Long-Term Sinonasal Carriage of Staphylococcus aureus and Anti-Staphylococcal Humoral Immune Response in Patients with Chronic Rhinosinusitis.

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.

Long-Term Clinical Follow-Up of Patients With Chronic Rhinosinusitis.

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.

Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment.

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.

Staphylococcus aureus in chronic rhinosinusitis: the effect on the epithelial chloride channel (cystic fibrosis transmembrane conductance regulator, CFTR) and the epithelial sodium channel (ENaC) physiology.

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.

Bacterial findings in optimised sampling and characterisation of S. aureus in chronic rhinosinusitis.

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.

Comparison of Clinical Factors Between Patients With Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema and Cough.

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.

Molecular characteristics of Staphylococcus aureus associated with chronic rhinosinusitis.

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.

Isolation and culture of primary human nasal epithelial cells from anesthetized nasal epithelia.

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.

Peritonsillar abscess and cellulitis and their relation to a positive antigen detection test for streptococcal infection.

The microbiological cause of peritonsillar abscess and the role of group A ß-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.

Incidence of peritonsillar abscess and relationship to age and gender: retrospective study.

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.

Long-term follow-up of children with bacterial meningitis with emphasis on behavioural characteristics.

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.