Pekka Malmberg

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.

Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study)

Objective: To compare the effect of inhaled budesonide given daily or as-needed on mild persistent childhood asthma. Patients, design and interventions: 176 children aged 5–10 years with newly detected asthma were randomly assigned to three treatment groups: (1) continuous budesonide (400 μg twice daily for 1 month, 200 μg twice daily for months 2–6, 100 μg twice daily for months 7–18); (2) budesonide, identical treatment to group 1 during months 1–6, then budesonide for exacerbations as needed for months 7–18; and (3) disodium cromoglycate (DSCG) 10 mg three times daily for months 1–18. Exacerbations were treated with budesonide 400 μg twice daily for 2 weeks. Main outcome measures: Lung function, the number of exacerbations and growth. Results: Compared with DSCG the initial regular budesonide treatment resulted in a significantly improved lung function, fewer exacerbations and a small but significant decline in growth velocity. After 18 months, however, the lung function improvements did not differ between the groups. During months 7–18, patients receiving continuous budesonide treatment had significantly fewer exacerbations (mean 0.97), compared with 1.69 in group 2 and 1.58 in group 3. The number of asthma-free days did not differ between regular and intermittent budesonide treatment. Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed. The latter was associated with catch-up growth. Conclusions: Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed. The dose of ICS could be reduced as soon as asthma is controlled. Some children do not seem to need continuous ICS treatment.

Mechanisms of asthma in Olympic athletes – practical implications

Athletes’ symptoms may only occur in extreme conditions, which are far from normal. Exercise may increase ventilation up to 200 l/min for short periods in speed and power athletes, and for longer periods in endurance athletes such as swimmers and cross‐country skiers. Increasing proportions of young athletes are atopic, i.e. they show signs of IgE‐mediated allergy which is, along with the sport event (endurance sport), a major risk factor for asthma and respiratory symptoms. Mechanisms in the etiology and clinical phenotypes vary between disciplines and individuals, and it may be an oversimplification to discuss athlete’s asthma as a distinct and unambiguous disease. Nevertheless, the experience on Finnish Olympic athletes suggests at least two different clinical phenotypes, which may reflect different underlying mechanisms. The pattern of ‘classical asthma’ is characterized by early onset childhood asthma, methacholine responsiveness, atopy and signs of eosinophilic airway inflammation, reflected by increased exhaled nitric oxide levels. Another distinct phenotype includes late onset symptoms (during sports career), bronchial responsiveness to eucapnic hyperventilation test, but not necessarily to inhaled methacholine, and a variable association with atopic markers and nitric oxide. A mixed type of eosinophilic and neutrophilic airway inflammation seems to affect especially swimmers, ice‐hockey players, and cross‐country skiers. The inflammation may represent a multifactorial trauma, in which both allergic and irritant mechanisms play a role. There is a significant problem of both under‐ and overdiagnosing asthma in athletes and the need for objective testing is emphasized. Follow‐up studies are needed to assess the temporal relationship between asthma and competitive sporting, taking better into account individual disposition, environmental factors (exposure), intensity of training and potential confounders.

Airway inflammation in probiotic-treated children at 5 years

To cite this article: Kukkonen AK, Kuitunen M, Savilahti E, Pelkonen A, Malmberg P, Mäkelä M. Airway inflammation in probiotic‐treated children at 5 years. Pediatr Allergy and Immunol 2011; 22: 249–251.

Efficacy of prednisolone in children hospitalized for recurrent wheezing

Data on the efficacy of corticosteroids on respiratory picornavirus‐induced wheezing are limited. To determine whether prednisolone is effective in rhinovirus‐ or enterovirus‐induced recurrent wheezing, we conducted a controlled trial comparing oral prednisolone (2 mg/kg/day in three divided doses for 3 days) with placebo in hospitalized wheezing children and studied post hoc virus‐specific efficacy in early wheezing (<3 episodes, reported elsewhere) and in recurrent wheezing (≥3 episodes). Virus‐negative children where excluded. Our primary endpoint was the time until children were ready for discharge. Secondary endpoints included oxygen saturation and exhaled nitric oxide during hospitalization, duration of symptoms, blood eosinophil count, and impulse oscillometry 2 wk after discharge, and occurrence of relapses during the following 2 months. Virus‐specific effects were analyzed with interaction analysis in a multivariate regression model. During the study period, 661 patients were hospitalized, 293 randomized, and 59 were accepted in this analysis (mean age 2.6 yr, s.d. 1.3). Prednisolone did not significantly decrease the time until ready for discharge in all patients (prednisolone vs. placebo, medians, 18 vs. 24 h, p = 0.11). However, prednisolone decreased the time until ready for discharge in children with picornavirus infection (respectively, 12 vs. 24 h, p = 0.0022) and more specifically, in children with enterovirus infection (6 vs. 35 h, p = 0.0007). In the secondary endpoints, prednisolone decreased the duration of cough and dyspnea in rhinovirus‐affected children (p = 0.033 for both). Prospectively designed clinical trial is needed to test the hypothesis that prednisolone reduces symptoms in picornavirus‐affected wheezing children.

Respiratory symptoms, bronchial hyper‐responsiveness, and eosinophilic airway inflammation in patients with moderate‐to‐severe atopic dermatitis

Background Patients with atopic dermatitis (AD) often have symptoms suggestive of asthma or rhinitis. The prevalence and signs of respiratory disease in AD patients have been studied to a limited extent.

Can We Use Portable Nitric Oxide Analyzer in Young Children

Management of asthma could be improved by measuring exhaled nitric oxide (FENO). Portable hand‐held FENO analyzer (NIOX MINO) is practical and small and could be used also in the primary care office. It has demonstrated good repeatability and correlation with stationary device (NIOX) in adults and school aged children, but so far there have been no reports on young children. The aim of this study was to compare conventional chemiluminescence device (NIOX) with a hand‐held electrochemical device (NIOX MINO) in young children.

Vascular laboratory for the surgeon

The introduction of a noninvasive vascular laboratory emerged from the need for more accurate differential diagnosis, localization of disease, measurement of severity, and documentation of progression of occlusive arterial disease and efficacy of treatment. Plethysmographic and Doppler techniques have been the cornerstones in the development of noninvasive studies. Our vascular laboratory experience during 1977–1994 includes 36,573 examinations performed on 19,646 patients. Occlusive arterial disease of the lower limb was evaluated by 7408 complete lower limb examinations, of which 4939 included also a treadmill exercise test, 4539 toe pressure measurements, and 10,585 follow-up examinations. Altogether, 9102 miscellaneous examinations included ambulatory ECG and systemic blood pressure monitoring, assessment of limb viability by tcpO2, Laser Doppler flowmetry and skin perfusion pressure measurement, as well as upper extremity studies, among others. Although new techniques were introduced and tested during the years, the routine examinations have remained rather simple. Workup for claudication contains a structured questionnaire, segmental pressures and plethysmographic evaluation, and exercise test on treadmill, whereas diabetes and suspicion of CLI also necessitate toe pressures. Diabetic patients and those evaluated for aortic surgery also undergo ambulatory or stress test ECG monitoring. Carotid patients are noninvasively assessed by Duplex in the Radiological Department. A vascular laboratory managed by the vascular surgeon serves surgical needs well, as the tests can be tailor made to specifically answer relevant clinical questions.

Nonlinear Local Projection Filter for Impedance Pneumography

The ability of impedance pneumography (IP) for recording tidal flow during long periods of free breathing make it a promising tool for assessing temporal complexity of respiration. However, techniques quantifying complexity may be sensitive to the noise in the IP signal resulting from the current processing method. A nonlinear local projection filter (NLPF) is presented as the solution to the current linear processing method, failing to reduce noise without distorting the flow signal. Current and proposed NLPF methods were applied to and existing data set of raw IP recorded in 21 infants during a methacholine challenge test. Methods’ performance was compared in a battery of test using mouth flow as a reference. NLPF achieved lower sample-by-sample error, and higher frequency attenuation, while linearity with mouth flow was maintained. Therefore, we concluded that NLPF superiorly reduces noise without distorting respiratory information.

Spirometry-adjusted fraction of exhaled nitric oxide increases accuracy for assessment of asthma control in children

Spirometry and exhaled nitric oxide are two important complimentary tools to identify and assess asthma control in children. We aimed to determine the ability of a new suggested spirometry‐adjusted fraction of exhaled nitric oxide (NO) index in doing that. A random sample of 1602 schoolchildren were screened by a health questionnaire, skin prick tests, spirometry with bronchodilation and exhaled NO. A total of 662 children were included with median (IQR) exhaled NO 11(14) ppb. Receiver operating characteristic (ROC) curves using exhaled NO equations from Malmberg, Kovesi and Buchvald, and spirometry‐adjusted fraction of exhaled NO values were applied to identify asthmatic children and uncontrolled asthma. Receiver operating characteristic (ROC) curves failed to identify asthmatic children (all AUC < 0.700). Spirometry‐adjusted fraction of exhaled NO/FEV1 (AUC = 0.712; P = .010) and NO/FEF25%‐75% (AUC = 0.735 P = .004) had a fair and increased ability to identify uncontrolled disease compared with exhaled NO (AUC = 0.707; P = .011) or the Malmberg equation (AUC = 0.701; P = .014). Sensitivity and specificity identifying non‐controlled asthma were 59% and 81%, respectively, for the cut‐off value of 9.7 ppb/L for exhaled NO/FEV1, and 40% and 100% for 15.7 ppb/L/s for exhaled NO/FEF25%‐75%. Exhaled NO did not allow to identify childhood asthma. Spirometry‐adjusted fraction of exhaled NO performed better‐assessing asthma control in children. Thus, although more validation studies are needed, we suggest its use in epidemiological studies to assess asthma control.