Silvia Demoulin-Alexikova

Impact of Air Pollution on Age and Gender Related Increase in Cough Reflex Sensitivity of Healthy Children in Slovakia

Background: Numerous studies show higher cough reflex sensitivity (CRS) and cough outcomes in children compared to adults and in females compared to males. Despite close link that exists between cough and environment the potential influence of environmental air pollution on age- and gender -related differences in cough has not been studied yet. Purpose: The purpose of our study was to analyse whether the effects of exposure to environmental tobacco smoke (ETS) from parental smoking and PM10 from living in urban area are implied in age- and gender-related differences in cough outcomes of healthy, non-asthmatic children. Assessment of CRS using capsaicin and incidence of dry and wet cough was performed in 290 children (mean age 13.3 ± 2.6 years (138 females/152 males). Results: CRS was significantly higher in girls exposed to ETS [22.3 μmol/l (9.8–50.2 μmol/l)] compared to not exposed girls [79.9 μmol/l (56.4–112.2 μmol/l), p = 0.02] as well as compared to exposed boys [121.4 μmol/l (58.2–253.1 μmol/l), p = 0.01]. Incidence of dry cough lasting more than 3 weeks was significantly higher in exposed compared to not exposed girls. CRS was significantly higher in school-aged girls living in urban area [22.0 μmol/l (10.6–45.6 μmol/l)] compared to school-aged girls living in rural area [215.9 μmol/l (87.3–533.4 μmol/l); p = 0.003], as well as compared to teenage girls living in urban area [108.8 μmol/l (68.7–172.9 μmol/l); p = 0.007]. No CRS differences were found between urban and rural boys when controlled for age group. No CRS differences were found between school-aged and teenage boys when controlled for living area. Conclusions: Our results have shown that the effect of ETS on CRS was gender specific, linked to female gender and the effect of PM10 on CRS was both gender and age specific, related to female gender and school-age. We suggest that age and gender related differences in incidence of cough and CRS might be, at least partially, ascribed to the effect of environmental pollutants. The role of age and gender in the effect of air pollution on cough strongly suggest some interplay of development with biological and behavioral factors.

Lack of desensitization of the cough reflex in ovalbumin-sensitized rabbits during exercise

Introduction Cough is a major symptom of asthma frequently experienced during exercise but little is known about interactions between cough and exercise. The goal of our study was to clarify the potential modulation of the cough reflex (CR) by exercise in a spontaneously breathing anaesthetized animal model of airway eosinophilic inflammation. Materials & methods Ten ovalbumin (OVA) sensitized adult rabbits and 8 controls were studied. The ventilatory response to direct tracheal stimulation, performed both at rest and during exercise was determined to quantify the incidence and the sensitivity of the CR. Broncho-alveolar lavages (BAL) and cell counts were performed to assess the level of the airway inflammation following OVA-induced sensitization. Exercise was mimicked by Electrically induced hindlimb Muscular Contractions (EMC). Results Among 494 tracheal stimulations, 261 were performed at rest and 233 at exercise. OVA challenges in sensitized rabbits caused a significant increase in the percentage of eosinophils (p = 0.008) in BAL. EMC increased minute ventilation by 36% and 35% in OVA and control rabbits respectively, compared to rest values. The sensitivity of the CR decreased during exercise compared to baseline in control rabbits (p = 0.0313) while it remained unchanged in OVA rabbits. Conclusion The desensitization of the CR during exercise in control rabbits was abolished in OVA rabbits. The precise role of airway inflammation in this lack of CR desensitization needs to be further investigated but it might contribute to the exercise-induced cough in asthmatics.

Down-Regulation of Cough during Exercise Is Less Frequent in Healthy Children than Adults. Role of the Development and/or Atopy?

Cough is typically associated with physical activity in children with asthma, but the characteristics of the relationship between cough and exercise has not been established under physiological conditions. The aim of the study was to describe the effect of exercise on the reflex cough response elicited by a single breath of capsaicin in non-asthmatic children. A group of non-asthmatic adults was studied as reference. Thirty children and 29 adults were recruited. The cough reflex sensitivity to capsaicin was first determined to establish the dose that provokes 5 cough efforts (C5). The number of coughs elicited by C5 (NC5) was then compared at baseline and during a standardized submaximal treadmill exercise. Data are expressed as median (interquartile range). Children and adults showed a significant decrease in NC5 (respectively from 5.0 (4.0–6.0) to 2.5 (2.0–4.0), p < 0.0005 and from 6.0 (5.0–7.0) to 2.0 (0.0–3.0, p < 0.0005). During exercise, NC5 was observed to decrease in all adult subjects, but in only 24/30 children (80%, p = 0.02). A trend for a higher incidence of personal and familial atopy was observed in children that lacked cough down-regulation during exercise compared with other children. It is concluded that the cough reflex response to capsaicin is down regulated by exercise in both children and adults. The effect however is less consistently observed in the former. The difference may reflect maturation of descending inhibitory pathways of the cough reflex, but may also be associated to atopy. The data stress the importance of assessing the time relationship of cough and exercise in questionnaire studies of asthma.

Epinephrine but not vasopressin attenuates the airway response to anaphylactic shock in rats

ABSTRACT Purpose: The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm. Guidelines recommend epinephrine as first-line treatment. Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension. These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall. Aim of the Study: To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS. Materials and Methods: Thirty-two ovalbumin-sensitized rats were randomized into four groups: control (CON), AS without treatment (OVA), AS treated with epinephrine (EPI), and AS treated with AVP (AVP). Mean arterial pressure (MAP), respiratory resistance and elastance and microvascular leakage in the airways were measured. Results: All OVA rats died within 20 minutes following ovalbumin injection. Ovalbumin induced severe arterial hypotension and airway obstruction (221 ± 36 hPa.s.L−1 vs. vehicle 52 ± 8 hPa.s.L−1; p < 0.0001) associated with microvascular leakage distributed throughout the trachea, bronchi and intra-pulmonary airways. EPI and AVP extended survival time; EPI restored a higher level of MAP than AVP. Airway obstruction was attenuated by epinephrine (146 ± 19 hPa.s.L−1; p < 0.0001), but not by AVP (235 ± 58 hPa.s.L−1; p = 0.42). Conclusions: Epinephrine was superior to AVP for alleviating the airway response in a rat model of AS. When bronchospasm and severe arterial hypotension are present during AS, epinephrine should be the drug of choice.

Modulation of defensive airway reflexes during continuous positive airway pressure in the rabbit

Lung hyperinflation may alter the pattern of ventilatory reflexes in chronic respiratory disorders. The aim of the study was to test the effect of continuous positive airway pressure (CPAP) on ventilatory responses to mechanical stimulation of the trachea.

Expiratory Flow – Vital Capacity: Airway – Lung Dysanapsis in 7 Year Olds Born Very Preterm?

An index normalizing airway dimension for lung size derived from spirometry was found inversely correlated to lung size in school children born very preterm, indicating larger alveolar volumes draining into comparatively smaller airways. In contrast in children born full term the index was independent of lung size.

Maturation of Airway Defensive Reflexes Is Related to Development of Feeding Behavior during Growth in Rabbits

Introduction: Cough and expiration reflex are major lower airway defense mechanisms that have not been studied throughout development in relation with the feeding behavior. Aim: To describe airway defense reflexes evoked by mechanical stimulation of the trachea in developing rabbit pups. Material and Methods: Sixty one pups were allocated to 3 groups according to their feeding behavior: suckling (n = 22), weanling (n = 21) and weaning (n = 18) group. The incidence and sensitivity of defense reflexes triggered by mechanical tracheal stimulation were studied in anesthetized and tracheotomized animals. Data are expressed as median (25th to 75th percentile). Results: The overall incidence of defensive responses (cough and/or expiration reflex) was found to be significantly higher in suckling [100% (50–100%); p = 0.01] and weanling [75% (40–100%); p = 0.05] animals when compared to weaning ones [37.5% (0–75%)]. However, cough motor pattern accounted for only 29% (0–62%) of all defensive responses in suckling rabbits and its frequency was significantly lower in this group when compared with weanling [100%(50–100%); p = 0.006] or weaning group [62%(50–100%), p = 0.05]. In other word the expiration reflex was the dominant response in suckling animals. Conclusion: Incidence and motor pattern of defensive responses were found to be linked to the pup feeding behavior and the expiration reflex was the major response triggered in suckling pups. The results suggest that this reflex is especially fitted to occur during the coordinated swallowing - breathing fast activities of sucking.

Specific airway resistance in preschool children: why not panting after all?

Specific airway resistance (sRaw) is measured with minimal cooperation in the preschool child during tidal breathing [1]. Methodological difficulties have been encountered in modern plethysmographs when the warming and humidification of the inspired gas [2] are replaced by numerical algorithms to eliminate the thermo hygrometric artefact [1, 3, 4]. Measuring sRaw during panting [5] had been dismissed in preschool children based on the assumption that the ventilatory manoeuvre would be difficult to perform and standardise. The feasibility of such an assumption, however, has not been verified. Therefore, the aim of this study was to assess the feasibility of measuring sRaw during panting in preschool children with asthma and compare the outcome with the tidal breathing method. Specific airway resistance may be measured in preschool children during routine lung function http://ow.ly/pvxr3034Bo8

A Calibration Device to Compare Body Plethysmographs Among Pediatric Lung Function Laboratories

Multi-center studies in specific airway resistance have shown significant inter laboratory variability. Comparison of plethysmographic equipment using a lung model easily transportable from one site to another should be of help to international normative studies. A resistor made of parallel capillary tubes – insuring adequate linearity within 1 L/sec – was connected to a glass bottle. Thermal time constants were measured while the bottle was empty and while stuffed with steel wool. In the latter, isothermal condition was estimated to occur only at very low frequency (around 0.01 Hz) and gas compression was polytropic up to 0.6 Hz. With the empty analog, adiabatic gas compression was estimated to occur at frequencies ≥0.2 Hz, and more accurate volume estimation was obtained. The empty analog volume and specific resistance measured in a body plethysmograph on different days indicated within 5% accuracy as well as intersession repeatability. It is concluded that a physical analog built out of simple material provides accurate measurements of specific resistance. The apparatus should be of help to compare plethysmographic equipments from different laboratories.

More Relaxation by Deep Breath on Methacholine- Than on Exercise-Induced bronchoconstriction during the Routine Testing of Asthmatic Children

Deep inspiration (DI) dilates normal airway precontracted with methacholine. The fact that this effect is diminished or absent in asthma could be explained by the presence of bronchial inflammation. The hypothesis was tested that DI induces more relaxation in methacholine induced bronchoconstriction—solely determined by the smooth muscle contraction—than in exercise induced bronchoconstriction, which is contributed to by both smooth muscle contraction and airway wall inflammation. The respiratory conductance (Grs) response to DI was monitored in asthmatic children presenting a moderately positive airway response to challenge by methacholine (n = 36) or exercise (n = 37), and expressed as the post- to pre-DI Grs ratio (GrsDI). Both groups showed similar change in FEV1 after challenge and performed a DI of similar amplitude. GrsDI however was significantly larger in methacholine than in exercise induced bronchoconstriction (p < 0.02). The bronchodilatory effect of DI is thus less during exercise- than methacholine-induced bronchoconstriction. The observation is consistent with airway wall inflammation—that characterizes exercise induced bronchoconstriction—rendering the airways less responsive to DI. More generally, it is surmised that less relief of bronchoconstriction by DI is to be expected during indirect than direct airway challenge. The current suggestion that airway smooth muscle constriction and airway wall inflammation may result in opposing effects on the bronchomotor action of DI opens important perspective to the routine testing of asthmatic children. New crossover research protocols comparing the mechanical consequences of the DI maneuver are warranted during direct and indirect bronchial challenges.