From modeling to remodeling of upper airways: Centrality of hyaluronan (hyaluronic acid).

After traumatic events (accidental or surgical), the respiratory tract activates specific and prolix repairing mechanisms which tend to claw back the primitive differentiated state. The attempt of reactivation of the normal tissue functions is called 'remodeling' and its aim is to reinstate the modeling mechanisms that existed before the damaging event or the pathology's establishment. Endoscopic sinus surgery represents the gold standard treatment for inflammatory, malformative, benign, and, in selected cases, malignant diseases. The surgical technique is commonly described as minimally invasive as the nostrils are used as an access route and therefore does not leave any external scars. Currently, the surgical procedures, even though minimally invasive regarding the way in, are in fact widely destructive towards the surgical target. The healing process and re-epithelialization will depend on the amount of bony tissue that has been exposed and it will be important to stratify the different surgical typologies in order to foresee the increasing difficulty of mucosal healing process. As far as upper inflammatory diseases are concerned, recent studies demonstrated how intranasal hyaluronic acid can positively regulate mucosal glands secretion and modulate inflammatory response, being a useful tool for the improvement of remodeling after endoscopic sinus surgery. Acid has shown to be able to regulate mucosal glands secretion and modulate the inflammatory response.

Post-traumatic optic neuropathy: our surgical and medical protocol.

Post-traumatic optic neuropathy (TON) is a rare, but very much feared event. It is a traumatic injury of the optic nerve at any level along its course (often inside the optic canal), with partial or total loss of visual acuity, temporarily or permanently. Until now, an univocal treatment strategy does not exist. The clinical records of 26 patients, treated from 2002 to 2013, were reviewed. The most frequent cause of injury was road traffic accident (63%), followed by iatrogenic damage, work injuries, sport or home accidents. All patients underwent pre-operative ophthalmological evaluation, neuro-imaging (angio-CT or angio-MRI scans) and systemic corticosteroid therapy. All patients required a surgical treatment, due to poor response to medical therapy; it consisted of an endonasal endoscopic decompression of the intracanalicular segment of the optic nerve, performed by removing the bony wall of the optical canal and releasing the perineural sheath. Improvement of visual acuity was reached in 65% of cases. No minor or major complication occurred intra- or post-operative, with a maximum follow-up time of 41 months. An improvement in visual acuity was achieved, although very limited in some cases, when surgery was performed as close as possible to the traumatic event. In the literature, there is no evidence-based data evaluating both of the two main treatment options (medical therapy versus surgical decompression), to state which is the gold standard in the treatment for TON. We discuss the pro and cons of our protocol: medical endovenous steroid treatment, within 8 h of injury, and endoscopic surgical decompression within 12-24 since the beginning of medical therapy, represent the best solution in terms of risk-benefit ratio for the patients.

Effects of sodium hyaluronate in children with recurrent upper respiratory tract infections: results of a randomised controlled study.

Hyaluronic acid is a major component of many extracellular matrices that plays a role in the regulation of vasomotor tone and mucous gland secretion, and in the modulation of the inflammatory process in upper and lower airways. This pilot study was aimed at evaluating the effects of nasal washes with 9 mg nebulised sodium hyaluronate given for 15 days per month over 3 months in 75 paediatric patients with recurrent upper respiratory tract infections (URTI). Eligible patients were randomized to treatment with nasal washes containing 9 mg sodium hyaluronate plus saline solution or saline alone, according to an open-label, parallel group design, with blind observer assessment. Ciliary motility, which was assessed based on a 0-3 point rating scale (0 = absent, 1 = less than 5 minutes, 2 = greater than or equal to 5 and ≤ 10 minutes, 3 = greater than 10 minutes) was the primary study endpoint. The secondary efficacy variables included cytological (presence of neutrophils, eosinophils and mast cells), microbiological (presence of bacteria and mycetes), endoscopical (presence of adenoid hypertrophy and biofilm) and clinical (presence of rhinitis, post-nasal drip, nasal dyspnoea) parameters. The two treatment groups (mean age 7.5 years, 53percent of males) were comparable for baseline data, except a higher mean age in the control group than in the treated group. Treatment with 9 mg sodium hyaluronate was associated with significantly greater improvements (p less than 0.001 between groups) in primary outcome ciliary motility [odds ratio (OR) 13.61; 95 percent CI 4.51-41.00 in the univariate regression analysis that examined the probability of improvement]. Treatment with 9 mg sodium hyaluronate was also significantly superior to saline alone in adenoid hypertrophy (p less than 0.001; OR 14.72; 95 percent CI 4.74-45.68), presence of bacteria (p = 0.026; OR 2.95; 95 percent CI 1.15-7.55), neutrophils (p = 0.002; OR 4.51; 95 percent CI 1.75-11.62), rhinitis (p = 0.040; OR 10.47; 95 percent CI 3.10-35.31), nasal dyspnoea (p = 0.047; OR 3.80; 95 percent CI 1.09-13.19) and biofilm (p = 0.049; OR 9.90; 95 percent CI 2.61-37.47). Advantages of 9 mg of sodium hyaluronate over control on post-nasal drip and presence of mycetes (although evident) did not reach the level of statistical significance. The superiority of the treated group over saline alone was confirmed in a multivariate logistic regression analysis that took into account age as confounding factor. The number of days of absence from school was significantly lower in the 9 mg sodium hyaluronate group compared to controls (p less than 0.001 between groups). A 3-month intermittent treatment with 9 mg sodium hyaluronate with nasal washes plus saline solution was associated with significant improvements in ciliary motility and in cytological, microbiological, endoscopic and clinical outcomes compared to saline, in children with recurrent URTI.

Hyaluronan plus saline nasal washes in the treatment of rhino-sinusal symptoms in patients undergoing functional endoscopic sinus surgery for rhino-sinusal remodeling.

Hyaluronic acid is a major component of many extracellular matrices and plays a central role in the homeostasis of physiology in upper and lower airways. When topically administered following endoscopic sinus surgery, hyaluronic acid may be effective in functional recovery and in the prevention of recurrence of chronic rhinosinusistis. This pilot study was aimed at evaluating the effects of nebulised 9 mg of sodium hyaluronate given for 15 days per months over 3 months in 46 patients aged greater than 4 years who underwent functional endoscopic sinus surgery (FESS) for rhino-sinusal remodelling. Eligible patients were randomized to receive nebulised 9 mg sodium hyaluronate nasal washes plus saline solution or 5 ml saline alone (23 patients in each group), according to an open-label, parallel group design, with blind observer assessment. Treatment was administered by means of a nasal ampoule that allows nebulisation of particles with a median aerodynamic diameter greater than 10 micron, i.e. suitable for upper respiratory airways deposition. The efficacy variables included clinical (presence of nasal dyspnoea), endoscopical (ostium of paranasal sinuses, oedema, respiratory patency, synechiae, and appearance of nasal mucosa) and cytological (ciliary motility and presence of neutrophils, eosinophils, mast cells, bacteria, mycetes and bio film) measures. At the end of the study, patients expressed an opinion on the overall tolerability of treatment. The two treatment groups were comparable at baseline. Treatment with 9 mg of sodium hyaluronate was associated with significantly greater improvements compared to controls in nasal dyspnoea (p less than 0.001), presence of mycetes (p = 0.044), ciliary motility (p less than 0.001) and abnormalities in nasal secretions. A univariate logistic model, in which the odd ratio (OR) indicates the probability of success in the 9 mg sodium hyaluronate group compared to the control group, showed that the highest OR was observed for presence of nasal dyspnoea (OR = 21.36; 95 percent CI: 1.07 to 426.56), normal mucosa at endoscopy (OR: 9.62; 95 percent CI: 1.82 to 50.89), ciliary motility (OR: 7.27; 95 percent CI: 1.68 to 31.42) and presence of bio film (OR: 4.41; 95 percent CI: 1.26 to 15.40). Treatment with 9 mg sodium hyaluronate plus saline was well tolerated. A 3-month intermittent treatment with 9 mg sodium hyaluronate plus saline solution nasal washes following FESS for rhino-sinusal remodelling was associated with significant improvements in nasal dyspnoea, appearance of nasal mucosa at endoscopy and ciliary motility compared to saline alone.