Acute effects of hypertonic saline inhalation on nitric oxide pulmonary diffusing capacity in healthy adults.

We investigated acute effects of inhalation of hypertonic saline solution (HSS) and oxygen (O2, control exposure) on pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO). In a randomized crossover study, 20 healthy, non-smoking subjects were allocated to short-term inhalation of HSS or O2. Spirometry [(forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] and combined single-breath DLNO-DLCO measurements were performed before and immediately after inhalation of either HSS or O2. Percent changes were presented as median values (interquartile range). After HSS inhalation, DLNO, FEV1 and FVC were decreased by -3.0% (-7.3, 0.5), -3.1% (-4.2, -1.6) and -1.2% (-3.3, 0.6), respectively (all P < 0.05), without significant effect on DLCO. No changes in spirometry and diffusing capacity were observed following O2 inhalation. Acute inhalation of HSS causes a slight decrease in membrane conductance, probably as a result of fluid imbalance at the alveolar surface and interstitial fluid accumulation, both of which could impair gas exchange.

Pregnancy and perinatal conditions and atopic disease prevalence in childhood and adulthood.

BACKGROUND: Previous studies showed controversial results for the influence of pregnancy-related and perinatal factors on subsequent respiratory and atopic diseases in children. The aim of this study was to assess the association between perinatal variables and the prevalence of asthma, bronchial hyperreactivity (BHR), flexural eczema (FE), allergic rhinitis, and sensitization in childhood and early adulthood. METHODS: The studied population was first examined in Munich and Dresden in 1995/1996 at age 9-11 years. Participants were followed until age 19-24 years using questionnaires and clinical examinations. Associations between perinatal data and subsequent atopic diseases were examined using logistic regression analyses adjusting for potential confounders. RESULTS: Cesarean section was statistically significantly associated with BHR in early adulthood (odds ratio 4.8 [95% confidence interval 1.5-15.2]), while assisted birth was associated with presence of asthma symptoms in childhood (2.2 [1.2-3.9]), FE symptoms (2.2 [1.2-4.3]) and doctor's diagnosis of atopic dermatitis (1.9 [1.0-3.4]) in childhood, and sensitization in early adulthood (2.2 [1.1-4.3]). Lower birth length (1.9 [1.1-3.2]), lower birthweight (0.5 [0.3-0.9]), and higher birthweight (0.6 [0.4-1.0]) were predictive of sensitization in early adulthood compared to average birth length and birthweight, respectively. None of the other perinatal factors showed statistically significant associations with the outcomes. CONCLUSIONS: Our results indicate that children who are born by cesarean section and especially by assisted birth, might be at greater risk for developing asthma, FE, and sensitization and should hence be monitored. Prenatal maternal stress might partly explain these associations, which should be further investigated.

Effects of growth and aging on the reference values of pulmonary nitric oxide dynamics in healthy subjects.

The lung just like all other organs is affected by age. The lung matures by the age of 20 and age-related changes start around middle age, at 40-50 years. Exhaled nitric oxide (FENO) has been shown to be age, height and gender dependent. We hypothesize that the nitric oxide (NO) parameters alveolar NO (CANO), airway flux (JawNO), airway diffusing capacity (DawNO) and airway wall content (CawNO) will also demonstrate this dependence. Data from healthy subjects were gathered by the current authors from their earlier publications in which healthy individuals were included as control subjects. Healthy subjects (n = 433) ranged in age from 7 to 78 years. Age-stratified reference values of the NO parameters were significantly different. Gender differences were only observed in the 20-49 age group. The results from the multiple regression models in subjects older than 20 years revealed that age, height and gender interaction together explained 6% of variation in FENO at 50 ml s-1 (FENO50), 4% in JawNO, 16% in CawNO, 8% in DawNO and 12% in CANO. In conclusion, in this study we have generated reference values for NO parameters from an extended NO analysis of healthy subjects. This is important in order to be able to use these parameters in clinical practice.

[Children and Adolescents in Need of Long-Term Care. An Analysis of Data Obtained by the Medical Service of Compulsory Health Insurance Funds, MDK Bavaria]. / Pflegebedürftigkeit nach SGB XI bei Kindern und Jugendlichen. Eine Analyse der Pflegebegutachtung des MDK Bayern.

Children and adolescents among those in need of long-term care differ significantly from older long-term care patients. The aim of this investigation was to characterise the features of this group. We analysed 6,141 records of children and adolescents produced in 2011 by the medical service of the statutory health insurance of Bavaria. The need for long-term care usually occurred before school age, initially mainly to care level 1. Typically, support for long-term care was initially applied for with the diagnosis of severe developmental disorder. Most likely, a care level was recommended for children with malignant diseases. The majority of children requiring long-term care suffered from Down syndrome, developmental disorders and cerebral palsy. In the population group, 60% were male. Typically, most of the assistance was needed for personal hygiene, however the higher the care level required the more time was needed for nourishment. Only few children regained age-appropriate independence. The majority of the children requiring long-term care for congenital diseases or those present at a young age stay dependent on outside assistance permanently.

Management of occupational asthma: cessation or reduction of exposure? A systematic review of available evidence.

Reduction of exposure to sensitising agents causing occupational asthma has been proposed as an alternative to total avoidance in order to minimise the adverse socio-economic impact of the condition. The aim of this systematic review was to compare the effects of these two management options on asthma and socio-economic outcomes. A bibliographic search was conducted to identify studies examining the outcome of workers with occupational asthma after reduction or cessation of exposure to the causal agent. The changes in asthma symptoms and nonspecific bronchial hyperresponsiveness after reduction or cessation of exposure were described in nine and five studies, respectively. The meta-analysis of pooled data showed that a reduction of exposure was associated with a lower likelihood of improvement (OR 0.16, 95% CI 0.03-0.91) and recovery (OR 0.30, 95% CI 0.11-0.84) of asthma symptoms and a higher risk of worsening of the symptoms (OR 10.23, 95% CI 2.97-35.28) and nonspecific bronchial hyperresponsiveness (OR 5.65, 95% CI 1.11-28.82), compared with complete avoidance of exposure. This systematic review indicates that reduction of exposure cannot be routinely recommended as an alternative to cessation of exposure in the management of occupational asthma. However, further investigations are required before drawing evidence-based conclusions on the cost-effectiveness of this approach.

Educational intervention in farmers with occupational asthma: long-term effect on exhaled nitric oxide.

BACKGROUND: The fraction of exhaled nitric oxide (FE(NO)) has been found reduced 4 to 6 weeks after an educational intervention in farmers with occupational asthma. OBJECTIVE: To reveal whether long-term changes in FE(NO) would still be detectable a year after the intervention. METHODS: We evaluated airway inflammation and obstruction at baseline and after 1 year in animal farmers with occupational asthma (n = 43, 16 women, mean [SD] age, 46.5 [8.9] years) who participated in a 1-day educational program, and in a control group of farmers without intervention (n = 15, 3 women, mean age, 44.1 [10.7] years). FE(NO), spirometry results, and questionnaire data were compared between measurements and between the intervention and control group. RESULTS: In the intervention group, geometric mean (SEM) FE(NO) decreased from 31.5 (1.1) to 25.0 (1.1) parts per billion (ppb) (P = .001), whereas in the control group there was a slight but not statistically significant increase from 27.2 (1.2) to 30.7 (1.2) ppb. Spirometric values remained unchanged in both groups. CONCLUSIONS: We found that FE(NO) was still decreased 1 year after an educational intervention in farmers with occupational asthma. It would thus seem that FE(NO), a noninvasive marker of airway inflammation that can be easily assessed in occupational field work, may be suitable for the evaluation of both short-term and long-term effects of preventive measures in occupational asthma.

Educational intervention decreases exhaled nitric oxide in farmers with occupational asthma.

Allergic occupational asthma is frequent in farming populations. As educational interventions can improve disease management, the short-term effect of an educational intervention in asthmatic farmers was evaluated on the basis of spirometric indices and exhaled nitric oxide fraction (F(eNO)). Farmers with occupational asthma (n = 81), mostly sensitised against cow dander and storage mites, participated in a 1-day educational programme. Outcome measures were assessed at baseline and after 4-6 weeks, using F(eNO), lung function and a questionnaire. Results were compared with those of a control group without intervention (n = 24). In the educational group, the proportion of subjects reporting work-related symptoms was reduced after the intervention. The F(eNO) decreased from a geometric mean of 28.2 to 25.7 ppb, and, in subjects with an elevated (>35 ppb) baseline F(eNO) (n = 32), from 59.7 to 49.2 ppb. The corresponding changes in the control group were 25.6 versus 27.7 ppb and 49.5 versus 48.1 ppb. Spirometric results were unaltered in the two groups. Thus exhaled nitric oxide fraction, a marker of allergic airway inflammation, indicated a beneficial effect of a short-term educational intervention in farmers with occupational asthma. This suggests a potential for exhaled nitric oxide fraction in assessing the efficacy of preventive measures within a short time with higher sensitivity than spirometry.

Leisure time activity and new onset of wheezing during adolescence.

Asthma prevalence is increasing in adult and paediatric patients. In the present study, the association between different leisure time activities and new onset of wheezing was analysed in adolescents aged 16-18 yrs taking part in a questionnaire-based follow-up of the International Study on Asthma and Allergies in Childhood in Munich and Dresden, Germany. Of the 3,785 adolescents who took part in the follow-up (76% response), 2,910 adolescents without earlier episodes of wheezing in childhood were included in the analyses. Of these, 330 (11.3%) reported new onset of wheeze during the previous 12 months. In the bivariate analyses, exercising more than once per week or performing computer work >1 h.day(-1) were inversely related to new onset of wheeze. In contrast, visiting discotheques on a regular basis increased the risk of new onset of wheeze (12.9 versus 9.9%). The observed inverse relationship between physical activity and new onset of wheeze was not an independent effect but mediated by differences in active smoking. The association between physical activity and new onset of wheeze disappeared when active smoking was taken into account. However, the present data do not allow for determining whether smoking operated as a confounder or as an intermediate factor, i.e. whether physical activities prevented active smoking.

First months of employment and new onset of rhinitis in adolescents.

The aim of the present study was to investigate the incidence of rhinitis in adolescents, taking into account the duration and type of employment in holiday and vocational jobs, and to study latency until development of symptoms. Participants of the International Study of Asthma and Allergies in Childhood (ISAAC)-II study in Munich and Dresden (Germany), who were enrolled in 1995, were re-contacted by a postal questionnaire in 2002 (aged 16-18 yrs). The questionnaire focused on allergic rhinitis, type and duration of all jobs, and potential confounders. All jobs held for >/=8 h.week(-1) and >/=1 month were coded and occupational exposure was assigned by a job-exposure matrix. Out of the 3,785 participants, 964 reported an employment history. The median (25th-75th percentile) duration of employment was 10 (1-16) months. After adjusting for potential confounders, those working in high-risk occupations (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0-2.1) had an increased risk for new onset of rhinitis, especially those exposed to low molecular weight agents (OR 1.8, 95% CI 1.1-2.8). The incidence of rhinitis was highest among those currently employed in a high-risk job for <10 months. Teenagers who start working in high-risk occupations have a higher incidence of rhinitis compared with those not working. This increased risk might occur early on during employment.

[Acute effects on the health of children after accidental exposure to epichlorohydrine]. / Akute gesundheitliche Effekte bei Kindern nach einer akzidentellen Freisetzung von Epichlorhydrin.

PURPOSE: In September 2002, two freight trains collided at Bad Muender, Germany. The inhabitants were potentially exposed to combustion products and to the human carcinogen epichlorohydrine (ECH). We aimed to describe the geographical distribution of and potential risk factors for acute symptoms among children residing in Bad Muender. METHODS: The parents of a random sample of children were invited to answer a mail-in questionnaire (response rate 63%). The main outcome measures were self-reported acute symptoms potentially associated with combustion products (e. g., irritation of the eyes, nose, or throat) and stress-related unspecific symptoms (e. g., gastrointestinal complaints, sleep problems, headaches). The main location during the first 26 hours after the train accident served as exposure proxy measure. In addition, potential predictors for the symptoms under study were assessed. RESULTS: The prevalence of symptoms associated with combustion products was 5.9%. Unspecific symptoms were reported for 6.3% of the children. Main location and prevalence of symptoms were not significantly associated. Physician-diagnosed asthma and nasal allergies were the main predictors of symptoms. CONCLUSION: The prevalence of acute symptoms was relatively high in a random sample of children living close to the incident. However, associations between exposure to the accident and symptoms could not be established conclusively.

Do respiratory symptoms predict job choices in teenagers?

Existing guidelines advise adolescents with asthma and allergies against high-risk occupations. The aim of the current authors' analyses was to investigate the resulting self-selection in a prospective cohort study. The participants of Phase II of the International Study of Asthma and Allergies in Childhood in Germany (aged 9-11 yrs at baseline) were re-contacted after 7 yrs (response rate was 77%) and were asked to complete a questionnaire, which included items on atopic diseases. The subjects were also asked about the type of job they would like to have in the future (preferred job choice). Exposure to agents with potential asthma risk was evaluated using a job exposure matrix. The analyses were restricted to those in school-based vocational training programmes without occupational exposures. A total of 33% of subjects chose jobs with high asthma risk, 23% selected low asthma risk jobs and the remaining adolescents indicated jobs without known asthma risk (reference category). There were no statistically significant associations between asthma, allergic rhinitis or atopic dermatitis and selecting jobs with asthma risk. Participants with allergic rhinitis tended to select high risk jobs less frequently. In conclusion, self-selection into low risk jobs seems to play a minor role in teenagers with asthma or allergies.

Smoking and the incidence of asthma during adolescence: results of a large cohort study in Germany.

BACKGROUND: The association between smoking and asthma or wheeze has been extensively studied in cross sectional studies, but evidence from large prospective cohort studies on the incidence of asthma during adolescence is scarce. METHODS: We report data from a cohort study in two German cities, Dresden and Munich. The study population (n = 2936) was first studied in 1995/6 at age 9-11 years as part of phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II) and followed up in 2002/3. At baseline the parents completed a questionnaire and children underwent clinical examination and blood sampling. At follow up the young adults completed questionnaires on respiratory health, living, and exposure conditions. Incidence risk ratios (IRR) were calculated and adjusted for potential confounders using a modified Poisson regression approach. RESULTS: The adjusted IRR for incident wheeze for active smokers compared with non-smokers was 2.30 (95% confidence interval (CI) 1.88 to 2.82). The adjusted IRR was slightly higher for incident wheeze without a cold (2.76, 95% CI 1.99 to 3.84) and the incidence of diagnosed asthma (2.56, 95% CI 1.55 to 4.21). Analysis of duration and intensity of active smoking indicated dose dependent associations. Stratified analyses showed that the risk of incident wheeze without a cold in atopic smokers increased with decreasing plasma alpha(1)-antitrypsin levels at baseline (1.64, 95% CI 1.22 to 2.20 per interquartile range). CONCLUSIONS: Active smoking is an important risk factor for the incidence of asthma during adolescence. Relatively lower plasma levels of alpha(1)-antitrypsin, although well above currently accepted thresholds, may increase susceptibility to respiratory disease among atopic smokers.

Farming exposure in childhood, exposure to markers of infections and the development of atopy in rural subjects.

BACKGROUND: Within the context of the hygiene hypothesis, we aimed to study the potential association between farming-related risk factors and Toxoplasma gondii (T. gondii) as well as Helicobacter pylori (H. pylori) seropositivity. METHODS: The study included questionnaire data and serum samples of 321 young adults living in a rural environment. Serum samples were analysed for specific IgE to a common panel of aeroallergens (SX1) as well as IgG against T. gondii and H. pylori. RESULTS: Regular contact with animal stables before the age of 3 years (odds ratio (OR) (95% confidence interval): 2.0 [1.0; 4.0]) and unpasteurized milk consumption at age 6 years (1.8 [1.0; 3.3]) were the strongest risk factors for T. gondii infection. None of the farming-related factors were significantly associated with H. pylori infection. Current consumption of raw farm milk was not significantly associated with H. pylori infection (2.1 [0.8; 5.3]). Regular contact with animal houses before the age of 7 years was the strongest predictor for atopy (0.49 [0.26-0.96]). The reduction in risk could not be further decreased by any other factor under consideration. After adjustment for animal house contact, the OR for atopy was decreased by raw milk consumption and H. pylori infection in an additive manner. CONCLUSION: Exposure to farming environments in childhood might predict T. gondii seropositivity in rural subjects. Nevertheless, the strongest predictor for atopy in rural subjects seems to be regular contact with farm animals. Whether T. gondii infection is an intermediate factor in the association between farm contact and atopy needs to be confirmed in larger studies.

Toxoplasma gondii infection, atopy and autoimmune disease.

While for many allergens a dose-response relationship has clearly been established the association between early childhood exposure to cat allergens and risk of sensitisation is still controversial and even inverse relations have been described. At the same time, a negative association between Toxoplasma gondii (T. gondii) infection and atopic diseases has been found in epidemiologic studies. As cats are the major source of T. gondii oocysts, we hypothesize that cat allergen exposure might be a confounder in the association between T. gondii infection and allergic diseases. Furthermore, it is well known that atopic diseases are T helper cell 2 (Th2) driven while autoimmune diseases are dominated by a Th1 response. A counterbalance between Th1 and Th2 cells has been postulated. However, it has been shown recently that subjects with autoimmune disease are more likely to suffer from atopic diseases. Therefore, similar cytokine profiles might underlie these disorders. If this holds true it can be hypothesised that T. gondii infection is associated with a lower prevalence of autoimmune disease.

Changes in blood volume and hematocrit during acute preoperative volume loading with 5% albumin or 6% hetastarch solutions in patients before radical hysterectomy.

BACKGROUND: The impact of acute preoperative volume loading with colloids on blood volume has not been investigated sufficiently. METHODS: Before surgery, in 20 patients undergoing major gynecologic procedures, volume loading was performed during anesthesia by infusing approximately 20 ml/kg of colloid at a rate of 90 ml/min (group I: 5% albumin solution; group II: 6% hetastarch solution; n = 10 each). Plasma volume (indocyanine green dilution technique), erythrocyte volume (labeling erythrocytes with fluorescein), hematocrit, total protein, and hetastarch plasma concentrations (group II) were measured before and 30 min after the end of infusion. RESULTS: More than 1,350 ml of colloid (approximately 50% of the baseline plasma volume) were infused within 15 min. Thirty minutes after the infusion had been completed, blood volume was only 524 +/- 328 ml (group I) and 603 +/- 314 ml (group II) higher than before volume loading. The large vessel hematocrit (measured by centrifugation) dropped more than the whole body hematocrit, which was derived from double-label measurements of blood volume. CONCLUSIONS: The double-label measurements of blood volume performed showed that 30 min after the infusion of approximately 20 ml/kg of 5% albumin or 6% hetastarch solution (within 15 min), only mean 38 +/- 21% and 43 +/- 26%, respectively, of the volume applied remained in the intravascular space. Different, i.e., earlier or later, measuring points, different infusion volumes, infusion rates, plasma substitutes, or possibly different tracers for plasma volume measurement might lead to different results concerning the kinetics of fluid or colloid extravasation.

[The effects and properties of sodium nucleinate as a pyrogen working-standard. 9. Pyrogen detection with epinephrine-skin-, dactinomycin- and LAL-tests. The suitability of sodium nucleinate as a pyrogen standard]. / Uber Wirkungen und Eigenschaften des als Pyrogen-Arbeitsstandard verwendeten Natriumnucleinats. 9. Mitteilung: Pyrogennachweis mit Epinephrin-Haut-, Dactinomycin- und LAL-Test/Zur Eignung des Natriumnucleinats als Pyrogen-Standard.

Sodium nucleinate (NN) as well as bacterial lipopolysaccharide (LPS) can be detected by epinephrine-skin, dactinomycin and LAL tests. In the quantitative determination of two pyrogen standards for rabbit tests, consisting of NN, a smaller value was found by LAL test for the standard of greatest pyrogenic effect than for that less pyrogenically effective in rabbits. A standard consisting of NN can be used for the pyrogen test in rabbits. But in the future, if necessary a standard consisting of endotoxin will be used, due to its better comparability of results obtained by LAL and rabbit tests.

[False positive and false negative results in testing for pyrogenic impurities]. / Falschpositive und falschnegative Resultate bei der Prüfung auf pyrogene Verunreinigungen.

Causes of the occurrence of pyrogenic impurities in injection and infusion preparations as well as false-positive and false-negative results possible in the pyrogen test are reported. Possibilities of excluding pyrogenic impurities in the preparations concerned and of avoiding false-positive and false-negative results in the pyrogen test are discussed.