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Airway mucociliary clearance (MCC) is the main mechanism of lung defense keeping airways free of infection and mucus obstruction. Airway surface liquid volume, ciliary beating, and mucus are central for proper MCC and critically regulated by sodium absorption and anion secretion. Impaired MCC is a key feature of muco-obstructive diseases. The calcium-activated potassium channel KCa.3.1, encoded by Kcnn4, participates in ion secretion, and studies showed that its activation increases Na+ absorption in airway epithelia, suggesting that KCa3.1-induced hyperpolarization was sufficient to drive Na+ absorption. However, its role in airway epithelium is not fully understood. We aimed to elucidate the role of KCa3.1 in MCC using a genetically engineered mouse. KCa3.1 inhibition reduced Na+ absorption in mouse and human airway epithelium. Furthermore, the genetic deletion of Kcnn4 enhanced cilia beating frequency and MCC ex vivo and in vivo. Kcnn4 silencing in the Scnn1b-transgenic mouse (Scnn1btg/+), a model of muco-obstructive lung disease triggered by increased epithelial Na+ absorption, improved MCC, reduced Na+ absorption, and did not change the amount of mucus but did reduce mucus adhesion, neutrophil infiltration, and emphysema. Our data support that KCa3.1 inhibition attenuated muco-obstructive disease in the Scnn1btg/+ mice. K+ channel modulation may be a therapeutic strategy to treat muco-obstructive lung diseases.

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The chloride channels, sodium and bicarbonate channels, and aquaporin water channels are coordinated to maintain the airway surface liquid that is necessary for mucociliary clearance. The general mechanism for the transport of electrolytes and fluids depends mainly on the differential expression and distribution of ion transporters and pumps. Ions and water move through the paracellular or transcellular pathways. The transcellular route of electrolyte transport requires an active transport (dependent on ATP) or passive (following electrochemical gradients) of ions. The paracellular pathway is a passive process that is ultimately controlled by the predominant transepithelial electrochemical gradients. Cystic fibrosis is a hereditary disease that is produced by mutations in the gene that encode cystic fibrosis transmembrane conductance regulatory protein (CFTR) that acts as a chloride channel and performs functions of hydration of periciliary fluid and maintenance of luminal pH. The dysfunction of the chlorine channel in the respiratory epithelium determines an alteration in the bronchial secretions, with an increase in its viscosity and alteration of the mucociliary clearance and that associated with infectious processes can lead to irreversible lung damage. CFTR dysfunction has also been implicated in the pathogenesis of acute pancreatitis, chronic obstructive pulmonary disease, and bronchial hyperreactivity in asthma. There are drugs that exploit physiological mechanisms in the transport of ions with a therapeutic objective.

Los canales de cloruros, de sodio, de bicarbonato y los de agua (aquaporinas) se coordinan para mantener la cubierta líquido superficial de las vías respiratorias, que es necesaria para el aclaramiento mucociliar. El mecanismo general para el transporte de electrolitos y agua depende principalmente de la expresión diferencial y distribución de los transportadores y bombas de iones. Los iones y el agua se mueven a través de las vía paracelular o transcelular. La ruta transcelular del transporte de electrolitos requiere un transporte activo (dependiente de ATP) o pasivo (siguiendo gradientes electroquímicos) de iones. La ruta paracelular es un proceso pasivo que está controlado, en última instancia, por los gradientes electroquímicos transepiteliales predominantes. La fibrosis quística es una enfermedad hereditaria que se produce por mutaciones en el gen que codifica la proteína reguladora de la conductibilidad transmembrana de la fibrosis quística (CFTR) que actúa como un canal de cloro y cumple funciones de hidratación del líquido periciliar y mantenimiento del pH luminal. La disfunción del canal de cloro en el epitelio respiratorio determina una alteración en las secreciones bronquiales, con aumento de su viscosidad y alteración de la depuración mucociliar y que asociado a procesos infecciosos puede conducir a daño pulmonar irreversible. La disfunción del CFTR, también se ha visto implicado en la patogénesis de la pancreatitis aguda, en la enfermedad pulmonar obstructiva crónica y la hiperreactividad en el asma. Existen fármacos que aprovechan los mecanismos fisiológicos en el transporte de iones, con un objetivo terapéutico.

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Los canales de cloruros, de sodio, de bicarbonato y los de agua (aquaporinas) se coordinan para mantener la cubierta líquido superficial de las vías respiratorias, que es necesaria para el aclaramiento mucociliar. El mecanismo general para el transporte de electrolitos y agua depende principalmente de la expresión diferencial y distribución de los transportadores y bombas de iones. Los iones y el agua se mueven a través de las vía paracelular o transcelular. La ruta transcelular del transporte de electrolitos requiere un transporte activo (dependiente de ATP) o pasivo (siguiendo gradientes electroquímicos) de iones. La ruta paracelular es un proceso pasivo que está controlado, en última instancia, por los gradientes electroquímicos transepiteliales predominantes. La fibrosis quística es una enfermedad hereditaria que se produce por mutaciones en el gen que codifica la proteína reguladora de la conductibilidad transmembrana de la fibrosis quística (CFTR) que actúa como un canal de cloro y cumple funciones de hidratación del líquido periciliar y mantenimiento del pH luminal. La disfunción del canal de cloro en el epitelio respiratorio determina una alteración en las secreciones bronquiales, con aumento de su viscosidad y alteración de la depuración mucociliar y que asociado a procesos infecciosos puede conducir a daño pulmonar irreversible. La disfunción del CFTR, también se ha visto implicado en la patogénesis de la pancreatitis aguda, en la enfermedad pulmonar obstructiva crónica y la hiperreactividad en el asma. Existen fármacos que aprovechan los mecanismos fisiológicos en el transporte de iones, con un objetivo terapéutico.

The chloride channels, sodium and bicarbonate channels, and aquaporin water channels are coordinated to maintain the airway surface liquid that is necessary for mucociliary clearance. The general mechanism for the transport of electrolytes and fluids depends mainly on the differential expression and distribution of ion transporters and pumps. Ions and water move through the paracellular or transcellular pathways. The transcellular route of electrolyte transport requires an active transport (dependent on ATP) or passive (following electrochemical gradients) of ions. The paracellular pathway is a passive process that is ultimately controlled by the predominant transepithelial electrochemical gradients. Cystic fibrosis is a hereditary disease that is produced by mutations in the gene that encode cystic fibrosis transmembrane conductance regulatory protein (CFTR) that acts as a chloride channel and performs functions of hydration of periciliary fluid and maintenance of luminal pH. The dysfunction of the chlorine channel in the respiratory epithelium determines an alteration in the bronchial secretions, with an increase in its viscosity and alteration of the mucociliary clearance and that associated with infectious processes can lead to irreversible lung damage. CFTR dysfunction has also been implicated in the pathogenesis of acute pancreatitis, chronic obstructive pulmonary disease, and bronchial hyperreactivity in asthma. There are drugs that exploit physiological mechanisms in the transport of ions with a therapeutic objective.

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INTRODUCTION: Elastic tubing was recently investigated as an alternative to the conventional resistance training (RT) in chronic obstructive pulmonary disease (COPD). The effects of RT on the mucociliary system have not yet been reported in the literature. OBJECTIVE: The aim of this study was to evaluate the effects of two RT programs on mucociliary clearance in subjects with COPD. METHODS: Twentyeight subjects with COPD were randomly allocated by strata, according to individual strength of lower limbs, to defined groups: conventional resistance training (GCT) or resistance training using elastic tubing (GET). Nineteen subjects (GET: n=9; GCT: n=10) completed the study and were included in the analysis. The measurement of vital signs (blood pressure, heart rate and respiratory rate), lung function (spirometry) and the primary outcome mucociliary clearance analysis (saccharin transit time test (STT)) were performed before and after the 12 weeks of RT. RESULTS: In relation to the mucociliary transportability analysis, no differences were observed between the baseline evaluations of the training groups (p=0.05). There was a significant reduction in the STT values in both training groups, GET (10.64±5.06 to 6.01±4.91) and GCT (12.07±5.10 to 7.36±2.54) with p=0.03. However, no differences between groups were observed on the magnitude of SST changes after interventions (GET: -43.51%; GCT: -38.94%; p=0.97). CONCLUSION: The present study demonstrated that both RT with elastic tubing and conventional training with weights promoted similar gains in the mucociliary transportability of subjects with COPD.

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BACKGROUND: The respiratory epithelium is mainly constituted by caliciform (produces mucus, responsible of keeping moisture and trapping particles) and ciliated cells (transports mucus into the pharynx, by the movement of multiple cilia). For centuries, nasal lavages have been used for different rhinosinusal conditions. Some studies suggest not only a direct effect on the mobilisation of secretions, but also an improvement in mucociliary clearance rates. To our knowledge, the impact of temperature in nasal lavages has been scarcely studied. METHODOLOGY/PRINCIPAL: We used the saccharin test-applying it in the inferior turbinate and timing the detection of its taste-, to estimate mucociliary clearance rates before and after nasal lavages with saline solution at room (20 °C) or body (37 °C) temperatures. RESULTS: 78 healthy subjects were studied, with a mean saccharin test time of 13.88 min. Then, a nasal lavage was performed, half with 20 °C saline and the other with 37 °C. In both, times improved from baseline (from 13.66 to 11.59 and 14.06 to 9.4 min, respectively) with p values < 0.05. CONCLUSIONS: Nasal lavages with saline solution improve mucociliary clearance as measured by saccharin test. Temperature seems to matter, which should be taken into account when indicating nasal lavages to our patients.

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Abstract Introduction: Female smoker's present increased susceptibility to several diseases when compared to the opposite gender. However, there are no studies showing differences in nasal mucociliary transport behavior between male and female smokers. Objective: To compare the nasal mucociliary transportability in male and female smokers and non-smokers, taking into consideration age, anthropometric data, smoking load and pulmonary function. Methods: The analysis included 139 individuals (33 men and 37 women smokers and 32 men and 37 women non-smokers). All participants answered an initial interview to obtain personal data and smoking load. Anthropometric data and carbon monoxide in the exhaled air were assessed. Individuals also performed pulmonary function test and Saccharin Transit Time test. To compare saccharin transit time values between men and women, smokers and non-smokers, stratification of all independent variables was performed (sociodemographic, smoking and respiratory variables) into two categories: below and above the median values. Results: There was no difference between men and women, smokers and non-smokers, regarding nasal mucociliary transportability. Significant differences were only observed between non-smokers. Among those with less forced vital capacity values (<97.37% of predicted), women presented mucociliary transport faster than men. Moreover, it was observed influence of BMI and COex (women smokers), FCV and FEV1 (men non-smokers) and FEF25-75% (women non-smokers) on saccharin transit time values. Conclusion: Based on the findings of this study, nasal mucociliary transport in male and female adult smokers, apparently healthy, are similar.

Resumo Introdução: Mulheres tabagistas apresentam maior susceptibilidade à diversas doenças quando comparadas ao sexo masculino. No entanto, não há estudos mostrando diferenças no comportamento do transporte mucociliar nasal entre tabagistas do sexo masculino e feminino. Objetivo: Comparar a transportabilidade mucociliar nasal em homens e mulheres fumantes e não fumantes, levando em consideração idade, dados antropométricos, carga tabágica e função pulmonar. Método: A análise incluiu 139 indivíduos (33 homens e 37 mulheres fumantes e 32 homens e 37 mulheres não fumantes). Todos os participantes responderam a uma entrevista inicial para a obtenção de dados pessoais e a carga tabágica. Dados antropométricos e monóxido de carbono no ar expirado foram avaliados. Os indivíduos também fizeram teste de função pulmonar e o teste de trânsito de sacarina. Para comparar os valores do teste de trânsito de sacarina entre homens e mulheres, fumantes e não fumantes, foi feita a estratificação de todas as variáveis independentes (variáveis sociodemográficas, tabágicas e respiratórias) em duas categorias: abaixo e acima dos valores médios. Resultados: Não houve diferenças entre homens e mulheres, fumantes e não fumantes, em relação à transportabilidade mucociliar nasal. Diferenças significativas foram observadas apenas entre não fumantes. Entre os que apresentaram valores menores de capacidade vital forçada (< 97,37% do previsto), as mulheres apresentaram transporte mucociliar mais rápido do que os homens. Além disso, observou-se influência do IMC e COex (mulheres fumantes), CVF e VEF1 (homens não fumantes) e FEF25%-75% (mulheres não fumantes) sobre os valores do teste de trânsito de sacarina. Conclusão: Com base nos achados deste estudo, o transporte mucociliar nasal em tabagistas masculinos e femininos adultos, aparentemente saudáveis, são semelhantes.

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INTRODUCTION: Female smoker's present increased susceptibility to several diseases when compared to the opposite gender. However, there are no studies showing differences in nasal mucociliary transport behavior between male and female smokers. OBJECTIVE: To compare the nasal mucociliary transportability in male and female smokers and non-smokers, taking into consideration age, anthropometric data, smoking load and pulmonary function. METHODS: The analysis included 139 individuals (33 men and 37 women smokers and 32 men and 37 women non-smokers). All participants answered an initial interview to obtain personal data and smoking load. Anthropometric data and carbon monoxide in the exhaled air were assessed. Individuals also performed pulmonary function test and Saccharin Transit Time test. To compare saccharin transit time values between men and women, smokers and non-smokers, stratification of all independent variables was performed (sociodemographic, smoking and respiratory variables) into two categories: below and above the median values. RESULTS: There was no difference between men and women, smokers and non-smokers, regarding nasal mucociliary transportability. Significant differences were only observed between non-smokers. Among those with less forced vital capacity values (<97.37% of predicted), women presented mucociliary transport faster than men. Moreover, it was observed influence of BMI and COex (women smokers), FCV and FEV1 (men non-smokers) and FEF25-75% (women non-smokers) on saccharin transit time values. CONCLUSION: Based on the findings of this study, nasal mucociliary transport in male and female adult smokers, apparently healthy, are similar.

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OBJECTIVE:: To evaluate the effects of passive inhalation of cigarette smoke on the respiratory system of guinea pigs. METHODS:: Male guinea pigs were divided into two groups: control and passive smoking, the latter being exposed to the smoke of ten cigarettes for 20 min in the morning, afternoon and evening (30 cigarettes/day) for five days. After that period, inflammatory parameters were studied by quantifying mesenteric mast cell degranulation, as well as oxidative stress, in BAL fluid. In addition, we determined MIP, MEP, and mucociliary transport (in vivo), as well as tracheal contractility response (in vitro). RESULTS:: In comparison with the control group, the passive smoking group showed a significant increase in mast cell degranulation (19.75 ± 3.77% vs. 42.53 ± 0.42%; p < 0.001) and in the levels of reduced glutathione (293.9 ± 19.21 vs. 723.7 ± 67.43 nM/g of tissue; p < 0.05); as well as a significant reduction in mucociliary clearance (p < 0.05), which caused significant changes in pulmonary function (in MIP and MEP; p < 0.05 for both) and airway hyperreactivity. CONCLUSIONS:: Passive inhalation of cigarette smoke caused significant increases in mast cell degranulation and oxidative stress. This inflammatory process seems to influence the decrease in mucociliary transport and to cause changes in pulmonary function, leading to tracheal hyperreactivity. OBJETIVO:: Avaliar os efeitos da inalação passiva da fumaça de cigarro no sistema respiratório de cobaias. MÉTODOS:: Foram utilizadas cobaias machos, divididas em dois grupos: controle e tabagismo passivo, esse último exposto à fumaça de dez cigarros por 20 min pela manhã, tarde e noite (30 cigarros/dia) por 5 dias. Após esse período, parâmetros inflamatórios foram estudados através da contagem de degranulação de mastócitos no mesentério e de estresse oxidativo a partir do LBA. Adicionalmente, foram verificadas PImáx, PEmáx, transporte mucociliar (in vivo) e contratilidade traqueal (in vitro). RESULTADOS:: Na comparação com o grupo controle, o grupo tabagismo passivo apresentou um aumento significativo na degranulação de mastócitos (19,75 ± 3,77% vs. 42,53 ± 0,42%; p < 0,001), nos níveis de glutationa reduzida (293,9 ± 19,21 vs. 723,7 ± 67,43 nM/g de tecido; p < 0,05) e uma redução significativa no transporte mucociliar (p < 0,05), provocando alterações significativas na função pulmonar, tanto na PImáx como na PEmáx (p < 0,05 para ambas), e hiper-reatividade nas vias aéreas. CONCLUSÕES:: A inalação passiva da fumaça de cigarro ocasionou aumentos significativos na degranulação de mastócitos e no estresse oxidativo. Esse processo inflamatório parece ter influenciado a diminuição do transporte mucociliar e causado alterações na função pulmonar, proporcionando um quadro de hiper-reatividade traqueal.

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ABSTRACT Objective: To evaluate the effects of passive inhalation of cigarette smoke on the respiratory system of guinea pigs. Methods: Male guinea pigs were divided into two groups: control and passive smoking, the latter being exposed to the smoke of ten cigarettes for 20 min in the morning, afternoon and evening (30 cigarettes/day) for five days. After that period, inflammatory parameters were studied by quantifying mesenteric mast cell degranulation, as well as oxidative stress, in BAL fluid. In addition, we determined MIP, MEP, and mucociliary transport (in vivo), as well as tracheal contractility response (in vitro). Results: In comparison with the control group, the passive smoking group showed a significant increase in mast cell degranulation (19.75 ± 3.77% vs. 42.53 ± 0.42%; p < 0.001) and in the levels of reduced glutathione (293.9 ± 19.21 vs. 723.7 ± 67.43 nM/g of tissue; p < 0.05); as well as a significant reduction in mucociliary clearance (p < 0.05), which caused significant changes in pulmonary function (in MIP and MEP; p < 0.05 for both) and airway hyperreactivity. Conclusions: Passive inhalation of cigarette smoke caused significant increases in mast cell degranulation and oxidative stress. This inflammatory process seems to influence the decrease in mucociliary transport and to cause changes in pulmonary function, leading to tracheal hyperreactivity.

RESUMO Objetivo: Avaliar os efeitos da inalação passiva da fumaça de cigarro no sistema respiratório de cobaias. Métodos: Foram utilizadas cobaias machos, divididas em dois grupos: controle e tabagismo passivo, esse último exposto à fumaça de dez cigarros por 20 min pela manhã, tarde e noite (30 cigarros/dia) por 5 dias. Após esse período, parâmetros inflamatórios foram estudados através da contagem de degranulação de mastócitos no mesentério e de estresse oxidativo a partir do LBA. Adicionalmente, foram verificadas PImáx, PEmáx, transporte mucociliar (in vivo) e contratilidade traqueal (in vitro). Resultados: Na comparação com o grupo controle, o grupo tabagismo passivo apresentou um aumento significativo na degranulação de mastócitos (19,75 ± 3,77% vs. 42,53 ± 0,42%; p < 0,001), nos níveis de glutationa reduzida (293,9 ± 19,21 vs. 723,7 ± 67,43 nM/g de tecido; p < 0,05) e uma redução significativa no transporte mucociliar (p < 0,05), provocando alterações significativas na função pulmonar, tanto na PImáx como na PEmáx (p < 0,05 para ambas), e hiper-reatividade nas vias aéreas. Conclusões: A inalação passiva da fumaça de cigarro ocasionou aumentos significativos na degranulação de mastócitos e no estresse oxidativo. Esse processo inflamatório parece ter influenciado a diminuição do transporte mucociliar e causado alterações na função pulmonar, proporcionando um quadro de hiper-reatividade traqueal.

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BACKGROUND: The impact of cardiac surgery using cardiopulmonary bypass (CPB) on the respiratory mucociliary function is unknown. This study evaluated the effects of CPB and interruption of mechanical ventilation on the respiratory mucociliary system. METHODS: Twenty-two pigs were randomly assigned to the control (n = 10) or CPB group (n = 12). After the induction of anesthesia, a tracheostomy was performed, and tracheal tissue samples were excised (T0) from both groups. All animals underwent thoracotomy. In the CPB group, an aorto-bicaval CPB was installed and maintained for 90 minutes. During the CPB, mechanical ventilation was interrupted, and the tracheal tube was disconnected. A second tracheal tissue sample was obtained 180 minutes after the tracheostomy (T180). Mucus samples were collected from the trachea using a bronchoscope at T0, T90 and T180. Ciliary beat frequency (CBF) and in situ mucociliary transport (MCT) were studied in ex vivo tracheal epithelium. Mucus viscosity (MV) was assessed using a cone-plate viscometer. Qualitative tracheal histological analysis was performed at T180 tissue samples. RESULTS: CBF decreased in the CPB group (13.1 ± 1.9 Hz vs. 11.1 ± 2.1 Hz, p < 0.05) but not in the control group (13.1 ± 1 Hz vs. 13 ± 2.9 Hz). At T90, viscosity was increased in the CPB group compared to the control (p < 0.05). No significant differences were observed in in situ MCT. Tracheal histology in the CPB group showed areas of ciliated epithelium loss, submucosal edema and infiltration of inflammatory cells. CONCLUSION: CPB acutely contributed to alterations in tracheal mucocilliary function.

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AIM: To report quantitative evidence for the accuracy of the defining characteristics of ineffective airway clearance in different settings and populations. BACKGROUND: Defining characteristics are tests used by nurses to clinically indicate the presence or absence of a particular nursing diagnosis. A few studies have reported the accuracy of certain defining characteristics of ineffective airway clearance, but these studies address specific populations with particular needs. DESIGN: A systematic review with meta-analysis was conducted to provide a synthesis and critical appraisal of the included studies. DATA SOURCES: The electronic databases CINAHL, PubMed, Scopus and LILACS were searched using a systematic search strategy for studies published in any year. The last search was performed on 31 July 2013. REVIEW METHODS: Using the recommendations from Cochrane Collaboration for Systematic Reviews of Diagnostic Test Accuracy and the Standards for Reporting of Diagnostic Accuracy (STARD), a systematic review was conducted using studies investigating the presence of ineffective airway clearance and its defining characteristics. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used to evaluate the quality of the studies. RESULTS: Seven papers met the search criteria. The studies were developed in different clinical settings and most of them fulfilled QUADAS criteria. Summary measures indicated the following defining characteristics with higher accuracy values: adventitious breath sounds, changes in respiratory rate, difficult vocalizing, diminished breath sounds, dyspnoea, ineffective cough, orthopnoea and restlessness. CONCLUSION: This systematic review showed that the variability in clinical indicators of ineffective airway clearance is related to differences in the clinical settings and patients.

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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.

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INTRODUCTION: Smoking cessation promotes health benefits and, despite cigarette smoking be an important pro inflammatory stimulus, there are few studies concerning the nasal and systemic inflammation; as well as the mucociliary clearance behavior in smokers after short period of smoking cessation. AIM: To evaluate the nasal and systemic inflammatory markers and mucociliary clearance behavior after 30 days of cigarette smoking abstinence. METHODS: Twenty-five smokers were included and divided into two groups: abstinent smokers (n = 14) and current smokers (n = 11). Tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-8 and IL-10 were measured on nasal lavage and blood serum samples by ELISA at baseline and after 30 days. The mucociliary clearance, exhaled carbon monoxide (exCO) and carboxyhemoglobin (HbCO) were also measured at the same moments. RESULTS: There was a decrease of TNF-α level only in blood serum at 30 days of abstinence compared to current smokers. The mucociliary clearance improved and there was a reduction in exCO and HbCO (p < 0.05 for all) after 30 days of smoking cessation. CONCLUSION: The short term smoking abstinence decreased systemic inflammation and improved nasal mucociliary clearance, despite not having changed the nasal inflammation.

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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.

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BACKGROUND: Pneumonia is observed in horses after long-distance transportation in association with confinement of head position leading to reduction in tracheal mucociliary clearance rate (TMCR). HYPOTHESIS/OBJECTIVES: Clenbuterol, a beta-2 agonist shown to increase TMCR in the horse, will ameliorate the effects of a fixed elevated head position on large airway contamination and inflammation in a model of long-distance transportation model. ANIMALS: Six adult horses. METHODS: A cross-over designed prospective study. Horses were maintained with a fixed elevated head position for 48 hours to simulate long-distance transport, and treated with clenbuterol (0.8 µg/kg PO q12h) or a placebo starting 12 hours before simulated transportation. TMCR was measured using a charcoal clearance technique. Data were collected at baseline and 48 hours, and included TMCR, tracheal wash cytology and quantitative culture, rectal temperature, CBC, fibrinogen, and serum TNFα, IL-10, and IL-2 levels. There was a 18-21 day washout between study arms, and data were analyzed using regression analysis and Wilcoxon rank-sum tests. RESULTS: Tracheal mucociliary clearance rate was significantly decreased after transportation in both treatment (P = .002) and placebo (P = .03) groups. There was a significant effect of treatment on TMCR, with the treatment group showing half the reduction in TMCR compared with the placebo group (P = .002). Other significant differences between before- and after-transportation samples occurred for serum fibrinogen, peripheral eosinophil count, quantitative culture, tracheal bacteria, and degenerate neutrophils, though no treatment effect was found. CONCLUSIONS AND CLINICAL IMPORTANCE: Treatment with clenbuterol modestly attenuates the deleterious effects of this long-distance transportation model on tracheal mucociliary clearance.

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OBJECTIVE: To characterise and compare the in vitro transport properties of respiratory mucoid secretion in individuals with no lung disease and in stable patients with chronic obstructive pulmonary disease (COPD) and bronchiectasis. METHODOLOGY: Samples of mucus were collected, from 21 volunteers presenting no lung disease who had undergone surgery, from 10 patients presenting chronic COPD, and from 16 patients with bronchiectasis. Mucociliary transport (MCT), transport by cough (SCM), and contact angle (CAM) were evaluated. RESULTS: MCT was found to be greater in healthy individuals (1.0±0.19) than in COPD (0.91±0.17) and bronchiectasis (0.76±0.23) patients (p<0.05), whereas SCM was greater in COPD patients (16.31±7.35 cm) than in patients with bronchiectasis (12.16±6.64 cm) and healthy individuals (10.50±25.8 cm) (p<0.05). No significant differences were observed between the groups regarding CAM. CONCLUSION: Mucus from healthy individuals allows better mucociliary transport compared to that from patients with lung diseases. However, the mucus from COPD patients allows a better transport by coughing, demonstrating that these individuals have adapted to a defence mechanism compared to patients with bronchiectasis, who have impairment in their ciliary and cough transport mechanisms.

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BACKGROUND: Smoking impairs mucociliary clearance and increases respiratory infection frequency and severity in subjects with and without smoking-related chronic lung diseases. OBJECTIVE: This study evaluated the effects of smoking intensity on mucociliary clearance in active smokers. METHODS: Seventy-five active smokers were grouped into light (1-10 cigarettes/day; n = 14), moderate (11-20 cigarettes/day; n = 34) and heavy smokers (≥21 cigarettes/day; n = 27) before starting a smoking cessation programme. Smoking behaviour, nicotine dependence, pulmonary function, carbon monoxide in exhaled air (exCO), carboxyhaemoglobin (COHb) and mucociliary clearance measured by the saccharin transit time (STT) test were all evaluated. An age-matched non-smoker group (n = 24) was assessed using the same tests. RESULTS: Moderate (49 ± 7 years) and heavy smokers (46 ± 8 years) had higher STT (p = 0.0001), exCO (p < 0.0001) and COHb (p < 0.0001) levels compared with light smokers (51 ± 15 years) and non-smokers (50 ± 11 years). A positive correlation was observed between STT and exCO (r = 0.4; p < 0.0001), STT and cigarettes/day (r = 0.3, p = 0.02) and exCO and cigarettes/day (r = 0.3, p < 0.01). CONCLUSION: Smoking impairs mucociliary clearance and is associated with cigarette smoking intensity.

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BACKGROUND: We showed previously that nasal mucociliary clearance was decreased in critically ill elderly subjects, most of whom had diabetes mellitus (DM) and/or hypertension (HTN). To determine if these changes were due to the effects of aging, disease, or critical illness, we studied nasal mucociliary clearance and mucus properties in an ambulatory population consisting of young, elderly, and healthy subjects and those with DM, HTN, or both. METHODS: Of 440 subjects contacted, 252 entered the study. The subjects were divided into the following groups: (1) healthy (n 5 79, 18-94 years, 50 men) and (2) DM and/or HTN, of which 37 had DM (14-90 years, 12 men), 52 had HTN (23-90 years, 12 men), and 84 had both DM and HTN (25-82 years, 33 men). Subjects were also grouped by age: , 40 years, 40 to 59 years, and 60 years. We assessed demographic and clinical data, quality of life using the 36-Item Short Form Health Survey (SF-36) questionnaire, nasal mucociliary clearance using the saccharine transit test (STT), and in vitro mucus properties by examining the sneeze (high airflow) clearability and contact angle. A logistic regression analysis for prolonged STT . 12 min was used, and we controlled for age, sex, and diseases. RESULTS: Subjects aged . 60 years reported a decreased SF-36 physical component relative to other age groups. Sex, BMI, BP, heart rate, pulse oximetry, blood glucose level, and mucus properties were not associated with prolonged STT. Aging and DM and/or HTN independently increased the risk of prolonged STT. CONCLUSIONS: Aging and DM, HTN, or both diseases are independently associated with decreased nasal mucociliary clearance. This may predispose toward respiratory infections.

Assuntos

RESUMO

OBJECTIVE: Infections have been and remain the major cause of morbidity and mortality after lung transplantation. Because mucociliary clearance plays an important role in human defense mechanisms, the influence of drugs on the mucociliary epithelium of patients undergoing lung transplantation must be examined. Prednisone is the most important corticosteroid used after lung transplantation. The aim of this study was to evaluate the effects of bronchial transection and prednisone therapy on mucociliary clearance. METHODS: A total of 120 rats were assigned to 4 groups according to surgical procedure or drug therapy: prednisone therapy (1.25 mg/kg/day); bronchial section and anastomosis + prednisone therapy (1.25 mg/kg/day); bronchial section + saline solution (2 ml/day); and saline solution (2 ml/day). After 7, 15, or 30 days, the animals were sacrificed, and the lungs were removed from the thoracic cavity. The in situ mucociliary transport velocity, ciliary beat frequency and in vitro mucus transportability were evaluated. RESULTS: Animals undergoing bronchial section surgery and anastomosis had a significant decrease in the ciliary beat frequency and mucociliary transport velocity 7 and 15 days after surgery (p<0.001). These parameters were normalized 30 days after the surgical procedure. Prednisone improved mucous transportability in the animals undergoing bronchial section and anastomosis at 15 and 30 days (p<0.05). CONCLUSION: Bronchial section and anastomosis decrease mucociliary clearance in the early postoperative period. Prednisone therapy improves mucus transportability in animals undergoing bronchial section and anastomosis.

Assuntos

RESUMO

BACKGROUND: Positive expiratory pressure (PEP) is used for airway clearance in cystic fibrosis (CF) patients. Hypertonic saline (HTS) aerosol increases sputum expectoration volume and may improve respiratory secretion properties. CPAP may also be used to maintain airway patency and mobilize secretions. To evaluate if CPAP would increase the beneficial clearance effect of HTS in subjects with CF, we investigated the effects of CPAP alone and CPAP followed by HTS on sputum physical properties and expectoration volume in CF subjects. METHODS: In this crossover study, 15 CF subjects (mean age 19 y old) were randomized to interventions, 48 hours apart: directed coughs (control), CPAP at 10 cm H(2)O, HTS 7%, and both CPAP and HTS (CPAP+HTS). Sputum collection was performed at baseline and after interventions. Expectorated volume was determined and in vitro sputum properties were analyzed for contact angle and cough clearability. RESULTS: There were no significant differences between any treatment in arterial blood pressure, heart rate, or pulse oximetry, between the 2 time points. HTS and CPAP+HTS improved cough clearability by 50% (P = .001) and expectorated volume secretion by 530% (P = .001). However, there were no differences between control and CPAP on sputum contact angle, cough clearability, or volume of expectorated secretion. CONCLUSIONS: CPAP alone had no effect on mucus clearance, sputum properties, or expectorated volume, and did not potentiate the effect of HTS alone in CF subjects.

Assuntos