Is secondary tracheomalacia associated with airway inflammation and infection?

BACKGROUND: Recurrent lower respiratory tract infections are among the most prevalent symptoms in secondary tracheomalacia due to mediastinal vascular anomalies (MVAs). It is not known whether this condition could result in persistent lower respiratory tract inflammation and subclinical infection. METHODS: A retrospective study was performed on records of children with tracheomalacia due to MVAs and recurrent respiratory infections who underwent computed tomography scan, bronchoscopy, and bronchoalveolar lavage (BAL) as part of their clinical evaluation. RESULTS: Thirty-one children were included in the study: 21 with aberrant innominate artery, four with right aortic arch, one with double aortic arch, and five with aberrant innominate artery associated with right aortic arch. Cytological evaluation of bronchoalveolar lavage fluid showed increased neutrophil percentages and normal lymphocyte and eosinophil proportions. Microorganism growth was detected in 13 BAL samples, with a bacterial load ≥104 colony-forming units/mL in eight (25.8%) of them. Most isolates were positive for Haemophilus influenzae. Bronchiectasis was detected in four children, all with BAL culture positive for H. influenzae. Four patients underwent MVA surgical correction and 27 conservative management, i.e., respiratory physiotherapy in all and high-dose amoxicillin/clavulanic acid (40 mg/kg/day) for 2-4 weeks in those with significant bacterial growth. There was an excellent outcome in most of them. CONCLUSIONS: Neutrophilic alveolitis is detectable in secondary tracheomalacia but is associated with a clinically significant bacterial load only in a quarter of the patients. Caution should be used regarding inappropriate antibiotic prescriptions to avoid the emergence of resistance, whilst airway clearance maneuvers and infection preventive measures should be promoted.

Can Resveratrol-Inhaled Formulations Be Considered Potential Adjunct Treatments for COVID-19?

The pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has led to an extraordinary threat to the global healthcare system. This infection disease, named COVID-19, is characterized by a wide clinical spectrum, ranging from asymptomatic or mild upper respiratory tract illness to severe viral pneumonia with fulminant cytokine storm, which leads to respiratory failure. To improve patient outcomes, both the inhibition of viral replication and of the unwarranted excessive inflammatory response are crucial. Since no specific antiviral drug has been proven effective for the treatment of patients and the only upcoming promising agents are monoclonal antibodies, inexpensive, safe, and widely available treatments are urgently needed. A potential anti-inflammatory molecule to be evaluated, which possesses antiviral activities in several experimental models, is the polyphenol resveratrol. This compound has been shown to inhibit SARS-CoV-2 replication in human primary bronchial epithelial cell cultures and to downregulate several pathogenetic mechanisms involved in COVID-19 severity. The use of resveratrol in clinical practice is limited by the low bioavailability following oral administration, due to the pharmacokinetic and metabolic characteristics of the molecule. Therefore, topical administration through inhaled formulations could allow us to achieve sufficiently high concentrations of the compound in the airways, the entry route of SARS-CoV-2.

Climate Change and Childhood Respiratory Health: A Call to Action for Paediatricians.

Climate change (CC) is one of the main contributors to health emergencies worldwide. CC appears to be closely interrelated with air pollution, as some pollutants like carbon dioxide (CO2), nitrogen oxides (NOx) and black carbon are naturally occurring greenhouse gases. Air pollution may enhance the allergenicity of some plants and, also, has an adverse effect on respiratory health. Children are a uniquely vulnerable group that suffers disproportionately from CC burden. The increasing global warming related to CC has a big impact on plants' lifecycles, with earlier and longer pollen seasons, as well as higher pollen production, putting children affected by asthma and allergic rhinitis at risk for exacerbations. Extreme weather events may play a role too, not only in the exacerbations of allergic respiratory diseases but, also, in favouring respiratory infections. Even though paediatricians are already seeing the impacts of CC on their patients, their knowledge about CC-related health outcomes with specific regards to children's respiratory health is incomplete. This advocates for paediatricians' increased awareness and a better understanding of the CC impact on children's respiratory health. Having a special responsibility for children, paediatricians should actively be involved in policies aimed to protect the next generation from CC-related adverse health effects. Hence, there is an urgent need for them to take action and successfully educate families about CC issues. This paper aims at reviewing the evidence of CC-related environmental factors such as temperature, humidity, rainfall and extreme events on respiratory allergic diseases and respiratory infections in children and proposing specific actionable items for paediatricians to deal with CC-related health issues in their clinical practice.

Airway inflammation and injury in children with prevalent weakly acidic gastroesophageal refluxes.

BACKGROUND: In children with gastroesophageal reflux (GER) both acid refluxes (AR) and weakly acidic refluxes (WAR) can induce respiratory symptoms (RS). METHODS: To characterize the airway inflammation in children with more prevalent WAR or AR (defined according a ROC curve analysis), we performed a 3 year-retrospective review of the medical records of patients who underwent fiberoptic bronchoscopy for difficult-to-treat chronic/recurrent respiratory symptoms and who had a positive multiple intraluminal esophageal impedance (pH/MII) monitoring. RESULTS: In the 13 WAR and 11 AR children, the number of cells recovered by bronchoalveolar lavage (BAL) was similar [0.78 (0.29-1.28) x 106 cells, and 1.05 (0.68-1.64) x 106 cells, respectively] (P = 0.22). A neutrophilic alveolitis and an elevated lipid-laden-macrophage (LLM) index were detected in both groups: no differences were found in neutrophils and lymphocyte percentages or in LLM index between WAR and AR children. In contrast, higher BAL epithelial cell proportions were seen in WAR [10.4 (4.85-23.45) %], as compared to AR [2.5 (1.25-7.25) %] children (P = 0.0045), suggesting greater airway damage in the formers. In the whole patient population a significant correlation was found between the proportions of BAL epithelial cells and the number of WAR events (r = 0.43; P = 0.037). Finally, elevated BAL concentrations of substance P and of pepsin were observed, not statistically different in the WAR and AR groups. CONCLUSIONS: In this patient population, WAR events can be associated with a significant airway inflammation and injury that, because of the biochemical mechanisms involved, are likely not completely preventable and/or counteracted by anti-acid treatments.

The impact of the recent AAP changes in palivizumab authorization on RSV-induced bronchiolitis severity and incidence.

Following the most recent modification by the American Academy of Pediatrics, based on American studies on RSV epidemiology, the Italian Drug Agency (AIFA) decided to limit the total financial coverage of the palivizumab prescription by the National Health Service only to the < 29 wGA group and age ≤ 12 months at the beginning of the RSV epidemic season. However, the vulnerability of otherwise healthy premature infants ≥ 29 wGA has been demonstrated in Italian analyses. We retrospectively reviewed records from children ≤ 1 years of age admitted for RSV-induced ALRI at the Gaslini Hospital, over three consecutive RSV epidemic seasons (RES) (2014-2017). We found that the prescription limitation on RSV immunoprophylaxis in preterms was associated in the 2016-2017 RES with: a) a high proportion of admission for the < 36 wGA infants, the great majority born at 33- < 36 wGA and a chronological age of < 6 months; b) a high proportion of preterms treated with high flow nasal cannula ventilation. These results strongly point to a need to reevaluate the role of palivizumab prophylaxis in the >= 29 wGA subpopulation when specific risk factors are present.

Recurrence of right lower lobe pneumonia 3 years after the first episode in an otherwise healthy 13-year-old girl.

Recurrent pneumonia is one of the most frequent reasons for referral to paediatric chest physicians. The diagnostic work-up is dependent on whether infection repeatedly occurs in the same lung lobe, or affects multiple lobes and/or different areas in different episodes. A 13-year-old girl was admitted with a second episode of right lower lobe pneumonia. The chest x-ray demonstrated an inhomogeneous opacity, without a clearly recognizable segmental distribution. A contrast-enhanced CT scan, was therefore performed that showed a polycyclic consolidation with blood supply from a systemic artery, originated from the thoracic aorta. A diagnosis of superinfection of an intralobar sequestration was made. The patient was treated with systemic antibiotics and, four weeks later, a segmental resection of the lesion was performed. The histological evaluation of the surgical specimen confirmed the diagnosis.

Immune response to hepatitis B virus vaccine in celiac subjects at diagnosis.

AIM: To evaluate hepatitis B virus (HBV) vaccine response and correlation with human leukocyte antigens (HLA) and/or gluten intake in celiac patients at diagnosis. METHODS: Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania (Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody (anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease. RESULTS: The entire study population was divided into three groups according to age: 24 patients aged between 0 to 5.5 years (48.9%, group A); 16 aged between 5.5 and 9.5 years (30.61%, group B); 9 aged between 9.5 and 17 years (18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups (P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes (homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences (P > 0.05). CONCLUSION: This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.

YKL-40 as marker of severe lung disease in cystic fibrosis patients.

BACKGROUND: YKL-40 is a chitinase-like protein present in serum of healthy subjects and its levels are increased in several human inflammatory diseases. The aim of this study was to evaluate the levels of both serum and sputum YKL-40 in cystic fibrosis (CF) patients. METHODS: Serum and sputum YKL-40 levels were measured in a cohort of twenty-eight patients with a diagnosis of CF and twenty healthy controls. RESULTS: Serum YKL-40 levels were significantly higher in CF patients (88.8±56.7 vs 18.6±2.9ng/ml, P<0.001), as well as sputum YKL-40 levels (138.5±132.7 vs 28.2±24.34, P<0.001) than in healthy controls. Serum YKL-40 levels were closely related to YKL-40 levels assessed in sputum samples (r=0.71; P<0.01). CONCLUSIONS: YKL-40 is elevated in CF patients and is further elevated during severe exacerbations. Longitudinal studies in infant are needed to establish its role in disease pathogenesis.

Granuloma annulare as first clinical manifestation of diabetes mellitus in children: a case report.

Granuloma annulare has been widely described in adults in association with systemic diseases such as type 1 diabetes mellitus. However in childhood this relationship remains unclear. We report the case of an 8-year-old girl, with multiple granuloma annulare as first clinical manifestation of type one diabetes mellitus.