Persistent Asthma Is Associated With Carotid Plaque in MESA.

Background Asthma and atherosclerotic cardiovascular disease share an underlying inflammatory pathophysiology. We hypothesized that persistent asthma is associated with carotid plaque burden, a strong predictor of atherosclerotic cardiovascular disease events. Methods and Results The MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults free of known atherosclerotic cardiovascular disease at baseline. Subtype of asthma was determined at examination 1. Persistent asthma was defined as asthma requiring use of controller medications, and intermittent asthma was defined as asthma without controller medications. B-mode carotid ultrasound was performed to detect carotid plaques (total plaque score [TPS], range 0-12). Multivariable regression modeling with robust variances evaluated the association of asthma subtype and carotid plaque burden. The 5029 participants were a mean (SD) age of 61.6 (10.0) years (53% were women, 26% were Black individuals, 23% were Hispanic individuals, and 12% were Chinese individuals). Carotid plaque was present in 50.5% of participants without asthma (TPS, 1.29 [1.80]), 49.5% of participants with intermittent asthma (TPS, 1.25 [1.76]), and 67% of participants with persistent asthma (TPS, 2.08 [2.35]) (P≤0.003). Participants with persistent asthma had higher interleukin-6 (1.89 [1.61] pg/mL) than participants without asthma (1.52 [1.21] pg/mL; P=0.02). In fully adjusted models, persistent asthma was associated with carotid plaque presence (odds ratio, 1.83 [95% confidence interval, 1.21-2.76]; P<0.001) and TPS (ß=0.66; P<0.01), without attenuation after adjustment for baseline interleukin-6 (P=0.02) or CRP (C-reactive protein) (P=0.01). Conclusions Participants with persistent asthma had higher carotid plaque burden and higher levels of inflammatory biomarkers, compared with participants without asthma. Adjustment for baseline inflammatory biomarkers did not attenuate the association between carotid plaque and asthma subtype, highlighting the increased atherosclerotic cardiovascular disease risk among those with persistent asthma may be multifactorial.

The effect of inhaled hypertonic saline on lung structure in children aged 3-6 years with cystic fibrosis (SHIP-CT): a multicentre, randomised, double-blind, controlled trial.

BACKGROUND: In the Saline Hypertonic in Preschoolers (SHIP) study, inhaled 7% hypertonic saline improved the lung clearance index in children aged 3-6 years with cystic fibrosis, but it remained unclear whether improvement is also seen in structural lung disease. We aimed to assess the effect of inhaled hypertonic saline on chest CT imaging in children aged 3-6 years with cystic fibrosis. METHODS: Children with cystic fibrosis were enrolled in this multicentre, randomised, double-blind, controlled study at 23 cystic fibrosis centres in Spain, Denmark, the Netherlands, Italy, France, Belgium, the USA, Canada, and Australia. Eligible participants were children aged 3-6 years who were able to cooperate with chest CT imaging and comply with daily nebuliser treatment. Participants were randomly assigned 1:1 to receive inhaled 2 puffs of 100 µg salbutamol followed by 4mL of either 7% hypertonic saline or 0·9% isotonic saline twice per day for 48 weeks. Randomisation was stratified by age in North America and Australia, and by age and country in Europe. Chest CTs were obtained at baseline and 48 weeks and scored using the Perth-Rotterdam Annotated Grid Morphometric Analysis for Cystic Fibrosis (PRAGMA-CF) method. The primary outcome was the difference between groups in the percentage of total lung volume occupied by abnormal airways (PRAGMA-CF %Disease) measured by chest CT at 48 weeks. Analysis was by intention-to-treat. This study is registered with Clinicaltrials.gov, NCT02950883. FINDINGS: Between May 24, 2016, and Dec 18, 2019, 134 children were assessed for inclusion. 18 patients were excluded (nine had incomplete or unsuccessful chest CT at enrolment visit, two could not comply with CT training, two had acute respiratory infection, two withdrew consent, two for reasons unknown, and one was already on hypertonic saline). 116 participants were enrolled and randomly assigned to hypertonic saline (n=56) or isotonic saline (n=60). 12 patients dropped out of the study (seven in the hypertonic saline group and five in the isotonic saline group). Mean PRAGMA-CF %Disease at 48 weeks was 0·88% (95% CI 0·60-1·16) in the hypertonic saline group and 1·55% (1·25-1·84) in the isotonic saline group (mean difference 0·67%, 95% CI 0·26-1·08; p=0·0092) based on a linear regression model adjusted for baseline %Disease values and baseline age. Most adverse events in both groups were rated as mild, and the most common adverse event in both groups was cough. INTERPRETATION: Inhaled hypertonic saline for 48 weeks had a positive effect on structural lung changes in children aged 3-6 years with cystic fibrosis relative to isotonic saline. This is the first demonstration of an intervention that alters structural lung disease in children aged 3-6 years with cystic fibrosis. FUNDING: Cystic Fibrosis Foundation.

Persistent Asthma Is Associated With Increased Risk for Incident Atrial Fibrillation in the MESA.

BACKGROUND: Asthma and atrial fibrillation (AF) share an underlying inflammatory pathophysiology. We hypothesized that persistent asthmatics are at higher risk for developing AF and that this association would be attenuated by adjustment for baseline markers of systemic inflammation. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective longitudinal study of adults free of cardiovascular disease at baseline. Presence of asthma was determined at exam 1. Persistent asthma was defined as asthma requiring use of controller medications. Intermittent asthma was defined as asthma without use of controller medications. Participants were followed for a median of 12.9 (interquartile range, 10-13.6) years for incident AF. Multivariable Cox regression models were used to assess associations of asthma subtype and AF. RESULTS: The 6615 participants were a mean (SD) 62.0 (10.2) years old (47% male, 27% black, 12% Chinese, and 22% Hispanic). AF incidence rates were 0.11 (95% CI, 0.01-0.12) events/10 person-years for nonasthmatics, 0.11 (95% CI, 0.08-0.14) events/10 person-years for intermittent asthmatics, and 0.19 (95% CI, 0.120.49) events/10 person-years for persistent asthmatics (log-rank P=0.008). In risk-factor adjusted models, persistent asthmatics had a greater risk of incident AF (hazard ratio, 1.49 [95% CI, 1.03-2.14], P=0.03). IL (Interleukin)-6 (hazard ratio, 1.26 [95% CI, 1.13-1.42]), TNF (tumor necrosis factor)-α receptor 1 (hazard ratio, 1.09 [95% CI, 1.08-1.11]) and D-dimer (hazard ratio, 1.10 [95% CI, 1.02-1.20]) predicted incident AF, but the relationship between asthma and incident AF was not attenuated by adjustment for any inflammation marker (IL-6, CRP [C-reactive protein], TNF-α R1, D-dimer, and fibrinogen). CONCLUSIONS: In a large multiethnic cohort with nearly 13 years follow-up, persistent asthma was associated with increased risk for incident AF. This association was not attenuated by adjustment for baseline inflammatory biomarkers.