| 51. |
- Burgel, PR, et al.
(författare)
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Intranasal steroids decrease eosinophils but not mucin expression in nasal polyps
- 2004
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 24:4, s. 594-600
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Tidskriftsartikel (refereegranskat)abstract
- Increased mucin expression is a feature of nasal polyposis. Corticosteroids reduce polyp size and symptoms, but their effect on mucin production remains unknown. In this study, the effects of intranasal corticosteroids on MUC5AC mucin expression, nasal resistance, eosinophil and neutrophil infiltration, epidermal growth factor receptor (EGFR), interleukin (IL)-8, and tumour necrosis factor (TNF)-alpha expression was assessed in nasal polyps. In nine subjects, one nasal polyp was removed surgically before treatment and another was removed after 8 weeks of intranasal fluticasone (400 mug.day(-1)). Tissues were processed for in situ hybridisation and immunohistochemical staining. Described effects of fluticasone on nasal polyps (reduction in nasal resistance and in eosinophil infiltration) were evaluated. Morphometric analysis was performed to assess the effect of fluticasone on epithelial-, MUC5AC-, EGFR- and IL-8-stained areas, TNF-alpha-stained cells, and neutrophil numbers. Treatment with fluticasone decreased nasal resistance and intra-epithelial eosinophils. The MUC5AC-stained area in the epithelium was unchanged by treatment; MUC5AC mRNA expression was unaffected by treatment. EGFR-stained area, intraepithelial neutrophil numbers, IL-8 and TNF-alpha expression were also unchanged by therapy. Intranasal fluticasone was effective in decreasing nasal airflow resistance and intra-epithelial eosinophils but had no effect on mucin or epidermal growth factor receptor expression or on neutrophil recruitment.
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| 52. |
- Cai, Yan, et al.
(författare)
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Infliximab alleviates inflammation and ex vivo airway hyperreactivity in asthmatic E3 rats
- 2011
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Ingår i: International Immunology. - : Oxford University Press (OUP). - 1460-2377 .- 0953-8178. ; 23:7, s. 443-451
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Tidskriftsartikel (refereegranskat)abstract
- Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of asthma, and neutralization of TNF-alpha is an effective therapy for inflammatory diseases. The present study tested the idea that a TNF-alpha antibody, infliximab, may be useful in the management of asthma. E3 rats were immunized with ovalbumin (OVA)/alum and received infliximab intra-peritoneally. Two weeks later, OVA-PBS was instilled intranasally daily for 7 days. Bronchoalveolar lavage fluids (BALFs), serum and lung homogenates were collected for analysis of cells and inflammatory mediators. Contractile responses of lobar-bronchus segments to agonists were functionally tested. Pulmonary tissues were investigated using histological examination. The results showed that the sensitized 'model E3 rats' exhibited an increase in the total amount of inflammatory cells, primarily eosinophils, in BALF and pulmonary tissue, as well as epithelial damage. Serum levels of IgE increased and so did the levels of nitric oxide, inducible nitric oxide synthase, TNF-alpha and IL-4, IL-5 and IL-13 in lung homogenate and serum. Furthermore, the contractile responses in bronchi induced by endothelin-1, sarafotoxin 6c and bradykinin increased and isoprenaline-induced relaxations decreased. All these changes induced by the sensitization procedure were reduced by the infliximab treatment. The results suggest that infliximab prevents the development of local airway inflammation and antagonizes changes of the bronchial smooth muscle receptor phenotype, thereby blocking the development of airway smooth muscle hyperreactivity of asthmatic rats.
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| 53. |
- Cardell, Lars-Olaf, et al.
(författare)
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Downregulation of peroxisome proliferator-activated receptors (PPARs) in nasal polyposis
- 2005
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Peroxisome proliferator-activated receptor (PPAR) alpha, beta delta and gamma are nuclear receptors activated by fatty acid metabolites. An anti-inflammatory role for these receptors in airway inflammation has been suggested. Methods: Nasal biopsies were obtained from 10 healthy volunteers and 10 patients with symptomatic allergic rhinitis. Nasal polyps were obtained from 22 patients, before and after 4 weeks of local steroid treatment (fluticasone). Real-time RT-PCR was used for mRNA quantification and immunohistochemistry for protein localization and quantification. Results: mRNA expression of PPAR alpha, PPAR beta delta, PPAR gamma was found in all specimens. No differences in the expression of PPARs were obtained in nasal biopsies from patients with allergic rhinitis and healthy volunteers. Nasal polyps exhibited lower levels of PPAR alpha and PPAR gamma than normal nasal mucosa and these levels were, for PPAR gamma, further reduced following steroid treatment. PPAR gamma immunoreactivity was detected in the epithelium, but also found in smooth muscle of blood vessels, glandular acini and inflammatory cells. Quantitative evaluation of the epithelial immunostaining revealed no differences between nasal biopsies from patients with allergic rhinitis and healthy volunteers. In polyps, the PPAR gamma immunoreactivity was lower than in nasal mucosa and further decreased after steroid treatment. Conclusion: The down-regulation of PPAR gamma, in nasal polyposis but not in turbinates during symptomatic seasonal rhinitis, suggests that PPAR gamma might be of importance in long standing inflammations.
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| 54. |
- Cardell, Lars-Olaf, et al.
(författare)
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Interleukin-1beta up-regulates tumor necrosis factor receptors in the mouse airways.
- 2008
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Ingår i: Pulmonary Pharmacology & Therapeutics. - : Elsevier BV. - 1522-9629 .- 1094-5539. ; May 2, s. 675-681
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Tidskriftsartikel (refereegranskat)abstract
- Cytokines like interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha), released during the inflammatory process, play important roles in the development of airway hyperresponsiveness. The effects of these cytokines are mediated by cell surface receptors, specific for each cytokine. The expression of cytokine receptors is a dynamic process, where receptors can be up- or down-regulated in response to changes in the environment. One such environmental factor is the presence of cytokines per se. The present study was designed to evaluate the effects of IL-1beta on the expression of its corresponding receptor IL-1 RI, as well as on the closely related TNFalpha receptors TNF RI and TNF RII in airways using a mouse organ culture assay and intranasal inoculation model. Immunohistochemical staining was used to quantify expressional differences between fresh and cultured tracheal segments. In the fresh, uncultured, segments, IL-1 RI and TNF RI were seen in the epithelial layer and TNF RI in the smooth muscle layer. After 4 days of culture, the expression of TNF RI decreased in the epithelial layer, whereas the corresponding expression of IL-1 RI and TNF RI in the smooth muscle remained unchanged. When culture was performed in the presence of IL-1beta, the expression of IL-1 RI and TNF RI in the epithelial cells and TNF RI in the smooth muscle cells increased. TNF RII was not detected in either fresh or cultured trachea, but after treatment with IL-1beta an expression was found in both the epithelial layer and in the smooth muscle cells. The IL-1beta-induced increased expression, on TNF RI and TNF RII in the smooth muscle ex vivo and in the lung parenchyma after intranasal challenge in vivo, was verified at the mRNA level using real-time RT PCR. To summarize, presence of IL-1beta increases the expression of IL-1 R1 and TNF RI and induces expression of TNF RII in the airway wall. It is not inconceivable that these alterations of the IL-1 and TNF receptors may have important functional implications for the development of hyperresponsiveness in inflammatory airway diseases like asthma.
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| 55. |
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| 56. |
- Cardell, Lars-Olaf, et al.
(författare)
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Modelling the Costs of Sublingual Immunotherapy versus Subcutaneous Immunotherapy Based on Clinical Appointments and Impacts of Patient Travel in Sweden
- 2024
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Ingår i: CLINICOECONOMICS AND OUTCOMES RESEARCH. - 1178-6981. ; 16, s. 493-506
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Tidskriftsartikel (refereegranskat)abstract
- Aim: In Sweden, allergy immunotherapy (AIT) is available as either subcutaneous immunotherapy (SCIT) injections or sublingual immunotherapy (SLIT) tablets and is used to treat moderate -severe allergic rhinitis (AR). This study sought to determine direct and indirect annual costs stemming from treatment -related travel, appointments, waiting times and medication costs, before exploring likely CO 2 emission -related cost -savings for 20,330 patients receiving SCIT or SLIT -tablets in Sweden. Methods: A model was developed in Python to capture each category of costs in the target patient population. Absenteeism costs arising from treatment -related travel were determined by obtaining average hourly pay data from Swedish Government sources. Absenteeism costs were also calculated for 30 -minute post -dose observation times, which occurred during one clinical appointment for SLIT patients, and all clinical appointments for SCIT patients. Clinical appointment costs were obtained from healthcare price lists for Sweden. Medication costs were retrieved from the Pharmaceutical Specialities in Sweden (Fass) website, and treatment doses required for SCIT and SLIT -tablets were determined based on product labels and previously -calculated dosage regimes. High -cost protection and reimbursement scheme payment caps were applied when determining patient appointment and medication costs, respectively, and when identifying financial burdens for individual payers. Results: Mean total annual costs for SCIT were Swedish Krona (SEK) 604.1 million (m), with clinical appointments contributing the largest share of these costs (52.7%), followed by medication (34.4%), travel -related absenteeism (8.9%), waiting time -related absenteeism (2.7%) and private transportation (1.3%). Mean total annual costs for SLIT -tablets were SEK 336.2m. Medication contributed the most to these costs (72.3%), followed by clinical appointments (22.7%), travel -related absenteeism (3.8%), waiting time -related absenteeism (0.6%) and private transportation (0.6%). Conclusion: For patients with moderate -severe AR receiving AIT in Sweden, SLIT -tablets displayed large potential cost savings to patients, the healthcare system, and the government, whilst possessing reduced societal costs of carbon emissions relative to SCIT.
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| 57. |
- Cardell, Lars Olaf, et al.
(författare)
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Modelling the impact of sublingual immunotherapy versus subcutaneous immunotherapy on patient travel time and CO2 emissions in Sweden
- 2024
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Ingår i: Scientific Reports. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- In Sweden, allergy immunotherapy (AIT) is available as either subcutaneous immunotherapy (SCIT) injections or sublingual immunotherapy (SLIT) tablets and is used to treat moderate-severe allergic rhinitis (AR). This study sought to determine treatment-related CO2 emissions and travel times in Swedish patients receiving either SCIT or SLIT-tablets. A list of specialized Swedish AR clinics that administer AIT was determined, and respective co-ordinates retrieved. Swedish municipality population data were obtained from a national database. The mean distance from each Swedish municipality to the nearest AR clinic was calculated, adjusted using a detour index, and weighted by estimated patient population size. Transport modality data were obtained from a Swedish urban transport study and CO2 emissions were obtained from Government sources. The mean number of annual SLIT-tablets and SCIT doses required were calculated based on product labels and clinical expert input. The annual number of healthcare professional interactions were layered into the model to estimate changes in mean patient travel time, distance, and travel-related CO2 emissions associated with using SCIT versus SLIT-tablets. Mean annual travel-related CO2 emissions were 410 tonnes (to two significant figures [s.f.]; standard deviation [SD] 90) with SLIT-tablets, versus 1700 tonnes (SD 380) for SCIT, resulting in mean annual savings of approximately 1300 tonnes (SD 290) of CO2 if all AIT patients were to receive SLIT-tablets instead of SCIT, over 380 times greater than 2021 average Swedish CO2 emissions per capita. Approximate mean annual travel times for patients taking SLIT-tablets were 66,500 h (three s.f.; SD 14,400), and 278,000 h (SD 60,200) for SCIT, resulting in mean annual savings of 211,000 h (SD 45,800) if all AIT patients were to receive SLIT-tablets instead of SCIT. Compared with SCIT injections, SLIT-tablets led to substantial reductions in treatment-related CO2 emissions and travel times for Swedish patients.
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| 58. |
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| 59. |
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| 60. |
- Cardell, Lars-Olaf, et al.
(författare)
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TOTALL: high cost of allergic rhinitis-a national Swedish population-based questionnaire study.
- 2016
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Ingår i: NPJ primary care respiratory medicine. - : Springer Science and Business Media LLC. - 2055-1010. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- Allergic rhinitis is a global illness with a well-recognised impact on quality of life and work performance. Comparatively little is known about the extent of its economic impact on society. The TOTALL study estimates the total cost of allergic rhinitis using a sample representing the entire Swedish population of working age. A questionnaire focused on allergic rhinitis was mailed out to a random population of Swedish residents, aged 18-65 years. Health-care contacts, medications, absenteeism (absence from work) and presenteeism (reduced working capacity at work) were assessed, and the direct and indirect costs of allergic rhinitis were calculated. Medication use was evaluated in relation to the ARIA guidelines. In all, 3,501 of 8,001 (44%) answered the questionnaire, and 855 (24%) of these reported allergic rhinitis. The mean annual direct and indirect costs because of allergic rhinitis were €210.3 and €750.8, respectively, resulting in a total cost of €961.1 per individual/year. Presenteeism represented 70% of the total cost. Antihistamines appear to be used in excess in relation to topical steroids, and the use of nasal decongestants was alarmingly high. The total cost of allergic rhinitis in Sweden, with a population of 9.5 million, was estimated at €1.3 billion annually. These unexpectedly high costs could be related to the high prevalence of disease, in combination with the previously often underestimated indirect costs. Improved adherence to guidelines might ease the economic burden on society.
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