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Biomedical subjects

P Malmberg

Publications and source records attributed to P Malmberg.

At least 55 records · Page 3Linked to original sources

Altered regulation of breathing after bilateral lung transplantation.

In our previous animal studies on dogs, regulation of breathing was found to be altered after en bloc transplantation of the heart and both lungs. During carbon dioxide (CO2) inhalation the minute volume was increased due to an increase of tidal volume after transplantation whereas before transplantation both respiratory frequency and tidal volume increased. The success of the heart-lung transplantation was based on experiments on baboons as no long-term survivors were obtained in dogs. It was thought that the regulation of breathing is different in dogs and primates. We therefore decided to study the regulation of breathing in humans after bilateral lung transplantation during CO2 stimulation. The regulation of breathing was tested 2 to 4 months after bilateral lung transplantation in six patients. Six healthy subjects with intact lungs were tested as controls. The test persons were allowed to breathe first room air, then 5% CO2 in air for 4 min and then room air again. The frequency of respiration, tidal volume and minute ventilation were recorded using a phneumotachograph. Simultaneously samples of arterial blood were drawn from a cannulated brachial artery for analysis of pressure of arterial oxygen (PaO2), pressure of arterial carbon dioxide (PaCO2), base excess (BE) and pH. During inhalation of CO2 for 4 min the minute volume doubled in both transplant patients and in controls. The tidal volume of the transplant patients increased significantly more than that of the controls (P < 0.005) whereas respiratory frequency increased significantly only in the controls with intact lungs (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Allergic sensitization is associated with increased bronchial responsiveness: a prospective study of allergy to laboratory animals.

The purpose of this prospective study was to investigate the extent of change in bronchial responsiveness and the prognostic value of methacholine provocation in early sensitization to laboratory animals. Thirty eight laboratory technicians were studied during training (before first exposure) and after having been exposed to laboratory animals for a median 18 (range 5-33) months. On both occasions they were subjected to spirometry, bronchial methacholine challenge, skin-prick tests and blood sampling, and responded to questionnaires. Nine (24%) developed laboratory animal allergy (LAA), defined as animal work-related symptoms (n = 8), or specific immunoglobulin E (IgE) (n = 7) or both. In the LAA group, bronchial responsiveness was normal before employment, but had increased significantly at follow-up compared to technicians who had not developed LAA. Six of the nine LAA subjects had a more than threefold increase in bronchial responsiveness, and three of these reported chest symptoms. Spirometric values were not different between the groups prior to exposure or at follow-up, and had no prognostic value. However, a pre-employment level of total IgE > 100 kU.L-1 predicted the development of LAA (relative risk 2.8). Thus, early LAA was associated with increased bronchial responsiveness in most subjects. In contrast to total IgE, the level of pre-employment bronchial responsiveness or lung function did not influence the magnitude of change in responsiveness, nor predict sensitization.

Adolescent↗

Coking to death?

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Air Pollutants↗

Asthma, lung function, and bronchial responsiveness in welders.

The incidence of asthma was compared in welders welding in stainless steel (SS) or mild steel (MS). The study was comprised of welders who had been welding for at least 6 months during the preceding 10 year period in four companies, but who had not been welding occupationally prior to this time. The inclusion criteria were met by 42 SS welders with a total welding time of 196 years. Sixteen of these had left work, six because of airway symptoms. Eighty-five MS welders with a total welding time of 403 years were included. Forty-eight of these had left work, 10 citing airway symptoms as a main reason for leaving work, according to responses in a mailed questionnaire. Ex-welders with airway symptoms were in some cases further investigated with spirometry and bronchial provocation tests. In other cases, medical records gave a clear diagnosis. In addition, bronchial responsiveness and lung function were measured and airway symptoms were recorded in presently active welders. Twenty-three of the 26 active SS steel welders and 23 of the 37 active MS steel welders were examined, together with a reference group of 26 (out of 30 invited) vehicle assemblers. There was no difference in the incidence of welding-associated asthma (5% for SS, 7% for MS welders per 1,000 welding-years). Bronchial responsiveness and lung function in active welders was normal and did not differ between MS and SS welders or between welders and a reference group of vehicle fitters. Welders had a significantly higher prevalence of airway symptoms as compared to vehicle fitters.

Adult↗

Prospective study of laboratory-animal allergy: factors predisposing to sensitization and development of allergic symptoms.

In a prospective study of laboratory technicians, selected indicators of allergy and atopy were studied in an attempt to determine predictors of laboratory-animal allergy (LAA). Laboratory technicians underwent spirometry, methacholine provocation tests, and blood sampling, and responded to a questionnaire during training and after 2 years' work. Among 38 laboratory-animal-exposed subjects, total IgE before exposure gave the best correlation (P < 0.01; Mann-Whitney U-test) to reported symptoms caused by laboratory animals (n = 8) at follow-up. The prevalence of atopy and allergic symptoms had increased in exposed technicians at follow-up, but this was also found among unexposed matched referents (n = 36 pairs). One subject in the exposed group reported asthma before exposure, compared with seven at follow-up (P < 0.05; Fisher's exact test). However, the prevalence of asthma had increased from two to six (not significant) also among unexposed technicians. There were no significant differences between the groups in any measured variable at follow-up. Among 43 subjects who later worked with laboratory animals, 21% had a positive skin prick test for common allergens, as compared with 37% among 112 without animal exposure (P = 0.06; chi2 test), suggesting selection for laboratory animal work.

Adolescent↗

High prevalence of asthma in cross country skiers.

OBJECTIVES: To study the prevalence of asthma (asthma symptoms and bronchial hyperresponsiveness) in Swedish cross country skiers compared with non-skiers and monitor changes in symptoms and bronchial hyperresponsiveness during the year. DESIGN: Cross sectional study during the winter ski season and in the summer. SETTING: Six ski clubs for élite skiers (total 47) in two different areas of Sweden. SUBJECTS: 42 élite cross country skiers and 29 non-skiing referents. MAIN OUTCOME MEASURES: Bronchial responsiveness, asthma symptoms, and lung function. RESULTS: Bronchial responsiveness was significantly greater and asthma symptoms more prevalent in the skiers than in the referents. There was no difference in bronchial responsiveness within either group between winter and summer. 15 of the 42 skiers used antiasthmatic drugs regularly and 23 had a combination of asthma symptoms and hyperresponsive airways or physician diagnosed asthma, or both. Altogether 33 skiers had symptoms of asthma or bronchial hyperresponsiveness. One of the referents had symptoms of asthma and bronchial hyperresponsiveness, and none used antiasthmatic drugs regularly. CONCLUSIONS: Asthma, asthma-like symptoms, and bronchial hyperresponsiveness are much more common in cross country skiers than in the general population and non-skiers. Strenuous exercise at low temperatures entailing breathing large volumes of cold air is the most probable explanation of persistent asthma in skiers.

Adolescent↗

Importance of the time interval between FEV1 measurements in a methacholine provocation test.

We examined the hypothesis that a forced expiratory volume in one second (FEV1) manoeuvre (and the preceding deep inhalation) before inhalation of methacholine might influence FEV1 measured after methacholine, if the time between measurements was short. Six to nine healthy subjects inhaled a single dose of methacholine, known to cause about 20% decrease in FEV1, on different days in different test protocols. If an FEV1 manoeuvre was performed immediately before methacholine, the first FEV1 measured 3 min after provocation was higher (77% of basal FEV1) than if a pre-methacholine FEV1 manoeuvre was not performed (64%). This effect of a pre-methacholine FEV1 manoeuvre was also demonstrated at 2, 4 and 6, but not at 10 min after the start of methacholine inhalation. If an FEV1 manoeuvre was not performed before methacholine, the second and subsequent FEV1 measured in constricted airways was higher than the first, and of similar magnitude to the first FEV1 in tests where a pre-challenge FEV1 manoeuvre was performed. In another trial, 10 healthy subjects performed two stepwise methacholine tests, with either 6 or 3 min between dose steps. The percentage decrease in FEV1 per mg of inhaled methacholine decreased from 2.6 (1.9-5.2) to 1.7 (0.8-2.3) (median, interquartile-range) when the time interval was shortened. The results suggest that the deep inhalation associated with the FEV1 manoeuvre decreases the bronchial tone in airways constricted by methacholine for up to 6 min, possibly due to yielding of cross-links in airway smooth muscles.

Adult↗

Changes in lung function of granite crushers exposed to moderately high silica concentrations: a 12 year follow up.

45 granite crushers and 45 age and smoking matched referents underwent pulmonary function tests in 1976 and 1988. On average, the granite crushers at follow up had worked for 22 years, were 52 (range 36-78) years old, and had inhaled a cumulated amount of 7 mg of silica in the respirable dust fraction. Between 1976 and 1988 the average concentration of respirable quartz in air was 0.16 mg/m3 (threshold limit value (TLV) = 0.10 mg/m3). In 1988 the granite crushers had somewhat lower forced expiratory flows (forced expiratory volume in one second/vital capacity (FEV1/VC) -4.5% and forced midexpiratory flow FEF50 -15%) compared with the referents and a more uneven ventilation distribution (17% higher slope of phase III in the nitrogen single breath curve). Five smoking granite crushers, but none of the referents, had an FEV1 < 80% of the predicted. During the 12 year interval the granite crushers had--compared with the matched referents--a greater decrease in FEV1 (-4.6%), FEV1/VC (-5.4%), maximal expiratory flow, (-8%) and FEF50 (-14%), and a larger increase in phase III and static compliance (p < 0.02 in all variables). The functional changes suggest the presence of airways obstruction and increased compliance of the lungs. Exposure to silica at concentrations of about twice the present TLV was thus associated with airways obstruction and loss of elastic recoil rather than fibrosis and a restrictive function loss as seen in silicosis. The changes were on average small, but in some tobacco smokers more pronounced changes were found.

Adult↗

Exposure to microorganisms associated with allergic alveolitis and febrile reactions to mold dust in farmers.

STUDY OBJECTIVE: To compare exposure to microorganisms associated with allergic alveolitis (AA) and with febrile reactions to inhaled mold dust (organic dust toxic syndrome [ODTS]) in farmers and in normal subjects. DESIGN: A prospective study in which exposure was evaluated within two weeks of medical consultation for AA or ODTS. Samples were collected during normal farming (background) and during the handling of materials associated with disease or causing maximal exposure in reference farms (worst case). SETTING: Swedish farms PARTICIPANTS: Eleven farmers with a confirmed diagnosis of AA from ten farms, 16 subjects with symptoms of ODTS from 12 farms, and 17 reference farmers. MEASUREMENTS AND RESULTS: Worst-case samples representative of the exposure preceding disease were obtained on four farms where five farmers had had AA; the samples contained on average 2.6 +/- 1.8 x 10(9) (SD) spores/m3 of air. On six farms where nine farmers had had ODTS, representative samples averaged 13 +/- 13 x 10(9) spores/m3, and on reference farms this figure was 0.12 +/- 0.20 x 10(9) spores/m3. The daily spore dose associated with allergic alveolitis was 2 x 10(9) spores/d, which was ten times higher than on reference farms. The average dose associated with ODTS was 2 x 10(10) spores. Worst-case samples, collected during 10 to 30 min, contributed to more than 90 percent of the day exposure on farms where AA or ODTS had occurred. CONCLUSION: Allergic alveolitis was associated with high exposure levels on most weekdays for weeks, and ODTS was associated with extreme exposure occurring on a single day. There was no correlation with individual spore types and disease and the present results are compatible with a hypothesis that common cell wall components of microorganisms may cause "toxic" symptoms and stimulate immune reactions.

Adult↗

Acute exposure to swine dust causes bronchial hyperresponsiveness in healthy subjects.

Six urban subjects, with little or no previous experience of farm-work, were exposed to dust while weighing swine for 2-5 h. Three subjects experienced toxic symptoms 4-5 h after the beginning of exposure. Bronchial responsiveness increased in all subjects within 6 h (more than three doubling steps difference in a methacholine test). One week later, airway responsiveness had partly normalized. The mean (interquartile range) cumulative dose of methacholine causing a 20% decrease in forced expiratory volume in one second (FEV1) was 3.1 (1.0-6.6) mg, before exposure, fell to 0.13 (0.01-0.76) mg 6 h after exposure (p < 0.02), and was 0.99 (0.42-1.5) mg one week later (n = 5, p < 0.05), Mean (SD) FEV1 decreased 5 (2)%. The concentration of total dust varied between 9 and 14 mg.m-3 and of endotoxin between 0.1 and 0.5 mu g.m-3. Thus inhalation of swine farm dust, caused a marked increase in bronchial responsiveness in non-sensitized subjects.

Adult↗

Hyaluronic acid (hyaluronan) in BAL fluid distinguishes farmers with allergic alveolitis from farmers with asymptomatic alveolitis.

Pulmonary function measurements, bronchoalveolar lavage (BAL), and analyses of precipitating antibodies in blood were performed in 12 farmers wtih no symptoms from the airways and 12 farmers who were admitted to the hospital due to acute symptoms of alveolitis (all nonsmokers). In addition, a bronchial methacholine provocation test was performed in the asymptomatic farmers. In 11 of the 12 symptomatic farmers but in none of the asymptomatic farmers, precipitating antibodies against one or more of the microorganisms which usually occur in a farmer's environment were found. In the farmers with symptomatic alveolitis, a restrictive impairment of pulmonary function was found, while pulmonary function was normal in all asymptomatic farmers. Findings in the BAL fluid showed increased concentrations of total cells, lymphocytes, and neutrophils and elevated levels of albumin, fibronectin, and angiotensin-converting enzyme in asymptomatic farmers compared with our own reference group. The same analyses in BAL fluid from the symptomatic farmers revealed a further increase in all parameters compared with the asymptomatic farmers. The BAL fluid from asymptomatic farmers had normal levels of hyaluronic acid (hyaluronan) and procollagen 3 N-terminal peptide, while these levels were significantly increased in the symptomatic group. We conclude that inflammation in the alveolar space and signs of activation of alveolar macrophages are present in farmers regardless of respiratory symptoms, although these findings are more pronounced in the presence of symptoms of acute alveolitis; however, the findings of impaired pulmonary function and the occurrence of precipitins and elevated levels of hyaluronic acid and procollagen 3 N-terminal peptide in BAL fluid were exclusively found in the farmers with airways symptoms. We postulate the hyaluronic acid, due to its pronounced ability to immobilize water, may be of importance in the development of the pulmonary function impairment observed in farmer's lung disease.

Acute Disease↗

Alterations in bronchoalveolar lavage fluid but not in lung function and bronchial responsiveness in swine confinement workers.

Testing of lung function and bronchial reactivity, bronchoalveolar lavage (BAL), and a skin prick test with a standard panel and six "swine" extracts obtained from swine and swine environment were performed in 20 randomly selected nonsmoking swine confinement workers. In addition, blood samples for detection of antibodies by the diffusion in gel-enzyme-linked immunosorbent assay (DIG-ELISA) technique and precipitating antibodies were drawn. Air samples for measurement of dust and endotoxin levels were collected. All the farmers regarded themselves as healthy. The results were compared with reference groups consisting of urban nonsmoking subjects who had not been exposed to pig farming environment. The pig farmers had normal lung function and the bronchial reactivity was not different from the reference group. In the BAL fluid of the farmers, the concentration of total cells and granulocytes was increased while the concentrations of lymphocytes and macrophages were normal. The BAL fluid concentrations of albumin, fibronectin, and hyaluronan were elevated in the farmers. Skin prick tests with swine extracts were negative in all farmers. Antibodies (assessed by DIG-ELISA) against swine dander, swine dust, and pig feed were increased and precipitating antibodies against swine dander were found in 14, against pig food in five, and against swine confinement dust in three of the 20 pig farmers. The concentration of airborne total dust was 7.4 mg/cu mm and the endotoxin concentration was 37 (22 to 60) ng/cu mm during tending the pigs and increased, during feeding, to 13.8 mg/cu mm and 315 (194 to 716) ng/cu mm, respectively. There was no correlation between exposure and lung function or lavage findings. In conclusion, randomly selected pig farmers had signs of airway inflammatory reaction and activation of the immune system without alteration in lung function and bronchial reactivity.

Adult↗