Anssi Sovijärvi

Effects of Reducing or Discontinuing Inhaled Budesonide in Patients with Mild Asthma

BACKGROUND In a previous study, we found that two years of treatment with an inhaled corticosteroid, budesonide, was more effective than treatment with an inhaled beta 2-agonist, terbutaline, in patients with newly diagnosed, generally mild asthma. We continued this study for a third year to investigate whether the steroid dose could be reduced or discontinued and what effect crossover of patients from beta 2-agonist therapy to corticosteroid therapy would have. METHODS A total of 37 patients treated for two years with inhaled budesonide at a dose of 1200 micrograms per day were randomly assigned to treatment with 400 micrograms of budesonide per day (19 patients) or placebo (18 patients) in a double-blind manner. Another 37 patients, who had received terbutaline during the first two years, were crossed over in an open-label manner to treatment with 1200 micrograms of budesonide per day during the third year. RESULTS Treatment with the reduced dose of budesonide was sufficiently effective in 74 percent of the patients to maintain bronchial responsiveness at a level similar to that achieved with the higher dose. In contrast, improvement was maintained in only 33 percent of the patients receiving placebo, and the differences in pulmonary function between the steroid and placebo groups were significant (for forced expiratory volume in one second, P = 0.007; for bronchial responsiveness to histamine, P = 0.025; and for peak expiratory flow in the morning, P = 0.040). The condition of patients who were crossed over from terbutaline therapy to treatment with 1200 micrograms of budesonide per day improved. However, the degree of improvement in these patients appeared to be less than in those who were treated with budesonide at the beginning of the three-year study. CONCLUSIONS Early treatment with inhaled budesonide results in long-lasting control of mild asthma. Maintenance therapy can usually be given at a reduced dose, but discontinuation of treatment is often accompanied by exacerbation of the disease.

Intense physical training decreases circulating antioxidants and endothelium-dependent vasodilatation in vivo

Physical training increases free radical production and consumes antioxidants. It has previously been shown that acute exercise markedly increases the susceptibility of LDL to oxidation but whether such changes are observed during physical training is unknown. We measured circulating antioxidants, lipids and lipoproteins, and blood flow responses to intrabrachial infusions of endothelium-dependent (acetylcholine, ACh, L-N-monomethyl-arginine, L-NMMA) and -independent (sodium nitroprusside, SNP) vasoactive agents, before and after 3 months of running in 9 fit male subjects. Maximal aerobic power increased from 53 +/- 1 to 58 +/- 2 ml/kg min (P < 0.02). All circulating antioxidants (uric acid, SH-groups, alpha-tocopherol, beta-carotene, retinol) except ascorbate decreased significantly during training. Endothelium-dependent vasodilatation in forearm vessels decreased by 32-35% (P < 0.05), as determined from blood flow responses to both a low (10.8 +/- 2.1 vs. 7.3 +/- 1.5 ml/dl min, 0 vs. 3 months) and a high (14.8 +/- 2.6 vs. 9.6 +/- 1.8) ACh dose. The % endothelium-dependent blood flow (% decrease in basal flow by L-NMMA), decreased through training from 37 +/- 3 to 22 +/- 7% (P < 0.05). Blood flow responses to SNP remained unchanged. The decrease in uric acid was significantly correlated with the change in the % decrease in blood flow by L-NMMA (r = 0.74, P < 0.05). The lag time for the susceptibility of plasma LDL to oxidation in vitro, LDL size and the concentration of LDL cholestetol remained unchanged. We conclude that relatively intense aerobic training decreases circulating antioxidant concentrations and impairs endothelial function in forearm vessels.

Does non-responder bias have a significant effect on the results in a postal questionnaire study?

Background and aim: In epidemiological questionnaire studies results can be influenced by non-responder bias. However, in respiratory epidemiology this has been analysed in very few recently published papers. The aim of our paper is to assess if the results found in our previous postal questionnaire study in an adult population in Northern Finland were biased by non-response. Methods: A random sample of 385 persons from the 1284 non-responders in a previous postal questionnaire study was examined. The same questionnaire as in the original study was again mailed to these persons, and those still not answering were contacted by phone. Results: Totally 183 complete answers (48%) were collected. Lack of interest (56%) and forgetting to mail the response letter (22%) were the most common reasons to non-response. Typical non-responders were young men and current smokers who less frequently reported respiratory symptoms in exercise and asthma than the responders in the original study. Answers collected by phone gave for some questions higher prevalence rates than postal answers. Conclusion: Firstly, in this population the response rate (83.6%) in the original study was high enough to provide reliable results for respiratory symptoms and diseases, only the prevalence of current smoking was biased by non-response. Secondly, the methods used for collecting responses in a non-response study may influence the results.

Quantitative functional lung imaging with synchrotron radiation using inhaled xenon as contrast agent

Small airways play a key role in the distribution of ventilation and in the matching of ventilation to perfusion. The purpose of this study was to introduce an imaging method that allows measurement of regional lung ventilation and evaluation of the function of airways with a small diameter. The experiments were performed at the Medical Beamline of the European Synchrotron Radiation Facility. Monochromatic synchrotron radiation beams were used to obtain quantitative respiration-gated images of lungs and airways in two anaesthetized and mechanically ventilated rabbits using inhaled stable xenon (Xe) gas as a contrast agent. Two simultaneous images were acquired at two different energies, above and below the K-edge of Xe. Logarithmic subtraction of the two images yields absolute Xe concentrations. This technique is known as K-edge subtraction (KES) radiography. Two-dimensional planar and CT images were obtained showing spatial distribution of Xe concentrations within the airspaces, as well as the dynamics of filling with Xe. Bronchi down to 1 mm in diameter were visible both in the subtraction radiographs and in tomographic images. Absolute concentrations of Xe gas were calculated within the tube carrying the inhaled gas mixture, small and large bronchi, and lung tissue. Local time constants of ventilation with Xe were obtained by following the evolution of gas concentration in sequential computed tomography images. The results of this first animal study indicate that KES imaging of lungs with Xe gas as a contrast agent has great potential in studies of the distribution of ventilation within the lungs and of airway function, including airways with a small diameter.

Degree and clinical relevance of sensitization to common allergens among adults: a population study in Helsinki, Finland

Background We aimed to assess the prevalence of allergic sensitization and multiple sensitization, risk factors, and the clinical impact of being sensitized in the adult population of Helsinki, Finland.

Quantitative measurement of regional lung gas volume by synchrotron radiation computed tomography

The aim of this study was to assess the feasibility of a novel respiration-gated spiral synchrotron radiation computed tomography (SRCT) technique for direct quantification of absolute regional lung volumes, using stable xenon (Xe) gas as an inhaled indicator. Spiral SRCT with K-edge subtraction using two monochromatic x-ray beams was used to visualize and directly quantify inhaled Xe concentrations and airspace volumes in three-dimensional (3D) reconstructed lung images. Volume measurements were validated using a hollow Xe-filled phantom. Spiral images spanning 49 mm in lung height were acquired following 60 breaths of an 80% Xe-20% O2 gas mixture, in two anaesthetized and mechanically ventilated rabbits at baseline and after histamine aerosol inhalation. Volumetric images of 20 mm lung sections were obtained at functional residual capacity (FRC) and at end-inspiration. 3D images showed large patchy filling defects in peripheral airways and alveoli following histamine provocation. Local specific lung compliance was calculated based on FRC/end-inspiration images in normal lung. This study demonstrates spiral SRCT as a new technique for direct determination of regional lung volume, offering possibilities for non-invasive investigation of regional lung function and mechanics, with a uniquely high spatial resolution. An example of non-uniform volume distribution in rabbit lung following histamine inhalation is presented.

Increasing prevalence of asthma but not of chronic bronchitis in Finland? Report from the FinEsS-Helsinki study

To assess the prevalence of asthma, chronic bronchitis and respiratory symptoms, and to calculate risk factors for them, we performed a postal survey in Helsinki, the capital of Finland. During the spring of 1996, questionnaires were mailed to a random sample of 8000 individuals aged 20-69. The total response rate was 76%, with 6062 complete answers. The prevalence of having ever had asthma was 7.2%, physician-diagnosed asthma was 6.6% and physician-diagnosed chronic bronchitis was 3.7%. Asthma was significantly more common among women than men, but no gender differences existed in prevalence of chronic bronchitis. The most common respiratory symptom was sputum production when coughing, reported by 27%. During the previous 12 months, wheezing had occurred in 20% and attacks of shortness of breath in 13% of subjects. Generally, the prevalence of different respiratory symptoms were significantly higher among smokers. The most important risk factor for asthma was a family history of asthma (Odds ratio:OR 3.3). Multivariate analysis revealed that being a member of the socioeconomic group, manual workers, was associated with a significantly increased risk for chronic productive cough (OR 1.7), and for wheezing during the previous 12 months (OR 1.7). Manual workers of both genders had the highest prevalence of asthma, chronic productive cough and wheezing during the previous 12 months. The prevalence of asthma in Helsinki was higher than previously found in Finland, and was at a similar level to that of other Nordic countries. In contrast, prevalence of chronic bronchitis was lower than previously shown in Finland.

Diffusing capacity of the lung in school-aged children born very preterm, with and without bronchopulmonary dysplasia

The aim of this study was to determine the extent to which bronchopulmonary dysplasia (BPD) affects the diffusing properties of lung tissue in childhood. Pulmonary function in 31 prematurely born children (BW. < 1250 g) was examined at ages 7–11 years. Twenty out of 31 prematurely born children met the criteria for BPD. The remaining 11 children had milder forms of neonatal lung disease. Twenty healthy children of the same age and born at term served as a control group. The diffusing capacity of the lung for carbon monoxide (DLCO) was measured by the single breath method. Lung volumes were determined in a body plethysmograph and expiratory flow rates with a flow/volume spirometer. DLCO values of children with histories of BPD did not differ significantly from those of the prematurely born children without BPD. However, DLCO values in both prematurely born study groups were significantly lower than those in controls born at term. Thoracic gas volumes measured with a body plethysmograph were similar in all groups. Spirometry demonstrated reduced flow rates in both BPD and non‐BPD prematurely born children. The results suggest that some structural changes in lung tissues and airways persist for years in children who are born very preterm regardless of whether they develop BPD or not. Pediatr Pulmonol. 1996; 21:353–360.

Tracheobronchial rupture due to blunt chest trauma: a follow-up study

From 1970 to 1988, 9 patients were treated for tracheobronchial rupture arising from nonpenetrating thoracic trauma. All patients had dyspnea and pneumothorax. Four patients had rupture of the right main bronchus, 3 had rupture of the left main bronchus, 1 had rupture of the right intermediate bronchus, and 1 had rupture of the trachea. Four patients were operated on within 24 hours. Three of them had a massive air leak into the suction drainage and underwent thoracotomy. The fourth patient presented difficulties with endotracheal intubation and required a collar incision. Primary reconstruction was performed in all 4 patients. Five patients had a delay of nine to 89 days before operation. All of them had good primary healing but later developed dyspnea. Bronchoscopy revealed scar obstruction in all 5. The stenosed segment was resected in 4 patients at thoracotomy. The fifth patient, who had an intermediate bronchus rupture, underwent lobectomy. Seven patients were followed from 6 months to 18 years. One of them, who had a nine-day delay in treatment, needed further operation 6 months after the accident because of scar obstruction. The other 6 patients were interviewed, examined, and studied with spirometry, body plethysmography, bronchoscopy, and bronchography. In these 6 patients no stricture was seen, and there was no reduced pulmonary function due to the rupture even when operation was delayed.

Increased oxidative stress in asymptomatic current chronic smokers and GOLD stage 0 COPD

BackgroundChronic obstructive pulmonary disease (COPD) is associated with increased oxidative and nitrosative stress. The aim of our study was to assess the importance of these factors in the airways of healthy smokers and symptomatic smokers without airway obstruction, i.e. individuals with GOLD stage 0 COPD.MethodsExhaled NO (FENO) and induced sputum samples were collected from 22 current smokers (13 healthy smokers without any respiratory symptoms and 9 with symptoms i.e. stage 0 COPD) and 22 healthy age-matched non-smokers (11 never smokers and 11 ex-smokers). Sputum cell differential counts, and expressions of inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE) were analysed from cytospins by immunocytochemistry. Eosinophil cationic protein (ECP) and lactoferrin were measured from sputum supernatants by ELISA.ResultsFENO was significantly decreased in smokers, mean (SD) 11.0 (6.7) ppb, compared to non-smokers, 22.9 (10.0), p < 0.0001. Induced sputum showed increased levels of neutrophils (p = 0.01) and elevated numbers of iNOS (p = 0.004), MPO (p = 0.003), nitrotyrosine (p = 0.003), and 4-HNE (p = 0.03) positive cells in smokers when compared to non-smokers. Sputum lactoferrin levels were also higher in smokers than in non-smokers (p = 0.02). Furthermore, we noted four negative correlations between FENO and 1) total neutrophils (r = -0.367, p = 0.02), 2) positive cells for iNOS (r = -0.503, p = 0.005), 3) MPO (r = -0.547, p = 0.008), and 4) nitrotyrosine (r = -0.424, p = 0.03). However, no major differences were found between never smokers and ex-smokers or between healthy smokers and stage 0 COPD patients.ConclusionOur results clearly indicate that several markers of oxidative/nitrosative stress are increased in current cigarette smokers compared to non-smokers and no major differences can be observed in these biomarkers between non-symptomatic smokers and subjects with GOLD stage 0 COPD.