Update of the consensus document on the aetiology, diagnosis and treatment of acute otitis media and sinusitis.

Update of the consensus on acute otitis media (AOM) (2012) and sinusitis (2013) following the introduction of pneumococcal vaccines in the immunization schedule, and related changes, such as epidemiological variation, colonization by of nonvaccine serotypes and emerging antimicrobial resistances. A majority of studies show that the introduction of the pneumococcal 13-valent conjugate vaccine has been followed by a reduction in the nasopharyngeal carriage of pneumococcus, with an increase in the proportion of drug-resistant nonvaccine serotypes. The diagnosis of AOM is still clinical, although more stringent criteria are proposed, which are based on the visualization of abnormalities in the tympanic membrane and the findings of pneumatic otoscopy performed by trained clinicians. The routine diagnosis of sinusitis is also clinical, and the use of imaging is restricted to the assessment of complications. Analgesia with acetaminophen or ibuprofen is the cornerstone of AOM management; watchful waiting or delayed antibiotic prescription may be suitable strategies in select patients. The first-line antibiotic drug in children with AOM and sinusitis and moderate to severe disease is still high-dose amoxicillin, or amoxicillin-clavulanic acid in select cases. Short-course regimens lasting 5-7 days are recommended for patients with uncomplicated disease, no risk factors and a mild presentation. In allergic patients, the selection of the antibiotic agent must be individualized based on severity and whether or not the allergy is IgE-mediated. In recurrent AOM, the choice between watchful waiting, antibiotic prophylaxis or surgery must be individualized based on the clinical characteristics of the patient.

Sequential Biotherapy Targeting IL-5 and IL-4/13 in Patients with Eosinophilic Asthma with Sinusitis and Otitis Media.

Type 2 (T2) inflammation plays an important role in the pathogenesis of allergic diseases such as asthma, eosinophilic chronic rhinosinusitis (ECRS), or eosinophilic otitis media (EOM). Currently, in severe asthma with the T2 phenotype, biologics targeting mediators of T2 inflammation dramatically improve the management of severe asthma. While treatment with a single biologic is common, little is known about cases of the sequential use of two biologics. Here, we report a case of severe asthma with refractory ECRS and EOM in which total control of these allergic diseases could not be achieved with a single biologic but could be achieved via the sequential use of the anti-IL-5 receptor antibody and human anti-IL-4/13 receptor monoclonal antibody. It is suggested that it is necessary to control multiple T2 inflammatory pathways to achieve total control of severe allergic diseases. Sequential biotherapy may help solve the clinical challenges associated with single-agent molecular-targeted therapies.

Working towards consensus in the management of pediatric chronic rhinosinusitis in cystic fibrosis.

OBJECTIVE: The prevalence of chronic rhinosinusitis (CRS), defined by mucosal thickening on imaging, approaches 100% in the cystic fibrosis (CF) population. CRS is associated with significant morbidity in CF, including its ability to trigger pulmonary exacerbations. CRS in CF is typically managed by pediatricians, otolaryngologists and pulmonologists. This survey evaluates the variance in practice patterns of CRS in CF amongst specialists. METHODS: This is a cross-sectional, electronic survey in which maximum variation purposive sampling was used by a multi-disciplinary group of pediatric, otolaryngology and pulmonology providers in order to select a survey population with expertise in CRS in CF patients. The survey was distributed to 381 practitioners from September to October 2019. RESULTS: 175 participants responded (45% response rate). Ten (of 54) statements achieved 75% consensus agreement. Consensus statements included: The decision to pursue surgical intervention for CRS in CF is a multi-disciplinary approach (94%; n = 146); maximal medical management should include nasal saline irrigation (93%; n = 142), topical steroids (75%; n = 117), maximal medical management should not include intravenous steroids (79%; n = 122); image guidance in surgery is necessary for all surgery involving the frontal sinuses (77%; n = 43), and all revision surgery(80%, n = 45); the appropriate setting for sinus surgery in a CF patient varies depending on patient presentation (89%; n = 133); post-operative regimen should include nasal saline (93%; n = 137); but does depend on the severity of disease discovered intra-operatively (84%; n = 124); post-operative antibiotics should be guided by intra-operative culture data (82%; n = 121). CONCLUSIONS: There is a great deal of variation amongst specialists in the treatment of CRS in CF, however 10 statements met consensus criteria and should be considered when forming clinical care guidelines in this population.

Limiting Dietary Sugar Improves Pediatric Sinonasal Symptoms and Reduces Inflammation.

Excessive sugar consumption is associated with many chronic inflammatory diseases in adults. The effects of excessive sugar consumption in children have not been determined. In this study, we hypothesized that sinonasal symptoms and proinflammatory cytokine levels would be related and could be altered through reduction in sugar-sweetened beverage (SSB) consumption. To test this, we conducted a pilot study involving behavior modification and a 2-week follow-up. Seventeen children participants were recruited, and eleven completed the study. The experimental group presented with chronic nasal congestion or rhinorrhea defined by daily symptoms without acute illness for at least 3 months. The control group presented for non-nasal problems. Both groups received counseling to decrease SSB consumption. The Sinus and Nasal Quality of Life (SN-5) Survey was administered, and a blood sample was obtained by venipuncture at baseline and 2 weeks after counseling. Participants kept a 2-week food diary to document sugar intake. Serum lipid profile and inflammatory cytokines were measured. The experimental group reduced daily sugar intake, 46% versus 11% in the control. Baseline SN-5 scores were significantly worse in the experimental group and normalized to controls after intervention. Inflammatory cytokine levels were not different at baseline, but the experimental group significantly reduced in proinflammatory markers and increased the levels of anti-inflammatory markers after intervention. Our pilot data demonstrate higher sugar consumption may be associated with increased inflammatory stress and sinonasal symptoms. Reducing SSB and controlling inflammation in early childhood may have future health benefits.

Overuse of diagnostic tools and medications in acute rhinosinusitis in Spain: a population-based study (the PROSINUS study).

OBJECTIVES: Acute rhinosinusitis (ARS) has a high incidence. Diagnosis is clinical, and evolution is mostly self-limited. The aim of this study was to describe the sociodemographic characteristics and use of diagnostic tools and medications in patients with ARS. DESIGN: This is a prospective observational study in real-life clinical practice. SETTING: Patients with clinical diagnosis of ARS (n=2610) were included from ear, nose and throat clinics in Spain. A second visit at resolution was done. PARTICIPANTS: Patients were classified according to the duration of symptoms: viral ARS (≤10 days), postviral ARS (>10 days, ≤12 weeks) and chronic rhinosinusitis (>12 weeks). MAIN OUTCOME MEASURES: Sociodemographic characteristics, symptoms, disease severity, quality of life (Sino-Nasal Outcome Test-16), used diagnostic tools and medications, and the management performed by primary care physicians (PCPs) and by otorhinolaryngologists (ORLs) were assessed. RESULTS: Of the patients 36% were classified as having viral ARS, 63% postviral ARS and 1% as chronic rhinosinusitis. Working in a poorly air-conditioned environment was a risk factor (OR: 2.26, 95% CI 1.27 to 4.04) in developing postviral ARS. A higher number of diagnostic tools (rhinoscopy/endoscopy: 80% vs 70%; plain X-ray: 70% vs 55%; CT scan: 22% vs 12%; P<0.0001) were performed in postviral than viral cases. PCPs performed more X-rays than ORLs (P<0.0001). Patients, more those with postviral than viral ARS, received a high number of medications (oral antibiotics: 76% vs 62%; intranasal corticosteroids: 54% vs 38%; antihistamines: 46% vs 31%; mucolytic: 48% vs 60%; P<0.0001). PCPs prescribed more antibiotics, antihistamines and mucolytics than ORLs (P<0.0068). More patients with postviral than viral ARS reported symptoms of potential complications (1.5% vs 0.4%; P=0.0603). Independently of prescribed medications, quality of life was more affected in patients with postviral (38.7±14.2 vs 36.0±15.3; P=0.0031) than those with viral ARS. ARS resolution was obtained after 6.04 (viral) and 16.55 (postviral) days, with intranasal corticosteroids being associated with longer (OR: 1.07, 95% 1.02 to 1.12) and phytotherapy with shorter (OR: 0.95, 95% CI 0.91 to 1.00) duration. CONCLUSIONS: There is a significant overuse of diagnostic tools and prescribed medications, predominantly oral antibiotics, by PCPs and ORLs, for viral and postviral ARS.

Kartagener's syndrome: a case report.

BACKGROUND: Kartagener's syndrome is a subset of primary ciliary dyskinesia, an autosomal recessive inherited disorder characterized by the clinical triad of chronic sinusitis, bronchiectasis, and situs inversus. Abnormal ciliary structure or function leading to impaired ciliary motility is the main pathophysiologic problem in Kartagener's syndrome. CASE PRESENTATION: A 24-year-old man from Gondar town, North-West Ethiopia, presented to University of Gondar Hospital with recurrent episodes of nasal congestion with itching and paranasal discomfort, and productive cough for more than a decade. Clinical and imaging findings revealed chronic sinusitis, bronchiectasis, dextrocardia, and situs inversus. He was treated with orally administered antibiotics, mucolytic, and chest physiotherapy. He was symptomatically better with the above therapy, and started on a long-term low-dose prophylactic antibiotic. CONCLUSIONS: Patients with Kartagener's syndrome exist in Ethiopia as cases of chronic recurrent sinopulmonary infections. As there is no easy, reliable non-invasive diagnostic test for Kartagener's syndrome and the correct diagnosis is often delayed by years, it may cause chronic respiratory problems with reduced quality of life. Genetic counseling and fertility issues should be addressed once Kartagener's syndrome is diagnosed.

Sino nasal inhalation of isotonic versus hypertonic saline (6.0%) in CF patients with chronic rhinosinusitis - Results of a multicenter, prospective, randomized, double-blind, controlled trial.

BACKGROUND: Chronic rhinosinusitis is a hallmark of Cystic fibrosis (CF) impairing the patients' quality of life and overall health. However, therapeutic options have not been sufficiently evaluated. Bronchial inhalation of mucolytic substances is a gold standard in CF therapy. Previously, we found that sinonasal inhalation of dornase alfa as vibrating aerosol reduces symptoms of chronic rhinosinusitis more effectively than NaCl 0.9% (net treatment benefit: -5.87±2.3 points, p=0.017; SNOT-20 total score). This multicenter study compares the effect of NaCl 6.0% vs. NaCl 0.9% following the protocol from our preceding study with dornase alfa. METHODS: Sixty nine CF patients with chronic rhinosinusitis in eleven German CF centers were randomized to receive sinonasal vibrating inhalation of either NaCl 6.0% or NaCl 0.9% for 28days. After 28days of wash-out, patients crossed over to the alternative treatment. The primary outcome parameter was symptom score in the disease-specific quality of life Sino-Nasal Outcome Test-20 (SNOT-20). Additionally, pulmonary function was assessed, as well as rhinomanometry and inflammatory markers in nasal lavage (neutrophil elastase, interleukin (IL)-1ß, IL-6, and IL-8) in a subgroup. RESULTS: Both therapeutic arms were well tolerated and showed slight improvements in SNOT-20 total scores (NaCl 6.0%: -3.1±6.5 points, NaCl 0.9%: -5.1±8.3 points, ns). In both treatment groups, changes of inflammatory parameters in nasal lavage from day 1 to day 29 were not significant. We suppose that the irritating properties of NaCl 6.0% reduced the suitability of the SNOT-20 scores as an outcome parameter. Alternative primary outcome parameters such as MR-imaging or the quantity of sinonasal secretions mobilized with both saline concentrations were, however, not feasible. CONCLUSION: Sinonasal inhalation with NaCl 6.0% did not lead to superior results vs. NaCl 0.9%, whereas dornase alfa had been significantly more effective than NaCl 0.9%.

[Conservative therapy of chronic sinusitis]. / Therapie der chronischen Rhinosinusitis.

The chronic rhinosinusitis is defined as chronic inflammation of the nose and nasal sinuses, with or without nasal polyps. Patients suffering from chronic rhinosinusitis report about nasal obstruction and secretion, olfactory impairment, head and facial pain. These symptoms cause also considerable impact on quality of life. Therefore, an adequate rhinological diagnostics as well as therapies are essential. This paper reviews the pharmacologic and non-pharmacologic therapy of chronic rhinosinusitis. First choice of therapy should be topical glucocorticoids. The application of glucocorticoids causes anti-inflammatory and certain curative effects. Hypertonic salt solutions improve nasal symptoms. Long-term therapy with oral macrolides might improve median to severe symptoms of chronic rhinosinusitis without nasal polyps. An additional therapy with antihistamines is possible in patients with an allergy. Adaptive desensitization in patients suffering from analgesic-intolerance associating among other with nasal polyps is currently the single causal therapy. Therefore, frequency of endonasal revision surgery is reduced after desensitization.

Role of medical therapy in the management of nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the nasal and paranasal sinus mucosa that, despite differing hypotheses regarding its cause, remains poorly understood. Major symptoms are nasal congestion or blockage, loss of smell, rhinorrhea, postnasal drip, and facial pain or pressure. Among the objectives of CRSwNP management are to eradicate nasal polyps from nasal and sinusal cavities, eliminate symptoms, and prevent recurrences. Corticosteroids are the mainstay of treatment and are the most effective drugs for treating CRSwNP. Other potential treatments are nasal saline irrigation and antihistamines (in allergic conditions). Endoscopic sinus surgery is recommended when medical treatment fails. After surgery, medical treatment, including nasal and oral corticosteroids, is recommended.

Treatment of acute rhinosinusitis with the preparation from Pelargonium sidoides EPs 7630: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of the herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630) compared to placebo. DESIGN: Double-blind, randomized, placebo-controlled, parallel-group, multicenter trial with a group-sequential adaptive design. SUBJECTS: Patients with sinonasal symptoms of at least 7 days duration, and radiographically and clinically confirmed acute rhinosinusitis of presumably bacterial origin with a Sinusitis Severity Score (SSS) of at least 12 out of 24 points at inclusion. INTERVENTIONS: EPs 7630, a herbal drug preparation from the roots of Pelargonium sidoides (1: 8-10; extraction solvent: ethanol 11% (w/w)), or matching placebo at a dose of 60 drops three times daily for maximum 22 days. MAIN OUTCOME MEASURES: Change in the SSS after 7 days. RESULTS: 103 patients were recruited until the planned interim analysis. The mean decrease in the SSS was 5.5 points in the EPs 7630 group compared to 2.5 points in the placebo group, a difference of 3.0 points (95% confidence interval 2.0 to 3.9, p < 0.00001). This result was confirmed by all secondary parameters indicating a more favourable course of the disease and a faster recovery in the EPs 7630 group. According to the pre-specified decision rule, the study was stopped after obtaining proof of efficacy for EPs 7630. CONCLUSIONS: EPs 7630 was well tolerated and superior in efficacy compared to placebo in the treatment of acute rhinosinusitis of presumably bacterial origin.

Middle meatus bacteriology of acute rhinosinusitis in patients after irradiation of nasopharynx.

BACKGROUND: Patients who undergo radiotherapy for nasopharyngeal carcinoma (NPC) tend to suffer from rhinosinusitis because irradiation causes damage to sinonasal tissue; however, their bacteriology is lacking in the literature. The aim of this study was to determine the bacteriology and antibiotic resistance in acute rhinosinusitis (ARS) of these patients. METHODS: We collected nasal purulent discharge for bacteriology and antibiotic susceptibility tests in irradiated NPC patients with ARS. Middle meatus discharge was aspirated for culture with endoscopic assistance. RESULTS: A total of 33 episodes of ARS were documented in 25 patients. Staphylococcus aureus comprised 42% of all aerobes. Thirty-six percents of aerobic isolates were Gram-negative bacilli. Peptostreptococcus micros and Veillonella spp were the most frequently isolated anaerobes. CONCLUSION: The bacteriology in irradiated NPC patients with ARS was distinctive in the following: first, the most common pathogen was S. aureus; second, frequently isolated Gram-negative bacilli and anaerobes; and third, polymicrobial infections. The beta-lactamase-producing pathogens were highly prevalent.

[Rhinosinusitis: etiopathogenesis and antimicrobial therapy, an update]. / Le rinosinusiti: aggiornamenti in tema di eziopatogenesi e antibioticoterapia.

The aim of the current study is to underline once again the etiopathogenetic aspects of rhinosinusitis, by a revision of most significative and updated study in otorhinolaryngologic literature to guide the right management of this disease. The focal role of ostio-meatal complex is reported; epidemiological data on old and emergent pathogens are described together with their role on acute or chronic or recurrent rhinosinusitis pathogenesis. According to recent evidence based medicine documents, diagnostic criteria and methodologies are reported to control surgical and medical long-term results. On the bases of the current etiopathogenetic concepts, medical treatment is suggested. The central role of medical management is based on the choice of antimicrobial treatment. The fundamental concepts on pharmacocinetic and pharmacodinamic are reported, togther with updated data on antimicrobial resistance.

[Clinical study of the paranasal sinuses of patients with Japanese Cedar pollinosis].

To clarify paranasal sinus change in patients with Japanese cedar pollinosis, we studied reactions to medical treatment via X-ray images of patients during the 2000 cedar pollen season. Medication was administered to 577 patients consulting facilities in 3 regions--Kyoto, Fukui and Osaka--having different pollen counts i.e., 4555/cm2 in Fukui, 801/cm2 in Kyoto and 531/cm2 in Osaka. The paranasal sinus was X-rayed by Water's method, and the degree of positivity was classified by Katagiri'shadow classification. Patients were grouped into 334 suffering extensive Fukui pollen dispersion and 243 suffering relatively limited Kyoto and Osaka pollen dispersion. At 3-4 weeks after pollen dispersion, contrast shadow positivity was 22.2%, with no difference before pollen dispersion (22.2%) in Kyoto and Osaka. In Fukui, positivity was 39.7%, a clear increase over pre pollen dispersion (19.2%). In the initial treatment group, positivity was 25.8% in Fukui and 28.6% in Kyoto and Osaka. Our results suggest that the incidence of sinusitis in patients with Japanese cedar pollinosis tended to increase with exposure to extensive pollen dispersion and to be suppressed by initial treatment.

Targeting cysteinyl leukotrienes in patients with rhinitis, sinusitis and paranasal polyps.

Leukotrienes have been known in the field of immunology since the 1930s. At that time they were referred to as the slow reacting substance of anaphylaxis. They were not, however, characterized until the 1980s, when they were noted to be formed during the breakdown of arachidonic acid by the enzyme 5-lipoxygenase. The leukotrienes consist of leukotriene (LT) A4, LTB4, LTC4, LTD4 and LTE4, so named because the molecule was originally isolated from leukocytes and therefore its carbon backbone contains three double bonds in series, which constitutes a trion. This structural information provided the key to the oxidative pathway of lipometabolism, known as the 5-lipoxygenase. Leukotrienes are classified as inflammatory mediators, and therefore they are produced by a number of cell types, particularly mast cells, eosinophils, basophils, macrophages and monocytes. With the identification of asthma, allergic rhinitis and paranasal sinusitis associated with inflammatory pathways, the leukotrienes have been implicated in the pathogenesis of these conditions and have become targets for therapeutic modulation. Leukotriene synthesis inhibitors have been used successfully in the treatment of patients with asthma where they have demonstrated the ability to induce bronchial dilatation, provide protection against broncho-provocation tests and significantly diminish symptoms. When it was serendipitously noted that patients who had concomitant nasal pathology also showed improvement, leukotriene synthesis inhibitors were used as adjuvant therapy in the management of patients with rhinitis, sinusitis and nasal polyposis. Preliminary studies have demonstrated improvements in nasal airflow and reduced recurrence of nasal polyps as noted by endoscopy and imaging studies. Leukotriene synthesis inhibitors therefore appear to be a novel treatment modality for patients with rhinitis, sinusitis and nasal polyps when used as adjunctive therapy.