Suchit Kumbhare

Characteristics and Prevalence of Asthma/Chronic Obstructive Pulmonary Disease Overlap in the United States.

RATIONALE The asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) occurs in patients with fixed airway obstruction that defines COPD and with symptoms more typical of asthma. ACOS prevalence and the comorbidities associated with this syndrome have been inadequately characterized. OBJECTIVES Because this population is prone to more frequent exacerbations, we hypothesized that comorbidities associated with ACOS are higher than those with COPD, asthma, and control populations in the United States. METHODS We examined the self-reported demographics, smoking status, comorbidities, and hospitalization or emergency department (ED) visitation experience among study respondents older than 35 years of age (n = 90,851) in the Behavioral Risk Factor Surveillance System survey and compared participants with ACOS to COPD, asthma, and control groups. We used logistic regression to compare ACOS and COPD populations to model the impact of comorbid conditions and hospitalization/ED visits after adjusting for demographic factors and smoking status to generate odds ratios and confidence intervals. MEASUREMENTS AND MAIN RESULTS The U.S. prevalence of ACOS was 3.2%, COPD alone was 6.0%, and both increased with age. Respondents with ACOS were younger (64.0 ± 11.7 yr) than respondents with COPD (67.1 ± 11.8 yr) and older than respondents with asthma (59.0 ± 13.1 yr; P < 0.0001). The prevalence of comorbidities was higher in the group with ACOS and COPD than in asthma or control groups. The ACOS group had a higher body mass index, lower income, and lower education than other groups. The ACOS group was more likely to have at least one comorbidity (90.2 vs. 84%, P < 0.0001), more hospitalization or ED visits (22.0 vs. 13.2%, P < 0.0001), less exercise (50.0 vs. 58.6%, P = 0.0024), and more disability (70.8 vs. 58.6%, P < 0.0001) than the COPD group. CONCLUSIONS The patients with a dual diagnosis of asthma and COPD are younger and with more disparities than those diagnosed with COPD alone. ACOS has a higher burden of self-reported comorbidity, disability, and hospitalization or ED visitation than COPD alone.

The United States Alpha-1 Foundation Research Registry: Genesis, Impact and Future

Abstract The Alpha-1 Foundation Research Registry has a long history of facilitating research studies in the United States. The current contact registry is used to invite participants to research studies. However, the next generation of individuals diagnosed with alpha-1 antitrypsin deficiency may look quite different from historical cohorts. This paper uses data from the Alpha Coded Testing (ACT) study, a home genetic testing program in which deficient individuals are invited to participate in the Registry, to demonstrate the impact that selection bias can introduce into registry data. Environmental tobacco smoke (ETS) exposure is rapidly declining in the United States. We queried whether consecutive non-smokers with or without childhood ETS in ACT (N = 801) had been diagnosed with COPD more often if deficiency genes were defined in subsequent testing. The prevalence of COPD was not different between cohorts with or without ETS exposure between normal (PiMM and PiMS), moderately deficient (PiMZ, PiMNull, and PiSS), and severely deficient (PiSZ, PiZZ, PiSNull, and PiZNull) genotypes. Surprisingly, age adjusted COPD Severity Scores in this cohort were higher for individuals with normal genotypes compared to moderately (P<0.001) and severely (P = 0.04) deficient genotypes. Ascertainment bias of testing within families (which yields the highest incidence of deficiency genotypes) also finds many family members without symptoms, even over the age of 40. We conclude that the future utility of registries will depend on accurate determination of testing mechanics. Larger database initiatives using the COPD Patient Powered Research Network are described.

Characteristics of COPD Patients Using United States Emergency Care or Hospitalization

Rationale: Several chronic obstructive pulmonary disease (COPD) studies have evaluated risk factors for emergency department (ED) visits or hospitalizations, and found insufficient data available about social and demographic factors that drive these behaviors. This U.S. study was designed to describe the characteristics of COPD patients with ED visits or a hospitalization and to investigate how often common COPD comorbidities are present in these individuals. Methods: Data for 7180 COPD patients regarding demographic factors, comorbidities, smoking status, and ED visits or hospitalization was obtained from the 2012 Behavioral Risk Factor Surveillance System (BRFSS) survey. Logistic regression analysis was used to adjust demographic factors and smoking status to model the correlation between patients with ED visits or hospitalizations and morbidities generating odds ratios (OR) and confidence intervals (CI). Results: Among diagnosed COPD patients in the BRFSS, 16.5% had ED visits or hospitalization in the previous year. These individuals were younger, had a lower socio-economic status (lower education, lower income, and more often unemployed) and 23.4% of the individuals could not visit a doctor because of the financial difficulties compared to 16.7% who had no visit (p<0.0001 for all comparisons). The prevalence of comorbidities was higher in those with ED visits or hospitalization compared to those without. Conclusion: In a population representative of COPD patients, lower socio-economic status and higher comorbidities are associated with ED visits or hospitalization. Studies are needed to further elucidate the complex relationship between COPD, comorbidities, and ED visits or hospitalization.

Sequencing Alpha-1 MZ Individuals Shows Frequent Biallelic Mutations

Rationale Individuals with a single Z mutation in the SERPINA1 gene that codes for alpha-1 antitrypsin (AAT) are at increased risk for COPD if they have ever-smoked. Whether additional variants alter the risk for COPD in this population remains unknown. Objectives To determine whether additional SERPINA1 variants impact COPD development in a previously identified MZ (carrier) cohort. Methods Individuals with prior MZ results and AAT serum level <16uM were recruited from the Alpha-1 Coded Testing study and Alpha-1 Foundation Research Registry. Participants completed smoking history, demographics, and COPD Severity Score (Range 0-33) using REDCap data capture. At-home finger-stick tests were performed for next generation sequencing (NGS) at the Biocerna LLC laboratory. A genetic counselor reviewed records and interviewed participants with additional variants by NGS. A Wilcoxon Rank Sum test was used to assess correlation between variants and the COPD severity score. Results A second SERPINA1 variant of known or possible significance was identified in 6 (5.8%) participants. One each of ZZ, SZ, FZ, ZSmunich, ZM2obernburg, and Z/c.922G>T genotypes were identified. ZZ, SZ, and FZ are known pathogenic genotypes. Smunich is a likely pathogenic variant. M2obernburg and c.922G>T are variants of uncertain significance. The ZZ individual was on augmentation therapy when determined MZ by protease inhibitor (Pi) phenotyping; the others had limited targeted genotyping with MZ results. These six participants with biallelic variants had positive COPD severity scores >1. Presence of additional variants was not significantly associated with COPD symptoms in this small sample size. Conclusions Some diagnosed MZ individuals instead have biallelic variants. Larger studies are needed to determine COPD-risk liability of variants. Accurate diagnosis impacts medical management and familial risk assessment. Pi phenotyping can be confounded by augmentation therapy and liver transplantation. Because a normal M allele may be reported in the absence of tested mutation(s) in AATD genotyping, clinicians should consider clinical circumstances and laboratory methods when selecting and interpreting AATD tests. Advanced testing, including NGS, may be beneficial for select individuals with prior MZ results. Clinical Trial Registration This study was registered with clinicaltrials.gov (NCT NCT02810327).

Hypertension Prevalence in the US Population Varies with Differences in Alpha-1 Antitrypsin Genotype: A Cross Sectional Study

Background: The prevalence of hypertension (HTN) associated with alpha -1 antitrypsin deficiency (AATD) has been studied with indeterminate results . The aim of the study was to prospectively compare the prevalence of HTN before testing in 3 groups of individuals with subsequently normal, moderately deficient, and severely deficient genotypes of AATD with adjustment for differences in demographics and clinical variables. Methods: We performed a cross sectional study using data from the Alpha -1 Coded Testing (ACT) study. The univariate demographic and clinical factors associated with HTN were further analyzed by logisticregression analysis. Results: The prevalence of HTN was 27.2%, 20.6%, and 27.9% for individuals with normal, moderate and severe AATD, respectively (p<0.02). The prevalence of HTN increased with age and