Dementia risk factors in former contact sports participants: prospective cohort study.

Background: The elevated dementia incidence in retired contact sport participants might be explained by a higher prevalence of established risk factors for the disease relative to the general population. Methods: In this cohort study, former elite participants active between 1920 and 1965 in soccer (N=303), boxing (N=281), and wrestling (N=318) were recruited using sports yearbooks and records of sports associations. Men in a population control group were identified using records from a compulsory medical examination (N=1712). All study members were linked to hospital registers (1970-2015) and self-completion questionnaires were circulated (1985, 1995) from which we captured data on nine established risk factors for dementia: hypertension and diabetes status, alcohol intake, loneliness, depressive symptoms, cigarette smoking, body weight, educational attainment, and physical activity. Results: There was little suggestion that former participants in contact sports had a higher prevalence of dementia risk factors relative to the general population. Rather, the balance of evidence was for more favourable risk factor levels in former athletes, as was particularly evident for ever having smoked cigarettes (range in odds ratios [95% confidence interval]: 0.32 [0.21, 0.48] for wrestling to 0.52 [0.36, 0.75] for soccer) and leisure-time physical activity (range in beta coefficients [95% confidence interval]: 1.34 [0.66, 2.02] for soccer to 1.80 [1.07, 2.52] for boxing). Conclusions: The increased dementia rates in retired contact sport participants evident in epidemiological studies is unlikely to be explained by the risk factors examined here. This implicates other characteristics of contact sports, including a history of repeated head impact.

Risk of gastric carcinoma will be low in generations born at turn of the 20th and 21st centuries in Finland. Modelling NORDCAN data of the age group specific incidence rates of gastric cancer with PLS-regression and with attention to age ('age effect') and year of the birth ('cohort effect').

BACKGROUND AND METHODS: We examined in NORDCAN database how the annual age group-specific incidence rates (IR) of gastric cancer (GCA), and correspondingly the GCA risk, have declined in Finland during the twentieth century, and whether this decline corresponds to a decrease in the cohort-specific prevalence rate of Helicobacter pylori (Hp) gastritis that is considered an important precancerous risk condition for GCA. RESULTS: In modelling with partial least squares regression (PLSR), the logarithmically transformed IRs (ln(IR) of GCA were well explained with age and birth cohort as explanatory model variables. By considering the observed (actual) and the PLSR-modelled IRs, the IR of GCA (and the risk of GCA) has decreased gradually in Finland from 1900 onward, cohort by cohort. By prediction of the future with PLSR, the IRs of GCA will be markedly lower in all cohorts during the twenty-first century than in the twentieth century. By PLSR modelling, less than 10 GCA cases per 100,000 people are predicted to appear annually in cohorts (generations) born at the turn of the 20th and 21st centuries, even when these people will be 60-80 years old in the years 2060-2070. CONCLUSIONS: The IR of GCA and GCA risk progressively declined by cohort in Finland during the whole twentieth century. This decline corresponds in extent and time window to earlier observations in the decline of the prevalence rate of Hp gastritis in the same birth cohorts and supports the hypothesis of the role of Hp gastritis as an important risk condition of GCA.

When will Helicobacter pylori gastritis disappear in history in Finland?

OBJECTIVES: To predict how the10-year birth cohort specific prevalence rates of chronic non-atrophic (CG) and atrophic gastritis (AG), related to Helicobacter pylori (Hp) infection, will decline during the 21st century among the native adult Finns. MATERIALS AND METHODS: The predictions are based as continuums of our earlier observations of gradual and significant declines in birth cohort specific prevalence rates of CG and AG in endoscopic biopsies from gastric antrum and corpus of 2298 adult dyspeptic outpatients or asymptomatic volunteers born 1890-1977 that were endoscopied in 1972-1997 in Finland. RESULTS AND DISCUSSION: We could predict that the Hp related CG and AG will gradually disappear in history among the native Finns during the 21st century. From the 2020s onward, the CG and AG would decrease with time in prevalence rate, cohort-by-cohort, and would be more and more highlighted in the middle aged or elderly age groups only. Finally, since all birth cohorts (generations) infected with Hp have passed away by 2080, the Hp related gastrites would not appear anymore in notable counts among the native Finns. Correspondingly, gastric cancers and peptic ulcers (both duodenal and gastric), which are etiopathogenetically linked with Hp gastrites, would similarly become gradually more and more infrequent and rare disorders among native Finns during the 21st century.

Physical activity, use of alcohol and smoking in middle-aged and aging men. A longitudinal study among Finnish male former athletes and controls.

It is not known whether decrease in physical activity (PA) is associated with binge drinking among former athletes. The purpose of this study was to investigate the reciprocal associations between PA and use of alcohol among former athletes and controls at four time points. Furthermore, we examined whether there were longitudinal latent profiles related to use of alcohol, smoking and PA during the follow-up. Finnish male former elite athletes (n = 1633) and matched controls (n = 1099) questionnaire-reported their PA, alcohol consumption and smoking at four time points in 1985, 1995, 2001 and 2008. Former athletes were more physically active and smoked less than controls, but in all profiles smoking decreased during the follow-up. Former athletes consumed alcohol significantly more compared to controls in 1985, especially if their athletic career had ended suddenly by sports injury. At other time points, no differences were seen. Five latent profiles were found, and there were significant differences between former athletes and controls in the probabilities to belong to four of them. PA decreased in four of five profiles, while alcohol consumption decreased or increased in some profiles. But PA did not predict later alcohol consumption at any time point. Cross-lagged path model indicated that the mutual associations of alcohol use and PA were weak at most. Although risk of excessive alcohol consumption may increase in individuals, whose athletic career has ended suddenly by sports injury, overall PA and alcohol affected each other's development only modestly among former athletes and controls during the 23-year follow-up.

Airway hyperresponsiveness, remodeling and inflammation in infants with wheeze.

BACKGROUND: The relationship of airway hyperresponsiveness to airway remodeling and inflammation in infants with wheeze is unclear. OBJECTIVE: To investigate airway hyperresponsiveness, remodeling and inflammation in infants with wheeze and troublesome breathing. METHODS: Inclusion criteria were as follows: full-term, 3-23 months of age; doctor -diagnosed wheeze and persistent recurrent troublesome breathing; without obvious structural defect, suspicion of ciliary dyskinesia, cystic fibrosis, immune deficiency or specified use of corticosteroids. Airway hyperresponsiveness (AHR) was evaluated by performing a methacholine bronchial challenge test combined with whole body plethysmography and rapid thoracoabdominal compression. Endobronchial biopsies were analysed for remodeling (thickness of reticular basement membrane and amount of airway smooth muscle) and for inflammation (numbers of inflammatory cells). Correlation analyses were performed. RESULTS: Forty-nine infants fulfilled the inclusion criteria for the present study. Median age was 1.06 years (IQR 0.6; 1.5). Lung function was impaired in 39/49 (80%) children, at the median age of 1.1 years. Methacholine challenge was successfully performed in 38/49 children. Impaired baseline lung function was correlated with AHR (P = .047, Spearman). In children with the most sensitive quartile of AHR, the percentage of median bronchial airway smooth muscle % and the number of bronchial mast cells in airway smooth muscle were not significantly higher compared to others (P = .057 and 0.056, respectively). No association was found between AHR and thickness of reticular basement membrane or inflammatory cells. Only a small group of children with both atopy and AHR (the most reactive quartile) had thicker airway smooth muscle area than non-atopics with AHR (P = .031). CONCLUSIONS AND CLINICAL RELEVANCE: These findings do not support the concept that AHR in very young children with wheeze is determined by eosinophilic inflammation or clear-cut remodeling although it is associated with impaired baseline lung function. The possible association of increased airway smooth muscle area among atopic children with AHR remains to be confirmed.

The difference in risk of chronic pulmonary disease morbidity and mortality between former elite athletes and ordinary men in Finland.

The impact of a history of competitive sports on later smoking behaviour and occurrence of chronic pulmonary diseases is poorly known. We investigated how a history of elite level sports predicted later pulmonary disease morbidity and mortality. Chronic pulmonary disease incidence was assessed from national hospital and cause-of-death registers from 1970 to 2015 among Finnish male former elite athletes (n = 2078) and matched controls (n = 1453) alive in 1970 (mean age 45.0 years). Hazard ratios (HRs) were calculated by Cox proportional hazards model. In 1985, cohort members reported on their smoking habits, engagement in physical activity/sports and physician-diagnosed chronic diseases. The risk of any chronic pulmonary disease or death was lower among former athletes than controls (age-adjusted HR 0.61; 95% CI 0.46-0.83). The risk was significantly lower among endurance (HR 0.54), mixed (HR 0.61), and power sports athletes (HR 0.66) compared to controls. The age- and smoking pack-year-adjusted HRs of incident diseases from the time of the 1985 questionnaire until the end of follow-up in former athletes was 0.58 (95% CI 0.37-0.93) compared to controls. In 1985 athletes smoked less and their cumulative smoking quantity was lower than that of controls. Former athletes were more physically active and self-reported less physician-diagnosed emphysema. The risk of any chronic pulmonary disease was lower among former athletes than controls even after considering smoking status and cumulative smoking quantity. Ability to compete at the highest level of sports in young adulthood associated with a reduced risk of pulmonary disease in later life.

Mortality and health-related habits in 900 Finnish former elite athletes and their brothers.

BACKGROUND: There is conflicting evidence on the associations between participation in vigorous sports, health habits, familial factors and subsequent mortality. We investigated all-cause mortality and health-related behaviour among former elite athletes and their brothers. METHODS: The mortality of Finnish male former elite athletes, who had represented Finland between 1920 and 1965 (n=900) and their age-matched brothers (n=900), was followed from the time when athlete started an elite athlete career until 31 December 2015. The age-adjusted HRs were calculated by a paired Cox proportional hazards model. In 2001, surviving participants (n=199 athletes and n=199 age-matched brothers) reported their self-rated health (SRH), physical activity, alcohol consumption and smoking habits in the questionnaire. RESULTS: During the total follow-up period, 1296 deaths (72% of the cohort) occurred. The age-adjusted HRs for all-cause mortality in former athletes was 0.75 (95% CI 0.65 to 0.87, P<0.001) compared with their age-matched brothers. Median age at death was 79.9 years for endurance, 75.9 years for mixed sports and 72.2 years for power sports athletes, and 77.5, 73.7 and 72.2 years for their age-matched brothers, respectively. In 2001, compared with their brothers, former athletes smoked less (P<0.001), were more physically active (P<0.05) and rated their health more often as very good (P<0.05). CONCLUSIONS: Former elite athletes are more physically active, smoke less, have better self-rated health and live longer than their brothers. Genetic differences between athletes and brothers, aerobic training for endurance elite sports and a healthier lifestyle may all contribute to reduced mortality.

Use of Alcohol and Alcohol-Related Morbidity in Finnish Former Elite Athletes.

INTRODUCTION: The effect of a history of competitive sports on later use of alcohol and occurrence of alcohol-related diseases is poorly known. We investigated how a history of elite level sports was associated with alcohol consumption in middle-age and with alcohol-related morbidity and mortality. METHODS: The occurrence of alcohol-related diseases and deaths were followed using national registers from 1970 to 2008 among Finnish male former elite athletes (n = 2202) and matched controls (n = 1403) alive in 1970 (mean age = 45.1 yr). Hazard ratios were calculated by Cox proportional hazards model. In 1985, surviving participants questionnaire-reported their alcohol consumption and engagement in physical activity/sports. RESULTS: The risk of any alcohol-related diseases or deaths did not differ between former athletes and controls (hazard ratio = 0.93, 95% confidence interval [CI] = 0.73-1.20, P = 0.59), although the risk was higher among both combat sports athletes and weightlifters compared with endurance sports athletes, shooters or jumpers, and hurdlers (P < 0.05). In 1985, athletes consumed more alcohol (417 g·month, 95% CI = 386-447) compared with controls (397 g·month, 95% CI = 355-441) (P < 0.05). Consumption was lower among endurance sports athletes than among controls (P < 0.05). Team sports athletes consumed more alcohol (P < 0.05), especially beer (P < 0.01), compared with other athletes and controls. Athletes no longer engaged in leisure-time sports consumed more alcohol than those who continued to be physically active (P < 0.05). CONCLUSIONS: Overall, former athletes reported higher alcohol consumption than controls. There was no difference in alcohol-related morbidity, but the risk varied between different sports groups. Alcohol consumption after top sports career was greater if participation in leisure-time sports was discontinued.

Lung function, airway remodeling, and inflammation in infants: outcome at 8 years.

BACKGROUND: Associations between early deficits of lung function, infant airway disease, and outcome at school age in symptomatic infants are still unclear. OBJECTIVE: To report follow-up data on a unique cohort of children investigated invasively in infancy to determine predictive value of airway disease for school-aged respiratory outcomes. METHODS: Fifty-three infants previously studied using bronchoscopy and airway conductance were approached at 8 years of age. Symptoms, lung volumes, and airway responsiveness were reassessed. Data on lifetime purchase of asthma medication were obtained. Lung function was compared with that of 63 healthy nonasthmatic children. RESULTS: Forty-seven children were reevaluated. Physician-diagnosed asthma was present in 39 children (83%). Twenty-five children (53%) had current and 14 children (30%) had past asthma. No pathologic feature in infancy correlated with any outcome parameter. As expected, study children had significantly reduced lung function and increased airway responsiveness compared with healthy controls, and very early symptoms were risk factors for reduced lung function. Current asthma was associated with reduced infant lung function and parental asthma. Reduced lung function in infancy was associated with purchase of inhaled corticosteroids when 6 to 8 and 0 to 8 years of age. CONCLUSION: The lack of predictive value of any pathologic measure in infancy, reported here for the first time to our knowledge, demonstrates that pathologic processes determining the inception of asthma, which are as yet undescribed, are different from the eosinophilic inflammation associated with ongoing disease.

All-cause and disease-specific mortality among male, former elite athletes: an average 50-year follow-up.

AIM: To investigate life expectancy and mortality among former elite athletes and controls. METHODS: HR analysis of cause-specific deaths sourced from the national death registry for former Finnish male endurance, team and power sports athletes (N=2363) and controls (N=1657). The median follow-up time was 50 years. RESULTS: Median life expectancy was higher in the endurance (79.1 years, 95% CI 76.6 to 80.6) and team (78.8, 78.1 to 79.8) sports athletes than in controls (72.9, 71.8 to 74.3). Compared to controls, risk for total mortality adjusted for socioeconomic status and birth cohort was lower in the endurance ((HR 0.70, 95% CI 0.61 to 0.79)) and team (0.80, 0.72 to 0.89) sports athletes, and slightly lower in the power sports athletes (0.93, 0.85 to 1.03). HR for ischaemic heart disease mortality was lower in the endurance (0.68, 0.54 to 0.86) and team sports (0.73, 0.60 to 0.89) athletes. HR for stroke mortality was 0.52 (0.33 to 0.83) in the endurance and 0.59 (0.40 to 0.88) in the team sports athletes. Compared to controls, the risk for smoking-related cancer mortality was lower in the endurance (HR 0.20, 0.08 to 0.47) and power sports (0.40, 0.25 to 0.66) athletes. For dementia mortality, the power sports athletes, particularly boxers, had increased risk (HR 4.20, 2.30 to 7.81). CONCLUSIONS: Elite athletes have 5-6 years additional life expectancy when compared to men who were healthy as young adults. Lower mortality for cardiovascular disease was in part due to lower rates of smoking, as tobacco-related cancer mortality was especially low.

Telomere length in circulating leukocytes is associated with lung function and disease.

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (ß= -0.0452, p=0.024) as well as COPD (ß= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10(-7)), FVC (p=2.07×10(-5)), and FEV1/FVC (p=5.27×10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

Lifetime physical activity and cancer incidence--a cohort study of male former elite athletes in Finland.

OBJECTIVES: Physical activity has been shown to decrease the risk of certain cancers. Objective of this study was to assess the effect of physical activity on cancer incidence in former male athletes in older age. DESIGN: A cohort of 2448 elite male athletes and 1712 referents was followed-up for cancer incidence during 1986-2010 through the Finnish Cancer Registry. METHODS: Standardised incidence ratios were calculated with the general male population as the reference. Self-reported questionnaire-based data on covariates were used in Cox regression analyses comparing the risk of cancer in athletes and referents. RESULTS: The overall cancer incidence was lower in athletes than in the general population, standardised incidence ratio 0.89 (95% confidence interval 0.81-0.97). It was lowest among middle-distance runners (standardised incidence ratio 0.51, 95% confidence interval 0.22-1.01), long-distance runners (standardised incidence ratio 0.57, 95% confidence interval 0.35-0.88) and jumpers (standardised incidence ratio 0.60, 95% confidence interval 0.37-0.92). The standardised incidence ratio of lung cancer among athletes was 0.40 (95% confidence interval 0.27-0.55) and that of kidney cancer 0.23 (95% confidence interval 0.06-0.57). The hazard ratio for lung cancer between athletes and referents increased from the unadjusted ratio of 0.29 (95% confidence interval: 0.18-0.48) to 0.61 (95% confidence interval: 0.30-1.26) after adjustment for smoking status and pack-years of smoking. CONCLUSIONS: Former male elite athletes evidently have less cancer than men on the average. The lesser risk can be attributed to lifestyle factors, notably less frequent smoking among the athletes.

Dose-dependent association of smoking and bronchial hyperresponsiveness.

Our aim was to study the association of smoking habits and environmental tobacco smoke (ETS) exposure with bronchial hyperresponsiveness (BHR). A random sample of 292 adults was examined using a structured interview, spirometry, skin prick tests, exhaled nitric oxide fraction (FeNO) and bronchial histamine challenge. A large majority of subjects with BHR were smokers or ex-smokers. Starting to smoke before 20 years of age was significantly associated with BHR, as was current smoking, quantity of smoking and ETS exposure. The severity of BHR increased significantly with increasing pack-years of exposure (p<0.001). Current smokers with decreased lung function were at a particularly high risk of BHR. Impaired forced expiratory volume in 1 s and mean maximal expiratory flow were independent determinants for more severe BHR, regardless of age. In multivariate analysis, smoking remained an independent determinant for BHR after adjustment for impaired lung function and other covariates: ≥15 pack-years yielded an odds ratio of 3.00 (95% CI 1.33-6.76) for BHR. The association between BHR and FeNO was dependent on smoking habits. The results indicate that smoking is a significant risk factor for BHR, with a dose-dependent pattern, and that the severity of BHR increases with pack-years. The findings strongly suggest assessment of smoking habits in subjects with BHR.

COPD in Helsinki, Finland: socioeconomic status based on occupation has an important impact on prevalence.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is globally a major, but often undiagnosed, cause of morbidity and mortality. The aims of this study were to assess the prevalence of COPD in Helsinki, Finland, with international diagnostic criteria and to analyse risk factors including socioeconomic status, and disease severity. METHODS: A general population sample of 628 adults (368 women) completed flow-volume spirometry with bronchodilation test and a structured interview. Post-bronchodilation spirometry was assessed both using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and relative to the fifth percentile of the reference value (lower limit of normal, LLN). RESULTS: According to GOLD criteria, 37 (5.9%), and by using the LLN criteria, 43 subjects (6.8%) had airway obstruction consistent with COPD. Using the GOLD criteria, four subjects or 0.6% of the population had severe, 3.0% moderate, and 2.2% mild COPD. Of those with post-bronchodilator obstruction, 49% had no previous diagnosis of obstructive airways disease and did not use medication for any respiratory disease. The prevalence of undiagnosed COPD defined by GOLD was 2.9% (LLN 3.3%). In addition to age, smoking history, and prior history of asthma, socioeconomic status based on occupation was significantly related to COPD in the population. Manual workers in industry (GOLD 10.0%, LLN 11.7%) and non-manual assistant employees (10.2%, 10.2%) had a significantly higher prevalence of COPD than professionals (2.8%, 2.3%). CONCLUSIONS: Although smoking is the main modifiable risk factor for COPD, the disease was significantly related to manual workers and non-manual assistant employees, i.e. socioeconomic groups reflecting occupation.

Maternal smoking affects lung function and airway inflammation in young children with multiple-trigger wheeze.

BACKGROUND: Exposure to tobacco smoke is a well-known risk factor for childhood asthma and reduced lung function, but the effect on airway inflammation in preschool-aged children is unclear. OBJECTIVE: To examine the effect of parental smoking on lung function and fractional concentration of exhaled nitric oxide (Feno) in relation to both parental reports and children's urine cotinine concentrations in preschool-aged children with multiple-trigger wheeze. METHODS: A total of 105 3- to 7-year-old children with multiple-trigger wheeze and lung function abnormalities were recruited. Lung function was assessed by impulse oscillometry, and Feno measurements were performed. Exposure to tobacco smoke was determined by parental reports and measurement of children's urinary cotinine concentrations. RESULTS: Forty-three percent of the children were exposed to environmental tobacco smoke according to parental reports. The Feno level was significantly higher in children with a smoking mother (n = 27) than in children with a nonsmoking mother (23.4 vs 12.5 ppb, P = .006). The Feno level expressed as z score and the cotinine level correlated significantly (P = .03). Respiratory resistance at 5 Hz was higher in children exposed to maternal smoking than in others (0.99 vs 0.88 kPas/L, P = .005). Urinary cotinine concentrations reflected well parental reports on their daily smoking and increased relative to the number of cigarettes smoked in the family (P < .01). Atopy was found in 75% of the children, but it was not associated with the Feno value (P = .65). CONCLUSION: Maternal smoking was associated with increased Feno value and poorer lung function in steroid-naive preschool children with multiple-trigger wheeze. Larger controlled trials are needed to generalize the results.

Neuron navigator 3 alterations in nervous system tumors associate with tumor malignancy grade and prognosis.

Copy number changes or reduced expression of the Neuron navigator 3 (NAV3) gene occurs in neuroblastomas and malignancies of epithelial or lymphoid origin. To elucidate whether NAV3 has a role in the tumorigenesis of nervous system tumors in general, we studied central and peripheral nervous system tumors for NAV3 copy number changes. In search for common tumorigenic denominators, we analyzed 113 central and peripheral nervous system tumors, including glial tumors (grades I-IV gliomas), medulloblastomas, and neuroblastomas. NAV3 copy number changes were studied by fluorescence in situ hybridization and correlated to survival analyses. To identify target genes of NAV3 deletion, NAV3 was silenced by siRNA in glioblastoma cell lines and gene expression profiles were analyzed by Agilent 4×44k dual-color microarrays. Selected upregulations were confirmed by immunohistochemistry and quantitative polymerase chain reaction. We found NAV3 amplifications to dominate in neuronally differentiated tumors, whereas glial tumors showed almost equal proportions of NAV3 deletion and amplification. However, Grade IV gliomas had more frequent NAV3 deletions than grades I-III gliomas. Silencing of NAV3 in glioma cell lines led to the upregulation of receptor genes associated with gonadotropin-releasing hormone and Jak-Stat signaling pathways. Kaplan-Meier analysis of the entire clinical tumor material showed association between NAV3 amplifications and favorable prognosis, as well as NAV3 deletions and unfavorable prognosis. With Cox regression model, a hazard ratio of 0.51 was observed for NAV3 amplifications and 1.36 for NAV3 deletions. We conclude that NAV3 may be a potential new prognostic biomarker and a potential therapeutic target.

Lung function, airway remodelling and inflammation in symptomatic infants: outcome at 3 years.

BACKGROUND: Relationships between early deficits of lung function, infant airway pathology and outcome in symptomatic infants are unclear. A study was undertaken to determine the associations between early lung function, airway histology and inflammation in symptomatic infants with the continuance of respiratory symptoms, lung function and subsequent use of inhaled asthma medication at the age of 3 years. METHODS: 53 children who underwent lung function measurements and bronchoscopy following referral to a specialist children's hospital for recurrent lower respiratory symptoms at a mean age of 1 year were followed up at 3 years of age. Assessments were made of respiratory symptoms during the previous year, lung function by oscillometry and atopy by skin prick testing. Individual data on the purchase of asthma medications were obtained from the Social Insurance Institution for the 12 months preceding the follow-up visit. RESULTS: 50 children (94%) were re-evaluated, of whom 40 had ongoing airway symptoms. 11/39 (28%) who underwent successful oscillometry had reduced lung function, 31/50 (62%) used inhaled corticosteroids (ICS) regularly and 12/50 (24%) used ICS intermittently. Abnormal lung function at infancy was associated with ongoing airway symptoms (p<0.001) and with the purchase of ICS (p=0.009) and ß agonists (p=0.002). Reticular basement membrane thickness in infancy and the numbers of mucosal mast cells, but not eosinophils, correlated significantly with the amount of ICS purchased at 3 years (p=0.003 and p=0.018, respectively). CONCLUSIONS: Reduced lung function, thickening of the reticular basement membrane and increased density of mucosal mast cells in infancy are associated with respiratory morbidity and treatment needs at age 3 years in this highly selected group of children.

Gastric cancers in Finnish patients after cure of Helicobacter pylori infection: A cohort study.

Helicobacter pylori infection is associated with gastric cancer. A total of 97% of the infected subjects have elevated levels of H. pylori antibodies. The antibody titers have been shown to decline rapidly (40-60% within 4-12 months) only after successful eradication therapy. We allocated 26,700 consecutive patients tested during 1986-1998 for H. pylori antibodies to 3 subcohorts: seropositive patients with rapidly falling antibody titers (Hp+CURED, n = 3,650), seropositive patients where no serological information indicating cure was obtained (Hp+NoInfo, n = 11,638) and seronegative patients (Hp-, n = 11,422). In the subcohorts, the standardised incidence ratios (SIRs) with 95% confidence intervals (CI) were defined for subsequent cancers of stomach, pancreas, colon, rectum, breast and prostate separately and for all cancers except stomach combined. The mean follow-up time was 10.1 years and the number of gastric cancers was 72. For the Hp+CURED, the SIR for gastric cancers for the first 5 follow-up years was 1.62 but decreased from the sixth follow-up year thereon to 0.14 (CI: 0.00-0.75). Likewise, the risk ratio, defined in a Poisson regression analysis using the Hp+NoInfo group as the reference, decreased from 1.60 to 0.13 (CI: 0.02-1.00, p = 0.049). The SIR for Hp- was not significantly higher than that for Hp+NoInfo for any of the cancers analysed. To conclude, cured H. pylori infection led to a significantly decreased incidence of gastric cancers from the sixth follow-up year. Advanced atrophic gastritis would be a plausible contributor to the elevated SIR in elderly Hp- patients.

Esophageal morbidity and function in adults with repaired esophageal atresia with tracheoesophageal fistula: a population-based long-term follow-up.

OBJECTIVE: We assessed esophageal morbidity and relationships between surgical complications, symptoms, endoscopic findings, immunohistochemistry, and esophageal motility in adults with repaired esophageal atresia (EA). SUMMARY OF BACKGROUND DATA: There exist no previous population-based long-term follow-up studies on EA. METHODS: Participants were interviewed, and they underwent esophageal endoscopy and manometry. Matched control subjects (n = 287) served as controls. RESULTS: A total of 101 (42%) individuals representative of the entire study population participated at a mean age of 36 years (range, 21-57). Symptomatic gastroesophageal reflux had occurred in 34% and dysphagia in 85% of the patients and in 8% and 2% of the controls (P < 0.001 for both). Endoscopic findings included hiatal hernia (28%), Barrett's esophagus (11%), esophagitis (8%), and anastomotic stricture (8%). Immunohistochemistry revealed esophagitis in 25%, and CDX2-positive columnar epithelial metaplasia in 21%, with additional goblet cells and MUC2 positivity in 6%. Gastroesophageal reflux and dysphagia were equally common in individuals with normal histology, esophagitis, or epithelial metaplasia. Manometry demonstrated nonpropagating peristalsis in 80% of the patients, and low distal wave amplitudes of the esophagus in all the changes being significantly worse in those with epithelial metaplasia (P < or = 0.022 metaplasia vs. esophagitis/normal). Anastomotic complications (odds ratio [OR]: 8.6-24, 95% confidence interval [CI]: 1.7-260, P = 0.011-0.008), age (OR: 20, 95% CI: 1.3-310, P = 0.034), low distal esophageal body pressure (OR: 2.6, 95% CI: 0.7-10, P = 0.002), and defective esophageal peristalsis (OR: 2.2, 95% CI: 0.4-11, P = 0.014) predicted development of epithelial metaplasia. CONCLUSIONS: Significant esophageal morbidity associated with EA extends into adulthood. Surgical complications, increasing age, and impaired esophageal motility predict development of epithelial metaplasia after repair of EA.