Combination Antifungal Therapy for Invasive Mold Infections Among Pediatric Patients with Hematological Malignancies: Data from A Real-Life Case-Series.

BACKGROUND: Invasive mold infections in children with hematological malignancies are associated with high mortality rates. The use of combination antifungal therapy in cases with a severe clinical course is increasing, although information on the efficacy and safety of this approach is limited. METHODS: We present a case series of 13 children affected by hemato-oncological disorders who received combination antifungal therapy for invasive mold infections at our center (Pediatric Hematology, San Gerardo Hospital, Monza, Italy) from 2011 to 2016, with the aim of describing their clinical characteristics, types of infections, treatment regimens, clinical outcomes, and treatment safety. Medical records were retrospectively reviewed in order to describe patients' characteristics. RESULTS: Combination antifungal therapy included liposomal amphotericin associated with caspofungin (5/13, 38.4%), voriconazole (5/13, 38.4%), or posaconazole (3/13, 23.1%). The 12-week treatment response rate was 69.2% (6/13 patients showed complete response, 3/13 partial response). The crude mortality was 30.7% (4/13): half was related to invasive mold infections (2/13, 15.38%) and half to disease progression (2/13, 15.38%). Overall, treatment was well tolerated, and we did not observe any permanent discontinuation of antifungals due to related side effects. CONCLUSIONS: In our experience, combination antifungal therapy seems to be a safe option in immunocompromised children with invasive mold infections. Well-designed studies are needed to confirm the safety of this approach and to better understand its efficacy in the pediatric setting.

Children with recurrent pneumonia and non-cystic fibrosis bronchiectasis.

BACKGROUND: Recurrent pneumonia (RP) is one of the most frequent causes of pediatric non-cystic fibrosis (CF) bronchiectasis (BE) and a consequent accelerated decline in lung function. The aim of this study was to analyse the clinical records of children with RP in attempt to identify factors that may lead to an early suspicion of non-CF BE. METHODS: We recorded the demographic and clinical data, and lung function test results of children without CF attending our outpatient RP clinic between January 2009 to December 2013 who had undergone chest high-resolution computed tomography ≥ 8 weeks after an acute pneumonia episode and ≤ 6 months before enrolment. RESULTS: The study involved 42 patients with RP: 21 with and 21 without non-CF BE. The most frequent underlying diseases in both groups were chronic rhinosinusitis with post-nasal drip and recurrent wheezing (81 % and 71.4 % of those with, and 85.7 % and 71.4 % of those without BE). FEV1 and FEF25-75 values were significantly lower in the children with non-CF BE than in those without (77.9 ± 17.8 vs 96.8 ± 12.4, p = 0.004; 69.3 ± 25.6 vs 89.3 ± 21.9, p = 0.048). Bronchodilator responsiveness was observed in seven children with BE (33.3 %) and two without (9.5 %; p = 0.13). CONCLUSIONS: Reduced FEV1 and FEF25-75 values seem associated with an increased risk of developing non-CF BE in children with RP. This suggests a need for further studies to confirm the diagnostic usefulness use of spirometry in such cases.

Impact of air pollution on respiratory diseases in children with recurrent wheezing or asthma.

BACKGROUND: Air pollution has many negative health effects on the general population, especially children, subjects with underlying chronic disease and the elderly. The aims of this study were to evaluate the effects of traffic-related pollution on the exacerbation of asthma and development of respiratory infections in Italian children suffering from asthma or wheezing compared with healthy subjects and to estimate the association between incremental increases in principal pollutants and the incidence of respiratory symptoms. METHODS: This prospective study enrolled 777 children aged 2 to 18 years (375 with recurrent wheezing or asthma and 402 healthy subjects). Over 12 months, parents filled out a daily clinical diary to report information about respiratory symptoms, type of medication used and healthcare utilization. Clinical data were combined with the results obtained using an air pollution monitoring system of the five most common pollutants. RESULTS: Among the 329 children with recurrent wheezing or asthma and 364 healthy subjects who completed follow-up, children with recurrent wheezing or asthma reported significantly more days of fever (p=0.005) and cough (p<0.001), episodes of rhinitis (p=0.04) and tracheitis (p=0.01), asthma attacks (p<0.001), episodes of pneumonia (p<0.001) and hospitalizations (p=0.02). In the wheezing/asthma cohort, living close to the street with a high traffic density was a risk factor for asthma exacerbations (odds ratio [OR]=1.79; 95% confidence interval [CI], 1.13-2.84), whereas living near green areas was found to be protective (OR=0.50; 95% CI, 0.31 -0.80). An increase of 10 µg/m3 of particulates less than 10 microns in diameter (PM10) and nitrogen dioxide (NO2) increased the onset of pneumonia only in wheezing/asthmatic children (continuous rate ratio [RR]=1.08, 95% CI: 1.00-1.17 for PM10; continuous RR=1.08, 95% CI: 1.01-1.17 for NO2). CONCLUSIONS: There is a significant association between traffic-related pollution and the development of asthma exacerbations and respiratory infections in children born to atopic parents and in those suffering from recurrent wheezing or asthma. These findings suggest that environmental control may be crucial for respiratory health in children with underlying respiratory disease.

Clinical profile of recurrent community-acquired pneumonia in children.

BACKGROUND: The aim of this case-control study was to analyse the clinical characteristics of children with recurrent community-acquired pneumonia (rCAP) affecting different lung areas (DLAs) and compare them with those of children who have never experienced CAP in order to contribute to identifying the best approach to such patients. METHODS: The study involved 146 children with ≥2 episodes of radiographically confirmed CAP in DLA in a single year (or ≥3 episodes in any time frame) with radiographic clearing of densities between occurrences, and 145 age- and gender-matched controls enrolled in Milan, Italy, between January 2009 and December 2012. The demographic and clinical characteristics of the cases and controls were compared, and a comparison was also made between the cases with rCAP (i.e. ≤3 episodes) and those with highly recurrent CAP (hrCAP: i.e. >3 episodes). RESULTS: Gestational age at birth (p = 0.003), birth weight (p = 0.006), respiratory distress at birth (p < 0.001), and age when starting day care attendance (p < 0.001) were significantly different between the cases and controls, and recurrent infectious wheezing (p < 0.001), chronic rhinosinusitis with post-nasal drip (p < 0.001), recurrent upper respiratory tract infections (p < 0.001), atopy/allergy (p < 0.001) and asthma (p < 0.001) were significantly more frequent. Significant risk factors for hrCAP were gastroesophageal reflux disease (GERD; p = 0.04), a history of atopy and/or allergy (p = 0.005), and a diagnosis of asthma (p = 0.0001) or middle lobe syndrome (p = 0.001). Multivariate logistic regression analysis, adjusted for age and gender, showed that all of the risk factors other than GERD and wheezing were associated with hrCAP. CONCLUSIONS: The diagnostic approach to children with rCAP in DLAs is relatively easy in the developed world, where the severe chronic underlying diseases favouring rCAP are usually identified early, and patients with chronic underlying disease are diagnosed before the occurrence of rCAP in DLAs. When rCAP in DLAs does occur, an evaluation of the patients' history and clinical findings make it possible to limit diagnostic investigations.

Association between radiological findings and severity of community-acquired pneumonia in children.

BACKGROUND: There are few published data concerning radiological findings and their relationship with community-acquired pneumonia (CAP) severity. The aim if this study was to assess radiographic findings in children with CAP of different severity in order to evaluate whether some parameters are associated with severe CAP. METHODS: We analysed the characteristics of parenchymal densities in 335 chest radiographs of otherwise healthy children (173 males; mean age ± standard deviation, 7.5 ± 4.5 years) admitted to our Emergency Room for CAP. Upon admission, chest radiographs were obtained in the two standard projections, and the children with severe or mild/moderate CAP were compared in order to identify any correlations between CAP severity and the radiological findings. RESULTS: Seventy-six of the 335 enrolled children (22.7%) fulfilled the criteria for severe CAP. In comparison with the children with mild/moderate CAP, in severe CAP there was a significantly greater frequency of a bilateral multifocal distribution (p = 0.01), the simultaneous involvement of ≥ 3 sites (p = 0.007), and the involvement of the right hilum (p = 0.02). The same results were confirmed in the multiple logistic regression model. CONCLUSIONS: This study shows that radiological findings such as a multifocal bilateral distribution, the simultaneous involvement of at least three sites, and right hilar consolidation are associated with severe CAP in otherwise healthy children, and could be considered markers of disease severity in children with CAP.

Influenza vaccination in children with cystic fibrosis.

Cystic fibrosis (CF) is an inherited autosomal recessive disease characterized by progressive pulmonary damage and respiratory failure. It is known that bacterial infections play a critical role in the development of significant lung damage, whereas the role of respiratory viruses in CF pulmonary exacerbations and the relationship between viral infections and the progression of lung damage are uncertain. Health authorities throughout the world recommend influenza vaccination for CF patients. The aim of this review is to analyze the impact of seasonal and pandemic influenza on CF patients and data concerning influenza vaccination in order to assess the current situation and identify areas for future study. As data are limited, further well-constructed clinical studies of the effectiveness of influenza vaccination on the main clinical outcome measures of pulmonary function and nutritional status in patients with CF are required.

Influenza vaccination in children at high risk of respiratory disease.

Chronic respiratory diseases (CRDs) are a heterogeneous group of diseases that can affect the pediatric population and health authorities throughout the world recommend influenza vaccination because of the significant risk of influenza-related complications. However, despite this recommendation, vaccine coverage is generally unsatisfactory. The aim of this review is to analyze the impact of influenza on children at high risk of respiratory disease, and the immunogenicity, safety and efficacy of influenza vaccination in such children. The results show that there is a significant risk of influenza-related complications in preterm neonates and infants, in whom influenza vaccines are immunogenic and safe (although their efficacy has not been specifically studied). There are conflicting data concerning the effect of influenza infection on asthma morbidity in children, and whether or not influenza vaccination helps to prevent asthma exacerbations. Recent data provide no evidence that influenza is more frequent in patients with cystic fibrosis than in healthy subjects, or that it is responsible for increased lower respiratory tract morbidity. The lack of any clear correlate of protection suggests that future studies should also consider the efficacy of the different influenza vaccines and not only evaluate them in terms of immunogenicity. Furthermore, there is a need for clinical studies to assess the effectiveness of the available vaccines in patients with other rare CRDs and other chronic underlying diseases with possibly severe respiratory involvement. It is also important to determine whether children with recurrent respiratory tract infections should be included in the list of those for whom influenza vaccination is recommended. In the meantime, given the increasing evidence of the burden of influenza on the population as a whole and the benefits associated with vaccination, annual influenza vaccinations should be recommended for all children at high risk of respiratory disease and the members of their households.