Clinical findings in relation to mortality in non-tuberculous mycobacterial infections: patients with Mycobacterium avium complex have better survival than patients with other mycobacteria.

We compared the clinical findings and survival in patients with Mycobacterium avium complex (MAC) and other non-tuberculous mycobacteria (NTM). A total of 167 adult non-human immunodeficiency virus (HIV) patients with at least one positive culture for NTM were included. Medical records were reviewed. The patients were categorised according to the 2007 American Thoracic Society (ATS) criteria. MAC comprised 59 % of all NTM findings. MAC patients were more often female (70 % vs. 34 %, p < 0.001) and had less fatal underlying diseases (23 % vs. 47 %, p = 0.001) as compared to other NTM patients. Symptoms compatible with NTM infection had lasted for less than a year in 34 % of MAC patients but in 54 % of other NTM patients (p = 0.037). Pulmonary MAC patients had a significantly lower risk of death compared to pulmonary other NTM (hazard ratio [HR] 0.50, 95 % confidence interval [CI] 0.33-0.77, p = 0.002) or subgroup of other slowly growing NTM (HR 0.55, 95 % CI 0.31-0.99, p = 0.048) or as rapidly growing NTM (HR 0.47, 95 % CI 0.25-0.87, p = 0.02). The median survival time was 13.0 years (95 % CI 5.9-20.1) for pulmonary MAC but 4.6 years (95 % CI 3.4-5.9) for pulmonary other NTM. Serious underlying diseases (HR 3.21, 95 % CI 2.05-5.01, p < 0.001) and age (HR 1.07, 95 % CI 1.04-1.09, p < 0.001) were the significant predictors of mortality and female sex was a predictor of survival (HR 0.38, 95 % CI 0.24-0.59, p < 0.001) in the multivariate analysis. Pulmonary MAC patients had better prognosis than pulmonary other NTM patients. The symptom onset suggests a fairly rapid disease course.

Impact of intrauterine and post-natal nutritional determinants on blood pressure at 4 years of age.

BACKGROUND: To prospectively study how the early nutritional environment can programme blood pressure in a well-nourished population of children. METHODS: By means of multivariate modelling, we assessed whether gestational and post-natal dietary intakes and growth influence childhood blood pressure programming in a cohort of 109 healthy mother-child pairs. They had been followed from early pregnancy until the children reached 4 years of age. Dietary intakes were evaluated using 3-day food diaries. Blood pressure levels in the children were measured using an automated oscillometric DINAMAP ProCare 100 (Criticon, Tampa, FL, USA) at the age of 4 years. RESULTS: In the final multivariate model, the predictor variables of childhood systolic blood pressure were maternal dietary carbohydrate and fat intake during pregnancy, as well as childhood weight and dietary fat intake at 4 years of age. Systolic blood pressure levels in the children were found to be positively associated with the maternal carbohydrate intake (P = 0.003), whereas blood pressure levels were lowest in children exposed to the middle tertile of maternal dietary fat intake during pregnancy (P = 0.003) and whose own dietary fat intake was in the middle tertile at the age of 4 years (P = 0.013). The model also showed that heavier children have a higher systolic blood pressure (P < 0.001). None of the maternal clinical characteristics fulfilled the criterion to be included in the model. The only determinant underlying childhood diastolic blood pressure was childhood weight at 4 years of age (r = 0.289, P = 0.026). CONCLUSIONS: Interventions focusing on cardiovascular health in young women during pregnancy and their children should be considered to reduce cardiovascular diseases risk factors in these children.

Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy.

BACKGROUND: Hypertension (HTN) is a common toxicity of anti-VEGF (vascular endothelial growth factor) antibody treatment. It may be a marker of VEGF signalling pathway inhibition and therefore represent a cancer biomarker in metastatic colorectal cancer (mCRC) patients treated with chemotherapy and bevacizumab. METHODS: A total of 101 consecutive patients with mCRC were treated with standard chemotherapy combined with bevacizumab at dose of 2.5 mg kg(-1) per week in a single centre. The median follow-up time of the patients alive was 64 months. Blood pressure was measured before each bevacizumab infusion, and HTN was graded according to common toxicity criteria for adverse events version 3.0. RESULTS: Overall, 57 patients (56%) developed ≥grade 1 HTN (median blood pressure 168/97 mm Hg), whereas 44 (44%) remained normotensive when treated with bevacizumab-containing chemotherapy regimen. Overall response rate was higher among patients with HTN (30 vs 20%; P=0.025). Hypertension was associated with improved progression-free survival (10.5 vs 5.3 months; P=0.008) and overall survival (25.8 vs 11.7 months; P<0.001), and development of HTN within 3 months had an independent, prognostic influence in a multivariate landmark survival analysis together with other known mCRC prognostic factors (P=0.007). There was no association between HTN and development of thromboembolic complications. CONCLUSION: Hypertension may predict outcome of bevacizumab-containing chemotherapy in mCRC. These data require confirmation in prospective studies including pharmacodynamic and pharmacokinetic analyses.

Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.

BACKGROUND: Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known. OBJECTIVE: Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy-prone infants. METHODS: In a randomized double-blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C-reactive protein (CRP), total IgA and IgE, food-specific IgA, IgG, and IgE, IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years. RESULTS: Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL-10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17-0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16-0.87), P=0.023] at age 2 years, when adjusted with probiotic use. CONCLUSION: The association of CRP with a decreased risk of eczema at 2 years of age in allergy-prone children supports the view that chronic, low-grade inflammation protects from eczema. Probiotic-induced low-grade inflammation was characterized by elevation of IgE, IgA, and IL-10, the changes typically observed in helminth infection-associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.

Removing lactose from milk does not delay bowel function or harden stool consistency in lactose-tolerant women.

OBJECTIVES: To investigate whether removing lactose from milk delays bowel function in lactose-tolerant women. We also examined how well the participants' subjective evaluation of the stool consistency according to the Bristol Stool Form Scale correlated with values obtained by dry matter analysis and penetrometry. SUBJECTS AND METHODS: A randomized double-blind cross-over trial. Thirty-three lactose-tolerant women consumed, in random order, 800 ml of lactose-free or ordinary milk per day for 2 weeks, with their main meal, but otherwise followed a lactose-free diet. The subjects estimated stool consistency according to the Bristol Stool Form Scale, registered stool frequency and gastrointestinal symptoms and collected stool samples. RESULTS: The mean intake of lactose was 3.5 and 38.4 g/day during the lactose-free and the ordinary milk periods, respectively. There were no statistically significant differences between the lactose-free and the ordinary milk periods in stool frequency, gastrointestinal symptoms, stool hardness or faecal dry matter. Faecal pH was lower during the lactose-free milk period than in the ordinary milk period. The subjective estimation of stool hardness correlated well with the values obtained by dry matter analysis and penetrometry. CONCLUSIONS: Lactose-free milk does not delay bowel function in lactose-tolerant women. The Bristol Stool Form Scale is a useful method of evaluating stool hardness.

Probiotics reduce the prevalence of oral candida in the elderly--a randomized controlled trial.

Overgrowth of oral yeast is a common problem among the elderly. Probiotic bacteria are known to inhibit the growth of pathogenic microbes. We tested the hypothesis that cheese containing probiotic bacteria can reduce the prevalence of oral Candida. During this 16-week, randomized, double-blind, placebo-controlled study, 276 elderly people consumed daily 50 g of either probiotic (n = 136) or control cheese (n = 140). The primary outcome measure was the prevalence of a high salivary yeast count (>or= 10(4) cfu/mL) analyzed by the Dentocult method. The prevalence decreased in the probiotic group from 30% to 21% (32% reduction), and increased in the control group from 28% to 34%. Probiotic intervention reduced the risk of high yeast counts by 75% (OR = 0.25, 95%CI 0.10-0.65, p = 0.004), and the risk of hyposalivation by 56% (OR = 0.44, 95%CI 0.19-1.01, p = 0.05). Thus, probiotic bacteria can be effective in controlling oral Candida and hyposalivation in the elderly.

Fermented cereal with specific bifidobacteria normalizes bowel movements in elderly nursing home residents. A randomized, controlled trial.

OBJECTIVE: To assess how fermented oat drink with two selected Bifidobacterium longum strains influences bowel movements among elderly nursing home residents. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: 12 wards in two nursing homes in Finland. PARTICIPANTS: 209 residents. INTERVENTION: Wards were randomized to receive daily a fermented oat drink with 1) 109 CFU/day Bifidobacterium longum strains or 2) 109 CFU/day Bifidobacterium lactis Bb12 or 3) without viable bacteria (placebo) for 7 months. MEASUREMENTS: Regularity of bowel movements (no movements or functioning) and consistency of stools (normal, soft or diarrhoea) were recorded for each resident on a daily basis. RESULTS: The fermented oat drinks were well taken by the subjects, compliance being 85%. The groups receiving active products had more frequent bowel movements than did the placebo group (B. longum group normal functioning 28.5% of follow-up days, B.lactis group 26.9%, and placebo group 20.0%, respectively). The differences between the B. longum and the placebo group (mean 7.1, 95% CI 2.3 - 11.9, p=0.004) and between the B.lactis group and the placebo (mean 6.7, 95% CI 2.5 - 10.9, p = 0.002) were significant even when diarrhoea and constipation in the 3 months prior to the study were used as covariates. CONCLUSIONS: It is possible to normalize bowel movements in frail nursing home.

Lactobacillus bacteremia, species identification, and antimicrobial susceptibility of 85 blood isolates.

BACKGROUND: Data regarding antimicrobial susceptibility of clinical Lactobacillus isolates are scarce, and appropriate interpretation criteria for susceptibility tests are not available. METHODS: We examined 85 cases of Lactobacillus bacteremia, of which 47 cases have been included in our previous studies. Overall, 14 antimicrobial agents were evaluated by the E-test method, and these results were compared with disk diffusion test findings. The clinical outcomes of the patients and their antimicrobial treatments were registered. RESULTS: The antimicrobial susceptibility of Lactobacillus strains was species dependent. The considerable number of Lactobacillus rhamnosus (n=46), Lactobacillus fermentum (n=12), and Lactobacillus casei (n=12) strains available for testing made it possible to compare the susceptibilities within 1 species, as well. Of the 46 L. rhamnosus isolates, 22 were identified as L. rhamnosus GG type by pulsed-field gel electrophoresis. All Lactobacillus isolates demonstrated low minimum inhibitory concentrations (MICs) of imipenem, piperacillin-tazobactam, erythromycin, and clindamycin. MICs of vancomycin were high (>256 microg/mL) for all other species except Lactobacillus gasseri and Lactobacillus jensenii. Disk diffusion and E-test results were concordant. The MICs of cephalosporins varied; cefuroxime demonstrated a higher level of activity than did ceftriaxone. Benzylpenicillin and ampicillin MICs had variable ranges between different species. Combination therapy was given to 83% of the patients, but, in 54% of them, therapy included only 1 microbiologically active agent, according to results of the susceptibility tests. Mortality at 1 week was 12% among patients who presumably were receiving adequate treatment and 27% among patients who were receiving inadequate treatment (P=.131, by E-test). CONCLUSION: Most clinical Lactobacillus blood isolates demonstrated low MICs of imipenem, piperacillin-tazobactam, erythromycin, and clindamycin, but they had variable susceptibility to penicillin and cephalosporins.

Effects of low-fat hard cheese enriched with plant stanol esters on serum lipids and apolipoprotein B in mildly hypercholesterolaemic subjects.

OBJECTIVE: To investigate the cholesterol-lowering effects of a low-fat cheese enriched with plant stanol esters in mildly hypercholesterolaemic subjects, as part of their normal diet. DESIGN: A randomized double-blind parallel-group study. SETTING: Valio Ltd, Helsinki. SUBJECTS: Sixty-seven mildly hypercholesterolaemic volunteers (24 men, 43 women) participated in the study, which all of them completed. INTERVENTIONS: The subjects were randomly assigned to the plant stanol ester group or the control group. During the 5-week intervention, the subjects in the stanol group consumed a cheese enriched with 2 g of plant stanols per day, and the subjects in the control group, a control cheese with no plant stanols. RESULTS: In the stanol ester group, as compared to the control group, both serum total and low-density lipoprotein (LDL) cholesterol decreased significantly, that is, by 5.8% (-0.32 mmol/l, 95% CI -0.50 to -0.15 mmol/l, P < 0.001) and 10.3% (-0.36 mmol/l, 95% CI -0.53 to -0.18 mmol/l, P < 0.001), respectively. There were no significant changes in high-density lipoprotein cholesterol (HDL), triglycerides or apolipoprotein B concentrations between the groups. CONCLUSION: Cheese enriched with 2 g of plant stanol in the form of fatty acid esters decreases serum total and LDL cholesterol significantly.

Absence of adverse events in healthy individuals using probiotics--analysis of six randomised studies by one study group.

Consumption of live bacteria as probiotic supplements is increasing. There is, however, a lack of information on the safety of ingested probiotics. The main objective of this study was to investigate the adverse events (AEs) of specific probiotics (Lactobacillus rhamnosus GG (LGG) alone or LGG in combination with L. rhamnosus Lc705, Propionibacterium freudenreichii JS, Bifidobacterium lactis BB12, or Bifidobacterium breve 99) studied in six of our study groups' clinical trials, by analysing individual participant data. A secondary objective was to study AEs associated with the consumed probiotic species and mixtures in three specific categories; 'gastrointestinal disorders', 'respiratory, thoracic and mediastinal disorders' and 'infections and infestations'. Six randomised, double-blind, placebo-controlled clinical studies by our study group were included in this AE analysis (study population n=1,909). All AE data were classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v4.0. From the 26 CTCAE System Organ Classes, we identified AEs in 20 classes among 1,909 subjects. Probiotic ingestion did not result in statistically significant differences in AEs in different groups, when compared to placebo. A subgroup analysis of gastrointestinal, respiratory, thoracic and mediastinal disorders, infections and infestations, found no differences between the intervention groups or for different probiotic combinations (risk ratio (RR) = 0.97, 95% confidence interval (CI): 0.93-1.02, P=0.30; RR=0.99, 95% CI: 0.97-1.01, P=0.35; RR=0.99, 95% CI: 0.93-1.06, P=0.62, respectively). As a conclusion, ingestion of probiotic supplementations containing LGG alone, or LGG in combination with L. rhamnosus Lc705, P. freudenreichii JS, B. breve 99, or B. lactis BB12 did not seem to cause AEs in young and elderly subjects in this analysis.

Randomised clinical trial: low-FODMAP rye bread vs. regular rye bread to relieve the symptoms of irritable bowel syndrome.

BACKGROUND: Grains are high in FODMAPs (Fermentable Oligo-, Di-, Monosaccharides And Polyols) and often considered as triggers of IBS symptoms. AIM: To evaluate if rye bread low in FODMAPs would be better tolerated than regular rye bread in subjects with IBS. METHODS: The study was conducted as a randomised double blind controlled cross-over study (n = 87). Participants were supplied with both regular rye bread and low-FODMAP rye bread for 4 weeks. Symptoms were measured with a symptom severity scoring system (IBS-SSS) and visual analogue scale (VAS) assessments of individual symptoms. Quality of life was monitored. Colonic fermentation was measured by the breath hydrogen test and dietary intake by food diaries. RESULTS: Dietary fibre intake increased during both study periods compared to baseline. Many signs of IBS i.e. flatulence, abdominal pain, cramps and stomach rumbling were milder on the low-FODMAP rye bread (P-values: 0.04; 0.049; 0.01 and 0.001). The mean of VAS measurements was favourable towards LF bread [-3 (95% CI): -6 to -1, P = 0.02] but no differences were detected in IBS-SSS or quality of life. The AUC of breath hydrogen values was significantly lower during the low-FODMAP bread period (median 52.9 vs. 72.6; P = 0.01). CONCLUSIONS: Low-FODMAP rye bread helps IBS patients to control their symptoms and reduces gastrointestinal gas accumulation. However, replacing regular rye bread by low-FODMAP bread without concomitant broader dietary changes does not improve quality of life or IBS-SSS. Nonetheless, inclusion of low-FODMAP rye bread in diet might be one way that IBS patients could increase their fibre intake.

A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention.

BACKGROUND: Irritable bowel syndrome is a gastrointestinal disorder of unknown aetiology. The effect of probiotics in this syndrome remains unclear. AIM: To investigate whether a probiotic mixture containing Lactobacillus rhamnosus GG, L. rhamnosus LC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii ssp. shermanii JS is effective in alleviating irritable bowel syndrome symptoms. METHODS: A total of 103 patients fulfilling the Rome I or II criteria took part in this 6-month, randomized, double-blind placebo-controlled trial. The patients received a probiotic capsule or a placebo capsule daily. Gastrointestinal symptoms and bowel habits were recorded. RESULTS: At the end the total symptom score (abdominal pain + distension + flatulence + borborygmi) was 7.7 (95% CI: -13.9 to -1.6) points lower in the probiotic group (P = 0.015). This represents a median reduction of 42% in the symptom score of the probiotic group compared with 6% in the placebo group. In individual symptoms, borborygmi was milder in the probiotic group (P = 0.008), and for the rest of the symptoms there was a non-significant trend. CONCLUSIONS: The results indicate that this probiotic mixture is effective in alleviating irritable bowel syndrome symptoms. Considering the high prevalence of irritable bowel syndrome and the lack of effective therapies, even a slight reduction in symptoms could have positive public health consequences.

Prevalence of asthma, aspirin intolerance, nasal polyposis and chronic obstructive pulmonary disease in a population-based study.

BACKGROUND: Remarkable overlap exists in symptoms between asthma and chronic obstructive pulmonary disease (COPD), and the symptoms of the patients with mild asthma are often falsely thought to be caused by smoking. The objective of the study was to determine the prevalence of doctor-diagnosed asthma, asthmatic symptoms and doctor-diagnosed COPD in an adult population. The prevalence and relation to asthma of aspirin intolerance, nasal polyposis, allergic rhinitis and smoking habits were also examined. METHODS: Postal questionnaire survey of a population-based random sample (4300) of adult women and men aged 18-65 years served by the Päijät-Häme Central Hospital in southern Finland (a region with 208 000 inhabitants) was performed. RESULTS: The non-response-adjusted prevalence (Drane's linear method) of doctor-diagnosed asthma was 4.4% (95% CI: 3.3-5.5%) and of COPD 3.7% (95% CI: 2.7-4.8%). The prevalence of allergic rhinitis was 37.3% (95% CI: 33.3-41.2%), and of overall aspirin intolerance 5.7% (95% CI: 4.4-7.1%). The observed prevalence of aspirin intolerance causing shortness of breath or attacks of asthma was 1.2% and it was higher in patients with doctor-diagnosed asthma than without (8.8% versus 0.8%, relative risk [RR] = 11.4, P < 0.0001), and higher in those with allergic-like rhinitis than without (2.6% versus 0.3%, RR = 7.7, P < 0.0001). The prevalence of nasal polyposis was 4.3% (95% CI : 2.8-5.8%). CONCLUSIONS: The current prevalence of doctor-diagnosed asthma among adults is 4.4%, and allergic rhinitis, nasal polyposis and aspirin intolerance are associated with an increased risk of asthma. There is also association between aspirin-induced asthma and allergic-like rhinitis.

Plasma peroxyl radical trapping capacity in lung cancer patients: a case-control study.

Increasing evidence suggests that cancer patients express oxidative disturbances. The main objective of this cross-sectional case-control study (n = 57 + 76) was to explore whether lung cancer patients, when compared to healthy controls, have alterations in their plasma peroxyl radical trapping capacity (TRAP). Group matching was used with respect to age, sex and smoking history. A secondary objective was to observe the effects of life-long cigarette consumption on plasma TRAP and its components. Mean TRAP values were significantly lower in the cancer patients than in the control group (1143 vs 1273 mumol/l, p = 0.0002). Moreover, all the components of TRAP (except uric acid) were significantly lower in the cancer group: protein SH-groups 442 vs 571 mumol/l, ascorbic acid 34.0 vs 46.5 mumol/l and vitamin E 25.0 vs 33.8 mumol/l. The as yet unidentified antioxidant compounds in plasma contributed 26.5% of plasma TRAP in the cancer group and 30.2% in the control group. There was no correlation between cigarette consumption in pack-years and plasma TRAP; however, plasma concentrations of uric acid and ascorbic acid were negatively correlated with cigarette consumption.

Breast cancer patients have unmet needs for dietary advice.

GOAL: This study investigated ideas and attitudes of breast cancer patients in two countries with reference to information on diet and their need for dietary counselling. PATIENTS AND METHODS: Australian breast cancer (ABC) patients (n=215) surveyed for alterations in dietary habits after diagnosis were compared with breast cancer patients in Finland (FBC; n=139). A validated questionnaire was used. Logistic regression models were used to adjust for differences in demographic patient characteristics between the groups. RESULTS: Eight per cent of FBC and 54% of ABC patients saw diet as a factor contributing to their disease (P<0.00001). Thirty per cent of FBC and 39% of ABC reported changing their diet after being informed of the diagnosis (P=0.033). Higher education, younger age and longer (>1 year) time to diagnosis were significantly associated with the probability of changing diet among the Australian patients. The main reason given was the desire for cure. The most common source of information was the mass media, and a need for more information on dietary factors relating to disease was expressed by 32% of patients in each group. CONCLUSION: Ideas about the importance of diet varied significantly among ABS and FBC patients. The lack of precise dietary recommendations for the individual situation was commonly mentioned, and patients depended on information obtained from outside their treatment centre.

A rapid dosimetric methacholine challenge in asthma diagnostics: a clinical study of 230 patients with dyspnoea, wheezing or a cough of unknown cause.

The rapid methacholine challenge test using a pocket turbine spirometer (Micro Spirometer) and the Spira Elektro 2 dosimeter was performed with 230 consecutive patients who had dyspnoea, wheezing or a prolonged cough of unknown cause. Patients with previous asthma diagnoses as well as those who had used inhaled steroids during the preceding 4 weeks were excluded. Seventy-eight patients (34%) were methacholine positive (PD20FEV1 < or = 6900 micrograms) 47 (60%) of whom had a final diagnosis of American Thoracic Society (ATS) criteria fulfilling bronchial asthma. One hundred and fifty-two patients (66%) were methacholine negative (PD20FEV1 > 6900 micrograms) 14 (9%) of whom had bronchial asthma according to clinical evaluation. Increased bronchial responsiveness was strongly associated with ATS criteria fulfilling asthma (P < 0.0001). When PD20FEV1 was used, 47 (77%) of the asthmatic patients were hyper-responsive (range 40-6900 micrograms) compared to 31 (18%) of the non-asthmatic patients (range 160-6900 micrograms). When using PD15FEV1, 51 (84%) of the asthmatic patients (range 28-6900 micrograms) and 52 (31%) of the non-asthmatic patients (range 100-6900 micrograms) were hyper-responsive. The level of bronchial responsiveness measured by both PD20FEV1 and PD15FEV1 differed significantly between asthmatic and non-asthmatic patients (P < 0.0001). Hyper-responsiveness was associated with an increased daily variation in peak expiratory flow (PEF) (P < 0.0001) and an increased number of blood eosinophils (P < 0.0001). Hyper-responsiveness was also associated with decreased levels of FEV1 and percentages of predicted FEV1 (P = 0.04 and P < 0.0001, respectively). Stepwise logistic regression analysis showed that the number of positive prick results (OR = 1.15, 95% CI 1.01-1.31), blood eosinophils (1.004, 1.00-1.01), level of FEV1 (0.56, 0.36-0.87) and current smoking (2.36, 1.00-5.59) were factors significantly associated with the probability of hyper-responsiveness. Age, gender, atopy, pets and a history of ex-smoking were not significantly associated with hyper-responsiveness, neither in univariate nor in multivariate analyses. The Bayesian analysis was used to investigate the diagnostic value of the rapid methacholine challenge test. A receiver operator characteristic curve demonstrated that PD20FEV1 separated asthmatic and non-asthmatic patients better than PD15FEV1. The best cutoff value of PD20FEV1 was 6000 micrograms, but the difference from 6900 micrograms was minimal. The best results of the test using a PD20FEV1 cutoff point of 6900 micrograms (PPV: 0.80, NPV: 0.79) were obtained when the pre-test probability was 0.48. The interval security of the test was established by a pre-test probability between 0.19 and 0.78. Maximal positive (0.34) and negative (0.31) final gains were achieved when pre-test probabilities were 0.33 and 0.65, respectively. The cutoff level of 150 micrograms gave 100% of specificity and predictive value of a positive test for clinical asthma diagnosis. The Bayesian analysis approach demonstrated that the test is useful in asthma diagnostics if not performed on patients with lowest or highest probabilities of asthma.

Serum ECP and MPO, but not urinary LTE4, are associated with bronchial hyper-responsiveness.

A random population-based sample of 131 subjects was used to assess the value of serum eosinophil cationic protein (ECP), serum myeloperioxidase (MPO), and urinary leukotriene E4 (LTE4) in predicting bronchial hyper-responsiveness measured by methacholine challenge. Special interest was focused on the history of aspirin intolerance and on smoking as contributing factors. The mean serum ECP and MPO were higher in hyper-reactive [provocational dose causing a 20% fall in forced expiratory volume in 1 sec. (PD20) < or = 6900 micrograms] than in non-hyper-reactive subjects (22.3 vs. 13.2 micrograms l-1, P < 0.001 and 377 vs. 278 micrograms l-1, P = 0.001, respectively). This was also seen in current smokers vs. never smokers (17.2 vs. 12.9 micrograms l-1, P = 0.03 and 372 vs. 286 micrograms l-1, P = 0.04, respectively). There were no differences in baseline urinary excretion of LTE4 between hyper-reactive and non-hyper-reactive subjects. During the 2 h after methacholine challenge, urinary LTE4 excretion increased from 53.8 and 69.0 ng mmol-1 creatinine in non-hyper-reactive subjects, but there was no change in hyper-reactive subjects (non-hyper-reactive vs. hyper-reactive, P = 0.06). The increase was greatest in subjects with aspirin intolerance causing urticaria or angioedema but not aggravation of asthma (from 58.5 to 87.2 ng mmol-1 creatinine), probably due to extrapulmonary leukotriene production. Our results indicate that serum ECP and MPO, but not urinary LTE4 (even in subjects with a history of aspirin intolerance), predict bronchial hyper-responsiveness to methacholine. The subject's smoking history must be taken into account when these parameters are considered.

Comparison of high and low dose of the inhaled steroid, budesonide, as an initial treatment in newly detected asthma.

The importance of early initiation of inhaled steroids even in mild asthma has been documented in several studies. It is not, however, clear whether the treatment should be started with a high or a low dose of the inhaled steroid. We have compared the effects of high and low dose inhaled steroid, budesonide, in patients with newly detected asthma. We studied 101 adult patients with newly detected bronchial asthma who were without inhaled steroid or any regular pharmacological treatment for their asthma. The patients were randomly allocated to two treatment groups: one to receive 800 microg inhaled budesonide per day and the other to receive 200 microg inhaled budesonide per day. The drugs were given with a Turbuhaler dry powder inhaler. During the 3-month treatment period, no significant differences between the treatment groups were noted in morning or evening PEF values, in spirometric parameters, in asthmatic symptoms or in the use of rescue beta2-agonists. The decrease in bronchial hyperresponsiveness was, however, more marked in the high dose budesonide group, reaching a borderline significance (P=0.10 high vs. low dose budesonide). In addition, in serum markers of asthmatic inflammation significant differences were shown between the treatment groups. The decrease in the number of blood eosinophils during the treatment was more marked in the high dose budesonide group (P=0.02; high vs. low dose budesonide). In serum ECP no change was observed in the low dose budesonide group, but a marked decrease in the high-dose budesonide group (P=0.008; high vs. low dose budesonide). The change was even more marked with regard to serum EPX (P=0.005; high vs. low dose budesonide). Our results support the view that the treatment of newly detected asthma should be started with a high dose of inhaled steroid. The low dose may not be enough to suppress asthmatic inflammation despite good clinical primary response.

Dietary attitudes and changes as well as use of supplements and complementary therapies by Australian and Finnish women following the diagnosis of breast cancer.

OBJECTIVE: This study investigated self-reported dietary attitudes and changes, and use of complementary approaches among breast cancer patients in relation to age, education and time since diagnosis. DESIGN AND SETTING: Australian (ABC, N=215) and Finnish (FBC, N=139) breast cancer patients were surveyed at the university cancer centres with voluntary participation. Logistic regression models were used to adjust for differences in demographic patient characteristics between the groups. The influence of demographic variables was further studied separately or combined. RESULTS: In all, 30% of FBC patients and 39% of ABC patients reported having changed their diet (P=0.033). Higher education, younger age and longer time from diagnosis were significantly associated with the probability of changes. The main changes reported included reduced consumption of animal fat, sugar and red meat, and increased consumption of fruits and vegetables. In all, 6% of ABC and 4% of FBC patients had stopped smoking and 24% of ABC and 27% of FBC patients reported to have increased their level of physical exercise. Choices were associated with age (P<0.007), length of the disease history (P <0.01) and level of education (P <0.002). CONCLUSION: One-third of breast cancer patients surveyed reported to have changed their dietary habits. Both populations reported a need for dietary and lifestyle counselling. This need was experienced as poorly recognised by the physicians at present, and warrants future studies in dietary behaviour of breast cancer patients.

Milk hypersensitivity in young adults.

OBJECTIVE: To estimate the prevalence of milk hypersensitivity in Finnish adults. DESIGN: Cross-sectional study. SUBJECTS: Two hundred men and 206 women aged 27 y randomly recruited from the population register in southwestern Finland. INTERVENTIONS: The subjects were interviewed about their dairy product consumption, abdominal discomfort after dairy product intake and lactose intolerance. From serum samples, serum reactivity to milk protein and milk-specific IgG1, IgG2, IgG3 and IgA were measured. RESULTS: About 20% of the subjects reported abdominal discomfort after dairy product intake, whereas only 6.4% had been diagnosed to have lactose intolerance. The amount of milk consumed correlated well with the serum assay results in subjects reporting abdominal discomfort but not in subjects who were free from these symptoms. Among subjects with no record of dairy product restriction or lactose intolerance, those experiencing abdominal discomfort after dairy product intake had significantly higher serum reactivity to milk protein than those without such discomfort. The concentrations of serum milk-specific antibodies did not differ between these two groups. The prevalence of milk hypersensitivity in this population was estimated to be 3-6%. CONCLUSIONS: Milk hypersensitivity may be as common in adults as in infants. The measurement of serum reactivity to milk protein may prove useful in screening milk hypersensitivity in subjects who have not restricted their dairy product consumption.