Safety of anti-inflammatory drugs in children with asthma.

PURPOSE OF REVIEW: Inhaled corticosteroids (ICS) are widely used as the first-line treatment of asthma. When the disease is not controlled by standard doses of ICS, other anti-inflammatory drugs should be considered. The aim of this report is to review the main adverse events induced by anti-inflammatory drugs in children with asthma and discuss possible actions to prevent or mitigate these effects. RECENT FINDINGS: Proper interpretation of ICS safety studies requires knowledge of the pharmaceutical properties and delivery device systems of the different ICS available. Genetic variants affecting susceptibility to corticosteroid-induced adrenal suppression were found in children and adults who use ICS to treat their asthma. There is evidence of the association between montelukast use and neuropsychiatric events. SUMMARY: Benefits of ICS, properly prescribed and used, outweigh their potential adverse effects. There is substantial evidence that the combination of ICS with long-acting beta2 agonists is safe for asthmatic children. Awareness of the potential risks of neuropsychiatric events in children taking montelukast should inform the clinicians' prescribing practices. Omalizumab is generally well-tolerated, but the evidence on the safety of other biologic agents in children is scanty. The risk of systemic adverse events with anti-inflammatory drugs must be balanced against the risks of uncontrolled asthma and/or frequent oral steroid use.

Respiratory manifestations of gastro-oesophageal reflux in children.

Gastro-oesophageal reflux disease (GORD) is a complex problem in children. Suspected respiratory manifestations of GORD, such as asthma, chronic cough and laryngitis, are commonly encountered in the paediatric practice, but continue to be entities with more questions than answers. The accuracy of diagnostic tests (ie, pH or pH-impedance monitoring, laryngoscopy, endoscopy) for patients with suspected extraoesophageal manifestations of GORD is suboptimal and therefore whether there is a causal relationship between these conditions remains largely undetermined. An empiric trial of proton pump inhibitors can help individual children with undiagnosed respiratory symptoms and suspicion of GORD, but the response to therapy is unpredictable, and in any case what may be being observed is spontaneous improvement. Furthermore, the safety of these agents has been called into question. Poor response to antireflux therapy is an important trigger to search for non-gastro-oesophageal reflux causes for patients' symptoms. Evidence for the assessment of children with suspected extraoesophageal manifestations of GORD is scanty and longitudinal studies with long-term follow-up are urgently required.

Infantile wheeze: rethinking dogma.

Wheeze is a common symptom in young children and is usually associated with viral illnesses. It is a major source of morbidity and is responsible for a high consumption of healthcare and economic resources worldwide. A few children have a condition resembling classical asthma. Rarer specific conditions may have a wheezy component and should be considered in the differential diagnosis. Over the last half century, there have been many circular discussions about the best way of managing preschool wheeze. In general, intermittent wheezing should be treated with intermittent bronchodilator therapy, and a controller therapy should be prescribed for a young child with recurrent wheezing only if positively indicated, and only then if carefully monitored for efficacy. Good multidisciplinary support, attention to environmental exposition and education are essential in managing this common condition. This article analyses the pathophysiological basis of wheezing in infancy and critically discusses the evolution of the scientific progress over time in this unique field of respiratory medicine.

Tuberculosis care among refugees arriving in Europe: a ERS/WHO Europe Region survey of current practices.

No evidence exists on tuberculosis (TB) and latent TB infection (LTBI) management policies among refugees in European countries.A questionnaire investigating screening and management practices among refugees was sent to 38 national TB programme representatives of low and intermediate TB incidence European countries/territories of the WHO European Region.Out of 36 responding countries, 31 (86.1%) reported screening for active TB, 19 for LTBI, and eight (22.2%) reporting outcomes of LTBI treatment. Screening for TB is based on algorithms including different combinations of symptom-based questionnaires, bacteriology and chest radiography and LTBI screening on different combinations of tuberculin skin test and interferon-γ release assays. In 22 (61.1%) countries, TB and LTBI screening are performed in refugee centres. In 22 (61.1%) countries, TB services are organised in collaboration with the private sector. 27 (75%) countries answered that screening for TB is performed as per national and international guidelines, while 19 (52.7%) gave the same answer with regards to LTBI screening. Infection control measures are inadequate in several of the countries surveyed.There is need for improved coordination of TB screening in Europe to implement the End TB Strategy and achieve TB elimination.

IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis.

Dysregulated inflammasome activation contributes to respiratory infections and pathologic airway inflammation. Through basic and translational approaches involving murine models and human genetic epidemiology, we show here the importance of the different inflammasomes in regulating inflammatory responses in mice and humans with cystic fibrosis (CF), a life-threatening disorder of the lungs and digestive system. While both contributing to pathogen clearance, NLRP3 more than NLRC4 contributes to deleterious inflammatory responses in CF and correlates with defective NLRC4-dependent IL-1Ra production. Disease susceptibility in mice and microbial colonization in humans occurs in conditions of genetic deficiency of NLRC4 or IL-1Ra and can be rescued by administration of the recombinant IL-1Ra, anakinra. These results indicate that pathogenic NLRP3 activity in CF could be negatively regulated by IL-1Ra and provide a proof-of-concept evidence that inflammasomes are potential targets to limit the pathological consequences of microbial colonization in CF.

Asthma in childhood.

Several topics on childhood asthma were addressed in the Paediatric Clinical Year in Review session at the 2015 European Respiratory Society International Congress. With regard to the relationship between lower respiratory tract infections and asthma, it emerges that is the number of respiratory episodes in the first years of life, but not the particular viral trigger, to be associated with later asthma development. Understanding which characteristics of individual patients are associated with an increased risk for asthma exacerbation is a critical step to implement strategies preventing these seasonal events. Recent data suggest the possibility that exhaled volatile organic compounds may qualify as biomarkers in detecting early signs of asthma. Adding information of exhaled volatile organic compounds and expression of inflammation genes to a clinical tool significantly improves asthma prediction in preschool wheezy children. Personal communication with children and adolescents is likely more important than the tools actually used for monitoring asthma. Systemic corticosteroids do not affect the long-term prognosis in children with first viral-induced wheezing episode and should be used cautiously during acute episodes. Finally, stress and a polymorphism upstream of a specific gene are both associated with reduced bronchodilator response in children with asthma.

Severe asthma features in children: a case-control online survey.

BACKGROUND: Very few studies have explored the distinguishing features of severe asthma in childhood in Europe, and only one study was conducted in Southern Europe. The aim of this study was to provide a detailed characterization of children with severe asthma treated in specialized pediatric asthma centers across Italy. METHODS: We conducted a web-based data collection of family, environmental, clinical and laboratory characteristics of 41 patients aged 6-17 years with severe asthma, defined according to the recent guidelines of the European Respiratory Society and the American Thoracic Society, and 78 age-matched peers with non-severe persistent asthma. The patients have been enrolled from 16 hospital-based pediatric pulmonology and allergy centers in Northern, Central, and Southern Italy. Logistic regression analysis assessed the relationship between patients' characteristics and severe asthma or non-severe persistent asthma. RESULTS: Features independently and significantly associated with severe asthma included lifetime sensitization to food allergens [Odds ratio (OR), 4.73; 95 % Confidence Interval (CI), 1.21-18.53; p = 0.03], lifetime hospitalization for asthma (OR, 3.71; 95 % CI, 1.11-12.33; p = 0.03), emergency-department visits for asthma during the past year (OR = 11.98; 95 % CI, 2.70-53.11; p = 0.001), and symptoms triggered by physical activity (OR = 12.78; 95 % CI, 2.66-61.40; p = 0.001). Quality-of-life score was worse in patients with severe asthma than in subjects with non-severe persistent asthma (5.9 versus 6.6, p = 0.005). Self-perception of wellbeing was compromised in more than 40 % of patients in both groups. Children with severe asthma had lower spirometric z scores than non-severe asthmatic peers (all p < 0.001), although 56 % of them had a normal forced expiratory volume in 1 s. No differences were found between the two groups for parental education, home environment, patients' comorbidities, adherence to therapy, exhaled nitric oxide values, and serum eosinophils and IgE . CONCLUSIONS: As expected, children with severe asthma had more severe clinical course and worse lung function than peers with non-severe persistent asthma. Unlike previous reports, we found greater sensitization to food allergens and similar environmental and personal characteristics in patients with severe asthma compared to those with non-severe persistent asthma. Psychological aspects are compromised in a large number of cases and deserve further investigation.

The burden of bacteremia and invasive diseases in children aged less than five years with fever in Italy.

BACKGROUND: Invasive diseases (ID) caused by Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae), and Neisseria meningitidis are a major public health problem worldwide. Comprehensive data on the burden of bacteremia and ID in Italy, including data based on molecular techniques, are needed. METHODS: We conducted a prospective, multi-centre, hospital-based study (GSK study identifier: 111334) to assess the burden of bacteremia and ID among children less than five years old with a fever of 39 °C or greater. Study participation involved a single medical examination, collection of blood for polymerase chain reaction (PCR) and blood culture, and collection of an oropharyngeal swab for colonization analysis by PCR. RESULTS: Between May 2008 and June 2009, 4536 patients were screened, 944 were selected and 920 were enrolled in the study. There were 225 clinical diagnoses of ID, 9.8 % (22) of which were bacteremic. A diagnosis of sepsis was made for 38 cases, 5.3 % (2) of which were bacteremic. Among the 629 non-ID diagnoses, 1.6 % (10) were bacteremic. Among the 34 bacteremic cases, the most common diagnoses were community-acquired pneumonia (15/34), pleural effusion (4/34) and meningitis (4/34). S. pneumoniae was the most frequently detected bacteria among bacteremic cases (29/34) followed by H. influenzae (3/34). Ninety percent (27/30) of bacteremic patients with oropharyngeal swab results were colonized with the studied bacterial pathogens compared to 46.1 % (402/872) of non-bacteremic cases (p < 0.001). PCV7 (7-valent pneumococcal conjugate vaccine) vaccination was reported for 55.9 % (19/34) of bacteremic cases. S. pneumoniae serotypes were non-vaccine serotypes in children who had been vaccinated. Mean duration of hospitalization was longer for bacteremic cases versus non-bacteremic cases (13.6 versus 5.8 days). CONCLUSIONS: These results confirm that S. pneumoniae is one of the pathogens frequently responsible for invasive disease.

Ground zero: not asthma at all.

Upper airway obstruction is commonly misdiagnosed as asthma. We report on four children with recurrent respiratory symptoms who had been erroneously diagnosed as having asthma and who received anti-asthma medication for several years. The evaluation of spirometry tracing was neglected in all cases. Subglottic stenosis, tracheomalacia secondary to tracheo-esophageal fistula, double aortic arch, and vocal cord dysfunction were suspected by direct inspection of the flow-volume curves and eventually diagnosed. The value of clinical history and careful evaluation of spirometry tracing in children with persistent respiratory symptoms is critically discussed.

Hyperventilation syndrome in adolescents with and without asthma.

BACKGROUND: Data on the prevalence of hyperventilation syndrome (HVS) in adolescents are scanty. OBJECTIVES: To determine the prevalence of HVS in a population of adolescents with and without asthma, and to verify whether HVS was related to asthma activity. METHODS: A population of adolescents was asked to self-complete a questionnaire, including the Nijmegen questionnaire to assess HVS, and a standardized asthma questionnaire. RESULTS: Seven hundred and sixty questionnaires were suitable for analysis. One hundred and twenty subjects (15.8%) were classified as asthmatic. Forty-seven subjects (6.2%) had a Nijmegen score ≥ 23, which was suggestive of HVS. Symptoms indicative of HVS were ten times more common in subjects with asthma (25%) than in those without asthma (2.5%). Nijmegen score was significantly higher in subjects with lifetime asthma (P < 0.001), current episodic asthma (P < 0.05) and current active asthma (P < 0.001) than in those with no asthma. In the whole population, girls presented HVS more frequently than boys (P < 0.001). There was a significant effect of gender (females, OR 3.2) and status of asthma (lifetime asthma, OR 11.2; current episodic asthma, OR 8.9; current active asthma, OR 41.5) on the probability of suffering from HVS. CONCLUSIONS: The prevalence of symptoms indicative of HVS in an unselected population of adolescents was relatively high. Symptoms were more common in girls and in subjects with asthma, and there was a significant effect of asthma activity on the probability of suffering from HVS. Further studies need to be performed in order to validate a screening tool for HVS in both adolescents and asthmatic subjects.

Cytophagic histiocytic panniculitis, hemophagocytic lymphohistiocytosis and undetermined autoimmune disorder: reconciling the puzzle.

Cytophagic histiocytic panniculitis is a rare disease, associated with either nonmalignant conditions or subcutaneous panniculitis-like T-cell lymphoma, and often also associated with hemophagocytic lymphohistiocytosis (HLH). We report the case of a 11-year-old boy with a history of secondary HLH who, after a local trauma, developed a painful, indurated plaque over the right thigh associated with relapsing HLH. Histopathologic findings from skin biopsy specimens revealed significant lobular panniculitis with benign histiocytes showing hemophagocytosis. High-dose intravenous methylprednisolone and cyclosporine A treatment was highly effective. A genetic study after a new, relapsing episode of HLH revealed an heterozygous missense mutation on STX 11 gene inherited from the mother.