Cystic fibrosis patients at risk for disease progression marked by decline in FEV1% predicted: development of the cystic fibrosis risk of disease progression score

BackgroundCystic fibrosis (CF) is one of the most common recessively inherited disorders diagnosed in early childhood in the United States. Determining the phenotype of CF patients likely to experience a significant drop in FEV1% predicted will help target efforts for mitigating this deleterious disorder.MethodsThis retrospective cohort study evaluated potential risk variables that account for the decline in FEV1% predicted in 81 CF patients treated at Miller Children's and Women's Hospital, CA. Cystic fibrosis risk of disease progression (CF RD-Pro) score was evaluated as a tool to identify high-risk patients for accelerated disease progression (event = drop in FEV1% predicted ≥10 percentage points) based on risk variables identified as significant.ResultsROC analysis determined classification of high versus low-moderate risk of FEV1% decline during year two based on RD-Pro score. Scores ≥2 applied as threshold for high-risk revealed relatively good validity estimates: sensitivity =82.8%, specificity =66.7%, PVP =77.4%, PVN =73.7%, and correct classification =76%. Patients with CF RD-Pro scores suggestive of high (≥2 points) vs. low-moderate (<2 points) risk were nearly 10 times more likely to experience significant disease progression (OR 9.6, 95% CI, 2.6-36.1, P=0.001).ConclusionsIdentification of patients at high risk for significant decline in lung function will enable address of potential therapeutic modalities, environmental exposures, and behavioral variants that may improve outcomes in these patients. The power of the CF RD-Pro Score lies in its simplicity. Our study provides a novel readily available score, which incorporates body mass index (BMI) and Staphylococcus aureus infection, both being alterable targets for slowing CF progression

Immune Response to SARS-CoV-2 in an Asymptomatic Pediatric Allergic Cohort

Disease-specific COVID-19 pediatric comorbidity has not been studied effectively to date. Atopy and food anaphylaxis disease states require improved characterization of SARS-CoV-2 infection risk. To provide the first such characterization, we assessed serum samples of a highly atopic, food anaphylactic, asymptomatic pediatric cohort from across the US during the height of the pandemic. From our biobank, 172 pediatric patient serum samples were characterized specific to atopic, food anaphylactic, and immunologic markers in the US at the beginning of the pandemic, from 1 February to 20 April 2020. Clinical and demographic data were further analyzed in addition to sample analysis for SARS-CoV-2 IgM and IgG ELISA. SARS-CoV-2 antibody results were positive in six patients (4%). Nearly half of the pediatric patients had a history of asthma (49%). Total IgE, total IgG, and IgG1-3 were similar in those positive and negative to SARS-CoV-2. Median total IgG4 in the SARS-CoV-2 positive group was nearly three times (p-value = 0.02) that of the negative group. Atopy controller medications did not confer additional benefit. Our data suggest that food anaphylaxis and highly atopic children are not at increased risk for SARS-CoV-2 seropositivity. This specific population appears either at equal or potentially less risk than the general population. Total and specific IgG4 may be a novel predictor of SARS-CoV-2 infection risk specific to the allergic pediatric population

Impact of a Large Fire and Subsequent Pollution Control Failure at a Coke Works on Acute Asthma Exacerbations in Nearby Adult Residents

Clairton, Pennsylvania, is home to the largest coke works facility in the United States (US). On 24 December 2018, a large fire occurred at this facility and damaged pollution control equipment. Although repairs were not completed for several months, production continued at pre-fire capacity and daily emissions increased by 24 to 35 times, with multiple exceedances of monitored levels of outdoor air pollution (OAP). The aim of this study was to objectively evaluate the impact of this industrial incident and resultant OAP exceedances on asthma morbidity. We assessed pre-fire and post-fire rate ratios (RR) of outpatient and emergency department (ED) visits for asthma exacerbations among nearby adult residents. Pre-fire versus post-fire RRs increased for both visit types: RR = 1.82 (95% CI: 1.30, 2.53; p < 0.001) and 1.84 (95% CI: 1.05, 3.22; p = 0.032) for outpatient and ED visits, respectively. Additionally, total visit rates increased on days with OAP exceedances: RR = 2.47 (95% CI: 1.52, 4.01; p < 0.0001), 1.58 (95% CI: 1.00, 2.48; p = 0.048) and 1.79 (95% CI: 1.27, 2.54; p = 0.001) for PM2.5, SO2, and H2S exceedance days, respectively. These results show a near doubling of acute visits for asthma exacerbations in nearby adult residents during this industrial incident and underscore the need for prompt remediation and public notification of OAP exceedances to prevent adverse health impacts

The relationship of the bronchodilator response phenotype to poor asthma control in children with normal spirometry.

To determine the relationship of poor asthma control to bronchodilator response (BDR) phenotypes in children with normal spirometry.Children with asthma were assessed for clinical indexes of poorly controlled asthma. Pre- and post-bronchodilator spirometry were performed, and the percent BDR was determined. Multivariate logistic regression assessed the relationship of the clinical indices to BDR at ≥ 8%, ≥ 10%, and ≥ 12% BDR thresholds.There were 510 controller naïve children and 169 on controller medication. In the controller naïve population the mean age (± 1 SD) was 9.5 (3.4); 57.1% were male, 85.7% Hispanic. Demographics were similar in both populations. In the adjusted profile, significant clinical relationships were found particularly to positive BDR phenotypes ≥ 10% and ≥ 12% versus negative responses including younger age, (OR 2.0, 2.5; P < .05), atopy (OR 1.9, 2.6; P < .01), nocturnal symptoms in females (OR 3.4, 3.8; P < .01); β₂ agonist use (OR 1.7, 2.8; P < .01); and exercise limitation (OR 2.2, 2.5; P < .01) only in the controller naïve population.The BDR phenotype ≥ 10% is significantly related to poor asthma control, providing a potentially useful objective tool in controller naïve children even when the pre-bronchodilator spirometry result is normal

The relationship of the bronchodilator response phenotype to poor asthma control in children with normal spirometry.

To determine the relationship of poor asthma control to bronchodilator response (BDR) phenotypes in children with normal spirometry.Children with asthma were assessed for clinical indexes of poorly controlled asthma. Pre- and post-bronchodilator spirometry were performed, and the percent BDR was determined. Multivariate logistic regression assessed the relationship of the clinical indices to BDR at ≥ 8%, ≥ 10%, and ≥ 12% BDR thresholds.There were 510 controller naïve children and 169 on controller medication. In the controller naïve population the mean age (± 1 SD) was 9.5 (3.4); 57.1% were male, 85.7% Hispanic. Demographics were similar in both populations. In the adjusted profile, significant clinical relationships were found particularly to positive BDR phenotypes ≥ 10% and ≥ 12% versus negative responses including younger age, (OR 2.0, 2.5; P < .05), atopy (OR 1.9, 2.6; P < .01), nocturnal symptoms in females (OR 3.4, 3.8; P < .01); β₂ agonist use (OR 1.7, 2.8; P < .01); and exercise limitation (OR 2.2, 2.5; P < .01) only in the controller naïve population.The BDR phenotype ≥ 10% is significantly related to poor asthma control, providing a potentially useful objective tool in controller naïve children even when the pre-bronchodilator spirometry result is normal

The Relationship of the Bronchodilator Response Phenotype to Poor Asthma Control in Children with Normal Spirometry

To determine the relationship of poor asthma control to bronchodilator response (BDR) phenotypes in children with normal spirometry.Children with asthma were assessed for clinical indexes of poorly controlled asthma. Pre- and post-bronchodilator spirometry were performed, and the percent BDR was determined. Multivariate logistic regression assessed the relationship of the clinical indices to BDR at ≥ 8%, ≥ 10%, and ≥ 12% BDR thresholds.There were 510 controller naïve children and 169 on controller medication. In the controller naïve population the mean age (± 1 SD) was 9.5 (3.4); 57.1% were male, 85.7% Hispanic. Demographics were similar in both populations. In the adjusted profile, significant clinical relationships were found particularly to positive BDR phenotypes ≥ 10% and ≥ 12% versus negative responses including younger age, (OR 2.0, 2.5; P < .05), atopy (OR 1.9, 2.6; P < .01), nocturnal symptoms in females (OR 3.4, 3.8; P < .01); β₂ agonist use (OR 1.7, 2.8; P < .01); and exercise limitation (OR 2.2, 2.5; P < .01) only in the controller naïve population.The BDR phenotype ≥ 10% is significantly related to poor asthma control, providing a potentially useful objective tool in controller naïve children even when the pre-bronchodilator spirometry result is normal