Christian Grabow Westergaard

The effect of Varenicline on smoking cessation in a group of young asthma patients

BACKGROUND Tobacco use causes long-term morbidity and mortality. In patients with asthma, the frequency of smokers is high; however, asthmatic smokers experience more pronounced symptoms, accelerated loss of lung function and treatment resistance. Varenicline is an effective drug in smoking cessation, when investigated in COPD patients and general populations. The aim of the present study was to evaluate the effect of Varenicline on tobacco cessation in young asthmatics. METHODS In a randomized, placebo-controlled, double-blinded trial, 52 asthmatic current smokers (age 19-40) ≥ 10 cigarettes daily and ≥10 packyears (mean 15.6) were recruited to a 12 week treatment period with Varenicline or placebo (1:1) in parallel design. Evaluation of smoking status, asthma symptom score, general health quality score and methacholine challenge were performed at week 0, week 6, week 12 and week 24. RESULTS In the Varenicline group, at week 12, 69% of the patients quit smoking vs. 36% in the placebo group (p = 0.017, intended-to-treat analysis), but after 24 weeks, a high relapse rate was present (quit rates 19% vs. 16%, NS). After 6 weeks of treatment, significant improvements in airway hyperresponsiveness (AHR) in the Varenicline group was found (from 88% to 58%, p = 0.016), whereas no change was observed in the placebo group. Symptom score and general health quality improved in both the Varenicline and the placebo group. CONCLUSION We demonstrated that Varenicline can be used with a high probability of success with tobacco cessation in young smokers with asthma, but relapse rate after end of treatment is high. Quitting smoking can improve asthma control.

Smoking Cessation and the Microbiome in Induced Sputum Samples from Cigarette Smoking Asthma Patients.

Asthma is a common disease causing cough, wheezing and shortness of breath. It has been shown that the lung microbiota in asthma patients is different from the lung microbiota in healthy controls suggesting that a connection between asthma and the lung microbiome exists. Individuals with asthma who are also tobacco smokers experience more severe asthma symptoms and smoking cessation is associated with improved asthma control. In the present study we investigated if smoking cessation in asthma patients is associated with a change in the bacterial community in the lungs, examined using induced sputum. We found that while tobacco smokers with asthma have a greater bacterial diversity in the induced sputum compared to non-smoking healthy controls, smoking cessation does not lead to a change in the microbial diversity.

A review of mometasone furoate/formoterol in the treatment of asthma

Introduction: Asthma is a common chronic respiratory disease affecting the airways causing inflammation, airway hyperreactivity (AHR), and respiratory symptoms. Frequently, asthma can be effectively treated with inhaled corticosteroids (ICS) but in more severe cases additional drugs are required, such as long-acting β2-agonists (LABA). Mometasone furoate (MF) is a synthetic steroid exhibiting a strong affinity for the glucocorticoid receptor as well as a low bioavailability and a high plasma protein binding. In most cases, MF only requires once daily administration. Formoterol fumarate (F) is a full β2-agonist with a rapid onset and 12 h of duration. Areas covered: The present paper reviews the current knowledge of the novel combination of MF and F for the treatment of asthma. Furthermore, a description of the individual components is included. Expert opinion: At present, only few clinical studies of MF/F are available for review and more studies of MF/F efficacy are needed, especially comparative studies on other ICS/LABA drugs. However, it does not appear from the reviewed literature that MF/F or its individual components are inferior to other equivalent treatments.

Predictors of neutrophilic airway inflammation in young smokers with asthma.

Abstract Introduction: Asthma is one of the most widespread chronic diseases worldwide. In spite of numerous detrimental effects on asthma, smoking is common among asthma patients. These smoking-induced aggravations of asthma may be attributed to changes in airway inflammation, which is characterized by a higher degree of neutrophilic inflammation than in non-smokers. A state of neutrophilic inflammation may lead to increased steroid resistance and an accelerated loss of lung function owing to tissue destruction. The aim of this study was to elucidate predictors of neutrophilic inflammation in young asthmatic smokers not on steroid treatment, including analysis of tobacco history and bacterial colonization. Methods: In a cross-sectional study, 52 steroid-free, current smokers with asthma were examined with induced sputum, fractional exhaled nitric oxide (FeNO), lung function, ACQ6 score, mannitol and methacholine challenge. A sample from the sputum induction was taken for bacterial analysis using 16S gene PCR technique and sequencing. Results: Using one-way analysis of variance and binary and linear regression models, only age and ACQ6 score were found to be significant predictors for airway neutrophilia. The investigation also included analysis for effect of pack years, current tobacco consumption, body mass index, lung function, FeNO; methacholine and mannitol responsiveness, atopy, gender, asthma history and presence of bacteria. The most common potentially pathogenic bacteria found were Streptococcus spp., Haemophilus spp. and Mycoplasma spp. Conclusion: In this study, no tobacco-related predictors of airway neutrophilia were found, indicating that in the younger years of asthma patients who smoke, the amount of tobacco smoked in life does not influence the degree of neutrophilia. Conversely, for asthmatic smokers, neutrophilia may be induced when a certain threshold of tobacco consumption is reached.

Emerging corticosteroid agonists for the treatment of asthma

Introduction: Asthma is one of the most frequent chronic diseases worldwide. For decades, asthma has been treated with bronchodilators and inhaled corticosteroids (ICS). However, adverse effects of ICS and disease heterogeneity necessitate improvements in the existing treatment regimes. Recently approved ICS show improved pharmocodynamic properties. Nevertheless, emerging drugs acting on the same receptor as the ICS, glucocorticoid receptor agonists (GRAs), are under current research. These drugs exhibit selective action on the glucocorticoid receptor (GR), which may improve their adverse effect profile, compared to the currently approved ICS that act unselectively on the GR. Areas covered: The present article reviews emerging GRAs for the treatment of asthma. Furthermore, the more recently approved ICS with improved safety profiles are reviewed. Expert opinion: Compared with drugs acting on other pathological pathways, research in GRAs for asthma is sparse. However, a few promising agents acting selectively on the GR are currently under investigation and may reach approval for asthma treatment. These drugs exhibit improved pharmacodynamic properties due to selectivity in the mechanism of action, including promotion of transrepression and reduction of transactivation. However, competition from already approved ICS and other emerging treatment options may lead to cessation of development of the new GRAs.

Stability of FeNO and airway hyperresponsiveness to mannitol in untreated asthmatics.

ABSTRACT Objective: Airway hyperresponsiveness and airway inflammation are important hallmarks of asthma and are useful in asthma diagnosing, monitoring and treatment. The aim of the study was to assess whether two commonly used clinical tests, the mannitol challenge and Fraction of exhaled NO (FeNO), were stable clinical indicators over time in stable untreated asthmatics. Methods: 54 non-smoking, asthma patients not treated with steroids were enrolled in the study and assessed at baseline and a median of 6 months later. At baseline and follow-up, FeNO and airway hyperesponsiveness to mannitol were measured, and asthma control was assessed with the Asthma Control Questionnaire (ACQ). Results: A total of 41 subjects completed both visits. Mean (SD) FEV1% at baseline was 94.1% (17.7) and at re-examination 94.6% (19.7) (ns). The ACQ score was unchanged from baseline (Mean (SD): 0.90 (± 0.73)) to follow-up 0.90 (± 0.74) (ns), as was the FEV1% (94.1% (±17.1%) vs 94.6% (19.7%)(ns) indicating that patients were clinically stable during follow-up. The response to mannitol was unchanged at follow-up (Geometric mean (CI) of Response Dose Ratio (RDR) to mannitol: 0.026(0.013–0.046) vs 0.026(0.012–0.050) (ns). There was a slight decrease in FeNO at follow-up (25.5 ppb (19.7–32.9) to 21.9 ppb (17.1–28.2) (p < 0.001). Conclusions: In steroid-free non-smoking asthmatics with constant symptom scores and lung function, airway responsiveness to mannitol remained at the same level over a period of months, while a minor change in exhaled FeNO was reported. These results suggest that mannitol is a stable, reliable marker of clinical disease activity.