Comparison of Isotonic Seawater Nasal Spray Containing Chamomile Liquid Extract and Other Isotonic Seawater Nasal Washing Solutions for Allergic Rhinitis.

OBJECTIVE: We aim to demonstrate the effect of an isotonic seawater spray containing chamomile liquid extract on symptoms and nasal mucociliary clearance in patients with allergic rhinitis by comparing it with other isotonic seawater nasal washing solutions. METHODS: The study included 123 patients. Based on Allergic Rhinitis and its Impact on Asthma guidelines, mometasone furoate intranasal spray treatment was started for all patients in the group diagnosed with allergic rhinitis. In addition to this treatment, isotonic seawater spray with chamomile liquid extract was added to Group A, isotonic seawater spray to Group B, and isotonic seawater nasal irrigation to Group C. The fourth group (Group D) was given only nasal steroid spray without nasal washing treatment. Before and after treatment in all patients, the Sino-Nasal Outcome Test-22 was performed, and nasal mucociliary clearance times were measured by the saccharin test. RESULTS: The differences in duration of nasal mucociliary clearance and Sino-Nasal Outcome Test-22 values were taken before and after treatment. In Group A, B, C, and D the Sino-Nasal Outcome Test-22 differences were statistically significant (P ≤.001; P ≤ .001; P ≤ .001, and P = .048, respectively). Only Group A and Group B experienced a significant difference in nasal mucociliary clearance times (P ≤ .001; P = .010, respectively). When the Sino-nasal Outcome Test-22 score and nasal mucociliary clearance time differences before and after treatment were compared between all groups, the Sino-Nasal Outcome Test-22 score difference was higher in Group A than in Groups B, C, and D, the differences were found as statistically significant (P = .010; P = .003; P ≤ .001, respectively). The nasal mucociliary clearance time difference was higher in Group A than in Groups C and D, the differences were found as statistically significant (P = .010; P = .001, respectively). CONCLUSION: Isotonic seawater spray containing chamomile liquid extract is seen as a good alternative treatment option for allergic rhinitis patients.

Design and evaluation of thermo-responsive nasal in situ gelling system dispersed with piribedil loaded lecithin-chitosan hybrid nanoparticles for improved brain availability.

Piribedil (PBD) is a compound that has shown efficacy in clinical trials to treat motor and non-motor symptoms of Parkinson's disease. However, drug delivery issues like low oral bioavailability, high dosing frequency (3-5 tablets/day), gastrointestinal side-effects reduced the clinical use of PBD. In this work, we have developed lecithin-chitosan hybrid nanoparticles (PBD-LCNs) to improve the direct nose to brain uptake of PBD. PBD-LCNs were optimized using hybrid design approach based on DoE. The mean particle size and drug loading of PBD-LCNs were 147 nm, and 12%, respectively. The PBD-LCNs showed good stability and were found to be nearly spherical in shape. Further, the optimized LCNs were loaded in methylcellulose thermo-responsive in situ gel (PBD-LCN-ISG) to overcome rapid mucociliary clearance upon intranasal administration. Plasma and brain pharmacokinetic studies in rats showed that PBD-LCN-ISG increased the relative bioavailability of PBD in brain (AUCbrain) by about 6.4-folds and reduced the (Cmax)plasma by 3.7-folds when compared to plain intranasal suspension of PBD (PBD-Susp). Further, PBD-Susp showed limited direct nose to brain uptake with DTP values less than 0, while the optimized PBD-LCNs showed DTP value of 56% indicating efficient direct nose to brain uptake. Overall, the development of nanoformulations significantly improved the direct nose to brain uptake of PBD.

Higher throughput drug screening for rare respiratory diseases: readthrough therapy in primary ciliary dyskinesia.

BACKGROUND: Development of therapeutic approaches for rare respiratory diseases is hampered by the lack of systems that allow medium-to-high-throughput screening of fully differentiated respiratory epithelium from affected patients. This is a particular problem for primary ciliary dyskinesia (PCD), a rare genetic disease caused by mutations in genes that adversely affect ciliary movement and consequently mucociliary transport. Primary cell culture of basal epithelial cells from nasal brush biopsies followed by ciliated differentiation at the air-liquid interface (ALI) has proven to be a useful tool in PCD diagnostics but the technique's broader utility, including in pre-clinical PCD research, has been restricted by the limited number of basal cells that can be expanded from such biopsies. METHODS: We describe an immunofluorescence screening method, enabled by extensive expansion of basal cells from PCD patients and the directed differentiation of these cells into ciliated epithelium in miniaturised 96-well transwell format ALI cultures. As proof-of-principle, we performed a personalised investigation in a patient with a rare and severe form of PCD (reduced generation of motile cilia), in this case caused by a homozygous nonsense mutation in the MCIDAS gene. RESULTS: Initial analyses of ciliary ultrastructure, beat pattern and beat frequency in the 96-well transwell format ALI cultures indicate that a range of different PCD defects can be retained in these cultures. The screening system in our proof-of-principal investigation allowed drugs that induce translational readthrough to be evaluated alone or in combination with nonsense-mediated decay inhibitors. We observed restoration of basal body formation but not the generation of cilia in the patient's nasal epithelial cells in vitro. CONCLUSION: Our study provides a platform for higher throughput analyses of airway epithelia that is applicable in a range of settings and suggests novel avenues for drug evaluation and development in PCD caused by nonsense mutations.

[Comparative efficacy of various treatment regimens for children 2-5 years old with symptoms of acute viral rhinosinusitis]. / Sravnitel'naya effektivnost' razlichnykh skhem lecheniya detei 2­5 let s simptomatikoi ostrogo virusnogo rinosinusita.

In an open, randomized prospective comparative clinical study in parallel groups of patients with a diagnosis of acute respiratory infection, acute rhinosinusitis, 107 children aged 4-5 years took part. The purpose of this study was to compare the effectiveness of various treatment regimens for acute viral rhinosinusitis in children. We compared the treatment effectiveness of acute viral rhinosinusitis using the herbal medicine Sinupret in the form of oral drops, standard treatment and standard treatment supplemented with topical antibacterial drugs. The objectivity of treatment effectiveness evaluation was based on the complaints' dynamics, the changes' presence in the mucous membrane of the nasal cavity within 10 days: at the initial visit, after 3 days, on the 7th and 10th days after the initial examination. A follow-up visit was also scheduled for the 14th day. The analysis of the obtained data revealed that the Sinupret usage in the complex treatment of children with viral etiology acute rhinosinusitis contributes to a more pronounced positive symptoms' dynamics compared to children who did not receive Sinupret. Sinupret eliminates mucostasis, which contributes to a faster restoration of the drainage and ventilation function of the auditory tube, restores mucociliary clearance, improves the condition and well-being of children, improves the effectiveness of therapy and shortens the treatment time.

Standardized Extract of Atractylodis Rhizoma Alba and Fructus Schisandrae Ameliorates Coughing and Increases Expectoration of Phlegm.

Cough and phlegm frequently occur in respiratory diseases like upper respiratory tract infections, acute bronchitis, and chronic obstructive pulmonary diseases. To relieve these symptoms and diseases, various ingredients are being used despite the debates on their clinical efficacy. We aimed to investigate the effects of the extract CKD-497, composed of Atractylodis Rhizoma Alba and Fructus Schisandrae, in relieving cough and facilitating expectoration of phlegm. CKD-497 was found to inhibit inflammatory mediators such as interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) in lipopolysaccharide (LPS)-treated mouse macrophages and transient receptor potential cation channel 1 (TRPV-1)-overexpressed human bronchial epithelial cells stimulated by capsaicin. CKD-497 decreased the viscosity of the mucin solution. During in vivo experiments, CKD-497 reduced coughing numbers and increased expectoration of phlegm via mucociliary clearance enhancement. Collectively, these data suggest that CKD-497 possesses potential for cough and phlegm expectoration treatment.

Oscillating devices for airway clearance in people with cystic fibrosis.

BACKGROUND: Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis. Oscillating devices generate intra- or extra-thoracic oscillations orally or external to the chest wall. Internally they create variable resistances within the airways, generating controlled oscillating positive pressure which mobilises mucus. Extra-thoracic oscillations are generated by forces outside the respiratory system, e.g. high frequency chest wall oscillation. This is an update of a previously published review. OBJECTIVES: To identify whether oscillatory devices, oral or chest wall, are effective for mucociliary clearance and whether they are equivalent or superior to other forms of airway clearance in the successful management of secretions in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conference proceedings. Latest search of the Cystic Fibrosis Trials Register: 29 July 2019. In addition we searched the trials databases ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Latest search of trials databases: 15 August 2019. SELECTION CRITERIA: Randomised controlled studies and controlled clinical studies of oscillating devices compared with any other form of physiotherapy in people with cystic fibrosis. Single-treatment interventions (therapy technique used only once in the comparison) were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria to publications, assessed the quality of the included studies and assessed the evidence using GRADE. MAIN RESULTS: The searches identified 82 studies (330 references); 39 studies (total of 1114 participants) met the inclusion criteria. Studies varied in duration from up to one week to one year; 20 of the studies were cross-over in design. The studies also varied in type of intervention and the outcomes measured, data were not published in sufficient detail in most of these studies, so meta-analysis was limited. Few studies were considered to have a low risk of bias in any domain. It is not possible to blind participants and clinicians to physiotherapy interventions, but 13 studies did blind the outcome assessors. The quality of the evidence across all comparisons ranged from low to very low. Forced expiratory volume in one second was the most frequently measured outcome and while many of the studies reported an improvement in those people using a vibrating device compared to before the study, there were few differences when comparing the different devices to each other or to other airway clearance techniques. One study identified an increase in frequency of exacerbations requiring antibiotics whilst using high frequency chest wall oscillation when compared to positive expiratory pressure (low-quality evidence). There were some small but significant changes in secondary outcome variables such as sputum volume or weight, but not wholly in favour of oscillating devices and due to the low- or very low-quality evidence, it is not clear whether these were due to the particular intervention. Participant satisfaction was reported in 13 studies but again with low- or very low-quality evidence and not consistently in favour of an oscillating device, as some participants preferred breathing techniques or techniques used prior to the study interventions. The results for the remaining outcome measures were not examined or reported in sufficient detail to provide any high-level evidence. AUTHORS' CONCLUSIONS: There was no clear evidence that oscillation was a more or less effective intervention overall than other forms of physiotherapy; furthermore there was no evidence that one device is superior to another. The findings from one study showing an increase in frequency of exacerbations requiring antibiotics whilst using an oscillating device compared to positive expiratory pressure may have significant resource implications. More adequately-powered long-term randomised controlled trials are necessary and outcomes measured should include frequency of exacerbations, individual preference, adherence to therapy and general satisfaction with treatment. Increased adherence to therapy may then lead to improvements in other parameters, such as exercise tolerance and respiratory function. Additional evidence is needed to evaluate whether oscillating devices combined with other forms of airway clearance is efficacious in people with cystic fibrosis.There may also be a requirement to consider the cost implication of devices over other forms of equally advantageous airway clearance techniques. Using the GRADE method to assess the quality of the evidence, we judged this to be low or very low quality, which suggests that further research is very likely to have an impact on confidence in any estimate of effect generated by future interventions.

Can exercise replace airway clearance techniques in cystic fibrosis? A survey of patients and healthcare professionals.

Airway clearance techniques (ACTs) are recommended in cystic fibrosis (CF) to prevent accumulation of secretions and lung infection. "Can exercise replace chest physiotherapy for people with CF?" is one of the CF community's top 10 research questions. We conducted an online survey of the CF community to gather data on current ACT use, recommendations, reported adherence levels and exercise strategies used. There were 488 respondents: 194 (40%) people with CF (pwCF), 141 (29%) family and 153 (31%) healthcare professionals (HCPs) (mostly physiotherapists). Only 10/285 (4%) of pwCF do no exercise at present and 163/303 (54%) already incorporate exercise into ACTs. ACTs were omitted by 128/267 (48%) of pwCF when they exercised. Nearly all (110/129, 93%) of HCPs currently recommend exercise to support ACTs. A trial replacing some or all ACTs with exercise, was supported by 80/110 (73%) of HCPs, with an additional 9/110 (8%) willing to consider in selected patients.

[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.

Mucociliary transport as a link between chronic rhinosinusitis and trace element dysbalance.

Chronis rhinosinusitis is considered as a widespread public health issue with a prevalence of 10%. The disease significantly reduces quality of life and increases the risk of cardiovascular diseases as well as certain forms of cancer. Alteration of mucociliary clearance frequently observed in the patients and plays a significant role in disease pathogenesis. Certain studies have demonstrated that patients with chronic rhinosinusitis are characterized by significant reduction of essential trace elements and toxic metal overload. However, the particular mechanisms of the role of trace element dysbalance in chronic rhinosinusitis are unclear. We hypothesize that exposure to toxic trace elements (arsenic, nickel, cadmium) damages ciliary mucosal epithelium thus affecting mucociliary transport. In turn, altered mucociliary transport results in reduced removal of the inhaled metal-containing particles from nasal mucosa leading to their absorption and further aggravation of toxicity. Essential trace elements (zinc, selenium) play a significant role in regulation of mucociliary transport and immunity, thus their deficiency (either dietary or due to antagonism with toxic metals) may be associated with impaired functions and increased toxic metal toxicity. Therefore, a vicious circle involving metal accumulation and toxicity, essential element deficiency, impairment of mucociliary transport and metal particle removal, resulting in further accumulation of metals and aggravation of toxic effects is formed. The present hypothesis is supported by the findings on the impact of trace elements especially zinc and arsenic on mucociliary clearance, the role of mucociliary transport in heavy metal particles elimination from the airways, trace element dysbalance in chronic rhinosinusitis, as well as toxic and essential metal antagonism. The data from hypothesis testing and its verification may be used for development of therapeutic approach for management of chronic rhinosinusitis. Particularly, the use of essential elements (zinc, selenium) may reduce toxic metal toxicity thus destroying the vicious circle of heavy metal exposure, toxicity, alteration of mucociliary clearance, and aggravation of chronic rhinosinusitis. Essential element supplementation may be considered as a tool for management of chronic refractory rhinosinusitis. In addition, analysis of essential and toxic trace element status may provide an additional diagnostic approach to risk assessment of chronic rhinosinusitis in highly polluted environments.

Airway clearance, mucoactive therapies and pulmonary rehabilitation in bronchiectasis.

This paper aims to provide physiological rationale for airway clearance, mucoactive therapy and pulmonary rehabilitation (PR) (or exercise interventions) in bronchiectasis. There is increasing emphasis on the role of airway clearance techniques (ACT) in the management of bronchiectasis. No single ACT has currently shown superior effect over another. Given the large range of different techniques available, consideration of the physiological effects underpinning a technique including expiratory flow, ventilation and oscillation, is essential to effectively personalize ACT. Key clinical trials of mucoactives in bronchiectasis are underway and will provide clarity on the role of these agents in the management of patients with bronchiectasis. Prescription of mucoactive therapies should be done in conjunction with ACT and therefore the mechanism of action of mucoactive drugs and their timing with ACT should be taken into consideration. PR and/or exercise training are recommended in all current bronchiectasis guidelines. There is a clear physiological rationale that muscle weakness and physical inactivity may play a role in disease progression as well as impacting health-related quality of life, frequency of pulmonary exacerbations and ability to mobilize sputum. However, there are residual unanswered questions surrounding the delivery and accessibility to PR. This review summarizes the physiological principles and supporting evidence for airway clearance, mucoactive medication and PR, which are key components in the management of bronchiectasis.

Herbal dry extract BNO 1011 improves clinical and mucociliary parameters in a rabbit model of chronic rhinosinusitis.

BACKGROUND: Enhancing chloride (Cl- ) secretion in sinus epithelia represents a novel therapeutic approach to chronic rhinosinusitis (CRS). Herbal dry extract BNO 1011 enhances mucociliary clearance (MCC) via upregulation of Cl- secretion in sinonasal cultures in vitro and murine epithelium in vivo. The objective of this study is to evaluate whether the BNO 1011 improves MCC and clinical parameters in a rabbit model of CRS. METHODS: After the development of CRS in 30 New Zealand white rabbits, animals were randomly assigned to receive oral placebo (n = 10), BNO 1011 (low dose [LD], 25 mg/kg/daily) (n = 10), or BNO1011 (high dose [HD], 125 mg/kg/daily) (n = 10) for 4 weeks. Outcomes included sinus opacification (Kerschner's rabbit sinus CT grade), maxillary epithelial Cl- secretion (sinus potential difference [PD] assay), airway surface liquid (ASL) depth using micro-optical coherence tomography (µOCT), and submucosal gland density (SMD) on histopathology. Outcome parameters were analyzed by 2 blinded investigators. RESULTS: BNO 1011 significantly cleared sinus opacification (HD = 1.21 ± 0.63, LD = 1.26 ± 0.37,) compared to placebo (4.02 ± 0.92) (p = 0.009). BNO 1011 resulted in markedly greater mean sinus PD polarization (HD = -12.23 ± 1.4 mV, LD = -12.0 ± 3.0 mV) when compared to rabbits treated with placebo (-4.1 ± 1.1 mV) (p = 0.03). ASL depth was significantly improved when treated with HD (4.08 ± 0.06 µm) and LD (4.05 ± 0.06 µm) compared to placebo (3.5 ± 0.05 µm) (post hoc analysis, p < 0.0001). Histologically, epithelial thickness (HD = 10.0 ± 0.7 µm; LD = 13.7 ± 0.9 µm; placebo = 21.1 ± 2.3 µm; p < 0.005), subepithelial thickness (HD = 63.1 ± 6.6 µm; LD = 103.2 ± 6.7 µm; placebo = 113.3 ± 6.0 µm; p < 0.001), and SMD (HD = 22.2 ± 2.9%; LD = 31.8 ± 1.1%; placebo = 43.8 ± 1.7%; p < 0.0001) were noticeably better with the HD. CONCLUSION: Herbal dry extract BNO 1011 improves radiographic, histologic, and MCC parameters in a rabbit model of CRS.

Hypertonic Saline Versus Isotonic Saline Nasal Irrigation: Systematic Review and Meta-analysis.

Background Saline nasal lavage is one of the treatments of sinonasal diseases. Evidence from basic research favors hypertonic saline (HS) over isotonic saline (IS) for mucociliary clearance, but evidence from clinical studies is controversial. Conversely, HS may carry greater side effects. Objective To compare the effects of HS and IS nasal irrigation in treating sinonasal diseases. Methods Systematic search with Ovid MEDLINE, Scopus, PubMed, Google Scholar, and Manual additional sources was conducted. Randomized controlled trials comparing HS with IS nasal irrigation in treating any sinonasal diseases, including rhinitis and rhinosinusitis, were included. Data were pooled for meta-analyses. Outcomes were symptom scores, sinonasal outcome test (SNOT), and adverse events. Heterogeneity was explored by subgroup analyses. Results Nine studies (740 patients) were included. HS nasal irrigation brought greater benefits over IS in symptom reduction (standardized mean difference (SMD) -0.58; 95% confidence interval [CI]: -0.76, -0.40); however, no difference was shown in SNOT-20 improvement (mean difference 1.81; 95% CI: -0.68, 4.30). In subgroup analyses, effects favoring HS on symptoms were larger in 4 subgroups. These were (1) patients with rhinitis (SMD -1.09; 95% CI: -1.42, -0.76) compared with rhinosinusitis (SMD -0.37; 95% CI: -0.58, -0.15), P < .01; (2) patients under the age of 18 years (SMD -1.22; 95% CI: -1.53, -0.91) compared with patients over the age of 18 years (SMD -0.26; 95% CI: -0.49, -0.04), P < .01; (3) saline irrigation using high volume (SMD -0.89; 95% CI: -1.18, -0.60) compared with low volume (SMD -0.39; 95% CI: -0.62, -0.16), P < .01; and (4) saline irrigation with hypertonicity of <3% (SMD -1.09; 95% CI: -1.42, -0.76) and hypertonicity of 3%-5% (SMD -1.20; 95% CI: -1.61, -0.78) compared with hypertonicity of >5% (SMD 0.20; 95% CI: -0.15, 0.55), P < .01. Buffered saline and operative status did not have impact. HS brought greater minor adverse effects. No major adverse effects were reported. Conclusion HS improves symptoms over IS nasal irrigation in treating sinonasal diseases. There is no difference in disease-specific quality of life. However, HS brings greater minor side effects than IS.

Does Heating up Saline for Nasal Irrigation Improve Mucociliary Function in Chronic Rhinosinusitis?

Background Mucociliary function is affected by temperature. Exposure to cold air may impair ciliary beat frequency. While saline nasal irrigation improves in ciliary beat activity, there is no evidence supporting the use of heated saline irrigation in treating patients with chronic rhinosinusitis. Objective To compare the effects of heated saline to room-temperature saline nasal irrigation on mucociliary clearance in chronic rhinosinusitis patients. Methods Adult patients with chronic rhinosinusitis were randomized into two groups receiving either heated saline or room-temperature saline nasal irrigation. Healthy subjects were included as control. Saccharin transit time was measured before and after nasal irrigation. Nasal patency was assessed by peak nasal inspiratory flow, anterior rhinomanometry, acoustic rhinometry, nasal obstruction score, and breathe-comfort score. Any adverse events were reported. Results Twenty-three patients with chronic rhinosinusitis and nine healthy subjects were enrolled. Saccharin transit time was decreased after nasal irrigation in both heated saline subgroup (baseline 12.3 ± 4.5 min vs. postirrigation 8.4 ± 4.9 min, p = 0.05) and room-temperature subgroup (baseline 12.8 ± 5.0 min vs. postirrigation 8.9 ± 4.2 min, p = 0.01). The saccharin transit time improvement was not different between heated saline (3.8 ± 6.2 min) and room-temperature saline (3.8 ± 4.0 min), p = 0.13. Postheated saline irrigation saccharin transit time of chronic rhinosinusitis patients (8.4 ± 4.9 min) was not different to healthy subjects (9.2 ± 3.7 min), p = 0.69. Nasal patency was not different between groups. There was no adverse event reported. Conclusion Nasal saline irrigation is beneficial to patients with chronic rhinosinusitis on mucociliary improvement. Warming saline is not necessary and adds no additional benefit to room-temperature saline irrigation.

Isotonic saline nasal irrigation in clinical practice: a literature review / O uso da ducha nasal com solução salina na prática clínica: uma revisão da literatura

Abstract Introduction: Nasal instillation of saline solution has been used as part of the treatment of patients with upper respiratory tract diseases. Despite its use for a number of years, factors such as the amount of saline solution to be used, degree of salinity, method and frequency of application have yet to be fully explained. Objective: Review the reported outcomes of saline nasal irrigation in adults with allergic rhinitis, acute or chronic sinusitis and after functional endoscopic sinus surgery (FESS), and provide evidence to assist physiotherapists in decision making in clinical practice. Methods: A search was conducted of the Pubmed and Cochrane Library databases between 2007 and 2014. A combination of the following descriptors was used as a search strategy: nasal irrigation, nasal lavage, rhinitis, sinusitis, saline, saline solution. Results: Eight clinical trials were included, analyzed according to participant diagnosis. Conclusion: The evidence found was heterogeneous, but contributed to elucidating uncertainties regarding the use of nasal lavage in the clinical practice of physical therapy, such as the protocols used.

Resumo Introdução: A instilação nasal de solução salina tem sido utilizada como parte do tratamento de pacientes com doenças do trato respiratório superior. Apesar de ser utilizada há vários anos, fatores como: quantidade da solução a ser instilada, grau de salinidade, modo e frequência de aplicação ainda não foram totalmente elucidados. Objetivo: Revisar os desfechos evidenciados no uso da irrigação nasal salina em adultos com rinite alérgica, sinusite aguda ou crônica e em pós-operatório de cirurgia endoscópica dos seios da face (CES) além de fornecer evidências para a tomada de decisões do fisioterapeuta na sua prática clínica. Métodos: Realizou--se uma busca nas bases de dados Pubmed e Cochrane Library no período compreendido entre 2007 e 2014. Foi utilizada como estratégia a combinação dos seguintes descritores: nasal irrigation, nasal lavage, rhinits, sinusitis, saline, saline solution. Resultados: Foram incluídos oito ensaios clínicos, analisados de acordo com o diagnóstico dos participantes. Conclusão: As evidências encontradas mostraram-se heterogêneas, mas contribuíram para elucidar alguns pontos obscuros na prática clínica da fisioterapia com relação ao uso da ducha nasal, como por exemplo, os protocolos utilizados.

Therapeutic effect of hyaluronic acid in reducing nasal mucosa recovery time after septoplasty.

Mucociliary clearance represents a host defense mechanism of airways that can be compromised by various pathologic conditions, such as nasal septal deviation. Although septoplasty can resolve obstruction, it impairs mucociliary clearance in the immediate postoperative period. Clinical studies have demonstrated how hyaluronic acid can interfere with this function. Our study aims to provide evidence of a therapeutic effect of hyaluronic acid on nasal mucosa recovery after septoplasy. Sixty-five patients underwent septoplasty. On postoperative day 1, patients were randomized to a control arm that was treated with mupirocin ointment or an experimental arm that received additional treatment with sodium hyaluronate solution. Pre- and postoperatively, anterior rhinoscopy was performed to analyze mucosal status, and mucociliary clearance was measured by using the saccharin transit time (STT) method. The t test was used for independent groups. During the preoperative evaluation, we observed a significant difference in STT between the convex and concave side in both groups. Fifteen days after surgery, we observed a significant difference preoperatively to postoperatively for both the convex and the concave side (p < 0.02 and p < 0.008, respectively). One month after surgery, we observed a reduction of STT when comparing preoperative control group values and, after 1 month, postoperative values in both sides (p < 0.015 and p < 0.005, convex and concave side, respectively). Our results show a significant reduction of the STT for both nasal sides as soon as 15 days after septoplasty in patients randomized to additional treatment. Our experience provides further evidence for the therapeutic effect of hyaluronic acid in accelerating nasal mucosa recovery after septoplasty.

Oscillating devices for airway clearance in people with cystic fibrosis.

BACKGROUND: Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis. Oscillating devices generate intra- or extra-thoracic oscillations orally or external to the chest wall. Internally they create variable resistances within the airways, generating controlled oscillating positive pressure which mobilises mucus. Extra-thoracic oscillations are generated by forces outside the respiratory system, e.g. high frequency chest wall oscillation. This is an update of a previously published review. OBJECTIVES: To identify whether oscillatory devices, oral or chest wall, are effective for mucociliary clearance and whether they are equivalent or superior to other forms of airway clearance in the successful management of secretions in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conference proceedings. Latest search of the Cystic Fibrosis Trials Register: 27 April 2017.In addition we searched the trials databases ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Latest search of trials databases: 26 April 2017. SELECTION CRITERIA: Randomised controlled studies and controlled clinical studies of oscillating devices compared with any other form of physiotherapy in people with cystic fibrosis. Single-treatment interventions (therapy technique used only once in the comparison) were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria to publications and assessed the quality of the included studies. MAIN RESULTS: The searches identified 76 studies (302 references); 35 studies (total of 1138 participants) met the inclusion criteria. Studies varied in duration from up to one week to one year; 20 of the studies were cross-over in design. The studies also varied in type of intervention and the outcomes measured, data were not published in sufficient detail in most of these studies, so meta-analysis was limited. Few studies were considered to have a low risk of bias in any domain. It is not possible to blind participants and clinicians to physiotherapy interventions, but 11 studies did blind the outcome assessors.Forced expiratory volume in one second was the most frequently measured outcome. One long-term study (seven months) compared oscillatory devices with either conventional physiotherapy or breathing techniques and found statistically significant differences in some lung function parameters in favour of oscillating devices. One study identified an increase in frequency of exacerbations requiring antibiotics whilst using high frequency chest wall oscillation when compared to positive expiratory pressure. There were some small but significant changes in secondary outcome variables such as sputum volume or weight, but not wholly in favour of oscillating devices. Participant satisfaction was reported in 15 studies but this was not specifically in favour of an oscillating device, as some participants preferred breathing techniques or techniques used prior to the study interventions. The results for the remaining outcome measures were not examined or reported in sufficient detail to provide any high level evidence. AUTHORS' CONCLUSIONS: There was no clear evidence that oscillation was a more or less effective intervention overall than other forms of physiotherapy; furthermore there was no evidence that one device is superior to another. The findings from one study showing an increase in frequency of exacerbations requiring antibiotics whilst using an oscillating device compared to positive expiratory pressure may have significant resource implications. More adequately-powered long-term randomised controlled trials are necessary and outcomes measured should include frequency of exacerbations, individual preference, adherence to therapy and general satisfaction with treatment. Increased adherence to therapy may then lead to improvements in other parameters, such as exercise tolerance and respiratory function. Additional evidence is needed to evaluate whether oscillating devices combined with other forms of airway clearance is efficacious in people with cystic fibrosis.There may also be a requirement to consider the cost implication of devices over other forms of equally advantageous airway clearance techniques. Using the GRADE method to assess the quality of the evidence, we judged this to be low or very low quality, which suggests that further research is very likely to have an impact on confidence in any estimate of effect generated by future interventions.

Nasal rinsing with an atomized spray improves mucociliary clearance and clinical symptoms during peak grass pollen season.

BACKGROUND: Nasal rinsing with an atomizer spray was found to be effective in the treatment of allergic rhinitis. Two parameters express the nasal functions: (1) mucociliary clearance (MCC), and (2) the pH and its stability. MCC is the main factor that defines the time of pollen transition on the nasal mucosa and, therefore, the amount of the allergen glycoprotein elution. OBJECTIVE: We hypothesized that the nasal wash efficacy could be due to the reduction of contact time of the grass pollen on the nasal mucosa (improving MCC). METHODS: Forty patients with seasonal grass pollen oculorhinitis were randomized in two groups: 20 received three times daily nasal rinsing with hypertonic solution buffered to pH 6.1, before and during the peak pollen season in 2015 (active group), and another 20 patients were allocated to the control group and received no nasal treatment. The daily symptoms score and the use of oral antihistamines when required were evaluated during the grass pollen peak season. All the patients completed the study. RESULTS: In comparison with the control group, in the active group, a significant decrease of both nasal symptoms (p = 0.01) and consumption of antihistamines (p = 0.035) was found. Furthermore, the MCC was significantly worse (p = 0.011) only in the control group. CONCLUSION: The nasal treatment maintained the efficiency of the MCC in the patients in the active group, who showed a significant reduction of symptoms and medication score. The MCC decreased the transit time of the pollen on the nasal mucosa, which favored an elution of the allergenic proteins.

The Effects of Short- and Long-Term Exposure to Hyperbaric Oxygen on Nasal Mucociliary Clearance.

The aim of this study is to assess the effects of short- and long-term exposure to hyperbaric oxygen (HBO) on nasal mucociliary clearance (MCC). This study included 47 consecutive nondiabetic patients treated with hyperbaric oxygen therapy (HBOT). Participants were divided into 2 groups according to the taken number of HBOT sessions. Nineteen patients who received <11 HBOT sessions comprised short-term HBOT group, 28 patients who received more than 15 sessions comprised the long-term HBOT group. Mucociliary clearance was measured using a saccharin clearance test, which was performed 3 times on patients: prior to, at completion of, and 6 months after HBOT. The average number of HBOT sessions was 8 ±â€Š1.9 in short-term HBOT group and 20 ±â€Š4.8 in long-term group. Both short- and long-term exposure to HBO led to significant influence on MCC upon treatment completion (both P < 0.001). In addition, only long-term exposure to HBO caused significant elongation of MCC at long-term evaluation (6 months after HBOT). From these objective measurements, the authors can conclude that long-term exposure to HBO can cause irreversible damage to MCC compared with short-term exposure and HBOT appears to affect MCC in a dose-dependent manner. The clinical significance of this effect is of concern for patients undergoing HBOT for middle ear, sinonasal, or respiratory tract infections. Patients who undergo chronic HBOT should be monitored closely and informed about the possible negative effects.

Rhinophototherapy in persistent allergic rhinitis.

Previous published results have revealed that Rhinolight® intranasal phototherapy is safe and effective in intermittent allergic rhinitis. The present objective was to assess whether phototherapy is also safe and effective in persistent allergic rhinitis. Thirty-four patients with persistent allergic rhinitis were randomized into two groups; twenty-five subjects completed the study. The Rhinolight® group was treated with a combination of UV-B, UV-A, and high-intensity visible light, while the placebo group received low-intensity visible white light intranasal phototherapy on a total of 13 occasions in 6 weeks. The assessment was based on the diary of symptoms, nasal inspiratory peak flow, quantitative smell threshold, mucociliary transport function, and ICAM-1 expression of the epithelial cells. All nasal symptom scores and nasal inspiratory peak flow measurements improved significantly in the Rhinolight® group relative to the placebo group and this finding persisted after 4 weeks of follow-up. The smell and mucociliary functions did not change significantly in either group. The number of ICAM-1 positive cells decreased non-significantly in the Rhinolight® group. No severe side-effects were reported during the treatment period. These results suggest that Rhinolight® treatment is safe and effective in persistent allergic rhinitis.