Inflammatory response in acute viral exacerbations of COPD.

BACKGROUND: Respiratory viruses are important triggers of acute exacerbations of COPD (AE-COPD). However, the inflammatory response in virus-positive exacerbations is still not fully understood. METHODS: We investigated CRP, IL-6, IL-8, IL-10, IFN-gamma, blood and sputum cells in patients with acute exacerbation (n = 36) and in stable disease (n = 20) and correlated these parameters to virus detection in respiratory secretions. RESULTS: Similar to other studies we found a significant increase in systemic CRP and absolute numbers of blood leukocytes in AE-COPD patients. Sputum IL-6 levels and sputum eosinophils tended to be higher during exacerbation. In patients with detection of respiratory viruses in nasal lavage, local IL-6 production in sputum was significantly increased; FEV(1) was significantly decreased and both parameters were inversely correlated to each other. CONCLUSION: This study supports previous findings of both, increased local and systemic inflammation in acute exacerbation of COPD. In virus-associated exacerbations, IL-6 is significantly increased and negatively correlated to FEV1 indicating a relation between virus-induced inflammation and airway obstruction. However, regarding our finding and previous data, it is becoming increasingly clear that the mediators investigated so far do not permit identifying the etiology of AE-COPD. Hence, further studies are needed to better define the inflammatory response in AE-COPD in general and in viral exacerbations in particular.

Inhalation of stable dust extract prevents allergen induced airway inflammation and hyperresponsiveness.

BACKGROUND: Recent epidemiological studies have shown that growing up on a traditional farm provides protection from the development of allergic disorders such as hay fever and allergic asthma. We present experimental evidence that substances providing protection from the development of allergic diseases can be extracted from dust collected in stables of animal farms. METHODS: Stable dust was collected from 30 randomly selected farms located in rural regions of the Alps (Austria, Germany and Switzerland). The dust was homogenised with glass beads and extracted with physiological sodium chloride solution. This extract was used to modulate immune response in a well established mouse model of allergic asthma. RESULTS: Treatment of mice by inhalation of stable dust extract during sensitisation to ovalbumin inhibited the development of airway hyperresponsiveness and airway eosinophilia upon challenge, as well as the production of interleukin 5 by splenocytes and of antigen specific IgG(1) and IgE. Dust extract also suppressed the generation of human dendritic cells in vitro. The biological activity of the dust extract was not exclusively mediated by lipopolysaccharide. CONCLUSIONS: Stable dust from animal farms contains strong immune modulating substances. These substances can interfere with the development of both cellular and humoral immunity against allergens, thus suppressing allergen sensitisation, airway inflammation, and airway hyperresponsiveness in a murine model of allergic asthma.

Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are a common cause of hospital admission. Many exacerbations are believed to be due to upper and/or lower respiratory tract viral infections, but the incidence of these infections in patients with COPD is still undetermined. METHODS: Respiratory syncytial virus (RSV), influenza A and B, parainfluenza 3, and picornaviruses were detected by nested reverse transcription polymerase chain reaction (RT-PCR) in upper (nasal lavage) and lower respiratory tract specimens (induced sputum). In a 2:1 case-control set up, 85 hospitalised patients with AE-COPD and 42 patients with stable COPD admitted for other medical reasons were studied. RESULTS: Respiratory viruses were found more often in sputum and nasal lavage of patients with AE-COPD (48/85, 56%) than in patients with stable COPD (8/42, 19%, p<0.01). The most common viruses were picornaviruses (21/59, 36%), influenza A (15/59, 25%), and RSV (13/59, 22%). When specimens were analysed separately, this difference was seen in induced sputum (exacerbation 40/85 (47%) v stable 4/42 (10%), p<0.01) but was not significant in nasal lavage (exacerbation 26/85 (31%) v stable 7/42 (17%), p=0.14). In patients with AE-COPD, fever was more frequent in those in whom viruses were detected (12/48, 25%) than in those in whom viruses were not detected (2/37, 5%, p=0.03). CONCLUSION: Viral respiratory pathogens are found more often in respiratory specimens of hospitalised patients with AE-COPD than in control patients. Induced sputum detects respiratory viruses more frequently than nasal lavage in these patients. These data indicate that nasal lavage probably has no additional diagnostic value to induced sputum in cross-sectional studies on hospitalised patients with AE-COPD and that the role of viral infection in these patients is still underestimated.

Assessing basic HIV transmission risks and the contextual factors associated with HIV risk behavior in men who have sex with men.

HIV/AIDS remains a substantial health threat to men who have sex with men. Although new HIV medications have provided great benefits for many HIV-positive individuals, they have done little to protect HIV-negative men. Consequently, changing one's sexual practices remains the most effective way to reduce risk for HIV. However, to develop an effective intervention for reducing HIV risk, it is important to fully understand risk behavior. In this article, we detail the essential elements for conducting an HIV risk assessment as well as those contextual factors that may support risk behaviors. Further, we discuss the importance of procuring an HIV test and the critical issues that may arise because of testing for HIV as well as the critical issues that may result from testing HIV-positive. Finally, we illustrate how we integrate an HIV health risk assessment into a clinical interview.

Polymerase chain reaction-single strand conformation polymorphism or how to detect reliably and efficiently each sequence variation in many samples and many genes.

A simple and fast method with high reliability is necessary for the identification of mutations, polymorphisms and sequence variants (MPSV) within many genes and many samples, e.g. to clarify the genetic background of individuals with multifactorial diseases. We evaluated polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis to identify MPSV in several genes, which are thought to be involved in the pathogenesis of multifactorial autoimmune diseases like multiple sclerosis. The method is based on the property, that the electrophoretic mobility of single-stranded nucleic acids depends not only on its size but also on its sequence. The target sequence was amplified, digested into fragments ranging from 50-200 bp, heat-denatured and analyzed on native gels. The analysis of 55 PCR systems, including a total of 145 fragments demonstrates, that the detection rate of MPSV depends primarily on the fragment lengths. Appropriate dilutions of samples enhances the proportion of ssDNA compared to dsDNA. Changing the gel conditions, glycerol concentrations and/or the addition of urea may increase fragment resolution in some cases. In general, the detection of MPSV is neither influenced by their location within the fragment nor by the type of substitution, i.e. transitions or transversions. The standard PCR-SSCP system described here provides high reliability and detection rates and allows the efficient analysis of many samples and many genes.

Situational factors associated with AIDS risk behavior lapses and coping strategies used by gay men who successfully avoid lapses.

While most gay men have reduced behavior practices at high risk for HIV infection, there is growing evidence that many also lapse to unsafe sex. This study examined situational factors related to risk behavior lapses as well as coping strategies used by men who successfully resist lapse urges. A convenience sample of 470 men patronizing gay bars or attending social organization meetings in four cities was surveyed. Forty-five percent of men were classified as "lapsers" (those who had had unprotected anal intercourse in the previous 6 months) and 24% were classified as "resisters" (those who successfully resisted urges to engage in this behavior). All provided information concerning the importance of factors related to the most recent occurrence of either unsafe sex or resisting unsafe urges. Most episodes of unsafe sex occurred outside monogamous relationships and with partners of unknown HIV serostatus, although simply inquiring about partner serostatus was relatively common. Lapsers rated affectionate feelings and wishing to please a partner as well as spontaneity of unsafe sex as the most important situational factors surrounding high-risk behavior. Resisters of unsafe sex urges reported active cognitive self-guidance, experience in safe sex, and recall of both AIDS fears and safety benefits as their most important coping strategies. Gay men who continue high-risk behavior may be overrelying on partner reports of negative serostatus. Lapse prevention approaches tailored to situations that create increased risk vulnerability must be developed. Teaching skills already used by men who successfully resist unsafe sex urges might be one approach.

Reliability of retrospective assessments of sexual HIV risk behavior: a comparison of biweekly, three-month, and twelve-month self-reports.

A review of 30 AIDS behavioral research studies revealed that almost half employed retrospective sexual activity assessment periods of 12 months or longer. The present study examined the correspondence between retrospective reports of sexual activity for 3 overlapping time-frames (past 2 weeks, past 3 months, and past 12 months) for 61 gay men. Adjusted for equivalent 12-month intervals, the reported mean frequencies of sexual practices were considerably higher for shorter recall periods than for longer recall periods, a discrepancy greater than would be expected by normal activity fluctuation. The study also found that behavior reported across shorter retrospective time-frames was more consistent, while reliability for frequently occurring and unsafe sexual activities decreased as the recall period lengthened. Studies utilizing recall periods of 12 months or more may produce data of questionable reliability.

Validation of depression measures in adolescent populations.

Four measures of depression were administered to a normative sample (n = 44) and two psychiatric groups of adolescents (n = 40). Measures included the Adolescent Activity Checklist (AAC), Beck Depression Inventory (BDI), Automatic Thoughts Questionnaire (ATQ), and Dysfunctional Attitudes Scale (DAS). Only the BDI and ATQ were able to discriminate among the three populations. The DAS and frequency of unpleasant activity (FRUA) subscales of the AAC only differentiated between nondepressed and depressed psychiatric subjects. Adolescent behavioral activity related to depression differed from adults with only mixed support found for cognitive depression among adolescents.