A Patient-Centered Walking Program for COPD.

Background: Pulmonary rehabilitation programs improve dyspnea and health status associated with chronic obstructive pulmonary disease (COPD), but benefits wane when patients return to a sedentary lifestyle. This study tested a simple, low-resource, low-cost home walking program. Methods: In this single center, 3-month study, 115 COPD patients were randomized to a control cohort or a goal setting cohort. Each patient met with study staff and received 5 telephone calls at 2-week intervals. During these contacts, the Goal group was assisted by a wellness coach who helped them set personal activity goals. All patients wore a pedometer to record daily steps, the primary study outcome. Results: Over the 12-week interval, the average step-per-days was 36% higher for the Goal cohort patients (Week 12 mean = 4390) than for Control patients (mean = 3790). No group differences emerged on the modified Medical Research Council (mMRC) dyspnea scale, the COPD Assessment Test, or the St. George's Respiratory Questionnaire. Secondary analyses indicated that even patients with greater disease severity, including those with an mMRC score >2 or forced expiratory volume in 1 second (FEV1) % predicted below 50%, increased their walking relative to Control patients. Almost half (48%) of Goal patients successfully reached at least one personal goal such as increasing stamina and activity, or decreasing shortness of breath or weight. Conclusions: A relatively low-resource wellness coaching, goal-setting intervention resulted in a small improvement in the activity level of COPD patients over a 12-week period including those with marked pulmonary impairment. Further investigation should be directed at understanding the optimal blend of in person and remote coaching needed to produce the greatest cost-to-benefit ratio.

Gene-environment interactions influence airways function in laboratory animal workers.

BACKGROUND: Most diseases, including asthma, result from the interaction between environmental exposures and genetic variants. Functional variants of CD14 negatively affect lung function in farm workers and children exposed to animal allergens and endotoxin. OBJECTIVE: We hypothesized that CD14 polymorphisms interact with inhaled endotoxin, mouse allergen, or both to decrease airways function in laboratory animal workers. METHODS: Three hundred sixty-nine Caucasian workers completed a symptom and work exposure questionnaire, skin prick testing, and spirometry. Individual exposure estimates for endotoxin and murine allergen were calculated by weighting task-based breathing zone concentrations by time reported for each task and length of time in the current job. Real-time PCR was used to assess CD14/-1619, -550, and -159 alleles. Multiple linear regression predicting airways function included an interaction term between genotype and exposure. RESULTS: Workers at the highest quartile of the natural log-transformed cumulative endotoxin exposure and with the endotoxin-responsive CD14/-1619 G allele had significantly lower FEV(1) and forced expiratory flow, midexpiratory phase (FEF(25-75)) percent predicted compared with workers with an AA genotype, with no significant differences noted at lower endotoxin levels for either genotype. The gene-environment effect was marked for atopic workers. Laboratory animal allergy, murine allergen exposure, CD14/-159 or -550 genotype, and a gene-exposure interaction term for these genotypes and exposures did not predict changes in lung function. CONCLUSIONS: A significant gene-environment interaction affects airways function in laboratory animal workers. More highly endotoxin-exposed workers with CD14/-1619G alleles have significantly lower FEV(1) and FEF(25-75) percent predicted than those with CD14/-1619AA alleles. Atopic workers are particularly affected by cumulative endotoxin exposures.

Association of Toll-like receptor 4 alleles with symptoms and sensitization to laboratory animals.

BACKGROUND: Researchers and technicians working with laboratory animals (LAs) are exposed to animal allergen and endotoxin, which can interact to potentiate or inhibit symptoms or allergic responses. We hypothesized that functional genetic variants of Toll-like receptor 4 (TLR4), a key surface receptor for endotoxin, interface between worker and workplace and affect animal sensitization, symptoms, or both. OBJECTIVE: We sought to determine whether TLR4/8551 variants alter the risk for LA sensitization, symptoms, or both. METHODS: Three hundred thirty-five researchers, 195 of whom worked with animals, completed questions on workplace practices and symptoms and underwent skin prick tests or RASTs to common and animal allergens. Real-time PCR assessed TLR4/8551 and TLR4/8851 variants. Nominal logistic regression was used to analyze the contribution of demographic, exposure, and genetic variables to outcomes of interest. RESULTS: Twenty-one percent of workers were LA sensitized, and 29% reported 1 or more symptoms to LAs. The TLR4/8551 G variant, which is less responsive to endotoxin, was detected in 9% and in linkage disequilibrium with the TLR4/8851 T allele. The G variant significantly associated with atopy and LA sensitization. Workers with the G variant spent significantly longer hours in high endotoxin/animal allergen tasks compared with those with the AA variant, which is perhaps less affected by endotoxin exposures. In multivariate analyses the G variant and longer animal research hours increased the risk of LA sensitization. Job tasks and LA sensitization, but not TLR4 variants, were predictors of LA-induced symptoms. CONCLUSION: Workers with TLR4 variants that reduce responsiveness to endotoxin have higher risks for LA and other allergen sensitization but spend longer hours in tasks with high endotoxin and animal allergen exposures.