Asthma exacerbations and worsenings in patients aged 1-75 years with add-on tiotropium treatment

This review explores the effect of tiotropium Respimat® add-on therapy on asthma exacerbations and worsenings, adverse events (AEs) related to exacerbations and symptoms and any effects on seasonality across the 10 UniTinA-asthma® clinical trials comprising over 6000 patients. When added on to inhaled corticosteroids ± additional therapies, tiotropium significantly reduced the risk of exacerbations and worsenings in adults with symptomatic severe asthma and provided a non-significant improvement in worsenings in adults with symptomatic moderate and mild asthma, which was significant for patients with moderate asthma receiving tiotropium 2.5 µg once daily vs. placebo. Trials in paediatric patients were not powered to assess exacerbations or worsenings, but when AEs related to asthma exacerbations and symptoms were grouped into a composite endpoint and pooled, tiotropium improved outcomes vs. placebo (rate ratio 0.76; 95% confidence interval 0.63, 0.93). The reduction in exacerbations with tiotropium is apparent across all patients during the observed seasonal peaks of these events

Initiation of home mechanical ventilation at home:A randomised controlled trial of efficacy, feasibility and costs

SummaryIntroductionHome mechanical ventilation (HMV) in the Netherlands is normally initiated in hospital, but this is expensive and often a burden for the patient. In this randomised controlled study we investigated whether initiation of HMV at home in patients with chronic respiratory failure is non-inferior to an in hospital based setting.MethodsSeventy-seven patients were included, of which 38 patients started HMV at home. All patients were diagnosed with chronic respiratory failure due to a neuromuscular or thoracic cage disease. Primary outcome was the arterial carbon dioxide (PaCO2) while quality of life and costs were secondary outcomes. Telemonitoring was used in the home group to provide therapeutic information, for example; transcutaneous carbon dioxide, oxygen saturation and ventilator information, to the caregivers. Follow-up was six months.ResultsPaCO2, improved by 0.72 (SE ± 0.16) kPa in the hospital group and by 0.91 (±0.20) in the home group, both improvements being significant and the latter clearly not inferior.There were also significant improvements in quality of life in both groups, again not being inferior with home treatment.ConclusionThis study is the first to show that initiation of HMV at home in a selective group of patients with chronic respiratory failure is as effective for gas exchange and quality of life as hospital initiation. In addition we found that it is safe, technically feasible and that more than € 3000 per patient can be saved compared to our standard care

Responsivity and Reproducibility of Sputum Inflammatory Biomarkers During COPD Exacerbation and Stable Phases - A Pilot Study

Introduction: There is a great interest to identify airway biomarkers to evaluate the potential and efficacy of anti-inflammatory therapeutic interventions. In this pilot study, we compared cytokine mRNA and protein levels of IL-6, IL-8, CCL2, CCL4, and TNF-α, as well as LTB-4 expression regarding their reproducibility and responsivity in induced sputum in COPD patients. Methods: We recruited a cohort of 17 patients with a moderate COPD exacerbation, necessitating antibiotics and/or oral corticosteroids. Patients were followed for two consecutive stable phase visits. Cytokine mRNA and protein levels were measured in induced sputum samples. Results: IL-6 and CCL4 protein levels decreased from exacerbation to stable phase, whereas their mRNA expression showed the same trend (not statistically significant). Coefficients of variation were overall lower (ie, more favorable for responsiveness) at protein levels compared to mRNA levels. No significant differences were observed in the reproducibility between cytokine mRNA expression and protein measurements. IL-6, IL-8, CCL2, and TNF-α gene expression levels yielded moderate to high intraclass correlation coefficients and/or Spearman correlation coefficients between both stable phase samples in contrast to their protein levels. Conclusion: Our findings suggest that several protein levels yield better responsivity with lower noise-to-signal ratios compared to their respective mRNA levels. In contrast, cytokine mRNA expression was more reproducible as it varied less in a stable state than proteins. Future studies are needed with a larger sample size to further evaluate the differences of responsivity and reproducibility between cytokine mRNA and protein measurements, not only during exacerbations

Provision of Palliative Care in Patients with COPD:A Survey Among Pulmonologists and General Practitioners

Contains fulltext : 232084.pdf (Publisher’s version ) (Open Access

A cluster randomized controlled trial on a multifaceted implementation strategy to promote integrated palliative care in COPD:study protocol of the COMPASSION study

Contains fulltext : 226222.pdf (publisher's version ) (Open Access

Sputum microbiome profiling in COPD: beyond singular pathogen detection.

Culture-independent microbial sequencing techniques have revealed that the respiratory tract harbours a complex microbiome not detectable by conventional culturing methods. The contribution of the microbiome to chronic obstructive pulmonary disease (COPD) pathobiology and the potential for microbiome-based clinical biomarkers in COPD are still in the early phases of investigation. Sputum is an easily obtainable sample and has provided a wealth of information on COPD pathobiology, and thus has been a preferred sample type for microbiome studies. Although the sputum microbiome likely reflects the respiratory microbiome only in part, there is increasing evidence that microbial community structure and diversity are associated with disease severity and clinical outcomes, both in stable COPD and during the exacerbations. Current evidence has been limited to mainly cross-sectional studies using 16S rRNA gene sequencing, attempting to answer the question 'who is there?' Longitudinal studies using standardised protocols are needed to answer outstanding questions including differences between sputum sampling techniques. Further, with advancing technologies, microbiome studies are shifting beyond the examination of the 16S rRNA gene, to include whole metagenome and metatranscriptome sequencing, as well as metabolome characterisation. Despite being technically more challenging, whole-genome profiling and metabolomics can address the questions 'what can they do?' and 'what are they doing?' This review provides an overview of the basic principles of high-throughput microbiome sequencing techniques, current literature on sputum microbiome profiling in COPD, and a discussion of the associated limitations and future perspectives

Chronic non-invasive ventilation for chronic obstructive pulmonary disease

BACKGROUND: Chronic non-invasive ventilation (NIV) is increasingly being used to treat people with COPD who have respiratory failure, but the evidence supporting this treatment has been conflicting.OBJECTIVES: To assess the effects of chronic non-invasive ventilation at home via a facial mask in people with COPD, using a pooled analysis of IPD and meta-analysis.SEARCH METHODS: We searched the Cochrane Airways Register of Trials, MEDLINE, Embase, PsycINFO, CINAHL, AMED, proceedings of respiratory conferences, clinical trial registries and bibliographies of relevant studies. We conducted the latest search on 21 December 2020.SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing chronic NIV for at least five hours per night for three consecutive weeks or more (in addition to standard care) versus standard care alone, in people with COPD. Studies investigating people initiated on NIV in a stable phase and studies investigating NIV commenced after a severe COPD exacerbation were eligible, but we reported and analysed them separately. The primary outcomes were arterial blood gases, health-related quality of life (HRQL), exercise capacity (stable COPD) and admission-free survival (post-exacerbation COPD). Secondary outcomes for both populations were: lung function, COPD exacerbations and admissions, and all-cause mortality. For stable COPD, we also reported respiratory muscle strength, dyspnoea and sleep efficiency.DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. After inclusion of a study, we requested the IPD. We analysed continuous and time-to-event data using linear- and cox-regression mixed-effect models with a random effect on study level. We analysed dichotomous IPD using generalised estimating equations. We adjusted all models for age and sex. We assessed changes in outcomes after three and 12 months. We also conducted a meta-analysis on aggregated trial data.MAIN RESULTS: We included 14 new RCTs in this review update, in addition to the seven previously included. Seventeen studies investigated chronic NIV in stable COPD and four studies investigated chronic NIV commenced after a severe COPD exacerbation. Three studies compared NIV to sham continuous positive airway pressure (2 to 4 cmH2O). Seven studies used a nasal mask, one study used an oronasal mask and eight studies used both interfaces. Five studies did not report the interface. The majority of trials (20/21) were at high risk of performance bias due to an unblinded design. We considered 11 studies to have a low risk of selection bias and 13 to have a low risk of attrition bias. We collected and analysed the IPD from 13 stable COPD studies (n = 778, 68% of the participants included) and from three post-exacerbation studies (n = 364, 96% of the participants included). In the stable COPD group, NIV probably results in a minor benefit on the arterial partial pressure of oxygen (PaO2) after three months (adjusted mean difference (AMD) 0.27 kPa, 95% CI 0.04 to 0.49; 9 studies, 271 participants; moderate-certainty evidence), but there was little to no benefit at 12 months (AMD 0.09 kPa, 95% CI -0.23 to 0.42; 3 studies, 171 participants; low-certainty evidence). The arterial partial pressure of carbon dioxide (PaCO2) was reduced in participants allocated to NIV after three months (AMD -0.61 kPa, 95% CI -0.77 to -0.45; 11 studies, 475 participants; high-certainty evidence) and persisted up to 12 months (AMD -0.42 kPa, 95% CI -0.68 to -0.16; 4 studies, 232 participants; high-certainty evidence). Exercise capacity was measured with the 6-minute walking distance (minimal clinical important difference: 26 m). There was no clinically relevant effect of NIV on exercise capacity (3 months: AMD 15.5 m, 95% CI -0.8 to 31.7; 8 studies, 330 participants; low-certainty evidence; 12 months: AMD 26.4 m, 95% CI -7.6 to 60.5; 3 studies, 134 participants; very low-certainty evidence). HRQL was measured with the Severe Respiratory Insufficiency and the St. Georges's Respiratory Questionnaire and may be improved by NIV, but only after three months (3 months: standardised mean difference (SMD) 0.39, 95% CI 0.15 to 0.62; 5 studies, 259 participants; very low-certainty evidence; 12 months: SMD 0.15, 95% CI -0.13 to 0.43; 4 studies, 200 participants; very low-certainty evidence). Lastly, the risk for all-cause mortality is likely reduced by NIV (adjusted hazard ratio (AHR) 0.75, 95% CI 0.58 to 0.97; 3 studies, 405 participants; moderate-certainty evidence). In the post-exacerbation COPD group, there was little to no benefit on the PaO2 after three months, but there may be a slight decrease after 12 months (3 months: AMD -0.10 kPa, 95% CI -0.65 to 0.45; 3 studies, 234 participants; low-certainty evidence; 12 months: -0.27 kPa, 95% CI -0.86 to 0.32, 3 studies; 170 participants; low-certainty evidence). The PaCO2 was reduced by NIV at both three months (AMD -0.40 kPa, 95% CI -0.70 to -0.09; 3 studies, 241 participants; moderate-certainty evidence) and 12 months (AMD -0.52 kPa, 95% CI -0.87 to -0.18; 3 studies, 175 participants; high-certainty evidence). NIV may have little to no benefit on HRQL (3 months: SMD 0.25, 95% CI -0.01 to 0.51; 2 studies, 219 participants; very low-certainty evidence; 12 months: SMD 0.25, 95% -0.06 to 0.55; 2 studies, 164 participants; very low-certainty evidence). Admission-free survival seems improved with NIV (AHR 0.71, 95% CI 0.54 to 0.94; 2 studies, 317 participants; low-certainty evidence), but the risk for all-cause mortality does not seem to improve (AHR 0.97, 95% CI 0.74 to 1.28; 2 studies, 317 participants; low-certainty evidence).AUTHORS' CONCLUSIONS: Regardless of the timing of initiation, chronic NIV improves daytime hypercapnia. In addition, in stable COPD, survival seems to be improved and there might be a short term HRQL benefit. In people with persistent hypercapnia after a COPD exacerbation, chronic NIV might prolong admission-free survival without a beneficial effect on HRQL. In stable COPD, future RCTs comparing NIV to a control group receiving standard care might no longer be warranted, but research should focus on identifying participant characteristics that would define treatment success. Furthermore, the optimal timing for initiation of NIV after a severe COPD exacerbation is still unknown.</p

'Exacerbation-free time' to assess the impact of exacerbations in patients with chronic obstructive pulmonary disease (COPD):a prospective observational study

COPD exacerbations are commonly quantified as rate per year. However, the total amount of time a patient suffers from exacerbations may be stronger related to his or her disease burden than just counting exacerbation episodes. In this study, we examined the relationship between exacerbation frequency and exacerbation-free time, and their associations with baseline characteristics and health-related quality of life. A total of 166 COPD patients reported symptom changes during 12 months. Symptom-defined exacerbation episodes were correlated to the number of exacerbation-free weeks per year. Analysis of covariance was used to examine the effects of baseline characteristics on annual exacerbation frequency and exacerbation-free weeks, Spearman's rank correlations to examine associations between the two methods to express exacerbations and the Chronic Respiratory Questionnaire (CRQ). The correlation between exacerbation frequency and exacerbation-free weeks was -0.71 (p < 0.001). However, among frequent exacerbators (i.e., ≥3 exacerbations/year, n = 113) the correlation was weak (r = -0.25; p < 0.01). Smokers had less exacerbation-free weeks than non-smokers (β = -5.709, p < 0.05). More exacerbation-free weeks were related to better CRQ Total (r = 0.22, p < 0.05), Mastery (r = 0.22, p < 0.05), and Fatigue (r = 0.23, p < 0.05) scores, whereas no significant associations were found between exacerbation frequency and CRQ scores. In COPD patients with frequent exacerbations, there is substantial variation in exacerbation-free time. Exacerbation-free time may better reflect the burden of exacerbations in patients with COPD than exacerbation frequency does

Developmental Delay in Moderately Preterm-Born Children at School Entry

Objective To determine the prevalence and nature of developmental delay at preschool age in infants born moderately preterm compared with those born full-term and early preterm. Study design Parents of 927 moderate preterm infants (32-35+6 weeks gestation), 512 early preterm infants (<32 weeks gestation) and 544 full-term infants (38-41+6 weeks gestation) completed the Ages and Stages Questionnaire (ASQ) when the child was aged 43-49 months. We analyzed rates of abnormal ASQ scores and odds ratios for abnormal ASQ scores in both preterm groups compared with the full-term group. We repeated the analyses after adjustment for socioeconomic status, sex, being part of a multiple birth, and small for gestational age status. Results Abnormal (ie, >2 SDs below the mean) ASQ total scores were noted in 8.3% of moderate preterm infants, in 4.2% of full-term infants, and in 14.9% of early preterm infants. ORs of abnormal ASQ total scores were 2.1 (95% CI, 1.3-3.4) for moderate preterm infants and 4.0 (95% CI, 2.4-6.5) for early preterm infants. Both moderate and early preterm infants had more frequent problems with fine motor, communication, and personal-social functioning compared with full-term infants. Compared with full-term infants, moderate preterm infants did not have a greater prevalence of problems with gross motor functioning and problem solving, whereas early preterms did. Socioeconomic status, small for gestational age status, and sex were associated with abnormal ASQ scores in moderate preterm infants. Conclusions At preschool age, the prevalence of developmental delay in moderate preterm infants was 2-fold of that in full-term infants and one-half of that in early preterm infants