Fabiano Di Marco

Anxiety and depression in asthma.

Purpose of review There is growing awareness of the correlation between psychological factors, the course of asthma, and the outcomes of asthma treatment. However, the implications of this correlation are still poorly understood. Here, we review the role of anxiety and depression in asthma with a focus on recent literature. Recent findings Recent studies suggest an interaction between behavioral, neural, endocrine, and immune processes and suggest that psychological factors play an active role in the genesis of asthma. Notably, the role of chronic stress has been investigated, including the parental psychological state during pregnancy. There is evidence that in patients with asthma, such stress may induce hyporesponsiveness of the hypothalamus–pituitary–adrenal axis, resulting in reduced cortisol secretion. Summary Even though it is generally accepted that anxiety and depression are more common in asthmatic patients and that there is a close correlation between psychological disorders and asthma outcomes, such as poorer control of asthma symptoms, the implications and practical consequences of this link remain weak. New studies are introducing an intriguing model of the links between emotional stress, brain centers, the immune system, and the hypothalamus–pituitary–adrenal axis that is far removed from the original concept of ‘asthma nervosa’.

Can lung ultrasound replace chest radiography for the diagnosis of pneumonia in hospitalized children

Background: Lung ultrasound is a non-radiating accurate alternative tool to chest X-ray (CXR) in the diagnosis of community-acquired pneumonia (CAP) in adults. Objectives: The aim of our study was to define the accuracy of ultrasound in the diagnosis of CAP in children. Methods: 107 consecutive children with suspected CAP underwent clinical examination, blood sample analysis, CXR and lung ultrasound on admission to the Pediatric Department of the San Paolo Hospital. The diagnosis of pneumonia was made by an independent committee of physicians on the basis of the overall clinical and CXR data. Results: The diagnosis of CAP was confirmed by the committee in 81 patients (76%). Ultrasound and CXR were performed in all patients. Ultrasound had a sensitivity of 94% and specificity of 96%, while CXR showed a sensitivity of 82% and a specificity of 94%. In patients with CAP, ultrasound revealed subpleural consolidations with air bronchogram in 70 cases and focal B-lines in 6. A parapneumonic pleural effusion was detected in 17 patients by ultrasound, while only 11 of them could be detected by CXR. Conclusions: In our series, lung ultrasound was highly accurate for the diagnosis of CAP in hospitalized children. These results provide the rationale for a multicenter study in children.

Positive end-expiratory pressure-induced functional recruitment in patients with acute respiratory distress syndrome.

Objective:In acute respiratory distress syndrome, alveolar recruitment improves gas exchange only if perfusion of the recruited alveolar units is adequate. To evaluate functional recruitment induced by positive end-expiratory pressure, we assessed pulmonary conductance for gas exchange based on lung diffusion for carbon monoxide and its components, including pulmonary capillary blood volume. Design:Prospective, randomized, crossover study. Setting:Medical intensive care unit of a university hospital. Patients:Sixteen patients with lung injury/acute respiratory distress syndrome as well as eight control patients under invasive ventilation and eight healthy volunteers. Interventions:Mechanical ventilation with two levels of positive end-expiratory pressure (5 and 15 cm H2O). Measurements and Main Results:Lung diffusion for carbon monoxide and lung volumes, arterial blood gas analysis, and pressure-volume curves. In patients with acute respiratory distress syndrome, high positive end-expiratory pressure induced a 23% mean lung diffusion for carbon monoxide increase (4.4 ± 1.7 mm Hg−1 · min−1 vs. 3.6 ± 1.4 mL · mm Hg−1 · min−1). In control patients and in healthy volunteers, lung diffusion for carbon monoxide values were (median [interquartile range]) 5.5 [3.8-8.0] mm Hg−1 · min−1 and 19.6 [15.1-20.6] mL · mm Hg−1 · min−1, respectively. Among patients with acute respiratory distress syndrome, eight showed a >20% lung diffusion for carbon monoxide increase (responders) when increasing positive end-expiratory pressure. In the other eight, lung diffusion for carbon monoxide decreased or showed a <5% increase (nonresponders) with high positive end-expiratory pressure. Compared with nonresponders, responders at low positive end-expiratory pressure had smaller lungs with higher capillary blood volume-to-lung-volume ratio, higher values of the lower inflection point, and significantly greater increases in pulmonary capillary blood volume with high positive end-expiratory pressure. High positive end-expiratory pressure increased PaO2/Fio2 only in the responders. Conclusions:The functional response to positive end-expiratory pressure in patients with acute lung injury/acute respiratory distress syndrome seems better when the lungs are smaller and with a higher capillary blood-volume-to-lung-volume ratio. Lung diffusion for carbon monoxide measurement supplies additional information about functional lung recruitment, which is not synonymous with mechanical recruitment.

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.

Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine

Abstract The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a “multilevel cycle” responsible for the control of the oxidant/antioxidant homeostasis. Several studies have demonstrated the presence of increased oxidative stress and decreased antioxidants (e.g. reduced glutathione [GSH]) in subjects with chronic obstructive pulmonary disease (COPD), but the contribution of oxidative stress to the pathophysiology of COPD is generally only minimally discussed. The aim of this review was to provide a comprehensive overview of the role of oxidative stress in the pathogenesis of respiratory diseases, particularly COPD, and to examine the available clinical and experimental evidence on the use of the antioxidant N-acetylcysteine (NAC), a precursor of GSH, as an adjunct to standard therapy for the treatment of COPD. The proposed concept of “multilevel cycle” helps understand the relationship between respiratory diseases and oxidative stress, thus clarifying the rationale for using NAC in COPD. Until recently, antioxidant drugs such as NAC have been regarded only as mucolytic agents. Nevertheless, several clinical trials indicate that NAC may reduce the rate of COPD exacerbations and improve small airways function. The most plausible explanation for the beneficial effects observed in patients with COPD treated with NAC lies in the mucolytic and antioxidant effects of this drug. Modulation of bronchial inflammation by NAC may further account for these favorable clinical results.

Optimization of ventilator setting by flow and pressure waveforms analysis during noninvasive ventilation for acute exacerbations of COPD: a multicentric randomized controlled trial

IntroductionThe analysis of flow and pressure waveforms generated by ventilators can be useful in the optimization of patient-ventilator interactions, notably in chronic obstructive pulmonary disease (COPD) patients. To date, however, a real clinical benefit of this approach has not been proven.MethodsThe aim of the present randomized, multi-centric, controlled study was to compare optimized ventilation, driven by the analysis of flow and pressure waveforms, to standard ventilation (same physician, same initial ventilator setting, same time spent at the bedside while the ventilator screen was obscured with numerical data always available). The primary aim was the rate of pH normalization at two hours, while secondary aims were changes in PaCO2, respiratory rate and the patients tolerance to ventilation (all parameters evaluated at baseline, 30, 120, 360 minutes and 24 hours after the beginning of ventilation). Seventy patients (35 for each group) with acute exacerbation of COPD were enrolled.ResultsOptimized ventilation led to a more rapid normalization of pH at two hours (51 vs. 26% of patients), to a significant improvement of the patients tolerance to ventilation at two hours, and to a higher decrease of PaCO2 at two and six hours. Optimized ventilation induced physicians to use higher levels of external positive end-expiratory pressure, more sensitive inspiratory triggers and a faster speed of pressurization.ConclusionsThe analysis of the waveforms generated by ventilators has a significant positive effect on physiological and patient-centered outcomes during acute exacerbation of COPD. The acquisition of specific skills in this field should be encouraged.Trial registrationClinicalTrials.gov NCT01291303.

Assessment of acute bronchodilator effects from specific airway resistance changes in stable COPD patients

BACKGROUND In COPD patients, reversibility is currently evaluated from the changes of forced expiratory volume at 1s (ΔFEV1) and forced vital capacity (ΔFVC). By lowering peripheral airway smooth muscle tone, bronchodilators should decrease dynamic hyperinflation, gas trapping, and possibly dyspnea at rest. Hence, we hypothesize that specific airway resistance changes (ΔsRAW) should better characterize the acute response to bronchodilators. METHODS On two days, 60 COPD patients underwent dyspnea evaluation (VAS score) and pulmonary function testing at baseline and one hour after placebo or 300μg indacaterol administration. RESULTS Spirographic and ΔsRAW-based criteria identified as responders 24 and 45 patients, respectively. ΔsRAW correlated with changes of intrathoracic gas volume (ΔITGV) (r=0.61; p<0.001), residual volume (ΔRV) (r=0.60; p<0.001), ΔFVC (r=0.44; p=0.001), and ΔVAS (r=0.73; p<0.001), while ΔFEV1 correlated only with ΔFVC (r=0.34; p=0.008). Significant differences in terms of ΔITGV (p=0.002), ΔRV (p=0.023), and ΔVAS (p<0.001) occurred only if patients were stratified according to ΔsRAW. CONCLUSIONS In assessing the acute functional effect of bronchodilators, ΔsRAW-based criterion is preferable to FEV1-FVC-based criteria, being more closely related to bronchodilator-induced improvements of lung mechanics and dyspnea at rest.

Accuracy and precision of end-expiratory lung-volume measurements by automated nitrogen washout/washin technique in patients with acute respiratory distress syndrome

IntroductionEnd-expiratory lung volume (EELV) is decreased in acute respiratory distress syndrome (ARDS), and bedside EELV measurement may help to set positive end-expiratory pressure (PEEP). Nitrogen washout/washin for EELV measurement is available at the bedside, but assessments of accuracy and precision in real-life conditions are scant. Our purpose was to (a) assess EELV measurement precision in ARDS patients at two PEEP levels (three pairs of measurements), and (b) compare the changes (Δ) induced by PEEP for total EELV with the PEEP-induced changes in lung volume above functional residual capacity measured with passive spirometry (ΔPEEP-volume). The minimal predicted increase in lung volume was calculated from compliance at low PEEP and ΔPEEP to ensure the validity of lung-volume changes.MethodsThirty-four patients with ARDS were prospectively included in five university-hospital intensive care units. ΔEELV and ΔPEEP volumes were compared between 6 and 15 cm H2O of PEEP.ResultsAfter exclusion of three patients, variability of the nitrogen technique was less than 4%, and the largest difference between measurements was 81 ± 64 ml. ΔEELV and ΔPEEP-volume were only weakly correlated (r2 = 0.47); 95% confidence interval limits, -414 to 608 ml). In four patients with the highest PEEP (≥ 16 cm H2O), ΔEELV was lower than the minimal predicted increase in lung volume, suggesting flawed measurements, possibly due to leaks. Excluding those from the analysis markedly strengthened the correlation between ΔEELV and ΔPEEP volume (r2 = 0.80).ConclusionsIn most patients, the EELV technique has good reproducibility and accuracy, even at high PEEP. At high pressures, its accuracy may be limited in case of leaks. The minimal predicted increase in lung volume may help to check for accuracy.

Physical Activity Impairment in Depressed COPD Subjects

BACKGROUND: Limited exercise tolerance is a cardinal clinical feature in COPD. Depression and COPD share some clinical features, such as reduced physical activity and impaired nutritional status. The aim of the present study was to evaluate maximum and daily physical activities and the nutritional status of COPD patients affected or not by depression. METHODS: In 70 COPD out-patients, daily and maximum physical activities were assessed by multisensor accelerometer armband, 6-min walk test, and cardiopulmonary exercise test. Mental status, metabolic/muscular status, and systemic inflammation were evaluated using the Hospital Anxiety and Depression Scale, by bioelectrical impedance analysis, and with regard to fibrinogen/C-reactive protein, respectively. RESULTS: Depressed subjects (27% of the sample) showed a similar level of respiratory functional impairment but a higher level of shortness of breath and a worse quality of life compared to non-depressed subjects (P < .05). Specifically, they displayed a physical activity impairment consisting of a reduced number of steps per day, a lower peak of oxygen consumption, an early anaerobic threshold, and a reduced distance in the 6-min walk test (P < .05) but the same nutritional status compared to non-depressed subjects. In the multivariate analysis, a reduced breathing reserve, obesity, and a higher level of shortness of breath, but not depression, were found to be independent factors associated with a reduced daily number of steps. CONCLUSIONS: Our study found that depressed COPD patients have a reduced daily and maximum exercise capacity compared to non-depressed patients. This further suggests the potential utility of screening for depression in COPD.

How Do Dual Long-Acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?

&NA; Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long‐acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long‐acting &bgr;2‐adrenergic agonists (LABAs) and long‐acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long‐acting bronchodilators or LABA/inhaled corticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease.