Health impact of e-cigarettes and heated tobacco products in chronic obstructive pulmonary disease: current and emerging evidence.

INTRODUCTION: Quitting is the only proven method to attenuate the progression of chronic obstructive pulmonary disease (COPD). However, most COPD smokers do not seem to respond to smoking cessation interventions and may benefit by lessening the negative health effects of long-term cigarette smoke exposure by switching to non-combustible nicotine delivery alternatives, such as heated tobacco products (HTPs) and e-cigarettes (ECs). AREAS COVERED: Compared with conventional cigarettes, HTPs and ECs offer substantial reduction in exposure to toxic chemicals and have the potential to reduce harm from cigarette smoke when used as tobacco cigarette substitutes. In this review, we examine the available clinical studies and population surveys on the respiratory health effects of ECs and HTPs in COPD patients. EXPERT OPINION: The current research on the impact of ECs and HTPs on COPD patients' health is limited, and more high-quality studies are needed to draw definitive conclusions. However, this review provides a comprehensive overview of the available literature for health professionals looking to advise COPD patients on the use of these products. While ECs and HTPs may offer some benefits in reducing harm from cigarette smoke, their long-term effects on COPD patients' health are still unclear.

Implications of incidental findings from lung screening for primary care: data from a UK pilot.

Regional lung cancer screening (LCS) is underway in England, involving a "lung health check" (LHC) and low-dose CT scan for those at high risk of cancer. Incidental findings from LHCs or CTs are usually referred to primary care. We describe the proportion of participants referred from the West London LCS pilot to primary care, the indications for referral, the number of general practitioner (GP) attendances and consequent changes to patient management, and provide an estimated cost-burden analysis for primary care. A small proportion (163/1542, 10.6%) of LHC attendees were referred to primary care, primarily for suspected undiagnosed chronic obstructive pulmonary disease (55/163, 33.7%) or for QRISK® (63/163, 38.7%) assessment. Ninety one of 159 (57.2%) participants consenting to follow-up attended GP appointments; costs incurred by primary care were estimated at £5.69/LHC participant. Patient management changes occurred in only 36/159 (22.6%) referred participants. LHCs result in a small increase to primary care workload provided a strict referral protocol is adhered to. Changes to patient management arising from incidental findings referrals are infrequent.

Health outcomes in COPD smokers using heated tobacco products: a 3-year follow-up.

Given that many patients with chronic obstructive pulmonary disease (COPD) smoke despite their symptoms, it is important to understand the long-term health impact of cigarette substitution with heated tobacco products (HTPs). We monitored health parameters for 3 years in COPD patients who substantially attenuated or ceased cigarette consumption after switching to HTPs. Changes in daily cigarette smoking, annualized disease exacerbations, lung function indices, patient-reported outcomes (CAT scores) and 6-minute walk distance (6MWD) from baseline were measured in COPD patients using HTPs at 12, 24 and 36 months. These were compared to a group of age- and sex-matched COPD patients who continued smoking. Complete data sets were available for 38 patients (19 in each group). Subjects using HTPs had a substantial decrease in annualized COPD exacerbations within the group mean (± SD) from 2.1 (± 0.9) at baseline to 1.4 (± 0.8), 1.2 (± 0.8) and 1.3 (± 0.8) at 12-, 24- and 36-month follow-up (p < 0.05 for all visits). In addition, substantial and clinically significant improvements in CAT scores and 6MWD were identified at all three time points in the HTP cohort. No significant changes were observed in COPD patients who continued smoking. This study is the first to describe the long-term health effects of HTP use in COPD patients. Consistent improvements in respiratory symptoms, exercise tolerance, quality of life, and rate of disease exacerbations were observed in patients with COPD who abstained from smoking or substantially reduced their cigarette consumption by switching to HTP use.

COPD smokers who switched to e-cigarettes: health outcomes at 5-year follow up.

BACKGROUND AND AIMS: The long-term health effects of the use of electronic cigarettes (ECs) in patients with chronic obstructive pulmonary disease (COPD) are largely unexplored. We present findings from a 5-year prospective assessment of respiratory parameters in a cohort of COPD patients who substantially reduced conventional smoking or achieved abstinence by switching to ECs. METHODS: Patients were evaluated prospectively for their measurements of respiratory exacerbations, spirometric indices, quality of life using the COPD assessment tool (CAT), 6-min walk distance (6MWD), as well as conventional cigarette consumption. Baseline measurements prior to switching to EC use were compared with follow-up visits at 12-, 24-, 48- and 60-months. Age- and sex-matched COPD patients reporting to be regular smokers (not using ECs) were the reference group for the analysis. RESULTS: Complete data were available from 39 patients. Those in the EC user group achieved a marked decline in cigarette smoking or abstinence. COPD EC users had a significant diminution in COPD exacerbations; with the mean (±SD) exacerbation rate falling from 2.3 (±0.9) at baseline to 1.1 (±1.0) at 5 years (p < 0.001), whereas no significant changes were observed in the control group.Significant and constant improvements in lung function, CAT scores and 6MWD were reported in the EC user group over the 5-year observation period compared with the reference group (p < 0.05). CONCLUSION: The present study suggests that EC use may ameliorate objective and subjective COPD outcomes, and that the benefits gained appear to persist long term. EC use for abstinence and smoking reduction may ameliorate some of the harm resulting from tobacco smoking in COPD patients.

Baseline Results of the West London lung cancer screening pilot study - Impact of mobile scanners and dual risk model utilisation.

OBJECTIVES: The West London lung screening pilot aimed to identify early-stage lung cancer by targeting low-dose CT (LDCT) to high risk participants. Successful implementation of screening requires maximising participant uptake and identifying those at highest risk. As well as reporting pre-specified baseline screening metrics, additional objectives were to 1) compare participant uptake between a mobile and hospital-based CT scanner and 2) evaluate the impact on cancer detection using two lung cancer risk models. METHODS: From primary care records, ever-smokers aged 60-75 were invited to a lung health check at a hospital or mobile site. Participants with PLCOM2012 6-yr risk ≥1.51 % and/or LLPv2 5-yr risk ≥2.0 % were offered a LDCT. Lung cancer detection rate, stage, and recall rates are reported. Participant uptake was compared at both sites (chi-squared test). LDCT eligibility and cancer detection rate were compared between those recruited under each risk model. RESULTS: Of 8366 potential participants invited, 1047/5135 (20.4 %) invitees responded to an invitation to the hospital site, and 702/3231 (21.7 %) to the mobile site (p = 0.14). The median distance travelled to the hospital site was less than to the mobile site (3.3 km vs 6.4 km, p < 0.01). Of 1159 participants eligible for a scan, 451/1159 (38.9 %) had a LLPv2 ≥2.0 % only, 71/1159 (6.1 %) had a PLCOM2012 ≥1.5 % only; 637/1159 (55.0 %) met both risk thresholds. Recall rate was 15.9 %. Lung cancer was detected in 29/1145 (2.5 %) participants scanned (stage 1, 58.6 %); 5/29 participants with lung cancer did not meet a PLCOM2012 threshold of ≥1.51 %; all had a LLPv2 ≥2.0 %. CONCLUSION: Targeted screening is effective in detecting early-stage lung cancer. Similar levels of participant uptake at a mobile and fixed site scanner were demonstrated, indicating that uptake was driven by factors in addition to scanner location. The LLPv2 model was more permissive; recruitment with PLCOM2012 alone would have missed several cancers.

Symptoms and exacerbations in asthma: an apparent paradox?

BACKGROUND: There is a dearth of data on prospectively recorded symptoms in patients with uncontrolled asthma. Asthma symptoms and exacerbation rate are commonly thought to be associated. The aim of this study was to analyse asthma symptoms of cough, wheeze, chest tightness and breathlessness in an uncontrolled asthma cohort. We also examined the effect of maintenance and reliever therapy (MART) on these symptoms and its effect on exacerbation rate. METHODS: Adults with uncontrolled asthma electronically recorded their asthma symptom severity scores twice-daily over a period of 48 weeks following randomisation to beclometasone/formoterol twice daily plus pro re nata (prn) salbutamol or MART. Subjects with symptom scores of ⩾2 (ranging from 0 to 3 for each symptom) were considered more symptomatic, whereas those below a score of 2 were considered less severe. The influence treatment on exacerbation frequency and symptom profiles were then correlated. RESULTS: Of the 1701 subjects in the analyses, 1403 were symptomatic with ⩾100 symptom episodes for one symptom. The remaining 298 subjects were classified as pauci-symptomatic. There was poor association between the frequency and symptom severity score for each symptom. Surprisingly, wheeze was the least reported symptom. Females were more likely to be polysymptomatic. MART compared with prn salbutamol markedly attenuated severe asthma exacerbations. This effect was most notable in subjects with fewer symptoms. CONCLUSIONS: In uncontrolled asthma, there is a poor correlation between reported symptoms and exacerbation frequency. This post hoc analysis suggests that MART should not be reserved for symptomatic subjects but achieves the greatest benefit in pauci-symptomatic patients with asthma. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00861926.

An evaluation of mepolizumab for the treatment of severe asthma.

Introduction: Asthma is considered one of the most common chronic conditions globally, characterized by variable airflow obstruction and symptoms. Severe asthma is diagnosed when asthma control requires high-intensity therapy or continues to remain uncontrolled despite treatment. Eosinophilic inflammation is known to be perpetuated by the activity of IL-5 in a proportion of severe asthma subjects, and targeting IL-5 may offer a therapeutic option. Areas covered: In this review, we discuss the role and pathogenesis of IL-5 and eosinophils in asthma and rationale of antagonizing IL-5 in severe eosinophilic asthma. Mepolizumab is the first of three anti-IL-5 biologics licensed in 2015 for use in this subgroup of patients. We discuss clinical and real-life studies leading up to its approval and post-marketing outcomes in terms of efficacy and safety to-date, as well as its pros and cons. Expert opinion: IL-5 antagonism has paved the way for an additional personalized therapeutic opportunity for use in severe asthma with eosinophilic inflammation, though there is limited evidence on the long-term implications of suppressing/depleting eosinophils and the duration for which they should be administered.

Mepolizumab in the management of severe eosinophilic asthma in adults: current evidence and practical experience.

Asthma is a chronic inflammatory condition involving the airways with varying pathophysiological mechanisms, clinical symptoms and outcomes, generally controlled by conventional therapies including inhaled corticosteroids and long-acting ß2 agonists. However, these therapies are unable to successfully control symptoms in about 5-10% of severe asthma patients. Atopic asthma, characterized by high immunoglobulin (Ig)E or eosinophilia, represents about 50% of asthmatic patients. Interleukin (IL)-5 is the main cytokine responsible of activation of eosinophils, hence therapeutic strategies have been investigated and developed for clinical use. Biologics targeting IL-5 and its receptor (first mepolizumab and subsequently, reslizumab and benralizumab), have been recently approved and used as add-on therapy for severe eosinophilic asthma resulting in a reduction in the circulating eosinophil count, improvement in lung function and exacerbation reduction in asthma patients. Despite these biologics having been approved for stratified severe asthma patients that remain uncontrolled with high doses of conventional therapy, a number of patients may be eligible for more than one biologic. Presently, the lack of head-to-head studies comparing the biological agents among themselves and with conventional therapy make the choice of optimal therapy for each patient a challenge for clinicians. Moreover, discontinuation of these treatments, implications for efficacy or adverse events, in particular in long-term treatment, and needs for useful biomarkers are still matters of debate. In this review we evaluate to date, the evidence on mepolizumab that seems to demonstrate it is a well-tolerated and efficacious regimen for use in severe eosinophilic asthma, though more studies are still required.

Treatment of Allergic Rhinitis as a Strategy for Preventing Asthma.

PURPOSE OF REVIEW: To evaluate the impact of allergic rhinitis (AR) on the development of asthma and to update readers on recent literature suggesting that early treatment of allergic subjects with immunotherapy may prevent asthma onset. RECENT FINDINGS: AR is frequently associated with asthma, leading to the concept that these two conditions are different aspects of the same disease. There is increasing evidence that AR precedes the onset of asthmatic symptoms and current treatment strategies are beneficial in symptom control with no impact prevention. There is limited knowledge about the risk factors responsible for the progression of AR to asthma, though recent data supports the notion that it is possible to prevent asthma onset by allergen immunotherapy. Despite significant advances in specific immunotherapy (SIT) therapy strengthening its efficacy in AR and possible prevention of progression to asthma, the adoption of this therapeutic strategy is still restricted in comparison to therapies directed towards treatment of AR symptoms. Unlike corticosteroids and other symptomatic therapies, the benefit of SIT treatment in allergic individuals has been shown to prevent the development of allergic conditions. Hence, large well-conducted randomized clinical trials with long-term efficacy of SIT are required to confirm or refute the concept that SIT may abrogate the progression of AR to asthma in patients.

Asthma phenotypes: do cough and wheeze predict exacerbations in persistent asthma?

Little is known of the long-term symptom profile in uncontrolled asthma and whether symptoms can predict distinct phenotypes. The primary objective of these analyses was to assess diurnal profile of cough and wheeze in an uncontrolled asthma population. Secondary outcomes were to examine how these symptom profiles influence response to treatment.Twice-daily electronically recorded data from 1701 patients were examined in relation to the population demographics. Reliever treatment with salbutamol was then compared with extra-fine beclometasone/formoterol maintenance and reliever therapy (MART). Exacerbation frequency was then correlated with the symptom profile.Symptoms were commoner in older patients with an increased body mass index. In most patients, reported cough and wheeze were closely correlated (r=0.73). Two phenotypes of cough- and wheeze-predominant patients were identified; the former were overweight, older females and the latter older males. Diurnal symptoms of cough and wheeze were similarly attenuated by both therapies. MART reduced exacerbation frequency by a third compared with salbutamol, and this effect was greatest in patients with fewest reported symptoms.While cough and wheeze are highly correlated in uncontrolled asthma, some patients predominantly have cough whereas others wheeze. Symptoms and exacerbation frequency appear poorly associated, suggesting an alternative pathophysiology. MART may be the preferred option in those with fewest symptoms.

Inhaled Corticosteroid use and the Risk of Pneumonia and COPD Exacerbations in the UPLIFT Study.

RATIONALE: Unlike many other COPD studies, the 4-year UPLIFT trial permitted inhaled corticosteroid (ICS) use during run-in and treatment phases. This provided the opportunity to prospectively observe the continuing effects of ICS on respiratory events in closely observed COPD population. OBJECTIVES: We aimed to determine rate and number of episodes of pneumonia and exacerbations of COPD in patients entering the study on no ICS, fluticasone proprionate (FP), and other ICS. METHODS: The UPLIFT dataset was examined retrospectively, and patients were divided into three groups based on their medications at entry: no ICS, FP and other ICS. Poisson regression was used to compare the frequency of respiratory adverse events. MEASUREMENTS AND MAIN RESULTS: At entry, the groups were well matched apart from a higher FEV1% predicted (38 vs. 41%; ICS vs. no ICS, respectively) and prevalence of current smoking (26 vs. 36%; ICS vs. no ICS, respectively). Incidence rates of pneumonia were significantly higher in patients taking ICS compared to no ICS (0.068 vs. 0.056 respectively; p = 0.012). When the FP group was compared to the other ICS, the event rate was even higher (0.077 vs. 0.058, respectively; p < 0.001). COPD exacerbations were more frequent in patients taking ICS, with significantly greater rate in the FP group compared to that seen with other ICS (0.93 vs. 0.84 respectively; p = 0.013). CONCLUSIONS: ICS use was associated an increase in respiratory adverse event rates, but whether this was due to more severe illness at entry is unknown. In subgroup analysis, the excess of morbidity in the ICS group appeared to be mainly associated with those receiving FP at randomisation.

Investigational beta-2 adrenergic agonists for the treatment of chronic obstructive pulmonary disease.

INTRODUCTION: Long-acting bronchodilators are pivotal in the therapeutic management of COPD patients with moderate-to-severe airflow obstruction. New ultra-long-acting ß2-agnoists (ultra-LABAs) have been developed, some of which have been licensed for use as monotherapy and/or in combination with other bronchodilators or inhaled corticosteroids, for use in COPD patients with persistent symptoms and worsening airflow limitation. These new agents are faster in onset and have a prolonged duration of action, with a similar safety profile to the traditional twice-daily bronchodilators which may have an impact on patient concordance. Areas covered: A number of these ultra-LABAs are still under development and bi-functional hybrid molecules containing regions functioning as ß2-agonists, and as muscarinic agonists (MABAs) has been developed. This review summarizes these (excluding the licensed ultra-LABAs) with attention on phase II studies data available to-date on their pharmacological profiles, clinical efficacy and safety, and future perspectives. Expert opinion: Despite all the new agents' available, the challenges that persist include any differences in efficacy and safety between the various possible LAMA/LABA combinations, relative advantages of MABAs over fixed-dose LAMA/LABAs, and the impact of these new molecules in terms of long term safety, especially in certain populations in co-morbidities frequently associated with COPD.

Blood Pressure Control in Smokers with Arterial Hypertension Who Switched to Electronic Cigarettes.

Electronic cigarettes (ECs) are battery-operated devices designed to vaporise nicotine, which may help smokers with quitting or reducing their tobacco consumption. No data is available regarding the health effects of ECs use among smokers with arterial hypertension and whether regular use results in blood pressure (BP) changes. We investigated long-term changes in resting BP and level of BP control in hypertensive smokers who quit or reduced substantially their tobacco consumption by switching to ECs. A medical records review of patients with hypertension was conducted to identify patients reporting regular daily use of ECs on at least two consecutive follow-up visits. Regularly smoking hypertensive patients were included as a reference group. A marked reduction in cigarette consumption was observed in ECs users (n = 43) though consumption remained unchanged in the control group (n = 46). Compared to baseline, at 12 months (follow-up visit 2) decline in cigarette consumption was associated with significant reductions in median (25th-, 75th-centile) systolic BP (140 (134.5, 144) to 130 (123.5, 138.5) mmHg; p < 0.001) and diastolic BP (86 (78, 90) to 80 (74.5, 90) mmHg; p = 0.006). No significant changes were observed in the control group. As expected, decline in cigarette consumption in the ECs users was also associated with improved BP control. The study concludes that regular ECs use may aid smokers with arterial hypertension reduce or abstain from cigarette smoking, with only trivial post-cessation weight gain. This resulted in improvements in systolic and diastolic BP as well as better BP control.

Changes in breathomics from a 1-year randomized smoking cessation trial of electronic cigarettes.

BACKGROUND: Electronic cigarette (EC) use is an emerging behaviour that has been shown to help smokers to reduce cigarette consumption. The aim of this study was to illustrate long-term changes in exhaled breath measurements and respiratory symptoms in smokers invited to quit or reduce their cigarette consumption by switching to ECs. MATERIALS AND METHODS: Prospective evaluation of cigarette consumption, fractional nitric oxide concentration in exhaled breath (FeNO), exhaled carbon monoxide (eCO) and symptom scores was performed in a 1-year randomized, controlled trial of 'healthy' smokers receiving 2·4% nicotine, 1·8% nicotine or no nicotine ECs. FeNO and eCO data are presented on the basis of participants' pooled continuous smoking phenotype classification (failures, reducers and quitters). RESULTS: A significant effect of quitting classification was found on FeNo and eCO at all time points (P < 0·0001). Among quitters, FeNO (medians and interquartile range) rose from 5·5 (4·5-6·9) ppb to 17·7 (13·3-18·9) ppb by week 52. Baseline eCO (medians and interquartile range) decreased from 17 (12-20) ppm to 3 (1-4) ppm by week 52. No significant changes in FeNO and eCO levels were observed in failures and reducers. Improvements in FeNO and eCO levels were correlated with attenuations in symptom scores. CONCLUSIONS: Smokers invited to switch to electronic cigarettes who completely abstained from smoking showed steady progressive improvements in their exhaled breath measurements and symptom scores. FeNo and eCO normalization is highly supportive of improved respiratory health outcomes and adds to the notion that quitting from tobacco smoking can reverse harm in the lung.

Vilanterol trifenatate for the treatment of COPD.

INTRODUCTION: Currently the treatment of chronic obstructive pulmonary disease (COPD) has limited effectiveness and there is a need to develop new drugs. International guidelines recommend the use of long-acting bronchodilators (ß2 agonists and anti-cholinergics/muscarinics), inhaled steroids and associations between these drugs in the maintenance treatment of moderate-to-severe COPD. AREA COVERED: Vilanterol trifenate is a new once-daily highly selective ß2-agonist available in USA and Europe in association with umeclidinium bromide (a long-acting anti-muscarnic agent) and fluticasone furoate (an inhaled corticosteroid) for the once-daily maintenance treatment of COPD. Vilanterol combined in fixed-dose treatments has been tested in numerous clinical trials involving thousands of patients. Expert commentary: These new once-daily formulations have the potential to improve compliance to long-term inhaled therapy. This paper will review the clinical and experimental data regarding vilanterol use in the regular treatment of COPD as well as provide a critical discussion of possible future treatment settings.

Persisting long term benefits of smoking abstinence and reduction in asthmatic smokers who have switched to electronic cigarettes.

BACKGROUND: Improvements in asthma outcomes have been recently reported in asthmatic smokers who have substantially reduced their tobacco consumption by switching to ECs. Confirmation of these preliminary findings is necessary to reassure patients, healthcare professionals and policy makers. Here, we present findings from long term prospective assessment of objective and subjective asthma outcomes as well as safety and tolerability in this group of EC users with asthma. METHODS: We prospectively re-evaluated respiratory symptoms, lung function, airway hyperresponsiveness, asthma control, asthma exacerbations and tobacco consumption in adult daily ECs users with asthma who were previously studied in a retrospective study. Measurements recorded at baseline prior to switching were compared with those at the follow-up visits at 6, 12, and 24 months. RESULTS: Eighteen ECs users with mild to moderate asthma were followed up prospectively. Complete data was obtained from sixteen EC users and two relapsers. Significant and stable improvements in respiratory symptoms, lung function, AHR, ACQ, and tobacco consumption were observed in the 16 ECs users with asthma, but no significant changes in exacerbation rates were reported. Similar findings were found in the dual users. CONCLUSION: This prospective study confirms that EC use ameliorates objective and subjective asthma outcomes and shows that these beneficial effects may persist in the long term. EC use can reverse harm from tobacco smoking in asthma patients who smoke. The evidence-based notion that substitution of conventional cigarettes with EC is unlikely to raise significant respiratory concerns, can improve counseling between physicians and their asthmatic patients who are using or intend to use ECs.

Clinicopharmacological profile of the fixed-dose combination of aclidinium bromide and formoterol fumarate in the management of chronic obstructive pulmonary disease.

The recent Global Initiative for Chronic Obstructive Lung Disease (GOLD) chronic obstructive pulmonary disease (COPD) guidelines consider symptoms and exacerbation history in addition to the degree of airflow obstruction for classifying patients. The improvement of symptoms is principally provided by bronchodilators, using ß2 agonists and antimuscarinic agents. Aclidinium bromide is a novel long-acting antimuscarinic agent licensed for use in patients with COPD. Novel fixed-dose combinations that are either licensed or in their late phase of development include vilanterol/umeclidinium, indacaterol/glycopyrronium, olodaterol/tiotropium and formoterol/aclidinium. Fixed-dose combinations of aclidinium/formoterol have been evaluated in COPD patients and evidence suggests that this is efficacious, safe, has a quick onset of action and is well tolerated. This review provides a clinico-pharmacological profile of this compound.