Long-Term SGRQ Stability in a Cohort of Individuals with Alpha-1 Antitrypsin Deficiency-Associated Lung Disease.

Background: Health-related quality of life (HRQoL) assessments such as St. George's Respiratory Questionnaire (SGRQ) are often used as outcome measures to evaluate patient-perceived changes in health status among individuals with lung disease. Several factors have been linked to deterioration in SGRQ, including symptoms (dyspnea, wheezing) and exercise intolerance. Whether these findings apply to individuals with alpha-1 antitrypsin deficiency (AATD) remains incompletely studied. This longitudinal study examines the trajectory of SGRQ scores in a cohort of United States individuals with AATD-associated lung disease and defines factors associated with longitudinal change. Methods: Individuals with AATD-associated lung disease enrolled in AlphaNet, a disease management program, who had ≥3 SGRQ measurements collected between 2009 and 2019, and baseline data for clinically important variables were included in these analyses. Data collected after lung transplants were excluded. Mixed-effects model analyses were used to evaluate the changes in SGRQ total and subscale scores over time and by modified Medical Research Council (mMRC) Scale, use of oxygen, age, sex, productive cough, and exacerbation frequency at baseline. Sensitivity analyses were conducted to examine the potential effect of survivor bias. Results: Participants (n=2456, mean age 57.1±9.9 years, 47% female) had a mean SGRQ total score of 44.7±18.9 at baseline, 48% used oxygen regularly, and 55% had ≥2 exacerbations per year. The median length of follow-up was 6 (IQR 3-9) years. The SGRQ total score and subscales remained stable throughout the observation period. Age, mMRC categories, presence or absence of productive cough, frequency of exacerbations, and use of oxygen at baseline were significantly associated with the rate of change of SGRQ total (p<0.0001). Conclusion: We observed long-term stability in HRQoL and an association between the rate of change in SGRQ and baseline mMRC, exacerbation frequency, productive cough, and use of oxygen in this cohort of individuals with AATD-associated lung disease.

Characteristics associated with SF-36 in alpha-1 antitrypsin deficiency-associated COPD: a cross-sectional analysis.

BACKGROUND: Generic measures of health-related quality of life (HRQoL), such as the 36-Item Short Form Survey (SF-36), are widely used in assessing chronic conditions. These tools have an advantage over disease-specific instruments, as they allow comparisons across different health conditions and with the general population. In alpha-1 antitrypsin deficiency (AATD)-associated chronic obstructive pulmonary disease (COPD), HRQoL research remains scarce. This cross-sectional study evaluates the factors associated with HRQoL in a cohort of patients with AATD-associated COPD. METHODS: Our study included participants of AlphaNet (2008-2019), a health management organization for people with AATD in the US who are prescribed augmentation therapy. Norm-based SF-36 scores for the mental and physical component summary scores (MCS and PCS, mean of 50 ± 10 in the general US population) and 8 individual scales were evaluated. Individuals with lung disease and data available on ≥1 measurement on any SF-36 scale and clinically relevant characteristics such as modified Medical Research Council (mMRC) scale, exacerbation frequency, productive cough, and use of oxygen were included in these analyses. Generalized linear regression models were fit to examine the association of baseline characteristics with MCS and PCS scores. Age, sex, regular use of oxygen, exacerbation frequency, mMRC, and productive cough were included in these models. RESULTS: Participants (n=4398, mean age 57.6 [SD=10.6] years, 45.4% female) had a mean MCS score of 51.2 ± 10.8 and PCS of 36.3 ± 9.8. The average mMRC score was 2.4 ± 1.3, and 56.4% had 2 or more exacerbations per year. Overall, the physical component of SF-36 was more severely impacted compared to the mental component. In multivariable regression analyses, PCS scores were significantly associated with exacerbation frequency, mMRC, regular use of oxygen, and productive cough; MCS was associated with age, sex, exacerbation frequency, mMRC, and productive cough. CONCLUSIONS: These findings demonstrate that patient-perceived physical health is significantly impaired in this cohort of people with AATD-associated COPD compared to mental health. Longitudinal studies are needed to evaluate the change in physical and mental health status over time in this population.

Prevalence of Cardiovascular Disease and Rate of Major Adverse Cardiovascular Events in Severe Alpha-1 Antitrypsin Deficiency COPD.

Aim: Alpha-1 antitrypsin deficiency is an autosomal co-dominant condition that predisposes individuals to early-onset emphysema. As with COPD, AATD-COPD is associated with pulmonary exacerbations, which impacts on overall mortality and quality of life. Though there is evidence that COPD is associated with a higher prevalence of cardiovascular disease and major adverse cardiovascular events (MACE), it is unclear if this is true for patients with AATD-COPD. Methods: Prevalence of cardiovascular disease was determined in two separate severe AATD cohorts: AlphaNet, USA and the Birmingham AATD registry, UK. All patients had preexisting lung disease. Cardiovascular disease was defined as presence of any of the following: heart failure, ischaemic heart disease, atrial fibrillation, stroke, and myocardial infarction. A Cox proportional hazards model was used to assess the impact of prior cardiovascular disease and frequent exacerbator phenotype on risk of future MACE. Results: Out of 3493 patients with severe AATD, 14.7% had prior cardiovascular disease, including stroke (2.3%), myocardial infarction (2.2%), and heart failure (2.5%). Frequent exacerbators were more likely to have preexisting cardiovascular disease compared with those with one or no exacerbations in the preceding year (63% vs 44.8%, p = 0.001). There was increased risk of future MACE in frequent exacerbators (HR 1.85, 95% CI 1.24 to 2.75), former and current smokers (HR 1.80, 95% CI 1.07 to 3.02, p = 0.026, and HR 4.04, 95% CI 1.44 to 11.32, p = 0.008, respectively), and those with prior cardiovascular disease (HR 3.81, 95% CI 2.60 to 5.58, p < 0.001). Conclusion: In severe AATD-COPD, MACE are associated with an increased exacerbation frequency, previous cardiovascular disease, and a history of smoking.

A Hybrid Effectiveness/Implementation Clinical Trial of Adherence to Long-Term Oxygen Therapy for Chronic Obstructive Pulmonary Disease.

Rationale: Interventions to promote adherence to long-term oxygen therapy (LTOT) in chronic obstructive pulmonary disease (COPD) are needed. Objectives: To examine the real-world effectiveness of phone-based peer coaching on LTOT adherence and other outcomes in a pragmatic trial of patients with COPD. Methods: In a hybrid effectiveness/implementation pragmatic trial, patients were randomized to receive phone-based proactive coaching (educational materials, five phone-based peer coaching sessions over 60 d), reactive coaching (educational materials, peer coaching when requested), or usual care. Study staff members collected baseline and outcome data via phone at 30, 60, and 90 days after randomization. Adherence to LTOT over 60 days, the primary effectiveness outcome, was defined as mean LTOT use ⩾17.7 h/d. LTOT use was calculated using information about home oxygen equipment use in worksheets completed by study participants. Comparisons of adherence to LTOT between each coaching group and the usual care group using multivariable logistic regression models were prespecified as the primary analyses. Secondary effectiveness outcomes included Patient Reported Outcome Management Information System measures for physical, emotional, and social health. We assessed early implementation domains in the reach, adoption, and implementation framework. Results: In 444 participants, the proportions who were adherent to LTOT at 60 days were 74% in usual care, 84% in reactive coaching, and 70% in proactive coaching groups. Although reach, adoption by stakeholder partners, and intervention fidelity were acceptable, complete LTOT adherence data were available in only 73% of participants. Reactive coaching (adjusted odds ratio, 1.77; 97.5% confidence interval, 0.80-3.90) and proactive coaching (adjusted odds ratio, 0.70; 97.5% confidence interval, 0.34-1.46) did not improve adherence to LTOT compared with usual care. However, proactive coaching significantly reduced depressive symptoms and sleep disturbance compared with usual care and reduced depressive symptoms compared with reactive coaching. Unexpectedly, LTOT adherence was significantly lower in the proactive compared with the reactive coaching group. Conclusions: The results were inconclusive about whether a phone-based peer coaching strategy changed LTOT adherence compared with usual care. Further studies are needed to confirm the potential benefits of proactive peer coaching on secondary effectiveness outcomes and differences in LTOT adherence between proactive and reactive peer coaching. Clinical trial registered with ClinicalTrials.gov (NCT02098369).

Augmentation Therapy for Alpha-1 Antitrypsin Deficiency: Patient Experiences With Self-Infusion, Home Providers, and Clinics.

Background: Currently approved therapies for individuals with alpha-1 antitrypsin deficiency (AATD) are intravenously infused products. The burdens and demographics of infusion practices in the United States are not well-characterized. Research Question: What is the prevalence of different infusion practices in the United States? Study Design and Methods: AlphaNet disease management participants completed a survey that captured current and past infusion practices. Data regarding the reasons for choosing their current infusion practice, problems with past infusion practices, resources required, and support services utilized were collected from February 8, 2022 through July 1, 2022. Results: Among 5266 individuals, infusions happened at home by health care providers (60.2%), at infusion clinics (30.6%), and by self-infusion (8.1%). Self-infusion prevalence increased with time on therapy and was more prevalent in younger individuals (61.2 ± 10.5 years) compared to users of other infusion practices (64.1 ± 11.0 years), (p<0.001). The perceived benefits of self-infusion included: (1) freedom and flexibility (77.9%), (2) ability to travel (44.5%), (3) avoidance of infusion clinics (41.8%), (4) time-savings (35.9%), (5) less absence from work (26.6%), (6) less exposure to infections (22.1%), and (7) less cost (16.4%). Self-infusion was done through permanent intravenous catheters in 41.2% and peripheral intravenous catheters in 58.3%. Self-infusers were more satisfied (93.1% "very satisfied") than other groups. Among individuals currently infusing with home nurses or in clinics, 21.4% would consider self-infusing in the future. Interpretation: Self-infusion of alpha-1 antitrypsin is feasible and associated with high satisfaction scores. Recommendations for catheter care, infusion support, and cost management are informed by survey results.

Impact of Coronavirus Disease 2019 and Vaccination Attitudes on Alpha-1 Antitrypsin Deficiency.

Background: Individuals with alpha-1 antitrypsin deficiency (AATD)-associated chronic obstructive pulmonary disease (COPD) may be at increased risk of coronavirus disease 2019 (COVID-19) pneumonia since COPD is associated with an increased risk of severe COVID-19 infection. Research Question: We hypothesized that the AlphaNet disease management program would lower COVID-19 burdens. We evaluated the prevalence of COVID-19 infection, severe COVID-19, interruptions in augmentation therapy, and intention to vaccinate. Study Design and Methods: Data regarding COVID-19 were collected monthly from March 2020 through February 2022. Responses from 8019 individuals were analyzed to evaluate the prevalence and severity of COVID-19 infections, interruptions in AATD care, and the likelihood of vaccination. Results: By the end of 2020, 4% of patients reported a positive COVID-19 test. Of those, 35.3% were hospitalized, with 8.6% admitted to the intensive care unit (ICU). By February 2022, the prevalence of COVID-19 infections had increased to 18.6%, with hospitalization rates of 22.1% and ICU admissions at 4.7%. Attitudes about COVID-19 vaccination assessed in December 2020 before the vaccine was widely available suggested 10.3% of patients would definitely not get the vaccine. Notably, 38.2% of those subsequently self-reported receipt of a COVID-19 vaccine. Interpretation: The prevalence of COVID-19 infections in patients with AATD was lower than the prevalence in the general U.S. population during 2020, although with a higher hospitalization rate. This health-managed population has a high vaccination intent. Those with an initially low vaccination intent changed their minds over time. We interpret these results as showing that most AlphaNet individuals with AATD had success at navigating the COVID-19 pandemic with lower case rates than the general U.S. population.

Adherence to behavioral recommendations of cognitive behavioral therapy for insomnia predicts medication use after a structured medication taper.

STUDY OBJECTIVES: Cognitive behavioral therapy for insomnia (CBTI) has been paired with supervised medication tapering to help hypnotic-dependent individuals discontinue their hypnotics. This study examined the hypothesis that higher participant adherence to behavioral recommendations of CBTI will predict lower odds of using sleep medications 3 months after completion of a combined CBTI/sleep medication tapering protocol. METHODS: Fifty-eight individuals who used sedative hypnotics completed four CBTI sessions followed by sleep medication tapering. Logistic regression was used to examine the association of stability of time in bed and stability of rise time (measured as the within-person standard deviation) at completion of CBTI with two outcomes at 3-month follow-up: use of sedative hypnotics and use of any medication/substance for sleep. RESULTS: Participants with more stability in their rise time after CBTI than at baseline (ie, a decrease in their within-person standard deviation) had 69.5% lower odds of using sedative hypnotics at follow-up (odds ratio = 0.305, 95% confidence interval = 0.095-0.979, P = .046) than individuals who had no change or a decrease in the stability of their rise time. Results were similar for time in bed: participants with more stability in their time in bed after CBTI than at baseline had 83.2% lower odds of using sedative hypnotics (odds ratio = 0.168, 95% confidence interval = 0.049-0.580, P = .005). Increase in stability of rise time and stability of time in bed was also associated with reduced odds of using any medication/substance for sleep at follow-up. CONCLUSIONS: Participants who implement behavioral recommendations of CBTI appear to have more success with discontinuing use of sleep medications. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: The Role of Tapering Pace and Selected Traits on Hypnotic Discontinuation; URL: https://clinicaltrials.gov/ct2/show/NCT02831894; Identifier: NCT02831894. CITATION: Edinger JD, Wamboldt FS, Johnson RL, et al. Adherence to behavioral recommendations of cognitive behavioral therapy for insomnia predicts medication use after a structured medication taper. J Clin Sleep Med. 2023;19(8):1495-1503.

Quality of Life and Mortality Outcomes for Augmentation Naïve and Augmented Patients with Severe Alpha-1 Antitrypsin Deficiency.

Background: Intravenous alpha-1 antitrypsin (AAT) augmentation therapy is the only specific treatment available for alpha-1 antitrypsin deficiency (AATD)-related lung disease. It is widely used worldwide but remains unavailable to patients with AATD in the United Kingdom. While randomized trials of augmentation therapy have demonstrated biochemical efficacy and lung tissue preservation using computed tomography (CT) densitometry, these studies were not adequately powered to demonstrate effectiveness in well-accepted clinical endpoints such as quality of life (QOL) or survival. We used large, prospectively followed AATD patient populations in the United States and United Kingdom to explore these important clinical endpoints. Methods: Our inclusion criterion was adults with severe AATD and associated lung disease. The treatment group was U.S. AATD patients receiving augmentation therapy for lung disease. The control group was augmentation therapy naïve AATD patients. Multivariable regression and survival analyses were used to assess QOL and mortality outcomes respectively. Results: Mean annual deterioration of the St George's Respiratory Questionnaire total score was 1.43 points greater/year in the control group compared to those receiving augmentation therapy (95% confidence interval [CI] 0.47 to 2.39, p=0.003). At 7 years, median survival was 82.7% (95% CI 75.3 to 90.7) for the control group versus 87.8% (95% CI 82.8 to 93.2) in the augmentation group, p=0.66. There was significant heterogeneity between cohorts. Conclusions: A comparison of 2 highly characterized AATD cohorts was not able to reliably determine if AAT augmentation therapy improves QOL or mortality in patients with severe AATD-related lung disease. Alternative surrogate biomarkers of disease progression, such as CT lung density, may be a more pragmatic option.

Clinical Markers Associated With Risk of Suicide or Drug Overdose Among Individuals With Smoking Exposure: A Longitudinal Follow-up Study of the COPDGene Cohort.

BACKGROUND: Studies have shown that COPD and smoking are associated with increased suicide risk. To date, there are no prospective studies examining suicide risk among individuals with smoking exposure along a spectrum of pulmonary diseases ranging from normal spirometry to severe COPD. RESEARCH QUESTION: Which clinical variables predict death by suicide or overdose of indeterminate intent in a large cohort of individuals with smoking exposure within the Genetic Epidemiology of COPD (COPDGene) study? STUDY DESIGN AND METHODS: We studied data from 9,930 participants involved in COPDGene, a multisite, prospective cohort study of individuals with smoking exposure. Primary cause of adjudicated deaths was identified by using death certificates, family reports, and medical records. Time to death by suicide/overdose was examined as the primary outcome in Cox regression models including age, sex, race, BMI, pack-years, current smoking status, airflow limitation (FEV1 % predicted), dyspnea (modified Medical Research Council scale score ≥ 2), 6-min walk distance, supplemental oxygen use, and severe exacerbations in the prior year with time-varying covariates and other causes of death as a competing risk. RESULTS: The cohort was 47% female and 33% Black (67% White); they had a mean ± SD age of 59.6 ± 9.0 years and a mean FEV1 % predicted of 76.1 ± 25.5. Sixty-three individuals died by suicide/overdose. Factors associated with risk of suicide/overdose were current smoking (hazard ratio [HR], 6.44; 95% CI, 2.64-15.67), use of sedative/hypnotics (HR, 2.33; 95% CI, 1.24-4.38), and dyspnea (HR, 2.23; 95% CI, 1.34-3.70). Lower risk was associated with older age (per-decade HR, 0.45; 95% CI, 0.31-0.67), higher BMI (HR, 0.95; 95% CI, 0.91-0.99), and African-American race (HR, 0.41; 95% CI, 0.23-0.74). Severity of airflow limitation (FEV % predicted) was not associated with suicide risk. INTERPRETATION: In this well-characterized cohort of individuals with smoking exposure with and without COPD, risk factors for suicide/overdose were identified that emphasize the subjective experience of illness over objective assessments of lung function.

Patient-Reported Pulmonary Symptoms, Exacerbations, and Management in a Cohort of Patients With Alpha-1 Antitrypsin Deficiency.

Rationale: Identifying pulmonary exacerbations in patients with alpha-1 antitrypsin deficiency (AATD) is critical as they are associated with disease progression and poor health-related quality of life. Not all changes in usual respiratory symptoms will be identified as exacerbations by patients with AATD. Methods: Data collected via regular monthly telephone calls during the first year of the AlphaNet Step Forward Study were analyzed. AlphaNet subscribers were asked about changes in their usual respiratory symptoms, whether they considered changes in symptoms to be pulmonary exacerbations, and their management. Participants who reported changes in their usual respiratory symptoms throughout the year were included in the study. Per-patient and per-event analyses were performed. Results: Participants (n=316, age 58±10 years, 53% female) reported 797 events of changes in their usual respiratory symptoms in 1 year. Almost half (48%) of these symptom events were identified as pulmonary exacerbations by the study participants. The average number of symptoms was higher in events recognized by participants as exacerbations than those not identified as exacerbations (3.3±1.5 versus 1.8±1.1, respectively). A greater proportion of the exacerbation events were managed by taking antibiotics or corticosteroids or both (81%, 53%, and 41% of the events, respectively). With exacerbations, participants mainly spoke to the pulmonary specialist (39%) or went to the doctor's office (37%). Symptom events not recognized as exacerbations were mostly self-treated (56%). Conclusions: Changes in usual pulmonary symptoms are not universally recognized as exacerbations. Patients' perspectives in recognizing changes in pulmonary symptoms as exacerbation events are critical.

Pilot RCT of a telehealth intervention to reduce symptoms of depression and anxiety in adults with cystic fibrosis.

BACKGROUND: Adults with cystic fibrosis (awCF) have higher levels of depression and anxiety than community samples. The Coping and Learning to Manage Stress with CF (CALM) intervention was developed for awCF reporting elevated symptoms of depression or anxiety. METHODS: In this pilot study, awCF were randomly assigned to either six telehealth sessions (CALM; n = 15) or treatment-as-usual (TAU; n = 16). Primary outcomes were depression and anxiety. Secondary outcomes were coping self-efficacy and health-related quality of life (HrQOL). Tertiary outcomes were feasibility, acceptability, and satisfaction. Assessments were completed at baseline, post-intervention, and 3-month follow-up. Group differences were examined via independent samples t-tests. Effect size (ES) was calculated via Cohen's d to provide a measure of the magnitude of the treatment effect. RESULTS: At post-intervention, the CALM group had a lower mean score than the TAU group for depression (medium ES) and anxiety (large ES). The CALM group had higher (i.e., better) mean scores than the TAU group for coping (large ES) and HrQOL domains of Social Functioning (large ES) and Vitality (large ES). Most treatment gains were not sustained at 3-month follow-up. CALM was feasible, requiring <12 min. for setup and scheduling, and allowed seamless participation when hospitalized. Mean scores for acceptability and satisfaction indicated that most participants either agreed or strongly agreed that CALM was acceptable and satisfactory. CONCLUSIONS: CALM shows promise as an intervention to reduce symptoms of depression and anxiety and improve coping and HrQOL. Next steps are to add a booster session and examine CALM via a multi-site RCT.

Intimate Partner Violence and Adult Asthma Morbidity: A Population-Based Study.

BACKGROUND: The etiologies for difficult-to-control asthma are complex and incompletely understood. Intimate partner violence (IPV) is a pervasive problem and may play a role in difficult-to-control asthma. IPV is associated with increased prevalence of asthma. There are no prior studies evaluating IPV's association with adult asthma exacerbations. OBJECTIVE: This study hypothesized that IPV exposure would be associated with increased asthma exacerbations, higher symptom burden, and poorer asthma control among adults. METHODS: Analyses are based on 2634 adults who participated in the 2005 Behavioral Risk Factor Surveillance System survey, reported active asthma, and completed the asthma and IPV questions. We used multivariate logistic regression to examine the association of IPV with asthma morbidity outcomes while controlling for the following potential confounders: sex, race, education, health care coverage, smoking status, age, and body mass index. RESULTS: The prevalence of IPV was 32.4%. IPV was associated with increased odds of an asthma exacerbation (adjusted odds ratio [AOR] = 1.75, 95% confidence interval [CI] = 1.26-2.43), higher symptom burden (AOR = 2.33, 95% CI = 1.53-3.55), and lack of asthma control (AOR = 2.23, 95% CI = 1.22-4.09) when using composite measures for these outcomes. When using single-item measures for outcomes, IPV was also associated with increased asthma-related emergency department or urgent care visits (AOR = 2.35, 95% CI = 1.56-3.54), other urgent provider visits (AOR = 1.84, 95% CI = 1.28-2.64), perceived asthma attacks (AOR = 1.53, 95% CI = 1.12-2.09), limitations (AOR = 2.07, 95% CI = 1.49-2.89), daytime symptoms (AOR = 1.92, 95% CI = 1.35-2.72), and nocturnal awakenings (AOR = 1.88, 95% CI = 1.32-2.69). CONCLUSIONS: IPV is prevalent in adult asthmatics and consistently and significantly associated with worsened adult asthma morbidity, even after adjusting for key confounders. Further research is needed to more fully understand the mechanisms underlying these relationships.

Impact of a Medical Diagnosis on Decision to Stop Smoking and Successful Smoking Cessation.

INTRODUCTION: Smoking cessation counseling is a central part of the Medicare guidelines for lung cancer screening. With increasing age, many heavy smokers eventually stop smoking, however, factors influencing the decision to stop smoking are poorly understood. We postulated that declining health or physician-diagnosis of a medical condition may be associated with successful smoking cessation. METHODS: A total of 4448 current and former smokers in Phase 2 of the COPD Genetic Epidemiology (COPDGene®) study answered a question about reasons for stopping smoking. Participants were classified as successful quitters (n=3345), and unsuccessful quitters (n=1003). Reasons cited for quitting were grouped as: medical diagnoses, social factors, symptoms. Logistic modeling of factors associated with successful quitting were adjusted for age, gender, race, and education. RESULTS: The most common factors cited for a quit attempt by all respondents were medical diagnoses (48%), followed by social factors (47%), and respiratory symptoms (36%). Successful quitters were more likely to be older, male, and non-Hispanic White. An adjusted model found increased age, White race, education beyond high school, and male sex favored successful quitting while the cited medical diagnoses, social factors, and "other" reasons were associated with unsuccessful quitting. Fagerstrom Nicotine Dependence scores were ³ 5 in 54% of the unsuccessful group compared to 45% for successful quitters(p<0.0001) suggesting some increased nicotine dependence in the unsuccessful quitters. CONCLUSIONS: Medical diagnosis was the most common factor cited for considering a quit attempt by both successful and unsuccessful quitters; however, successful quitting was influenced by demographic factors and potentially the severity of nicotine dependence.

Daily Activities: The Impact of COPD and Cognitive Dysfunction.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation; however, pulmonary function does not fully account for patients' functional difficulties. The primary aim of the study was to determine the association between several domains of cognition and daily activity among those with COPD. METHOD: Eighty-nine former smokers completed a neuropsychological battery including measures across multiple domains of cognition, pulmonary function measures, and daily activity questionnaires. Using a cross-sectional design, we compared daily activity between former smokers with and without COPD using two measures (St. George's Respiratory Questionnaire [SGRQ] Activity Subscale and Lawton Instrumental Activities of Daily Living [IADL] Scale) and examined the association between cognition and daily activity among those with COPD. RESULTS: As expected, former smokers with COPD reported more difficulty than those without COPD on both activity measures (SGRQ Activity Subscale p < .001; Lawton IADL Scale p = .040). Among former smokers with COPD, poorer delayed recall was associated with more difficulty with daily activities (SGRQ Activity Subscale) (p = .038) while adjusting for severity of airflow limitation, exercise tolerance, oxygen use, dyspnea, and symptoms of anxiety and depression. CONCLUSION: The findings suggest that cognition is associated with daily activity in patients with COPD. Future research should examine whether cognitive interventions may help to maximize patients' engagement in daily activities.

Home-Based Multicomponent Intervention Increases Exercise Activity and Improves Body Mass Index: Results of a 5-Year Randomized Trial Among Individuals with Alpha-1 Antitrypsin Deficiency-Associated Lung Disease.

BACKGROUND: The Step Forward Study (SFS) was designed to increase exercise activity and improve body mass index (BMI) among individuals with alpha-1 antitrypsin deficiency (AATD)-associated lung disease. METHODS: The SFS is a randomized trial of an intensive distance intervention that was delivered via a series of mailings and teleconferences versus no additional intervention. All participants (n=500) were also enrolled in a disease management program designed for individuals with AATD-associated lung disease who have been prescribed augmentation therapy. The primary outcome was self-reported number of exercise minutes per week. The secondary outcome was BMI. Linear mixed model analyses were used to assess the difference in average weekly exercise minutes between the intervention arms over time. T-tests, signed rank and Wilcoxon rank-sum tests were used to evaluate changes in BMI between the intervention arms and within each BMI category. RESULTS: The study included 429 individuals with evaluable primary outcome data.There was a significant effect of intervention on exercise minutes over time (p=0.018). Participants in the intervention group reported an average of 167.14 minutes (standard deviation [SD]=10.68) of weekly exercise and those in the standard care group reported 148.31 minutes (SD=10.96). There was a significant difference in BMI change between the intervention (mean BMI decrease 0.74, SD=2.16) and the standard care group (mean BMI decrease 0.27, SD=1.63); p=0.0122. CONCLUSION: Individuals who were randomly assigned to the intervention group reported more exercise activity and improvements in BMI over the course of this multicomponent intervention compared to individuals assigned to standard care.

Carotid Artery Stiffness is Associated With Cognitive Performance in Former Smokers With and Without Chronic Obstructive Pulmonary Disease.

Background Heavy smokers perform worse on neuropsychological assessment than age-matched peers. However, traditional pulmonary measures of airflow limitation and hypoxemia explain only a modest amount of variance in cognition. The current objective was to determine whether carotid artery stiffness is associated with cognition in former smokers beyond the effects of amount of smoking and pulmonary function. Methods and Results Eighty-four former smokers including individuals across a spectrum of airflow limitation severity were included: 30 without chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] 0 with normal spirometry and lung computed tomography), 31 with mild-moderate chronic obstructive pulmonary disease (GOLD 1-2), and 23 with severe-very severe chronic obstructive pulmonary disease (GOLD 3-4). Participants completed questionnaires, spirometry, carotid ultrasonography, and neuropsychological testing. Multiple linear regression was used to determine whether carotid artery stiffness is associated with neuropsychological performance in 4 cognitive domains after adjusting for age, sex, pack-years of smoking, estimated premorbid intellectual functioning, and airflow limitation. Higher carotid artery ß-stiffness index was associated with reduced executive functioning-processing speed in the fully adjusted model (ß=-0.49, SE=0.14; P=0.001). Lower premorbid intellectual function, male sex, and presence of airflow limitation (GOLD 1 or 2 and GOLD 3 or 4) were also associated with worse executive functioning-processing speed. ß-Stiffness index was not significantly associated with performance in other cognitive domains. Conclusions Carotid artery stiffness is associated with worse performance on executive functioning-processing speed in former smokers beyond the effects of aging, amount of past smoking, severity of airflow limitation, and hypoxemia. Future research should examine whether carotid stiffness can be used to identify former smokers at risk for subsequent cognitive impairment.

Reduced Attention in Former Smokers with and without COPD.

BACKGROUND: Attention difficulties are often reported by patients with chronic obstructive pulmonary disease (COPD); however, limited research exists using objective tests designed specifically to measure attention in this population. This study aimed to (1) identify specific attention deficits in COPD and (2) determine which demographic/clinical characteristics are associated with reduced attention. METHODS: Eighty-four former smokers (53 COPD, 31 no COPD) completed questionnaires, pulmonary function testing, and the Conner's Continuous Performance Test II (CPT-II). Participants with and without COPD were compared on CPT-II measures of inattention, impulsivity, and vigilance. CPT-II measures that differed significantly between the two groups were further examined using hierarchical regression modeling. Demographic/clinical characteristics were entered into models with attention as the dependent variable. RESULTS: Participants with COPD performed worse than those without COPD on CPT measures of inattention and impulsivity (i.e., detectability [discrimination of target from non-target stimuli], perseverations [reaction time under 100 ms], omissions [target stimuli response failures], and commissions [responses to non-target stimuli]). More severe COPD (measured by greater airflow limitation) was associated with poorer ability to detect targets vs. foils and perseverative responding after adjusting for age and other covariates in the model. CONCLUSION: Former smokers with COPD experience problems with attention that go beyond slowed processing speed, including aspects of inattention and impulsivity. Clinicians should be aware that greater airflow limitation and older age are associated with attention difficulties, as this may impact functioning.

Symptoms of anxiety and depression and use of anxiolytic-hypnotics and antidepressants in current and former smokers with and without COPD - A cross sectional analysis of the COPDGene cohort.

OBJECTIVES: To compare the frequency of anxiety/depressive symptoms and use of anxiolytic-hypnotics/antidepressants in smokers with and without COPD and to identify characteristics associated with having unmedicated symptoms. METHODS: Cross-sectional analysis of ambulatory, current/former smokers ≥10 pack years enrolled in the COPDGene study. We measured anxiety/depressive symptoms using the Hospital Anxiety and Depression Scale (subscales ≥8), recorded anxiolytic-hypnotic/antidepressant use, and defined unmedicated symptoms as elevated anxiety/depressive symptoms and not on medications. Regression analysis identified characteristics associated with having unmedicated symptoms. KEY RESULTS: Of 5331 current/former smokers (45% with and 55% without COPD), 1332 (25.0%) had anxiety/depressive symptoms. Anxiety symptoms were similar in frequency in smokers with and without COPD (19.7% overall), while depressive symptoms were most frequent in severe-very severe COPD at 20.7% (13.1% overall). In the entire cohort, 1135 (21.2%) were on medications. Anxiolytic-hypnotic use was highest in severe-very severe COPD (range 7.6%-12.0%), while antidepressant use showed no significant variation in smokers with and without COPD (range 14.7%-17.1%). Overall, 881 (66% of those with symptoms) had unmedicated symptoms, which was associated with African American race (adjusted OR 2.95, 95% CI 2.25-3.87), male gender (adjusted OR 1.93, 95% CI 1.57-2.36), no health insurance (adjusted OR 2.38, 95% CI 1.30-4.35), severe-very severe COPD (adjusted OR 1.48, 95% CI 1.04-2.11), and higher respiratory symptoms/exacerbation history (adjusted OR 2.21, 95% CI 1.62-3.02). CONCLUSIONS: Significant unmet mental health care needs exist in current and former smokers with and without COPD. One in five have unmedicated symptoms, identified by key demographic and clinical characteristics. PRIMARY FUNDING SOURCE: National Institutes of Health and The COPD Foundation.

GWAS and systems biology analysis of depressive symptoms among smokers from the COPDGene cohort.

BACKGROUND: Large sample GWAS is needed to identify genetic factors associated with depression. This study used genome-wide genotypic and phenotypic data from the COPDGene study to identify genetic risk factors for depression. METHODS: Data were from 9716 COPDGene subjects with ≥10 pack-year history. Depression was defined as antidepressant use and/or a HADS depression subscale score ≥8. Non-Hispanic White (6576) and African-American (3140) subsets were analyzed. A GWAS pipeline identified SNPs associated with depression in each group. Network analysis software analyzed gene interactions through common biological pathways, genetic interactions, and tissue-specific gene expression. RESULTS: The mean age was 59.4 years (SD 9.0) with 46.5% female subjects. Depression was in 24.7% of the NHW group (1622) and 12.5% of the AA group (391). No SNPs had genome-wide significance. One of the top SNPs, rs12036147 (p = 1.28 × 10-6), is near CHRM3. Another SNP was near MDGA2 (rs17118176, p = 3.52 × 10-6). Top genes formed networks for synaptic transmission with a statistically significant level of more co-expression in brain than other tissues, particularly in the basal ganglia (p = 1.00 × 10-4). LIMITATIONS: Limitations included a depression definition based on antidepressant use and a limited HADS score subgroup, which could increase false negatives in depressed patients not on antidepressants. Antidepressants used for smoking cessation in non-depressed patients could lead to false positives. CONCLUSIONS: Systems biology analysis identified statistically significant pathways whereby multiple genes influence depression. The gene set pathway analysis and COPDGene data can help investigate depression in future studies.