Allergic bronchopulmonary aspergillosis: diagnostic and treatment challenges

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder, occurring mostly in asthmatic and cystic fibrosis patients, caused by an abnormal T-helper 2 lymphocyte response of the host to Aspergillus fumigatus antigens. ABPA diagnosis is defined by clinical, laboratory and radiological criteria including active asthma, immediate skin reactivity to A. fumigatus antigens, total serum IgE levels>1000 IU/mL, fleeting pulmonary parenchymal opacities and central bronchiectases that represent an irreversible complication of ABPA. Despite advances in our understanding of the role of the allergic response in the pathophysiology of ABPA, pathogenesis of the disease is still not completely clear. In addition, the absence of consensus regarding its prevalence, diagnostic criteria and staging limits the possibility of diagnosing the disease at early stages. This may delay the administration of a therapy that can potentially prevent permanent lung damage. Long-term management is still poorly studied. Present primary therapies, based on clinical experience, are not yet standardized. These consist in oral corticosteroids, which control acute symptoms by mitigating the allergic inflammatory response, azoles and, more recently, anti-IgE antibodies. The latter two are used as a steroid-sparing agent to prolong the remission stage of the disease. Anti-IgE antibodies also have immunomodulatory properties. At present, the only way to bypass these limits and allow for an early diagnosis, is to assume ABPA in all patients with difficult-to-control asthma or cystic fibrosis. They should then be screened for sensitization to A. fumigatus antigens and, if positive, monitored more closely. Future controlled studies are needed to standardize present therapy, standardize cut-off values of various investigations, define the role of different novel immunomodulatory therapies, define the role of novel assays (such as recombinant A. fumigatus antigens and CCL17) and confirm new diagnostic and staging criteria

Vascular endothelial growth factor (VEGF) serological and lacrimal signaling in patients affected by vernal keratoconjunctivitis (VKC)

Background. Vernal keratoconjunctivitis (VKC) is a rare inflammatory disease involving the ocular surface, with seasonally exacerbated symptoms. Both type-1 and type-4 hypersensitivity reactions play a role in the development of VKC. Purpose. The aim of the present study was to assess the presence and evaluate the concentration of the vascular endothelial growth factor (VEGF) in tear and blood samples from patients with VKC, during the acute phase, based on the histopathological vasculostromal structure of the tarsal papillae. Methods. Two groups of children aged between 6 and 16 years of life were enrolled: 21 patients (16 males, 76%) affected by VKC, tarsal or mixed form, and 13 healthy children (5 males, 38%) used as controls. Blood and tear samples were obtained from all patients, in order to specifically assess the presence of VEGF. Statistical analyses were performed with one-way ANOVA, followed by post hoc comparisons with the Bonferroni tests. Pearson's correlation was chosen as statistical analysis to assess the relationship between the expression levels of VEGF in tears and blood and the clinical parameters measured. Results. Comparing the 2 groups for VEGF concentration, a statistically significant difference was found in tear samples: the mean value was 12.13 pg/mL (±5.54 SD) in the patient group and 7 pg/ml (±4.76 SD) in controls (p<0.05). However, no statistically significant difference was found when comparing VEGF concentration in blood samples (p>0.05), with a mean value of 45.17 pg/mL (±18.67 SD) in VKC patients and 38.08 pg/mL (±19.43 SD) in controls. Conclusions. This pilot study highlights the importance of lacrimal and vascular inflammatory biomarkers that can be detected in VKC patients during the acute phase, but not in healthy children. The small group of patients warrants additional studies on a larger sample, not only to further investigate the role of VEGF but also to evaluate the angiogenic biomarkers before and after topical treatment

Tear ferning test and pathological effects on ocular surface before and after topical cyclosporine in vernal keratoconjunctivitis patients

Background: Vernal keratoconjunctivitis (VKC) is a rare ocular surface inflammatory disease that affects mainly boys in the first decade of life. Clinical observations show that it generally regresses spontaneously with the onset of puberty, but therapeutic measures must be taken before then to control the course of the disease. Purpose: To evaluate the role of the lacrimal mucous component in VKC patients and compare tear ferning test (TFT) modifications, MUC5AC levels in tears, and density of conjunctival goblet cells to clinical characteristics before and after treatment with cyclosporine A (CY) in eye drops. Methods: Forty-seven patients affected by VKC and 30 healthy subjects aged between 3 and 16 years of life were enrolled. All individuals were submitted to complete eye examination and skin prick test (SPT) for the most common allergens. Then, they were subjected to collection of the tears and to impression cytology to evaluate TFT, MUC5AC levels, and conjunctival goblet cell density, before and after treatment with CY in eye drops. Results: Comparing the VKC group vs. the control group at baseline, a significant alteration in the degree of the ferns was found, indicating a pathological condition of the lacrimal mucous layer. In addition, an increased number of goblet cells were observed in the patients. The concentration of lacrimal secretory mucins (MUC5AC) did not show significant differences between the 2 groups. Patients treated with CY have reported improvements of some signs and symptoms of disease activity, including TFT, and a tendency of conjunctival goblet cell density to normalise. Conclusions: The results obtained demonstrated for the first time a significant alteration of the lacrimal mucin component evaluated in the VKC group, and an improvement of the latter after CY therapy

Stroke and migraine is there a possible comorbidity?

The association between migraine and stroke is still a dilemma for neurologists. Migraine is associated with an increased stroke risk and it is considered an independent risk factor for ischaemic stroke in a particular subgroup of patients. The pathogenesis is still unknown even if several studies report some common biochemical mechanisms between these two diseases. A classification of migraine-related stroke that encompasses the full spectrum of the possible relationship between migraine and stroke includes three main entities: coexisting stroke and migraine, stroke with clinical features of migraine, and migraine-induced stroke. The concept of migraine-induced stroke is well represented by migrainous infarction and it is described in the revised classification of the International Headache Society (IHS), representing the strongest demonstration of the relationship between ischaemic stroke and migraine. A very interesting common condition in stroke and migraine is patent foramen ovale (PFO) which could play a pathogenetic role in both disorders. The neuroradiological evidence of subclinical lesions most typical in the white matter and in the posterior artery territories in patients with migraine, opens a new field of research. In conclusion the association between migraine and stroke remains an open question. Solving the above mentioned issues is fundamental to understand the epidemiologic, pathogenetic and clinical aspects of migraine-related stroke

Rapid maxillary expansion and upper airway morphology: a systematic review on the role of cone beam computed tomography

OBJECTIVE: This study aimed to investigate the quality of cone beam computed tomography (CBCT) studies evaluating the effects of rapid maxillary expansion on upper airway morphology. MATERIALS AND METHODS: A database search was conducted using PubMed, Ovid, and Cochrane Library up to December 2016. Studies in which CBCT was adopted to visualize the upper airway before and after rapid maxillary expansion were included. The population target was growing patients. Methodological quality assessment was performed. RESULTS: The screening process resulted in the exclusion of 1079 references, resulting in only 9 remaining papers that fulfilled the inclusion criteria. No randomized clinical trials were found. The quality scores ranged from 36% to 68% of the maximum achievable, and the mean quality score of the studies was 50%. No good quality studies were detected in our sample. CONCLUSIONS: Inconsistencies in the CBCT protocols utilized were detected between studies. Head posture, tongue position, and segmentation protocols were not consistent. These discrepancies were reflected in the different results obtained in the studies. A valid and consistent protocol with regard to head and tongue positioning, as well as nasal cavity volume segmentation, is required

Prevalence and risk factors for atopic disease in a population of preschool children in Rome: Challenges to early intervention

Background: Allergic diseases are complex identities determined by an interplay of genetic and environmental factors, resulting in the clinical manifestation of the disease. So far in Italy, updated data about the prevalence and risk factors of respiratory and allergic diseases in preschool children are not available. Methods: Children aged 3-5 years, attending four different nursery schools in an urban district of the city of Rome. A standardized questionnaire developed under the SIDRIA-2 protocol was administered to the parents of the children for the assessment of the potential risk factors and the outcomes. Results: A total of 494 children were enrolled in the study; 289 of them (60.3%) performed a skin prick test (SPT). In the 12 months preceding the interviews, 15% of children experienced at least one episode of wheezing, 5.5% of allergic rhinitis, 11% of children had a doctor diagnosis of asthma, 12% of children who underwent the SPT were positive to at least one of the tested allergens, being diagnosed as atopic. The univariate analysis for the health outcomes of the study shows that asthma was positively associated with daycare attendance, mother's history of atopy, siblings' history of atopy, recurrent siblings' bronchitis, and dermatitis. Atopy was positively associated with mother's history of atopy and dermatitis, whereas there is a borderline protective association with recurrent siblings' bronchitis. Conclusions: This study represents a first comprehensive epidemiological evaluation of prevalence of respiratory and allergic diseases in children aged 3-5 years in the city of Rome and an updating of the evolution of allergic diseases

Cardiorespiratory fitness and sports activities in children and adolescents with solitary functioning kidney

Background: An increasing number of children with chronic disease require a complete medical examination to be able to practice physical activity. Particularly children with solitary functioning kidney (SFK) need an accurate functional evaluation to perform sports activities safely. The aim of our study was to evaluate the influence of regular physical activity on the cardiorespiratory function of children with solitary functioning kidney. Method: Twenty-nine patients with congenital SFK, mean age 13.9 ± 5.0 years, and 36 controls (C), mean age 13.8 ± 3.7 years, underwent a cardiorespiratory assessment with spirometry and maximal cardiopulmonary exercise testing. All subjects were divided in two groups: sedentary (S) and trained (T) patients, by means of a standardized questionnaire about their weekly physical activity. Results: We found that mean values of maximal oxygen consumption (VO2max) and exercise time (ET) were higher in T subjects than in S subjects. Particularly SFK-T presented mean values of VO2max similar to C-T and significantly higher than C-S (SFK-T: 44.7 ± 6.3 vs C-S: 37.8 ± 3.7 ml/min/kg; p < 0.0008). We also found significantly higher mean values of ET (minutes) in minutes in SFK-T than C-S subjects (SFK-T: 12.9 ± 1.6 vs C-S: 10.8 ± 2.5 min; p <0.02). Conclusion: Our study showed that regular moderate/high level of physical activity improve aerobic capacity (VO2max) and exercise tolerance in congenital SFK patients without increasing the risks for cardiovascular accidents and accordingly sports activities should be strongly encouraged in SFK patients to maximize health benefit

Malocclusion and rhinitis in children: an easy-going relationship or a yet to be resolved paradox? A systematic literature revision

Objective: The relation between nasal flow and malocclusion represents a practical concern to pediatricians, otorhinolaryngologists, orthodontists, allergists and speech therapists. If naso-respiratory function may influence craniofacial growth is still debated. Chronic mouth-breathing is reported to be associated also with a characteristic pattern of dental occlusion. On the other hand, also malocclusion may reduce nasal air flows promoting nasal obstruction. Hereby, the aim of this review was to describe the relationship between rhinitis and malocclusion in children. Methods: An electronic search was conducted using online database including Pubmed, Web of Science, Google Scholar and Embase. All studies published through to January 30, 2017 investigating the prevalence of malocclusion in children and adolescents (aged 0-20 years) affected by rhinitis and the prevalence of rhinitis in children with malocclusion were included. The protocol was registered at PROSPERO - International prospective register of systematic reviews under CRD42016053619. Results: Ten studies with 2733 patients were included in the analysis. The prevalence of malocclusion in children with rhinitis was specified in four of the studies ranging from as high as 78.2% to as low as 3%. Two out of the studies reported the prevalence of rhinitis in children with malocclusion with a rate ranging from 59.2 to 76.4%. Conclusion: The results of this review underline the importance of the diagnosis and treatment of the nasal obstruction at an early age to prevent an altered facial growth, but the data currently available on this topic do not allow to establish a possible causal relationship between rhinitis and malocclusion

Measurement of Interrupter Respiratory Resistance and Spirometry in Preschool Children: Influence of Respiratory Symptoms:

Pulmonary function tests play an important role in the diagnosis and management of respiratory diseases in children. The purpose of the study was to evaluate lung function using the interrupter resistance technique (Rint) and spirometry (flow-volume and volume-time) in preschool children and to correlate the findings with respiratory symptoms. We studied 103 children (65 males, 38 females; mean age 5.2±0.7 years; range 3.6–5.8). For each child we collected family history concerning: respiratory diseases, skin prick tests, smoking during maternal pregnancy, history of gestational and neonatal period. All children performed lung function tests (Rint and spirometry) and skin prick test for inhalant and food allergens. Twenty-eight subjects (27.2%) had respiratory symptoms (RS). Expiratory Rint were performed in all subjects and spirometry was carried out on 76 children (73.8%). Spirometric indices were not statistically different between subjects without respiratory symptoms (controls) and RS children except for FEF25–75 expressed as a percentage of the predicted value (RS: 81.5±13.7% vs controls: 94.5±15.8%; p <0.001). Rint mean values were significantly higher in RS children than in controls (RS: 135.6 ±24.8% vs controls: 102.4 ±21.7%; p< 0.0001). We found a statistically negative correlation between Rint and the following Spirometric indices: FEV0.5 (R= −0.696; p < 0.0001), FEV, (R= − 0.728; p < 0.0001) and FEF25–75 (R= −0.681; p < 0.0001). In preschool children with respiratory disease we found significantly higher mean values of Rint and lower FEF25-75 than in the control group and a significant negative relationship between Rint and Spirometric indices

Follow-up about two case reports after posaconazole therapy

Zygomycosis is a rare opportunistic fungal infection, that often complicates patients with uncontrolled Diabetes Mellitus, primary and acquired immunodeficiencies as defects of the cell-mediated immunity, myelodisplastic syndrome, hematological malignancies undergoing chemotherapy , HIV and long term therapy with steroid [1]. Mortality rate of these patient is very high, until 85% [2]. The causative organism is an aerobic saprophytic fungus, releasing spores, belonging to the order of Mucorales of the class Zygomycetes [3]. Inhalation and direct contamination of skin lesions are the major causes of infection, so the sporangiospores can migrate up to the lungs, nasal cavity and paranasal sinuses, gut and cutaneous tissues causing primary infection, hyphae invade vassels producing thrombi. Rhinocerebral Zygomycosis occurs with cranial nerve palsies, eye proptosis, pain and often blindness. Zygomicetes can invade central nervous system (CNS) from paranasal sinuses or remote site of infecton [1]. This life-threatening infection could be defeat through early detection, surgical excision and appropriate debridement, aggressive antifungal therapy, and control of risk factors, like diabetes mellitus like in our cases. We reported the follow up after long term therapy with Posaconazole in two Italian girls with Diabetes Mellitus Type 1 previously published [1,4]