Vincenzo Valenti

Acute exacerbations of asthma in adults: role of Chlamydia pneumoniae infection

Respiratory infections precipitate wheezing in many asthmatic patients and may be involved in the aetiopathogenesis of asthma. Several studies have demonstrated that viral infections may provoke asthma. Bacterial infections seem to play a minor role. However, Chlamydia pneumoniae has been recently reported as a possible cause of asthma. The aim of the present study was to evaluate the role of C. pneumoniae infection in acute exacerbations of asthma in adults. Seventy four adult out-patients with a diagnosis of acute exacerbation of asthma were studied. Acute and convalescent (> or = 3 weeks) serological determination of antibodies to cytomegalovirus, respiratory syncytial virus, adenovirus, influenza A and B, parainfluenza 1 and 3, Mycoplasma pneumoniae and Legionella pneumophila were performed by means of immunofluorescence tests. C. pneumoniae specific antibodies were detected by two microimmunofluorescence tests using a specific antigen (TW-183) and a kit with three chlamydial antigens. Pharyngeal swab specimens were also obtained for C. pneumoniae identification. Samples for bacterial culture were obtained in patients with productive cough (15 out of 74 patients). Fifteen patients (20%) presented seroconversion to at least one of the studied pathogens. Seven were found to be infected by virus, six by C. pneumoniae alone, and one by M. pneumoniae. One more patient showed seroconversion to C. pneumoniae and cytomegalovirus.(ABSTRACT TRUNCATED AT 250 WORDS)

A systematic review on tracheostomy decannulation: A proposal of a quantitative semiquantitative clinical score

BackgroundTracheostomy is one of the most common surgical procedures performed in critical care patient management; more specifically, ventilation through tracheal cannula allows removal of the endotracheal tube (ETT). Available literature about tracheostomy care and decannulation is mainly represented by expert opinions and no certain knowledge arises from it.MethodsIn lack of statistical requirements, a systematic and critical review of literature regarding tracheostomy tube removal was performed in order to assess predictor factors of successful decannulation and to propose a predictive score. We combined 3 terms and a literature search has been performed using the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE via Ovid SP; EMBASE via Ovid SP; EBSCO. Abstracts were independently reviewed: for those studies fitting the inclusion criteria on the basis of the title and abstract, full-text was achieved. We included studies published from January 1, 1995 until March 31, 2014; any sort of review and expert opinion has been excluded by our survey. English language restriction was applied. Ten studies have been considered eligible for inclusion in the review and were analysed further.ResultsCough effectiveness and ability to tolerate tracheostomy tube capping are the most considered parameters in clinical practice; other parameters are taken into different consideration by many authors in order to proceed to decannulation. Among them, we distinguished between objective quantitative parameters and semi-quantitative parameters more dependent from clinician’s opinion. We then built a score (the Quantitative semi Quantitative score: QsQ score) based on selected parameters coming from literature.ConclusionsOn our knowledge, this review provides the first proposal of decannulation score system based on current literature that is hypothetical and requires to be validated in daily practice. The key point of our proposal is to give a higher value to the objective parameters coming from literature compared to less quantifiable clinical ones.

Effect of indacaterol on lung deflation improves cardiac performance in hyperinflated COPD patients: an interventional, randomized, double-blind clinical trial

Background COPD is often associated with cardiovascular comorbidity. Treatment guidelines recommend therapy with bronchodilators as first choice. We investigated the acute effect of single-dose indacaterol on lung hyperinflation in COPD subjects, for the first time evaluating the potential effects on right heart performance. Methods In this Phase IV, randomized, interventional, double-blind, crossover clinical study, we recruited 40 patients (50–85 years of age) with stable COPD. Patients were treated with 150 μg indacaterol or placebo and after 60 minutes (T60) and 180 minutes (T180) the following tests were performed: trans-thoracic echocardiography (TTE), plethysmography, diffusing capacity of the lung for carbon monoxide, saturation of peripheral oxygen, and visual analog scale dyspnea score. Patients underwent a crossover re-challenge after a further 72 hours of pharmacological washout. All TTE measurements were conducted blindly by the same operator and further interpreted by two different blinded operators. Consensus decisions were taken on every value and parameter. The primary outcome was the effect of the reduction of residual volume and functional residual capacity on right heart systolic and diastolic function indexes evaluated by TTE in patients treated with indacaterol, as compared to placebo. Results Vital capacity, inspiratory capacity, and forced expiratory volume in 1 second were significantly increased by indacaterol, when compared with placebo, while residual volume, intrathoracic gas volume, and specific airway resistance were significantly reduced in patients treated with indacaterol. Tricuspid annular plane systolic excursion was significantly increased versus placebo, paralleled by an increase of tricuspid E-wave deceleration time. The cardiac frequency was also significantly reduced in indacaterol-treated patients. Conclusion Indacaterol significantly reduces lung hyperinflation in acute conditions, with a clinically relevant improvement of dyspnea. These modifications are associated with a significant increase of the right ventricular compliance indexes and may have a role in improving left ventricular preload leading to a reduction in cardiac frequency.

Acute myocardial infarction versus other cardiovascular events in community- acquired pneumonia

The aim of the present study was to define the prevalence, characteristics, risk factors and impact on clinical outcomes of acute myocardial infarction (AMI) versus other cardiovascular events (CVEs) in patients with community-acquired pneumonia (CAP). This was an international, multicentre, observational, prospective study of CAP patients hospitalised in eight hospitals in Italy and Switzerland. Three groups were identified: those without CVEs, those with AMI and those with other CVEs. Among 905 patients, 21 (2.3%) patients experienced at least one AMI, while 107 (11.7%) patients experienced at least one other CVE. Patients with CAP and either AMI or other CVEs showed a higher severity of the disease than patients with CAP alone. Female sex, liver disease and the presence of severe sepsis were independent predictors for the occurrence of AMI, while female sex, age >65 years, neurological disease and the presence of pleural effusion predicted other CVEs. In-hospital mortality was significantly higher among those who experienced AMI in comparison to those experiencing other CVEs (43% versus 21%, p=0.039). The presence of AMI showed an adjusted odds ratio for in-hospital mortality of 3.57 (p=0.012) and for other CVEs of 2.63 (p=0.002). These findings on AMI versus other CVEs as complications of CAP may be important when planning interventional studies on cardioprotective medications. Acute myocardial infarction is associated with specific risk factors and accounts for worse outcomes in CAP patients http://ow.ly/QhT2t

Newer antibiotics for the treatment of respiratory tract infections

Purpose of review In this review, we highlight some of the developments achieved over the past 2 years in the field of novel antimicrobial compounds. Recent findings Modification of existing compound classes to create more powerful compounds capable of overcoming pathogen resistance and the introduction of completely new classes of antibiotics and inhibitors of new bacterial targets or inhibitors of genes relating to virulence or pathogenesis are the strategies more commonly employed in pharmacologic research. Ketolides, oxazolidinones, streptogramins, glycylcyclines, and peptide deformylase inhibitors are among the most promising classes of antibiotics. Recently, several lines of research have documented that it is effective to target the infection process rather than killing bacteria. This is important because it is likely that such a therapeutic strategy could ablate infection without inducing resistance. Summary Emergence of resistance to the antibiotics currently employed in clinical practice is a continual stimulus for further research aimed at identifying novel antimicrobial compounds. These drugs will perhaps effectively fight against bacteria that now are scarcely controlled by the traditional antimicrobial agents. Health care personnel must appreciate that only judicious use of antimicrobial drugs will prevent the further uncontrolled spread of bacterial resistance. Implementation of reference guidelines would probably be an effective way to limit antibiotic misuse.

A 13-year-old female with shortness of breath and pleuritic chest pain

A 13-yr-old Caucasian female was referred to the Dept of Paediatric Diseases (Havana, Cuba) with shortness of breath and pleuritic chest pain located in her right hemithorax. The pain had occurred the day before while doing physical activity and lasted ∼1 h. The patient reported a 2-month history of recurrent episodes of pleuritic chest pain, which were either self-limited or relieved by paracetamol, as well as growing fatigue in the previous few weeks. Her past history was remarkable for a diagnosis of pneumonia after exposure to fumigation during a dengue haemorrhagic fever epidemic 2 yrs earlier, which was treated with steroids and antibiotics. On admission, the patient had no weight loss, no fever or dyspnoea. Physical examination showed decreased breathing sounds in the inferior part of both hemithoraces. Cardiovascular, abdominal and neurological examination, as well as ear, nose and ophthalmologic investigations were unremarkable. The chest radiograph showed bilateral pneumonia with moderate right-sided pleural effusion. The leukocyte count was 9.8×109 cells·L−1 with 54% neutrophils and 32% lymphocytes. The erythrocyte sedimentation rate was 85 mm·h−1. Serum chemistry, renal and liver function tests were in the normal range. Blood cultures were negative. Antibiotic therapy with ceftriaxone and amikacin was started. During the treatment the patient reported 2 days of moderate fever and various episodes of left-sided pleuritic chest pain, which occurred especially during forceful diaphragm contractions ( i.e. sneezing, laughing and coughing). Following a short stay in the Cuban hospital, the patient was transferred to an Italian hospital (Como). Amikacin was discontinued and clarithromycin added. A new chest radiograph (fig. 1⇓), 14 days after the previous one, and a computed tomography (CT) scan of the thorax were performed. Echocardiography and abdominal ultrasound were both negative. An increased value of the tumour marker CA-125 (220 U·mL−1, versus a normal value <35 U·mL−1) was found. Microbiological …

Telithromycin in lower respiratory tract infections

Telithromycin is a ketolide, a semisynthetic derivative of the 14-membered ring macrolide antibiotics, with an expanded spectrum of activity relative to macrolides. Its good tissue pharmacokinetic characteristics allows once-daily administration, and it has been successfully employed in lower respiratory tract infections. Recent data indicate that telithromycin may exert anti-inflammatory/immunomodulatory effects that may be of use in the treatment of both acute and chronic airway diseases. This review examines the role of telithromycin in lower respiratory tract infections, analyzing published data on exacerbations of chronic bronchitis, community-acquired pneumonia and asthma in adults. In addition, pharmacokinetic and pharmacodynamic properties of the drug are considered.

Macrolide therapy is associated with lower mortality in community-acquired bacteraemic pneumonia

BACKGROUND Community-acquired pneumonia (CAP) has a potential complication of bacteremia. The objective of this study was to define the clinical outcomes of patients with CAP and bacteremia treated with and without a macrolide. MATERIALS AND METHODS Secondary analysis of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP. Patients with a positive blood culture were categorized based on the presence or absence of a macrolide in their initial antimicrobial regimen, and severity of their CAP. Outcomes included in-hospital all-cause mortality, 30-day mortality, length of stay, and time to clinical stability. RESULTS Among 549 patients with CAP and bacteremia, 247 (45%) were treated with a macrolide and 302 (55%) were not. The primary pathogen was Streptococcus pneumoniae (74%). Poisson regression with robust error variance models were used to compare the adjusted effects of each study group on the outcomes. The unadjusted 30-day mortality was 18.4% in the macrolide group, and 29.6% in the non-macrolide group (adjusted relative risk (aRR)0.81; 95% confidence interval (CI)0.50-1.33; P = 0.41). Unadjusted in-hospital all-cause mortality was 7.3% in the macrolide group, and 18.9% in the non-macrolide group (aRR 0.54, 95% CI 0.30-0.98; P = 0.043). Length of stay and time to clinical stability were not significantly different. CONCLUSIONS In-hospital mortality, but not 30-day mortality, was significantly better in the macrolide group. Our data support the use of a macrolide in hospitalized patients with CAP and bacteraemia.

Role of nebulized glycopyrrolate in the treatment of chronic obstructive pulmonary disease

In the upcoming years, the proportion of elderly patients with chronic obstructive pulmonary disease (COPD) will increase, according to the progressively aging population and the increased efficacy of the pharmacological treatments, especially considering the management of chronic comorbidities. The issue to prescribe an appropriate inhalation therapy to COPD patients with significant handling or coordination difficulties represents a common clinical experience; in the latter case, the choice of an inadequate inhalation device may jeopardize the adherence to the treatment and eventually lead to its ineffectiveness. Treatment options that do not require particular timing for coordination between activation and/or inhalation or require high flow thresholds to be activated should represent the best treatment option for these patients. Nebulized bronchodilators, usually used only in acute conditions such as COPD exacerbations, could fulfill this gap, enabling an adequate drug administration during tidal breathing and without the need for patients’ cooperation. However, so far, only short-acting muscarinic antagonists have been available for nebulization. Recently, a nebulized formulation of the inhaled long-acting muscarinic antagonist glycopyrrolate, delivered by means of a novel proprietary vibrating mesh nebulizer closed system (SUN-101/eFlow®), has progressed to Phase III trials and is currently in late-stage development as an option for maintenance treatment in COPD. The present critical review describes the current knowledge about the novel nebulizer technology, the efficacy, safety, and critical role of nebulized glycopyrrolate in patients with COPD. To this end, PubMed, ClinicalTrials.gov, Embase, and Cochrane Library have been searched for relevant papers. According to the available results, the efficacy and tolerability profile of nebulized glycopyrrolate may represent a valuable and dynamic treatment option for the chronic pharmacological management of patients with COPD.

Formoterol fumarate + glycopyrrolate for the treatment of chronic obstructive pulmonary disease.

ABSTRACT Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by a high disability and increasing mortality. Bronchodilators are the cornerstone of pharmacological treatment in COPD, while therapeutic optimization with an improvement in symptoms and compliance represent the actual goals. This has led to the development of devices that combine different classes of inhalatory drugs. Recently, a novel combination of the long acting antimuscarinic agent glycopyrronium bromide and the beta2-agonist formoterol fumarate has been developed in a metered dose inhaler delivery system. Areas covered: The present article will discuss the current unmet needs in pharmacological therapy of COPD, will then briefly cover the pharmacokinetic and pharmacodynamic characteristics of the formoterol/glycopyrronium fixed dose combination and present the novel delivery system based on engineered microparticles and the co-suspension technology. Finally, efficacy and safety results of phase I, II and III trials will be reviewed. Expert commentary: The novel combination therapy of formoterol/glycopyrronium is the first available as a metered dose inhaler and proved to have a good efficacy and safety profile compared to monocomponents and tiotropium. Although still limited, data from phase III trials provide good evidence to consider it a valid option in the pharmacological management of patients with COPD.