Reduce Exacerbation Frequency Research Articles

The Efficacy and Safety of Inhaled Antibiotics for the Treatment of Bronchiectasis in Adults: Updated Systematic Review and Meta-Analysis

BackgroundInhaled antibiotics are conditionally recommended by international bronchiectasis guidelines for the treatment of patients with bronchiectasis but results of individual studies are inconsistent. A previous meta-analysis demonstrated promising results regarding the efficacy and safety of inhaled antibiotics in bronchiectasis. Subsequent publications have further supplemented the existing body of evidence in this area. Research questionTo what extent do inhaled antibiotics demonstrate both efficacy and safety as a treatment option for adults with bronchiectasis? Study design And methodsSystematic review and meta-analysis of randomised controlled trials of inhaled antibiotics in adult patients with bronchiectasis. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for eligible studies. Studies were included if they enrolled adults with bronchiectasis diagnosed by CT and trials had a treatment duration of at least 4 weeks. The primary endpoint was exacerbation frequency, with additional key efficacy endpoints including severe exacerbations, bacterial load, symptoms, quality of life and FEV1. Data were pooled through random-effects meta-analysis. Results20 studies involving 3468 patients were included. Inhaled antibiotics were associated with reduced number of subjects with exacerbations (risk ratio 0.85 95%CI 0.75-0.96), a slight reduction in exacerbation frequency (rate ratio 0.78 95%CI 0.68-0.91), a probable reduction in the frequency of severe exacerbations (rate ratio 0.48 95%CI 0.31-0.74) and a likely slight increase in time to first exacerbation (hazard ratio 0.80 95%CI 0.68-0.94). Inhaled antibiotics likely lead to a slight increase in the Quality of Life-Bronchiectasis Respiratory Symptom Score (2.51, 95%CI 0.44 to 4.31) and may reduce scores on the St. George’s Respiratory Questionnaire (-3.13, 95%CI -5.93 to -0.32). Bacterial load was consistently reduced but FEV1 was not changed with treatment. Evidence suggests little to no difference in adverse effects between groups (odds ratio 0.99 95%CI 0.75-1.30). Antibiotic resistant organisms were likely increased by treatment. InterpretationInhaled antibiotics result in a slight reduction in exacerbations, a probable reduction in severe exacerbations and a likely slight improvement in symptoms and quality of life in adults with bronchiectasis. Trial registrySystematic review registration number PROSPERO CRD42023384694

Clinical efficacy of a triple combination of budesonide/ glycopyrronium bromide/formoterol in the treatment of chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterized by persistent airflow limitation, caused by chronic inflammation in response to exposure to inhaled damaging particles or gases. Exacerbations of COPD lead to the progression of symptoms, worsening lung function, reduced physical tolerance, and, as a result, contribute to an increase mortality. Therefore, the prevention of exacerbations is a primary objective in the management of COPD. The foundation of COPD therapy involves prescribing long-acting bronchodilators, and for some patients, the use of anti-inflammatory agents, such as inhaled corticosteroids (ICS). ICS are used in combination with long-acting beta2-agonists (LABA) or as part of triple therapy (ICS/LABA/ LAMA). The choice of triple therapy depends on the patient’s exacerbation history, severity of symptom, level of peripheral blood eosinophilia, risk of infectious complications, and the presence of a concomitant diagnosis of bronchial asthma. Triple therapy offers advantages in terms of improving lung function, disease symptoms, reducing exacerbation frequency, and significantly decreasing mortality compared to other inhaled therapy options for COPD. A significant advantage of this therapy has been shown in patients with eosinophilic COPD. Currently, three combined inhalation medications containing ICS/LABA/LAMA are available for COPD treatment in our country. This review provides basic information on the clinical efficacy and safety profile of one of them, budesonide/glycopyrronium bromide/formoterol, in patients with various COPD phenotypes.

The Effectiveness and Safety of Long-Term Macrolide Therapy for COPD in Stable Status: A Systematic Review and Meta-Analysis.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition with fewer treatments available as the severity increases. Previous systematic reviews have demonstrated the benefits of long-term macrolide use. However, the therapeutic differences between different macrolides and the optimal duration of use remain unclear. Methods: A systematic review and meta-analysis were conducted to assess the effectiveness of long-term macrolide use in reducing COPD exacerbations, compare the therapeutic differences among macrolides, and determine the appropriate treatment duration. Four databases (PubMed, Cochrane Library, Web of Science, and ICHU-SHI) were searched until 20 March 2023, and a random-effects model was used to calculate the pooled effect. Results: The meta-analysis included nine randomized controlled trials involving 1965 patients. The analysis revealed an odds ratio (OR) of 0.34 (95% confidence interval [CI] 0.19, 0.59, p < 0.001) for the reduction in exacerbation frequency. Notably, only azithromycin or erythromycin showed suppression of COPD exacerbations. The ORs for reducing exacerbation frequency per year and preventing hospitalizations were -0.50 (95% CI: -0.81, -0.19; p = 0.001) and 0.60 (95% CI: 0.3, 0.97; p = 0.04), respectively. Statistical analyses showed no significant differences between three- and six-month macrolide prescriptions. However, studies involving a twelve-month prescription showed an OR of 0.27 (95% CI: 0.11, 0.68; p = 0.005; I2 = 81%). Although a significant improvement in St George's Respiratory Questionnaire (SGRQ) total scores was observed with a mean difference of -4.42 (95% CI: -9.0, 0.16; p = 0.06; I2 = 94%), the minimal clinically important difference was not reached. While no adverse effects were observed between the two groups, several studies have reported an increase in bacterial resistance. Conclusions: Long-term use of azithromycin or erythromycin suppresses COPD exacerbations, and previous studies have supported the advantages of a 12-month macrolide prescription over a placebo.

Real-World Effectiveness of IL-5/5Ra Targeted Biologics in Severe Eosinophilic Asthma With Comorbid Bronchiectasis.

Bronchiectasis is a common comorbidity in patients with asthma and is associated with increased disease severity. In patients with severe eosinophilic asthma, biologics targeting IL-5/5Ra have beneficial effects on oral corticosteroid (OCS) use and exacerbation frequency. However, how coexisting bronchiectasis affects the response to such treatments is unknown. To evaluate the real-world effectiveness of anti-IL-5/5Ra therapy in patients with severe eosinophilic asthma and comorbid bronchiectasis on exacerbation frequency and daily maintenance and cumulative OCS dose. This real-world study evaluated data from 97 adults with severe eosinophilic asthma and computed tomography-confirmed bronchiectasis from the Dutch Severe Asthma Registry, who initiated anti-IL5/5Ra biologics (mepolizumab, reslizumab, and benralizumab) and had follow-up data for 12 months or greater. The analysis was performed for the total population and subgroups with or without maintenance OCS use. Anti-IL-5/5Ra therapy significantly reduced exacerbation frequency in patients with maintenance OCS use as well as in those without it. In the year before biologic initiation, 74.5% of all patients had two or more exacerbations, which decreased to 22.1% in the follow-up year (P < .001). The proportion of patients on maintenance OCS decreased from 47% to 30% (P < .001), and in the OCS-dependent patients (n= 45) maintenance OCS dose decreased from median (interquartile range) of 10.0 mg/d (5-15 mg/d) to 2.5 mg/d (0-5 mg/d) after 1 year (P < .001). This real-world study shows that anti-IL-5/5Ra therapy reduces exacerbation frequency and daily maintenance as well as the cumulative OCS dose in patients with severe eosinophilic asthma and comorbid bronchiectasis. Although it is an exclusion criterion in phase 3 trials, comorbid bronchiectasis should not preclude anti-IL-5/5Ra therapy in patients with severe eosinophilic asthma.

Biological therapy of severe bronchial asthma

Bronchial asthma is a major public health problem in the world. A considerable proportion of patients suffer from severe asthma, which is manifested by a decrease in the quality of life, an increase in the frequency of exacerbations, hospitalisations, and mortality. The ineffectiveness of conventional therapy in such patients contributes to the development of biological treatment methods with higher specificity, aimed at the pathogenetic links of the disease. The purpose of the study was to analyse the effectiveness of the treatment of severe bronchial asthma with monoclonal antibodies based on literature data. The study examines publications over the past 5 years that are available on the Internet. The following terms were used for the search: monoclonal antibodies, endotype, phenotype. Five monoclonal antibody biological agents targeting IgE, IL-5, IL-4, and IL-13, which are approved for use in patients with severe asthma, were analysed: omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab. The use of these medications has led to progress in the treatment of bronchial asthma. It was found that determining disease endotypes based on the assessment of biomarkers such as eosinophil count in blood and sputum, fractional exhaled nitric oxide, and serum periostin contributes to the greater effectiveness of biological therapy. It was investigated that monoclonal antibody treatment improves lung function, reduces exacerbation frequency, and decreases the need for additional medications. Many other biological agents, particularly those targeting key cytokines, are in the clinical development stage. Approved monoclonal antibodies targeting IgE, IL-5, and IL-4/IL13 demonstrate high efficacy in the treatment of severe bronchial asthma. The use of these agents in patients with severe asthma and high Th2 levels considerably improves lung function, symptom control, and reduces the frequency of disease exacerbations

Clinical evidence for acupuncture for adult asthma: Systematic review and meta-analysis of randomised sham/placebo-controlled trials

ObjectiveAcupuncture is a widely used asthma therapy, but the benefits remain uncertain. This study aimed to access the effectiveness of acupuncture for treatment of asthma in adults. MethodsFive English databases and four Chinese databases were searched from inception to November 2021. Randomised sham/placebo-controlled trials meeting inclusion criteria were included. Risk of bias was evaluated according to the Cochrane Review Handbook, and data analysis was performed in RevMan 5.4.1. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) profiler. ResultsSixteen randomised controlled trials (RCTs) were included in the meta-analysis. Results indicated that acupuncture was well-tolerated and could improve FEV1% compared with sham/placebo acupuncture [MD 6.11, 95% CI 0.54–11.68, I2 = 93%, number of participants (n) = 603]. Acupuncture also improved Cai’s Asthma Quality of Life Questionnaire (AQLQ) (MD 7.26, 95% CI 5.02–9.50, I2 = 0, n = 358), and reduced the asthma symptom score (SMD −2.73, 95% CI −3.59 to −1.87, I2 = 65%, n = 120). One study showed acupuncture increased the Asthma Control Test (ACT) score (MD 2.00, 95% CI 0.90–3.10, n = 111), and decreased exacerbation frequency (MD −1.00, 95% CI −1.55 to −1.45, n = 111). Other lung function and medication use parameters were not statistically significant. ConclusionsAcupuncture versus sham/placebo control appeared to improve quality of life, FEV1%, symptoms, and asthma control, and reduced exacerbation frequency per year. Further studies with appropriate controls, more participants, and high-quality evidence are needed.

Dipeptidyl peptidase-1 inhibition with brensocatib reduces the activity of all major neutrophil serine proteases in patients with bronchiectasis: results from the WILLOW trial

BackgroundBrensocatib is an oral, selective, reversible inhibitor of dipeptidyl peptidase-1 (DPP-1), responsible for activating neutrophil serine proteases (NSPs) including neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG). In chronic inflammatory lung diseases such as non-cystic fibrosis bronchiectasis (NCFBE), neutrophils accumulate in the airways resulting in excess active NSPs that cause damaging inflammation and lung destruction.MethodsThe 24-week WILLOW trial (NCT03218917) was a randomized, double-blind, placebo-controlled, parallel-group trial in patients with NCFBE conducted at 116 sites across 14 countries. In this trial, treatment with brensocatib was associated with improvements in clinical outcomes including time to first exacerbation, reduction in exacerbation frequency and a reduction in NE activity in sputum. An exploratory analysis of NE activity in white blood cell (WBC) extracts and NE, PR3 and CatG activity in sputum was conducted to further characterize brensocatib’s effect and identify potential correlated effects.ResultsNE, PR3 and CatG activities were reduced in sputum and NE activity was reduced in WBC extracts in a dose-dependent manner after four weeks of brensocatib treatment, with a return to baseline four weeks after the end of treatment. Brensocatib produced the greatest reduction in the sputum activity of CatG, followed by NE and then PR3. Positive correlations among the sputum NSPs were observed both at baseline and in response to treatment, with the strongest correlation among the sputum NSPs for NE and CatG.ConclusionsThese results suggest a broad anti-inflammatory effect of brensocatib underlying its clinical efficacy observed in NCFBE patients.Trial registration: The study was approved by the corresponding ethical review boards of all participating centers. The trial was approved by the Food and Drug Administration and registered at clinicaltrials.gov (NCT03218917) on July 17, 2017 and approved by the European Medicines Agency and registered at the European Union Clinical trials Register (EudraCT No. 2017-002533-32). An independent, external data and safety monitoring committee (comprising physicians with pulmonary expertise, a statistician experienced in the evaluation of clinical safety, and experts in periodontal disease and dermatology) reviewed all adverse events.

Thoracic Society of Australia and New Zealand (TSANZ) position statement on chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand.

This position statement, updated from the 2015 guidelines for managing Australian and New Zealand children/adolescents and adults with chronic suppurative lung disease (CSLD) and bronchiectasis, resulted from systematic literature searches by a multi-disciplinary team that included consumers. The main statements are: Diagnose CSLD and bronchiectasis early; this requires awareness of bronchiectasis symptoms and its co-existence with other respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease). Confirm bronchiectasis with a chest computed-tomography scan, using age-appropriate protocols and criteria in children. Undertake a baseline panel of investigations. Assess baseline severity, and health impact, and develop individualized management plans that include a multi-disciplinary approach and coordinated care between healthcare providers. Employ intensive treatment to improve symptom control, reduce exacerbation frequency, preserve lung function, optimize quality-of-life and enhance survival. In children, treatment also aims to optimize lung growth and, when possible, reverse bronchiectasis. Individualize airway clearance techniques (ACTs) taught by respiratory physiotherapists, encourage regular exercise, optimize nutrition, avoid air pollutants and administer vaccines following national schedules. Treat exacerbations with 14-day antibiotic courses based upon lower airway culture results, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients with severe exacerbations and/or not responding to outpatient therapy are hospitalized for further treatments, including intravenous antibiotics and intensive ACTs. Eradicate Pseudomonas aeruginosa when newly detected in lower airway cultures. Individualize therapy for long-term antibiotics, inhaled corticosteroids, bronchodilators and mucoactive agents. Ensure ongoing care with 6-monthly monitoring for complications and co-morbidities. Undertake optimal care of under-served peoples, and despite its challenges, delivering best-practice treatment remains the overriding aim.

Chronic Obstructive Pulmonary Disease and Telehealth: Remote Monitoring and Patient Outcomes

The integration of telehealth interventions into the management of Chronic Obstructive Pulmonary Disease (COPD) represents a transformative approach to improving patient outcomes and reducing the burden on healthcare systems. With the global prevalence of COPD on the rise, innovative care models, including remote monitoring and teleconsultation, have emerged as essential tools in the early detection and management of COPD exacerbations. These interventions not only lead to a significant reduction in exacerbation frequency and severity but also enhance patients' quality of life by empowering them to take an active role in their healthcare. Improved pulmonary function, medication adherence, and cost-effectiveness further underscore the value of telehealth in COPD care. The high levels of patient satisfaction and the potential for reduced mortality rates emphasize the promising future of telehealth in COPD management. As we continue to advance in technology and healthcare delivery, the comprehensive and personalized care offered by telehealth is poised to make a lasting impact on the lives of COPD patients worldwide.

Severe asthma with fungal sensitization is associated with worse small airway dysfunction but similar symptom control

Severe asthma with fungal sensitization is associated with worse small airway dysfunction but similar symptom control

Effects of long-term tobramycin inhalation solution (TIS) once daily on exacerbation rate in patients with non-cystic fibrosis bronchiectasis

BackgroundUse of long-term tobramycin inhalation solution (TIS) has been shown beneficial in cystic fibrosis (CF) and earlier findings also suggest a benefit in non-CF bronchiectasis. We investigated the efficacy and safety of maintenance TIS once daily (OD) in frequent exacerbating bronchiectasis patients chronically infected by different pathogens sensitive for tobramycin.ObjectiveThe primary outcome was the frequency of exacerbations during the 12-month study period. Secondary outcomes were time to first exacerbation, change in lung function and quality of life (QoL), bacterial analysis and safety.Materials/patientsIn this multicenter RCT patients aged ≥ 18-year-old were included with confirmed bronchiectasis and ≥ 2 exacerbations in the preceding year. Patients were assigned (1:1) to receive TIS or placebo OD for 1-year.Results58 patients were included of which 52 were analyzed in the mITT analysis. TIS reduced exacerbation frequency with a RR of 0.74 (95% CI 0.49–1.14) (p = 0.15). Within the TIS population a decrease in number of exacerbations was found (2; p = 0.00), which was also seen in the placebo-treated patients (1.5; p = 0.00). In the TIS-treated patients the QoL improved (LRTI-VAS p = 0.02 Leicester Cough p = 0.02) without additional safety concerns. No differences were found for the other secondary outcomes.ConclusionLong-term TIS OD is a safe treatment modality and showed a non-significant reduced exacerbation frequency of 0.74 as compared to placebo in bronchiectasis patients chronically infected by tobramycin sensitive pathogens. TIS OD may be a potential therapeutic strategy in selected patients with bronchiectasis suffering from a high burden of disease.Trail registration number: The BATTLE study was registered at Clinical trials.gov number: NCT02657473. Date: 13 august 2016.

Evaluation of telehealth support in an integrated respiratory clinic

Supporting self-management is key in improving disease control, with technology increasingly utilised. We hypothesised the addition of telehealth support following assessment in an integrated respiratory clinic could reduce unscheduled healthcare visits in patients with asthma and COPD. Following treatment optimisation, exacerbation-prone participants or those with difficulty in self-management were offered telehealth support. This comprised automated twice-weekly telephone calls, with a specialist nurse triaging alerts. We performed a matched cohort study assessing additional benefits of the telehealth service, matching by: confirmed diagnosis, age, sex, FEV1 percent predicted, smoking status and ≥1 exacerbation in the last year. Thirty-four telehealth participants were matched to twenty-nine control participants. The telehealth cohort generated 165 alerts, with 29 participants raising at least one alert; 88 (53.5%) alerts received a call discussing self-management, of which 35 (21%) received definitive advice that may otherwise have required an unscheduled healthcare visit. There was a greater reduction in median exacerbation rate across both telehealth groups at 6 months post-intervention (1 to 0, p < 0.001) but not in control groups (0.5 to 0.0, p = 0.121). Similarly, there was a significant reduction in unscheduled GP visits across the telehealth groups (1.5 to 0.0, p < 0.001), but not the control groups (0.5 to 0.0, p = 0.115). These reductions led to cost-savings across all groups, but greater in the telehealth cohorts. The addition of telehealth support to exacerbation-prone patients with asthma or COPD, following comprehensive assessment and treatment optimisation, proved beneficial in reducing exacerbation frequency and unscheduled healthcare visits and thus leads to significant cost-savings for the NHS.Clinical Trial Registration: ClinicalTrials.gov: NCT03096509

Corticosteroid Responsiveness Following Mepolizumab in Severe Eosinophilic Asthma—A Randomized, Placebo-Controlled Crossover Trial (MAPLE)

Mepolizumab inhibits IL-5 activity and reducesexacerbation frequency and maintenance oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma(SEA). Some patients remain dependent on OCS despite anti-IL-5 treatment, suggesting residual corticosteroid-responsive mechanisms. To determine the clinical and anti-inflammatory effects of OCS in patients with SEA on mepolizumab. We conducted a randomized, triple-blind, placebo-controlled crossover trial of prednisolone (0.5 mg/kg/d, maximum 40 mg/d, for 14 ± 2 days) in adults with SEA after 12 or more weeks of mepolizumab. We compared change in asthma symptoms, quality of life, lung function measured by spirometry and airwave oscillometry, fractional exhaled nitric oxide, and blood and sputum eosinophil cell count after prednisolone and placebo treatment. A total of 27 patients completed the study. Prednisolone did not improve 5-item Asthma Control Questionnaire (mean difference in change for prednisolone vs placebo,-0.23; 95% CI,-0.58 to 0.11), mini-Asthma Quality of Life Questionnaire (0.03; 95% CI,-0.26 to 0.42), St. George's Respiratory Questionnaire (0.24; 95% CI,-3.20 to 3.69), or Visual Analogue Scale scores for overall asthma symptoms (0.11; 95% CI,-0.58 to 0.80). The mean difference for FEV1 in favor of prednisolone was 105 mL (95% CI,-4 to 213 mL); forced expiratory flow at 25% and 75% 484 mL/s (95% CI, 151 to 816 mL/s); fractional exhaled nitric oxide reduction 41% (95% CI, 25% to 54%); blood eosinophil count reduction 49% (95% CI, 31% to 62%); and percentage of sputum eosinophil reduction 71% (95% CI, 26% to 89%). OCS improved small-airway obstruction and reduced biomarkers of type 2 inflammation but had no significant effect on symptoms or quality of life in patients with SEA receiving treatment with mepolizumab.

Impact of mepolizumab in patients with high-burden severe asthma within a managed care population

Objective To evaluate the real-world impact of mepolizumab on the incidence of asthma exacerbations, oral corticosteroid (OCS) use and asthma exacerbation-related costs in patients with high-burden severe asthma. Methods This was a retrospective study of the MarketScan Commercial and Medicare Databases in patients with high-burden severe asthma (≥80th percentile of total healthcare expenditure and/or significant comorbidity burden). Patients were ≥12 years of age upon mepolizumab initiation (index date November 1, 2015–December 31, 2018) and had ≥2 mepolizumab administrations during the 6 months post-index. Asthma exacerbation frequency (primary outcome), use of OCS (secondary outcome), and asthma exacerbation-related costs (exploratory outcome) were assessed during the 12 months pre-index (baseline) and post-index (follow-up). Results In total, 281 patients were analyzed. Mepolizumab significantly reduced the proportion of patients with any asthma exacerbation (P < 0.001) or exacerbations requiring hospitalization (P = 0.004) in the follow-up versus baseline period. The mean number of exacerbations decreased from 2.5 to 1.5 events/patient/year (relative reduction: 40.0%; P < 0.001). The proportion of patients with ≥1 OCS claim also decreased significantly from 94.0% to 81.9% (relative reduction: 12.9%; P < 0.001), corresponding to a decrease from 6.6 to 4.7 claims/person/year (P < 0.001). Of the 264 patients with ≥1 OCS claim during baseline, 191 (72.3%) showed a decrease in mean daily OCS use by ≥50% in 117 patients (61.3%). Total asthma exacerbation-related costs were significantly lower after mepolizumab was initiated (P < 0.001). Conclusions Mepolizumab reduced exacerbation frequency, OCS use and asthma exacerbation-related costs in patients with high-cost severe asthma. Mepolizumab provides real-world benefits to patients, healthcare systems and payers.

Bronchiectasis enters the inflammation era.

Bronchiectasis enters the inflammation era.

Non-typeable Haemophilus influenzae–Moraxella catarrhalis vaccine for the prevention of exacerbations in chronic obstructive pulmonary disease: a multicentre, randomised, placebo-controlled, observer-blinded, proof-of-concept, phase 2b trial

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with changes in the sputum microbiome, including an increased prevalence of pathogenic bacteria. Vaccination against the most frequent bacteria identified in AECOPD might reduce exacerbation frequency. We assessed the efficacy, safety, and immunogenicity of a candidate vaccine containing surface proteins from non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) in patients with COPD. This multicentre, randomised, observer-blinded, placebo-controlled, proof-of-concept, phase 2b trial recruited patients with stable COPD, moderate-to-very severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2, 3, or 4), at 67 clinical sites in Belgium, Canada, France, Germany, Italy, Spain, UK, and USA. Eligible patients were aged 40-80 years and had a history of at least one moderate or severe exacerbation in the previous year. Patients were allocated (1:1) using a minimisation algorithm to receive two intramuscular injections of NTHi-Mcat vaccine or placebo 60 days apart, in addition to standard care. The allocation algorithm considered age category, number of previous exacerbations, COPD severity at study entry, and country as minimisation factors, to guarantee treatment balance within each factor. Vaccine recipients and those responsible for evaluating study endpoints were masked to group allocation. In the analysis of efficacy, the primary outcome was the rate of any moderate or severe AECOPD occurring within a 1-year period, starting 1 month after the second dose in patients who received two vaccine doses (modified total vaccinated cohort). Safety was assessed in the total vaccinated cohort. The trial is registered with ClinicalTrials.gov, number NCT03281876, and is complete. Between Nov 27, 2017, and Nov 30, 2018, 606 adults were enrolled and included in the total vaccinated cohort (304 in the NTHi-Mcat vaccine group, 302 in the placebo group); 571 received two doses and were included in the primary efficacy analysis (279 in the NTHi-Mcat vaccine group, 292 in the placebo group). 23 participants dropped-out in the NTHi-Mcat vaccine group and 39 in the placebo group; this included 4 patients in the NTHi-Mcat vaccine group and 15 in the placebo group who withdrew from the study because of an adverse event. The primary analysis included 340 exacerbations (in follow-up time 102 123 days) in the NTHi-Mcat vaccine group and 333 (in 104 443 days) in the placebo group, with a yearly rate of moderate or severe AECOPD of 1·22 in the NTHi-Mcat vaccine group and 1·17 in the placebo group, with vaccine efficacy in reducing the yearly rate of moderate or severe AECOPD estimated to be zero (vaccine efficacy point estimate 2·26% [87% CI -18·27 to 11·58]; p=0·82). Solicited local adverse events were more frequent in the NTHi-Mcat vaccine group (216 [72%] of 301 patients) than with placebo (34 [11%] of 299 patients), and the frequency of solicited general adverse events was similar between groups (239 [79%] of 301 vs 235 [79%] of 299 patients). There was one death in the NTHi-Mcat vaccine group (acute respiratory failure, not related to vaccination) and ten in the placebo group (seven due in part to COPD or respiratory failure). There were 158 serious adverse events (89 [29%] of 304 patients) in the NTHi-Mcat vaccine group, not related to vaccination, and 214 (99 [33%] of 302 patients) in the placebo group. NTHi-Mcat vaccine administered to patients with COPD did not show efficacy in reducing the yearly rate of moderate or severe exacerbations. No safety concerns were identified. GlaxoSmithKline Biologicals SA.

Intermittent prophylactic antibiotics for bronchiectasis.

Intermittent prophylactic antibiotics for bronchiectasis.

Advanced Dental Cleaning is Associated with Reduced Risk of COPD Exacerbations - A Randomized Controlled Trial.

PurposeInfections from the oral microbiome may lead to exacerbations of chronic obstructive pulmonary disease (COPD). We investigated whether advanced dental cleaning could reduce exacerbation frequency. Secondary outcomes were disease-specific health status, lung function, and whether the bacterial load and composition of plaque microbiome at baseline were associated with a difference in outcomes.Patients and MethodsOne-hundred-one primary and secondary care patients with COPD were randomized to intervention with advanced dental cleaning or to dental examination only, repeated after six months. At baseline and at 12 months, data of exacerbations, lung function, COPD Assessment Test (CAT) score, and periodontal status were collected from questionnaires, record review, and periodontal examination. Student’s t-test and Mann–Whitney-U (MWU) test compared changes in outcomes. The primary outcome variable was also assessed using multivariable linear regression with adjustment for potential confounders. Microbiome analyses of plaque samples taken at baseline were performed using Wilcoxon signed ranks tests for calculation of alpha diversity, per mutational multivariate analysis of variance for beta diversity, and receiver operating characteristic curves for prediction of outcomes based on machine learning models.ResultsIn the MWU test, the annual exacerbation frequency was significantly reduced in patients previously experiencing frequent exacerbations (p = 0.020) and in those with repeated advanced dental cleaning (p = 0.039) compared with the non-treated control group, but not in the total population including both patients with a single and repeated visits (p = 0.207). The result was confirmed in multivariable linear regression, where the risk of new exacerbations was significantly lower in patients both in the intention to treat analysis (regression coefficient 0.36 (95% CI 0.25–0.52), p < 0.0001) and in the population with repeated dental cleaning (0.16 (0.10–0.27), p < 0.0001). The composition of microbiome at baseline was moderately predictive of an increased risk of worsened health status at 12 months (AUC = 0.723).ConclusionAdvanced dental cleaning is associated with a reduced frequency of COPD exacerbations. Regular periodontal examination and dental cleaning may be of clinical importance to prevent COPD exacerbations.

VOICE-BASED MONITORING OF COPD

TOPIC: Pulmonary Rehabilitation TYPE: Original Investigations PURPOSE: COPD is a common, preventable and treatable disease characterized by persistent respiratory symptoms and airflow limitation with a projected increase in prevalence over the coming decades. Periodic assessment of COPD is needed to determine the level of airflow limitation and assess impact on a patient’s health status, risk of future exacerbations, hospital admissions, mortality and to help guide therapy. Previously, COPD was viewed as a disease mostly characterized by dyspnea, now it is recognized that COPD impacts patients beyond this. As a result, a comprehensive assessment of symptoms is recommended. The COPD assessment test (CAT) is an 8 item measure of health status impairment and is commonly used to assess symptoms. Voice is an important biomarker of many medical conditions including diseases of the respiratory system which leave signatures in breath and speech. We build on our previous work of voice-based prediction of FEV1 and FVC (Ashraf, Obaid, et al. Chest 158.4 (2020): A1687, Walter, Kristin. JAMA 325.12 (2021): 1130-1131) to create a voice based early warning system for COPD exacerbation utilizing the CAT score. METHODS: We present the results of a prospective cohort study correlating voice and breath samples to CAT scores. We collected a total of 418 sessions from 9 participants aged 42 to 75 at a large suburban general hospital in Western Pennsylvania over the course of a year. Each participant provided biweekly voice and breath samples, along with self-reported CAT scores. We recorded audio samples on a commodity smart tablet using a proprietary software and analyzed recorded data off-line on the secure Telling.ai cloud. Based on input from health care providers, we weighted CAT questions pertaining to cough, sputum, wheezing and tightness of the chest more heavily than other questions. We extracted audio features from the recordings and developed a regression algorithm using k fold cross validation to predict deviation in the weighted CAT score from a baseline, and a binary classification retrospective prediction algorithm to predict a clinically important weighted CAT score increase (2 point or more) upto 7 days in advance. RESULTS: Our weighted CAT deviation from baseline regressor and retrospective exacerbation classification models had the following results, averaged across all folds, for all participants:(R squared = 0.972, Mean absolute error =0.449, Mean squared error = 0.572, Pearson Coefficient Correlation r = 0.998, two-tailed p-value < 0.0000001)and(Accuracy = 94.086%, Sensitivity = 94.229%, Specificity = 94.414%)respectively. CONCLUSIONS: We demonstrate that changes in voice and breath correlate strongly with changes in symptoms scores 0.97 R^2and MAE = 0.45 and furthermore, that signatures in voice can be detected even before the symptoms present themselves (2 point or more weighted CAT score increase upto 7 days in advance) with 94.23% sensitivity and 94.41% specificity . This technology requires no additional custom-built hardware, is cost effective, non-invasive and practical for ubiquitous and frequent use on mobile phones. CLINICAL IMPLICATIONS: The solution is ideally suited for personalized, predictive and frequent monitoring to enable the development of clinical decision support systems. This technique offers the promise of early interventions to reduce exacerbation frequency and severity, advancing personalized medicine for chronic and acute respiratory care. DISCLOSURES: Employee relationship with Telling.ai Please note: $20001 - $100000 by Mir Mohammed Daanish Ali Khan, source=Web Response, value=Salary Employee relationship with Telling.ai Please note: $20001 - $100000 by Rajat Kulshreshtha, source=Web Response, value=Salary Employee relationship with Telling.ai Please note: >$100000 by Prakhar Pradeep Naval, source=Web Response, value=Salary Speaker/Speaker's Bureau relationship with boeringer Ingleheim Please note: 2019-2020 Added 04/29/2021 by Anil Singh, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with astra zeneca Please note: 2019-2020 Added 04/29/2021 by Anil Singh, source=Web Response, value=Honoraria Chief Technical Officer relationship with Telling.ai Please note: >$100000 by Satya Venneti, source=Web Response, value=Salary

Management of chronic Pseudomonas aeruginosa infection with inhaled levofloxacin in people with cystic fibrosis.

People with cystic fibrosis (CF) are highly susceptible to bacterial infections of the airways. By adulthood, chronic Pseudomonas aeruginosa (Pa) is the most prevalent infective organism and is difficult to eradicate owing to its adaptation to the CF lung microenvironment. Long-term suppressive treatment with inhaled antimicrobials is the standard care for reducing exacerbation frequency, improving quality of life and increasing measures of lung function. Levofloxacin (a fluoroquinolone antimicrobial) has been approved as an inhaled solutionin Europe and Canada, for the treatment of adults with CF with chronic P. aeruginosa pulmonary infections. Here, we review the clinical principles relating to the use of inhaled antimicrobials and inhaled levofloxacin for the management of P. aeruginosa infections in patients with CF.