The Visual Analog Scale detects exercise-induced bronchoconstriction in children with asthma.

Objective: Exercise-induced bronchoconstriction (EIB) is a specific morbidity of childhood asthma and an important sign of uncontrolled asthma. The occurrence of EIB is insufficiently identified by the Childhood Asthma Control Test (C-ACT) and Asthma Control Test (ACT). This study aimed to (1) evaluate the Visual Analog Scale (VAS) for dyspnea as a tool to detect EIB in asthmatic children and (2) assess the value of combining (C-)ACT outcomes with VAS scores. Methods: We measured EIB in 75 asthmatic children (mean age 10.8 years) with a standardized exercise challenge test (ECT) performed in cold and dry air. Children and parents reported VAS dyspnea scores before and after the ECT. Asthma control was assessed by the (C-)ACT. Results: Changes in VAS scores (ΔVAS) of children and parents correlated moderately with fall in forced expiratory volume in 1 second (FEV1), respectively rs=0.57 (p < .001) and rs=0.58 (p < .001). At a ΔVAS cutoff value of ≥3 in children, sensitivity and specificity for EIB were 80% and 79% (AUC 0.82). Out of 38 children diagnosed with EIB, 37 had a (C-)ACT score of ≤19 and/or a ΔVAS of ≥3, corresponding with a sensitivity of 97% and a negative predictive value of 96%. Conclusion: This study shows that the VAS could be an effective additional tool for diagnosing EIB in children. A reported difference in VAS scores of ≥3 after a standardized ECT combined with low (C-)ACT scores was highly effective in detecting and excluding EIB.

WEARCON: wearable home monitoring in children with asthma reveals a strong association with hospital based assessment of asthma control.

BACKGROUND: Asthma is one of the most common chronic diseases in childhood. Regular follow-up of physiological parameters in the home setting, in relation to asthma symptoms, can provide complementary quantitative insights into the dynamics of the asthma status. Despite considerable interest in asthma home-monitoring in children, there is a paucity of scientific evidence, especially on multi-parameter monitoring approaches. Therefore, the aim of this study is to investigate whether asthma control can be accurately assessed in the home situation by combining parameters from respiratory physiology sensors. METHODS: Sixty asthmatic and thirty non-asthmatic children were enrolled in the observational WEARCON-study. Asthma control was assessed according to GINA guidelines by the paediatrician. All children were also evaluated during a 2-week home-monitoring period with wearable devices; a physical activity tracker, a handheld spirometer, smart inhalers, and an ambulatory electrocardiography device to monitor heart and respiratory rate. Multiple logistic regression analysis was used to determine which diagnostic measures were associated with asthma control. RESULTS: 24 of the 27 uncontrolled asthmatic children and 29 of the 32 controlled asthmatic children could be accurately identified with this model. The final model showed that a larger variation in pre-exercise lung function (OR = 1.34 95%-CI 1.07-1.68), an earlier wake-up-time (OR = 1.05 95%-CI 1.01-1.10), more reliever use (OR = 1.11 95%-CI 1.03-1.19) and a longer respiratory rate recovery time (OR = 1.12 95%-CI 1.05-1.20) were significant contributors to the probability of having uncontrolled asthma. CONCLUSIONS: Home-monitoring of physiological parameters correlates with paediatrician assessed asthma control. The constructed multivariate model identifies 88.9% of all uncontrolled asthmatic children, indicating a high potential for monitoring of asthma control. This may allow healthcare professionals to assess asthma control at home. TRIAL REGISTRATION: Netherlands Trail Register, NL6087 . Registered 14 February 2017.

The impact of discussing exercise test results of young asthmatic children on adherence to maintenance medication.

OBJECTIVE: Parents' awareness of their child's asthma may improve by discussing an exercise challenge test (ECT) result with them. We investigated the influence of discussing an ECT result with parents on adherence to inhaled maintenance medication, parental illness perceptions and medication beliefs in young asthmatic children. METHODS: A total of 79 children, 4-7 years old and enrolled in our standard comprehensive asthma care program, performed an ECT to assess exercise induced bronchoconstriction (EIB). The result of the ECT was immediately discussed with the parents. Median medication adherence level was measured with electronic medication loggers from six weeks before the ECT till six weeks afterwards. Parental beliefs about medicines and illness perceptions were measured with the Beliefs about Medicines Questionnaire (BMQ) and the Brief Illness Perceptions Questionnaire (B-IPQ). RESULTS: The median baseline adherence level was high (83%) and showed a small significant decline after the ECT. There was no significant difference in the decrease in median adherence level between the children with or without EIB. Most parents (82.1%) showed a positive necessity-concern ratio at baseline, as measured with the BMQ. There was no clinical relevant change in medication concerns and necessity scores or in illness perceptions. CONCLUSION: Discussing ECT results with parents does not modify median adherence levels to inhaled maintenance medication nor medication beliefs of highly adherent young asthmatic children who are already enrolled in a comprehensive asthma care program.

Volatile organic breath components and exercise induced bronchoconstriction in asthmatic children.

INTRODUCTION: Asthma is one of the most common chronic diseases in childhood and is generally characterized by exercise induced bronchoconstriction (EIB). Assessing EIB is time consuming and expensive as it requires a fully equipped pulmonary function laboratory. Analysis of volatile organic compounds (VOCs) in breath is a novel technique for examining biomarkers which may associate with asthma features. The aim of this pilot study was to identify potential markers in the relationship between EIB and VOCs. METHODS: Children between four and 14 years old were asked to provide a breath sample prior to undergoing an exercise challenge test to assess for EIB. RESULTS: Breath samples were collected and analyzed in 46 asthmatic children, 21 with EIB and 25 without EIB (NO-EIB). Molecular features (MFs) were not significantly different between EIB and NO-EIB controls. 29 of the 46 children were corticosteroid naïve, 10 with EIB and 13 without. In the corticosteroid naïve group EIB was associated with increased MF23 and MF14 in the lower breath sample (p-value < 0.05). CONCLUSION: This pilot study shows that EIB was related to an increased MF14 and MF23 in corticosteroid naïve children. The tentative identities of these compounds are octanal and dodecane/tetradecane respectively. These candidate biomarkers have a potential to enable non-invasive diagnosis of EIB in steroid-naïve children. Trial registration This study is registered in the Netherlands trial register (trial no. NL6087) at 14 February 2017.

Does exercise-induced bronchoconstriction affect physical activity patterns in asthmatic children?

Exercise-induced bronchoconstriction (EIB) is a sign of uncontrolled childhood asthma and classically occurs after exercise. Recent research shows that EIB frequently starts during exercise, called breakthrough-EIB (BT-EIB). It is unknown whether this more severe type of EIB forces children to adapt their physical activity (PA) pattern in daily life. Therefore, this pilot study aims to investigate daily life PA (amount, intensity, duration, and distribution) in children with BT-EIB, 'classic' EIB, and without EIB. A Fitbit Zip activity tracker was used for one week to objectively measure daily life PA at one-minute intervals. Thirty asthmatic children participated. Children with BT-EIB were less physically active compared to children without EIB (respectively 7994 and 11,444 steps/day, p = .02). Children with BT-EIB showed less moderate-to-vigorous PA compared to the children without (respectively 117 and 170 minutes/day, p = .02). Children with EIB (both BT and classic) had significant shorter bouts of activity and a less stretched distribution of bout lengths compared to the non-EIB group (all p < .05). These results emphasize a marked association between EIB severity and PA patterns in daily life, stressing the need for a thorough clinical evaluation of exercise-induced symptoms in childhood asthma.

Use of anti-depressants and the risk of fracture of the hip or femur.

SUMMARY: Anti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients. INTRODUCTION: Anti-depressants are known to have serious side effects. We examined the association between the use of anti-depressants and the risk of hip/femur fractures with a special focus on the relation with the degree of 5-hydroxytryptamine transporter (5-HTT) inhibition and the duration of use. METHODS: A case-control study was conducted within the Dutch PHARMO-RLS database. Cases (n = 6,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (n = 26341) were matched by age, gender and geographic region. RESULTS: The risk of hip/femur fracture increased with current use of SSRIs (adjusted odds ratio (OR(adj)) 2.35 [95% confidence interval (CI) 1.94-2.84]) and TCAs (ORadj 1.76 [95% CI 1.45-2.15]). The risk of hip/femur fracture declined rapidly after discontinuation of use. The risk of hip/femur fracture increased as the degree of 5-HTT inhibition of all anti-depressants increased from OR(adj) 1.64 [95% CI 1.14-2.35] for drugs with low 5-HTT inhibition to OR(adj) 2.31 [95% CI 1.94-2.76] for those with high 5-HTT inhibiting properties. CONCLUSION: Current use of both SSRIs and TCAs increase hip/femur fracture risk. Further studies are needed to elucidate the mechanistic pathways and the relation with the underlying pathophysiology. Until then, the elevated fracture risk should be considered when prescribing anti-depressants.

Distribution and Prevalence of Parasitic Nematodes of Cowpea (Vigna unguiculata) in Burkina Faso.

A comprehensive survey of the plant parasitic nematodes associated with cowpea (Vigna unguiculata) production fields was carried out in the three primary agro-climatic zones of Burkina Faso in West Africa. Across the three zones, a total of 109 samples were collected from the farms of 32 villages to provide a representative coverage of the cowpea production areas. Samples of rhizosphere soil and samples of roots from actively growing cowpea plants were collected during mid- to late-season. Twelve plant-parasitic nematode genera were identified, of which six appeared to have significant parasitic potential on cowpea based on their frequency and abundance. These included Helicotylenchus, Meloidogyne, Pratylenchus, Scutellonema, Telotylenchus, and Tylenchorhynchus. Criconemella and Rotylenchulus also had significant levels of abundance and frequency, respectively. Of the primary genera, Meloidogyne, Pratylenchus, and Scutellonema contained species which are known or suspected to cause losses of cowpea yield in other parts of the world. According to the prevalence and distribution of these genera in Burkina Faso, their potential for damage to cowpea increased from the dry Sahelian semi-desert zone in the north (annual rainfall < 600 mm/year), through the north-central Soudanian zone (annual rainfall of 600-800 mm/year), to the wet Soudanian zone (annual rainfall ≥ 1000 mm) in the more humid south-western region of the country. This distribution trend was particularly apparent for the endoparasitic nematode Meloidogyne and the migratory endoparasite Pratylenchus.

Can Pediatricians Assess Exercise-Induced Bronchoconstriction From Post-exercise Videos?

Objective: Exercise-induced bronchoconstriction (EIB) is a highly prevalent morbidity of childhood asthma and defined by a transient narrowing of the airways during or after physical exercise. An exercise challenge test (ECT) is the reference standard for the diagnosis of EIB. Video evaluation of EIB symptoms could be a practical alternative for the assessment of EIB. We studied the ability of pediatricians to assess EIB from post-exercise videos. Methods: A clinical assessment was performed in 20 asthmatic children (mean age 11.6 years) and EIB was measured with a standardized ECT performed in cold, dry air. EIB was defined as a fall in forced expiratory volume in 1 s (FEV1) of ≥10% post-exercise. Children were filmed before and after exercise in frontal position and bare chested. The clinical assessment results and videos were shown to 20 pediatricians (mean experience 14.4 years). Each assessed EIB severity in 5 random children providing 100 assessments, scored on a continuous rating scale (0-10) and in severity classifications (no, mild, moderate, severe) using a scoring list including physical asthma symptoms. Correlations between predicted scores and objective scores were calculated with Spearman's rho and Cohen's Kappa. A generalized linear model was used to assess the relationship between physical symptoms and fall in FEV1. Results: Median fall in FEV1 after exercise was 15.1% (IQR 1.2-65.1). Pediatricians detected EIB with a sensitivity of 78% (95% CI 66-87%) and a specificity of 40% (95% CI 27-55%). The positive predictive value for a pediatricians' diagnosis of EIB was 61% (95% CI 50-72%). The negative predictive value was 60% (95% CI 42-76%). The agreement between predicted EIB severity classifications and the validated classifications based on the ECT's, was fair [Kappa = 0.36 (95% CI 0.23-0.48)]. The correlation between predicted EIB severity scored on a continuous rating scale and fall in FEV1 after exercise was weak (rs = 0.39, p < 0.001). Independent predictive variables for fall in FEV1 were wheezing (-11%), supraclavicular retractions (-8.4%) and a prolonged expiratory phase (-8.8%). Conclusion: The ability of pediatricians to assess EIB from post-exercise videos is fair at best, implicating that standardized ECT's are still vital in the assessment of EIB.

[Acne vulgaris: endocrine aspects]. / Acne vulgaris: endocriene aspecten.

Androgens play an important part in the development of acne vulgaris. Androgen levels in patients with acne are higher than those in controls and people with the androgen insensitivity syndrome do not develop acne. Local factors other than androgen plasma levels, also play a part in the development of acne. The skin contains enzymes that convert precursor hormones to the more potent androgens such as testosterone and dihydrotestosterone. Androgen synthesis can therefore be regulated locally. The effects of androgens on the skin are the result of circulating androgens and enzyme activity in local tissues and androgen receptors. Acne is a clinical manifestation of some endocrine diseases. The polycystic ovary syndrome has the highest prevalence. In women with acne that persists after puberty, in 10-200% of cases polycystic ovary syndrome is later diagnosed. The mechanism of hormonal anti-acne therapy may work by blocking the androgen-production (oestrogens) or by blocking the androgen receptor (cyproterone, spironolactone).

Intracellular K+, Na+ and Cl- concentrations and membrane potential in human monocytes.

The relationship between the resting membrane potential and the intracellular ionic concentrations in human monocytes was investigated. Cell volume, cell water content, and amount of intracellular K+, Na+, and Cl- were measured to determine the intracellular concentrations of K+ (Ki), Na+ (Nai) and Cl- (Cli) of monocytes, and of lymphocytes and neutrophils. Values found for monocytes were similar to those for neutrophils, i.e., cell volumes were 346 and 345 micron3, respectively, cell water content 78%, and Ki, 128 and 125, Nai, 24 and 26, and Cli, 102 and 103 mmol/l cell water, respectively. Lymphocytes, however, had different values: 181 micron3 cell volume, 77% cell water content, and for Ki, Nai, and Cli, 165, 37, and 91 mmol/l cell water, respectively. The resting membrane potential of cultured human monocytes (range -30 to -40 mV), determined by measurement of the peak potential occurring within the first milliseconds after microelectrode entry, was most dependent on extracellular K+, followed by Cl-, and Na+. The membrane permeability ratio of Cl- to K+ was estimated by use of the constant field equation to be 0.23 (range 0.22 to 0.30).

Reversibility of pulmonary function after inhaling salbutamol in different doses and body postures in asthmatic children.

RATIONALE: Pulmonary medication is often delivered in the form of medical aerosols designed for inhalation. Recently, breath actuated inhalers (BAI's) gained popularity as they can be used without spacers. A major drawback of BAI's is the impaction in the upper airway. Stretching the upper airway by a forward leaning body posture with the neck extended ("sniffing position") during inhalation may reduce upper airway impaction and improve pulmonary deposition. Aim of this study was to investigate the reversibility of lung function with different doses salbutamol inhaled with a BAI in the forward leaning posture compared to the standard posture in asthmatic children. METHODS: 22 clinically stable asthmatic children, 5-14 years old, performed four reversibility measurements. Children inhaled 200 µg or 400 µg salbutamol with a BAI in the standard or in the forward leaning posture with the neck extended in a randomized single-blinded cross-over design. RESULTS: Reversibility of lung function after inhaling salbutamol in the forward leaning posture was not significantly different compared to inhalation in the standard posture. Mean FEV1 reversibility was significantly greater after inhaling 400 µg salbutamol compared to 200 µg salbutamol in the standard posture (9.4% ± 9.5% versus 4.5% ± 7.5%, difference 4.9% (95CI 0.9; 9.0%); p = 0.021). CONCLUSION: In clinically stable asthmatic children, inhalation of salbutamol with a BAI in a forward leaning posture does not increase reversibility of lung function. Inhalation of 400 µg compared to 200 µg salbutamol with a BAI does improve reversibility.

Reversibility after inhaling salbutamol in different body postures in asthmatic children: a pilot study.

RATIONALE: Pulmonary medication is mostly delivered in the form of medical aerosols to minimize systemic side effects. A major drawback of inhaled medication is that the majority of inhaled particles impacts in the oropharynx at the sharp bend of the airway. Stretching the airway by a forward leaning body posture with the neck extended ("sniffing position") may improve pulmonary deposition and clinical effects. METHODS: 41 asthmatic children who were planned for standard reversibility testing at the pulmonary function lab, alternately inhaled 200 µgr salbutamol with an Autohaler(®) in the standard or in the forward leaning body posture. Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), Peak Expiratory Flow (PEF), Mean Expiratory Flow at 25% of vital capacity (MEF25) and Mean Expiratory Flow at 75% of vital capacity (MEF75) were analysed. RESULTS: The children in the forward leaning body posture group showed a significantly higher mean FEV1 reversibility than the control group after inhalation of 200 µgr salbutamol (10.2% versus 4.1%, p = 0.019). Additionally, mean MEF75 was significantly more reversible in the forward leaning body posture group versus the standard body posture group (32.2% resp. 8.9%, p = 0.013). CONCLUSION: This pilot study showed a higher reversibility of FEV1 and MEF75 after inhaling salbutamol in a forward leaning body posture compared to the standard body posture in asthmatic children. This suggests that pulmonary effects of salbutamol can be improved by inhaling in a forward leaning body posture with the neck extended. This effect is possibly due to a higher pulmonary deposition of salbutamol and should be confirmed in a randomized controlled trial.

Protective effect of a low single dose inhaled steroid against exercise induced bronchoconstriction.

OBJECTIVE: Daily use of inhaled corticosteroids (ICS) reduces exercise induced bronchoconstriction (EIB) in asthmatic children. A high single dose of ICS also provided acute protection against EIB. Objective of this study is to investigate whether a low single dose of ICS offers protection against EIB in asthmatic children. METHODS: 31 Mild asthmatic children not currently treated with inhaled corticosteroids, 5-16 years, with EIB (fall in FEV0.5/1 ≥ 13%) were included in a prospective intervention study. They performed two ECT's within 2 weeks. Four hours before the second test children inhaled 200 µg beclomethasone-dipropionate (BDP) with a breath-actuated inhaler (BAI). RESULTS: The median fall in FEV0.5/1 after 200 µg BDP was significantly reduced from 30.9% at baseline to 16.0% (P < 0.001). Twenty children (64.5%) showed a good response to 200 µg BDP (≥ 50% decrease in fall of FEV0.5/1), while 8 children showed a moderate response (25-50%), and three children showed no response at all (< 25%). CONCLUSION: A low single dose ICS offers acute protection against EIB in the majority of asthmatic children not currently treated with inhaled corticosteroids.

Effects of monomethylfumarate on human granulocytes.

Monomethylfumarate (MMF) is the most active metabolite of the new antipsoriasis drug Fumaderm. Because granulocytes play an important role in the pathophysiology of psoriasis, the effects of this drug on the functional activities of these cells were investigated. MMF stimulated polarization and elastase release, and enhanced the intracellular killing of bacteria by granulocytes. This compound suppressed the formyl-Met-Nle-Phe (FMLP)-stimulated respiratory burst in these cells. MMF and dimethylfumarate but not its stereoisomer dimethylmaleate, fumaric acid, or dimethylmalate stimulated polarization of and elastase release by granulocytes, indicating that methylated fumarate derivatives interact with granulocytes in a specific fashion. MMF did not affect the binding of formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein isothiocyanate to the FMLP receptor on granulocytes. This compound induced an increase in the intracellular Ca++ ([Ca++]i) and cyclic adenosine monophsphate concentration. The agonistic effects of MMF on granulocytes are thought to be mediated by the rise in the [Ca++]i and the antagonistic effects by the increase in the cyclic adenosine monophosphate concentration. These effects of MMF on granulocytes may in part explain the beneficial action of methylated fumarate derivatives on psoriatic skin lesions.

Red blood cell sodium in the DOCA hypertensive pig.

The influence of deoxycorticosterone acetate (DOCA) on the sodium content of the red blood cell was determined in the pig. DOCA (100 mg/kg), impregnated in Silastic, was implanted subcutaneously (s.c.) in six male pigs; seven additional pigs received Silastic implants without the DOCA. Those receiving DOCA had an increase in mean arterial pressure (MAP) that was significant in 48 hours and reached a plateau that was 24 mm Hg greater than that of the controls after 15 days. These animals also developed hypokalemia and polydipsia over approximately the same time course. Red blood cell sodium content increased in DOCA-treated pigs 24 hours after implant (5.57 +/- 0.17 vs 5.23 +/- 0.05, mEq/liter cells). The sodium content continued to rise, reaching a plateau 28% above that of control value by the 5th postimplant day (6.37 +/- 0.40 mEq/liter cells). In vitro tests of possible mechanisms that might have caused the in vivo increase in red blood cell sodium content gave the following results: 1) Incubations of red blood cells in a physiological salt solution (PSS) containing deoxycorticosterone failed to cause an increase in cell sodium content. 2) No ouabain-like factor was demonstrated in plasma from the DOCA hypertensive pigs. 3) An elevation in bicarbonate concentration in the PSS caused an increase in red blood cell sodium content. 4) A decrease in potassium concentration in the PSS also caused an increase in red blood cell sodium content.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional absence of extraocular photoreception in hamster circadian rhythm entrainment.

The mammalian circadian pacemaker is entrainable by light via the retina. The putative role of extraocular light perception was investigated in blinded hamsters. These animals were shaved and exposed to a light-emitting pad for either 30 min or 3 h. The absence of any phase-shifting effects on wheel running activity rhythms indicates that extraocular light perception plays no functional role in photic entrainment of the circadian pacemaker in the hamster.

Effects of single-dose fluticasone on exercise-induced asthma in asthmatic children: a pilot study.

A single high dose of inhaled corticosteroid (ICS) can increase airway caliber in children with asthma attacks and laryngitis subglottica. Presumably the effect is due to the vasoconstrictive and antiedematous properties of topical steroids. Enlarged vessels have been suggested to play a role in the pathophysiology of exercise-induced bronchial obstruction (EIB). To investigate this, we evaluated the effect of a single high dose of fluticasone propionate (FP) on EIB in asthmatic children. Nine children aged 8-16 years with mild to moderate asthma were included. All children had a history of EIB, which was confirmed by an exercise test. None was taking ICS maintenance therapy. The children inhaled either a single dose of 1 mg FP or placebo on 2 separate days within 7-14 days. After inhalation, airway caliber (FEV(1)) was assessed for 4 hr before exercise. Then an exercise challenge was performed on a treadmill to assess EIB (% fall FEV(1)). A significant increase in FEV(1) was observed 1 hr after inhalation of FP compared to placebo. Response to exercise was expressed as maximal % fall in FEV(1) from baseline (% fall) and as area under the curve (AUC) of the 30-min time/response curve. The % fall FEV(1) after exercise and the AUC were significantly reduced when FP was inhaled compared to placebo inhalation (% fall 9.7% vs. 19.2%, respectively, P = 0.038 and AUC 92.0%.min vs. 205.7%.min, respectively, P = 0.03). There was considerable individual variability in reduction of EIB, with 5 out of 9 children having a clinically significant response. We conclude that a single high dose of inhaled FP has an acute protective effect on the bronchial response to exercise in a substantial proportion of asthmatic children.

[A cluster of lymphogranuloma venereum among homosexual men in Rotterdam with implications for other countries in Western Europe]. / Cluster van lymphogranuloma venereum onder homoseksuele mannen in Rotterdam, met grensoverschrijdende gevolgen.

In mid-December 2003, a cluster of 15 cases of lymphogranuloma venereum (LGV) among male homosexuals was reported to the Municipal Health Service in Rotterdam by the Erasmus Medical Centre's outpatient clinic for sexually transmitted infections (STI). Most patients presented with proctitis and some with constipation. All were Caucasian and between 26 and 48 years of age. Thirteen of them were HIV-positive and eight had a concomitant STI. All men reported having had unprotected insertive and receptive anal sexual contact. Many sexual contacts were anonymous and were reported to have taken place in Germany, Belgium, the United Kingdom and France. This outbreak of LGV may extend through a large part of western Europe. In view of the patients' international contacts, international warnings and alertness are needed. Concerted action of professionals in infectious disease control and curative care is called for.

Effects of a single dose inhaled corticosteroid on the dynamics of airway obstruction after exercise.

RATIONALE: Exercise-induced bronchoconstriction (EIB) is defined as a transient narrowing of the airways induced by exercise. Repetitive measurements of spirometric parameters, such as FEV(1) and expiratory flows, and forced oscillation technique (FOT) measurements can be used to analyze the dynamics of EIB. A single high dose of fluticasone propionate (FP) protects against EIB. The aim of the study was to analyze the effect of FP on the dynamics of exercise-induced airway narrowing as measured with FOT and spirometry. METHODS: Twelve children performed an exercise challenge on 2 separate days, 4 hr after inhalation of 1 mg FP (pressurized metered dose inhaler) or a placebo. Before and after the exercise flow-volume loops as well as the FOT (frequency range: 4-32 Hz) were measured. RESULTS: The FEV(1) , and FEF(50) fell significantly after exercise within groups; the peak fall in FEV(1) after FP was significantly smaller than after placebo (respectively, 19.3 ± 14.6% and 29.2 ± 14.8%, P = 0.03, 95% CI: 0.9-18.8%). The fall in FEV(1) and FEF(50) peaked 3 min after exercise and showed a subsequent partial recovery. The fall in the FEV(1) /FVC ratio showed a later peak fall (12 min after exercise). The resistance increased while the reactance decreased significantly after exercise. FP significantly decreased the maximal increase in Rrs(6) when compared to the placebo (respectively 176.5 ± 59.1% and 201.0 ± 63.8%, P = 0.05, 95% CI: 0.5-48.7%). The maximal decrease in Xrs(6) was not significantly affected by FP (P = 0.06). CONCLUSION: Repetitive spirometric and FOT measurements after exercise show a rapid narrowing and steady recovery of the patency of the conducting airways, and indicate a delayed and prolonged recovery of the smaller airways. A single high dose of inhaled FP seems to employ its effect mainly in the conducting airways.

Pilot study: The effect of reducing treatment on exercise induced bronchoconstriction.

UNLABELLED: SUMMARY RATIONALE: Asthma therapy should be stepped up or stepped down in response to changes in asthma control. However, there is little evidence available on the optimal timing, sequence, and degree of medication reductions. In this study we analyzed clinically stable asthmatic children who underwent a medication reduction from a combination preparation consisting of an inhaled corticosteroid (ICS) and long acting beta2-agonist (LABA) to monotherapy with the same dose of the ICS. We hypothesized that the extent of exercise-induced bronchoconstriction (EIB) would not increase after the cessation of the LABA. METHODS: Nineteen children, aged 8-16 years, with clinically stable asthma, receiving LABA/ICS combination therapy, were analyzed in this open-label pilot study. Children performed an exercise challenge at baseline and 3 weeks after the medication reduction. Best values of spirometric measurements of the forced expiratory volume in 1 sec (FEV(1)) were used for statistical calculations. RESULTS: Maximum percent fall in FEV(1) was significantly lower after 3 weeks of ICS monotherapy (P = 0.03). Eight of 19 children had a >or=15% fall in FEV(1) after exercise at the initial exercise challenge. In this subgroup, maximum percent fall in FEV(1) after the medication reduction was significantly lower (P < 0.01), and in six children it decreased to <15%, indicating they no longer had EIB. CONCLUSION: In clinically stable asthmatic children on LABA/ICS combination therapy, the cessation of the LABA can reduce and in most cases abolish EIB.