How Effective and Safe Is Bronchial Thermoplasty in "Real Life" Asthmatics Compared to Those Enrolled in Randomized Clinical Trials?

There is limited information on the efficacy and safety of bronchial thermoplasty (BT) in real life. We evaluated the outcomes of the randomized clinical trials for BT in severe asthmatics, in whom the exclusion criteria were not strictly controlled. A case series of seven asthmatics (M/F: 4/3; age: 54.6 ± 2.9 years) is reported. Subjects had a statistically significant improvement in AQLQ (from a mean of 3.96 ± 1.1 to 4.5 ± 1.2 and 5.5 ± 0.6 after 6 and 12 months of treatment; p = 0.0007) and in the ACQ score (from 2.77 ± 0.8 to 1.83 ± 1.2 and 1.5 ± 0.8 after 6 and 12 months; p < 0.001). In the year after BT, severe exacerbations, salbutamol use, and OCS use were significantly lower compared with the 1-yr pretreatment period (p < 0.001). No ED visits and hospitalization occurred in the year after BT. No changes in functional parameters were recorded. Our investigation confirms the safety and efficacy of BT in severe asthmatics in real life settings.

Exhaled nitric oxide is associated with cyclic changes in sexual hormones.

BACKGROUND: We hypothesized that changes in the levels of sexual hormones during the menstrual cycle influence the concentration of nitric oxide in the exhaled air (FeNO) and alveolar exhaled nitric oxide (CANO). METHODS: Twelve healthy, non allergic women in their reproductive age (age range 25-37 years) were recruited. Subjects were studied, on alternate days, over the course of their menstrual cycle. At each visit, measurements of FeNO and CANO were performed. Progesterone and 17-ß-estradiol concentrations were measured in salivary samples. RESULTS: Eight subjects completed the study. The levels of FeNO and CANO were 13 ± 4.7 pbb and 3.5 ± 1.9 pbb, respectively (mean ± SD). The mean salivary concentration of progesterone was 65.1 ± 16.2 pg/ml (mean ± SD), with a range of 32.4-107.7 pg/ml, and the concentration of 17 ß-estradiol was 6.0 ± 1.6 pg/ml, with a range of 3.1-12.9 pg/ml. The Generalized Estimating Equations procedure demonstrated that levels of progesterone influenced both FeNO and CANO (Wald χ2 = 11.60, p = 0.001; and Wald χ2 = 87.55, p = 0.001, respectively). On the contrary, the salivary levels of 17 ß-estradiol were not significantly associated with FeNO (Wald χ2 = 0.087, p = 0.768) or CANO (Wald χ2 = 0.58, p = 0.448). CONCLUSION: In healthy women, the menstrual cycle-associated hormonal fluctuations selectively influence the levels of bronchial and alveolar NO. The current findings may have important clinical implications for the interpretation of eNO levels, by identifying a patient-related factor that influences the eNO measurements.

Lung penetration and patient adherence considerations in the management of asthma: role of extra-fine formulations.

The mainstay of management in asthma is inhalation therapy at the target site, with direct delivery of the aerosolized drug into the airways to treat inflammation and relieve obstruction. Abundant evidence is available to support the concept that inflammatory and functional changes at the level of the most peripheral airways strongly contribute to the complexity and heterogeneous manifestations of asthma. It is now largely accepted that there is a wide range of clinical phenotypes of the disease, characterized primarily by small airways involvement. Thus, an appropriate diagnostic algorithm cannot exclude biological and functional assessment of the peripheral airways. Similarly, achievement of optimal control of the disease and appropriate management of specific phenotypes of asthma should be based on drugs (and delivery options) able to distribute uniformly along the bronchial tree and to reach the most peripheral airways. Products developed with the Modulite(®) technology platform have been demonstrated to meet these aims. Recent real-life studies have shown clearly that extra-fine fixed-combination inhaled therapy provides better asthma control than non-extra-fine formulations, thus translating the activity of the drugs into greater effectiveness in clinical practice. We suggest that in patients with incomplete asthma control despite good lung function, involvement of the peripheral airways should always be suspected. When this is the case, treatments targeting both the large and small airways should be used to improve asthma control. Above all, it is emphasized that patient adherence with prescribed medications can contribute to clinical success, and clinicians should always be aware of the role played by patients themselves in determining the success or failure of treatment.

Clinical and anti-inflammatory effects of ultra-short preseasonal vaccine to Parietaria in asthma.

OBJECTIVE: The ultra-short course preseasonal allergy vaccine, containing the adjuvant monophosphoryl lipid A (MPL), is effective in treating allergic symptoms; however, the efficacy in controlling asthmatics symptoms has not been fully demonstrated. We aimed at evaluating whether the ultra-short preseasonal course of immunotherapy contributes to asthma control. METHODS: Four subcutaneous injections of the active product (Pollinex Quattro) were administered, before the pollen season, to 20 Parietaria-sensitive mild, untreated asthmatics (M/F: 12/8; age: 38 ± 14 years). After the screening visit (visit 1), asthma control was assessed by the Asthma Control Test (ACT) immediately before the first (visit 2) and immediately after the last (visit 5) injections, as well as during the pollen season (visit 6). Bronchial and alveolar exhaled nitric oxide (NO) concentrations were also measured. Nine Parietaria-sensitive mild asthmatics (M/F: 3/6; age: 40 ± 12 years) served as untreated controls. RESULTS: The ACT remained constant during allergen exposure in specific immunotherapy (SIT)-treated asthmatics (visit 2: 22 ± 3.2; visit 5: 23 ± 2.8; visit 6: 22 ± 3.6; analysis of variance [ANOVA], p = 0.47), whereas it dropped during pollen exposure in controls (visit 2: 20 ± 2.5; visit 5: 21 ± 2.8; visit 6: 16 ± 5.7; ANOVA, p = 0.01). The forced expiratory NO (FENO) values significantly increased during pollen exposure in both groups; however, the alveolar NO concentrations remained stable in SIT-treated asthmatics (p = 0.11), whereas they doubled in controls (p = 0.01). CONCLUSIONS: The current findings show that the preseasonal vaccine adjuvated with MPL contributes to the maintenance of control of asthma during the pollen season.

Effects of exercise training on airway closure in asthmatics.

We previously reported that responsiveness to methacholine (Mch) in the absence of deep inspiration (DI) decreased in healthy subjects after a short course of exercise training. We assessed whether a similar beneficial effect of exercise on airway responsiveness could occur in asthmatics. Nine patients (male/female: 3/6; mean age ± SD: 24 ± 2 yr) with mild untreated asthma [forced expiratory volume in 1 s (FEV(1)): 100 ± 7.4% pred; FEV(1)/vital capacity (VC): 90 ± 6.5%] underwent a series of single-dose Mch bronchoprovocations in the absence of DI in the course of a 10-wk training rowing program (6 h/wk of submaximal and maximal exercise), at baseline (week 0), and at week 5 and 10. The single-dose Mch was established as the dose able to induce ≥ 15% reduction in inspiratory vital capacity (IVC) and was administered to each subject at every challenge occasion. Five asthmatics (male/female: 1/4; mean age ± SD: 26 ± 3 yr) with similar baseline lung function (FEV(1): 102 ± 7.0% predicted; FEV(1)/VC: 83 ± 6.0%; P = 0.57 and P = 0.06, respectively) not participating in the exercise training program served as controls. In the trained group, the Mch-induced reduction in IVC from baseline was 22 ± 10% at week 0, 13 ± 11% at week 5 (P = 0.03), and 11 ± 8% at week 10 (P = 0.028). The Mch-induced reduction in FEV(1) did not change with exercise (P = 0.69). The reduction in responsiveness induced by exercise was of the same magnitude of that previously obtained in healthy subjects (50% with respect to pretraining). Conversely, Mch-induced reduction in IVC in controls remained unchanged after 10 wk (%reduction IVC at baseline: 21 ± 20%; after 10 wk: 29 ± 14%; P = 0.28). This study indicates that a short course of physical training is capable of reducing airway responsiveness in mild asthmatics.

The effect of intranasal corticosteroids on asthma control and quality of life in allergic rhinitis with mild asthma.

BACKGROUND: The mechanisms through which rhinitis affects asthma have not been completely elucidated. We explored whether the effect of nasal treatment on asthma control and respiratory-related quality of life (HRQoL) is mediated by inflammatory changes of the upper and lower airways. METHODS: Allergic rhinitics with mild asthma were randomized to a 14-day treatment period with either nasal budesonide 100 µg, 1 puff per nostril twice a day, or placebo. Clinical, functional, and biological evaluations were performed before and after treatment. RESULTS: Twenty subjects (M/F: 10/10; age: 31 ± 15 years; mean ± SD) were enrolled, and a total of 17 individuals completely participated in the study. Lung function was within the normal range. The total asthma control test (ACT) score was 20 ± 5.3 and the RHINASTHMA Global Summary (GS) was 44 ± 15. The percentage proportion of eosinophils in nasal lavage was 9.9% and significantly correlated with spirometric parameters reflecting peripheral airway function (for FEF(50): r = 0.48, p = .03; for FEF(25): r = 0.47, p = .03). The pH of the exhaled breath condensate (EBC) was 7.33 ± 0.4. After nasal treatment, the percentage proportion of eosinophils fell significantly (p = .002), and changes in percentage proportion of eosinophils were associated with changes both in the ACT score (r = 0.76, p = .04) and in the RHINASTHMA GS (r = 0.77, p = .02). The increase in the pH of the EBC was not associated with changes in the ACT score or with the RHINASTHMA GS. CONCLUSIONS: These findings confirm that, in subjects with allergic rhinitis with mild asthma, nasal inflammation impacts on asthma control and HRQoL. The improved control of respiratory symptoms obtained with nasal corticosteroids seems to be mediated by functional changes in the peripheral airways.