Abstract

Background

Accurate risk prediction of exacerbations is pivotal in severe asthma management. Multiple risk factors are at play, but the pathway of risk prediction remains unclear.

Research Question

How do the interplays of clinically relevant predictors lead to severe exacerbations in patients with severe asthma?

Study Design and Methods

Patients with severe asthma (n = 6,814, aged ≥ 18 years), biologic naive, were identified from the Severe Asthma Registry (2017-2021). Relevant predictors covered demographics, lung function, inflammation biomarkers, health care use, medications, exacerbation history, and comorbidities. A Bayesian network, representing the prediction process of severe exacerbations, was obtained by combining expert knowledge and machine learning algorithms. Internal validation was performed. The proposed influence diagram integrated decision and utility nodes into the prediction pathway.

Results

The Bayesian network analysis revealed that blood eosinophil count, fractional exhaled nitric oxide level, and FEV1 directly influenced the transition between prior and future severe exacerbations. The presence of chronic rhinosinusitis indirectly affected such transition by directly influencing blood eosinophil count, fractional exhaled nitric oxide, and % predicted FEV1. Macrolide use independently affected history of exacerbations to influence future severe asthma exacerbations. Model discrimination was moderate in 10-fold cross-validation and leave-1-country-out cross-validation, and model calibration was high in train-test data.

Interpretation

This study identified an essential prediction pathway of severe exacerbation, which involves the influence of chronic rhinosinusitis on the immediate predictors of risk transition from current to future severe asthma exacerbations. Macrolide use was another essential prediction pathway identified. The findings support shared clinical decision-making in severe asthma treatment.

BACKGROUND: Because of risk of severe asthma exacerbations, current Global Initiative for Asthma recommendations advise against use of short-acting beta-agonists (SABAs) alone as the first step in treating mild asthma. It is unclear if everyone with mild asthma carries equal risk for severe asthma exacerbations. RESEARCH QUESTION: Is there a subgroup of patients with mild asthma with very low risk of severe asthma exacerbations? STUDY DESIGN AND METHODS: This study cohort used administrative claims data for patients ages 2 to 18 years with intermittent asthma enrolled in Ohio Medicaid Managed Care Plans for 3 consecutive years. A low-risk group was identified for the first 2 years; in the third year, risk of severe asthma exacerbations was compared among the low-risk group and the rest of the cohort. RESULTS: A total of 13,208 patients met inclusion criteria. In the third year, among 3,935 low-risk patients, rates of asthma hospitalization, emergency department visits, and urgent care visits for those with 0 to 2 SABA canisters dispensed per year were 3 (0.08%), 37 (0.97%), and 21 (0.55%), respectively, with a relative risk of hospitalization of 0.17 (95% CI, 0.06-0.52) and a relative risk of severe asthma exacerbation of 0.18 (95% CI, 0.13-0.27) compared with high-risk patients. In the low-risk cohort, the number of patients needed to treat to prevent 1 hospitalization was 5,535. The cost to prevent 1 hospitalization using a single inhaler of inhaled corticosteroids per year was $779,716. INTERPRETATION: Our results show that among patients with mild asthma, there is a subgroup of low-risk patients with lower risk of hospitalization and severe asthma exacerbation in which current Global Initiative for Asthma recommendations for first-step treatment may neither be needed nor cost-effective.

https://journal.chestnet.org/article/S0012-3692(25)05124-4/fulltext

Background

High doses of a maintenance inhaled corticosteroids (ICSs) in asthma may achieve only modest additional clinical benefit beyond low-to-medium doses and are associated with an increased risk of adverse systemic effects. The ICS dose-response relationship when administered as maintenance combination ICS/long-acting beta2-agonist (LABA) therapy is uncertain.

Research Question

What is the ICS dose-response of maintenance ICS/LABA therapy?

Study Design and Methods

A systematic review was conducted using MEDLINE, Embase, the Cochrane Register of Controlled Trials, and ClinicalTrials.gov databases to identify randomized controlled trials that allocated participants to > 1 ICS dose category, per Global Initiative for Asthma categorization, administered in combination with ICS/LABA inhalers. Meta-analysis compared outcomes of high-dose (HD) and medium-dose (MD), HD and low-dose (LD), and MD and LD ICS/LABA. The primary outcome was the proportion of participants with ≥ 1 severe asthma exacerbation; secondary outcomes were patient-reported outcome measures of asthma control, spirometry, and serious adverse events. Certainty of evidence was assessed by using the Grading of Recommendations, Assessment, Development and Evaluations domains.

Results

Twelve randomized controlled trials (6,373 participants) were identified: 7 comparing HD vs MD ICS/LABA, 1 HD vs LD ICS/LABA, and 4 MD vs LD ICS/LABA. HD vs MD ICS/LABA reduced the odds of a severe asthma exacerbation (Peto’s OR, 0.81; 95% CI, 0.67-0.98) with high certainty. There were no other clinically important differences in efficacy or safety outcomes of HD vs MD ICS/LABA. There was no difference in all outcomes comparing HD with LD or MD with LD ICS/LABA.

Interpretation

Our results showed that maintenance HD ICS/LABA reduced the odds of a severe exacerbation by about 20% compared with MD ICS/LABA. The absolute reduction in severe exacerbation risk with HD ICS/LABA is determined by patients’ exacerbation risk, and this effect size may be clinically relevant for patients if this risk is high. Comparisons of other doses of ICS/LABA were limited by the number of identified studies, although no large difference in effect sizes were observed.

BACKGROUND

Air pollution, particularly fine particulate matter (PM_2.5), has been consistently linked to respiratory morbidity, including asthma exacerbations. However, few studies have examined these relationships using statewide zip code–level panels with within-zip identification at a granular zip code level over time.

OBJECTIVE

To assess the association between short-term PM_2.5 exposure and the odds of any pediatric asthma admission from 2006 to 2021 across zip codes, with the goal of identifying patterns of environmental risk for asthma exacerbations.

METHODS

We analyzed zip code–level (zip-day) data from 2006 to 2021, combining hospitalization records for asthma admissions with environmental measures of conventional short-term PM_2.5 exposures, moving averages MA(0–1) and MA(0–3). Zip fixed-effects logistic regression was used to estimate the association between PM_2.5 exposure and the odds of asthma admission, adjusting for day of week, season, flexible calendar time within year, and meteorology (temperature and vapor pressure).

RESULTS

Higher short-term PM_2.5 was associated with higher odds of asthma admission at the zip-day level. Specifically, each +10 μg/m³ increase corresponded to approximately 4% to 5% higher odds (odds ratio ≈ 1.045; 95% CI 1.006–1.085). This relationship was observed under standard moving-average windows after adjustment for meteorological and temporal factors.

CONCLUSIONS

Acute increases in PM_2.5 are associated with a statistically detectable increase in asthma admission odds at the zip code level. Targeted strategies at the zip code level that respond to short-term air quality fluctuations may help reduce asthma-related health burdens.

POLICY IMPLICATIONS

These findings highlight the urgent need for public health interventions and environmental regulations that address short-term increases in air pollution, not just annual averages. Local and state-level policies aimed at monitoring, forecasting, and rapidly mitigating PM_2.5 surges could play a critical role in preventing asthma exacerbations, particularly in urban and vulnerable communities.

Objectives: A fixed combination of long-acting 2-agonists (LABA) plus inhaled corticosteroids

(ICS) has never been proven to reduce asthma exacerbations vs ICS alone in children. This

12-month, double-blind, randomized study in 341 children (age range, 4 to 11 years) with asthma

uncontrolled on ICS investigated whether a novel regimen using budesonide/formoterol for

maintenance and reliever therapy (Symbicort maintenance and relief therapy [SMART]) [Symbicort;

AstraZeneca R&D; Lund, Sweden] could reduce exacerbations.

Methods: Patients received SMART (budesonide/formoterol 80/4.5 g qd maintenance plus

additional inhalations for symptom relief), budesonide/formoterol 80/4.5 g qd for maintenance

(fixed combination), or higher-dose budesonide 320 g qd (fixed-dose budesonide). Blinded

as-needed medication (terbutaline 0.4 g) was provided in both fixed-dose groups.

Results: SMART prolonged the time to first exacerbation vs fixed-dose budesonide (p0.02) and

fixed-dose combination (p<0.001). Rates of exacerbation requiring medical intervention were reduced

by 70 to 79% with SMART vs fixed-dose budesonide and fixed-dose combination (0.08/patient vs

0.28/patient and 0.40/patient, respectively; both p<0.001). Mild exacerbation days and awakenings were

significantly lower with SMART; yearly growth improved by 1.0 cm vs fixed-dose budesonide (p<0.01).

Conclusion: The SMART regimen using budesonide/formoterol for both maintenance and as-needed

symptom relief reduces the exacerbation rate compared with both fixed-dose combination and higher

fixed-dose ICS alone in children with asthma. (CHEST 2006; 130:1733–1743)

Key words: asthma; budesonide/formoterol; inhaled corticosteroids; long-acting 2-agonist; pediatric; Symbicort

Abbreviations: ACTHadrenocorticotrophic hormone; AEadverse events; ANOVAanalysis of variance;EDemergency

department; ICSinhaled corticosteroids; LABAlong-acting 2-agonists; PEFpeak expiratory flow; SMARTSymbicort

maintenance and relief therapy

Bisgaard et. al. (Chest, 2008) Budesonide-Formoterol Maintenance Plus Reliever Therapy, a New Strategy in Pediatric Asthma (1).pdf

Background

Combination inhaled corticosteroid–formoterol reliever monotherapy reduces the rate of asthma attacks compared to short-acting β2-agonist (SABA) reliever monotherapy in adults. Its comparative efficacy in children has not been established.

Methods

CARE was a 52-week, open-label, parallel-group, multicenter, superiority, randomized controlled trial in children aged 5–15 years with asthma using SABA reliever monotherapy at 15 clinical trials sites in New Zealand. Participants were randomly assigned (1:1) to either budesonide 50 μg–formoterol 3 μg, two actuations as needed, or salbutamol 100 μg, two actuations as needed. The primary outcome was asthma attacks as rate per participant per year. This trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12620001091998.

Findings

From Jan 28, 2021, to June 23, 2023, we assessed 382 participants for eligibility. We randomly assigned 360 (94%) participants to treatment (179 [50%] to the budesonide–formoterol group and 181 [50%] to the salbutamol group). The annualized rate of asthma attacks was lower in the budesonide–formoterol group than in the salbutamol group—cluster-adjusted rates 0·23 versus 0·41 per participant per year (relative rate 0·55 [95% CI 0·35–0·86]; p=0·012). The number of participants with at least one adverse event was 162 (91%) in the budesonide–formoterol group and 167 (92%) in the salbutamol group (odds ratio 0·79 [95% CI 0·35–1·79]).

Interpretation

In children aged 5–15 years with mild asthma, budesonide–formoterol reliever monotherapy is superior to salbutamol for preventing asthma attacks, with a similar safety profile.

Funding

Health Research Council of New Zealand, Cure Kids New Zealand, and the Barbara Basham Medical Charitable Trust (managed by Perpetual Guardian).

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00861-X/fulltext

Abstract

This study evaluates how long-term use (i.e., at least one year) of three types of residential ventilation interventions, some of which are coupled with improved central filtration, affects asthma outcomes in adults by reducing exposure to indoor air pollutants. We conducted a quasi-randomized, parallel-group intervention trial involving 51 adults with physician-diagnosed asthma across 40 homes. Each home received one of three interventions: continuous energy recovery ventilators (ERVs), intermittent central-fan-integrated supply (CFIS) systems, or continuous bathroom exhaust fan(s). Homes with ERV or CFIS systems also received central air filtration upgrades to MERV 10 filters, replaced quarterly. Indoor and outdoor air pollutants were measured quarterly. Asthma Control Test (ACT) scores were collected monthly and health-related quality of life and stress were assessed at baseline and endline. Overall, the interventions led to a 6.3 % increase in ACT scores (p < 0.001) over a > 12-month duration, while the increase was 5.4 % when comparing ACT scores within the initial 12-month window following interventions (p < 0.001). The ERV group experienced the greatest improvement, with an 8.4 % increase in ACT scores (p < 0.001) and an increase in the proportion of participants with well-controlled asthma from 50 % to 86 % (p = 0.030). Additionally, the association between reduced indoor pollutant concentrations and asthma outcomes showed that a one standard deviation decrease in indoor NO₂ (IQR: 9.3 ppb) was associated with a 7.1 % increase in ACT scores (p = 0.034). Subgroup analysis indicates that asthma improvements were greater among participants aged ≥45, Black/African American individuals, and those with incomes below $75,000, compared to their respective comparison groups, driven in part by having lower baseline ACT scores.

Abstract

Purpose

The effects of in-home environmental exposures (IHEEs) on asthma are challenging to examine in populations because information on asthma triggers is usually absent. We leveraged data from electronic health records (EHRs) to investigate the associations of residential cockroach and rodent exposures with lung function among children with asthma.

Methods

We merged clinical pulmonary function test data from EHRs for children with asthma from a large safety net hospital in the Northeast United States with publicly available geospatial data matched to patient addresses. Predicted presence of key IHEE asthma triggers, cockroaches and rodents, were included as main exposures and housing parcel features and census tract characteristics were included as potential confounders in a sensitivity analysis. We fit latent Bayesian hierarchical models of percent predicted forced expiratory volume in one second (FEV1%).

Results

The study population of 1070 children had a mean age of 10.2 years and 75 % identified as Black, many living in historically segregated neighborhoods. In models adjusted for individual characteristics, we observed 2.26 (95 % credible interval, 95 %CrI: − 3.72, − 0.79) and 2.58 (95 %CrI: − 4.54, − 0.66) percentage points (pp) lower FEV1% from a one-unit increase in the log-odds of the probability of cockroach and rodent presence, respectively. The association with lung function increased in magnitude for cockroach exposure but attenuated for rodent exposure in sensitivity analyses.

Conclusions

IHEEs were associated with worse lung function among children with asthma in a safety net population. The observed associations underscore how injustices in housing and neighborhood characteristics contribute to asthma morbidity.

Families often struggle to manage their child's asthma. Clinicians caring for children with asthma struggle too as they are tasked with balancing the limited time available in clinic and the need to provide comprehensive care. As a direct consequence, critical gaps in asthma care remain with respect to asthma education and the identification and reduction of environmental asthma triggers in the home. A home visit model that augments clinic-based care is a viable way to fill gaps in understanding, address incomplete adherence patterns, improve disease control by shifting the focus of asthma management to reduction of environmental asthma triggers, and bring cost savings to the health care system.Home Visits, Reduction of Triggers in the Home.pdf

Abstract

Purpose Home Modification and Asthma Triggers.pdf

The study was conducted to investigate the effects of a nursing intervention aimed at home environment modification on symptom control, quality of life, and the number of triggers in children with allergic rhinitis.

Design and methods

This one-to-one, parallel-arm, randomized controlled trial was conducted with a pre-test/post-test design. The study used stratified sampling method. A total of 52 participants were randomly assigned to the intervention group (n = 26) and the control group (n = 26). The intervention group received education on home environment modification and the child was provided with anti-allergic bedding set. The control group continued with routine practices. Statistical significance was set at p < 0.05.

Results

After the nursing intervention for home environment modification, a significant difference was found between the groups in terms of the number of home environment triggers (p < 0.05). According to the mean scores of the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire, no significant difference was found between the groups (p > 0.05). There was no significant difference between the groups in terms of the mean scores for nasal discharge, nasal congestion, sneezing, nasal itching, and eye itching (p > 0.05) after the nursing intervention for home environment modification.

Conclusion

The findings indicate that the nursing intervention for home environment modification is an effective method in reducing the number of triggers in the home environment. However, no significant impact was observed on symptom control and quality of life.