Reference values of spirometry for Finnish adults.

BACKGROUND: Diagnostic assessment of lung function necessitates up-to-date reference values. The aim of this study was to estimate reference values for spirometry for the Finnish population between 18 and 80 years and to compare them with the existing Finnish, European and the recently published global GLI2012 reference values. METHODS: Spirometry was performed for 1380 adults in the population-based FinEsS studies and for 662 healthy non-smoking volunteer adults. Detailed predefined questionnaire screening of diseases and symptoms, and quality control of spirometry yielded a sample of 1000 native Finns (387 men) healthy non-smokers aged 18-83 years. Sex-specific reference values, which are estimated using the GAMLSS method and adjusted for age and height, are provided. RESULTS: The predicted values for lung volumes are larger than those obtained by GLI2012 prediction for the Caucasian subgroup for forced vital capacity (FVC) by an average 6·2% and 5·1% and forced expiratory volume in 1 s (FEV1) by an average 4·2% and 3·0% in men and women, respectively. GLI2012 slightly overestimated the ratio FEV1/FVC with an age-dependent trend. Most reference equations from other European countries, with the exception of the Swiss SAPALDIA study, showed an underestimation of FVC and FEV1 to varying degrees, and a slight overestimation of FEV1/FVC. CONCLUSION: This study offers up-to-date reference values of spirometry for native Finns with a wide age range. The GLI2012 predictions seem not to be suitable for clinical use for native Finns due to underestimation of lung volumes.

Diffusion capacity of the lung in young and old endurance athletes.

Lung diffusion capacity (D LCO) declines with age. A significant proportion of older endurance athletes develop exercise-induced hypoxemia (SaO2<95%). We hypothesised that master endurance athletes have a lower D LCO than age-matched non-athletes. We recruited 33 control (16 young; 17 old) and 29 male endurance athletes (13 young; 16 old) during the World Masters Athletics Indoor Championships, 2012 (Jyväskylä, Finland). To measure D LCO the participant exhaled to residual volume and then quickly inhaled to ≥ 90% total lung capacity from a gas source with 0.3% carbon monoxide. The D LCO and transfer coefficient (K CO) were corrected for the actual haemoglobin concentration. Spirometric function was similar in athletes and age-matched controls. D LCO and K CO were 33% and 25% lower in old and young controls, respectively (P<0.001). Although predicted D LCO and K CO were 11%-points higher in athletes than age-matched controls (P<0.001), they were 23% and 16% lower in old athletes than young controls, respectively (P<0.001). D LCO did not correlate with age-graded performance or weekly training hours. The better lung diffusion capacity in male endurance athletes than age-matched controls might be an adaptation to training, self-selection and/or attrition bias. However, the diffusion capacity of the older athlete is lower than that of the young non-athlete.

Relation between body composition, abdominal obesity, and lung function.

Reference values of spirometry and diffusion capacity are usually adjusted for age, sex, height and ethnic origin. However, also other factors, mainly weight and body composition, have an effect on pulmonary function. Therefore, we examined how body composition and abdominal obesity are related to lung function in normal population and whether they should be taken into account in the reference values. Two hundred and eighty-four healthy Finnish non-smoking adults were included in the study. Height, waist circumference, abdominal sagittal diameter and body composition were measured, and spirometry and diffusion capacity (DLCO) were performed. Muscle mass (r = 0.29, P = 0.000) and lean body mass (r = 0.29, P = 0.000) correlated positively with DLCO. However, no significant correlation between body composition and spirometry results was observed. Abdominal sagittal diameter (r = -0.21, P = 0.000) and waist circumference (r = -0.22, P = 0.000) correlated inversely with the forced expiratory volume in 1 s/forced vital capacity ratio (FEV1/FVC). In our study population, subjects with higher muscle and lean body mass had higher DLCO. This indicates a need for future re-evaluation of reference values. Besides, already minor abdominal obesity is associated with obstructive changes in spirometry results.

Hourly variation in fine particle exposure is associated with transiently increased risk of ST segment depression.

OBJECTIVES: To evaluate whether hourly changes in fine particle (PM(2.5), diameter<2.5 microm) exposure or outdoor particle concentrations are associated with rapid ischaemic responses. METHODS: 41 non-smoking elderly people with coronary heart disease were followed up with biweekly clinic visits in Helsinki, Finland. The occurrence of ST segment depressions >0.1 mV was recorded during submaximal exercise tests. Hourly variations in personal PM(2.5) exposure and outdoor levels of PM(2.5) and ultrafine particles (<0.1 microm) were recorded for 24 h before a clinic visit. Associations between particulate air pollution and ST segment depressions were evaluated using logistic regression. RESULTS: Both personal and outdoor PM(2.5) concentrations, but not outdoor ultrafine particle counts, were associated with ST segment depressions. The odds ratio (per 10 microg/m(3)) for personal PM(2.5) concentration during the hour preceding a clinic visit was 3.26 (95% CI 1.07 to 9.99) and for 4 h average outdoor PM(2.5) it was 2.47 (95% CI 1.05 to 5.85). CONCLUSIONS: Even very short-term elevations in fine particle exposure might increase the risk of myocardial ischaemia. The precise mechanism is still unknown but could involve changes in autonomic nervous control of the heart.

Daily variation in fine and ultrafine particulate air pollution and urinary concentrations of lung Clara cell protein CC16.

BACKGROUND: Daily variations in ambient particulate air pollution have been associated with respiratory mortality and morbidity. AIMS: To assess the associations between urinary concentration of lung Clara cell protein CC16, a marker for lung damage, and daily variation in fine and ultrafine particulate air pollution. METHODS: Spot urinary samples (n = 1249) were collected biweekly for six months in subjects with coronary heart disease in Amsterdam, Netherlands (n = 37), Erfurt, Germany (n = 47), and Helsinki, Finland (n = 47). Ambient particulate air pollution was monitored at a central site in each city. RESULTS: The mean 24 hour number concentration of ultrafine particles was 17.3x10(3) cm(-3) in Amsterdam, 21.1x10(3) cm(-3) in Erfurt, and 17.0x10(3) cm(-3) in Helsinki. The mean 24 hour PM2.5 concentrations were 20, 23, and 13 microg/m3, respectively. Daily variation in ultrafine particle levels was not associated with CC16. In contrast, CC16 concentration seemed to increase with increasing levels of PM2.5 in Helsinki, especially among subjects with lung disorders. No clear associations were observed in Amsterdam and Erfurt. In Helsinki, the CC16 concentration increased by 20.2% (95% CI 6.9 to 33.5) per 10 microg/m3 increase in PM2.5 concentration (lag 2). The respective pooled effect estimate was 2.1% (95% CI -1.3 to 5.6). CONCLUSION: The results suggest that exposure to particulate air pollution may lead to increased epithelial barrier permeability in lungs.

Effects of fine and ultrafine particles on cardiorespiratory symptoms in elderly subjects with coronary heart disease: the ULTRA study.

The ULTRA Study, a study investigating the association between fine and ultrafine particulate air pollution and cardiorespiratory health, was conducted during the winter of 1998-1999 in Amsterdam, the Netherlands; Erfurt, Germany; and Helsinki, Finland. At each study center, a panel of elderly subjects with coronary heart disease recorded cardiac and respiratory symptoms in a diary. Exposure to ambient air pollution was characterized by measuring daily mass concentrations of particles smaller than 10 micro m (PM(10)) and 2.5 micro m (PM(2.5)), number concentrations of ultrafine particles (NC(0.01-0.1)), and gases. Odds ratios for the relation of symptoms to air pollution, adjusted for time trend, respiratory infections, and meteorologic variables, were mostly homogeneous across the centers. No association was found between air pollution and chest pain. A 10- micro g/m(3) increase in PM(2.5) was positively associated with the incidence of shortness of breath (odds ratio (OR) = 1.12, 95% confidence interval (CI): 1.02, 1.24) and with avoidance of activities (OR = 1.09, 95% CI: 0.97, 1.22). NC(0.01-0.1) was only associated with the prevalence of avoidance of activities (OR = 1.10, 95% CI: 1.01, 1.19). In conclusion, PM(2.5) was associated with some cardiac symptoms in three panels of elderly subjects. PM(2.5 )was more strongly related to cardiorespiratory symptoms than ultrafine particles were.

Associations between markers of respiratory morbidity in European children.

School-aged children often experience acute respiratory symptoms. In a multicentre European study, the association between chronic respiratory symptoms (reported in a questionnaire), skin-prick test results, and lung function, and the occurrence of acute respiratory morbidity, was examined among children aged 6-12 yrs with chronic respiratory symptoms. Children with chronic respiratory symptoms, living in 10 European countries, were selected from a parent-completed questionnaire (n=4,307). Atopy was measured with skin-prick tests, and lung function with spirometry. A total of 1,854 (86% of those in the initial cohort) children kept a successful daily diary regarding their respiratory symptoms for 2-3 months. In multivariate logistic regression analyses, children with asthmatic symptoms, particularly those with doctor-diagnosed asthma, had a greater risk of occurrence of lower respiratory symptoms (odds ratio (OR): 6.12; 95% confidence interval (CI): 4.99-8.35) than children with a dry nocturnal cough as their only symptom. Atopy, particularly a positive reaction to indoor allergens, was significantly associated with occurrence of lower respiratory symptoms. For atopy the OR was 1.62 (95% CI: 1.34-1.96). A reduced level of maximal mid-expiratory flow was associated with an increased risk of lower respiratory symptoms, cough and phlegm. The associations were similar in Scandinavia, Central Eastern, Western and Southern Europe. To conclude, asthmatic symptoms reported in a questionnaire, atopic status and a reduced level of maximal mid-expiratory flow were associated with the occurrence of acute respiratory symptoms, especially those of lower respiratory symptoms.

Effects of air pollution on changes in lung function induced by exercise in children with chronic respiratory symptoms.

OBJECTIVE: To investigate how daily variations in ambient air pollution, especially in particles, during the cold of winter affect repeated measurements of baseline lung function and exercise induced bronchial responsiveness among primary school children with chronic respiratory symptoms. METHODS: During alternate school weeks (maximum five) from February to April 1994, 33 children took part in exercise challenge tests (n=141 tests). The exercise challenges were conducted outdoors in a school yard in the centre of Kuopio, Finland. Spirometric lung functions were measured indoors before the exercise, and 3 and 10 minutes after. Daily mean concentrations of PM(10), black smoke (BS), NO(2), CO, SO(2), and particle size and numbers were monitored at a nearby fixed monitoring site. RESULTS: Daily variations in ambient air pollution were not associated with enhanced bronchial responsiveness. However, increased concentrations of BS, PM(10), particle numbers, NO(2), and CO were consistently associated with an impairment of baseline lung functions. The reductions in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV(1)) were 0.5% and 0.6%, respectively, for each 10 microg/m(3) increase in BS (lag 2). CONCLUSION: Particles derived from combustion affect baseline lung function rather than bronchial responsiveness among children with chronic respiratory symptoms.

Ultrafine particles in urban air and respiratory health among adult asthmatics.

Airborne particles are associated with adverse health effects and contribute to excess mortality in epidemiological studies. A recent hypothesis proposes that the high numbers of ultrafine (<0.1 microm diameter) particles in ambient air might provoke alveolar inflammation and subsequently cause exacerbations in pre-existing cardiopulmonary diseases. To test the hypothesis adult asthmatics were followed with daily peak expiratory flow (PEF) measurements and symptom and medication diaries for six months, while simultaneously monitoring particulate pollution in ambient air. The associations between daily health endpoints of 57 asthmatics and indicators of air pollution were examined by multivariate regression models. Daily mean number concentration of particles, but not particle mass (PM10 (particle mass <10 microm), PM2.5-10, PM2.5, PM1), was negatively associated with daily PEF deviations. The strongest effects were seen for particles in the ultrafine range. However, the effect of ultrafine particles could not definitely be separated from other traffic generated pollutants, namely nitric oxide, nitrogen dioxide and carbon monoxide. No associations were observed with respiratory symptoms or medication use. Particle mass measurements can be strongly influenced by mechanically produced, soil-derived particles, which may not be associated with adverse health effects. Therefore, air quality monitoring should include particle number concentrations, which mainly reflect ultrafine particles.

Number concentration and size of particles in urban air: effects on spirometric lung function in adult asthmatic subjects.

Daily variations in ambient particulate air pollution are associated with variations in respiratory lung function. It has been suggested that the effects of particulate matter may be due to particles in the ultrafine (0.01-0.1 microm) size range. Because previous studies on ultrafine particles only used self-monitored peak expiratory flow rate (PEFR), we assessed the associations between particle mass and number concentrations in several size ranges measured at a central site and measured (biweekly) spirometric lung function among a group of 54 adult asthmatics (n = 495 measurements). We also compared results to daily morning, afternoon, and evening PEFR measurements done at home (n = 7,672-8,110 measurements). The median (maximum) 24 hr number concentrations were 14,500/cm(3) (46,500/cm(3)) ultrafine particles and 800/cm(3) (2,800/cm(3)) accumulation mode (0.1-1 microm) particles. The median (maximum) mass concentration of PM(2.5) (particulate matter < 2.5 microm) and PM(10) (particulate matter < 10 microm in aerodynamic diameter) were 8.4 microg/m(3) (38.3 microg/m(3)) and 13.5 microg/m(3) (73.7 microg/m(3)), respectively. The number of accumulation mode particles was consistently inversely associated with PEFR in spirometry. Inverse, but nonsignificant, associations were observed with ultrafine particles, and no associations were observed with large particles (PM(10)). Compared to the effect estimates for self-monitored PEFR, the effect estimates for spirometric PEFR tended to be larger. The standard errors were also larger, probably due to the lower number of spirometric measurements. The present results support the need to monitor the particle number and size distributions in urban air in addition to mass.

Homozygous variegate porphyria: 20 y follow-up and characterization of molecular defect.

The long-term follow-up of a homozygous variegate porphyria patient revealed severe photosensitivity accompanied by mild sensory neuropathy and IgA nephropathy. A 35T to C transition in exon 2 (I12T) and a 767C to G transversion in exon 7 (P256R) of the protoporphyrinogen oxidase gene were identified from both alleles of the patient's cDNA and genomic DNA samples. Both prokaryotic and eukaryotic expression studies showed that the first mutation in the evolutionary conserved region resulted in a decrease in the protoporphyrinogen oxidase activity in contrast to the polymorphic substitution in exon 7, which affected the function of the enzyme assayed in Escherichia coli but not COS-1 cells.

Vascular changes in erythropoietic protoporphyria: histopathologic and immunohistochemical study.

BACKGROUND: Erythropoietic protoporphyria (EPP) is an inherited disease caused by deficient activity of ferrochelatase in the heme biosynthetic pathway. Accumulation of protoporphyrins and light exposure results in acute phototoxic skin reactions. The histopathologic findings of the light-exposed skin are thickening of the superficial dermal vessel walls and amorphous deposits around the vessels, but the origin and detailed composition of the perivascular material have been unclear. OBJECTIVE: The vascular morphology and composition of the perivascular material were studied in the skin samples of patients with EPP. METHODS: Skin biopsy specimens of 8 patients with EPP representing 7 Finnish EPP families with different genotypes were studied by means of light and electron microscopy and immunohistochemical methods. RESULTS: The characteristic finding was thickened, periodic acid-Schiff-positive vessel walls caused by concentric reduplication of basal lamina and excess of fine granular material at the basal membrane zone in the superficial dermis. The perivascular deposits in the vicinity of vessel walls had a homogeneous or fine granular appearance without filaments. Direct immunofluorescence showed constant IgG deposits together with IgA, IgM, and C3 in the vessel walls. In immunohistochemistry, collagen IV and laminin could be demonstrated at the vascular basal membrane together with serum amyloid P protein, kappa and lambda light chains, and a 90-kd glycoprotein. CONCLUSION: The vascular involvement indicates that the blood vessel walls in the papillary dermis are the primary tissues affected during an acute photoreaction. The repeated acute damage and repair processes in the basement membrane zone result in thickening of the vessel walls. Perivascular deposits are a secondary and irreversible phenomenon resulting from the leakage and accumulation of different serum components. These changes were not found in the nonexposed skin, indicating that an increased level of erythrocyte protoporphyrin per se is not responsible for the cutaneous manifestations, but the interaction of solar radiation is mandatory. Amorphous deposits distinguish EPP from variegate porphyria and porphyria cutanea tarda; a histopathologic examination may be a helpful tool in differentiating porphyric and nonporphyric photosensitivity.

Personal exposure to fine particulate matter in elderly subjects: relation between personal, indoor, and outdoor concentrations.

The time-series correlation between ambient levels, indoor levels, and personal exposure to PM2.5 was assessed in panels of elderly subjects with cardiovascular disease in Amsterdam, the Netherlands, and Helsinki, Finland. Subjects were followed for 6 months with biweekly clinical visits. Each subject's indoor and personal exposure to PM2.5 was measured biweekly, during the 24-hr period preceding the clinical visits. Outdoor PM2.5 concentrations were measured at fixed sites. The absorption coefficients of all PM2.5 filters were measured as a marker for elemental carbon (EC). Regression analyses were conducted for each subject separately, and the distribution of the individual regression and correlation coefficients was investigated. Personal, indoor, and ambient concentrations were highly correlated within subjects over time. Median Pearson's R between personal and outdoor PM2.5 was 0.79 in Amsterdam and 0.76 in Helsinki. For absorption, these values were 0.93 and 0.81 for Amsterdam and Helsinki, respectively. The findings of this study provide further support for using fixed-site measurements as a measure of exposure to PM2.5 in epidemiological time-series studies.

Fixed drug eruption due to fluconazole.

We report a case of fixed drug eruption caused by fluconazole. A local provocation with 10% fluconazole test in petrolatum applied at the site of a previous lesion of fixed drug eruption reproduced the eruption clinically and histopathologically.

Respiratory effects of environmental tobacco smoke in a panel study of asthmatic and symptomatic children.

The effect of environmental tobacco smoke (ETS) on respiratory health was investigated among 7- to 12-yr-old children with asthmatic (n = 74) or cough (n = 95) symptoms. For 3 mo the children measured their peak expiratory flow rate (PEFR) every morning and evening, and kept a daily diary of respiratory symptoms. They also noted daily whether they had used respiratory medication and whether someone had smoked inside their home. Eleven percent of the asthmatic children and 14% of the children with cough had exposure to ETS at home during the study. In multiple regression and analyses controlling for potential confounders, any exposure to ETS during the study was associated with a reduction of 42 L/min (95% confidence interval [CI]: 10 to 74 L/min) in morning and 41 L/min (95% CI: 8 to 74 L/min) in evening PEFR among asthmatic children. Among these children, a dose-dependent increase in the effect of ETS was also seen. Daily variation in ETS exposure was only weakly (-9.2 L/min; 95% CI: 2.9 to 21.2 L/min) associated with PEFR, but the previous day's ETS exposure was a risk factor for bronchodilator use (relative risk [RR]: 10.3; 95% CI: 1.3 to 83.7), as well as for cough (RR: 12.4; 95% CI: 2.4 to 63.3) and phlegm production (RR: 7. 8; 95% CI: 1.4 to 41.7), on any given day. Among children with cough only, there was only a weak suggestion of any possible ETS effect. In conclusion, we found that exposure to ETS was associated with a decline in peak flow and increases in respiratory symptoms and use of bronchodilator drugs among asthmatic children.

Fine particulate air pollution, resuspended road dust and respiratory health among symptomatic children.

The short-term association of particulate air pollution with peak expiratory flow rate (PEF) and respiratory symptoms was examined. Forty-nine children with chronic respiratory symptoms aged 8-13 yrs were followed daily for six weeks in spring, 1995, in Kuopio, Finland. Daily concentrations of particulate material with a 50% cut-off aerodynamic diameter < or = 10 microm and < or = 2.5 microm (PM10 and PM2.5, respectively), black carbon, and the number concentrations of particles from 0.01-10 microm diameter were measured. During the study period, PM10 were mainly resuspended soil and street dust, and the concentration was estimated using aluminum content of PM10 samples. No consistent effect of particles was found as the associations varied by lag. Of the lags examined, only 1-day lagged PM2.5 was statistically significantly associated with morning PEF (beta=-1.06, SE=0.52 (per interquartile increase in pollutant)). Evening PEF was significantly associated with the 1-day lagged number of particles in the size range 0.1-1.0 microm (beta=-1.56, SE=0.72). One-day lagged PM10, PM2.5-10, PM2.5 and resuspended PM10, and 4-day average of PM2.5 were significantly associated with increased risk of cough. Given the short duration of the study, separating the effects of different types of particles was difficult. The present study demonstrates the highly variable size and number distribution and chemical composition of particles in Finland, and underlines the importance of measuring the size and chemical composition of particles to determine which types of particles are associated with health effects.

Chronic respiratory symptoms, skin test results, and lung function as predictors of peak flow variability.

We examined how chronic respiratory symptoms, reported in a questionnaire, and results of skin prick tests and spirometry predicted variability in peak expiratory flow (PEF) among 6-12-yr-old children (n = 1,854). After characterization with skin tests and spirometry, children were followed for 2-3 mo during the winter of 1993-1994. Peak expiratory flow was measured daily in the morning and evenings. Children with asthmatic symptoms (wheeze and/or attacks of shortness of breath with wheeze in the past 12 mo and/or ever doctor diagnosed asthma) had a greater variation in PEF than children with dry nocturnal cough as their only chronic respiratory symptom. Similarly, doctor-diagnosed asthma was associated with a greater variation in PEF, also among children with asthmatic symptoms. Peak flow variability increased with an increasing number of symptoms reported in the questionnaire. Atopy, positive skin test reactions to house dust mite and cat and lowered level (as % of predicted) in FEV1 and in MMEF were also associated with an increased variation in PEF. All the differences were observed in both diurnal and day-to-day variation in PEF. In conclusion, chronic respiratory symptoms reported in a questionnaire, spirometric lung function and skin prick test results among asthmatic children predicted variation in PEF measured during a 2-3 mo follow-up. The difference in morning PEF coefficient of variation (CV) between children with asthmatic symptoms and children with cough only was somewhat bigger in girls than in boys. The effect of atopy on morning PEF CV was somewhat bigger in young than in older children.

Air pollution and respiratory health among children with asthmatic or cough symptoms.

During the winter of 1994, the association between daily changes in air pollution and in the respiratory health of children 7 to 12 yr of age were studied in Kuopio, Finland. Seventy-four children with asthmatic symptoms and 95 children with cough only, living either in urban or suburban areas, were followed for 3 mo. During the study period, the mean daily concentration of particulate air pollution (PM10) was 18 micrograms/m3 in the urban area and 13 micrograms/m3 in the suburban area. Lagged concentrations of PM10, black smoke, and NO2 were significantly associated with declines in morning peak expiratory flow (PEF) among asthmatic children. The regression coefficient (x10) for a 2-d lag of PM10 was -0.911 (SE, 0.386) in the urban and -1.05 (0.596), in the suburban area. Among children with cough only, PM10, black smoke, and NO2 were not significantly associated with PEF. In the urban area, there was a significant association between SO2 and morning and evening PEF and incidence of upper respiratory symptoms among children who cough only. No other associations between air pollution and evening PEF or respiratory symptoms were observed. This study suggests that particulate air pollution is associated with respiratory health, especially among children with asthmatic symptoms.

Childhood asthma in four regions in Scandinavia: risk factors and avoidance effects.

BACKGROUND: The high and increasing prevalence of childhood asthma is a major public health issue. Various risk factors have been proposed in local studies with different designs. METHODS: We have made a questionnaire study of the prevalence of childhood asthma, potential risk factors and their relations in four regions in Scandinavia (Umeå and Malmö in Sweden, Kuopio in eastern Finland and Oslo, Norway). One urban and one less urbanized area were selected in each region, and a study group of 15962 children aged 6-12 years was recruited. RESULTS: The prevalence of symptoms suggestive of asthma varied considerably between different areas (dry cough 8-19%, asthma attacks 4-8%, physician-diagnosed asthma 4-9%), as did the potential risk factors. Urban residency was generally not a risk factor. However, dry cough was common in the most traffic polluted area. Exposure to some of the risk factors. such as smoking indoors and moisture stains or moulds at home during the first 2 years of life, resulted in an increased risk. However, current exposure was associated with odds ratios less than one. CONCLUSIONS: Our findings were probably due to a combination of early impact and later avoidance of these risk factors. The effects of some risk factors were found to differ significantly between regions. No overall pattern between air pollution and asthma was seen, but air pollution differed less than expected between the areas.