Dataset Information

COPD-associated miR-145-5p is downregulated in early-decline FEV₁ trajectories in childhood asthma.

ABSTRACT:

Background

Many microRNAs (miRNAs) have been associated with asthma and chronic obstructive pulmonary disease (COPD). Longitudinal lung function growth trajectories of children with asthma-normal growth, reduced growth (RG), early decline (ED), and RG with an ED (RGED)-have been observed, with RG and RGED associated with adverse outcomes, including COPD.

Objective

Our aim was to determine whether circulating miRNAs from an early age in children with asthma would be prognostic of reduced lung function growth patterns over the next 16 years.

Methods

We performed small RNA sequencing on sera from 492 children aged 5 to 12 years with mild-to-moderate asthma from the CAMP clinical trial, who were subsequently followed for 12 to 16 years. miRNAs were assessed for differential expression between previously assigned lung function growth patterns.

Results

We had 448 samples and 259 miRNAs for differential analysis. In a comparison of the normal and the most severe group (ie, normal growth compared with RGED), we found 1 strongly dysregulated miRNA, hsa-miR-145-5p (P < 8.01E-05). This miR was downregulated in both ED groups (ie, ED and RGED). We verified that miR-145-5p was strongly associated with airway smooth muscle cell growth in vitro.

Conclusion

Our results showed that miR-145-5p is associated with the ED patterns of lung function growth leading to COPD in children with asthma and additionally increases airway smooth muscle cell proliferation. This represents a significant extension of our understanding of the role of miR-145-5p in COPD and suggests that reduced expression of miR-145-5p is a risk factor for ED of long-term lung function.

SUBMITTER: Tiwari A

PROVIDER: S-EPMC8184594 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundSmall airways are known to be affected early in the course of COPD; however, traditional spirometric indices may not accurately identify small airways disease.Research questionCan forced expiratory volume in 3 s/forced expiratory volume in 6 s (FEV3/FEV6) identify early airflow abnormalities and predict future clinically important respiratory-related outcomes, including development of COPD?Study design and methodsThe study included 832 current and former smokers with post-bronchodilator FEV1/FVC ≥ 0.7 from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Participants were classified as having a reduced pre-bronchodilator FEV3/FEV6 based on lower limit of normal (LLN) values. Repeatability analysis was performed for FEV3 and FEV6. Regression modeling was used to evaluate the relationship between baseline FEV3/FEV6 and outcome measures, including functional small airways disease, on thoracic imaging and respiratory exacerbations. Interval-censored analysis was used to assess progression to COPD.ResultsFEV3/FEV6 less than the LLN at baseline, defined as reduced compared with FEV3/FEV6 at or above the LLN, was associated with lower FEV1, poorer health status (St. George's Respiratory Questionnaire score), more emphysema, and more functional small airways disease on quantitative imaging. FEV3 and FEV6 showed excellent agreement between repeat measurements. A reduced FEV3/FEV6 was associated with increased odds of a severe respiratory exacerbation within the first year of follow-up and decreased time to first exacerbation. A low FEV3/FEV6 was also associated with development of COPD according to spirometry results (post-bronchodilator FEV1/FVC < 0.7) during study follow-up.InterpretationFEV3/FEV6 is a routinely available and repeatable spirometric index that can be useful in the evaluation of early airflow obstruction in current and former smokers without COPD. A reduced FEV3/FEV6 can identify those at risk for future development of COPD and respiratory exacerbations.Clinical trial registrationClinicalTrials.gov; No.: NCT01969344; URL: www.Clinicaltrialsgov: ClinicalTrials.gov.

Project description:Rate of FEV1 decline in COPD is heterogeneous and the extent to which inhaled corticosteroids (ICS) influence the rate of decline is unclear. The majority of previous reviews have investigated specific ICS and non-ICS inhalers and have consisted of randomised control trials (RCTs), which have specific inclusion and exclusion criteria and short follow up times. We aimed to investigate the association between change in FEV1 and ICS-containing medications in COPD patients over longer follow up times.MEDLINE and EMBASE were searched and literature comparing change in FEV1 in COPD patients taking ICS-containing medications with patients taking non-ICS-containing medications were identified. Titles, abstract, and full texts were screened and information extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool and a descriptive synthesis of the literature was carried out due to high heterogeneity of included studies.Seventeen studies met our inclusion criteria. We found that the difference in change in FEV1 in people using ICS and non-ICS containing medications depended on the study follow-up time. Shorter follow-up studies (1 year or less) were more likely to report an increase in FEV1 from baseline in both patients on ICS and in patients on non-ICS-containing medications, with the majority of these studies showing a greater increase in FEV1 in patients on ICS-containing medications. Longer follow-up studies (greater than 1 year) were more likely to report a decline in FEV1 from baseline in patients on ICS and in patients on non-ICS containing medications but rates of FEV1 decline were similar.Further studies are needed to better understand changes in FEV1 when ICS-containing medications are prescribed and to determine whether ICS-containing medications influence rate of decline in FEV1 in the long term. Results from inclusive trials and observational patient cohorts may provide information more generalisable to a population of COPD patients.

Project description:BackgroundThere are conflicting views as to whether childhood wheezing represents several discreet entities or a single but variable disease. Classification has centered on phenotypes often derived using subjective criteria, small samples, and/or with little data for young children. This is particularly problematic as asthmatic features appear to be entrenched by age 6/7. In this paper we aim to: identify longitudinal trajectories of wheeze and other atopic symptoms in early childhood; characterize the resulting trajectories by the socio-economic background of children; and identify potentially modifiable processes in infancy correlated with these trajectories.Data and methodsThe Millennium Cohort Study is a large, representative birth cohort of British children born in 2000-2002. Our analytical sample includes 11,632 children with data on key variables (wheeze in the last year; ever hay-fever and/or eczema) reported by the main carers at age 3, 5 and 7 using a validated tool, the International Study of Asthma and Allergies in Childhood module. We employ longitudinal Latent Class Analysis, a clustering methodology which identifies classes underlying the observed population heterogeneity.ResultsOur model distinguished four latent trajectories: a trajectory with both low levels of wheeze and other atopic symptoms (54% of the sample); a trajectory with low levels of wheeze but high prevalence of other atopic symptoms (29%); a trajectory with high prevalence of both wheeze and other atopic symptoms (9%); and a trajectory with high levels of wheeze but low levels of other atopic symptoms (8%). These groups differed in terms of socio-economic markers and potential intervenable factors, including household damp and breastfeeding initiation.ConclusionUsing data-driven techniques, we derived four trajectories of asthmatic symptoms in early childhood in a large, population based sample. These groups differ in terms of their socio-economic profiles. We identified correlated intervenable pathways in infancy, including household damp and breastfeeding initiation.

Dataset Information

COPD-associated miR-145-5p is downregulated in early-decline FEV₁ trajectories in childhood asthma.

Background

Objective

Methods

Results

Conclusion

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

COPD-associated miR-145-5p is downregulated in early-decline FEV1 trajectories in childhood asthma.

Background

Objective

Methods

Results

Conclusion

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

COPD-associated miR-145-5p is downregulated in early-decline FEV₁ trajectories in childhood asthma.