Karl Paul

BCG infection suppresses allergic sensitization and development of increased airway reactivity in an animal model

BACKGROUND Epidemiologic studies suggest an inverse correlation between infections and development of atopy. The purpose of this study was to test the hypothesis whether a preexisting Th1-type immune response elicited by BCG immunization could suppress allergic sensitization and airway hyperreactivity in an animal model. METHODS BALB/c mice were immunized with BCG and/or sensitized to ovalbumin. RESULTS BCG immunization alone resulted in cutaneous type-IV hypersensitivity reactions to tuberculin and granulomatous lesions in the liver. Splenic mononuclear cells (MNCs) produced increased levels of IFN-gamma after activation by Concanavalin A (ConA). Ovalbumin sensitization alone resulted in increased production of IL-4 after activation by ConA. Ovalbumin-sensitized animals also demonstrated markedly elevated anti-ovalbumin IgE/IgG1 serum antibody titers and increased airway reactivity after allergen challenges by means of the airways. BCG immunization 14 days before the start of ovalbumin sensitization markedly hindered the development of allergic responses as indicated by (1) increased IFN-gamma and normalized IL-4 and IL-10 production by splenic MNCs after activation with ConA, (2) a reduced proliferation rate of splenic MNCs after ovalbumin restimulation, (3) partial prevention of ovalbumin-specific IgE/IgG1 serum antibody titers but elevated (nonallergic) anti-ovalbumin IgG2a serum antibody titers, (4) prevention of airway responsiveness, (5) reduced eosinophilic influx into the airway lumen, and (6) reduced levels of IL-4 and IL-5 in broncho alveolar lavage fluids. CONCLUSION In this model BCG immunization established a Th1-type immune response that hinders allergic sensitization and the development of increased airway reactivity.

Decreased levels of nitrosothiols in the lower airways of patients with cystic fibrosis and normal pulmonary function

Airway S-nitrosothiols (SNOs) are naturally occurring bronchodilators. SNOs, nitrate, and nitrite were measured in bronchoalveolar lavage fluid of 23 patients with cystic fibrosis (CF) and mild pulmonary disease (aged 6-16 years) and 13 healthy children (aged 8-15 years). Concentrations of SNOs were decreased in the lower airways of patients with CF and mild pulmonary disease (median, range: 0, 0-320 nmol/L vs 80, 0-970 nmol/L) despite normal levels of the inert nitric oxide metabolites nitrate and nitrite (mean +/- SEM: 3.7 +/- 0.5 micromol/L vs 4.8 +/- 0.9 micromol/L). S-nitrosolation- mediated bioreactivities may be impaired by depletion of the CF airway SNO reservoir.

Bronchiolitis obliterans organizing pneumonia and chronic graft-versus-host disease in a child after allogeneic bone marrow transplantation

We report an 8-year-old boy who developed cough and respiratory failure 7 months after bone marrow transplantation (BMT) coinciding with the onset of chronic graft-versus-host disease (GVHD). Lung function data, imaging studies, lung biopsy and bronchoalveolar lavage were consistent with the diagnosis of bronchiolitis obliterans organizing pneumonia. While this has been reported in association with chronic graft-versus-host disease in one adult case previously, we report the simultaneous occurrence of BOOP and chronic GVHD in a child after bone marrow transplantation for the first time.

Vocal cord dysfunction in three children - misdiagnosis of bronchial asthma?

Vocal cord dysfunction (VCD) is a paradoxical function of the vocal cords, leading to intermittent predominantly inspiratory dyspnea, but with no response to bronchodilator and anti‐inflammatory drug therapy. We report on three children with VCD: 1) A 12‐year old boy, who was treated for many years for bronchial asthma and who presented with inspiratory dyspnea and a functional reduction of the inspiratory and expiratory flow‐volume curve, 2) a 13‐year old girl who was also treated for bronchial asthma on a long‐term basis and in whom the paradoxical vocal cord movement could be demonstrated by laryngoscopy, and 3) a 17‐year old girl who, besides clinical symptoms of bronchial asthma in her anamnesis, suffered from an intermittent severe inspiratory dyspnea, refractory to bronchodilator treatment. Laryngoscopy proved the diagnosis of VCD. No patient showed a deterioration on discontinuation of their antiasthmatic therapy. VCD is best diagnosed by assessment of the vocal cords during laryngoscopy. The following therapeutic measures are helpful: 1) Demonstration of diagnosis (e.g. videodocumentation of laryngoscopy) and reassurance of patients and parents, 2) speech therapy, and 3) psychological intervention and/or psychotherapy. Our three cases point to a differential diagnosis of recurrent dyspnea in children and adolescents which may be overlooked. It is important to question earlier diagnoses, and to objectively evaluate the type of dyspnea.

Sequential analysis of surfactant, lung function and inflammation in cystic fibrosis patients

BackgroundIn a cross-sectional analysis of cystic fibrosis (CF) patients with mild lung disease, reduced surfactant activity was correlated to increased neutrophilic airway inflammation, but not to lung function. So far, longitudinal measurements of surfactant function in CF patients are lacking and it remains unclear how these alterations relate to the progression of airway inflammation as well as decline in pulmonary function over time.MethodsAs part of the BEAT trial, a longitudinal study to assess the course of airway inflammation in CF, we studied lung function, surfactant function and endobronchial inflammation using bronchoalveolar lavage fluid from 20 CF patients with normal pulmonary function (median FEV1 94% of predicted) at three times over a three year period.ResultsThere was a progressive loss of surfactant function, assessed as minimal surface tension. The decline in surfactant function was negatively correlated to an increase in neutrophilic inflammation and a decrease in lung function, assessed by FEV1, MEF75/25%VC, and MEF25%VC. The concentrations of the surfactant specific proteins A, C and D did not change, whereas SP-B increased during this time period.ConclusionOur findings suggest a link between loss of surfactant function driven by progressive airway inflammation and loss of small airway function in CF patients with limited lung disease.

Life-Threatening Vallecular Cyst in a 3-month-old Infant: Case Report and Literature Review

Laryngeal cysts represent an inhomogeneous collection of benign laryngeal abnormalities.1,2 Several classifications are reported according to their histologic structures, their size, their contents, or their localization within the larynx. Etiology and pathogenesis are still not fully understood, and a variety of terms for the same histopathologic subject cause confusion. The vallecular cyst for instance has been named in the literature as mucus retention cyst, epiglottic cyst, baseof-the-tongue cyst, and ductal cyst.3 In this case a laryngeal cyst localized in the vallecular space of a 3-month-old infant is reported. The lesion led to a life-threatening event during anesthesia. Case Report

Effects of an Exercise Program in Children with Cystic Fibrosis: Are There Differences between Females and Males?

OBJECTIVE To investigate the adaptive responses of an in-patient exercise program in children with cystic fibrosis (CF) and evaluate the effects of sex. STUDY DESIGN In total, 158 female and 186 male subjects with CF (age, 12 to 43 years) were studied during a 6-week rehabilitation course. A maximal incremental cycling test was used to determine exercise capacity and responses after 6 weeks of exercise training. Measures included lung function, peak oxygen uptake, peak workload, and peak heart rate. RESULTS Lung function values were lower in males (P < .05). Females had a lower aerobic capacity (P < .05) at the beginning and at the end of the exercise training program. Similar training effects (P > .05) were seen between sexes in peak oxygen uptake (mL/min, mL/kg/min) and peak heart rate (beats/min) but not in peak workload (Watts, W/kg). CONCLUSIONS The exercise program improved the fitness level similarly in females and males with CF. Basic physiological sex differences were still seen at the beginning and end of the training, despite the better lung function in females. Moreover, the finding suggested that fitness level and not lung function determined the response to training in CF, with those who were less fit at baseline having the largest response to training.

The 12-min walk test as an assessment criterion for lung transplantation in subjects with cystic fibrosis.

Timing for the evaluation and listing of patients with cystic fibrosis who are candidates for lung transplantation is still uncertain. Our study goal was to determine the value of the 12-min walk test as a simple and easy-to-use adjunctive assessment tool for pre-transplant evaluation. A total of 34 cystic fibrosis patients (17 male, mean age 22 years) with end-stage lung disease were evaluated in this retrospective analysis. The 12-min walk test was carried out according to an established protocol. Before walking, body plethysmography was performed and a capillary sample was taken for blood gas analysis. Walking distance and SaO(2) via continuous pulse oximetry were recorded online. There was a strong correlation between survival time and walking distance (r=0.7, P=0.003). No other single parameter, such as FEV(1), SaO(2,) pCO(2) or BMI, showed a statistically significant correlation with survival time. Subjects who walked < or =700 m had a lower cumulative survival (P=0.02). There was a statistically significant positive correlation between walking distance and SaO(2) at rest and after 12 min of walking (r=0.5, P=0.001; and r=0.5, P=0.04, respectively). There was no correlation between walking distance and pCO(2) at rest, BMI, FEV(1), or degree of change in SaO(2) during the walk test. This study demonstrates that in CF patients with end-stage lung disease, walking distance during a 12-min walk test is more informative with respect to survival than single parameters such as SaO(2,) pCO(2), FEV(1) or BMI.

Treatment of allergic alveolitis with methylprednisolone pulse therapy

We report on a 13‐year‐old‐boy who had been admitted to our hospital for dyspnea, hypoxia, and pulmonary infiltrates. The diagnosis of allergic alveolitis was based on history (provocation by exposure), lung function tests, bronchoalveolar lavage, and transbronchial lung biopsy. No specific allergen could be identified. Five courses of methylprednisolone pulse therapy (15 mg/kg on three consecutive days) stabilized the patient with normalization of lung function and blood gas analysis. Between pulses the boy returned to his home on a farm without relapse. It is estimated that the effect of a single pulse lasted for at least 2–4 weeks. We conclude that pulse therapy can be used instead of continuous therapy in this rare disease in childhood.

Motor performance is better than normal in preschool children with cystic fibrosis

The aim of the present study was to assess the motor performance in preschool children with a reliable and valid test battery developed to identify motor dysfunction and normal motor development in children aged from 4 to 6 years. Several aspects of motor performance were examined in 29 preschool children with cystic fibrosis (CF) age range 4–6 years (mean 5.2 ± 0.8 years), FEV1 97.2 ± 15.3pred and compared to with 22 healthy children of the same age 5.5 ± 0.8 years. All children performed the “Motoriktest fuer 4‐6jaehrige Kinder” (MOT) assessing seven different aspects of motor performance. Compared to healthy children, test score “Motor Quotient” (MQ) as the mean of all test items was significantly higher (P < 0.05) in children with CF (108.1 ± 16 vs. 93.5 ± 17.9). In both groups, the MQ can be classified as normal. Children with CF scored higher in MOT subtests “Agility and Coordination” (P < 0.05) and “Balance” (P < 0.01) than healthy children but not in the other subtests. We speculate that chest physiotherapy in preschool children with CF may have an effect on motor performance in general and in some aspects of motor performance. Pediatr Pulmonol. 2010; 45:527–535.