Cigarette smoking among asthma patients is associated with worsening symptoms and accelerated decline in lung function. Smoking asthma is also characterized by increased levels of neutrophils and macrophages, and greater small airway remodeling, resulting in increased airflow obstruction and impaired response to corticosteroid therapy. As a result, smokers are typically excluded from asthma randomized controlled trials (RCTs). The strict inclusion/exclusion criteria used by asthma RCTs limits the extent to which their findings can be extrapolated to the routine care asthma population and to reflect the likely effectiveness of therapies in subgroups of particular clinical interest, such as smoking asthmatics. The inclusion of smokers in observational asthma studies and pragmatic trials in asthma provides a way of assessing the relative effectiveness of different treatment options for the management of this interesting clinical subgroup. Exploratory studies of possible treatment options for smoking asthma suggest potential utility in: prescribing higher-dose ICS; targeting the small airways of the lungs with extra-fine particle ICS formulations; targeting leukotreines, and possibly also combinations of these options. However, further studies are required. With the paucity of RCT data available, complementary streams of evidence (those from RCTs, pragmatic trials and observational studies) need to be combined to help guide judicious prescribing decisions in smokers with asthma.
Airway Remodeling ; Asthma* ; Humans ; Lung ; Macrophages ; Neutrophils ; Pragmatic Clinical Trials as Topic ; Rivers ; Smoke* ; Smoking

Despite international and national guidelines, poor asthma control remains an issue. Asthma exacerbations are costly to both the individual, and the healthcare provider. Improvements in our understanding of the therapeutic benefit of asthma therapies suggest that, in general, while long-acting bronchodilator therapy improves asthma symptoms, the anti-inflammatory activity of inhaled corticosteroids reduces acute asthma exacerbations. Studies have explored factors which could be predictive of exacerbations. A history of previous exacerbations, poor asthma control, poor inhaler technique, a history of lower respiratory tract infections, poor adherence to medication, the presence of allergic rhinitis, gastro-oesophageal reflux disease, psychological dysfunction, smoking and obesity have all been implicated as having a predictive role in the future risk of asthma exacerbation. Here we review the current literature and discuss this in the context of primary care management of asthma.
Adrenal Cortex Hormones ; Asthma ; Disease Progression ; Gastroesophageal Reflux ; Health Personnel ; Humans ; Nebulizers and Vaporizers ; Obesity ; Primary Health Care ; Respiratory Tract Infections ; Rhinitis ; Rhinitis, Allergic, Perennial ; Smoke ; Smoking

PURPOSE: Smoking has detrimental effects on asthma symptom control and response to treatment and is prevalent among asthma patients in South Korea. The aim of this study is to determine the prevalence of smoking among asthma patients in South Korea and to compare the medication regimens of asthma patients who do and do not smoke. METHODS: A cross-sectional survey was conducted from August 2010 to January 2011. Participating physicians (N=25) recorded demographic and clinical data on all asthma patients presenting during the study period (N=2,032), and then recruited a subset of patients (N=500) for the survey such that half were self-reported current smokers. Recruited patients were between the ages of 18 and 60. RESULTS: Among presenting asthma patients, 17.3% were current smokers, 19.2% were former smokers, and 63.5% had never smoked. Within the analyzable study population (N=471), 212 patients reported smoking currently, 79 smoking formerly, and 180 never smoking. Among current and former smokers, 79.7% and 81.0%, respectively, were men, while women represented 80.5% of patients who had never smoked. Agreement was strong between physician-determined smoking status and patient-reported smoking status (kappa=0.82; P<0.001). However, asthma medication regimens examined according to GINA treatment steps did not differ by smoking status. In addition, mean quality of life scores and level of asthma control did not differ by smoking status. CONCLUSIONS: In South Korea, physicians are well aware of the smoking status of their patients. However, smoking status did not affect the prescribed medication regimens of this population of asthma patients.
Asthma* ; Cross-Sectional Studies ; Female ; Humans ; Korea ; Male ; Prevalence ; Quality of Life ; Seoul ; Smoke* ; Smoking*

OBJECTIVEOur previous study shows that PURNE2 mRNA plays an important role in the differential diagnosis of leiomyosarcoma and gastrointestinal stromal tumor (GIST). Non-coding RNA PCA3 locates in the intron of PRUNE2 and may play a role in PRUNE2 expression. The aim of this study was to explore the expression of PCA3 mRNA and PRUNE2 in leiomyosarcoma and their correlation.

METHODSThe expression of PRUNE2 mRNA was analyzed by agilent gene expression microarray CHIP in 31 leiomyosarcomas and 37 GISTs, and the correlation of the PRUNE2 expression and prognosis of leiomyosarcoma was predicted. Real-Time PCR assay was used to detect the mRNA levels of PCA3 and PRUNE2 in 13 leiomyosarcomas and to investigate their correlation. Seven prostate cancer tissues were used as control of PCA3.

RESULTSThe level of PRUNE2 mRNA expression was significantly higher in the 31 leiomyosarcomas than that in the 37 GISTs, and the level of PRUNE2 mRNA expression was correlated with survival of the leiomyosarcoma patients. Compared with prostate cancer, the non-coding RNA PCA3 expression level was significantly lower in leiomyosarcoma, and it had no correlation with the prognosis of leiomyosarcoma. Most importantly, the PRUNE2 and PCA3 mRNA expressions were both upregulated in leiomyosarcoma and showed a significant positive correlation.

CONCLUSIONSOur findings demonstrate for the first time that PRUNE2 expression is correlated with the survival of leiomyosarcoma patients. Furthermore, non-coding RNA PCA3, which locates in the intron of PRUNE2, has a significant positive correlation with PRUNE2 and may play an important role in the pathogenesis of leiomyosarcoma.

Antigens, Neoplasm ; genetics ; metabolism ; Female ; Gastrointestinal Neoplasms ; genetics ; metabolism ; Gastrointestinal Stromal Tumors ; genetics ; metabolism ; Humans ; Leiomyosarcoma ; genetics ; metabolism ; Male ; Neoplasm Proteins ; genetics ; metabolism ; Prostatic Neoplasms ; genetics ; metabolism ; RNA, Messenger ; metabolism ; RNA, Untranslated ; metabolism ; Retroperitoneal Neoplasms ; genetics ; metabolism ; Survival Rate ; Uterine Neoplasms ; genetics ; metabolism

PURPOSE: Correct use of inhaler devices is fundamental to effective asthma management but represents an important challenge for patients. The correct inhalation manoeuvre differs markedly for different inhaler types. The objective of this study was to compare outcomes for patients prescribed the same inhaler device versus mixed device types for asthma controller and reliever therapy. METHODS: This retrospective observational study identified patients with asthma (ages 4-80 years) in a large primary care database who were prescribed an inhaled corticosteroid (ICS) for the first time. We compared outcomes for patients prescribed the same breath-actuated inhaler (BAI) for ICS controller and salbutamol reliever versus mixed devices (BAI for controller and pressurised metered-dose inhaler [pMDI] for reliever). The 2-year study included 1 baseline year before the ICS prescription (to identify and correct for confounding factors) and 1 outcome year. Endpoints were asthma control (defined as no hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection) and severe exacerbations (hospitalisation or oral corticosteroids for asthma). RESULTS: Patients prescribed the same device (n=3,428) were significantly more likely to achieve asthma control (adjusted odds ratio, 1.15; 95% confidence interval [CI], 1.02-1.28) and recorded significantly lower severe exacerbation rates (adjusted rate ratio, 0.79; 95% CI, 0.68-0.93) than those prescribed mixed devices (n=5,452). CONCLUSIONS: These findings suggest that, when possible, the same device should be prescribed for both ICS and reliever therapy when patients are initiating ICS.
Adrenal Cortex Hormones ; Albuterol ; Anti-Bacterial Agents ; Asthma ; Humans ; Inhalation ; Nebulizers and Vaporizers ; Odds Ratio ; Prescriptions ; Primary Health Care ; Respiratory System ; Retrospective Studies

PURPOSE: To develop a profiling tool which accurately assigns a patient to the appropriate attitudinal cluster for the management of asthma. METHODS: Attitudinal data from an online survey of 2,467 patients with asthma from 8 Asian countries/region, aged 18-50 years, having had ≥2 prescriptions in the previous 2 years and access to social media was used in a discriminant function analysis to identify a minimal set of questions for the Profiling Tool. A split-sample procedure based on 100 sets of randomly selected estimation and validation sub-samples from the original sample was used to cross-validate the Tool and assess the robustness of its predictive accuracy. RESULTS: Our Profiling Tool contained 10 attitudinal questions for the patient and 1 GINA-based level of asthma control question for the physician. It achieved a predictive accuracy of 76.2%. The estimation and validation sub-sample accuracies of 76.7% and 75.3%, respectively, were consistent with the tool's predictive accuracy at 95% confidence level; and their 1.4 percentage-points difference set upper-bound estimate for the degree of over-fitting. CONCLUSIONS: The Profiling Tool is highly predictive (>75%) of the attitudinal clusters that best describe patients with asthma in the Asian population. By identifying the attitudinal profile of the patient, the physician can make the appropriate asthma management decisions in practice. The challenge is to integrate its use into the consultation workflow and apply to areas where Internet resources are not available or patients who are not comfortable with the use of such technology.
Asia ; Asian Continental Ancestry Group ; Asthma* ; Discriminant Analysis ; Disease Management ; Humans ; Internet ; Prescriptions ; Social Media

PURPOSE: Inhaled corticosteroids (ICSs) are often considered an empirical therapy in the management of patients with cough. However, ICS responsiveness is difficult to interpret in daily clinical practice, as the improvements may include placebo effects or self-remission. We aimed to evaluate ICS and placebo treatment effects in adult patients with cough. METHODS: Electronic databases were searched for studies published until June 2018, without language restriction. Randomized controlled trials reporting the effects of ICSs compared with placebo in adult patients with cough were included. Random effects meta-analyses were conducted to estimate the treatment effects. Therapeutic gain was calculated by subtracting the percentage change from baseline in the cough score in the ICS treatment group from that in the placebo treatment group. RESULTS: A total of 9 studies were identified and 8 studies measuring cough severity outcomes were included for meta-analyses. Therapeutic gain from ICSs ranged from −5.0% to +94.6% across the studies included; however, it did not exceed +22%, except for an outlier reporting very high therapeutic gains (+45.6% to +94.6%, depending on outcomes). Overall ICS treatment effects in cough severity outcomes were small-to-moderate (standardized mean difference [SMD], −0.38; 95% confidence interval [CI], −0.54, −0.23), which were comparable between subacute and chronic coughs. However, pooled placebo treatment effects were very large in subacute cough (SMD, −2.58; 95% CI, −3.03, −2.1), and modest but significant in chronic cough (SMD, −0.46; 95% CI, −0.72, −0.21). CONCLUSIONS: Overall therapeutic gain from ICSs is small-to-moderate. However, placebo treatment effects of ICS are large in subacute cough, and modest but still significant in chronic cough. These findings indicate the need for careful interpretation of ICS responsiveness in the management of cough patients in the clinic, and also for rigorous patient selection to identify ICS-responders.
Adrenal Cortex Hormones ; Adult ; Cough ; Humans ; Overall ; Patient Selection ; Placebo Effect ; Steroids

PURPOSE: Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone). METHODS: This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year. Co-primary endpoints were 1-year severe exacerbation rates, risk-domain asthma control, and overall asthma control; secondary endpoints included therapy change. RESULTS: Each cohort included 1,244 patients (median age 45 years; 65% women). Patients in the ciclesonide cohort were comparable to those in the fine-particle ICS cohort apart from higher baseline prevalence of hospitalization, gastroesophageal reflux disease, and rhinitis. Median (interquartile range) prescribed doses of ciclesonide and fine-particle ICS were 160 (160-160) µg/day and 500 (250-500) µg/day, respectively (P<0.001). During the outcome year, patients prescribed ciclesonide experienced lower severe exacerbation rates (adjusted rate ratio [95% CI], 0.69 [0.53-0.89]), and higher odds of risk-domain asthma control (adjusted odds ratio [95% CI], 1.62 [1.27-2.06]) and of overall asthma control (2.08 [1.68-2.57]) than those prescribed fine-particle ICS. The odds of therapy change were 0.70 (0.59-0.83) with ciclesonide. CONCLUSIONS: In this matched cohort analysis, we observed that initiation of ICS with ciclesonide was associated with better 1-year asthma outcomes and fewer changes to therapy, despite data suggesting more difficult-to-control asthma. The median prescribed dose of ciclesonide was one-third that of fine-particle ICS.
Adrenal Cortex Hormones* ; Anti-Asthmatic Agents ; Asthma ; Cohort Studies ; Comparative Effectiveness Research ; Diethylpropion ; Disease Progression ; Gastroesophageal Reflux ; Hospitalization ; Humans ; Odds Ratio ; Prevalence ; Rhinitis