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Examines the reduction in the impact of a deep inhalation on forced expiratory flow due to ozone exposure among non-smoking subjects. Antioxidant status in nasal lavage and of nasal cavity dimensions during exposure to clean air and ozone; Maximal flows after saline exposure; Role of parasympathetic nervous system in acute lung response to ozone.

Antibodies to antigens in humidifier water were detected by double immunodiffision in 30 of 63 (47.6%) persons who were exposed to aerosols from a water humidification unit in a cigar plant, whereas no antibodies could be detected in 49 unexposed blood donors (P<0.001). The presence of antibodies could not be related to fever or pulmonary symptoms (cough, expectoration, dyspnoe). Antibodies were found in 14 (93.3%) of 15 nonsmokers and in only 13 (317%) of 41 smokers (P<0.001), and the titres were highest in nonsmokers. Serum IgG and IgA levels were higher in nonsmokers than in smokers, and the variances within the groups were significantly different (F<0.05 and F<0.05, respectively). The mean serum IgM values were not significantly different in the two groups. Antibodies to Candida albicans and Escherichia coli 04 and 075 were detected with equal prevalences and titres in smokers and nonsmokers. These findings suggest that tobacco smoking may suppress the humoral immune response to inhaled antigens but not to antigens which are supposed to be absorbed through membranes other than those of the bronchopulmonary system. They may partly explain the reported increased incidence of allergic alveolitis in nonsmokers. [ABSTRACT FROM AUTHOR]

Spirometric lung function is partly determined by sex, age and height (Ht). Commonly, lung function is expressed as a percentage of the predicted value (PP) in order to account for these effects. Since the PP method retains sex, age and Ht bias, forced expiratory volume in 1 s (FEV(1)) standardised by powers of Ht and by a new sex-specific lower limit (FEV(1) quotient (FEV(1)Q)) were investigated to determine which method best predicted all-cause mortality in >26,967 patients and normal subjects. On multivariate analysis, FEV(1)Q was the best predictor, with a hazard ratio for the worst decile of 6.9 compared to 4.1 for FEV(1)PP. On univariate analysis, the hazard ratios were 18.8 compared to 6.1, respectively; FEV(1) x Ht(-3) was the next-best predictor of survival. Median survival was calculated for simple cut-off values of FEV(1)Q and FEV(1) x Ht(-3). These survival curves were accurately fitted (r(2) = 1.0) by both FEV(1)Q and FEV(1) x Ht(-3) values expressed polynomially, and so an individual's test result could be used to estimate survival (with sd for median survival of 0.22 and 0.61 yrs, respectively). It is concluded that lung function impairment should be expressed in a new way, here termed the FEV(1)Q, or, alternatively, as FEV(1) x Ht(-3), since these indices best relate spirometric lung function to all-cause mortality and survival.

Conventional measures of bronchial hyperresponsiveness (BHR) are only weakly associated with respiratory symptoms in epidemiological studies. Partial and maximal forced expiratory manoeuvres were recorded during histamine challenge testing in 1,959 young male farmers. Analysis was performed to test whether novel measures of BHR, using alternative flow and time domain indices, are more closely associated with asthma symptoms, smoking status and atopy than forced expiratory volume in one second (FEV1) and conventional measures of BHR. The first moments to 75% and 90% of the forced vital capacity (FVC) were calculated from full (F) and partial (P) forced expiratory manoeuvres (i.e. alpha1 75%F, alpha1 75%P), together with the instantaneous flows when 40% and 30% of the FVC remained to be expired (MEF40 and MEF30). BHR was measured by the provocative dose causing a 20% change (PD20) in the FEV1 and alpha1 75%, and also by the method of log dose slopes (LDS). Asthma was diagnosed from symptoms associated with asthma in 158 (8.1%) of the subjects. PD20 FEV1 could only be recorded in 190 subjects (9.7%), of whom only 48 had asthma, whereas LDSFEV1 was recorded in 1,725 (88%) subjects. From the prechallenge data, alpha1 75%, expressed as standardised residuals, showed the largest difference between smokers with and without asthma symptoms, and no indices showed significant differences between nonsmokers with and without asthma symptoms. From BHR data in both smokers and nonsmokers, LDSFEV1 showed one of the largest differences between those with and without asthma symptoms. With smoking status and atopy accounted for, the greatest partial correlation with asthma diagnosis was found for LDSMEF40P, and then for LDSFEV1, but LDSMEF40P was measurable in only just over one-half of the subjects. The authors conclude that time-domain indices are promising measures for longitudinal epidemiological studies concerning the relationship between bronchial hyperresonsiveness and environmental exposures. However, indices from the partial flow-volume loop suffer from censored data.

We have measured bronchial responsiveness (BR) to histamine on two occasions between 5 and 24 h apart, to determine if conventional and new indices of BR are repeatable. A random sample of 29 healthy male subjects with a mean age of 19 (SD 3.44) years from a larger study repeated a Yan method test of BR, recording both partial and maximal expiratory flow volume (PEFV and MEFV) curves. From the MEFV curves log-dose slopes (LDS) for forced expiratory volume in 1 sec (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity (FVC) (FEF(25-75%)), mean expiratory flow at 30% and 40% of FVC (MEF30, MEF40), and the first moment of the spirogram (alpha1) truncated at 75% and 90% of FVC were calculated, as well as the provocative dose that induces a 20% fall in FEV1 (PD20FEV1). From the PEFV curves LDS for alpha(1)75% and alpha(1)90%, and MEF30 and MEF40 were derived. Apart from MEF30 and alpha(1)90% the second test was significantly lower (P<0.05) than the first when measuring the repeatability of spirometric indices, whereas the LDS of the indices showed no significant change. The repeatability expressed as intra-class correlation coefficient (ICC) was highest for LDS FEV1 (0.87), second highest for LDS MEF40 (0.67) and LDS MEF30 (0.65). The LDS for moment indices were much less repeatable and the lowest ICC was found in all LDS indices derived from PEFV curves. Within-subject variance was not influenced by atopic status, smoking habits or recordable PD20FEV1. As tests for bronchial hyper-responsiveness (BHR) the LDS of FEV1, MEF40 and MEF30 seem to be acceptable for use in population studies.

Chronic inflammation and extracellular remodeling of the airway wall characterize asthma. The purpose of this study was to examine whether these features cause a change in airway mechanical properties. We examined 14 healthy and 10 young adults with long-lasting asthma, the latter treated with inhaled bronchodilators and corticosteroids. To obtain area-versus-transmural pressure (A-Ptm) curves during forced expiration (Pedersen, O. F., et al. J. Appl. Physiol. 1982;52:357-369), we used an esophageal balloon and a Pitot static probe positioned at five locations between the right lower lobe and midtrachea. Cross-sectional area (A), airway compliance (Caw = dA/dPtm), and specific airway compliance (sCaw = Caw/A) were obtained from the A-Ptm curves. Results showed that: (1) A was larger in males than in females; (2) Caw and sCaw decreased with a more downstream position; and (3) Caw and sCaw were significantly lower in the patients with asthma, with the differences between the asthmatic patients and the healthy subjects becoming smaller toward the trachea. The lower Caw and sCaw in the patients with long-lasting asthma support the concept that chronic inflammation and remodeling of the airway wall may result in stiffer dynamic elastic properties of the asthmatic airway.

Several studies have found an association between the rare Pi-alleles and asthma or bronchial hyperresponsiveness (BHR). This study deals with the effect of Pi-type on BHR among 2,308 young Danish people living in rural areas with a mean +/- SD age of 19.7+/-2.4 yrs. Interviews, pulmonary function testing, bronchial histamine provocation and skin-prick tests were performed. Serum alpha1-antitrypsin levels were determined and phenotyping was performed by means of isoelectric focusing and the subjects categorized into four groups: 1) MM and MX; 2) MS; 3) MZ; and 4) rare, i.e. SZ, SS and ZZ. Among the farmers, a significant positive trend for sensitization towards house dust mites was found, ranging from 12% in the MM group to 22% in the rare Pi-group. A positive test for trend was found within the Pi-groups in a one-sided test for doctor-diagnosed asthma with a peak prevalence of 40% for these symptoms among smokers in the rare Pi-group. On multiple logistic regression analysis, an increased odds ratio (OR) for BHR was found among farming school attendants with the rare Pi-alleles. The OR (95% confidence interval) was 1.71 (0.84-3.49) for MS, 1.93 (1.10-3.39) for MZ and 4.34 (1.19-15.8) for the rare Pi-group. Such a relationship was not found among the conscripts. These results show that a gene/environment interaction may exist between the farming occupation and the rare Pi-alleles, leading to a higher proportion of bronchial hyperresponsiveness related to the rare Pi-alleles in farming school attendants, in contrast to what is found among other young people living in rural areas.

The aim of this study was to assess the cytokine response after nasal exposure to organic dusts. In a double blinded, crossover study five garbage workers with occupational airway symptoms and five healthy garbage workers were intranasally exposed to endotoxin (lipopolysaccharide LPS), beta-1,3-D-glucan (GLU), Aspergillus sp., compost or the saline dilute for 15 min. Nasal cavity volume and nasal lavage (NAL) were performed at baseline and 3, 6, 11 h postexposure. NAL was analysed with differential cell counts, cysteinyl-leukotrienes, tumour necrosis factor alpha, interleukin (IL)-1beta, IL-6 and IL-8. A whole blood assay on cytokine-release was performed with LPS and GLU. NAL cytokines neutrophils, lymphocytes and albumin increased significantly at 6 h after LPS exposure. GLU induced an increase in albumin and a slight increase in IL-1beta 6-11 h post exposure. In the WBA a significant increase in all cytokines after exposure to LPS as well as GLU was found. Significantly more cells were seen in NAL of the control group 6 h post LPS exposure. In conclusion lipopolysaccharide is the most potent inducer of inflammation in the nasal mucosa whereas compost and beta-1,3-D-glucan only induce minor changes. This reaction to lipopolysaccharide is attenuated in workers with occupational airway symptoms. In whole blood assay, however, beta-1,3-D-glucan also induces cytokine release, indicating a different protective effect of the nasal mucosa towards lipopolysaccharide and beta-1,3-D-glucan.

Previous studies have shown that the added resistance of a mini-Wright peak expiratory flow (PEF) meter reduced PEF by approximately 8% in normal subjects because of gas compression reducing thoracic gas volume at PEF and thus driving elastic recoil pressure. We undertook a body plethysmographic study in 15 patients with chronic obstructive pulmonary disease (COPD), age 65.9 +/- 6.3 yr (mean +/- SD, range 53-75 yr), to examine whether their recorded PEF was also limited by the added resistance of a PEF meter. The PEF meter increased alveolar pressure at PEF (Ppeak) from 3.7 +/- 1.4 to 4.7 +/- 1.5 kPa (P = 0.01), and PEF was reduced from 3.6 +/- 1.3 l/s to 3.2 +/- 0.9 l/s (P = 0.01). The influence of flow limitation on PEF and Ppeak was evaluated by a simple four-parameter model based on the wave-speed concept. We conclude that added external resistance in patients with COPD reduced PEF by the same mechanisms as in healthy subjects. Furthermore, the much lower Ppeak in COPD patients is a consequence of more severe flow limitation than in healthy subjects and not of deficient muscle strength.

Pump systems are currently used to test the performance of both spirometers and peak expiratory flow (PEF) meters, but for certain flow profiles the input signal (i.e., requested profile) and the output profile can differ. We developed a mathematical model of wave action within a pump and compared the recorded flow profiles with both the input profiles and the output predicted by the model. Three American Thoracic Society (ATS) flow profiles and four artificial flow-versus-time profiles were delivered by a pump, first to a pneumotachograph (PT) on its own, then to the PT with a 32-cm upstream extension tube (which would favor wave action), and lastly with the PT in series with and immediately downstream to a mini-Wright peak flow meter. With the PT on its own, recorded flow for the seven profiles was 2.4 +/- 1.9% (mean +/- SD) higher than the pump's input flow, and similarly was 2.3 +/- 2.3% higher than the pump's output flow as predicted by the model. With the extension tube in place, the recorded flow was 6.6 +/- 6.4% higher than the input flow (range: 0.1 to 18.4%), but was only 1.2 +/- 2.5% higher than the output flow predicted by the model (range: -0.8 to 5.2%). With the mini-Wright meter in series, the flow recorded by the PT was on average 6.1 +/- 9.1% below the input flow (range: -23.8 to 2. 5%), but was only 0.6 +/- 3.3% above the pump's output flow predicted by the model (range: -5.5 to 3.9%). The mini-Wright meter's reading (corrected for its nonlinearity) was on average 1.3 +/- 3.6% below the model's predicted output flow (range: -9.0 to 1. 5%). The mini-Wright meter would be deemed outside ATS limits for accuracy for three of the seven profiles when compared with the pump's input PEF, but this would be true for only one profile when compared with the pump's output PEF as predicted by the model. Our study shows that the output flow from pump systems can differ from the input waveform depending on the operating configuration. This effect can be predicted with reasonable accuracy using a model based on nonsteady flow analysis that takes account of pressure wave reflections within pump systems.

The objective of the study was to examine the effect of farming exposure, respiratory symptoms and smoking on the shape of the MEFV-curve in 1,691 male farming students and 407 male controls and to relate the slope ratio with FEV(1) and FEV(1) /FVC. Each subject underwent a medical interview and the slope ratios from the MEFV-curve at 75 (SR75), 50 (SR50) and 25 (SR25) %FVC together with FEV1 and FVC were recorded. Histamine bronchial reactivity (Yan method) was measured and skin prick test with inhalant allergens was performed. In smokers, SR75 increased with increasing exposure to: general farming, swine and dairy cattle (p< or =0.020). SR50 increased with increasing exposure to farming (p=0.015). In non-smokers, SR25 increased with increasing exposure to swine and dairy cattle (p=0. 021) and increased SR25 was associated with sensitisation to house dust mite (p=0.017). Data revealed an interaction between smoking and exposure to farming. FEV(1) and FEV(1)/FVC was not associated with farming exposure or production animals. FEV1 and FEV(1)/FVC (p< or =0.003) were lower among subjects wi bronchial hyperresponsiveness and asthma (FEV(1) and asthma only in smokers). SR75 (p=0.037) and SR50 (p=0.024) were increased in subjects with asthma and SR75 was increased in subjects with bronchial hyperresponsiveness, but only in smokers (p=0.002). In conclusion, exposure to farming seems to influence the shape of the MEFV-curve and there are indications of interaction between exposure to organic dust and smoking. These changes are seen only in the slope ratios and not in FEV(1) and FEV(1)/FVC. However, FEV(1) and FEV(1)/FVC are superior to slope ratios in differentiating healthy subjects from those with respiratory symptoms.

The aim of this study was to assess the prevalence of asthma (self-reported) and relate this to lung function and factors associated with asthma in young farmers. Two hundred and ten female and 1,691 male farming students together with 407 males controls were studied. Each subject underwent a medical interview; forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were recorded using a dry wedge spirometer. Histamine bronchial reactivity was measured using the Yan method. Skin prick testing was performed using inhalant allergens. Nonsmokers had lower prevalence of asthma (5.4-10.8%) than smokers (11.3-21.0%) (p<0.05). Females reported symptoms of asthma nearly twice as often as males. Sex, smoking and a family history of asthma/allergy were significantly associated with asthma. Controls had higher standardized FEV1 and FVC residuals than male students, both nonsmokers (0.21 and 0.24) versus (-0.06 and -0.05) and smokers (0.29 and 0.33) versus (-0.11 and 0.13) (p<0.032). Bronchial hyperresponsiveness, asthma, siblings with allergy and working with cattle (controls only) were significantly associated with reduced lung function. In conclusion, the prevalence of asthma was significantly related to smoking, female sex, family history of asthma and allergy. Whilst bronchial hyperresponsiveness was associated with reduced lung function and lung function was slightly reduced in the male farming students, there was no association found between occupational farming exposure and either lung symptoms or lung function.

The response of peak expiratory flow (PEF) meters may be affected by the magnitude of PEF, the time taken to get to PEF, and the duration that the peak is sustained. We undertook a retrospective study to define the 10 to 90% rise time (RT) and dwell time for flow above 90% (DT90) and 95% (DT95) of PEF. Blows were analyzed that had been recorded using a pneumotachograph from 912 patients older than 17 yr of age (556 men) who routinely attended a lung function laboratory. For each subject, that blow with the largest PEF was used to derive the PEF, FEV1, FVC, RT, DT90, and DT95. The values for RT, DT90, and DT95 were negatively skewed with the median values for men of 58, 29, and 19 ms, respectively, being significantly shorter than those for the women of 67, 49, and 31 ms. From the 912 subjects, there were 277 (153 men) who had all their spirometric indices within the normal range, and 305 (220 men) had both PEF and FEV1 more than 1. 645 SD below predicted, indicating airflow limitation. For subjects with airflow limitation the median RT was significantly smaller than in the normal subjects (men: 46 versus 72 ms, women: 50 versus 72 ms), and the same was found for DT90 (men: 22 versus 40 ms, women: 27 versus 56 ms) and DT95 (men: 15 versus 26 ms, women: 18 versus 34 ms). We conclude that the dwell times for PEF are shorter in men, and the rise and dwell times are shorter in patients with airflow limitation. Profiles used to test PEF meters should encompass the range of rise and dwell times found in subjects most likely to be using PEF meters, that is, those with airflow limitation.

The accuracy of the acoustic reflections method for the evaluation of human nasal airway geometry is determined by the physical limitations of the technique and also by the in vivo deviations from the assumptions of the technique. The present study 1) examines the sound loss caused by nonrigidity of the nasal mucosa and viscous loss caused by complex geometry and its influence on the estimation of the acoustic area-distance function; 2) examines the optimal relation between sampling frequency and low-pass filtering, and 3) evaluates advantages of breathing He-O2 during the measurements on accuracy. Measurements made in eight plastic models, with cavities exactly identical to the "living" nasal cavities, revealed only minor effects of nonrigidity of the nasal mucosa. This was confirmed by an electrical analog model, based on laser vibrometry admittance measurements of the nasal mucosa, which indicated that the error in the acoustic measurements caused by wall motion is insignificant. The complex geometry of the nasal cavity per se (i.e., departure from circular) showed no significant effects on the measurements. Low-pass filtering of the signal is necessary to cut off cross modes arising in the nasal cavity. Computer simulations and measurements in models showed that the sampling frequency should be approximately four times the low-pass filtering frequency (i.e., twice the Nyquist frequency) to avoid influence on the result. No advantage was found for the the use of He-O2 vs. air in the nasal cavity.

The exact temperature of the head of an unheated Fleisch pneumotachograph (PT) during recording is not known, and variation in its temperature may lead to errors in measuring spirometric indexes. We measured PT head temperature during blows from five normal subjects, recorded by using a PT with and without an upstream heat exchanger to condition the air to the ambient temperature that was set in a climate chamber. Group mean (+/- SD) temperature of a thermocouple (TC) placed inside the PT head was 11.8 +/- 1.9 degrees C with 7 degrees C ambient, 25.4 +/- 1.3 degrees C at 23 degrees C, and was 37.2 +/- 0.3 degrees C at 37 degrees C. The between-subject range of temperature for this TC was 7.5 degrees at 7 degrees C, 5.5 degrees at 23 degrees C, and 1.1 degrees at 37 degrees C. The mean within-subject within-blow variation of temperature for this TC was 10.0 degrees and 3.3 degrees C for ambient of 7 degrees and 23 degrees C, respectively. At the usual ambient temperature in a laboratory, these differences in temperature lead to a 3.6% between-subject bias in recording, and the within-subject differences lead to 2.6% underreading of peak expiratory flow and a 0.5% overreading later in the blow, which makes ATPS-to-BTPS correction erroneous or difficult to perform. With the use of an upstream heat exchanger, the group mean temperature was 8.7 +/- 0.4 degrees, 23.2 +/- 0.2 degrees, and 37.1 +/- 0.2 degrees C at the three ambient temperatures, respectively, and the within-subject within-blow variation was reduced to < 1 degrees C. A heat exchanger placed upstream of the PT satisfactorily conditioned expired air to the ambient temperature and removed the error.

The purpose of this study was to examine whether the resistance of the peak flow meter influences its recordings. One hundred and twelve subjects, (healthy nonsmokers and smokers and subjects with lung diseases) performed three or more peak expiratory flow (PEF) manoeuvres through a Fleisch pneumotachograph with and without a mini-Wright peak flow meter added in random order as a resistance in series. The results were as follows. In comparison with a pneumotachograph alone, peak flow measured with an added mini-Wright meter had a smaller within-test variation, defined as the difference between the highest and second highest values of PEF in a series of blows. The mean (SE) variation was 14 (1.3) L.min-1 and 19 (1.5) L.min-1 with and without meter added, respectively. In comparison with the pneumotachograph alone, the addition of the mini-Wright meter caused PEF to be underread, especially at high flows. The difference (PEF with meter minus PEF without meter) = -0.064 (average PEF) -8 L.min-1; R2 = 0.13. The mean difference was -7.8 (1.1) %, and increased numerically for a given PEF, when maximal expiratory flow when 75% forced vital capacity remains to be exhaled (MEF75%FVC) decreased. The reproducibility criteria for repeated measurements of peak flow are more appropriately set at 30 L.min-1 than the commonly used 20 L.min-1, because a within-test variation of less than 30 L.min-1 was achieved in 76% of the subjects without PEF meter inserted and in 88% with meter inserted, with no difference between healthy untrained subjects and patients. The resistance of the peak expiratory flow meter causes less variation in recordings but reduces peak expiratory flow, especially at high values and when the peak is large as compared with the rest of the maximal expiratory flow-volume curve.

Little is known about the response of variable orifice peak flow meters to high frequency flow input. The purpose of this study was to define and test dynamic requirements for such peak flow meters. In a population sample we measured peak expiratory flow (PEF), rise time (tr), from 10-90% PEF and the duration of the flow in excess of 97.5, 95 and 90% of PEF, by use of a carefully calibrated Fleisch pneumotachograph with known and adequate frequency response. Three peak flow meters (Mini Wright, Vitalograph and Ferraris) were tested with an explosive decompression calibrator adjusted to values for PEF and tr as close as possible to the 95th and 5th percentile values, respectively, both for males and females, and with peak durations between 5 and more than 100 ms. The 95th percentile values of PEF were 597 L.min-1 for females and 894 L.min-1 for males. The 5th percentile values of tr were, respectively 55 and 45 ms. The duration of flow in excess of 95% PEF was longer than 10 ms in 99% of the subjects. For all meters, the deviation of PEF corrected for alinearity were less than 5% at a peak duration of 10 ms. We conclude that PEF, rise time, and peak duration can be used for description of dynamic properties of variable orifice meters, and that the tested meters had a satisfactory frequency response for recording PEF in mostly normal subjects.

Little is known about the linearity of portable peak flow meters, or about physical gas factors affecting peak expiratory flow (PEF) readings. We therefore tested five portable peak flow meters of three types in an altitude chamber (sea level to 5,500 m) and in a climate chamber at sea level (7-37 degrees C) to determine the influence of the physical conditions of the gas on the reading of the meters. The nonlinear response of the variable orifice meters was confirmed and, when this was corrected for, the readings of these meters were found to be significantly reduced by higher altitude and lower temperature. The readings from a turbine type of peak flow meter were not affected by altitude but were reduced at low temperature. A mathematical model for the variable orifice meters could correct for both their nonlinear behaviour and the effect of gas density (altitude, temperature and humidity). The model showed that correction is not necessary for the differences in gas conditions between calibration and taking of measurements under normal laboratory conditions. All the meters tested had impedances higher than recommended (0.05 kPa.l-1.s) and this may influence PEF at high flows. The mean uncorrected PEF of six healthy subjects when measured with a Mini Wright peak flow meter at sea level and at 3,000 m fell by 5%, but the mean corrected PEF increased by 12%. This increase in PEF was about 60% of that predicted for fully density-dependent flow and agreed with the findings of other similar studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Sixty-two subjects selected among 287 persons with indoor air complaints were exposed to a standard mixture of 22 different organic gases and vapors normally found in Danish houses. Persons were randomly assigned to one of four exposure groups, and each subject stayed during the test day from 10:00 AM to 4:00 PM under standardized conditions in a climate chamber. During exposure the blink frequency was recorded, and after exposure the tear fluid contents of serum albumin, potassium, and sodium were measured. It was found that the persons had an increased concentration of serum albumin in the tear fluid, and that exposure to high concentrations of organic gases and vapors induced a tear reflex-mediated dilution of the tears.