Blochgottlieb5085

17 (1.10-1.25) per 10 µg·m

for NO

, and 1.15 (1.08-1.23) per 0.5 10

m

for BC. Hazard ratios were larger in cohort subsets with exposure levels below the EU and US limit values and possibly WHO guidelines for PM

and NO

. NO

and BC estimates remained unchanged in two-pollutant models with PM

, whereas PM

estimates were attenuated to unity. The concentration response curves showed no evidence of a threshold.

Long-term exposure to air pollution, especially from fossil fuel combustion sources such as motorised traffic, was associated with adult-onset asthma, even at levels below the current limit values.

Long-term exposure to air pollution, especially from fossil fuel combustion sources such as motorised traffic, was associated with adult-onset asthma, even at levels below the current limit values.

LAM is a rare multisystem disease with variable clinical manifestations and differing rates of progression that make management decisions and giving prognostic advice difficult. We used machine learning to identify clusters of associated features which could be used to stratify patients and predict outcomes in individuals.

Using unsupervised machine learning we generated patient clusters using data from 173 women with LAM from the UK and 186 replication subjects from the NHLBI LAM registry. read more Prospective outcomes were associated with cluster results.

Two and three-cluster models were developed. A three-cluster model separated a large group of subjects presenting with dyspnoea or pneumothorax from a second cluster with a high prevalence of angiomyolipoma symptoms (p=0.0001) and TSC (p=0.041). The third cluster were older, never presented with dyspnoea or pneumothorax (p=0.0001) and had better lung function. Similar clusters were reproduced in the NHLBI cohort. Assigning patients to clusters predicted prospective outcomes in a two-cluster model future risk of pneumothorax was 3.3 fold (95% C.I. 1.7-5.6) greater in cluster one than two (p=0.0002). Using the three-cluster model, the need for intervention for angiomyolipoma was lower in clusters two and three than cluster one (p<0.00001). In the NHLBI cohort, the incidence of death or lung transplant was much lower in clusters two and three (p=0.0045).

Machine learning has identified clinically relevant clusters associated with complications and outcome. Assigning individuals to clusters could improve decision making and prognostic information for patients.

Machine learning has identified clinically relevant clusters associated with complications and outcome. Assigning individuals to clusters could improve decision making and prognostic information for patients.We investigated the prevalence of chronic cough, and its association with work ability and sick leave in the general population.Data were analysed from the Respiratory Health in Northern Europe (RHINE) III cohort (n=13 500), of which 11 252 had also participated in the RHINE II 10 years earlier, a multi-centre study in Northern Europe. Participants answered a questionnaire on chronic cough, employment factors, smoking, and respiratory comorbidities.Non-productive chronic cough was found in 7% and productive chronic cough in 9% of the participants. Participants with non-productive cough were more often female, and participants with productive cough were more often smokers and had a higher BMI than those without cough. Participants with chronic cough more often reported >7 days of sick leave in the preceding year than those without cough ("non-productive cough" 21%; "productive cough" 24%; p7 days of sick leave at follow-up than those without cough. These associations remained significant after adjusting for cough at follow-up and other confounding factors.Chronic cough was found in around one in six participants and was associated with more sick leave. Chronic cough 10 years earlier was associated with lower work ability and sick leave at follow-up. These associations were not explained by studied comorbidities. This indication of negative effects on employment from chronic cough needs to be recognised.

Early disease morbidity has been associated with asthma persistence in wheezing preschoolers; however, whether asthma control trajectories shortly after diagnosis could influence remission is unknown. We examined the association between asthma control trajectories 2 years post-diagnosis in preschoolers and subsequent disease remission.

We conducted a multicenter population-based retrospective cohort study consisting of 48 687 children with asthma diagnosed before 5 years old and born between 1990 and 2013 in 4 Canadian provinces who had prolonged disease activity post-diagnosis. Prolonged disease activity was defined as ≥1 medical visit or medication for asthma every 6-month period for ≥4 of the 6 periods post-diagnosis. Follow-up began at 3 years post-diagnosis (at cohort entry). Remission was defined as two consecutive years without drug claims or medical visits for asthma or asthma-like conditions following cohort entry. Asthma control trajectories, ascertained over four 6-month periods following diagnosis using a validated index, were classified as

,

,

,

, and

. Adjusted Cox models estimated associations between asthma control trajectories and time-to-remission. A random-effects meta-analysis summarised province-specific Hazard Ratios (HRs).

The pooled remission rate was 8.91 (95%CI 8.80,9.02)/100 person-years. Compared to children

, poorer asthma control was associated with incrementally lower HRs (95%CI) of remission in 4 other trajectories

, 0.89 (0.82,0.96);

, 0.78 (0.71,0.85);

, 0.68 (0.62,0.75);

, 0.52 (0.45,0.59).

Asthma control trajectories 2 years following a diagnosis in preschool were associated with remission, highlighting the clinical relevance of documenting control trajectories in early life.

Asthma control trajectories 2 years following a diagnosis in preschool were associated with remission, highlighting the clinical relevance of documenting control trajectories in early life.

Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies.

A genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 European-descent children treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed.

Ten independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10

).