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Biomedical subjects

E O Vianna

Publications and source records attributed to E O Vianna.

13 recordsLinked to original sources

Eotaxin-2 in sputum cell culture to evaluate asthma inflammation.

The aim of the present study was to elucidate whether the culture of cells recovered from induced sputum may represent a suitable model to evaluate cytokine and chemokine production by airway inflammatory cells. Sputum induction was performed in 21 normal subjects and 30 asthmatic patients. A total of 21 out of the 30 asthmatic patients were taking inhaled corticosteroids, while the remaining nine were steroid-naive asthmatics. The steroid-naive group was evaluated before and after a 14-day treatment with oral prednisone (40 mg.day(-1)). The supernatant of lysed and centrifuged sputum and the supernatant of sputum cell culture were analysed. Tumour necrosis factor-alpha, interleukin (IL)-8 (CXCL8), IL-1beta, IL-13 and eotaxin-2 (CCL24) concentrations were determined by specific ELISA. Eotaxin-2 production by cell culture was higher in the asthma group (131+/-108 pg.mL(-1)) than in the control group (36+/-41 pg.mL(-1)) and treatment with oral corticosteroids eliminated this difference. In addition, reduction of eotaxin-2 levels by corticosteroid treatment was greater in cell culture (81.3% reduction) than in sputum (26.4%). There was correlation between the decrease in eotaxin-2 production and the decrease in blood eosinophil number and between eotaxin-2 and eosinophils in sputum. Eotaxin-2 may play an important role in asthma and the response to corticosteroid treatment suggests that analysis of sputum cell culture is relevant as an inflammatory parameter.

Administration, Inhalation↗

Prevalence and risk factors for work related asthma in young adults.

OBJECTIVES: To investigate the prevalence and predictors of work related asthma in young adults from the general population. METHODS: A total of 1922 subjects randomly selected from a birth cohort 1978/79 in Brazil, aged 23-25 years, completed a respiratory symptoms questionnaire based on the European Community Respiratory Health Survey, and underwent spirometry, bronchial challenge test with methacholine, and skin prick test. For subjects presenting with bronchial hyperresponsiveness, workplace exposure and its relationship with symptoms were assessed by a specific questionnaire and individualised job description to define cases of work related asthma. RESULTS: The prevalence of work related asthma was 4.2% (81 cases): 1.5% (29 cases) were classified as aggravated asthma and 2.7% (52 cases) as occupational asthma. Work related asthma was associated with atopy and education. Lower educational level (1-8 years of schooling) was associated with work related asthma (odds ratio 7.06, 95% CI 3.25 to 15.33). There was no association between work related asthma and smoking, gender, or symptoms of rhinitis. CONCLUSION: The prevalence of work related asthma was high (4.2%), and was associated with low schooling, probably because of low socioeconomic level. The disease may therefore be a consequence of poverty.

Adult↗

Comparison of morning and afternoon exercise training for asthmatic children.

Fitness improvement was used to compare morning with afternoon exercise periods for asthmatic children. Children with persistent moderate asthma (according to GINA criteria), 8 to 11 years old, were divided into 3 groups: morning training group (N = 23), afternoon training group (N = 23), and non-training group (N = 23). The program was based on twice a week 90-min sessions for 4 months. We measured the 9-min running distance, resting heart rate and abdominal muscle strength (sit-up number) before and after the training. All children took budesonide, 400 microg/day, and an on demand inhaled ss-agonist. The distance covered in 9 min increased (mean +/- SEM) from 1344 +/- 30 m by 248 +/- 30 m for the morning group, from 1327 +/- 30 m by 162 +/- 20 m for the afternoon group, and from 1310 +/- 20 m by 2 +/- 20 m for the control group (P < 0.05 for the comparison of morning and afternoon groups with the control group by ANOVA and P > 0.05 for morning with afternoon comparison). The reduction of resting heart rate from 83 +/- 1, 85 +/- 2 and 86 +/- 1 bpm was 5.1 +/- 0.8 bpm in the morning group, 4.4 +/- 0.8 bpm in the afternoon group, and -0.2 +/- 0.7 bpm in the control group (P > 0.05 for morning with afternoon comparison and P < 0.05 versus control). The number of sit-ups in the morning, afternoon and control groups increased from 22.0 +/- 1.7, 24.3 +/- 1.4 and 23 +/- 1.1 sit-ups by 9.8 +/- 0.9, 7.7 +/- 1.4, and 1.9 +/- 0.7 sit-ups, respectively (P > 0.05 for morning with afternoon comparison and P < 0.05 versus control). No statistically significant differences were detected between the morning and afternoon groups in terms of physical training of asthmatic children.

Abdominal Muscles↗

Pulmonary function, cholinergic bronchomotor tone, and cardiac autonomic abnormalities in type 2 diabetic patients.

This prospective study analyzed the involvement of the autonomic nervous system in pulmonary and cardiac function by evaluating cardiovascular reflex and its correlation with pulmonary function abnormalities of type 2 diabetic patients. Diabetic patients (N = 17) and healthy subjects (N = 17) were evaluated by 1) pulmonary function tests including spirometry, He-dilution method, N2 washout test, and specific airway conductance (SGaw) determined by plethysmography before and after aerosol administration of atropine sulfate, and 2) autonomic cardiovascular activity by the passive tilting test and the magnitude of respiratory sinus arrhythmia (RSA). Basal heart rate was higher in the diabetic group (87.8 +/- 11.2 bpm; mean +/- SD) than in the control group (72.9 +/- 7.8 bpm, P<0.05). The increase of heart rate at 5 s of tilting was 11.8 +/- 6.5 bpm in diabetic patients and 17.6 +/- 6.2 bpm in the control group (P<0.05). Systemic arterial pressure and RSA analysis did not reveal significant differences between groups. Diabetes intragroup analysis revealed two behaviors: 10 patients with close to normal findings and 7 with significant abnormalities in terms of RSA, with the latter subgroup presenting one or more abnormalities in other tests and clear evidence of cardiovascular autonomic dysfunction. End-expiratory flows were significantly lower in diabetic patients than in the control group (P<0.05). Pulmonary function tests before and after atropine administration demonstrated comparable responses by both groups. Type 2 diabetic patients have cardiac autonomic dysfunction that is not associated with bronchomotor tone alterations, probably reflecting a less severe impairment than that of type 1 diabetes mellitus. Yet, a reduction of end-expiratory flow was detected.

Adult↗

Rapid effect of inhaled steroids on nocturnal worsening of asthma.

BACKGROUND: Inhaled steroids are the most commonly used anti-inflammatory agents for asthma and are increasingly recognised as having a more rapid onset of action than was previously thought. We have investigated the effect of a single dose of inhaled steroid on nocturnal worsening of asthma. METHODS: Ten patients with steroid naive moderate asthma and nocturnal asthma participated in a randomised, double blind, placebo controlled, crossover trial. Participants spent three nights in the laboratory, one week apart. On each night they underwent spirometric testing at 16.00 hours and received one of the three treatments (placebo, beclomethasone 1000 micro g, or fluticasone 1000 micro g) delivered by metered dose inhaler. Spirometric tests were repeated at 04.00 hours the following morning. RESULTS: Following placebo administration the mean (SE) overnight fall in FEV(1) was 0.65 (0.27) l compared with -0.02 (0.13) l following fluticasone (p=0.019) and 0.23 (0.12) l following beclomethasone (p=0.048 v placebo). CONCLUSION: A single dose of inhaled steroid (within the therapeutic range) reduced the fall in FEV(1) in patients with nocturnal asthma when administered at 16.00 hours. Nocturnal worsening of asthma is a useful model for testing inhaled steroid activity in a single night study.

Administration, Inhalation↗

Do steroids interfere in dyspnoea sensation?

Dyspnoea remains a remarkable clinical problem and a therapeutic challenge, mainly in chronic respiratory conditions. This study investigated the potential effects of steroids on dyspnoea sensation regardless of their pulmonary anti-inflammatory actions. Sixteen healthy men (mean age +/- SD = 22.5 +/- 1.6 years) developed uncomfortable breathing by the use of inspiratory resistors (loads of 0, 7, 14 and 21 cm H2O/l/s) and breathholding 6 h after taking 40 mg of prednisone (Pred) or placebo (Plac). Respiratory discomfort during breathing with loads was evaluated with a 100 mm visual analog scale. The maximum voluntary apnoea time did not differ between the prednisone and placebo days (Plac = 96 +/- 11.8 s x Pred = 105 +/- 12.2 s) and prednisone did not influence the dyspnoea sensation induced by different inspiratory loads (0 cm H2O/l/s: Pred = 2.8 mm x Plac = 1.9 mm; 7 cm H2O/l/s: Pred = 18.3 mm x Plac = 18.6 mm; 14 cm H2O/l/s; Pred = 33.0 mm x Plac = 34.1 mm; 21 cm H2O/l/s: Pred = 48.1 mm x Plac = 49.6 mm). Prednisone intake was associated with a significant increase in minute ventilation during breathing with no inspiratory loads (Pred = 11.91 +/- 1.28 l/min- x Plac = 9.95 +/- 0.86 l/min). Although steroids certainly may improve respiratory conditions due to anti-inflammatory actions, available evidence does not support any specific beneficial effect of these drugs on these perception of dyspnoea itself.

Administration, Oral↗

Dyspnea scales in the assessment of illiterate patients with chronic obstructive pulmonary disease.

BACKGROUND: Multiple physiological, psychological, social and environmental factors may affect the perception of dyspnea. Although different scales have been used to record the severity of dyspnea in subjects with chronic obstructive pulmonary disease (COPD), none has reported evaluating the properties of such tools in illiterate patients. The objective of this study was to evaluate the reliability and features of concurrent validity of 4 dyspnea scales in illiterate (IL) subjects with COPD. METHODS: One hundred COPD patients submitted to spirometry and were asked to score their breathlessness using a visual analogue scale (VAS), a numerical rating scale (NRS), the Borg scale (BS), and the basal dyspnea index (BDI). Each scale was presented to the patients before and after they had performed spirometry and measurement of residual volume. The obtained scores were analyzed according to the literacy status of the patients. RESULTS: Thirty-three patients were classified as IL and 67 as literate (L). Both groups showed similar respiratory impairment and median scores of dyspnea (VAS, L = 45.0, IL = 49.0; NRS, L = 5.0, IL = 5.0; BS, L = 3.0, IL = 3.0; BDI, L = 5.0, IL = 4.0). No significant differences were found between the dyspnea scores obtained before and after spirometry for all scales in both groups. The degree of correlation between forced expiratory volume in 1 second (FEV1) and usual dyspnea evaluated by BDI did not show a statistical difference between the two groups (L, r = 0.37; IL, r = 0.51). CONCLUSION: The employed dyspnea scales showed comparable reliability in both L and IL COPD subjects.

Adult↗

Allergic airway inflammation in hypothyroid rats.

BACKGROUND: Hormones play a modulating role in allergic inflammation. Hyperthyroidism may increase the severity of asthma, and hypothyroidism may ameliorate coexistent asthma. The mechanisms regulating this interaction are not completely understood. OBJECTIVE: The purpose of this study was to test the hypothesis that thyroid hormones influence the development of allergic airway inflammation after antigen challenge in rats. METHODS: The experimental design included either sensitized or nonsensitized surgically thyroidectomized and sham-operated rats. Experiments were performed 50 days after surgery. Thyroidectomized rats and sham-operated controls were sensitized by subcutaneous injection of ovalbumin (OVA) and Al(OH)(3) and challenged 14 days later by OVA inhalation. Bronchoalveolar lavages were performed 24 hours after challenge. RESULTS: Compared with controls, thyroidectomized animals presented markedly decreased cell yields from bronchoalveolar lavage fluid after OVA challenge. The impaired response was not related to changes in the number of circulating leukocytes. Determination of antibody serum concentrations indicated that thyroidectomized rats presented a marked reduction in the level of anti-OVA IgE compared with controls, without significant differences in IgG(1) and IgG(2a) serum concentrations. Reversal of the impaired responses was attained by 16-day treatment of hypothyroid animals with thyroxine, but not by 1- or 3-day treatment. CONCLUSION: The data presented suggest that the continuing deficiency of thyroid hormones influences the development of the inflammatory component of asthma. This is due, at least in part, to a decrease in the production of IgE.

Animals↗

The effects of upper respiratory infection on T-cell proliferation and steroid sensitivity of asthmatics.

BACKGROUND: The common cold is a potent trigger for asthma symptoms. Although the mechanisms are not completely understood, inflammatory events may play an important role. OBJECTIVE: We tested the hypothesis that changes in steroid responsiveness are implicated in the relationship between asthma and the common cold. METHODS: We investigated the steroid sensitivity of T cells from 10 patients with asthma (not taking steroids) and 10 control subjects, during upper respiratory infection and at recovery (6 weeks later). We stimulated peripheral blood mononuclear cells with phytohemagglutinin to measure T-cell proliferation, sensitivity to the inhibitory effects of steroids, and cytokine production. RESULTS: During infection compared with recovery, the asthma group exhibited lower responsiveness to dexamethasone at 10(-10) and 10(-9)mol/L and to 10(-10)mol/L hydrocortisone (P <.05) and both groups had decreased T-cell proliferation (P <.05). During recovery, patients with asthma had greater T-cell proliferation than control subjects (P <.02); the values expressed as uptake of [3H]-thymidine were 60119+/-3944 cpm (asthma) and 39078+/-6459 cpm (control subjects). The asthma group had higher TNF-alpha and IFN-gamma production during infection (P <.05); changes in IL-8 and IL-10 levels were not significant, and IL-4 was not detected. CONCLUSION: During infection, asthmatic subjects exhibit decreased T-cell responsiveness to steroids. The T-cell proliferative response to phytohemagglutinin, higher in asthma, is decreased with a common cold. These findings are associated with changes in the cytokine profile. Thus viral-induced upper respiratory infections can produce an inflammatory milieu with altered steroid function and selective increases in cytokines.

Adult↗

Bronchodilators and corticosteroids in the treatment of asthma.

Despite advancements in treatment, the incidence of asthma, asthma-related deaths and hospitalizations for asthma have increased significantly during the past decade. Although asthma mortality may now be decreasing, reasons for the worsening of morbidity and mortality in asthma remain unclear. These unexpected changes in asthma severity have sparked renewed interest in research into the pathogenesis and treatment of the condition. Beta(2)-Adrenergic agonists are the most commonly used class of drugs for the treatment of asthma. Recent concerns about safety issues for beta-agonists caused reevaluation of prescribing practices, and using them on an as-needed basis is now more frequently accepted and recommended. In acute asthma, a beta(2)-adrenergic agonist is still the medication of choice. Long-acting salmeterol and formoterol, administered only twice daily, can decrease symptoms of asthma during day and nighttime. On the other hand, the role of tolerance to their bronchodilator and bronchoprotective effects is still to be determined in the treatment of asthma. Theophylline, whose use has been limited by the potential for serious toxicity, may regain an important position in asthma treatment with the development of the knowledge about its antiinflammatory actions. Dosing theophylline on a time- related basis also improves the risk/benefit ratio and makes it a useful drug for nocturnal asthma. Ipratropium bromide, an anticholinergic drug, still awaits a defined role in the treatment of asthma. Studies on its use for acute asthma have not achieved consensus and, for nocturnal asthma, the short duration of effect limits the benefits. Corticosteroids, including inhaled steroids, have measurable effects on symptoms, lung function, bronchial responsiveness and inflammation associated with asthma. Side effects of chronic use limit systemic, but not inhaled administration. Newer preparations, like budesonide, flunisolide and fluticasone, decrease the incidence of possible side effects related to inhaled steroids by having better ratio of topical to systemic potency. Daily doses up to 1600 micro g of beclomethasone (or equivalent) are considered safe and higher doses should be reserved for patients with moderate to severe asthma. Although future trials are necessary to clarify many issues related to dosing of inhaled steroids, chronotherapy studies have shown that single administration between 3 and 5:30 p.m. may be as effective as 4 times a day dosing.

Journal Article↗

Recent innovations in asthma therapy.

Guidelines for the diagnosis and management of asthma have been published since 1990 and already new versions are being published. The recommendations for the treatment of asthma were organized around four components of effective asthma management: i) use of objective measures of lung function to assess the severity of asthma and to monitor the course of therapy, ii) environmental control measures to avoid or eliminate factors that precipitate asthma symptoms or exacerbations, iii) comprehensive pharmacologic therapy for long-term management designed to reverse and prevent the airway inflammation characteristic of asthma as well as pharmacologic therapy to manage asthma exacerbations, and iv) patient education that fosters a partnership among the patient, family and clinicians. Newly released medications include anti-leukotriene (LTs) agents which function either by blocking the interaction of LTs with receptors (receptor antagonists) or by inhibiting leukotriene synthesis (synthesis inhibitors). Representatives of the antagonists discussed here are zafirlukast, pranlukast and montelukast. Zafirlukast (20 mg twice daily) improves pulmonary function indices and days without symptoms and decreases the asthma exacerbation frequency. Pranlukast, the first leukotriene receptor antagonist to be marketed, improves lung function and symptoms when 450 mg twice daily is used. A study with montelukast demonstrated similar positive results irrespective of the use of concomitant inhaled corticosteroid. This indicates that leukotriene receptor antagonists may have additive effects to steroid therapy. They may also be a potential alternative to inhaled steroids, although more studies need to be performed before defining the role of receptor antagonists in the treatment of asthma. Zileuton, a leukotriene synthesis inhibitor, has been shown to improve lung function, reduce symptoms and reduce use of beta-agonists and asthma exacerbations. These positive effects are dose-dependent and liver function abnormalities seem to be a relevant issue during zileuton use in some patients. Other compounds that inhibit LTs synthesis are in development and, like zileuton, need more tests. Phosphodiesterases (PDE), enzymes that break down cAMP and cGMP, have been a target for new compounds developed to treat asthma. Inhibition of PDE enzymes increases intracellular cAMP or cGMP which then produces bronchodilation. Recent studies have also shown antiinflammatory effects by suppressing some PDE isoenzymes, including PDE III and PDE IV. These effects were detected by studies in vitro and in animal models. Clinical trials are necessary to determine which PDE inhibitors can be useful for the treatment of asthma.

Journal Article↗

Human corticotropin-releasing hormone improves overnight FEV1 in nocturnal asthma.

Corticotropin-releasing hormone (CRH) exhibits anti-inflammatory properties independent of its effect on adrenal function. We investigated the safety and effect of CRH in nocturnal asthma, a disease where inflammation is prominent. Five subjects underwent an overnight infusion of placebo on the first night, CRH at a 2.5 micrograms/kg/hr on the second night, and three subjects received CRH at 4.0 micrograms/kg/hr on the third night. A significant improvement occurred in overnight change in forced expiratory volume 1 sec. % (delta FEV1) with CRH (+17.4 +/- 9.1%) as opposed to placebo (-25.9 +/- 7.1%), p = 0.024, CRH was well tolerated. Further research with CRH may clarify the pathophysiology of nocturnal asthma.

Adult↗

Allergen-induced airway inflammation in rats. Role of insulin.

Clinical asthma appears to be less severe when diabetes mellitus is superimposed. To examine whether insulin influences the development of allergic reactions in the airway mucosa antigen challenge, normal and diabetic rats sensitized against ovalbumin (OA) were used. Compared with controls, animals rendered diabetic by the injection of alloxan presented markedly decreased cell yields from bronchoalveolar lavage after OA challenge. The impaired response was not related to antibody production because enhanced IgE antibody titers of the same magnitude were found in both control and diabetic animals. Similarly, the mechanism underlying the inhibited responses could not be ascribed to hyperglycemia or intracellular glucopenia, first, because correction of blood glucose levels through fasting did not restore the decreased response, and second, because administration of 2-deoxyglucose, which blocks glucose utilization, did not affect the bronchoalveolar reaction to OA challenge in normal animals. Reversal of the impaired responses was attained by treatment of diabetic animals with insulin. There is evidence that insulin exerts proinflammatory effects. We conclude that insulin might modulate the inflammatory component of asthmatic responses.

Animals↗