Effects of cigarette smoking on the respiratory epithelium and its role in the pathogenesis of chronic rhinosinusitis

O crescente consumo de cigarro tem despertado preocupações com o desenvolvimento e agravamento de doenças, em especial às relacionadas ao trato respiratório. OBJETIVO: Neste artigo revisamos as evidências que apontam os efeitos da fumaça de cigarro sobre o epitélio respiratório bem como o seu papel na fisiopatogenia na rinossinusite crônica. CONCLUSÃO: Embora existam dados que fortaleçam um vínculo entre o hábito de fumar e a RSC, em seu conjunto, os estudos demonstram que deve haver grande dependência da susceptibilidade individual na resposta à fumaça de cigarro para o desenvolvimento ou manutenção da RSC. Uma adequada orientação a esses pacientes para interrupção do consumo de cigarro, assim como o reforço de campanhas de combate ao tabagismo, são de extrema importância para o controle dessa doença de grande impacto sócio-econômico.The increasing consumption of cigarettes has aroused concerns about the development and worsening of diseases, particularly those related to the respiratory tract. AIM: In this paper we review the evidence suggesting the effects of cigarette smoking on the respiratory epithelium and its role in the pathogenesis in chronic rhinosinusitis. CONCLUSIONS: Although there is evidence supporting a link between smoking and CRS, studies suggest that there might be individual susceptibility to cigarette smoking causing the development and/or maintenance of CRS. Proper patient educations to quit smoking as well as reinforcement of antismoking campaigns are extremely important to control this disease of major socio-economic impact

Position statement of the Brazilian Academy of Rhinology on the use of antihistamines, antileukotrienes, and oral corticosteroids in the treatment of inflammatory sinonasal diseases

Introduction: Inflammatory conditions of the nose and paranasal sinuses are very prevalent in the general population, resulting in marked loss of quality of life in affected patients, as well as significant work, leisure, and social activity losses. These patients require specific and specialized treatment. A wide range of oral medications are available. Objective: The present document is aimed to clarify, for professionals treating patients with inflammatory sinonasal diseases, both specialists and general practitioners, specific oral therapies in noninfectious nasal inflammatory conditions. Methods: The methodology used to create this article included the search for the key words: oral corticosteroids, antihistamines, antileukotrienes, rhinitis, rhinosinusitis in the MEDLINE and EMBASE databases in the last 5 years. Since no relevant article was found for the text on the subject of interest in the last 5 years, the search was extended for another 5 years, and so on, according to the authors' needs. Results: Relevant literature was found regarding the use of antihistamines, antileukotrienes and oral corticosteroids in these conditions. The Brazilian Academy of Rhinology emphasizes, after extensive discussion by the collegiate, key points in the treatment with these drugs. Conclusion: There is support in the literature for the use of these drugshowever, final considerations about the role of each of them have been made. (C) 2017 Published by Elsevier Editora Ltda. on behalf of Associacao Brasileira de Otorrino-laringologia e Cirurgia Cervico-Facial.Univ Sao Paulo, Disciplina Otorrinolaringol, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Dept Otorrinolaringol, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Otorrinolaringol, Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Ciencias Saude, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Otorrinolaringol, Sao Paulo, SP, BrazilUniv Fed Minas Gerais, Fac Med, Belo Horizonte, MG, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, SP, BrazilUniv Fed Bahia, Fac Med, Disciplina Otorrinolaringol, Salvador, BA, BrazilHosp Inst Paranaense Otorrinolaringol, Centro Rinite & Alergia, Curitiba, PR, BrazilUniv Estado Rio De Janeiro, Rio De Janeiro, RJ, BrazilUniv Brasilia, Fac Med, Brasilia, DF, BrazilUniv Fed Sao Paulo, Dept Otorrinolaringol & Cabeca & Pescoco, Sao Paulo, SP, BrazilUniv Luterana Brasil, Fac Med, Otorrinolaringol, Canoas, RS, BrazilMt Sinai Hosp, Dept Othorhinolaryngol, Toronto, ON, CanadaUniv Sao Paulo, Fac Med, Ciencias, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Oftalmol Otorrinolaringol & Cirurgia Cabeca, Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Ciencias Saude, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Otorrinolaringol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Otorrinolaringol & Cabeca & Pescoco, Sao Paulo, SP, BrazilWeb of Scienc

How to avoid the inappropriate use of antibiotics in upper respiratory tract infections? A position statement from an expert panel

Introduction: Bacterial resistance burden has increased in the past years, mainly due to inappropriate antibiotic use. Recently it has become an urgent public health concern due to its impact on the prolongation of hospitalization, an increase of total cost of treatment and mortality associated with infectious disease. Almost half of the antimicrobial prescriptions in outpatient care visits are prescribed for acute upper respiratory infections, especially rhinosinusitis, otitis media, and pharyngotonsillitis. In this context, otorhinolaryngologists play an important role in orienting patients and non-specialists in the utilization of antibiotics rationally and properly in these infections. Objectives: To review the most recent recommendations and guidelines for the use of antibiotics in acute otitis media, acute rhinosinusitis, and pharyngotonsillitis, adapted to our national reality. Methods: A literature review on PubMed database including the medical management in acute otitis media, acute rhinosinusitis, and pharyngotonsillitis, followed by a discussion with a panel of specialists. Results: Antibiotics must be judiciously prescribed in uncomplicated acute upper respiratory tract infections. The severity of clinical presentation and the potential risks for evolution to suppurative and non-suppurative complications must be taken into 'consideration'. Conclusions: Periodic revisions on guidelines and recommendations for treatment of the main acute infections are necessary to orient rationale and appropriate use of antibiotics. Continuous medical education and changes in physicians' and patients' behavior are required to modify the paradigm that all upper respiratory infection needs antibiotic therapy, minimizing the consequences of its inadequate and inappropriate use. (C) 2018 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license.Introdução: A resistência bacteriana a antibióticos nos processos infecciosos é um fato crescente nos últimos anos, especialmente devido ao seu uso inapropriado. Ao longo dos anos vem se tornando um grave problema de saúde pública devido ao prolongamento do tempo de internação, elevação dos custos de tratamento e aumento da mortalidade relacionada às doenças infecciosas. Quase a metade das prescrições de antibióticos em unidades de pronto atendimento é destinada ao tratamento de alguma infecção de vias aéreas superiores, especialmente rinossinusites, otite média aguda supurada e faringotonsilites agudas, sendo que uma significativa parcela dessas prescrições é inapropriada. Nesse contexto, os otorrinolaringologistas têm um papel fundamental na orientação de pacientes e colegas não especialistas, para o uso adequado e racional de antibióticos frente a essas situações clínicas. Objetivos: Realizar uma revisão das atuais recomendações de utilização de antibióticos nas otites médias, rinossinusites e faringotonsilites agudas adaptadas à realidade nacional. Método: Revisão na base PubMed das principais recomendações internacionais de tratamentos das infecções de vias aéreas superiores, seguido de discussão com um painel de especialistas. Resultados: Os antibióticos devem ser utilizados de maneira criteriosa nas infecções agudas de vias aéreas superiores não complicadas, a depender da gravidade da apresentação clínica e dos potenciais riscos associados de complicações supurativas e não supurativas. Conclusões: Constantes revisões a respeito do tratamento das principais infecções agudas são necessárias para que sejam tomadas medidas coletivas no uso racional e apropriado de antibióticos. Somente com orientação e transformações no comportamento de médicos e pacientes é que haverá mudanças do paradigma de que toda infecção de vias aéreas superiores deva ser tratada com antibióticos, minimizando por consequência os efeitos de seu uso inadequado.Univ Fed Rio Grande do Sul, Dept Oftalmol & Otorrinolaringol, Fac Med FAMED, Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, EPM, Sao Paulo, SP, BrazilUniv Estadual Campinas, UNICAMP, Dept Otorrinolaringol & Oftalmol, Campinas, SP, BrazilUniv Sao Paulo, FM, Disciplina Otorrinolaringol, Sao Paulo, SP, BrazilUniv Sao Paulo, FM, Otorrinolaringol, Sao Paulo, SP, BrazilHosp Infantil Sabara, Otorrinolaringol, Sao Paulo, SP, BrazilHosp Paranaense Otorrinolaringol IPO, Inst Paranaense Otorrinolaringol, Curitiba, Parana, BrazilFac Ciencias Med Santa Casa de Sao Paulo, Sao Paulo, SP, BrazilUniv Fed Pernambuco UFPE, Dept Cirurgia, Div Otorrinolaringol, Recife, PE, BrazilUniv Luterana Brasil, Fac Med, Porto Alegre, RS, BrazilUniv Sao Paulo, FM, Sao Paulo, SP, BrazilHosp Albert Einstein, Sao Paulo, SP, BrazilUniv Sao Paulo, FMRP, Dept Oftalmol Otorrinolaringol & Cirurgia Cabeca, Ribeirao Preto, SP, BrazilUniv Fed Ciencias Saude Porto Alegre, Hosp Crianca St Antonio, Serv Otorrinolaringol Pediat, Porto Alegre, RS, BrazilUniv Estado Rio De Janeiro, Fac Ciencias Med, Disciplina Otorrinolaringol, Rio De Janeiro, RJ, BrazilUniv Fed Goias, Goiania, Go, BrazilPontificia Univ Catolica Goias PUC GO, Goiania, Go, BrazilCtr Univ Anapolis, Anapolis, Go, BrazilUniv Fed Sao Paulo UNIFESP, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, EPM, Sao Paulo, SP, BrazilSciEL

Clearance of Pneumococcal Colonization in Infants Is Delayed through Altered Macrophage Trafficking.

Infections are a common cause of infant mortality worldwide, especially due to Streptococcus pneumoniae. Colonization is the prerequisite to invasive pneumococcal disease, and is particularly frequent and prolonged in children, though the mechanisms underlying this susceptibility are unknown. We find that infant mice exhibit prolonged pneumococcal carriage, and are delayed in recruiting macrophages, the effector cells of clearance, into the nasopharyngeal lumen. This lack of macrophage recruitment is paralleled by a failure to upregulate chemokine (C-C) motif ligand 2 (Ccl2 or Mcp-1), a macrophage chemoattractant that is required in adult mice to promote clearance. Baseline expression of Ccl2 and the related chemokine Ccl7 is higher in the infant compared to the adult upper respiratory tract, and this effect requires the infant microbiota. These results demonstrate that signals governing macrophage recruitment are altered at baseline in infant mice, which prevents the development of appropriate innate cell infiltration in response to pneumococcal colonization, delaying clearance of pneumococcal carriage

Infant mice are impaired in macrophage recruitment during colonization.

<p>(A-C) Adult (6 week old) and infant (7d old) mice were inoculated with strain P1121 for the indicated number of days. Nasal lavages were obtained and fixed and stained for flow cytometry to identify macrophages (F4/80+, CD11b-) and neutrophils (CD11b+, Ly6G+). CD11b surface expression was measured on myeloid cells and displayed as median fluorescence intensity. Samples represent at least 10 mice per timepoint. (D) Serum was obtained from adult and infant mice colonized with pneumococci for 21 days, or mock-colonized. Samples were analyzed by ELISA for the presence of antibodies specific to strain P1121. (E) Infant mice of the indicated genotype were colonized at 7d of age. Mice were sacrificed at the indicated timepoints and nasal lavages obtained and plated to measure bacterial load. Data are represented as mean +/- SEM. n.s. = not significant, * = p < 0.05, ** = p < 0.01.</p

Pneumococcal carriage is prolonged in infant mice.

<p>(A) Adult (6 weeks old) and infant (7d old) mice were inoculated with pneumococcal strain P1121, and at the indicated number of days postinoculation (dpi), mice were sacrificed and nasal lavages obtained and plated to determine the load of colonizing pneumococci. (B) Adult and infant mice were inoculated with pneumococcal strain TIGR4 (type 4). Mice were sacrificed at 21 dpi and nasal lavages obtained and plated to determine the load of colonizing pneumococci. (C) Mice were inoculated with strain P1121 (type 23F) at different ages, ranging from 7 to 42 days. At 21 dpi, mice were sacrificed and nasal lavages obtained and plated to measure bacterial density. Points in (A) represent mean +/- SEM, with 5–18 mice per group. Horizontal lines indicate median values. Dotted lines indicate limit of detection. n.s. = not significant, ** = p < 0.01, *** = p < 0.001.</p

Infant mice do not form a gradient of CCL2 expression during colonization.

<p>(A) Adult (42d old) and infant (7d old) mice were inoculated with PBS (mock) or pneumococci. At 3d post-inoculation, nasal lavages were obtained with RLT lysis buffer, and RNA was isolated and reverse transcribed to cDNA. qRT-PCR was performed to measure relative expression of <i>Ccl2</i>. (B) Serum was obtained from adult and infant mice, and ELISA used to measure CCL2 levels. (C-D) Peritoneal macrophages from adult and infant mice were lysed with RLT buffer and RNA isolated. qRT-PCR was used to measure relative expression of <i>Ccl2</i> (C) and <i>Ccr2</i> (D). In (C), cultured macrophages were incubated overnight with PBS (Mock) or heat-killed bacterial lysates (Stim) prior to lysis. (E-H) Uncolonized adult and infant mice were sacrificed, and nasal lavages obtained with RLT lysis buffer. RNA was isolated and reverse-transcribed into cDNA. qRT-PCR was used to measure relative expression of <i>Ccl7</i>, (E) <i>Il6</i>, (F) <i>Cxcl1</i>, (G) and <i>Cxcl2</i> (H). Data are represented as mean +/- SEM. n.s., not significant. * = p < 0.05, ** = p < 0.01, *** = p < 0.001.</p