Comparisons of exacerbations and mortality among regular inhaled therapies for patients with stable chronic obstructive pulmonary disease: Systematic review and Bayesian network meta-analysis.

BACKGROUND: Although exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined. METHODS AND FINDINGS: We performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration ≥ 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50-0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.59-0.93, P[OR > 1] = 0.004; and OR = 0.86, 95% CrI 0.76-0.98, P[OR > 1] = 0.015, respectively). The results minimally changed, even in various sensitivity and covariate-adjusted meta-regression analyses. ICS/LAMA/LABA tended to lower the risk of cardiovascular mortality but did not show significant results. ICS/LAMA/LABA increased the probability of pneumonia (OR for triple therapy = 1.56; 95% CrI 1.19-2.03; P[OR > 1] = 1.000). The main limitation is that there were few RCTs including only less symptomatic patients or patients at a low risk. CONCLUSIONS: These findings suggest that triple therapy can potentially be the best option for stable COPD patients in terms of reducing exacerbation and all-cause mortality.

The therapy of idiopathic pulmonary fibrosis: what is next?

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease, characterised by progressive scarring of the lung and associated with a high burden of disease and early death. The pathophysiological understanding, clinical diagnostics and therapy of IPF have significantly evolved in recent years. While the recent introduction of the two antifibrotic drugs pirfenidone and nintedanib led to a significant reduction in lung function decline, there is still no cure for IPF; thus, new therapeutic approaches are needed. Currently, several clinical phase I-III trials are focusing on novel therapeutic targets. Furthermore, new approaches in nonpharmacological treatments in palliative care, pulmonary rehabilitation, lung transplantation, management of comorbidities and acute exacerbations aim to improve symptom control and quality of life. Here we summarise new therapeutic attempts and potential future approaches to treat this devastating disease.

Chest physiotherapy for pneumonia in children.

BACKGROUND: Pneumonia is a lung infection that causes more deaths in children aged under five years than any other single cause. Chest physiotherapy is widely used as adjuvant treatment for pneumonia. Physiotherapy is thought to help remove inflammatory exudates, tracheobronchial secretions, and airway obstructions, and reduce airway resistance to improve breathing and enhance gas exchange. This is an update of a review published in 2013. OBJECTIVES: To assess the effectiveness of chest physiotherapy with regard to time until clinical resolution in children (from birth to 18 years) of either gender with any type of pneumonia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE (22 February 2018), Embase (22 February 2018), CINAHL (22 February 2018), LILACS (22 February 2018), Web of Science (22 February 2018), and PEDro (22 February 2018). We also searched clinical trials registers (ClinicalTrials.gov and WHO ICTRP) to identify planned, ongoing, and unpublished trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any type of chest physiotherapy with no chest physiotherapy for children with pneumonia. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The primary outcomes of interest were mortality, duration of hospital stay, and time to clinical resolution. We used Review Manager 5 software to analyse data and GRADE to assess the quality of the evidence for each outcome. MAIN RESULTS: We included three new RCTs for this update, for a total of six included RCTs involving 559 children aged from 29 days to 12 years with pneumonia who were treated as inpatients. Pneumonia severity was described as moderate in one trial, severe in two trials, and was not stated in three trials. The studies assessed five different interventions: effects of conventional chest physiotherapy (3 studies, 211 children), positive expiratory pressure (1 study, 72 children), continuous positive airway pressure (CPAP) (1 study, 94 children), bubble CPAP (bCPAP) (1 study, 225 children), and assisted autogenic drainage (1 studies, 29 children). The included studies were conducted in Bangladesh, Brazil, China, Egypt, and South Africa. The studies were overall at low risk of bias. Blinding of participants was not possible in most studies, but we considered that the outcomes were unlikely to be influenced by the lack of blinding.All included studies evaluated mortality. However, three studies assessed mortality as an outcome, and only one study of bCPAP reported that deaths occurred. Three deaths occurred in children in the physiotherapy group (N = 79) and 20 deaths in children in the control group (N = 146) (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.08 to 0.90; 559 children; low-quality evidence). It is uncertain whether chest physiotherapy techniques (bCPAP, assisted autogenic drainage, and conventional chest physiotherapy) reduced hospital stay duration (days) (mean difference (MD) 0.10, 95% CI -0.56 to 0.76; 4 studies; low-quality evidence).There was variation among clinical parameters used to define clinical resolution. Two small studies found no difference in resolution of fever between children in the physiotherapy (conventional chest physiotherapy and assisted autogenic drainage) and control groups. Of five studies that considered peripheral oxygen saturation levels, only two reported that use of chest physiotherapy (CPAP and conventional chest physiotherapy) showed a greater improvement in peripheral oxygen saturation levels. However, it was unclear whether respiratory rate (breaths/min) improved after conventional chest physiotherapy (MD -2.25, 95% CI -5.17 to 0.68; 2 studies, 122 children; low-quality evidence). Two studies assessed adverse events (number of events), but only one study reported any events (RR 1.28, 95% CI 0.98 to 1.67; 2 studies, 254 children; low-quality evidence). AUTHORS' CONCLUSIONS: We could draw no reliable conclusions concerning the use of chest physiotherapy for children with pneumonia due to the small number of included trials with differing study characteristics and statistical presentation of data. Future studies should consider the following key points: appropriate sample size with adequate power to detect expected differences, standardisation of chest physiotherapy techniques, appropriate outcomes (such as duration of leukocytosis, and airway clearance), and adverse effects.

Home-based telerehabilitation in older patients with chronic obstructive pulmonary disease and heart failure: a randomised controlled trial.

Background: chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) frequently coexist in older people, reducing patients' quality of life (QoL) and increasing morbidity and mortality. Objective: we studied the feasibility and efficacy of an integrated telerehabilitation home-based programme (Telereab-HBP), 4 months long, in patients with combined COPD and CHF. The primary outcome was exercise tolerance evaluated at the 6-min walk test (6MWT). Secondary outcomes were time-to-event (hospitalisation and death), dyspnoea (MRC), physical activity profile (PASE), disability (Barthel) and QoL (MLHFQ and CAT). Study design: randomised, open, controlled, multicenter trial. Methods: the Telereab-HBP included remote monitoring of cardiorespiratory parameters, weekly phone-calls by the nurse, and exercise programme, monitored weekly by the physiotherapist. All outcomes were studied again after 2 months of a no-intervention period. Results: in total, 112 patients were randomised, 56 per group. Their mean (SD) age was 70 (9) years, and 92 (82.1%) were male. After 4 months, the IG were able to walk further than at baseline: mean (95% CI) Δ6MWT was 60 (22.2,97.8) m; the CG showed no significant improvement: -15 (-40.3,9.8) m; P = 0.0040 between groups. In IG, the media time to hospitalisation/death was 113.4 days compared with 104.7 in the CG (P = 0.0484, log-rank test). Other secondary outcomes: MRC (P = 0.0500), PASE (P = 0.0015), Barthel (P = 0.0006), MLHFQ (P = 0.0007) and CAT (P = 0.0000) were significantly improved in the IG compared with the CG at 4 months. IG maintained the benefits acquired at 6 months for outcomes. Conclusions: this 4-month Telereab-HBP was feasible and effective in older patients with combined COPD and CHF.

The Burden of Respiratory Disease in Very-Low-Birth-Weight Infants: Changes in Perinatal Care and Outcomes in a Decade in Spain.

BACKGROUND: Advances in perinatal care have led to a significant reduction in morbidity and mortality among very-low-birth-weight (VLBW) infants. Much of this progress is related to the prevention and management of respiratory disease. OBJECTIVES: To evaluate changes in perinatal care and its influence on respiratory morbidity and mortality among VLBW infants in Spain in 2 consecutive periods (2002-2006 and 2007-2011). METHODS: This is a retrospective analysis of data prospectively collected of all VLBW infants included in the Spanish SEN1500 network. Patients with major congenital anomalies, those who died in the delivery room (DR) and infants <230 or >346 weeks of gestational age (GA) were excluded. RESULTS: During the study period, out of 27,205 eligible VLBW infants, 24,598 (90.4%) met inclusion criteria. The most striking and statistically significant results found in the second period were: (i) reduction in the proportion of "outborn" patients; (ii) an increase in prenatal steroid administration; (iii) enhanced non-invasive respiratory support in the DR and NICU; (iv) reduction in invasive mechanical ventilation, surfactant administration, and steroids for bronchopulmonary dysplasia (BPD). Moreover, survival to hospital discharge increased (83.5 vs. 84.7%; p = 0.015); however, survival without BPD increased only among the most immature (230 to 266 weeks' GA) from 26.6 to 31.6% (p < 0.001). CONCLUSIONS: Enhanced adherence to international recommendations in perinatal care and a significant reduction in mortality were found during the second period. Survival without BPD increased only among the most immature. Further investigation is needed to optimize the strategies to prevent and manage respiratory disease in this group of patients.

Pulmonary support on day 30 as a predictor of morbidity and mortality in congenital diaphragmatic hernia.

PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with significant in-hospital mortality, morbidity and length-of-stay (LOS). We hypothesized that the degree of pulmonary support on hospital day-30 may predict in-hospital mortality, LOS, and discharge oxygen needs and could be useful for risk prediction and counseling. METHODS: 862 patients in the CDH Study Group registry with a LOS ≥ 30 days were analyzed (2007-2010). Pulmonary support was defined as (1) room-air (n=320) (2) noninvasive supplementation (n=244) (3) mechanical ventilation (n=279) and (4) extracorporeal membrane oxygenation (ECMO, n=19). Cox Proportional hazards and logistic regression models were used to determine the case-mix adjusted association of oxygen requirements on day-30 with mortality and oxygen requirements at discharge. RESULTS: On multivariate analysis, use of ventilator (HR 5.1, p=.003) or ECMO (HR 19.6, p<.001) was a significant predictor of in-patient mortality. Need for non-invasive supplementation or ventilator on day-30 was associated with a respective 22-fold (p<.001) and 43-fold (p<.001) increased odds of oxygen use at discharge compared to those on room-air. CONCLUSIONS: Pulmonary support on Day-30 is a strong predictor of length of stay, oxygen requirements at discharge and in-patient mortality and may be used as a simple prognostic indicator for family counseling, discharge planning, and identification of high-risk infants.