Absolute Change In FEV1 Research Articles

Variability in forced expiratory volume in 1 s in children with symptomatically well-controlled asthma

AimsSpirometry is used by many clinicians to monitor asthma in children but relatively little is understood about its variability over time. The aim of this study was to determine the...

Lung function decline in people with serious mental illness: A call to action

This prospective observational study aimed to evaluate the rate of change in forced expiratory volume in the first second (FEV1) and to explore the factors associated with changes in FEV1 in people with serious mental illness (SMI). Sixty subjects diagnosed with schizophrenia or bipolar disorder who were smokers and without history of respiratory illness agreed to participate. The mean (range) follow-up period was 3.54 (3.00–4.98) years. The mean (standard deviation) annual rate of change in FEV1 decreased by 39.1 (105.2) mL/year. Thirty-one (51.7 %) patients experienced a decrease in the FEV1 ≥40 mL/year (i.e. a rapid decline). The factors associated with the absolute change in FEV1 were the baseline International Physical Activity Questionnaire activity score in metabolic equivalents of tasks (β 0.145, 95 % confidence interval [CI] 0.043 to 0.246; p = 0.005), baseline FEV1 (β -0.025, 95 % CI -0.076 to 0.027; p = 0.352), and the interaction term of both variables (β -3.172e-05, 95 % CI -6.025e-05 to -0.319e-05; p = 0.029). The factors associated with rapid FEV1 decline were income (odds ratio [OR] 0.999, 95 % CI 0.995 to 1.003; p = 0.572), the rate of change in abdominal circumference (OR 0.000, 95 % CI 0.000 to 0.890; p = 0.081), and the interaction term of both variables (OR 1.038, 95 % CI 1.010 to 1.082; p = 0.026). In conclusion, a substantial proportion of people with SMI experienced a rapid decrease in FEV1. If our results are confirmed in larger samples, the routine evaluation of lung function in people with SMI would be an opportunity to identify individuals at greater risk of morbidity and mortality.

Inhaled Dry Powder Mannitol Treatment in Pediatric Patients with Cystic Fibrosis: Evaluation of Clinical Data in a Real-World Setting.

Background: Cystic fibrosis (CF) is a genetic disorder, in which defective clearance of airway secretions leads to progressive lung function loss. Inhaled mannitol is used to increase sputum and mucociliary clearance. There are little data from real-world studies on the effectiveness of mannitol in children. Our objective was to evaluate the spirometry and clinical results of mannitol in pediatric patients. Methods: We retrospectively reviewed the records of 30 children and adolescents with CF receiving inhaled mannitol who were already on recombinant human deoxyribonuclease (rhDNase) treatment. The change in forced expiratory volume in 1 second (FEV1) from baseline at 2-4 months was the primary outcome. Secondary measures were other spirometry results, body mass index (BMI), hospital admissions, sputum characteristics, and positive bacterial colonization. Results: Compared to baseline, we found significant improvement in percent predicted FEV1 at 2-4 months of treatment; 84.50 (58.00-99.00) vs. 96.00 (66.00-106.00) (P = 0.0007). The absolute change in FEV1 was +11.5% at 2-4 months, +6.5% at 5-7 months, and +4% at 8-12 months. Also, significant improvements in other spirometry results were observed. Adolescents had significantly lower FEV1 results, but the improvement in their lung function was sustained for a more extended period than children. Mannitol provided easier sputum removal, increased sputum volume, significant decline in hospitalizations, and significantly fewer patients with positive sputum cultures. A significant increase in BMI at 8-12 months was observed. Cough was the most frequent adverse effect. Conclusion: In a real-world setting, our results demonstrated that adding mannitol to rhDNase therapy is tolerable in pediatric patients with CF and may provide improved spirometry and clinical outcomes. In addition, our results showed that mannitol provided recovery in overall lung function at 2-4 months, which was sustained up to 12 months together with improved BMI, easier sputum removal, and a decline in bacterial colonization and hospital admissions. However, cough was the most frequent side effect.

Comparison of inhaled mannitol/dornase alfa combination and daily dornase alfa alone in children with cystic fibrosis.

Inhaled recombinant human deoxyribonuclease (dornase alfa) and osmotic agents such as inhaled mannitol are used for improving the clearance of secretions of cystic fibrosis (CF) patients. We aimed to evaluate the long-term clinical effects of adding dry powder inhaled (DPI) mannitol in subjects with CF who are taking daily dornase alfa. We conducted a retrospective case-control study on subjects with CF. The effect of DPI mannitol was assessed by comparing DPI mannitol and dornase alfa combination with daily dornase alfa alone in children with CF during a 12-month period. The primary outcome measures of the study were absolute changes in percent predicted forced expiratory volume in 1 s (FEV1) and FEV1 z-scores and the secondary outcomes included other spirometry indices, body mass index, frequency of pulmonary exacerbations, SPO2 , and sputum microbiology. Of a total of 28 patients who committed to use DPI mannitol treatments during the study period, five had a positive challenge with DPI mannitol and two were aged over 18 years. Therefore, the mannitol treatment group consisted of 21 patients. However, the effect of DPI mannitol was analyzed using 15 patients in the mannitol treatment group who received DPI mannitol for at least 12 months, and 18 patients who only used dornase alfa constituted the control group. The median absolute change in FEV1 between baseline and the third month; and baseline and the 12th month were significantly higher in the mannitol treatment group (p = 0.038, p = 0.004, respectively). When the groups are compared with respect to absolute z-score changes, all spirometry indices, except FVC at the end of 3 months, showed statistically significant improvements in the mannitol treatment group. Some secondary outcomes like pulmonary exacerbation frequency during the study year and median absolute body mass index z-score changes from baseline to the end of the study showed no significant differences between the groups (p = 0.735, p = 0.161, respectively). No colonization changes were observed in the treatment group. This study showed that in those patients who tolerated long-term (12 months) treatment with DPI mannitol and dornase alfa made greater improvements in FEV1, FVC, FEV1/FVC, FEF25-75 z-scores than treatment with dornase alfa alone in children with CF.

Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).

Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).

A SINGLE-CENTER RETROSPECTIVE EVALUATION OF ENDOBRONCHIAL VALVES FOR LUNG VOLUME REDUCTION IN EMPHYSEMA PATIENTS

SESSION TITLE: Wednesday Electronic Posters 4 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM PURPOSE: Lung volume reduction (LVR) surgery was shown to improve exercise tolerance in patients with emphysema. Criner et al. (LIBERATE) reinforced the utility of endobronchial valve (EBV) placement in patients with emphysema and hyperinflation to improve lung function. In this study we report our experience with bronchoscopic LVR following the commercial availability of EBVs. METHODS: Retrospective review of patients who were treated by bronchoscopic LVR over a 6-month period at a single site. Inclusion criteria were age ≥40 with emphysema and hyperinflation with Total Lung Capacity (TLC) >100% predicted and Residual Volume (RV) >150% predicted. Data gathered include baseline characteristics, 45-day spirometric data, and complications (pneumothorax, pleural effusion, COPD exacerbation, arrhythmia). The primary endpoint was post bronchodilator response FEV1 ≥ 15% increase from baseline. Secondary endpoints were TLC change, absolute change in FEV1, and complication rates of EBV. RESULTS: A total of 18 patients were treated during this period. The average age of the patients evaluated was 69 years-old. 61% of patients were female (11) and 88.9% were Caucasian (16). Baseline 6 minute walk distance (6MWD) was 251 meters. The average baseline RV was 4.54L (217% of predicted) and baseline post-bronchodilator FEV1 was 750mL (30.3% predicted). At the 45-day mark, our patients had a FEV1 increase of 79.2mL (increase of 3% predicted), 30.7% showed an improvement in FEV1 ≥15% from baseline. RV decrease was on average 190mL. Total lung volume reduction on average was 610mL with 75% exhibiting a decrease ≥350mL. Regarding complications, 38.9% of our patients did have post-procedure pneumothorax with 22.2% of the patients requiring partial or total EBV removal. 27.8% of patients did have post procedure COPD exacerbation requiring medical attention with 80% of those patients having COPD exacerbations in the first 45 days. One patient had a previous treatment with vapor to the contralateral lung and another had alpha 1 antitrypsin deficiency. Both had positive outcomes. CONCLUSIONS: At the 45-day point, our center’s experience provided similar positive results as the LIBERATE study. Additionally, our patients exhibited a comparable incidence of pneumothorax post EBV placement. To our knowledge, this is the first and largest published single center experience on EBV for lung volume reduction since the Food and Drug Administration (FDA) approved the device in June 2018. We anticipate similar positive results at the one-year mark. CLINICAL IMPLICATIONS: Heterogeneous and homogeneous emphysema can be effectively treated with endobronchial valves to improve patients’ lung function. DISCLOSURES: No relevant relationships by Raed Alalawi, source=Web Response No relevant relationships by Richard Sue, source=Web Response No relevant relationships by Steve Tseng, source=Web Response No relevant relationships by Leigha Vick, source=Web Response

Potentiators (specific therapies for class III and IV mutations) for cystic fibrosis.

Potentiators (specific therapies for class III and IV mutations) for cystic fibrosis.

Retrospective observational study of French patients with cystic fibrosis and a Gly551Asp-CFTR mutation after 1 and 2 years of treatment with ivacaftor in a real-world setting

BackgroundIvacaftor has been shown to improve lung function and body weight in patients with CF and a gating mutation. Real-world evaluation is warranted to examine its safety and effectiveness over the long term. MethodsA retrospective observational multicentre study collected clinical data in the year before and the 2years after ivacaftor initiation in patients with CF and a Gly551Asp-CFTR mutation. ResultsFifty-seven patients were included. Mean absolute change in FEV1% predicted improved from baseline to Year 1 (8.4%; p<0.001) and Year 2 (7.2%; p=0.006). Statistically significant benefits were observed with increased body mass index, fewer Pseudomonas aeruginosa and Staphylococcus aureus positive cultures, and decreased IV antibiotics and maintenance treatment prescriptions (including azithromycin, Dornase alpha and nutritional supplements). No significant adverse events were reported. ConclusionThe clinical benefits of ivacaftor reported in previous clinical trials were confirmed in a real-world setting two years post-initiation, also reducing treatment burden.

Real-life initiation of lumacaftor/ivacaftor combination in adults with cystic fibrosis homozygous for the Phe508del CFTR mutation and severe lung disease

ObjectiveTo investigate the short-term adverse events and effectiveness of lumacaftor/ivacaftor combination treatment in adults with cystic fibrosis (CF) and severe lung disease in a real life setting. MethodsA multicentre observational study investigated adverse events, treatment discontinuation, FEV1 and body mass index (BMI) one month and three months after lumacaftor/ivacaftor initiation in adults with CF and FEV1 below 40% predicted. ResultsRespiratory adverse events (AEs) were reported by 27 of 53 subjects (51%) and 16 (30%) discontinued treatment. The mean absolute change in FEV1 was +2.06% after one month of treatment (P=0.086) and +3.19% after 3 months (P=0.009). BMI was unchanged. ConclusionsTreatment with lumacaftor/ivacaftor in patients with CF and severe lung disease was discontinued more frequently than reported in clinical trials, due to respiratory AEs. Nevertheless, the patients who continued treatment had an increase in lung function comparable to what was observed in pivotal trials.

Early Trends in Bronchoscopic Lung Volume Reduction: A Systematic Review and Meta-analysis of Efficacy Parameters.

The goal of our systematic review and meta-analysis is to examine the therapeutic effectiveness of bronchoscopic lung volume reduction (BLVR), and to compare it with medical management and lung volume reduction surgery. Variables of interest were absolute change in FEV1, 6MWT, and SGRQ. Meta-analysis was performed for the BLVR modalities with ≥3 trials. Of the 18 shortlisted publications, only valves (four trials; n=159) and coils (six trials; n=194) qualified for meta-analysis. To avoid redundant reporting for valves, only the data for intact fissure subjects were analyzed. Outcome data are presented as the mean difference from baseline with 95% confidence interval at 6-months follow-up. For BLVR using valves, the pooled mean difference (PMD) for FEV1 was 0.146L (95% CI 0.111-0.181; p<0.001), 6MWT was 45.225 meters (95% CI 26.954-63.495; p<0.001), and SGRQ was -8.825 points (95% CI -14.824 to -2.825; p=0.004). All the PMDs were statistically significant and higher than their respective minimal clinically important difference (MCID). For BLVR using coils, the PMD for FEV1 was 0.080L (95% CI 0.057-0.104; p<0.001), 6MWT was 45.320 meters (95% CI 28.040-62.600; p<0.001), and SGRQ was -10.570 points (95% CI -13.299 to -7.841; p<0.001). All three variables showed statistically significant PMDs but that for FEV1 was smaller than the MCID. Data from BLVR modalities with <3 major publications are reviewed in the discussion section. BLVR offers early promise in the palliation of advanced emphysema. Better characterization of patients to identify phenotypes that will derive sustained benefit is needed.

Long-term safety and efficacy of ivacaftor in patients with cystic fibrosis who have the Gly551Asp-CFTR mutation: a phase 3, open-label extension study (PERSIST)

Ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, is approved for the treatment of patients with cystic fibrosis aged 6 years or older with Gly551Asp-CFTR. We assessed the safety and efficacy of ivacaftor during 96 weeks of PERSIST in patients with cystic fibrosis who completed a previous 48-week, placebo-controlled trial of the drug (STRIVE or ENVISION). In this phase 3, open-label extension study, patients received ivacaftor 150 mg every 12 h in addition to their prescribed cystic fibrosis therapies. Patients who received placebo in their previous study initiated ivacaftor in this extension study. Patients were eligible if they had a Gly551Asp-CFTR mutation on at least one allele. The primary objective was to assess the long-term safety profile of ivacaftor as assessed by adverse events, clinical laboratory assessments, electrocardiograms, vital signs, and physical examination; secondary measures included change in forced expiratory volume in one second (FEV1), weight, and pulmonary exacerbations. This study is registered with ClinicalTrials.gov, number NCT01117012 and EudraCT, number 2009-012997-11. Between July 8, 2010, and April 8, 2013, 144 adolescents/adults (≥12 years) from STRIVE and 48 children (6-11 years) from ENVISION were enrolled. Across both trials, 38 (20%) patients had a serious adverse event during the first 48 weeks and 44 (23%) during the subsequent 48 weeks. Two adults (1%) and one child (<1%) discontinued because of adverse events. The most common adverse events were pulmonary exacerbation, cough, and upper respiratory tract infection. Patients previously treated with ivacaftor had sustained improvements in FEV1, weight, and rate of pulmonary exacerbations for up to 144 weeks of treatment. Among adolescents/adults and children who previously received ivacaftor, absolute change in FEV1 at week 96 (144 weeks ivacaftor) was 9·4 and 10·3 % points and absolute increase in weight was 4·1 kg and 14·8 kg, respectively. For adolescents/adults only, the pulmonary exacerbation rate remained suppressed compared with that of patients who received placebo in the placebo-controlled study. At 144 weeks of treatment, ivacaftor was well tolerated, with no new safety concerns. Ivacaftor also provided durable effects for 144 weeks in patients who had received active treatment in the placebo-controlled study. Those patients who previously received placebo had improvements comparable to those of patients treated with ivacaftor in the placebo-controlled study. Vertex Pharmaceuticals Inc.

Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation

BackgroundIvacaftor is used to treat patients with CF and a G551D gating mutation; the KONNECTION study assessed the efficacy and safety of ivacaftor in patients with CF and a non-G551D gating mutation. MethodsPatients with CF ≥6-years- old with non-G551D gating mutations received ivacaftor 150mg q12h or placebo for 8weeks in this 2-part, double-blind crossover study (Part 1) with a 16-week open-label extension (Part 2). The primary efficacy outcome was absolute change in FEV1 through 8 and 24weeks of ivacaftor treatment; secondary outcomes were changes in BMI, sweat chloride, and CFQ-R and safety through 8 and 24weeks of treatment. ResultsEight weeks of ivacaftor resulted in significant improvements in percent predicted FEV1, BMI, sweat chloride, and CFQ-R scores that were maintained through 24weeks. Ivacaftor was generally well tolerated. ConclusionsIvacaftor was efficacious in a group of patients with CF who had selected non-G551D gating mutations.

Tobramycin inhalation powder manufactured by improved process in cystic fibrosis: the randomized EDIT trial

Background:Tobramycin inhalation powder (TIP) was reported to be effective in two Phase III studies in patients with cystic fibrosis (CF) chronically infected with Pseudomonas aeruginosa (Pa). The EDIT study evaluated the efficacy and safety of TIP manufactured by an improved process in CF subjects aged 6–21 years.Methods:CF patients with a forced expiratory volume in 1 second (FEV1) ≥25% to ≤80% predicted, positive Pa cultures and inhaled antipseudomonal therapy naïve (or at least for past 4 months) were enrolled into this double-blind, multicenter trial. Patients were randomized to receive TIP or placebo (1:1) twice daily for one treatment cycle (28.5 days on drug, 28 days off drug). The primary endpoint was relative change in FEV1 percentage predicted from baseline to day 29. A pre-specified sensitivity analysis evaluated absolute change in FEV1% predicted. Other endpoints included Pa sputum density and safety.Results:A total of 62 patients out of a target of 100 (mean age 12.9 years, baseline FEV1 59.2% predicted, Pa sputum density 7.4 log10 colony forming units [CFU] per gram) were randomized. Mean treatment differences (TIP - placebo) were 5.9% (p = 0.148) and 4.4% (p < 0.05) for relative and absolute change in FEV1% predicted respectively. TIP significantly reduced Pa sputum density by −1.2 log10 CFU (p = 0.002). Treatment with TIP was well tolerated.Conclusions:Relative change in FEV1% predicted with TIP treatment was in the expected range based on the literature, but did not reach statistical significance versus placebo. Placebo control and use of treatment naïve patients led to significant recruitment challenges and an underpowered study with consequent impact on the generated data. However, significant improvements in other outcomes including absolute change in FEV1% predicted and reduction in Pa sputum density indicate that TIP is efficacious and well tolerated in CF patients.ClinicalTrials.gov identifier:ClinicalTrials.gov identifier: NCT00918957.

The Effect of Heliox-Driven Bronchodilator Aerosol Therapy on Pulmonary Function Tests in Patients with Asthma

To compare the effects of heliox-driven (He 80:O2 20) to air-driven (N 79:O2 21) β2-agonist aerosol therapy on pulmonary function tests (PFTs) in patients with asthma, a prospective randomized crossover study was undertaken in the asthma clinic of the university-affiliated county hospital in Houston, TX. Thirty-one patients (22 female, age range 18–44) with clinically stable asthma consented. All patients were studied on two different days with both heliox and air as driving gas, therefore serving as their own controls. The PFTs including forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), maximal mid-expiratory flow rate (FEF25–75), and maximal expiratory flow rate (FEFmax) were obtained while breathing ambient air at baseline and 30 min after the bronchodilator treatment. Albuterol sulfate 2.5 mg was nebulized with either heliox or compressed air at 8 L/min for 8 min. When heliox was used as driving agent, additional heliox was delivered via a closed system and no entrainment of external air was allowed. Primary outcome measure was absolute change in FEV1 (ΔFEV1). There were no statistically significant differences in baseline PFTs on the two days of the study. All patients had good bronchodilator response (≥12% improvement in FEV1) with either driving gas. The ΔFEV1 after heliox-driven bronchodilator (HDBD) and air-driven bronchodilator (ADBD) were 0.68±0.38 L/sec (CI: 0.54–0.82) vs. 0.51±0.26 L/sec (CI: 0.42–0.60), respectively (p=0.004). The ΔFEV1 with HDBD was 49±90% (range −36% to 433%) more than ADBD. A subgroup analysis showed this was largely due to better response rates in patients with moderate to severe obstruction. There was more improvement in both FVC and FEFmax with HDBD than ADBD (p<0.05). The changes in FEF25–75 were similar. We conclude that HDBD therapy improves FEV1, FVC, and FEFmax significantly more than ADBD in patients with asthma. Further large randomized studies are needed to better characterize responders and the impact on clinical outcomes.

Short term variability in FEV1: relation to pretest activity, level of FEV1, and smoking habits.

The natural variability in forced expiratory volume in one second (FEV1) over 20 minutes was determined in 54 fit hospital employees and 13 patients with restrictive lung disorders. Initial FEV1 ranged from 1.1 to 6.3 1 BTPS. Variability when expressed as absolute change was similar at all levels of FEV1, so that, when expressed as percentage change, variability decreased with increasing FEV1. Smoking habits did not appear to affect variability but activity before the test did. On the basis of these results an absolute change in FEV1 of 190 ml would be necessary for 95% confidence that the change in FEV1 occurred other than by chance in any one individual. This suggests that the absolute change in FEV1 might be a more reliable criterion than percentage change when distinguishing between natural variability and a response to inhalation of bronchodilators.