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RationaleCOPD is a chronic and progressive disease and requires self-administration of inhaled medications. As the disease progresses, reduced respiratory muscle strength may affect patients generating sufficient inspiratory effort to effectively use DPIs.MethodsSymbicort*(100 µg budesonide (BUD)+6 µg formoterol fumarate (FF)) inhaled via either DPI (Turbuhaler,n= 5) or MDI (Vannair,n= 5) with an AeroChamber Plus* Flow Vu* VHC (Trudell) was assessed. 10 males ranging in age from 57–83 inhaled from placebos of their medication. Inhalation profiles were recorded, and later recreated via breathing simulator, coupled to the mouthpiece of the inhaler via an adult oropharynx (OP) model. The simulator was located distal to a collection filter, at the exit of the OP, capturing medication likely to have deposited at the carinal region and potentially available for delivery to the lungs.ResultsThe mass (µg) of FF and BUD recovered from the model OP and filter (CARINA) from each simulation are summarized in table 1.The mass of APIs retrieved from the CARINA for MDI+VHC was greater than the outcomes obtained by simulating the DPI profiles (p ≤ 0.03).Abstract P184 Table 1 Inhaler OP CARINA BUD FF BUD FF DPI 20.3±7.9 1.0±0.4 21.1±8.1 1.0±0.4 MDI+VHC 18.3±11.7 0.8±0.6 28.7±10.0 1.8±0.6 ConclusionsThese data indicate the MDI+VHC can deliver more medication than the DPI evaluated to the carinal region. They also demonstrate a need for continued patient inhaler assessment to ensure they can generate the necessary inspiratory effort for sufficient drug delivery

Patient reported symptom severity (Evaluating Respiratory Symptoms in COPD [E-RS:COPD], Transitional Dyspnoea Index [TDI], and Global Rating of Change in COPD Severity), rescue medication use, and inhaler preference were also assessed. Methods: The E-RS:COPD and daily rescue medication use were completed each evening by participants in an e-diary, a self-administered computerized version of the TDI was completed at week 4 (W4) and week 24 (W24), and Global Rating of Change in COPD Severity was completed at all study visits.

Rationale: The randomized, phase III FULFIL trial demonstrated statistically significant improvements in lung function, St George's Respiratory Questionnaire (SGRQ) total score, and COPD exacerbations with once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100pg/62.5pg/25pg via a single ELLIPTA· inhaler versus twice-daily budesonide/formoterol (BUD/FOR) 400pg/12pg via the Turbuhaler· in patients aged >40 years with advanced, symptomatic COPD at risk of exacerbations (Lomas, et al. Participants completed the CAT and SGRQ for COPD at day 1 (D1), week 4 (W4), and week 24 (W24); answered a daily question on activity limitation using an e-diary; and completed Global Ratings of Activity Limitation at D1 and W24 and the Global Impression of Change in Activity Limitation (compared with previous visit) at all visits.

Pulmonary drug delivery is currently the focus of accelerated research and development because of the potential to produce maximum therapeutic benefit to patients by directly targeting drug to the site of pathology in the lungs. Among the available delivery options, the dry powder inhaler (DPI) is the preferred device for the treatment of an increasingly diverse range of diseases. However, because drug delivery from a DPI involves a complex interaction between the device and the patient, the engineering development of this medical technology is proving to be a great challenge. Development of DPI systems that target the delivery of fine drug particles to the deeper airways in the lungs using a combination of improved drug formulations and enhanced delivery device technologies means that each of these factors contributes to overall performance of the aerosol system. There are a large range of devices that are currently available, or under development, for clinical use, however no individual device shows superior clinical efficacy. A major concern that is very relevant in day-to-day clinical practice is the inter- and intra-patient variability of the drug dosage delivered to the deep lungs from the inhalation devices, where the extent of variability depends on the drug formulation, the device design, and the patient’s inhalation profile. This variability may result in under-dosing of drug to the patient and potential loss of pharmacological efficacy. This article reviews recent advances in capsule-based DPI technology and the introduction of the ‘disposable’ DPI device.

Patients’ peak inspiratory flow rate (PIFR) may help clinicians select a suitable inhaler device. The In-Check® device has gained some status as a simple tool to estimate PIFR (scale reflecting inhaler resistance from R0 to R5). It has been suggested that some patients with asthma may not be able to generate sufficient PIFR with high resistance devices (R5) to satisfy the minimum requirements of 30 L/min.We conducted a prospective service evaluation study to identify what proportion of patients with asthma are able to generate a correct PIFR at In-Check device R0-R5 resistance settings and what the phenotypical features of those patients are.As part of UK general practice asthma review service, sequential patients were recruited from 41 centres by 10 respiratory specialist nurses. Patients had PIFR checked at the resistance corresponding to their current preventer inhaler device, at R5 (high resistance dry powder inhaler (DPI) setting), and, at R0 (no resistance, pressurised metered dose inhaler (pMDI) setting. Correct PIFR (pass) was defined for R5 as 30–90 L/min, and, for R0 as 20–60 L/min.994 adults (female 64.3%) were included, of whom 90.4% currently used a preventer inhaler (71.5% MDI (R0), 0% R1, 6.3% R2, 14.5% R3, 4.9% R4, 2.8% R5). 93.7% of patients passed at R5 resistance, compared to 70.5% at R0 (p<0.0001). This difference was observed in all age groups: among younger patients (18–24 years) 100% passed at R5 compared to 73.7% at R0, and among the older patients (>71 years) 90.2% passed at R5 compared to 71.0% at R0.ConclusionPatients with asthma can achieve adequate inspiratory flow 30–90 L/min with high resistance DPI (R5).

BackgroundThis analysis combines two randomised controlled trials with similar protocols recruiting adults with asthma to explore the effects of covariates on the comparison of combination inhaled corticosteroid (ICS)/fast-onset long-acting beta-agonist (LABA) as reliever therapy versus maintenance ICS plus short-acting beta-agonist (SABA) reliever therapy.MethodsA combined individual participant analysis of the Novel START (ACTRN12615000999538) and PRACTICAL (ACTRN1261000377437) studies. These were 52-week, open-label, parallel-group, randomised controlled trials in adults with asthma. Novel START randomised 675 adults using only as-needed SABA to : salbutamol pMDI 100µg two inhalations as-needed for symptom relief, or budesonide Turbuhaler 200µg one inhalation twice daily plus salbutamol pMDI 100µg two inhalations as-needed, or budesonide/formoterol Turbuhaler 200/6µg one inhalation as-needed. PRACTICAL randomised 890 adults using as-needed SABA for symptom relief, with or without maintenance ICS to: budesonide-formoterol Turbuhaler 200/6 one inhalation as-needed; or budesonide Turbuhaler 200µg one inhalation twice daily plus terbutaline Turbuhaler 500µg as-needed. The analysis compared as-needed budesonide-formoterol with maintenance budesonide plus SABA reliever therapy. The primary outcome was the rate of severe exacerbations per participant per year: i.e. hospital/emergency department systemic corticosteroid treatment or the use of at least 3 days of systemic corticosteroids for asthma in the community. Novel START participants were withdrawn if they experienced a severe exacerbation. The other outcomes were moderate or severe exacerbations, and the Asthma Control Questionnaire (ACQ-5) score. Covariates were: age, sex, ethnicity, smoking status, baseline SABA use, baseline ICS use ever, severe exacerbation in previous 12 months, ACQ-5, blood eosinophil count, and FeNO.ResultsThe severe exacerbation rate was 0.096 per patient-year for as-needed budesonide/formoterol and 0.150 for maintenance budesonide plus as-needed SABA; adjusted relative rate 0.63 (95% CI: 0.45 to 0.89), P=0.01. The adjusted relative rate of any exacerbation was 0.66 (95% CI: 0.49 to 0.88), P<0.001. ACQ-5 did not differ between treatments. There was no evidence of any sub-group differences in response to as-needed budesonide/formoterol versus budesonide maintenance.ConclusionsThe rate of severe exacerbations was lower for as-needed budesonide/formoterol therapy compared to budesonide plus as-needed SABA. No evidence of sub-group differences suggests the findings are generalisable across the spectrum of mild asthma in adults.

Background Poor inhaler technique has been linked to poor asthma outcomes. Training can reduce the number of inhaler errors, but it is unknown which errors have the greatest impact on asthma outcomes. Objective The CRITical Inhaler mistaKes and Asthma controL study investigated the association between specific inhaler errors and asthma outcomes. Methods This analysis used data from the iHARP asthma review service-a multicenter cross-sectional study of adults with asthma. The review took place between 2011 and 2014 and captured data from more than 5000 patients on demographic characteristics, asthma symptoms, and inhaler errors observed by purposefully trained health care professionals. People with asthma receiving a fixed-dose combination treatment with inhaled corticosteroids and long-acting beta agonist were categorized by the controller inhaler device they used-dry-powder inhalers or metered-dose inhalers: inhaler errors were analyzed within device cohorts. Error frequency, asthma symptom control, and exacerbation rate were analyzed to identify critical errors. Results This report contains data from 3660 patients. Insufficient inspiratory effort was common (made by 32%-38% of dry-powder inhaler users) and was associated with uncontrolled asthma (adjusted odds ratios [95% CI], 1.30 [1.08-1.57] and 1.56 [1.17-2.07] in those using Turbohaler and Diskus devices, respectively) and increased exacerbation rate. In metered-dose inhaler users, actuation before inhalation (24.9% of patients) was associated with uncontrolled asthma (1.55 [1.11-2.16]). Several more generic and device-specific errors were also identified as critical. Conclusions Specific inhaler errors have been identified as critical errors, evidenced by frequency and association with asthma outcomes. Asthma management should target inhaler training to reduce key critical errors.

BackgroundThe formation of cardiac fibroid deposits due to intense exercise may be involved in cardiac arrhythmias. Galectin-3 (Gal-3) and suppression of tumorogenicity2 (ST2) are considered as markers for fibrosis development and cardiac remodeling.ObjectiveThe aim of our study was to examine the evolution of both in trailers who ran the Tor des Géants (TdG).DesignLongitudinal, cohort studySettingThe TdG, a 330 km long ultra-distance trail running, with +24,000m elevation changes, is considered as one of the most difficult mountain marathon race in the world.Patients (or Participants)51 participants have been followed and the study was conducted on 33 subjects having reached at least half of the race.Interventions (or assessment of risk factors)Blood and urine samples collection were carried out at 4 key time points: before, during (mid-point) and after the race (less than 1h) and 3 days after the end of the race.Main outcome measurementsLevels of plasma Gal-3 and ST2 were determined at the 4 times. We calculated the difference between the different times in delta. Results were considered as significant with p<0.05.ResultsWe observed an increase for Gal-3 and ST2, above the reference values only for ST2. We noted for both a decrease up to the normal values 3 days after the trail. For the correlation between deltas, we observed that Gal-3 and ST2 are correlated for each delta.ConclusionsThe results of this study demonstrate that this exercise was associated with biochemical abnormalities that may reflect adverse consequences on cardiac structure as fibrosis. ST2 values were higher, perhaps due to a mechanical stress more than a cardiac stress.

BackgroundApproximately 70% of elite swimmers experience exercise-induced-bronchoconstriction (EIB), with the eucapnic-voluntary-hyperpnoea (EVH) challenge recommended to provide objective evidence to support diagnosis. Research on the impact of inhaler therapy in elite swimmers with a positive EVH challenge (EIBpositive) is limited, and the repeatability of the EVH challenge questioned.ObjectiveInvestigate impact of inhaler therapy on hyperpnoea-induced-bronchoconstriction in EIBpositive elite swimmers adherent to therapy. Evaluate long-term test-retest repeatability of EVH challenge in those non-adherent to inhaler therapy.DesignRetrospective data analysis.SettingGreat Britain swimming team.ParticipantsNineteen elite-international swimmers (8 males, 11 females; 20±3 yrs).InterventionsFollowing initial assessment, EIBpositive athletes were prescribed appropriate inhaler therapy in accordance to greatest fall in FEV1 (FEV1max) and asked to maintain therapy throughout the year. Athletes were grouped dependent on adherence to inhaler therapy (Non-adherent = EVH1→EVH2;n=13; adherent = EVHOFF→EVHON;n=6).Main outcome measurementsDifferences in FEV1max between screening visits separated by a calendar year were analysed using paired t-tests and presented as mean ± SD. The test-retest repeatability between EVH1→EVH2 was expressed as mean bias with 95% limits of agreement and Pearson’s correlation coefficient (rp).ResultsFEV1max was significantly lower in EVHON (-9.17±-3.4%) than EVHOFF (-26.7±-13.3%; p=0.02) and a trend for baseline FEV1 to be greater in EVHON than EVHOFF (p=0.06). EVH1→EVH2 FEV1max did not differ significantly between screening visits (p≥0.05). There was acceptable repeatability of FEV1max in EVH1→EVH2 (0.85%; -5.97, 7.67), and significant strong positive correlation (rp=0.72, p=0.01).ConclusionsElite swimmers adherent to inhaler therapy demonstrated significant reduction in FEV1max severity. The EVH challenge result was repeatable in elite swimmers with EIB non-adherent to inhaler therapy. Therefore, the EVH challenge is effective to initially assess elite swimmers for EIB, and use as a follow-up assessment after initiation of inhaler therapy.