A time-series study of the health effects of water-soluble and total-extractable metal content of airborne particulate matter.

OBJECTIVES: To assess whether adverse acute cardiopulmonary health outcomes are associated with concentration of trace metals in airborne particulate matter. METHODS: Daily PM(10) and PM(2.5) were collected for 1 year in Edinburgh, UK, and the water-soluble and total-extractable content of 11 trace metals determined in each sample. Time series were analysed using generalised additive Poisson regression models, including adjustment for minimum temperature and less smoothing of trends. Methods were explored of extending the time series of metal concentration in daily PM(10) for the previous 7 years using multiple regression of the variation in metal content for the 1 year of measurements and the associated variation in air mass source region and other concurrently-measured potential predictor variables. RESULTS: The 1 year of direct measurements showed no evidence of significant associations of particle-bound metal concentration with health outcomes beyond that expected by chance. Analysis of the extended time series showed significant positive associations with cardiovascular admissions both for total PM(10) and for a number of the metals (eg, Cu, Fe, Ni, V, Zn) but the metal effects were no longer significant after adjusting for PM(10). CONCLUSIONS: Within the limitations of the study power, the epidemiological results have not provided evidence for associations between particle-bound metal concentrations and adverse health outcomes that are substantially greater than for total PM. The generally strong correlations between metal and total PM suggest that quantifying independent effects of PM metal exposure on health will be difficult, even using more powerful time series of direct measurements.

Poisons admissions in Edinburgh 1981-2001: agent trends and predictors of hospital readmissions.

Self-poisoning is a major public health problem. This study describes patterns of admissions and readmissions from self-poisoning to the Royal Infirmary of Edinburgh from 1981 to 2001. A database on hospital discharges with a diagnosis (ICD-9/10) of poisoning between 1981 and 2001 was used. Annual admissions were described for seven main drug categories, and proportions of patients readmitted within 1-5 years from first admission, were computed for each category. Cox proportional hazards regression was used to evaluate prognostic factors for readmission risk over 1981-2001. For both sexes, admissions increased from the early to mid 1990s, and declined thereafter. The proportion readmitted varied with the drug taken at first admission, from 11.9% (95% CI: 10.8-13%) for non-opiate analgesics, to 17.6% (16.5-18.7%) for benzodiazepines. Deprivation was positively related to readmission risk after first admissions with paracetamol (P < 0.001) and benzodiazepines (P < 0.001). Timing of first admissions involving paracetamol (P < 0.01), benzodiazepines (P < 0.001), antidepressants (P < 0.001), non-opiate analgesics (P < 0.001), and opiates (P < 0.05), was inversely associated with readmission risk. In patients admitted for drug overdose, readmission risk is influenced by type of drug taken at first admission. Information on drug type used in self-poisoning may assist in identifying patients at risk for future events, and in reducing hospital readmissions.

Unintentional home injury in preschool-aged children: looking for the key--an exploration of the inter-relationship and relative importance of potential risk factors.

OBJECTIVE: To investigate the physical, social and psychological environment of families with preschool-age children to identify the most significant risk factors for unintentional injury. DESIGN: A 1-year prospective case-control study, using a health-visitor-administered questionnaire. SETTING: East and Midlothian, Scotland. SUBJECTS: Seventy-nine children under 5 years of age presenting to an accident and emergency (A&E) department during 1998-1999 with an unintentional home injury and 128 matched controls. RESULTS: Of 264 families, 207 responded (78.4% response rate). The main carers of cases had a lower level of educational attainment than controls (P<0.01). This factor explained the case carer leaving fulltime education earlier, being less likely to be married and more often in receipt of government benefits. Cases lived in households with larger numbers of children, were more likely to have a physical illness, were less likely to have had a non-medically attended injury in the previous year (P<0.01) but more likely to have had another A&E injury attendance. Case households had lower electrical socket cover utilization (P<0.01) and fewer thought their child had adequate access to safe play areas. The main carers of cases tended to have a more negative life event experience in the preceding 6 months, but showed no significant differences in physical or mental well-being or social support. Cases seemed to be slightly more deprived members of their community. CONCLUSIONS: The main carer's educational attainment and socket cover utilization were lower in case families. These risk factors could be used to target families for injury-prevention work. Initiatives to raise educational achievement in the general population could lead to reductions in childhood injuries.

Comparison of 5% povidone-iodine solution against 1% povidone-iodine solution in preoperative cataract surgery antisepsis: a prospective randomised double blind study.

BACKGROUND/AIM: Povidone-iodine (PI, Betadine) is routinely used as a preoperative topical antiseptic in cataract surgery as it has been shown to reduce the incidence of postoperative endophthalmitis. However, the concentration used clinically is variable. In vitro studies have shown that PI is paradoxically more effective at lower concentration. This study was undertaken to determine if this effect was reproducible in vivo. METHODS: A prospective randomised double blind study was carried out in the ophthalmic theatre in a district general hospital. 105 patients attending for routine cataract surgery were randomly allocated to have their conjunctival fornices irrigated preoperatively with either PI 1% (group A) or PI 5% (group B). Conjunctival swabs were taken, in identical fashion, both before and 1 minute after irrigation. The number and species of bacterial colonies cultured from each swab was counted. The difference in the median number of bacterial colonies from pre-irrigation to post-irrigation cultures was then compared between the groups. RESULTS: Bacterial cultures were gained from 100 patients (33 male, 67 female, mean age 74 years, range 30-95 years). Group B (5% PI) showed a decrease in median colony forming units (CFU) pre-irrigation from 100 to 40 CFU post-irrigation (a drop of 60%). This was greater than in group A (1% PI) where the reduction was 120 CFU pre-irrigation to 100 CFU post-irrigation (a drop of 16.7%) (Mann-Whitney test, p<0.05). At higher initial bacterial loads (CFU pre-irrigation >1000), the difference in median between the two groups became larger as the number of pre-irrigation bacteria increased. In group B pre-irrigation CFU reduced from 3340 to 110 post-irrigation (a drop of 96.7%) compared with group A: 5000 CFU pre-irrigation to 3000 post-irrigation (a drop of 40%) (Mann-Whitney test, p=0.0014). CONCLUSION: Despite in vitro evidence of higher bactericidal efficacy of PI at more dilute concentrations, 5% PI is more effective than 1% PI in decreasing the human conjunctival bacterial flora in vivo, particularly in the presence of heavier initial bacterial load.

Linear and knemometric growth in the early phase of rehabilitation from severe malnutrition.

The relationship between ponderal, linear and lower leg growth in children recovering from severe malnutrition remains unclear. We report on the early growth of 141 severely malnourished Bangladeshi children aged 6 to 36 months of age who were followed for 90 d. Mean (sd) weight for height (WHZ) and height for age (HAZ) catch-up growth z scores over the 90 d were 1.6 (0.85) and 0.47 (0.325) respectively. Mean (sd) lower leg length growth was 10.35 (4.5) mm. Change in HAZ was significantly associated with initial WHZ, but linear growth occurred in the presence of severe wasting and no threshold WHZ score was identified. Lower leg length gain correlated throughout with ponderal indices but with change in HAZ score only after day 45. Only initial WHZ score and maternal height predicted for linear growth and only accounted for 20 % of total variance. We conclude that linear growth occurs early in severely malnourished children but that knemometry behaves as a ponderal index acutely.

Monitoring breastfeeding rates and setting local targets: the Glasgow experience.

OBJECTIVE: The objective was to provide baseline data on infant feeding intention and practice in Glasgow. DESIGN: Information was collected from a prospective cohort of women who booked for maternity care in Glasgow during the months November 1995 and May 1996. Figures on feeding intention and practice were collected at five points from maternity booking until six weeks postnatal age. SETTING: Women were recruited at the four maternity units in Glasgow. Follow-up information was collected at birth, discharge from the maternity hospital at four days, and then at 12 days at home by the community midwife, and finally at six weeks by the health visitor. SUBJECTS: One thousand seven hundred and ninety two women were recruited at maternity booking. Breastfeeding information was available at birth for 1723, at discharge for 1743, at 12 days for 1513, and at six weeks for 1394. Multiple logistic regression determined maternal and infant factors predicting feeding intention and duration. RESULTS: At booking 50% planned to breastfeed. Fifty percent breastfed at birth; by four days the rate had dropped to 42%, by 12 days to 36% and by six weeks to 27%. Five factors: deprivation score, maternal age, parity, maternal smoking and previous breastfeeding experience independently predicted feeding intention. Maternal factors explained differences in breastfeeding rates between the four hospitals. CONCLUSION: Original breastfeeding targets for Glasgow have been revised to take account of local circumstances. An alternative method using routinely collected data is needed to monitor progress.

Quantitative assessment of IgG antibodies to Helicobacter pylori and outcome of ischaemic heart disease.

Criticisms of serological studies on Helicobacter pylori and ischaemic heart disease (IHD) include: undiagnosed heart disease in live controls; no assessment of severity or outcome of IHD; and qualitative not quantitative measurements of IgG to the bacteria. The aim was to assess quantitatively IgG levels specific for H. pylori (ng ml(-1)) among patients who survived a myocardial infarction (MI) with those who died of IHD. Sera were from four groups: (1) men who survived one MI; (2) men matched for age and socioeconomic background to group 1; (3) individuals who died suddenly of IHD; (4) accidental deaths matched for age and sex to group 3. Levels of IgG to H. pylori increased with age (P<0.005) but were not associated with smoking or socioeconomic groups. There was a correlation between IgG to the bacteria and decreasing socioeconomic levels only among group 1 (P<0.01). IgG levels were higher for subjects who died of heart disease (median=151 ng ml(-1)) compared with survivors (median=88 ng ml(-1)) (P=0.034) and higher for survivors compared with their controls (median=58 ng ml(-1)) (P=0.039). Future serological studies of H. pylori in relation to IHD should be quantitative and severity of disease considered in analyses.

No effect of dietary trans isomers of alpha-linolenic acid on platelet aggregation and haemostatic factors in european healthy men. The TRANSLinE study.

The aim of this study was to investigate the effect of trans alpha-linolenic acid on platelet aggregation and blood haemostasis. A randomized, double blind dietary intervention trial was carried out with healthy male volunteers (n=88) in three European centers. After a 6-week washout period where subjects avoided foods containing all trans fats, subjects either continued for 6 weeks with a low trans diet or a diet where trans alpha-linolenic acid provided 0.6% of energy (supplied as oil, margarine, cheese, muffins, and biscuits). At the end of the washout period the intake of trans polyunsaturated fats was 58+/-115 mg/day; this increased in patients on the high trans diet by +1344+/-328 mg/day, compared with +10+/-67 mg/day in patients on the low trans diet (p<0.01). The change in trans alpha-linolenic acid in plasma cholesteryl esters was 0.26+/-0. 20 on the high trans and 0.00+/-0.07% of fatty acids on the low trans diet (p<0.001). No effect of the high trans diet was observed on platelet aggregation: collagen EC(50) high trans 157+/-100, low trans 152+/-90 ng/mL (NS); U44619 EC(50) high trans 81+/-61, low trans 59+/-27 nM (NS). The high trans diet did not affect platelet thromboxane production, fibrinogen levels, factor VII, activated factor VIIa, or plasminogen activator inhibitor activity. There were no center-specific differences in response to the high trans diet. A relatively high amount of trans alpha-linolenic acid for 6 weeks does not increase the risk of coronary heart disease by promoting platelet aggregation and blood coagulation.

Adult cardiovascular risk factors in premature babies.

Among babies born at term, low birthweight predicts cardiovascular risk factors and disease in adulthood. This study shows that babies born prematurely, whether or not they have intrauterine growth retardation, are predisposed to similar risks as adults.

Vitamin C and the risk of acute myocardial infarction.

BACKGROUND: Low-fat soluble-antioxidant status is associated with an increased risk of heart disease. OBJECTIVE: The aim of this study was to examine whether low plasma concentrations of vitamin C confer an independent risk of acute myocardial infarction (AMI). DESIGN: Male patients (n = 180) aged <65 y with a first AMI and without an existing diagnosis of angina (>6 mo) who were admitted within 12 h after onset of symptoms were compared with apparently healthy volunteers (n = 177). Plasma concentrations and dietary intakes of vitamin C were determined during hospitalization and 3 mo later. RESULTS: Compared with the control subjects, the patients had higher total cholesterol and lower HDL-cholesterol concentrations and more of them smoked. The relative risk of AMI for the lowest compared with the highest quintile of plasma vitamin C during hospitalization (14.5 and >60.5 micromol/L, respectively) was 8.37 (95% CI: 3.28, 21. 4) after adjustment for classic risk factors. At 3 mo, mean (+/-SEM) plasma vitamin C concentrations in patients had increased significantly, from 19.6 +/- 1.2 to 35.1 +/- 1.9 micromol/L (P < 0. 001) and no longer conferred a risk of AMI [relative risk: 1.02 (95% CI: 0.51, 2.03)]. Habitual dietary vitamin C intake of patients (before AMI) did not differ significantly from that of control subjects. The increase in plasma vitamin C after recovery from the infarction could not be explained by a similarly large increase in dietary vitamin C. CONCLUSIONS: A low plasma concentration of vitamin C was not associated with an increased risk of AMI, irrespective of smoking status. The apparent risk of AMI due to a low plasma vitamin C concentration was distorted by the acute phase response.

Analysis of muscle function in the lower limb after fracture of the diaphysis of the tibia in adults.

We examined the recovery of power in the muscles of the lower limb after fracture of the tibial diaphysis, using a Biodex dynamometer. Recovery in all muscle groups was rapid for 15 to 20 weeks following fracture after which it slowed. Two weeks after fracture the knee flexors and extensors have about 40% of normal power, which rises to 75% to 85% after one year. The dorsiflexors and plantar flexors of the ankle and the invertors and evertors of the subtalar joint are much weaker two weeks after injury, but at one year their mean power is more than that of the knee flexors and extensors. Our findings showed that age, the mode of injury, fracture morphology, the presence of an open wound and the Tscherne grade of closed fractures correlated with muscle power. It is age, however, which mainly determines muscle recovery after fracture of the tibial diaphysis.

Bactericidal activity of a monocytic cell line (THP-1) against common respiratory tract bacterial pathogens is depressed after infection with respiratory syncytial virus.

Non-typable Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis and respiratory syncytial virus (RSV) are commonly isolated from patients during the course of chronic obstructive pulmonary disease (COPD). Earlier studies found that virus infection enhanced binding of bacterial respiratory pathogens to epithelial cells in vitro. The objective of the present study was to assess the effect of RSV infection of a human monocytic cell line on bactericidal activity and cytokine production in response to these bacterial respiratory pathogens. The effect of RSV infection on binding, uptake and intracellular killing of bacteria by a human monocytic leukaemia cell line, THP-1, was assessed. Cell culture supernates were examined with a mouse fibroblast cell assay for tumour necrosis factor-alpha (TNF-alpha) bioactivity. Expression of CD14, CD11a, CD18, CD15 and CD29 on uninfected and RSV-infected THP-1 cells was assessed by flow cytometry in relation to differences in bacterial binding. RSV infection of THP-1 cells significantly decreased their ability to bind and kill bacteria. Compared with uninfected cells, fewer bacteria bound to RSV-infected THP-1 cells and the surface antigens that have been reported to bind bacteria were expressed at lower levels on RSV-infected cells. RSV-infected cells incubated with bacteria exhibited less TNF-alpha bioactivity than uninfected cell incubated with bacteria. The results elucidate some of the mechanisms involved in the increased susceptibility of virus-infected patients to secondary bacterial infection. Reduced bacterial killing by virus-infected monocytes might contribute to reduced clearance of bacteria from the respiratory tract and damage elicited by the bacteria or cytokine response in COPD patients.

Investigation of factors which might indicate susceptibility to particulate air pollution.

OBJECTIVES: To determine whether previous symptoms or recognized risk factors of cardiovascular ill health, are associated with an increased likelihood of adverse health effects related to particulate air pollution. METHODS: Cardiovascular event rates were studied relative to urban concentrations of particulate air pollution and baseline risk factors. The Edinburgh artery study consisted of a cohort of 1592 subjects aged 55-74 and was followed up to the end of March 1998 for a median of 10 years resulting in about 5 million person-days of observation. Baseline measurements included plasma fibrinogen and blood and plasma viscosity. A nested case-control approach was used to investigate a possible interaction between effects of these selected baseline risk factors and particulate air pollution, on subsequent event rates. RESULTS: During the follow up period there were 343 fatal and non-fatal myocardial infarctions or strokes. Trends in adverse cardiovascular outcomes related to pollution were identified among subjects belonging to the highest baseline quintile of plasma fibrinogen. Evidence for interactions between concentrations of particulate pollution and fibrinogen was not established at conventional levels of significance. CONCLUSIONS: People with high concentrations of plasma fibrinogen might be more susceptible to adverse cardiovascular effects of particulate air pollution, but limitations of power mean that evidence relating to such an interaction is not conclusive. A range of cardiopulmonary risk factors warrant investigation in relation to possible susceptibility to air pollution.

Toxigenic bacteria and sudden infant death syndrome (SIDS): nasopharyngeal flora during the first year of life.

Many developmental and environmental risk factors for sudden infant death syndrome (SIDS) are similar to those for susceptibility to respiratory tract infection, and toxigenic bacteria have been implicated in some SIDS cases. We assessed nasopharyngeal flora of healthy infants in relation to risk factors to determine which species best lit the mathematical model proposed for the common bacterial toxin hypothesis and if these findings complemented results obtained from SIDS cases which occurred during the period of the survey. Longitudinal studies were carried out between April 1993 and March 1996 on 253 healthy infants and their mothers. 150 from a multiply deprived area, 103 from an affluent area. Concurrent SIDS infants (37) were screened for nasopharyngeal flora. Among healthy infants < or = 3 months of age, the predominant isolate was Staphylococcus aureus 57% compared with 86% for SIDS infants in that age range (P< 0.02). There were significant associations between isolation of different species from both mother and baby but no association between isolation of any species with: area of residence: parental smoking habits; breast or bottle feeding; symptoms of viral infection: seasonality. We conclude that S. aureus fits the mathematical model for SIDS. Both staphylococci and/or their toxins were identified in a significant proportion of SIDS cases. Isolation of staphylococci from healthy infants was associated with the 2-4-month age range, a risk factor consistently found in all epidemiological studies of SIDS. This might reflect the developmental stage in which 80-90% of infants express the Lewis(a) antigen which we have shown to be one of the receptors for S. aureus.

Exposure to cigarette smoke, a major risk factor for sudden infant death syndrome: effects of cigarette smoke on inflammatory responses to viral infection and bacterial toxins.

Exposure to cigarette smoke is a major risk factor for sudden infant death syndrome and also for respiratory infections in children. It has been suggested that toxigenic bacteria colonizing the respiratory tract might play a role in some cases of sudden infant death syndrome and nicotine has been demonstrated to enhance the lethality of bacterial toxins in a model system. Pyrogenic toxins of Staphylococcus aureus have been identified in tissues of infants who died of sudden infant death syndrome. It has been suggested that some of these deaths were due to induction of inflammatory mediators by infectious agents during a period when infants are less able to control these responses. The aim of this study was to assess the effects of a water-soluble cigarette smoke extract on the production of tumor necrosis factor alpha and nitric oxide from human monocytes in response to staphylococcal toxic shock syndrome toxin 1 or infection of the monocytes with respiratory syncytial virus. Cell culture supernatants were examined by a bioassay using mouse fibroblasts (L-929 cell line) for tumor necrosis factor alpha activity and by a spectrophotometric method for nitrite. Compared with monocytes incubated with medium only, monocytes incubated with any of the factors or their combinations tested in the study released higher levels of tumor necrosis factor alpha and lower levels of nitric oxide. Incubation with cigarette smoke extract increased tumor necrosis factor alpha from respiratory syncytial virus-infected cells while it decreased tumor necrosis factor alpha from cells incubated with toxic shock syndrome toxin. Incubation with cigarette smoke extract decreased the nitric oxide production from respiratory syncytial virus-infected cells while it increased the nitric oxide production from cells incubated with toxic shock syndrome toxin. Monocytes from a minority of individuals demonstrated extreme tumor necrosis factor alpha responses and/or very high or very low nitric oxide. The proportion of samples in which extreme responses with a very high tumor necrosis factor alpha and very low nitric oxide were detected was increased in the presence of the three agents to 20% compared with 0% observed with toxic shock syndrome toxin 1 or 4% observed with cigarette smoke extract or respiratory syncytial virus.

The protective effect of breast feeding in relation to sudden infant death syndrome (SIDS): I. The effect of human milk and infant formula preparations on binding of toxigenic Staphylococcus aureus to epithelial cells.

Epidemiological studies indicate that breast-fed infants are at a decreased risk of sudden infant death syndrome (SIDS) compared to formula-fed infants. Increasing evidence suggests that infectious agents might be involved in some of these deaths, in particular bacteria which colonise mucosal surfaces and produce superantigenic toxins. One species implicated in recent studies of SIDS infants is Staphylococcus aureus. We tested the hypothesis that in comparison to infant formula, human milk might be a better inhibitor of binding of S. aureus to epithelial cells. In this study, two protocols were used for the binding assays which were assessed by flow cytometry: the in vitro method in which bacteria were treated with milk or formula, washed and added to epithelial cells; and a method more closely reflecting the competitive interactions in vivo in which cells, bacteria, and milk or infant formula were added at the same time. With the in vivo method, breast milk caused enhancement of bacterial binding to cells whilst infant formula caused inhibition; however, for the in vitro method, both human milk and infant formula caused consistent enhancement of binding. Flow cytometry and light microscopy studies indicated that the enhancement was due to the formation of bacterial aggregates. Human milk and infant formula preparations were also compared for components (antibodies or oligosaccharides) that could inhibit binding of S. aureus using the in vitro method. Human milk contained both IgA and IgG. Neither human milk nor infant formula contained oligosaccharides reactive with the Ulex europaeus lectin but both contained components that bound monoclonal antibodies to Lewis(a) and Lewis(b) antigens which can act as receptors for S. aureus. With both methods, synthetic Lewis(a) and Lewis(b) inhibited S. aureus binding in a dose-dependent manner. With human milk, however, the only component which showed a significant correlation with inhibition of binding was the IgA specific for the staphylococcal surface component that binds Lewis(a). Both human milk and infant formula contain components which could potentially inhibit bacterial binding but only breast milk contains the IgA specific for the bacterial adhesin that binds Lewis(a). Studies using the in vivo method suggest that protection associated with breast feeding in relation to SIDS could be due mainly to the formation of bacterial aggregates. The studies have implications for further research into constituents of infant formula.

The protective effect of breast feeding in relation to sudden infant death syndrome (SIDS): II. The effect of human milk and infant formula preparations on binding of Clostridium perfringens to epithelial cells.

Breast feeding is known to protect an infant against gastrointestinal pathogens and epidemiological studies indicate that compared to breast fed infants, formula fed infants are at a greater risk of dying from sudden infant death syndrome (SIDS). Many SIDS infants have symptoms of gastrointestinal infections prior to death and one gastrointestinal pathogen associated with SIDS is Clostridium perfringens. Studies have found that a significantly higher number of formula fed SIDS infants have C perfringens and its enterotoxin in their faeces compared to breast fed infants. The aim of the study was to compare the effects of human milk and infant formula on binding of C perfringens to epithelial cells. Two protocols were used to assess the effect of human milk and infant formula to inhibit binding of C perfringens to epithelial cells. Binding was assessed by flow cytometry. For the in vivo protocol which more closely represents interactions on the mucosal surface, breast milk enhanced bacterial binding but infant formula caused inhibition of binding; however for the in vitro method, both human milk and infant formula resulted in consistent enhancement of binding. Flow cytometry studies indicated that enhancement of binding was due to the formation of bacterial aggregates. Lewis(a) and Lewis(b) antigens, found in both breast milk and infant formula, inhibited C. perfringens binding in a dose dependent manner. The Lewis(a) and Lewis(b) antigens in human milk and infant formula can inhibit C. perfringens binding to epithelial cells. While infant formula reduced binding of C. perfringens to epithelial cells in the experiments carried out with the in vivo protocol, the protective effects of breast feeding in relation to colonisation with C. perfringens are more likely to be due to formation of bacterial aggregates. These findings have implications for improving infant formula preparations.

Infection with respiratory syncytial virus and water-soluble components of cigarette smoke alter production of tumour necrosis factor alpha and nitric oxide by human blood monocytes.

Cigarette smoke and virus infections contribute to the pathogenesis and exacerbation of chronic obstructive pulmonary disease and asthma. The objective of this study was to examine the effects of a water-soluble cigarette smoke extract (CSE) and/or respiratory syncytial virus (RSV) infection on release from monocytes of the blood from donors of tumour necrosis factor alpha (TNF-alpha) and nitric oxide (NO). Both RSV infection and CSE stimulated TNF-alpha release from monocytes and there was an additive effect if both the agents were present. There was a decrease in NO release, but the effect was significant only with CSE or a combination of CSE and RSV infection. Interferon gamma significantly increased TNF-alpha release and cotinine significantly increased NO release. Nicotine decreased both TNF-alpha and NO responses. The general pattern observed for individual donors was increased TNF-alpha and decreased NO. The proportion of extreme responses with very high TNF-alpha and very low NO in the presence of both RSV and CSE increased to 20% compared with 5% observed with CSE or RSV alone. The results show that RSV infection and components of cigarette smoke elicit inflammatory responses that could contribute to damage to the respiratory tract and these individual factors could be more harmful in combination.