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Background: Severe exacerbation of chronic obstructive pulmonary disease (COPD) is a trajectory-changing life event for patients and a major contributor to health system costs. This study evaluates the real-world impact of a primary care, integrated disease management (IDM) programme on acute health service utilisation (HSU) in the Canadian health system.

Methods: Interrupted time series analysis using retrospective health administrative data, comparing monthly HSU event rates 3 years prior to and 3 years following the implementation of COPD IDM. Primary outcomes were COPD-related hospitalisation and emergency department (ED) visits. Secondary outcomes included hospital bed days and all-cause HSU.

Results: There were 2451 participants. COPD-related and all-cause HSU rates increased in the 3 years prior to IDM implementation. With implementation, there was an immediate decrease (month 1) in COPD-related hospitalisation and ED visit rates of -4.6 (95% CI: -7.76 to -1.39) and -6.2 (95% CI: -11.88, -0.48) per 1000 participants per month, respectively, compared with the counterfactual control group. After 12 months, COPD-related hospitalisation rates decreased: -9.1 events per 1000 participants per month (95% CI: -12.72, -5.44) and ED visits -19.0 (95% CI: -25.50, -12.46). This difference nearly doubled by 36 months. All-cause HSU also demonstrated rate reductions at 12 months, hospitalisation was -10.2 events per 1000 participants per month (95% CI: -15.79, -4.44) and ED visits were -30.4 (95% CI: -41.95, -18.78).

Conclusions: Implementation of COPD IDM in a primary care setting was associated with a changed trajectory of COPD-related and all-cause HSU from an increasing year-on-year trend to sustained long-term reductions. This highlights a substantial real-world opportunity that may improve health system performance and patient outcomes.

Objective: The existence of catch-up lung function growth and its predictors is uncertain. We aimed to identify lung function trajectories and their predictors in a population-based birth cohort.

Methods: We applied group-based trajectory modelling to z-scores of forced expiratory volume in 1 second (zFEV₁) and z-scores of forced vital capacity (zFVC) from 1151 children assessed at around 4, 7, 9, 10, 11, 14 and 18 years. Multinomial logistic regression models were used to test whether potential prenatal and postnatal predictors were associated with lung function trajectories.

Results: We identified four lung function trajectories: a low (19% and 19% of the sample for zFEV₁ and zFVC, respectively), normal (62% and 63%), and high trajectory (16% and 13%) running in parallel, and a catch-up trajectory (2% and 5%) with catch-up occurring between 4 and 10 years. Fewer child allergic diseases and higher body mass index z-score (zBMI) at 4 years were associated with the high and normal compared with the low trajectories, both for zFEV₁ and zFVC. Increased children's physical activity during early childhood and higher zBMI at 4 years were associated with the catch-up compared with the low zFEV₁ trajectory (relative risk ratios: 1.59 per physical activity category (1.03-2.46) and 1.47 per zBMI (0.97-2.23), respectively). No predictors were identified for zFVC catch-up growth.

Conclusion: We found three parallel-running and one catch-up zFEV₁ and zFVC trajectories, and identified physical activity and body mass at 4 years as predictors of zFEV₁ but not zFVC catch-up growth.

Rationale: Life course trajectories of lung function development and decline influence the risk for lung disease but are poorly documented.

Objective: To document lung function trajectories from childhood to mid-adult life.

Methods: We modelled forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and FEV₁/FVC at ages 9, 11, 13, 15, 18, 21, 26, 32, 38 and 45 years from a population-based cohort using latent profile analysis to identify distinct subgroups of participants with similar lung function trajectories. Regression analyses were used to assess associations between the trajectories, early life factors and postbronchodilator airflow obstruction at age 45.

Results: Among 865 participants with ≥6 measures of lung function, we identified 10 distinct FEV₁ trajectories. Most were approximately parallel except for a childhood airway hyper-responsiveness-related persistently low trajectory (3% of study population); two accelerated-decline trajectories, one of which (8%) was associated with smoking and higher adult body mass index (BMI) and a catch-up trajectory (8%). Findings for FEV₁/FVC trajectories were similar. Nine trajectories were identified for FVC: most were also approximately parallel except for a higher BMI-related accelerated-decline trajectory. The three FEV₁ trajectories leading to the lowest FEV₁ values comprised 19% of the cohort but contributed 55% of airflow obstruction at age 45.

Conclusions: Lung function trajectories to mid-adult life are largely established before adolescence, with a few exceptions: a childhood airway hyper-responsiveness-related persistently low trajectory, which starts low and gets worse with age, and accelerated adult decline trajectories associated with smoking and obesity. Adverse trajectories are associated with a high risk of airflow obstruction in mid-adult life.

Introduction: Lung graft allocation can be based on a score (Lung Allocation Score) as in the USA or sequential proposals combined with a discrete priority model as in France. We aimed to analyse the impact of allocation policy on the outcome of urgent lung transplantation (LT).

Methods: US United Network for Organ Sharing (UNOS) and French Cristal databases were retrospectively reviewed to analyse LT performed between 2007 and 2017. We analysed the mortality risk of urgent LT by fitting Cox models and adjusted Restricted Mean Survival Time. We then compared the outcome after urgent LT in the UNOS and Cristal groups using a propensity score matching.

Results: After exclusion of patients with chronic obstructive pulmonary disease/emphysema and redo LT, 3775 and 12 561 patients underwent urgent LT and non-urgent LT in the USA while 600 and 2071 patients underwent urgent LT and non-urgent LT in France. In univariate analysis, urgent LT was associated with an HR for death of 1.24 (95% CI 1.05 to 1.48) in the Cristal group and 1.12 (95% CI 1.05 to 1.19) in the UNOS group. In multivariate analysis, the effect of urgent LT was attenuated and no longer statistically significant in the Cristal database (HR 1.1 (95% CI 0.91 to 1.33)) while it remained constant and statistically significant in the UNOS database (HR 1.12 (95% CI 1.05 to 1.2)). Survival comparison of urgent LT patients between the two countries was significantly different in favour of the UNOS group (1-year survival rates 84.1% (80.9%-87.3%) vs 75.4% (71.8%-79.1%) and 3-year survival rates 66.3% (61.9%-71.1%) vs 62.7% (58.5%-67.1%), respectively).

Conclusion: Urgent LT is associated with adverse outcome in the USA and in France with a better prognosis in the US score-based system taking post-transplant survival into account. This difference between two healthcare systems is multifactorial.

Introduction: Novel therapeutic strategies are urgently needed for Mycobacterium avium complex pulmonary disease (MAC-PD). Human mesenchymal stromal cells (MSCs) can directly inhibit MAC growth, but their effect on intracellular bacilli is unknown. We investigated the ability of human MSCs to reduce bacterial replication and inflammation in MAC-infected macrophages and in a murine model of MAC-PD.

Methods: Human monocyte-derived macrophages (MDMs) were infected with M. avium Chester strain and treated with human bone marrow-derived MSCs. Intracellular and extracellular colony-forming units (CFUs) were counted at 72 hours. Six-week-old female balb/c mice were infected by nebulisation of M. avium Chester. Mice were treated with 1×10⁶ intravenous human MSCs or saline control at 21 and 28 days post-infection. Lungs, liver and spleen were harvested 42 days post-infection for bacterial counts. Cytokines were quantified by ELISA.

Results: MSCs reduced intracellular bacteria in MDMs over 72 hours (median 35% reduction, p=0.027). MSC treatment increased extracellular concentrations of prostaglandin E2 (PGE2) (median 10.1-fold rise, p=0.002) and reduced tumour necrosis factor-α (median 28% reduction, p=0.025). Blocking MSC PGE2 production by cyclo-oxygenase-2 (COX-2) inhibition with celecoxib abrogated the antimicrobial effect, while this was restored by adding exogenous PGE2. MSC-treated mice had lower pulmonary CFUs (median 18% reduction, p=0.012), but no significant change in spleen or liver CFUs compared with controls.

Conclusion: MSCs can modulate inflammation and reduce intracellular M. avium growth in human macrophages via COX-2/PGE2 signalling and inhibit pulmonary bacterial replication in a murine model of chronic MAC-PD.