Evaluation of treatment and long-term management of anaphylaxis in pediatric departments of Greece: a 2-year nationwide survey.

BACKGROUND: Anaphylaxis proportions of incidence are increasing globally. However, limited data are available regarding anaphylaxis in the pediatric population of Greece. PURPOSE: The aim of the study was to evaluate management of anaphylaxis in Greek pediatric departments. METHODS: We performed a questionnaire-based study of children aged less than 16 years presenting with anaphylaxis in 10 national pediatric hospitals over a period of 2 years. Management of anaphylaxis was assessed prior to and after an informative intervention. RESULTS: In all, 127 cases of anaphylaxis were identified. Epinephrine was administered in almost half of all cases (51.2%), predominantly through intramuscular route (88.5%), while the majority of anaphylaxis patients were treated with antihistamines (92.9%) and corticosteroids (70.1%). Epinephrine was more likely administered by physicians if the elicitor was a drug (P < 0.003). Regarding long-term management, an epinephrine auto-injector was prescribed in 66.9% of patients. Follow-up information was available for most of the patients (92.9%), the majority of whom (76.3%) were referred to an allergist. More than half of these patients (63.6%) had a documented allergy follow-up, which identified a causative allergen in 53.3% of cases. No statistically significant differences were recorded prior to and after the intervention regarding management of anaphylaxis. CONCLUSIONS: This nationwide study highlighted the necessity of further improvement in terms of anaphylaxis treatment and secondary prevention measures. This presupposes appropriate education and training of healthcare professionals, thus contributing to proper and comprehensive care of the pediatric population.

Study of Greek children and youths with cystic fibrosis identifies immunisation gaps and delays.

AIM: Data about immunisation rates in cystic fibrosis (CF) patients are scarce. We estimated the rates and timeliness of immunisations in CF patients aged 0.55-22 years. METHODS: We studied 122 subjects at a hospital in Greece in 2014. A standard questionnaire was used to collect data and parents' opinions about immunisations. RESULTS: The complete immunisation rates were 92.6% for diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis-Haemophilus influenzae (DTaP-IPV-Hib), 96.7% for hepatitis A, 97.4% for hepatitis B, 97.4% for measles-mumps-rubella, 85.1% for the varicella zoster virus, 85.1% for the meningococcus C conjugate, 84.3% for the pneumococcus conjugate and 58.9% for the bacillus Calmette-Guérin vaccine. Immunisation rates in youths were 64.4% for DTaP-IPV, 26.8% for the tetravalent meningococcus conjugate vaccine and 54.1% for the human papilloma virus vaccine. In addition, 30.1% received the 23-valent pneumococcal polysaccharide vaccine and 45.6% received annual influenza vaccines. Complete, up-to-date immunisation rates fell from 61.4% at 12 months of age to 14.5% at six and 12 years. All vaccines experienced delays. Most parents believed vaccines were necessary to protect their child's health. CONCLUSION: Our study of children with CF found immunisation gaps with no catch-up immunisations and these need to be administered at follow-up visits.

Efficacy of pulse methylprednisolone in a pediatric case of postinfectious bronchiolitis obliterans.

Postinfectious bronchiolitis obliterans is a chronic incapacitating disease with persistent airway inflammation. However, the efficacy of systemic corticosteroids has never been studied systematically. In the presented case, serial spirometry, plethysmography measurements, and nocturnal oximetry demonstrated progressive decline in lung hyperinflation and air-trapping and improvement in expiratory function and nocturnal oxygenation during and after six three-day courses of high-dose methylprednisolone (30 mg/kg/day). At four months post treatment, most gain in lung function was lost suggesting the need for sustained immunosuppression. Randomized, controlled trials using serial plethysmography measurements, spirometry, and nocturnal oximetry could provide evidence for the management of postinfectious bronchiolitis obliterans.

Viral croup: diagnosis and a treatment algorithm.

Viral croup is a frequent disease in early childhood. Although it is usually self-limited, it may occasionally become life-threatening. Mild croup is characterized by the presence of stridor without intercostal retractions, whereas moderate-to-severe croup is accompanied by increased work of breathing. A single dose of orally administered dexamethasone (0.15-0.6 mg/kg) is the mainstay of treatment with addition of nebulized epinephrine only in cases of moderate-to-severe croup. Nebulized budesonide (2 mg) can be given alternatively to children who do not tolerate oral dexamethasone. Exposure to cold air or administration of cool mist are treatment interventions for viral croup that are not supported by published evidence, but breathing heliox can potentially reduce the work of breathing related to upper airway obstruction. In summary, corticosteroids may decrease the intensity of viral croup symptoms irrespective to their severity on presentation to the emergency department.

Omalizumab therapy for allergic bronchopulmonary aspergillosis in children with cystic fibrosis: a synthesis of published evidence.

Allergic bronchopulmonary aspergillosis (ABPA) complicating cystic fibrosis (CF) is treated with corticosteroids. Since elevated IgE is a cardinal abnormality, anti-IgE has been used sporadically as adjuvant treatment. In eight case reports, 13 children with CF and ABPA received anti-IgE resulting in improved FEV1 , fewer respiratory symptoms and decreased corticosteroid use.

Oxidative stress and inflammatory markers in the exhaled breath condensate of children with OSA.

INTRODUCTION: Obstructive sleep apnea (OSA) in children has been associated with systemic inflammation and oxidative stress. Limited evidence indicates that pediatric OSA is associated with oxidative stress and inflammation in the airway. OBJECTIVE: The objective of this study is to assess the hypothesis that levels of oxidative stress and inflammatory markers in the exhaled breath condensate (EBC) of children with OSA are higher than those of control subjects. METHODS: Participants were children with OSA and control subjects who underwent overnight polysomnography. Morning levels of hydrogen peroxide (H(2)O(2)) and sum of nitrite and nitrate (NO(x)) in EBC of participants were measured. RESULTS: Twelve subjects with moderate-to-severe OSA (mean age ± standard deviation: 6.3 ± 1.7 years; apnea-hypopnea index--AHI, 13.6 ± 10.1 episodes/h), 22 subjects with mild OSA (6.7 ± 2.1 years; AHI, 2.8 ± 1 episodes/h) and 16 control participants (7.7 ± 2.4 years; AHI, 0.6 ± 0.3 episodes/h) were recruited. Children with moderate-to severe OSA had higher log-transformed H(2)O(2) concentrations in EBC compared to subjects with mild OSA, or to control participants: 0.4 ± 1.1 versus -0.9 ± 1.3 (p = 0.015), or versus -1.2 ± 1.2 (p = 0.003), respectively. AHI and % sleep time with oxygen saturation of hemoglobin <95% were significant predictors of log-transformed H(2)O(2) after adjustment by age and body mass index z score (p < 0.05). No significant differences were demonstrated between the three study groups in terms of EBC NO(x) levels. CONCLUSIONS: Children with moderate-to-severe OSA have increased H(2)O(2) levels in morning EBC, an indirect index of altered redox status in the respiratory tract.

Exhaled NO and exhaled breath condensate pH in the evaluation of asthma control.

BACKGROUND: Asthma is a chronic inflammatory airways disorder. However, no biomarker of airways inflammation has been included in the assessment of asthma control. OBJECTIVE: To evaluate exhaled NO (FeNO) and exhaled breath condensate (EBC) pH in patients with asthma according to the level of control, and their performance in the identification of not well-controlled patients. METHODS: FeNO and EBC pH after Argon deaeration were measured in 274 consecutive patients. Asthma control was evaluated by two asthma specialists blinded to FeNO and pH measurements according to GINA guidelines, as well as by asthma control test (ACT) and asthma control questionnaire (ACQ). RESULTS: FeNO was higher and EBC pH was lower in patients with not well-controlled compared to controlled asthma. In ROC analysis, FeNO presented an AUC of 0.790 for the identification of not well-controlled asthma performing better in non-smokers; EBC pH presented an AUC of 0.791 for the identification of not well-controlled asthma, performing better in smokers. The performance of both biomarkers was inferior to that of ACT and ACQ. FeNO values >30 ppb presented positive predictive values (PPV) > 0.85 with the exception of smokers treated with inhaled corticosteroids. EBC pH values ≤7.20 presented PPV >0.80 in all groups. The presence of FeNO >30 ppb and/or EBC pH ≤7.20 was indicative of not well-uncontrolled asthma in 88.3% of the patients. CONCLUSION: FeNO and EBC pH levels may identify patients with not well-controlled asthma. However, their performance was inferior to clinical judgment and may be limited to selected subgroups of asthmatic patients.

COPD prevalence and the differences between newly and previously diagnosed COPD patients in a spirometry program.

AIMS: To evaluate the prevalence and severity of COPD in a primary care population participating in a spirometry program. Differences between newly and previously diagnosed COPD patients were identified. METHODS: A spirometry program was conducted in 15 primary care centres. Visitors aged over 30 years who were willing to perform spirometry were included in this program. RESULTS: A total of 1,526 subjects provided acceptable spirometries. COPD prevalence in our population was 18.4%, of whom 69.0% were newly diagnosed. Most patients were classified as GOLD stages I and II (26.0% and 54.0%, respectively). COPD diagnosis was related to gender (men), age (older subjects), history of repeated respiratory infection in childhood, smoking (>10 pack-years) and presence of symptoms (cough, dyspnoea, wheezing). Variables related to newly diagnosed COPD were younger age and absence of chronic cough. CONCLUSIONS: A primary care spirometry program may identify a large proportion of undiagnosed COPD patients especially in the early stages of the disease. Newly diagnosed COPD patients were of younger age and presented with less symptoms. These results support the need for spirometry programs in primary care for early COPD detection.

Systemic and airway inflammation and the presence of emphysema in patients with COPD.

The aim of this study was to determine the impact of HRCT-confirmed emphysema on biomarkers evaluating airway and systemic inflammation in COPD patients. Forty-nine consecutive male COPD outpatients with stable COPD were divided in two groups according to the presence or absence of emphysema on HRCT. Patients underwent pulmonary function tests, plus assessment of exercise capacity, body composition and quality of life. Biomarkers were measured in serum (CRP, interleukin-6, TNF-alpha, leptin, adiponectin, osteocalcin, insulin growth factor-1, and systemic oxidative stress), in plasma (fibrinogen and VEGF) and in whole blood (B-type natriuretic peptide). TNF-alpha, 8-isoprostane and pH were additionally measured in exhaled breath condensate. Patients with emphysema had more severe lung function impairment, lower body-mass index and fat-free mass index, and poorer quality of life. Additionally, they presented increased systemic oxidative stress and plasma fibrinogen and lower BNP compared to patients without emphysema. After proper adjustment for disease severity, all differences remained with the exceptions of body-mass index, fat-free mass index and BNP. COPD patients with HRCT-confirmed emphysema present increased systemic oxidative stress and fibrinogen, suggesting that they may be more prone to the systemic consequences of COPD compared to patients without emphysema.

Matrix metalloproteinases in respiratory diseases: from pathogenesis to potential clinical implications.

Matrix metalloproteinases (MMPs) are zinc-endopeptidases responsible for degradation of the extracellular matrix (ECM) components including basement membrane collagen, interstitial collagen, fibronectin, and various proteoglycans, during normal remodeling and repair processes. The turnover and remodeling of ECM must be tightly regulated since excessive or inappropriate expression of MMPs may contribute to the pathogenesis of tissue destructive processes associated with lung inflammation and disease. Despite the fact that our knowledge in the field of MMP biology is rapidly expanding, the role of MMPs in the pathogenesis of lung diseases is still not clear. The aim of the present review is to present the basic principles of MMP biology and, subsequently, to focus on the clinical and experimental evidence related to MMP activity in various lung disorders, including lung cancer, pleural effusions, chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome and interstitial lung diseases.

Clinical, functional and biochemical changes during recovery from COPD exacerbations.

The pathways underlying chronic obstructive pulmonary disease exacerbations (ECOPD) remain unclear. This study describes the clinical, functional and biochemical changes during recovery from ECOPD. Thirty hospitalized patients with Anthonisen's type-I ECOPD were evaluated on days 0 (admission), 3, 10 and 40. A five-symptom score (TSS), performance status and quality of life were evaluated. Post-bronchodilator spirometry, blood gases, oxidative stress, C-reactive protein (CRP), serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and fibrinogen were also measured. Patients were classified as early- or late-recoverers, based on whether dyspnea had returned to pre-exacerbation level by day 10. Most clinical, functional and biochemical parameters improved during follow-up. CRP and IL-6 levels reduced on Day 3 (p<0.05), whereas SAA on Day 10 (p<0.01). TNF-alpha was reduced on Days 3 and 10, but on Day 40 its levels returned to baseline. Fibrinogen and WBC reduced only by day 40. TSS and dyspnea were correlated inversely with FEV(1) on days 3, 10 and 40. Although late-recoverers had lower FEV(1) on admission, none of the reported measurements on admission and day 3 predicted early recovery. During recovery from ECOPD, symptomatic improvement correlates only with post-bronchodilator FEV(1) whereas systemic inflammatory burden subsidence does not correlate with clinical and functional changes. Although late-recoverers have lower FEV(1) on admission, none of the measured parameters is able to predict early symptomatic recovery.

Nasal continuous positive airway pressure treatment reduces systemic oxidative stress in patients with severe obstructive sleep apnea syndrome.

OBJECTIVE: To evaluate whether nasal continuous positive airway pressure (nCPAP) reduces oxidative stress in patients with severe obstructive sleep apnea (OSA) syndrome. MATERIALS AND METHODS: Forty-six patients with severe OSA (AHI> or =30) requiring nasal CPAP treatment and 46 controls (subjects without OSA and with mild OSA as defined by an AHI<15) were enrolled. Oxidative stress was evaluated in blood samples with a commercially available automated spectrophotometric assay (D-ROMs test, Diacron, Grosseto, Italy). Blood samples were collected the evening before (10:00 p.m.) and the morning after (07:00 a.m.) a diagnostic polysomnography. Patients with severe OSA syndrome were subsequently submitted to a second polysomnography with nasal CPAP titration the following night. Using the same schedule we collected blood samples from the patients the morning after the nCPAP titration and after two months of nCPAP treatment. RESULTS: Patients with severe OSA presented higher levels of oxidative stress than patients with AHI<15 in the evening and in the morning (357.57+/-13.07 UCarr vs. 319.28+/-12.66 UCarr, p=0.038, and 371.83+/-12.83 UCarr vs. 328.09+/-11.76 UCarr, p=0.014, respectively). Patients with severe OSA presented a significant reduction the levels of oxidative stress the morning after the nCPAP titration study (371.83+/-12.83 UCarr vs. 298.21+/-9.62 UCarr, p=0.001) and this reduction was further preserved after a period of two months of nCPAP treatment (293.72+/-6.55 UCarr, p=0.001 vs. baseline). Statistically significant correlations were observed between levels of oxidative stress and nocturnal polysomnography (NPSG) markers as oxygen desaturation index (ODI), arousal index (AI), lowest oxygen saturation of hemoglobin, and mean oxygen saturation of hemoglobin. CONCLUSIONS: Patients with severe OSA syndrome presented increased systemic oxidative stress. A single night of nCPAP treatment significantly reduced the levels of oxidative stress in patients with severe OSA syndrome, and this reduction was maintained at least after two months of nCPAP treatment.

VEGF, TNF-alpha and 8-isoprostane levels in exhaled breath condensate and serum of patients with lung cancer.

The aim of the present study was to evaluate the levels of VEGF, 8-isoprostane and TNF-alpha in EBC and serum of patients with primary lung cancer prior to the initiation of any treatment, in order to evaluate their possible diagnostic role. Furthermore, associations between VEGF, 8-isoprostane and TNF-alpha levels in EBC and serum with clinicopathologic factors were investigated. We enrolled 30 patients with lung cancer (mean age 65.2+/-10.5 years) and 15 age and gender-matched healthy smokers as controls. Serum and EBC were collected before any treatment. TNF-alpha, VEGF and 8-isoprostane levels in EBC and serum were analyzed by an immunoenzymatic method (ELISA). A statistically significant difference was observed between lung cancer patients and the control group regarding the values of TNF-alpha, both in EBC (52.9+/-5.0 pg/ml vs. 19.4+/-3.9 pg/ml, p<0.0001) and serum (44.5+/-6.3 pg/ml vs. 22.2+/-4.3 pg/ml, p=0.035). Moreover, EBC VEGF levels were higher in patients with T3-T4 tumor stage compared to T1-T2 (9.3+/-2.8 pg/ml vs. 2.3+/-0.7pg/ml, p=0.047). A statistically significant correlation was also observed between serum and EBC values of VEGF (r=0.52, p=0.019). In addition, serum levels of VEGF were higher in lung cancer patients than in controls (369.3+/-55.1 pg/ml vs. 180.5+/-14.7 pg/ml, p=0.046). VEGF serum levels were also found higher in patients with advanced stage of disease (IIIB-IV) and distant nodal metastasis (N2-N3). No differences were observed in 8-isoprostane in EBC between lung cancer patients and controls. In contrast, serum 8-isoprostane levels were higher in lung cancer patients compared to controls (24.9+/-3.6 pg/ml vs. 12.9+/-1.6 pg/ml, p=0.027) and were higher in patients with advanced disease. All three biomarkers presented acceptable reproducibility in the EBC on two consecutive days. In conclusion, we have shown that TNF-alpha, VEGF and 8-isoprostane are elevated in the serum of lung cancer patients and increased serum VEGF and 8-isoprostane levels are related to advanced disease. In EBC, increased TNF-alpha levels were observed in lung cancer patients, whereas increased VEGF levels were observed in advanced T-stage. Further longitudinal studies are warranted for the evaluation of the prognostic role of these biomarkers in lung cancer.

Portable exhaled nitric oxide as a screening tool for asthma in young adults during pollen season.

BACKGROUND: The fraction of exhaled NO (FeNO) is valuable for the follow-up of asthmatic patients. However, its usefulness as a screening tool for asthma is not established. METHODS: We screened a population of 961 university students with a modified European Community Respiratory Health Survey questionnaire that has been previously used for the screening of respiratory symptoms related to asthma. All subjects with a positive answer to at least one question (n = 149) were submitted to FeNO measurement with a portable nitric oxide analyzer. Subsequently, they were submitted to spirometry and evaluated by a physician blinded to FeNO measurements. Seventy students with no respiratory symptoms served as control subjects. RESULTS: Asthma was diagnosed in 63 subjects, and allergic rhinitis was diagnosed in 57 subjects. Asthmatics presented higher FeNO values than control subjects (median, 20 parts per billion [ppb]; interquartile range, 14 to 31 ppb; vs median, 11 ppb; interquartile range, 7 to 13 ppb, respectively; p < 0.0001), whereas they did not differ from patients with allergic rhinitis (median, 17 ppb; interquartile range, 12 to 23 ppb; p = 0.28). FeNO values > 19 ppb presented 85.2% specificity and 52.4% sensitivity for the diagnosis of asthma (area under the curve [AUC], 0.723). The diagnostic performance of FeNO was better in nonsmokers (AUC, 0.805), yet FeNO values > 25 ppb were characterized by specificity > 90% for the diagnosis of asthma both in smokers and in nonsmokers. However, FeNO was not a good marker for the differentiation between asthma and allergic rhinitis. CONCLUSIONS: FeNO measurement with a portable analyzer is useful for the screening for asthma in young adults. Significant confounding factors are allergic rhinitis and current smoking.

Sleep-disordered breathing in 3,680 Greek children.

The goal of the present investigation was to describe the prevalence of and clinical factors associated with sleep-disordered breathing in children and adolescents. Children and adolescents (3,680 in all, 1-18 years old) attending schools in central Greece were surveyed by questionnaires distributed to parents. We found a similar prevalence of habitual snoring (present every night) among three different age groups (5.3%, 4%, and 3.8% in 1-6-, 7-12-, and 13-18-year-old subjects, P = NS). Several children with an adenoidectomy and/or tonsillectomy were snoring every night (6.1%), whereas sleepiness at school was more common in habitual snorers than in nonhabitual snorers (4.6 vs. 2%, P = 0.03). Seventy randomly selected subjects among 307 snorers without adenoidectomy and/or tonsillectomy underwent polysomnography. The estimated frequency of obstructive sleep apnea-hypopnea among children without adenoidectomy and/or tonsillectomy was 4.3%. Factors associated with snoring were: male gender (odds ratio 1.5 (confidence interval, 1.2-1.9)); chronic rhinitis (2.1 (1.6-2.7)); snoring in father (1.5 (1.2-1.9)), mother (1.5 (1.1-2.0)), or siblings (1.7 (1.2-2.4)); adenoidectomy in mother (1.5 (1.0-2.2)); and passive smoking (1.4 (1.1-1.8)). In conclusion, snoring every night was equally prevalent in younger and older ages, more frequent in males, and present even in some children with a history of adenoidectomy and/or tonsillectomy. Chronic rhinitis, family history of snoring, and exposure to cigarette smoke were associated with an increased frequency of habitual snoring.