Comparison of peak inspiratory flow rate via the Breezhaler®, Ellipta® and HandiHaler® dry powder inhalers in patients with moderate to very severe COPD: a randomized cross-over trial.

BACKGROUND: The chronic and progressive nature of chronic obstructive pulmonary disease (COPD) requires self-administration of inhaled medication. Dry powder inhalers (DPIs) are increasingly being used for inhalation therapy in COPD. Important considerations when selecting DPIs include inhalation effort required and flow rates achieved by patients. Here, we present the comparison of the peak inspiratory flow rate (PIF) values achieved by COPD patients, with moderate to very severe airflow limitation, through the Breezhaler®, the Ellipta® and the HandiHaler® inhalers. The effects of disease severity, age and gender on PIF rate were also evaluated. METHODS: This randomized, open-label, multicenter, cross-over, Phase IV study recruited patients with moderate to very severe airflow limitation (Global Initiative for Obstructive Lung Disease 2014 strategy), aged ≥40 years and having a smoking history of ≥10 pack years. No active drug or placebo was administered during the study. The inhalation profiles were recorded using inhalers fitted with a pressure tap and transducer at the wall of the mouthpiece. For each patient, the inhalation with the highest PIF value, out of three replicate inhalations per device, was selected for analysis. A paired t-test was performed to compare mean PIFs between each combination of devices. RESULTS: In total, 97 COPD patients were enrolled and completed the study. The highest mean PIF value (L/min ± SE) was observed with the Breezhaler® (108 ± 23), followed by the Ellipta® (78 ± 15) and the HandiHaler® (49 ± 9) inhalers and the lowest mean pressure drop values were recorded with the Breezhaler® inhaler, followed by the Ellipta® inhaler and the HandiHaler® inhaler, in the overall patient population. A similar trend was consistently observed in patients across all subgroups of COPD severity, within all age groups and for both genders. CONCLUSIONS: Patients with COPD were able to inhale with the least inspiratory effort and generate the highest mean PIF value through the Breezhaler® inhaler when compared with the Ellipta® and the HandiHaler® inhalers. These results were similar irrespective of patients' COPD severity, age or gender. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov NCT02596009 on 4 November 2015.

INSTEAD: a randomised switch trial of indacaterol versus salmeterol/fluticasone in moderate COPD.

The Indacaterol: Switching Non-exacerbating Patients with Moderate COPD From Salmeterol/Fluticasone to Indacaterol (INSTEAD) study investigated the effect of switching patients at low risk of chronic obstructive pulmonary disease (COPD) exacerbations from salmeterol/fluticasone (SFC; inhaled corticosteroid (ICS) regimen) to indacaterol monotherapy (non-ICS regimen). This 26-week, double-blind, double-dummy, parallel-group, phase IV study, randomised 581 patients with moderate COPD to indacaterol 150 µg once daily or SFC 50/500 µg twice daily. Patients had been receiving SFC 50/500 µg for ≥3 months, with no COPD exacerbations for more than a year before the study (patients for whom ICS is not recommended). The primary objective was to demonstrate non-inferiority of indacaterol to SFC, measured by trough forced expiratory volume in 1 second (FEV1) after 12 weeks (non-inferiority margin of 0.06 L). The primary objective was met, with a mean treatment difference of 9 mL (95% CI -45-26 mL). There were no significant differences between treatments in terms of breathlessness (transition dyspnoea index) or health status (Saint George's Respiratory Questionnaire) at weeks 12 or 26, or rescue medication use or COPD exacerbation rates over 26 weeks. Safety profiles of both treatments were as expected. This study demonstrated that patients with moderate COPD and no exacerbations in the previous year can be switched from SFC to indacaterol 150 µg with no efficacy loss.

Progressive nicotine patch dosing prior to quitting smoking: feasibility, safety and effects during the pre-quit and post-quit periods.

BACKGROUND AND AIMS: Nicotine replacement therapy (NRT) may be more effective in aiding smoking cessation if higher doses of nicotine from it can be tolerated. We examined the responses to, and 4-week abstinence rates observed, when titrating the dose of transdermal nicotine patch up to 84 mg/day over 4 weeks prior to a target quit date and titrating down again over 4 weeks afterwards. DESIGN: Clinical cohort study. SETTING: Tobacco dependence clinic, Mar del Plata, Argentina. PARTICIPANTS: Fifty smokers seeking help with stopping smoking. INTERVENTION: Participants started on one 21-mg/24-hour patch 4 weeks prior to their target quit day (TQD). The dose was increased weekly by adding a 21-mg patch unless participants reported adverse effects and/or did not wish to increase the dose. The dose was reduced by 21 mg/day each week from 1 week post-TQD, until it reverted to the standard dose (21 mg/day) at 4 weeks post-TQD. Participants received weekly behavioural support and could also use oral NRT from the TQD. Participants were advised to smoke ad libitum during the pre-quit period. MEASUREMENTS: Proportion of participants progressing through each stage of dosing, adherence, adverse effects, changes in cigarette consumption, smoke intake and enjoyment of smoking during the pre-quit period; withdrawal symptoms; carbon monoxide-validated abstinence during 4 weeks post-TQD. FINDINGS: Of the 50 participants, 72.0% (n = 36) progressed to the 84-mg nicotine dose and 94.0% (n = 47) completed the trial. Adverse effects consisted primarily of nausea and were mild and well tolerated. Cigarette consumption, smoke intake and enjoyment of smoking declined significantly during the pre-quit period. Forty-one (82%) participants achieved 4 weeks validated abstinence. Abstainers experienced no detectable cigarette withdrawal symptoms. CONCLUSIONS: Most smokers seeking help with stopping appear to be able to tolerate doses of transdermal nicotine patch up to 84 mg/day during a 4-week pre-quit up-titration period with minimal side effects.

Want, need and habit as drivers of smoking behaviour: A preliminary analysis.

BACKGROUND AND AIMS: Models of tobacco smoking behaviour propose that anticipated pleasure or satisfaction, the need to alleviate a nicotine-induced drive state and a stimulus-driven impulse potentially play an important role. This study aimed to provide a preliminary assessment of how far urges to smoke are reported by smokers and whether the strength of such urges prior to a quit attempt predicts short-term success at quitting. METHODS: In a prospective study, 566 smokers attending a treatment programme to help smokers quit completed a written questionnaire covering frequency of different types of urge to smoke (automatic impulse - 'automatic urges', anticipated pleasure - 'pleasure urges', and fulfilling a need - 'need urges'). They were asked to rate this for whichever of these urges was dominant for them. The questionnaire also assessed daily cigarette consumption, time to first cigarette of the day, age and gender. Carbon monoxide verified smoking status was recorded at 1 and 4weeks after the target quit date. FINDINGS: A total of 47.9% (271) of smokers reported that automatic urges were dominant, 21.7% (123) reported pleasure urges to be dominant, and 30.4% (172) reported need urges to be dominant. The strength of automatic urges predicted abstinence at both 1week (OR=0.74, p=0.005, 95%CI=0.60-0.92) and 4weeks (OR=0.73, p=0.008, 95%CI=0.59-0.92). Associations between other urge types and abstinence were not statistically significant. CONCLUSIONS: A substantial proportion of smokers attending a clinic for help with quitting report that their dominant urges to smoke occur without any anticipation of pleasure or relief and the strength of the automatic urges predicts failure to sustain abstinence following a quit attempt.

Smoking and smoking cessation in Latin America: a review of the current situation and available treatments.

Tobacco smoking is a growing problem throughout Latin American countries, especially in underdeveloped countries where poverty and lack of education about the dangers of smoking may make people more susceptible to becoming smokers. Moreover, the economies of many Latin American countries have become dependent on the production of tobacco. Furthermore, because of the associated promotion of tobacco, smoking has integrated into many Latin American cultures. Nevertheless, the harmful health effects of tobacco use are well documented, including greatly increased risks of developing chronic obstructive pulmonary disease, cardiovascular disease, and many forms of cancer. The medical costs associated with treating these diseases far outweigh the economic benefits of producing and selling this deadly crop. To control the tobacco pandemic in Latin American countries, nicotine addiction must be recognized and treated as a disease. Governments, both national and local, need to be more involved in enacting anti-smoking policies such as higher tobacco taxation, control of illegal tobacco smuggling, and reimbursement of medical smoking cessation interventions. The training of health professions in the area of nicotine addiction must also be improved, so that they may better assist smokers in their quit attempts and advise patients on, and prescribe, effective smoking cessation pharmacotherapies.