Publications

Caesarean-section (CS) delivery increases risk of childhood obesity, and is associated with a distinct early-life gut microbiome, which may contribute to obesity. Household pets may alter human gut microbiome composition. We examined if pet-keeping modified the association of CS with obesity at age 2 years in 639 Wayne County Health, Environment, Allergy and Asthma Longitudinal Study birth cohort participants. Pet-keeping was defined as having a dog or cat (indoors ≥1 h/day) at child age 2 years. We used logistic regression to test for an interaction between CS and pet-keeping with obesity (BMI ≥ 95th percentile) at age 2 years, adjusted for maternal obesity. A total of 328 (51.3 %) children were male; 367 (57.4 %) were African American; 228 (35.7 %) were born by CS; and 55 (8.6 %) were obese. After adjusting for maternal obesity, CS-born children had a non-significant (P = 0.25) but elevated 1.4 (95 % CI 0.8, 2.5) higher odds of obesity compared to those born vaginally. There was evidence of effect modification between current pet-keeping and delivery mode with obesity at age 2 years (interaction P = 0.054). Compared to children born vaginally without a pet currently in the home, children born via CS without a pet currently in the home had a statistically significant (P = 0.043) higher odds (odds ratio 2.00; 95 % CI 1.02, 3.93) of being obese at age 2 years. Pets modified the CS-BMI relationship; whether the underlying mechanism is through effects on environmental or gut microbiome requires specific investigation.

Autoimmune diseases affect up to approximately 10% of the population. While rare Mendelian autoimmunity syndromes can result from monogenic mutations disrupting essential mechanisms of central and peripheral tolerance, more common human autoimmune diseases are complex disorders that arise from the interaction between polygenic risk factors and environmental factors. Although the risk attributable to most individual nucleotide variants is modest, genome-wide association studies (GWAS) have the potential to provide an unbiased view of biological pathways that drive human autoimmune diseases. Interpretation of GWAS requires integration of multiple genomic datasets including dense genotyping, cis-regulatory maps of primary immune cells, and genotyped studies of gene expression in relevant cell types and cellular conditions. Improved understanding of the genetic basis of autoimmunity may lead to a more sophisticated understanding of underlying cellular phenotypes and, eventually, novel diagnostics and targeted therapies.

BACKGROUND

Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF).

METHODS

To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling.

RESULTS

We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts.

CONCLUSIONS

Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft.

BACKGROUND

Obesity is associated with poor asthma control, increased asthma morbidity, and decreased response to inhaled corticosteroids. We hypothesized that obesity would be associated with decreased bronchodilator responsiveness in children and adolescents with asthma. In addition, we hypothesized that subjects who were obese and unresponsive to bronchodilator would have worse asthma control and would require more asthma controller medications.

METHODS

In the Study of African Americans, Asthma, Genes, and Environments (SAGE II) and the Genes-environments and Admixture in Latino Americans (GALA II) study, two identical, parallel, case-control studies of asthma, we examined the association between obesity and bronchodilator response in 2,963 black and Latino subjects enrolled from 2008 to 2013 using multivariable logistic regression. Using bronchodilator responsiveness, we compared asthma symptoms, controller medication usage, and asthma exacerbations between nonobese (< 95th% BMI) and obese (≥ 95th% BMI) subjects.

RESULTS

The odds of being bronchodilator unresponsive were 24% (OR, 1.24; 95% CI, 1.03-1.49) higher among obese children and adolescents compared with their not obese counterparts after adjustment for age, race/ethnicity, sex, recruitment site, baseline lung function (FEV1/FVC), and controller medication. Bronchodilator-unresponsive obese subjects were more likely to report wheezing (OR, 1.38; 95% CI, 1.13-1.70), being awakened at night (OR, 1.34; 95% CI, 1.09-1.65), using leukotriene receptor inhibitors (OR, 1.33; 95% CI, 1.05-1.70), and using inhaled corticosteroid with long-acting β2-agonist (OR, 1.37; 95% CI, 1.05-1.78) than were their nonobese counterpart. These associations were not seen in the bronchodilator-responsive group.

CONCLUSIONS

Obesity is associated with bronchodilator unresponsiveness among black and Latino children and adolescents with asthma. The findings on obesity and bronchodilator unresponsiveness represent a unique opportunity to identify factors affecting asthma control in blacks and Latinos.

Asthma is a common condition affecting many children in child-care centers. The National Asthma Education and Prevention Program offers recommendations about creating an asthma-friendly child-care setting. However, no studies have investigated the extent to which child-care centers adhere to these recommendations. This study describes the development of a novel instrument to determine the ability of child-care centers to meet national recommendations for asthma. The Preparing for Asthma in Child Care (PACC) Instrument was developed using information from existing recommendations and standards, the peer-reviewed literature, site visits, and expert interviews. The survey questions were pilot-tested at 36 child-care centers throughout San Francisco. The instrument is composed of 43 items across seven domains: smoking exposure, presence of a medical consultant and policies, management of ventilation and triggers, access to medication, presence of asthma action plans, staff training, and encouragement of physical activity. The PACC Instrument is an evidence-based and comprehensive tool designed to identify areas to target to improve asthma care for children in child-care centers.

IMPORTANCE

Lower extremity revascularization often seeks to allow patients with peripheral arterial disease to maintain the ability to walk, a key aspect of functional independence. Surgical outcomes in patients with high levels of functional dependence are poorly understood.

OBJECTIVE

To determine functional status trajectories, changes in ambulatory status, and survival after lower extremity revascularization in nursing home residents.

DESIGN

Using full Medicare claims data for 2005 to 2009, we identified nursing home residents who underwent lower extremity revascularization. With the Minimum Data Set for Nursing Homes activities of daily living summary score, we examined changes in their ambulatory and functional status after surgery. We identified patient and surgery characteristics associated with a composite measure of clinical and functional failure-death or nonambulatory status 1 year after surgery.

SETTING

All nursing homes in the United States participating in Medicare or Medicaid.

PARTICIPANTS

Nursing home residents who underwent lower extremity revascularization.

MAIN OUTCOMES AND MEASURES

Functional status, ambulatory status, and death.

RESULTS

During the study period, 10,784 long-term nursing home residents underwent lower extremity revascularization. Prior to surgery, 75% of the residents were not walking; 40% had experienced functional decline. One year after surgery, 51% of patients had died, 28% were nonambulatory, and 32% had sustained functional decline. Among 1672 residents who were ambulatory before surgery, 63% had died or were nonambulatory at 1 year; among 7188 who were nonambulatory, 89% had died or were nonambulatory. After multivariate adjustment, factors independently associated with death or nonambulatory status were 80 years or older (adjusted hazard ratio [AHR], 1.28; 95% CI, 1.16-1.40), cognitive impairment (AHR, 1.23; 95% CI, 1.18-1.29), congestive heart failure (AHR, 1.16; 95% CI, 1.11-1.22), renal failure (AHR, 1.09; 95% CI, 1.04-1.14), emergent surgery (AHR, 1.29; 95% CI, 1.23-1.35), nonambulatory status before surgery (AHR, 1.88; 95% CI, 1.78-1.99), and decline in activities of daily living before surgery (AHR, 1.23; 95% CI, 1.18-1.28).

CONCLUSIONS AND RELEVANCE

Of nursing home residents in the United States who undergo lower extremity revascularization, few are alive and ambulatory 1 year after surgery. Most who were still alive had gained little, if any, function.

OBJECTIVE

More than 1 in 4 Medicare beneficiaries with rheumatoid arthritis use high-cost biologic disease-modifying antirheumatic drugs (DMARDs), and spending for these drugs has risen sharply for Medicare Part D. Our aim was to conduct the first systematic, national investigation of how Part D plans cover biologic DMARDs and to determine patients' financial burden under current cost-sharing structures.

METHODS

We performed a cross-sectional analysis of Part D plan formularies (n = 2,737) in 50 states and Washington, DC using the January 2013 Centers for Medicare and Medicaid Services Prescription Drug Plan Formulary and Pharmacy Network Files. We calculated the percentage of plans covering each DMARD as well as the percentage requiring prior authorization and/or coinsurance. We also compared biologic drug coverage in Medicare Advantage prescription drug plans to that in Medicare Part D stand-alone plans.

RESULTS

All plans covered at least 1 biologic DMARD, but the vast majority required prior authorizations (95%). Nearly all plans (81-100%) required patients to pay a coinsurance percentage (averaging 29.6% of drug costs) rather than a fixed dollar copayment. This translated into mean out-of-pocket costs of $2,712-$2,774 before reaching the catastrophic phase of coverage, during which beneficiaries pay 5% of drug costs. Medicare Advantage prescription drug plans covered more individual biologic DMARDs (55-100%) than did Medicare Part D stand-alone plans (22-100%), but Medicare Advantage prescription drug plans required higher average coinsurance (31.1% versus 29.0%). In contrast, 6 of 9 nonbiologic DMARDs were covered by nearly all plans without prior authorizations at fixed copayments averaging $5-$10/month.

CONCLUSION

Nationally, nearly all Part D plans cover at least 1 biologic DMARD, but the vast majority require cost sharing sufficiently high to risk significant financial burden to patients.