Nasopharyngeal Carriage in Children After the Introduction of Generalized Infant Pneumococcal Conjugate Vaccine Immunization in Germany.

Epidemiological data on nasopharyngeal (NP) bacterial carriage in children in Germany are scarce. We prospectively characterized NP colonization to evaluate the impact of pneumococcal immunization. We longitudinally collected NP swabs from 2-month-old infants (visit 1; V1) at eight representative pediatric offices 10/2008-06/2009. The second swabs were taken at age 9-12 months (V2); the third swab was taken 3-6 months after the booster vaccination at age 17-19 months (V3), and the fourth swab (V4) at age 59-61 months. Samples were broth enriched, cultured for bacteria, and isolates were serotyped. Demographic risk factors for colonization were evaluated. Among 242 vaccinees, bacterial NP carriage increased with age [from 27.2% (V1) to 70.1% (V4)]; leading isolates were S. pneumoniae, H. influenzae, M. catarrhalis, and S. pyogenes. Overall pneumococcal carriage increased [14.7% (V1), 31.5% (V2), 34.8% (V3), 42.2% (V4)], being even greater among day-care attendees. Serotype distribution changed during the study period, with vaccine serotypes declining. At visit 4, 10-valent pneumococcal conjugate vaccine (PCV10) serotypes were no longer among the NP flora, while some serotypes unique to 13-valent pneumococcal conjugate vaccine (PCV13; 3 and 19A) were found. In Germany, universal infant PCV immunization was associated with an almost complete eradication of PCV-serotypes and concomitant increase of non-PCV-serotypes, mainly 11A, 22F, and 23A.

Risk Factors for Complicated Lymphadenitis Caused by Nontuberculous Mycobacteria in Children.

Nontuberculous mycobacteria (NTM) are an emerging cause of infections, including chronic lymphadenitis in children. To identify risk factors for NTM lymphadenitis, particularly complicated disease, we collected epidemiologic, clinical, and microbiological data on 138 cases of NTM lymphadenitis in children across 13 centers in Germany and Austria. We assessed lifestyle factors but did not identify specific risk behaviors. We noted that more cases of NTM lymphadenitis occurred during cold months than during warm months. Moreover, we noted female sex and age <5.5 years as potential risk factors. Complete extirpation of the affected lymph node appeared to be the best therapeutic measure. We integrated the study data to develop a simple risk score to predict unfavorable clinical outcomes for NTM lymphadenitis.

Therapy of 645 children with parapneumonic effusion and empyema-A German nationwide surveillance study.

OBJECTIVE: To evaluate the initial management of pediatric parapneumonic effusion or pleural empyema (PPE/PE) with regard to length of hospital stay (LOS). METHODS: Collection of pediatric PPE/PE cases using a nationwide surveillance system (ESPED) from 10/2010 to 06/2013, in all German pediatric hospitals. Inclusion of PPE/PE patients <18 years of age requiring drainage or with a PPE/PE persistence >7 days. Staging of PPE/PE based on reported pleural sonographic imaging. Comparison of LOS after diagnosis between children treated with different forms of initial invasive procedures performed ≤3 days after PPE/PE diagnosis: pleural puncture, draining catheter, intrapleural fibrinolytic therapy, surgical procedures. RESULTS: Inclusion of 645 children (median age 5 years); median total LOS 17 days. Initial therapy was non-invasive in 282 (45%) cases and invasive in 347 (55%) cases (pleural puncture: 62 [10%], draining catheter: 153 [24%], intrapleural fibrinolytic therapy: 89 [14%], surgical procedures: 43 [7%]). LOS after diagnosis did not differ between children initially treated with different invasive procedures. Results remained unchanged when controlling for sonographic stage, preexisting diseases, and other potential confounders. Repeated use of invasive procedures was observed more often after initial non-invasive treatment or pleural puncture alone than after initial pleural drainage, intrapleural fibrinolytic therapy or surgery. CONCLUSIONS: Initial treatment with intrapleural fibrinolytic therapy or surgical procedures did not result in shorter LOS than initial pleural puncture alone. Larger prospective studies are required to investigate which children benefit significantly from more intensive forms of initial invasive treatment. Pediatr Pulmonol. 2017;52:540-547. © 2016 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc.

Mucosal Immunity and acute viral gastroenteritis.

Acute gastroenteritis is a major killer of the very young worldwide. Rotavirus is the most common intestinal virus, causing acute gastroenteritis and extra-intestinal complications especially in young and chronically ill subjects. As early as 1991, the WHO recommended as high priority the development of a vaccine against rotavirus, the major pathogen causing enteric infections. Since the introduction of rotavirus vaccines for infant immunization programmes in different parts of the world in 2006, vaccination against rotavirus has resulted in substantial declines in severe gastroenteritis. The oral rotavirus vaccines RotaTeq(®) and Rotarix(®) are excellent examples for their unique features and principles of mucosal immunization. We elaborate on rotavirus immunity and the success of rotavirus vaccination and aspects also beyond infants' acute gastroenteritis.

Mucosal immunization in perspective.

Pandemic and seasonal influenza viruses are a constant public health threat with substantial morbidity and mortality worldwide. Prophylaxis is hard to realize, but immunization provides an efficient tool to control the disease. Despite most infections occurring at or through mucosal surfaces, vaccines are predominantly administered parenterally. Recently it has been suggested that vaccines applied via mucosal surfaces may be a viable novel approach. A number of clinical studies have proven live attenuated influenza vaccine given intranasally to have equivalent or superior immunogenicity and efficacy at the upper and lower respiratory tract compared with systemic intramuscular vaccination. Intranasal application provides easy administration facilitating mass immunization campaigns which requires no strictly sterile injection and is painless to recipients.

The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study.

BACKGROUND: Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany. METHODS: A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion. RESULTS: In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children. CONCLUSIONS: Our results demonstrate that vaccinating children 2-17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany.

An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine.

BACKGROUND: In two clinical trials, low-grade fever was observed more frequently after coadministration than after separate administration of two recommended routine pediatric vaccines. Since fever is an important issue with vaccine tolerability, we performed this open-label study on the efficacy and safety of prophylactic use of paracetamol (acetaminophen, Benuron®) in children administered routine 7-valent pneumococcal conjugate vaccine (PCV-7) coadministered with hexavalent vaccine (diphtheria-tetanus-acellular pertussis-hepatitis B, poliovirus, Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]) in Germany. METHODS: Healthy infants (N = 301) who received a 3-dose infant series of PCV-7 and DTPa-HBV-IPV/Hib plus a toddler dose were randomly assigned 1:1 to prophylactic paracetamol (125 mg or 250 mg suppositories, based on body weight) at vaccination, and at 6-8 hour intervals thereafter, or a control group that received no paracetamol. Rectal temperature and local and other systemic reactions were measured for 4 days post vaccination; adverse events were collected throughout the study. RESULTS: In the intent-to-treat population, paracetamol reduced the incidence of fever ≥38°C, but this reduction was only significant for the infant series, with computed efficacy of 43.0% (95% confidence interval [CI]: 17.4, 61.2), and not significant after the toddler dose (efficacy 15.9%; 95% CI: -19.9, 41.3); results were similar in the per protocol (PP) population. Fever >39°C was rare during the infant series, such that there were too few cases for assessment. After the toddler dose, paracetamol effectively reduced fever >39°C, reaching statistical significance in the PP population only (efficacy 79%; 95% CI: 3.9, 97.7). Paracetamol also reduced reactogenicity, but there were few significant differences between groups after any dose. No vaccine-related serious adverse events were reported. CONCLUSIONS: Paracetamol effectively prevented fever and other reactions, mainly during the infant series. However, as events were generally mild and of no concern in either group our data support current recommendations to administer paracetamol to treat symptoms only and not for routine prophylaxis. TRIAL REGISTRATION: NCT00294294.

Bronchial allergen challenges in children - safety and predictors.

BACKGROUND: In allergic asthma, the diagnosis of house dust mite (HDM) allergy is mainly based on the patient's history, allergy testing by the skin prick test (SPT) or the levels of allergen-specific IgE. We retrospectively analysed data from 350 bronchial provocations with HDM and related it to the following parameters: specific IgE, bronchial hyperresponsiveness (BHR) to methacholine testing (MCT) and exhaled NO (eNO). METHODS: Approximately 350 patients (5-18 yr of age) with allergic asthma and a positive SPT to HDMs were included. To define the sensitivity and specificity for the detection method of an early asthmatic response (EAR), a receiver-operating characteristic (ROC) curve was plotted. The accuracy was measured by the area under the ROC curve (AUC). A logistic regression model was used to predict the individual probability of a positive challenge. The results of the regression model were validated in a prospective group of n = 75 patients. RESULTS: The following cut-off values showed the best combination of sensitivity and specificity: specific IgE Dermatophagoides farinae 19.6 kU/l (AUC, 0.88), PD(20) FEV(1) 0.13 mg methacholine (AUC, 0.73) and eNO 20.1 ppb (AUC, 0.71). The following equation predicted the individual probability of a positive challenge in the retrospective and prospective group: p = 1(.) [1 + exp[-(-1.78 + 2.46.(10) log D. far - 1.25(.10) logPD(20) metha)]](-1) , (AUC = 0.88). CONCLUSIONS: The value of using the specific IgE and MCT as predictors was confirmed in a large number of patients. We also showed, for the first time, that the eNO predicted the EAR. The logistic regression model is repeatable with a good accuracy.

Airway responses and inflammation in subjects with asthma after four days of repeated high-single-dose allergen challenge.

BACKGROUND: Both standard and low-dose allergen provocations are an established tool in asthma research to improve our understanding of the pathophysiological mechanism of allergic asthma. However, clinical symptoms are less likely to be induced. Therefore, we designed a protocol for repetitive high-dose bronchial allergen challenges to generate clinical symptoms and airway inflammation. METHODS: A total of 27 patients aged 18 to 40 years with positive skin-prick tests and mild asthma underwent repetitive high-dose allergen challenges with household dust mites for four consecutive days. Pulmonary function and exhaled NO were measured at every visit. Induced sputum was analysed before and after the allergen challenges for cell counts, ECP, IL-5, INF-γ, IL-8, and the transcription factor Foxp3. RESULTS: We found a significant decrease in pulmonary function, an increased use of salbutamol and the development of a late asthmatic response and bronchial hyperresponsiveness, as well as a significant induction of eNO, eosinophils, and Th-2 cytokines. Repeated provocation was feasible in the majority of patients. Two subjects had severe adverse events requiring prednisolone to cope with nocturnal asthma symptoms. CONCLUSIONS: Repeated high-dose bronchial allergen challenges resulted in severe asthma symptoms and marked Th-2-mediated allergic airway inflammation. The high-dose challenge model is suitable only in an attenuated form in diseased volunteers for proof-of-concept studies and in clinical settings to reduce the risk of severe asthma exacerbations. TRIAL REGISTRATION: ClinicalTrials.govNCT00677209.

Mucosal immunity and nasal influenza vaccination.

Influenza remains a threat to public health, with immunization being a suitable method of infection prevention and control. Our understanding of the immunological regulations at the mucosa, antigen processing and presentation, and B-cell activation has improved, enabling research and targeted induction of immune responses at the site of antigen delivery. Nasal influenza immunization has distinct features compared with intramuscular vaccines, providing protection at the pathogen's entry site, higher levels of mucosal antibodies, cross-protection and needle-free application. This review summarizes our knowledge about mucosal immunity and the experience from clinical trials on the impact and safety of nasal influenza vaccination.

Vocal cord dysfunction in adolescents.

RATIONALE FOR THE STUDY: Vocal cord dysfunction (VCD) often presents with dramatic and abrupt symptoms. To diagnose VCD, visualization by direct laryngoscopy is required and because patients are usually asymptomatic, a specific method to provoke VCD is needed. Approaches to predict VCD by alterations of the flow-volume loop have been investigated. METHODS: Adolescents with clinical suspicion of VCD were invited to participate. After an initial pulmonary function test (PFT), direct laryngoscopy was performed. This was followed by a methacholine challenge test (MCT); the methacholine dose causing a 20% drop in forced expiratory volume after 1 sec (FEV(1) ) (PD(20) FEV(1) ) was calculated. Then a second laryngoscopy was conducted. PFT changes before and after MCT were compared with the data of 14 healthy controls (HCs). RESULTS: Thirty-five patients (8-19 years) were investigated. Three showed anatomical alterations. Of the remaining 32 patients, 14 had VCD and 18 had bronchial hyperresponsiveness (non-VCD). In 29 patients with a positive MCT, PD(20) FEV(1) methacholine was significantly lower in VCD compared with non-VCD (VCD 0.24 ± 0.4 mg, non-VCD 0.73 ± 0.73 mg, P = 0.0006). A PD(20) FEV(1) < 0.24 mg methacholine predicted VCD with a sensitivity of 85% and a specificity of 75%. VCD patients showed significantly lower PFT parameters after challenge; FEV(1) : VCD 58.5 ± 20.1%, non-VCD 80.2 ± 18.0%, and HCs 98.7 ± 16.6% (P < 0.0001). CONCLUSIONS: The combination of MCT and laryngoscopy may be able to differentiate between VCD and non-VCD. VCD patients showed a positive reaction at lower methacholine doses and displayed greater airway obstruction after MCT. PFTs and MCT do not replace direct laryngoscopy in the diagnosis of VCD in adolescents.

Methacholine challenge in young children as evaluated by spirometry and impulse oscillometry.

BACKGROUND: In young children, it is difficult to obtain a reproducible flow-volume curve throughout all stages of bronchial challenge. The forced oscillation technique (FOT) is especially established in paediatrics because this method does not require forced or maximal manoeuvres and is less cooperation-dependent than conventional spirometry. OBJECTIVES: To evaluate the association of spirometric and impulse oscillometric (IOS) indices in a short protocol for methacholine provocation. METHODS: The primary endpoint was the methacholine dose that caused a 20% decrease in FEV(1) (PD(-20)FEV(1)) compared to baseline. Changes in respiratory resistance (Rrs5) and reactance (Xrs5) acquired by IOS were compared with FEV(1). RESULTS: Forty-eight children (5.3 ± 0.9 years) were challenged. The mean maximal reduction in FEV(1) was 29.8% ± 14.7 (p < 0.0001), the mean increase in Rsr5 was 55.3% ± 31.7, and the mean decrease in Xrs5 was 0.37 kPa s L(-1) ± 0.23 (p < 0.001). An increase in Rrs5 of 45.2% and a decrease in Xrs5 of 0.69 kPa s L(-1) showed the optimal combination of sensitivity and specificity to detect a 20% reduction in FEV(1) (0.72 and 0.73; 0.80 and 0.76, respectively), and the area under the ROC curve was 0.76 and 0.81, respectively (p < 0.005). In 28 patients with significant changes in FEV(1) and Rsr5, the PD(-20)FEV(1) was 0.48 mg methacholine ±0.59 and the PD(+40)Rrs5 was 0.28 mg methacholine ±0.45 (p = 0.03). CONCLUSIONS: A short protocol for methacholine challenge testing is feasible in young children. IOS detected 70-80% of patients who responded in spirometry. During the challenge, the Rrs5 response preceded the FEV(1) response.

Early impact of smoking on lung function, health, and well-being in adolescents.

BACKGROUND: Smoking is the single most important risk factor for the development of chronic obstructive pulmonary disease, and more than 80% of adult smokers started smoking before the age of 20. The aim of our study was to evaluate the early impact of smoking on lung function, health, and well-being in adolescents. METHODS: Twenty-four non-smokers (10 male, 14 female, mean age 17.6 years) and 24 smokers (mean of 3.5 pack-years; 15 male, 9 female, mean age 17.8 years) were compared in terms of lung function, bronchial hyperreactivity (BHR), levels of exhaled carbon monoxide (eCO), exhaled nitric oxide (eNO), and blood counts. A questionnaire containing items from the ISAAC study was used to detect differences in health and well-being. RESULTS: There were no significant differences in lung function values between non-smokers and smokers (VC 95% vs. 103%, FEV(1) 106% vs. 116%, FEV(1) %/VC MAX 94.6% vs. 95.2%), whereas BHR significantly differed (P < 0.05). Furthermore, significant differences were found for eCO, eNO, Hb, leukocytes, and neutrophils. Health and well-being in terms of sleep and physical activity were significantly worse in smokers. CONCLUSION: Our results suggest an early impact of smoking on health after as few as 3.5 pack-years. Early signs of smoking are an increase in BHR, changes in blood count and a decrease of eNO even before changes in lung function become apparent.

Bronchial allergen challenge using the Medicaid dosimeter.

BACKGROUND: Bronchial allergen provocations are well established in asthma research. We evaluated the reproducibility of single-concentration, single-step allergen challenges in volunteers with grass pollen allergy. METHODS: Forty-seven subjects underwent bronchial challenges using the aerosol provocation system nebulizer (Medicaid Sidestream) with incremental doses of grass pollen to define the individual allergen dose that causes a 20% drop in FEV(1) (PD(20)FEV(1)). In 39 subjects this procedure was followed by single-step challenges. Early and late asthmatic responses were monitored, and increases in exhaled nitric oxide were measured before and 24 h after single-step challenges. RESULTS: After the first single-step challenge, the maximum drop in FEV(1) was 21.3% ± 8.0. A comparison of the drop in FEV(1) to the initial incremental challenge (29.7% ± 7.5) revealed an intraclass correlation of -0.30 (p < 0.05). In the second single-step challenge, the mean drop in FEV(1) was 20.9% ± 7.2. Compared with the first single-step challenge, the intraclass correlation was 0.37 (p < 0.05) and the 95% limits of agreement according to Bland and Altman were -17.5 to 18.1%. The increases in exhaled nitric oxide revealed substantial agreement in repeated single-step challenges (26.8 ppb ± 27.8 and 21.8 ppb ± 21.9, ICC 0.62, p < 0.001). CONCLUSIONS: The use of aerosol provocation system to calculate the PD(20)FEV(1) allergen is a timesaving procedure and is less prone to errors because only one dilution of the allergen is used. The repeatability in well-defined subjects is excellent to study the mechanisms of allergen-induced airway inflammation and the development of new treatments for allergic diseases.

Safety, tolerability, and impact on allergic inflammation of autologous E.coli autovaccine in the treatment of house dust mite asthma--a prospective open clinical trial.

BACKGROUND: Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases. METHODS: Prospective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination. RESULTS: In nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p = 0.334) compared to initial values (from 32.6 to 42.2 ppb; p = 0.046) (p = 0.034). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, Β-microglobuline) were within normal limits. Vital signs undulated within the physiological variability. CONCLUSION: The administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed. TRIAL REGISTRATION: EudraCT Nr. 2005-005534-12ClinicalTrials.gov ID NCT00677209.

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

UNLABELLED: RATIO: 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. METHODS: We 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. RESULTS: Ratios 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 (p = 0.040). 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.). CONCLUSION: When 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.

Health care workers and pertussis: an underestimated issue.

PURPOSE: Communicable and vaccine-preventable airway infections are a major public and occupational health issue. The epidemiology of pertussis has changed, with unprotected adults being the main source of infections. Thus, the prevention of a transmission from health care workers (HCWs) to patients is an important strategy to control this communicable infection. The Standing Committee on Vaccination (STIKO) at the Robert Koch-Institute in Germany has explicitly recommended that HCWs ought to be vaccinated against pertussis. However, vaccination rates among HCWs remain low. This study was meant to evaluate the attitudes of HCWs towards the pertussis vaccination and to determine the correlation between the influenza and pertussis vaccination status of HCWs. METHODS: An anonymous questionnaire was distributed to HCWs at a German university hospital. RESULTS: Overall, we found a disturbingly low level of awareness concerning official recommendations as to immunizations (35.6%) and the personal risk assessment of acquiring a work-related pertussis infection (23.2%). In general, both aspects were frequently associated with a refusal to get immunized. A strong correlation between the immunization status of pertussis and influenza was found among physicians: overall, 93.1% of physicians who were vaccinated against pertussis were also vaccinated against influenza. Nurses showed significantly weaker correlation rates as well as lower vaccination rates (p<0.05). CONCLUSIONS: Misconceptions about pertussis and low vaccination rates were prevalent among HCWs, particularly nurses. Hospital-based pertussis vaccination campaigns should focus on the risk of nosocomial pertussis transmission and on the new recommendations for pertussis immunization among adults and HCWs.

Predicting short term response to anti-inflammatory therapy in young children with asthma.

BACKGROUND: Currently available anti-inflammatory treatment for young children with asthma includes inhaled corticosteroids (ICS) and the leukotriene receptor antagonist (LTRA) montelukast. OBJECTIVE: To evaluate potential biomarkers of predicting short-term (6-week) response to ICS and LTRAs in children with asthma. METHODS: A total of 102 children aged 4 to 7 years with episodic asthma were enrolled in an open labelled single-centre study. Biomarkers and asthma characteristics were evaluated as predictors of treatment. Of 102 patients 45 became symptomatic during observation and were randomised to treatment either to montelukast or fluticasone for 6 weeks. RESULTS: Forced Expiratory Volume in one second (FEV1) increased with both treatments: FEV1 at randomisation was 90.2% and after therapy 106.8% with fluticasone vs. 90.8% and 103.7% for montelukast, respectively, showing that montelukast and fluticasone were equally effective in this age group (p = 0.44). Strong correlations to a favourable treatment response were pre-bronchodilatory FEV1 (p < 0.001) and airway reversibility (p = 0.04) at time of randomisation. None of the other biomarkers (methacholine testing, exhaled nitric oxide [eNO], presence of allergy, total Immunoglobulin E [IgE], cumulative specific IgE, eosinophils and parental smoking) were predictive. CONCLUSION: Despite the small sample size and the open-label design, the study suggests that the use of pre-bronchodilatory FEV1 and airway reversibility appears to be a good indicator of short-term anti-inflammatory therapy in young children with asthma.