Project description:RATIONALE:Ineffective peak inspiratory flow rate (PIFR) generation in patients using inhalers results in insufficient drug delivery to the lungs and poor clinical outcomes. Low inspiratory muscle strength is associated with suboptimal PIFR. OBJECTIVE:To examine in a prospective study the relationship between PIFR and skeletal muscle strength using hand grip strength (HGS) as a surrogate. METHODS:Adult patients admitted with acute exacerbation of chronic obstructive pulmonary disease (COPD) were enrolled. PIFR was measured within 48 hours before discharge. PIFR below 60L/min was considered suboptimal. HGS was measured using a handheld dynamometer. Any readmissions and emergency department visit data were collected. The associations between PIFR, HGS, 30 and 90-day COPD and all-cause readmissions were examined, without and with adjustment for age, race and gender. RESULTS:Of the 75 enrolled patients, 56% had suboptimal PIFR; they were older (63.9±9.7 vs. 58.2±7.7 years) and had significantly lower HGS (24.2±11.1 vs. 30.9±10.9 Kg) compared to those with optimal PIFR. There were no significant differences between the two PIFR groups by gender, race, history of coronary artery disease, congestive heart failure, hypertension or functional scores. Each kilogram increase in HGS was associated with 0.50 (95%CI 0.18-0.89, p = 0.003) L/min increase in PIFR. We did not observe an association between PIFR and 30 or 90-day readmission rates. CONCLUSION:We found a significant association between HGS and PIFR in hospitalized patients with acute exacerbations of COPD. Whether interventions aimed at increasing skeletal muscle strength also result in improvement in PIFR remains unclear and need further study.
Project description:Optimal peak inspiratory flow rate (PIFR) is crucial for inhalation therapy in patients with chronic obstructive pulmonary disease (COPD). However, little is known about the impact of PIFR-guided inhalation therapy on the clinical outcomes among patients with varying severities of COPD. A PIFR-guided inhalation therapy, including PIFR assessment and PIFR-guided inhaler education, was introduced in a pay-for-performance COPD management program in National Taiwan University Hospital. Among 383 COPD patients, there was significant reduction in incidence of severe acute exacerbation in the PIFR-guided inhalation therapy (PIFR group) than conventional inhaler education (control group) (11.9 vs. 21.1%, p = 0.019) during one-year follow-up. A multivariable Cox's proportional-hazards analysis revealed that the PIFR-guided inhalation therapy was a significant, independent factor associated with the reduced risk of severe exacerbation (adjusted hazard ratio = 0.49, 95% confidence interval, 0.28-0.84, p = 0.011). Subgroup analysis found PIFR-guided inhalation therapy was more beneficial to patients with older age, short body stature, COPD stage 1&2, group C&D (frequent exacerbation phenotype), and using multiple inhalers. This study showed the PIFR-guided inhalation therapy significantly reduced the incidence of severe acute exacerbation than conventional inhaler education in patients with COPD. Careful PIFR-assessment and education would be crucial in the management of COPD.
Project description:Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease with complex pathological features and largely unknown etiologies. Identification and validation of biomarkers for this disease could facilitate earlier diagnosis, appreciation of disease subtypes and/or determination of response to therapeutic intervention. To identify gene expression markers for COPD, we performed genome-wide expression profiling of lung tissue from 56 subjects using the Affymetrix U133 Plus 2.0 array. Lung function measurements from these subjects ranged from normal, un-obstructed to severely obstructed. Analysis of differential expression between cases (FEV1<70%, FEV1/FVC<0.7) and controls (FEV1>80%, FEV1/FVC>0.7) identified a set of 65 probe sets representing discrete markers associated with COPD. Correlation of gene expression with quantitative measures of airflow obstruction (FEV1 or FEV1/FVC) identified a set of 220 probe sets. A total of 31 probe sets were identified that showed evidence of significant correlation with quantitative traits and differential expression between cases and controls. Keywords: Disease state marker
Project description:IntroductionThere is increasing pressure to use environmentally friendly dry powder inhalers (DPI) instead of pressurized metered-dose inhalers (pMDI). However, correct inhalation technique is needed for effective inhaler therapy, and there is persistent concern whether patients with chronic obstructive pulmonary disease (COPD) can generate sufficient inspiratory effort to use DPIs successfully. The aims of this study were to find clinical predictors for peak inspiratory flow rate (PIF) and to assess whether patients with COPD had difficulties in generating sufficient PIF with a high resistance DPI.MethodsPooled data of 246 patients with COPD from previous clinical trials was analyzed to find possible predictors of PIF via the DPI Easyhaler (PIFEH) and to assess the proportion of patients able to achieve an inhalation flow rate of 30 l/min, which is needed to use the Easyhaler successfully.ResultsThe mean PIF was 56.9 l/min and 99% (243/246) of the study patients achieved a PIF ≥ 30 l/min. A low PIF was associated with female gender and lower forced expiratory volume in 1 s (FEV1), but the association was weak and a statistical model including both only accounted for 18% of the variation seen in PIFEH.ConclusionsBased on our results, impaired expiratory lung function or patient characteristics do not predict patients' ability to use DPIs in COPD; 99% of the patients generated sufficient PIFEH for successful dose delivery. Considering the targets for sustainability in health care, this should be addressed as DPIs are a potential option for most patients when choosing the right inhaler for the patient.Trial registrationTwo of three included trials were registered under numbers NCT04147572 and NCT01424137. Third trial preceded registration platforms and therefore, was not registered.
Project description:Patients with chronic obstructive pulmonary disease (COPD) and suboptimal peak inspiratory flow rate (sPIFR) may not benefit optimally from dry powder inhalers (DPI) because of inadequate inspiratory flow. Nebulized bronchodilators may provide a better alternative. We compared bronchodilation with the long-acting muscarinic antagonist (LAMA) revefenacin for nebulization versus the DPI LAMA tiotropium, in patients with COPD and sPIFR (< 60 L/min against the resistance of Diskus®). This was a randomized, double-blind, double-dummy, 28-day Phase 3b study in patients with COPD enrolled based on sPIFR. The primary endpoint was trough forced expiratory volume in 1 second (FEV1) on Day 29 for revefenacin for nebulization versus tiotropium HandiHaler® DPI. We enrolled 206 patients with mean (standard deviation) age, 65 (8) years; percent predicted FEV1, 37 (16)%; PIFR, 45 (12) L/min. In the intent-to-treat (ITT) population, revefenacin improved trough FEV1 from baseline; however, the difference versus tiotropium was not significant (least squares [LS] mean difference [standard error], 17.0 [22.4] mL, P=0.4461). In a prespecified analysis of patients with FEV1 < 50% predicted, revefenacin produced an LS mean difference (95% confidence interval [CI]), 49.1 (6.3-91.9) mL in trough FEV1 and 103.5 (7.7-199.3) mL in forced vital capacity versus tiotropium. Revefenacin produced >100 mL increase in FEV1 in 41.6% versus 34.4% of patients with tiotropium in ITT and 41.4% versus 25.7% of patients in FEV1 < 50% predicted populations. Revefenacin did not produce significant improvements in FEV1 versus tiotropium in the ITT population, but increased trough FEV1 in patients with FEV1 < 50% predicted and sPIFR. Clinical Trial Registration (www.Clinicaltrials.gov): Study 0149 (NCT03095456).
Project description:Diaphragm muscles in Chronic Obstructive Pulmonary Disease (COPD) patients undergo an adaptive fast to slow transformation that includes cellular adaptations. This project studies the signaling mechanisms responsible for this transformation. Keywords: other
Project description:PurposeThe purpose of the present review was to assess the quality of evidence in the literature regarding the specific benefits of inspiratory muscle training (IMT) with an emphasis on training intensity and the relationships between changes in inspiratory muscle function and other clinical outcome measures.MethodsArticles were found by searching CINAHL, PubMed, Medline via First Search, and ProQuest databases. Articles used in the review were randomized trials of IMT vs. sham IMT or no intervention, published in English in a peer-reviewed journal, included patients with chronic obstructive pulmonary disease (COPD), and specified the intensity of training. The quality of the studies was evaluated by 2 independent reviewers using the methodological rigor scale described by Medlicott and Harris as well as Sackett's levels of evidence. Fifteen articles met the inclusion criteria and were used in this review.ResultsConsistent improvements in maximal inspiratory pressures (ranging from -11 to -30 cm H(2)O) and inspiratory muscle endurance were found. Improvements in dyspnea and health-related quality of life were also observed. Inspiratory muscle training may result in improved exercise tolerance as measured using walking tests. High-intensity IMT resulted in improved training efficiency with respect to inspiratory muscle strength, but evidence of the effect of high-intensity IMT on other clinical outcomes is lacking.ConclusionDespite research spanning decades, there are numerous limitations in the literature regarding IMT. IMT appears to improve dyspnea, waking test distance, and health-related quality of life in individuals with COPD, but it is not clear whether this improvement is mediated through improved inspiratory muscle strength and endurance. This review discussed several considerations critical to the design of future trials.