Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 251
Filtrar
1.
JAMA ; 331(10): 866-877, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470381

RESUMO

Importance: Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations: Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance: Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.


Assuntos
Glucocorticoides , Antagonistas dos Receptores Histamínicos , Rinite Alérgica , Humanos , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Cetirizina/uso terapêutico , Fluticasona/administração & dosagem , Fluticasona/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Imunoglobulina E/imunologia , Furoato de Mometasona/administração & dosagem , Furoato de Mometasona/uso terapêutico , Cloridrato de Olopatadina/administração & dosagem , Cloridrato de Olopatadina/uso terapêutico , Prurido/etiologia , Rinite Alérgica/complicações , Rinite Alérgica/diagnóstico , Rinite Alérgica/imunologia , Rinite Alérgica/terapia , Rinorreia/etiologia , Espirro , Triancinolona/administração & dosagem , Triancinolona/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Rinite/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/uso terapêutico , Administração Intranasal
2.
Pharm Res ; 39(2): 317-327, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35137359

RESUMO

BACKGROUND: Optimising intranasal distribution and retention of topical therapy is essential for effectively managing patients with chronic rhinosinusitis, including those that have had functional endoscopic sinus surgery (FESS). This study presents a new technique for quantifying in vitro experiments of fluticasone propionate deposition within the sinuses of a 3D-printed model from a post-FESS patient. METHODS: Circular filter papers were placed on the sinus surfaces of the model. Deposition of fluticasone on the filter paper was quantified using high-performance liquid chromatography (HPLC) assay-based techniques. The deposition patterns of two nasal drug delivery devices, an aqueous nasal spray (Flixonase) and metered dose inhaler (Flixotide), were compared. The effects of airflow (0 L/min vs. 12 L/min) and administration angle (30° vs. and 45°) were evaluated. RESULTS: Inhaled airflow made little difference to sinus deposition for either device. A 45° administration angle improved frontal sinus deposition with the nasal spray and both ethmoidal and sphenoidal deposition with the inhaler. The inhaler provided significantly better deposition within the ethmoid sinuses (8.5x) and within the maxillary sinuses (3.9x) compared with the nasal spray under the same conditions. CONCLUSION: In the post-FESS model analysed, the inhaler produced better sinus deposition overall compared with the nasal spray. The techniques described can be used and adapted for in vitro performance testing of different drug formulations and intranasal devices under different experimental conditions. They can also help validate computational fluid dynamics modelling and in vivo studies.


Assuntos
Fluticasona/administração & dosagem , Glucocorticoides/administração & dosagem , Modelos Anatômicos , Seios Paranasais/metabolismo , Administração por Inalação , Composição de Medicamentos , Feminino , Fluticasona/química , Fluticasona/metabolismo , Glucocorticoides/química , Glucocorticoides/metabolismo , Humanos , Inaladores Dosimetrados , Pessoa de Meia-Idade , Sprays Nasais , Seios Paranasais/anatomia & histologia , Seios Paranasais/cirurgia , Impressão Tridimensional , Distribuição Tecidual , Cirurgia Endoscópica Transanal
3.
Sci Rep ; 12(1): 446, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013387

RESUMO

Steroid resistance in asthma has been associated with neutrophilic inflammation and severe manifestations of the disease. Macrolide add-on therapy can improve the quality of life and the exacerbation rate in refractory cases, possibly with greater effectiveness in neutrophilic phenotypes. The mechanisms leading to these beneficial effects are incompletely understood and whether macrolides potentiate the modulation of bronchial remodeling induced by inhaled corticosteroids (ICS) is unknown. The objective of this study was to determine if adding azithromycin to ICS leads to further improvement of lung function, airway inflammation and bronchial remodeling in severe asthma. The combination of azithromycin (10 mg/kg q48h PO) and inhaled fluticasone (2500 µg q12h) was compared to the sole administration of fluticasone for five months in a randomized blind trial where the lung function, airway inflammation and bronchial remodeling (histomorphometry of central and peripheral airways and endobronchial ultrasound) of horses with severe neutrophilic asthma were assessed. Although the proportional reduction of airway neutrophilia was significantly larger in the group receiving azithromycin, the lung function and the peripheral and central airway smooth muscle mass decreased similarly in both groups. Despite a better control of airway neutrophilia, azithromycin did not potentiate the other clinical effects of fluticasone.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Antibacterianos/uso terapêutico , Asma/veterinária , Azitromicina/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Administração por Inalação , Animais , Antibacterianos/farmacologia , Asma/tratamento farmacológico , Asma/imunologia , Azitromicina/farmacologia , Broncodilatadores/administração & dosagem , Quimioterapia Combinada , Feminino , Fluticasona/administração & dosagem , Doenças dos Cavalos/imunologia , Cavalos , Masculino , Neutrófilos
4.
Rev. clín. med. fam ; 14(3): 162-164, Oct. 2021. ilus
Artigo em Espanhol | IBECS | ID: ibc-230128

RESUMO

La mezcla de la henna natural con parafenilendiamina (PPD), un colorante sintético potenciador del color y la duración de los tatuajes, puede producir una reacción infrecuente de hipersensibilidad tipo IV. Presentamos el caso clínico de una mujer que presentó una reacción cutánea intensa un mes después de hacerse un tatuaje con henna negra. Dicha reacción se manifestó con maculopápulas sobreelevadas que reproducen el dibujo del tatuaje.(AU)


Mixing natural henna with paraphenyldiamine (PPD), a synthetic dye that enhances the colour and duration of tattoos, can produce a rare type IV hypersensitivity reaction. We report the case study of a woman with an intense skin reaction one month after undergoing a tattoo with black henna. This reaction manifested with raised maculopapules that reproduced the tattoo's pattern.(AU)


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Lawsonia (Planta)/efeitos adversos , Tatuagem/efeitos adversos , Hipersensibilidade , Pele/lesões , Tratamento Farmacológico , Fluticasona/administração & dosagem , Pacientes Internados , Exame Físico
5.
Immunopharmacol Immunotoxicol ; 43(6): 767-777, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34581242

RESUMO

OBJECTIVE: Atopic dermatitis (AD) is a pruritic, chronic, relapsing inflammatory skin disease. The research aims to study the effects of Sarsasapogenin and its combination with Fluticasone in 2, 4-Dinitrofluorobenzene (DNFB) induced atopic dermatitis in BALB/c mice. MATERIAL AND METHODS: Thirty male Balb/c mice were divided into 5 groups: (i) Normal control (NC), (ii) Disease control (DNFB), (iii) Sarsasapogenin (SG) (50 µg/mice), (iv) Fluticasone (FC) (50 µg/mice), (v) Sarsasapogenin + Fluticasone (SG + FC) combination (25 µg/mice). Dermatitis was induced by repeated application of DNFB in Balb/c mice. On topical application of SG, FC, and SG + FC combination on the ear and skin lesions, body weight, ear weight, ear thickness, erythema score, spleen weight, cytokines, immunoglobulin E (IgE) levels, nitric oxide (NO) level, hematological parameters, and oxidative stress markers were evaluated. Histological analysis of the ear tissue was also done. RESULTS: The results stated that SG and SG + FC treatment to mice considerably decrease the ear weight, ear thickness, spleen weight, serum IgE, cytokines, NO levels, and restoration of antioxidant stress markers with elevation in the hematological parameters. The observations were further confirmed by histopathological analysis of ear tissue. CONCLUSION: These data specify that SG has been demonstrated as a probable therapy for the treatment of allergic skin diseases in combination with FC by decreasing its dose from 50 to 25 µg/mice to avoid the chronic side effects of FC. Hence, it can be concluded that SG and SG + FC combination significantly improved the AD-like symptoms in the DNFB sensitized mice through mitigating the production of proinflammatory mediators and restoration of oxidative stress markers.


Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Dinitrofluorbenzeno/toxicidade , Medicamentos de Ervas Chinesas/administração & dosagem , Fluticasona/administração & dosagem , Espirostanos/administração & dosagem , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/metabolismo , Quimioterapia Combinada , Feminino , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Toxicidade Aguda/métodos
6.
J Laryngol Otol ; 135(9): 755-758, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34387182

RESUMO

BACKGROUND: There are significant drug-drug interactions between human immunodeficiency virus antiretroviral therapy and intranasal steroids, leading to high serum concentrations of iatrogenic steroids and subsequently Cushing's syndrome. METHOD: All articles in the literature on cases of intranasal steroid and antiretroviral therapy interactions were reviewed. Full-length manuscripts were analysed and the relevant data were extracted. RESULTS: A literature search and further cross-referencing yielded a total of seven reports on drug-drug interactions of intranasal corticosteroids and human immunodeficiency virus protease inhibitors, published between 1999 and 2019. CONCLUSION: The use of potent steroids metabolised via CYP3A4, such as fluticasone and budesonide, are not recommended for patients taking ritonavir or cobicistat. Mometasone should be used cautiously with ritonavir because of pharmacokinetic similarities to fluticasone. There was a delayed onset of symptoms in many cases, most likely due to the relatively lower systemic bioavailability of intranasal fluticasone.


Assuntos
Corticosteroides/efeitos adversos , Síndrome de Cushing/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , HIV , Administração Intranasal , Corticosteroides/administração & dosagem , Adulto , Cobicistat/administração & dosagem , Cobicistat/efeitos adversos , Interações Medicamentosas , Fluticasona/administração & dosagem , Fluticasona/efeitos adversos , Inibidores da Protease de HIV/administração & dosagem , Humanos , Masculino , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos
7.
Int Arch Allergy Immunol ; 182(11): 1026-1035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34082425

RESUMO

Allergic rhinitis (AR) is prevalent, and many patients present with moderate-to-severe symptomatic disease. The majority of patients are not satisfied with their AR treatment, despite the use of concurrent medications. These gaps underscore the need for treatment with more effective options for moderate-to-severe AR. The authors' objective was to review systematically the efficacy and safety of MP-AzeFlu for the treatment of AR. The primary outcomes studied were nasal, ocular, and total symptoms. Other outcomes included time to onset and of AR control, quality of life, and safety. Searches of PubMed and Cochrane databases were conducted on May 14, 2020, with no date restrictions, to identify publications reporting data on MP-AzeFlu. Clinical studies of any phase were included. Studies were excluded if they were not in English, were review articles, did not discuss the safety and efficacy of MP-AzeFlu for AR symptoms. Treatment of AR with MP-AzeFlu results in effective, sustained relief of nasal and ocular symptoms, and faster onset and time to control compared with intranasal azelastine or fluticasone propionate. Long-term use of MP-AzeFlu was safe, with benefits in children, adults, and adults aged ≥65 years. Other treatment options, including fluticasone propionate and azelastine alone or the combination of intranasal corticosteroids and oral antihistamine, do not provide the same level of efficacy as MP-AzeFlu in terms of rapid and sustained relief of the entire AR symptom complex. Furthermore, MP-AzeFlu significantly improves patient quality of life. MP-AzeFlu is a currently available combination that may satisfy all these patient needs and expectations.


Assuntos
Corticosteroides/administração & dosagem , Antialérgicos/administração & dosagem , Fluticasona/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Ftalazinas/administração & dosagem , Rinite Alérgica/tratamento farmacológico , Corticosteroides/efeitos adversos , Antialérgicos/efeitos adversos , Combinação de Medicamentos , Fluticasona/efeitos adversos , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Humanos , Ftalazinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença
8.
Undersea Hyperb Med ; 48(2): 149-152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33975404

RESUMO

Middle ear barotrauma (MEB) is a common complication of hyperbaric oxygen (HBO2) therapy. It has been reported in more than 40% of HBO2 treatments and can interrupt the sequence of HBO2. MEB may lead to pain, tympanic membrane rupture, and even hearing loss. The aim of this study was to determine if pretreatment with intranasal fluticasone and oxymetazoline affected the incidence of MEB. We conducted a retrospective chart review of subjects undergoing HBO2 at our institution between February 1, 2014, and May 31, 2019. Subjects in the fluticasone/oxymetazoline (FOT) treatment group used intranasal fluticasone 50 mcg two times per day and oxymetazoline 0.05% one spray two times per day beginning 48 hours prior to initial HBO2. Oxymetazoline was discontinued after four days. Fluticasone was continued for the duration of HBO2 therapy. A total of 154 unique subjects underwent 5,683 HBO2 treatments: 39 unique subjects in the FOT group underwent 1,501 HBO2; 115 unique subjects in the nFOT (no oxymetazoline or fluticasone treatment) group underwent 4,182 HBO2 treatments. The incidence of MEB was 15.4% in the FOT group and 16.2% in the nFOT group. This was not a statistically significant difference (OR = 0.77; p = 0.636). Treatment pressure, age over 65 years, male sex, and BMI were not associated with a difference in MEB incidence. In summary, pretreatment with intranasal oxymetazoline and fluticasone in patients undergoing HBO2 did not significantly reduce MEB. More investigation with larger numbers of participants and prospective studies could further clarify this issue.


Assuntos
Anti-Inflamatórios/uso terapêutico , Barotrauma/prevenção & controle , Orelha Média/lesões , Fluticasona/uso terapêutico , Oxigenoterapia Hiperbárica/efeitos adversos , Descongestionantes Nasais/uso terapêutico , Oximetazolina/uso terapêutico , Administração Intranasal , Idoso , Anti-Inflamatórios/administração & dosagem , Barotrauma/epidemiologia , Barotrauma/etiologia , Esquema de Medicação , Feminino , Fluticasona/administração & dosagem , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Descongestionantes Nasais/administração & dosagem , Sprays Nasais , Oximetazolina/administração & dosagem , Estudos Retrospectivos
9.
Ann Allergy Asthma Immunol ; 127(3): 342-348.e2, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34000435

RESUMO

BACKGROUND: Although it is known that oral antihistamine-pseudoephedrine combination tablets have a faster onset than intranasal corticosteroid sprays in the treatment of allergic rhinitis after the first dose, the magnitude of change has not been measured in a comparative manner. Furthermore, the sensation of sprayed liquid in the nose may lead patients to mistakenly believe that intranasal steroid sprays work instantly. OBJECTIVE: To evaluate, numerically, nasal airflow changes provided by a single dose of loratadine-pseudoephedrine tablet (LP) and fluticasone propionate nasal spray (FP) in participants experiencing allergic rhinitis symptoms, including nasal congestion. METHODS: This single-center, double-blinded, placebo-controlled, crossover study evaluated objective nasal airflow changes in patients with a documented sensitivity to ragweed pollen. Participants were randomized to receive 1 of 4 treatment sequences, and their peak nasal inspiratory flow (PNIF) was measured in a span of 4 hours after pollen exposure in an environmental exposure unit. RESULTS: Average change in PNIF was 31% with LP in the course of the study, significantly greater than with placebo and FP (12% and 15%, respectively; P < .001). Nevertheless, FP did not produce a significant change compared with its placebo. At hour one post-dose, LP had a clinically significant 31% increase in PNIF, whereas FP only yielded an 8.6% increase (P < .001). Measurable nasal airflow improvements are associated with the opening of nasal passages, allowing congested patients to breathe more freely. CONCLUSION: A single dose of LP quickly and significantly (P < .001) improved nasal airflow after ragweed pollen challenge in an environmental exposure unit. Comparatively, FP did not display this same benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03443843.


Assuntos
Antialérgicos/administração & dosagem , Fluticasona/administração & dosagem , Loratadina/administração & dosagem , Descongestionantes Nasais/administração & dosagem , Pseudoefedrina/administração & dosagem , Rinite Alérgica/tratamento farmacológico , Administração Intranasal , Adulto , Antialérgicos/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Fluticasona/efeitos adversos , Humanos , Loratadina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/fisiologia , Descongestionantes Nasais/efeitos adversos , Sprays Nasais , Pseudoefedrina/efeitos adversos , Fenômenos Fisiológicos Respiratórios , Rinite Alérgica/fisiopatologia , Comprimidos , Adulto Jovem
11.
Cochrane Database Syst Rev ; 4: CD007694, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33852162

RESUMO

BACKGROUND: Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta2-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta2-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments. OBJECTIVES: To assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid. SEARCH METHODS: We searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers' websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was  24 February 2021. SELECTION CRITERIA: We included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks' duration. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect. MAIN RESULTS: Twenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229). In total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol. In all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence). Only 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation. The two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-related serious adverse events were reported in these studies. Four all-cause serious adverse events were reported: three in the formoterol arm, and one in the salmeterol arm (Peto OR 2.72, 95% CI 0.38 to 19.46; 548 participants, 2 studies; low-certainty evidence). AUTHORS' CONCLUSIONS: Overall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome. We found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.


Assuntos
Antiasmáticos/efeitos adversos , Asma/tratamento farmacológico , Fumarato de Formoterol/administração & dosagem , Glucocorticoides/efeitos adversos , Xinafoato de Salmeterol/administração & dosagem , Administração por Inalação , Adolescente , Adulto , Antiasmáticos/administração & dosagem , Asma/mortalidade , Beclometasona/administração & dosagem , Beclometasona/efeitos adversos , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Budesonida/administração & dosagem , Budesonida/efeitos adversos , Criança , Doença Crônica , Quimioterapia Combinada/efeitos adversos , Fluticasona/administração & dosagem , Fluticasona/efeitos adversos , Fumarato de Formoterol/efeitos adversos , Glucocorticoides/administração & dosagem , Humanos , Furoato de Mometasona/administração & dosagem , Furoato de Mometasona/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Xinafoato de Salmeterol/efeitos adversos
12.
AAPS J ; 23(3): 48, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33768368

RESUMO

In the context of streamlining generic approval, this study assessed whether pharmacokinetics (PK) could elucidate the pulmonary fate of orally inhaled drug products (OIDPs). Three fluticasone propionate (FP) dry powder inhaler (DPI) formulations (A-4.5, B-3.8, and C-3.7), differing only in type and composition of lactose fines, exhibited median mass aerodynamic diameter (MMAD) of 4.5 µm (A-4.5), 3.8 µm (B-3.8), and 3.7 µm (C-3.7) and varied in dissolution rates (A-4.5 slower than B-3.8 and C-3.7). In vitro total lung dose (TLDin vitro) was determined as the average dose passing through three anatomical mouth-throat (MT) models and yielded dose normalization factors (DNF) for each DPI formulation X (DNFx = TLDin vitro,x/TLDin vitro,A-4.5). The DNF was 1.00 for A-4.5, 1.32 for B-3.8, and 1.21 for C-3.7. Systemic PK after inhalation of 500 µg FP was assessed in a randomized, double-blind, four-way crossover study in 24 healthy volunteers. Peak concentrations (Cmax) of A-4.5 relative to those of B-3.8 or C-3.7 lacked bioequivalence without or with dose normalization. The area under the curve (AUC0-Inf) was bio-IN-equivalent before dose normalization and bioequivalent after dose normalization. Thus, PK could detect differences in pulmonary available dose (AUC0-Inf) and residence time (dose-normalized Cmax). The differences in dose-normalized Cmax could not be explained by differences in in vitro dissolution. This might suggest that Cmax differences may indicate differences in regional lung deposition. Overall this study supports the use of PK studies to provide relevant information on the pulmonary performance characteristics (i.e., available dose, residence time, and regional lung deposition).


Assuntos
Broncodilatadores/farmacocinética , Medicamentos Genéricos/farmacocinética , Fluticasona/farmacocinética , Administração por Inalação , Adolescente , Adulto , Aerossóis , Área Sob a Curva , Broncodilatadores/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Liberação Controlada de Fármacos , Medicamentos Genéricos/administração & dosagem , Inaladores de Pó Seco , Feminino , Fluticasona/administração & dosagem , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Pós , Equivalência Terapêutica , Adulto Jovem
13.
J Microencapsul ; 38(3): 177-191, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33583315

RESUMO

This work aimed to elaborate an optimised fluticasone propionate (FP)-loaded solid lipid nanoparticles (SLNs) to enhance FP effectiveness for topical inflammatory remediation. The influences of drug amount, lipid, and surfactant ratios, on drug release pattern and stability were investigated utilising Box-Behnken design. Elaboration, characterisation, and pharmacodynamic evaluation in comparison with the marketed formulation (Cutivate® cream, 0.05%w/w FP), were conducted for the optimised SLNs. The optimised SLNs with a size of 248.3 ± 1.89 nm (PDI = 0.275) and -32.4 ± 2.85 mV zeta potential were evidenced good stability physiognomies. The optimised SLNs pre-treated rats exhibited non-significant difference in paw volume from that of the control group and showed a significant reduction in both PGE2 and TNF-α levels by 51.5 and 61%, respectively, in comparison with the Carrageenan group. The optimised FP-loaded SLNs maximised the efficacy of FP towards inflammation alleviation that increase its potential as efficient implement in inflammatory skin diseases remediation.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Fluticasona/administração & dosagem , Fluticasona/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Carragenina , Dinoprostona/metabolismo , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Fluticasona/farmacocinética , Pé/patologia , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Lipídeos/química , Masculino , Nanopartículas , Tamanho da Partícula , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
14.
Immunopharmacol Immunotoxicol ; 43(2): 160-170, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33435764

RESUMO

OBJECTIVE: Ulcerative colitis is common types of severe, progressive, idiopathic inflammatory bowel disease that involves the mucosal lining of the large intestine. The purpose of the study is to explore the effects of hecogenin in TNBS (2, 4, 6- trinitrobenzene sulfonic acid) induced ulcerative colitis model in rats. MATERIAL AND METHODS: Thirty Wistar rats were randomized into five groups: (i) Normal Control (NC), (ii) Disease Control (DC), (iii) Hecogenin (HG) (50 µg/rat), (iv) Fluticasone (FC) (50 µg/rat), (v) Hecogenin + Fluticasone (HG + FC) combination (25 µg/rat). Colitis was induced by trans-rectal administration of TNBS using a catheter inserted 8 cm into the rectal portion of the rat. Colitis was evaluated by an independent observer who was blinded to the treatment. All treatment group results were compared to the TNBS group results. RESULTS: The study results revealed that treatment of rats with HG and HG + FC significantly improved the body weight and colon length whereas; decreased the spleen weight, colon weight/length ratio, macroscopic lesions score, diarrhea score and adhesion score. The drug treatment in rats substantially decreased the development of inflammatory cytokines, levels of serum immunoglobulin E, colonic nitric oxide contents and restoration of antioxidant stress markers. Histopathological colon sample study significantly reduced colonic inflammation with a substantial decrease in inflammation score. CONCLUSION: Thus, HG and HG + FC combination could change the pathogenesis of the disease and may be a potential therapeutic target for the treatment of ulcerative colitis by a reduction in dose in conjunction with FC to prevent the persistent adverse effects associated with FC.


Assuntos
Colite Ulcerativa/prevenção & controle , Regulação para Baixo/efeitos dos fármacos , Fluticasona/administração & dosagem , Mediadores da Inflamação/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Sapogeninas/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Regulação para Baixo/fisiologia , Quimioterapia Combinada , Feminino , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Ácido Trinitrobenzenossulfônico/toxicidade
15.
Am J Otolaryngol ; 42(3): 102892, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33493729

RESUMO

BACKGROUND: To study the outcome of fluticasone nasal sprays in smell disorders and triamcinolone paste in taste dysfunction in a population of laboratory-confirmed SARS-CoV-2 patients as the test group. The control group will not be given any intervention and only monitoring of these symptoms will be done to compare the recovery time. METHODS: This prospective interventional study was conducted from June to Nov 2020 at, Datta Meghe University during the COVID-19 outbreak. The 120 enrolled patients were tested at days 1 and 5 after proven infection by RT-PCR test. RESULT: The mean age for all cases is 50.88 ± 15.93 years, whereas for the controls mean age is 51.2 ± 14.89. 2. Among cases 45 (75%) were males and 15 (25%) were females, among controls 43 (71.66%) were males and 17 (28.33%) were females. Among the case group, after the use of fluticasone spray in the nose and triamcinolone paste in the mouth there was a statistically significant improvement in recognizing all the odours and taste on day 5 compared to day 1. On comparing the smell and taste of cases and control group, either there is no improvement or worsening in smell or taste on day 5 in the control group. CONCLUSION: The use of fluticasone nasal spray and triamcinolone paste had immensely influenced the basic senses such as smell and taste. Our study showed that olfactory and taste function significantly improved in patients with COVID-19. For all anosmia and dysgeusia cases who received fluticasone nasal spray and triamcinolone medications the recovery of smell senses and the taste was within a week.


Assuntos
Anosmia/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , COVID-19/complicações , Disgeusia/tratamento farmacológico , Fluticasona/uso terapêutico , Triancinolona/uso terapêutico , Administração Oral , Anti-Inflamatórios/administração & dosagem , COVID-19/epidemiologia , Estudos de Casos e Controles , Feminino , Fluticasona/administração & dosagem , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Sprays Nasais , Estudos Prospectivos , Triancinolona/administração & dosagem
16.
Can J Vet Res ; 85(1): 61-67, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33390654

RESUMO

The objective of this study was to compare inhaled glucocorticoids with oral glucocorticoids for treatment of naturally occurring feline asthma. Secondary goals were to evaluate serum allergy testing results in cats and to quantify the effect of an inhaled glucocorticoid (fluticasone) on glucose homeostasis. Nine cats with asthma were enrolled on the basis of clinical signs, thoracic radiographic findings, and airway eosinophilia. Cats were randomized and 4 cats were treated with oral glucocorticoids and 5 cats with inhaled glucocorticoids, with a 7-day course of oral glucocorticoids overlapping at the start of therapy. Cats were evaluated at baseline and at 8 wk with thoracic radiographs, bronchoalveolar lavage, lung function testing, and fructosamine levels. Serum allergen panels were evaluated. All cats were clinically normal after treatment and had significantly improved airway eosinophilia and decreased nucleated cell count. No improvement was seen in radiographic changes after treatment with either therapy. Oral, but not inhaled glucocorticoids, caused a decrease in airway resistance, although cats in the inhaled group had a higher baseline resistance than those in the oral group. Fructosamine levels did not change with treatment. Fifty percent of cats tested positive for immunoglobulin E (IgE) antibodies. Asthma is a heterogeneous condition; individual cats responded well to both oral and inhaled glucocorticoids. Ongoing evaluation of the potential underlying causes and therapeutic options is warranted with a larger group of cats.


L'objectif de l'étude était de comparer le traitement de l'asthme félin avec des glucocorticoïdes inhalés et administrés par voie entérale. Les objectifs secondaires étaient d'évaluer les résultats de tests d'allergies de chats atteints d'asthme félin et de quantifier l'effet d'un glucocorticoïde inhalé (fluticasone) sur l'homéostasie du glucose. Neuf chats atteints d'asthme félin ont été recrutés selon les signes cliniques, les trouvailles radiographiques et les évaluations cytologiques des voies aériennes (éosinophilie). Les chats ont été randomisés. Quatre chats ont été traités avec des glucocorticoïdes par voie entérale et cinq chats avec des glucocorticoïdes inhalés dont les 7 premiers jours ont été associés à l'administration de glucocorticoïdes par voie orale. Les chats ont initialement été évalués au moment du recrutement et puis à huit semaines avec des radiographies thoraciques, lavage bronchoalvéolaire, tests de fonction pulmonaire et dosage de la fructosamine. Des tests sériques d'allergènes ont également été évalués. Tous les chats ont eu une résolution des signes cliniques après le traitement et avaient une amélioration significative du compte éosinophilique du LBA. Aucune amélioration des lésions radiographiques suivant le traitement soit inhalé ou entéral n'a été observée. Seuls les glucocorticoïdes entéraux ont causés une diminution de la résistance des voies respiratoires. Toutefois les chats du groupe de traitement de glucocorticoïdes inhalés avaient, avant l'initiation du traitement, une résistance pulmonaire plus importante. Les niveaux de fructosamine n'ont pas changé significativement, et ce dans les deux groupes de traitement. 50 % des chats ont testé positif pour des anticorps IgE contre des allergènes inhalés communs. L'asthme est une entité clinique hétérogène; les chats ont individuellement bien répondu autant au traitement inhalé qu'au traitement entéral. L'étude des potentielles causes sous-jacente et des différentes options thérapeutiques sont recommandées dans une population plus grande de chats.(Traduit par les auteurs).


Assuntos
Asma , Doenças do Gato , Fluticasona , Prednisolona , Animais , Gatos , Feminino , Masculino , Administração por Inalação , Administração Oral , Asma/tratamento farmacológico , Asma/veterinária , Doenças do Gato/tratamento farmacológico , Fluticasona/administração & dosagem , Fluticasona/uso terapêutico , Projetos Piloto , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico
17.
J Appl Lab Med ; 6(2): 486-490, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33367709

RESUMO

BACKGROUND: While it is presumed that immunosuppressed patients, such as solid organ transplant recipients on immunosuppression, are at greater risk from SARS-CoV-2 infection than the general population, the antibody response to infection in this patient population has not been studied. METHODS: In this report, we follow the anti-SARS-CoV-2 antibody levels in patients with COVID-19 who are undergoing exogenous immunosuppression. Specifically, we studied the antibody response of 3 solid organ transplant recipient patients, 3 patients who take daily inhaled fluticasone, and a patient on etanercept and daily inhaled fluticasone, and compared them to 5 patients not on exogenous immunosuppression. RESULTS: We found that the solid organ transplant patients on full immunosuppression are at risk of having a delayed antibody response and poor outcome. We did not find evidence that inhaled steroids or etanercept predispose patients to delayed immune response to SARS-CoV-2. CONCLUSION: The data presented here suggest that solid organ transplant recipients may be good candidates for early targeted intervention against SARS-CoV-2.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , SARS-CoV-2/imunologia , Administração por Inalação , Adulto , Idoso , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/virologia , Teste Sorológico para COVID-19/estatística & dados numéricos , Inibidores de Calcineurina/efeitos adversos , Etanercepte/efeitos adversos , Feminino , Fluticasona/administração & dosagem , Fluticasona/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/imunologia , Transplantados/estatística & dados numéricos , Adulto Jovem
18.
Psychopharmacology (Berl) ; 238(1): 165-179, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33011818

RESUMO

RATIONALE: Allergic asthma, typically controlled with inhaled corticosteroids (ICS), is the leading chronic health condition for youth under 18 years of age. During this peri-adolescent period, significant brain maturation occurs. Prior studies indicate that both chronic inflammation and corticosteroid medications increase risk for developing an internalizing disorder like anxiety. OBJECTIVES: To determine if chronic ICS treatments exacerbate or alleviate anxiety symptoms associated with developmental allergic asthma, we used a mouse model to isolate the influence of ICS (fluticasone propionate, FLU) vs. airway inflammation (induced with house dust mite extract, HDM). METHODS: During development, male and female BALB/cJ mice were repeatedly exposed to HDM or saline plus one of four FLU doses (none/vehicle, low, moderate, or high). In adulthood, we assessed lung inflammation, circulating and excreted corticosteroids, anxiety-like behavior, and gene expression in stress and emotion regulation brain regions. RESULTS: FLU treatment decreased body weight and anxiety-like behavior and increased fecal corticosterone metabolite concentrations and Crhr2 gene expression in ventral hippocampus. FLU effects were only observed in saline/non-HDM-exposed mice, and the FLU doses used did not significantly decrease HDM-induced airway inflammation. Females had greater serum and fecal corticosterone concentrations, less anxiety-like behavior, and lower Crhr1 gene expression in ventral hippocampus and prefrontal cortex than males. CONCLUSIONS: These findings suggest that steroid medications for youth with allergic asthma may not exacerbate anxiety-related symptoms, and that they should be avoided in children/adolescents without a health condition. The results are informative to future work on the use of corticosteroid medications during childhood or adolescent development.


Assuntos
Corticosteroides/efeitos adversos , Envelhecimento/efeitos dos fármacos , Ansiedade , Asma/tratamento farmacológico , Fluticasona/efeitos adversos , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Envelhecimento/imunologia , Envelhecimento/psicologia , Alérgenos/imunologia , Animais , Ansiedade/induzido quimicamente , Ansiedade/imunologia , Ansiedade/psicologia , Asma/imunologia , Asma/psicologia , Modelos Animais de Doenças , Feminino , Fluticasona/administração & dosagem , Fluticasona/uso terapêutico , Humanos , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pyroglyphidae/imunologia
19.
Ear Nose Throat J ; 100(5): 309-313, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33305974

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is a common sinonasal disorder which results in significant inflammation in the nasal cavity and paranasal sinuses. Topical nasal steroids play an important role in the treatment of CRS. Exhalation delivery system with fluticasone (EDS-FLU) utilizes a patient's forced exhalation to power the delivery of topical steroids to deeper areas of the nasal cavity and paranasal sinuses most affected by CRS. This review focuses on evidence surrounding the safety and efficacy of the EDS-FLU system. METHODS: Literature search was conducted of articles investigating the safety and efficacy of EDS-FLU. Relevant efficacy and safety data were examined and summarized from the studies. RESULTS: The efficacy and safety of EDS-FLU in CRS, both with and without polyps, has been established in open-label and placebo-controlled phase 3 trials. There was significant improvement in the cardinal symptoms of CRS and subjective patient-reported outcomes scores. Additionally, there was objective improvement in sinonasal inflammation as measured by polyp grade. Recent studies have also established significant improvement in health status and general quality of life following treatment using EDS-FLU. Emerging data have also examined patients who have previously had endoscopic sinus surgery and on appropriate medical therapy and noted improvement in polyp burden and overall Lund-Kennedy scores after using EDS-FLU. CONCLUSION: Exhalation delivery system with fluticasone demonstrates significant results in both patient-oriented outcomes and objective measures of sinonasal inflammation in patients with CRS with and without polyps. Further research is needed to investigate the long-term outcomes of EDS-FLU and to compare the effects of EDS-FLU with ESS. Exhalation delivery system with fluticasone provides an additional effective treatment modality for patients suffering from CRS.


Assuntos
Administração Intranasal/métodos , Corticosteroides/administração & dosagem , Sistemas de Liberação de Medicamentos , Fluticasona/administração & dosagem , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Doença Crônica , Expiração , Humanos , Cavidade Nasal , Seios Paranasais , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
20.
PLoS One ; 15(12): e0244681, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33378384

RESUMO

BACKGROUND: Inhaled corticosteroids (ICS) are the mainstay of asthma treatment, but evidence suggests a link between ICS usage and increased rates of respiratory infections. We assessed the composition of the asthmatic airways microbiome in asthma patients taking low and high dose ICS and the stability of the microbiome over a 2 week period. METHODS: We prospectively recruited 55 individuals with asthma. Of these, 22 were on low-dose ICS and 33 on high-dose ICS (16 on budesonide, 17 on fluticasone propionate). Sputum from each subject underwent DNA extraction, amplification and 16S rRNA gene sequencing of the bacterial component of the microbiome. 19 subjects returned for further sputum induction after 24 h and 2 weeks. RESULTS: A total of 5,615,037 sequencing reads revealed 167 bacterial taxa in the asthmatic airway samples, with the most abundant being Streptococcus spp. No significant differences in sputum bacterial load or overall community composition were seen between the low- and high-dose ICS groups. However, Streptococcus spp. showed significantly higher relative abundance in subjects taking low-dose ICS (p = 0.002). Haemophilus parainfluenzae was significantly more abundant in subjects on high-dose fluticasone propionate than those on high-dose budesonide (p = 0.047). There were no statistically significant changes in microbiota composition over a 2-week period. DISCUSSION: Whilst no significant differences were observed between the low- and high-dose ICS groups, increased abundance of the potential pathogen H. parainfluenzae was observed in patients taking high-dose fluticasone propionate compared to those taking high-dose budesonide. The microbiota were stable over fourteen days, providing novel evidence of the established community of bacteria in the asthmatic airways. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02671773.


Assuntos
Corticosteroides/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/microbiologia , Microbiota/efeitos dos fármacos , Infecções Respiratórias/induzido quimicamente , Escarro/microbiologia , Administração por Inalação , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiasmáticos/efeitos adversos , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Budesonida/administração & dosagem , Budesonida/efeitos adversos , Budesonida/uso terapêutico , Relação Dose-Resposta a Droga , Fluticasona/administração & dosagem , Fluticasona/efeitos adversos , Fluticasona/uso terapêutico , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Respiratórias/microbiologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...