Richard Kitz

Lipid-laden alveolar macrophages (LLAM): A useful marker of silent aspiration in children

At present there is no test available which identifies children suffering from silent aspiration due to gastroesophageal reflux (GER). The purpose of this study was to determine whether lipid‐laden alveolar macrophage (LLAM) scoring is a useful method to arrive at the diagnosis. We evaluated bronchoalveolar lavage fluid (BALF) from 68 children aged 6 months to 14 years (median 3.75 years) for the presence of lipid‐laden alveolar macrophages. We compared children with chronic chest disease (CCD) and GER to healthy surgical controls without known lung disease, and to children with recurrent pneumonia without GER. By grading the amount of intracellular Sudan Red‐positive material, we determined a semiquantitative lipid‐laden macrophage (LLAM) score for each patient.

New Immunoassay in Stool Provides an Accurate Noninvasive Diagnostic Method for Helicobacter pylori Screening in Children

Objective. The noninvasive13C-urea breath test (UBT) is a reliable diagnostic method for detection of Helicobacter pylori infection in children, and it avoids invasive gastrointestinal endoscopy. In this study, we compared a noninvasive, newly developed fecal H pylori antigen test with the UBT. Methodology. One hundred sixty-two children (76 girls and 86 boys) were tested for H pylori infection using the UBT and a new antigen test in stool samples. The H pylori stool test is based on a sandwich enzyme immunoassay with antigen detection. Results. Twenty-four of the children (14.8%) with dyspepsia tested positive for H pylori according to the breath test results. In 22 of the 24 patients, H pyloriantigen could be detected in the stool (sensitivity: 91.6%). Of 138 patients with negative UBT results, 136 were H pylori-negative in the stool test (specificity: 98.6%). Conclusions. The new, noninvasive, low-cost H pylori antigen test in stool can replace the UBT for detection of H pylori infection in children with comparable reliability and accuracy.

Effect of n–3 Polyunsaturated Fatty Acids in Asthma after Low-Dose Allergen Challenge

Background: We investigated the anti-inflammatory potential of n–3 polyunsaturated fatty acids (PUFA) on specific bronchial inflammation. Allergic asthmatics were challenged using a low-dose allergen provocation model. Methods: Our parallel double-blinded study randomly assigned 23 house dust mite-allergic asthmatics (aged 22–29 years; 13 females, 10 males) to dietary supplementation with either an n–3 PUFA-enriched fat blend (0.69 g/day) or placebo for 5 weeks. After 3 weeks, the patients were challenged daily with low doses of mite allergen for 2 weeks. Primary outcome parameters were effects on lung function (forced expiratory volume in 1 s, FEV1) and exhaled nitric oxide (eNO) as a marker of bronchial inflammation. Results: Even before the bronchial challenge, eNO was significantly lower in the n–3 PUFA group (p = 0.014). Levels of eNO increased during allergen exposure in both groups, but differences in means were significantly lower in the n–3 PUFA group (p = 0.022). During the low-dose allergen challenge, there were no differences between the groups with regard to symptoms, FEV1 or the allergen dose required to induce deterioration of lung function (PD20). Numbers of sputum eosinophils did not differ significantly, while serum eosinophils (10.1 ± 0.1.84 vs. 5.79 ± 0.69%) as well as changes in eosinophilic cationic protein (20.5 ± 9.93 vs. –1.68 ± 4.36 ng/ml) and in vitro cysteinyl leukotriene release (2,889 ± 872 vs. 1,120 ± 173 ng/ml) were significantly lower in the n–3 PUFA group (p < 0.05 each). Conclusion: Our results provide evidence that dietary supplementation with n–3 PUFA is able to reduce bronchial inflammation even after low-dose allergen challenge.

Surgical treatment of tracheomalacia by bronchoscopic monitored aortopexy in infants and children.

BACKGROUNDnAortopexy has become an established surgical procedure for the treatment of severe tracheomalacia (TM) in infancy. However, postoperative outcome may be improved by intraoperative bronchoscopic control of the aortopexy.nnnMETHODSnBetween 1992 and 2000, 16 infants and children (2 female, 14 male) with TM were treated by pexis of the aorta via a right (15 patients) or left (1 patient) anterior thoracotomy. Patients age ranged from 4 to 122 months (mean, 26 mon). Three infants had previous surgery for esophagus atresia and tracheoesophageal fistula. Another four patients were operated for gastroesophageal reflux. In all cases, the aortopexy was monitored intraoperatively by bronchoscopy. Respiratory function was verified for each patient by comparing pre- and postoperative tidal expiratory flow values (TEF 25% in ml/sec).nnnRESULTSnMean follow-up was 36 months (range, 2 to 60 mo). There was no intraoperative or postoperative mortality. 13 patients showed permanent relief of symptoms. Postoperative median TEF 25% increased significantly compared with preoperative values (81 ml/sec vs. 56 ml/sec; p = 0.016). In one patient repeat aortopexy was necessary.nnnCONCLUSIONSnAortopexy through a right anterior thoracotomy is an efficient and feasible method in the surgical treatment of TM in infancy and, therefore, can improve postoperative respiratory function. Intraoperative bronchoscopy is advantageous.

Systemic and bronchial inflammation following LPS inhalation in asthmatic and healthy subjects

Background: Inhaled endotoxin is known to induce airway inflammation, causing bronchial hyper-reactivity. Objective: We characterized the response to lipopolysaccharide-inhalation by measuring exhaled nitric oxide (eNO) and inflammatory mediators. Patients and Methods : A total of 43 adult volunteers (13 asthmatics, 30 healthy controls) inhaled stepwise LPS every 30 min up to a cumulative dose of 100 µg (2.5, 10.5, 42, 45 µg). After each provocation and up to 24 h later, FEV1 was determined; the procedure was stopped when FEV1 declined more than 12.5%. We measured eNO, leucocytes, eosinophils, polymorphonuclear neutrophils (PMNs), C-reactive protein (CrP), lipopolysaccharide binding protein (LBP), eosinophilic cationic protein (ECP), leucotriene B4 (LTB4), thromboxane B2 (TXB2), and body temperature. Results: Initial eNO values were higher in asthmatics (P < 0.01), but only increased in an asthmatic subgroup. Marked differences were observed in the systemic response to LPS inhalation. Significant increases were found for CrP, LBP, and PMNs. There was no correlation between FEV1 decrease and basal eNO levels. Conclusions: Inhalation of endotoxin was followed by clinical and laboratory signs of systemic inflammation, with asthmatics responding to the challenge similar as healthy subjects. Bronchial eNO increased only temporarily in asthmatics.

Omega-3 polyunsaturated fatty acids and bronchial inflammation in grass pollen allergy after allergen challenge

UNLABELLEDnRATIO: Asthma is a major public health problem, with bronchial inflammation as the therapeutic target. The role of dietary fish oil derived polyunsaturated fatty acids (PUFAs) in allergic inflammation is controversial. Most asthmatics suffer from mild disease and non-pharmacologic interventions are attractive. This study investigates the anti-inflammatory potential of nutritional PUFAs in an experimentally induced bronchial inflammation.nnnMETHODSnWe examined 38 grass pollen allergic asthmatics and 19 controls. History of dietary PUFA intake was compared with levels of PUFAs in erythrocyte membranes, and stratified according to low (25th quartile; Q25) and high (75th quartile; Q75) ratios of omega-3 (n-3) to omega-6 (n-6) PUFAs as a surrogate for anti-inflammatory (Q75) or proinflammatory (Q25) effects. Bronchial inflammation was simulated with one-step inhalation of grass pollen. Bronchial response (exhaled nitric monoxide, eNO as surrogate for inflammation, decrease of FEV(1)) was correlated with levels of PUFAs in erythrocyte membranes.nnnRESULTSnRatios of n-3/n-6 PUFA were significantly lower in asthmatics than in healthy controls. Levels of eNO were significantly higher in Q25 asthmatics than in Q75 asthmatics (pxa0=xa00.040). There was a trend of higher bronchial hyperreactivity in Q25 asthmatics (median PD(20) 0.27 vs. 0.14; n.s.), induced by specific bronchial challenge with grass pollen (FEV(1) decrease 16.7 vs. 23.1%; n.s.).nnnCONCLUSIONnWhen stratifying for erythrocyte membrane PUFA content as a surrogate for alimentary intake, we found mild effects on bronchial allergic inflammation. Future intervention studies with pharmacological PUFA doses appear suitable to clarify dietary PUFA role as an adjunctive intervention to the established treatment of asthma. ClinicalTrials.gov No. NCT00519740.

LPS inhalation challenge: a new tool to characterize the inflammatory response in humans

Inhaling bacterial endotoxin and its derivative LPS can induce a distinct inflammatory response, varying among hosts. Experimental LPS-inhalation is an established procedure in inflammation research. We evaluated experimental LPS-inhalation in 20 young healthy volunteers to determine the safety and the reproducibility of markers of inflammation and clinical findings (symptoms, lung function, exhalative NO, and body temperature). LPS was increased every 30xa0min up to cumulative 100xa0μg, the protocol was repeated after 2, 4, and 6xa0weeks. During 71 provocations, 13 episodes of clinical complaints were observed in 10 subjects. Those were a total of 11 local reactions (15.5%, e.g., cough), and six systemic reactions (8.5%, e.g., fatigue). All adverse events resolved spontaneously within 10xa0h. Changes of FEV1 and eNO showed no significant differences between the four visits. In the majority of our subjects (88.2% on visit 1–3, 76.5% on visit 4), a rise in body temperature (>0.5°C) was recorded and normalised latest after 24xa0h. On the first and the last visit, serum concentrations of CrP and LBP increased significantly and correlated well with each other (rxa0=xa00.71; Pxa0<xa00.001). LPS-challenge is a safe and tolerable tool to investigate inflammatory response in humans and could lead to better characterization of patients with chronic inflammatory disease.

Immunoglobulin levels in bronchoalveolar lavage fluid of children with chronic chest disease.

The concentration and distribution of immunoglobulin isotypes (IgG, IgM, sIgA) and IgG‐subclass levels (IgG‐1–4) were measured in bronchoalveolar lavage fluid (BALF) in 47 children with chronic chest disease (age range 1.0–9.9 years) and 18 healthy controls (age range 1.0–6.25 years). Of these patients, 19 had nonallergic asthma (Group A), 19 suffered from recurrent pneumonia or chronic bronchitis (Group B), and 9 patients had IgG‐2 deficiency (Group C).

Impact of early dietary gamma‐linolenic acid supplementation on atopic eczema in infancy

Polyunsaturated fatty acids (PUFAs) are components of cell membranes and may play an immunomodulating role in the pathogenesis of atopic dermatitis (AD). The goal was to determine the impact of PUFAs on AD by dietary supplementation of infants. Based on the parents’ decision on their babies’ primary feeding, mothers and newborns were randomized to the supplementation with gamma‐linolenic acid (GLA) or placebo for up to 6u2003months. Breastfed infants received GLA by supplementing their mothers. Formula diet was commercial whey hydrolysate unsupplemented with PUFAs. Of 131 eligible infants, 24 developed AD within the first year of life. Of these, nine belonged to the exclusively breastfed group (nu2003=u200358), 14 to the combined‐fed group (nu2003=u200353), and one to the never breastfed group (nu2003=u200320). We could not find an influence of GLA on the development of AD. In subjects with AD, at 1u2003yr of age the serum‐immunoglobulin E (IgE) was the lowest in the GLA‐supplemented group A‐subjects. In the GLA‐supplemented group, GLA‐levels in breast milk were similar in atopic and non‐atopic infants. In the non‐supplemented group the GLA‐content of breast milk was 0.07% of total fatty acids in atopic infants vs. 0.17% in non‐atopic infants (pu2003<u20030.01). Dietary GLA‐supplementation could not prevent AD. Interestingly, the number of infants developing AD was the lowest in never breastfed children. In infants suffering from AD, GLA‐supplementation seemed to reduce total IgE in the first year of life.

Immunoglobulins and immunogenicity of pneumococcal vaccination in preschool asthma

Pneumococcal vaccination is advocated for asthmatics. Although routinely performed, data supplying evidence for this recommendation are limited. We examined the immunological background of 215 asthmatic children (2–5u2003year old) at a university childrens hospital and compared the immunogenicity of the recommended pneumococcal vaccines. Testing encompassed serum immunoglobulins, immunoglobulin G (IgG)‐subclasses, and pneumococcal antibodies against serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. An infection‐prone subgroup received one dose of 23‐valent pneumococcal polysaccharide vaccine (PPV‐23; nu2003=u200338, median age 45u2003months) or of 7‐valent conjugate vaccine (PCV‐7; nu2003=u200323; median age 35u2003months). Pneumococcal antibodies were determined again after 4u2003weeks. Low immunoglobulin‐ and/or IgG‐subclass levels were found in 27 subjects (14 infection‐prone). Prevaccination pneumococcal antibody levels ranged from 0.36 to 1.06u2003μg/ml, depending on the serotype. The percentage of subjects with putative protective antibody levels ≥1.0u2003μg/ml ranged only from 19.9% to 54.1%, over all. Postvaccination, antibody geometric mean concentrations increased significantly higher in PCV‐7 vaccinees for serotype 14 (pu2003<u20030.01) and 23F (pu2003<u20030.05). Now the percentage of putatively protected subjects ranged from 40.9% (serotype 6B) to 90.9% (serotype 19F) following PCV‐7 compared with 31.6% (serotype 6B and 23F) to 81.6% (serotype 19F) in PPV‐23 vaccinees. Our data give further evidence for pneumococcal vaccination of asthmatic children. PCV‐7 is at least as immunogenic as PPV‐23. Moreover, for children suffering from persistent asthma, PCV immunisation should be considered.