Ermanno Puxeddu

The prevalence of asthma and COPD in Italy: A practice-based study

We conducted a population-based cross-sectional epidemiologic survey of asthma and COPD in an adult representative national sample using information obtained from the Health Search Database owned by the Italian College of General Practitioners. General Practitioners who had a list of patient population of 909,638 individuals (429,962 men and 479,676 women; man/woman ratio [M/WR]: 0.89) ≥ 14 years old at the end of December 2009 were selected to be representatives of the whole Italian population. Cases of asthma and COPD were identified on the basis of the ICD-9 codes. The total sample included 55,500 (6.10% of the entire population; 5.49% of men and 6.64% of women; M/WR: 0.74) subjects suffering from asthma and 25,762 (2.83% of the entire population; 3.51% of men and 2.23% of women; M/WR: 1.41) subjects suffering from COPD. The asthma/COPD ratio in general population was 2.16. The odds ratio (OR) was chosen because asthma and COPD had a prevalence less than 10%. The OR of developing asthma decreased with age both in men and women, but in the first group of age (15-34 years) it was higher in men vs. women (1.69 vs. 1.00) although it became lower than 1 from 35 years old and up in men and from 75 years old and up in women. On the contrary, the OR of developing COPD became higher than 1 from 55 years old and up both in men and in women and progressively increased with age (in the group 75-84 years, it was 6.16 in men and 4.07 in women, respectively).

Searching for the synergistic effect between aclidinium and formoterol: From bench to bedside.

Aim of our study was to understand if the interaction between aclidinium and formoterol administered at therapeutic doses leads to a synergistic rather than additive broncholytic effect. We tested the type of effect ex vivo on isolated human bronchi and then in vivo in COPD patients. The analysis of the interaction between aclidinium and formoterol in vitro was measured by applying the Unified Theory, whereas that in COPD patients was measured by applying the Bliss Independence criterion. Aclidinium and formoterol administered alone completely relaxed human isolated bronchial tissues sub-maximally pre-contracted with ACh in a concentration-dependent manner with similar potency (EC50: aclidinium 4.64 ± 0.78 nM, formoterol 2.71 ± 0.21), whereas the interaction of aclidinium plus formoterol produced moderate to strong synergism. Changes in FEV1 values showed that inhaled aclidinium and formoterol induced a significant and time-dependent bronchodilatory effect during the study time. The inhalation of aclidinium and formoterol in combination significantly anticipated at 5 min post-administration the bronchodilatory effect of FEV1, compared with the effect of drugs administered alone. There was a synergistic interaction for FEV1 at 5 min and from 120 min to 240 min post-inhalation, whereas from 30 min to 60 min post-administration the drug interaction was additive. This study shows that aclidinium and formoterol can produce a significant synergistic interaction that may have a role also in the clinic setting.

Optimizing drug delivery in COPD: The role of inhaler devices

BACKGROUND Inhaled medication is the cornerstone of the pharmacological treatment for patients with asthma and chronic obstructive pulmonary disease (COPD). Several inhaler devices exist, and each device has specific characteristics to achieve the optimal inhalation of drugs. The correct use of inhaler devices is not granted and patients may incur in mistakes when using pressurized metered-dose inhalers (pMDIs) or dry-powder inhaler (DPIs). The incorrect use of inhaler devices can lead to a poorly controlled disease status. Unfortunately, guidelines provide limited guidance regarding the choice of devices. This article presents a review of the literature on different inhaler device requirements. Data from literature (PubMed and Google Scholar) on the commercially available inhaler devices have been evaluated and the history of inhaler medicine described. Furthermore, advantages and disadvantages of each type of device have been analyzed. The evaluation of literature indicated the availability of robust data on the devices characteristics and factors influencing selection of delivery devices. Each type of device has its own pro and cons. The age, cognitive status, visual acuity, manual dexterity, manual strength and ability to coordinate the inhaler actuation with inhalation may be as important as the disease severity in determining the correct approach to delivery of respiratory medication. The administration of effective therapies via a device that is simple to use and accepted by patients may help to improve treatment outcomes in patients with COPD.

LABA/LAMA combination in copd: A meta-analysis on the duration of treatment

When there are no randomised clinical trials directly comparing all relevant treatment options, an indirect treatment comparison via meta-analysis of the available clinical evidence is an acceptable alternative. However, meta-analyses may be very misleading if not adequately performed. Here, we propose and validate a simple and effective approach to meta-analysis for exploring the effectiveness of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations in chronic obstructive pulmonary disease. 14 articles with 20 329 patients (combinations n=9292; monocomponents n=11 037) were included in this study. LABA/LAMA combinations were always more effective than the monocomponents in terms of the improvement in trough forced expiratory volume in 1 s, transition dyspnoea index and St Georges Respiratory Questionnaire scores after 3, 6 and 12 months of treatment. No significant publication bias was identified. Significant discrepancies with previous network meta-analyses have been found, with overall differences ranging from 26.7% to 43.3%. Results from previous network meta-analyses were misleading because no adequate attention was given to formulating the review question, specifying eligibility criteria, correctly identifying studies, collecting appropriate information and deciding what it would be pharmacologically relevant to analyse. The real gradient of effectiveness of LABA/LAMA fixed-dose combinations remains an unmet medical need; however, it can be investigated indirectly using a high-quality meta-analytic approach. We propose a simple and effective meta-analytic approach for exploring the impact of LABA/LAMA combinations in COPD http://ow.ly/8Zd9302154B

Interaction between corticosteroids and muscarinic antagonists in human airways

BACKGROUND To date there is emerging clinical evidence to add long-acting anti-muscarinic agents (LAMAs) with inhaled corticosteroid (ICSs) in asthma, but the pharmacological rationale that supports the use of such a combination has not yet been explained. The aim of this study was to pharmacologically investigate the interaction between the ICS beclomethasone and the LAMA glycopyrronium on the human airway smooth muscle (ASM) tone. METHODS We investigated the rapid non-genomic bronchorelaxant effect of beclomethasone and glycopyrronium, administered alone and in combination, in human isolated bronchi and bronchioles. Experiments were carried out also in passively sensitized airways and the pharmacological analysis of drug interaction was performed by Bliss Independence method. RESULTS The acute administration of beclomethasone and glycopyrronium induced a significant relaxation of passively sensitized ASM pre-contracted with histamine, by causing submaximal/maximal inhibition of the contractile tone in both medium bronchi and bronchioles. Beclomethasone was characterized by a rapid non-genomic and epithelium independent bronchorelaxant effect. In passively sensitized airways, this effect seemed to be dependent by the activation of a Gsα--cyclic adenosine monophosphate (cAMP)--protein kinase A cascade. While no synergistic interaction was detected in non-sensitized bronchi, the beclomethasone/glycopyrronium combination synergistically enhanced the relaxation of passively sensitized medium and small bronchi. The synergistic interaction between beclomethasone and glycopyrronium was associated with an increase of cAMP concentrations. CONCLUSIONS Our study provides for the first time the pharmacological rationale for combining low doses of an ICS plus a LAMA.

Effect of an additional dose of indacaterol in COPD patients under regular treatment with indacaterol

AIM In this randomized, double-blind, crossover study, we explored the acute effects on respiratory function and safety of an additional dose of indacaterol 150 μg in stable COPD patients regularly treated with a conventional dose of indacaterol 150 μg. METHODS On two non-consecutive days, patients inhaled indacaterol 150 μg. After 180 min, they inhaled an additional dose of indacaterol 150 μg or placebo. Lung function, oxygen saturation by pulse oximetry (SpO(2)) and heart rate were measured before the first drug administration and up to 360 min thereafter. RESULTS In both treatment groups, indacaterol induced a significant (P < 0.05) bronchodilation during all the study time. The difference between the FEV(1) AUCs(0-180 min) was not statistically significant (P = 0.971). On the contrary, the difference between the FEV(1) AUCs(180-360 min) was significant (P < 0.0001). However, only 8 out of 20 patients showed a further increase of at least 100 ml from the peak obtained after the first administration of indacaterol 150 μg with the second dose of 150 μg. Indacaterol 150 μg induced a modest but significant decrease in SpO(2) up to 60 min and a second dose of indacaterol 150 μg significantly decreased the SpO(2) mean value up to 360 min. CONCLUSION This study suggests that it is reasonable and safe to increase the dose of indacaterol in those stable COPD patients who are under regular therapy with indacaterol 150 μg from which they do not draw the maximum benefit because they are unable to perceive bronchodilation. However, only a minority of patients seem to benefit from this dose escalation, at least in terms of spirometric improvement.

Airflow obstruction: is it asthma or is it COPD?

Despite the availability of guideline recommendations, diagnostic confusion between COPD and asthma appears common, and often it is very difficult to decide whether the obstruction is caused by asthma or COPD in a patient with airway obstruction. However, there are well-defined features that help in differentiating asthma from COPD in the presence of fixed airflow obstruction. Nonetheless, the presentations of asthma and COPD can converge and mimic each other, making it difficult to give these patients a diagnosis of either condition. The association of asthma and COPD in the same patient has been designated mixed asthma–COPD phenotype or overlap syndrome. However, since the absence of a clear definition and the inclusion of patients with different characteristics under this umbrella term, it may not facilitate treatment decisions, especially in the absence of clinical trials addressing this heterogeneous population. We are realizing that neither asthma nor COPD are single diseases, but rather syndromes consisting of several endotypes and phenotypes, consequently comprising a spectrum of diseases that must be recognized and adequately treated with targeted therapy. Therefore, we must treat patients by personalizing therapy on the basis of those treatable traits present in each subject.

Acute COPD exacerbation: 3 T MRI evaluation of pulmonary regional perfusion – Preliminary experience

OBJECTIVES To compare pulmonary perfusion parameters by means of dynamic perfusion magnetic resonance in patients affected by chronic obstructive pulmonary disease (COPD), during and after acute exacerbation. METHODS Fifteen patients were successfully evaluated with perfusional MRI during an acute exacerbation of COPD and upon clinical stabilization. Inclusion criteria were a PaCO2 > 45 mmHg and respiratory acidosis (arterial blood pH < 7.35) at admittance. RESULTS In the acute phase a reduction of pulmonary blood flow (PBF) and pulmonary blood volume (PBV), and a significant prolonging of the mean transit time (MTT) and time to peak (TTP) were observed in all patients. In the stabilization phase a significant increase of PBF and PBV and a significant reduction of MTT and TTP were observed in 6 patients; no significant variations were observed in the other 9 patients. CONCLUSION 3D time-resolved contrast-enhanced MRI allows quantitative evaluation of pulmonary regional perfusion in patients affected by COPD, identifying patients in which perfusion defects are resolved in the clinical-stabilization phase. This technique might allow the identification of patients in whom vasospasm may be the main responsible of pulmonary hypoperfusion during acute COPD exacerbation, with potential advantages on the clinical management of these patients.

A 6MWT index to predict O2 flow correcting exercise induced SpO2 desaturation in ILD

INTRODUCTION Ambulatory oxygen (O2) is prescribed to interstitial lung disease (ILD) patients with mild hypoxemia, breathlessness and dyspnea on exertion. Oxygen titration is generally done with the 6 minute walk test (6MWT) to determine the O2 flow preventing oxygen saturation by pulse oximetry (SpO2) from falling below 88%. His study was designed to generate a 6MWT index predicting the O2 flow allowing completion of the 6MWT without oxygen desaturation. METHODS Oxygen titration data from a group of 66 ILD patients and 30 controls, were used to generate the algorithm determining an index (O2-GAP) predicting oxygen flow required to complete a 6MWT without desaturation below 88%. This index was validated in a group of 93 ILD patients. RESULTS The O2-GAP index, as obtained from the derivation population, (r(2) = 0.97, p < 0.001) was shown to correctly predict the oxygen flow required to complete the 6MWT without SpO2 falling below 88% validated in the validation population (r(2) = 0.842; p < 0.001). CONCLUSIONS The O2-GAP index appears to be a useful tool to titrate ambulatory O2 with a single 6MWT on room air in ILD patients with breathlessness and dyspnea on exertion.

Adherence to COPD treatment: Myth and reality

COPD is a chronic disease in which effective management requires long-term adherence to pharmacotherapies but the level of adhesion to the prescribed medications is very low and this has a negative influence on outcomes. There are several approaches to detect non-adherence, such as pharmacy refill methods, electronic monitoring, and self-report measures, but they are all burdened with important limitations. Medication adherence in COPD is multifactorial and is affected by patients (health beliefs, cognitive abilities, self-efficacy, comorbidities, psychological profile, conscientiousness), physicians (method of administration, dosing regimen, polypharmacy, side effects), and society (patient-prescriber relationship, social support, access to medication, device training, follow-up). Patient-health care professional communication, especially that between patient and physician or pharmacist, is central to optimizing patient adherence. However, the most realistic approach is to keep in mind that non-adherence is always possible, indeed, probable.