Despite aggressive antibiotic therapy, bronchopulmonary colonization by Pseudomonas aeruginosa causes persistent morbidity and mortality in cystic fibrosis (CF). Chronic P. aeruginosa infection in the CF lung is associated with structured, antibiotic-tolerant bacterial aggregates known as biofilms. We have demonstrated the effects of non-bactericidal, low-dose nitric oxide (NO), a signaling molecule that induces biofilm dispersal, as a novel adjunctive therapy for P. aeruginosa biofilm infection in CF in an ex vivo model and a proof-of-concept double-blind clinical trial. Submicromolar NO concentrations alone caused disruption of biofilms within ex vivo CF sputum and a statistically significant decrease in ex vivo biofilm tolerance to tobramycin and tobramycin combined with ceftazidime. In the 12-patient randomized clinical trial, 10 ppm NO inhalation caused significant reduction in P. aeruginosa biofilm aggregates compared with placebo across 7 days of treatment. Our results suggest a benefit of using low-dose NO as adjunctive therapy to enhance the efficacy of antibiotics used to treat acute P. aeruginosa exacerbations in CF. Strategies to induce the disruption of biofilms have the potential to overcome biofilm-associated antibiotic tolerance in CF and other biofilm-related diseases.
The traditional viewpoint that inflammation, owing to a genetic T-helper type 2 (Th2)-directed imbalance, is the cause of allergic rhinitis has meant that the potential coexistence of other genetic defects and the relevance of any airway remodelling changes to disease pathogenesis and persistence have received scant attention, and as such remain controversial areas. This is particularly so in view of the limited published work in this field, which has so far reported markedly conflicting findings. This review endeavours to outline what is known about the nature of the remodelling response within the upper airway in allergic rhinitis, in addition to highlighting specific areas where further research is warranted.
This study has validated the use of the culture-independent technique T-RFLP in sinonasal samples. Preliminary characterization of the microbial diversity in CRS suggests a complex range of common and novel bacterial species within the upper airway in CRS, providing further evidence for the polymicrobial etiology of CRS.
Intranasal corticosteroids and intranasal antihistamines are efficacious topical therapies in the treatment of allergic rhinitis. This review addresses their relative roles in the management of this disease, focusing on their safety and tolerability profiles. The intranasal route of administration delivers drug directly to the target organ, thereby minimising the potential for the systemic adverse effects that may be evident with oral therapy. Furthermore, the topical route of delivery enables the use of lower doses of medication. Such therapies, predominantly available as aqueous formulations following the ban of chlorofluorocarbon propellants, have minimal local adverse effects. Intranasal application of therapy can induce sneezing in the hyper-reactive nose, and transient local irritation has been described with certain formulations. Intranasal administration of corticosteroids is associated with minor nose bleeding in a small proportion of recipients. This effect has been attributed to the vasoconstrictor activity of the corticosteroid molecules, and is considered to account for the very rare occurrence of nasal septal perforation. Nasal biopsy studies do not show any detrimental structural effects within the nasal mucosa with long-term administration of intranasal corticosteroids. Much attention has focused on the systemic safety of intranasal application. When administered at standard recommended therapeutic dosage, the intranasal antihistamines do not cause significant sedation or impairment of psychomotor function, effects that would be evident when these agents are administered orally at a therapeutically relevant dosage. The systemic bioavailability of intranasal corticosteroids varies from <1% to up to 40-50% and influences the risk of systemic adverse effects. Because the dose delivered topically is small, this is not a major consideration, and extensive studies have not identified significant effects on the hypothalamic-pituitary-adrenal axis with continued treatment. A small effect on growth has been reported in one study in children receiving a standard dosage over 1 year, however. This has not been found in prospective studies with the intranasal corticosteroids that have low systemic bioavailability and therefore the judicious choice of intranasal formulation, particularly if there is concurrent corticosteroid inhalation for asthma, is prudent. There is no evidence that such considerations are relevant to shorter-term use, such as in intermittent or seasonal disease. Intranasal therapy, which represents a major mode of drug delivery in allergic rhinitis, thus has a very favourable benefit/risk ratio and is the preferred route of administration for corticosteroids in the treatment of this disease, as well as an important option for antihistaminic therapy, particularly if rapid symptom relief is required.
YouTube appears to be an unreliable resource for accurate and up to date medical information relating to rhinosinusitis. However, it may provide some useful information if mechanisms existed to direct lay people to verifiable and credible sources.
Allergic rhinitis represents a global health issue affecting between 10% to 25% of the world population, with increasing prevalence over the last decade. Although often trivialized by patients and doctors, allergic rhinitis is a significant cause of morbidity, in addition to its substantial economic impact. While allergic rhinitis is an inflammatory disorder of the upper airways, inflammation alone is insufficient to explain the chronic nature of the disease. An exciting concept which has recently emerged in asthma concerns the role of the bronchial epithelium as a key regulator of airway inflammatory and remodelling responses in asthma. It has been shown by our group that the disruption and alteration in the function of the lower airway epithelium in asthma leads to the generation of a variety of stimuli that lead to the restructuring of the airway wall. This raises interesting questions regarding a similar role for the upper airway epithelium in allergic rhinitis. This review aims to interpret past and current research into allergic rhinitis, and to address specific areas where future research is warranted, particularly in relation to the possibility of an altered upper airway epithelial phenotype in allergic rhinitis.
Non-allergic rhinitis may be a contributing factor in up to 60% of rhinitis patients and a sole contributor in a quarter. It is a highly heterogeneous condition with poorly understood pathophysiological mechanisms. Compelling evidence is emerging of a localized nasal mucosal allergic response in some non-allergic rhinitic subjects in the absence of systemic atopy. While the inflammatory disease pathway in non-allergic rhinitis may share some of the features of its allergic counterpart, overall the mechanisms remain unclear, and there are likely to be differences. In particular, symptoms of nasal congestion and rhinorrhoea tend to be more prominent and persistent in non-allergic rhinitic patients compared with allergic rhinitis. Our aim is to review the literature relating to mechanisms and mediators of nasal symptoms in non-allergic rhinitis. Better understanding of the underlying pathophysiological basis should enable the development of more accurate testing, and better targeted therapeutic options in the future.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.