Prevention of bronchial hyperreactivity in a rat model of precapillary pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>The development of bronchial hyperreactivity (BHR) subsequent to precapillary pulmonary hypertension (PHT) was prevented by acting on the major signalling pathways (endothelin, nitric oxide, vasoactive intestine peptide (VIP) and prostacyclin) involved in the control of the pulmonary vascular and bronchial tones.</p> <p>Methods</p> <p>Five groups of rats underwent surgery to prepare an aorta-caval shunt (ACS) to induce sustained precapillary PHT for 4 weeks. During this period, no treatment was applied in one group (ACS controls), while the other groups were pretreated with VIP, iloprost, tezosentan via an intraperitoneally implemented osmotic pump, or by orally administered sildenafil. An additional group underwent sham surgery. Four weeks later, the lung responsiveness to increasing doses of an intravenous infusion of methacholine (2, 4, 8 12 and 24 μg/kg/min) was determined by using the forced oscillation technique to assess the airway resistance (Raw).</p> <p>Results</p> <p>BHR developed in the untreated rats, as reflected by a significant decrease in ED₅₀, the equivalent dose of methacholine required to cause a 50% increase in Raw. All drugs tested prevented the development of BHR, iloprost being the most effective in reducing both the systolic pulmonary arterial pressure (Ppa; 28%, p = 0.035) and BHR (ED₅₀= 9.9 ± 1.7 vs. 43 ± 11 μg/kg in ACS control and iloprost-treated rats, respectively, p = 0.008). Significant correlations were found between the levels of Ppa and ED₅₀(R = -0.59, p = 0.016), indicating that mechanical interdependence is primarily responsible for the development of BHR.</p> <p>Conclusions</p> <p>The efficiency of such treatment demonstrates that re-establishment of the balance of constrictor/dilator mediators via various signalling pathways involved in PHT is of potential benefit for the avoidance of the development of BHR.</p

Humidity regulation in the management of asthma patients sensitized to house dust mites.

Substances in the faeces of house dust mites are well-recognized as common allergens in the pathogenesis of asthma. There have been many trials of interventions aimed at reducing mite populations in the home, but most have been uncontrolled, too small, or too short to determine with confidence any beneficial effects. Of those which succeeded, very few used methods which reduced mite populations on a permanent basis. House dust mites are sensitive to humidity. Their geographical distribution is closely correlated to the availability of moisture. Very little work has been done on the effects of reducing humidity in the home environment in the long term, with a view to controlling dust mite populations. Two different methods which might reduce humidities to levels which could successfully reduce dust mite numbers are dehumidifiers, and mechanical ventilation with heat recovery (MVHR). To date there has been no work assessing the effectiveness of dehumidifiers and very little (although promising) work on MVHR. We discuss the potential of humidity control as an adjunct to the clinical treatment of asthma

A comparison between trap and flotation methods of sampling in quantifying mite exposure

Background: Quantification of mite exposure by determining mite levels in dust using a flotation technique has considerable shortcomings due to non-reproducibility of vacuum sampling, and high variability in the mite extraction efficiency. Mite traps have been reported to be more efficient, simpler and more standardised than dust sampling as the mite extraction phase is not required. The trap-method was used alongside dust sampling in a study investigating the role of dehumidifiers in dust mite control. Thus a comparison of the methods was possible. Methods: Dust from the top surface of mattresses in 51 homes, 25 with dehumidifiers in the bedroom, was collected in two rounds of sampling, 12 months apart. After vacuum sampling on each occasion, two pieces of 20x 22.5 cm transparent adhesive film were placed on the mattress-top to trap mites. The dust was quantified for mite and Der p 1 levels by the flotation method and enzyme immunoassay. Mite levels obtained from the dust and traps were compared using Wilcoxson's test, and Bland and Altman's test for the agreement between the two methods. Results: Both methods correlated with the Der p 1 levels. There was agreement between the trap and flotation techniques as &gt;95% of the differences between the two methods lay within two standard deviations. The traps gave significantly higher mite counts than the dust samples (p&lt;0.001) when the median was &gt;11/m 2 (range 0-4144), but no difference at very low counts. A significant reduction in the mite levels in the dehumidifier group was detected at the end of the trial only in the trap data (p&lt;0.03), but not in the dust data (p&gt;0.2). Conclusion: The trap method was more effective than the flotation method in sampling mites. Although both methods could be used interchangeably, traps were more sensitive in detecting small changes. The compliance and practicability of the trap method was excellent. It can be used in field studies for quantifying mite exposure

Treprostinil for pulmonary hypertension

Treprostinil (Remodulin, United Therapeutics) is a stable, long-acting prostacyclin analog, which has been shown to improve clinical state, functional class, exercise capacity and quality of life in patients with pulmonary arterial hypertension, an uncommon disease with poor prognosis. The drug is administered as a continuous subcutaneous infusion using a portable miniature delivery system. Side effects include facial flush, headache, jaw pain, abdominal cramping and diarrhea. These are all typical of prostacyclin impregnation and manageable by symptom-directed dose adjustments. Infusion site pain, a more serious side effect, may limit the treatment in 10% of patients. Otherwise, treprostinil has an excellent safety profile and compares favorably with reference continuous intravenous epoprostenol (Flolan, GlaxoSmithKline) therapy. Treprostinil has a place in currently proposed treatment algorithms of pulmonary arterial hypertension.SCOPUS: ar.jinfo:eu-repo/semantics/publishe