Comparison of innate immune responses towards rhinovirus infection of primary nasal and bronchial epithelial cells.

BACKGROUND AND OBJECTIVE Rhinoviruses (RV) replicate in both upper and lower airway epithelial cells. We evaluated the possibility of using nasal epithelial cells (NEC) as surrogate of bronchial epithelial cells (BEC) for RV pathogenesis cell culture studies. METHODS We used primary paired NEC and BEC cultures established from healthy subjects and compared the replication of RV belonging to the major (RV16) and minor (RV1B) group, and the cellular antiviral and proinflammatory cytokine responses towards these viruses. We related antiviral and pro-inflammatory responses of NEC isolated from CF and COPD patients with those of BEC. RESULTS RV16 replication and major group surface receptor (ICAM-1) expression were higher in healthy NEC compared with BEC (P < 0.05); RV1B replication and minor group surface receptor (LDLR) expression were similar. Healthy NEC and BEC produced similar levels of IFN-β and IFN-λ2/3 upon RV infection or after simulation with poly(IC). IL-8 production was similar between healthy NEC and BEC. IL-6 release at baseline (P < 0.01) and upon infection with RV16 (P < 0.05) and poly(IC) stimulation (P < 0.05) was higher in NEC. RV1B viral load in NEC was related to RV1B viral load in BEC (r = 0.49, P = 0.01). There was a good correlation of IFN levels between NEC and BEC (r = 0.66, P = 0.0004 after RV1B infection). IL-8 production in NEC was related to IL-8 production in BEC (r = 0.48, P = 0.02 after RV1B infection). CONCLUSION NEC are a suitable alternative cellular system to BEC to study the pathophysiology of RV infections and particularly to investigate IFN responses induced by RV infection.

The nasal microbiota in infants with cystic fibrosis in the first year of life: a prospective cohort study.

BACKGROUND Respiratory tract infections and subsequent airway inflammation occur early in the life of infants with cystic fibrosis. However, detailed information about the microbial composition of the respiratory tract in infants with this disorder is scarce. We aimed to undertake longitudinal in-depth characterisation of the upper respiratory tract microbiota in infants with cystic fibrosis during the first year of life. METHODS We did this prospective cohort study at seven cystic fibrosis centres in Switzerland. Between Feb 1, 2011, and May 31, 2014, we enrolled 30 infants with a diagnosis of cystic fibrosis. Microbiota characterisation was done with 16S rRNA gene pyrosequencing and oligotyping of nasal swabs collected every 2 weeks from the infants with cystic fibrosis. We compared these data with data for an age-matched cohort of 47 healthy infants. We additionally investigated the effect of antibiotic treatment on the microbiota of infants with cystic fibrosis. Statistical methods included regression analyses with a multivariable multilevel linear model with random effects to correct for clustering on the individual level. FINDINGS We analysed 461 nasal swabs taken from the infants with cystic fibrosis; the cohort of healthy infants comprised 872 samples. The microbiota of infants with cystic fibrosis differed compositionally from that of healthy infants (p=0·001). This difference was also found in exclusively antibiotic-naive samples (p=0·001). The disordering was mainly, but not solely, due to an overall increase in the mean relative abundance of Staphylococcaceae in infants with cystic fibrosis compared with healthy infants (multivariable linear regression model stratified by age and adjusted for season; second month: coefficient 16·2 [95% CI 0·6-31·9]; p=0·04; third month: 17·9 [3·3-32·5]; p=0·02; fourth month: 21·1 [7·8-34·3]; p=0·002). Oligotyping analysis enabled differentiation between Staphylococcus aureus and coagulase-negative Staphylococci. Whereas the analysis showed a decrease in S aureus at and after antibiotic treatment, coagulase-negative Staphylococci increased. INTERPRETATION Our study describes compositional differences in the microbiota of infants with cystic fibrosis compared with healthy controls, and disordering of the microbiota on antibiotic administration. Besides S aureus, coagulase-negative Staphylococci also contributed to the disordering identified in these infants. These findings are clinically important in view of the crucial role that bacterial pathogens have in the disease progression of cystic fibrosis in early life. Our findings could be used to inform future studies of the effect of antibiotic treatment on the microbiota in infants with cystic fibrosis, and could assist in the prevention of early disease progression in infants with this disorder. FUNDING Swiss National Science Foundation, Fondation Botnar, the Swiss Society for Cystic Fibrosis, and the Swiss Lung Association Bern.

Efficacy of a Nasal Spray from Citrus limon and Cydonia oblonga for the Treatment of Hay Fever Symptoms - A Randomized, Placebo Controlled Cross-Over Study

Nasal spray from lemon and quince (LQNS) is used to treat hay fever symptoms and has been shown to inhibit histamine release from mast cells in vitro. Forty-three patients with grass pollen allergy (GPA) were randomized to be treated either with placebo or LQNS for one week, respectively, in a cross-over study. At baseline and after the respective treatments patients were provoked with grass pollen allergen. Outcome parameters were nasal flow measured with rhinomanometry (primary), a nasal symptom score, histamine in the nasal mucus and tolerability. In the per protocol population absolute inspiratory nasal flow 10 and 20 min after provocation was higher with LQNS compared to placebo (-37 ± 87 mL/s; p = 0.027 and -44 ± 85 mL/s; p = 0.022). The nasal symptom score showed a trend (3.3 ± 1.8 in the placebo and 2.8 ± 1.5 in the LQNS group; p = 0.070) in favor of LQNS; the histamine concentration was not significantly different between the groups. Tolerability of both, LQNS and placebo, was rated as very good. LQNS seems to have an anti-allergic effect in patients with GPA. Copyright © 2016 John Wiley & Sons, Ltd.

Type IV delayed-type hypersensitivity of the respiratory tract due to budesonide use: report of two cases and a literature review

Respiratory type-IV hypersensitivity reactions due to corticosteroids is a rare phenomenon. We describe two such cases. The first is a 37- year-old atopic woman who developed labial angioedema and nasal itching after the use of budesonide nasal spray. A month later, after the first puffs of a formoterol/budesonide spray prescribed for asthma, she noticed symptoms of tongue and oropharyngeal itching and redness with subsequent dysphagia, labial and tongue angioedema, and facial oedema. The second is a 15-year-old non-atopic woman who reported pruritic eruptions around the nostrils after using a budesonide nasal spray. A year later she presented with nasal pruritus with intense congestion and labial and facial oedema after using the same spray. Both patients were evaluated with patch-tests using the commercial T.R.U.E. test, a budesonide solution, and corticosteroid creams. Test evaluation was performed at 48 and 96 hours. In both patients, patch tests were positive to budesonide (++) on the second day. The first patient also had a positive (+) reaction to tixocortol-21-pivalate. All the other patch tests were negative. Clinicians should be aware that hypersensitivity reactions may occur during the use of nasal or inhaled corticosteroids.

The CFTR frameshift mutation 3905insT and its effect at transcript and protein level

Cystic fibrosis (CF) is one of the most common genetic diseases in the Caucasian population and is characterized by chronic obstructive pulmonary disease, exocrine pancreatic insufficiency, and elevation of sodium and chloride concentrations in the sweat and infertility in men. The disease is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which encodes a protein that functions as chloride channel at the apical membrane of different epithelia. Owing to the high genotypic and phenotypic disease heterogeneity, effects and consequences of the majority of the CFTR mutations have not yet been studied. Recently, the frameshift mutation 3905insT was identified as the second most frequent mutation in the Swiss population and found to be associated with a severe phenotype. The frameshift mutation produces a premature termination codon (PTC) in exon 20, and transcripts bearing this PTC are potential targets for degradation through nonsense-mediated mRNA decay (NMD) and/or for exon skipping through nonsense-associated alternative splicing (NAS). Using RT-PCR analysis in lymphocytes and different tissue types from patients carrying the mutation, we showed that the PTC introduced by the mutation does neither elicit a degradation of the mRNA through NMD nor an alternative splicing through NAS. Moreover, immunocytochemical analysis in nasal epithelial cells revealed a significantly reduced amount of CFTR at the apical membrane providing a possible molecular explanation for the more severe phenotype observed in F508del/3905insT compound heterozygotes compared with F508del homozygotes. However, further experiments are needed to elucidate the fate of the 3905insT CFTR in the cell after its biosynthesis.

Intensity-modulated radiotherapy for a rendu-osler-weber disease patient with recurrent severe epistaxis: a case report

We present a case of a Rendu-Osler-Weber disease patient with recurrent life threatening epistaxis demanding multiple blood transfusions despite of repetitive endoscopic laser and electrocoagulations, endovascular embolisation, septodermoplasty, and long-term intranasal dressings. As alternative treatment modalities repeatedly failed and the patient became almost permanently dependent on nasal dressing, we performed a highly conformal intensity-modulated radiotherapy of the nasal cavity; a total dose of 50 Gy in 2 Gy single fractions was applied. The therapy was very well tolerated, no acute toxicities occurred. Two weeks after the last radiation dose had been applied, the nasal dressing could be removed without problems. Endoscopical control revealed an almost avascular white mucosa without any trace of bleeding spots; previously existing hemangiomas and crusts had disappeared. After a 1-year-follow up, the patient had no significant recurrent epistaxis.

[Spontaneous dural arterio-venous fistula at the cavernous sinus: detected by decompensation following endoscopic sinus surgery]

Spontaneous dural arterio-venous fistulas can imperceptibly develop over a long time period before they suddenly develop symptoms like bruit, loss of vision, exophthalmos and conjunctival injection. We present the rare case of an occult, para-infectious, dural arterio-venous fistula which became symptomatic after endoscopic sinus surgery. Conjunctival injection and slight exophthalmos developed due to decompensation of venous drainage probably by intraoperative positioning of the patient, positive pressure ventilation and nasal packing.

Prosthetic Rehabilitation, Implant Survival and Quality of Life 2 to 5 Years after Resection of Oral Tumors

Background: After oral tumor resection, structural and functional rehabilitation by means of dental prostheses is complex, and positive treatment outcome is not always predictable. Purpose: The objective of the study was to report on oral rehabilitation and quality of life 2-5 years after resection of malignant oral tumors. Materials and Methods: Data of 46 patients (57 ± 7 years) who underwent oral tumor surgery were available. More than 50% of tumors were classified T3 or T4. Open oro-nasal defects resulted in 12 patients and full mandibulary block resections in 23 patients. Comprehensive planning, implant placement, and prosthetic rehabilitation followed an interdisciplinary protocol. Analysis comprised tumor location, type of prostheses, implant survival, and quality of life. Results: Because of advanced tumor status, resections resulted in marked alteration of the oral anatomy requiring complex treatment procedures. Prosthetic rehabilitation comprised fixed and removable prostheses, with 104 implants placed in 28 patients (60%). Early implant loss was high (13%) and cumulative survival rate of loaded implants was <90% after 5 years. Prosthetic plans had to be modified because of side effects of tumor therapy, complications with implants and tumor recurrence. The majority of patients rated quality of life favorable, but some experienced impaired swallowing, dry mouth, limited mouth opening, appearance, and soreness. Conclusions: Some local effects of tumor therapy could not be significantly improved by prosthetic rehabilitation leading to functional and emotional disability. Many patients had passed away or felt too ill to fill the questionnaires. This case series confirms the complex anatomic alterations after tumor resection and the need for individual treatment approaches especially regarding prosthesis design. In spite of disease-related local and general restrictions, most patients gave a positive assessment of quality of life.

Paediatric traffic accident and obstructive sleep apnoea by antrochoanal polyps: case report and literature review

Antrochoanal polyps are hyperplasias of the nasal mucosa, which have their origin in the maxillary sinus and extend through the nasal cavity and the choanae into the naso- and oropharynx. In children antrochoanal polyps represent one of the more frequent manifestations of paediatric nasal polyposis. Most studies on antrochoanal polyps in children report only on nasal obstruction, hyponasal speech and snoring, which are also encountered in the most common cause of obstructive sleep apnoea syndrome; i.e. adenoid or tonsillar hyperplasia. Only very few studies report on additional health hazards by antrochoanal polyps ranging from obstructive sleep apnoea syndrome to swallowing disorders and cachexia. We present the case of an 8 year old girl with a bicycle accident caused by excessive daytime sleepiness and obstructive sleep apnoea syndrome due to an extensive antrochoanal polyp. After a transnasal polypectomy and meatotomy type II the obstructive sleep apnoea and day time sleepiness resolved completely. Awareness of this additional health hazard is important and correct evaluation and timely diagnosis of a potential antrochoanal polyp is mandatory because minimally invasive rhinosurgery is highly curative in preventing further impending problems.

Primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is an autosomal recessive disease with an incidence estimated between 1:2,000 and 1:40,000. Ciliated epithelia line the airways, nasal and sinus cavities, Eustachian tube and fallopian tubes. Congenital abnormalities of ciliary structure and function impair mucociliary clearance. As a consequence, patients present with chronic sinopulmonary infections, recurrent glue ear and female subfertility. Similarities in the ultrastructure of respiratory cilia, nodal cilia and sperm result in patients with PCD also presenting with male infertility, abnormalities of left-right asymmetry (most commonly situs inversus totalis) and congenital heart disease. Early diagnosis is essential to ensure specialist management of the respiratory and otological complications of PCD. Diagnostic tests focus on analysis of ciliary function and electron microscopy structure. Analysis is technically difficult and labour intensive. It requires expertise for interpretation, restricting diagnosis to specialist centres. Management is currently based on the consensus of experts, and there is a pressing need for randomised clinical trials to inform treatment.

Giulio Cesare Aranzio (Arantius) (1530-89) in the pageant of anatomy and surgery

Giulio Cesare Aranzio in Italian (Julius Caesar Arantius in Latin) has not received full acclaim for his achievements in the field of anatomy and surgery that remain unknown to most physicians. His anatomical books Observationes Anatomicas, and De Humano Foetu Opusculum and surgical books De Tumoribus Secundum Locos Affectos and Hippocratis librum de vulneribus capitis commentarius brevis printed in Latin and additional existing literature on Aranzio from medical history books and journals were analysed extensively. Aranzio became Professor of Anatomy and Surgery at the University of Bologna in 1556. He established anatomy as a distinguished branch of medicine for the first time in medical history. Aranzio combined anatomy with a description of pathological processes. He discovered the 'Nodules of Aranzio' in the semilunar valves of the heart. He gave the first description of the superior levator palpebral and the coracobrachialis muscles. Aranzio wrote on surgical techniques for a wide spectrum of conditions that range from hydrocephalus, nasal polyp, goitre and tumours to phimosis, ascites, haemorrhoids, anal abscess and fistulae, and much more. Aranzio had an extensive knowledge in surgery and anatomy based in part on the ancient Greek and his contemporaries in the 16th century but essentially on his personal experience and practice.

Therapy options and long-term results of sinonasal malignancies

Nasal and paranasal sinus malignancies are rare. The most common lesions are located in the nasal cavity and the maxillary sinus, although they also occur in the ethmoid, sphenoid and frontal sinuses. Treatment often combines surgery, radiotherapy and chemotherapy. Endoscopic surgical approaches are increasingly used in order to reduce the morbidity associated with standard open resection. The aim of our study was to analyse the long-term treatment results of sinonasal malignancies (SNM), with a special focus on surgical approaches.

Nasolabial symmetry and aesthetics in children with complete unilateral cleft lip and palate

The objective of this study was to evaluate the association between nasolabial symmetry and aesthetics in children with complete unilateral cleft lip and palate (CUCLP). Frontal and basal photographs of 60 consecutively treated children with CUCLP (cleft group: 41 boys and 19 girls, mean (SD) age 11 (2) years) and 44 children without clefts (control group: 16 boys and 28 girls, mean (SD) age 11(2) years), were used for evaluation of nasolabial symmetry and aesthetics. Nasal and labial measurements were made to calculate the coefficient of asymmetry (CA). The 5-grade aesthetic index described by Asher-McDade et al. was used to evaluate nasolabial appearance. Correlation and regression analysis were used to identify an association between aesthetics and CA, sex, and the presence of CUCLP. Ten measurements in the cleft, and 2 in the control, group differed significantly between the cleft and non-cleft (or right and left) sides, respectively. The significantly higher values of 9 of 11 CA in the children with CUCLP indicated that they had more asymmetrical nasolabial areas than children without clefts. However, the regression analyses showed that only a few CA were associated with nasolabial aesthetics. In conclusion, nasolabial aesthetics and nasolabial symmetry seem to be only weakly associated in patients with CUCLP.

Low rate of methicillin-resistant coagulase-positive staphylococcal colonization of veterinary personnel in Hong Kong

Elevated rates of methicillin-resistant Staphylococcus aureus (MRSA) carriage have been reported in veterinary personnel, suggesting an occupational colonization risk. Hong Kong veterinary personnel (n = 150) were sampled for coagulase-positive staphylococci (CPS) nasal colonization. Risk factors for colonization were assessed by questionnaire. Isolates were identified and antibiotic susceptibility determined. All CPS isolates were investigated for mecA carriage, SCCmec type and PVL genes. Two subjects were colonized with methicillin-resistant CPS: one with MRSA (spa type t002 (CC5), SCCmec type II) and one with methicillin-resistant Staphylococcus pseudintermedius (MRSP) (MLST type ST71, SCCmec type II-III). MLST type ST71 S. pseudintermedius strain is the predominant MRSP clone circulating in dogs in Europe and in Hong Kong. The low MR-CPS colonization rate may be associated with low levels of large animal exposure or low rates of MRSA colonization of companion animals in Hong Kong. Colonization with non-aureus CPS, which may cause human infection, must also be considered in veterinary personnel.

Owner assessment in judging the efficacy of airway disease treatment

REASONS FOR PERFORMING STUDY: Efficacy of medications for recurrent airway obstruction is typically tested using clinical, cytological and lung function examinations of severely affected animals. These trials are technically challenging and may not adequately reflect the spectrum of disease and owner complaints encountered in clinical practice. OBJECTIVE: To determine if owners of horses with chronic airway disease are better able to detect drug efficacy than a veterinarian who clinically examines horses infrequently. METHOD: In a double-blinded randomised controlled trial, owners and a veterinarian compared the efficacy of dexamethasone (0.1 mg/kg bwt per os, q. 24 h, for 3 weeks; n = 9) to placebo (n = 8) in horses with chronic airway disease. Before and after treatment, owners scored performance, breathing effort, coughing and nasal discharge using a visual analogue scale (VAS). The clinician recorded vital parameters, respiratory distress, auscultation findings, cough and nasal discharge, airway mucus score, bronchoalveolar lavage fluid (BALF) cytology and arterial blood gases. RESULTS: The VAS score improved significantly in dexamethasone- but not placebo-treated horses. In contrast, the clinician failed to differentiate between dexamethasone- and placebo-treated animals based on clinical observations, BALF cytology or endoscopic mucus score. Respiratory rate (RR) and arterial oxygen pressure (PaO(2)) improved with dexamethasone but not placebo. CONCLUSIONS AND CLINICAL RELEVANCE: In the design of clinical trials of airway disease treatments, more emphasis should be placed on owner-assessed VAS than on clinical, cytological and endoscopic observations made during brief examinations by a veterinarian. Quantifiable indicators reflecting lung function such as RR and PaO(2) provide a good assessment of drug efficacy.