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1.
Int J Mol Sci ; 25(15)2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39125792

RESUMO

In recent years, there has been growing interest in understanding the potential role of microbiota dysbiosis or alterations in the composition and function of human microbiota in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). This systematic review evaluated the literature on CRSwNP and host microbiota for the last ten years, including mainly nasal bacteria, viruses, and fungi, following the PRISMA guidelines and using the major scientific publication databases. Seventy original papers, mainly from Asia and Europe, met the inclusion criteria, providing a comprehensive overview of the microbiota composition in CRSwNP patients and its implications for inflammatory processes in nasal polyps. This review also explores the potential impact of microbiota-modulating therapies for the CRSwNP treatment. Despite variability in study populations and methodologies, findings suggest that fluctuations in specific taxa abundance and reduced bacterial diversity can be accepted as critical factors influencing the onset or severity of CRSwNP. These microbiota alterations appear to be implicated in triggering cell-mediated immune responses, cytokine cascade changes, and defects in the epithelial barrier. Although further human studies are required, microbiota-modulating strategies could become integral to future combined CRSwNP treatments, complementing current therapies that mainly target inflammatory mediators and potentially improving patient outcomes.


Assuntos
Microbioma Gastrointestinal , Pólipos Nasais , Rinossinusite , Humanos , Doença Crônica , Disbiose/microbiologia , Microbiota , Pólipos Nasais/microbiologia , Rinossinusite/microbiologia
2.
Lung ; 201(3): 275-286, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37160771

RESUMO

PURPOSE: Chronic cough (cough that persists for ≥ 8 weeks) can cause a range of physical symptoms and psychosocial effects that significantly impair patients' quality of life. Refractory chronic cough (RCC) and unexplained chronic cough (UCC) are challenging to diagnose and manage, with substantial economic implications for healthcare systems. METHODS: This retrospective multicenter non-interventional study aimed to characterize the profile and health resource consumption of patients with RCC or UCC who attended outpatient clinics at Spanish hospitals. Data were collected from medical records of patients with RCC or UCC for up to 3 years before study inclusion. RESULTS: The patient cohort (n = 196) was representative of the chronic cough population (77.6% female, mean age 58.5 years). Two-thirds of patients (n = 126) had RCC. The most frequently visited doctors were pulmonologists (93.4% of patients) and primary care physicians (78.6%), with a mean of 5 visits per patient over three years' observation. The most common diagnostic tests were chest x-ray (83.7%) and spirometry with bronchodilation (77.0%). The most commonly prescribed treatments were proton pump inhibitors (79.6%) and respiratory medications (87.8%). Antibiotics were prescribed empirically to 56 (28.6%) patients. Differences between RCC or UCC groups related mainly to approaches used to manage cough-associated conditions (gastroesophageal reflux disease, asthma) in patients with RCC. CONCLUSION: RCC and UCC are responsible for high health resource utilization in Spanish hospitals. Specific treatments targeting the pathological processes driving chronic cough may provide opportunities to reduce the associated burden for patients and healthcare systems.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Tosse/diagnóstico , Tosse/etiologia , Tosse/terapia , Espanha/epidemiologia , Pacientes Ambulatoriais , Qualidade de Vida , Instituições de Assistência Ambulatorial , Hospitais , Doença Crônica
3.
J Pediatr ; 223: 108-113.e2, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32532647

RESUMO

OBJECTIVE: To evaluate the costs associated with evaluation of ß-lactam allergy in children labeled as allergic. STUDY DESIGN: We performed a prospective year-long real life observational study designed to evaluate all pediatric patients with suspected ß-lactam allergy who consulted for allergy evaluation. Direct and indirect costs were systematically recorded. Direct healthcare costs were calculated by taking into account the number of visits and all complementary and diagnostic tests performed. Direct nonhealthcare costs were calculated by considering the number of visits and the kilometers from their homes to the clinic. Finally, indirect costs were evaluated by considering the absenteeism of parents or other companions who took the children to the clinic. RESULTS: A total of 40 children with suspected allergy to ß-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct healthcare costs were $5038.03, with an average cost per patient of $125.95. Direct nonhealthcare costs reached $901.87 ($22.55 per patient) and indirect nonhealthcare costs reached $6384.35 ($159.61 per patient). The total cost was $12 324.25, a cost of $308.11 per patient. CONCLUSIONS: Elective evaluation of ß-lactam allergy and delabeling children who are not allergic is not expensive. In addition, it could save future expenses because of an unnecessary lifelong use of alternative antibiotics that are usually more expensive, less effective, and more frequently associated with antimicrobial resistance and different side effects.


Assuntos
Antibacterianos/administração & dosagem , Hipersensibilidade a Drogas/diagnóstico , beta-Lactamas/efeitos adversos , Criança , Análise Custo-Benefício , Hipersensibilidade a Drogas/economia , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Estudos Prospectivos , Testes Cutâneos/economia
4.
J Allergy Clin Immunol ; 144(3): 809-824, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30826363

RESUMO

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most prevalent primary immunodeficiencies, but their B-cell defects and underlying genetic alterations remain largely unknown. OBJECTIVE: We investigated patients with PADs for the distribution of 41 blood B-cell and plasma cell (PC) subsets, including subsets defined by expression of distinct immunoglobulin heavy chain subclasses. METHODS: Blood samples from 139 patients with PADs, 61 patients with common variable immunodeficiency (CVID), 68 patients with selective IgA deficiency (IgAdef), 10 patients with IgG subclass deficiency with IgA deficiency, and 223 age-matched control subjects were studied by using flow cytometry with EuroFlow immunoglobulin isotype staining. Patients were classified according to their B-cell and PC immune profile, and the obtained patient clusters were correlated with clinical manifestations of PADs. RESULTS: Decreased counts of blood PCs, memory B cells (MBCs), or both expressing distinct IgA and IgG subclasses were identified in all patients with PADs. In patients with IgAdef, B-cell defects were mainly restricted to surface membrane (sm)IgA+ PCs and MBCs, with 2 clear subgroups showing strongly decreased numbers of smIgA+ PCs with mild versus severe smIgA+ MBC defects and higher frequencies of nonrespiratory tract infections, autoimmunity, and affected family members. Patients with IgG subclass deficiency with IgA deficiency and those with CVID showed defects in both smIgA+ and smIgG+ MBCs and PCs. Reduced numbers of switched PCs were systematically found in patients with CVID (absent in 98%), with 6 different defective MBC (and clinical) profiles: (1) profound decrease in MBC numbers; (2) defective CD27+ MBCs with almost normal IgG3+ MBCs; (3) absence of switched MBCs; and (4) presence of both unswitched and switched MBCs without and; (5) with IgG2+ MBCs; and (6) with IgA1+ MBCs. CONCLUSION: Distinct PAD defective B-cell patterns were identified that are associated with unique clinical profiles.


Assuntos
Subpopulações de Linfócitos B/imunologia , Síndromes de Imunodeficiência/imunologia , Plasmócitos/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulinas/deficiência , Imunoglobulinas/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Environ Monit Assess ; 192(7): 414, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32500317

RESUMO

In this paper, differences in the pollen levels detected in two parts of Salamanca (a city in central-western Spain) have been revealed using two volumetric samplers. One sampler was located in the city centre and the other in a semi-natural zone. The two sampling devices were separated by a distance of 1.4 km. During the two-year study period, the most abundant allergenic pollen type was Poaceae, with peak values being detected in May. Maximum values were registered between April and June. The values obtained in both zones with regard to pollen seasonality were similar during the peak day, but the abundance of pollen grains detected in the semi-urban was higher, except for Olea pollen type. The atmospheric pollen season was similar in duration, except for some types belonging to the genera Plantago and Urticaceae, which showed divergent values most probably due to the influence of climatic conditions. The meteorological parameter most significantly correlated to pollen concentration was temperature, being negative for winter species and positive for plants preferring warmer climates. In addition, rainfall showed a negative correlation in most cases due to the influence of precipitation on the behaviour of atmospheric airborne pollen.


Assuntos
Alérgenos , Monitoramento Ambiental , Pólen , Alérgenos/análise , Cidades/estatística & dados numéricos , Estações do Ano , Espanha
8.
Pediatr Allergy Immunol ; 29(4): 369-374, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29369414

RESUMO

BACKGROUND: The overlapping grass and olive pollen seasons in Spain and the phenomenon of cross-reactivity can make it difficult to determine the true causative agent of seasonal allergic rhinitis when only skin prick tests with whole extracts are used. The aim of the GRAMOLE study was to determine sensitization patterns to the major grass and olive pollen allergens detected using specific recombinant IgE and to explore how this knowledge affected physicians' choice of allergen-specific immunotherapy. METHODS: Epidemiological, observational, multicenter, cross-sectional study. Results from children under 18 years of age diagnosed with seasonal allergic rhinitis by positive skin prick tests to olive and grass pollen were analyzed. Specific IgE to Phl p 1+5, Ole e 1, and Phl p 7+12 was determined. Investigators specified the optimal composition of allergen immunotherapy before and after knowing the results of the molecular diagnosis. RESULTS: A total of 281 patients with a mean age of 13.4 years were included. Double sensitization to both major allergens was found in vitro in 76% of children for an IgE cutoff point of 0.35 kU/L. When the molecular diagnosis results were known, specialists changed the composition of the prescribed immunotherapy in 52.87% of cases. CONCLUSIONS: Double sensitization to grass and olive pollen is common in Spain and also occurs in the pediatric population. Molecular diagnosis using specific IgE may help improve immunotherapy selection in polysensitized patients.


Assuntos
Alérgenos/imunologia , Dessensibilização Imunológica/métodos , Imunoglobulina E/sangue , Olea/imunologia , Poaceae/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/diagnóstico , Adolescente , Alérgenos/efeitos adversos , Antígenos de Plantas/imunologia , Biomarcadores/sangue , Criança , Pré-Escolar , Reações Cruzadas , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Olea/efeitos adversos , Poaceae/efeitos adversos , Pólen/efeitos adversos , Rinite Alérgica Sazonal/sangue , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/terapia , Espanha
9.
Int J Mol Sci ; 18(6)2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28635659

RESUMO

Asthma is an airway disease characterised by chronic inflammation with intermittent or permanent symptoms including wheezing, shortness of breath, chest tightness, and cough, which vary in terms of their occurrence, frequency, and intensity. The most common associated feature in the airways of patients with asthma is airway inflammation. In recent decades, efforts have been made to characterise the heterogeneous clinical nature of asthma. The interest in improving the definitions of asthma phenotypes and endotypes is growing, although these classifications do not always correlate with prognosis nor are always appropriate therapeutic approaches. Attempts have been made to identify the most relevant molecular and cellular biomarkers underlying the immunopathophysiological mechanisms of the disease. For almost 50 years, immunoglobulin E (IgE) has been identified as a central factor in allergic asthma, due to its allergen-specific nature. Many of the mechanisms of the inflammatory cascade underlying allergic asthma have already been elucidated, and IgE has been shown to play a fundamental role in the triggering, development, and chronicity of the inflammatory responses within the disease. Blocking IgE with monoclonal antibodies such as omalizumab have demonstrated their efficacy, effectiveness, and safety in treating allergic asthma. A better understanding of the multiple contributions of IgE to the inflammatory continuum of asthma could contribute to the development of novel therapeutic strategies for the disease.


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Asma/tratamento farmacológico , Imunoglobulina E/imunologia , Omalizumab/uso terapêutico , Animais , Asma/imunologia , Asma/fisiopatologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia
10.
Int J Mol Sci ; 18(3)2017 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-28264494

RESUMO

Omalizumab is marketed for chronic severe asthma patients who are allergic to perennial allergens. Our purpose was to investigate whether omalizumab is also effective in persistent severe asthma due to seasonal allergens. Thirty patients with oral corticosteroid-dependent asthma were treated with Omalizumab according to the dosing table. For each patient with asthma due to seasonal allergens, we recruited the next two consecutive patients with asthma due to perennial allergens. The dose of oral methyl prednisolone was tapered at a rate of 2 mg every two weeks after the start of treatment with omalizumab depending on tolerance. At each monthly visit, a forced spirometry and fractional exhaled nitric oxide (FeNO) measurement were performed and the accumulated monthly methyl prednisolone dose was calculated. At entry, there were no differences between groups in terms of gender, body mass index or obesity, year exacerbation rate, monthly dose of methyl-prednisolone (MP), FeNO and blood immunoglobuline E (IgE) MP, FeNO and IgE values, or spirometry (perennial: FVC: 76%; FEV1: 62%; seasonal: FVC: 79%; FEV1: 70%). The follow-up lasted 76 weeks. One patient in each group was considered a non-responder. Spirometry did not worsen in either group. There was a significant intragroup reduction in annual exacerbation rate and methyl prednisolone consumption but no differences were detected in the intergroup comparison. Omalizumab offered the same clinical benefits in the two cohorts regardless of whether the asthma was caused by a seasonal or a perennial allergen. These results strongly suggest that allergens are the trigger in chronic asthma but that it is the persistent exposure to IgE that causes the chronicity.


Assuntos
Corticosteroides/administração & dosagem , Alérgenos/imunologia , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/imunologia , Omalizumab/uso terapêutico , Estações do Ano , Administração Oral , Adulto , Idoso , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Asma/diagnóstico , Progressão da Doença , Eosinófilos , Expiração , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Omalizumab/administração & dosagem , Omalizumab/efeitos adversos , Testes de Função Respiratória , Índice de Gravidade de Doença , Testes Cutâneos , Resultado do Tratamento
12.
Pediatr Allergy Immunol ; 27(8): 867-870, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27612327

RESUMO

BACKGROUND: The objective of the OLFAPEDRIAL study was to assess the olfactory dysfunction in allergic paediatric population, which has been scarcely studied. METHODS: Observational, cross-sectional and multicentre study evaluated the sense of smell in untreated allergic rhinitis (AR) paediatric patients aged 6-12 years. RESULTS: Forty-four per cent (551 of 1260) of children with AR reported smell dysfunction, with both loss of smell frequency (52.1%, p < 0.001) and intensity (0.75 ± 0.84, p < 0.0001) being more frequent in patients with persistent than intermittent AR (38.0% and 0.51 ± 0.73, respectively). In addition, both loss of smell frequency and intensity increased according to disease severity (m-ARIA classification) but always being significantly higher in persistent (p < 0.0001) than in intermittent AR. CONCLUSIONS: Children with allergic rhinitis present a mild-moderate loss of smell frequency and intensity which is clearly related to the disease duration and severity. The loss of smell can be considered, as in adults, a clinical marker of disease severity.


Assuntos
Transtornos do Olfato/epidemiologia , Rinite Alérgica/epidemiologia , Olfato , Adulto , Criança , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Espanha/epidemiologia
16.
Clin Chem Lab Med ; 52(6): 799-807, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24445243

RESUMO

BACKGROUND: CYP2D6, a major drug-metabolizing enzyme, is encoded by a highly polymorphic and complex gene locus. We have identified a patient who failed to produce a CYP2D6 genotype with the AmpliChip P450 Test (AmpliChip), whereas his CYP2C19 genotype was readily determined. The aim of this investigation was to fully characterize the patient's CYP2D6 gene locus to resolve the AmpliChip no-call. METHODS: The case, a brother, and son were genotyped with the AmpliChip and subsequently characterized using long-range (XL)-PCR coupled with TaqMan assay technology. Copy number variation was assessed by XL-PCR and quantitative PCR. Selected XL-PCR products were sequenced. RESULTS: The AmpliChip also produced a no-call for the son; the brother produced a result. The two alleles of the case were subsequently found to carry additional gene units that likely caused the AmpliChip no-calls. One was characterized as a CYP2D6*68+*4 tandem (CYP2D6*68 is a hybrid gene composed of 2D6 and 2D7), the other as a rare CYP2D6*13+*2 tandem (CYP2D6*13 is a 2D7/2D6 hybrid formerly known as CYP2D6*77). A novel CYP2D6*2 subvariant was identified in the son; the brother also carried the CYP2D6*68+*4 tandem. CONCLUSIONS: The implementation of pharmacogenetics-guided drug therapy relies on accurate clinical-grade genotype analysis. Although the AmpliChip is deemed to be a reliable platform, numerous more recently discovered allelic variants and gene arrangements are not detected or trigger no-calls. Although such cases may be rare, the clinical/genetic testing community must be aware of the challenges of CYP2D6 testing on the AmpliChip platform and implications regarding accuracy of test results.


Assuntos
Citocromo P-450 CYP2D6/genética , Análise Mutacional de DNA/métodos , Genótipo , Idoso , Alelos , Simulação por Computador , Variações do Número de Cópias de DNA/genética , Reações Falso-Negativas , Loci Gênicos/genética , Humanos , Masculino
18.
Front Allergy ; 5: 1427279, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091349

RESUMO

Dysregulation of type 2 (T2) immune response leads to an aberrant inflammatory reaction that constitutes the pathophysiological basis of diseases involving various organs. For this reason, several disorders can coexist in a single patient; however, as different specialists often treat these pathologies, T2 dysregulation, particularly when mild, is not always the first diagnostic suspicion. A breakdown in interdisciplinary communication or the lack of adequate tools to detect these entities can delay diagnosis, and this, together with a lack of coordination, can lead to suboptimal care. In this context, a multidisciplinary group of specialists in pneumology, immunology, allergology, dermatology and otorhinolaryngology compiled a list of the cardinal symptoms reported by patients presenting with T2 inflammation-related diseases: asthma, chronic rhinosinusitis, allergic rhinitis, allergic conjunctivitis, IgE-mediated food allergy, atopic dermatitis, eosinophilic oesophagitis, and NSAID-exacerbated respiratory disease (NERD). Using this information, we propose a simple, patient-friendly questionnaire that can be administered at any level of care to initially screen patients for suspected coexisting T2 diseases and referral to the appropriate specialist.

19.
Ther Adv Respir Dis ; 18: 17534666241257166, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38888181

RESUMO

People with chronic cough (a cough lasting more than 8 weeks) are often referred to different specialists and undergo numerous diagnostic tests, but clear guidance is lacking. This work summarizes a consensus (an agreement) among medical specialists who are involved in managing people with chronic cough: primary care physicians (family doctors), pulmonologists (doctors who specialize in lung conditions), allergists (medical professionals specializing in allergies) and ear, nose and throat (ENT) specialists. They discussed how to perform a basic assessment of people with chronic cough in primary care (day-to-day healthcare given by a general practitioner or family doctor) and how to refer them to different specialists based on clinical findings or test results.


Assuntos
Tosse , Atenção Primária à Saúde , Encaminhamento e Consulta , Humanos , Tosse/diagnóstico , Tosse/fisiopatologia , Doença Crônica , Consenso , Especialização , Valor Preditivo dos Testes , Tosse Crônica
20.
Int J Clin Pharm ; 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38642250

RESUMO

BACKGROUND: Patients with a penicillin allergy label are at risk of an associated increase in adverse antibiotic events and hospitalization costs. AIM: We aimed to study the economic savings derived from the correct diagnosis and delabeling inpatients with suspected beta-lactam allergy, considering the acquisition cost of antimicrobials prescribed during a patient's hospital stay. METHOD: We prospectively evaluated patients admitted to the University Hospital of Salamanca who had been labeled as allergic to beta-lactams and performed a delabeling study. Subsequently, cost differences between antibiotics administered before and after the allergy study and those derived from those patients who received alternative antibiotics during admission and those who switched to beta-lactams after the allergy study were calculated. RESULTS: One hundred seventy-seven inpatients labeled as allergic to beta-lactams underwent a delabeling study; 34 (19.2%) were confirmed to have allergy to beta-lactams. Of the total number of patients, 136 (76.8%) received antibiotics during their hospitalization, involving a mean (SD) cost of €203.07 (318.42) and a median (IQR) cost of €88.97 (48.86-233.56). After delabeling in 85 (62.5%) patients, the antibiotic treatment was changed to beta-lactams. In this group of patients, the mean cost (SD) decreased from €188.91 (351.09) before the change to 91.31 (136.07) afterward, and the median cost (IQR) decreased from €72.92 (45.82-211.99) to €19.24 (11.66-168). The reduction was significant compared to the median cost of patients whose treatment was not changed to beta-lactams (p<0.001). CONCLUSION: Delabeling hospitalized patients represents a cost-saving measure for treating patients labeled as allergic to beta-lactams.

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