Tiotropium in Asthma Poorly Controlled with Standard Combination Therapy.

N Engl J Med. 2012 Sep 2;

Authors: Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, Sigmund R, Seibold W, Moroni-Zentgraf P, Bateman ED

Abstract
Background Some patients with asthma have frequent exacerbations and persistent airflow obstruction despite treatment with inhaled glucocorticoids and long-acting beta-agonists (LABAs). Methods In two replicate, randomized, controlled trials involving 912 patients with asthma who were receiving inhaled glucocorticoids and LABAs, we compared the effect on lung function and exacerbations of adding tiotropium (a total dose of 5 μg) or placebo, both delivered by a soft-mist inhaler once daily for 48 weeks. All the patients were symptomatic, had a post-bronchodilator forced expiratory volume in 1 second (FEV(1)) of 80% or less of the predicted value, and had a history of at least one severe exacerbation in the previous year. Results The patients had a mean baseline FEV(1) of 62% of the predicted value; the mean age was 53 years. At 24 weeks, the mean (±SE) change in the peak FEV(1) from baseline was greater with tiotropium than with placebo in the two trials: a difference of 86±34 ml in trial 1 (P=0.01) and 154±32 ml in trial 2 (P<0.001). The predose (trough) FEV(1) also improved in trials 1 and 2 with tiotropium, as compared with placebo: a difference of 88±31 ml (P=0.01) and 111±30 ml (P<0.001), respectively. The addition of tiotropium increased the time to the first severe exacerbation (282 days vs. 226 days), with an overall reduction of 21% in the risk of a severe exacerbation (hazard ratio, 0.79; P=0.03). No deaths occurred; adverse events were similar in the two groups. Conclusions In patients with poorly controlled asthma despite the use of inhaled glucocorticoids and LABAs, the addition of tiotropium significantly increased the time to the first severe exacerbation and provided modest sustained bronchodilation. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov numbers, NCT00772538 and NCT00776984 .).

PMID: 22938706 [PubMed - as supplied by publisher]

An integrated approach in the diagnosis of smoking-related interstitial lung diseases.

Eur Respir Rev. 2012 Sep 1;21(125):207-17

Authors: Caminati A, Cavazza A, Sverzellati N, Harari S

Abstract
Cigarette smoke consists of several chemical compounds with a variety of effects in many organs. In the lung, apart being the main cause of chronic obstructive pulmonary disease, carcinoma and idiopathic spontaneous pneumothorax, tobacco smoke is associated with interstitial lung diseases (ILDs), including respiratory bronchiolitis-associated ILD (RB-ILD), desquamative interstitial pneumonia (DIP), pulmonary Langerhans' cell histiocytosis (PLCH), idiopathic pulmonary fibrosis, acute eosinophilic pneumonia, ILD in rheumatoid arthritis and pulmonary haemorrhage in Goodpasture syndrome. This review will focus on the diseases with a stronger epidemiological association with tobacco smoke, namely RB-ILD, DIP and PLCH. Although the exact pathogenetic evidence linking smoking with these disorders is still not completely understood, there is growing evidence that tobacco smoke targets the terminal or respiratory bronchioles in these diseases, and the differences are reflective of the degree of severity of small airway and parenchymal reaction to the smoke exposure. Despite considerable clinical, radiological and histological overlap between RB-ILD, DIP and PLCH, it is useful to retain the separate classifications for prognostic and therapeutic implications.

PMID: 22941885 [PubMed - in process]

Do endobronchial valves improve outcomes in patients with emphysema?

Interact Cardiovasc Thorac Surg. 2012 Sep 3;

Authors: Barua A, Vaughan P, Wotton R, Naidu B

Abstract
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether endobronchial valves improve outcomes in patients with severe emphysema. Eighty-seven papers were found using the reported search, of which seven represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Endobronchial Valve for Emphysema Palliation Trial demonstrated that endobronchial valve increased forced expiratory volume in one second by 4.3% (95% confidence interval 1.4-7.2) and decreased by 2.5% in the control group (95% confidence interval -5.4 to 0.4) at a 6-month interval. This benefit is more marked in patients who do not have collateral ventilation into the area of lung being isolated as mapped by bronchoscopic physiological mapping (Chartis) or by computed tomography imaging documenting intact fissures. This evidence is reflected in the Endobronchial Valve for Emphysema Palliation Trial. Patients treated with endobronchial valve with high heterogeneity and complete fissures had greater improvement in forced expiratory volume in one second at 6- and 12-month intervals. We conclude that endobronchial valve placement improves lung function, exercise capacity and quality of life in selected patients with emphysematous diseases.

PMID: 22945849 [PubMed - as supplied by publisher]

The expanding role(s) of eosinophils in health and disease.

Blood. 2012 Aug 30;

Authors: Jacobsen EA, Helmers RA, Lee JJ, Lee NA

Abstract
Surprisingly, the role(s) of eosinophils in health and disease is often summarized by clinicians and basic research scientists as a pervasive consensus opinion first learned in medical/graduate school: Eosinophils are rare white blood cells whose activities are primarily destructive and are only relevant in parasitic infections and asthma. However, is this consensus correct? This review will argue that the wealth of available studies investigating the role(s) of eosinophils in both health and disease demonstrate that the activities of these granulocytes are far more expansive and complex than previously appreciated. In turn, this greater understanding has led to the realization that eosinophils have significant contributory roles in a wide range of diseases. Furthermore, published studies even implicate eosinophil-mediated activities in otherwise healthy individuals! We suggest that the collective reports in the literature showing a role for eosinophils in an ever-increasing number of novel settings highlight the true complexity and importance of this granulocyte. Indeed, discussions of eosinophils are no longer simple and more often than not now begin with the question/statement "Did you know...?".

PMID: 22936660 [PubMed - as supplied by publisher]