Sandra Smith

Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.

Abstract Objective: To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community. Design: Community based 13 month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses. Subjects: 108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire. Setting: Southampton and surrounding community. Main outcome measures: Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions. Results: Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 1/min. The most commonly identified virus type was rhinovirus. Conclusions: This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children. Key messages Key messages In this study common cold viruses were found in 80-85% of reported exacerbations of asthma in children Rhinoviruses, which cause most common colds, accounted for two thirds of viruses detected Analysis of diary cards also showed large numbers of similar but less severe episodes that may also be viral in origin

Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study.

BACKGROUND Rhinovirus infections cause exacerbations of asthma. We postulated that people with asthma are more susceptible to rhinovirus infection than people without the disease and compared the susceptibility of these groups. METHODS We recruited 76 cohabiting couples. One person in every couple had atopic asthma and one was healthy. Participants completed daily diary cards of upper-respiratory-tract (URT) and lower-respiratory-tract (LRT) symptoms and measured peak expiratory flow twice daily. Every 2 weeks nasal aspirates were taken and examined for rhinovirus. Mixed models were used to compare risks of infection between groups. We also compared the severity and duration of infections. FINDINGS We analysed 753 samples. Rhinovirus was detected in 10.1% (38/378) of samples from participants with asthma and 8.5% (32/375) of samples from healthy participants. After adjustment for confounding factors, asthma did not significantly increase risk of infection (odds ratio 1.15, 95% CI 0.71-1.87). Groups did not differ in frequency, severity, or duration of URT infections or symptoms associated with rhinovirus infection. First rhinovirus infection was associated more frequently with LRT infection in participants with asthma than in healthy individuals (12 of 28 infections vs four of 23, respectively, p=0.051). Symptoms of LRT associated with rhinovirus infection were significantly more severe (p=0.001) and longer-lasting in participants with asthma than in healthy participants (p=0.005). INTERPRETATION People with atopic asthma are not at greater risk of rhinovirus infection than healthy individuals but suffer from more frequent LRT infections and have more severe and longer-lasting LRT symptoms.

Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced asthma in children

Summary Background A link between exposure to the air pollutant nitrogen dioxide (NO2) and respiratory disease has been suggested. Viral infections are the major cause of asthma exacerbations. We aimed to assess whether there is a relation between NO2 exposure and the severity of asthma exacerbations caused by proven respiratory viral infections in children. Methods A cohort of 114 asthmatic children aged between 8 and 11 years recorded daily upper and lower respiratory-tract symptoms, peak expiratory flow (PEF), and measured personal NO2 exposures every week for up to 13 months. We took nasal aspirates during reported episodes of upper respiratory-tract illness and tested for infection by common respiratory viruses and atypical bacteria with RT-PCR assays. We used generalised estimating equations to assess the relation between low (<7·5 μg/m3), medium (7·5–14 μg/m3), and high (>14 μg/m3) tertiles of NO2 exposure in the week before or after upper respiratory-tract infection and the severity of asthma exacerbation in the week after the start of an infection. Findings One or more viruses were detected in 78% of reported infection episodes, and the medians of NO2 exposure were 5 (IQR 3·6–6·3), 10 (8·7–12·0), and 21 μg/m3 (16·8–42·9) for low, medium, and high tertiles, respectively. There were significant increases in the severity of lower respiratory-tract symptom scores across the three tertiles (0·6 for all viruses [p=0·05] and >2 for respiratory syncytial virus [p=0·01]) and a reduction in PEF of more than 12 L/min for picornavirus (p=0·04) for high compared with low NO2 exposure before the start of the virus-induced exacerbation. Interpretation High exposure to NO2 in the week before the start of a respiratory viral infection, and at levels within current air quality standards, is associated with an increase in the severity of a resulting asthma exacerbation.

Effect of inhaled corticosteroids on episodes of wheezing associated with viral infection in school age children: randomised double blind placebo controlled trial

Abstract Objectives: To determine the effect of regular prophylactic inhaled corticosteroids on wheezing episodes associated with viral infection in school age children. Design: Randomised, double blind, placebo controlled trial. Setting: Community based study in Southampton. Subjects: 104 children aged 7 to 9 years who had had wheezing in association with symptoms of upper and lower respiratory tract infection in the preceding 12 months. Interventions: After a run in period of 2–6 weeks children were randomly allocated twice daily inhaled beclomethasone dipropionate 200 μg or placebo through a Diskhaler for 6 months with a wash out period of 2 months. Children were assessed monthly. Main outcome measures: Forced expiratory volume in 1 second (FEV1); bronchial responsiveness to methacholine (PD20); percentage of days with symptoms of upper and lower respiratory tract infection with frequency, severity, and duration of episodes of upper and lower respiratory symptoms and of reduced peak expiratory flow rate. Results: During the treatment period there was a significant increase in mean FEV1 (1.63 v 1.53 l; adjusted difference 0.09 l (95% confidence interval 0.04 to 0.14); P=0.001) and methacholine PD20 (12.8 v 7.2 μmol/l; adjusted ratio of means 1.7 (1.2 to 2.4); P=0.007) in children receiving beclomethasone dipropionate compared with placebo. There were, however, no significant differences in the percentage of days with symptoms or in the frequency, severity, or duration of episodes of upper or lower respiratory symptoms or of reduced peak expiratory flow rate during the treatment period between the two groups. Conclusions: Although lung function is improved with regular beclomethasone dipropionate 400 μg/day, this treatment offers no clinically significant benefit in school age children with wheezing episodes associated with viral infection. Key messages Increasing evidence suggests that episodic wheezing in children in association with viral infections is a separate entity from atopic asthma Although inhaled corticosteroids are beneficial in asthma, their role in treating wheezing associated with viral infections is unclear In this study regular inhaled corticosteroids resulted in improved lung function and decreased bronchial responsiveness but did not have any effect on episodes of wheezing Inhaled corticosteroids are of little benefit in children with episodic wheezing associated with viral infection

Inhaled synthetic surfactant abolishes the early allergen-induced response in asthma

Allergen-induced inhibition of pulmonary surfactant in asthma may promote airway oedema and consequently potentiate the severity of the asthmatic response. A randomised, single-blind, cross-over study of an inhaled synthetic phospholipid dry-powder surfactant (Pumactant) was conducted in atopic, asthmatic subjects with previously documented early and late asthmatic responses (EAR and LAR) to an inhaled allergen. This was conducted to evaluate the role of exogenous surfactant administration on EAR and LAR. A total of seven subjects had complete evaluable data and received the full dose of Pumactant. Asthmatic subjects inhaled two separate doses of 400 mg Pumactant prior to an allergen exposure. The first dose was administered 8 h in advance and the second dose 30 min in advance. The dosage occurred through a purpose-built administration device. This was followed by a standard bronchial-provocation test, and forced expiratory volume in one second (FEV1) was measured at regular intervals over a 10-h period. Pumactant was well tolerated and, surprisingly, abolished the EAR but not the LAR in all seven subjects. The mean area under the curve between 0–2 h (EAR) following bronchial provocation test was 0.08 for the Pumactant treatment group (PT) and 13.29 for the no treatment (NT) group. The maximum drop in FEV1 for EAR was 4.19% and 23.98% in the PT and the NT group, respectively. The demonstration of inhibition of the early asthmatic response by exogenous surfactant, provides the first evidence that pulmonary surfactant dysfunction may also contribute to the very early asthmatic response to allergen. Exogenous surfactant administration could serve as a useful adjunct in controlling the early allergen-induced symptoms in patients with allergic asthma.

Differential inhibitory effect of regular inhaled corticosteroid on airway responsiveness to adenosine 5′ monophosphate, methacholine, and bradykinin in symptomatic children with recurrent wheeze

Indirect tests of bronchial responsiveness to agents such as adenosine 5′‐monophosphate (AMP) or bradykinin might be more specific markers of a therapeutic responses to anti‐inflammatory treatment than a test of direct responsiveness to agents such as methacholine. In children selected from the community on the basis of mildly symptomatic wheeze, we compared in a randomized, double‐blind study design the effect of 400 μg/day of beclomethasone dipropionate (BDP) or placebo on three separate ways of provoking bronchial responsiveness, using methacholine, bradykinin, and AMP as the provoking agents. Following pre‐treatment bronchial challenges, 29 children received paired monthly methacholine and AMP challenges for 3 months, while for the same period another 33 children received paired monthly methacholine and bradykinin challenges.

The effect of BAY u 3405, a thromboxane receptor antagonist, on prostaglandin D2-induced nasal blockage

BACKGROUND Nasal lavage and challenge studies in allergic rhinitis implicate prostaglandin (PG) D2 in the genesis of nasal blockage. PG D2 is known to act via at least two receptors, the thromboxane prostanoid receptor and the PG D2 prostanoid (DP) receptor; the lower airway effects are mediated chiefly by the TP receptor. The receptor involved in the genesis of PG D2-induced nasal blockage is unknown. BAY u 3405 is a potent selective competitive TP receptor antagonist, which inhibits the lower airway response to PG D2, and shifts the dose-response curve to the right by up to 16-fold. METHODS The efficacy of a single oral dose of 20 mg of BAY u 3405 was examined in comparison with PG D2 nasal insufflation in a randomized, double-blind, placebo-controlled crossover study, with objective measurement of nasal resistance by active posterior rhinomanometry. RESULTS BAY u 3405 afforded no protection against PG D2-induced nasal blockage. CONCLUSIONS This suggests that PG D2-induced nasal blockage may be mediated by the DP receptor rather than the TP receptor and that TP receptor antagonists are unlikely to be of benefit in the treatment of allergic rhinitis. In vivo investigation with specific potent DP receptor antagonists is awaited.

Longitudinal changes in skin‐prick test reactivity over 2 years in a population of schoolchildren with respiratory symptoms

As part of a larger epidemiological study, 114 children with respiratory symptoms, born between 1978 and 1980, were skin‐prick tested to Dermatophagoides pteronyssinus (DP), mixed grass pollens (G) and cat dander (C), and to histamine and saline controls (Bencard, U.K.) using 1 mm prick‐lancets (Dome/Hollister‐Stier), between July and September 1987 and again in October 1989. A weal ≥ 2 mm to one or more allergens was regarded as a positive result. Each child was tested by the same investigator on each occasion, using similar techniques. Three children were excluded from analysis as they had failed to respond to histamine testing on one of the two occasions. In 1987, of the 111 children analysed, 58 (52%) children were skin‐test positive, and 53 (48%) skin‐test negative, while in 1989 62 (56%) were positive and 49 (44%) negative. Twelve children (11%) changed status from negative to positive, while eight (7%) changed from positive to negative. For the group as a whole the percentage agreement between the results obtained 2 years apart was 82%. In comparison to previous studies a greater number of subjects in this population than expected changed atopic status. We therefore further examined the data from those who had changed status and classified as borderline those subjects with no difference in weal size of greater than 2 mm for any allergen between 1987 and 1989. Only five children then changed status from negative to positive, none from positive to negative and 15 demonstrated only borderline changes. The coefficients of repeatability for the 106 children who did not change status were 3.37 mm, 2.80 mm and 2.33 mm for D. pteronyssinus, mixed grass pollens and cat dander respectively. The good short‐term repeatability of the testing method was demonstrated in a group of 29 similar children; the coefficients of repeatability were 0.38 mm for DP and G, and 0.72 mm for C. These data demonstrate that, in a population of children with respiratory symptoms, skin‐prick testing within individuals is highly repeatable over the short term, but poorly repeatable over a 2 year period. However, the percentage agreement in skin‐prick test status for the group as a whole was high (82%). While no child became unequivocally skin‐test negative having been previously positive, a small number of children changed status from negative to unequivocally positive, suggesting a genuine but small (4%) increase in the prevalence of skin‐test positivity in this population.