Therapeutic Advances in Respiratory Disease recent issues

Characterisation of exacerbations of chronic bronchitis and COPD in Europe: the GIANT study

Miravitlles, M., Anzueto, A., Ewig, S., Legnani, D., Stauch, K. — Tue, 24 Nov 2009 08:59:09 PST

Objective: The GIANT study collected information on patients with acute exacerbations of chronic bronchitis (AECB) and chronic obstructive pulmonary disease (COPD) and the effect of treatment with moxifloxacin.

Methods: AECB history, concomitant diseases, moxifloxacin treatment, concomitant medication, clinical symptoms and adverse events were recorded. A questionnaire at the end of treatment recorded the impact on patients’ daily lives.

Results: Among 9225 patients from eight European countries, marked variation was seen in characteristics including age, smoking history and type of exacerbation. Spirometry use was more common among chest physicians (66.7%) than GPs (15.5%). Patients with Anthonisen type 1 and 2 exacerbations had more frequent exacerbations and these patients experienced a greater impact on daily activities compared with patients with type 3 episodes. Patient symptoms improved with moxifloxacin treatment after a mean (SD) of 3.4 (1.8) days, allowing return to normal daily activities after 5.4 (4.4) days and with full recovery taking 6.5 (3.1) days.

Conclusions: Characteristics of patients with AECB and acute exacerbations of COPD differ among European countries. Spirometry is under-used, particularly in primary care and antibiotic treatment does not always follow current guidelines. Results confirm the efficacy of moxifloxacin in the treatment of AECB in real-life conditions.

Effectiveness of pharmacotherapy and behavioral interventions for smoking cessation in actual clinical practice

Tue, 24 Nov 2009 08:59:09 PST

Objectives: This study evaluated the effectiveness of behavioral interventions (brief counseling, nonspecific psychological support in groups — NSGS and cognitive behavioral group therapy — CBGT) in combination with bupropion SR for smoking cessation in the field, through a smoking cessation clinic.

Methods: Two-hundred-and-five smokers were enrolled in a 19-week course during 2007/ 2008, and were randomly assigned to: bupropion SR combined with brief counseling (group A), bupropion SR combined with NSGS (group B), bupropion SR combined with CBGT (group C), or CBGT as the only approach (group D).

Results: Continuous abstinence rates at the end of therapy were 53.2% for group A, 62.9% for group B, 50.0% for group C, and 22.2% (p < 0.05) for group D. Sustained abstinence rates in 12 months were 29.6%, 28.1%, 34.3% and 19.4% (p > 0.05), respectively.

Conclusions: Bupropion SR is an effective aid for smoking cessation in clinical practice. NSGT increased the chances for success at the end of therapy when combined with bupropion SR, while CBGT as monotherapy was less effective compared with the approaches including pharmacotherapy. It is suggested that smoking cessation interventions in real-life healthcare settings should be implemented through comprehensive programs using pharmacotherapy where applicable, combined with NSGT, and integrated by specialized healthcare professionals.

Reduction of amiodarone pulmonary toxicity in patients treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers

Tue, 24 Nov 2009 08:59:09 PST

Background: Amiodarone (AM) is a widely used anti-arrhythmic medication. Its utility is, however, limited by adverse side effects. The mechanism of amiodarone-induced toxicity (APT) in the lungs is attributed primarily to stimulation of the angiotensin enzyme system leading to lung cell apoptosis and cell death. This mechanism has been demonstrated by in vitro and in vivo experimental animal studies. To date, however, no in vivo human studies have confirmed this mechanism for APT.

Purpose: This study was undertaken to determine whether angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) offer a protective effect against APT in humans. Demonstration of a protective effect of an ACE-I or ARB would suggest that stimulation of the angiotensin enzyme system may be a key process in APT.

Design: An 8-year retrospective analysis of all patients on AM therapy at the James H. Quillen Veterans Affairs Medical Center was undertaken.

Results: A total of 1000 patients on AM were identified. One-hundred-and-seventeen were excluded from the study. Five-hundred-and-twenty-four patients were simultaneously on an ACE-I or ARB. The remaining 359 patients were not. Pulmonary toxicity attributed to AM was identified in five and 14 patients with and without concomitant ACE-I or ARB therapy, respectively. The APT rate for the entire patient sample was 2.2%. APT occurred in 1% of patients on an ACE-I or ARB and in 3.9% of patients not taking an ACE-I or ARB. This observed difference in percentage of APT was statistically significant.

Conclusion: The concomitant use of ACE-I or ARB in patients taking AM appears to offer a protective effect against APT. This observation suggests that the stimulation of the angiotensin enzyme system may play an important role in APT in humans.

Intrapleural hemorrhage after administration of tPA: a case report and review of the literature

Goralski, J. L., Bromberg, P. A., Haithcock, B. — Tue, 24 Nov 2009 08:59:09 PST

Objective: Intrapleural fibrinolytic enzymes have been used for over 60 years in the treatment of complicated pleural effusions to lyse loculations and promote resolution. Despite this extensive history of use, however, little is known about complications that may arise with the use of this therapy. Here we discuss a patient with chronic renal failure on hemodialysis who developed an intrapleural hemorrhage after the administration of intrapleural tPA to treat a complicated parapneumonic effusion. A review of the literature examines the efficacy and safety of this therapy, focusing on bleeding complications. Specific attention is paid to patients who have underlying coagulopathies or who are receiving anticoagulation.

Data sources: A review of the literature, as indexed in PubMed, was undertaken using the following search terms in combination: tPA, pleural effusion, complications of thrombolytics, and intrapleural hemorrhage. The search was inclusive of patients under the age of 18, but was limited by English language and human subjects.

Study selection/data extraction: All relevant articles identified during the search were reviewed. Those studies that reported on bleeding complications, or lack thereof, were included in this review. Limitations of each article are noted in the text.

Conclusions: Multiple studies, including a 2000 ACP consensus statement and a 2008 Cochrane review, indicate the need for further investigations to evaluate the safety and efficacy of intrapleural thrombolytics for the treatment of complicated pleural effusions and empyemas. Limited studies specifically address bleeding complications, especially in subpopulations of patients receiving concurrent anticoagulant therapy.

Spontaneous pneumomediastinum: an algorithm for diagnosis and management

Tue, 24 Nov 2009 08:59:09 PST

Spontaneous pneumomediastinum (SPM) is a rare disorder most often affecting young males which is generally self-limiting. Despite the benign prognosis with few complications and little morbidity, it frequently confuses clinicians in primary settings, who may have difficulty differentiating SPM from other serious organ ruptures, especially oesophageal rupture (the so-called Boerhaave syndrome), which may lead to mediastinitis and may be fatal, even with appropriate interventions. An overview of adult SPM is provided, reviewing 17 studies (414 patients), including our clinical experience, and finally an algorithm for diagnosis and management of SPM is proposed, based on the characteristics of SPM.

Sleep disorders and their management in patients with COPD

Sharafkhaneh, A., Jayaraman, G., Kaleekal, T., Sharafkhaneh, H., Hirshkowitz, M. — Tue, 24 Nov 2009 08:59:09 PST

Chronic obstructive pulmonary disease (COPD) is a prevalent progressive condition that adversely affects quality of life and sleep. Patients with COPD suffer from variety of sleep disorders including insomnia, sleep disordered breathing and restless leg syndrome. The sleep disorders in COPD patients may stem from poor control of primary disease or due to side effects of pharmacotherapy. Thus, optimization of COPD therapy is the main step in treating insomnia in these patients. Further, pharmacotherapy of sleep disorders may result in respiratory depression and related complications. Therefore, clear understanding of respiratory physiology during transition from wakefulness to sleep and during various stages of sleep plays an important role in therapies that are recommended in patients with significant airway obstruction. In this publication, we review respiratory physiology as it relates to sleep and discuss sleep disorders and their management in patients with COPD.

The traditional diagnosis and treatment of respiratory diseases: a description from Avicenna's Canon of Medicine

Hashemi, S. M., Raza, M. — Tue, 24 Nov 2009 08:59:09 PST

This article presents selected text on respiratory medicine from the famous book of medicine, Al-Qanun fi al-Tibb (the Canon of Medicine) by Avicenna (981—1037 AD), which was taught for 600 years as a standard text of medicine across medieval Europe. The authentic manuscript of the Canon of Medicine is located in the Central Library of the Tehran University of Medical Sciences, and the section on respiratory diseases was studied for the most relevant information — information that would be informative and interesting for present day physicians and pulmonologists. The results of the analysis are presented in the article. Respiratory diseases are discussed in depth in volume 3 of the Canon of Medicine. Avicenna discusses in detail the functional anatomy and physiopathology of the pulmonary diseases that were known in his time. He also describes the signs and symptoms of various respiratory diseases and conditions in the five chapters of volume 3 (breathing, voice, cough and hemoptysis, internal wounds and inflammations and principles of treatments) that are remarkably similar to those of modern pulmonary medicine. In addition, the herbal and nonherbal treatment of respiratory diseases and their signs and symptoms, mentioned in volume 2 of the Canon of Medicine, is also presented. In the time of Avicenna, the presentation of respiratory diseases, their treatment and their prognosis was much different than in modern times. There was more reliance on history, physical examination (which was mostly based on visual observation), individual variation, environmental factors, diet, and so on, for diagnosis and treatment. Nevertheless, going through a popular historic text such as the Canon of Medicine adds to our knowledge of the developments in the area of respiratory medicine at the time of Avicenna.

Acknowledgements

Tue, 24 Nov 2009 08:59:09 PST

The effect of the tachykinin NK2 receptor antagonist MEN11420 (nepadutant) on neurokinin A-induced bronchoconstriction in asthmatics

Schelfhout, V., Van De Velde, V., Maggi, C., Pauwels, R., Joos, G. — Fri, 30 Oct 2009 07:15:43 PDT

Objective: We previously reported that the nonpeptide tachykinin NK₂ receptor antagonist SR48968 (saredutant) significantly inhibits neurokinin A-induced bronchoconstriction in patients with asthma. MEN11420 (nepadutant) is a bicyclic peptide tachykinin NK₂ receptor antagonist. The aim of the trial was to examine the effect of nepadutant on neurokinin A-induced bronchoconstriction in man.

Methods: 12 patients with stable, mild to moderate asthma participated in a double-blind, placebo-controlled crossover trial and received, with intervals of 1 week, MEN11420 2 mg, MEN11420 8 mg and placebo (i.v.). Increasing concentrations of NKA (10^-9 to 10^-6 moles/ml) were inhaled immediately after (d1) and 24 hours after (d2) administration of treatment.

Results: On d1 both MEN11420 2 and 8 mg shifted the dose response curve for neurokinin A to the right (log PC₂₀ FEV₁ neurokinin A [moles/ml]; mean± SEM -6.38±0.26 after 2 mg, -6.11±0.23 after 8 mg, versus -6.95±0.27 after placebo]. On d2 MEN11420 had no effect on neurokinin A-induced bronchoconstriction.

Conclusion: In conclusion, the tachykinin NK₂ receptor antagonist nepadutant significantly inhibits bronchoconstriction induced by neurokinin A in patients with asthma.

Anxiety and the management of asthma in an adult outpatient population

Cordina, M., Fenech, A. G., Vassallo, J., Cacciottolo, J. M. — Fri, 30 Oct 2009 07:15:43 PDT

Background: Review of the literature suggests that anxiety is more common among patients with asthma than among the general population, yet it does not appear to be given the attention it deserves as part of the overall management of asthma. The aim of this study was to investigate the relationship between anxiety and asthma management, in terms of Global Initiative for Asthma steps, lung function and medication.

Methods: A total of 201 consecutive patients with respiratory physician-diagnosed asthma were recruited from an adult outpatient asthma clinic. Participants underwent a sociodemographic review, and a medical interview which included a detailed drug history. Forced expiratory volume in 1 second (FEV₁) and peak expiratory flow (PEF) values were recorded using a Micro Medical^® portable spirometer. The level of anxiety was assessed using the Beck Anxiety Inventory (BAI).

Results: A total of 51.5% of participants registered clinically significant levels of anxiety. Of these only 21% had already been diagnosed and were receiving treatment. Females reported significantly higher BAI scores than males (p < 0.01). More females (66.3%) registered clinically significant levels of anxiety as compared with males (33.7%) (p < 0.05). There was a positive correlation between the BAI score and the prescribed dose of inhaled glucocorticoids (r_s = 0.150, p < 0.05) and between anxiety and GINA treatment step (r_s = 0.139, p < 0.05). There was also a positive correlation between anxiety and the number of medicines taken by patients (r_s = 0.259, p < 0.001).

Conclusions: Physicians treating patients with asthma should be sensitised to the association between asthma and anxiety, and should also consider assessing patients for the possibility of anxiety disorders as part of asthma management plans.

Histone deacetylase-2 and airway disease

Barnes, P. J. — Fri, 30 Oct 2009 07:15:43 PDT

The increased expression of inflammatory genes in inflammatory lung diseases is regulated by acetylation of core histones, whereas histone deacetylase-2 (HDAC2) suppresses inflammatory gene expression. Corticosteroids suppress inflammatory genes in asthma by inhibiting histone acetyltransferase and in particular by recruiting HDAC2 to the nuclear factor-B-activated inflammatory gene complex. This involves deacetylation of the acetylated glucocorticoid receptor. In COPD, severe asthma and asthmatics who smoke, HDAC2 is reduced, thus preventing corticosteroids from suppressing inflammation. The reduction in HDAC2 appears to be secondary to increased oxidative and nitrative stress in the lungs. Antioxidants and inhibitors of nitric oxide synthesis may therefore restore corticosteroid sensitivity in COPD, but this can also be achieved by low concentrations of theophylline and curcumin, which act as HDAC activators. Theophylline is a direct inhibitor of oxidant-activated phosphoinositide-3-kinase-, which is involved in inactivation of HDAC2. In the future selective PI3K inhibitors and more direct activators of HDAC2 may be used to treat corticosteroid-resistant inflammatory diseases of the lung, including COPD, severe asthma and asthma in smokers.

Leukotriene modifiers in the treatment of asthma in children

Fri, 30 Oct 2009 07:15:43 PDT

Asthma is one of the most common respiratory disorders in clinical practice, affecting up to 13% of people worldwide. Inflammation is the most important component of asthma and inhaled corticosteroids (ICS) are recommended as the first line controller treatment for patients of all ages. Treatment with corticosteroids is often unable to fully control asthma symptoms and progression. Recently, leukotrienes have come to the forefront of research as they have been found play a pivotal role in the airway inflammatory process, and specific drugs have been developed to target them. Cysteiny leukotriene antagonists (LTRAs) have recently emerged as important therapeutic options that show a large potential clinical utility. Three specific LTRAs are licensed for clinical use: montelukast, zafirlukast and pranlukast, although montelukast is the only drug approved in the paediatric age range. It is well tolerated (although adverse effects such as headaches, abdominal pain, rashes, angioedema, pulmonary eosinophilia and arthralgia have been reported) and shows many positive effects in asthmatic patients. Current Global Initiative for Asthma guidelines recommend LTRAs as: (1) a second choice treatment to ICS for patients with mild persistent asthma, (2) an add-on therapy to reduce the dose of ICS in patients with moderate or severe asthma, due to the different and complementary mechanisms of action of these agents. LTRAs may be particularly appropriate choices in a number of clinical situations, including the following: patients with concomitant rhinitis; patients with viral-induced wheeze; patients with exercise-induced bronchoconstriction (EIB) and, in children aged 2-5 years, to reduce the frequency of asthma exacerbations.

An immunological overview of allergen specific immunotherapy -- subcutaneous and sublingual routes

Ozdemir, C. — Fri, 30 Oct 2009 07:15:43 PDT

Allergen-specific immunotherapy remains the most likely effective treatment modality for allergic disorders by targeting the underlying immune mechanisms and possibly causing modifications in the disease course, as well as treating the symptoms. Treatment and compliance experiences been gained over nearly a century in injection-type allergen-specific immunotherapy have motivated the development of newer, alternative routes. Adverse events and safety concerns, efficacy and ease of application seem to be the stimulating factors for the development of a sublingual form of this treatment modality, wherein the principal factor is the capture of the antigen (allergen) by dendritic cells, in the location where oral tolerance arises. Due to the presence of high numbers of tolerogenic dendritic cell subsets in this region, programming of the immune system towards a regulatory state with unresponsiveness to specific allergens occurs. Induction of peripheral tolerance through the generation of regulatory T cells is the key event, with several functional modulations in the allergic immune response. With an increase in understanding of the mechanism of regulatory pathways, promising progresses in the field of allergen-specific immunotherapy will ensue and may provide new options for the treatment of allergic disorders.

Retraction: High, but not low, molecular weight preparations of hyaluronic acid protect asthmatics against challenge-induced bronchoconstriction

Thu, 17 Sep 2009 07:52:01 PDT

Effect on lung function and morning activities of budesonide/formoterol versus salmeterol/fluticasone in patients with COPD

Partridge, M. R., Schuermann, W., Beckman, O., Persson, T., Polanowski, T. — Thu, 22 Oct 2009 05:44:33 PDT

Background: Patients with chronic obstructive pulmonary disease (COPD) often experience symptoms and problems with activities early in the morning. This is the first study to compare the effect of budesonide/formoterol and salmeterol/fluticasone on lung function, symptoms and activities early in the morning.

Methods: Lung function (peak expiratory flow [PEF] and forced expiratory volume in 1 second [FEV₁]) and symptoms were measured at bedside and activities were measured during the morning using a six-item questionnaire concerning basic morning routines. In a randomised, double-blind, multicentre, cross-over study, 442 patients with COPD aged ≥40 years (pre-bronchodilator FEV₁ ≤50%; FEV₁/vital capacity <70%) received budesonide/formoterol (320/9 µg, one inhalation twice daily) dry powder inhaler (DPI) or salmeterol/fluticasone (50/500 µg, one inhalation twice daily) DPI daily, for 1 week each, separated by a 1- to 2-week washout. Lung function (PEF and FEV₁) shortly after rising from bed in the morning, symptoms and basic morning activities were assessed by electronic diary (e-Diary) recordings.

Results: Budesonide/formoterol and salmeterol/fluticasone treatment increased morning PEF 5 minutes post-dose, measured as a mean improvement from baseline over the full study period (primary endpoint; adjusted mean change: 15.1 l/min and 14.2 l/min, respectively [difference 1.0 l/min; p = 0.603]). Mean morning FEV₁ improved more following budesonide/ formoterol treatment versus salmeterol/fluticasone at 5 minutes (0.12 l versus 0.09 l; p = 0.090) and 15 minutes (0.14 l versus 0.10 l; p < 0.05) post-dose. Budesonide/formoterol demonstrated a more rapid onset of effect as reflected by increases in e-Diary-recorded PEF and FEV₁ from pre-dose to 5 and 15 minutes post-dose (all p < 0.001) and spirometry at the clinic measured after the first dose (FEV₁ p < 0.001; 5 minutes post-dose). Improvements in symptom scores within 15 minutes after drug administration were similar for both drugs, but budesonide/formoterol treatment resulted in significantly greater improvements in total morning activities score (getting washed, dried, dressed, eating breakfast and walking around the home; 0.22 versus 0.12 respectively, p < 0.05). Both treatments were well tolerated.

Conclusions: Short-term treatment with budesonide/formoterol DPI or salmeterol/fluticasone DPI was effective in patients with COPD. Budesonide/formoterol had a more rapid onset of effect compared with salmeterol/fluticasone and resulted in greater improvements in ability to perform morning activities despite the lower inhaled corticosteroid dose.

Histologically proven isoniazid hepatoxicity in complicated tuberculous salpingitis

Semfke, A., Wackernagel, C., Vier, H., Schutz, A., Wiechmann, V., Gillissen, A. — Thu, 17 Sep 2009 07:52:01 PDT

Isoniazid (INH) hepatic injury is histologically indistinguishable from viral hepatitis and is related to individual susceptibility of patients who hydrolyze the drug to isonicotinic acid at different rates. We here present a case initially involving a complaint of lower abdominal pain, which was diagnosed after a long diagnostic work-up as tuberculous salpingitis and which is rare in women in developed countries. A lack of pulmonary effects further delayed correct diagnosis of the underlying tuberculosis infection. Based on the clinical follow up and liver histology, INH-induced severe hepatoxicity, which further contributed to the abdominal symptoms, could be confirmed. After adaptation of the standard therapeutic regimen no further complications occurred.

Noninflammatory mechanisms of airway hyper-responsiveness in bronchial asthma: an overview

Baroffio, M., Barisione, G., Crimi, E., Brusasco, V. — Thu, 17 Sep 2009 07:52:01 PDT

Airway hyper-responsiveness (AHR) is a cardinal feature of asthma. Its absence has been considered useful in excluding asthma, whereas it may be present in other diseases such as atopic rhinitis and chronic obstructive pulmonary disease. AHR is often considered an epiphenomenon of airway inflammation. Actually, the response of airways to constrictor stimuli is modulated by a complex array of factors, some facilitating and others opposing airway narrowing. Thus, it has been suggested that AHR, and perhaps asthma, might be present even without or before the development of airway inflammation. We begin this review by highlighting some terminological and methodological issues concerning the measurement of AHR. Then we describe the neurohumoral mechanisms controlling airway tone. Finally, the pivotal role of airway smooth muscle and internal and external modulation of airway caliber in vivo are discussed in detail.

Pharmacotherapy of asthma: regular treatment or on demand?

Montuschi, P., Pagliari, G., Fuso, L. — Thu, 17 Sep 2009 07:52:01 PDT

Some studies have raised the question of the need for chronic controller therapy in mild persistent asthma as suggested by international guidelines. Although the Improving Asthma Control (IMPACT) and Beclomethasone plus Salbutamol (BEST) studies suggest that on-demand therapy in some patients with mild persistent asthma achieves a similar degree of asthma control based on symptoms and functional outcomes, the IMPACT study indicates that regular and on-demand therapy is not equivalent for controlling airway inflammation. Persistent airway inflammation might lead to airway remodelling with onset or worsening of symptoms, deterioration in lung function, and reduced response to pharmacological therapy. However, the relationships between chronic airway inflammation and airway remodelling need to be clarified. Choosing the ‘right’ pharmacological strategy (regular versus on-demand treatment) for asthma control is currently difficult due to the fact that (1) inflammatory outcome measures were not generally incorporated into asthma clinical trials; (2) the relationships between chronic airway inflammation and airway remodelling are largely unknown; (3) current clinical asthma trials that are generally based on symptomatic and functional outcome measures are too short to assess the impact of regular anti-inflammatory therapy on natural history of asthma; (4) asthma is an heterogeneous disease and different phenotypes of asthma patients likely requiring a different therapeutic approach can be identified, even in the same class of asthma severity. Guidelines for asthma management are valuable tools, although they are necessarily based on a strategy directed to the best outcome in a group of patients. Asthma phenotyping is becoming central for asthma management. The issue of regular versus on-demand treatment of intermittent and mild persistent asthma would be better addressed if considered within an individualized approach to asthma management and assessment. Identification of clinical, functional, morphological and biochemical phenotypes of patients with asthma and its clinical implications is likely to lead to a tailored, individualized, pharmacological therapy and asthma management.

Are nicotine replacement therapy, varenicline or bupropion options for pregnant mothers to quit smoking? Effects on the respiratory system of the offspring

Maritz, G. S. — Thu, 17 Sep 2009 07:52:01 PDT

Nicotine occurs in tobacco smoke. It is a habit-forming substance and is prescribed by health professionals to assist smokers to quit smoking. It is rapidly absorbed from the lungs of smokers. It crosses the placenta and accumulates in the developing fetus. Nicotine induces formation of oxygen radicals and at the same time also reduces the antioxidant capacity of the lungs. Nicotine and the oxidants cause point mutations in the DNA molecule thereby changing the program that controls lung growth and maintenance of lung structure. The data available indicate that maternal nicotine exposure induces a persistent inhibition of glycolysis and a drastically increased AMP level. These metabolic changes are thought to contribute to the faster aging of the lungs of the offspring of mothers that are exposed to nicotine via the placenta and mother’s milk. The lungs of these animals are more susceptible to damage as shown by the gradual deterioration of the lung parenchyma. The rapid metabolic and structural aging of the lungs of the animals exposed to nicotine via the placenta and mother’s milk, and thus during phases of lung development characterized by rapid cell division, is likely due to ‘programming’ induced by nicotine. Since varenicline, a partial nicotine agonist, has basically the same structure as nicotine, and also binds to acetylcholine receptors in competition with nicotine (but with largely the same effect), it is not advisable to use nicotine or varenicline during gestation and lactation. Furthermore, the use of individual vitamin supplements is also not advisable because of the negative impact on the program that controls maintenance of lung structural and functional integrity and aging. A more appropriate smoking cessation program will also include a mixture of antioxidant nutrients such as in tomato juice.

Sarcoidosis-associated pulmonary hypertension: a role for endothelin receptor antagonists?

Fri, 07 Aug 2009 04:24:11 PDT

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.

Efficacy of tiotropium in the prevention of exacerbations of COPD

Anzueto, A., Miravitlles, M. — Fri, 07 Aug 2009 04:24:11 PDT

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 FEV₁ 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.

The possible role of granzyme B in the pathogenesis of chronic obstructive pulmonary disease

Ngan, D. A., Vickerman, S. V., Granville, D. J., Man, S. F. P., Sin, D. D. — Fri, 07 Aug 2009 04:24:11 PDT

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.

Sneeze reflex: facts and fiction

Songu, M., Cingi, C. — Fri, 07 Aug 2009 04:24:11 PDT

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.