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Biomedical subjects

O F Pedersen

Publications and source records attributed to O F Pedersen.

At least 19 recordsLinked to original sources

Ozone exposure decreases the effect of a deep inhalation on forced expiratory flow in normal subjects.

Sixteen healthy nonsmoking subjects (7 women), 21-49 yr old, were exposed in a climate chamber to either clean air or 300 parts/billion ozone on 4 days for 5 h each day. Before each exposure, the subjects had been pretreated with either oxidants (fish oil) or antioxidants (multivitamins). The study design was double-blind crossover with randomized allocation to the exposure regime. Full and partial flow-volume curves were recorded in the morning and before and during a histamine provocation at the end of the day. Nasal cavity volume and inflammatory markers in nasal lavage fluid were also measured. Compared with air, ozone exposure decreased peak expiratory flow, forced expiratory volume in 1 s, and forced vital capacity (FVC), with no significant effect from the pretreatment regimens. Ozone decreased the ratio of maximal to partial flow at 40% FVC by 0.08 +/- 0.03 (mean +/- SE, analysis of variance: P = 0.018) and at 30% FVC by 0.10 +/- 0.05 (P = 0.070). Ozone exposure did not significantly increase bronchial responsiveness, but, after treatment with fish oil, partial flows decreased more than after vitamins during the histamine test, without changing the maximal-to-partial flow ratio. The decreased effect of a deep inhalation after ozone exposure can be explained by changes in airway hysteresis relative to parenchymal hysteresis, due either to ozone-induced airway inflammation or to less deep inspiration after ozone, not significantly influenced by multivitamins or fish oil.

Adult↗

Inadequate peak expiratory flow meter characteristics detected by a computerised explosive decompression device.

BACKGROUND: Recent evidence suggests that the frequency response requirements for peak expiratory flow (PEF) meters are higher than was first thought and that the American Thoracic Society (ATS) waveforms to test PEF meters may not be adequate for the purpose. METHODS: The dynamic response of mini-Wright (MW), Vitalograph (V), TruZone (TZ), MultiSpiro (MS) and pneumotachograph (PT) flow meters was tested by delivering two differently shaped flow-time profiles from a computer controlled explosive decompression device fitted with a fast response solenoid valve. These profiles matched population 5th and 95th centiles for rise time from 10% to 90% of PEF and dwell time of flow above 90% PEF. Profiles were delivered five times with identical chamber pressure and solenoid aperture at PEF. Any difference in recorded PEF for the two profiles indicates a poor dynamic response. RESULTS: The absolute (% of mean) flow differences in l/min for the V, MW, and PT PEF meters were 25 (4.7), 20 (3.9), and 2 (0.3), respectively, at PEF approximately 500 l/min, and 25 (10.5), 20 (8.7) and 6 (3.0) at approximately 200 l/min. For TZ and MS meters at approximately 500 l/min the differences were 228 (36.1) and 257 (39.2), respectively, and at approximately 200 l/min they were 51 (23.9) and 1 (0.5). All the meters met ATS accuracy requirements when tested with their waveforms. CONCLUSIONS: An improved method for testing the dynamic response of flow meters detects marked overshoot (underdamping) of TZ and MS responses not identified by the 26 ATS waveforms. This error could cause patient misclassification when using such meters with asthma guidelines.

Analysis of Variance↗

Nasal patency is related to dust exposure in woodworkers.

OBJECTIVES: A cross sectional study of 54 furniture factories and three control factories was conducted to investigate the relation between subjective and objective nasal obstruction and exposure to wood dust. METHODS: Acoustic rhinometry was performed on 161 woodworkers and 19 controls. For each person, four measuring rounds were performed: before work, after 4 hours of work, and after 7 hours of work before and after decongestion. Before the first and third measuring round, each person rated the current feeling of nasal obstruction in the left and right nostril separately, using a visual analogue scale. Personal passive dust measurements were performed on 140 woodworkers. RESULTS: The mean (SD) of equivalent inhalable dust was relatively low, 1.17 (0.62) mg/m(3), range 0.17-3.44 mg/m(3). The exposure was divided into four levels: controls, low exposure, medium exposure, and high exposure. For the two highest concentrations of exposure, a significant increase in congestion--decreased nasal cavity volume and cross sectional areas--was found after 4 and 7 hours of work, compared with before work. Multivariate linear regression analysis showed positive correlations between concentration of dust and change in mucosal swelling. A significant increase in self rated nasal obstruction was found after work compared with before work for the two highest exposure groups. No correlation between objective nasal variables and self rated nasal obstruction was found. CONCLUSION: Exposure to wood dust was related in a dose dependent manner to acute nasal obstruction measured by acoustic rhinometry and self reported obstruction, but no correlation was found between measured and self reported obstruction.

Adult↗

Time domain and flow indices of bronchial hyperresponsiveness: association with asthma symptoms, atopy and smoking.

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.

Adult↗

The short-term repeatability of histamine bronchial testing in young males. The SUS study.

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.

Adult↗

S and Z alpha1-antitrypsin alleles are risk factors for bronchial hyperresponsiveness in young farmers: an example of gene/environment interaction.

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.

Adult↗

Cytokine release from the nasal mucosa and whole blood after experimental exposures to organic dusts.

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.

Allergens↗

Peak flowmeter resistance decreases peak expiratory flow in subjects with COPD.

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.

Aged↗

Peak expiratory flow profiles delivered by pump systems. Limitations due to wave action.

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.

Calibration↗

Central airways behave more stiffly during forced expiration in patients with asthma.

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.

Adult↗

Particle deposition in the nose related to nasal cavity geometry.

A number of studies have been made to characterise the deposition-pattern of inhaled airborne particles in the nose. Common to all results has been considerable differences in deposition fractions between normal human subjects. It was the aim of the current study to improve our understanding of individual differences in nasal deposition of inhaled particles. Depositions were measured in ten adult normal subjects and were related to dimensional measurements by acoustic rhinometry. Five litres of a polydisperse aerosol (MMAD = 0.7 micron, sigma g = 1.7) were inhaled through one nostril only during 5 inspirations with flows of 10, 20, and 30 L/min with decongested mucosa. Increasing flow was found to increase the fraction deposited in the nose, while there was an inverse correlation between nasal deposition fraction and minimum cross-sectional area of the nasal cavity (Amin). Information based on acoustic rhinometry measurements significantly reduced the amount of unexplained variation between subjects in nasal deposition fraction. We conclude that an estimate of maximum linear air velocity, calculated as airflow divided by Amin, was the best single predictor of nasal deposition fraction, which was found to increase with increasing air velocity raised to a power of approximately 4/3.

Adult↗

The shape of the maximum expiratory flow-volume curve reflects exposure in farming.

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.

Agricultural Workers' Diseases↗