A mouse model of progressive lung fibrosis with cutaneous involvement induced by a combination of oropharyngeal and osmotic minipump bleomycin delivery.

Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal models for candidate drug discovery. Existing bleomycin (BLM)-induced SSc-ILD mouse models feature spatially limited pulmonary fibrosis, spontaneously resolving after 28 days. Here, we present an alternative BLM administration approach in female C57BL/6 mice, combining oropharyngeal aspiration (OA) and subcutaneous mini-pump delivery (pump) of BLM to induce a sustained and more persistent fibrosis, while retaining stable skin fibrosis. A dose-finding study was performed with BLM administered as 10 µg (OA) +80 mg/kg (pump) (10 + 80), 10 + 100, and 15 + 100. Forty-two days after OA, micro-computed tomography (micro-CT) imaging and histomorphometric analyses showed that the 10 + 100 and 15 + 100 treatments induced significant alterations in lung micro-CT-derived readouts, Ashcroft score, and more severe fibrosis grades compared with saline controls. In addition, a marked reduction in hypodermal thickness was observed in the 15 + 100 group. A time-course characterization of the BLM 15 + 100 treatment at days 28, 35, and 42, including longitudinal micro-CT imaging, revealed progressing alterations in lung parameters. Lung histology highlighted a sustained fibrosis accompanied by a reduction in hypodermis thickness throughout the explored time-window, with a time-dependent increase in fibrotic biomarkers detected by immunofluorescence analysis. BLM-induced alterations were partly mitigated by Nintedanib treatment. Our optimized BLM delivery approach leads to extensive and persistent lung fibrotic lesions coupled with cutaneous fibrotic alterations: it thus represents a significant advance compared with current preclinical models of BLM-induced SSc-ILD.NEW & NOTEWORTHY This study introduces an innovative approach to enhance the overall performance of the mouse bleomycin (BLM)-induced model for systemic sclerosis with interstitial lung disease (SSc-ILD). By combining oropharyngeal aspiration and subcutaneous mini-pump delivery of BLM, our improved model leads to sustained lung fibrosis and stable skin fibrosis in female C57BL/6 mice. The optimized 15 + 100 treatment results in extensive and persistent lung fibrotic lesions and thus represents a significant improvement over existing preclinical models of BLM-induced SSc-ILD.

Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration.

Zinc oxide nanoparticles (ZnONPs) are frequently encountered nanomaterials in our daily lives. Despite the benefits of ZnONPs in a variety of applications, many studies have shown potential health hazards of exposure to ZnONPs. We have shown that oropharyngeal aspiration of ZnONPs in mice increases lung inflammation. However, the detailed mechanisms underlying pulmonary inflammatory cell infiltration remain to be elucidated. Endothelium functions as a barrier between the blood stream and the blood vessel wall. Endothelial barrier dysfunction may increase infiltration of immune cells into the vessel wall and underlying tissues. This current study examined the effects of ZnONPs exposure on endothelial barriers. ZnONPs exposure increased leukocyte infiltration in the mouse lungs. In endothelial cells, ZnONPs reduced the continuity of tight junction proteins claudin-5 and zonula occludens-1 (ZO-1) at the cell junctions. ZnONPs induced adherens junction protein VE-cadherin internalization from membrane to cytosol and dissociation with ß-catenin, leading to reduced and diffused staining of VE-cadherin and ß-catenin at cell junctions. Our results demonstrated that ZnONPs disrupted both tight and adherens junctions, compromising the integrity and stability of the junction network, leading to inflammatory cell infiltration. Thus, ZnONPs exposure in many different settings should be carefully evaluated for vascular effects and subsequent health impacts.

Studies of selective digestive decontamination as a natural experiment to evaluate topical antibiotic prophylaxis and cephalosporin use as population-level risk factors for enterococcal bacteraemia among ICU patients.

BACKGROUND: Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) regimens appear protective against ICU-acquired overall bacteraemia. These regimens can be factorized as topical antibiotic prophylaxis (TAP) with (SDD) or without (SOD) protocolized parenteral antibiotic prophylaxis (PPAP) using cephalosporins. Both TAP and cephalosporins are risk factors for enterococcal colonization although their impact on enterococcal bacteraemia within studies of SDD/SOD remains unclear. OBJECTIVES: To benchmark the enterococcal bacteraemia incidence within component (control and intervention) groups of SDD/SOD studies among ICU patients versus studies without intervention (observational groups). METHODS: The literature was searched for SDD/SOD studies reporting enterococcal bacteraemia incidence data. In addition, component groups of studies of various non-antibiotic interventions served to provide additional points of reference. RESULTS: The mean incidence per 100 patients (and 95% CI) for enterococcal bacteraemia among 19 SDD/SOD studies was equally increased among concurrent control (2.1; 1.0%-4.7%) and intervention (2.3; 2.0%-2.7%) groups versus the benchmark incidence (0.8; 0.6%-1.2%) derived from 16 observational study groups and also versus 9 component groups from non-antibiotic studies. These higher incidences remained apparent (P < 0.02) in a meta-regression model adjusting for groupwide factors such as PPAP use, mechanical ventilation proportion, group mean length of stay >7 days and publication year. CONCLUSIONS: The incidences of enterococcal bacteraemia within both concurrent control and intervention groups of SDD/SOD studies are unusually high compared with the literature-derived benchmark. The impact of parenteral cephalosporin used as PPAP additional to TAP on enterococcal bacteraemia incidence was indeterminate in this analysis.

Carriage of antibiotic-resistant Gram-negative bacteria after discontinuation of selective decontamination of the digestive tract (SDD) or selective oropharyngeal decontamination (SOD).

BACKGROUND: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) reduce colonization with antibiotic-resistant Gram-negative bacteria (ARGNB), incidence of nosocomial infections and improve survival in ICU patients. The effect on bacterial gut colonization might be caused by growth suppression by antibiotics during SDD/SOD. We investigated intestinal colonization with ARGNB after discharge from ICU and discontinuation of SDD or SOD. METHODS: We performed a prospective, observational follow-up study in regular hospital wards of three teaching hospitals in the Netherlands in patients discharged from the ICU, who were participating in a cluster randomized trial comparing SDD with SOD. We determined rectal carriage with ARGNB at ICU discharge (time (T) = 0) and 3, 6 and 10 days after discharge. The primary endpoint was time to first colonization with ARGNB that was not present at T = 0. Bacteria that are intrinsically resistant to antibiotics were not included in the primary analysis, but were included in post-hoc analysis. RESULTS: Of 1370 patients screened for inclusion, 996 patients had samples at T = 0 (507 after SDD and 489 after SOD). At ICU discharge, the prevalence of intestinal carriage with any ARGNB was 22/507 (4.3%) after SDD and 87/489 (17.8%) after SOD (p < 0.0001): 426 (SDD) and 409 (SOD) patients had at least one follow-up sample for analysis. The hazard rate for acquiring carriage of ARGNB after discontinuation of SDD, compared to SOD, in the ICU was 0.61 (95% CI 0.40-0.91, p = 0.02), and cumulative risks of acquisition of at least one ARGNB until day 10 were 13% (SDD) and 18% (SOD). At day 10 after ICU discharge, the prevalence of intestinal carriage with ARGNB was 11.3% (26/230 patients) after SDD and 12.5% (28/224 patients) after SOD (p = 0.7). In post-hoc analysis of all ARGNB, including intrinsically resistant bacteria, colonization at ICU discharge was lower after SDD (4.9 vs. 22.3%, p < 0.0001), but acquisition rates after ICU discharge were similar in both groups. CONCLUSIONS: Intestinal carriage at ICU discharge and the acquisition rate of ARGNB after ICU discharge are lower after SDD than after SOD. The prevalence of intestinal carriage with ARGNB at 10 days after ICU discharge was comparable in both groups, suggesting rapid clearance of ARGNB from the gut after ICU discharge. TRIAL REGISTRATION: Netherlands Trial Registry, NTR3311 . Registered on 28 february 2012.

Assessment of indomethacin oral spray for the treatment of oropharyngeal mucositis-induced pain during anticancer therapy.

PURPOSE: The efficacy and safety of indomethacin (IM) oral spray (OS) as a pain control therapy for oropharyngeal mucositis due to anticancer chemo- and radiotherapy were assessed in patients with head and neck carcinomas and haematological tumours. METHOD: We observed 35 patients (male/female, 20/15; 53 ± 17 years) with oropharyngeal mucositis who were treated with IM-OS preparation for pain relief at University of Tsukuba Hospital, Japan. Analgesic effects were assessed using the six-grade face scale for pain in 28 patients at the start of IM oral spray treatment. Systemic exposure was assessed by determining urinary excretions of IM in seven patients. RESULTS: Pain relief was achieved in 26 (93%) patients at 25 (5-60) min after applying the IM-OS preparation (15.6 ± 3.4 µg/kg) and analgesic effects were maintained for 120 (10-360) min. The pain was significantly decreased after using the spray (3.6 ± 0.7 vs. 2.4 ± 0.9, p < 0.01). Moreover, urinary IM excretion rates after applying the IM spray preparation were 1.8 ± 0.8% of the IM oral spray dose (130.5 ± 77.7 µg/kg/day), which was markedly lower than that following oral administration of IM (60%). No adverse events were observed following application of the spray. CONCLUSIONS: The present IM spray is an effective and safe preparation for pain relief and can be used as an alternative therapeutic option for oropharyngeal mucositis in cancer patients.

PDGF-AA mediates mesenchymal stromal cell chemotaxis to the head and neck squamous cell carcinoma tumor microenvironment.

BACKGROUND: The robust desmoplasia associated with head and neck squamous cell carcinoma (HNSCC) suggests that the tumor microenvironment may be an important component in the pathophysiology of this cancer. Moreover, the high recurrence rate and poor clinical response to chemotherapy and radiation treatment further underscores that the non-cancerous cells of the microenvironment, such as mesenchymal stromal cells (MSCs), cancer associated fibroblasts (CAFs), and pericytes, may be important in the pathophysiology of HNSCC. METHODS: Confocal microscopy and immunohistomchemistry approaches were used to identify MSCs tumor microenvironment from patients with oral cavity and oral pharyngeal squamous cell carcinoma (SCC). In vitro Boyden chamber assays and multiplex magnetic bead assays were used to measure MSC chemotaxis and to identify the chemokines secreted by JHU-011, -012, -019, three cells lines derived from patients with oral pharyngeal SCC. RESULTS: We show here that MSCs reside in the tumor microenvironment of patients with oral cavity and oral pharyngeal SCC and are recruited via paracrine mediated tumor cell secretion of (platelet derived growth factor) PDGF-AA. The MSC markers CD90+, CD105+, and gremlin-1+ were found to co-localize on cells within the tumor microenvironment in oral cavity SCC specimens distinct from α-smooth muscle actin staining CAFs. The conditioned media from JHU-011, -012, and -019 caused a significant increase in MSC migration (>60%) and invasion (>50%; p < 0.0001) compared to oral keratinocyte (OKT) controls. Tumor cell induced MSC chemotaxis appears to be mediated through paracrine secretion of PDGF-AA as inhibition of the PDGF-AA receptor, PDGFR-α but not PDGFR-ß, resulted in near arrest of MSC chemotaxis (p < 0.0001). CONCLUSIONS: Tumor microenvironment expression of PDGFR-α has been shown to correlate with a worse prognosis in patients with prostate, breast, ovarian, non-small cell lung cancer and osteosarcoma. This is the first evidence that a similar signaling paradigm may be present in HNSCC. PDGFR-α inhibitors have not been studied as adjunctive treatment options in the management of HNSCC and may prove to be an important driver of the malignant phenotype in this setting.

The role of Fusobacterium necrophorum in pharyngotonsillitis - A review.

Fusobacterium necrophorum is a gram-negative anaerobic bacterium that is the causative agent of the invasive disease Lemierre's syndrome. In addition, it is also associated with peritonsillar abscess formation and otitis media in small children. Recent research has shown that F. necrophorum may be involved in pharyngotonsillitis especially in adolescent and young adults and that it may be the second most common bacterial cause of pharyngotonsillitis after Streptococcus pyogenes (Group A streptococci). Peritonsillar abscesses and Lemierre's syndrome due to F. necrophorum are also found in this age group, suggesting that they may be complications of F. necrophorum pharyngotonsillitis. In this review we present the present knowledge about the role of F. necrophorum in pharyngotonsillitis with special emphasis on the age distribution. We argue that F. necrophorum is an important pathogen involved in pharyngotonsillitis in the age group of 13-40 years of age and we urge clinical microbiology labs to set up the appropriate techniques to be able to detect F. necrophorum from throat swabs.

Antibiotic-Induced Within-Host Resistance Development of Gram-Negative Bacteria in Patients Receiving Selective Decontamination or Standard Care.

OBJECTIVE: To quantify antibiotic-associated within-host antibiotic resistance acquisition rates in Pseudomonas aeruginosa, Klebsiella species, and Enterobacter species from lower respiratory tract samples of ICU patients receiving selective digestive decontamination, selective oropharyngeal decontamination, or standard care. DESIGN: Prospective cohort. SETTING: This study was nested within a cluster-randomized crossover study of selective digestive decontamination and selective oropharyngeal decontamination in 16 ICUs in The Netherlands. PATIENTS: Eligible patients were those colonized in the respiratory tract with P. aeruginosa, Klebsiella species, or Enterobacter species susceptible to one of the marker antibiotics and with at least two subsequent microbiological culture results from respiratory tract samples available. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Antibiotic resistance acquisition rates were defined as the number of conversions from susceptible to resistant for a specific antibiotic per 100 patient-days or 100 days of antibiotic exposure within an individual patient. The hazard of antibiotic use for resistance development in P. aeruginosa was based on time-dependent Cox regression analysis. Findings of this study cohort were compared with those of a previous cohort of patients not receiving selective digestive decontamination/selective oropharyngeal decontamination. Numbers of eligible patients were 277 for P. aeruginosa, 174 for Klebsiella species, and 106 for Enterobacter species. Resistance acquisition rates per 100 patient-days ranged from 0.2 (for colistin and ceftazidime in P. aeruginosa and for carbapenems in Klebsiella species) to 3.0 (for piperacillin-tazobactam in P. aeruginosa and Enterobacter species). For P. aeruginosa, the acquisition rates per 100 days of antibiotic exposure ranged from 1.4 for colistin to 4.9 for piperacillin-tazobactam. Acquisition rates were comparable for patients receiving selective digestive decontamination/selective oropharyngeal decontamination and those receiving standard care. Carbapenem exposure had the strongest association with resistance development (adjusted hazard ratio, 4.2; 95% CI, 1.1-15.6). CONCLUSION: Within-host antibiotic resistance acquisition rates for systemically administered antibiotics were comparable between patients receiving selective decontamination and those receiving standard care and were highest during carbapenem use.

Natural capsaicinoids improve swallow response in older patients with oropharyngeal dysphagia.

OBJECTIVE: There is no pharmacological treatment for oropharyngeal dysphagia (OD). The aim of this study was to compare the therapeutic effect of stimulation of oropharyngeal transient receptor potential vanilloid type 1 (TRPV1) with that of thickeners in older patients with OD. DESIGN: A clinical videofluoroscopic non-randomised study was performed to assess the signs of safety and efficacy of swallow and the swallow response in (1) 33 patients with OD (75.94 ± 1.88 years) while swallowing 5, 10 and 20 ml of liquid (20.4 mPa.s), nectar (274.4 mPa.s), and pudding (3930 mPa.s) boluses; (2) 33 patients with OD (73.94 ± 2.23 years) while swallowing 5, 10 and 20 ml nectar boluses, and two series of nectar boluses with 150 µM capsaicinoids and (3) 8 older controls (76.88 ± 1.51 years) while swallowing 5, 10 and 20 ml nectar boluses. RESULTS: Increasing bolus viscosity reduced the prevalence of laryngeal penetrations by 72.03% (p < 0.05), increased pharyngeal residue by 41.37% (p < 0.05), delayed the upper esophageal sphincter opening time and the larynx movement and did not affect the laryngeal vestibule closure time and maximal hyoid displacement. Treatment with capsaicinoids reduced both, penetrations by 50.% (p < 0.05) and pharyngeal residue by 50.% (p < 0.05), and shortened the time of laryngeal vestibule closure (p < 0.001), upper esophageal sphincter opening (p < 0.05) and maximal hyoid and laryngeal displacement. CONCLUSION: Stimulation of TRPV1 by capsaicinoids strongly improved safety and efficacy of swallow and shortened the swallow response in older patients with OD. Stimulation of TRPV1 might become a pharmacologic strategy to treat OD.

Synergistic effect of Salvadora persica and chitosan nanoparticles against oropharyngeal microorganisms.

Herbal medicine combined with nanoparticles has caught much interest in clinical dental practice, yet the incorporation of chitosan with Salvadora persica (S. persica) extract as an oral care product has not been explored. The aim of this study was to evaluate the combined effectiveness of Salvadora persica(S. persica) and Chitosan nanoparticles (ChNPs) against oropharyngeal microorganisms. Agar well diffusion, minimum inhibitory concentration, and minimal lethal concentration assays were used to assess the antimicrobial activity of different concentrations of ethanolic extracts of S. persica and ChNPs against selected fungal strains, Gram-positive, and Gram-negative bacteria. A mixture of 10% S. persica and 0.5% ChNPs was prepared (SChNPs) and its synergistic effect against the tested microbes was evaluated. Furthermore, the strain that was considered most sensitive was subjected to a 24-h treatment with SChNPs mixture; and examined using SEM, FT-IR and GC-MS analysis. S. persica extract and ChNPs exhibited concentration-dependent antimicrobial activities against all tested strains. S. persica extract and ChNPs at 10% were most effective against S. pneumoni, K. pneumoni, and C. albicans. SEM images confirmed the synergistic effect of the SChNPs mixture, revealing S. pneumonia cells with increased irregularity and higher cell lysis compared to the individual solutions. GC-MS and FT-IR analysis of SChNPs showed many active antimicrobial phytocompounds and some additional peaks, respectively. The synergy of the mixture of SChNPs in the form of mouth-rinsing solutions can be a promising approach for the control of oropharyngeal microbes that are implicated in viral secondary bacterial infections.

Pharyngeal chemosensitivity in patients with obstructive sleep apnea and healthy subjects.

Signs of pharyngeal neurodegeneration have been detected in patients with obstructive sleep apnea (OSA). Along with this neurodegeneration, a decreased pharyngeal sensitivity to mechanical stimulation has been described. The decreased sensitivity may play a role in the pathophysiology of this disease. The aim of the study was to investigate the chemosensitivity of the pharyngeal mucosa in patients with OSA compared with controls. Healthy controls and patients with OSA (age: 30-60 years) were included. Testing of oropharyngeal chemosensitivity was performed with subjective intensity ratings of capsaicin (SIR, visual analogue scale 0-10), air puffs (presented with an olfactometer), and stimulation with CO2 at the posterior pharyngeal wall. A 2-point discrimination test at the soft palate, an intensity rating of capsaicin at the tongue, and a nasal lateralization test were performed. Twenty-six patients with OSA and 18 healthy controls were included. No differences were detected in the SIR of capsaicin at the tongue or in the nasal lateralization test. At the pharynx, a decreased sensitivity to capsaicin (OSA: 6.8 ± 2.3; healthy control: 8.6 ± 1.3), air puffs (OSA: 2.8 ± 1.9; healthy control: 4.2 ± 1.6), and stimulation with CO2 (OSA: 1.5 ± 1.7; healthy control: 2.8 ± 1.8) were demonstrated in patients with OSA (all P < 0.05). Two-point discrimination at the soft palate was reduced with statistical significance in the OSA group (OSA: 11.5 ± 5.4 mm; healthy control: 5.0 ± 2.4 mm). The results suggest reduced pharyngeal chemosensitivity in OSA patients in addition to the reduced mechanical pharyngeal sensitivity shown with 2-point discrimination. This demonstrates peripheral neurodegeneration in the context of this disease.

Oropharyngeal syphilis among patients infected with human immunodeficiency virus.

OBJECTIVES: There has been a reemergence of syphilis among men who have sex with men over the past decade, especially in patients infected with human immunodeficiency virus (HIV). This study was aimed at describing the oropharyngeal manifestations of secondary syphilis in HIV-infected patients. We also sought to determine the clinical risk factors for the development of oropharyngeal syphilitic lesions in patients with secondary syphilis. METHODS: We performed an observational, comparative, retrospective study of HIV-infected patients who were admitted to a tertiary referral center in Mexico City and who had syphilis according to the criteria of the US Centers for Disease Control and Prevention. RESULTS: We identified 44 patients with syphilis, 31 of whom had secondary syphilis and 9 of whom had oropharyngeal manifestations. Lesions involving the anterior tonsillar pillar were the most common, observed in 5 patients; and tongue lesions were observed in 3 patients. In the patients with secondary syphilis, multivariate analysis showed that the development of oropharyngeal lesions was not associated with age, CD4 and CD8 cell counts, or HIV RNA viral load. CONCLUSIONS: The present work shows that oropharyngeal manifestations of secondary syphilis and overlapping stages of syphilis are frequent in HIV-infected patients. To the best of our knowledge, this is the first comparative study of the oropharyngeal manifestations of syphilis in HIV-infected patients.

Evaluation of the chemical model of vestibular lesions induced by arsanilate in rats.

Several animal models of vestibular deficits that mimic the human pathology phenotype have previously been developed to correlate the degree of vestibular injury to cognate vestibular deficits in a time-dependent manner. Sodium arsanilate is one of the most commonly used substances for chemical vestibular lesioning, but it is not well described in the literature. In the present study, we used histological and functional approaches to conduct a detailed exploration of the model of vestibular lesions induced by transtympanic injection of sodium arsanilate in rats. The arsanilate-induced damage was restricted to the vestibular sensory organs without affecting the external ear, the oropharynx, or Scarpa's ganglion. This finding strongly supports the absence of diffusion of arsanilate into the external ear or Eustachian tubes, or through the eighth cranial nerve sheath leading to the brainstem. One of the striking observations of the present study is the complete restructuring of the sensory epithelia into a non sensory epithelial monolayer observed at 3months after arsanilate application. This atrophy resembles the monolayer epithelia observed postmortem in the vestibular epithelia of patients with a history of lesioned vestibular deficits such as labyrinthectomy, antibiotic treatment, vestibular neuritis, or Ménière's disease. In cases of Ménière's disease, aminoglycosides, and platinum-based chemotherapy, vestibular hair cells are destroyed, regardless of the physiopathological process, as reproduced with the arsanilate model of vestibular lesion. These observations, together with those presented in this study of arsanilate vestibular toxicity, suggest that this atrophy process relies on a common mechanism of degeneration of the sensory epithelia.

The short-term effects of various oral care methods in dependent elderly: comparison between toothbrushing, tongue cleaning with sponge brush and wiping on oral mucous membrane by chlorhexidine.

OBJECTIVES: To explore the short-term effects from toothbrushing, tongue cleaning with sponge brush and wiping on oral mucous membrane by chlorhexidine. BACKGROUND: Numerous reports have been seen in recent years proving the effectiveness of mouth cleaning with a toothbrush for the prevention of respiratory infections among the dependent elderly. However, the short-term effects from each oral care method have not yet been clarified. Hence, an investigation was conducted by having each subject independently perform various oral care methods for five consecutive days. MATERIALS AND METHODS: The subjects consisted of 12 assistance-dependent elderly who have difficulties with tooth brushing by themselves, have 10 or more residual teeth and are not yet using plate dentures. After the pre-intervention examination, each of the following oral care methods were performed on the same subject on an approximately three week basis: 1) Tooth brushing 2) Tongue cleaning with sponge brush 3) Wiping on oral mucous with sponge brush by chlorhexidine. Each method was performed independently, once a day for 5 consecutive days and the subjects were reexamined on the sixth day for comparative verification. RESULTS: Consequently, toothbrushing decreased the plaque index and gingival index significantly and an improvement of oral malodour was also acknowledged (p < 0.01). Tongue cleaning with a sponge brush decreased the tongue coat score significantly (p < 0.05) and oral malodour was also improved (p < 0.01). Wiping on oral mucous with a sponge brush soaked in chlorhexidine significantly decreased opportunistic infections in the pharynx region (p < 0.05). CONCLUSIONS: It was suggested that the use of not only a toothbrush but also chlorhexidine gluconate may be indicated for dependent elderly people in whom pathogens of opportunistic infection are detected.

Risk factors of local oropharyngeal and laryngeal adverse effects from use of single inhaled corticosteroids and long-acting beta-agonists.

BACKGROUND: Single inhaled corticosteroids and long-acting beta-agonists (ICS/LABA) are clinically effective and safe. However, if local oropharyngeal and laryngeal adverse effects (LOLAE) appear, adherence to the use of ICS is impaired. To minimize the development of adverse effects, it is essential to identify the underlying risk factors. METHODS: The study included 481 asthmatic patients who were prescribed ICS/LABA for the first time in their life between January and September of 2010. Patients ranged in age from 14 to 86 years old and consisted of 281 never smokers and 200 smokers. All data were collected retrospectively by respirologists. RESULTS: Seventy-three out of 481 patients suffered from one or more adverse effects, with 54 of these exhibiting LOLAE. Patients with LOLAE (51.4 ± 16.2 yrs) were significantly older than those without LOLAE (43.7 ± 15.9 yrs) (p = 0.0011) and were also prescribed a significantly higher dose of ICS. The pack-years of patients with LOLAE (2.1 ± 4.9) were significantly lower than those without LOLAE (6.0 ± 13.0) (p = 0.0087). The type of administered ICS was also significantly associated with a risk of developing LOLAE. CONCLUSIONS: Our survey indicated that a greater age, a higher dose of ICS, and the type of ICS were potential risk factors of LOLAE. The identified factors should be considered in a clinical setting in order to prevent the development of LOLAE and provide optimal treatment to patients.

Oral care and oropharyngeal and tracheal colonization by Gram-negative pathogens in children.

BACKGROUND: Critical care nursing interventions to oral care can reduce microorganisms in the oropharynx available for translocation. OBJECTIVES: To analyse the effect of 0·12% chlorhexidine digluconate on the colonization of oropharyngeal and tracheal secretions by Gram-negative pathogens in mechanically ventilated children. METHODS: A randomized, controlled and double-blinded study was performed in the paediatric intensive care unit (PICU) of a Brazilian university hospital. Exclusion criteria included child age under 28 days, pneumonia diagnosis at admission, use of tracheostomy, PICU length of stay (LOS) less than 48 h and refusal to participate. Children were randomly allocated to the interventional group (IG), in which oral care with chlorhexidine was administered, or to the placebo group (PG), which received oral care without antiseptic use. The data were analysed through Pearson's χ(2) test, Fisher's exact and ANOVA tests with significance levels set at 0·05. RESULTS: The demographic characteristics of the 74 children were not statistically different between groups. No between-group differences in oropharyx colonization by Gram-negative pathogens were identified (p = 0·316). Pathogens were isolated in the tracheal secretions of two (10·0%) children in the PG and four (19·0%) children in the IG (p = 0·355). CONCLUSION: The use of chlorhexidine did not significantly influence the colonization of oropharyngeal and tracheal secretions by Gram-negative pathogens of the studied sample. RELEVANCE TO CLINICAL PRACTICE: This study demonstrated no influence of a specific antiseptic agent on colonization profile of mechanically ventilated children in PICU. Further research in this field is necessary to promote evidence-based nursing practice on oral care of critically ill children.

[Systemic and oropharyngeal side effects of inhaled corticosteroids]. / Effets secondaires systémiques et oropharyngés des corticostéroïdes inhalés.

The use of inhaled corticosteroids (ICS) is an important component of asthma management. Although their main impact is on airway inflammation, ICS are not devoid of systemic side effects (adrenal insufficiency, osteoporosis, brittle skin, ocular effects, growth retardation). Oropharyngeal side effects are also reported. These effects appear dose and duration dependent. They also vary according to the type of ICS used, its method of administration and drug interactions. It is recommended to titrate ICS to the lowest effective dose, to regularly reconsider their indication and to be aware of drug interactions. In addition, a change in ICS may have a favorable impact on side effects.

Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage.

The multidrug resistance protein 1 (MRP1) gene encodes a transporter protein that helps to protect cells against xenobiotics. Elevated levels of MRP1 in tumor cells can result in active extrusion of a wide range of (anticancer) drugs with different cellular targets, a phenomenon called multidrug resistance (MDR). To explore the protective function of the mouse mrp1 protein during drug treatment, we investigated the toxicity caused by the anticancer drug etoposide-phosphate (ETOPOPHOS) in mice lacking the mrp1 gene (mrp1(-/-) mice). We show here that the lack of mrp1 protein results in increased etoposide-induced damage to the mucosa of the oropharyngeal cavity and to the seminiferous tubules of the testis. The high concentrations of mrp1 that we find in the basal layers of the oropharyngeal mucosa and in the basal membrane of the Sertoli cells in the testis apparently protect wild-type mice against this tissue damage. We also find drug-induced polyuria in mrp1(-/-) mice, which correlates with the presence of mrp1 protein in the urinary collecting tubules, the major site of kidney water reabsorption. Our results indicate that specific inhibitors of MRP1 used to reverse MDR, in combination with carcinostatic drugs transported by MRP1, might lead to drug-induced mucositis, (temporary) infertility, and diabetes insipidus.

Bactericidal activity of hexylresorcinol lozenges against oropharyngeal organisms associated with acute sore throat.

OBJECTIVE: For the majority of people with acute sore throat, over-the-counter treatments represent the primary option for symptomatic relief. This study evaluated the in vitro bactericidal activity of lozenges containing the antiseptic hexylresorcinol against five bacteria associated with acute sore throat: Staphylococcus aureus, Streptococcus pyogenes, Moraxella catarrhalis, Haemophilus influenzae and Fusobacterium necrophorum. RESULTS: Hexylresorcinol 2.4 mg lozenges were dissolved into 5 mL of artificial saliva medium. Inoculum cultures were prepared in triplicate for each test organism to give an approximate population of 108 colony-forming units (cfu)/mL. Bactericidal activity was measured by log reduction in cfu. Greater than 3log10 reductions in cfu were observed at 1 min after dissolved hexylresorcinol lozenges were added to S. aureus (log10 reduction cfu/mL ± standard deviation, 3.3 ± 0.2), M. catarrhalis (4.7 ± 0.4), H. influenzae (5.8 ± 0.4) and F. necrophorum (4.5 ± 0.2) and by 5 min for S. pyogenes (4.3 ± 0.4). Hexylresorcinol lozenges achieved a > 99.9% reduction in cfu against all tested organisms within 5 min, which is consistent with the duration for a lozenge to dissolve in the mouth. In conclusion, in vitro data indicate that hexylresorcinol lozenges offer rapid bactericidal activity against organisms implicated in acute sore throat.