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P Latzin

Publications and source records attributed to P Latzin.

11 recordsLinked to original sources

Prospectively assessed incidence, severity, and determinants of respiratory symptoms in the first year of life.

Respiratory symptoms are common in infancy. Nevertheless, few prospective birth cohort studies have studied the epidemiology of respiratory symptoms in normal infants. The aim of this study was to prospectively obtain reliable data on incidence, severity, and determinants of common respiratory symptoms (including cough and wheeze) in normal infants and to determine factors associated with these symptoms. In a prospective population-based birth cohort, we assessed respiratory symptoms during the first year of life by weekly phone calls to the mothers. Poisson regression was used to examine the association between symptoms and various risk factors. In the first year of life, respiratory symptoms occurred in 181/195 infants (93%), more severe symptoms in 89 (46%). The average infant had respiratory symptoms for 4 weeks and 90% had symptoms for less than 12 weeks (range 0 to 23). Male sex, higher birth weight, maternal asthma, having older siblings and nursery care were associated with more, maternal hay fever with fewer respiratory symptoms. The association with prenatal maternal smoking decreased with time since birth. This study provides reliable data on the frequency of cough and wheeze during the first year of life in healthy infants; this may help in the interpretation of published hospital and community-based studies. The apparently reduced risk in children of mothers with hayfever but no asthma, and the decreasing effect of prenatal smoke exposure over time illustrate the complexity of respiratory pathology in the first year of life.

Asthma↗

alpha1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients.

The airways of cystic fibrosis (CF) patients are characterised by neutrophils that release high amounts of elastase overwhelming the local antiprotease shield. Inhalation of alpha(1)-antitrypsin (AAT) may restore the protease-antiprotease balance and attenuate airway inflammation in CF airways. The aims of the present study were: 1) to assess the best deposition region for inhaled AAT by two different inhalation strategies; and 2) to examine the effect of 4 weeks of AAT inhalation on lung function, protease-antiprotease balance and airway inflammation in CF patients. In a prospective, randomised study, 52 CF patients received a daily deposition by inhalation of 25 mg AAT for 4 weeks targeting their peripheral or bronchial compartment. The levels of elastase activity, AAT, pro-inflammatory cytokines, neutrophils, immunoglobulin G fragments and the numbers of Pseudomonas aeruginosa were assessed in induced sputum before and after the inhalation period. Inhalation of AAT increased AAT levels and decreased the levels of elastase activity, neutrophils, pro-inflammatory cytokines and the numbers of P. aeruginosa. However, it had no effect on lung function. No difference was found between the peripheral and bronchial inhalation mode. In conclusion, although no effect on lung function was observed, the clear reduction of airway inflammation after alpha(1)-antitrypsin treatment may precede pulmonary structural changes. The alpha(1)-antitrypsin deposition region may play a minor role for alpha(1)-antitrypsin inhalation in cystic fibrosis patients.

Administration, Inhalation↗

Inhaled glutathione decreases PGE2 and increases lymphocytes in cystic fibrosis lungs.

Reduced glutathione (GSH), a major antioxidant and modulator of cell proliferation, is decreased in the bronchoalveolar lavage fluid (BALF) of cystic fibrosis (CF) patients. We previously have shown that GSH inhalation in CF patients significantly increased GSH levels in BALF and improved lung function (M. Griese et al., 2004, Am. J. Respir. Crit. Care Med.169, 822-828). GSH depletion in vitro enhances susceptibility to oxidative stress, increases inflammatory cytokine release, and impairs T cell responses. We therefore hypothesized that an increase in GSH in BALF reduces oxidative stress, decreases inflammation, and modulates T cell responses in lungs of CF patients. BALF from 17 CF patients (median FEV1 67% (43-105%) of predicted) was assessed before and after GSH inhalation for total protein, markers of oxidative stress (8-isoprostane, myeloperoxidase, and ascorbic and uric acid), pattern of protein oxidation, prostaglandin E2 (PGE2), and proinflammatory cytokines. BALF cells were differentiated using cytospin slides, and lymphocytes were further analyzed by flow cytometry. Inhalation of GSH decreased BALF levels of PGE2 and increased CD4+ and CD8+ lymphocytes in BALF significantly but had no effect on markers of oxidative stress. BALF lymphocytes correlated positively with lung function, whereas levels of PGE2 showed an inverse correlation. The patients with the greatest improvement in lung function after GSH treatment also had the largest decline in PGE2 levels. We conclude that GSH inhalation in CF patients increases lymphocytes and suppresses PGE2 in the bronchoalveolar space. Thus, GSH primarily affected the pulmonary immune response rather than the oxidative status in CF patients. The effect of GSH inhalation on PGE2 levels and lymphocytes in CF warrants further investigation.

Administration, Inhalation↗

Anti-GM-CSF antibodies in paediatric pulmonary alveolar proteinosis.

BACKGROUND: Auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) may be central to the pathogenesis of adult sporadic pulmonary alveolar proteinosis (PAP). The role of anti-GM-CSF auto-antibodies in paediatric forms of PAP is as yet unclear. METHODS: Anti-GM-CSF auto-antibodies were determined with the help of an antigen capture assay using serum and/or bronchoalveolar lavage (BAL) fluid from 27 patients with PAP (nine adults, 15 children, three neonates) and from 185 children with different diseases as disease controls (various pulmonary conditions and patients with malignancies). RESULTS: Anti-GM-CSF auto-antibodies were detected in the serum of five of seven adult PAP patients. They were not found in the serum of any of the children or neonates with PAP nor in any of the disease control patients. Raised anti-GM-CSF titres were found in BAL fluid from three of four adult patients with PAP. Anti-GM-CSF auto-antibodies were detected in BAL fluid of only one of the 15 children (age at diagnosis 11 years, age at BAL 24 years) and in none of the neonates with PAP, nor in any of the disease control patients. CONCLUSIONS: The presence of anti-GM-CSF auto-antibodies seems to define an autoimmune disease underlying most of the adult sporadic type of PAP, but age at diagnosis may cause an overlap with children in some rare instances. In most of the children and all of the neonates the anti-GM-CSF titres were not significantly increased, indicating that alternative explanations are needed for the pathogenesis of the disease in these patients.

Adult↗

Exhaled carbon monoxide is not flow dependent in children with cystic fibrosis and asthma.

STUDY OBJECTIVES: Exhaled nitric oxide (eNO) and carbon monoxide (eCO) concentrations are elevated in inflammatory airway diseases like asthma and have been investigated as potential diagnostic markers. For eNO concentrations knowledge about the inverse flow dependency is essential for reproducibility and comparability of measurements. The aim of this investigation was to evaluate a possible expiratory flow dependency of eCO in children with different inflammatory airway diseases. DESIGN: ENO and eCO concentrations were measured electrochemically and via chemiluminescence in the exhaled air of 20 healthy children, 17 stable cystic fibrosis (CF)-patients and 15 steroid-naive asthmatics in a combined analyzer at five different expiratory flows (10, 20, 45, 86, 184 ml/sec). RESULTS: ECO was not flow dependent in any of the three groups. At 45 ml/sec the mean eCO-concentration of healthy children was 3.72 +/- 0.23 ppm, of CF-patients 3.67 +/- 0.37 ppm and of asthmatics 4.99 +/- 0.45 ppm. Elevated eCO (p<0.0122) was found in asthmatics but not in CF-children. There was no age dependency and no correlation between eNO and eCO. CONCLUSIONS: In contrast to CF-patients in the exhaled air of steroid-naive asthmatics elevated eCO concentrations are found that may serve as non-invasive inflammatory marker. In contrast to eNO, eCO did not show any expiratory flow dependency.

Adolescent↗

Comparison of exhaled breath condensate from nasal and oral collection.

BACKGROUND: Analysis of exhaled breath condensate may provide new insights into pulmonary inflammatory processes. A new collection method via suction of nasally expired air especially suitable for younger children was presented recently. Here we compare this nasal suction method with the more widely used oral collection method regarding the amount of condensate collected as well as the concentrations of hydrogen peroxide (H2O2), nitrite and nitrate, respectively. MATERIALS AND METHODS: Exhaled breath condensate was collected from 11 healthy adults for the measurements of the amount of condensate and H2O2 concentration and from 17 children for the measurements of nitrite and nitrate. Condensate was collected via nasal suction and oral exhalation from each subject. RESULTS: Overall, no differences between both collection methods were found for all variables assessed except the concentration of H2O2, whereas the latter closely correlated (Spearman r = 0.88, p = 0.0007) between both collection methods. No correlation was found for the amount of condensate collected and the concentration of nitrite and nitrate. The Bland-Altman limits of agreement scattered over a wide range with clinical impact, proving significant differences between both collection methods for all variables measured. CONCLUSIONS: Although nasal and oral collection method proved again suitable for the collection of exhaled breath condensate, the variability of the results obtained precludes the interchangeable usage of the inflammatory markers assessed here.

Adult↗

Exhaled hydrogen peroxide, nitrite and nitric oxide in healthy children: decrease of hydrogen peroxide by atmospheric nitric oxide.

Hydrogen peroxide (H2O2) and nitrite (NO2-) in exhaled breath condensate have recently been suggested as non-invasive markers of airway inflammation. The goal of this study was to clarify the role of factors that may potentially influence the measurement of H2O2 and nitrite and to look for possible correlations among these inflammatory markers. H2O2 and nitrite values were assessed fluorometrically in breath condensate of 102 healthy children (age 4-18 years) and a detailed status of atopy (including history, lung function and skin prick test) was taken in all children. To find out the role of atmospheric nitric oxide, eNO and envNO were measured via chemiluminescence in association with the sampling of the breath condensate. Median (interquartile range) H2O2 was 0.51 (0.26 - 0.74) microM and nitrite was 3.3 (2.7 4.1) microM. A significant negative correlation between H2O2 and envNO was observed (r = -0.50; p < 0.0001). ENO was independent of envNO at our envNO range up to 56 ppb. No further correlation was found. The inflammatory markers in exhaled breath condensate H2O2, nitrite and eNO are not interrelated to each other in healthy children. Whereas eNO was not dependent on envNO values, high envNO values must be taken into account when measuring H2O2 in exhaled breath condensate.

Adolescent↗

A noninvasive method to collect nasally exhaled air condensate in humans of all ages.

BACKGROUND: The analysis of exhaled breath condensate may provide valuable insights into inflammatory and other metabolic processes of the lungs. However, its collection by active exhalation with conventional methods is cumbersome, demands a substantial level of co-operation with high motivation and is very difficult or impossible in children younger than about 4-6 years or in the elderly. A comfortable, noninvasive and efficient method is desirable. DESIGN AND PATIENTS: For collection a high-performance pump connected to a cold trap and nasal prongs were used. The volume of the condensate collected was assessed in 141 children of all ages and five adults. As an example for a low molecular component, H2O2 a marker of oxidative stress, was determined fluorometrically. RESULTS: On average, in healthy children from 4 weeks to 18 years of age, 84.0 (79.4, 87.3) microL min(-1) of nasally exhaled air condensate were collected. The volume obtained was about 45% less in 1-6-year-old children, increased linearly with collection time, and averaged about 20-30% of the exhaled water vapour. The concentration of H2O2 in the healthy children was 0.49 (0.48, 0.61) microM and did not depend on age, the time of the day, family, or personal history of atopy and sex. CONCLUSIONS: The method described is generally applicable, comfortable, noninvasive, safe and efficient and allows the collection of nasally exhaled air condensate for the evaluation of metabolic processes of the lungs.

Adolescent↗

Asthma severity, recommended changes of inhaled therapy and exhaled nitric oxide in children: a prospective, blinded trial.

Orally exhaled nitric oxide (ENO) correlates with several variables of airway inflammation and might be useful to direct asthma therapy. If this is true, ENO should correlate with disease severity and the therapeutic decisions made. - In 74 children with allergic asthma (age 9.7 years, range 4-16) disease severity was determined by history, clinical symptoms, and lung function and inhaled therapy was adjusted according to the NIH criteria. ENO was also measured, but the patients, their parents and the physicians who made the therapeutic decision were left unaware of the results. 31 healthy children served as controls. ENO was higher in asthmatics than in controls, but did not differ with asthma severity. ENO was weakly correlated with the changes in asthma therapy recommended (r = 0.303, P = 0.009). ENO values above normal (> 13 ppb) had a sensitivity of 0.67 and a specificity of 0.65 to predict a step up in therapy. Due to the non-normal distribution of ENO there was a substantial overlap between the different groups. The lack of correlation with disease severity and the weak prediction of physician recommended inhaled therapy, suggest that ENO may be of some value to guide asthma therapy. Studies using ENO to direct therapy are necessary for a definite answer.

Asthma↗

Characteristics of flow dependency of nitric oxide in exhaled air in children with cystic fibrosis and asthma.

Nitric oxide (NO) is a free radical produced by the lungs which can easily be measured in exhaled air. NO may serve as a non-invasive marker for airway inflammation in chronic inflammatory diseases like asthma. However in patients with cystic fibrosis (CF) and severe airway involvemen normal or low levels of NO have been reported. To investigate this further we measured NO levels in exhaled air at 5 different flow rates in 14 asthmatics, 15 CF-patients and 13 healthy children. A dependency of exhaled NO on expiratory flow was demonstrated in all three groups. At slow flows lower NO levels in CF-patients and significantly higher levels in asthmatics compared to healthy individuals were found. When the data were fitted to a one compartment model of the lung described by NO(MOUTH) = NO(LUNG) - NO(LUNG) x e(-T/Vex) (T = transfer factor; Vex = expiratory flow), NO(LUNG) was increased in asthmatics (191.9 +/- 53.8 ppb) and low in CF (26.7 +/- 5.7 ppb) compared to healthy individuals (76.9 +/- 50.9 ppb; p(anova) = 0.0213). NO produced in the central compartment of the lung behaved similarly and was distinguished from a peripheral compartment with the two compartment model NO(MOUTH) = NO(central) - (NO(central) - NO(peripher) ) x e(-T/Vex). We conclude that NO in exhaled air is flow dependent and at slow expiratory flows elevated in asthmatics and reduced in CF-patients compared to healthy children. Concentrations extrapolated for the whole lung and for the central airways changed proportionally.

Adolescent↗