F. Di Marco

Effect of inhaled bronchodilators on inspiratory capacity and dyspnoea at rest in COPD

It has been shown that patients with chronic obstructive pulmonary disease (COPD) develop dynamic hyperinflation (DH), which contributes to dyspnoea and exercise intolerance. Formoterol, salmeterol and oxitropium have been recommended for maintenance therapy in COPD patients, but their effect on DH has only been assessed for salmeterol. The aim of the present study was to compare the acute effect of four inhaled bronchodilators (salbutamol, formoterol, salmeterol and oxitropium) and placebo on forced expiratory volume in one second, inspiratory capacity, forced vital capacity and dyspnoea in COPD patients. A cross-over, randomised, double-blind, placebo-controlled study was carried out on 20 COPD patients. Patients underwent pulmonary function testing and dyspnoea evaluation, in basal condition and 5, 15, 30, 60 and 120 min after bronchodilator or placebo administration. The results indicate that in chronic obstructive pulmonary disease patients with decreased baseline inspiratory capacity, there was a much greater increase of inspiratory capacity after bronchodilator administration, which correlated closely with the improvement of dyspnoea sensation at rest. For all bronchodilators used, inspiratory capacity reversibility should be tested at 30 min following the bronchodilator. On average, formoterol elicited the greatest increase in inspiratory capacity than the other bronchodilators used, though the difference was significant only with salmeterol and oxitropium. The potential advantage of formoterol needs to be tested in a larger patient population.

Asthma control in elderly asthmatics. An Italian observational study

BACKGROUND The exponential increase of individuals aged >64 yrs is expected to impact the burden of asthma. We aimed to explore the level of asthma control in elderly subjects, and factors influencing it. METHODS A multicenter observational study was performed on consecutive patients >64 years old with a documented physician-diagnosis of asthma. Sixteen Italian centers were involved in this 6-month project. FINDINGS A total of 350 patients were enrolled in the study. More than one-third of elderly asthmatic patients, despite receiving GINA step 3-4 antiasthmatic therapy, had an Asthma Control Test score ≤19, with a quarter experiencing at least one severe asthma exacerbation in the previous year. Twenty-nine percent of patients (n = 101) were classified as having Asthma-COPD Overlap Syndrome (ACOS) due to the presence of chronic bronchitis and/or CO lung diffusion impairment. This subgroup of patients had lower mean Asthma Control Test scores and more exacerbations compared to the asthmatic patients (18 ± 4 compared to 20 ± 4, p < 0.01, and 43% compared to 18%, p < 0.01, respectively). Modified Medical Research Council dyspnea mMRC scores and airway obstruction, assessed on the basis of a FEV(1)/FVC ratio below the lower limit of normal, were more severe in ACOS than in asthma, without any difference in responses to salbutamol. In a multivariate analysis, the mMRC dyspnea score, FEV(1)% of predicted and the coexistence of COPD were the only variables to enter the model. INTERPRETATION Our results highlight the need to specifically evaluate the coexistence of features of COPD in elderly asthmatics, a factor that worsens asthma control.

Effect of prasugrel in patients with asthma: results of PRINA, a randomized, double-blind, placebo-controlled, cross-over study.

Although experimental studies have demonstrated that platelets are proinflammatory cells, no randomized studies have tested the anti‐inflammatory effect of antiplatelet agents in humans. The platelet P2Y12 receptors mediated bronchial inflammation in a mouse model of asthma, suggesting that P2Y12 represents a pharmacologic target for asthma.

Comparison of the Bronchodilating Effect of Salmeterol and Zafirlukast in Combination with That of Their Use as Single Treatments in Asthma and Chronic Obstructive Pulmonary Disease

Background: It has been suggested that the effect of a β2-agonist is additive with that of a cysteinyl leukotriene 1 receptor antagonist. Objectives: The present study was designed to answer the question of whether combined administration of inhaled salmeterol and oral zafirlukast at the standard doses would result in greater bronchodilation in patients with chronic airway obstruction than the use of either drug alone. Methods: The study was performed using a double-blind, double-dummy, crossover, randomised design, and was conducted on 4 non-consecutive days. Sixteen patients with moderate to severe chronic obstructive pulmonary disease (COPD) and 10 non-smoker asthmatic patients received 40 mg of oral zafirlukast, 50 µg of inhaled salmeterol, 50 µg of inhaled salmeterol plus 40 mg of oral zafirlukast of placebo. Lung function was assessed before drug administration and 30, 60, 120, 180 and 240 min thereafter. At the end of the 4-hour period, each patient received 400 µg of inhaled salbutamol and spirometric testing was performed 30 min later. Results: In both asthmatic and COPD patients, the overall effect of salmeterol and zafirlukast on the forced expiratory volume in 1 s (FEV1) was considered extremely significant (p < 0.0001), with a maximum bronchodilation above baseline after 180 min (20.7 and 11.0%, respectively) in asthmatics and after 2 h (21.7 and 11.2%, respectively) in COPD subjects. Zafirlukast did not produce any further significant acute bronchodilation in addition to that achieved with salmeterol alone in either asthmatic or COPD patients. Nevertheless, 7 out of 16 COPD patients and 7 out of 10 asthmatic patients had a further improvement after the combination of salmeterol and zafirlukast. The mean difference in pre- and post-salbutamol FEV1 values in both asthmatic and COPD patients after zafirlukast was significant (p < 0.05), but that after salmeterol and the combination of the two drugs was not significant (p > 0.05). The difference between placebo and zafirlukast was not significant following inhaled salbutamol given 4 h after each treatment. Conclusions: Both salmeterol and zafirlukast induced a significant increase in FEV1, although salmeterol elicited a greater improvement in both asthmatic and COPD patients. Apparently, zafirlukast at the clinically recommended dose did not produce any further significant acute bronchodilation in addition to that achieved with salmeterol alone, either in asthma or COPD. In any case, evaluation of the effect of the combination over a 12-hour period is mandatory.

Bronchodilation test in COPD: effect of inspiratory manoeuvre preceding forced expiration

The effects of an inspiratory manoeuvre preceding forced expiration on functional tests performed under routine conditions before and after inhalation of a bronchodilator drug (salbutamol) were assessed on 150 consecutive chronic obstructive pulmonary disease outpatients. The patients performed forced vital capacity manoeuvres either immediately after a rapid inspiration (manoeuvre no. 1) or after a slow inspiration with a 4–6 s pause (manoeuvre no. 2). Under baseline conditions, forced expiratory volume in one second (FEV1) values were 8% (% control) larger with manoeuvre no. 1 than no. 2. FEV1 values increased with salbutamol administration by ∼8% and were, on average, still 7% larger with manoeuvre no. 1 than no. 2. The incidence of reversibility, assessed according to American Thoracic Society criteria, was 76% when manoeuvre no. 2 was selected to represent baseline conditions and manoeuvre no. 1 was chosen to represent the effects of bronchodilator administration, whereas the lowest incidence (2%) was found when manoeuvre no. 1 was selected to represent baseline conditions and manoeuvre no. 2 was chosen to represent the effects of bronchodilator administration. These results indicate that the time dependence of the forced vital capacity manoeuvre has an important impact on the assessment of routine lung function in a clinical setting and supports the notion that the time course of the inspiration preceding the forced vital capacity manoeuvre should be standardised.

Asthma-COPD overlap syndrome: recent advances in diagnostic criteria and prognostic significance

The term asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has been proposed for individuals with features of both asthma and COPD. Several attempts have been done to define ACOS on the basis of medical history, symptoms, and functional findings. The main diagnostic criteria include airflow obstruction with a strong although incomplete reversibility to bronchodilation tests, a significant exposure to cigarette or biomass smoke, and a history of atopy or asthma. Additional diagnostic elements include eosinophilic airway and systemic inflammation, a good response to corticosteroid treatment, and a high concentration of exhaled nitric oxide. ACOS should be distinguished from asthma with not fully reversible bronchial obstruction due to airway remodeling, thus the lack of smoking exposure should exclude the diagnosis of ACOS. In patients without a documented history of asthma before 40 years of age, an increase in FEV1 after bronchodilator >400 mL should be required to diagnose ACOS. ACOS has been found to be associated with impaired physical performance, functional ability, and health-related quality of life. The prevalence of ACOS increases with aging, then it is relatively stable in elderly individuals (>65 years). Long-term mortality of subjects with ACOS is similar to COPD, and worse than asthma and healthy controls. Future research is still needed to improve the understanding and management of ACOS.

Monitoring and Mechanical Ventilator Setting During Noninvasive Mechanical Ventilation: Key Determinants in Post-extubation Respiratory Failure

Extubation failure is usually defined as the need for reintubation within 48–72 h following extubation [1]. Patients may be unable to maintain spontaneous breathing for multiple reasons: increased workload of breathing, cardiovascular dysfunction, airway obstruction, or excessive secretions. The incidence of post-extubation respiratory failure ranges between 10 and 20 % [2]. Patients who fail extubation have higher mortality, consistently reported at about 20–50 % in intensive care units (ICUs), and longer ICU and hospital stays [3]. Reintubation is a risk factor for ventilator-associated pneumonia [4] and is independently associated with ICU mortality [3, 5, 6]. A minority of reintubated patients die in the first 24 h after reintubation, whereas mortality increases with time to reintubation [7]. Moreover, upper-airway obstruction is the reason for reintubation in about 5–15 % of cases, but no increase in mortality has been reported in this population [7]. Thus, three scenarios explain the higher mortality rate: (1) reintubation entails risks per se, (2) it is a marker for severity of illness, or (3) it is a consequence of a new event occurring between extubation and reintubation.