Treatment Of Upper Airway Diseases Research Articles

Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic Fibrosis.

ABSTRACTChronic rhinosinusitis (CRS) is a common, yet underreported and understudied manifestation of upper respiratory disease in people with cystic fibrosis (CF). Recently developed standard of care guidelines for the management of CF CRS suggest treatment of upper airway disease may ameliorate lower airway disease. We sought to determine whether changes to sinus microbial community diversity and specific taxa known to cause CF lung disease are associated with increased respiratory disease and inflammation. We performed 16S rRNA gene sequencing, supplemented with cytokine analyses, microscopy, and bacterial culturing, on samples from the sinuses of 27 adults with CF CRS. At each study visit, participants underwent endoscopic paranasal sinus sampling and clinical evaluation. We identified key drivers of microbial community composition and evaluated relationships between diversity and taxa with disease outcomes and inflammation. Sinus community diversity was low, and the composition was unstable, with many participants exhibiting alternating dominance between Pseudomonas aeruginosa and staphylococci over time. Despite a tendency for dominance by these two taxa, communities were highly individualized and shifted composition during exacerbation of sinus disease symptoms. Exacerbations were also associated with communities dominated by Staphylococcus spp. Reduced microbial community diversity was linked to worse sinus disease and the inflammatory status of the sinuses (including increased interleukin-1β [IL-1β]). Increased IL-1β was also linked to worse sinus endoscopic appearance, and other cytokines were linked to microbial community dynamics. Our work revealed previously unknown instability of sinus microbial communities and a link between inflammation, lack of microbial community diversity, and worse sinus disease.IMPORTANCE Together with prior sinus microbiota studies of adults with CF chronic rhinosinusitis, our study underscores similarities between sinus and lower respiratory tract microbial community structures in CF. We show how community structure tracks with inflammation and several disease measures. This work strongly suggests that clinical management of CRS could be leveraged to improve overall respiratory health in CF. Our work implicates elevated IL-1β in reduced microbiota diversity and worse sinus disease in CF CRS, suggesting applications for existing therapies targeting IL-1β. Finally, the widespread use of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has led to less frequent availability of spontaneous expectorated sputum for microbiological surveillance of lung infections. A better understanding of CF sinus microbiology could provide a much-needed alternative site for monitoring respiratory infection status by important CF pathogens.

Treatment of upper airway diseases in patients with cystic fibrosis

Chronic rhinosinusitis with nasal polyps (CRS NP) is the most prevalent ear, nose, and throat (ENT) disorder in cystic fibrosis (CF) patients. CRS NP can occur in CF children at the age of ≥ 8 months and becomes the chronic disease. Tenacious secret and bacterial infection cause obstruction, edema and hypoxia of paranasal sinuses and contribute to significant morbidity in CF patients. The active monitoring and treatment of CRS NP aimed at improvement of the aeration of paranasal sinuses, mucociliary clearance, and the control of chronic upper airway infection are necessary. Functional Endoscopic Sinus Surgery (FESS) may be the method of choice if surgical treatment is considered. FESS facilitates paranasal sinuses drainage. Due to recurrent course of CRS NP in most CF patients, lifelong follow-up by an ENT specialist and postoperative management using topical steroids and/or antibiotics are required.

Therapeutic Applications of Capsaicin in Upper Airways.

Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the substance responsible of the irritation caused by the contact of chili peppers with the skin or mucous membranes. This protoalkaloid acts by stimulating the transient receptor potential cation channel subfamily V member 1 (TRPV1), which is mainly expressed by nociceptive fibers of peripheral sensory neurons, but is also present in the central nervous system, and in some non-neuronal cells. Following the initial, intense neuronal excitation, a brief refractory period occurs. However, repeated and massive exposures to capsaicin can impair nociceptive fiber function for weeks or months. During this lapse of time, disorders related to the hyperreactivity of peripheral nociceptors are abolished or greatly reduced. Capsaicin has been utilized to treat several diseases of upper airways. The objective of this review was to report the latest findings on the use of Capsaicin in the treatment of upper airway diseases. Capsaicin effectiveness has been proved in non allergic rhinitis. Some studies suggest that this substance may be also effective in nasal polyposis and in the burning mouth syndrome. No clear evidence has been obtained about its use in allergic rhinitis. To date, the use of capsaicin to treat upper airway diseases is still limited in clinical practice. This may originate by the lack of strong, conclusive evidences of its effectiveness, by the variety of therapeutic schemes used in literature, and finally by the unpleasant effects of the exposure to capsaicin, which are only partly relieved by the pretreatment with local anesthetics.

Is the use of intranasal glucocorticosteroids (inGCSs) in children safe?

It's been 40 years since Niels Mygind publication in British Medical Journal on intranasal application of beclomethasonedipropionate aerosol in Allergic Rhinitis. Since then the new era in treatment of allergic and non-allergic upper airway diseases has begun. This publication presents current concepts on application of intranasal glucocorticosteroids in treatment of upper airway diseases and in particular of allergic rhinitis and rhinosinusitis. The non-questionable advantage of intranasal glucocorticosteroids is their strong anti-inflammatory local action with little impact on general health responsible for few and benign side effects. Main way of action of glucocorticosteroids is connected with binding to the intracellular glucocorticosteroid receptor and its impact on nuclear cytoplasmic transcriptional factors. Glucocorticosteroids suppress gene expression of factors responsible for generating and supporting inflammatory processes, pro-inflammatory cytokines and chemokines production, adhesive molecules expression. It appears that glucocorticosteroids has also other mechanisms of action, non-involving intracellular receptors, leading to inhibiting of early and late phase of allergic reaction. At the moment there are following glucocorticosteroids registered in Poland: beclomethasone, budesonide, fluticasone propionate, fluticasone fuorate, mometasonefuorate. Special attention earns fuorates as their lateral fuorate ester chain makes this molecules highly lipophilic, easily absorbed by nasal mucous membranes epithelium and cell membranes phospholipids. This minimizes their general action and maximizes local action. According to current state of knowledge topical glucocorticosteroids are used in the following upper airway diseases with different inflammatory mechanism: allergic rhinitis, non-allergic rhinitis, particularly NARES, acute rhinosinusitis, chronic rhinosinusitis with and without nasal polyps, adenoid hypertrophy and rhinitis in bronchial asthma.

Syk-kinase inhibition prevents mast cell activation in nasal polyps

Mast cells are crucial effector cells in the allergic cascade. The cross-linking of the high affinity IgE receptor (FcεRI) activates mast cells and basophils. Spleen tyrosine kinase (Syk) is positioned upstream of the IgE receptor signal transducing pathway and may represent an important target for the treatment of nasal inflammatory diseases. We measured effects of a specific Syk inhibitor in the release of mast cell mediators in human cord blood-derived mast cells (CBDMCs) (in-vitro) and in human nasal tissue (ex-vivo). Surgical samples were collected from patients with nasal polyposis who underwent sinus surgery. Tissue cubes of +- 0.9 mm3 were primed with myeloma IgE (1 microg/ml), preincubated with Syk inhibitor NVP-QAB205 in different concentrations and then stimulated with tissue culture medium, anti-IgE 10 microg/ml and anti-IgE 30 microg/ml. Supernatants were analysed for concentrations of histamine, LTC4/LTD4/LTE4 and PGD2. CBDMCs were likewise pre-incubated with compound, prior to stimulation with anti-IgE at 10 microg/ml. In CBDMCs, the Syk inhibitor prevented degranulation assessed by measurement of histamine release and the production of LTC4/LTD4/LTE4 and PGD2. Furthermore, the Syk inhibitor was similarly able to significantly inhibit the release of these granules and newly synthesized mediators by nasal polyp mast cells in a dose dependent manner. Although the critical role of Syk in the IgE receptor signal transduction pathway has been well documented in vitro, this study supports the importance of Syk in IgE receptor-mediated degranulation of mast cells ex-vivo within nasal tissue. Thus, inhibition of Syk may represent an important therapeutic strategy for the treatment of upper airway disease with mast cell involvement, such as allergic rhinitis.

Endoscopic surgery for treatment of paediatric upper airway diseases

Abstract In September 2005, the 3rd OPBG/Mayo Clinic Joint Conference was held in Rome to highlight current views in paediatric medicine. After an overview of the various pathologies, the Otolaryngology Unit of the Bambino Gesù Children's Hospital of Rome described their own experience with endoscopic surgery for the treatment of upper airway diseases between 2002 and 2004. During this period, 1500 paediatric endoscopies were performed for obstructive upper airway disease. A total of 80% of patients were under 2 years of age. The aetiological causes of upper airway obstruction most frequently cited were: foreign bodies (the most frequent reason for urgent endoscopic treatment), choanal atresia, severe laryngomalacia, laryngeal cysts, neurological lesions (vocal fold paralysis), laryngeal clefts, laryngeal haemangiomas, recurrent respiratory papilloma, tracheoesophageal fistula, tracheal granuloma and tubercular adenobronchial fistula. In all the patients, stridor disappeared following surgery. No complications, such as aspiration or supraglottic stenosis, were identified and no revision surgeries were required. Stenting was necessary in only three cases. This study described the OPBG management of paediatric airway obstruction and outcomes during a 3-year period and was the starting point for reflection on this topic.

Preclinical Modelling Using Nasal Epithelial Cells for the Evaluation of Herbal Extracts for the Treatment of Upper Airway Diseases

The epithelium constitutes the interface between the internal milieu and the external environment, and the nasal epithelium is the initial point of contact for respiratory viruses, airborne allergens and environmental pollutants. The major function of the nasal epithelium was regarded to be primarily that of a physical barrier, but recent studies clearly indicate that its cells are metabolically very active with the capacity to modulate a variety of inflammatory processes through the action of an array of receptor-mediated events. This review summarizes the current view of the active role of the nasal epithelium in the inflammation of the upper airways and its possible modulation by herbal extracts to treat diseases of the upper airways such as common cold and sinusitis.

A new approach to pharmacological effects on ciliary beat frequency in cell cultures—exemplary measurements under Pelargonium sidoides extract (EPs 7630)

The ciliary beat frequency (CBF) is an important parameter of the defence mechanism of the mucociliary system. We present a new method to determine pharmacological effects on CBF in vitro. Ciliated cell cultures of human nasal epithelium were obtained from partial resection of hyperplastic inferior turbinates in rhinosurgery. An adherent monolayer culture of ciliated cells was present after 10 days in vitro. This study exemplary examines, if a special extract from the roots of Pelargonium sidoides (EPs 7630) has an effect on the CBF in vitro. The influence of three concentrations of the extract (1, 30, 100 microg/ml) was tested. EPs 7630 significantly and concentration-dependently increased CBF to 123% at 30 microg/ml and to 133% at 100 microg/ml compared to the equilibration phase (100%). After rinsing with extract-free medium the CBF of cultured cells returned to nearly the normal range. In future, drug manipulation of the CBF by local application of rhinologics could be a new therapeutical concept in the treatment of upper airway diseases.

Benefit and risk management for steroid treatment in upper airway diseases.

Because of their efficacy, intranasal corticosteroids (INCS) remain the cornerstone in the treatment of upper airway diseases. Although INCS are extremely efficacious, local and systemic adverse effects have been associated with their use. However, none of these effects is of sufficient frequency or magnitude to warrant a reduction in their use or any action more than careful drug and dose selection and monitoring when indicated. Recent publications focus on newer aspects of efficacy in rhinitis and on the adverse effects of growth suppression, cataract formation, and histologic effects on the nasal mucosa. Optimizing mucosal delivery of INCS is a major goal because of the need to maximize efficacy and minimize systemic bioavailability and potential risks. One recent study examined the bioavailability and metabolism of beclomethasone dipropionate. Another study examined the tendency of patients to overdose when using betamethasone drops. A third study compared the two different delivery systems of fluticasone propionate and budesonide, and their efficacy in treating perennial rhinitis. Other studies examined the effect of INCS on the treatment of nasal polyps (budesonide) and on the common cold (beclomethasone dipropionate). These studies have continued to define safety and efficacy aspects, and the important role of INCS in treating rhinitis.