Respiratory comorbidities in severe asthma: focus on the pediatric age.

INTRODUCTION: Asthma comorbidities are a frequent cause of adverse outcomes, such as poor asthma control, frequent asthma attacks, reduced quality of life, and higher healthcare costs. Comorbidities are well-known treatable traits whose proper management can help achieve optimal asthma control. Although multimorbidity is frequent among asthmatics, comorbidities are still a potential cause of misdiagnosis and under or over treatments, and little is known about their impact on severe pediatric asthma. AREAS COVERED: We provided a comprehensive, 5-year updated review focusing on the main respiratory comorbidities in severe asthma, particularly in epidemiology, pathogenesis, and current and future therapies. EXPERT OPINION: Respiratory comorbidities have unique characteristics in childhood. Their management must be multidisciplinary, age-specific, and integrated. Further longitudinal studies are needed to understand better the mutual interrelation and synergistic effect between asthma and its respiratory comorbidities, the identification of common, treatable risk factors leading to potential asthma prevention, the effectiveness of actual and future target-therapies, and the correlation between long-lasting respiratory comorbidities and poor lung function trajectories.

Controversies in the treatment of mild asthma. What novelties and practical implications?

Mild asthma is prevalent in childhood and causes as many as 30%-40% asthma exacerbations requiring emergency visits. The management of "intermittent" and "mild persistent" asthma phenotypes is still a matter of debate, even if the role of inhaled corticosteroids, both continuous and intermittent, is a cornerstone in this field. Recent updates of the guidelines on the strategies to manage these patients are coming, since the role of inflammation in these asthma phenotypes is crucial, as well as the potential side effect and risks of short-acting beta 2 agonists overuse, prescribed as the only "as-needed" treatments. In this paper, we overview the new (r)evolution regarding intermittent and mild persistent asthma management.

Intermittent and mild persistent asthma: how therapy has changed.

In the last few years much attention has been focused on research on severe asthma and the role of biologicals in its treatment, also in children. However, mild asthma is way more common in childhood and still causes as many as 30-40% of asthma exacerbations requiring emergency consultation. The management of "intermittent" and "mild persistent" asthma phenotypes is still a matter of debate, even if the role of inhaled corticosteroids, both continuous and intermittent, is a cornerstone in this field. Nevertheless, updates on the strategies to manage these patients are coming, since evidence emerged on the role of inflammation also in these asthma phenotypes as well as on the potential side effect and risks of short-acting beta 2 agonists overuse, which is common in patients for which they have been prescribed as the only as-needed treatment. Unsurprisingly, international guidelines, including GINA, are starting to recommend associating a corticosteroid when using a reliver. In this paper we overview the (r)evolution regarding the management of intermittent and mild persistent asthma. We also focus on the importance of knowing the chemical and physical characteristics of drugs and inhaler devices in order to optimize the treatment and reach the distal airways, as well as of trying to achieve a good compliance to treatments, especially in adolescents, for which it is currently possible to rely also on new digital health technologies.

Asthma in children and adolescents: the ControL'Asma project.

The control of asthma is the objective of asthma management. However, it is difficult to obtain in clinical practice. The Italian Society of Allergy and Clinical Immunology promoted the nationwide project "ControL'Asma" to investigate the real situation in a group of children and adolescents with asthma. The preliminary outcomes demonstrated that many asthmatic subjects do not achieve adequate asthma control. Moreover, asthma in Italian children and adolescents was usually more frequent in males, had an early onset and allergic phenotype with very frequent rhinitis comorbidity, uncontrolled and partly controlled asthma affected about the half of subjects. However, this project suggested that the assessment of asthma symptom perception by VAS could be a reliable tool in the asthma management.

Negative Atopy Patch Test and Negative Skin Prick Test Reduce the Need for Oral Food Challenge in Children with Atopic Dermatitis.

Atopic dermatitis (AD) is commonly associated with food allergy. Oral food challenge is the gold standard in the diagnosis of food allergy, but still has some troubles. The aim of this study was to evaluate whether a single test among skin prick test (SPT), measurement of specific immunoglobulin E (IgE), and atopy patch test (APT) or a combination of them could make food challenges unnecessary in patients with AD. Twenty patients affected by AD, under 6 years of age, were evaluated. Every child was investigated for cow's milk and hen's egg allergy using SPT, measurement of serum IgE (sIgE), APT, diagnostic elimination diet for 4 weeks, and open food challenges for milk and egg. The diagnosis of food allergy was established according to the results of the food challenge. We compared the results of all the tests with those of the open food challenge and calculated for each test the following parameters: sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Eight of 40 open food challenges were assessed as positive. None of the diagnostic tools showed a sufficient accuracy to be able to replace the food challenge. However, SPT, APT, and the measurement of sIgE as single parameters showed an NPV of 90%, and the combination of SPT and APT showed an NPV of 92%. Food challenge remains the gold standard for food allergy diagnosis in young children with AD, but the combination of SPT and APT is useful when both tests are negative, because this result provides a guidance in excluding an allergy to the investigated food and could make the food challenge superfluous in this case.

Clinical presentation of acute rhinosinusitis in children reflects paranasal sinus development.

BACKGROUND: Acute rhinosinusitis (ARS) usually presents with respiratory symptoms that persist for more than 10 days without improving. The aim of the study was to establish whether age may have any influence on the clinical presentation during childhood. METHODS: This prospective study evaluated 287 consecutive children (152 males and 135 females, aged between 2 and 15 years), in whom mild-moderate ARS was clinically suspected. Nasal endoscopy was performed in all of them to confirm the diagnosis. RESULTS: Endoscopy confirmed clinical diagnosis of ARS in 256 patients (89.2%). The age has shown to have significant influence on the clinical presentation pattern. CONCLUSIONS: This study provides evidence that age significantly influences the clinical presentation in children with mild-moderate ARS.

Role of forced expiratory flow at 25-75% as an early marker of small airways impairment in subjects with allergic rhinitis.

A close link exists between allergic rhinitis and asthma. Small airway disease (SAD), defined by a reduction in forced expiratory flow at 25-75% of the pulmonary volume (FEF25-75) and normal spirometry (normal forced expiratory volume at 1 second [FEV1], forced vital capacity [FVC], and FEV1/FVC ratio), may be a marker for early allergic or inflammatory involvement of the small airways in subjects with allergic diseases and no asthma. The aim of this study was to determine if there is a relationship between SAD, the outcome variable, and several allergic predictors in patients without asthma but with allergic rhinitis. A cross-sectional study was performed. Two hundred eleven midshipmen attending the third and fifth course of the Navy Academy of Livorno were screened. Fifty-eight midshipmen showed slight spirometric anomalies. Thus, they were referred to the Navy Hospital of La Spezia for standardized tests: skin-prick test, nasal cytology, spirometry, and methacholine bronchial challenge. A reduced FEF(25-75) was arbitrarily defined as < 80% of predicted. All 58 subjects had a normal FEV1, FVC, and FEV1/FVC ratio. Twenty subjects had a reduced FEF(25-75), consistent with the definition of SAD. A mean value of FEF(25-75) of 70.3 (SD, 8.5) was measured in patients with a reduced FEF, and it was 108.0 (SD, 14.3) in patients with preserved FEF(25-75). All the candidate allergic predictors appeared to be strongly associated with a reduced FEF(25-75). The proportion of subjects with reduced FEF(25-75) appeared to increase with increasing severity of the allergic predictors, and, correspondingly, the mean value of FEF(25-75) appeared to decrease. This study provides evidence that there is a relationship between SAD and allergic parameters such as nasal symptoms and eosinophils.

Efficacy of Bacillus clausii spores in the prevention of recurrent respiratory infections in children: a pilot study.

Probiotic milk has been previously demonstrated to reduce the number of respiratory infections (RI) among children attending day care centres. Thus, this pilot study was aimed to assess the efficacy and the safety of 3 month treatment with Bacillus clausii in the prevention of recurrent respiratory infections (RRI) in children. Eighty children with RRI were studied: 40 of them were randomly treated with B. clausii for 3 months, and followed up for further 3 months; 40 were included in the control group during the same period. Children treated with B. clausii had shorter duration of RI in comparison with the control group both during the treatment phase (mean 11.7 days vs 14.37; p=0.037) and the follow-up period (mean 6.6 days vs 10.92; p=0.049). This effect was evident also in allergic children during the follow-up. In conclusion, this pilot study provides the first preliminary evidence that B. clausii may exert a significant and persistent impact on RI in children and is safe and well tolerated.

Acute isolated sphenoid sinusitis in children.

OBJECTIVE: Acute infection of the sphenoid sinus usually affects both pre-adolescent and adolescent subjects and is associated with infections of the other paranasal sinuses. Acute isolated sphenoiditis, though uncommon, is frequently misdiagnosed as symptoms are vague and there are few clinical findings. Indeed, it is not usually diagnosed until the patient develops neurological complications. The aim of this report is to discuss our cases of acute isolated sphenoiditis and compare them with those reported in the International literature. METHODS: We reviewed our 10-year records of paediatric patients affected by acute isolated sphenoid sinusitis, as confirmed by nasal endoscopy and/or CT scan, and compared them with paediatric cases of sphenoid sinusitis reported in literature. In particular, we focused on clinical findings, associated risk factors, diagnostic approach, and treatment. RESULTS: As previously stated at the Brussels Consensus Meeting, patients can be separated into two groups on the basis of clinical findings: the first including patients affected by severe acute sphenoiditis presenting fever and headache, and frequently associated with neurological symptoms, with swimming and diving as possible predisposing factors. The second group includes patients with non-severe acute sphenoiditis, mainly associated with headache, allergic rhinitis being a possible predisposing factor. CONCLUSIONS: Acute isolated sphenoid sinusitis appears to be difficult to diagnose, and there are few reports in peer-reviewed paediatric journals. We wish to alert paediatricians and ENT specialists of the importance of this rare but still potentially devastating disorder.

Influence of HLA antigens and OSAS in childhood: a preliminary report.

Several studies have emphasized the role of familial factors and familial aggregation in increasing susceptibility to obstructive sleep apnea syndrome (OSAS); the aim of the present study was to investigate the possible influence of human leukocyte antigen (HLA) in the development of sleep disordered breathing and OSAS of children. Between January 2000 and January 2003, all the 370 children [193 males; median age: 5.2 years (range: 1-12 years)] with sleep disordered breathing referred to our Center were screened by a 41-item multiple-choice questionnaire. All habitual snores children underwent a polisomnographic evaluation, and those with an apnea/hypopnea index >3 were diagnosed as having OSAS. All children with OSAS or primary snoring were HLA typed for class I and II. According to nocturnal polygraphic monitoring study, 41 patients were diagnosed as having OSAS and 32 as primary snoring. Patients in the two diagnostic groups were homogeneous for demographic and clinical characteristics. HLA-B65 was found to be significantly more expressed in children with sleep disordered breathing as compared with controls (10.5% versus 3.61; Pypc < 0.04) while no difference was found for the other tested antigens. A logistic regression analysis found cough (P < 0.02) and persistent wheeze (P < 0.008) the sole risk factors for OSAS development. Our preliminary data suggest that HLA does not play a key role in the pathogenesis of OSAS, however more studies are needed to clarify this issue.