Polimorfismo de Nucleotídeo Único/genética , Transdução de Sinais/imunologia
7.
bioRxiv ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33330864

RESUMO

INTRODUCTION: How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severity is controversial. We investigated the protein and mRNA expression of SARS-CoV-2 entry receptor ACE2 and proteinase TMPRSS2 in lungs from COPD patients and controls, and lung tissue from mice exposed acutely and chronically to CS. Also, we investigated the effects of CS exposure on SARS-CoV-2 infection in human bronchial epithelial cells. METHODS: In Cohort 1, ACE2-positive cells were quantified by immunostaining in FFPE sections from both central and peripheral airways. In Cohort 2, we quantified pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and TMPRSS2 mRNA levels by RT-qPCR. In C57BL/6 WT mice exposed to air or CS for up to 6 months, pulmonary ACE2 protein levels were quantified by triple immunofluorescence staining and ELISA. The effects of CS exposure on SARS-CoV-2 infection were evaluated after 72hr in vitro infection of Calu-3 cells. After SARS-CoV-2 infection, the cells were fixed for IF staining with dsRNA-specific J2 monoclonal Ab, and cell lysates were harvested for WB of viral nucleocapsid (N) protein. Supernatants (SN) and cytoplasmic lysates were obtained to measure ACE2 levels by ELISA. RESULTS: In both human cohorts, ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus both smoker and NS controls, but similar in central airways. TMPRSS2 levels were similar across groups. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice exposed to 3 and 6 months of CS. In Calu3 cells in vitro, CS-treatment abrogated infection to levels below the limit of detection. Similar results were seen with WB for viral N protein, showing peak viral protein synthesis at 72hr. CONCLUSIONS: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from uninfected COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-treatment did not affect ACE2 levels but potently inhibited SARS-CoV-2 replication in this in vitro model. These findings urge to further investigate the controversial effects of CS and COPD on SARS-CoV2 infection.

8.
Thorax ; 64(10): 894-900, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19581277

RESUMO

BACKGROUND: Previous studies on the relationship of chronic bronchitis to incident airflow limitation and all-cause mortality have provided conflicting results, with positive findings reported mainly by studies that included populations of young adults. This study sought to determine whether having chronic cough and sputum production in the absence of airflow limitation is associated with onset of airflow limitation, all-cause mortality and serum levels of C-reactive protein (CRP) and interleukin-8 (IL-8), and whether subjects' age influences these relationships. METHODS: 1412 participants in the long-term Tucson Epidemiological Study of Airway Obstructive Disease who at enrolment (1972-1973) were 21-80 years old and had FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) > or = 70% and no asthma were identified. Chronic bronchitis was defined as cough and phlegm production on most days for > or = 3 months in two or more consecutive years. Incidence of airflow limitation was defined as the first follow-up survey with FEV(1)/FVC <70%. Serum IL-8 and CRP levels were measured in cryopreserved samples from the enrolment survey. RESULTS: After adjusting for covariates, chronic bronchitis at enrolment significantly increased the risk for incident airflow limitation and all-cause mortality among subjects <50 years old (HR 2.2, 95% CI 1.3 to 3.8; and HR 2.2, 95% CI 1.3 to 3.8; respectively), but not among subjects > or = 50 years old (HR 0.9, 95% CI 0.6 to 1.4; and HR 1.0, 95% CI 0.7 to 1.3). Chronic bronchitis was associated with increased IL-8 and CRP serum levels only among subjects <50 years old. CONCLUSIONS: Among adults <50 years old, chronic bronchitis unaccompanied by airflow limitation may represent an early marker of susceptibility to the effects of cigarette smoking on systemic inflammation and long-term risk for chronic obstructive pulmonary disease and all-cause mortality.


Assuntos
Obstrução das Vias Respiratórias/mortalidade , Bronquite Crônica/mortalidade , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Obstrução das Vias Respiratórias/sangue , Obstrução das Vias Respiratórias/fisiopatologia , Bronquite Crônica/sangue , Bronquite Crônica/fisiopatologia , Proteína C-Reativa/metabolismo , Doença Crônica , Tosse/mortalidade , Tosse/fisiopatologia , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Interleucina-8/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Escarro/metabolismo , Capacidade Vital/fisiologia , Adulto Jovem
9.
J Clin Invest ; 100(12): 3184-8, 1997 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-9399966

RESUMO

The beta2-adrenergic receptor (beta2AR) agonists are the most widely used agents in the treatment of asthma, but the genetic determinants of responsiveness to these agents are unknown. Two polymorphic loci within the coding region of the beta2AR have been recently described at amino acids 16 and 27. It has been reported that glycine at codon 16 (Gly-16) is associated with increased agonist-promoted downregulation of the beta2AR as compared with arginine-16 (Arg-16). The form of the receptor with glutamic acid at codon 27 (Glu-27), on the other hand, has been shown to be resistant to downregulation when compared with glutamine-27 (Gln-27), but only when coexpressed with Arg-16. To assess if different genotypes of these two polymorphisms would show differential responses to inhaled beta2AR agonists, we genotyped 269 children who were participants in a longitudinal study of asthma. Spirometry was performed before and after administration of 180 microg of albuterol, and a positive response was considered an increase of >15.3% predicted FEV1. There was marked linkage disequilibrium between the two polymorphisms, with 97.8% of all chromosomes that carried Arg-16 also carrying Gln-27. When compared to homozygotes for Gly-16, homozygotes for Arg-16 were 5.3 times (95% confidence interval 1.6-17.7) and heterozygotes for beta2AR-16 were 2.3 times (1.3-4.2) more likely to respond to albuterol, respectively. Similar trends were observed for asthmatic and nonasthmatic children, and results were independent of baseline lung function, ethnic origin, and previous use of antiasthma medication. No association was found between the beta2AR-27 polymorphism and response to albuterol. These results may explain some of the variability in response to therapeutic doses of albuterol in children.


Assuntos
Albuterol/uso terapêutico , Asma/tratamento farmacológico , Asma/genética , Polimorfismo Genético , Receptores Adrenérgicos beta 2/genética , Agonistas Adrenérgicos beta/uso terapêutico , Alelos , Arginina/genética , Broncodilatadores/uso terapêutico , Criança , Ácido Glutâmico/genética , Glutamina/genética , Glicina/genética , Humanos , Desequilíbrio de Ligação , Estudos Longitudinais , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Sons Respiratórios/genética
10.
Artigo em Inglês | MEDLINE | ID: mdl-27567482

RESUMO

In light of the emerging field of Epi-informatics, ie, computational methods applied to epigenetic research, molecular docking, and dynamics, pharmacophore and activity landscape modeling and QSAR play a key role in the development of modulators of DNA methyltransferases (DNMTs), one of the major epigenetic target families. The increased chemical information available for modulators of DNMTs has opened up the avenue to explore the epigenetic relevant chemical space (ERCS). Herein, we discuss recent progress on the identification and development of inhibitors of DNMTs as potential epi-drugs and epi-probes that have been driven by molecular modeling and chemoinformatics methods. We also survey advances on the elucidation of their structure-activity relationships and exploration of ERCS. Finally, it is illustrated how computational approaches can be applied to identify modulators of DNMTs in food chemicals.


Assuntos
Metilases de Modificação do DNA/metabolismo , Epigênese Genética , Serviços de Informação , Modelos Moleculares , Simulação por Computador , Metilases de Modificação do DNA/química
12.
Pediatrics ; 87(2): 190-8, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1987530

RESUMO

Respiratory failure is almost certainly the cause of death in the majority of cases of sudden infant death syndrome (SIDS), but the mechanisms leading to it have not been elucidated. SIDS shares many environmental and socioeconomic risk factors with severe forms of bronchiolitis, and the age distribution of incident cases is similar. Present knowledge of lung and airway development during infancy, determinants of peripheral airway patency, changes in lung surface activity in infants with SIDS, and fluid film dynamics in small airways are reviewed. It is hypothesized that many cases of SIDS may be due to a final episode of progressive peripheral bronchial occlusion in infants with preceding critically diminished conductance of the smaller airways.


Assuntos
Obstrução das Vias Respiratórias/complicações , Morte Súbita do Lactente/etiologia , Obstrução das Vias Respiratórias/fisiopatologia , Humanos , Recém-Nascido , Ventilação Pulmonar/fisiologia
13.
Pediatrics ; 89(1): 21-6, 1992 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1728015

RESUMO

The relationship between parental smoking and both subsequent development of asthma and subsequent lung function (before age 12) was studied in more than 700 children enrolled before age 5. Children of mothers with 12 or fewer years of education and who smoked 10 or more cigarettes per day were 2.5 times more likely (95% confidence interval 1.42 to 4.59; P = .0018) to develop asthma and had 15.7% lower maximal midexpiratory flow (P less than .001) than children of mothers with the same education level who did not smoke or smoked fewer than 10 cigarettes per day. These relationships were independent of self-reported respiratory symptoms in parents. There was no association between maternal smoking and subsequent incidence of asthma or maximal midexpiratory flow among children of mothers with more than 12 years of education. It is concluded that children of lower socioeconomic status may be at considerable risk of developing asthma if their mothers smoke 10 or more cigarettes per day. It is speculated that recently reported increases in prevalence of childhood asthma may be in part related to the increased prevalence of smoking among less educated women.


Assuntos
Asma/epidemiologia , Mães , Fumar/efeitos adversos , Asma/etiologia , Asma/fisiopatologia , Pré-Escolar , Escolaridade , Feminino , Humanos , Incidência , Lactente , Estudos Longitudinais , Pulmão/fisiopatologia , Masculino , Testes de Função Respiratória
14.
Pediatrics ; 94(6 Pt 1): 895-901, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7971008

RESUMO

OBJECTIVE: To investigate the natural history of and risk factors for allergic rhinitis in the first 6 years of life. METHODS: Parents of 747 healthy children followed from birth completed a questionnaire when the child was 6 years old. Data were obtained regarding physician-diagnosed allergic rhinitis (PDAR), associated symptoms, and age at onset. Risk-factor data were taken from earlier questionnaires, and data regarding immunoglobulin E (IgE) and skin-test reactivity were obtained at age 6. RESULTS: By the age of 6, 42% of children had PDAR. Children whose rhinitis began in the first year of life had more respiratory symptoms at age 6 and were more likely to have a diagnosis of asthma. Early introduction of foods or formula, heavy maternal cigarette smoking in the first year of life, and higher IgE, as well as parental allergic disorders, were associated with early development of rhinitis. Risk factors for PDAR that remained significant in a multivariate model included maternal history of physician-diagnosed allergy (odds ratio: 2.2, 95% confidence interval: 1.35-3.54), asthma in the child (4.06, 2.06-7.99), and IgE greater than 100 IU/mL at age 6 (1.93, 1.18-3.17). The odds for atopic as opposed to nonatopic PDAR were significantly higher only among those with high IgE and those who had dogs. CONCLUSION: Allergic rhinitis developing in the first years of life is an early manifestation of an atopic predisposition, which may be triggered by early environmental mental exposures.


Assuntos
Médicos , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/epidemiologia , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/epidemiologia , Idade de Início , Arizona/epidemiologia , Criança , Humanos , Prevalência , Estudos Prospectivos , Rinite Alérgica Perene/classificação , Rinite Alérgica Perene/etiologia , Rinite Alérgica Sazonal/classificação , Rinite Alérgica Sazonal/etiologia , Fatores de Risco , Estatística como Assunto , Inquéritos e Questionários
15.
Pediatrics ; 91(5): 867-72, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8474804

RESUMO

OBJECTIVE: This study was designed to assess the relation of exclusive breast-feeding, independent of recognized risk factors, to acute and recurrent otitis media in the first 12 months of life. METHODS: Records of 1220 infants who used a health maintenance organization and who were followed during their first year of life as part of the Tucson Children's Respiratory Study were reviewed. Detailed prospective information about the duration and exclusiveness of breast-feeding was obtained, as was information relative to potential risk factors (socioeconomic status, gender, number of siblings, use of day care, maternal smoking, and family history of allergy). Acute otitis media and recurrent otitis media, defined as three or more episodes of acute otitis media in a 6-month period or four episodes in 12 months, were the outcome variables. RESULTS: Of the 1013 infants followed for their entire first year, 476 (47%) had at least one episode of otitis and 169 (17%) had recurrent otitis media. Infants exclusively breast-fed for 4 or more months had half the mean number of acute otitis media episodes as did those not breastfed at all and 40% less than those infants whose diets were supplemented with other foods prior to 4 months. The recurrent otitis media rate in infants exclusively breast-fed for 6 months or more was 10% and was 20.5% in those infants who breast-fed for less than 4 months. This protection was independent of the risk factors considered. CONCLUSION: These findings suggest that exclusive breast-feeding of 4 or more months protected infants from single and recurrent episodes of otitis media.


Assuntos
Aleitamento Materno , Otite Média/prevenção & controle , Doença Aguda , Intervalos de Confiança , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Razão de Chances , Otite Média/epidemiologia , Estudos Prospectivos , Recidiva , Fatores de Tempo
16.
Pediatrics ; 91(5): 885-92, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8474807

RESUMO

BACKGROUND: Day-care attendance has been associated with an increased risk of hospitalization for lower respiratory tract illnesses (LRIs). This study examines, in a health maintenance organization population of children, the associations between child day care and the occurrence of LRIs in the first 3 years of life. Smoking by caregivers and a possible protective effect of longer day-care enrollment in relation to LRIs are also addressed. METHODS: Information on day-care arrangements was elicited from 1006 parents of infants for five age intervals in the first 3 years of life: birth through 3 months, 4 to 6 months, 6 to 12 months, 1 to 2 years, and 2 to 3 years. Data on LRIs in the first 3 years of life were recorded by pediatricians at the time of the acute illnesses. RESULTS: After controlling for other risk factors, the presence of three or more unrelated children in the care setting was associated with significant risks of LRI of up to twofold or more from 4 months of age to 3 years. Type of care setting was not a significant risk factor during this time period. In the third year of life, the risk of wheezing LRI in the presence of a smoking caregiver was more than threefold for those in another residential home setting. No significant protective effect against LRIs in the third year of life associated with longer prior day-care enrollment was demonstrated. CONCLUSION: The presence of three or more unrelated children in the care setting and the presence of a smoking caregiver were significant independent risk factors for LRIs during the first 3 years of life. Prolonged day-care did not protect against LRIs in the third year of life.


Assuntos
Cuidadores , Creches , Infecções Respiratórias/etiologia , Fumar/efeitos adversos , Pré-Escolar , Humanos , Incidência , Lactente , Recém-Nascido , Análise Multivariada , Razão de Chances , Infecções Respiratórias/epidemiologia , Fatores de Risco , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/efeitos adversos
17.
Pediatrics ; 95(5): 670-7, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7724301

RESUMO

OBJECTIVE: This study examined, in a health maintenance organization population of children, the associations between parents' smoking and otitis media (OM) in their children while controlling for other known risk factors. METHODS: Healthy newborns (1246) in a large health maintenance organization were enrolled at birth, and 1013 (81%) were followed prospectively for the first year of life. Their medical records were reviewed for the diagnosis of otitis media. Information on risk factors for recurrent OM (ROM) was collected, including a number of variables related to parental smoking. RESULTS: After controlling for other known risk factors for ROM including gender, day care, other siblings in the home, parental history of hay fever, and method of feeding, it was found that heavy maternal smoking of 20 or more cigarettes per day was a significant risk factor for ROM but not for nonrecurrent otitis. Heavy maternal smoking was associated with a threefold risk for ROM if the infant weighed less than the mean at birth (3.5 kg) after controlling for other risk factors. No association was found with paternal smoking. CONCLUSIONS: Heavy maternal smoking is a significant risk factor for ROM in the first year of life. This smoking effect seems to be stronger among infants of lower birth weight.


Assuntos
Otite Média/etiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Análise de Variância , Peso ao Nascer , Pai , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Estudos Prospectivos , Recidiva , Fatores de Risco
18.
Arch Pediatr Adolesc Med ; 149(7): 758-63, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7795765

RESUMO

OBJECTIVES: To investigate the relationship of infant feeding to recurrent wheezing at age 6 years and to assess whether this relationship is altered by a history of wheezing lower respiratory tract illnesses. DESIGN: Prospective, longitudinal study of healthy infants followed up from birth to 6 years of age. SETTING: Nonselected health maintenance organization population in Tucson, Arizona. PARTICIPANTS: There were 1246 healthy infants enrolled at birth, 988 of whom had data on both infant feeding and wheezing at age 6 years. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Recurrent wheeze (four or more episodes in the past year) was assessed by a questionnaire that was completed by parents when the children were 6 years old. Children were classified by atopic status on the basis of skin prick tests. RESULTS: Breast-feeding information was collected prospectively, and lower respiratory tract illnesses in the first 3 years of life were diagnosed by the pediatrician. Being breast-fed was associated with lower rates of recurrent wheeze at age 6 years (3.1% vs 9.7%, P < .01) for nonatopic children; this relationship was not significant for atopic children. The relationship of breast-feeding with recurrent wheeze was apparent among nonatopic children both with and without a wheezing lower respiratory tract illness in the first 6 months of life. When potential confounders, including early wheezing lower respiratory tract illness, were included in a multivariate model, nonatopic children who had not been breast-fed had three times the odds of wheezing recurrently (odds ratio, 3.03; confidence interval, 1.06 to 8.69). Eleven percent of recurrent wheeze among nonatopic children could be attributed to not breast-feeding. CONCLUSIONS: Recurrent wheeze at age 6 years is less common among nonatopic children who were breast-fed as infants. This effect is independent of whether the child wheezed with a lower respiratory tract illness in the first 6 months of life.


Assuntos
Aleitamento Materno , Sons Respiratórios , Criança , Feminino , Humanos , Hipersensibilidade , Recém-Nascido , Modelos Logísticos , Estudos Longitudinais , Masculino , Razão de Chances , Prevalência , Recidiva , Infecções Respiratórias/epidemiologia , Fatores de Risco
19.
Pediatr Pulmonol ; 9(2): 91-5, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2399052

RESUMO

We studied maximal expiratory flows at functional residual capacity (VmaxFRC) obtained by use of the chest compression technique in 9 infants who had signs of upper respiratory illness (URI) at the time of testing, and in 9 infants who were symptom-free but whose parents reported they had a URI in the previous month. When compared to 109 infants with no URI, infants with current URI had 40% lower VmaxFRC (mean +/- SD: 125.7 +/- 54.5 mL/s vs. 73.6 +/- 53.6 mL/s; P less than 0.01). Infants with a past URI had mean values for VmaxFRC (120.2 +/- 50.2 mL/s) that were not significantly different from those of infants with no URI. Changes in the shape of the flow-volume loop analogous to those reported in infants with lower airway obstruction were also noticed in infants with current URI. These findings suggest that, as in older children and adults, clinically unapparent alterations in lower airway function occur during URI in infants.


Assuntos
Fluxo Expiratório Forçado/fisiologia , Fluxo Expiratório Máximo/fisiologia , Doenças Respiratórias/fisiopatologia , Análise de Variância , Resfriado Comum/fisiopatologia , Feminino , Capacidade Residual Funcional/fisiologia , Humanos , Lactente , Recém-Nascido , Masculino , Rinite/fisiopatologia , Fatores Sexuais
20.
Pediatr Pulmonol ; 22(3): 141-6, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8893251

RESUMO

The purpose of this study was to assess the prevalence of sinusitis in a nonselected sample of children, and the relation of sinusitis to allergic rhinitis (AR), atopy, asthma, and cough in the same population sample. Of 1246 children enrolled at birth in the Tucson Children's Respiratory Study, 835 were studied at a mean age +/-SD of 8.6 +/- 0.7 years. Questionnaires asking about MD-Sinusitis, MD-AR, MD-Asthma, and cough were completed by parents. Skin tests for seven common aeroallergens in the Tucson area had been performed in 630 of the participating children at the mean age +/-SD of 6.3 +/- 0.9 years. Prevalence of MD-Sinusitis was 13.1%; 78% of subjects with MD-Sinusitis also had MD-AR. Detailed analysis of the relation between MD-Sinusitis and individual environmental allergens tested for showed that only a response to Bermuda grass pollen was significantly associated with MD-Sinusitis after controlling for MD-AR [adjusted odds ratio 2.3 (95% CI 1.2-4.3)]. Having MD-Sinusitis was also significantly associated with MD-Asthma and cough [odds ratios 3.0 (95% CI 1.8-5.2)] and 2.5 (95% CI 1.6-3.8), respectively]. However, logistic regression demonstrated that, after controlling for MD-AR and skin test reactivity, MD-Sinusitis was no longer significantly associated with MD-Asthma or cough. We conclude that MD-Sinusitis is a common condition in childhood. The main independent risk factors in our community for MD-Sinusitis were grass pollen and current MD-AR. MD-Sinusitis was not associated with MD-Asthma or with cough after controlling for skin test reactivity and for MD-AR.


Assuntos
Asma/complicações , Hipersensibilidade Respiratória/complicações , Rinite Alérgica Sazonal/complicações , Sinusite/complicações , Alérgenos/imunologia , Arizona/epidemiologia , Asma/epidemiologia , Criança , Pré-Escolar , Tosse/complicações , Humanos , Lactente , Pólen/imunologia , Prevalência , Rinite Alérgica Sazonal/epidemiologia , Sinusite/epidemiologia , Testes Cutâneos , Inquéritos e Questionários
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