Limited treatment adaptation despite poor asthma control in asthma patients treated with inhaled corticosteroids

Objective: Current asthma guidelines recommend use of inhaled corticosteroids (ICS) in patients with persistent disease. This study was designed to investigate (1) the proportion of patients prescribed ICS-containing maintenance treatment who achieve asthma control, (2) determinants of control and (3) how physicians adapt treatment to the level of control. Methods: General practitioners (GPs) and chest physicians (CPs) in France recruited patients consulting for asthma and prescribed an ICS. Over a 2-year follow-up period, asthma symptoms in the previous 3 months and treatments prescribed were documented at each visit. Variables independently associated with asthma control were determined by multiple logistic regression. Results: Data were available for 924 patients recruited by GPs and 455 recruited by CPs. Asthma control was acceptable in only 24% of patients at inclusion, and in 33.6% at the last follow-up visit. Five factors were independently associated with asthma control: age (or time since diagnosis), gender, smoking status, allergic aetiology of asthma and treatment. Most patients (56.3%) were prescribed the same ICS dose regimen at the end of follow-up as at inclusion. The intensity of controller therapy had been increased in only 12.2% of patients unacceptably controlled at inclusion. Conclusions: Asthma was unacceptably controlled in most patients receiving ICS-containing maintenance treatment and remained so during follow-up. Despite this, treatment adaptations by GPs and CPs were very infrequent. This unsatisfactory situation may be improved by adopting a more dynamic approach to tailoring controller therapy to the needs of the patient.     

Critical analysis of the response to antihypertensive therapy. Report of 102 cases

One hundred and two patients with mild to moderate hypertension, non responding to a placebo therapy, were given an antihypertensive drug for a mean period of 6 weeks (range: 3-12 weeks). Their blood pressure (BP) was measured before and after active treatment by both a mercury manometer at the clinic and an ambulatory apparatus (Spacelabs 5200 or 90202). The clinic BP figures were poorly correlated with the 24 hour ambulatory BP levels, as well as the magnitude of decrease in clinic BP with the reduction in ambulatory BP. Twenty eight patients who were considered as "clinic responders" had in fact not significantly lowered their ambulatory DBP and, conversely, 16 patients were "clinic non responders" whereas they were "ambulatory responders". The patients were divided into 2 groups, according to White's and Morgan Roth's recommendations: group I (n = 61) with a percentage of pathological DBP readings (greater than 90 mmHg) during daytime as high as 50% or more, and group II (n = 41) with a percentage less than 50%. The correlations between the 2 methods of BP measurement were closer within the group I than within the group II and the rate of discrepancies between the "clinic" and "ambulatory responders" was lower. On the other hand, we identified the group II patients as being often "clinic responders" but rarely "ambulatory responders", whereas the inverse trend was observed in the group I. In conclusion: even in non placebo responding hypertensive patients the clinic BP measurement might be not sufficient for proper evaluation of an antihypertensive drug.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of neurokinin effects and receptor selectivity in human isolated bronchi

Sensitive afferent nerves and the neurokinins they release upon activation are considered to be important in controlling bronchomotor tone. Human isolated bronchi respond to neurokinin A (NKA), substance P (SP), and neurokinin B (NKB) with dose-dependent contractions. The order of potency of the three natural neurokinins is NKA greater than SP greater than NKB, suggesting the presence of NK-2 receptors. To further characterize the neurokinin receptors in human bronchi, we used selective agonists for each receptor type (i.e., NK-1, NK-2, and NK-3). In fact, NK-1 selective compounds, [Pro9]SP(1-11) sulfone and [beta-ala4,Sar9]SP(4-11) sulfone, did not induce significant contractions up to 10(-5) M. Similarly, the selective agonist for the NK-3 receptor, [MePhe7]NKB(4-10), was almost inactive. However, the NK-2 selective fragment [Nle]NKA(4-10) was a potent stimulant. The negative log of the peptide concentration that caused 50% of maximal effect (pD2) was 6.99 for NKA and 6.12 for [Nle10]NKA(4-10). Removal of the epithelium significantly enhanced the contractile responses to the three neurokinins and also to the NK-2 selective agonist. Phosphoramidon, an enkephalinase inhibitor, was more potent than epithelium removal in enhancing the contractile responses to these agonists. However, epithelium removal and phosphoramidon did not increase the weak responses to the NK-1 and NK-3 selective compounds. In the presence of phosphoramidon, removal of the epithelium slightly enhanced the contractile responses to NKA and [Nle]NKA(4-10) but not to SP and NKB.(ABSTRACT TRUNCATED AT 250 WORDS)     

Involvement of cysteinyl leukotrienes in angiotensin II-induced contraction in isolated aortas from transgenic (mRen-2)27 rats

OBJECTIVES : We have previously reported that 5-lipoxygenase-derived products, and particularly the cysteinyl leukotrienes (CysLTs), were involved in angiotensin II (Ang II)-induced contractions in isolated aortas from spontaneously hypertensive rats. DESIGN : The aim of this study was to assess the role of CysLTs in the vascular response to Ang II in an Ang II-dependent model of hypertension, the (mRen-2)27 transgenic rats (TGs). METHODS : Intact aortic rings from TG and normotensive Sprague-Dawley rats (SDs) were suspended in organ chambers for isometric tension development in response to Ang II. In addition, the release of CysLTs in response to Ang II (0.3 micromol/l) was measured by enzyme immunoassay. RESULTS : In isolated aortas from TG rats, pretreatment with the 5-lipoxygenase inhibitor (AA861, 10 micromol/l) or the CysLT1 receptor antagonist (MK571, 1 micromol/l) significantly (P < 0.05) reduced Ang II-induced contractions by 52 and 42%, respectively. In addition, Ang II induced a 2.6-fold increase in CysLT release (pg/mg dry weight tissue: 58.3 +/- 17.9 (Ang II, n = 7) versus 22.5 +/- 5.9 (basal, n = 7) P < 0.05), which was inhibited by the AT1 receptor antagonist losartan (1 micromol/l). In contrast, in aortas from SD rats, pretreatment with AA861 or MK571 did not alter Ang II-induced contraction and CysLT production remained unchanged after exposure to Ang II. CONCLUSION : These data suggest that CysLTs are involved in the contractile responses to Ang II in isolated aortas from TG but not from SD rats.