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Cristoforo Incorvaia,1 Marcello Montagni,2 Elena Makri,1 Gian Galeazzo Riario-Sforza,1 Erminia Ridolo21Allergy/Pulmonary Rehabilitation, Istituti Clinici di Perfezionamento Hospital, Milan, Italy; 2Department of Clinical and Experimental Medicine, University of Parma, Parma, ItalyAbstract: 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.Keywords: bronchodilators, β2-agonists, very long acting, olodaterol, efficacy, safety, COPD

Competing Interests: There are no conflicts of interest.

Background: Based on meta-analyses results, it is currently acknowledged that there is an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD) undergoing inhaled corticosteroids (ICS) treatment. However, this is not found to be true in those with asthma. No data on this risk are available for COPD patients involved in pulmonary rehabilitation program (PR)., Methods: For 1 year, we prospectively studied 2 cohorts of COPD patients-undergoing PR and not undergoing PR. The first group included 438 patients undergoing PR of which 353 were treated with ICS, and 85 were treated with bronchodilators only. The second group was comprised of 76 COPD patients who were treated with ICS, but not PR. The control group consisted of 49 ICS-treated patients with asthma. The diagnosis of pneumonia, when suspected, had to be confirmed with a chest x-ray., Results: Overall, 6 cases of pneumonia were diagnosed in the first study group: 5 ICS-treated patients and 1 patient treated only with bronchodilators. This corresponded to a rate of 1.41 and 1.17%, respectively, compared to a rate of 6.6% in COPD patients not treated with PR, which was significantly higher (p = 0.029) than that in the first study group. No case of pneumonia was registered among patients with asthma., Conclusions: These findings suggest that a significantly lower incidence of pneumonia is found in COPD patients treated with ICS and PR than in patients treated with ICS but not with PR. This observation deserves to be investigated in large populations of PR-treated COPD patients, possibly in multi-centric cohort studies.

The recent introduction of direct oral anticoagulants, including rivaroxaban, dabigatran, apixaban, and edoxaban, for the acute treatment and secondary prevention of venous thromboembolism and in atrial fibrillation has been shown to provide greater clinical benefit than oral vitamin K antagonists. However, direct oral anticoagulants are associated with adverse events, the most common being major bleeding; such events require the reversal of the anticoagulant effects by specific agents. In this case report, we describe an 87-year-old female with atrial fibrillation treated with dabigatran who had massive rectal bleeding. Idarucizumab 5 g (2 × 2.5 g/50 mL) was successfully used to reverse dabigatran effect; subsequent to this, treatment with dabigatran was resumed, and there were no further bleeding events. This suggests that dabigatran can be safely restarted after major bleeding, but this outcome needs to be confirmed in studies involving larger groups of patients., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Incorvaia reports personal fees from Bayer S.p.A., personal fees from Stallergenes Italy S.r.l., outside the submitted work.

Introduction: Atopic dermatitis (AD) is a chronic relapsing skin disease, characterized by flare-up due to the exposure to allergens in patients sensitized to them. Currently, therapy of AD is mainly based on symptomatic treatment and avoidance of irritating/allergenic factors, house dust mites being particularly important. Allergen immunotherapy (AIT) is suggested to be the only etiologic treatment, to modify the natural history of the disease. Areas covered: The aim of this review is investigating the putative role of AIT in AD through the evaluation of the most recent scientific literature. Several studies have been conducted since 1970, with promising results in improving the clinical outcome of AD, but they often lack the necessary scientific rigorousness. Moreover, heterogeneity of the studies makes it very difficult to compare and to analyze data in a systematic review or meta-analysis. Expert commentary: As a result of the above-mentioned limitations, the treatment of AD with causative aeroallergen can nowadays be suggested only as an add-on therapy in selected patients who are non-responsive to the traditional therapy.

Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a respiratory syndrome involving the lung parenchyma and specifically the alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic reaction. Such reaction is secondary to a repeated and prolonged inhalation of different types of organic dusts or other substances to which the patient is sensitized and hyper responsive, primarily consisting of organic dusts of animal or vegetable origin, more rarely from chemicals. The prevalence of HP is difficult to evaluate because of uncertainties in detection and misdiagnosis and lacking of widely accepted diagnostic criteria, and varies considerably depending on disease definition, diagnostic methods, exposure modalities, geographical conditions, agricultural and industrial practices, and host risk factors. HP can be caused by multiple agents that are present in work places and in the home, such as microbes, animal and plant proteins, organic and inorganic chemicals. The number of environment, settings and causative agents is increasing over time. From the clinical point of view HP can be divided in acute/subacute and chronic, depending on the intensity and frequency of exposure to causative antigens. The mainstay in managing HP is the avoidance of the causative antigen, though the complete removal is not always possible due to the difficulties to identify the agent or because its avoidance may lead to major changes in life style or occupational settings. HP is a complex syndrome that needs urgently for more stringent and selective diagnostic criteria and validation, including wider panels of IgG, and a closer collaboration with occupational physicians, as part of a multidisciplinary expertise.

Background: Allergen immunotherapy (AIT) in its two forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) is an effective treatment of respiratory allergy, but is particularly concerned by the issue of compliance., Objective: We aimed a real-life study at evaluating the compliance to SLIT and to SCIT administered by a short-course of four injections during a 3-year period of observation., Methods: A group of 145 patients (79 males, 66 females, age ranging from 14 to 69 years), suffering from pollen-induced rhino-conjunctivitis with or without asthma, were included in the study. Following adequate education on AIT and according to patient's preference, 72 patients chose to be treated with short-course SCIT and 73 chose to be treated with SLIT. The latter was performed by allergen extracts from different manufacturers according to the suggested schedules., Results: The rate of withdrawal was as follows: after one year, 15.6% for SCIT and 33.4 for SLIT; after two years, 25.6% for SCIT and 44.8% for SLIT; after three years, 26.7 for SCIT and 46% for SLIT. There was no significant difference in the rate of withdrawal between males and females. Regarding the safety, no systemic reaction requiring medical treatment was observed either in SCIT or SLIT group., Conclusion: The findings of this study confirm that involving the patient in the choice of the route of administration is associated to a satisfactory compliance to AIT. In particular, more than 70% of patients treated with a short schedule of SCIT completed the three-years course of treatment that is recommended for AIT, while this goal was reached by 54% of SLIT treated patients.

A large number of studies, evaluated by several meta-analyses, indicate that patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids have a significantly increased risk of pneumonia which, however, is not associated with a corresponding increase in mortality. The increased risk seems to be exclusive of COPD, since meta-analyses involving patients with asthma treated with inhaled corticosteroids did not show a risk of pneumonia higher than that of the general population. Possible interventions to reduce this risk are to improve adherence to guidelines for prescribing inhaled corticosteroids in COPD (often used even in mild to moderate disease, for which they are not indicated), and using lower doses.

Detecting an improvement of lung function in a patient with chronic obstructive pulmonary disease (COPD) following pulmonary rehabilitation (PR) may appear unexpected, but actually recent studies showed that is not so rare. In fact, in a prospective study comparing a group of 190 COPD patients undergoing PR to a group of 67 patients treated only with drugs a mean improvement of FEV1 from 1240 mL to 1252.4 mL was found in the former, while the values changed from 1367 mL to 1150 mL in the latter (p < 0.001). Such improvement was detected also in a study in patients with very severe COPD, as assessed by a FEV1 increasing from 970 mL at baseline to 1080 mL after a 3-week PR inpatient program (p < 0.001). These observations suggest that improvement of lung function in COPD patients undergoing PR should be included among the expected outcomes and routinely assessed as an index of clinical success during the treatment.

The international guidelines on chronic obstructive pulmonary disease (COPD) recommend inhaled bronchodilators for maintenance treatment of the disease. These drugs include β2-agonists and muscarinic antagonists, which are both available as short-acting agents (to be used as needed for dyspnea) and long-acting agents. To the latter belong salmeterol and formoterol (long-acting β2-agonists) and indacaterol, vilanterol and olodaterol (very long-acting β2-agonist) as β2-agonists, and tiotropium, aclidinium and glycopyrronium bromide as long-acting muscarinic antagonists. The efficacy and safety of indacaterol and glycopyrronium as monotherapies has been demonstrated in several controlled trials. However, in some patients with moderate-to-severe COPD, symptoms are poorly controlled by bronchodilator monotherapy; in these cases the addition of a second bronchodilator from a different pharmacological class may be beneficial. Here we review the evidence from published randomized trials concerning the efficacy and safety of the once-daily fixed-dose dual bronchodilator combining indacaterol and glycopyrronium., (© The Author(s), 2015.)