Metformin use and health care utilization in patients with coexisting chronic obstructive pulmonary disease and diabetes mellitus.

Background: Chronic obstructive pulmonary disease (COPD) is associated with persistent systemic inflammation. Anti-inflammatory therapies have been shown to decrease acute exacerbations of COPD. The antidiabetic medication metformin decreases oxidative stress and inflammation and may benefit patients with COPD. We aimed at investigating the effect of metformin on health care utilizations in patients with coexisting COPD and diabetes mellitus (DM). Methods: We studied 5% Medicare beneficiaries with coexisting COPD and DM prescribed metformin or other antidiabetics during the period 2007-2010. The primary outcome was COPD-specific emergency room (ER) visits and hospitalizations; the secondary outcome was all-cause ER visits and hospitalizations over the 2-year follow-up after the index antidiabetic prescription. The effects of metformin were examined by COPD complexity and compared with the effects of other antidiabetic medications. Results: Among 11,260 patients, 3,193 were metformin users and 8,067 were nonusers. Metformin users were younger, were less sick, were less likely to be on oxygen, and had fewer hospitalizations in the prior year compared with the nonusers. Over a 2-year period, metformin users had lower COPD-specific and all-cause ER visits and hospitalizations (7.11% vs 9.61%, p<0.0001; and 61.63% vs 71.27%, p<0.0001, respectively). In a stratified multivariable analysis, the odds of COPD-specific ER visits and hospitalizations were lower in patients with low-complexity COPD (adjusted odds ratio =0.66, 95% confidence interval =0.52-0.85). However, patients with all COPD complexities get benefits of metformin on all-cause ER visits and hospitalizations. Conclusion: The use of metformin in patients with coexisting COPD and DM was associated with fewer COPD-specific ER visits and hospitalizations, especially in low-complexity COPD.

Long-acting bronchodilators with or without inhaled corticosteroids and 30-day readmission in patients hospitalized for COPD.

BACKGROUND: The ability of a long-acting muscarinic antagonist (LAMA) and long-acting beta 2 agonists (LABAs; long-acting bronchodilators, LABDs) with or without inhaled corticosteroids (ICSs) to reduce early readmission in hospitalized patients with COPD is unknown. METHODS: We studied a 5% sample of Medicare beneficiaries enrolled in Medicare parts A, B and D and hospitalized for COPD in 2011. We examined prescriptions filled for LABDs with or without ICSs (LABDs±ICSs) within 90 days prior to and 30 days after hospitalization. Primary outcome was the 30-day readmission rate between "users" and "nonusers" of LABDs±ICSs. Propensity score matching and sensitivity analysis were performed by limiting analysis to patients hospitalized for acute exacerbation of COPD (AECOPD). Among 6,066 patients hospitalized for COPD, 3,747 (61.8%) used LABDs±ICSs during the specified period. The "user" and "nonuser" groups had similar rates of all-cause emergency room (ER) visits and readmissions within 30 days of discharge date (22.4% vs 20.7%, P-value 0.11; 18.0% vs 17.8%, P-value 0.85, respectively). However, the "users" had higher rates of COPD-related ER visits (5.3% vs 3.4%, P-value 0.0006), higher adjusted odds ratio (aOR) 1.47 (95% CI, 1.11-1.93) and readmission (7.8% vs 5.0%, P-value <0.0001 and aOR 1.48 [95% CI, 1.18-1.86]) than "nonusers". After propensity score matching, the aOR of COPD-related ER visits was 1.45 (95% CI, 1.07-1.96) and that of readmission was 1.34 (95% CI, 1.04-1.73). The results were similar when restricted to patients hospitalized for AECOPD. CONCLUSION: Use of LABDs±ICSs did not reduce 30-day readmissions in patients hospitalized for COPD.

Mixing It Up: Coadministration of tPA/DNase in Complicated Parapneumonic Pleural Effusions and Empyema.

BACKGROUND: A recent randomized controlled trial showed 12 serial doses of tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) is safe and effective in managing complicated parapneumonic pleural effusions and empyema (CPEE). However, this regimen is laborious, requiring trained personnel to open/close the chest tube 8 times daily for 3 days. We present our observational data using a simplified regimen of coadministered tPA/DNase. MATERIALS AND METHODS: This is a retrospective observational study of patients who received coadministered tPA/DNase for CPEE from January 2012 to April 2015 at the University of Texas Medical Branch. Patient demographics, pleural fluid, radiologic and treatment characteristics, and outcomes were collected. Data are presented as proportions and percentages. Our primary outcome was successful treatment without need of surgery and discharge home alive. Secondary outcomes were dose and length of treatment and hospital stay, treatment complications, and 90-day mortality. RESULTS: The study included 39 patients. All pleural effusions were loculated, 59% macroscopically purulent, 50% had a positive organism in Gram stain, and 40% were culture positive. A median of 6 (interquartile range, 3.5 to 6) doses were coadministered mainly via small bore chest tube (≤14 Fr in 79%) with a median of 14.5 (interquartile range, 9.5 to 21.5) hospital days. Overall, 85% were successfully treated without need for surgery. Treatment failures occurred in 15%: 3/39 (7%) received surgery; 3/39 (7%) died. Only 1 (2.5%) complication of hemorrhagic pleural effusion resolved after discontinuation of intrapleural treatment. CONCLUSIONS: Our study shows intrapleural coadministration of tPA/DNase was effective and safe in management of CPEE.

Epidemiologic link between tuberculosis and cigarette/biomass smoke exposure: Limitations despite the vast literature.

The geographic overlap between the prevalence of cigarette smoke (CS) exposure and tuberculosis (TB) in the world is striking. In recent years, relatively large number of studies has linked cigarette or biomass fuel smoke exposure and various aspects of TB. Our goals are to summarize the significance of the known published studies, graphically represent reports that quantified the association and discuss their potential limitations. PubMed searches were performed using the key words 'tuberculosis' with 'cigarette', 'tobacco', 'smoke' or 'biomass fuel smoke.' The references of relevant articles were examined for additional pertinent papers. A large number of mostly case-control and cross-sectional studies significantly associate both direct and second-hand smoke exposure with tuberculous infection, active TB, and/or more severe and lethal TB. Fewer link biomass fuel smoke exposure and TB. While a number of studies interpreted the association with multivariate analysis, other confounders are often not accounted for in these analyses. It is also important to emphasize that these retrospective studies can only show an association and not any causal link. We further explored the possibility that even if CS exposure is a risk factor for TB, several mechanisms may be responsible. Numerous studies associate cigarette and biomass smoke exposure with TB but the mechanism(s) remains largely unknown. While the associative link of these two health maladies is well established, more definitive, mechanistic studies are needed to cement the effect of smoke exposure on TB pathogenesis and to utilize this knowledge in empowering public health policies.

Tobacco exposure and susceptibility to tuberculosis: is there a smoking gun?

In many regions of the world, there is a great overlap between the prevalence of cigarette smoke exposure and tuberculosis. Despite the large body of epidemiologic evidence that tobacco smoke exposure is associated with increased tuberculosis infection, active disease, severity of disease, and mortality from tuberculosis, these studies cannot distinguish whether the mechanism is principally through direct impairment of anti-tuberculosis immunity by cigarette smoke or due to potential confounders that increase risk for tuberculosis and are commonly associated with smoking--such as poverty, malnutrition, and crowded living conditions. While there are several in vivo murine and in vitro macrophage studies showing cigarette smoke impairs control of tuberculous infection, little is known of the molecular and cellular mechanisms by which this impairment occurs. Herein, we highlight the key findings of these studies. Additionally, we review key immune cells that play critical roles in host-defense or pathogenesis of tuberculosis and generate a hypothesis-driven discussion of the possible mechanisms by which cigarette smoke impairs or enhances their functions, respectively, ultimately resulting in compromised immunity against tuberculosis.