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- Ekstrand, Y, et al.
(författare)
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Sensitivity to Environmental Irritants and Capsaicin Cough Reaction in Patients with a Positive Methacholine Provocation Test before and after Treatment with Inhaled Corticosteroids
- 2011
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Ingår i: JOURNAL OF ASTHMA. - 0277-0903. ; 48:5, s. 482-489
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increasing evidence points to a potential role for members of the transient receptor potential family of cation channels on several features of asthmatic disease. The cough sensitivity to inhaled capsaicin is known to reflect the reactivity of these airway sensory nerves. OBJECTIVE: The aim was to study, among patients having a positive methacholine provocation and diagnosed with asthma, capsaicin cough sensitivity, sensitivity to methacholine, and levels of exhaled nitric oxide before and after treatment with inhaled steroids, and further, to measure the self-reported impact from environmental irritants. METHODS: Eighteen steroid-naïve patients with a positive methacholine test underwent capsaicin inhalation provocation on two occasions, before and after regular use of inhaled steroids over at least 3 months. Comparisons were made to 21 healthy controls. Sensitivity to methacholine and levels of exhaled nitric oxide were measured before and after the treatment. The participants also answered a validated questionnaire regarding environmental irritants. RESULTS: The patients displayed higher capsaicin cough sensitivity than the controls before the treatment period, but not afterward. Before treatment, capsaicin cough answer correlated significantly with levels of exhaled nitric oxide, but not with methacholine sensitivity. After treatment with inhaled corticosteroids, the capsaicin cough sensitivity and the inflammatory parameters were normalized. In comparison to the control group, the patients reported more affective reactions to and behavioral disruptions induced by environmental irritants. CONCLUSIONS: In steroid-naïve patients with a positive methacholine test, there is a link between that part of the airway inflammation that is reflected by exhaled nitric oxide and that followed by an augmented reactivity of capsaicin-sensitive sensory nerves. This association disappears after steroid treatment.
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| 3. |
- Hellgren, Johan, 1965, et al.
(författare)
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Quality of life in non-infectious rhinitis and asthma
- 2004
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Ingår i: Rhinology. ; 42:4
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Tidskriftsartikel (refereegranskat)abstract
- In this study we evaluated how the quality of life in subjects with asthma was affected by a history of non-infectious rhinitis. The study comprised 180 persons with asthma and 156 controls, who answered the Short Form 36 quality of life questionnaire. Both the asthma subjects and the controls were stratified according to a history of non-infectious rhinitis (NIR). The global physical quality of life score (PCS) was significantly lower for all the asthma subjects regardless of their previous history of NIR compared to controls (NIR positive asthma, -8, p=O,001, NIR negative asthma, -9, p=0, 001). The subjects with asthma and a positive history of NIR obtained significantly lower scores for their global mental quality of life (MCS) than the controls (46 vs 51, p=0.004). The subjects with asthma and a negative history of NIR obtained MCS scores that were similar to those of the controls (50 and 51, p=0.9). In this population based study, the physical Qol of the subjects with asthma was lower regardless of a previous history of NIR compared to controls. A positive history of NIR in asthma was however associated with a poorer mental Qol.
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| 6. |
- Lindén, Anders, 1961, et al.
(författare)
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Bronchodilation by an inhaled VPAC(2) receptor agonist in patients with stable asthma
- 2003
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Ingår i: Thorax. - 0040-6376. ; 58:3, s. 217-21
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The synthetic vasoactive intestinal peptide (VIP) analogue Ro 25-1553 is a selective VIP-PACAP type 2 (VPAC(2)) receptor agonist that causes a bronchodilatory effect in guinea pigs in vivo. The effect of Ro 25-1553 given by inhalation to patients with asthma was studied and compared with that of a long acting beta(2) adrenoceptor agonist. METHODS: Twenty four patients with moderate stable asthma participated in a double blind, randomised, placebo controlled, crossover study. The primary variable was bronchodilatory effect (increase in forced expiratory volume in 1 second, FEV(1)) after inhalation of Ro 25-1553 (100 microg or 600 microg) and formoterol (4.5 microg), respectively. Putative side effects were characterised by monitoring sitting blood pressure, serum potassium, electrocardiography and echocardiography. RESULTS: Inhalation of 600 microg Ro 25-1553 caused a rapid bronchodilatory effect (geometric mean increase in FEV(1) compared with placebo) within 3 minutes of 6% (95% CI 4 to 9), as did inhalation of formoterol (8% (95% CI 5 to 10)). The corresponding maximum bronchodilatory effect during 24 hours was similar for 600 microg Ro 25-1553 (7% (95% CI 4 to 10)) and the reference bronchodilator formoterol (10% (95% CI 7 to 12)). However, for both doses of Ro 25-1553 the bronchodilatory effect was attenuated 5 hours after inhalation whereas formoterol still had a bronchodilatory effect 12 hours after inhalation. Neither Ro 25-1553 nor formoterol produced any clinically relevant side effects. No drug related difference in adverse events was observed. CONCLUSION: Inhalation of a synthetic selective VPAC(2) receptor agonist constitutes a promising approach for bronchodilation in patients with asthma.
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| 7. |
- Lötvall, Jan, 1956, et al.
(författare)
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Comparing the effects of two inhaled glucocorticoids on allergen-induced bronchoconstriction and markers of systemic effects, a randomised cross-over double-blind study
- 2011
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 1:1
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background Inhaled glucocorticoids are efficient in protecting against asthma exacerbations, but methods to compare their efficacy vs systemic effects have only been attempted in larger multi-centre studies. The aim of the current study was therefore to directly compare the effects of two separate inhaled glucocorticoids, mometasone and budesonide, to compare the effects on the early and late asthmatic responses to inhaled allergen in patients with mild allergic asthma, and sputum eosinophils, and to relate the clinical positive effects to any systemic effects observed. Methods Twelve patients with documented early and late asthmatic responses (EAR and LAR) to inhaled allergen at a screening visit were randomized in a double-blind fashion to treatment with mometasone (200 μg × 2 or 400 μg × 2), budesonide (400 μg × 2) or placebo in a double-blind crossover fashion for a period of seven days. Challenge with the total allergen dose causing both an EAR and LAR was given on the last day of treatment taken in the morning. Lung function was assessed using FEV1, and systemic glucocorticoid activity was quantified using 24 h urinary cortisol. Results Mometasone and budesonide attenuate both EAR and LAR to allergen to a similar degree. No significant dose-related effects on the lung function parameters were observed. Both treatments reduced the relative amount of sputum eosinophils (%) after allergen. At the dose of 800 μg daily, mometasone reduced 24 h urinary cortisol by approximately 35%. Both drugs were well tolerated. Conclusions Mometasone and budesonide are equieffective in reducing early and late asthmatic responses induced by inhaled allergen challenge. Mometasone 800 μg given for seven days partially affects the HPA axis.
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| 8. |
- Lötvall, Jan, 1956, et al.
(författare)
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The effect of formoterol over 24 h in patients with asthma: the role of enantiomers
- 2005
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Ingår i: Pulmonary Pharmacology & Therapeutics. - : Elsevier BV. - 1522-9629 .- 1094-5539. ; 18:2, s. 109-13
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Tidskriftsartikel (refereegranskat)abstract
- The single-dose effect of formoterol racemate and enantiomers on bronchodilatation up to 24 h was determined. Forty-six reversible asthmatic patients were randomised to this double blind, crossover study. Formoterol was inhaled by nebulizer (HaloLite(R)); 4.5 and 36 mug of the racemate (rac-formoterol), 2.25 and 18 mug of (R;R)-formoterol, 18 mug of (S;S)-formoterol, or placebo. Airway and systemic effects were assessed by serial measurements of forced expiratory volume during the first second, FEV1 (24 h), and heart rate (4 h). Rac- and (R;R)formoterol significantly and dose-dependently increased FEV1, with similar mean maximal effect. (S;S)-formoterol was without significant effects on FEV1 and heart rate. (R;R)- and rac-formoterol were still effective 22-24 h after single high doses, but this was associated with some systemic side effect (increased heart rate) initially. Average 22-24 h FEV1 was 8% (rac-formoterol 36 mug) and 11% ((R-R)-formoterol 18 mug) over placebo, respectively. No significant differences in effects were observed between rac- and (R;R)-formoterol. Thus, the single dose bronchodilatating effect of formoterol resides in (R;R)-formoterol. This study does not indicate a clinically important advantage of (R;R)-formoterol as acute bronchodilator compared to the racemate.
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| 9. |
- Nopp, A, et al.
(författare)
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Basophil allergen threshold sensitivity : A useful approach to anti-IgE treatment efficacy evaluation
- 2006
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 61:3, s. 298-302
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Tidskriftsartikel (refereegranskat)abstract
- Background: Monitoring of the allergen sensitivity of a patient is most important for optimal patient care and a basic prerequisite for immunomodulating treatment. The objective of this study was to investigate how basophil allergen sensitivity can be applied in the monitoring of anti-immunoglobulin E (IgE) treatment. Methods: Basophils from timothy grass pollen allergic patients were, by flow cytometry, analysed for allergen threshold sensitivity (CD-sens) by measuring CD63 up-regulation on CD203c-identified basophils. The results were compared with maximal percentage CD63 up-regulation at one allergen dose (CD-max), skin prick test end-point allergen titration, (SPT-sens), nasal provocation titration tests (nasal provocation titre) and serum IgE and IgE antibody concentrations. Results: There was a significant correlation (r = 0.50, P = 0.01) between CD-sens and SPT-sens, CD-sens and the IgE antibody concentration in percentage of 'total IgE' (relative IgE antibody concentration) (r = 0.72, P < 0.001) as well as between CD-sens and nasal provocation titre (r = 0.54, P < 0.05) but, in contrast, CD-max did not correlate with any of the sensitization parameters, i.e. SPT-sens, nasal provocation titre, absolute and relative IgE antibody concentration or CD-sens. CD-sens could be used to monitor omalizumab treatment efficacy while, based on CD-max, four of seven symptom-free patients on omalizumab would have been classified as having ongoing allergy. Conclusions: CD-sens seems to be very useful for the determination of a patient's allergen sensitivity and should be evaluated for the measurement and monitoring of anti-IgE treatment efficacy. CD-max, the conventional approach to basophil allergen challenge, which mirrors cell reactivity, gives incorrect information. Copyright © Blackwell Munksgaard 2006.
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| 10. |
- Nopp, A., et al.
(författare)
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CD-sens and clinical changes during withdrawal of Xolair after 6 years of treatment
- 2007
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 62:10, s. 1175-1181
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many clinical trials with omalizumab, Xolair, have been reported but the treatment period has always been short, i.e. < 12 months. After withdrawal, the clinical symptoms tend to return. A group of patients who stopped treatment after approx. 6 years allowed studies of the long-term effects of Xolair. Methods: The patient's cat or mite allergen sensitivity was quantitated as basophil allergen threshold sensitivity, CD-sens, and immunoglobulin E (IgE) and IgE- and IgG4-antibodies were determined before start and during treatment withdrawal. Asthma severity was evaluated from forced expiratory volume (FEV), peak expiratory flow (PEF) and a questionnaire. Results: At 6-14 months without Xolair 13 of the 18 cat and mite allergic asthmatics had either improved or remained the same as on treatment. Most of the patients were in a stable clinical condition reporting high quality of life, no increased nightly asthma attacks, no emergency visits as well as little or no increase in medication. The CD-sens to cat showed a peak 4 months after withdrawal but then decreased to levels below those of untreated patients with allergic asthma and at 12 months six of 14 had nonreactive basophils. Cat IgG4 antibody levels were higher than in cat allergics in general. Conclusion: Most of the patients 12-14 months had, after closing of 6-year Xolair treatment, a surprisingly mild asthma. Interestingly, and probably contributing to the clinical results, a downregulation of basophil, and presumably also mast cell, reactivity, was seen.
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