Significant Improvement In FEV1 Research Articles

Culturally Appropriate Outreach Specialist Respiratory Medical Care Improves the Lung Function of Children in Regional and Remote Queensland

Indigenous Respiratory Outreach Care (IROC) is a culturally appropriate specialist respiratory service established to deliver multidisciplinary respiratory care to regional and remote Queensland communities. Our objective was to evaluate the impact of an outreach specialist respiratory service on the spirometry of children attending IROC clinics, particularly Indigenous children with asthma and bronchiectasis. Retrospective single-arm cohort study of 189 children who performed spirometry at twelve sites across regional and remote Queensland between October 2010 and December 2017. Each child's baseline spirometry was compared to their best spirometry at follow-up visit occurring within (1) 12months of their most recent visit with at least 12months of specialist care and; (2) each year of their first 3years of care. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) z-scores improved significantly across the whole group from baseline to follow-up (change in z-scores (Δz) of FEV1 = 0.38, 95% CI 0.22, 0.53; ΔzFVC = 0.36, 95% CI 0.21, 0.51). In subgroup analyses, lung function significantly improved in Indigenous children (n = 141, ΔzFEV1 = 0.37, 95% CI 0.17, 0.57; ΔzFVC = 0.36, 95% CI 0.17, 0.55) including those with asthma (n = 117, ΔzFEV1 = 0.41, 95% CI 0.19, 0.64; ΔzFVC = 0.46, 95% CI 0.24, 0.68) and bronchiectasis (n = 38, ΔzFEV1 = 0.33, 95% CI 0.07, 0.59; ΔzFVC = 0.26, 95% CI - 0.03, 0.53). Significant improvements in FEV1 and FVC were observed within the first and second year of follow-up for Indigenous children, but not for non-Indigenous children. The IROC model of care in regional and remote settings leads to significant lung function improvement in Indigenous children with asthma and bronchiectasis.

Endobronchial Valve Treatment in Emphysema Patients with a Very Low DLCO

Background: For selected patients with severe emphysema, bronchoscopic lung volume reduction with endobronchial valves (EBV) is recognized as an additional treatment option. In most trials investigating EBV treatment, patients with a very low diffusing capacity (DLCO) were excluded from participation. Objectives: Our goal was to investigate whether EBV treatment in patients with emphysema with a very low DLCO is safe and effective. Methods: This was a single-center retrospective analysis including patients with emphysema and a DLCO ≤20%pred who underwent EBV treatment. Follow-up was performed 6 months post-treatment. Outcome parameters were compared to a historical matched control group (DLCO >20%pred, matched for sex, age, forced expiratory volume in 1 s [FEV₁], and residual volume [RV]). Results: Twenty patients (80% female, 64 ± 6 years, FEV₁ 26 ± 6%pred, RV 233 ± 45%pred, DLCO 18 ± 1.6%pred) underwent EBV treatment. At 6 months follow-up, we found a statistically significant improvement in FEV₁ (0.08 ± 0.12 L), RV (–0.45 ± 0.95 L), 6-min walking distance (38 ± 65 m), and St. George’s Respiratory Questionnaire (–12 ± 13 points). With the exception of FEV₁, all exceeded the minimal clinically important difference. The most common serious adverse event was a pneumothorax requiring intervention (15%). There were no significant differences in outcome compared to the DLCO >20%pred control group. Conclusions: In this single-center retrospective analysis, we showed statistically significant and clinically relevant improvements in lung function, exercise capacity, and quality of life up to 6 months after EBV treatment in emphysema patients with a DLCO ≤20% (14–20%) of predicted with no increased risk of serious adverse events.

Effects of nebulizer fill volume on the efficacy and safety of the bronchodilator

This study aimed to demonstrate the effect of adding saline to the respirable-solution of salbutamol placed in a nebulization chamber on the clinical status of the ventilated patient.A total of 160 (80 female) asthmatic subjects were randomly divided into 8 groups (gp1-gp8). They received 0.5 ml salbutamol respirable-solution (5000 μg\\ml), 0.5 ml salbutamol respirable-solution+1 ml saline, 0.5 ml salbutamol respirable-solution+2 ml saline, 0.5 ml salbutamol respirable-solution+3 ml saline, 1 ml salbutamol respirable-solution, 1 ml salbutamol respirable-solution+1 ml saline, 1 ml salbutamol respirable-solution+2 ml saline and 1 ml salbutamol respirable-solution+3 ml saline respectively using jet-nebulizer. Forced expiratory volume in 1 s as a percentage of predicted (FEV1%), oxygen-saturation, pulse-rate, and respiratory-rate were measured before and 10–20 min after the nebulization of the salbutamol.0.5 ml salbutamol respirable-solution had no significant improvement in FEV1%. However, 1 ml had a significant improvement in FEV1% (p < 0.001). Increasing fill volume increased the FEV1% significantly (p < 0.001). No significant difference in FEV1% when saline increased from 2 ml to 3 ml. There was no significant difference in oxygen-saturation before and after the administration of salbutamol. Pulse-rate increased significantly (p < 0.01) at higher fill-volumes especially in group 6–8. A few subjects complained of palpitation and headache at the end of nebulization.Increasing fill-volume with jet-nebulizer enhanced the bronchodilator effect of salbutamol and plateau occurs after 2 ml added saline.

Bronchoscopic lung volume reduction procedures for emphysema: A network meta-analysis.

Bronchoscopic lung volume reduction (BLVR) offers alternative novel treatments for patients with emphysema. Comprehensive evidence for comparing different BLVR remains unclear. To estimate the effects of different BLVR on patients with emphysema. PubMed, EMBASE, Cochrane Library, and Web of Science databases from January 2001 to August 2017 were searched. Randomized clinical trials evaluated effects of BLVR on patients with emphysema. The relevant information was extracted from the published reports with a predefined data extraction sheet, and the risk of bias was assessed with the Cochrane risk of bias tools. Pair-wise metaanalyses were made using the random-effects model. A random-effects network meta-analysis was applied within a Bayesian framework. The quality of evidence contributing to primary outcomes was assessed using the GRADE framework. 13 trials were deemed eligible, including 1993 participants. The quality of evidence was rated as moderate in most comparisons. Medical care (MC)was associated with the lowest adverse events compared with intrabronchial valve (IBV)(-2.5,[-4.70 to -0.29]), endobronchial valve (EBV) (-1.73, [-2.37 to -1.09]), lung volume reduction coils (LVRC) (-0.76, [-1.24 to -0.28]), emphysematous lung sealant (ELS) (-1.53, [-2.66 to -0.39]), and airway bypass(-1.57, [-3.74 to 0.61]). Adverse events in LVRC were lower compared with ELS (-0.77,[-2.00 to 0.47]). Bronchoscopic thermal vapor ablation (BTVA) showed significant improvement in FEV1 compared with MC (0.99, [0.37 to 1.62]), IBV (1.25, [0.25 to 2.25]), and LVRC (0.72, [0.03 to 1.40] ). Six minute walking distance (6 MWD) in ELS was significantly improved compared with other four BLVR, sham control, and MC (-1.96 to 1.99). Interestingly, MC showed less improvement in FEV1 and 6MWDcompared with EBV (-0.45, [-0.69 to -0.20] and -0.39, [-0.71 to -0.07], respectively). The mortality in MC and EBV was lower compared with LVRC alone (-0.38, [-1.16 to 0.41] and -0.50, [-1.68 to 0.68], respectively). BTVA and EBV led to significant changes in St George's respiratory questionnaire (SGRQ) compared with MC alone (-0.74, [-1.43 to -0.05] and 0.44, [0.11 to 0.78], respectively). BLVR offered a clear advantage for patients with emphysema. EBV had noticeable beneficial effects on the improvement of forced expiratory volume 1, 6MWD and SGRQ, and was associated with lower mortality compared with MC in different strategies of BLVR.

Effect of incentive spirometer exercise on pulmonary functions in children with spastic cerebral palsy

BackgroundSpastic cerebral palsy (CP) patients have lower pulmonary functions than normal healthy individuals as they usually have decreased chest wall mobility, deviation of optimal chest wall structure, and weak respiratory muscles.PurposeThe aim was to study the effect of incentive spirometer exercise (ISE) on spirometry pulmonary function in children with spastic CP.Materials and methodsFifty spastic CP patients were randomly divided into two groups: the study group consisted of 30 patients and the control group consisted of 20 patients. Both groups were following and doing physiotherapy in the National Institute of Neuromotor System, the study group added incentive spirometer exercise to their physiotherapy program. We assessed forced expiratory volume at first second (FEV1%), the forced vital capacity (FVC %), FEV1/ FVC ratio, and maximal mid-expiratory flow before and after 4 weeks of exercise and lastly after another 4 weeks of exercise.ResultsThe authors found significant improvements in FEV1%, FVC %, and maximal mid-expiratory flow in the study group, but not in the control group.ConclusionThe authors support the use of ISE for improving pulmonary functions in children with spastic CP.

Predicting the Response to Bronchial Thermoplasty

Although it is established that not all patients respond to bronchial thermoplasty (BT), the factors that predict response/nonresponse are largely unknown. To identify baseline factors that predict clinical response. The records of 77 consecutive patients entered into the Australian Bronchial Thermoplasty Registry were examined for baseline clinical characteristics, and outcomes measured at6and 12 months after BT, such as change in the Asthma ControlQuestionnaire (ACQ) score, exacerbation frequency, the requirement for short-acting beta-2 agonist (SABA) medication and oral corticosteroids, and improvement in spirometry. This was a cohort of patients with severe asthma: aged 57.7 ± 11.4 years, 57.1% females, 53.2% of patients taking maintenance oral steroids, 43% having been treated with an mAb, mean FEV1 of 55.8% ± 19.8% predicted. BT resulted in an improvement in the ACQ score from 3.2 ± 1.0 at baseline to 1.6 ± 1.1 at 6 months (P < .001). Exacerbation frequency in the previous 6 months reduced from 3.7 ± 3.3 to 0.7 ± 1.2 (P < .001). SABA requirement reduced from 9.3 ± 7.1 puffs/d to 3.5 ± 6.0 (P < .001), and 48.8% of patients were weaned completely off oral steroids. A significant improvement inFEV1 was observed. Using multiple linear regression models, baseline ACQ score strongly predicted improvement in ACQ score (P < .001). Patients with an exacerbation frequency greater than twice in the previous 6 months showed the greatest reduction in exacerbations (-5.3 ± 2.8; P < .001). Patients using more than 10puffs/d of SABA experienced the greatest reduction in SABA requirement (-12.4 ± 10.5 puffs, P < .001). The most severely afflicted patients had the greatest improvements in ACQ score, exacerbation frequency, and medication requirement.

Phase II Study of Single/Repeated Doses of Acumapimod (BCT197) to Treat Acute Exacerbations of COPD

Mitogen-activated protein kinase p38 is a key regulator in the inflammation pathway and is activated in the lungs of chronic obstructive pulmonary disease (COPD) patients. Acumapimod is a potent, selective, oral, p38 inhibitor under investigation for treatment of acute exacerbations of COPD (AECOPD). In this Phase II, double-blind, randomized, placebo-controlled dose-exploration study of acumapimod in patients with moderate or severe AECOPD (NCT01332097), patients presenting with AECOPD were randomized to receive single-dose acumapimod (20 mg or 75 mg) on Day 1, repeated single-dose acumapimod (20 mg or 75 mg) on Days 1 and 6, oral prednisone 40 mg (10 days), or placebo. Primary outcome: improvement in forced expiratory volume in 1 s (FEV1) versus placebo at Day 5 (single doses) and Day 10 (repeated doses). N = 183 patients were randomized; 169 (92%) patients completed the study. Although the primary endpoint (FEV1 at Day 10) was not met (p = 0.082), there was a significant improvement in FEV1 with acumapimod repeat-dose 75 mg versus placebo at Day 8 (p = 0.022) which, though not a prespecified endpoint, was part of an overall trend. Differences at lower doses did not achieve significance. Mean change in FEV1 AUC from baseline to Day 14 in the 75 mg repeat-dose group was significantly higher versus placebo (p = 0.02), prednisone (p = 0.01), and 20 mg single-dose groups (p = 0.015) (post-hoc analysis). EXACT-PRO showed numerical differences versus placebo that did not reach significance. Acumapimod was well tolerated. In conclusion, repeated single-dose acumapimod showed a clinically relevant improvement in FEV1 over placebo at Day 8, along with consistent numerical differences in EXACT-PRO. These data can be used to determine dose regimens for a proof-of-clinical-concept trial.

Vitamin D does not improve lung function decline in COPD: a meta-analysis.

Vitamin D deficiency plays an important role in chronic obstructive pulmonary disease (COPD). However, the effects of vitamin D supplementation on lung function decline in COPD were inconsistently reported and a meta-analysis is thus needed. Eligible cohort and randomized controlled trials (RCTs) were searched from databases including PubMed, Embase, and Web of Science. Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated in a random or fixed effects model. Eight studies reaching the inclusion criteria and involving 687 COPD patients were included. Pooled effect size showed vitamin D treatment resulted in no significant improvements in FEV1 (SMD: 0.38, 95% CI: -0.13 to 0.88, p= 0.144), FVC (SMD: 0.55, 95% CI: -0.49 to 1.58, p=0.299), and FEV1/FVC (SMD: 0.00, 95% CI: -0.27-0.27, p=0.995) in COPD patients. Subgroup analysis revealed neither short-term (<6 months) (SMD: 0.10, 95% CI: -0.17 to 0.37, p=0.479) nor long-term (≥6 months) (SMD: 0.52, 95% CI: -0.23 to 1.27, p=0.172) vitamin D exposure could significantly benefit lung function decline in COPD. This meta-analysis shows neither short-term nor long-term additional supplementation of vitamin D can benefit the lung function decline in COPD. Moreover, large scale RCTs focusing on COPD smokers with low level of vitamin D should be considered.

Effect of Statin Supplementation on Pulmonary Function and Inflammatory Markers in Patients of Chronic Obstructive Pulmonary Disease

Background:COPD being a systemic inflammatory disease is accompanied by alteration of various inflammatory cytokines which affect the metabolic equilibrium of body. Some therapeutic options, mainly statins via their wide range of pharmacologic actions alter the level of proinflammatory cytokines hence, helpful in attenuating various extra-pulmonary consequences of COPD. We did a randomised case-control study to study the effect of statin supplementation on pulmonary function and inflammatory markers in patients of COPD.Methods:We included 40 stable COPD subjects &amp; randomized them in two groups, Intervention &amp; Non-intervention. Intervention group received 40 mg atorvastatin once daily for 3 months in addition to the conventional treatment of COPD similar to the prior one. We studied levels of IL-6 &amp; CRP and correlated them with disease severity before and after the aforementioned intervention.Results:We observed that CRP levels decreased in both the groups after a follow up of 3 months, but neither of them was statistically significant (p=0.57 &amp; 0.63 respectively) nor the mean of their difference (p=0.969). IL-6 levels showed a persistent decline in intervention group but, was not significant (p=0.91). In this study, we noticed statistically significant improvement in FEV1 (p=0.008) in the intervention group which was in contrast to non-intervention group. Similarly, the exercise capacity also statistically increased in the intervention group (p=0.002). There was also evident negative correlation between exercise capacity and IL-6 as well CRP levels. FEV1 also showed statistically significant negative correlation with IL-6 levels (p=0.023).Conclusion:We can improve the disease outcome and alter its natural progression by altering the levels of inflammatory markers with the aid of some additional pharmacological interventions i.e., in this study was atorvastatin.

Omalizumab treatment in Samter's triad: case series and review of the literature.

Samter's triad is the combination of asthma, aspirin sensitization, and nasal polyposis. Few data are available on the use of omalizumab in this disease. The study aimed to describe the impact of omalizumab on clinical and functional parameters and the quality of life of a series of patients with Samter's triad. Moreover, we aimed to provide a review of the literature on this topic. We retrospectively described four patients with Samter's triad undergoing omalizumab therapy. Clinical, functional, and immunological data of these patients were collected at baseline and follow-up. Reduction of asthma exacerbations and salbutamol rescue therapy were observed in all patients after anti-IgE treatment together with an improvement in the quality of life. A significant improvement in FEV1, FVC, and FEF25-75 was observed. No major side-effects were observed. A total of 14 studies regarding omalizumab in aspirin-exacerbated respiratory diseases were included in the review, comprising 78 patients. All studies reported a good efficacy in improving asthma control; restoration of aspirin tolerance was repeatedly reported. The results of our case series and review of the literature suggest that omalizumab effectively improves asthma control, lung function tests, and quality of life in patients with Samter's triad.

Long-term macrolide antibiotics for the treatment of bronchiectasis in adults: an individual participant data meta-analysis

Bronchiectasis guidelines recommend long-term macrolide treatment for patients with three or more exacerbations per year without Pseudomonas aeruginosa infection. Randomised controlled trials suggest that long-term macrolide treatment can prevent exacerbations in adult patients with bronchiectasis, but these individual studies have been too small to do meaningful subgroup analyses. We did a systematic review and individual patient data (IPD) meta-analysis to explore macrolide benefit in subpopulations, including those in which macrolide therapy is not currently recommended. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science from Jan 1, 2000, to Sept 30, 2018, to identify double blind, randomised, placebo-controlled trials of macrolide antibiotics in adult patients with bronchiectasis. We applied no language restrictions. Randomised controlled trials were eligible if treatment was defined a priori as long term and had a primary or secondary outcome of bronchiectasis exacerbations. Studies in patients with cystic fibrosis bronchiectasis were excluded. The primary outcome of the meta-analysis was frequency of exacerbations requiring treatment with antibiotics. Secondary endpoints were time to first exacerbation, change in quality of life according to the St George's Respiratory Questionnaire (SGRQ), and change in FEV1. IPD meta-analysis was done using fixed effects models adjusting for age, sex, FEV1, and trial. We did prespecified subgroup analyses for each of the primary and secondary endpoints using one-step meta-analysis only. Subgroups were defined by age, sex, previous exacerbation frequency, smoking status, inhaled corticosteroid use at baseline, body-mass index at baseline, cause, C-reactive protein at baseline, baseline FEV1 percentage of predicted, SGRQ total score, and Pseudomonas aeruginosa in sputum culture at baseline. The meta-analysis is registered with the PROSPERO international register of systematic reviews, number CRD42018102908. Of 234 identified studies, we included three randomised controlled trials, and IPD was obtained for 341 participants. Macrolide antibiotics reduced the frequency of exacerbations (adjusted incidence rate ratio [IRR] 0·49, 95% CI 0·36 to 0·66; p<0·0001). We also found that macrolide treatment improved the time to first exacerbation (adjusted hazard ratio 0·46, 0·34 to 0·61; p<0·0001) and was associated with improved quality of life measured by the SGRQ (mean improvement 2·93 points, 0·03 to 5·83; p=0·048). Macrolides were not associated with a significant improvement in FEV1 (67 mL at 1 year, -22 to 112; p=0·14). Effect estimates in prespecified subgroup analyses revealed a reduced frequency of exacerbations in all prespecified subgroups, including a high level of benefit in patients with P aeruginosa infection (IRR 0·36, 0·18-0·72; p=0·0044) and in patients with one to two exacerbations per year (0·37, 0·16-0·88; p=0·025). Studies were rated as low risk of bias across all domains. Long-term macrolide treatment significantly reduces the frequency of exacerbations in patients with bronchiectasis, with similar benefits observed in all subgroups based on patient characteristics. This finding suggests that macrolides might be considered in patients in whom macrolides are not indicated according to the current guidelines, particularly if alternative approaches to reduce exacerbations have been unsuccessful. However, downsides of long-term macrolide treatment must also be taken into account. European Respiratory Society.

Posaconazole therapy in children with cystic fibrosis and Aspergillus-related lung disease.

There is emerging evidence for the role of posaconazole in the management of Aspergillus-related cystic fibrosis (CF) lung disease. The tolerability and efficacy of posaconazole in paediatric CF is not well established. We report a prospective study over a fifty-three month period evaluating the safety, tolerability, and efficacy of posaconazole in pediatric CF. Fourteen children (seven males, median age 13 years, range 3-17 years) received a total of twenty-three courses of posaconazole (13 oral suspension and 10 tablet formulation). Of these patient episodes, nine received posaconazole for emerging or active allergic bronchopulmonary aspergillosis (ABPA) and two required a combination of posaconazole and systemic corticosteroids for difficult-to-treat ABPA. A subgroup of patients (n = 12) with persistent isolates of Aspergillus fumigatus, in the absence of serological markers of ABPA, received posaconazole monotherapy for pulmonary exacerbations not responding to conventional broad-spectrum antibiotic treatment. Posaconazole levels, full blood count, electrolytes, and liver function were monitored on day 7 of treatment and then monthly. Posaconazole was well tolerated in all but three patients. Therapeutic plasma levels >1mg/l were achieved in all receiving the tablet formulation in comparison to 60% on the liquid preparation. There was a modest but significant improvement in FEV1 (% predicted) demonstrated for the cohort as a whole (p = 0.015) following posaconazole therapy. Posaconazole is well tolerated in children as young as six years old, improvements in lung function are observed, and therapeutic plasma levels are readily achieved in patients taking the tablet formulation and in adherent patients taking the liquid formulation.

Effect of ambient air quality on functional exercise capacity and pulmonary function in healthy young adults

Effect of ambient air quality on functional exercise capacity and pulmonary function in healthy young adults - IJCAP- Print ISSN No: - 2394-2118 Online ISSN No:- 2394-2126 Article DOI No:- 10.18231/2394-2126.2019.0026, Indian Journal of Clinical Anatomy and Physiology-Indian J Clin Anat Physiol

The efficacy and safety of azithromycin in asthma: Asystematic review.

Azithromycin is a potential therapeutic choice for asthma control, which is a heterogeneous airway inflammatory disease. Because of variable findings, we intend to evaluate the therapeutic effect and safety of azithromycin in asthma. Databases, including PubMed, EMBASE, Cochrane, and CNKI until 31 December 2017, were searched to identify available randomised controlled trials regarding azithromycin treatment for asthma. We identified seven studies involving 1520 cases that met our criteria. The mean difference for lung function (FEV 1, FVC, PEF), symptom assessment (ACQ, AQLQ), airway inflammation, and risk ratios for adverse events were extracted. Chi‐square and I 2 tests were applied to evaluate the heterogeneity among the studies towards each index with a random effect model or a fixed effect model. Pooled analysis shows that azithromycin administration results in no significant improvement in FEV 1 (MD: 0.09, 95% CI −0.10 to 0.29, P = 0.36), PEF (MD: 11.76; 95% CI, −2.86 to 26.38, P = 0.11), total airway inflammatory cells (MD: −0.29; 95% CI, −1.38 to 0.80, P = 0.60), ACQ (MD: 0.05; 95% CI, −0.08 to 0.19, P = 0.44), and AQLQ (MD: 0.12; 95% CI, −0.02 to 0.26, P = 0.10). Moreover, no significant difference was detected in adverse events (Risk ratio 0.99; 95% CI, 0.82‐1.19, P = 0.90). These findings demonstrate no beneficial clinical outcome of azithromycin in asthma control, and we propose that further prospective cohorts are warranted.

Nebulized Versus Dry Powder Long-Acting Muscarinic Antagonist Bronchodilators in Patients With COPD and Suboptimal Peak Inspiratory Flow Rate.

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).

Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis

BackgroundLymphangioleiomyomatosis is a rare disease caused by unregulated activation of mammalian target of rapamycin (mTOR) signalling pathway. Sirolimus showed efficacy in a phase 3 trial of patients with lymphangioleiomyomatosis, but the optimal dose remains unclear.MethodsWe investigated the efficacy and safety of low-dose compared with conventional-dose sirolimus. Clinical data of 39 patients with lymphangioleiomyomatosis (mean age, 34.8 years; median treatment period, 29.6 months) who received sirolimus were retrospectively reviewed. Low-dose sirolimus was defined as any dose that maintained mean blood trough levels lower than those maintained with conventional doses (5–15 ng/mL).ResultsFifty-one percent of patients received low-dose therapy. The rate of decline in lung function decreased after treatment in the whole group (forced expiratory volume in 1 s [FEV1], − 0.12 ± 0.47 [before] vs. 0.24 ± 0.48% predicted/month [after], p = 0.027; diffusing capacity for carbon monoxide [DLco], − 0.33 ± 0.61 vs. 0.03 ± 0.26% predicted/month, p = 0.006) compared with before treatment. In the low-dose group, the rate of decline in FEV1 (− 0.08 ± 0.38 [before] vs. 0.19 ± 0.51% predicted/month [after], p = 0.264) and DLco (-0.13 ± 0.62 vs. 0.02 ± 0.28% predicted/month, p = 0.679) showed a numeric trend towards improvement after treatment; however, the conventional-dose group showed significant improvement in FEV1 (− 0.26 ± 0.54 [before] vs. 0.22 ± 0.38 [after] % predicted/month, p = 0.024) and DLco (− 0.55 ± 0.58 vs. 0.04 ± 0.25% predicted/month, p = 0.002) after treatment. Adverse events (AEs) occurred in 89.7% of patients and the most common AEs was hypercholesterolaemia (43.6%), followed by stomatitis (35.9%). The occurrences of AE were similar between the low- and conventional-dose groups (85.0% vs. 94.7%, p = 0.605).ConclusionsLow-dose sirolimus may stabilise lung function decline in lymphangioleiomyomatosis patients, but its efficacy appears to be inferior to that of conventional-dose sirolimus.

IMPROVEMENT IN MORNING PEAK EXPIRATORY FLOW WITHIN THE FIRST WEEK OF TREATMENT WITH IV RESLIZUMAB

Introduction In duplicate 52-week placebo (PBO)-controlled Phase 3 trials, patients with inadequately controlled eosinophilic asthma (blood eosinophils ≥400 cells/µL) who received reslizumab (RES; 3mg/kg IV Q4W) achieved significant improvements in FEV1, FVC and FEF25-75% 4 weeks after the first dose. The objective of this post-hoc analysis was to assess earlier improvements in lung function based on ambulatory morning peak expiratory flow (PEF). Methods Patients used a PEF meter and recorded their pre-dose (prior to use of long-acting beta agonists and inhaled corticosteroids) PEF daily throughout the trials (Study 1 and Study 2). PEF technique was reviewed at scheduled clinic visits. Weekly averages of daily morning PEF measurements are reported. Results Study 1 included 489 patients (PBO 244, RES 245) and Study 2 included 464 patients (PBO 232, RES 232). Patients receiving RES demonstrated increases in mean morning PEF (L/min) versus placebo of 22.66±7.85 and 18.90±9.28 (p=0.004; p=0.042) at 52 weeks in Study 1 and Study 2, respectively. Improvement compared with placebo was evident within the first week (RES vs PBO, Study 1: 1.18±4.78 vs -8.22±4.02; Study 2: 0.850±6.03 vs -8.18±4.55). Between-treatment differences increased through week 7 (RES vs PBO, Study 1: 15.82±6.29 vs -10.98±5.41; Study 2: 27.33±8.06 vs -6.97±6.01) and were sustained through the 52-week treatment period. PEF improvements corresponded with FEV1 improvements at Week 4. Conclusions Treatment with IV RES was associated with rapid and sustained improvement in lung function as assessed by morning PEF in patients with severe eosinophilic asthma, confirming earlier FEV1 data. Overall change from baseline over 52 weeks of treatment in Studies 1 and 2, weekly average AM Peak Expiratory Flow Rate (PEFR) (L/min) In duplicate 52-week placebo (PBO)-controlled Phase 3 trials, patients with inadequately controlled eosinophilic asthma (blood eosinophils ≥400 cells/µL) who received reslizumab (RES; 3mg/kg IV Q4W) achieved significant improvements in FEV1, FVC and FEF25-75% 4 weeks after the first dose. The objective of this post-hoc analysis was to assess earlier improvements in lung function based on ambulatory morning peak expiratory flow (PEF). Patients used a PEF meter and recorded their pre-dose (prior to use of long-acting beta agonists and inhaled corticosteroids) PEF daily throughout the trials (Study 1 and Study 2). PEF technique was reviewed at scheduled clinic visits. Weekly averages of daily morning PEF measurements are reported. Study 1 included 489 patients (PBO 244, RES 245) and Study 2 included 464 patients (PBO 232, RES 232). Patients receiving RES demonstrated increases in mean morning PEF (L/min) versus placebo of 22.66±7.85 and 18.90±9.28 (p=0.004; p=0.042) at 52 weeks in Study 1 and Study 2, respectively. Improvement compared with placebo was evident within the first week (RES vs PBO, Study 1: 1.18±4.78 vs -8.22±4.02; Study 2: 0.850±6.03 vs -8.18±4.55). Between-treatment differences increased through week 7 (RES vs PBO, Study 1: 15.82±6.29 vs -10.98±5.41; Study 2: 27.33±8.06 vs -6.97±6.01) and were sustained through the 52-week treatment period. PEF improvements corresponded with FEV1 improvements at Week 4. Treatment with IV RES was associated with rapid and sustained improvement in lung function as assessed by morning PEF in patients with severe eosinophilic asthma, confirming earlier FEV1 data.

Follow-up outcomes of chronic obstructive pulmonary disease patients who underwent dilatation and curettage with the Karakoca resector balloon

We previously reported satisfactory results with the Karakoca resector balloon in 10 patients with stage IV chronic obstructive pulmonary disease (COPD) who did not respond to medical treatment. In this article, we present the outcomes of the Karakoca resector balloon dilatation and curettage technique in a larger case series (n = 188).A total of 188 COPD patients [mean age (SD): 69.2 (8.0) years; 46 females] classified as stage III to IV by the Global Initiative for Obstructive Lung Disease criteria underwent balloon desobstruction for segmental and subsegmental bronchi by therapeutic bronchoscopy. None of the patients could have achieved symptom relief even under high-dose inhaled bronchodilators and corticosteroids, oral corticosteroids, or oxygen and noninvasive mechanical ventilation therapy before the intervention. Forced expiratory volume in 1 s (FEV1) and oxygen saturation (SpO2) were measured, and modified Borg dyspnea scale (MBS) scores were determined before and 1 week and 1 month after the intervention.All patients were active smokers and 80% had concomitant chronic diseases. After the intervention, there was a notable reduction in the oxygen need of the patients. Comparison of lung function tests 1 week after the procedure with results before the procedure showed significant improvements in FEV1, MBS, and SpO2 levels (P < 0.001 for each), and the improvements were maintained for the entire postprocedural month (P < 0.001 for each). Except for 4 males, all patients were free of symptoms.These results confirmed our early observations that balloon dilatation and curettage is a safe and successful technique for medical treatment-resistant COPD.

History of lung volume reduction procedures.

Lung volume reduction (LVR) procedures for emphysematous patients were firstly introduced in the second half of the twentieth century. Over time, from the first invasive surgical procedures, new less invasive techniques have been conceived. In regards to the surgical approach, the adoption of VATS and the execution, in selected centers, of a non-resectional approach, with folding of less functional lung tissue, reduced mortality and adverse events risks. As regards to the bronchoscopic approach, endobronchial valves (EBV) and intrabronchial valves (IBV) were initially proposed in the early 2000s to obtain segmental or lobar atelectasis of the more compromised lung parenchyma. Despite showing promising results with respect to improvement of pulmonary function tests, particularly forced expiratory volume in 1st second (FEV1), and quality of life, and a good safety profile, valves showed disappointing results in presence of collateral ventilation, such as in cases of incomplete fissures. To overcome this technical issue, in the last 10 years, endobronchial coils have been designed and used. Having a compressive effect on the lung parenchyma where they are located, they are not affected by collateral ventilation. Randomized control trials (RCTs) on endobronchial coils showed a significant improvement in FEV1 and quality of life, however this technique was not immune to side effects, particularly low respiratory tract infections and pneumothoraces. Besides bronchial valves (BV) and coils, airway by-pass stents have also been evaluated in a RCT but without reaching the desired endpoints. Other innovative procedures recently considered and delivered through bronchoscopy regards thermal energy, with vapour therapy, to achieve a scarring reaction of the emphysematous lung parenchyma, and polymeric foams used as lung sealants to achieve absorptive atelectasis. In conclusion, LVR procedures may be considered in carefully selected patients with symptomatic emphysema and severe lung hyperinflation, and might be personalized according to the anatomical characteristics of emphysematous area.

Bronchoscopic Lung Volume Reduction Procedures for Emphysema: A Network Meta-Analysis

Importance: Bronchoscopic lung volume reduction (BLVR) offers alternative novel treatments for patients with emphysema. Comprehensive evidence for comparing different BLVR remains unclear. Objective: To estimate the effects of different BLVR on patients with emphysema. DataSources: PubMed, EMBASE, Cochrane Library, and Web of Science databases from January 2001 to August 2017were searched. Study Selection: Randomized clinical trials (RCT) evaluated effects of BLVR on patients with emphysema. Data Extraction and Synthesis: The relevant information was extracted from the published reports with a predefined data extraction sheet, and the risk of bias was assessed with the Cochrane risk of bias tools. Main Outcomes and Measures: Pair-wise meta-analyses were made using the random-effects model. A random-effects network meta-analysis was applied within a Bayesian framework. The quality of evidence contributing to each network estimate was assessed using the GRADE framework. Results: 13 trials were deemed eligible, including 1993 participants. The quality of evidence was rated as moderate in most comparisons. Medical care (MC)was associated with the lowest adverse events compared with intra-bronchial valve (IBV)(-2.5,[-4.70 to -0.29]), endobronchial valve (EBV) (-1.73, [-2.37 to -1.09]), lung volume reduction coils (LVRC) (-0.76, [-1.24 to -0.28]), emphysematous lung sealant (ELS) (-1.53, [-2.66 to -0.39]), and airway bypass(-1.57, [-3.74 to 0.61]).Adverse events in LVRC were lower compared with ELS (-0.77,[-2.00 to 0.47]).Bronchoscopic thermal vapor ablation (BTVA) showed significant improvement inFEV1 compared with MC (0.99, [0.37 to 1.62]), IBV (1.25, [0.25 to 2.25]), and LVRC (0.72,[0.03 to 1.40]).6 MWT in ELS was significantly improved compared with other four BLVR, sham control, and MC (-1.96 to 1.99).Interestingly, MC showed less improvement in FEV1 and 6 MWT compared with EBV (-0.45, [-0.69 to -0.20] and -0.39, [-0.71 to -0.07], respectively).The mortality in MC and EBV was lower compared with LVRC alone (-0.38, [-1.16 to 0*41] and -0.50, [-1.68 to 0*68], respectively). BTVA and EBV led to significant changes in SGRQ compared with MC alone (-0.74, [-1.43 to -0.05] and 0.44, [0.11 to 0.78], respectively). Conclusions and Relevance: BLVR offered a clear advantage for patients with emphysema. EBV had noticeable beneficial effects on the improvement of FEV1, 6MWTand SGRQ, and was associated with lower mortality compared with MC in different strategies of BLVR. Funding: This project was supported by National major research program on Natural Science of China (91542164). Competing interests: The authors declare that they have no competing financial interests. Ethics Approval Statement: ??