Inflammation and tissue damage in mouse lung by single and repeated dosing of urban air coarse and fine particles collected from six European cities.

The authors have previously demonstrated heterogeneities in the inflammatory activities of urban air fine (PM(2.5-0.2)) and coarse (PM(10-2.5)) particulate samples collected from six European cities with contrasting air pollution situations. The same samples (10 mg/kg) were intratracheally instilled to healthy C57BL/6J mice either once or repeatedly on days 1, 3, and 6 of the study week. The lungs were lavaged 24 h after the single dose or after the last repeated dosing. In both size ranges, repeated dosing of particles increased the total cell number in bronchoalveolar lavage fluid (BALF) more than the respective single dose, whereas cytokine concentrations were lower after repeated dosing. The lactate dehydrogenase (LDH) responses increased up to 2-fold after repeated dosing of PM(2.5-0.2) samples and up to 6-fold after repeated dosing of PM(10-2.5) samples. PM(10-2.5) samples evoked a more extensive interstitial inflammation in the mouse lungs. The constituents with major contributions to the inflammatory responses were oxidized organic compounds and transition metals in PM(2.5-0.2) samples, Cu and soil minerals in PM(10-2.5) samples, and Zn in both size ranges. In contrast, poor biomass and coal combustion were associated with elevated levels of polycyclic aromatic hydrocarbons (PAHs) and a consistent inhibitory effect on the inflammatory activity of PM(2.5-0.2) samples. In conclusion, repeated intratracheal instillation of both fine and coarse particulate samples evoked enhanced pulmonary inflammation and cytotoxicity compared to single-dose administration. The sources and constituents of urban air particles responsible for these effects appear to be similar to those encountered in the authors' previous single-dose study.

Seasonal variation in chemical composition of size-segregated urban air particles and the inflammatory activity in the mouse lung.

We investigated the seasonal variations in the chemical composition and in vivo inflammatory activity of urban air particulate samples in four size ranges (PM(10-2.5), PM(2.5-1), PM(1-0.2), and PM(0.2)). The samples were collected in Helsinki using a high-volume cascade impactor (HVCI). Healthy C57BL/6J mice were intratracheally instilled with a single dose (10 mg/kg) of the particulate samples. The lungs were lavaged and the bronchoalveolar lavage fluid (BALF) was assayed for indicators of inflammation and tissue damage: cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, and keratinocyte-derived chemokine [KC]) at 4 h, and total cell number and total protein concentration at 12 h. The PM(10-2.5) and PM(2.5-1) samples had much higher inflammatory potency than the PM(1-0.2) and PM(0.2) samples. The relative inflammatory activities of the autumn samples were the highest on an equal mass basis, but when estimated for the particulate mass per cubic meter of air, the springtime samples had the highest inflammatory potential. Resuspended soil material and other non-exhaust particulate material from traffic were associated with a high inflammatory activity of the PM(10-2.5) and PM(2.5-1) samples. Secondary inorganic ions in the PM(1-0.2) and PM(0.2) samples had inconsistent negative or positive correlations with the inflammatory activity. There were no systematic seasonal variations in the tracers of incomplete combustion and atmospherically oxidized organics in the PM(1-0.2) and PM(0.2) samples, which probably explains their low correlations with the inflammatory activity. In conclusion, in a relatively clean Nordic city, the resuspension of road dust and other non-exhaust particulate material from traffic were the major sources of inflammatory activity of urban air inhalable particles.

Dose and time dependency of inflammatory responses in the mouse lung to urban air coarse, fine, and ultrafine particles from six European cities.

We investigated the dose and time dependency of inflammatory and cytotoxic responses to size-segregated urban air particulate samples in the mouse lung. Coarse (PM10-2.5), fine (PM2.5-0.2), and ultrafine (PM0.2) particles were collected in six European cities (Duisburg, Prague, Amsterdam, Helsinki, Barcelona, Athens) in selected seasons using a modified Harvard high-volume cascade impactor. Healthy C57Bl/6J mice were intratracheally exposed to the particulate samples in a 24-h dose-response study (1, 3, and 10 mg/kg) and in 4-, 12-, and 24-h time course studies (10 mg/kg). After the exposures, the lungs were lavaged and the bronchoalveolar lavage fluid (BALF) was assayed for indicators of inflammation and tissue damage: total cell number, cell differential, total protein, and lactate dehydrogenase (LDH) and cytokine (tumor necrosis alpha [TNF-alpha], interleukin-6 [IL-6], and keratinocyte-derived chemokine [KC]) concentrations. In general, PM10-2.5 samples had higher inflammatory activity than PM2.5-0.2 samples. PM0.2 samples showed negligible inflammatory activity. PM10-2.5 and PM2.5-0.2 samples caused large increases in BALF cytokine concentrations at 4 h, but not at 12 or 24 h, after exposure. The BALF total cell number and total protein concentrations increased significantly at 12 h for both the PM10-2.5 and PM2.5-0.2 samples, but only PM10-2.5 samples produced consistent, significant increases at 24 h after exposure. There was more heterogeneity in BALF cytokine and neutrophil cell number responses to PM2.5-0.2 samples than to PM10-2.5 samples between the sampling campaigns. Thus, particle size, sources, and atmospheric transformation processes affect the inflammatory activity and response duration of urban air particulate matter in the mouse lung.

Performance of a high-volume cascade impactor in six European urban environments: mass measurement and chemical characterization of size-segregated particulate samples.

The performance of a modified Harvard high-volume cascade impactor (HVCI) was evaluated in six field campaigns with size-segregated particulate samplings for chemical and toxicological characterization. The 7-week sampling campaigns in 2002-2003 in Duisburg (autumn), Prague (winter), Amsterdam (winter), Helsinki (spring), Barcelona (spring), and Athens (summer) were selected to represent contrasting urban environments and seasons of public health interest due to high particulate concentrations or previous findings in epidemiological studies. Particulate samples were collected in parallel with the HVCI (PM(10-2.5), PM(2.5-1), PM(1-0.2), PM(0.2)), a virtual impactor (VI; PM(10-2.5), PM(2.5)), and a Berner low-pressure impactor (BLPI; 10 stages between 0.035 and 10 mum in particle diameter) using a 3- or 4-day sampling duration. The campaigns exhibited different profiles with regard to particulate mass concentration, size distribution, chemical composition and meteorological conditions, thus providing a demanding setup for an overall field comparison of the HVCI with the VI and BLPI reference samplers. Size-segregated particulate mass concentration could be reasonably well measured with the present HVCI configuration. The coarse (PM(10-2.5)) and fine (PM(2.5)) particulate mass agreed within 10% with the low-volume reference samplers, and the four-stage size distribution of the HVCI followed the modal pattern of urban aerosol. The concentrations of chemical constituents measured and integrated especially for the HVCI-PM(2.5) differed to some extent from those measured from the corresponding VI-PM(2.5) samples. This implies that when investigating the association of toxicological responses with the chemical constituents of particulate matter, it is necessary to use the chemical composition data of the same samples as used in toxicological experiments.

Effects of sample preparation on chemistry, cytotoxicity, and inflammatory responses induced by air particulate matter.

Methanol is used for high-efficiency extraction of air particulate (PM) mass from the sampling substrate in the high-volume cascade impactor. Sonication is needed during extraction and when dissolving dried PM samples in liquids used in exposure studies. We investigated the effects of these procedures on the PM chemistry and PM-induced cytotoxic and inflammatory responses in mouse macrophages. Untreated and methanol-treated ambient air reference PM samples (SRM1649a, EHC-93) and diesel PM (SRM1650) were tested after different sonication durations (530 min). Furthermore, the time dependency of the responses to SRM1649a, EHC-93, and a fine PM sample from Helsinki was investigated. Methanol pretreatment increased on average by 24% and 21% the recovery of water-soluble metals from SRM1649a and EHC-93, but not SRM1650. It had no systematic effect on the recoveries of inorganic secondary ions (NO3-, SO4(2-), NH4+) or the sum of genotoxic PAH compounds from the three reference samples. Nitric oxide (NO) response to SRM1650 was strongly enhanced by methanol pretreatment, whereas the cytotoxic or inflammatory responses to the ambient air PM samples (EHC-93, SRM1649a) were only slightly modified. Sonication duration was a modifying factor only in connection to SRM1650. Maximal interleukin (IL)-1 production was observed earlier (8 h) than maximal tumor necrosis factor (TNF) alpha and IL-6 productions (24 h), which indicates the importance to know the optimal time points for measurement of the selected response parameters. In conclusion, methanol extraction and reasonable sonication duration are not likely to modify the cytotoxic and inflammatory potency of ambient air PM samples, but some responses to air PM, rich in organic compounds, can be modified.

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.

In search of childhood asthma: questionnaire, tests of bronchial hyperresponsiveness, and clinical evaluation.

BACKGROUND: The definition or diagnosis of asthma is a challenge for both clinicians and epidemiologists. Symptom history is usually supplemented with tests of bronchial hyperresponsiveness (BHR) in spite of their uncertainty in improving diagnostic accuracy. METHODS: To assess the interrelationship between respiratory symptoms, BHR, and clinical diagnosis of asthma, the respiratory symptoms of 1633 schoolchildren were screened using a questionnaire (response rate 81.2%) and a clinical study was conducted in a subsample of 247 children. Data from a free running test and a methacholine inhalation challenge test were available in 218 children. The diagnosis of asthma was confirmed by a paediatric allergist. RESULTS: Despite their high specificity (>0.97), BHR tests did not significantly improve the diagnostic accuracy after the symptom history: area under the receiver operator characteristic (ROC) curve was 0.90 for a logistic regression model with four symptoms and 0.94 for the symptoms with free running test and methacholine inhalation challenge results. On the other hand, BHR tests had low sensitivity (0.35-0.47), whereas several symptoms had both high specificity (>0.97) and sensitivity (>0.7) in relation to clinical asthma, which makes them a better tool for asthma epidemiology than BHR. CONCLUSIONS: Symptom history still forms the basis for defining asthma in both clinical and epidemiological settings. BHR tests only marginally increased the diagnostic accuracy after symptom history had been taken into account. The diagnosis of childhood asthma should not therefore be overlooked in symptomatic cases with no objective evidence of BHR. Moreover, BHR should not be required for defining asthma in epidemiological studies.

Nitrogen dioxide exposure assessment and cough among preschool children.

The association between exposure to ambient air nitrogen dioxide and cough was evaluated in a panel study among 162 children aged 3-6 y. The weekly average nitrogen dioxide exposure was assessed with Palmes-tube measurements in three ways: (1) personally, (2) outside day-care centers, and (3) inside day-care centers. Ambient air nitrogen dioxide concentrations were obtained from the local network that monitored air quality. The parents recorded cough episodes daily in a diary. The risk of cough increased significantly (relative risk = 3.63; 95% confidence interval = 1.41, 9.30) in the highest personal nitrogen dioxide exposure category in winter, and a nonsignificant positive trend was noted for the other assessment groups. In spring, risk increased nonsignificantly in all exposure-assessment groups, except for the fixed-site monitoring assessment. It is important that investigators select an exposure-assessment method sufficiently accurate to reflect the effective pollutant dose in subjects.

Characterization of respiratory exposure to and effects of cold-air hyperventilation in guinea pigs.

The purpose of this study was to characterize the respiratory effects of single and repeated controlled exposures to clean warm humid and cold dry air in a new model of anesthetized, mechanically ventilated guinea pigs, and to compare findings with known effects in humans. Intratracheal air (T(tr)) and retrotracheal tissue (T(oe)) temperatures and peak expiratory airflow (PEF), tidal volume (V(T)), heart rate, and blood pressure of hyperventilating animals were measured continuously. Four consecutive 10-min exposures to warm humid air (n = 7) produced slight airway warming and minimal lung function changes during the exposure. In a single 10-min exposure to cold dry air (n = 39), T(tr) decreased from (means +/- SEM) 36.1 +/- 0.3 degrees C to 26.3 +/- 0.3 degrees C (Delta = -9.8 +/- 0.4 degrees C) and T(oe) from 36.4 +/- 0.2 degrees C to 35.5 +/- 0.2 degrees C (Delta = -0.9 +/- 0.1 degrees C). PEF and V(T) decreased in response to airway cooling with maximal decrements within the first 2-4 min from the beginning of the exposure period. The maximal decrease in PEF was from 21.7 +/- 0.3 ml s(-1) to 15.9 +/- 0.5 ml s(-1) (Delta = -26.7%) and that in V(T) from 5.2 +/- 0.1 ml to 4.2 +/- 0.1 ml (Delta = -19.2%) (p <.05 for both changes). The decreases in lung functions attenuated significantly during the course of the 10-min exposure to cold dry air, indicating adaptation. Consequently, the decrements in PEF and V(T) at 5, 7.5, and 10 min were significantly smaller than those at 3 min. In four consecutive 10-min exposures to cold dry air (n = 15), there were no statistically significant differences in T(tr) or T(oe) decreases between the exposure periods. The largest decreases in the lung function parameters were during the first exposure period, whereas there were significantly smaller responses during the second and third exposure periods (p <.05). Thus, a highly reproducible airway cooling and an immediate bronchoconstriction were produced in response to cold dry air hyperventilation in guinea pigs. During the course of cold-air exposure and in repeated exposures, there was a significant attenuation of the bronchial response, which resembled the refractoriness of the asthmatic airways to repeated hyperventilation of cold or warm dry air. The present guinea pig model seems to be well suited for production of complementary animal data on the pathophysiological effects of cold dry air on the tracheobronchial airways.

Combined respiratory effects of cold air with SO(2) or NO(2) in repeated 10-minute exposures of hyperventilating guinea pigs.

Previous studies in asthmatic subjects and guinea pigs have demonstrated attenuation of bronchoconstriction in repeated exposures to clean cold dry air. In the present animal study, we have simulated short-lasting human exposures to subfreezing urban air containing sulfur dioxide (SO(2)) and nitrogen dioxide (NO(2)). The anesthetized, paralyzed, and mechanically ventilated guinea pigs had 4 consecutive 10-min exposures either to clean cold dry air or to cold air with graded concentrations of SO(2) (0-5 ppm) or NO(2) (0-4 ppm). Peak expiratory flow (PEF) and tidal volume (V(T)) were continuously measured both during and after highly controlled exposures. Bronchoalveolar lavage fluid (BALF) and histological samples were obtained after finishing the consecutive exposures. Cold air + SO(2) at 1 and 2.5 ppm (n = 12) produced immediate concentration-dependent increases in the lung function responses compared to the preceding single exposure to clean cold dry air in the same animals (DeltaPEF = -32.7 +/- 6.1% and -35.6 +/- 6.5% vs. -27.0 +/- 3.1%; DeltaV(T) = -22.4 +/- 4.4% and -28.3 +/- 4.7% vs. -18.1 +/- 2.9%). In a multivariate analysis, these responses were significantly larger than the attenuated lung function responses to the corresponding second and third clean cold dry air exposures (p <. 05). The fourth exposure to cold air + SO(2) at 5 ppm produced a smaller response (DeltaPEF = -25.3 +/- 4.8% and DeltaV(T) = -17.8 +/- 3.7%) than cold air with the lower SO(2) concentrations. Cold air + NO(2) at 1 and 2.5 ppm (n = 12) produced roughly similar lung function responses to the preceding single exposure to clean cold dry air in the same animals, and there was no significant attenuation of bronchoconstriction as with the consecutive exposures to clean cold dry air. The largest decreases in lung functions (DeltaPEF = -33.8 +/- 6.7% and DeltaV(T) = -26.2 +/- 6.8%) were recorded during the fourth exposure, which was to cold air + NO(2) at 4 ppm. In the cold air + SO(2) group, there was a significantly lower proportion of macrophages in the differential count of BALF white cells compared to the clean cold dry air group. In addition, there was eosinophilic infiltration within and below the tracheal epithelium in all guinea pigs exposed to either clean cold dry air, cold air + SO(2), or cold air + NO(2). In conclusion, the addition of moderate concentrations of SO(2) or NO(2) to clean cold dry air counteracted the attenuation of bronchoconstriction induced by repeated cold dry air exposures in guinea pigs. Cold air + SO(2) also decreased the proportion of macrophages in BALF white cells.

Combined respiratory effects of cold air with SO(2) or NO(2) in single 1-hour exposures of hyperventilating guinea pigs.

The present study is a continuation of our previous experiments on repeated 10-min exposures of anesthetized, mechanically ventilated guinea pigs to clean cold dry air (Hälinen et al., 2000a), and to cold air plus gaseous air pollutants (Hälinen et al., 2000b). This time we made continuous 60-min exposures to clean cold dry air, cold air + SO(2) at 1 ppm, cold air + NO(2) at 1 ppm, and warm humid air + NO(2) at 1 ppm, and focused on responses at 10-60 min. Clean cold dry air and cold air + pollutants (n = 8-9 in each group) produced similar cooling in the guinea pig lower respiratory tract. The decreases in intratracheal temperature (T(tr)) reached a plateau at 20 min with mean maximal decreases of 9.7-11.3 degrees C from the pre-exposure control values of 36.0-37.3 degrees C. In contrast, there were progressive decreases in esophageal temperature (T(oe)) during the exposures, indicating constant conductive and evaporative heat losses from the tracheobronchial tissues. The mean maximal decreases in T(oe) were 1.2-1.4 degrees C from the preexposure control values of 37.8-38.0 degrees C. Clean cold dry air induced 4. 5-10.8% mean decreases in peak expiratory flow (PEF) at 10-60 min of exposure, which were statistically nonsignificant due to a relatively large variation between animals. Cold air + SO(2) at 1 ppm induced a mean decrease of 11.4% in PEF at 10 min (p <.05), which was spontaneously abolished during the next 10 min of exposure. Cold air + NO(2) at 1 ppm caused no decrease, but in fact small, nonsignificant increases in PEF at 30-60 min of exposure. Cold air + NO(2) at 1 ppm, and to some extent also cold air + SO(2) at 1 ppm, attenuated significantly the mechanical ventilation induced gradual decrease in tidal volume (V(T)), when compared to clean cold dry air exposure. Cold air + NO(2) at 1 ppm, but not warm humid air + NO(2) at 1 ppm, increased significantly the proportion of macrophages in the differential count of bronchoalveolar lavage fluid (BALF) white cells when compared to both clean warm humid air and cold dry air. None of the exposure conditions caused morphological or inflammatory changes in the respiratory tissues. In conclusion, continuous 60-min exposures to clean cold dry air, cold air + SO(2), and cold air + NO(2) produced weaker functional effects on the lower respiratory tract of guinea pigs than our previous consecutive 10-min exposures to these air conditions. After the first 10 min, there was a strong attenuation of the bronchoconstrictor responses, especially to cold air + NO(2) at 1 ppm. The small airway effects of prolonged mechanical ventilation were significantly modified by NO(2) at 1 ppm in both cold dry and warm humid breathing air. Finally, cold air + NO(2) at 1 ppm increased the proportion of macrophages in BALF white cells.

A Chemical and Toxicological Comparison of Urban Air PM10 Collected During Winter and Spring in Finland.

We have used a new high-volume, low-cutoff inertial impactor (HVLI) in a pilot study on chemical characterization and toxicity testing of ambient air PM10 in Helsinki, Finland. Ambient air PM10 was collected at 1100 L/min in 2- to 4-day periods. Two different PM10 samples were selected to represent wintertime combustion type and springtime resuspension type particulate matter (PM) pollution. The most abundant water-soluble ions and elements were analyzed by ion chromatography and inductively coupled plasma mass spectrometry, respectively. The proinflammatory activation ¡NO and interleukin 6 (IL-6) production] and viability of cultured murine RAW 264.7 macrophages were tested in 24-h incubations with increasing mass doses (30-2000 µg per 10(6) cells) from the collected PM10 samples. The winter sample had a higher assessed PM2.5 fraction and sulfate content, and lower chloride, sodium, calcium, aluminum, copper, manganese, and especially iron contents than the spring sample. Both PMjo samples induced dose-dependent NO production in murine macrophages, and the springtime PM10 produced also a strong, dose-dependent IL-6 production. In conclusion, the HVLI proved to be a suitable technique for short-term collection of relatively large ambient air PM masses, enabling extensive chemical characterization and toxicity testing from the same samples.

Simple forced oscillatory technique and spirometry in assessment of bronchial responsiveness in non-asthmatic and asthmatic subjects.

Simple validity controlled forced oscillatory respiratory resistance (Rrsfo) at 8 Hz frequency was compared with flow-volume spirometry in detection of bronchial changes during induced bronchoconstriction. The methacholine provocation test was performed in subjects with mild asthma (n = 18) and in non-asthmatic subjects (n = 61) of which 44 were classified as responders (delta FEV1 > or = 15% in methacholine test). According to the index of maximal response/coefficient of variation for immediately repeated measurements (delta max/Coeffvar), Rrsfo was shown to be at least as sensitive indicator of bronchoconstriction as FEV1, and better than MMEF and FVC. The shape of the dose-response curves were similar for all parameters. In the non-asthmatic group, there were similar plateaux in Rrsfo, FEV1, and FVC at the same methacholine concentrations. In the asthmatic group, the provocative concentrations for Rrsfo and spirometric parameters correlated significantly (PC60-Rrsfo versus PC10-FEV1, P < 0.05; PC60-Rrsfo versus PC25-MMEF, P < 0.01). In the non-asthmatic responsive subjects, the correlations between PC60-Rrsfo and PC25-MMEF were significant (P < 0.05). Thus, Rrsfo at a fixed 8 Hz frequency and built-in validity control was shown to be at least as sensitive an indicator for changes in lung function in asthmatic and non-asthmatic responsive subjects as spirometry. Compared to spirometry, it may give additional information with fewer confounding factors during performance.

Short-term variations in oscillatory and spirometric lung function parameters of non-asthmatic adults.

Oscillatory respiratory resistance (Rrsfo) at 8 Hz was compared to flow-volume spirometry with regard to immediate, within-day, day-to-day and week-to-week variations in seven female and four male non-smoking, non-asthmatic volunteers. The lung functions were measured at 08:00, 12:00, 16:00 and 20:00 h on each of the four study days, i.e. two consecutive days in two consecutive weeks. During each visit there were three immediately repeated measurements of Rrsfo, followed by three spirometric recordings. The intra-subject coefficient of variation (Coeffvar) for the immediately repeated measurements was largest for Rrsfo (11.8%). When a simple reliability index (+/- 2 SD of the differences between the repeated measurements) was applied to the Rrsfo data, the Coeffvar reduced to 7.5%. In spirometry, the airflow parameters at defined lung volumes showed larger immediate variations (MEF50 = 5.6%, MEF25 = 8.3%, MMEF = 4.4%) than FEV1 (1.5%) and PEF (3.2%). The within-day variations were larger than the day-to-day or week-to-week variations, and the variations were largest in Rrsfo. A significant diurnal pattern was shown in spirometric parameters but not in Rrsfo. About 38% of the total variance in Rrsfo was due to variation within subjects, while the corresponding proportions in spirometric parameters were 1.8-18.4%. In conclusion, Rrsfo showed larger intrasubject variations than the spirometric parameters at all time intervals. Application of a simple reliability index and standardization of the time of day of the measurement reduced the variations and improved the quality of the Rrsfo data.

Personally measured weekly exposure to NO2 and respiratory health among preschool children.

Nitrogen dioxide is known as a deep lung irritant. The aim of this study was to find out whether the relatively low ambient air NO2 concentrations in the northern city of Helsinki had an impact on the respiratory health of children. The association between personal exposure to ambient air NO2 and respiratory health was investigated in a 13-week follow-up study among 163 preschool children aged 3-6 yrs. Personal weekly average exposure to NO2 was measured by passive diffusion samplers attached to the outer garments. Symptoms were recorded daily in a diary by the parents. Among 53 children, peak expiratory flow (PEF) was measured at home in the mornings and evenings. The association between NO2 exposure and respiratory symptoms was examined with Poisson regression. The median personal NO2 exposure was 21.1 microg x m(-3) (range 4-99 microg x m(-3)). An increased risk of cough was associated with increasing NO2 exposure (risk ratio = 1.52; 95% confidence interval 1.00-2.31). There was no such association between personal weekly NO2 exposure and nasal symptoms, but a nonsignificant negative association was found between the exposure and the weekly average deviation in PEF. In conclusion, even low ambient air NO2 concentrations can increase the risk of respiratory symptoms among preschool children.

Diesel particles induce nitric oxide production in murine alveolar macrophages and rat airways.

The acute adverse health effects among respiratory and cardiovascular patients have been associated with particulate air pollution, containing diesel particles (DP). The mechanisms of these effects are unknown, but they may involve inflammation. We investigated the effects of DP (30-3000 µg/10(6) cells) on cell viability and production of nitric oxide (NO), interleukin-1 (IL-1), interleukin-6 (IL-6), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in murine RAW 264.7 macrophage cultures in vitro. DP caused a dose- and time-dependent NO-production and was cytotoxic in murine RAW 264.7 macrophages. Cytotoxicity preceded the increases in NO production. DP had minimal effects on cytokine production. A single intratracheal instillation of DP 1 and 5 mg/rat increased NO production and protein concentration in bronchoalveolar lavage fluid, and caused pulmonary edema and hemorrhage. The present results indicate that DP can induce both NO production and cytotoxicity in the lower respiratory tract, which may contribute to the short-term adverse respiratory effects of these particles.

A new guinea-pig model for acute inhalation studies on combined effects of cold air and pollutants.

We have developed a new small animal model for acute inhalation studies on combined effects of cold air and gaseous urban air pollutants. The anaesthetised, tracheostomised and paralysed guinea-pig was placed inside a small, sealed whole-body-box, in which it was ventilated mechanically by using cyclic negative pressure (Pbox) for active expansion of the chest. During a 2-h normal ventilation with warm humid air (n=6), there was a need for increasing Pbox with time to maintain the fixed tidal volume (VT) of 11 ml/kg. No such need was seen in the experiments with 15-min periods of isocapnic hyperventilation at 80 and 120 breaths/min (n=13). During the 2-h normal ventilation and in experiments with hyperventilation, there was a gradual increase in heart rate and small gradual decreases in PaCO2 and pH with time. Cold air + SO2 2.5 ppm produced a significantly stronger bronchoconstriction (deltaVT=-30.3+/-7.2%, n=6, P < 0.05) than clean cold dry air (deltaVT=-10.6+/-1.3%, n=6) and cold air + NO2 2.5 ppm (deltaVT=-13.2+/-3.3%, n=6), although these three exposure conditions produced similar decreases in tracheal air and retrotracheal tissue temperatures. With the present guinea-pig model, the combined respiratory effects of cold air and gaseous urban air pollutants can be investigated in a highly controlled manner.

Characterization of air quality problems in five Finnish indoor ice arenas.

The air quality in five Finnish ice arenas with different volumes, ventilation systems, and resurfacer power sources (propane, gasoline, electric) was monitored during a usual training evening and a standardized, simulated ice hockey game. The measurements included continuous recording of carbon monoxide (CO), nitric oxide (NO), and nitrogen dioxide (NO2) concentrations, and sampling and analysis of volatile organic compounds (VOCs). Emissions from the ice resurfacers with combustion engines caused indoor air quality problems in all ice arenas. The highest 1-hour average CO and NO2 concentrations ranged from 20 to 33 mg/m3 (17 to 29 ppm) and 270 to 7440 micrograms/m3 (0.14 to 3.96 ppm), respectively. The 3-hour total VOC concentrations ranged from 150 to 1200 micrograms/m3. The highest CO and VOC levels were measured in the arena in which a gasoline-fueled resurfacer was used. The highest NO2 levels were measured in small ice arenas with propane-fueled ice resurfacers and insufficient ventilation. In these arenas, the indoor NO2 levels were about 100 times the levels measured in ambient outdoor air, and the highest 1-hour concentrations were about 20 times the national and World Health Organization (WHO) health-based air quality guidelines. The air quality was fully acceptable only in the arena with an electric resurfacer. The present study showed that the air quality problems of indoor ice arenas may vary with the fuel type of resurfacer and the volume and ventilation of arena building. It also confirmed that there are severe air quality problems in Finnish ice arenas similar to those previously described in North America.

Nitrogen dioxide in indoor ice skating facilities: an international survey.

An international survey of nitrogen dioxide (NO2) levels inside indoor ice skating facilities was conducted. One-week average NO2 concentrations were measured inside and outside of 332 ice rinks located in nine countries. Each rink manager also completed a questionnaire describing the building, the resurfacing machines, and their use patterns. The (arithmetic) mean NO2 level for all rinks in the study was 228 ppb, with a range of 1-2,680 ppb, based on a sample collected at breathing height and adjacent to the ice surface. The mean of the second indoor sample (collected at a spectator's area) was 221 ppb, with a range of 1-3,175 ppb. The ratio of the indoor to outdoor NO2 concentrations was above 1 for 95% of the rinks sampled, indicating the presence of an indoor NO2 source (mean indoor:outdoor ratio = 20). Estimates of short-term NO2 concentrations indicated that as many as 40% of the sampled rinks would have exceeded the World Health Organization 1-hour guideline value of 213 ppb NO2 for indoor air. Statistically significant associations were observed between NO2 levels and the type of fuel used to power the resurfacer, the absence of a catalytic converter on a resurfacer, and the use of an ice edger. There were also indications that decreased use of mechanical ventilation, increased number of resurfacing operations per day, and smaller rink volumes were associated with increased NO2 levels. In rinks where the main resurfacer was powered by propane, the NO2 concentrations were higher than in those with gasoline-powered resurfacers, while the latter had NO2 concentrations higher than in those using diesel. Rinks where the main resurfacer was electric had the lowest indoor NO2 concentrations, similar to the levels measured outdoors.

Short-term variations in oscillatory and spirometric lung function indices among school children.

The aim of this study was to compare immediate, daily and weekly variation in respiratory resistance measured by means of the forced oscillation technique (Rrs,FOT) to spirometric indices in 7-12 year old children with chronic respiratory symptoms. The lung function measurements were performed in 19 children on 4 days, i.e. two consecutive days during two consecutive weeks. On each day, the measurements were carried out at the same time of day and always repeated three times. In addition, Rrs,FOT and spirometric lung function indices were compared with an exercise challenge test in 12 children. Intrasubject coefficients of variation (CoVs) for Rrs,FOT were larger than those for spirometric indices. Only in the immediately repeated measurements was the CoV of maximal expiratory flow at 25% vital capacity larger than that of Rrs,FOT (16.6 vs 14.9%). At all time intervals, the smallest CoVs were observed in forced vital capacity (FVC) or in the ratio of forced expiratory volume in one second to FVC (2.0-2.6%). When excluding Rrs,FOT values which were not within 2 SD (0.11 kPa.L-1.s) of the differences between the immediately repeated measurements, the CoV of the immediately repeated measurements of Rrs,FOT was reduced to 9.1%, being smaller than that of maximal mid-expiratory flow (10.1%). However, even then the day-to-day variation in Rrs,FOT was clearly larger (16.0%) than those of the airflow indices at specified lung volumes (7.2-8.3%). This was also true for the weekly variation. In the exercise challenge test, there were larger changes in Rrs,FOT values than in the spirometric indices, but Rrs,FOT was the most sensitive index to detect changes in the respiratory system. In conclusion, the variation in Rrs,FOT values was larger than that of most spirometric indices. When a reliability index was applied, the immediate variation in Rrs,FOT values was comparable to those of the airflow indices at specified lung volumes. Rrs,FOT was also the most sensitive index in the exercise challenge test, and therefore it seems to be suitable for detection of short-term functional changes in the respiratory system. However, the relatively low repeatability of Rrs,FOT over days and weeks may limit its applicability to longer-term follow-ups.