Striving for optimal bronchodilation: focus on olodaterol

β2-agonists were introduced in the 1940s as bronchodilators to be used in obstructive respiratory diseases. Long-acting β2-agonists have been a mainstay of bronchodilating treatment for decades. Recently, agents extending their effect to 24 hours and thus allowing the once-daily administration were introduced, defined as very-long-acting β2-agonists. Olodaterol is a new very-long-acting β2-agonist that has been shown, in controlled trials, to improve lung function as well as clinical outcomes and quality of life. Most of these trials included patients with moderate, severe, or very severe chronic obstructive pulmonary disease (COPD). Olodaterol has a rapid onset of action (comparable to formoterol) and provides bronchodilation over 24 hours. In controlled trials, olodaterol was shown to be as effective as formoterol twice daily, but significantly superior in terms of quality of life in patients with COPD. The safety profile of olodaterol was very good, with a rate of adverse events, including the cardiac events that are particularly important for β2-agonists, comparable to placebo. Also, the efficiency of the Respimat® device concurs to the effectiveness of treatment

Impairment of small airways in COPD patients with frequent exacerbations and effects of treatment with tiotropium

Disease exacerbations are an important aspect of COPD, because they affect its course and are associated with higher lung function decline. On the other hand, data obtained by biopsies have demonstrated that the progression of COPD is related to an increasing impairment of small airways. We sought to evaluate the small airway impairment (FEF25–75) in two groups of COPD patients (each group had 37 subjects) in relation to the frequency of exacerbations and the effectiveness of treatment with tiotropium bromide on the small airway impairment. The mean number of exacerbations was 3.6/year and 1.38/year in frequent and in infrequent exacerbators, respectively (p < 0.001). The mean value of FEF25–75 at baseline was 624 mL and 865 mL in frequent and in infrequent exacerbators respectively (p = 0.002). The changes in respiratory parameters versus baseline showed increases in mean FEV1, FVC, and FEF25–75 in both groups but only the increase in FEF25–75 in frequent exacerbators was statistically significantly (p = 0.013). During the 3-month period of the study the mean number of exacerbations was 0.66 in frequent and 0.12 in infrequent exacerbators. These findings indicate that COPD patients with frequent exacerbations have a higher impairment of small airways. Treatment with tiotropium in COPD subjects with frequent exacerbations proved to be effective in improving small airway impairment

Effectiveness of omalizumab in a patient with severe asthma and atopic dermatitis

The anti-IgE antibody omalizumab is currently indicated in severe asthma not controlled by standard drug therapy. Recently, new indications for omalizumab were suggested, which include atopic dermatitis (AD), a skin disorder characterized by elevated levels of IgE. We report the case of a 39-year old woman with severe asthma and severe AD, both resistant to conventional drug treatment. The patient had a IgE level of 1304 kU/L, which exceeded the recommended maximum level for treating asthma with omalizumab (stated in 700 Ku/L) but was far lower than previously reported in cases of AD treated with anti-IgE. The treatment consisted of a dose of omalizumab 375 mg every two weeks, and induced a rapid improvement of asthma, with no need of other drugs after three months, along with a progressive decline of severity of AD, which after five months was completely cured. These findings suggest the usefulness of omalizumab in patients with concomitant severe asthma and AD, also considering the pharmaco-economic balance obtained by withdrawing the multiple drugs used to treat both diseases

Current and future applications of the anti-IgE antibody omalizumab

IgE antibodies are a pivotal factor in pathophysiology of allergic diseases, and the possibility of reducing their level by anti-IgE has long been envisioned. Following several attempts, an effective biologic agent was obtained with the recombinant humanized mono-clonal antibody (rhuMAb)-E25, known as omalizumab. A number of controlled clinical trials demonstrated its efficacy and safety in the treatment of severe allergic asthma uncontrolled by standard drug treatment with maximal recommended doses, and treatment with omalizumab is currently included in international guidelines on asthma management. Other studies reported a clear effectiveness also in allergic rhinitis, but the cost of the anti-IgE treatment suggests its use in patients with rhinitis concomitant with asthma. Other indications to be further investigated are skin disorders such as atopic dermatitis and IgE-mediated urticaria, as well as adverse reactions to foods, with a particularly important role in preventing food-induced anaphylaxis. Finally, there are data indicating the usefulness of omalizumab when used in combination with allergen specific immunotherapy, in terms of reducing the adverse reactions to treatment and increasing the clinical efficacy

Different outcomes of pulmonary rehabilitation in patients with COPD with or without exacerbations

Background. Pulmonary rehabilitation is recognised as an effective treatment in reducing disability and improving the quality of life in patients with COPD. We evaluated the effects of a course of pulmonary rehabilitation in improving the physical performance and lung function in patients with or without COPD exacerbations. Methods. 74 patients with COPD were enrolled, 37 (24 males and 13 females, mean age 74.6 years) without exacerbations (group A), and 37 (23 males, 14 females, mean age 73.9 years) with exacerbations (group B). The latter must have had the latest exacerbation at least one month before the inclusion. All patients underwent to a rehabilitation programme of 8 visits in 4 weeks in a day-hospital setting, with exercise training, respiratory muscle training and education on COPD. The changes in physical performance and lung function in respect to baseline were measured by a 6-minute walking test, using phethysmography, and by an analogic manometer measuring maximal inspiratory and expiratory pressures (MIP, MEP). Results. Patients of group A showed a mean increase in timed walk distance of 58.38 ± 57.46 m, compared to a mean increase of 31.38 ± 44.78 m in group B patients (p = 0.028). As to lung function, a mean increase of 178.92 ± 132.28 ml in FEV1 in group A versus 67.84 ± 102.04 ml in group B (p < 0.0001) and a mean increase of 22.36 ± 25.06 cm H2O in MEP in group A versus 7.70 ± 12.28 cm H2O in group B (p = 0.002) was found. Conclusions. These findings indicate that patients with COPD with exacerbations achieve a less favourable outcome of pulmonary rehabilitation, with a significantly lower improvement of physical performance, respiratory muscle strength and lung function in respect to subjects without exacerbations

Sublingual immunotherapy: administration, dosages, use

Allergen extracts for sublingual immunotherapy (SLIT) are currently marketed by several manufacturers, with administration schedules and amount of allergen(s) quite variable in the different products, although almost all are standardized biologically or immunologically. The allergen extracts for SLIT are available in two main pharmaceutical forms: solution to be delivered by drop-counters, pre-dosed actuators (mini-pumps) or disposable single-dose vials; tablets with appropriate composition that allows a slow (1-2 minutes) dissolution in the mouth in contact with saliva. In Europe, SLIT is prescribed in general for one or a few allergens, and mixtures are less used, though there is no immunological contraindication to give multiple allergens. SLIT traditionally involves a build-up phase and a maintenance phase with the top dose. The build-up phase has usually the duration of 4 - 6 weeks. The patient must start with the lowest concentration and gradually increase, using the different dosage preparations, until the maintenance dose is reached. Rush and ultra-rush inductions have been introduced, based on the safety profile of SLIT that is very favorable. For these reasons it has been suggested that an updosing phase maybe even not necessary. The no-updosing approach would result in a treatment that is more patient-friendly and convenient to manage. Indeed, the most recent randomized trials were performed with the no-updosing regimen and their results in term of safety were as favorable as the studies performed with the traditional updosing approach. The currently recommended duration of SLIT is comprised between 3 and 4 years depending on the clinical response in single patients

Effects of pulmonary rehabilitation on exercise capacity in patients with COPD: A number needed to treat study

BACKGROUND: Pulmonary rehabilitation (PR) is recognized as an evidence-based treatment in improving dyspnea and quality of life in patients with COPD. We evaluated the number needed to treat (NNT) to achieve an increase in physical capacity, as defined by a significant improvement in the six-minute walk test (6MWT) in patients with COPD undergoing PR. METHODS: The study enrolled 284 patients aged 41 to 86 years (mean age 69.4 years) divided into two groups: a study group (222 patients) undergoing a PR program, and a control group (62 patients) treated only with drugs. The study group included patients with COPD divided in four subgroups according to GOLD stages. RESULTS: In the study group, 142 out of 222 patients (64%) had an increase of at least 54 m in the 6MWT following PR versus 8 out of 62 patients (13%) in the control group after the same time interval. The NNT in the overall study group was 2; the same NNT was obtained in GOLD stages 2, 3, and 4, but was 8 in stage 1. CONCLUSIONS: PR is highly effective in improving the exercise capacity of patients with COPD, as demonstrated by a valuable NNT, with better results in patients with a more severe disease

Dose dependence of efficacy and safety of subcutaneous immunotherapy

A number of experimental and clinical evidence has shown that exposure to high amounts of allergen molecules favours the development of tolerance. This is true also for subcutaneous immunotherapy (SCIT), for which a dose dependence of clinical efficacy was clearly demonstrated. The effective doses, measured as μg of major allergens, to be administered during maintenance treatment were established for the main allergens. Regarding pollens, the range of effectiveness corresponds to 25-41 and 13-20 μg of major allergens Phl p 5 and Phl p 6 for grasses, to 10-47 μg of Amb a 1 for ragweed, to 12 μg of Bet v 1 for birch, and to 6.2 μg of Par j 1 for Parietaria. With house dust mites, a maintenance dose of 5-11.5 μg of the major allergen from Dermatophagoides pteronyssinus Der p 1 is associated to clinically relevant effects, and with cat epithelium the clinical success is observed using a dose of 13-15 μg of Fel d 1. Nevertheless, there are adverse reactions facing SCIT, which are related to the amount of injected allergen. In fact, the safety decreases when the administered doses increase. This has led to “optimal doses” being defined which show a good balance between efficacy and safety (corresponding for example to a dose of 7 μg for Der p 1 and of 13 μg for Fel d 1). The dose dependency with respect to both efficacy and safety makes essential to accurately consider the risk/benefit ratio in each patient eligible for SCIT