Multidisciplinary Respiratory Medicine最新文献

Background: Horses commonly suffer from chronic respiratory disease and are also used in large animal models of spontaneous or induced airway inflammation. The anti-inflammatory properties of curcumin are largely described but its low bioavailability precludes its clinical use. NDS27, a lysin salt of curcumin incorporated in beta-cyclodextrine, has high bioavailability and can be administered by inhalation. The aim of this study was to investigate the effects of inhaled NDS27 on inflammatory cytokines and proteins in the broncho-alveolar lavage fluid using a model of neutrophilic airway inflammation.

Methods: Airway neutrophilia was induced in eight horses by inhalation of lipopolysaccharides (LPS). Horses were treated with either inhalation of NDS27 or with placebo in a randomized cross-over design. Broncho-alveolar lavages were performed 6 hours after stimulation with LPS. Percentage of neutrophils, concentrations of IL-1β, TNF-α, IL-6, Club cell secretory protein, myeloperoxidase (MPO) and elastase (ELT) concentrations were determined.

Results: LPS stimulation induced significant increases in neutrophil counts and concentrations of IL-6 (70.2 ± 66.0 pg/ml), TNF-α (43.9 ± 31.2 pg/ml), MPO (580.9 ± 327.0 ng/ml) and ELT (27.6 ± 16.7 ng/ml). Treatment with NDS27 significantly prevented the increase in active and total MPO (216.4 ± 118.1 ng/ml) and ELT (5.9 ± 3.2 ng/ml) while there was a trend towards reduced IL-6 concentration.

Conclusions: Results show that, although not reducing neutrophil recruitment, NDS27 largely abolishes LPS-induced neutrophil degranulation. Reduced levels of ELT and MPO, as well as reduced MPO activity may have beneficial effects via a reduced production of reactive oxygen species implicated in chronic inflammation and airway remodeling.

Recently, there has been increasing interest in the use of non invasive ventilation (NIV) to increase exercise capacity. In individuals with COPD, NIV during exercise reduces dyspnoea and increases exercise tolerance. Different modalities of mechanical ventilation have been used non-invasively as a tool to increase exercise tolerance in COPD, heart failure and lung and thoracic restrictive diseases. Inspiratory support provides symptomatic benefit by unloading the ventilatory muscles, whereas Continuous Positive Airway Pressure (CPAP) counterbalances the intrinsic positive end-expiratory pressure in COPD patients. Severe stable COPD patients undergoing home nocturnal NIV and daytime exercise training showed some benefits. Furthermore, it has been reported that in chronic hypercapnic COPD under long-term ventilatory support, NIV can also be administered during walking. Despite these results, the role of NIV as a routine component of pulmonary rehabilitation is still to be defined.

Dry powder inhalers (DPIs) are widely and increasingly used in clinical practice because they represent a substantial advancement in inhalation technology. The effectiveness of a powdered drug to inhale depends on the inspiratory flow rate generated by the patient and on the turbulence produced by the intrinsic resistance of the DPI. While the inspiratory flow is variable with the patient's ability and conditions, the turbulence is differently sized within each device because depending of its technical design. There are higher - medium-, and low-resistance devices. With low-resistance DPIs, the disaggregation and the microdispersion of the drug highly depend on the patient's inhalation airflow rate, because the role of the resistance-induced turbulence is obviously negligible in these cases. This flow-rate dependency is minimized in the presence of a sufficient regimen of turbulence as in the case of medium-resistance DPIs. Both the disaggregation and the micro-dispersion of the powdered drug are optimized in these circumstances even in the absence of a maximal inspiratory flow rate. The low resistance DPIs should not be regarded as the best performer DPIs because their intrinsic low-resistance regimen requires a higher inspiratory airflow rate and effort, which frequently cannot be achieved by subjects suffering from a disease-induced airflow limitation. Only when the ratio between the inhalation flow rate and the DPI intrinsic resistance is balanced, the speed of the particulate, the distribution of the drug within the lung, and the variability of the effective inhaled dose are optimized.

Background: For many years until now, Italy has been subjected to an inconsistent and contradictory media campaign. On one hand the "media" present us with bold and reassuring messages about the progress of medical science; on the other hand they are prone to kneejerk criticism every time medical treatment does not have the desired effect, routinely describing such cases as glaring examples of "malasanità", an Italian word of recent coinage used to denote medical malpractice. Newspaper reports of legal proceedings involving health treatment are frequently full of errors and lack any scientific basis.

Data sources: The published data confirm the unsustainably high number of lawsuits against doctors and medical structures, accompanied by demands for compensation arising from true or alleged medical errors or mistakes blamed on the work of health structures.

Conclusions and implications: Currently Italian citizens have a greater awareness of their right to health than in the past, and patients' expectations have risen. A discrepancy is emerging between the current state of medical science and the capacities of individual doctors and health structures. Lastly, there is a need for greater monitoring of the quality of health care services and a greater emphasis on health risk prevention.

We herein report a case of invasive candidiasis presenting rare findings on chest computed tomography (CT). The chest CT scan showed multiple small cavitary lesions and nodules with surrounding ground-glass opacity, and also bilateral pleural effusion. Although this CT finding is thought as specific for pulmonary aspergillosis, two sets of blood culture specimens were drawn which yielded Candida albicans in our case. Antifungal therapy was started and the chest CT findings showed a remarkable improvement. To our knowledge, this is the first case report describing multiple pulmonary cavitary lesions in invasive candidiasis.

This paper is a theoretical and empirically informed examination of the naturalist distinction between withholding and withdrawing life-support. Drawing on the history of mechanical ventilation and on a recent Israeli law containing a novel approach to disconnecting life-support at the end of life, it is argued that the design of machines predicates the division line between "active" and "passive" interventions, and that the distinction itself might be morally self-defeating. Informed by insights from moral psychology, behavioral economics and philosophies of technology, the paper warns against the placement of this old distinction at the heart of the moral and legal regulation of life-support at the end of life.

Background: Bronchial thermoplasty (BT) is a new therapeutic option for severe refractory asthma not controlled despite high dose inhaled corticosteroids plus long-acting bronchodilators and omalizumab in selected cases. Risk of pulmonary atelectasis after BT in severe asthma has been described in literature, but no details have been reported on the possible mechanisms of the complication.

Case presentation: A 49-year-old male with severe uncontrolled asthma was referred to BT. One hour after the first procedure, acute respiratory failure occurred with PaO2/FiO2 < 300. A CT scan showed atelectasis of the right lower and middle lobes. A new bronchoscopy was performed under non-invasive ventilation; the right lower and middle lobe bronchus were occluded by bronchus-shaped plugs, that were very difficult to remove despite repeated saline washings and fragmentation with forceps. The patient had a rapid resolution of respiratory failure. Four weeks later, 6 hours after the second session of BT, severe bronchospasm occurred with respiratory failure. Chest X-Ray showed atelectasis of the left lower lobe, prompting to perform a new flexible bronchoscopy on non-invasive ventilation. The exam showed again a plug occluding the left lower lobar bronchus, removed with forceps and washings. The histological analysis of the plugs demonstrated the massive presence of fibrin with mucus debris, rare Charcot-Leyden crystals, scattered macrophages, neutrophils, eosinophils and bronchial epithelial cells.

Conclusion: The originality of our case report is related to the recurrence of bronchial plugging with lobar atelectasis within one and five hours respectively, after two sequential BT procedures. At the histological evaluation the bronchial plugs appeared very different from the typical mucoid asthma plugs, being composed prevalently by fibrin. It can be hypothesized that intense thermal stimulation of the bronchial mucosa may represent a strong boost for inflammation in susceptible patients, with microvascular alteration induced directly by heat or through the release of mediators. Although in severe asthma a risk of atelectasis from the classical asthma mucoid plugs may be expected, the peculiarity of our case resides in the formation of fibrin plugs whose direct correlation with BT should be considered.

Background: We offer some perspectives and commentary on the sedation of obese patients in the intensive care unit (ICU).

Discussion: Sedation in morbidly obese patients should conform to the same broad principles now current in ICU practice. These include a general presumption against benzodiazepines as first-line agents. Opioids should be avoided in any situation where spontaneous breathing is required. Remifentanil is the preferred agent where continuous stable opioid levels using an infusion are required, because of its lack of context-sensitive accumulation. Volatile anaesthetics may be an option for the same reason but there are no substantial, controlled demonstrations of effectiveness/safety in short-term use in the ICU setting. Propofol is a valuable resource in the morbidly obese patients but the duration of continuous sedation should not exceed 6 days, in order to avoid propofol infusion syndrome. Alpha-2 agonists offer a range of theoretically positive features for the sedation of morbidly obese patients, but at present there is a lack of pharmacokinetic data and a critical mass of high-grade clinical data. Dexmedetomidine has the attraction of not causing respiratory depression or obstructive breathing during sedation and its sympatholytic effects should help deliver stable blood pressure and heart rate. Ketamine has a poor tolerability profile in adults so its use in the ICU context is largely confined to paediatrics.

Conclusion: None of the agents currently available is ideal for every situation encountered in the management of morbidly obese patients. This article identifies additional research needed to place sedation practice of obese patients on a more systematic footing.

Background: Data for the U.S adult population from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate risk factors for a restrictive pattern on spirometry and estimate the change in its prevalence from the 1988-1994 to 2007-2010 sampling periods. Several previous epidemiologic studies used the Global Initiative for Chronic Obstructive Lung Disease fixed forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 0.70 criteria for classifying restrictive pattern rather than the age-defined American Thoracic Society (ATS)/European Respiratory Society (ERS) lower limit of normal (LLN) criteria, which may lead to misclassification.

Methods: Spirometry measurements from NHANES data for the 1988-1994 and 2007-2010 periods were analyzed to estimate the age-standardized prevalence of a restrictive pattern on spirometry and the change in prevalence over time for adults aged 20-79. A restrictive pattern was defined based on ATS/ERS LLN criteria as FEV1/FVC > LLN and FVC < LLN, and a moderate to more severe restrictive pattern was further evaluated using FEV1 < 70% predicted. The associations between demographic and other individual risk factors for restrictive lung impairment were examined using multivariable logistic regression models for the two consecutive time periods.

Results: The overall age-standardized prevalence of restrictive pattern decreased significantly from 7.2% (1988-1994) to 5.4% (2007-2010) (p = 0.0013). The prevalence of moderate to more severe restrictive pattern also decreased significantly from 2.0% to 1.4% (p = 0.023). Factors positively associated with restrictive pattern on spirometry included age, female sex, white race, lower education, former and current smoking, and comorbidities including doctor-diagnosed cardiovascular disease, doctor-diagnosed diabetes, and abdominal obesity.

Conclusions: The overall prevalence of restrictive pattern and moderate to more severe restrictive pattern decreased between the 1988-1994 and 2007-2010 survey periods despite a population increase in the proportion of comorbidities associated with restrictive pattern (i.e. diabetes and abdominal obesity). This suggests a decline in individual risk factors for restrictive pattern and a need for future research.