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Biomedical subjects

L A Laitinen

Publications and source records attributed to L A Laitinen.

At least 55 records · Page 3Linked to original sources
PubMed1999

Incidence and prevalence of asthma among adult Finnish men and women of the Finnish Twin Cohort from 1975 to 1990, and their relation to hay fever and chronic bronchitis.

STUDY OBJECTIVES: To examine the prevalence of asthma and hay fever, and the incidence and temporal relationships of asthma, hay fever, and chronic bronchitis among adult twins during a 15-year period. DESIGN: Prospective cohort study. PARTICIPANTS: A population of 11,540 Finnish adult men and women, initially 18 to 45 years of age, who returned a health questionnaire in 1975, 1981, and 1990 as part of the Finnish Twin Cohort study. METHODS: Age-standardized prevalences and cumulative incidences among individuals were calculated for asthma, hay fever, and chronic bronchitis. The incidence of asthma among subjects with and without hay fever or chronic bronchitis was analyzed in the entire cohort as well as in twin pairs discordant for incident asthma. RESULTS: The prevalence of asthma increased slightly from 1975 (2.0% in men and 2.2% in women) to 1990 (2.9% in men and 3.1% in women). The prevalence of hay fever showed a larger increase in men and women (from 6.8% and 9.8% to 11.8% and 15.3%, respectively). Compared with figures for 1976 to 1981, no significant increase in asthma incidence occurred from 1982 to 1990, whereas the incidence of hay fever was lower during the latter period among men (incidence rate ratio, 0.7; 95% confidence interval, 0.6 to 0.9) as was the incidence of chronic bronchitis among women (incidence rate ratio, 0.7; 95% confidence interval, 0.6 to 0.9). Hay fever and chronic bronchitis were usually diagnosed before asthma. Both diseases increased the risk of asthma significantly on the basis of analyses of all individuals and of discordant twin pairs. CONCLUSIONS: The pattern of increase in asthma and hay fever prevalence with time was similar, and hay fever was a strong predictor of asthma. These diseases showed no significant increase in incidence.

Adolescent↗
PubMed1998

Verification of self-reported asthma and allergy in subjects and their family members volunteering for gene mapping studies.

Studies which aim at mapping genes contributing to the development of asthma and atopy demand that hundreds of patients and their family members be assessed. In Finland, the Social Insurance Institution (SII) grants substantial reimbursement for medication to all patients who meet diagnostic criteria of asthma, which include a history of asthmatic symptoms and a measured reversibility of bronchial obstruction. To recruit a large number of asthma patients efficiently in a short period of time, we took advantage of the national reimbursement procedure and retrospectively collective data on patients' medical history and lung function test results at the time of diagnosis. First, we wanted to investigate if the reimbursements could be regarded as objective verification for self-reported asthma. Altogether 335 adult self-reported asthma patients were evaluated, 87% of them were verified as having chronic asthma. Reimbursement for medication showed a sensitivity of 95% and a specificity of 76% for verified asthma. Second, we were interested to see if self-reported nasal allergic symptoms or self-reported physician diagnosed allergic rhinitis were sensitive and specific measures of allergy. The self-reported allergic nasal symptoms had a poor specificity (31% in the proband group and 59% in the family members group) when compared to the allergy screening test (Phadiatop). The best verification for self-reported asthma was achieved by combining the information on self-reported disease, granted reimbursement by the SII and the medical records. For allergies, the specificity of self-reporting was far too low to be used alone, and a positive allergy screening test together with relevant symptoms was chosen as a marker of allergy.

Adolescent↗
PubMed1998

The European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): recruitment methods and strategies.

The European Respiratory Society's study on chronic obstructive pulmonary disease (EUROSCOP) is a multicentre study performed initially in 12 countries to assess the effect of 3 years' treatment with inhaled corticosteroids on lung function decline in smokers with chronic obstructive pulmonary disease (COPD). It aimed at recruiting 50 subjects in 50 European centres. This study discusses the most successful, countrywise, recruitment strategies, an important issue since many multicentre European studies may follow in the future. The total number of recruited subjects was 2147 in 39 participating centres. In total, at least 25,000 screening spirometries were performed, and about 80,000 hospital records were checked. The most effective way of recruiting subjects was to screen subjects by spirometry after mass media campaigns (eight out of nine countries). Others used workplace screenings and different types of population survey, and only a few centres successfully recruited participants by hospital records. Inclusion criteria were slightly changed upon low initial accrual rate. Initial surveys in one country, where 2405 subjects were screened by spirometry, gave an important indication for the change of the inclusion criteria. Extension of the upper age limit from 60 to 65 yr considerably improved recruitment, as did a change of the upper limit of FEV1 from below 80% predicted normal to below 100% predicted normal, while maintaining the FEV1/VC ratio below 70%. A tremendous effort is needed to recruit individuals with preclinical COPD, but this is certainly feasible with adequate strategies adjusted to each country.

Administration, Inhalation↗
PubMed1998

Amplitude variation in static-charge-sensitive bed signal increased in obstructive airways disease.

The relationship between oesophageal pressure variation and amplitude variation in the static-charge-sensitive bed (SCSB) ballistocardiogram suggests that changes in intrathoracic pressure can be detected using the SCSB method. We investigated whether amplitude variation in the static-charge-sensitive bed ballistocardiogram (SAV) is related to severity of airway obstruction in patients with asthma and chronic obstructive pulmonary disease. The ability of SAV to detect an increase in airway obstruction induced by histamine challenge was also tested. Twenty-six patients suffering from asthma and 12 patients with chronic obstructive pulmonary disease (COPD) were enrolled in the study. SAV, amplitude from the SCSB ballistocardiogram, respiratory amplitude from the SCSB respiratory wave form and heart rate from the electrocardiogram (ECG) were computed using analysing software (Biorec, Helsinki, Finland) during a 7-min supine rest. SAV was related to forced expiratory volume in one second (FEV1) immediately after signal recording. Asthma patients participated in a standardized histamine challenge test to reveal the effect of acute bronchoconstriction on SAV. An inverse relationship existed between baseline FEV1 and SAV in asthma and COPD. In the histamine inhalation test, FEV1 fell by 0.7 +/- 0.3 l or 26% +/- 11% (P < 0.0001) and SAV increased by 12% +/- 5% (P < 0.0001) in 12 asthma patients. The fall in FEV1 induced by histamine followed regularly and correlated significantly with the rise in SAV (n = 24, r = -0.58, P = 0.002). Changes in respiratory amplitude or heart rate did not explain changes in SAV. SAV may not separate the upper airway obstruction from the bronchial obstruction but it is related to severity of airway obstruction. The clinically significant increase in airway obstruction induced by histamine inhalation increases amplitude variation in SCSB.

Administration, Inhalation↗
PubMed1998

Hay fever--a Finnish nationwide study of adolescent twins and their parents.

BACKGROUND: Like other atopic diseases, hay fever is known to cluster in families. This clustering is due either to effects of a shared family environment or to genetic inheritance. By comparing the occurrence of hay fever among monozygous (MZ) and dizygous (DZ) twin pairs, we were able to estimate the contribution of genetic and environmental factors in the development of hay fever. METHODS: A questionnaire mailed to a nationwide sample of 2483 families with 16-year-old twins furnished data for the cumulative incidence of physician-diagnosed hay fever among these adolescents and their parents. RESULTS: Among the 1765 twin pairs with data available for analysis, hay fever was reported for 14.1% of boys (95% CI=12.4-15.8%) and 10.0% of girls (95% CI=8.6-11.4%). The MZ twin pairs (probandwise concordance rate=60.3%, 95% CI =52-68%) were significantly more concordant for hay fever than were DZ twin pairs (31.5%, 95% CI=26-36%). Genetic factors accounted for 74-82% of the interindividual variability in liability to hay fever, variation in shared family environment for 7% at most, and unique (individual) environment for 18%. CONCLUSIONS: Familial occurrence of hay fever is mainly due to genes predisposing to the trait. Environmental exposures shared in common by family members but varying between families appear to account for at most a modest proportion of the variability in risk of developing hay fever.

Adolescent↗
PubMed1998

A new beclomethasone dipropionate multidose powder inhaler in the treatment of bronchial asthma.

The clinical efficacy, tolerability and acceptability of a new multidose powder inhaler (MDPI) containing beclomethasone dipropionate (BDP) were compared with those of a BDP aerosol administered with a large volume spacer (MDI-spacer) among adult asthmatics currently receiving from 500 to 1,000 microgram/day of an inhaled corticosteroid. During the study, the dosage of BDP from both devices was 400 microgram twice daily. Ninety-one patients were randomized to the MDPI group and 42 to the MDI-spacer group. The trial was performed as an open, randomized, parallel group multicenter study. The duration of the treatment period was 12 weeks, and the study was preceded by a 2-week run-in period. During the run-in period, the mean morning peak expiratory flow (PEF) was 487 and 466 1/min in the MDPI and MDI-spacer groups, respectively. After the 12-week treatment, the morning PEF was 491 1/min in the MDPI group and 463 1/min in the MDI-spacer group. The evening values were 500 and 479 1/min during the run-in period and 496 and 476 1/min after the 12-week treatment, respectively. Asthma symptom scores and the use of rescue medication were low in both groups, indicating good efficacy of the preparations tested. The median dose of histamine required to decrease forced expiratory volume in 1 s by 15% increased during the study from 800 to 1,098 microgram in the MDPI group and from 795 to 960 microgram in the MDI-spacer group. The most frequent adverse events in both groups were hoarseness and sore throat. There were no statistically significant differences between the treatment groups in serum cortisol values or in the number of patients with thrush. Seventy-two percent of the patients regarded the MDPI easier to use while 95% considered it more portable. Over 80% of the patients felt that the MDPI was also easier to clean and as easy or easier to learn to use than the MDI-spacer. To conclude, the novel powder inhaler is well tolerated and at least equally effective as the conventional MDI-spacer combination in the treatment of asthma with BDP. However, in everyday use, patients clearly favored the powder inhaler.

Administration, Inhalation↗
PubMed1998

Importance of genetic factors in adolescent asthma: a population-based twin-family study.

Gene-environment interactions and inheritance of asthma were studied in 16-yr-old twins and their parents who participated in the nationwide Finnish Twin Cohort Study. Between 1991 and 1994, questionnaires, including a question on physician-diagnosed asthma, were mailed to the members of 2,483 twin families. The individual response rate ranged from 82 to 93%. Information on parental asthma status allowed the genetic modeling of asthma data in two different groups of twins. In families where one of the parents was asthmatic, as much as 87% of the variation in susceptibility to asthma in twins was explained by genetic factors. On the other hand, for twins whose parents were unaffected, a model including environmental effect alone was sufficient to explain the development of asthma. Genetic influences could not be totally excluded, but their role was significantly smaller. These results indicate that the presence of asthma in successive generations is more likely caused by shared genes than shared environmental risk factors; however, substantial heterogeneity among families may exist. Genetic analysis, especially among the families with an obvious familial component in development of asthma, may enhance the chances of revealing the pathogenetic mechanisms

Adolescent↗
PubMed1998

Lymphoid aggregates in endobronchial biopsies from young elite cross-country skiers.

Observation of bronchus-associated lymphoid tissue (BALT) in whole lung specimens from healthy nonsmoking adults has questioned the hypothesis that BALT is not constitutively present in healthy adult human lungs. In our study, we investigated endobronchial biopsies of the second- and third-generation carinae from 44 cross-country ski athletes and 12 healthy control subjects, all nonsmoking young adults. The skiers had a prevalence of respiratory allergy (18%), asthma-like symptoms (59%), beta2 agonist medication (25%), and methacholine bronchial hyperresponsiveness (79%). Biopsy sections were stained by immunohistochemical and hematoxylin-eosin-saffran methods. Lymphoid aggregates of more than 50 cells were identified in 28 (64%) skiers and three (25%) control subjects (p = 0.02). They were small in comparison to those found in rabbits and rats, contained T and B lymphocytes and macrophages, and were seen more frequently in skiers using beta2 agonists (p = 0.04) and with bronchial hyperresponsiveness to methacholine (p = 0.053). The frequency of these aggregates was not significantly different at the two carinal levels (p = 0.6). The aggregates were not associated with a history of respiratory allergy or asthma-like symptoms. These aggregates share some resemblance with what is usually defined as BALT. However, their exact nature and function await further clarification.

Adult↗
PubMed1997

Genetic control of serum IgE levels and asthma: linkage and linkage disequilibrium studies in an isolated population.

Immunoglobulin E (IgE) concentration in serum is elevated in atopic diseases such as asthma. A large genomic region on chromosome 5 has previously been implicated in the control of IgE levels and bronchial hyperreactivity and may, therefore, harbor genes predisposing to asthma. In an effort to confirm this linkage and to delimit the critical region, we took advantage of an isolated founder subpopulation in Finland to study genetic linkage and haplotype associations. Sixteen polymorphic markers, including the Interleukin-4 and -9 genes (IL4, IL9), were physically ordered and genotyped in 157 nuclear families. Genetic linkage studies involving sib- and cousin-pair analyses found no evidence of genetic linkage between markers in 5q and either serum IgE levels or asthma. Haplotype association studies were also performed. Although initial inspection suggested the possibility of linkage disequilibrium in the region of IL9, we developed a rigorous permutation test for assessing association and determined that the association was no greater than would be expected by chance. Sequence analysis of the IL9 gene in three patients sharing a possibly conserved haplotype revealed a T113M coding polymorphism, but this variant showed no association with either serum IgE levels or asthma. We conclude that allelic variation at chromosome 5q31 is not likely to contribute to inheritance of serum IgE levels or the development of asthma in this Finnish subpopulation.

Adolescent↗
PubMed1997

Tenascin is increased in airway basement membrane of asthmatics and decreased by an inhaled steroid.

Tenascin and fibronectin are extracellular matrix glycoproteins expressed during morphogenesis and tissue repair. In the present study bronchial biopsies were studied by the morphometric method of immunocytochemistry to reveal the distribution of different tenascin and fibronectin isoforms as well as the presence of inflammatory cells in the airway mucosa of patients with chronic asthma (n = 32) and those with seasonal birch-pollen-sensitive asthma out of season (n = 17), both in comparison with healthy control subjects (n = 12). The results showed an increase in tenascin immunoreactivity in the bronchial subepithelial reticular basement membrane layer in patients with chronic asthma (p < 0.0001) and in those with seasonal asthma (p < 0.01) compared with control subjects. The tenascin immunoreactivity, appearing as an intense wide subepithelial band in asthma, was seen only occasionally in the basement membrane of control specimens. Instead, a diffuse immunoreaction against both total fibronectin and locally produced extradomain A fibronectin was similarly visible in the airway mucosa of both patients and control subjects. Despite the significant increase in the airway mucosa of eosinophils and lymphocytes in patients with chronic asthma (p < 0.0001 and p < 0.0001, respectively) and of eosinophils in patients with seasonal asthma (p < 0.001), there was no correlation between the number of these cell types and level of tenascin expression. In patients with birch-pollen-sensitive asthma during the birch-pollen season, inhaled corticosteroid treatment, budesonide 400 micrograms twice daily, decreased tenascin immunoreactivity, in comparison with effects of placebo (p = 0.01). Our results suggest that the higher amount of tenascin reflects disease activity in asthma and may be an indicator of a remodeling process rather than of injury itself.

Adult↗
PubMed1997

Hay fever, asthma and number of older siblings--a twin study.

BACKGROUND: It has been suggested that allergic sensitization is inversely related to the number of siblings in the family. OBJECTIVES: To study whether a similar relation can be observed for hay fever and asthma among Finnish adolescents in a population with relatively low prevalence of atopic diseases. METHODS: A questionnaire mailed to a nationwide sample of 1849 families with 16-year-old twins assessing the cumulative incidence of doctor-diagnosed hay fever and asthma among the adolescents and the number of older siblings in the family by parental report. RESULTS: The cumulative incidence of hay fever was significantly lower among the adolescents with three or more older siblings (3.9%, 95% CI = 1.2-6.5%) compared with adolescents with fewer older siblings (12.7%, 95% CI = 11.4-14.0%). There was no difference in the cumulative incidence of asthma among the adolescents according to the number of older siblings in the family. CONCLUSIONS: Large number of older siblings appears to be protective against the development of hay fever.

Adolescent↗
PubMed1996

The effects of midazolam and ephedrine on post-exercise autonomic chronotropic control of the heart in normal subjects.

Benzodiazepines may induce hypotension by inhibiting the pressor response. Ephedrine has adrenergic effects on the circulation. After exercise, changes in cardiovascular control impair orthostatic tolerance. The impaired pressure response can be compensated for by chronotropic control of the heart. We studied the effect of midazolam and ephedrine on post-exercise cardiac autonomic chronotropic control in six 21-year-old female volunteers, who received single doses of 15 mg midazolam, 50 mg ephedrine, or placebo orally according to a placebo-controlled, double-blind, crossover design. After exercise, the subjects assumed the supine position for rest, then a -10 degrees head-down position followed by a 70 degrees head-up position. Power spectral analysis of heart rate variability for 7 min and steady-state brachial arterial blood pressure were measured in each position. After administration of midazolam, three subjects had an abnormal fall in their arterial blood pressure (with one presyncope) as a response to head-up tilt. Changes in heart rate variability exceeded those seen during placebo treatment (p < 0.01) and involved oscillations, suggesting activation of both sympathetic and parasympathetic dynamics. After ephedrine administration, arterial blood pressure increased during head-down tilt, but parasympathetic dynamics to the heart were dampened. Head-up tilt induced increased sympathetic stimulation of the heart and a sympathicotonic cardiovascular response (p < 0.01). In conclusion, midazolam induced unexpectedly great changes in dynamic cardiac control during cardiovascular stimulation. Ephedrine increased tonic sympathetic activity and stabilized the neural circulatory control of the heart by immobilizing dynamic parasympathetic activation.

Adrenergic Agonists↗
PubMed1996

Differential expression of laminins and their integrin receptors in developing and adult human lung.

Laminins (Ln) appear to play an important role in the morphogenesis of airways. We studied the expression of different laminin chains and their integrin receptors in fetal and adult lung by immunohistochemistry. Special attention was focused on the changes in the expression of these proteins during the development from the pseudoglandular (PG) and canalicular stages to adult lung, and on the possible implications of the changes for the normal lung development. The most significant changes in the expression pattern were found during the development from the PG stage to the canalicular stage. Basement membranes (BM) of both the epithelial buds and the becoming bronchi showed reactivity for Ln-alpha 1, -alpha 3, and -beta 3 chains at all stages. The alpha 2 chain was expressed only in the epithelial buds at the PG stage, and could not be found in any epithelial structures at the canalicular stage. Similarly, at the PG stage the Ln-beta 2 chain was expressed in BMs of both epithelial buds and bronchi but disappeared from the bronchial BM before the canalicular stage. Ln-beta 1 chain appeared in the bronchial BM first in the mature lung, which suggests the presence of uncharacterized Ln-beta chains earlier in development. There were considerable changes in the expression of integrins (Int) concomitantly with alterations in the composition of the BMs. At the PG stage the epithelial buds showed reactivity for Int-alpha 2 -alpha 3, and -alpha 6 subunits, but at the canalicular stage the Int-alpha 2 and -alpha 6 subunits disappeared, and only Int-alpha 3 integrin subunit was found in evolving alveolar walls; Int-alpha 6 was found in capillaries. A similar distribution of Int subunits was also found in adult alveoli. The bronchi expressed Int-alpha 2, -alpha 3, and -alpha 6 subunits at all developmental stages, but the Int-beta 4 subunit emerged first at the canalicular stage. Our results suggest that there are major changes in the expression of Ln and their Int receptors during morphogenesis of the lung, which may be important for normal development.

Adult↗
PubMed1996

Expression of laminins in the airways in various types of asthmatic patients: a morphometric study.

Laminins (Ln) are crucial in airway morphogenesis. Because they are able to interact with inflammatory cells, they are likely to participate in inflammation accompanied by airway structural remodeling in asthma. Taking biopsies and using immunohistochemistry and quantitative image analysis, we characterized the distribution of Ln chains alpha 1, alpha 2, and beta 2 in the bronchial mucosa of patients with seasonal (n = 17), early occupational (n = 8), and chronic asthma (n = 16) for comparison with that of normal controls (n = 8). In all asthmatic patients, both Ln chains alpha 1 and beta 2 were confined to the superficial margin of the basement membrane (BM), blood vessels, and smooth muscle. The thickness of Ln beta 2 expression in BM was significantly greater in patients with chronic (1.9 +/- 0.1 microns; P < 0.001) and occupational asthma (1.7 +/- 0.1 microns; P < 0.05) than in controls (0.4 +/- 0.3 microns). Only in patients with occupational asthma was the thickness of the Ln alpha 1 layer (2.3 +/- 0.2 microns; mean +/- SEM) significantly different from that in controls (1.4 +/- 0.5 microns; P < 0.05). There was no immunoreactivity for the Ln alpha 2 chain in controls or patients with mild asthma, but in clinically severe chronic asthma we found a discontinuous staining along the epithelial margin of the BM. Since Ln chains alpha 2 and beta 2 appear to function only during morphogenesis, increased expression of these Ln chains in adult asthma patients suggests accelerated tissue turnover in the airways, possibly as a result of airway inflammation in asthma.

Adult↗
PubMed1996

Bronchial biopsy findings in intermittent or "early" asthma.

Bronchial biopsy specimens from subjects with intermittent or "early" asthma were compared with specimens taken from healthy subjects. Patients with early asthma included those with seasonal asthma and occupational asthma. There was a small but statistically significant increase in the thickness of the subepithelial extracellular matrix protein tenascin in subjects with seasonal and occupational asthma compared with control subjects. Collagen types IV and VII were increased only in patients with occupational asthma. Eosinophils were the only inflammatory cells that were significantly increased in subjects with seasonal asthma compared with control subjects. These data show that inflammation is present in the airways of patients with early asthma, and the increase in tenascin expression in the basement membrane zone suggests that structural changes are also initiated at an early stage of the disease.

Adult↗