Giuliana Ferrante

The Burden of Rhinitis and Rhinoconjunctivitis in Adolescents

Purpose Rhinitis and conjunctivitis are common diseases worldwide that are frequently associated. Nevertheless, the risk factors for rhinoconjunctivitis are not well-described and the impact of conjunctivitis on rhinitis and asthma in children remains unknown. This study explored the different risk factors and evaluated the burden of rhinoconjunctivitis among adolescents. Methods This was a cross-sectional study conducted on a random sample of schoolchildren, aged 10-17 years, using skin prick tests and a self-administered questionnaire on respiratory health investigating the impact of rhinitis and rhinoconjunctivitis on daily activities. Results A complete evaluation was obtained for 2,150 children. The prevalence of rhinitis alone was 18.2% and rhinitis associated with conjunctivitis was 20.5%. Rhinoconjunctivitis was more frequently associated with females, a parental history of atopy, domestic exposure to mold/dampness, passive smoke exposure, and reported truck traffic in residential streets. Moreover, rhinoconjunctivitis was associated with a higher level of allergic sensitization. The prevalence of current asthma was 1.7% in subjects without rhinitis or rhinoconjunctivitis, 5.1% in rhinitis and 10.7% in rhinoconjunctivitis. In a logistic model, rhinoconjunctivitis yielded a 2-fold risk for current asthma with respect to rhinitis. Subjects with rhinoconjunctivitis had poorer quality of life (QoL); there was an impact on daily activities in 4.6% of rhinitis and 10.7% of rhinoconjunctivitis. Conclusions Ocular symptoms increase the role of rhinitis as a risk factor for asthma and its impact on daily activities in children.

Environmental Effects on Fractional Exhaled Nitric Oxide in Allergic Children

Fractional exhaled nitric oxide (FeNO) is a non-invasive marker of airway inflammation in asthma and respiratory allergy. Environmental factors, especially indoor and outdoor air quality, may play an important role in triggering acute exacerbations of respiratory symptoms. The authors have reviewed the literature reporting effects of outdoor and indoor pollutants on FeNO in children. Although the findings are not consistent, urban and industrial pollution—mainly particles (PM2.5 and PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2)—as well as formaldehyde and electric baseboard heating have been shown to increase FeNO, whilst ozone (O3) tends to decrease it. Among children exposed to Environmental Tobacco Smoke (ETS) with a genetic polymorphisms in nitric oxide synthase genes (NOS), a higher nicotine exposure was associated with lower FeNO levels. Finally, although more studies are needed in order to better investigate the effect of gene and environment interactions which may affect the interpretation of FeNO values in the management of children with asthma, clinicians are recommended to consider environmental exposures when taking medical histories for asthma and respiratory allergy. Further research is also needed to assess the effects of remedial interventions aimed at reducing/abating environmental exposures in asthmatic/allergic patients.

Smoke exposure as a risk factor for asthma in childhood: a review of current evidence.

Asthma is a common chronic multifactorial disease that affects >300 million people worldwide. Outdoor and indoor pollution exposure has been associated with respiratory health effects in adults and children. Smoking still represents a huge public health problem and millions of children suffer the detrimental effects of passive smoke exposure. This study was designed to review the current evidences on exposure to passive smoke as a risk factor for asthma onset in childhood. A review of the most recent studies on this topic was undertaken to provide evidence about the magnitude of the effect of passive smoking on the risk of incidence of asthma in children. The effects of passive smoking are different depending on individual and environmental factors. Environmental tobacco smoke (ETS) is one of the most important indoor air pollutants and can interact with other air pollutants in eliciting respiratory outcomes during childhood. The increased risk of respiratory outcomes in children exposed to prenatal and early postnatal passive smoke might be caused by an adverse effect on both the immune system and the structural and functional development of the lung; this may explain the subsequent increased risk of incident asthma. The magnitude of the exposure is quite difficult to precisely quantify because it is significantly influenced by the childs daily activities. Because exposure to ETS is a likely cause for asthma onset in childhood, there is a strong need to prevent infants and children from breathing air contaminated with tobacco smoke.

Vitamin D, allergies and asthma: focus on pediatric patients

In recent years, the interest of the scientific world towards vitamin D gradually increased, and several studies have been conducted to dissect its possible role in modulating the development/course of allergic diseases. Also, Vitamin D supplementation has been assessed as a beneficial approach for treating allergies in some, but not all studies. We reviewed herein the available and relevant literature concerning the possible links between Vitamin D, its supplementation and allergic diseases. A literature search was made independently by the Authors, identifying articles for a narrative review. As per literature, Vitamin D plays a key role in calcium and phosphate metabolism, and it is essential for bone health in infants, children and adolescents. However, there is presently insufficient evidence to support vitamin D supplementation for prevention or treatment of allergic diseases in infants, children and adolescents, concerning allergic rhinitis, asthma, food allergy and atopic dermatitis.

The care pathway for children with urticaria, angioedema, mastocytosis

Cutaneous involvement characterized by urticarial lesions with or without angioedema and itch is commonly observed in routine medical practice. The clinical approach may still remain complex in real life, because several diseases may display similar cutaneous manifestations. Urticaria is a common disease, characterized by the sudden appearance of wheals, with/without angioedema. The term Chronic Urticaria (CU) encompasses a group of conditions with different underlying causes and different mechanisms, but sharing the clinical picture of recurring wheals and/or angioedema for at least 6 weeks. Hereditary Angioedema (HAE) is a rare disorder characterized by recurrent episodes of non-pruritic, non-pitting, subcutaneous or submucosal edema affecting the extremities, face, throat, trunk, genitalia, or bowel, that are referred as “attacks”. HAE is an autosomal dominant disease caused by a deficiency of functional C1 inhibitor, due to a mutation in C1-INH gene (serping 1 gene) characterized by the clonal proliferation of mast cells, leading to their accumulation, and possibly mediator release, in one or more organs. In childhood there are two main forms of mastocytosis, the Systemic and the Cutaneous. The clinical features of skin lesions in urticaria, angioedema and mastocytosis may differ depending on the aetiologic factors, and the underlying pathophysiological mechanisms. The diagnostic process, as stepwise approach in routine clinical practice, is here reviewed for CU, HAE and mastocytosis, resulting in an integrated method for improved management of these cutaneous diseases. Taking into account that usually these conditions have also a relevant impact on the quality of life of children, affecting social activities and behavior, the availability of care pathways could be helpful in disentangle the diagnostic issue achieving the most cost-effective ratio.

The value of FeNO measurement in childhood asthma: uncertainties and perspectives

Asthma is considered an heterogeneous disease, requiring multiple biomarkers for diagnosis and management. Fractional exhaled nitric oxide in exhaled breath (FeNO) was the first useful non-invasive marker of airway inflammation in asthma and still is the most widely used. The non-invasive nature and the relatively easy use of FeNO technique make it an interesting tool to monitor airway inflammation and rationalize corticosteroid therapy in asthmatic patients, together with the traditional clinical tools (history, physical examination and lung function tests), even if some controversies have been published regarding the use of FeNO to support the management of asthma in children. The problem of multiple confounding factors and overlap between healthy and asthmatic populations preclude the routine application of FeNO reference values in clinical practice and suggest that it would be better to consider an individual “best”, taking into account the context in which the measurement is obtained and the clinical history of the patient. Besides, there is still disagreement about the role of FeNO as a marker of asthma control, due to the complexity of balance among the different items involved in its determination and the lack of homogeneity in the population groups studied in the few studies conducted so far. Heterogeneity of problematic severe asthma greatly limits utility of FeNO alone as a biomarker of inflammation to optimize the disease management on an individual basis. None of the studies conducted so far demonstrated that the use of FeNO was better than current asthma guidelines in controlling asthma exacerbations. In summary, there is a large variation in FeNO levels between individuals, which may reflect the natural heterogeneity in baseline epithelial nitric oxide synthase activity and/or the contribution of other noneosinophilic factors to epithelial nitric oxide synthase activity. FeNO is a promising biomarker, but at present some limits are highlighted. We would recommend that further research can be carried out by organizing studies aimed to obtain reliable reference values of FeNO and in order to better interpret FeNO measurements in clinical settings, taking also into account the influence of genetic and environmental factors.

Children monosensitized to pine nuts have similar patterns of sensitization

Several cases of pine nut allergies and anaphylaxis have been reported in the literature, but only few pine nut allergens have been characterized. The aim of this research is to identify through immunoelectrophoretic techniques the major pine nut allergens in a group of children monosensitized to pine nuts.

Efficacy of Buffered Hypertonic Saline Nasal Irrigation for Nasal Symptoms in Children with Seasonal Allergic Rhinitis: A Randomized Controlled Trial.

Background: Saline nasal irrigation is labelled as an add-on treatment in patients with allergic rhinitis (AR). The primary aim of this study was to compare the efficacy of 21-day use of buffered hypertonic saline (BHS) versus normal saline solution (NSS) on reducing nasal symptoms in children with seasonal AR (SAR). Comparing their efficacy on nasal cytology counts (NCC), quality of life, and sleep quality was the secondary aim. Methods: In this 21-day, open-label, randomized controlled study, 36 SAR children (aged 6-13 years) with a Total 5 Symptom Score (T5SS) ≥5 received twice-daily BHS or NSS delivered through a nasal douche. Efficacy measures were least square mean changes (LSmc) in T5SS, NCC, Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), and Pittsburgh Sleep Quality Index (PSQI) scores. Results: BHS improved the T5SS total score to a greater extent than NSS (LSmc -6.45 vs. -5.45, p < 0.001). Concerning NCC, BHS significantly reduced the scores of neutrophils (LSmc -0.76, p = 0.004) and eosinophils (LSmc -0.46, p = 0.018), while NSS did not. Similarly, only BHS yielded a significant improvement in the PRQLQ score (LSmc -0.57, p = 0.009), whereas the improvement in PSQI score was comparable between the BHS (LSmc -0.77, p = 0.025) and NSS (LSmc -1.39, p < 0.001) groups. Overall, BHS was well tolerated. Conclusions: In children with SAR, BHS is effective in improving nasal symptoms and NCC, with an associated beneficial effect on quality of life.

Development of a nomogram to estimate the quality of life in asthmatic children using the Childhood Asthma Control Test

Pediatric Asthma Quality of Life Questionnaire (PAQLQ) provides detailed information on QoL in asthmatic children, whereas Childhood Asthma Control Test (C‐ACT) Questionnaire is the most validated instrument for asthma control. No study assessed the relationship between C‐ACT and QoL in children by means of those instruments. The aim of this study was to determine whether a QoL estimation is possible using the C‐ACT questionnaire in asthmatic children.

Reasons for inadequate asthma control in children: an important contribution from the “French 6 Cities Study”

Asthma represents the most common chronic illness in children [1] and an important clinical and public health problem. In fact, diagnosing and treating asthma in children still remain a challenge. There is evidence that children with asthmatic symptoms are often undiagnosed and undertreated [2]. Considering the prevalence of childhood asthma and its associated burden, it is mandatory to obtain an optimal control of the disease and improving outcomes for patients [3]. To achieve this goal, guidelines were published with indications about medication use, control of the environment and health education. Unfortunately, evidence exists that guidelines recommendations are often not applied within the clinical practice [4]. Therefore, asthma control, as recommended by guidelines, has been shown to be satisfactory in less than 30% of children [1]. Diagnosis and asthma treatment depend on a complex interplay among morbidity, physician practice and access to health care [2]. Relating to morbidity, the association between asthma control and atopic disease is well known. It has been demonstrated that atopic comorbidities, such as rhinitis and eczema, are related to more severe asthma [5] and that treatment of allergic disease may improve asthma control [1]. Undoubtedly, the clinical status and the severity level of the disease are fundamental aspects relevant to asthma control, even if children who suffer from severe asthma (more frequent exacerbations, sleep disturbances, a high number of school day missed, activity limitations) could not receive a proper diagnosis and treatment, mainly due to social deprivation. In this context the contact with a doctor, through a better knowledge of the disease, could help the child with asthma to self-manage his condition. The problem of perception of symptoms by the patient and the family is strictly related. Patient’s and parent’s ability to recognize asthma symptoms depend on a patient-physician partnership. Some educational programs have been shown as useful in reducing asthma morbidity in children [6]. Interventions should also take into account the environment that is an important factor relevant to asthma pathogenesis and control. It is well known that environmental triggers such as outdoor and indoor allergens, passive smoking and particulate matter can elicit and exacerbate acute attacks in asthmatic children. In particular, passive exposure to parental tobacco smoke is a risk factor for childhood wheeze [2] and is associated with poor asthma control in children [1]. Moreover, it has been demonstrated that proximity to traffic (living near heavily polluted roadways or bus stop) has a negative impact on respiratory health of children, with increased risk of wheezing, medication use and diminished lung function [3,7]. The most recent GINA guidelines underline the physician’s role in asthma management and care, emphasizing that a proper control of the disease depends on doctor’s ability and experience in recognizing symptoms (considering possible differential diagnoses), defining the severity level (also by evaluating the respiratory function, as recommended by international guidelines), prescribing the correct medication and educating the patient and his family [6]. Recent data demonstrate that physicians often ignore guidelines [4] and the importance of using asthma control tools [1]. Finally, significant disparities in health care based on patient’s insurance status, education level, income and race/ethnicity are relevant to asthma under-diagnosis and under-treatment. Some reports from Europe [1] and North America [2] show that over 50% of children with asthmatic symptoms don’t receive treatment according to guidelines [3] and are more likely to be hospitalized or visited in the emergency department [2]. A new study by Annesi-Maesano et al. [8] published in this issue of Multidisciplinary Respiratory Medicine added new evidence to this field of research. Using data from the “French 6 Cities Study” conducted on a sample of 7.798 schoolchildren, aged 9–10 yr, living in metropolitan France, the Authors identified the main risk factors associated with the presence or absence of asthma diagnosis and treatment. In particular, they considered individual, socio-demographic, clinical and environmental factors. Children underwent clinical tests while their parents completed a standardized medical questionnaire. The population-sample studied comprised 903 asthmatic children: 58% had a doctor diagnosis, only of them 67% were treated for their condition. The evaluation of the clinical condition showed some interesting evidences. First, the asthma severity level (evaluated according to GINA guidelines) was one of the main factors that influenced diagnosis and treatment. Most of undiagnosed and untreated children were in GINA level 1. Furthermore, in line with other studies [9], treatment was related to more severe asthma (more frequent exacerbations, sleep disturbances, hospitalizations, a high number of school days missed, activity limitations).Second, according to previous observations [10], diagnosed and treated asthmatic children had more allergic concomitant diseases, such as eczema and rhinitis. Therefore, co-morbidities and asthma severity seem to increase the likelihood of treatment. Relevant to under-treatment of asthma, the Authors also highlighted inconsistencies about the type of treatment used. In fact, most of the treated children used bronchodilators for both attacks prevention and therapy. Unexpectedly, in the sample of children without a doctor diagnosis of asthma, there was someone who took medications (bronchodilators or inhaled corticosteroids) to improve its respiratory symptoms. These observations may suggest both a poor adherence of physicians to guidelines within clinical practice [4], and a non-adherence of patients to the treatment plan. Previous studies reported that even patients with severe asthma do not follow the treatment properly. Therefore, it is necessary to improve physician’s compliance to guidelines within clinical practice through educational interventions that enrich their awareness about diagnostic tools and therapy. Furthermore, it is important to identify subjects non-adherent to treatment. Since the reasons for poor adherence may vary among patients, individualized interventions that improve patient’s compliance to therapy are strongly desirable [11]. In addition, Annesi-Maesano et al. [8] confirmed that a low socio-economic status still represents an important factor in asthma management and care, limiting the access to health care system and consequently the optimal control of the disease. At last, the Authors focused on environmental factors that can affect asthma management, particularly the exposure to passive smoking and urban traffic. They found that undiagnosed children were more exposed to maternal smoking and traffic. Moreover, they found that urban traffic (living near a bus stop) was the only environmental factor treatment-related. Proximity of an asthmatic’s house to a bus stop was an indicator of asthma severity and likelihood of treatment. Confirming existing data [1,3,7], these observations underline the necessity of taking into account the physical and social environment within clinical practice to improve management and care of asthmatic children. In summary, the study by Annesi-Maesano et al. [8] shows that childhood asthma is still under-diagnosed and under-treated in metropolitan France. The Authors, by identifying the clinical, social and environmental characteristics of undiagnosed and/or undertreated children, highlighted the main factors that can be associated with absence of asthma diagnosis and treatment. Since a poor asthma control can have detrimental effects on children’ health, similar studies are warranted to understand what interventions are necessary to achieve a better management of this disease.