| 1. |
- Alastruey-Izquierdo, A, et al.
(author)
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Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives
- 2018
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In: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 96:2, s. 159-170
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Journal article (peer-reviewed)abstract
- Chronic pulmonary aspergillosis (CPA) complicates conditions including tuberculosis, chronic obstructive pulmonary disease and sarcoidosis, and is associated with high morbidity and mortality. Surgical cure should be considered where feasible; however, many patients are unsuitable for surgery due to extensive disease or poor respiratory function. Azoles are the only oral drug with anti-<i>Aspergillus</i> activity and itraconazole and voriconazole are considered as first-line drugs. A randomized controlled trial demonstrated improvement or stability in three-quarters of patients given 6 months of itraconazole, but a quarter relapsed on stopping therapy. Long-term treatment may therefore be required in some cases. Itraconazole, voriconazole and posaconazole require therapeutic drug monitoring. No published data are yet available for isavuconazole. Adverse drug effects of azoles are common, including peripheral neuropathy, heart failure, elevated liver enzymes, QTc prolongation and sun sensitivity. Many serious drug-drug interactions occur, including major interactions with rifamycins, simvastatin, warfarin, clopidogrel, immunosuppressant drugs like sirolimus. Furthermore, drug resistance occurs, including cross-resistance to all azoles, but the true prevalence is not yet determined. Intravenous therapy is possible with echinocandins or amphotericin B, but long-term use is challenging. Hemoptysis complicates CPA and can be fatal. Tranexamic acid should be given acutely to reduce bleeding. Bronchial artery embolization can stop acute bleeds. In some circumstances, emergency surgery may be necessary to resect the source of the bleed. Current CPA treatments can be beneficial but have many drawbacks. New oral anti-<i>Aspergillus</i> agents are needed, along with optimization of currently available treatments.
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| 2. |
- Andersson, Sven, et al.
(author)
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Regulatory effects of aerosolized budesonide and adrenalectomy on the lung content of endothelin-1 in the rat
- 1995
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In: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 62:1, s. 34-39
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Journal article (peer-reviewed)abstract
- This study was designed to investigate the effect of inflammation and glucocorticosteroids (GCS) on the content of endothelin-1-like immunoreactivity (ET-LI) in the rat lung. Following intratracheal instillation of Sephadex beads, which induces a long-lasting inflammation in the lung, there was an increase in the lung content of ET-LI measured by RIA. This increase was abolished by locally administered aerosolized budesonide at doses that had only minor systemic effects (measured as a reduction in body weight). In a second series of experiments, rats were subjected to surgical adrenalectomy in order to reduce the levels of endogenous GCS. This procedure elevated the ET-LI levels in the lungs. In contrast, neither adrenalectomy nor high doses of budesonide administered systemically affected the concentration of ET-LI in the kidney. It is concluded that the lung ET levels are elevated in inflammatory conditions and that this increase is highly sensitive to locally administered GCS. Endogenous GCS may, directly or indirectly, play a role in the regulation of lung ET content but there seems to be no general GCS effect on basal tissue levels of ET.
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| 3. |
- Andersson, Sven, et al.
(author)
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Release of endothelin-1 into rat airways following Sephadex-induced inflammation; modulation by enzyme inhibitors and budesonide
- 1996
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In: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 63:2, s. 111-116
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Journal article (peer-reviewed)abstract
- The intratracheal (i.t.) instillation of Sephadex beads into rat induced inflammation and a 30-fold increase in the endothelin-1-like immunoreactivity (ET-1-LI) of broncho-alveolar lavage fluid. The levels were highest 24 h after the instillation and had declined significantly after 48 h. At a dose of 1 mg kg-1 i.t., the glucocorticosteroid budesonide almost abolished this response. Phosphoramidon, which inhibits neutral endopeptidase, an enzyme reported to degrade ET-1 and also to inhibit the endothelin-converting enzyme, potentiated the Sephadex-induced rise in ET-1-LI. Chymostatin and heparin, which are reported to reduce the formation of ET-1, did not affect the increase in ET-1-LI. The present model represents a very reactive system for analyzing the changes in ET-1 levels during inflammation.
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| 4. |
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| 5. |
- Bjermer, Leif
(author)
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The Importance of Continuity in Inhaler Device Choice for Asthma and Chronic Obstructive Pulmonary Disease.
- 2014
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In: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 88:4, s. 346-352
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Research review (peer-reviewed)abstract
- Inhaled therapies are central to the treatment of asthma and chronic obstructive pulmonary disease. Physicians consider many factors when selecting the most appropriate inhaler device, including device efficacy and the cost to the health care system. This review aims to discuss the factors that are important when considering inhaler devices and the importance of continuity in the choice of inhaler device. A large number of factors can contribute to therapeutic outcomes with inhalation devices. The inhalation technique is critical to treatment success and differs substantially between inhaler devices. Misuse of an inhaler is common, and thorough training of patients and physicians is important to ensure correct utilization. Patient satisfaction is an important consideration because it is significantly correlated with compliance and better outcomes. Financial pressures contribute to decision making: although selecting the less expensive inhaler device might reduce direct treatment costs, it can have a large impact on disease control and the patient's well-being. Switching may be associated with a poor inhalation technique, reduced disease control and quality of life, increased use of other treatments and health care resources, and a greater chance of unsuccessful treatment. Nonconsensual switches can result in patient discontent, reduced confidence in the medication, and uncertainty regarding the degree of disease control. It is recommended that patients with stable disease remain on their current device. If a switch is considered, the patient should be consulted and the physician should take into account the patient's preference, their ability to correctly use the device, and the availability of the preferred drug in the preferred device. © 2014 S. Karger AG, Basel.
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| 6. |
- Bodelsson, Mikael, et al.
(author)
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Substance P relaxes rat bronchial smooth muscle via epithelial prostanoid synthesis
- 1999
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In: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 66:4, s. 355-359
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Journal article (peer-reviewed)abstract
- BACKGROUND: Substance P is present in bronchial nerve fibres. The physiological actions of substance P are mediated via tachykinin NK(1) receptors. Immunochemical studies have demonstrated tachykinin NK(1) receptors in the rat airway epithelium. OBJECTIVE: To elucidate how epithelial tachykinin NK(1) receptors affect smooth muscle response to substance P. METHODS: Contractile response of isolated rat bronchial trunk with or without epithelium was recorded. RESULTS: In intact segments precontracted by 5-hydroxytryptamine, relaxation was induced by substance P and the nitric oxide donor, sodium nitroprusside. Removal of the epithelium abolished relaxation induced by substance P but did not affect relaxation induced by sodium nitroprusside. The cyclo-oxygenase inhibitor, indomethacin, but not the nitric oxide synthase inhibitor, L-N(G)-monomethylarginine, reduced the relaxation in response to substance P. CONCLUSIONS: Epithelial tachykinin NK(1) receptors mediate substance-P-induced relaxation of rat bronchial smooth muscle via release of prostanoids but not nitric oxide.
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| 7. |
- Bottai, M, et al.
(author)
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Percentiles of inspiratory capacity in healthy nonsmokers: a pilot study
- 2011
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In: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 82:3, s. 254-262
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Journal article (peer-reviewed)abstract
- <i>Background:</i> Over the past decade inspiratory capacity (IC) has received increasing attention, especially in studies on chronic obstructive pulmonary disease. Though a few recent studies provide reference values for IC, still little is known on the distribution of its values in healthy subjects. <i>Objective:</i> To estimate percentiles of IC in a sample of healthy nonsmokers by applying quantile regression. <i>Methods:</i> We applied quantile regression to estimate seven percentiles of IC from 5 to 95% for a given age, height and body mass index, separately in males and females, in a sample of 411 healthy nonsmokers, aged 8–73 years, drawn from the general population in Northern Italy. <i>Results:</i> The magnitude and statistical significance of the effect of age, height and body mass on IC varied across percentiles and between genders. When the 50th percentile of IC was compared with the predicted values of several studies, including those published by the European Community for Coal and Steel, the differences were as large as 0.86 liters in males and 0.90 liters in females. The possible advantage of the 5th percentile predicted from quantile regression over the ‘traditional 5th percentile’ as lower limit of normal was also illustrated. <i>Conclusions:</i> Inference on percentiles, rather than just the mean, of IC and other lung function measures may help in the future to better understand the effect of various risk factors, model growth curves and derive more accurate reference values.
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| 8. |
- Bredberg, Anna, et al.
(author)
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Comparison of Exhaled Endogenous Particles from Smokers and Non-Smokers Using Multivariate Analysis
- 2013
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In: Respiration. - : S. Karger AG. - 0025-7931 .- 1423-0356. ; 86:2, s. 135-142
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Journal article (peer-reviewed)abstract
- Background: Smoking, along with many respiratory diseases, has been shown to induce airway inflammation and alter the composition of the respiratory tract lining fluid (RTLF). We have previously shown that the phospholipid and protein composition of particles in exhaled air (PEx) reflects that of RTLF. In this study, we hypothesized that the composition of PEx differs between smokers and non-smokers, reflecting inflammation in the airways. Objective: It was the aim of this study to identify differences in the phospholipid composition of PEx from smokers and non-smokers. Methods: PEx from 12 smokers and 13 non-smokers was collected using a system developed in-house. PEx was analysed using time-of-flight secondary ion mass spectrometry, and the mass spectral data were evaluated using multivariate analysis. Orthogonal partial least squares (OPLS) was used to relate smoking status, lung function and pack years to the chemical composition of RTLF. The discriminating ions identified by OPLS were then used as explanatory variables in traditional regression analysis. Results: There was a clear discrimination between smokers and non-smokers according to the chemical composition, where phospholipids from smokers were protonated and sodiated to a larger extent. Poor lung function showed a strong association with higher response from all molecular phosphatidylcholine species in the samples. Furthermore, the accumulated amount of tobacco consumed was associated with variations in mass spectra, indicating a dose-response relationship. Conclusion: The chemical composition of PEx differs between smokers and nonsmokers, reflecting differences in the RTLF. The results from this study may suggest that the composition of RTLF is affected by smoking and may be of importance for lung function.
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| 9. |
- Canova, C R, et al.
(author)
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Increased prevalence of perennial allergic rhinitis in patients with obstructive sleep apnea
- 2004
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In: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 71:2, s. 138-143
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Journal article (peer-reviewed)abstract
- Background: Impaired nasal breathing is a risk factor for obstructive sleep apnea syndrome (OSAS). Objectives: The aim of this study was to determine whether atopy to perennial allergens and existence of perennial allergic rhinitis was a risk factor for OSAS. Methods: In a case-control study, we compared the proportions of OSAS patients with atopy to perennial allergens and perennial allergic rhinitis to the proportions in patients with chronic obstructive pulmonary disease (COPD). Seventy-two OSAS patients (mean age 60.7 years; 79.4% male) and 44 COPD patients (mean age 63.6 years; 88.6% male) were selected from a hospital outpatients' clinic in Switzerland. All patients completed a respiratory symptom questionnaire, performed spirometry and had a skin prick test for atopy. Results: OSAS patients were significantly heavier than COPD patients (BMI 32.4 +/- (SD) 6.6 vs. 29.2 +/- 6.6 kg/m(2), p = 0.04) and had a better lung function than COPD patients (FEV1% predicted 91.3 +/- 19.2 vs. 51.6 +/- 18.9%, p < 0.001). Patients with OSAS were more likely to be sensitized to perennial allergens such as house dust mite (23.6 vs. 4.5%, p = 0.009) and dog (18 vs. 4.5%, p = 0.04) than the COPD patients. Perennial allergic rhinitis ( having nose problems [ nasal obstruction and/or runny nose and/or sneezing] all year and being atopic to at least one perennial allergen) was reported in 11% of OSAS patients but in only 2.3% of COPD patients (p = 0.15). Conclusion: We conclude that subjects with OSAS may have an increased risk of being allergic to perennial allergens and suffer from perennial rhinitis. Awareness of this risk may have important consideration in the clinical situation.
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| 10. |
- Davidsson, Anette, 1960-, et al.
(author)
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Chlorine in Breath Condensate : A Measure of Airway Affection in Pollinosis?
- 2007
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In: Respiration. - : Karger. - 0025-7931 .- 1423-0356. ; 74:2, s. 184-191
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Journal article (peer-reviewed)abstract
- Background: Infiltration of inflammatory cells in bronchial mucosa and glandular hypersecretion are hallmarks of asthma. It has been postulated that exhaled breath condensate (EBC) mirrors events in epithelial lining fluid of airways, such as presence of local inflammation as well as glandular hypersecretion. It is also well known that eosinophil cationic protein (ECP) and cysteinyl-leukotrienes (cys-LT) are released by circulating inflammatory cells when triggered by antigen stimulation in asthma patients.Objectives: The aim of this study was to evaluate whether chlorine and/or cys-LT in EBC would reflect changes of exposure of airborne pollen in patients with asthma.Methods: EBC and serum were collected from 23 patients with allergic asthma during a pollen season and repeated 5 months later during a period with no aeroallergens. Chlorine was measured by means of a sensitive coulometric technique and cys-LT by an EIA technique. Serum ECP was measured and lung function tests were performed and symptoms noted during both occasions.Results: Significantly higher concentrations of chlorine in EBC (p = 0.007) and ECP in serum (p = 0.003) were found during the pollen season compared to post-season. Chlorine levels tended to be higher in patients who reported of chest symptoms compared to those who denied symptoms during the pollen season (p = 0.06). Areas under the receiver-operated characteristic curves (AUCROC) were compared and similar discriminative power to identify exacerbations of asthma was recorded by chlorine in EBC (range 0.67-0.78) and ECP in serum (range 0.64-0.78).Conclusion: It is concluded that chlorine in EBC and ECP in serum decreased significantly post-season, and this is suggested to mirror the decrement in airborne antigen. It is furthermore proposed that chlorine in EBC and ECP in serum tend to have a similar capacity to identify seasonal variations in airborne pollen in patients with asthma.
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