Bio-Inspired Magnetically Responsive Silicone Cilia: Fabrication Strategy and Interaction with Biological Mucus.

Cilia are biological structures essential to drive the mobility of secretions and maintain the proper function of the respiratory airways. However, this motile self-cleaning process is significantly compromised in the presence of silicone tracheal prosthesis, leading to biofilm growth and impeding effective treatment. To address this challenge and enhance the performance of these devices, we propose the fabrication of magnetic silicone cilia, with the prospect of their integration onto silicone prostheses. The present study presents a fabrication method based on magnetic self-assembly and assesses the interaction behavior of the cilia array with biological mucus. This protocol allows for the customization of cilia dimensions across a wide range of aspect ratios (from 6 to 85) and array densities (from 10 to 80 cilia/mm2) by adjusting the fabrication parameters, offering flexibility for adjustments according to their required characteristics. Furthermore, we evaluated the suitability of different cilia arrays for biomedical applications by analyzing their interaction with bullfrog mucus, simulating the airways environment. Our findings demonstrate that the fabricated cilia are mechanically resistant to the viscous fluid and still exhibit controlled movement under the influence of an external moving magnet. A correlation between cilia dimensions and mucus wettability profile suggests a potential role in facilitating mucus depuration, paving the way for further advancements aimed at enhancing the performance of silicone prostheses in clinical settings.

Tacrolimus impairs airway mucociliary clearance of rats.

OBJECTIVES: Tacrolimus (TAC) is the most widely used immunosuppressive agent after lung transplantation. Considering that the ciliary beat frequency (CBF) mainly depends on the cytoplasmic calcium concentration and that TAC can affect this due to its binding with the intracellular immunophilin FKBP12, we hypothesized that TAC could also impair the airway mucociliary clearance of rats. METHODS: Sixty rats were divided into two groups (n = 30 each): Control = water; TAC = tacrolimus. After 7, 15 or 30 days of treatment, ten animals from each group were euthanized and the following parameters were studied: mucus transportability, CBF, mucociliary transport velocity (MCTV), and neutral and acid mucus production. RESULTS: There was a significant decrease in CBF (Control vs TAC: 7 days, p = 0.008; 15 days, p = 0.007; 30 days, p = 0.001) and MCTV (Control vs TAC: 7 days, p = 0.004; 15 days, p < 0.001; 30 days, p < 0.001) in all immunosuppressed animals. TAC therapy also caused an increase in acid mucus production at all treatment times (Control vs TAC: 7 days, p = 0.001; 15 days, p = 0.043; 30 days, p = 0.001). CONCLUSIONS: TAC impairs airway mucociliary clearance of rats.

Benzbromarone as adjuvant therapy for cystic fibrosis lung disease: a pilot clinical trial

ABSTRACT Objective: Cystic fibrosis (CF) affects multiple organs, the most severe consequences being observed in the lungs. Despite significant progress in developing CF transmembrane conductance regulator-specific treatments for CF lung disease, exploring alternative CF-targeted medications seems reasonable. We sought to evaluate the potential beneficial effects of oral benzbromarone as an adjuvant therapy in CF patients with reduced lung function. Methods: This was a prospective open-label pilot study of oral benzbromarone (100 mg/day) administered once daily for 90 days. Patients were followed at a tertiary referral center in southern Brazil. Safety was assessed by the number of reported adverse events. Secondary objectives included percent predicted FEV1 (FEV1%) and pulmonary exacerbations. Results: Ten patients were enrolled. Benzbromarone was found to be safe, with no serious drug-related adverse events. Eight patients completed the study; the median relative change in FEV1% tended to increase during the treatment, showing an 8% increase from baseline at the final visit. However, a nonparametric test showed that the change was not significant (p = 0.06). Of a total of ten patients, only one experienced at least one pulmonary exacerbation during the study. Conclusions: Oral benzbromarone appears to be safe, and improved FEV1% has been observed in patients with CF. Further assessment in larger trials is warranted to elucidate whether oral benzbromarone can be a potential adjuvant therapy for CF.

Evaluation of nasal mucociliary clearance by saccharine test in rheumatoid arthritis

Abstract Objective: We aimed to reveal whether there is nasal involvement by examining the Nasal Mucociliary Clearance (NMC) and the relationship between this activity and disease severity in Rheumatoid Arthritis (RA) patients. Methods: In this prospective study, NMC time, disease activity (Disease Activity Score 28) and blood parameters of RA patients (n = 87) were investigated and compared with the healthy control group (n = 50). In addition, the relationship between DAS 28 and NMC was investigated. Results: The mean NMC of the RA group was 9.51 ± 3.54 min, the mean NMC of the control group was 8.69 ± 2.85 min, and there was no significant difference between the two groups. There was no correlation between NMC and disease duration, and DAS 28. The mean NMC of the RA patients with Anti Cyclic Citrulled Peptide (Anti-CCP) positive was significantly higher than the negative ones. Conclusion: Although there was no significant difference in NMC values between the RA and control group, the NMC of the Anti-CCP positive patients was higher. Level of evidence: Level 2.

Basiliximab Does Not Impair Airway Mucociliary Clearance of Rats.

Previous studies have shown that immunosuppressive drugs impair the airway mucociliary clearance of rats. However, considering the high specificity of basiliximab (BSX) and the absence of studies reporting its side effects, our aim was to investigate whether BSX, associated or not with triple therapy, impairs the mucociliary system. Forty rats were divided into 4 groups: Control, BSX, Triple, and BSX + Triple. After 15 days of treatment, animals were euthanized and the ciliary beating frequency (CBF), mucociliary transport velocity (MCTV), neutral and acid mucin production, Muc5ac and Muc5b gene expression, inflammatory cell number, and interleukin (IL)-6 concentration were analyzed. CBF and MCTV were lower in Triple and BSX + Triple groups (p < 0.05). Neutral mucin percentage was higher in Triple group (p < 0.05), and acid mucin percentage was higher in Triple and BSX + Triple groups (p < 0.05). The Muc5ac and Muc5b gene expression was higher in Triple and BSX + Triple groups (p < 0.05). Animals from Triple and BSX + Triple groups presented fewer mononuclear cells (p < 0.05). The number of polymorphonuclear cells was higher in the Triple group (p < 0.05). In the analysis of inflammatory cells in the blood, there was a decrease in lymphocytes and an increase in neutrophils in the Triple and BSX + Triple groups (p < 0.05). The concentration of IL-6 significantly increased in the animals of the Triple and BSX + Triple groups (p < 0.05). BSX did not change the mucociliary apparatus of rats.

Desvendando a técnica de compressão torácica em pacientes em ventilação mecânica: uma revisão narrativa / A deep look into the rib cage compression technique in mechanically ventilated patients: a narrative review

RESUMO O manejo deficiente das secreções é uma das complicações mais frequentes em pacientes em ventilação mecânica invasiva. A depuração das secreções por meio da fisioterapia respiratória é um aspecto crítico do tratamento desses pacientes. A compressão torácica manual é uma das técnicas de fisioterapia respiratória mais praticadas em pacientes ventilados, mas seu impacto nos desfechos clínicos permanece controverso devido a questões metodológicas e ao pouco conhecimento sobre sua ação. Nesta revisão, apresenta-se uma análise detalhada dos princípios físicos envolvidos na execução da técnica de compressão torácica. Também investigam-se os efeitos fisiológicos observados em estudos experimentais e clínicos, que mostram que o uso de compressão torácica curta e vigorosa, baseada no aumento de fluxos expiratórios (diferença de fluxo aéreo inspiratório-expiratório > 33L/minuto), pode melhorar o movimento do muco em direção à glote. Por outro lado, o uso de compressão torácica suave e gradual ao longo de toda a fase expiratória não afeta os fluxos expiratórios, resultando em efeitos ineficazes ou indesejados em alguns casos. Mais estudos fisiológicos são necessários para entender os princípios da técnica de compressão torácica em pacientes ventilados. No entanto, de acordo com as evidências, a compressão torácica tem mais benefícios potenciais do que riscos, o que incentiva sua implementação.

ABSTRACT Defective management of secretions is one of the most frequent complications in invasive mechanically ventilated patients. Clearance of secretions through chest physiotherapy is a critical aspect of the treatment of these patients. Manual rib cage compression is one of the most practiced chest physiotherapy techniques in ventilated patients; however, its impact on clinical outcomes remains controversial due to methodological issues and poor understanding of its action. In this review, we present a detailed analysis of the physical principles involved in rib cage compression technique performance, as well as the physiological effects observed in experimental and clinical studies, which show that the use of brief and vigorous rib cage compression, based on increased expiratory flows (expiratory-inspiratory airflow difference of > 33L/minute), can improve mucus movement toward the glottis. On the other hand, the use of soft and gradual rib cage compression throughout the whole expiratory phase does not impact the expiratory flows, resulting in ineffective or undesired effects in some cases. More physiological studies are needed to understand the principles of the rib cage compression technique in ventilated humans. However, according to the evidence, rib cage compression has more potential benefits than risks, so its implementation should be promoted.

Evaluation of nasal mucociliary clearance by saccharine test in rheumatoid arthritis.

OBJECTIVE: We aimed to reveal whether there is nasal involvement by examining the Nasal Mucociliary Clearance (NMC) and the relationship between this activity and disease severity in Rheumatoid Arthritis (RA) patients. METHODS: In this prospective study, NMC time, disease activity (Disease Activity Score 28) and blood parameters of RA patients (n = 87) were investigated and compared with the healthy control group (n = 50). In addition, the relationship between DAS 28 and NMC was investigated. RESULTS: The mean NMC of the RA group was 9.51 ±â€¯3.54 min, the mean NMC of the control group was 8.69 ±â€¯2.85 min, and there was no significant difference between the two groups. There was no correlation between NMC and disease duration, and DAS 28. The mean NMC of the RA patients with Anti Cyclic Citrulled Peptide (Anti-CCP) positive was significantly higher than the negative ones. CONCLUSION: Although there was no significant difference in NMC values between the RA and control group, the NMC of the Anti-CCP positive patients was higher. LEVEL OF EVIDENCE: Level 2.

Blocking ATP-releasing channels prevents high extracellular ATP levels and airway hyperreactivity in an asthmatic mouse model.

Allergic asthma is a chronic airway inflammatory response to different triggers like inhaled allergens. Excessive ATP in fluids from patients with asthma is considered an inflammatory signal and an important autocrine/paracrine modulator of airway physiology. Here, we investigated the deleterious effect of increased extracellular ATP (eATP) concentration on the mucociliary clearance (MCC) effectiveness and determined the role of ATP releasing channels during airway inflammation in an ovalbumin (OVA)-sensitized mouse model. Our allergic mouse model exhibited high levels of eATP measured in the tracheal fluid with a luciferin-luciferase assay and reduced MCC velocity determined by microspheres tracking in the trachea ex vivo. Addition of ATP had a dual effect on MCC, where lower ATP concentration (µM) increased microspheres velocity, whereas higher concentration (mM) transiently stopped microspheres movement. Also, an augmented ethidium bromide uptake by the allergic tracheal airway epithelium suggests an increase in ATP release channel functionality during inflammatory conditions. The use of carbenoxolone, a nonspecific inhibitor of connexin and pannexin1 channels reduced the eATP concentration in the allergic mouse tracheal fluid and dye uptake by the airway epithelium, providing evidence that these ATP release channels are facilitating the net flux of ATP to the lumen during airway inflammation. However, only the specific inhibition of pannexin1 with 10Panx peptide significantly reduced eATP in bronchoalveolar lavage and decreased airway hyperresponsiveness in OVA-allergic mouse model. These data provide evidence that blocking eATP may be a pharmacological alternative to be explored in rescue therapy during episodes of airflow restriction in patients with asthma.

Acute Effect of Resistance Exercise on Mucociliary Clearance in Active Smokers

Abstract Background: Nasal mucociliary clearance (NMC) responds to autonomic activity through exercise. However, there is a gap in the literature on how NMC responds to resistance exercise. Objective: To evaluate the acute effects of resistance tube exercise on NMC and the autonomic nervous system in smokers. Methods: Clinical trial was performed with 18 individuals. Personal, anthropometric, and smoking history data were collected, and a pulmonary function test was performed by spirometry. The fatigue resistance test was performed in order to obtain the number of repetitions for the prescription of exercise. Heart rate variability was captured using a monitor. Subsequently, the exhaled carbon monoxide (exCO) was measured and a saccharin transit test (STT) was performed for NMC. Results: The non-smoking group presented a significant decrease of 4.0±3.2 minutes in STT after P1 (p=0.021). Regarding HRV, the smoking group presented a significant decrease of mean RR (−90.3±53.0; p=0.011), SDNN (−560.0±1333.2; p=0.008), RMSSD (−13.6±10.5; p=0.011), LFms² (−567.3±836.1; p=0.008), HFms² (−223.8±231.8; p=0.008), SD1 (−9.7±7.4; p=0.011) and SD2 (−20.7±17.0; p=0.008), and an increase of mean HR (10.2±5.9; p=0.011) after P2. In the non-smoking group, a significant decrease was observed in the mean RR (−67.1±70.7; p=0.038), SDNN (−16.8±15.0; p=0.015), RMSSD (−12.3±14.7; p=0.011), LFms² (−831.2±1347.5; p=0.015), SD1 (−8.7±10.4; p=0.011), and SD2 (−22.0±19.1; p=0.015), while an increase in HR (7.1±7.3; p=0.028) was found after P1. Conclusions: The intensity of the resistance exercise applied to the patient was not enough to promote changes in smokers. By contrast, in non-smokers, the same intensity of exercise was effective in promoting alterations in the NMC and autonomic activity. (Int J Cardiovasc Sci. 2021; 34(2):223-230)

Mucociliary Clearance of Different Respiratory Conditions: A Clinical Study.

Introduction Mucociliary clearance (MCC) is the first line of defense of the pulmonary system. Mucociliary clearance impairment may lead to increased risk of respiratory infections, lung injury, pulmonary repair problems, chronic dysfunctions and progression of respiratory diseases. Objective To characterize the MCC of active and passive smokers and individuals with chronic obstructive pulmonary disease (COPD) and compare the MCC behaviors between men and women of different age groups. Methods Patients with COPD (current smokers and ex-smokers) and apparently healthy individuals (current smokers, passive smokers and nonsmokers) were evaluated. All of the subjects underwent lung function and MCC evaluation (saccharin transport test [STT]). Smokers (with or without COPD) were questioned about the smoking history. Results A total of 418 individuals aged 16 to 82 years old, of both genders, were evaluated. The STT values of active and passive smokers were statistically higher than those of the control group ( p < 0.01). Men of the control group had lower values of STT than active smokers (9.7 ± 7.1 and 15.4 ± 10.1 minute, respectively, p < 0.01). In addition, higher MCC velocity was observed in women that are current smokers (11.7 ± 6.8 minute) compared with men (15.4 ± 10.1 minute) in this group ( p = 0.01). Among the younger age groups (< 50 years old), only passive smokers presented higher STT in relation to the control group. Conclusion Passive and active smoking are factors that influence negatively the MCC, and passive smokers may present losses of this mechanism at a younger age. Additionally, male smokers present worse MCC than male nonsmokers.

Nasal Mucociliary Clearance in Smokers: A Systematic Review.

Introduction Smoking is one of the most important causes of mortality and morbidity in the world, as it is related to the risk factor and etiology of respiratory-tract diseases. Long-term smoking causes both structural and functional damage in the respiratory airways, leading to changes in nasal mucociliary clearance (NMC). Objectives The aim of the present study was to look systematically into the current literature and carefully collect and analyze results to explore NMC in smokers. Data Synthesis Two independent reviewers conducted a literature search on some Electronic database: Pubmed, Medline, Ebsco, Springer Link, Science Direct, Scopus, and Proquest searching for articles fulfilling the inclusion and exclusion criteria. The lead author independently assessed the risk of bias of each of the included studies and discussed their assessments with the other two authors to achieve consensus. Of the 1,654 articles identified in the database search, 16 met the criteria for this review. Most of the articles (15 out of 16) showed the impairment of NMC in smokers. Conclusion The present systematic review suggests that there is an impairment of NMC in smokers. The impairment is not only observed in cigarette smoking, but also in passive smoking, bidi smoking, electronic smoking, and hookah smoking. The impairment of NMC in chronic exposure to smoking is caused by the ciliotoxic effect, hypersecretion and viscoelastic change of mucous, airway surface liquid depletion, increased oxidative stress, and deteriorations in the inflammatory and immune systems.

Mucociliary Clearance of Different Respiratory Conditions: A Clinical Study

Abstract Introduction Mucociliary clearance (MCC) is the first line of defense of the pulmonary system. Mucociliary clearance impairment may lead to increased risk of respiratory infections, lung injury, pulmonary repair problems, chronic dysfunctions and progression of respiratory diseases. Objective To characterize the MCC of active and passive smokers and individuals with chronic obstructive pulmonary disease (COPD) and compare the MCC behaviors between men and women of different age groups. Methods Patients with COPD (current smokers and ex-smokers) and apparently healthy individuals (current smokers, passive smokers and nonsmokers) were evaluated. All of the subjects underwent lung function and MCC evaluation (saccharin transport test [STT]). Smokers (with or without COPD) were questioned about the smoking history. Results A total of 418 individuals aged 16 to 82 years old, of both genders, were evaluated. The STT values of active and passive smokers were statistically higher than those of the control group (p < 0.01). Men of the control group had lower values of STT than active smokers (9.7 ± 7.1 and 15.4 ± 10.1 minute, respectively, p < 0.01). In addition, higher MCC velocity was observed in women that are current smokers (11.7 ± 6.8 minute) compared with men (15.4 ± 10.1 minute) in this group (p = 0.01). Among the younger age groups (< 50 years old), only passive smokers presented higher STT in relation to the control group. Conclusion Passive and active smoking are factors that influence negatively the MCC, and passive smokers may present losses of this mechanism at a younger age. Additionally, male smokers present worse MCC than male nonsmokers.

Nasal Mucociliary Clearance in Smokers: A Systematic Review

Abstract Introduction Smoking is one of the most important causes of mortality and morbidity in the world, as it is related to the risk factor and etiology of respiratory-tract diseases. Long-term smoking causes both structural and functional damage in the respiratory airways, leading to changes in nasal mucociliary clearance (NMC). Objectives The aim of the present study was to look systematically into the current literature and carefully collect and analyze results to explore NMC in smokers. Data Synthesis Two independent reviewers conducted a literature search on some Electronic database: Pubmed, Medline, Ebsco, Springer Link, Science Direct, Scopus, and Proquest searching for articles fulfilling the inclusion and exclusion criteria. The lead author independently assessed the risk of bias of each of the included studies and discussed their assessments with the other two authors to achieve consensus. Of the 1,654 articles identified in the database search, 16 met the criteria for this review. Most of the articles (15 out of 16) showed the impairment of NMC in smokers. Conclusion The present systematic review suggests that there is an impairment of NMC in smokers. The impairment is not only observed in cigarette smoking, but also in passive smoking, bidi smoking, electronic smoking, and hookah smoking. The impairment of NMC in chronic exposure to smoking is caused by the ciliotoxic effect, hypersecretion and viscoelastic change of mucous, airway surface liquid depletion, increased oxidative stress, and deteriorations in the inflammatory and immune systems.

Influência de uma sessão de exercício aeróbico submáximo e máximo sobre o transporte mucociliar e função autonômica em tabagistas / Influencia de una sesión de ejercicio aeróbico submáximo y máximo sobre el transporte mucociliar y la función autonómica en fumadores / Influence of a submaximal and maximal aerobic exercise session on mucociliary clearance and autonomic function in smokers

RESUMO O objetivo do estudo foi avaliar e correlacionar o comportamento da depuração mucociliar e do sistema nervoso autônomo de fumantes após sessões de exercício aeróbico submáximo e máximo. Foram avaliados 25 fumantes e 15 não fumantes, entre 30 e 50 anos. Ambos os grupos foram submetidos ao teste do tempo de trânsito de sacarina (TTS) e variabilidade da frequência cardíaca (VFC) antes e após uma sessão de exercício submáximo (teste de caminhada de seis minutos) e máximo (teste de exercício cardiopulmonar). Teste t pareado ou Wilcoxon foi utilizado para análise intragrupos e o teste t não pareado ou Mann-Whitney para a análise intergrupos. A correlação foi realizada utilizando os coeficientes de Pearson ou Spearman (p <0,05). Houve redução significativa do TTS após exercícios submáximo e máximo em ambos os grupos. Após o exercício submáximo, ambos grupos apresentaram redução significativa do intervalo RR e aumento da FC em comparação ao repouso, no grupo de não fumantes houve reduções significativas nos índices RMSSD, HFms² e SD1. Após o exercício máximo, ambos grupos apresentaram reduções significativas no SDNN, RMSSD, intervalo RR, LF e HF, em ms² e un, SD1 e SD2, além do aumento da FC, LFun e da razão LF/HF. Houve correlação positiva entre TTS e LFms² (r = 0,520, p = 0,008) após o exercício máximo para o grupo de fumantes. Conclui-se que independentemente da intensidade do exercício aeróbio, houve um aumento na depuração mucociliar em fumantes, mas essa alteração parece ser influenciada pelo sistema nervoso autônomo apenas frente o exercício máximo.

RESUMEN El objetivo de este estudio fue evaluar y correlacionar el comportamiento de la depuración mucociliar y del sistema nervioso autónomo de fumadores después de sesiones de ejercicio aeróbico submáximo y máximo. Se evaluaron a 25 fumadores y a 15 no fumadores de entre 30 y 50 años de edad. Ambos grupos se sometieron a la prueba de tiempo de tránsito de sacarina (TTS) y la variabilidad de la frecuencia cardíaca (VFC) antes y después de una sesión de ejercicio submáximo (prueba de caminata de seis minutos) y de ejercicio máximo (prueba de esfuerzo cardiopulmonar). Para el análisis intragrupo se utilizó la prueba t pareada o Wilcoxon, y para el análisis intergrupal, la prueba t no pareada o Mann-Whitney. Para realizar la correlación se utilizaron los coeficientes de Pearson o Spearman (p<0,05). Hubo una reducción significativa en TTS después de ejercicios submáximo y máximo en ambos grupos. Después del ejercicio submáximo, ambos grupos mostraron una reducción significativa en el intervalo RR y un aumento en la FC en comparación con el reposo; en el grupo de no fumadores hubo reducciones significativas en los índices RMSSD, HFms² y SD1. Después del ejercicio máximo, ambos grupos mostraron reducciones significativas en SDNN, RMSSD, intervalo RR, LF y HF, en ms² y un, SD1 y SD2, además de un aumento de FC, LFun y la relación LF/HF. Hubo una correlación positiva entre TTS y LFms² (r=0,520, p=0,008) después del ejercicio máximo para el grupo de fumadores. Se concluye que, de manera independiente a la intensidad del ejercicio aeróbico, hubo un aumento de la depuración mucociliar en los fumadores, pero este cambio parece haber sido influido por el sistema nervioso autónomo solamente en el ejercicio máximo.

ABSTRACT The aim of this study was to evaluate and to correlate the behavior of mucociliary clearance and the autonomic nervous system of smokers after submaximal and maximal aerobic exercise sessions. We evaluated 25 smokers and 15 nonsmokers aged between 30 and 50 years. Both groups were submitted to the saccharin transit time (STT) test and heart rate variability (HRV) before and after a submaximal (six-minute walk test) and maximal (cardiopulmonary test) exercise. Paired t-test or Wilcoxon were used for intragroup analysis and the unpaired t-test or Mann-Whitney for intergroup analysis. The correlation was performed using Pearson or Spearman coefficients (p<0.05). Saccharine transit time reduced significantly after submaximal and maximal exercises in both groups. After the submaximal exercise, both groups presented significant reduction of the RR interval and increased heart rate (HR). In the nonsmoker group there were significant reductions in the RMSSD, HFms² and SD1 indexes. After maximal exercise, both groups showed significant reductions in SDNN, RMSSD, RR, LF and HF interval, in ms² and normalized units, SD1 and SD2, in addition to the increase in HR, LFun, and LF/HF ratio. STT positively correlated with LFms² (r = 0.520, p = 0.008) after the maximal exercise for the smoker group. We concluded, that regardless of the intensity of aerobic exercise, mucociliary clearance increases in smokers, but this alteration seems to be influenced by the autonomic nervous system only during maximum exercise.

Comparison of the effects of voluntary and involuntary breath stacking techniques on respiratory mechanics and lung function patterns in tracheostomized patients: a randomized crossover clinical trial / Comparação dos efeitos das técnicas breath stacking e air stacking sobre a mecânica respiratória e o padrão ventilatório em pacientes traqueostomizados: ensaio clínico cruzado randomizado

ABSTRACT Objective: To compare the effects of voluntary breath stacking (VBS) and involuntary breath stacking (IBS) techniques on respiratory mechanics, lung function patterns, and inspiratory capacity in tracheostomized patients. Methods: This was a randomized crossover clinical trial involving 20 tracheostomized patients admitted to the ICU and submitted to the VBS and IBS techniques, in random order, with an interval of 5 h between each. Ten cycles of each technique were performed with an interval of 30 s between each cycle. In VBS, patients performed successive inspirations for up to 30 s through a one-way valve, whereas in IBS, successive slow insufflations were performed with a resuscitator bag until the pressure reached 40 cmH2O. Respiratory mechanics, inspiratory capacity, and the lung function pattern were evaluated before and after the interventions. Results: After IBS, there was an increase in static compliance (p = 0.007), which was also higher after IBS than after VBS (p = 0.03). There was no significant difference between the pre-VBS and post-VBS evaluations in terms of static compliance (p = 0.42). Inspiratory capacity was also greater after IBS than after VBS (2,420.7 ± 480.9 mL vs. 1,211.3 ± 562.8 mL; p < 0.001), as was airway pressure (38.3 ± 2.6 cmH2O vs. 25.8 ± 5.5 cmH2O; p < 0.001). There were no changes in resistance or lung function pattern after the application of either technique. Conclusions: In comparison with VBS, IBS promoted greater inspiratory capacity and higher airway pressure, resulting in an increase in static compliance.

RESUMO Objetivo: Comparar os efeitos das técnicas breath stacking (BS) e air stacking (AS) sobre a mecânica respiratória, o padrão ventilatório e a capacidade inspiratória em pacientes traqueostomizados. Métodos: Ensaio clínico cruzado randomizado envolvendo 20 pacientes traqueostomizados internados em UTI e submetidos a ambas as técnicas, com intervalo de 5 h entre si, de acordo com a randomização. Foram realizados dez ciclos de cada técnica com intervalos de 30 segundos entre si. No BS, os pacientes realizaram inspirações sucessivas por até 30 s por meio de uma válvula unidirecional, enquanto no AS foram realizadas insuflações lentas sucessivas através de um ressuscitador manual até que a pressão atingisse 40 cmH2O. Os pacientes foram avaliados quanto a mecânica respiratória, capacidade inspiratória e padrão ventilatório antes e depois da realização das intervenções. Resultados: Com relação à mecânica respiratória no AS, houve aumento da complacência estática na comparação pré- e pós-intervenção (p = 0,007), assim como entre os momentos pós-AS e pós-BS (p = 0,03). Não houve diferença significativa da complacência estática na realização do BS (p = 0,42). A capacidade inspiratória foi maior após o AS que após o BS (2.420,7 ± 480,9 mL vs. 1.211,3 ± 562,8 mL; p < 0,001), bem como em relação à pressão nas vias aéreas (38,3 ± 2,6 cmH2O vs. 25,8 ± 5,5 cmH2O; p < 0,001). Não foram observadas alterações na resistência ou no padrão ventilatório em ambas as técnicas. Conclusões: Na presente amostra, o AS promoveu maior capacidade inspiratória e maior pressão nas vias aéreas que as observadas após o BS, com consequente aumento da complacência estática.

[Ion transporters in the lungs. Use as therapeutic targets]. / Transportadores de iones en pulmón. Uso como dianas terapéuticas.

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.

Transportadores de iones en pulmón: Uso como dianas terapéuticas / Ion transporters in the lungs. Use as therapeutic targets

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.

Particularities and Clinical Applicability of Saccharin Transit Time Test.

Introduction The importance of mucociliary clearance (MCC) for the respiratory system homeostasis is clear. Therefore, evaluating this defense mechanism is fundamental in scientific research and in the clinical practice of pulmonology and of associated areas. However, MCC evaluation has not been so usual due to the complexity of methods that use radiolabeled particles. Nevertheless, as an interesting alternative, there is the saccharin transit time (STT) test. This method is reproducible, simple to perform, noninvasive, does not demand high costs, and has been widely used in studies of nasal MCC. Although the STT test is widely used, there is still lack of a detailed description of its realization. Objective The present literature review aims to provide basic information related to the STT test and to present the findings of the previous studies that used this method, discussing variations in its execution, possible influences on the obtained results and limitations of the method, as well as to relate our experience with the use of STT in researches. Data Synthesis There are several factors that can alter the results obtained from STT tests, which would raise difficulties with proper interpretation and with the discussion of the results among different studies. Conclusions Saccharin transit time is a widely used method for the evaluation of nasal MCC, and therefore, the standardization related to the previous and concurrent to test orientations, and also its execution, become essential to improve its accuracy, and allow comparisons among different studies.

Resistance exercise training improves mucociliary clearance in subjects with COPD: A randomized clinical trial.

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.

Particularities and clinical applicability of saccharin transit time test

Introduction: The importance ofmucociliary clearance (MCC) for the respiratory system homeostasis is clear. Therefore, evaluating this defense mechanism is fundamental in scientific research and in the clinical practice of pulmonology and of associated areas. However, MCC evaluation has not been so usual due to the complexity ofmethods that use radiolabeled particles. Nevertheless, as an interesting alternative, there is the saccharin transit time (STT) test. This method is reproducible, simple to perform, noninvasive, does notdemand high costs, and has been widely used in studies of nasalMCC. Although the STT test is widely used, there is still lack of a detailed description of its realization. Objective: The present literature review aims to provide basic information related to the STT test andto present the findings of the previous studies that usedthismethod, discussing variations in its execution, possible influences on the obtained results and limitations of the method, as well as to relate our experience with the use of STT in researches. Data Synthesis: There are several factors that can alter the results obtained from STT tests, which would raise difficulties with proper interpretation and with the discussion of the results among different studies. Conclusions: Saccharin transit time is awidely usedmethod for the evaluation of nasal MCC, and therefore, the standardization related to the previous and concurrent to test orientations, and also its execution, become essential to improve its accuracy, and allow comparisons among different studies (AU)