Low incidence of pneumonia in COPD patients treated with inhaled corticosteroids undergoing pulmonary rehabilitation.

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.

Hypersensitivity pneumonitis: a complex lung disease.

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.

[Risk of pneumonia in patients with chronic obstructive pulmonary disease treated with inhaled corticosteroids: evidence and uncertainties]. / Il rischio di polmonite associato a terapia con corticosteroidi inalatori in pazienti con broncopneumopatia cronica ostruttiva: evidenze e incertezze.

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.

[Update on eosinophilic airway disorders]. / Aggiornamento sulle eosinofilie dell'apparato respiratorio.

Eosinophilic disorders of the airways affect the nose and paranasal sinuses, the bronchi and the lungs. Involvement of the nose includes the well known non allergic rhinitis with eosinophilia syndrome and new disorders characterized by co-participation of mast cells and neutrophils. Eosinophilic bronchitis must be distinguished from asthma, on the basis of some functional findings and a different cytokine profile. Eosinophilic pneumonia comprises acute and chronic forms, Churg-Strauss syndrome, hypereosinophilic syndrome, and eosinophilic granuloma, as well as secondary pneumonia such as Loeffler's syndrome.The treatment is mainly based on corticosteroids and the prognosis is variable, depending upon the development of acute respiratory failure (acute eosinophilic pneumonia, eosinophilic granuloma) or of vasculitis with multi-organ organ involvement in Churg-Strauss syndrome.

Allergen immunotherapy in atopic dermatitis.

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.

Safety and timing of resuming dabigatran after major gastrointestinal bleeding reversed by idarucizumab.

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.

Effects of replacing oxitropium with tiotropium on pulmonary function in patients with COPD: a randomized study.

BACKGROUND: Inhaled bronchodilators are first line drugs in the treatment of chronic obstructive pulmonary disease (COPD). Tiotropium bromide is a recently introduced long-acting anticholinergic agent able to reduce dyspnoea and COPD exacerbations and to improve pulmonary function and quality of life. We designed a study to compare the short-term efficacy of tiotropium bromide with that of oxitropium bromide in improving pulmonary function in patients with COPD. METHODS: Eighty patients were randomized either to continue oxitropium 800 mcg/day or to receive tiotropium 18 mcg/day. Seventy-six (39 in the tiotropium and 37 in the oxitropium group) completed the study. Plethysmography was performed at baseline and after 72 h in all patients. The changes in functional parameters in the two groups were compared by the Mann-Whitney U-test. RESULTS: There were no differences between the two groups regarding age (72.5 vs. 74.2 years), male/female ratio (25/14 vs. 23/14) and pulmonary function at baseline. The changes in spirometric parameters were significantly greater in tiotropium- than in oxitropium-treated patients: mean forced expiratory volume in 1s (FEV(1)) increased significantly by 15% vs. 3% (P=0.017), mean FVC by 10.5% vs. 2.2% (P=0.044), and FEF 25, 50, and 75 by 34% vs. 14% (P<0.05), 33% vs. 7% (P<0.05), and 50% vs. 6% (P<0.0001), respectively; mean FRC and RV decreased nonsignificantly by 7.5% and 10% with tiotropium vs. 4.3% and 6.5% with oxitropium, respectively. CONCLUSION: The replacement of oxitropium with tiotropium significantly increases pulmonary function in patients with COPD. The improvement involves also small airways that have not been investigated thus far.

About the effect of pulmonary rehabilitation on lung function in patients with chronic obstructive pulmonary disease.

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.

Striving for optimal bronchodilation: focus on olodaterol.

ß2-agonists were introduced in the 1940s as bronchodilators to be used in obstructive respiratory diseases. Long-acting ß2-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 ß2-agonists. Olodaterol is a new very-long-acting ß2-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 ß2-agonists, comparable to placebo. Also, the efficiency of the Respimat(®) device concurs to the effectiveness of treatment.

Glycopyrronium bromide for the treatment of chronic obstructive pulmonary disease.

Glycopyrronium bromide is a new long-acting muscarinic antagonist to be used once-daily, which is approved as a bronchodilator for the symptomatic maintenance treatment of adult patients with chronic obstructive pulmonary disease (COPD). In the Glycopyrronium bromide in chronic Obstructive pulmonary disease airWays trials, treatment with inhaled glycopyrronium bromide at 50 µg once daily achieved a significantly better lung function than placebo, as measured by the trough forced expiratory volume in 1 s in patients with moderate-to-severe COPD. The lung function improvement was maintained for up to 52 weeks. Other improved indexes were dyspnea scores, health status, exacerbation rates and time of exercise endurance. Studies comparing the efficacy of glycopyrronium versus tiotropium bromide found substantial equivalence of the two drugs. Glycopyrronium was generally well tolerated. These data add inhaled glycopyrronium bromide to the treatment of patients with moderate to severe COPD as an effective once-daily LAMA.

Combination therapy with indacaterol and glycopyrronium bromide in the management of COPD: an update on the evidence for efficacy and safety.

The international guidelines on chronic obstructive pulmonary disease (COPD) recommend inhaled bronchodilators for maintenance treatment of the disease. These drugs include ß2-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 ß2-agonists) and indacaterol, vilanterol and olodaterol (very long-acting ß2-agonist) as ß2-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.

Omalizumab, an anti-immunoglobulin E antibody: state of the art.

A large number of trials show that the anti-immunoglobulin (Ig) E antibody omalizumab is very effective in patients with severe allergic asthma. This is acknowledged in consensus documents. The drug also has a good safety profile and a pharmacoeconomic advantage due to a reduction in the number of hospitalizations for asthma attacks. In recent years, some studies have shown that omalizumab is effective also in nonallergic asthma. Effects on the complex signaling mechanisms leading to activation of effector cells and to mediator release may account for this outcome. Indeed, omalizumab has been reported to be effective in a number of IgE-mediated and non-IgE-mediated disorders. Concerning the former, clinical efficacy has been observed in rhinitis, allergic bronchopulmonary aspergillosis, latex allergy, atopic dermatitis, allergic urticaria, and anaphylaxis. In addition, omalizumab has been demonstrated to be able to prevent systemic reactions to allergen immunotherapy, thus enabling completion of treatment in patients who otherwise would have to stop it. Concerning non-IgE-mediated disorders, omalizumab has been reported to be effective in nasal polyposis, autoimmune urticaria, chronic idiopathic urticaria, physical urticaria, idiopathic angioedema, and mastocytosis. Current indications for treatment with omalizumab are confined to severe allergic asthma. Consequently, any other prescription can only be off-label. However, it is reasonable to expect that the use of omalizumab will be approved for particularly important indications, such as anaphylaxis, in the near future.

Role of indacaterol and the newer very long-acting ß2-agonists in patients with stable COPD: a review.

Bronchodilators are central drugs in the management of patients with chronic obstructive pulmonary disease (COPD). Indacaterol was the first agent of the novel family of very long-acting ß2-agonists to be used as an inhaled bronchodilator for COPD and provides 24-hour therapeutic action, thus allowing once-daily administration. Data from clinical trials show that indacaterol has a bronchodilator effect similar to that of the anticholinergic tiotropium bromide and slightly higher efficacy compared with the long-acting ß2-agonists, salmeterol and formoterol. Moreover, the safety profile is excellent and comparable with that of placebo. Concerning adherence with drug treatment and real-life management in respect to long-acting ß2-agonists, once-daily dosing makes indacaterol more convenient for COPD patients and is likely to enhance patient adherence. Other very long-acting ß2-agonists currently in development include vilanterol, olodaterol, and carmoterol, and these have shown good characteristics for clinical use in the studies reported thus far.

Shrinking the room for invasive ventilation in hypercapnic respiratory failure.

Noninvasive ventilation (NIV) was introduced as an alternative to invasive mechanical ventilation for acute respiratory failure caused from exacerbations of chronic obstructive pulmonary disease in the 1980s, and its use gradually rose worldwide. Seventy-eight patients (57 males, mean age 78.3 ± 9.2 years) undergoing NIV were evaluated. Of them, 48 (62.3%) had acute hypercapnic respiratory failure because of a chronic obstructive pulmonary disease exacerbation, and the remaining 30 had acute hypercapnic respiratory failure from other causes, mainly cardiac failure. All patients were treated by NIV using the bi-level positive airway pressure set up at high pressure/high backup rate. NIV was successful in 67 subjects (85.9%) and the patients were discharged, 57 of whom continued NIV at home and ten had spontaneous breathing. NIV was unsuccessful in eleven patients, ten of whom died and one was successfully treated by invasive mechanical ventilation. Significant differences were detected for a higher basal Glasgow Coma Scale score in successfully treated patients (P = 0.007), a higher basal Acute Physiology and Chronic Health Evaluation score in unsuccessfully treated patients (P = 0.004), and a lower pH after 1 hour in unsuccessfully treated patients (P = 0.015). These findings show a very high rate of success of NIV in patients with acute hypercapnic respiratory failure not only from chronic obstructive pulmonary disease but also from cardiac failure. This suggests that the use of invasive mechanical ventilation may be further reduced, with a decrease in its known complications as well.

Skin reaction to inhaled tiotropium bromide: a case report.

INTRODUCTION: Systemic reactions to inhaled drugs are rare. To the best of our knowledge, we report the first case of generalized itching related to the use of tiotropium bromide, a long acting inhaled anti-cholinergic agent commonly used to treat chronic obstructive pulmonary disease. CASE PRESENTATION: A 78-year-old Caucasian woman was referred to our facility for allergological evaluation. Our patient had been treated twice with tiotropium for chronic obstructive pulmonary disease and had experienced an allergic reaction with itching. We performed a double-blind placebo-controlled inhalation challenge for our patient with tiotropium and a placebo. Inhalation tests yielded positive results for tiotropium and negative results for the placebo. The results of a skin prick test with tiotropium were negative. CONCLUSIONS: These findings reveal that tiotropium may elicit immediate skin allergic reactions. The negative result from the skin test suggests that such a reaction is not immunoglobulin E-mediated.