A new paradigm in respiratory hygiene: modulating respiratory secretions to contain cough bioaerosol without affecting mucus clearance

<p>Abstract</p> <p>Background</p> <p>Several strategies and devices have been designed to protect health care providers from acquiring transmissible respiratory diseases while providing care. In modulating the physical characteristics of the respiratory secretions to minimize the aerosolization that facilitates transmission of airborne diseases, a fundamental premise is that the prototype drugs have no adverse effect on the first line of respiratory defense, clearance of mucus by ciliary action.</p> <p>Methods</p> <p>To assess and demonstrate the primary mechanism of our mucomodulators (XLs), we have built our evidence moving from basic laboratory studies to an <it>ex-vivo </it>model and then to an <it>in-vivo </it>large animal model. We exposed anesthetized dogs without hypersecretion to different dose concentrations of aerosolized XL "B", XL "D" and XL "S". We assessed: cardio-respiratory pattern, tracheal mucus clearance, airway patency, and mucus viscoelastic changes.</p> <p>Results</p> <p>Exposure of frog palate mucus to XLs did not affect the clearance of mucus by ciliary action. Dogs maintained normal cardio-respiratory pattern with XL administration. Tracheal mucociliary clearance in anesthetized dogs indicated a sustained 40% mean increase. Tracheal mucus showed increased filance, and there was no mucus retention in the airways.</p> <p>Conclusion</p> <p>The <it>ex-vivo </it>frog palate and the <it>in-vivo </it>mammalian models used in this study, appear to be appropriate and complement each other to better assess the effects that our mucomodulators exert on the mucociliary clearance defence mechanism. The physiological function of the mucociliary apparatus was not negatively affected in any of the two epithelial models. Airway mucus crosslinked by mucomodulators is better cleared from an intact airway and normally functioning respiratory system, either due to enhanced interaction with cilia or airflow-dependent mechanisms. Data obtained in this study allow us to assure that we have complied with the fundamental requirement criteria established in the initial phase of developing the concept of mucomodulation: Can we modulate the physical characteristics of the respiratory secretions to reduce aerosolization without affecting normal mucociliary clearance function, or even better improving it?</p

Challenge-induced plasma exudation and mucinous secretion in human airways

Secretion of mucins and exudation of plasma are distinct processes of importance to innate immunity and inflammatory disease. Yet, little is known about their relation in human airways. The objective of the present study was to use the human nasal airway to determine mucinous secretion and plasma exudation in response to common challenge agents and mediators. Ten healthy volunteers were subjected to nasal challenge-lavage procedures. Thus, the nasal mucosa was exposed to increasing doses of histamine (40 and 400 mu g ml(-1)), methacholine (12.5 and 25 mg) and capsaicin (30 and 300 ng ml(-1)). Fucose was selected as a global marker of mucinous secretion and alpha(2)-macroglobulin as an index of exudation of bulk plasma. All challenge agents increased the mucosal output of fucose to about the same level (P &lt; 0.01-0.05). Once significant secretion had been induced the subsequently increased dose of the challenge agent, in the case of histamine and methacholine, failed to further increase the response. Only histamine increased the mucosal output of alpha(2)-macroglobulin (P &lt; 0.01). We conclude that prompt but potentially rapidly depleted mucinous secretion is common to different kinds of airway challenges, whereas inflammatory histamine-type mediators are required to produce plasma exudation. Along with the acknowledged secretion of mucins, a practically non-depletable, pluripotent mucosal output of plasma emerges as an important component of the innate immunity of human airways

Comparison of deposition images obtained by use of an ultrafine 99m-technetium-labeled carbon dry aerosol with ventilation images obtained by use of 81m-krypton gas for evaluation of pulmonary dysfunction in calves.

OBJECTIVE: To characterize the accuracy of an ultrafine 99m-technetium-labeled carbon dry aerosol for use in assessment of regional ventilation in calves with pulmonary dysfunction. ANIMALS: 7 Belgian White and Blue calves. PROCEDURE: The ultrafine aerosol was assessed by comparing deposition (D) images with ventilation (V) images obtained by use of 81 m-krypton (81mKr) gas via D-to-V ratio (D:V) image analysis in calves during spontaneous breathing (SB) and during experimentally induced pulmonary dysfunction (ePD). RESULTS: Mismatching index (LrTot) calculated on the D:V images revealed a good match (LrTot, 0.96 +/- 0.01) between D and V distribution patterns in calves during SB. Calculation of the ultrafine aerosol penetration index relative to 81mKr (PIRel) revealed preferential distribution of the ultrafine aerosol in lung parenchyma (PIRel, 1.13 +/- 0.11). In ePD, heterogeneity in the D:V distribution was observed (LrTot, 0.78 +/- 0.10) as a result of ultrafine aerosol particles impaction in airways as indicated by PIRel (0.66 +/- 0.16) and a proportion of pixels more radioactive in D images, compared with V images, that was located in the central part of the lung (475 +/- 77% in ePD vs 32.8 +/- 5.7% in SB). However, this central deposition did not prevent visual examination of the entire ventilated lung. CONCLUSIONS AND CLINICAL RELEVANCE: The ultrafine aerosol appears suitable for use in examination of ventilated parts of lungs of cattle, even those with impaired pulmonary function. However, airway impaction of ultrafine aerosol particles impedes the quantification of regional ventilation in cattle with abnormal lung function

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%. 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.<br>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%. 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