Spirometry

Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial.

Posted by

0


Abstract

Background Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides.

Methods We performed a randomised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting β2agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ).

Results The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma (blood eosinophilia ≤200/µl): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci.

Conclusions Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study.

 

Source: Thorax

Blood mRNA biomarkers for detection of treatment response in acute pulmonary exacerbations of cystic fibrosis.

Posted by

0


Abstract

Background Acute pulmonary exacerbations accelerate pulmonary decline in cystic fibrosis (CF). There is a critical need for better predictors of treatment response.

Objective To test whether expression of a panel of leucocyte genes directly measured from whole blood predicts reductions in sputum bacterial density.

Methods A previously validated 10-gene peripheral blood mononuclear cell (PBMC) signature was prospectively tested in PBMC and whole blood leucocyte RNA isolated from adult subjects with CF at the beginning and end of treatment for an acute pulmonary exacerbation. Gene expression was simultaneously quantified from PBMCs and whole blood RNA using real-time PCR amplification. Test characteristics including sensitivity, specificity, positive and negative predictive values were calculated and receiver operating characteristic curves determined the best cut-off to diagnose a microbiological response. The findings were then validated in a smaller independent sample.

Results Whole blood transcript measurements are more accurate than forced expiratory volume in 1 s (FEV1) or C reactive protein (CRP) alone in identifying reduction of airway infection. When added to FEV1, the whole blood gene panel improved diagnostic accuracy from 64% to 82%. The specificity of the test to detect reduced infection was 88% and the positive predictive value for the presence of persistent infection was 86%. The area under the curve for detecting treatment response was 0.81. Six genes were the most significant predictors for identifying reduction in airway bacterial load beyond FEV1 or CRP alone. The high specificity of the test was replicated in the validation cohort.

Conclusions The addition of blood leucocyte gene expression to FEV1 and CRP enhances specificity in predicting reduced pulmonary infection and may bolster the assessment of CF treatment outcomes.

Source: Thorax.

 

Novartis data presented at ERS showcases once-daily COPD portfolio and further demonstrates efficacy of Ultibro® Breezhaler® (QVA149) .

Posted by

0


 

  • BLAZE study also demonstrated significant improvements in shortness of breath with QVA149 compared to tiotropium 18 mcg in patients with moderate-to-severe COPD[3]

 

  • SPARK study showed similar rates of reduction in exacerbations with once-daily Seebri® Breezhaler®(glycopyrronium bromide) and open-label tiotropium 18 mcg in patients with severe-to-very severe COPD[4],[5]

 

Novartis announced today new analyses of data for once-daily Ultibro® Breezhaler®(investigational QVA149 – indacaterol 85 mcg/glycopyrronium 43 mcg delivered dose, equivalent to 110 mcg/50 mcg metered dose per capsule), which showed significant improvements in lung function, shortness of breath and health-related quality of life for chronic obstructive pulmonary disease (COPD) patients versus all comparators[1],[2].These data were part of 39 respiratory abstracts presented at the European Respiratory Society (ERS) Annual Congress in Barcelona, Spain.

 

First results from a pooled analysis of 4,891 COPD patients in the IGNITE clinical trial program (SHINE, ILLUMINATE and SPARK studies) showed that QVA149 provided superior, rapid and sustained improvements in lung function, and significantly reduced shortness of breath, compared to placebo, once-daily indacaterol maleate 150 mcg,glycopyrronium 50 mcg, open-label (OL) tiotropium 18 mcg and twice-daily salmeterol/fluticasone fixed dose combination (FDC SFC) 50 mcg/500 mcg[1],[2]. These improvements were maintained throughout the duration of the trials[1],[2].

 

“COPD is known to affect an estimated 210 million people worldwide[6] and is projected to be the third leading cause of death by 2020[7].Many patients find COPD symptoms really tough to cope with – even if they’re already taking treatment,” said Tim Wright, Head of Development, Novartis Pharmaceuticals. “Novartis is pleased that these new analyses further support that the efficacy of dual therapy, which has the potential to make a real difference to peoples’ lives.”

 

Currently being assessed in a clinical trial program involving over 10,000 patients[8]-[18], investigational QVA149 is a Fixed-Dose Combination (FDC) of two bronchodilators, Onbrez® Breezhaler® (indacaterol maleate), a long-acting beta2-adrenergic agonist (LABA) and Seebri® Breezhaler® (glycopyrronium bromide), a long-acting muscarinic antagonist (LAMA). Both are currently used by healthcare professionals as individual therapies to treat COPD.

 

QVA149 recentlyreceived a positive opinion for approval from the European Medicine Agency’s (EMA) Committee for the Human use of Medicinal Products (CHMP) in July 2013 as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD.

 

About additional data presented at ERS

A new evaluation of patients with moderate-to-severe COPD from the BLAZE study showed that QVA149 provided significant improvements in patient-reported shortness of breath compared to tiotropium 18 mcg[3].

 

Clinical data for Seebri® Breezhaler® (glycopyrronium bromide) presented at ERS included efficacy and safety results from the SPARK study[4],[5]. At Week 64, once-daily glycopyrronium 50 mcg showed similar efficacy to OL tiotropium 18 mcg in reducing the rate of exacerbations, improving lung function and health-related quality of life, and reducing rescue medication use in patients with severe-to-very severe COPD[4].

 

In analyses from the SPARK study, glycopyrronium 50 mcg (via Breezhaler®) showed a safety profile in patients with severe-to-very severe COPD that was similar to OL tiotropium 18 mcg (via HandiHaler®)[5].

 

These results build upon the data previously presented from the glycopyrronium bromide Phase III GLOW trials and provide further evidence for Seebri® Breezhaler® as a once-daily LAMA option for COPD patients.

 

About the IGNITE clinical trial program

In the Phase III IGNITE clinical trial program, QVA149 is being investigated for the treatment of COPD patients as aninhaled, once-daily, FDC of indacaterol maleate and glycopyrronium bromide. IGNITE is one of the largest international clinical trial programs in COPD comprising 11 studies in total (ILLUMINATE, SHINE, BRIGHT, ENLIGHTEN, SPARK, BLAZE, ARISE, BEACON, RADIATE, LANTERN, FLAME) with more than 10,000* patients across 52 countries[8]-[20]. The first eight studies (ILLUMINATE, SHINE, BRIGHT, ENLIGHTEN, SPARK, BLAZE, ARISE, BEACON) completed in 2012. The studies are designed to investigate the efficacy, safety and tolerability, lung function, exercise endurance, exacerbations, shortness of breath and quality of life in patients treated with QVA149.

 

Results from the Phase III IGNITE trials[8]-[18]demonstrated statistically significant improvements in bronchodilation with QVA149 versus comparator treatments widely used as current standards of care[21]. Data showed that QVA149 significantly improved bronchodilation compared to OL tiotropium 18 mcg, SFC 50 mcg/500 mcg, indacaterol maleate 150 mcg, glycopyrronium 50 mcg and placebo providing a rapid onset within five minutes, and sustained bronchodilation during a 24 hour period which was maintained for up to 26 weeks[22]. In the IGNITE Phase III trial program, QVA149 also showed symptomatic improvements versus placebo in COPD patients[8],[9],[11],[21]. These symptomatic improvements included shortness of breath, exercise tolerance, rescue medication use and health-related quality of life[8],[9],[11],[21].

 

In clinical studies, QVA149 demonstrated an acceptable safety profile with no meaningful differences between the treatment groups (placebo, indacaterol 150 mcg, glycopyrronium 50 mcg, OL tiotropium 18 mcg, SFC 50 mcg/500 mcg) in the incidence of adverse and serious adverse events[8],[9],[10],[11],[22].

 

*Total refers to all 11 IGNITE studies.

 

About the Novartis COPD portfolio

Novartis is committed to addressing the unmet medical needs of COPD patients and improving their quality of life by providing innovative medicines and devices.

 

Onbrez® Breezhaler® (indacaterol maleate) is a long-acting beta2-adrenergic agonist (LABA) that offers clinically relevant 24 hour bronchodilation combined with a rapid onset of action within five minutes at first dose, as demonstrated in the INERGIZE Phase III trial program[23]-[27]. Onbrez® Breezhaler® 150 mcg once-daily provided greater clinical benefit in terms of reduced shortness of breath, lower use of rescue medication and improved health status, compared with blinded tiotropium bromide 18 mcg in patients with moderate-to-severe COPD[34]. Onbrez®Breezhaler®is approved in approximately 100 countries around the world for maintenance bronchodilator treatment of airflow obstruction in adult patients with COPD[38]. It was first launched in the EU (150 mcg and 300 mcg once-daily doses) and has since received approvals in markets worldwide including Japan (Onbrez® Inhalation Capsules 150 mcg once-daily) and US (ArcaptaTM NeohalerTM 75 mcg once-daily).

 

Once-daily Seebri® Breezhaler® (glycopyrronium bromide) is a novel inhaled long-acting muscarinic antagonist (LAMA; also referred to as a long-acting anticholinergic) indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD[39]. Glycopyrronium bromide was exclusively licensed to Novartis in April 2005 by Vectura and its co-development partner Sosei. Phase III data from the GLOW 1, 2 and 3 studies demonstrated that glycopyrronium 50 mcg delivered rapid and significant sustained improvements in lung function (measured by mean FEV1) from Day 1 compared with placebo and sustained this for 24 hours over 52 weeks, and significantly improved exercise endurance versus placebo[40]-[42]. Seebri® Breezhaler® is approved in the EU/EEA, Japan, Switzerland, Canada, Australia and a number of other countries.

 

Novartis continues development of respiratory products for delivery via a single-dose dry powder inhaler (SDDPI) called the Breezhaler® device which has low air flow resistance, making it suitable for patients with different severity of airflow limitation[43]. The Breezhaler® device allows patients to hear, feel and see that they have taken the full dose correctly[39].

 

Novartis is committed to addressing the unmet medical needs of COPD patients and improving their quality of life by providing innovative medicines and devices.

 

About COPD

COPD is a progressive life-threatening disease that makes it hard to breathe, with symptoms that have a destructive impact on patients’ function and quality of life[7],[44]. It affects an estimated 210 million people worldwide[7] and is projected to be the third leading cause of death by 2020[6]. COPD is often considered to be a disease of later years, but estimates suggest that 50% of those with COPD are now less than 65 years old, resulting in increases in absenteeism, premature retirement and reductions in workforce participation

Source: Novartis Newsletter.

Adverse respiratory effects associated with cadmium exposure in small-scale jewellery workshops in India.

Posted by

0


Abstract

Background Cadmium (Cd) is an important metal with both common occupational and environmental sources of exposure. Although it is likely to cause adverse respiratory effects, relevant human data are relatively sparse.

Methods A cross-sectional study of 133 workers in jewellery workshops using Cd under poor hygienic conditions and 54 referent jewellery sales staffs was performed. We assessed symptoms, performed spirometry, measured urinary Cd levels in all study subjects and quantified airborne total oxidant contents for 35 job areas in which the studied workforce was employed. We tested the association of symptoms with exposure relative to the unexposed referents using logistic regression analysis, and tested the association between urinary Cd levels and lung function using multiple regression analysis, adjusting for demographics, smoking and area-level airborne oxidants.

Results Exposed workers had 10 times higher urinary Cd values than referents (geometric mean 5.8 vs 0.41 µg/dl; p<0.01). Of the exposed subjects, 75% reported respiratory tract symptoms compared with 33% of the referents (OR=3.1, 95% CI 1.4 to 7.3). Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were also lower among the exposed workers than the referents (>600 ml decrement for each, p<0.001). For every 1 µg increase in urinary Cd there was a 34 ml decrement in FVC and a 39 ml decrement in FEV1(p<0.01), taking into account other covariates including workplace airborne oxidant concentrations.

Conclusions This cohort of heavily exposed jewellery workers experienced frequent respiratory symptoms and manifested a marked deficit in lung function, demonstrating a strong response to Cd exposure.

Source: Thorax

Are inhaled longacting β2 agonists detrimental to asthma?

Posted by

0


Possible adverse effects of adrenergic bronchodilators in asthma have been the subject of discussion for more than half a century, with recent intense debate about the safety of longacting β agonists (LABAs). In this Debate, we consider the issues of bronchodilator and bronchoprotective tolerance resulting from the frequent use of bronchodilators, which is noted particularly with shortacting drugs, but has also been shown to occur quicker and to a greater extent with LABAs. Increased allergen responsiveness and masking allowing inflammation to increase, while symptoms and lung function remain apparently controlled, have also been observed. Studies in which LABAs were used as monotherapy were associated with increased mortality. However, several studies have shown the benefits of adding LABAs to inhaled corticosteroids (ICS). Meta-analyses of asthma clinical trials involving LABAs showed that, when given with mandatory ICS, LABAs were not associated with an increased risk of death, intubations, or hospital admission for exacerbations when compared with use of the same dose of ICS only. Withdrawal of LABA therapy once symptom control is achieved is often associated with subsequent loss of symptom control. When used for appropriate indications, LABAs should be combined with ICS in one inhaler so that monotherapy is not possible.

Source: lancet

 

Inhaled corticosteroids in severe COPD.

Posted by

0


lung

Guidelines and care pathways recommend inhaled corticosteroids (ICSs) over longacting bronchodilators in the treatment of patients with severe chronic obstructive pulmonary disease (COPD).1, 2 A Cochrane review3 about the safety and efficacy of combined ICSs and longacting β2 agonists (LABAs) in one inhaler versus LABAs alone for COPD was published in September, 2012. Although the analysis was based on a large database (14 studies, 11 794 people), the conclusions were unclear about prevention of exacerbations, hospital admission, and mortality. Furthermore, moderate-quality evidence suggested an increased risk of pneumonia with ICS—LABA combinations. The authors concluded that more information about the relative benefits and adverse event rates of ICS—LABA combinations versus LABAs alone would be useful and that head-to-head comparisons are needed.3

Fluticasone furoate is a new ICS and vilanterol a new LABA. Both drugs are given once daily. A single inhaler combination of these drugs improved forced expiratory volume in 1 s (FEV1) after a short duration of treatment.4 In The Lancet Respiratory Medicine, Mark T Dransfield and colleagues5 report the results of the first long-term study comparing fluticasone furoate and vilanterol with vilanterol alone for major outcomes of COPD (ie, moderate or severe exacerbations). Two pooled multinational randomised controlled trials (study 1 and study 2) of 3255 patients with severe COPD ran for 52 weeks. Mean FEV1 after bronchodilators was 44—46% of predicted values. Three doses of fluticasone furoate were tested—50 μg, 100 μg, and 200 μg—all in combination with 25 μg vilanterol. The primary efficacy endpoint was the yearly rate of moderate or severe exacerbations. The authors defined moderate exacerbations as worsening symptoms of COPD (≥2 consecutive days) necessitating treatment with oral corticosteroids or antibiotics, or both; severe exacerbations were similar events that necessitated admission to hospital.

Dransfield and coworkers’ study5 is of great interest because it is, to my knowledge, the first investigating the combination of fluticasone furoate and vilanterol for major outcomes of COPD, and because it attempts to answer the queries that arose from the Cochrane review.3 Pneumonia occurrence was recorded and confirmed with chest radiographs. The study was very carefully done, although an independent expert panel did not assess severe adverse events, which might have led to underestimation of pneumonia risk.

The effect of fluticasone furoate and vilanterol compared with that of vilanterol alone is not large. In study 1, no significant difference in exacerbation rate was noted between the 200/25 μg fluticasone furoate/vilanterol group and the vilanterol only group. In study 2 and the prespecified pooled analysis, exacerbation rates were significantly lower in all fluticasone furoate/vilanterol groups than in the vilanterol only group. The frequency of only moderate exacerbations was significantly lower with fluticasone furoate and vilanterol than with vilanterol alone. Hospital admissions were uncommon in the studies and did not differ significantly between treatment groups. Thus, the additive effect of fluticasone furoate could not be shown—results that accord with those of the Cochrane review3 and reinforce the strength of evidence.

The safety of ICSs in COPD is a serious problem, which was underscored by Dransfield and colleagues’ results.5 Pneumonia (confirmed by radiography) and fractures were reported more frequently with fluticasone furoate and vilanterol than with vilanterol alone in studies 1 and 2 and the pooled analysis. Furthermore, severe cases of pneumonia were more frequent in the fluticasone furoate/vilanterol groups than in the vilanterol group. Eight pneumonia-related deaths were reported during treatment, seven participants taking 200 μg fluticasone furoate and one taking 100 μg fluticasone furoate. One case of fatal pneumonia was reported after treatment in the vilanterol only group. The authors raised concerns about the 200/25 μg dose. However, mortality was not increased in any study group, according with the results of Dong and colleagues.

Patients and clinicians should assess the potential benefits and risks of ICSs in severe COPD. For a practising physician, establishing which patients need ICSs (and which do not) is crucial. Randomised controlled studies published so far cannot answer this question because their results are based on means from large groups of patients. The phenotypic characteristics of patients who benefit from ICSs and those of patients prone to pneumonia would be of interest. Dransfield and coworkers’ study might enable an analysis of practical interest. It shows that the debate about ICSs in patients with severe COPD is not yet over, and suggests that a personalised medicine approach is needed for such patients.

Source: lancet

 

 

 

COPD treatment: time to change our algorithm?

Posted by

0


puff

For the past decade, clinicians have largely followed a set of similar algorithms for chronic obstructive pulmonary disease (COPD) therapy, initiating treatment with an inhaled longacting antimuscarinic (LAMA) and adding combination therapy with a longacting β agonist (LABA) plus an inhaled corticosteroid when symptom or exacerbation control is inadequate. This algorithm is also in accordance with the Global initiative for chronic Obstructive Lung Disease (GOLD) 2007 consensus statement.1 However, the GOLD 2013 consensus statement challenges clinicians to rethink this routine.2 A wide range of treatment options are proposed including LAMA/LABA dual therapy, which is recommended as a treatment alternative for group B (high symptoms/low risk), C (low symptoms/high risk), and D (high symptom/high risk) patients. However, few data have been available to support the efficacy of this combination therapy over single agent bronchodilator therapy. Good data already exist for the efficacy of LAMA monotherapy for symptom control and exacerbation reduction3 as well as for the efficacy of LABA monotherapy for symptom control,4 but scarce data have been available for whether dual agent therapy has additional benefit in terms of either symptom control or exacerbation reduction.

In The Lancet Respiratory Medicine, Jadwiga Wedzicha and colleagues5 present data from the SPARK study, a randomised, three-group, double-blind study in COPD comparing once-daily indacaterol plus glycopyrronium combination therapy (QVA149) versus glycopyrronium alone versus open-label tiotropium. The primary endpoint examined was superiority of QVA149 versus glycopyrronium in reducing the frequency of moderate to severe COPD exacerbations, with the comparison of QVA149 versus tiotropium as a major secondary endpoint. Inclusion criteria were post-bronchodilator forced expiratory volume in 1 s (FEV1) less than 50% and at least one exacerbation in the previous 12 months. This study showed a 12% reduction in the rate of moderate to severe exacerbations for QVA149 compared with glycopyrronium (rate ratio [RR] 0·88, 95% CI 0·77—0·99, p=0·038). The 10% reduction in moderate to severe exacerbations for QVA149 compared with tiotropium was not significant (RR 0·90, 95% CI 0·79—1·02, p=0·096). QVA149 also resulted in significantly higher trough FEV1 as compared to glycopyrronium (differences 70—80 mL, p<0·0001) and tiotropium (differences 60—80 mL, p<0·0001) and resulted in 8—9 unit improvements in St George’s Respiratory Questionnaire score (SGRQ) total score as opposed to 6 units with glycopyrronium and 5—6 units with tiotropium, both significant differences.

The real question is how these data should influence prescribing practices for COPD. These data support better lung function improvement, better symptom control, and greater exacerbation reduction with LAMA/LABA therapy as opposed to LAMA therapy alone in patients with severe to very severe disease. In reality, such patients are likely to be on some form of therapy before they progress to this level of disease severity. Hence for the patient already on LAMA therapy, the addition of a LABA, particularly if exacerbation reduction is a goal, as a next step in therapy is supported by these data.

These data must be interpreted in light of the fact that about 75% of patients were on concomitant inhaled corticosteroids, which has several implications. First, the magnitude of exacerbation reduction seen was 12%, which is arguably clinically significant but might have been attenuated owing to concomitant inhaled corticosteroid use. These results mirror the magnitude of reduction seen with tiotropium in the UPLIFT study,3 in which concomitant inhaled corticosteroid plus LABA therapy was allowed. Second, the high rates of concomitant inhaled corticosteroid use also mean that these data perhaps provide less support for the GOLD recommendation of LABA/LAMA as dual therapy for either groups C or D and perhaps provide greater support for triple therapy (addition of LABA to LAMA plus inhaled corticosteroids) for C and D patients.

In further thinking about how these data inform prescribing practices, one should also note that 22% of patients studied had two or more moderate or severe exacerbations in the previous year. Previous data suggest that group D patients who are judged to be at high risk by both FEV1 and exacerbation criteria are at even greater risk of moderate and severe exacerbations than are those meeting a single criterion, suggesting good efficacy in a relatively high risk population.6 On the other hand, another interesting finding of the study was that the greatest reduction was seen in mild exacerbations—15% with QVA149 compared with glycopyrronium and 16% compared with tiotropium—with mild exacerbations defined as an event with increase in symptoms but self-managed by the patient. Although exacerbation events requiring therapy are more frequently studied, the importance of untreated events should not be underestimated. Even events unreported to a health-care provider have been shown to be associated with significantly worse health status,7 which might explain the improvements in SGRQ score seen with QVA149 therapy.

Overall, these data support greater efficacy for dual bronchodilator therapy with QVA149 as compared with LAMA monotherapy. In view of the lack of data in the past, the use of combination LABA/LAMA therapy has not been embraced by medical practitioners for use in COPD, but these new data suggest dual therapy is an important therapeutic option when trying to maximise symptom improvement and exacerbation reduction.

Source: Lancet

 

Tiotropium Prevents Exacerbations in Some Patients with Severe Asthma.

Posted by

0


In patients with poorly controlled asthma, this agent might be a reasonable option.

Some patients with asthma continue to experience poor lung function despite receiving long-acting β-agonists (LABAs) in combination with inhaled corticosteroids (ICS). Tiotropium is a long-acting anticholinergic (approved for chronic obstructive pulmonary disease) that has shown promise in short-term trials for treating asthmatic patients (JW Gen Med Jun 14 2011).

In two replicate, industry-sponsored, randomized trials, 912 adult patients received tiotropium or placebo. All patients experienced at least one severe exacerbation in the previous year and had persistent airflow limitation (mean post-bronchodilator forced expiratory volume in 1 second [FEV1], 62% of predicted), despite therapy with high-dose ICS and LABAs, which were continued during the study. At 24 weeks, lung function in the tiotropium group had increased modestly (roughly 100 cc) from baseline FEV1. The interval at which 25% of patients had experienced severe exacerbations was significantly longer with tiotropium than with placebo (282 vs. 226 days). At 48 weeks, the number needed to treat with tiotropium to prevent 1 severe exacerbation was 15. Asthma symptom scores did not reach the predefined clinically significant endpoint. Adverse events were similar in both groups.

Comment: Overall, improvement in lung function and exacerbations was modest when tiotropium was added to therapy in patients who already were receiving high-dose ICS and LABAs. That said, we have little else to offer patients with severe asthma and fixed obstruction. Although tiotropium is not FDA-approved for asthma, I think it is a reasonable option for patients who continue to have exacerbations that require oral corticosteroids or hospitalizations despite maximal asthma therapy. In an accompanying editorial, the writer cautions against extending this finding to all asthmatics, because fixed obstruction might share features with COPD and thus be responsive to the anticholinergic effect. Also, she points out that tiotropium (especially in the fine-mist device used in this study versus the dry-powder device we have in the U.S.) might contribute to risk for death from cardiovascular causes and cautions against its use in patients with cardiovascular disease.

 David J. Amrol, MD

Dr. Amrol is an Associate Professor of Clinical Internal Medicine and Director of the Division of Allergy and Immunology at the University of South Carolina School of Medicine in Columbia.

Source: Journal Watch General Medicine