Abstract A major purpose of treating patients with cystic fibrosis (CF) is to prevent or delay chronic lung infections with CF-pathogenic Gram-negative bacteria. In the intermittent stage, bacteria ...can usually be eradicated from the lungs with antibiotics, but following eradication, the next lung colonisations often occur with bacteria of identical genotype. This may be due to re-colonisation from the patient's paranasal sinuses. In our study, we found that approximately two-thirds of CF patients having sinus surgery (FESS) had growth of CF-lung-pathogenic Gram-negative bacteria in their sinuses ( Pseudomonas aeruginosa , Achromobacter xylosoxidans , Burkholderia cepacia complex). The environment in the sinuses is in many ways similar to that of the lower respiratory tract, e.g. low oxygen concentration in secretions. Sinus bacteria are more difficult to eradicate than in the lungs, thus, having good conditions for adapting to the environment in the lungs. In the presence of bacteria, the environment of the sinuses differs from that of the lower respiratory tract by having a higher immunoglobulin A (IgA): IgG ratio, and reduced inflammation. We found a significant correlation between the concentration of IgA against P. aeruginosa (standard antigen and alginate) in nasal secretions and saliva and CF patients' infection status (not lung colonised, intermittently colonised or chronically lung-infected with P. aeruginosa ). This supports the hypothesis that infections often originate in the sinuses and can be a focus for initial lung colonisation or for maintaining lung infections in CF patients. We are confident that anti- P. aeruginosa IgA can be used as an early supplementary tool to diagnose P. aeruginosa colonisation; P. aeruginosa being the microorganism causing most morbidity and mortality in CF patients. This is important since urgent treatment reduces morbidity when CF patients are early colonised with P. aeruginosa , however, there is a lack of diagnostic tools for detecting the early colonisation in the lungs and in the sinuses. We initiated a treatment strategy for CF patients to prevent sino-nasal bacteria being seeded into the lower airways: we recommended extensive functional endoscopic FESS with creation of sufficient drainage from all involved sinuses with subsequent i.v. antibiotics and at least 6 months of twice daily nasal irrigation with saline and antibiotics. By this strategy, sinus bacteria could be eradicated in a large proportion of patients. Essentially, growth of CF-pathogenic bacteria from the lower respiratory tract was decreased following the treatment. Furthermore, a number of patients have been free from CF-pathogenic bacteria for more than one year after FESS, and thus re-classified as “not lung colonised”. We also corroborated that CF patients obtain an improved quality of life and reduction in their symptoms of chronic rhinosinusitis after FESS. It is primarily intermittently lung colonised CF patients with CF-pathogenic bacteria in their sinuses that seem to benefit from the treatment strategy. This is in accordance with the fact that we did not see a significant increase in lung function and only a small decrease in specific antibodies after FESS; a high systemic immune and inflammatory response and a decreasing lung function is generally not present in patients who primarily have sinus CF-pathogenic bacteria. It is important that guidelines are created for how CF patients with CF-pathogenic bacteria in the sinuses are to be treated, including criteria for who may likely benefit from FESS, and who may be treated exclusively with conservative therapy, e.g. saline and antibiotic irrigations.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The vast majority of people with cystic fibrosis (pwCF) have untreated secondary chronic rhinosinusitis (CRS). Whereas the introduction of the cystic fibrosis transmembrane conductance regulator ...modulator (CFTRm) treatment regime has improved the lung function of pwCF, few studies have been published examining the effect on sinonasal symptoms in children. Our aim was to explore the effect of double CFTRm treatment on CRS and olfaction in children with CF. pwCF were included in this non-randomized cross-sectional study, where an otolaryngologist performed a complete ENT examination before initiating treatment with elaxacaftor/tezacaftor/ivacaftor (ETI). Twenty-three pwCF aged 6-12 years were included. Eighteen of 23 patients were on a double CFTRm treatment, and 5 patients were CFTRm naive, respectively. Altogether, 19 had normal olfaction, 20 had none or mild CRS symptoms according to SNOT-22, and 14 had a normal endoscopy. None of the patients had symptoms of chronic rhinosinusitis lasting for more than 12 weeks, thus none of the patients fulfilled the criteria for CRS. Children with CF treated with double CFTRm have few to no symptoms of CRS and normal olfaction, which is an improvement compared with children following treatment modalities prior to CFTRm.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
3.
Diagnosis of biofilm infections in cystic fibrosis patients Høiby, Niels; Bjarnsholt, Thomas; Moser, Claus ...
APMIS : acta pathologica, microbiologica et immunologica Scandinavica,
April 2017, 2017-Apr, 2017-04-00, 20170401, Volume:
125, Issue:
4
Journal Article
Peer reviewed
Open access
Chronic Pseudomonas aeruginosa biofilm lung infection in cystic fibrosis patients is the best described biofilm infection in medicine. The initial focus can be the paranasal sinuses and then follows ...repeated colonization and infection of the lungs by aspiration. The matrix of the biofilms is dominated by alginate and the pathogenesis of tissue damage is immune complex‐mediated chronic inflammation dominated by polymorphonuclear leukocytes and their products (DNA, oxygen radicals and proteases). The P. aeruginosa biofilm infection can be diagnosed by microscopy of lung tissue, sputum and mucus from the paranasal sinuses, where aggregates of the bacteria are found surrounded by the abundant alginate matrix. Specific PNA‐FISH probes can be used to identify P. aeruginosa and other pathogens in situ in the biofilms. Growth of mucoid colonies from the locations mentioned above is also diagnostic for biofilm infection. Rise of specific anti‐P. aeruginosa antibodies is likewise diagnostic, IgG in serum in case of lung infection, sIgA in saliva or nasal secretions in case of paranasal sinus infection. Similar approaches have been developed to diagnose chronic biofilm infections in cystic fibrosis caused by other pathogens e.g., Stenotrophomonas, Burkholderia multivorans, Achromobacter xylosoxidans and Mycobacterium abscessus complex.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The opportunistic pathogen Pseudomonas aeruginosa is a frequent colonizer of the airways of patients suffering from cystic fibrosis (CF). Depending on early treatment regimens, the colonization will, ...with high probability, develop into chronic infections sooner or later, and it is important to establish under which conditions the switch to chronic infection takes place. In association with a recently established sinus surgery treatment program for CF patients at the Copenhagen CF Center, colonization of the paranasal sinuses with P. aeruginosa has been investigated, paralleled by sampling of sputum from the same patients. On the basis of genotyping and phenotypic characterization including transcription profiling, the diversity of the P. aeruginosa populations in the sinuses and the lower airways was investigated and compared. The observations made from several children show that the paranasal sinuses constitute an important niche for the colonizing bacteria in many patients. The paranasal sinuses often harbor distinct bacterial subpopulations, and in the early colonization phases there seems to be a migration from the sinuses to the lower airways, suggesting that independent adaptation and evolution take place in the sinuses. Importantly, before the onset of chronic lung infection, lineages with mutations conferring a large fitness benefit in CF airways such as mucA and lasR as well as small colony variants and antibiotic-resistant clones are part of the sinus populations. Thus, the paranasal sinuses potentially constitute a protected niche of adapted clones of P. aeruginosa, which can intermittently seed the lungs and pave the way for subsequent chronic lung infections.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, SBNM, UL, UM, UPUK
Unified airway disease where upper respiratory tract inflammation including chronic rhinosinusitis (CRS) affects lower airway disease is known from asthma, bronchiectasis, cystic fibrosis and primary ...ciliary dyskinesia but little is known about CRS and health related quality of life in COPD. We investigate firstly, the prevalence of CRS in COPD. Secondly the impact of CRS on HRQoL. Thirdly, risk factors for CRS in COPD.
cross-sectional study of CRS in 222 COPD patients from 2017 to 2019 according to EPOS2012/2020 and GOLD2019 criteria. Patients completed the COPD assessment test (CAT), Medical Research Council dyspnea scale and Sinonasal outcome test 22 (SNOT22) and questions on CRS symptoms. They then had a physical examination including flexible nasal endoscopy, CT-sinus scan and HRCT-thorax.
22.5% of COPD patients had CRS and 82% of these were undiagnosed prior to the study. HRQoL (CAT, SNOT22 and the SNOT22-nasal symptom subscore) was significantly worse in COPD patients with CRS compared with those without CRS and healthy controls. Multiple logistic regression analysis suggests that the most likely candidate for having CRS was a male COPD patient who actively smoked, took inhaled steroids, had a high CAT and SNOT22_nasal symptom subscore.
the largest clinical study of CRS in COPD and the only study diagnosing CRS according to EPOS and GOLD. This study supports unified airway disease in COPD. The SNOT22_nasal symptoms subscore is recommended as a standard questionnaire for COPD patients and patients at risk should be referred to an otorhinolaryngologist.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
When first-line chronic rhinosinusitis (CRS) treatment fails, patients can either be treated with oral or injected systemic corticosteroids. Although the EPOS and international guidelines for CRS do ...not mention injected corticosteroids, it is commonly used by ear, nose, and throat specialists. While the risks of systemic corticosteroids, in general, are known, the pros and cons of injected and oral corticosteroids (OCS) in CRS treatment are unclear.
A systematic review of studies that report the effects and/or side effects of injected and oral corticosteroids in the treatment of CRS was made according to the PRISMA guidelines.
Altogether, 48 studies were included, only five studies reported on injected corticosteroids, and five attended with side effects. Three studies found beneficial effects of OCS perioperatively on sinus surgery, while four articles found no effect. Nineteen articles reported that OCS resulted in an improvement in symptoms. Two articles presented a longer-lasting effect of injected corticosteroids than OCS. Three studies reported adverse side effects of systemic corticosteroids, while two studies showed no adverse side effects. One study showed less adrenal suppression after injected corticosteroids compared to OCS. The evidence is not strong but shows a positive effect of systemic corticosteroids that lasts longer with injections.
Although systemic corticosteroids are widely used to treat CRS, there is a lack of studies comparing the OCS and injected corticosteroids. The evidence is sparse, however, injected steroids show longer effects with fewer side effects. An RCT study is needed to compare OCS and injected corticosteroids.
Importance
Otorhinolaryngology is considered one of the medical specialties with a high risk for exposure to corona disease 2019 (COVID-19). Uncontrolled transmission in a hospital department poses a ...risk to both healthcare workers (HCWs) and patients.
Objective
To monitor SARS-CoV-2 incidence, transmission, and antibody development among HCWs to identify high risk procedures, pathways, and work areas within the department.
Methods
Prospective cohort study of HCWs using repetitive oro- and nasopharygeal swab samples, antibody tests, and self-reported symptoms questionnaires at a tertiary referral center in Copenhagen, Denmark.
Results
347/361 (96%) HCWs participated. Seven (1.9%) were positive on swab tests and none had symptoms. Fifteen (4.2%) developed antibodies. Only one case of potential transmission between HCWs was identified. Infection rates were low and no procedures or areas within the department were identified as exposing HCWs to a higher risk.
Conclusions and relevance
Adherence to the surveillance program was high. The low incidence among HCW during the first wave of the COVID-19 pandemic may reflect local transmission and infection control precautions, as well as a low infectious burden in the Danish society.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Cystic fibrosis (CF) chronic rhinosinusitis (CRS) has emerged as a distinct diagnostic entity, unique from other endotypes of CRS in its presentation, pathophysiology, diagnosis, ...treatment, and outcomes. As the sinonasal health of this patient population may have broad effects on pulmonary health and quality of life, a comprehensive understanding of the diagnostic and therapeutic approach to CF CRS is essential. In recognizing recent scientific advances and unique treatment modalities specific to this challenging patient population, in this review we systematically evaluate the scientific literature and provide an evidenced‐based review with recommendations (EBRR) for fundamental management principles of CF CRS.
Methods
A systematic review of the literature was performed. Studies evaluating interventions for the management of CF CRS were included. An iterative review process was implemented in accordance with EBRR guidelines. A treatment recommendation was generated based on an assessment of the benefits, harms, and the overall grade of evidence.
Results
We evaluated the published literature on 5 unique topics. Each of the following therapeutic categories was investigated explicitly for treatment outcomes in patients with CF CRS: (1) nasal saline; (2) intranasal corticosteroids (INCS); (3) topical antibiotics; (4) cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy; and (5) endoscopic sinus surgery (ESS).
Conclusion
Based on the currently available evidence, nasal saline, ESS, and CFTR modulators are recommended in the management of CF CRS when appropriate. INCS and topical antibiotics are options. Clinical judgment and experience are essential in caring for patients with this uniquely challenging disorder.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
The upper airways (UAW) are a niche and a reservoir of Pseudomonas aeruginosa strains that cause chronic infection of the lower airways (LAW) in cystic fibrosis (CF). Here, we assessed the ...role of anti‐P. aeruginosa immunoglobulin A (IgA) and IgG antibodies in upper and lower airway infections in cystic fibrosis patients.
Methods
Nasal lavage fluid and induced sputum samples of 40 CF patients were microbiologically cultured. We searched for correlations between anti‐P. aeruginosa IgA and IgG levels, measured by enzyme‐linked immunosorbent assay (optical density), and unspecific immune mediators in both specimens.
Results
Anti‐P. aeruginosa IgA (median optical density: 0.953 vs 0.298) and IgG (0.120 vs 0.059) were significantly higher in nasal lavage than in sputum, but not significantly different between patients with and without chronic P. aeruginosa infection in UAW. Matrix metallopeptidase‐9 (MMP‐9) in nasal lavage and neutrophil elastase (NE) in sputum were predictors of IgA in nasal lavage and IgA in sputum, respectively. IgA was a predictor of myeloperoxidase (MPO) in nasal lavage. Tissue inhibitor of metalloproteinases‐1 (TIMP‐1) was a predictor of IgG in sputum. IgG, TIMP‐1, and NE in sputum were predictors of IgG in nasal lavage.
Conclusion
The anti‐P. aeruginosa IgA response was more prominent in CF patients' UAW, indicating a lower degree of inflammatory responses. Proteases may play a role in the anti‐P. aeruginosa humoral response in the upper and LAW, and anti‐P. aeruginosa IgG may be involved in the crosstalk between upper and lower airways in cystic fibrosis patients.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
PDF
