Treatment Of COPD Research Articles

Ability of γ-tocotrienol to Mitigate Inflammation and Preserve Lung Function in a Model of E-Cigarette Induced Chronic Obstructive Pulmonary Disease

Abstract Objectives Chronic obstructive pulmonary disease (COPD) remains a leading cause of death and treatment options for this condition remain scant. This study aims to examine the ability of γ-tocotrienol to mitigate disease progression in an animal model of COPD induced by e-cigarettes. We hypothesize that γ-tocotrienol will attenuate inflammation and subsequently slow the progression of e-cigarette induced COPD. Methods Scnn1b-Tg + mice (n = 10/group), were exposed to e-cigarette vapor twice daily for 10 days in an acute model and daily for eight weeks in a chronic model with or without γ-tocotrienol at a dose of 100 mg/kg/day. Following the treatment, animals underwent pulmonary function testing. Upon sacrifice, bronchoalveolar lavage (BAL) fluid and serum were collected for analysis of cytokine expression through cytokine array. Markers of oxidative stress, inflammation, and fibrosis in the lung were assessed via western blot. Mucus accumulation and structural changes (i.e., emphysema) were measured through Periodic Acid-Schiff and Hematoxylin and Eosin staining, respectively. Collagen deposition were evaluated by Sirius Red staining and Sircol Collagen assay. Cell morphology in BAL fluid was analyzed by Diff staining. Results In the acute model, γ-tocotrienol was evidenced to decrease collagen deposition and mucus accumulation in the bronchioles. Additionally, γ-tocotrienol reduced expression of cytokines C-X3-C motif chemokine ligand (CX3CL) 1 (P = 0.017), interleukin (IL) 4 (P = 0.0038) and T-cell immunoglobulin and mucin domain (TIM) 1 (P = 0.0215). Evidenced by large effect size, pulmonary function tests evidenced the ability of γ-tocotrienol to preserve lung function following 8 weeks of e-cigarette exposure. In addition, macrophage presence in BAL fluid was decreased following in mice supplemented with γ-tocotrienol following e-cigarette exposure. Conclusions Our results show the ability of γ-tocotrienol to attenuate the inflammatory response, and preserve lung function in models of e-cigarette induced COPD. These results indicate potential beneficial effects of γ-tocotrienol as an ancillary treatment in COPD. Funding Sources This work was supported by FAMRI foundation “METABOLIC REPROGRAMMING IN PATIENTS WITH COPD”, YCSA 2015.

Mechanism of YuPingFeng in the Treatment of COPD Based on Network Pharmacology.

YuPingFeng (YPF) granules are a classic herbal formula extensively used in clinical practice in China for the treatment of COPD. However, the pathological mechanisms of YPF in COPD remain undefined. In the present research, a network pharmacology-based strategy was implemented to elucidate the underlying multicomponent, multitarget, and multipathway modes of action of YPF against COPD. First, we identified putative YPF targets based on TCMSP databases and constructed a network containing interactions between putative YPF targets and known therapeutic targets of COPD. Next, two topological parameters, “degree” and “closeness,” were calculated to identify target genes in the network. The major hubs were imported to the MetaCore database for pathway enrichment analysis. In total, 23 YPF active ingredients and 83 target genes associated with COPD were identified. Through protein interaction network analysis, 26 genes were identified as major hubs due to their topological importance. GO and KEGG enrichment analysis results revealed YPF to be mainly associated with the response to glucocorticoids and steroid hormones, with apoptotic and HIF-1 signalling pathways being dominant and correlative pathways. The promising utility of YPF in the treatment of COPD has been demonstrated by a network pharmacology approach.

Targeted lung denervation in sheep: durability of denervation and long-term histologic effects on bronchial wall and peribronchial structures

BackgroundTargeted lung denervation (TLD), a novel bronchoscopic procedure which attenuates pulmonary nerve input to the lung to reduce the clinical consequences of neural hyperactivity, may be an important emerging treatment for COPD. While procedural safety and impact on clinical outcomes have recently been reported, the mechanism of action has not been reported. We explored the long-term pathologic and histopathologic effects in a sheep model of ablation of bronchial branches of the vagus nerve using a novel dual-cooled radiofrequency ablation catheter.MethodsNineteen sheep underwent circumferential ablation of both main bronchi with simultaneous balloon surface cooling using a targeted lung denervation system (Nuvaira, Inc., USA). Animals were followed over an extended time course (30, 365, and 640 days post procedure). At each time point, lung denervation (axonal staining in bronchial nerves), and effect on peribronchial structures near the treatment site (histopathology of bronchial epithelium, bronchial cartilage, smooth muscle, alveolar parenchyma, and esophagus) were quantified. One way analysis of variance (ANOVA) was performed to reveal differences between group means on normal data. Non-parametric analysis using Kruskal-Wallis Test was employed on non-normal data sets.ResultsNo adverse clinical effects were observed in any sheep. Nerve axon staining distal to the ablation site was decreased by 60% at 30 days after TLD and efferent axon staining was decreased by >70% at 365 and 640 days. All treated airways exhibited 100% epithelial integrity. Effect on peribronchial structures was strictly limited to lung tissue immediately adjacent to the ablation site. Tissue structure 1 cm proximal and distal to the treatment area remained normal, and the pulmonary veins, pulmonary arteries, and esophagus were unaffected.ConclusionsThe denervation of efferent axons induced by TLD therapy is durable and likely a contributing mechanism through which targeted lung denervation impacts clinical outcomes. Further, long term lung denervation did not alter the anatomy of the bronchioles or lung, as evaluated from both a gross and histologic perspective.

Should physicians still be prescribing steroid inhalers as a first-line treatment for COPD?

Many people with chronic obstructive pulmonary disease are given steroids despite a lack of evidence underpinning their use. Many people with chronic obstructive pulmonary disease are given steroids despite a lack of evidence underpinning their use.

Determinants of self-reported adherence to inhaler therapy in patients with chronic obstructive pulmonary disease.

BackgroundAdherence to therapy is crucial for COPD patients, since non-adherence leads to worse quality of life, increased health-care expenditure and poor clinical outcome. The aim of this study was to identify the main determinants of suboptimal adherence to therapy in a cohort of COPD patients.MethodsGeneral information (age, BMI, smoking, comorbidities, education, life style), lung function, exacerbations, symptoms and COPD treatment were collected. Adherence to therapy was assessed by self-reported 4-item Morisky Medication Adherence Scale (MMAS-4), and was related to anthropometric, socio/economic and health status data, obtained by questionnaires (COPD Assessment Test, CAT; Treatment Satisfaction Questionnaire, HRQoL; Katz Index of Independence of Daily Living Activities, Lawton Instrumental Activities of Daily Living Scale).Results136 COPD patients were studied (age 72±8 yrs; 73.5% men; BMI 28.5±7.4 kg/m2; FEV1 53.5±19.0 % predicted). Nearly half of the patients (46.3%) had suboptimal adherence to therapy (score >0) and, as compared to those with optimal adherence, had higher prevalence of women and coronary artery disease, heavier smoking history and worse CCQ overall score. The results of multivariate analysis showed that the determinants of suboptimal adherence were female sex (OR 4.339, 95%CI 1.509-12.474, p=0.006), amount of pack/years smoked (OR 1.947, 95%CI 1.141-3.323, p=0.015), higher CCQ overall score (OR 3.318, 95%CI 1.050-9.892, p=0.049) and higher education (OR 2.758, 95%CI 1.083-7.022, p=0.033). Adherence was better in patients assuming triple inhaler therapy.ConclusionsSuboptimal adherence is frequent among COPD patients, particularly in women, heavy smokers and subjects with high educational level. Interventions to improve adherence should be especially addressed to patients with these characteristics.

A randomized, controlled, repeat-dose study of batefenterol/fluticasone furoate compared with placebo in the treatment of COPD

BackgroundBatefenterol (BAT) is a bi-functional molecule with both muscarinic antagonist and β2-adrenoceptor agonist pharmacology. This Phase II, randomized, placebo-controlled, double-blind study evaluated the safety and tolerability of BAT 300 μg with fluticasone furoate (FF) 100 μg administered via the ELLIPTA inhaler (BAT/FF 300/100).MethodsSubjects with stable chronic obstructive pulmonary disease were randomized 2:1 to receive BAT/FF 300/100 or placebo once daily for 6 weeks. The primary endpoint was change from baseline in 0–4-h weighted mean (WM) heart rate (HR, measured by electrocardiogram [ECG]) on Day 42. Other endpoints included WM and maximum 0–4-h corrected QT interval (ECG on Days 1, 28, and 42), HR measured by Holter monitoring (Day 42), and standard safety assessments. Study protocol was approved by an Investigational Review Board.ResultsSixty-two patients were randomized and received ≥1 dose of study medication (BAT/FF 300/100 n = 42; placebo n = 20). Mean age was 62.5 years (standard deviation [SD] 8.17). Study completion rates were 83% (BAT/FF 300/100) and 100% (placebo). Screening mean (SD) post-bronchodilator percentage-predicted forced expiratory volume in 1 s was 57.57 (11.42) in the BAT/FF 300/100 group and 55.68 (14.03) in the placebo group. BAT/FF 300/100 was non-inferior to placebo for the primary endpoint, treatment difference: − 2.2 beats per minute (bpm), 95% confidence interval [CI]: − 6.2, 1.7). There were no clinically relevant differences between treatment groups in WM or maximum 0–4-h corrected QT interval, or mean HR based on Holter monitoring on Day 42 (BAT/FF 300/100: 76.3 bpm [SD 11.38]; placebo: 84.8 bpm [SD 9.87]). Adverse events (AEs) occurred in 38% (BAT/FF 300/100) and 35% (placebo) of patients. AEs in ≥2 subjects with BAT/FF 300/100 were dysgeusia (10%), diarrhea (7%), nasopharyngitis (7%), and cough (5%). AEs leading to discontinuation occurred in two subjects who received BAT/FF 300/100: post-treatment severe pneumonia (serious AE) and non-serious AEs of moderate vomiting and severe gastroenteritis; both were not considered drug-related. No deaths occurred.ConclusionsSix weeks of BAT/FF 300/100 treatment was non-inferior to placebo for change from baseline in HR, with no new clinically relevant general or cardiovascular safety signals.Trial registrationClinicaltrials.gov: NCT02573870 (submitted October 12, 2015).

PRS42 COMORBIDITIES IN MEDICARE OLDER ADULTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Both aging and COPD are associated with increased comorbidities that may interfere with COPD treatment and contribute to poor outcomes. We quantified the prevalence and incidence of comorbidities in older patients with COPD using Medicare claims. A retrospective cohort study using a 5% Medicare beneficiary sample between 2012 and 2015. We included adults aged 65+ and diagnosed with COPD by 12/31/2014. Prevalence, co-prevalence, and incidence of 40 comorbidities were identified using the Medicare Chronic Conditions files. Of 461,268 eligible beneficiaries, 60% were female, 86% were white, with mean (standard deviation [SD]) age of 79 (8) years. Among these, 89.2% had at least five and 50.4% had at least ten comorbidities. Most prevalent comorbidities included hypertension (92.6%), hyperlipidemia (86.4%), anemia (74.9%), rheumatoid arthritis (RA) (68.0%), congestive heart failure (CHF) (49.6%), diabetes (46.7%), depression (43.7%), peripheral vascular disease (PVD) (42.9%), chronic kidney disease (CKD) (38.6%), asthma (38.3%), hypothyroid (36.3%), and pain (34.4%). Top co-prevalence of two conditions included hypertension-hyperlipidemia (82.4%), hypertension-anemia (71.7%), and hyperlipidemia-anemia (66.9%). Most common co-prevalence of three comorbidities were hypertension-hyperlipidemia-anemia (65.0%), hypertension-hyperlipidemia-RA (59.1%), and hypertension-anemia-RA (54.1%). Conditions with greater 1-year cumulative incidence pre-COPD diagnosis than 1-year incidence post-COPD included RA (71.4% vs 15.2%), anxiety (5.7% vs 4.2%), and tobacco use disorder (8.3% vs 7.3%). Some comorbidities had greater incidence in the 1-year post-period (hyperlipidemia: 28.2% vs 65.7%, anemia: 14.8% vs 18.9%, CHF: 8.7% vs14.4%, hyperlipidemia: 23.7% vs 35.9%, diabetes: 7.8% vs 11.0%, and cancer: 1.6% vs 3.4%). Older COPD patients encounter high prevalence and co-prevalence of comorbidities. Understanding comorbidity patterns may provide insights into outcomes research and care management. The multimorbidity burden in this population highlights the importance of integrated care to improve health outcomes.

2019 Year in Review: Aerosol Therapy.

Relevant publications related to medicinal and toxic aerosols are discussed in this review. Treatment of COPD includes a combination of long-acting bronchodilators and long-acting muscarinic antagonists. A combination of aclidinium bromide and formoterol fumarate was approved in the United States. The combination was superior to its components alone, as well as tiotropium and a salmeterol-fluticasone combination. Increased risk of an asthma exacerbation was reported in children exposed to electronic nicotine delivery systems. A smart inhaler capable of recording inspiratory flow was approved in the United States. The use of as-needed budesonide-formoterol was reported to be superior to scheduled budesonide and as-needed terbutaline for the treatment of adults with mild-to-moderate asthma. A survey among teens with asthma and their caregivers revealed a disagreement in the number of inhaled controller medications the teen was taking. Treatment with inhaled hypertonic saline resulted in a decreased lung clearance index in infants and preschool children with cystic fibrosis. Surgical masks were well tolerated and significantly decreased the burden of aerosolized bacteria generated by coughing in adults with cystic fibrosis. Inhaled liposomal amikacin in addition to guideline-based therapy was reported to be superior to guideline-based therapy alone in achieving negative sputum cultures in adult subjects with Mycobacterium avium complex pulmonary disease. During 2019, lung injury associated to e-cigarette or vaping was reported, including 60 casualties.

Influence of treatment and rehabilitation programs on clinical and functional indicators of occupational obstructive pulmonary disease

Based on the existing concept of COPD pathogenesis, treatment and rehabilitation measures should be aimed at normalizing the functioning of the mucociliary system and forming an energy-saving stereotype of breathing. In this regard, the inclusion of flutters as breathing simulators in the complex of treatment and rehabilitation programs is scientifically justified. 43 patients with moderate-severity PCOS were examined without exacerbation. The subjects were divided into 2 groups: 1 (main) — 22 patients receiving FT, and 2 (comparison) — 21 patients without FT. To assess the effectiveness, we used data from functional indicators, the results of the 6-minute walking test (6MWD) and standard questionnaires CAT, mMRC, SGRQ. The state of the respiratory muscles was assessed by the size of the chest area and indicators of endurance to static loads of the back and abdominal muscles. Studies were conducted before the start of therapy and 3 months after its end. Use of FT leads to a signifi cant regression of clinical symptoms, a signifi cant increase in OFB1, positive shifts in the CAT, mMRC and 6MWD test results, increased strength and endurance of respiratory muscles and improved quality of life. This proves the feasibility of including FT in the complex of treatment and rehabilitation measures for PHOBL.

Socioeconomic variations in chronic obstructive pulmonary disease prevalence, diagnosis, and treatment in rural Southwest China

BackgroundChronic obstructive pulmonary disease (COPD) is a major and growing cause of morbidity and mortality throughout the world. However, there remains a limited understanding of the association between individual socioeconomic status (SES) and COPD diagnosis and treatment worldwide, including in China. This study investigates socioeconomic variations in prevalence, diagnosis, and treatment of COPD in rural China.MethodsThe present study employed a cross-sectional survey design. The study population was composed of Han majority as well as Na Xi and Bai ethnic minority individuals 35 years of age and older living in Yunnan Province from 2017 to 2019. In total, 7534 individuals consented to participate in the study and complete a structured interview as well as a post-bronchodilator spirometry test. Multivariate logistic regression was used to analyze the association between individual socioeconomic status variables and the prevalence, diagnosis, and treatment of COPD.ResultsThe age-standardized prevalence of COPD in the present study was 14.3%. Prevalence differed by gender: prevalence for men was 17.1%, versus 11.4% for women (P = 0.0001). Overall, levels of diagnosis and treatment of COPD for participants with COPD were 24.2 and 23.1%, respectively. Multivariate logistic regression indicated that higher educational levels and good access to medical services was associated with an overall lower risk of COPD (P = 0.032 vs. P = 0.018) as well as a higher probability of COPD diagnosis among those with COPD (P = 0.0001 vs. P = 0.002). Participants with COPD with higher educational levels (P = 0.0001) and higher annual household incomes (P = 0.0001) as well as good access to medical services (P = 0.016) were more likely to receive COPD medications and treatment than their counterparts. While Na Xi and Bai participants had a higher probability of having COPD (P = 0.0001), they had a lower probability of having received a diagnosis or treatment for COPD than Han participants (P = 0.0001 vs. P = 0.0012).ConclusionsFuture interventions to further control COPD and improve diagnosis and treatment should focus on ethnic minority communities, and those with low education levels, low annual household incomes, and poor access to medical services.

Ablation of PDE4B Protects from Lung Injury in a Mouse Model of Acute P. aeruginosa Infection

RationaleNon‐selective inhibitors of Type 4 cAMP‐phosphodiesterases (PDE4s) exert well established anti‐inflammatory effects in non‐infectious models of lung inflammation, such as upon exposure to lipopolysaccharide or ovalbumin, and have demonstrated clinical efficacy in the treatment of COPD. However, they also produce side effects, including emesis, nausea, diarrhea, and weight loss, that limit their clinical utility. The PDE4 family comprises 4 subtypes (PDE4A‐D). As each plays unique and non‐overlapping physiological roles, targeting individual subtypes may serve to separate the therapeutically beneficial from side effects resulting from non‐selective PDE4 inhibition. PDE4B has been proposed as a primary target by which PAN‐PDE4 inhibitors exert anti‐inflammatory effects. Here, we assessed whether genetic ablation of PDE4B is per se sufficient to protect mice infected with live P.aeruginosa from acute lung injury and whether PDE4B ablation can dampen immune responses without worsening the bacterial infection.MethodsPDE4B knockout (PDE4BKO) mice and their wildtype (WT) littermates were infected intranasally with P.aeruginosa lab strain PA01 and bronchoalveolar lavage fluid (BALF) and lungs were harvested 16 h later to assess lung infection/inflammation.ResultsAt 16 h post‐infection, the levels of pro‐inflammatory cytokines in BALF and lung tissue (TNFα, IL1β, IL‐6, and KC) as well as lung histopathological scores were reduced in PDE4BKO mice compared to their WT littermates indicating anti‐inflammatory benefits of PDE4B ablation, whereas the total number of leukocytes or neutrophils in BALF was unchanged. Unexpectedly, despite dampening the immune response, bacterial load in BALF and lungs was significantly decreased in PDE4BKO compared to WT controls. The ability of PDE4BKO mice to clear the bacteria more efficiently correlates with their ability to alleviate the significant PA‐induced hypothermia observed in WT controls. Indeed, when differences in hypothermia between WT and PDE4BKO mice are equalized by externally warming the animals, the bacterial load in WT and KO mice are comparable whereas anti‐inflammatory benefits, such as reduced cytokines levels in PDE4BKO mice, are retained.ConclusionsOur results suggest that ablation of PDE4B per se is sufficient to alleviate lung inflammation in a model of acute P.aeruginosa infection without worsening the bacterial infection. Thus, PDE4B may represent a therapeutic target for inflammatory lung diseases associated with P.aeruginosa infections, such as ventilator associated pneumonia or cystic fibrosis.Support or Funding InformationSupported by grants from the Cystic Fibrosis Foundation (SALEH18H0, RICHTE16GO) and the NIH (HL76125, HL141473, HL066299).

Inhaled Corticosteroids in COPD: Trying to Make a Long Story Short.

The use of inhaled corticosteroids (ICSs) in long-term treatment of COPD has been a debated topic for a long time. According to the evidence produced till now, ICSs are presently advocated in combination with long-acting bronchodilators for high-risk symptomatic COPD patients with a history of frequent COPD exacerbations. However, the heterogeneity of COPD patients in terms of prevalent underlying disease, with its associated biological and functional characteristics, and different types of exacerbation makes this recommendation highly questionable. This review aims to discuss the usefulness of ICSs in the pharmacological management of COPD and trys to detect those aspects that may likely anticipate a beneficial response following their therapeutic use related to respiratory function, functional decline, prevention of exacerbation, and quality of life. In this respect, the BERN acronym, meaning Bronchiolitis, Eosinophilia, Responsiveness to bronchodilator, and Non-smoker, may be of practical utility to select among COPD patients those that can take more advantage from ICS adoption when positive and vice versa when negative.

Relative Bioavailability of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Administered With and Without a Spacer: Results of a Phase I, Randomized, Crossover Trial in Healthy Adults

PurposeThe triple combination therapy budesonide/glycopyrrolate/formoterol fumarate in a metered dose inhaler (BGF MDI), formulated by using innovative co-suspension delivery technology, is a new inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist fixed-dose combination for the maintenance treatment of COPD. For some patients, the use of an MDI may be optimized with a spacer. This Phase I study assessed the effect of a spacer on lung exposure, total systemic exposure, and safety of BGF MDI 320/36/9.6 μg in healthy subjects. Methods: This randomized, open-label, crossover study assessed the pharmacokinetic and safety profiles of BGF MDI in healthy adult subjects who received a single dose of BGF MDI 320/36/9.6 μg (administered as 2 inhalations with 160/18/4.8 μg per actuation) in 4 regimens: without spacer and no charcoal; with spacer and no charcoal; without spacer and with charcoal; and with spacer and with charcoal. Primary objectives were to assess total systemic exposure (without charcoal) and lung exposure (with charcoal) of budesonide, glycopyrronium, and formoterol administered as BGF MDI with and without a spacer. Safety was also assessed. FindingsIn total, 56 subjects were randomized (mean age, 29.9 years; 60.7% male, 17.9% former smokers). For systemic exposure (without charcoal), the spacer/without spacer ratio, expressed as a percentage (intrasubject %CV) of Cmax and AUC0–tlast, respectively, was 152.0 (47.5) and 132.8 (43.6) for budesonide, 240.6 (80.2) and 154.7 (73.4) for glycopyrronium, and 165.6 (50.7) and 98.6 (53.8) for formoterol. For lung exposure (with charcoal), the spacer/without spacer ratio percentage (%CV) of Cmax and AUC0–tlast, respectively, was 183.6 (65.9) and 198.4 (71.5) for budesonide, 262.0 (91.8) and 373.9 (120.7) for glycopyrronium, and 222.9 (56.3) and 385.2 (147.0) for formoterol. Subjects who were judged to have suboptimal inhalation technique without a spacer (those in the lowest drug exposure quartile based on AUC0–tlast) had the greatest increase in both total systemic and lung exposure when a spacer was used versus no spacer. Subjects in the highest quartile had a minimal change in both total systemic and lung exposure when the spacer was used. Treatment-emergent adverse events (TEAEs) (all mild/moderate) reported by >1 subject per regimen were headache, cough, and dizziness. One subject withdrew because of TEAEs of headache and presyncope (neither considered treatment-related). ImplicationsDrug delivery can be improved for subjects with suboptimal MDI inhalation technique when using a spacer device with BGF MDI triple therapy. ClinicalTrials.gov identifier: NCT03311373.

Elderly age group patients with COPD continuing to smoke -a problem that cannot be ignored

IntroductionAccording to the WHO, 30.9% of the adult population of the Russian Federation are active smokers. From 30% to 43% of smoking patients with COPD are not able to give up nicotine despite the diagnosis and deterioration of health. Most of the publications related to the treatment of COPD do not distinguish smoking patients into a separate group. The purpose of this study is a comparative analysis of the effectiveness of LAMA (Tiotropium bromide and Glycopyrronium bromide) and LABA \\ LAMA (Olodaterol + tiotropium and Indacaterol + Glycopyrronium bromide). Materials and methodsThe study involved 102 patients with a high degree of nicotine addiction and irreversible bronchial obstruction. All the patients were submitted to the treatment of nicotine addiction syndrome on the basis of Otkrytie Medical Center LLC. All the patients continue to receive bronchodilatory therapy. Respondents were divided into two groups: patients who quit smoking and patients who continued to smoke. In turn, each group was divided into two subgroups depending on the drugs being taken - LAMA and LAMA / LABA. As comparison criteria, we selected the dynamics of FEV1 and the dynamics of CAT. ResultsAs a result of the analysis of the obtained data FEV1 increase was detected in both study groups, regardless of the treatment regimen. FEV1 increase within the group of smoking patients was lower than of those who quit smoking - 11% and 22% respectively (p < .05). CAT dynamics showed a downward trend in both groups. However, the patients who quit smoking demon-strated greater reduction of symptoms during therapy than the smoking patients — -10 and − 1 points respectively (p < .05). No statis-tically significant difference was found either on CAT (p = .31) or spirometry - FEV1 (p = .22) for the LAMA and LAMA / LABA subgroups. Combined therapy (LAMA / LABA) applied to the group of patients who quit smoking found to be more effective than monotherapy (LAMA) both in terms of spirometry (an increase in FEV1 came to 26% and 13% respectively (p < .05)), and the de-gree of reduction of the symptoms (CAT) - -11 and − 5 respectively (p < .05). ConclusionWhile maintaining nicotine status, long-acting anticholinergic (LAMA) and combined long-acting bronchodila-tors produce a moderate and comparable effect. Therefore, when choosing the tactics of COPD treatment, it is necessary to take into consideration the current nicotine status of the patient as well as the nicotine addiction degree.

Therapeutic Effect Observation of Tiotropium Bromide in the Treatment of Overlap Syndrome

Objective: To study the M receptor blocker on inhalation in patients with overlap syndrome (chronic obstructive pulmonary disease and Obstructive sleep apnea syndrome) curative effect analysis. Methods: 25 patients with overlap syndrome as the experimental group, chronic obstructive pulmonary disease patients (30) as control group, patients with overlap syndrome use inhaled tiotropium powder treat 30 days, to observe the changes of pulmonary function, polysomnography, and other indicators after treatment. Results: Overlap syndrome were treated by tiotropium bromide inhalation powder, has improved the pulmonary function, the sleep apnea index and lowest nocturnal oxygen saturation after treatment. Conclusion: tiotropium bromide has a preferable effective in treatment of overlap syndrome, COPD and OSAHS are interacting with each other.

18 Stop the Burn: A Smoking and Home Oxygen Safety Initiative with Use of Firebreaks

Abstract Introduction COPD is a chronic pulmonary disease treated with home oxygen. The single most common cause of COPD is cigarette smoking. Approximately 1.4 million people in the US use long-term oxygen therapy for treatment of hypoxic COPD. Smoking is an addictive risky behavior and smoking on oxygen therapy is responsible for the majority of home oxygen fires and deaths. Up to 52% of patients who use oxygen therapy continue to smoke in spite of these risks. At least 1,000 burn injuries per year occur when oxygen cannula tips ignite after coming in close contact with cigarettes, lighters, or matches. Flames travel externally and internally along the tubing toward the oxygen concentrator, which can explode. Previous prevention efforts have focused on counseling and education of patients and their caregivers; however, the habit continues, causing burn injury admissions and increasing health care costs. Methods Our ABA verified burn center admitted 90 burn injuries during July 2015 to September 2019 related to smoking on oxygen. Given the mechanism of injury, further preventive efforts were researched, and firebreak devices were identified as a secondary preventive measure to attempt to reduce negative consequences of smoking on oxygen. A firebreak device is fitted in the oxygen tubing near the patient and also near the oxygen concentrator. The firebreak acts as a thermal fuse by stopping the oxygen supply when triggered, preventing the flames from burning to the oxygen concentrator. Our program goal was to develop a safety initiative using educational information and firebreak devices. Information was shared at the regional Trauma committee and with local EMS, Fire and on Facebook. The program was initiated in 2018. We worked with local EMS and Fire agencies to install the firebreak devices in nursing homes, assisted living facilities and in patients’ homes who use oxygen. Results Our program distributed 225 firebreak kits, which included no smoking signs, a home oxygen safety checklist, an educational video link, nasal cannula tubing and 2 firebreak devices. Since the initiation of the program, the number of burn injury admissions from smoking on oxygen decreased from an average of 24/year to an average of 9/year. Conclusions Standardizing the use of firebreak kits in the community for those smoking on oxygen or using oxygen stops a fire by halting the oxygen supply thereby potentially decreasing burn admissions. Therefore, we recommend the consideration of firebreak kits for patients who continue to smoke while using oxygen to Stop the Burn. Applicability of Research to Practice Future research is recommended to determine the effectiveness of firebreak kits as a safety measure for all individuals who use oxygen.

Adding a Second Bronchodilator in COPD: A Meta-Analysis on the Risk of Specific Cardiovascular Serious Adverse Events of Tiotropium/Olodaterol Fixed-Dose Combination

Dual bronchodilation therapy represents the cornerstone for the treatment of COPD. A large retrospective study reports that adding a second long-acting bronchodilator in patients with COPD significantly increases the risk of heart failure. Nevertheless, retrospective studies are characterized by limitations including misdiagnosis and inaccuracy of recordkeeping. This study aimed to ascertain whether tiotropium/olodaterol (T/O) 5/5 μg fixed-dose combination (FDC) may modulate the risk of main cardiovascular outcomes in COPD patients enrolled in randomized controlled trials (RCTs). A meta-analysis (CRD42017070100) was performed by selecting RCTs reporting raw data from the ClinicalTrials.gov database concerning the impact of T/O 5/5 µg FDC vs. monocomponents on the occurrence of specific cardiovascular serious adverse events: arrhythmia, heart failure, myocardial infarction, and stroke. Data were reported as relative risk and 95% Confidence Interval, and the risk of publication bias assessed via Egger’s test. Eighty six full text articles were identified, and 10 RCTs published in 7 studies between 2015 and 2018 were included into the analysis. Data obtained from 12,690 COPD patients (44.47% T/O FDC, 55.53% monocomponents) were extracted. T/O 5/5 μg FDCs did not significantly modulate (p-value > 0.05) the risk of arrhythmia (1.02, 0.55 - 1.92), heart failure (0.88, 0.41 - 1.92), myocardial infarction (1.15, 0.70 - 1.87), and stroke (0.98, 0.44 - 2.16) vs. monocomponents. No significant publication bias affected the effect estimates of this meta-analysis. The results of this quantitative synthesis indicate that dual bronchodilation with T/O 5/5 μg FDC is characterized by an acceptable cardiovascular safety profile in COPD patients.

Manejo clínico de la EPOC en situación de vida real. Análisis a partir de big data

ObjectiveThe aim of this study was to evaluate the quality of diagnosis and treatment of COPD using Big Data methodology on the Savana Manager 2.1 clinical platform. Materials and methodsA total of 59,369 patients with a diagnosis of COPD were included from a population of 1,219,749 adults over 40 years of age. ResultsIn total, 78% were men. Spirometry data were available for only 26,453 (43.5%) subjects. Disease severity was classified in 18,172 patients: 4,396 mild, 7,100 moderate, and 6,676 severe, although only 27%, 34%, and 28%, respectively, presented obstructive spirometry.The clinical management of COPD is mainly the responsibility of the primary care and pulmonology departments, while internal medicine and, to a lesser extent, geriatrics also participate. Drug treatment was based on bronchodilators and inhaled corticosteroids (ICS). A marked decline in the use of long-acting beta-2 agonists (LABA) in monotherapy and a slight reduction in ICS/LABA combinations, associated with a LAMA in 74% of cases, was observed.All-cause in-hospital mortality among the overall population was 5.6% compared to 1% of the general population older than 40 years. In total, 35% were admitted to hospital, with an average stay of 6.6 days and a rate of hospital mortality in this group of 10.74%. DiscussionThis study identifies the main features of an unselected COPD population and the major errors made in the management of the disease.

The effect of doxofylline in asthma and COPD.

Theophylline is still one of the most widely prescribed drugs for the treatment of asthma and COPD in developing countries because the majority of asthma and COPD medicines are largely unavailable and also because it is a cheap option. In any case, its anti-inflammatory effects and capacity to reverse corticosteroid resistance deserve consideration, but it can induce numerous side effects and drug-drug interactions and frequently requires measurement of drug levels in plasma. In order to overcome the problems posed by theophylline, other xanthines have been developed. Doxofylline is a newer generation xanthine with both bronchodilating and anti-inflammatory activities and for this reason it has been called "novofylline". It differs substantially from theophylline at the pharmacological level. Clinical studies have shown substantial differences between doxofylline and theophylline. In particular, efficacy/safety profile of doxofylline is better than that of theophylline.

Hydrogen sulfide alleviates cigarette smoke-induced COPD through inhibition of the TGF-β1/smad pathway.

Smoking has become a major cause of chronic obstructive pulmonary disease through weakening of the respiratory mucus-ciliary transport system, impairing cough reflex sensitivity, and inducing inflammation. Recent researches have indicated that hydrogen sulfide is essential in the development of various lung diseases. However, the effect and mechanism of hydrogen sulfide on cigarette smoke-induced chronic obstructive pulmonary disease have not been reported. In this study, rats were treated with cigarette smoke to create a chronic obstructive pulmonary disease model followed by treatment with a low concentration of hydrogen sulfide. Pulmonary function, histopathological appearance, lung edema, permeability, airway remodeling indicators, oxidative products/antioxidases levels, inflammatory factors in lung, cell classification in bronchoalveolar lavage fluid were measured to examine the effect of hydrogen sulfide on chronic obstructive pulmonary disease model. The results showed that hydrogen sulfide effectively improved pulmonary function and reduced histopathological changes, lung edema, and permeability. Airway remodeling, oxidative stress, and inflammation were also reduced by hydrogen sulfide treatment. To understand the mechanisms, we measured the expression of TGF-β1, TGF-βIand TGF-βII receptors and Smad7 and phosphorylation of Smad2/Smad3. The results indicated that the TGF-β1 and Smad were activated in cigarette smoke-induced chronic obstructive pulmonary disease model, but inhibited by hydrogen sulfide. In conclusion, this study showed that hydrogen sulfide treatment alleviated cigarette smoke-induced chronic obstructive pulmonary disease through inhibition of the TGF-β1/Smad pathway. Impact statement COPD has become a severe public health issue in the world and smoking has become a major cause of COPD. As a result, it is a demandingly needed to explore new potential therapy for cigarette smoke-associated COPD. The present study suggested that H2S treatment improved pulmonary function and reduced histopathological changes, lung edema, permeability, inflammation, airway remodeling and oxidative injury in a COPD model induced by cigarette smoke. Although additional studies are required to elucidate the pharmacodynamics, pharmacokinetics, and pharmacology of H2S in the cigarette smoke-associated COPD, our findings provide an experimental basis for the potential clinical application of H2S in COPD treatment.