Analysis and evaluation of environmental tobacco smoke exposure as a risk factor for chronic cough

Exposure to environmental tobacco smoke (ETS) and active tobacco smoking has been shown to increase symptoms of bronchial asthma such as bronchoconstriction but effects on other respiratory symptoms remain poorly assessed. Current levels of exposure to tobacco smoke may also be responsible for the development of chronic cough in both children and adults. The present study analyses the effects of tobacco smoke exposure as potential causes of chronic cough. A panel of PubMed-based searches was performed relating the symptom of cough to various forms of tobacco smoke exposure. It was found that especially prenatal and postnatal exposures to ETS have an important influence on children's respiratory health including the symptom of cough. These effects may be prevented if children and pregnant women are protected from exposure to ETS. Whereas the total number of studies adressing the relationship between cough and ETS exposure is relatively small, the present study demonstrated that there is a critical amout of data pointing to a causative role of environmental ETS exposure for the respiratory symptom of cough. Since research efforts have only targeted this effect to a minor extent, future epidemiological and experimental studies are needed to further unravel the relation between ETS and cough

Molecular mechanism underlying the impact of vitamin D on disease activity of MS

Objective: Some previous studies suggest modest to strong effects of 25-hydroxyvitamin D (25(OH)D) on multiple sclerosis (MS) activity. The objective of this study was to explore the mechanistic rationale that may explain potential clinical effects of 25(OH)D. Methods: This study measured serum 25(OH)D levels and global gene expression profiles over a course of up to 2 years in patients starting treatment with interferon beta-1b (IFNB-1b) after a clinically isolated syndrome. MS disease activity was assessed by the number of gadolinium-enhancing lesions present on repeated magnetic resonance imaging (MRIs). Results: The number of gadolinium-enhancing lesions was highly significantly associated with 25(OH)D levels. Conducting various systems-level analyses on the molecular level, multiple lines of evidence indicated that 25(OH)D regulates expression dynamics of a large gene–gene interaction system which primarily regulates immune modulatory processes modulating MS activity. The vitamin D response element was significantly enriched in this system, indicating a direct regulation of this gene interaction network through the vitamin D receptor. With increasing 25(OH)D levels, resulting regulation of this system was associated with a decrease in MS activity. Within the complex network of genes that are regulated by 25(OH)D, well-described targets of IFNB-1b and a regulator of sphingosine-1-phosphate bioavailability were found. The 25(OH)D effects on MS activity were additively enhanced by IFNB-1b. Interpretation Here, we provide mechanistic evidence that an unbalanced 25(OH)D gene expression system may affect MS activity. Our findings support a potential benefit of monitoring and managing vitamin D levels (e.g., through supplementation) in early MS patients treated with IFN-beta-1b

The 11-year long-term follow-up study from the randomized BENEFIT CIS trial

L

Causes of death among commercially insured multiple sclerosis patients in the United States.

BACKGROUND: Information on causes of death (CODs) for patients with multiple sclerosis (MS) in the United States is sparse and limited by standard categorizations of underlying and immediate CODs on death certificates. Prior research indicated that excess mortality among MS patients was largely due to greater mortality from infectious, cardiovascular, or pulmonary causes. OBJECTIVE: To analyze disease categories in order to gain insight to pathways, which lead directly to death in MS patients. METHODS: Commercially insured MS patients enrolled in the OptumInsight Research database between 1996 and 2009 were matched to non-MS comparators on age/residence at index year and sex. The cause most-directly leading to death from the death certificate, referred to as the "principal" COD, was determined using an algorithm to minimize the selection of either MS or cardiac/pulmonary arrest as the COD. Principal CODs were categorized into MS, cancer, cardiovascular, infectious, suicide, accidental, pulmonary, other, or unknown. Infectious, cardiovascular, and pulmonary CODs were further subcategorized. RESULTS: 30,402 MS patients were matched to 89,818 controls, with mortality rates of 899 and 446 deaths/100,000 person-years, respectively. Excluding MS, differences in mortality rate between MS patients and non-MS comparators were largely attributable to infections, cardiovascular causes, and pulmonary problems. Of the 95 excessive deaths (per 100,000 person-years) related to infectious causes, 41 (43.2%) were due to pulmonary infections and 45 (47.4%) were attributed to sepsis. Of the 46 excessive deaths (per 100,000 person-years) related to pulmonary causes, 27 (58.7%) were due to aspiration. No single diagnostic entity predominated for the 60 excessive deaths (per 100,000 person-years) attributable to cardiac CODs. CONCLUSIONS: The principal COD algorithm improved on other methods of determining COD in MS patients from death certificates. A greater awareness of the common CODs in MS patients will allow physicians to anticipate potential problems and, thereby, improve the care that they provide

Distribution of patients with MS and non-MS comparators.

a<p>Due to the matching, the MS and comparator cohorts had the same distribution of demographic factors.</p>b<p>The birth year for patients born before 1920 was set to 1920 to protect privacy.</p>c<p>Includes gaps in coverage.</p><p>DMT, disease modifying therapy. MS, multiple sclerosis. OIR, OptumInsight Research.</p

The 11-year long-term follow-up study from the randomized BENEFIT CIS trial

To assess outcomes for patients treated with interferon beta-1b immediately after clinically isolated syndrome (CIS) or after a short delay.status: publishe

Number of deaths and mortality rate/100,000 person-years (95% confidence interval) by major disease/injury category according to principal, underlying, and immediate cause of death (COD).

a<p>Includes all ICD-10 codes not assigned to one of the other categories; examples include diabetes mellitus, all gastrointestinal diseases, hematologic diseases, etc.</p>b<p>Includes 333 deaths that did not have death certificate information because they were identified from Social Security records, but not from the national death index (NDI), plus a small number of individuals identified from the NDI whose death certificate data were insufficient to assign a cause of death.</p>c<p>One subject in the comparator group developed MS post-entry into the study.</p><p>MS, multiple sclerosis.</p

Algorithm for determining principal cause of death (COD) and primary disease/injury categories.

<p>The algorithm used to determine the principal COD based on ICD-10 codes. These codes were then sorted into 10 major disease/injury categories. ^aIncludes all ICD-10 codes not assigned to one of the other categories; examples include diabetes mellitus, all gastrointestinal diseases, hematologic diseases, etc.</p