Recurrent Wheezy Bronchitis Research Articles

Lipid-Laden Alveolar Macrophages and pH Monitoring in Gastroesophageal Reflux-Related Respiratory Symptoms.

Lipid-laden alveolar macrophages and pH monitoring have been used in the diagnosis of chronic aspiration in children with gastroesophageal reflux (GER). This study was conducted to prove a correlation between the detection of alimentary pulmonary fat phagocytosis and an increasing amount of proximal gastroesophageal reflux. It was assumed that proximal gastroesophageal reflux better correlates with aspiration than distal GER. Patients from 6 months to 16 years with unexplained recurrent wheezy bronchitis and bronchial hyperreactivity, or recurrent pneumonia with chronic cough underwent 24-hour double-channel pH monitoring and bronchoscopy with bronchoalveolar lavage (BAL). Aspiration of gastric content was determined by counting lipid laden alveolar macrophages from BAL specimens. There were no correlations between any pH-monitoring parameters and counts of lipid-laden macrophages in the whole study population, even when restricting analysis to those with abnormal reflux index expressing clinically significant GER. Quantifying lipid-laden alveolar macrophages from BAL in children with gastroesophageal-related respiratory disorders does not have an acceptable specificity to prove chronic aspiration as an underlying etiology. Therefore, research for other markers of pulmonary aspiration is needed.

Reduced breath condensate pH in asymptomatic children with prior wheezing as a risk factor for asthma

Early noninvasive detection of increased risk of asthma with exhaled breath condensate (EBC) pH measurement has not been applied to preschool children. We sought to evaluate the ability of EBC pH measurement to identify young asymptomatic children at risk of asthma using the combination of recurrent wheezing and atopic sensitization as a proxy for a high risk of asthma. pH values were measured in deaerated EBC from 191children (median age, 4.4 years [interquartile range, 2.2 years]). Children were divided into one of 5 groups: asymptomatic children with recurrent wheezy bronchitis with (group 1, n= 34) or without (group 2, n= 64) allergic sensitization, acute wheezy bronchitis (group 3, n= 18), allergic rhinoconjunctivitis without recurrent wheezy bronchitis (group 4, n= 15), and healthy control subjects (group 5, n= 60). The Asthma Predictive Index score was calculated for groups 1 and 2. Statistical significance was evaluated with the appropriate nonparametric tests, and the discriminatory accuracy was evaluated with receiver operating characteristic analysis. Deaerated EBC pH values were significantly lower in groups 1 and 3 than in groups 2, 4, and 5 (median, 7.49 [interquartile range, 0.94] and 7.44 [interquartile range, 0.70] vs 7.93 [interquartile range, 0.23], 8.02 [interquartile range, 0.17], and 7.96 [interquartile range, 0.25], respectively; P< .001 and area under the receiver operating characteristic curve ≥0.80 in all comparisons). The area under the curve for the differentiation between groups 1 and 2 improved from 0.80 to 0.94 (sensitivity, 0.94; specificity, 0.84; positive predictive value, 0.76) when breath condensate pH values and Asthma Predictive Index scores were combined. A reduced deaerated EBC pH value might help identify young asymptomatic children at high risk of asthma.

Exhaled breath condensate pH in infants and children with acute and recurrent wheezy bronchitis

The analysis of exhaled breath condensate (EBC) is a promising new method to measure airway inflammation. So far only limited data exist about methodological issues of EBC sampling in infants and young children. We evaluated 18 children with acute wheezy bronchitis (median age 24.3 months (min-max: 4-89.9)), 54 children with recurrent wheezy bronchitis (median age 52.5 months (7.2-94.8)), and 32 healthy controls (median age 49.6 months (25.3-67.8)). EBC was sampled with a modified commercially available EBC-sampler, pH was measured after deaeration. EBC volume was significantly correlated to age (r = 0.56, P < 0.001). EBC pH was significantly decreased in all patients compared to the healthy controls (acute wheezy bronchitis 7.87 (7.16-8.19), P = 0.003, recurrent wheezy bronchitis 7.86 (6.95-8.39), P = 0.002, and healthy controls 8.04 (7.81-8.87), respectively). There were no significant differences of the EBC pH between the disease groups. When divided into different subgroups, an influence of inhaled steroid treatment was found with steroid-naive recurrent wheezers having significantly lower EBC pH levels compared to healthy controls (7.80 (6.95-8.37), P = 0.018), but not so steroid treated (7.94 (7.24-8.39), P = 0.055). Both, recurrent wheezers with or without a positive allergy test had significantly lower EBC pH compared to healthy controls (7.91 (6.95-8.37), P = 0.007 and 7.82 (7.32-8.39), P = 0.005, respectively). This study indicates that EBC can be collected with a modified commercially available EBC sampler in infants and young children. Further studies need to be performed to evaluate the relevance and meaning of pH differences of EBC in this age group.

Factor XIII in bronchoalveolar lavage fluid from children with chronic bronchoalveolar inflammation.

Extravascular activation of the coagulation system and consequent fibrin deposition is involved in the pathomechanism of chronic bronchoalveolar inflammatory diseases. The turnover of extravascular fibrin is attenuated by its cross-linking with activated factor XIII (FXIII). Determination of cellular and plasmatic forms of FXIII and their correlation with D-dimer level in the bronchoalveolar lavage fluid (BALF) from healthy children and from children with bronchoalveolar inflammation. Highly sensitive immunoassays were used for the quantitation of cellular and plasma FXIII and D-dimer in the BALF of children with recurrent wheezy bronchitis and fibrosing alveolitis. BALF was investigated for FXIII-containing cells by flow cytometry. In the BALF of controls a low amount of the cellular form of FXIII (FXIII A2) and D-dimer were measured, while plasma FXIII (FXIII A2B2) was absent. Alveolar macrophages represented the single cell population in BALF that contained FXIII. In the BALF of both patients' groups the concentration and the total amount of FXIII A2 was significantly elevated, and plasma FXIII also appeared in the BALF of most patients. The D-dimer concentration was also elevated in the patients' groups and it correlated both with plasma FXIII and neutrophil count. These findings suggest that FXIII A2 is released from activated or injured alveolar macrophages into the bronchoalveolar lining fluid and in bronchoalveolar inflammatory diseases, FXIII A2B2 also leaks out from the capillaries. By cross-linking fibrin and inhibitors of fibrinolysis to fibrin, FXIII might be a key regulator of fibrin turnover in the extravascular compartment.

Immunomodulatory treatment strategies for allergic diseases.

Over the last decades the prevalence of allergic disorders, such as hayfever and asthma has increased worldwide, mostly in westernised countries where up to 20 % of the population are affected. The "hygiene hypothesis" suggests that modernised lifestyles such as improved housing conditions, altered dietary habits and smaller family sizes may be responsible for the decrease in infectious and the increase in allergic diseases. Childhood atopic diseases, like eczema, food allergies and recurrent wheezy bronchitis represent a considerable health problem and a major socioeconomic burden due to the chronicity of these disorders. In recent years, a better understanding of the immunopathogenesis of allergic diseases has evolved, which has contributed to the development of novel more targeted forms of therapy. Allergen injection immunotherapy is the only treatment in current use with the potential for modifying the course of allergic disease. In order to better target mucosal allergies, new approaches of administering allergen, via the sublingual or intranasal route, are being developed. The use of modified allergens, allergen peptides, DNA immunization and the use of novel adjuvants represent alternatives to conventional immunotherapy with potential for improved efficacy with less side effects. For atopic asthma, novel treatment strategies aim at locally targeting inflamed airways. Nebulized monoclonal blocking antibodies and soluble interleukin receptors against "Th(2)-type" cytokines have been designed. An alternative approach has been the administration of "Th(1) -type" cytokines. Although, immunomodulatory strategies provide a promising outlook for the treatment of allergic patients, more studies are needed in the future to address issues of efficacy, safety and long-term effects of altered immune responses.

Bronchoalveolar Cells in Children < 3 Years Old With Severe Recurrent Wheezing

To determine the cell profile of BAL from infants with severe recurrent wheezing who were not acutely ill at the time of investigation, suggesting an ongoing inflammation. In a retrospective study, we determined BAL cell profiles for 83 children with wheezing aged 4 to 32 months (mean +/- SD, 11.3 +/- 5.5 months). Fiberoptic bronchoscopy was performed in children with severe recurrent wheezy bronchitis unresponsive to inhaled steroids. These children were compared with 17 children aged 6 to 36 months (mean, 15.1 +/- 7.5 months) with various nonwheezing pulmonary diseases. Children were included as control subjects if they had no endobronchial inflammation and no atopy. The BAL cell profile of young children with wheezing typically includes a significantly higher cell count (mean, 644.4 +/- 956.8 x 10(3)/mL vs 313 +/- 203.2 x 10(3)/mL, p = 0.008), a significantly higher percentage of neutrophils (mean, 9 +/- 12.1% vs 2.1 +/- 2.2%, p = 0.003), and a higher neutrophil count (mean, 43.2 +/- 81.6 x 10(3)/mL vs 7.9 +/- 11.8 x 10(3)/mL, p = 0.003), as compared with control subjects. The larger number of neutrophils in children with wheezing was not correlated with bacterial or viral infection, or with age, sex, or atopic status. In contrast to the situation in asthmatic adults, eosinophil levels were not higher in children with wheezing than in control subjects (mean, 0.09 +/- 0.27% vs 0.08 +/- 0.25%). Neutrophil-mediated inflammation in the airways appears to better characterize severe recurrent wheezing in children < 3 years old.

Early use of inhaled corticosteroids in infancy

The inability to accurately predict the outcome of infants with recurrent wheezy bronchitis makes the early use of inhaled corticosteroids (ICS) controversial. Data from bronchoalveolar lavages and epidemiological surveys suggest a persistent inflammation of the airways in the more severe cases. Prospective studies, mostly with nebulized corticosteroids, have demonstrated clinical efficacy on daytime and nightime symptoms, reduced requirements for rescue bronchodilators and a real steroid sparing effect. In infants with episodic viral-associated wheeze with or without interval symptoms, ICS use carries the risk of overtreatment and of adverse effects. Long-term prospective studies are urgently required to assess the efficacy and safety of ICS and their possible effects on the natural history of infantile asthma.

Popeye ‐ an unusual phobia

A girl aged 3 years, 8 months was referred in May 1990 because of recurrent wheezy bronchitis. Routine enquiry concerning possible allergies showed that her parents thought she might be allergic to dogs, and she often played with cats at a friend's house. It also revealed an extraordinary aversion to the name and image of the cartoon character Popeye. For example, when she saw a boy in the same nursery class wearing Popeye shoes, she began to retch, cough and become upset. It was wondered whether she might also have an allergy to spinach, because this was Popeye's favourite food, but this possibility was eliminated. There were no abnormal physical findings. Her wheezy bronchitis was treated by a salbutamol nebuliser three times daily, and she was referred to a psychologist. She was treated by behavioural therapy and she improved so rapidly that only two months later she was able to watch Popeye cartoons. Phobias are unjustified or exaggerated fears, which may be recognised as such by the victim, who is nevertheless powerless to overcome them. This can lead to severe physical and intellectual impairment. In children, they are a frequent reaction to stress and anxiety and may be accompanied by abdominal pain and vomiting. By far the commonest is school phobia in which the child shows great anxiety about leaving home for school, panics and refuses to go, while older children indulge in truanting - leaving home but not arriving at school. Less commonly, phobias relate to more specific fears, e.g. button phobia from the accidental near ingestion of a button that had fallen into food. In this unusual case, the phobia took the form of a strong illogical aversion to the cartoon character Popeye, and was highly responsive to simple behavioural therapy.

Sensitization to mite allergens is a risk factor for early and late onset of asthma and for persistence of asthmatic signs in children

Background: To describe the natural history of asthma between the ages of 7 and 10 years and to analyze risk factors for prevalences, as well as new onset of asthma-like symptoms, a longitudinal study of 1812 children was conducted. Methods: In four surveys, each 1 year apart, four asthma-like symptoms and several hypothetical risk factors were ascertained through standardized questionnaires. Sensitization to seven common inhalant allergens was measured by skin prick testing. Exposure to mite allergens (Der p I, Der f I) was assessed by measuring the antigen concentrations in the dust of each child's mattress. Occurrence of more than one asthma-like symptom closely related to the practitioner's diagnoses of bronchial asthma and recurrent wheezy bronchitis was used as the outcome variable. Results: After an initial prevalence of 14.5%, new onset of symptoms in children unaffected at the beginning was reported in 7.2% during the 3 years. Of the factors explaining prevalence and persistence of asthma-like symptoms (sensitization to mite allergens and animal danders, history of hay fever and eczema, low gestational age, male gender, parental atopy), only sensitization to mite allergens (odds ratio = 2.3, 95% confidence interval = 1.1-4.7) and parental atopy (odds ratio = 2.1, 95% confidence interval = 1.2-3.7) were also significantly associated with new onset. In a relatively small number of sensitized subjects with new onset of symptoms ( n = 31), mite antigen concentration did not appear to be associated with incidence of symptoms. Conclusion: Sensitization to mite allergens antedated the onset of asthma-like symptoms, and no strong effect of allergen exposure on clinical development could be found. Thus the primary focus should be on preventing sensitization to mite allergens by implementing avoidance measures in infancy or at early school age in order to reduce the onset of asthma at a later stage. (J A LLERGY C LIN I MMUNOL 1995;95:655-62.)

Risk factors for childhood asthma and recurrent wheezy bronchitis

Using cross-sectional data of an epidemiological study, risk factors for asthma and recurrent wheezy bronchitis were investigated in 1812 primary school children. Children with asthma (n = 63) had a similar pattern but a higher frequency of chronic respiratory symptoms than those with recurrent wheezy bronchitis (n = 136). Logistic regression analyses showed similar risk factors for both disorders, however, more pronounced for asthma. Prematurity was a significant risk factor for asthma and for recurrent wheezy bronchitis. Children with asthma more often had a family history of paternal or maternal asthma and their mothers tended to be younger. Effects of paternal asthma and prematurity were also found when the atopic status of the child (defined as skin test positivity to any of seven aero allergens) was taken into account. Next to genetic effects, adverse circumstances in early life seem to be important for the development of asthma. In school children recurrent wheezy bronchitis and asthma seem to be similar disorders which differ in quantitative but not qualitative aspects.

93 MUNICH ASTHMA-AND ALLERGY SURVEY. IS ASTHMA BEING UNDERDIAGNOSED?

There is evidence that morbidity and mortality from asthma as well as the prevalence of allergic diseases is increasing. As data were missing in Germany, we studied in a crossectional design 9 403 schoolchildren (age 9-11 years) in an urban and rural area of Bavaria using a questionnaire, skin prick tests and pulmonary function tests before and after cold air challenge. The responserates were: 87% for questionnaires, 77% for allergy or pulmonary function tests. Evaluation of the questionnaires gave the following prevalences: 18,1% allergic rhinitis, 19,7% atopic dermatitis, 2,5% asthma and 5,5% recurrent wheezy bronchitis. Beyond this 8,3% had recurrent wheezing and 3,4% chronic cough by night or exercise without any diagnose of asthma or wheezy bronchitis. 42 % of all german children are atopic, ie exhibit at least one positive prick test reaction for the six aeroallergens tested. Bronchial hyperreactivity was found in 9% of german children. Atopic diseases and asthma are more frequent in the urban than the rural area. In summary there is an important underdiagnosis of asthma in this pediatric population.

Recurrent wheezy bronchitis and viral respiratory infections.

Fifty four patients aged from 1 to 6 years who had had recurrent attacks of wheezy bronchitis were prospectively followed up for three months to find out if there was an association between different viral respiratory infections and episodes of wheezing. Of the 115 episodes of upper or lower respiratory tract symptoms, virus or Mycoplasma pneumoniae infection were diagnosed in 52 (45%). Thirty four of rhinoviruses. The patients had an average of 2.1 episodes of respiratory tract symptoms the total mean (SD) duration of which was 30 (2) days of the 92 days that followed. Wheezing occurred during 76 (66%) of the 115 episodes and during a third of these the patient was admitted to hospital because of severe dyspnoea. Wheezing started a mean (SD) of 43 (7) hours after the first symptoms of respiratory infection and persisted for 3.8 (4.2) days in patients in whom virus infection was diagnosed. The incidence of wheezing was not associated with IgE mediated atopy, with positive virological tests, or with fever during virus infection, but was associated with parental smoking and more than one sibling.

368 Recurrent wheezy bronchitis in relation to environmental risk factors in infancy A prospective study of 276 Danish infants

368 Recurrent wheezy bronchitis in relation to environmental risk factors in infancy A prospective study of 276 Danish infants

Mycoplasma pneuminia infection. A follow-up study of 50 children with respiratory illness.

Fifty children with a previous history of Mycoplasma pneumoniae respiratory tract infection were assessed clinically, and pulmonary function tests carried out after an interval ranging from 1 1/2 to 9 1/2 years (median 2 1/2). 23 suffered from recurrent wheezy bronchitis or asthma, and in 5 the index illness appeared to precipitate the wheezing tendency. All were symptom-free when respiratory function tests were performed. Simple tests of ventilatory function (PEFR, FEV, and FVC) were within normal limits. Increased bronchial reactivity after exercise (a fall in PEFR greater than 15% resting value) was demonstrated only in children known to have asthma. Maximum expiratory flow rates in air at 50% of vital capacity (V mas50) were within the normal range in all patients with the exception of two. The response in flow rate at 50% of vital capacity after inalation of an 80% helium and 20% oxygen mixture delta V max50) was reduced (P less than 0.001) in asymptomatic patients with a history of M. pneumoniae respiratory infection, when compared with normal data from 48 healthy schoolchildren without a background of significant respiratory illnesses. These findings indicate impairment of small airways function, even in totally symptom-free children in the study group.

Management of Childhood Asthma in Britain

THE nature of bronchial asthma is still not entirely clear. The basic anomaly seems to be the increased lability of the bronchial tree so that it reacts excessively to a variety of stimuli, including inhalation of allergens, exercise, infection, and emotional stress. There is good evidence that this anomaly is common to children bearing the diagnostic labels of recurrent wheezy bronchitis and bronchial asthma. 1,2 Some older children whose clinical history clearly points to one specific allergen and in whom skin tests are confirmatory may benefit from desensitization. This is not the case in those sensitive to a wide range of allergens. The place in therapy of the desensitization of children to the house dust mite is not yet clear. It seems reasonable to advise measures to reduce dust in the home of any asthmatic child and to advocate avoidance of exposure to domestic animals only when there is a