Therapeutic Advances in Respiratory Disease (Ther Adv Respir Dis)

Publications in this journal

• Article: Sneeze reflex: facts and fiction.

  Murat Songu, Cemal Cingi
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  ABSTRACT: Sneezing is a protective reflex, and is sometimes a sign of various medical conditions. Sneezing has been a remarkable sign throughout the history. In Asia and Europe, superstitions regarding sneezing extend through a wide range of races and countries, and it has an ominous significance. Although sneezing is a protective reflex response, little else is known about it. A sneeze (or sternutation) is expulsion of air from the lungs through the nose and mouth, most commonly caused by the irritation of the nasal mucosa. Sneezing can further be triggered through sudden exposure to bright light, a particularly full stomach and physical stimulants of the trigeminal nerve, as a result of central nervous system pathologies such as epilepsy, posterior inferior cerebellar artery syndrome or as a symptom of psychogenic pathologies. In this first comprehensive review of the sneeze reflex in the English literature, we aim to review the pathophysiology, etiology, diagnosis, treatment and complications of sneezing.
  Therapeutic Advances in Respiratory Disease 08/2009; 3(3):131-41.
• Article: Sarcoidosis-associated pulmonary hypertension: a role for endothelin receptor antagonists?

  Georgia G Pitsiou, Dionysis Spyratos, Ioannis Kioumis, Afroditi K Boutou, Chrysanthi Nakou, Ioannis Stanopoulos
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  ABSTRACT: Data on the treatment of sarcoidosis-associated pulmonary hypertension are scarce, while the variety of underlying pathophysiologic mechanisms are a major limitation in the implementation of a universal therapy. We report a 47-year-old male patient who presented with stage II sarcoidosis and associated severe pulmonary hypertension. Corticosteroid treatment resolved parenchymal lesions of the lung while vascular involvement did not respond, with the patient remaining in poor functional status. Addition of bosentan, a dual endothelin receptor antagonist, resulted in marked improvement in functional class and exercise capacity of the patient, allowing gradual tapering of steroids.
  Therapeutic Advances in Respiratory Disease 08/2009; 3(3):99-101.
• Article: Efficacy of tiotropium in the prevention of exacerbations of COPD.

  Antonio Anzueto, Marc Miravitlles
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  ABSTRACT: Exacerbations are the most frequent cause of medical visits, hospital admissions and death among patients with chronic obstructive pulmonary disease (COPD). Tiotropium bromide is a long-acting bronchodilator that has demonstrated clinical efficacy in significantly improving the FEV(1) and health-related quality of life (HRQL) in patients with COPD. The prolonged and persistent bronchodilation achieved with tiotropium may reduce the exacerbation and COPD-related hospitalisation rates. The effect of tiotropium treatment on the incidence of exacerbations has been determined (as a secondary outcome) in registration trials. There are studies designed specifically to demonstrate the effect of tiotropium on the reduction in the frequency of exacerbations. Two of these studies of 6-month and 1-year duration demonstrated an additional significant benefit in the reduction of exacerbations and hospitalisations. The recent UPLIFT trial included 5993 patients followed for 4 years and, compared with control, tiotropium significantly delayed time-to-first exacerbation (16.7 versus 12.5 months) and time-to-first hospitalisation for exacerbations (lower risk of hospitalisation; HR, 0.86 [95% CI = 0.78-0.95]; p = 0.002). Tiotropium also reduced the mean number of exacerbations by 14% (rate per patient-year, 0.73 versus 0.85; HR, 0.86 [95% CI = 0.81-0.91]; p < 0.001). It is important to highlight that the control group in the UPLIFT trial consisted of patients with usual treatment for COPD, which included inhaled corticosteroids and/or long-acting beta-2 agonists in up to 62% of cases at baseline and up to 73% of cases at any time during follow-up. The new clinical trials have demonstrated a significant reduction in exacerbations and hospitalisations, even in patients treated with other drugs that can potentially prevent exacerbations.
  Therapeutic Advances in Respiratory Disease 08/2009; 3(3):103-11.
• Article: The possible role of granzyme B in the pathogenesis of chronic obstructive pulmonary disease.

  David A Ngan, Shawna V Vickerman, David J Granville, S F Paul Man, Don D Sin
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  ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a highly prevalent inflammatory lung condition characterized by airways disease and emphysema, and the precise mechanism of pathogenesis is poorly understood. The consistent features of COPD include protease-antiprotease imbalance, inflammation and accelerated aging caused by apoptosis or senescence. One family of molecules involved in all of these processes is the granzymes, serine proteases with the best-known member being granzyme B (GzmB). The majority of GzmB is released unidirectionally towards target cells, but GzmB can also be released nonspecifically and escape into the extracellular environment. GzmB is capable of cleaving extracellular matrix (ECM) proteins in vitro, and the accumulation of GzmB in the extracellular milieu during chronic inflammation in COPD could contribute to ECM degradation and remodelling and, consequently, the emphysematous phenotype in the lung. Preliminary studies suggest that increased GzmB expression is associated with increased COPD severity, and this may represent a promising new target for drug and biomarker discovery in COPD. In this paper, we review the potential pathogenic contributions of GzmB to the pathogenesis of COPD.
  Therapeutic Advances in Respiratory Disease 08/2009; 3(3):113-29.
• Article: Evaluation of a 24-hour emergency bronchoscopy service in a tertiary care hospital.

  Thomas Fuehner, Detlef Lueders, Jost Niedermeyer, Stefan Ziesing, Tobias Welte, Marius M Hoeper
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  ABSTRACT: Flexible bronchoscopy has become an important diagnostic and therapeutic tool for the management of patients with various diseases of the chest. Availability of a 24-hour bronchoscopy service equipped with experienced personnel is becoming increasingly important especially for intensive care patients. However, such services have been implemented only in a few medical centres. The aim of this study was to evaluate the usage of a 24-hour emergency service in a large university hospital with a 1 year prospective analysis of emergency bronchoscopy service in a tertiary care centre. Frequencies, indications and efficiency of therapeutic interventions were evaluated after each bronchoscopy using a specially designed questionnaire. All bronchoscopies were performed as emergency procedures out of operational schedule. A total of 614 emergency bronchoscopies were performed, 88% of them in intensive care units. The vast majority (84.5%) of the procedures were necessary for therapeutic interventions; that is, atelectasis, airway secretion, aspiration or bronchopulmonary bleeding. According to prespecified criteria, 37.6% (n = 195) of therapeutic procedures were assessed as 'very helpful' and 3.9% (n = 20) as 'life saving'. Diagnostic bronchoscopies were performed mainly to collect airway material for microbiological evaluations in immunocompromised patients. In these cases, the diagnostic yield was approximately 50%. The availability of a 24-hour bronchoscopy service has been found to improve patient care and was occasionally considered life saving. Thus, comparable services should be made more widely available.
  Therapeutic Advances in Respiratory Disease 06/2009; 3(2):65-71.
• Article: Use of dry powder inhalers in acute exacerbations of asthma and COPD.

  Olof Selroos, Lars Borgström, Jarl Ingelf
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  ABSTRACT: To investigate whether dry powder inhalers (DPIs) function in a constrained situation, a literature analysis was performed to evaluate the use of DPIs compared with established therapies in the treatment of acute asthma and COPD, irrespective of rapid-acting beta(2)-agonist used. The external databases Medline, Embase, Biosis and Current Contents and AstraZeneca's internal literature database Planet were searched up to April 2008. Only publications or congress abstracts describing clinical trials in patients treated at EDs or hospitals were considered, and then only those in which exacerbation severity (measured as FEV(1)) were included. Fifteen clinical studies met these criteria; twelve in acute asthma and three in acute COPD. For acute asthma, eight studies were double-blind, randomised studies (six in adults and two in children), two were open-label studies (one in adults and one in children), and two were investigational (methacholine challenge) studies. For the acute COPD studies, one was double-blind and randomised, one was single-blind and randomised, and one was open-label. This review found that administration of fast-acting bronchodilators via DPIs, the majority of which were Turbuhaler, is effective during an asthma or COPD worsening. Our literature review finds that DPIs function in patients with acute asthma or COPD equally well as established therapies with other inhaler devices. Patients can therefore rely upon DPIs in the same way that they rely upon other inhaler devices.
  Therapeutic Advances in Respiratory Disease 06/2009; 3(2):81-91.
• Article: Clinical and pharmacoeconomic profile of COPD patients with FEV1 50--60% predicted: pilot study on the impact of the extended indication of ICS/LABA.

  Roberto Walter Dal Negro, Luca Bonadiman, Claudio Turati, Paola Turco
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  ABSTRACT: The use of inhaled corticosteroids (ICS) and long-acting beta(2) adrenergics (LABA) in fixed combination (ICS/LABA) was recently extended to COPD patients with a baseline FEV(1) 50-60% predicted, thus broadening the original guideline indications (GOLD 2006) that limited their use only to stages III and IV. The present study was carried out to assess the clinical profile of this new subset of patients, with a view to providing data for future studies on the impact of this novel extension of ICS/LABA use in COPD. Data from the present observational cross-sectional study suggest that COPD patients with FEV(1) 50-60% predicted depict a dichotomic condition: actually, even though resembling milder patients in terms of frequency and severity of their respiratory symptoms, they are much more similar to severer patients in terms of rate of hospital admissions and resource consumption (p50.01). In other words, this subset of patients seems to represent a peculiar condition in the evolutional phase of COPD during which therapeutic treatment should be intensified in order to slow down the disease progression effectively. Nevertheless, independently of the severity, the general therapeutic approach to COPD was found to be greatly inadequate when compared to GOLD guidelines, particularly in terms of appropriateness. These findings should pave the way for future studies aimed to long-term monitoring of main outcomes and to evaluate the overall impact of earlier ICS/LABA use on disease progression and lung function decline in COPD.
  Therapeutic Advances in Respiratory Disease 06/2009; 3(2):51-8.
• Article: Value of adding a polyvalent mechanical bacterial lysate to therapy of COPD patients under regular treatment with salmeterol/fluticasone.

  Mario Cazzola, Paolo Noschese, Felice Di Perna
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  ABSTRACT: This study investigated the value of adding Ismigen, a polyvalent mechanical bacterial lysate, to therapy of COPD patients (FEV(1) <60% predicted) under regular treatment with salmeterol/fluticasone (SFC). 63 patients enrolled from September to December 2007 were randomly divided into two groups (A and B). All patients were treated with salmeterol/fluticasone (SFC) 50/500 microg BID. Thirty-three subjects also received Ismigen one capsule daily the first 10 days of three consecutive months (group B). This treatment was reaped three months after the end of the first course. We assessed at inclusion and at scheduled (every 2 months) or intercurrent visit: symptoms (amount and colour of sputum, severity of dyspnoea, frequency of cough, fever), diagnosis of exacerbation, concomitant medications (antibiotics and oral corticosteroids) and hospitalization. During the course of the study two patients died. At the end of the observation period (12 months), another six patients could not be visited because they had withdrawn. Compared with SFC, adding on Ismigen reduced the total number of exacerbations (23 out of 30 patients in group A and 21 out of 33 patients in group B), the number (rate) of exacerbations per patient per year (18 out of 27 patients [0.67] in group A and 15 out of 28 patients [0.54] in group B), the number of exacerbations that needed treatment with oral corticosteroids (12 out of 23 [52%] in group A and 9 out of 21 [43%] in group B) and the total number (rate) of hospitalizations (4/30 [0.13] in group A and 3/33 [0.09] in group B). There were no significant differences between treatments with respect to their effect on the symptoms of exacerbations. A decrease in the need for antibiotics was also observed in group B. Our data suggest that COPD patients benefit from the addition of Ismigen on top of the routine maintenance treatment with SFC.
  Therapeutic Advances in Respiratory Disease 06/2009; 3(2):59-63.
• Article: The effects of inhaled and oral corticosteroids on serum inflammatory biomarkers in COPD: an exploratory study.

  S F Paul Man, Xuekui Zhang, Rupert Vessey, Terry Walker, Kwan Lee, Dan Park, Don D Sin
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  ABSTRACT: Several studies suggest that inhaled and oral corticosteroids repress systemic inflammation in chronic obstructive pulmonary disease (COPD). However, the cytokines that may respond to these medications are unclear. We used data from 41 patients with a history of stable moderate COPD (average age 64 years) who were randomised to inhaled fluticasone (500 microg twice daily from a Diskus inhaler), oral prednisone (30 mg daily) or placebo for 2 weeks. Using a multiplexed array system, different serum cytokines that have been implicated in COPD pathogenesis were measured. We found that compared with placebo, inhaled fluticasone significantly reduced levels of soluble tumour necrosis factor receptor-2 (sTNF-R2) by 24% (95% CI, 7-38%; p = 0.01), monocyte chemoattractant protein-1 by 20% (95% CI, 5-32%; p = 0.01), interferon gamma inducible CXCL10 (IP-10) by 43% (95% CI, 3-66%; p = 0.04), and soluble L-selectin levels by 15% (95% CI, 1-28%; p = 0.04). Compared with placebo, oral prednisone reduced levels of sTNF-R2 by 26% (95% CI, 15-36%; p < 0.001), L-selectin by 22% (95% CI, 8-34%; p = 0.004), intercellular adhesion molecule-1 by 31% (95% CI, 9-48%; p = 0.01), pulmonary and activation-regulated chemokine (PARC) by 18% (95% CI, 2-32%; p = 0.03) and IP-10 by 40% (95% CI, 0-64%; p = 0.05). sTNF-R2, L-selectin and IP-10 were significantly reduced by both oral and inhaled corticosteroids. The other cytokines were not significantly repressed by either oral or inhaled corticosteroids. In summary, inhaled and oral corticosteroids significantly repressed a selected number of systemic cytokines in patients with stable, moderate COPD; most of the steroid-responsive cytokines appear to be chemoattractants.
  Therapeutic Advances in Respiratory Disease 04/2009; 3(2):73-80.
• Article: From large clinical trials to management of COPD in the real world.

  Mario Cazzola
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  ABSTRACT: Large clinical trials in chronic obstructive pulmonary disease [COPD] are analyzed and discussed. Unfortunately, all of them have failed to reach their primary endpoint, which has mainly been the effect on the rate of decline in mean FEV(1) [forced expiratory volume in 1 second]. Nonetheless, almost all trials have demonstrated benefits in important outcomes such as exacerbation frequency, symptoms, quality of life and other measures of health status, which are arguably more meaningful to individual patients than FEV( 1) per se.
  Therapeutic Advances in Respiratory Disease 03/2009; 3(1):39-46.
• Article: Antiprotozoal drugs in the treatment of respiratory allergy: a side that should be explored.

  Rafael Martínez-Girón
  Therapeutic Advances in Respiratory Disease 03/2009; 3(1):47-8.
• Article: Successful switch to sitaxsentan in a patient with HIV-related pulmonary arterial hypertension and late intolerance to nonselective endothelin receptor blockade.

  Valerio Zacà, Marco Metra, Rossella Danesi, Carlo Lombardi, Giulia Verzura, Livio Dei Cas
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  ABSTRACT: Pulmonary arterial hypertension [PAH] is a rare but well-known cardiovascular condition potentially associated with human immunodeficiency virus [HIV] infection and is currently recognized to be one of the most ominous noninfectious HIV complications. Although there is no clear evidence supporting the use of any medication for the treatment of HIV-related PAH, many of the currently available agents have been shown to exert some clinical benefits HIV-PAH patients. To date, no data are available regarding the potential effects of sitaxsentan, a selective endothelin type-A receptor antagonist, in this peculiar patient population. We report the case of a successful switch to sitaxsentan in a HIV-infected patient with PAH initially receiving bosentan who developed a late treatment-related side-effect.
  Therapeutic Advances in Respiratory Disease 03/2009; 3(1):11-4.
• Article: Effect of bosentan upon pulmonary hypertension in chronic obstructive pulmonary disease.

  Giuseppe Valerio, Pierluigi Bracciale, Anna Grazia D'Agostino
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  ABSTRACT: Pulmonary hypertension (PH) in chronic obstructive pulmonary disease [COPD] is mainly determined by hypoxemia under respiratory failure by means of the functional hypoxemic vasoconstrictor response. Organic changes of vessels, pulmonary vascular remodelling, is gaining increasing relevance. An imbalance of endothelial products takes place with overload of vasoconstrictors and thrombogenic autacoids over vasodilators and anticoagulant factors. Among vasoconstrictors, endothelin is claimed to be an important factor. Our aim is to assess the effect of the anti-endothelin drug Bosentan on pulmonary hemodynamics and lung function in patients affected by COPD and PH. Bosentan was administered to 16 patients for a period of 18 months, while another 16 patients with overlapping features was used as a control group. Pulmonary function test, hemodynamics, effort performance, dyspnoea ratings and quality of life were recorded at the beginning and after 18 months under stable state. Bosentan treatment resulted in a significant improvement of PH from 37 + 5 to 31 + 6mm Hg and pulmonary vascular resistance from 442 + 192 to 392 + 180dynes cm(2) and 6MWD from 256 + 118 to 321 + 122m and BODE index from 6.6 + 2.8 to 5.5 + 3U. The effect was most striking in the 30% of patients in GOLD stage III and IV. Most patients in stage IV did not improve, but in all patients the treatment stopped the progressive worsening of hemodynamics over time. The study also highlights the need to identify patients with high pulmonary arterial pressure contrasting with moderate respiratory disease stages, in whom the predominant problem is evidently vascular disease. This preliminary report suggests that the use of Bosentan in the treatment of PH in COPD is beneficial.
  Therapeutic Advances in Respiratory Disease 03/2009; 3(1):15-21.
• Article: Polymorphisms of the beta2 adrenoreceptor gene in chronic obstructive pulmonary disease.

  Gabriela Vacca, Kerstin Schwabe, Ramona Dück, Hans-Peter Hlawa, Arite Westphal, Stefan Pabst, Christian Grohé, Adrian Gillissen
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  ABSTRACT: The beta2-adrenergic receptors are cell surface receptors playing a central role in the pharmacological targeting asthma and chronic obstructive pulmonary disease [COPD]. Recent studies suggest that patients who are homozygous for one of the two important polymorphisms of the beta2-adrenergic receptor [ADRB2] gene at codon 16 (arginine to glycine) and 27 (glutamine to glutamate) may have a reduced response to ss2-agonists. Since smoking patients who are Gly16 homozygotes have an increased risk of airway obstruction we hypothesized that beta2-adrenoreceptor gene polymorphisms may be also a cofounder for COPD development and disease severity. We investigated 190 COPD patients and 172 healthy volunteers in a case-control study. DNA was isolated from whole blood and beta2-AR gene polymorphisms Arg/Gly16 and Gln/Glu27 were determined using allele-specific polymerase chain reaction [PCR]. In COPD patients with Gly/Gly16 was found more frequently than in healthy smokers [29.47% COPD versus 18.18% controls, p = 0.026]. All other gene polymorphisms of the ADRB2 gene at codon 16 were equally distributed between groups. ss2-adrenoreceptor gene polymorphisms were neither a cofounder for COPD exacerbations [>or= 3 hospitalizations within the last 3 years] nor for disease severity [FEV1 <or= 30% predicted]. Our study suggests that the Gly16 allele of the beta2-AR gene predisposes to COPD development but not for exacerbation rates and disease severity. In contrast, Gln/Glu27 polymorphism was irrelevant in our COPD cohort.
  Therapeutic Advances in Respiratory Disease 02/2009; 3(1):3-10.
• Article: Matrix metalloprotease polymorphisms are associated with gas transfer in alpha 1 antitrypsin deficiency.

  Christopher J McAloon, Alice M Wood, Stephen C Gough, Robert A Stockley
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  ABSTRACT: Alpha-1-antitrypsin deficiency [AATD] is associated with variable development of emphysema and other features of chronic obstructive pulmonary disease [COPD]. Matrix metalloproteinases [MMPs] are believed to be important in the pathophysiology of COPD, and may therefore confer susceptibility to this phenotype in patients with AATD. to assess the role of polymorphism of MMP1, MMP3 and MMP12 in AATD phenotypes. 424 PiZZ subjects from the UK AATD Registry were assessed for history of chronic bronchitis [CB], post-bronchodilator lung function impairment and decline of lung function. Tag single nucleotide polymorphisms (SNPs) for MMP1, MMP3 and MMP12 were chosen using HapMap [r(2)>0.8, MAF>0.05] and were genotyped using TaqMan genotyping technologies. Quantitative genetic association was assessed using regression modelling to correct for covariates. in patients with AATD, carriers of the G allele of rs678815 [MMP3] had lower gas transfer [KCO] [P = 0.025, B =-7.766] than the homozygous wild type, while carriers of the T allele of rs470358 [MMP1] had higher KCO [P = 0.025, B = 6.130]. variations in MMP1 and MMP3 are associated with gas transfer in AATD, supporting a previous family study showing linkage of KCO to this gene region. Replication of these preliminary data is now required particularly if MMP inhibitors are to be considered as a therapeutic option.
  Therapeutic Advances in Respiratory Disease 02/2009; 3(1):23-30.
• Article: Managing TB in the 21st century: existing and novel drug therapies.

  Elizabeth S Guy, Antara Mallampalli
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  ABSTRACT: With an estimated one-third of the world's population infected with Mycobacterium tuberculosis (MTB) and approximately 1.6 million deaths in 2006 attributed to tuberculosis (TB) world-wide, TB remains a major public health concern today. Considerable advances have been made in the effective treatment of TB, in particular with the adoption of directly observed therapy short course (DOTS), in national TB control programs, but in spite of this the currently available regimens are suboptimal. The long courses of therapy required, together with significant medication side-effects and resulting difficulties with adherence to therapy all contribute to increasing problems with emerging drug resistance. There is thus an urgent need for new antituberculous drug development, especially to enable effective shorter course therapy for drug-susceptible and resistant TB, to find effective drugs for treatment of drug-resistant TB, to shorten therapy for latent TB infection and to reduce drug interactions in combination with antiretroviral therapy, a major issue in the treatment of HIV co-infected patients. This review will attempt to summarize the current recommendations for treatment of TB and then describe the most promising new antimicrobials with activity against MTB, focusing on the ones currently undergoing clinical trials.
  Therapeutic Advances in Respiratory Disease 01/2009; 2(6):401-8.
• Article: Antioxidant therapeutic advances in COPD.

  Irfan Rahman
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  ABSTRACT: Chronic obstructive pulmonary disease (COPD) is associated with a high incidence of morbidity and mortality. Cigarette smoke-induced oxidative stress is intimately associated with the progression and exacerbation of COPD and therefore targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to have beneficial outcome in the treatment of COPD. Among the various antioxidants tried so far, thiol antioxidants and mucolytic agents, such as glutathione, N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine and carbocysteine; Nrf2 activators; and dietary polyphenols (curcumin, resveratrol, and green tea catechins/quercetin) have been reported to increase intracellular thiol status along with induction of GSH biosynthesis. Such an elevation in the thiol status in turn leads to detoxification of free radicals and oxidants as well as inhibition of ongoing inflammatory responses. In addition, specific spin traps, such as alpha-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a SOD mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo in the lung. Since a variety of oxidants, free radicals and aldehydes are implicated in the pathogenesis of COPD, it is possible that therapeutic administration of multiple antioxidants and mucolytics will be effective in management of COPD. However, a successful outcome will critically depend upon the choice of antioxidant therapy for a particular clinical phenotype of COPD, whose pathophysiology should be first properly understood. This article will review the various approaches adopted to enhance lung antioxidant levels, antioxidant therapeutic advances and recent past clinical trials of antioxidant compounds in COPD.
  Therapeutic Advances in Respiratory Disease 01/2009; 2(6):351-74.
• Article: Novel targets in the management of pneumonia.

  Luis A Díaz, Eric M Mortensen, Antonio Anzueto, Marcos I Restrepo
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  ABSTRACT: Community-acquired pneumonia (CAP) is the leading cause of death from infectious diseases in the US. It accounts each year for 500,000 hospitalizations and 45,000 deaths and represents one of the most common causes of intensive care unit (ICU) admission. The mortality rate due to severe CAP has shown little improvement in the past three decades, remaining between 21% and 58% in patients admitted to the intensive care unit. Antimicrobial agents are the cornerstone of therapy against CAP, but there are some novel antibiotic and nonantibiotic therapies that have been recently tested that may potentially impact outcomes of patients with severe CAP. We will review the most recent data regarding novel therapies in patients with the highest risk of death such as those with severe CAP.
  Therapeutic Advances in Respiratory Disease 01/2009; 2(6):387-400.
• Article: Omalizumab in the treatment of severe asthma: efficacy and current problems.

  Girolamo Pelaia, Teresa Renda, Pasquale Romeo, Maria Teresa Busceti, Rosario Maselli
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  ABSTRACT: Omalizumab is a humanized monoclonal anti-IgE antibody recently approved for the treatment of severe allergic asthma. This drug inhibits allergic responses by binding to serum IgE, thus preventing their interactions with cellular IgE receptors. Omalizumab is also capable of downregulating the expression of high-affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both blood and induced sputum. The clinical effects of omalizumab include relevant improvements in respiratory symptoms and quality of life, paralleled by a marked reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Omalizumab is relatively well tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent allergic asthma, inadequately controlled by high doses of standard inhaled treatments.
  Therapeutic Advances in Respiratory Disease 01/2009; 2(6):409-21.