Rami J. Salib

Safety and Tolerability Profiles of Intranasal Antihistamines and Intranasal Corticosteroids in the Treatment of Allergic Rhinitis

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.

Remodelling of the upper airways in allergic rhinitis: is it a feature of the disease?

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.

Mechanisms and mediators of nasal symptoms in non-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.

Characterization of bacterial community diversity in chronic rhinosinusitis infections using novel culture-independent techniques

Background Chronic rhinosinusitis (CRS) with or without polyps is a common chronic upper airway condition of multifactorial origin. Fundamental to effective treatment of any infection is the ability to accurately characterize the underlying cause. Many studies have shown that only a small fraction of the total range of bacterial species present in CRS is detected through conventional culture-dependent techniques. Consequently, culture data are often unrepresentative of the true diversity of the microbial community within the sample. These drawbacks, along with the length of time required to complete the analysis, strongly support the development of alternative means of assessing which bacterial species are present. As such, molecular microbiological approaches that assess the content of clinical samples in a culture-independent manner could significantly enhance the range and quality of data obtained routinely from such samples. We aimed to characterize the bacterial diversity present in tissue and mucus samples taken from the CRS setting using molecular nonculture-dependent techniques. Methods Through 16S ribosomal RNA (rRNA) gene clone sequencing and terminal restriction fragment length polymorphism (T-RFLP) analysis, the bacteria present in 70 clinical samples from 43 CRS patients undergoing endoscopic sinus surgery were characterized. Results Bacterial T-RFLP profiles were generated for 70 of 73 samples and a total of 48 separate bands were detected. Species belonging to 34 genera were identified as present by clone sequence analysis. Of the species detected, those within the genera Pseudomonas, Citrobacter, Haemophilus, Propionibacterium, Staphylococcus, and Streptococcus were found numerically dominant, with Pseudomonas aeruginosa the most frequently detected species. Conclusion 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.

The novel use of the human nasal epithelial cell line RPMI 2650 as an in vitro model to study the influence of allergens and cytokines on transforming growth factor-beta gene expression and protein release.

Background The epithelial accumulation of mast cells is a feature of allergic rhinitis and this has been linked to the expression of the known mast cell chemoattractant transforming growth factor‐β (TGF‐β) at this site. Little is known concerning the regulation of TGF‐β gene expression or protein release by nasal epithelial cells. To address this we have utilized the RPMI 2650 human nasal epithelial cell line, which has some features that closely resemble normal nasal epithelium and has been reported to secrete a TGF‐β‐like molecule.

Transforming growth factor‐β in allergic inflammatory disease of the upper airways: friend or foe?

TGF‐β is a multi‐functional cytokine with a huge array of effects on a variety of cell types. It is rapidly emerging as a key major player in the way the airway epithelium behaves and its ability to repair itself. This is not only of relevance to allergic airway diseases such as asthma and allergic rhinitis, which are increasing in prevalence worldwide, but in many other diseases. The full impact any disruption of TGF‐β signalling may have in the development and persistence of allergic inflammatory airway diseases is yet to be fully realized and remains the subject of ongoing research. There has been a recent revival of interest in the role of regulatory T cells in controlling allergic inflammation. Evidence is emerging of a significant contribution by TGF‐β to this regulatory process. This review aims to summarize current knowledge relating to TGF‐β in relation to allergic inflammatory upper airways disease, and attempts to clarify some of the discrepancies and inconsistencies in this area. It also considers the therapeutic implications of novel TGF‐β therapy, including potential future applications in the treatment of nasal polyposis and reduction of post‐operative scar tissue formation following endoscopic sinus surgery.

Surgical emphysema following dental treatment.

Surgical emphysema is a relatively rare complication of dental surgery. Many cases go unrecognized or are misdiagnosed. Although the majority of cases resolve spontaneously, some can lead to potentially life-threatening complications requiring emergency intervention. A case of surgical emphysema following a routine restorative dental procedure is presented. The differential diagnosis and management of this condition is discussed.

Traumatic fracture of the stapes suprastructure following minor head injury.

Traumatic fracture of the stapes occurs rarely following head injury. Ossicular dislocation is more commonly encountered. When present, stapes fractures are usually associated with an underlying temporal bone fracture. A higher incidence has been reported in childhood, possibly because of the greater flexibility of the skull in this age group. This report highlights the fact that these fractures can be associated with a relatively minor head injury. This possibility should be kept in mind when evaluating patients, especially children, who have a persistent conductive deafness of more than 30 dB with an intact tympanic membrane following any form of head injury. An exploratory tympanotomy with appropriate ossicular reconstruction, as described in this case, can yield excellent results.

Nasal lavage fluid concentrations of eotaxin‐1 (CCL11) in naturally occurring allergic rhinitis: relationship to disease activity, nasal luminal eosinophil influx, and plasma protein exudation

Background Eotaxin‐1 (CCL11) is a CC chemokine whose nasal eosinophilic chemotactic activity in vivo and in vitro has been demonstrated primarily using nasal allergen challenge models. The extension of these challenge findings to the in vivo setting has been limited.

The crucial role of imaging in detection of facial nerve haemangiomas.

Facial nerve haemangioma is a rare benign neoplasm accounting for 0.7 per cent of all tumours involving the temporal bone. The diagnosis of a facial nerve tumour is often missed or delayed. Early diagnosis is imperative as it influences the eventual outcome for facial nerve function. Prognosis is related to the size of the tumour, the severity and the duration of pre-operative paralysis. The definitive diagnosis of a facial nerve tumour rests exclusively with high resolution imaging of the temporal bone using enhanced magnetic resonance imaging (MRI) and thin-sectioned computed tomography (CT). This case emphasizes the crucial role that high quality imaging can play in the diagnosis of facial nerve tumours, and elegantly illustrates the imaging features of facial nerve haemangiomas.