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Objectives:We studied the incidence and bacterial epidemiology of acute epiglottitis presenting in the first 16 years following the introduction of general childhood vaccination against Haemophilus influenzae type b. Our main objectives were to analyse (1) the incidence of Streptococcus pneumoniae epiglottitis in adults and (2) the distribution of pneumococcal serotypes involved.Materials and methods:The medical records of patients with acute epiglottitis (International Classification of Disease code J05.1) were investigated. Streptococcus pneumoniae serotyping was performed using gel precipitation.Results:The overall incidence of acute epiglottitis was 0.98 cases/100 000/year, compared with 4.5 cases/100 000/year before the vaccination programme. The incidence was reduced both in children and adults, compared with pre-vaccination values. However, the incidence of Streptococcus pneumoniae epiglottitis in adults increased from 0.1 to 0.28 cases/100 000/year over the same time period. The causative agent was Streptococcus pneumoniae in 10 adults. Nine of 10 pneumococcal strains could be serotyped. All but one serotype is represented in the 23-valent pneumococcal polysaccharide vaccine (PPV23) used in adults.Conclusion:In acute epiglottitis, now a disease of adults, the most important bacterial aetiology is Streptococcus pneumoniae. The serotype distribution found in this study indicates that the infection is preventable by PPV-23 vaccination with the 23-valent polysaccharide vaccine. [ABSTRACT FROM PUBLISHER]

Summary: Background. Patients show varied results to allergen immunotherapy (AIT. The reason for this variability is unclear. Objective. To describe the relationship between AIT efficacy and demographic characteristics, as well as pre-treatment plasma levels of specific IgE-antibodies to grass and birch pollen. Methods. A retrospective study was performed based on medical records of 128 patients who received AIT. The patients completed a questionnaire and pre-AIT plasma levels of allergen-specific IgE to grass and birch pollen were measured using EUROLINE DPA-Dx pollen 1 method. Results. Seventy percent of patients classified their allergic symptoms as less severe after AIT. Twenty-seven percent had received AIT targeting only grass pollen, 19% targeting only birch pollen, and 55% targeting both grass and birch. A total of 35 different IgE profiles were found across our study population. On comparison of the demographic characteristics and concentration of allergen-specific IgE-antibodies, no statistically significant differences could be found. Conclusions. The majority of patients rated their allergic symptoms as less severe after AIT. No clear relationship could be demonstrated between pre-treatment allergen-specific IgE concentration, or demographic characteristics, and effect of AIT. There may be other factors underlying the different responses to AIT.

Objective: This study comprised a long-term follow-up of a cohort of patients with chronic rhinosinusitis (CRS) regarding clinical features and symptomatology., Methods: Data from 42 patients with CRS were available from a previous study. Forty of these patients were alive and were contacted for inclusion after approximately 10 years. Patients completed a questionnaire about disease and symptoms, and underwent a clinical examination., Results: Thirty-four patients (85%) responded and could be included and evaluated. For the participants in this follow-up study median length of time between initial inclusion (C1) and follow-up (C2) was 11 years (range: 8-15). In some patients the CRS shifted phenotype over time, from CRS with nasal polyposis to CRS without nasal polyposis or vice versa. The median total visual analogue score for combined sinonasal symptoms for all patients was statistically significantly reduced at follow-up. For individual patients, scores for nasal congestion, nasal discharge, facial pressure, and hyposmia were also statistically significantly reduced. The most frequently reported symptom-relieving treatments were nasal steroids and saline rinsing of the nose. Self-reported general quality of life was statistically significantly improved at C2 compared to C1., Conclusion: At long-term follow-up, symptoms were generally reduced and patients reported an improved quality of life. Patients can be given hope for eventual symptom relief. CRS is a chronic condition that seems to harbor the ability to alter its phenotype after several years. Topical corticosteroids and saline rinsing of the nose should be emphasized, since patients consider these treatments to be of high value.

We investigated Staphylococcus aureus diversity, genetic factors, and humoral immune responses against antigens via genome analysis of S. aureus isolates from chronic rhinosinusitis (CRS) patients in a long-term follow-up. Of the 42 patients who provided S. aureus isolates and serum for a previous study, 34 could be included for follow-up after a decade. Clinical examinations were performed and bacterial samples were collected from the maxillary sinus and nares. S. aureus isolates were characterized by whole-genome sequencing, and specific anti-staphylococcal IgG in serum was determined using protein arrays . S. aureus was detected in the nares and/or maxillary sinus at both initial inclusion and follow-up in 15 of the 34 respondents (44%). Three of these (20%) had S. aureus isolates from the same genetic lineage as at inclusion. A low number of single-nucleotide polymorphisms (SNPs) were identified when comparing isolates from nares and maxillary sinus collected at the same time point. The overall change of antibody responses to staphylococcal antigens over time showed great variability, and no correlation was found between the presence of genes encoding antigens and the corresponding anti-staphylococcal IgG in serum; thus our findings did not support a role, in CRS, of the specific S. aureus antigens investigated.

Angioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 × 10 -5 ). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 × 10 -8 ). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05-2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi- and ARB-induced angioedema.

Background: Chronic rhinosinusitis (CRS) is an inflammatory disease of the nose and the paranasal sinuses, often associated with an infection by Staphylococcus aureus (S. aureus) . Disturbance in the function of ion channels is regarded as an etiological factor for pathogenesis of CRS. Aims: The study aims to measure the mRNA expression of the ENaC and CFTR ion channels in nasal epithelial cells (NECs) and to investigate the effect of both the budesonide and S. aureus on these ion channels. Materials and method: NECs biopsies obtained from healthy volunteers and patients with CRS. NECs were infected with S. aureus strains and/or budesonide to study the mRNA expression levels of the ENaC and CFTR ion channels. Results: The mRNA expression level of CFTR was increased while that of ENaC was decreased . S. aureus infection and budesonide treatment induced a significant modulation of ENaC and CFTR ion channels expression. Conclusion: The CFTR and ENaC ion channel physiology are of importance in the pathogenesis of CRS. Exposure to S. aureus infection and treatment with budesonide modulated the mRNA expression of CFTR and ENaC ion channels. Significance: Better understanding of the pathophysiology of CRS.

Background: Angioedema is a rare and serious adverse drug reaction (ADR) to angiotensin-converting enzyme (ACE) inhibitor treatment. Dry cough is a common side effect of ACE inhibitors and has been identified as a possible risk factor for angioedema., Objective: We compared characteristics between patients with ACE inhibitor-induced angioedema and cough with the aim of identifying risk factors that differ between these adverse events., Methods: Data on patients with angioedema or cough induced by ACE inhibitors were collected from the Swedish database of spontaneously reported ADRs or from collaborating clinicians. Wilcoxon rank sum test, Fisher's exact test, and odds ratios (ORs) with 95% CIs were used to test for between-group differences. The significance threshold was set to P <0.00128 to correct for multiple comparisons., Results: Clinical characteristics were compared between 168 patients with angioedema and 121 with cough only. Smoking and concomitant selective calcium channel blocker treatment were more frequent among patients with angioedema than cough: OR = 4.3, 95% CI = 2.1-8.9, P = 2.2 × 10 -5 , and OR = 3.7, 95% CI = 2.0-7.0, P = 1.7 × 10 -5 . Angioedema cases were seen more often in male patients (OR = 2.2, 95% CI = 1.4-3.6, P = 1.3 × 10 -4 ) and had longer time to onset and higher doses than those with cough ( P = 3.2 × 10 -10 and P = 2.6 × 10 -4 ). A multiple model containing the variables smoking, concurrent calcium channel blocker treatment, male sex, and time to onset accounted for 26% of the variance between the groups., Conclusion: Smoking, comedication with selective calcium channel blockers, male sex, and longer treatment time were associated with ACE inhibitor-induced angioedema rather than cough.

The bacterial spectrum in chronic rhinosinusitis (CRS) is clinically relevant. This study aimed to compare two sampling techniques and to characterise Staphylococcus aureus isolated from CRS patients. Bacterial specimens were collected from the nares and maxillary sinus in 42 CRS patients and from the nares in 57 healthy controls. Maxillary sinus sampling was performed in two ways in each patient: with a cotton-tipped aluminium swab through the enlarged sinus ostium, and with a protected brush. S. aureus was characterised by DNA-sequencing of the repeat region of the S. aureus protein A gene, spa typing. The protected brush technique was superior to the cotton-tipped aluminium swab in reducing contamination rate. However, the two sampling methods were consistent in terms of clinically relevant bacterial findings, and the easy-to-handle cotton-tipped swab can still be recommended when culturing the maxillary sinus. Patients showed a significantly higher presence of S. aureus in the nares compared with healthy controls, and healthy controls showed a significantly higher presence of coagulase-negative staphylococci in the nares compared with patients. The spa types were identical for the nares and maxillary sinus in all patients except one. The sampling techniques showed equivalent results, indicating a low risk of unnecessary antibiotic treatment when using the easy-to-handle cotton-tipped aluminium swab. The high rate of identical spa types of S. aureus isolated from the nares and maxillary sinus of CRS patients might indicate colonisation of the maxillary sinus from the nares., Competing Interests: Compliance with ethical standardsConflict of interestBo Söderquist has been a consultant for Pfizer and Janssen-Cilag.Ethical approvalAll procedures performed in this study were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration. The study was approved by the regional ethical review board in Uppsala, Sweden.

The anterior nares have been regarded as the major carriage site of Staphylococcus aureus. From here, the organism can spread to other parts of the body where it might act as harmless commensal or cause mild to severe infections. Nasal sinuses are normally sterile, but in patients with chronic rhinosinusitis (CRS), the finding of S. aureus in maxillary sinus cultures is common. Isolates were obtained from the nares and maxillary sinus of patients with CRS and the nares of healthy controls. A significantly higher frequency of S. aureus was found in nares samples from patients (24/42) compared to controls (16/57) (p = 0.004). There is no consensus regarding whether S. aureus is a relevant pathogen in CRS. A DNA microarray was used to investigate the prevalence of S. aureus virulence genes with focus on staphylococcal enterotoxins, toxic shock syndrome toxin-1, agr types, and cell wall-associated proteins. The genotyping of S. aureus isolates revealed only small and non-significant differences in gene prevalence between isolates collected from patients with CRS and those collected from healthy nasal carriers. This study provides an increased knowledge of the genetic pattern of virulence genes among S. aureus collected in CRS., (© 2014 APMIS. Published by John Wiley & Sons Ltd.)

Conclusion: Using a local anesthetic agent before obtaining nasal biopsies by nasal brushing makes the sampling procedure smooth, avoids lacrimation, nasal itching/irritation, and/or sneezing and provides enough viable cells to establish primary cultures., Objectives: To examine the use of local anesthesia to avoid the irritation experienced by the subject when nasal biopsies are obtained by nasal brushing in order to culture viable nasal epithelial cells., Methods: Nasal epithelial cells were collected from the mid-part of the inferior turbinate of healthy volunteers by brushing with interdental brushes, after spraying a topical anesthetic on the nasal mucosa. Immunocytochemistry was performed to assess the purity of epithelial cells., Results: Cell samples ranging from 1.16 × 10(5) to 3.06 × 10(5) cells/per sample were obtained. Of 11 samples, 7 formed confluent cultures, while the remaining 4 samples showed only patches of epithelial cells. Neither fungal nor bacterial contamination posed a problem. Immunocytochemistry of the cytospin slides confirmed the presence of epithelial cells in the cultures. No adverse effects were experienced by the volunteers.

The microbiological cause of peritonsillar abscess and the role of group A β-haemolytic Streptococcus (GAS) are unclear. We performed a retrospective study at the ear, nose and throat clinic (ENT) of Orebro University Hospital, Sweden, and included 376 events of peritonsillitis between 2002 and 2004. We determined if the patients had visited a primary healthcare centre (PHCC) within 30 days prior to inclusion. The results of the rapid antigen detection test for GAS (Strep A) taken at the PHCC were compared with the occurrence of peritonsillar abscess (PTA) and peritonsillar cellulitis (PTC). A Strep A test was performed in 61% (229/376) of the events studied. Strep A was positive in 22% of PTA events and in 35% of PTC events (p = 0.036). Of 48,000 Strep A tests taken in primary healthcare, mainly for sore throat, 22% were positive. We examined the relationship between age, the incidence of PTA, and positive Strep A tests. We also determined if there was a monthly correlation between number of positive Strep A tests and number of PTA events. We found no significant correlations. In conclusion, our findings indicate that GAS does not play a major role in the development of PTA/PTC.

The incidence of peritonsillitis is not very well known. A retrospective study was performed at the Ear, Nose and Throat clinic (ENT) at the University Hospital of Orebro Sweden. We studied every case from 2002 to 2004 and related it to a well-defined catchment area of 179,200 inhabitants. We identified 283 events of peritonsillitis, of which 85 were defined as peritonsillar cellulitis (PTC). Peritonsillar abscess (PTA) was found in 198 events in patients between 7 and 82 y of age. 13 patients had 2 episodes of PTA during the study period. The overall incidence was 37/100,000/y. The highest incidence was found between 14 and 21 y of age, with 124/100,000/y. The male: female ratio was 1: 1. Affected females were younger than males (p=0.04), and the peak incidence was earlier for females. This may be due to differences in immunological response, owing to hormonal maturation. The annual incidence of PTA was higher in this study than found in previous studies, which is probably attributable to the fact that our study identified almost all cases in the population.

Unlabelled: The sequelae and behaviour in children several years after an episode of bacterial meningitis were studied. All children in Sweden aged 0-4 years with bacterial meningitis between 1987 and 1989 caused by Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis were identified. After exclusion of 16 children who died, 12 with severe concomitant diseases, ten with severe neurological damage obvious already at discharge from hospital and 34 with unknown address, questionnaires were sent to the parents of the remaining 463 children The nearest-age siblings were used as a comparison group. The questionnaires included questions concerning general health, schooling, motor function, speech, hearing and behaviour (inattention, hyperactivity and impulsiveness). The children were 6-14 years old when the questionnaires were completed. Questionnaires were completed for 304 pairs of patients and siblings and for 154 patients without siblings. The majority of post-meningitic children were healthy and attended normal school but they had more hearing impairment, headaches and problems with balance than their siblings. When the distributions of answers regarding behaviour were compared, the post-meningitic children had significantly more symptoms in the fields of inattention, hyperactivity and impulsiveness than their siblings., Conclusion: Except for hearing impairment, severe sequelae after bacterial meningitis which are not discovered at discharge do not appear later. Children who appear well after bacterial meningitis have more non-specific symptoms like headache, and more signs and symptoms indicating inattention, hyperactivity and impulsiveness than their siblings.

Background: Acute epiglottitis is an important manifestation of invasive Haemophilus influenzae type b (Hib) infection. In 1992 and 1993 Hib vaccination was introduced in the general childhood vaccination program in Sweden. The aim of the present investigation was to study the impact of Hib vaccination on the diagnosis of epiglottitis in Sweden in children as well as adults., Methods: A retrospective national population-based study on the incidence of epiglottitis in Sweden was performed for the 10-year period 1987 to 1996. The incidence calculations were based on figures from the national register of all patients treated at Swedish hospitals. The incidence (cases/100,000/year) for the prevaccination period 1987 to 1991 was compared with the incidence after Hib vaccination was introduced., Results: In children a substantial decrease was found after introduction of large scale vaccination against Hib. Below 5 years of age the annual incidence decreased from 20.9 in 1987 to 0.9 in 1996. In adults a tendency toward a decrease in incidence was evident., Conclusions: Introduction of Hib vaccination in a general childhood program was followed not only by a >90% reduction in the incidence in the youngest age group but also by a reduction in the incidence in the older age groups and among adults.

In order to determine the aetiology of acute epiglottitis in adults, blood cultures, paired sera and a urine sample were obtained from 54 patients with fever and epiglottitis visualized by indirect laryngoscopy or by direct fibreoptic nasolaryngoscopy. Antibodies were determined against the capsular polysaccharide of Haemophilus influenzae type b (Hib), 3 pneumococcal antigens (a mixture of 23 capsular polysaccharides, C-polysaccharide and pneumolysin) and antistreptolysin O. Acute sera were examined by the polymerase chain reaction (PCR) for DNA of Hib and pneumococci. The urine samples were examined for Hib capsular antigen. Blood cultures were positive in 15 patients. In another 16, serology and/or PCR verified the aetiology. Hib was the cause in 14, pneumococci in 12 and group A streptococci in 5 patients. The aetiology remained unknown in 23/54 patients (43%). In conclusion, the addition of serology and PCR to blood cultures doubled the possibilities of verifying the aetiology of acute epiglottitis in adults.

The number of patients with meningitis and bacteremia due to Haemophilus influenzae was studied in Sweden over the period 1987-1994. Conjugated H. influenzae type b vaccines were introduced in Sweden in 1992, and all children born after December 31, 1992, were offered vaccination free of charge. A rapid decline of H. influenzae meningitis and bacteraemia was observed in the autumn of 1993, when the expected peak incidence failed to appear. In the prevaccination period 1987-1991, the average annual incidence (cases/100,000) was 34.4 in children aged 0-4 years. In 1994, the annual incidence fell to 3.5. No significant decline was observed in older children or adults. There was a 92% reduction in the number of meningitis cases and an 83% reduction in cases of bacteraemia. A similar decline was noted in 2 regions which followed different strategies for the introduction of the vaccination programme.

The incidence, concomitant conditions and case fatality rate of Haemophilus influenzae (Hi) and pneumococcal meningitis and of invasive meningococcal infections were studied retrospectively in Sweden (population 8.4 million) for the years 1987-89, the period before vaccination against Hi type b started. A total of 1,019 cases with culture-verified infection were found. The incidence rates per 100,000 per year were 1.8 for Hi meningitis, 1.2 for pneumococcal meningitis and 1.0 for invasive meningococcal infections. The age-specific incidence was highest in the 3-23 months age group for the 3 bacterial species. Pneumococcal meningitis was common in individuals > or = 60 years and meningococcal infections in the age-group 10-24 years. A serious concomitant condition was known in 57% of all patients with pneumococcal meningitis while this was uncommon for the other organisms. The case fatality rate was 2% for Hi meningitis, 24% for pneumococcal meningitis and 10% for meningococcal infections. All 81 pneumococcal isolates which had been serotyped belonged to serotypes in the 23-valent pneumococcal vaccine. Of the meningococcal isolates, 65% belonged to serogroup B. In conclusion, the high incidence of Hib meningitis justifies general Hib vaccination. Development of a vaccine against N. meningitidis group B should have high priority. Furthermore, improved pneumococcal vaccines are needed for patients with predisposing conditions. The currently available pneumococcal polysaccharide vaccine seems to be underused.

A retrospective study of the incidence, aetiology and case fatality rate of acute epiglottitis in children and adults was performed. The study covered the whole of Sweden (population 8.4 million) during the years 1987-89, before general vaccination against Haemophilus influenzae (Hi) type b was started. Patients were included if it was documented that they fulfilled all 3 of the following criteria: (a) red and swollen epiglottis visualized by indirect laryngoscopy, (b) inspiratory stridor or difficulties in swallowing, and (c) a temperature > or = 38 degrees C. A total of 306 children and adolescents (0-19 years) and 502 adults (> or = 20 years) were found. The age-specific incidence was highest in children aged 0-4 years, (14.7/100,000 per year). The total incidence was 3.2/100,000 per year. In the age group 0-19 years, blood cultures had been obtained from 195 (64%) and Hi was isolated from 154 (79%). In adults (> or = 20 years), 114 of 298 blood cultures yielded Hi, while pneumococci were isolated from 5 and group A streptococci from 3 patients. A total of 220 children (72%) and 114 adults (23%) needed an artificial airway. Five children and 12 adults died. In conclusion, the incidence of acute epiglottis in Sweden is very high. Compared to a previous country-wide study covering the years 1981-83 that used the same methods for case finding and case definition, the incidence in children had decreased while the incidence in adults had increased.

In a prospective study between January 1987 and December 1992, 103 patients with invasive Haemophilus influenzae (Hi) infection were identified in a well-defined population before large-scale Haemophilus influenzae type b (Hib) vaccination was introduced. The incidence (case/100,000/year) of invasive Hi infection was 5.9 for the whole population, 55 for children 0-4 years old and as high as 2.8 for adults. Hib was the predominant cause of the infection (83 cases) in children but, in adults, 13/39 (30%) cases were caused by non-typable Hi and 6/39 (19%) by Hi serotype f. Three patients (3%) died and 6 (5.8%) suffered a permanent sequel from the infection. All patients with such a sequel had invasive Hib infection. No significant difference between patients 0-6 years old and matched controls regarding the frequency of subnormal serum levels of immunoglobulins was found.

Over a period of 18 years 219 consecutive cases of acute epiglottitis were diagnosed and subsequently investigated in order to elucidate the aetiology, epidemiology and outcome of this disease in a well-defined population in Sweden before general vaccination against Haemophilus influenzae type b infection was introduced. Compared with the results from other parts of the industrialized world, high incidence rates were found in both children (14/100,000/year) and adults (2.3/100,000/year). The annual trend showed a significant decline in incidence among children, whereas in adults it remained unchanged. In cases where the aetiological agent could be determined, infection with H. influenzae type b was the main cause of disease in all age groups. However, in adults 27% (6/22) had a disease caused by micro-organisms other than H. influenzae type b that were verified with a blood culture. Sixty-eight per cent had a negative blood culture. The mortality rate was 0.5% (1/219) and 6% (13/219) developed a significant complication of the disease.