Dinámica y patología del barrido mucociliar como mecanismo defensivo del pulmón y alternativas farmacológicas de tratamiento / Mucociliary clearance system in lung defense

The first line of defense to maintain the sterility of the intrapulmonary airways is the mucociliary clearance system. This rapidly responding, non-specific, immune defensive system is challenged by approximately 12,000 liters of air filtered by the lungs each day, containing millions of particles like spores, environmental and eventually toxic pollutants. The main components of this system are the floating mucus "blanket", the underlying mucus propelling cilia with periciliary fluid, and the airway epithelium with secretory and ciliated type of cells. The fine and coordinated regulation of these three components is critical for an effective performance. Deregulation resulting from continuous insults, inherited ion channel disease, infections or abnormal immune response may lead to mucus alterations, goblet cell hyperplasia and metaplasia, airway obstruction, air trapping and chronic lung disease. Options for treatment are limited. Understanding this system may reveal new targets for treatment of lung disease.

Adesividade e purulência de secreções respiratórias: implicações no transporte mucociliar em pacientes com bronquiectasias / Adhesiveness and purulence of respiratory secretions: implications for mucociliary transport in patients with bronchiectasis

OBJETIVO: Analisar e comparar as propriedades de transporte de secreções respiratórias, classificadas através de parâmetros selecionados, de indivíduos com bronquiectasias não secundárias à fibrose cística. MÉTODOS: Foram avaliadas amostras de muco respiratório, classificadas como com propriedades de superfície adesivas ou não adesivas, assim como com aspecto mucoide ou purulento, de 35 participantes com bronquiectasias não secundárias à fibrose cística, quanto a velocidade relativa de transporte (VRT), deslocamento em máquina simuladora de tosse (MST) e ângulo de contato (AC). Para as comparações propostas, foram utilizados modelos de ANOVA, com nível de significância estabelecido em 5 por cento. RESULTADOS: Houve uma diminuição significativa no deslocamento em MST, assim como um aumento significativo no AC, das amostras adesivas quando comparadas às não adesivas (6,52 ± 1,88 cm vs. 8,93 ± 2,81 cm e 27,08 ± 6,13º vs. 22,53 ± 5,92º, respectivamente; p < 0,05 para ambos). O mesmo ocorreu na comparação entre as amostras purulentas e mucoides (7,57 ± 0,22 cm vs. 9,04 ± 2,48 cm e 25,61 ± 6,12º vs. 21,71 ± 5,89º; p < 0,05 para ambos). Não houve diferença na VRT entre os grupos, embora os valores estivessem diminuídos, independentemente da adesividade (adesivas: 0,81 ± 0,20; não adesivas: 0,68 ± 0,24) ou do aspecto (purulentas: 0,74 ± 0,22; mucoides: 0,82 ± 0,22) das amostras. CONCLUSÕES: A secreção respiratória de pacientes com bronquiectasia apresentou uma diminuição do transporte ciliar. Maior adesividade e purulência favorecem a piora das propriedades de transporte, demonstradas pela diminuição do deslocamento em MST e pelo aumento do AC.

OBJECTIVE: To analyze and compare the transport properties of respiratory secretions, classified by selected parameters, in individuals with bronchiectasis unrelated to cystic fibrosis. METHODS: We collected mucus samples from 35 individuals with bronchiectasis unrelated to cystic fibrosis. The samples were first classified by their surface properties (adhesive or nonadhesive), as well as by their aspect (mucoid or purulent). We then tested the samples regarding relative transport velocity (RTV), displacement in a simulated cough machine (SCM), and contact angle (CA). For the proposed comparisons, we used ANOVA models, with a level of significance set at 5 percent. RESULTS: In comparison with nonadhesive samples, adhesive samples showed significantly less displacement in the SCM, as well as a significantly higher CA (6.52 ± 1.88 cm vs. 8.93 ± 2.81 cm and 27.08 ± 6.13º vs. 22.53 ± 5.92º, respectively; p < 0.05 for both). The same was true in the comparison between purulent and mucoid samples (7.57 ± 0.22 cm vs. 9.04 ± 2.48 cm and 25.61 ± 6.12º vs. 21.71 ± 5.89º; p < 0.05 for both). There were no significant differences in RTV among the groups of samples, although the values were low regardless of the surface properties (adhesive: 0.81 ± 0.20; nonadhesive: 0.68 ± 0.24) or the aspect (purulent: 0.74 ± 0.22; mucoid: CONCLUSIONS: The respiratory secretions of patients with bronchiectasis showed decreased mucociliary transport. Increased adhesiveness and purulence cause the worsening of transport properties, as demonstrated by the lesser displacement in the SCM and the higher CA.

Analysis of the sputum and inflammatory alterations of the airways in patients with common variable immunodeficiency and bronchiectasis

INTRODUCTION: Common variable immunodeficiency is characterized by defective antibody production and recurrent pulmonary infections. Intravenous immunoglobulin is the treatment of choice, but the effects of Intravenous immunoglobulin on pulmonary defense mechanisms are poorly understood. OBJECTIVE: The aim of this study was to verify the impact of intravenous immunoglobulin on the physical properties of the sputum and on inflammatory alterations in the airways of patients with Common variable immunodeficiency associated with bronchiectasis. METHOD: The present study analyzed sputum physical properties, exhaled NO, inflammatory cells in the sputum, and IG titers in 7 patients with Common variable immunodeficiency and bronchiectasis with secretion, immediately before and 15 days after Intravenous immunoglobulin. A group of 6 patients with Common variable immunodeficiency and bronchiectasis but no sputum was also studied for comparison of the basal IgG level and blood count. The 13 patients were young (age=36±17 years) and comprised predominantly of females (n=11). RESULTS: Patients with secretion presented significantly decreased IgG and IgM levels. Intravenous immunoglobulin was associated with a significant decrease in exhaled NO (54.7 vs. 40.1 ppb, p<0.05), sputum inflammatory cell counts (28.7 vs. 14.6 cells/mm³, p<0.05), and a significant increase in respiratory mucus transportability by cough (42.5 vs. 65.0 mm, p < 0.05). CONCLUSION: We concluded that immunoglobulin administration in Common variable immunodeficiency patients results in significant improvement in indexes of inflammation of the airways with improvement in the transportability of the respiratory mucus by cough.

Mucocele apendicular gigante / Gigantic mucocele of the vermiform appendix

Se informa el caso de una paciente femenina de 44 años de edad, quien acudió al servicio de urgencias del Hospital General de Zona con Medicina Familiar Núm. 1 en Pachuca, Hidalgo, por tumoración abdominal de tres meses de evolución localizada en fosa iliaca derecha. Después de diversos exámenes de gabinete, se diagnosticó mucocele apendicular gigante. El mucocele apendicular puede resolverse mediante apendicectomía simple, pero en el caso que se presenta, por encontrar una lesión tan grande, difícil de distinguir de las de tipo maligno dado su aspecto y la presencia de múltiples ganglios, se juzgó conveniente efectuar resección intestinal de íleon terminal junto con resección cecal y de la mitad inferior del colon derecho, más íleo coloanastomosis de primera intención. No se presentaron complicaciones y la paciente evolucionó satisfactoriamente. Se analiza la etiología, fisiopatología y pronóstico de esta rara patología quirúrgica.

Methods for studying respiratory mucus and mucus clearance

We describe some basic procedures for studying the properties of mucus. These techniques can be applied in both clinical and physiological studies to improve the understanding of the mechanisms related to epithelial defense in health and disease. Mucus collection - A major difficulty is the lack of simple and noninvasive methods for collecting normal mucus in sufficient quantity for later analysis. Physical properties of mucus - A. Rheology: Mucus exhibits both solid and liquid properties and the important factor governing the actual behavior is time. The magnetic microrheometer provides an elegant method for measuring rheological properties of microsamples. B. Adhesivity: It characterizes the forces of attraction between an adherent surface and an adhesive system and can be calculated by measuring the contact angle between a mucus drop and a surface. Mucus Transport - A. Mucus transport by cilia: Mucus is primarily cleared by the continuous ciliary beating, which can be studied using techniques such as the frog palate preparation as well as direct measurement. i.e., in situ mucus clearance. B. Cough clearance: It is essential for elimination of secretions in diseases leading to hypersecretory states. The cough machine simulates the flow-time profile of human coughing. Transepithelial potential difference - A potential difference exists between the epithelial surface and the submucosa and is the net result of the activity of the ion-transport system of the pulmonary epithelium. The potential can be measured using appropriate microelectrodes. Quantitative morphology - Methods may be used to characterize the epithelial surface condition that continuously changes during aggressive conditions.

La úlcera péptica: es una falla de los mecanismos de defensa de la mucosa gastroduodenal? / Peptic ulcer: a failure of defense mechanisms of gastroduodenal mucosa?

La úlcera péptica es una enfermedad heterogénea y multifactorial. La secreción de ácido/pepsina es un factor crítico permisivo en la ulceración péptica gastroduodenal. En este principio se ha basado mayormente la terapéutica de la enfermedad. La sola presencia del factor agresivo ácido/pepsina, no es suficiente para explicar satisfactoriamente la patogenia de la úlcera péptica. La defensa/resistencia de la mucosa representa otro factor crítico involucrado en la patogenia de la enfermedad. Varios mecanismos defensivos gastroduodenales se han demostrado deficientes en los pacientes ulcerosos. Entre ellos: la síntesis y liberación de prostaglandinas, la secreción de mucus y bicarbonato, y la magnitud de la capa hidrofóbica de la mucosa. Tanto el dictum "no ácido-no úlcera" como el corolario "defesa/resistencia normal-no úlcera" parecen ser válidos. La correción de una posible deficiencia en al defensa/resistencia de la mcuosa gastroduodenal puede ser un principio de utilidad práctica en el manejo del paciente ulceroso

Effect of inspiratory and expiratory air flow on congestion and decongestion in the nasal cycle.

The role of the inspiratory and expiratory airflow through nostrils during the process of breathing in the reflex reciprocal congestion and decongestion of the nasal cycle was examined in this study. Air flow through each nostril was measured separately in male subjects before and after four types of breathing practices for 15 min each consisting of (1) inspiration through the patent nostril and expiration through the congested nostril, (2) inspiration through congested nostril and expiration through patent nostril, (3) inspiration through both nostrils and expiration through mouth and (4) inspiration through mouth and expiration through both nostrils. The breathing practices had no effect on the congested nostril but caused decrease in air flow through the patent nostril, indicating congestion. It is suggested that the inspiratory and expiratory air flow through the nostrils caused reflex congestion of the patent nostril. The stimuli arising from the nasal mucosa due to air flow during breathing may form the basis for the reflex reciprocal congestion and decongestion of nostrils in the nasal cycle.

Mecanismos de defesa da mucosa gastroduodenal: uma visäo atual / Defense mechanisms of gastroduodenal mucosa: a present view

A mucosa gastroduodenal representa uma obra-prima de estrutura funcional. Seu epitélio possui notável habilidade para resistir à autodigestäo resultante das altas concentraçöes de ácido, às quais está continuamente exposto. Como os valores das secreçöes de ácido e pepsina säo usualmente normais na úlcera gástrica e freqüentemente normais na úlcera duodenal, é muito provável que o defeito nestas doenças resulte muito mais da diminuiçäo dos fatores defensivos do que do aumento dos fatores agressivos. É, entretanto, cada mais evidente que o simples conceito de barreira mucosa näo define completamente os vários fatores defensivos do que do aumento dos fatores agressivos. É, entretanto, cada vez mais camada de muco que recobre a superfície epitelial, o bicarbonato secretado pelo epitélio colunar, a rápida renovaçäo e restituiçäo celular após lesäo superficial da mucosa, a integridade da microcirculaçäo, o bicarbonato intersticial e a hidrofobicidade do epitélio de revestimento. A importância relativa de cada um fatores näo está ainda definida mas é muito provável que a primeira linha de defesa se encontra no próprio ambiente extracelular, representado pela camada de muco. O muco tem a propriedade de reduzir a difusäo dos íons hidrogênio, formando uma camada näo agitada, em contato direto com o epitélio superficial. O bicarbonato é secretado por um processo ativo, estimulado pelas prostaglandinas e inibido pela aspirina. A combinaçäo de bicarbonato e muco produz um gradiente de pH na superfície da mucosa, através do qual a superficie epitelial mantém-se neutra em relaçäo ao ácido luminal. Esta barreira muco-bicarbonato tem, entretanto, capacidade limitada para resistir a retrodifusäo de ácido, e, quando ela é sobrepujada ou inibida, outros mecanismos protetores entram em jogo, incluindo a hidrofobicidade da membrana da célula epitelial, a neutralizaçäo do ácido, que consegue ultrapassar a referida barreira, pelo bicarbonato intersticial, sua remoçäo pela microcirculaçäo e a rápida reconstituiçäo do epitélio. Os distintos mediadores que modulam estes vários processos defensivos säo ainda desconhecidos, mas as prostaglandinas endógenas säo fortes candidatos. Säo substancias existentes em abundância na mucosa gastroduodenal de todos os animais estudados, inclusive o homem, e parecem interferir positivamente na maioria, senäo em todos, dos mecanismos considerados importantes na sua defesa