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Biomedical subjects

S Saarelainen

Publications and source records attributed to S Saarelainen.

At least 19 recordsLinked to original sources
PubMed2006

Chest CT screening of asbestos-exposed workers: lung lesions and incidental findings.

The objective of the present study is to determine the feasibility of chest computed tomography (CT) in screening for lung cancer among asbestos-exposed workers. In total, 633 workers were included in the present study and were examined with chest radiography and high-resolution CT (HRCT). A total of 180 current and ex-smokers (cessation within the previous 10 yrs) were also screened with spiral CT. Noncalcified lung nodules were considered positive findings. The incidental CT findings not related to asbestos exposure were registered and further examined when needed. Noncalcified lung nodules were detected in 86 workers. Five histologically confirmed lung cancers were found. Only one of the five cancers was also detected by plain chest radiography and three were from the group of patients with a pre-estimated lower cancer probability. Two lung cancers were stage Ia and were radically operated. In total, 277 individuals presented 343 incidental findings of which 46 required further examination. Four of these were regarded as clinically important. In conclusion, computed tomography and high-resolution computed tomography proved to be superior to plain radiography in detecting lung cancer in asbestos-exposed workers with many confounding chest findings. The numerous incidental findings are a major concern for future screenings, which should be considered for asbestos-exposed ex-smokers and current smokers.

Aged↗
PubMed2005

The DR4-DQ8 haplotype and a specific T cell receptor Vbeta T cell subset are associated with absence of allergy to Can f 1.

BACKGROUND: The significance of specific T cell receptor (TCR) Vbeta subtypes and human leucocyte antigen (HLA) class II alleles for the development of allergy to lipocalin allergens such as the major dog allergen Can f 1 is not clear at present. OBJECTIVE: To characterize the TCR Vbeta usage in the Can f 1-specific T cell lines and the HLA class II genotypes of Can f 1-allergic and non-allergic subjects. METHODS: T cell lines were induced with recombinant Can f 1 from the peripheral blood mononuclear cells of 12 non-atopic dog owners and 26 dog-allergic patients. Thirteen of the dog-allergic subjects were sensitized to Can f 1. Expression of the TCR Vbeta subtypes on CD4(+) T cells in the T cell lines was measured by flow cytometry. The subjects were HLA genotyped for DRB1, DQB1 and DPB1 loci. RESULTS: Can f 1-specific T cell lines were obtained from 18 subjects, with either positive (n=8) or negative (n=10) skin prick tests (SPTs) to recombinant Can f 1. The frequency of TCR Vbeta5.1(+) T cells was significantly higher in the T cell lines of subjects with negative SPTs to the allergen. Moreover, DR4-DQ8 haplotype was over-represented among these subjects. CONCLUSION: The DR4-DQ8 haplotype and the TCR Vbeta5.1(+) CD4(+) T cells may be protective against allergy to Can f 1.

Allergens↗
PubMed2004

Long-term follow-up study of pulmonary findings in patients with primary Sjögren's syndrome.

BACKGROUND: In a previous study pulmonary hyperinflation was observed frequently in patients with primary Sjogren's syndrome (pSS) and elevated serum beta-2 microglobulin (beta2m) concentrations were associated with hyperinflation. OBJECTIVE: To evaluate the significance of baseline serum beta2m concentration and to identify other possible risk factors for pulmonary involvement in long-term follow-up of patients with pSS. METHODS: Nineteen pSS patients whose pulmonary function tests (PFTs) had been previously studied were reexamined after a median follow-up of 10 years. Pulmonary symptoms were recorded, chest radiograph, and high-resolution computed tomography (HRCT) were evaluated and methacholine provocation and PFTs including flow-volume spirometry, body plethysmography, and diffusing capacity performed. RESULTS: Baseline serum beta2m concentrations correlated inversely with follow-up total lung capacity (TLC), vital capacity (VC), and diffusing capacity (DL), and positively with residual volume (RV), all expressed as percentage of predicted values. Diminished airways resistance (Raw) and, correspondingly, elevated specific conductance (SGaw) were frequent findings in pSS patients at follow-up, indirectly implying stiffness of the lungs and a restrictive decrease in lung volumes. Baseline serum protein concentration was higher and IgG concentration tended to be higher in pSS patients who at follow-up had elevated SGaw compared with others. Interstitial changes in HRCT were found more frequently in patients with elevated SGaw than in those without. CONCLUSION: Our results suggest that subtle restrictive changes in pulmonary function are more prone to develop in the long term in pSS patients with elevated serum beta2m concentration and other signs of immunological activity at baseline.

Follow-Up Studies↗
PubMed2004

Assessment of recombinant dog allergens Can f 1 and Can f 2 for the diagnosis of dog allergy.

BACKGROUND: The use of recombinant allergens for the diagnosis and immunotherapy of allergy may offer several advantages over allergen extracts. OBJECTIVE: To produce recombinant dog allergens Can f 1 and Can f 2 in Pichia pastoris yeast and to assess their suitability for the diagnosis of dog allergy. METHODS: Clinically diagnosed dog-allergic patients' and healthy non-atopic dog owners' reactivities against recombinant Can f 1 and Can f 2 and commercial dog epithelial extract were studied by a panel of methods including skin prick test (SPT), ELISA and IgE immunoblotting. RESULTS: Recombinant Can f 1 and Can f 2 were found immunologically functional: they bound dog-allergic patients' IgE in immunoblotting and inhibited specifically the binding of IgE to their natural counterparts in the dog allergen extract. Moreover, patients' IgE reactivity in immunoblotting to natural Can f 1 and their SPT with the recombinant allergen were perfectly concordant (phi coefficient 1.0, P<0.001). The concordance was slightly lower with recombinant Can f 2 (phi coefficient 0.92, P<0.001). A lower number of dog-allergic patients, 52%, reacted against Can f 1 than previously reported. About one-third of the patients reacted to Can f 2. In immunoblotting, the highest prevalence of reactivity, 60%, was directed to an 18 kDa component. Aminoterminal sequencing showed this to be a previously unidentified allergenic protein. CONCLUSIONS: The recombinant allergens can be used reliably to identify Can f 1 and Can f 2-sensitized individuals. However, the two allergens are insufficient as reagents for diagnosing dog allergy.

Adult↗
PubMed2003

Probing the mechanisms of low immunogenicity of a lipocalin allergen, Bos d 2, in a mouse model.

BACKGROUND: Bos d 2, a major bovine allergen of the lipocalin family, stimulates very weakly cow dust-asthmatic subjects' peripheral blood mononuclear cells and the spleen cells of several inbred mouse strains immunized with the allergen. OBJECTIVE: To identify the immune mechanisms accounting for the weak stimulatory capacity of Bos d 2. METHODS: The spleen cell responses of BALB/c mice immunized with the allergen and with hen egg lysozyme and tetanus toxoid as control antigens were examined using several in vitro methods. RESULTS: Analysis of the numbers of spleen cells in the antigen-stimulated in vitro cultures with the vital dye 7-amino-actinomycin D showed that Bos d 2 induced a smaller expansion of cells in comparison with the control antigens. Increased cell death in vitro did not account for the weak response against Bos d 2. The number of spleen cells reacting against Bos d 2 also proved to be the lowest when they were analysed by labelling the stimulated cells with 5-6-carboxyfluorescein diacetate succinimidyl ester or by enumerating cytokine-secreting cells by ELISPOT. Eliminating CD8+ cells in the in vitro culture did not enhance the response against Bos d 2. Bos d 2 was also the weakest of the antigens to stimulate the production of soluble cytokines. Adding IL-2, IL-4 or antibody against TGF-beta in the antigen-stimulated spleen cell cultures enhanced the proliferative responses against all the antigens, whereas adding IL-12 or antibody against IL-4 or IL-10 did not enhance the responses. CONCLUSION: The results exclude several mechanisms of peripheral tolerance as an explanation for the poor immune response against Bos d 2, and suggest that the allergen is recognized by a low number of specific T cells. The weak immunogenicity of Bos d 2 may be related to its allergenicity.

Allergens↗
PubMed2002

Increased alveolar nitric oxide concentration in asthmatic patients with nocturnal symptoms.

Nocturnal asthma symptoms and impaired lung function at night are related to inflammatory activity in the peripheral lung compartment. Exhaled nitric oxide (NO) measurement at multiple exhalation flow rates can be used to separately assess alveolar and bronchial NO production and inflammation. The authors hypothesised that asthmatic patients with nocturnal symptoms have a higher alveolar NO concentration than those with only daytime symptoms. The authors asked 40 patients with newly-diagnosed steroid-naïve asthma about their nocturnal asthma symptoms through the use of a written questionnaire. Alveolar NO concentration and bronchial NO flux were assessed in the 40 asthmatics and 40 healthy controls. Nineteen of the 40 patients reported nocturnal symptoms. Patients with nocturnal symptoms had a higher alveolar NO concentration (1.7+/-0.3 (mean+/-SEM) parts per billion (ppb)) than patients without nocturnal symptoms (0.8+/-0.3 ppb, p=0.012) or healthy controls (1.0+/-0.1 ppb, p=0.032). Bronchial NO flux was higher both in patients with (2.4+/-0.4 nL x s(-1), p<0.001) and without (2.6+/-0.4 nL x s(-1), p<0.001) nocturnal symptoms, compared to controls (0.7+/-0.1 nL x s(-1)). Nocturnal symptoms in asthmatic patients are related to a higher alveolar nitric oxide concentration. The results suggest that assessment of alveolar nitric oxide concentration can be used to detect the parenchymal inflammation in asthmatic patients with nocturnal symptoms.

Adult↗
PubMed2001

Extended exhaled NO measurement differentiates between alveolar and bronchial inflammation.

Lower respiratory tract inflammation can be detected by measuring exhaled nitric oxide (NO) concentration at a single exhalation flow rate, but this does not differentiate between alveolar and bronchial NO production. We assessed alveolar NO concentration and bronchial NO flux with an extended method of measuring exhaled NO at several exhalation flow rates in 40 patients with asthma, 17 patients with alveolitis, and 57 healthy control subjects. Bronchial NO flux was higher in asthma (2.5 +/- 0.3 nl/s, p < 0.001) than in alveolitis (0.7 +/- 0.1 nl/s) and healthy control subjects (0.7 +/- 0.1 nl/s). Alveolar NO concentration was higher in alveolitis (4.1 +/- 0.3 ppb, p < 0.001) than in asthma (1.1 +/- 0.2 ppb) and healthy control subjects (1.1 +/- 0.1 ppb). In asthma, bronchial NO flux correlated with serum level of eosinophil protein X (EPX) (r = 0.60, p < 0.001) and bronchial hyperresponsiveness (r = 0.55, p < 0.001). In alveolitis, alveolar NO concentration correlated inversely with pulmonary diffusing capacity (r = -0.55, p = 0.022) and pulmonary restriction. Glucocorticoid treatment or allergen avoidance normalized bronchial NO flux in asthma and decreased alveolar NO concentration toward normal in alveolitis. In conclusion, extended exhaled NO measurement can be used to separately assess alveolar and bronchial inflammation and to assess disease activity/severity in asthma and alveolitis.

Adult↗
PubMed2001

Inhaled fluticasone decreases bronchial but not alveolar nitric oxide output in asthma.

Exhaled nitric oxide (NO) concentration is a noninvasive measure of airway inflammation and is increased in asthma. Inhaled glucocorticoids decrease exhaled NO concentration, but the relative contributions of alveolar and bronchial levels to the decrease in exhaled NO concentration are unknown. Alveolar NO concentration and bronchial NO flux can be separately approximated by measuring exhaled NO at several exhalation flow rates. The effect of steroid treatment on alveolar and bronchial NO output in asthma was studied. Alveolar NO concentration and bronchial NO flux were assessed in 16 patients with asthma before and during treatment with inhaled fluticasone for 8 weeks and in 16 healthy controls. Before the treatment, asthmatics had increased bronchial NO flux (mean+/-SEM: 3.6+/-0.4 versus 0.7+/-0.1 nL x s(-1), p<0.001) but normal alveolar NO concentration (1.2+/-0.5 versus 1.0+/-0.2 parts per billion (ppb), p>0.05) compared with controls. Inhaled fluticasone decreased bronchial NO flux from 3.6+/-0.4 to 0.7+/-0.1 nL x s(-1) (p<0.01) but had no effect on alveolar NO concentration (before: 1.2+/-0.5; after: 1.2+/-0.1 ppb, p>0.05). The forced expiratory volume in one second improved, whereas asthma symptom score and serum levels of eosinophil cationic protein and eosinophil protein X decreased during the treatment. In conclusion, inhaled fluticasone decreases bronchial but not alveolar nitric oxide output simultaneously with clinical improvement in patients with asthma.

Administration, Inhalation↗
PubMed2000

Increased bronchial nitric oxide production in patients with asthma measured with a novel method of different exhalation flow rates.

The concentration of nitric oxide (NO) in exhaled air is increased in patients with asthma, suggesting that measuring fractional exhaled NO concentration (FE(NO)) may be used to monitor asthmatic airway inflammation. However, increased FE(NO) is not specific for asthma, as other inflammatory lung diseases may also increase FE(NO). To augment the specificity of FE(NO) measurement, we tested a novel theoretical modelling of pulmonary NO dynamics that allows the approximation of alveolar NO concentration and bronchial NO flux separately by measuring FE(NO) at several exhalation flow rates. We measured FE(NO) at four exhalation flow rates in 10 steroid-naive asthmatics, 5 patients with extrinsic allergic alveolitis, and in 10 healthy controls. Both the asthmatics and the patients with alveolitis had significantly higher FE(NO) than the healthy controls. The increased NO concentration originated from the bronchial level in the asthmatics and from the alveolar level in the patients with alveolitis. In the second part of the study we assessed the repeatability of FE(NO) test, within-day and day-to-day (during two weeks) variation in FE(NO), and the effects of mouth pressure and cigarette smoking on FE(NO) in healthy volunteers. Repeatability of 10 subsequent measurements was high (coefficient of variation (CV) 4.6% +/- 0.4%), and no diurnal variation was found. The day-to-day variation during a 2-week period gave a CV of 10.6% +/- 1.0%. The magnitude of mouth pressure (5-20 cmH2O in adults, 5-40 cmH2O in children) during measurement had no effect on FE(NO). Smoking a cigarette caused a small and transient but statistically significant increase in FE(NO) at 1 and 5 min after smoking. In conclusion, FE(NO) measurement is highly repeatable with low day-to-day variation among healthy subjects. Our results also suggest that the present novel method of measuring FE(NO) at several exhalation flow rates can be used to approximate alveolar and bronchial contributions to FE(NO) separately and thus increase the clinical value of this test.

Adult↗
PubMed1999

Oral steroid-sparing effect of two doses of nebulized fluticasone propionate and placebo in patients with severe chronic asthma.

Inhaled steroids, delivered by metered dose aerosol and dry powder inhalers, have proved effective in reducing the need for oral steroids in patients with oral steroid-dependant asthma. This randomized, double-blind study, compared the efficacy and tolerability of nebulized fluticasone propionate (FP Nebules), 2 mg b.d. (FP 4 mg) and 0.5 mg b.d. (FP 1 mg) with placebo, on the reduction of oral steroid requirement in 301 adult patients with oral steroid-dependent asthma. Primary efficacy was assessed by the reduction in daily oral steroid dose. Secondary efficacy parameters included daily diary card peak expiratory flow (PEF), day and night-time symptoms and clinic lung function measurements. Safety was assessed by adverse event monitoring and serum cortisol levels. After 12 weeks of treatment the adjusted mean +/- SEM reduction in oral prednisolone was significantly greater in the FP 4 mg group (4.44 +/- 0.98 mg day-1) compared with FP 1 mg (2.16 +/- 1.00 mg day-1, P = 0.039) and placebo (1.20 +/- 1.02 mg day-1, P = 0.004). A higher percentage of patients discontinued the use of oral steroids with FP 4 mg (37%) compared with FP 1 mg (26%, P = 0.038) and placebo (18%, P < 0.001). Following treatment, the adjusted mean morning PEF showed a trend in favour of FP 4 mg (280 +/- 41 min-1) compared with placebo (270 +/- 51 min-1, P = 0.053) and the evening PEF was significantly higher with FP 4 mg (305 +/- 41 min-1) compared with FP 1 mg (292 +/- 41 min-1, P = 0.010). FP 4 mg resulted in a significantly higher percentage of days when the patients were free from daytime (P = 0.036) and night-time (P = 0.021) wheeze, compared with placebo. Significantly fewer patients withdrew from the FP 4 mg group compared with the other two groups (vs. FP 1 mg, P = 0.003; vs. placebo, P = 0.032). All three treatments were well tolerated and the incidence of adverse events was similar between the groups. FP Nebules at a daily dose of between 1 and 4 mg are a safe and effective means of reducing the oral steroid requirement of patients with chronic oral steroid dependent asthma.

Adolescent↗
PubMed1999

Autoantibodies against oxidised low-density lipoprotein in patients with obstructive sleep apnoea.

Autoantibodies against oxidised low-density lipoprotein (OxLDL-Abs) have been proposed to be an indicator of endothelial dysfunction and a novel tool for finding individuals with a high cardiovascular risk. In a cross-sectional study, OxLDL-Abs were measured in 297 patients with obstructive sleep apnoea (OSA) and 54 controls using an enzyme-linked immunosorbent assay. The autoantibodies were increased in patients with OSA when compared to controls (age, body mass index (BMI) and gender adjusted, p = 0.001). However, within the OSA patients, OxLDL-Abs were not related to smoking, hypertension or BMI, and there was a weak negative correlation (r = -0.16, P = 0.007) between age and levels of OxLDL-Abs. In conclusion, at present the measurement OxLDL-Abs still remains a method for basic research and is not applicable for screening of at-risk patients with OSA.

Adult↗
PubMed1998

No relation between apolipoprotein E alleles and obstructive sleep apnea.

Apolipoprotein E (ApoE) is a genetic risk factor influencing the development of cardiovascular diseases and Alzheimer's disease. Patients with obstructive sleep apnea (OSA) suffer an excess mortality and morbidity from cardiovascular diseases. The frequencies of ApoE alleles were determined in 291 patients with OSA and 728 controls. The distribution of ApoE alleles and genotypes showed no difference between OSA and controls.

Adult↗