Effectiveness and Patient Satisfaction with Budesonide/Formoterol Easyhaler ® Among Patients with Asthma or COPD Switching from Previous Treatment: a Real-World Study of Patient-Reported Outcomes Abstract Introduction Persistent symptoms, poor disease control, and reduced quality of life (QoL) are common in patients with asthma and chronic obstructive pulmonary disease (COPD). Current therapies are only partially effective and inhaler misuse contributes to insufficient disease control and poor outcomes. This real-world study aimed to evaluate the effectiveness of budesonide/formoterol fumarate (B/F) Easyhaler® in everyday clinical practice in Hungary. Methods Post hoc, subgroup analyses of this 12-week, real-world, multicenter, open-label study were conducted in adults diagnosed with asthma or COPD. Endpoints included the change in patient-reported outcome measures; i.e., symptoms and disease control measured by Asthma Control Test or COPD Assessment Test and health-related (HR)QoL measured by mini-Asthma Quality of Life Questionnaire or modified Medical Research Council dyspnea scale. Changes in lung function and patient satisfaction with B/F Easyhaler versus their previous inhaler were also evaluated. Results were stratified by the inhaler device used at visit 1 (baseline, when patients switched device); comparisons were made with B/F Easyhaler use after 12 weeks, assessed at visit 3. Results In total, 398 and 563 patients with asthma and COPD, respectively, were analyzed. Significant improvements (p < 0.0001) in symptoms and disease control, HRQoL, and lung function were reported 12 weeks after switching treatment to B/F Easyhaler from the most commonly used devices (≥ 10% of patients). Significant increases in patient satisfaction were also reported versus comparators. Conclusions Patients with asthma or COPD who switched to B/F Easyhaler from their previous inhaler due to lack of disease control achieved significant improvements in symptoms and disease control, HRQoL, and lung function within 12 weeks of real-world use with significant increase in patient satisfaction also observed. Such comparative information may reassure clinicians and patients that may be viewed as an appropriate and potentially beneficial treatment option. Trial Registration Number OGYÉI/13942-5/2016 (National Pharmaceutical Institute of Pharmacy and Nutrition of Hungary). Funding Orion Corporation, Orion Pharma. Plain Language Summary Plain language summary available for this article.

Classification of Patients with COPD on LAMA Monotherapy Using the GOLD Criteria: Analysis of a Claims-Linked Patient Survey Study Abstract Introduction To address the burden of chronic obstructive pulmonary disease (COPD), the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends treatment according to classification of patients by symptom severity and exacerbation risk. This post hoc analysis of a previously reported claims-linked, cross-sectional survey [study 205862 (HO-16-16642)] classified patients with COPD receiving long-acting muscarinic antagonist (LAMA) monotherapy based on the GOLD 2017 categories. Methods Eligible patients who were ≥ 40 years of age, with ≥ 2 claims with International Classification of Diseases-10th Revision-Clinical Modification COPD diagnosis codes J40–J44 ≥ 30 days apart during the 12-month baseline period, and ≥ 2 claims for LAMA monotherapy in the 6 months prior to identification, were identified using claims data from the Optum Research Database. Patients completed a survey assessing modified Medical Research Council (mMRC) Dyspnea Scale and COPD Assessment Test (CAT) scores and demographics; clinical characteristics were assessed from claims and survey data, while exacerbation history was assessed from claims data. GOLD symptom severity classifications were low (groups A and C) for patients with low scores on both the CAT and mMRC scales (scores of < 10 and 0–1, respectively), and high (groups B and D) for patients with high scores on either scale (scores of ≥ 10 and 2–4, respectively). Results Of 433 patients included, 85.5% reported a CAT total score ≥ 10, and 45.5% reported mMRC grades 2–4. During the baseline period, 63.7% of patients had ≤ 1 moderate and 0 severe (hospitalized) exacerbations, and 36.3% had ≥ 1 severe or ≥ 2 moderate exacerbation(s). The proportions of patients with each GOLD classification were: A: 9.0%; B: 54.7%; C: 4.6%; D: 31.6%. Conclusions In this population, over 85% of LAMA monotherapy users have symptoms and/or exacerbation risk that may necessitate therapy escalation according to 2017 GOLD guidelines. Funding GlaxoSmithKline [study 205862 (HO-16-16642)].

Can the Number of Radiofrequency Activations Predict Serious Adverse Events after Bronchial Thermoplasty? A Retrospective Case-Control Study Abstract Introduction Bronchial thermoplasty (BT) is a bronchoscopic procedure that involves the delivery of thermal radiofrequency energy to the bronchial wall for treating severe asthma. It has been suggested that too many radiofrequency activations could induce serious adverse events (SAEs) at an early stage. We aimed to examine the number of radiofrequency activations at each session and early lung function changes from baseline to determine whether these are related to SAEs. Methods We retrospectively investigated 13 consecutive patients who underwent three sessions each of BT for severe asthma from February 2015 to January 2016. Lung function tests were performed on the day before and after each BT procedure. Since we compared the number of activations and lung function changes from baseline after each session, a total of 39 sessions were reviewed. The relationship between the number of radiofrequency activations and each lung function change from baseline was also examined by linear regression analysis. Results A total of 10 SAEs (4 of pneumonia, 3 of atelectasis, 2 of bronchial asthma exacerbation and 1 of hemoptysis) were observed following the 39 BT sessions. When we compared sessions with and without SAEs, there were no differences in the number of activations (mean ± SD, 71.5 ± 28.6 times in sessions with SAEs; 66.5 ± 25.1 times in sessions without SAEs; p = 0.772) and lung function changes (mean changes in FVC/%FVC/FEV1/%FEV1/%PEF from baseline; − 0.49 l/− 14.2%/− 0.36 l/− 11.7%/− 9.6% in sessions with SAEs; − 0.43 l/− 13.3%/− 0.34 l/− 12.1%/− 9.4% in sessions without SAEs; p > 0.05 for all the above). Increase in the number of activations correlated with decreased FEV1 (R2 = 0.17, p = 0.0088) and %FEV1 (R2 = 0.11, p = 0.0357). Conclusions Increase in the number of radiofrequency activations during BT is related to a decrease in FEV1 and %FEV1 from baseline. The number of radiofrequency activations, however, is not associated with SAEs after BT.

Exploring the Asthma Network in People with Allergic Rhinitis Utilizing an Egocentric Social Network Analysis Abstract Introduction Asthma and allergic rhinitis (AR) are chronic respiratory diseases of a united airway. Poor AR control is a risk factor for uncontrolled asthma. We know that people with AR feel confident in making their own treatment choices with over-the-counter therapies, yet only 16% of purchases were the optimal selection. With the high level of poor asthma control and overuse of over-the-counter, short-acting beta-agonists, we must consider whether poor AR self-management behaviours are extended to asthma management in those with both diseases. This study aims to investigate asthma management from the perspective of the patient with asthma and AR and understand the influences behind their asthma management decisions. Methods This study utilized a mixed methods approach based on the theoretical and analytical framework of social network theory, including mapping of the asthma network and exploring the roles and influence of those that appear within the network. Results Twenty-two people with asthma and allergic rhinitis participated in this study. General practitioners (GPs), pharmacists and respiratory physicians were the most commonly reported influences behind participants’ asthma management decisions. Although non-healthcare professional (HCP) influences appear within the asthma network, they represented a smaller proportion. Conclusion The asthma network of people with AR is dominated by HCP influences. This network is unique and different to other previously published asthma and AR networks. Further research on the impact of AR on asthma management patient behaviour is required.

Why Is It Difficult to Diagnose My Child’s Asthma? A Patient Physician Perspective of Asthma Management Abstract This article is co-authored by the mother of a patient living with asthma, and two consultants in respiratory medicine from Birmingham Women’s and Children’s Hospital. The commentary article describes the mother’s experience of the diagnosis and treatment process of her son’s asthma. The consultants then discuss paediatric asthma diagnosis and management in the context of the patient’s experiences.

Dehydroepiandrosterone Supplementation May Benefit Women with Asthma Who Have Low Androgen Levels: A Pilot Study ABSTRACT Introduction Among individuals with severe asthma, FEV1 is low in individuals with low dehydroepiandrosterone (DHEA) sulfate (DHEAS) levels. In the Severe Asthma Research Program (SARP), no women with DHEAS > 200 μg/dL had an FEV1 < 60% predicted. DHEA has benefited patients with COPD and pulmonary hypertension in small trials. Therefore, we hypothesized that DHEA supplementation may improve FEV1 in asthmatic women with low DHEAS. Methods Premenopausal, nonsmoking, otherwise healthy women, 18-50 years old, with mild or moderate asthma and baseline FEV1 > 60% predicted received 100 mg DHEA orally every 12 h for 2 weeks. Spirometry and DHEAS were measured at the initial visit and 2 weeks later, after completion of DHEA treatment. Based on our previous work, the primary outcome variable for this pilot study was post-albuterol spirometry in the low-DHEAS group. Subjects also continued their other routine asthma management. Results Serum DHEAS increased with DHEA treatment in women with starting DHEAS < 200 µg/dL: this increase was from 71 ± 23 to 725 ± 295 µg/dL (n = 10; p = 0.0001). The increase in the high-DHEAS group was smaller. Post-albuterol FEV1 increased by 51 mL, from 3.026 ± 0.5 to 3.077 ± 0.49 L (n = 10; p = 0.034 by paired t test, significant after Bonferroni), in women with low DHEAS. In the high-DHEAS group (baseline DHEAS ≥ 200 µg/dl), post-albuterol FEV1 did not change significantly (n = 3, p = NS). Three subjects were excluded: one had comorbid COPD, one could not perform spirometry, and one did not take the DHEA. There were no adverse effects of DHEA treatment in this trial. Conclusions Endocrine treatments (corticosteroids) are a mainstay of anti-inflammatory management for moderate and severe asthma. Their use has improved asthma outcomes. Androgens also reduce airway inflammation and promote airway smooth muscle relaxation, but are rarely used clinically for asthma treatment. Our results suggest that the over-the-counter steroid DHEA may improve lung function in asthma outcomes among women with DHEAS < 200 ug/dL.

Comparison of Phospholipid-Based Particles for Sustained Release of Ciprofloxacin Following Pulmonary Administration to Bronchiectasis Patients Abstract The rapid clearance of ciprofloxacin hydrochloride from the lungs following administration as an aerosol leads to poor efficacy in the treatment of pulmonary infections. The development of formulations capable of sustaining ciprofloxacin concentrations in the lungs has the potential to significantly improve antibacterial activity. The present review compares two approaches for sustaining levels of ciprofloxacin in the lungs, a liposomal formulation where ciprofloxacin is encapsulated in small unilamellar vesicles, and a dry powder formulation of the practically insoluble zwitterionic form of the drug. These two formulations recently completed large multicenter, phase 3 clinical studies in bronchiectasis patients. As such, they present a unique opportunity to examine the chemistry, manufacturing, and control of the dosage forms in addition to their tolerability and efficacy in more than 1000 bronchiectasis patients. Both formulations were generally well tolerated with most adverse events found to be mild to moderate in intensity. While the formulations were effective in reducing and/or eradicating infections, this did not lead to reductions in pulmonary exacerbations, the primary endpoint. The failures speak more to the heterogeneous nature of the disease and the difficulty in identifying bronchiectasis patients likely to exacerbate, rather than an inherent limitation of the formulations. While the formulations are similar in many respects, they also present some interesting differences. This review explores the implications of these differences on the treatment of respiratory infections.

A Phase 1b Study of Vismodegib with Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis Abstract Introduction Components of the hedgehog signaling pathway are upregulated in patients with idiopathic pulmonary fibrosis (IPF). Vismodegib, a small-molecule inhibitor of hedgehog signaling, when used in combination with currently available antifibrotic therapy, may be more efficacious than antifibrotics alone. The objective of this study was to evaluate the safety and tolerability of vismodegib plus pirfenidone in patients with IPF. Methods Twenty-one patients were enrolled in a phase 1b open-label trial to receive vismodegib 150 mg plus pirfenidone 2403 mg/day once daily. Key endpoints were safety, tolerability, and pharmacokinetics. Exploratory endpoints included change from baseline to week 24 in % predicted forced vital capacity (FVC) and University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOBQ) scores, as well as pharmacodynamic changes in hedgehog biomarker C-X-C motif chemokine ligand 14 (CXCL14). Results All patients reported at least one treatment-emergent adverse event (AE), most frequently muscle spasms (76.2%). Serious AEs were reported in 14.3% of patients; one event of dehydration was considered related to vismodegib. One patient died due to IPF progression, unrelated to either treatment. More patients discontinued vismodegib than pirfenidone (42.9% vs. 33.3%, respectively). Changes from baseline to week 24 in % predicted FVC and UCSD-SOBQ scores were within known endpoint variability. In contrast to findings in basal cell carcinoma, vismodegib had no effect on circulating CXCL14 levels. Conclusion The safety profile was generally consistent with the known profiles of both drugs, with no new safety signals observed in this small cohort. There was no pharmacodynamic effect on CXCL14 levels. Future development of vismodegib for IPF may be limited due to tolerability issues. Trial Registration ClinicalTrials.gov NCT02648048. Plain Language Summary Plain language summary available for this article. Funding F. Hoffmann-La Roche Ltd. and Genentech, Inc.

Predictors of Symptom Burden in Patients with COPD on LAMA Monotherapy: Multivariable Analysis of a Claims-Linked Survey Study Abstract Introduction Many patients with chronic obstructive pulmonary disease (COPD) prescribed long-acting muscarinic antagonist (LAMA) monotherapy remain symptomatic. This multivariable analysis of a previously reported claims-linked, cross-sectional survey assessed symptom burden measured by the COPD assessment test (CAT) in patients treated with LAMA monotherapy. Methods Eligible patients aged ≥ 40 years with COPD (≥ 2 International Classification of Diseases-10th Revision-Clinical Modification [ICD-10-CM] diagnosis codes ≥ 30 days apart during the 12-month baseline period) and ≥ 2 claims for LAMA monotherapy in the latter half of the baseline period were identified using claims data from the Optum Research Database. Patients completed a survey and 7-day daily diary; baseline clinical characteristics and resource utilization were assessed from claims data. Association between symptom burden and baseline characteristics was assessed using generalized linear regression modeling with normal distribution and identity link. Results Overall, 433 patients prescribed LAMA monotherapy with claims-linked survey and diary data were included in the analysis. Most patients (85.5%) had a mean CAT score ≥ 10; 39.0% had scores ≥ 21. Overall, the factors most related to a clinically meaningful increase in CAT score (≥ 2 points) were being diagnosed with COPD for > 5 years and being a current smoker (2.25 points, P = 0.003 and 2.22 points, P = 0.025, respectively). Conclusions Results demonstrate that many patients with COPD receiving LAMA monotherapy remain symptomatic, especially those diagnosed > 5 years ago or those who continue to smoke. Use of patient-reported outcomes such as the CAT should be considered part of routine visits for patients with COPD. Funding GlaxoSmithKline (GSK study number 205862 [HO-16-16642]).

Triple Therapy Versus Dual Bronchodilation and Inhaled Corticosteroids/Long-Acting β-Agonists in COPD: Accumulating Evidence from Network Meta-Analyses Abstract Guidelines are mainly based on evidence of well-designed randomized controlled trials (RCTs), but there are limitations to the transferability of conclusions of RCTs to usual care mainly because the patients enrolled in RCTs are selected and not representative of the population encountered in daily practice; moreover, the research environment is substantially different from that of the real world. Because of the scarcity of data generated in large unselected populations in everyday clinical practice, the possibility of using meta-analyses can be considered. Recently, several meta-analyses have attempted to clarify the role of triple therapy containing a long-acting β-agonist (LABA), a long-acting muscarinic antagonist (LAMA) and an inhaled corticosteroid (ICS) delivered from a single inhaler in chronic obstructive pulmonary disease (COPD), also considering that there is a big difference in the use of triple therapy between what is recommended by COPD guidelines or strategies and the prescriptive behaviour of clinicians. Taking into account the results of the most recent meta-analyses, we believe that triple therapy provides modest clinical benefit in the general COPD population, but in patients on LABA/LAMA combination therapy, who still experience acute exacerbations of COPD (AECOPDs) and have blood eosinophil counts ≥ 300 cells·μl−1, it is of clinical relevance. On the contrary, adding a LAMA to an ICS/LABA combination elicits relevant clinical benefit in the general COPD population, supporting the role of dual bronchodilation therapy for the treatment of COPD. The quantitative synthesis of the currently available clinical evidence seems to suggest that, in patients with COPD already on ICS/LABA combination, the therapy can be improved without an increase of cardiovascular severe adverse events (SAEs) when a LAMA is added to the combination.