Nasal endoscopy in asthmatic children: assessment of rhinosinusitis and adenoiditis incidence, correlations with cytology and microbiology

BACKGROUND: Upper respiratory airway diseases may induce a worsening of asthma. Sinusitis represents one of the most common chronic diseases. The association of asthma and sinusitis varies greatly in different studies, depending on diagnostic procedures. OBJECTIVE: The aims were: (i) to demonstrate that nasal endoscopy may be easily feasible in asthma at paediatric age; (ii) to evaluate the incidence of rhinosinusitis and adenoiditis in children with asthma by nasal endoscopy; (iii) to correlate inflammatory parameters such as cytology and microbiological cultures with nasal endoscopy findings. SUBJECTS AND METHODS: One hundred and forty-five asthmatic children were evaluated, 48 males and 97 females, with an average age of 7.27 years. Evaluated parameters were the incidence of rhinosinusal infections in asthmatic children, and the role of: (i) nasal endoscopy, (ii) nasal cytology, and (iii) nasal microbiology in their diagnoses. RESULTS: Nasal endoscopy was successfully performed on 128 patients. Twenty-six children had endoscopic rhinosinusitis alone, 10 had adenoiditis alone, and 35 showed endoscopic rhinosinusitis associated with adenoiditis. There were significant correlations between endoscopic rhinosinusitis and adenoiditis (P < 0.001), between clinical and endoscopic rhinosinusitis (P < 0.001), between endoscopic rhinosinusitis and adenoiditis and microbiology (P < 0.05 and P < 0.0001, respectively), and between microbiology and cytology (P < 0.05). CONCLUSION: This study shows that rhinosinusal infections are common in asthmatic children. Moreover, nasal endoscopy might represent a fruitful tool in the management of asthmatic children.     

Density of eosinophils reflects activity of disease in allergic asthmatic children

Background Low density eosinophils are more prominent in asthmatic patients compared with healthy subjects, LDH are metabolically more active and produce more tissue-injuring and spasmogenic proteins than normal cosinophils. Objective and methid With a method providing information about eosinophils of 12 different densities we were able to study eosinophil density characierislics in 24 young patients in detail with allergic asthma in a stable phase, and in 21 patients after a bronchial allergen challenge. Results Study of the eosinophil density profile of patients and healthy controls revealed two density populations. Patients had more low density eosinophils than controls. In the patients eosinophil density characteristics and in particular the number of low density eosinophils correlated strongly with both FEV₁% predicted (ρ=?0.66, P < 0.001) and REV₁/FVC (ρ=?0.47, P < 0.01) as well as with bronchial responsiveness to histamine (ρ=?0.68, P < 0.001) and house dust mite (ρ=?0.37, P < 0.05). Allergen induced bronchial reactions were associated with an increase in the number (P < 0.001) and percentage (P < 0.05) of low density eosinophils. A selective rise in the number of eosinophils collected from fractions with a low density accounted for the observed rise in the total number of eosinophils, Density changes did not differ between patients with an isolated early reaction and patients with both an early and a late reaction, nor was there a relation between the severity of the late reaction and the shift in eosinophil density. Conclusion In conclusion, peripheral blood eosinophil density characteristics and in particular numbers of low density eosinophils are closely related with indicators of the asthma severity under stable conditions. Allergen inhalation induces a further shift towards lower density suggesting additional activation of the eosinophils.     

The link between allergic rhinitis and asthma: the united airways disease

Rhinitis and asthma are often associated and the two disorders interact at various levels. Rhinitis typically precedes the development of asthma and can contribute to unsatisfactory asthma control. The presence and type of asthma is influenced by sensitization, and the duration and severity of allergic rhinitis. Nasal symptoms, airflow and markers of inflammation directly correlate with lower airway involvement. Local tissue factors, such as microbial stimuli and systemic inflammatory mechanisms, play a role in the clinical expression of the allergic airway syndrome. There is increasing evidence that suggests a major involvement of airway epithelial cells in the pathogenesis of both asthma and allergic rhinitis. Even in patients with rhinitis who do not have asthma, subclinical changes in the lower airways and inflammatory mediators can be detected. The pathogenic role of paranasal sinus infections in respiratory allergy has been better elucidated but there remains a need for further research. Treatment of established rhinitis may affect asthma control and could have some impact on airway obstruction, but a direct effect of rhinitis therapy on lower airway inflammation remains to be clearly established.     

Vitamin D3 correlates inversely with systemic dendritic cell numbers and bone erosion in chronic rhinosinusitis with nasal polyps and allergic fungal rhinosinusitis

Vitamin D₃ (VD₃) is a steroid hormone that regulates bone health and numerous aspects of immune function and may play a role in respiratory health. We hypothesized that T helper type 2 (Th2) disorders, chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic fungal rhinosinusitis (AFRS) would have VD₃ deficiencies, resulting in increased mature dendritic cells (DCs) and bone erosion. We conducted a retrospective study examining VD₃ levels in patients with AFRS (n = 14), CRSwNP (n = 9), chronic rhinosinusitis without nasal polyps (CRSsNP) (n = 20) and cerebrospinal fluid leak repair (non‐diseased controls) (n = 14) at time of surgery. Circulating immune cell levels were determined by immunostaining and flow cytometric analysis. Plasma VD₃ and immune regulatory factors (granulocyte–macrophage colony‐stimulating factor and prostaglandin E₂) were measured by enzyme‐linked immunosorbent assay. It was observed that CRSwNP and AFRS demonstrated increased circulating DCs, while chronic rhinosinusitis without nasal polyps displayed increased circulating macrophages. CRSwNP and AFRS were to found to have insufficient levels of VD₃ which correlated inversely with circulating numbers of mature DCs, DC regulatory factors and bone erosion. CRSsNP displayed no change in circulating DC numbers or VD₃ status compared to control, but did display increased numbers of circulating macrophages that was independent of VD₃ status. Lastly, VD₃ deficiency was associated with more severe bone erosion. Taken together, these results suggest support a role for VD₃ as a key player in the immunopathology of CRSwNP and AFRS.     

Effects of body weight and posture on pulmonary functions in asthmatic children

BackgroundAsthma is one of the most common chronic illnesses in the world. Pulmonary function tests are important tools in monitoring of asthmatic patients. There is need for investigating if spirometric indices were affected by body weight or posture or not.ObjectivesThe aim of this study was to evaluate the spirometric measurements in standing and sitting positions in a group of Egyptian asthmatic children with different body weights.MethodsSixty patients were included. They were stable asthmatics and were following up in the allergy clinic. Spirometry was conducted at pulmonary functions laboratory of Pediatric Allergy and Chest Unit of New Children''s University Hospital, Cairo. The one-way analysis of variance was used to test the differences between groups. The Duncan multiple comparison test was used to test the significant differences between each pair of groups.ResultsThe study found that sitting FEV1/FVC is significantly lower in overweight/obese asthmatic children compared to normal weight asthmatic children (p value=0.046).ConclusionThere was no effect of weight on standing spirometric data. Weight showed significant negative correlation with asthma control level. We concluded that in overweight/obese asthmatic children, spirometric position might affect the results.     

The first 20 minutes after a single dose of inhaled salmeterol in asthmatic children

Very little is known as yet about the effect of salmeterol in pediatric asthma, so a trial was performed on children with mild asthma to compare salmeterol with salbutamol in terms of how quickly they took effect. The double-blind study involved 11 children (mean age 13.4 years) randomly assigned to inhale salmeterol 50 μg, salbutamol 200 μg, or a placebo three times on alternate days. Peak expiratory flow (PEF), heart rate, and blood pressure were measured before and 5, 10, 15, and 20 min after administering the medication. With salbutamol, PEF was higher at 5 and 10 min, subsequently dropping off at 15 and 20 min; with salmeterol, PEF was better at 10 and 20 min. Forced expiratory volume at 1 s (FEV₁) measurements taken at the baseline and after 10 and 20 min revealed an important and consistent rise in values after salmeterol, whereas salbutamol was more effective after 10 min than after 20 min. No significant changes were recorded in heart rate or blood pressure after salbutamol; after salmeterol, there was a significant increase in heart rate after 5 min, but not at subsequent measurements. In conclusion, salmeterol begins to take effect already within 10 min of a single administration in asthmatic children, although the onset of its effect is slower than with salbutamol.     

Cytokine production in peripheral blood cells during and outside the pollen season in birch-allergic patients and non-allergic controls

BACKGROUND: The naturally occurring pollen season permits observation of the kinetic changes in the process of allergic inflammation. We examined cytokine production in peripheral blood (PB) T cells and monocytes obtained from birch-allergic patients both during and outside the pollen season. METHODS: PB from 16 patients and six healthy controls was obtained during the alder pollen season, at the beginning and the peak of the birch pollen season and outside the pollen season. Mononuclear cells (MNC) were stimulated with allergen and polyclonal activators. For flow cytometric analysis, MNC were stained with monoclonal antibodies (MoAbs) against the cell surface markers CD3, CD8, CD14 and the intracellular cytokines IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte macrophage-colony stimulating factor (GM-CSF) and IFN-gamma. RESULTS: In allergic patients, significant increases in clinical symptoms, use of medication, eosinophil numbers and birch-specific IgE were found during the pollen season. In vitro allergen stimulation increased the number of GM-CSF+ monocytes (P<0.01) and this increase was dependent on allergen exposure. The IL-4/IFN-gamma ratio rose (P<0.001) at the peak of birch pollen season and the ratio correlated with symptom scores during the birch season. In the CD4+ cell population, the numbers of GM-CSF+ cells were higher throughout the alder and birch seasons compared with outside the pollen season (P<0.05). No such changes were seen in the healthy controls. CONCLUSIONS: The main finding of our study was the increased percentage of GM-CSF+ monocytes in atopic subjects compared with healthy controls. In allergic patients, natural seasonal pollen exposure resulted in increased numbers of GM-CSF+ cells among both monocytes and CD4+ T cells. We have also shown that a seasonal change in Th2/Th1 cytokine ratio requires an adequate and prolonged allergen stimulation that is seen late in the pollen season.     

Highlights in the advances of chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a complex upper airway inflammatory disease with a broad spectrum of clinical variants. As our understanding of the disease pathophysiology evolves, so too does our philosophy towards the approach and management of CRS. Endotyping is gaining favour over phenotype-based classifications, owing to its potential in prognosticating disease severity and delivering precision treatment. Endotyping is especially useful in challenging CRS with nasal polyposis cases, for whom novel treatment options such as biologicals are now available. The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) reflects these changes with updated rhinosinusitis classifications and new integrated care pathways. With the coronavirus disease 2019 (COVID-19) pandemic, physicians and rhinologists have to balance the responsibility of managing their patients’ upper airway while adequately protecting themselves from droplet and aerosol transmission. This review summarises the key updates from EPOS2020, endotype-based classification and biomarkers. The role of biologicals in CRS and the lessons we can draw from their use in severe asthma will be examined. Finally, the principles of CRS management during COVID-19 will also be discussed.     

Role of imbalance of eicosanoid pathways and staphylococcal superantigens in chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a multifactorial disease of the upper airways with a high prevalence (approximately 11%) in the general population. Different immune and inflammatory mechanisms are involved in its pathogenesis. Alterations in the arachidonic acid pathway (leading to an imbalanced production of eicosanoids) have been linked to the pathophysiology of different diseases especially nasal polyposis, asthma, and aspirin‐exacerbated respiratory disease. Furthermore, viral and bacterial infections have been identified as important factors amplifying the pro‐inflammatory reactions in these pathologies. This review summarizes the impact of an imbalance in the eicosanoid pathway and the effect of Staphylococcus aureus enterotoxins on the regulation of the pro‐inflammatory network in CRS and their translation into disease severity.     

Pathogenic T cell subsets in allergic and chronic inflammatory bowel disorders

Homeostasis in the gastrointestinal tract relies on a sensitive equilibrium between permissive and protective functions. This is closely reflected in the regulation of the intestinal immune system and especially T cells in the gut. This balance, however, is susceptible to disturbances as demonstrated by pathological conditions like food allergy, celiac disease, or inflammatory bowel disease. In these allergic and chronic inflammatory bowel disorders, luminal antigens get access to the lamina propria where they trigger a dysregulated immune response with crucial involvement of different T cell subsets. We will begin this review with some comprehensive remarks on current concepts on the pathogenesis of these diseases before taking a closer look at the life cycle of intestinal T cells consisting of priming, homing, differentiation and proliferation and apoptosis respectively. Subsequently we will discuss the specific implication of distinct T cell subsets in allergic and chronic inflammatory conditions of the gastrointestinal tract in detail and comment on current and future approaches to targeted therapy in this context.     

Relationships between allergic inflammation and nasal airflow in children with persistent allergic rhinitis due to mite sensitization

BACKGROUND: Allergic rhinitis is associated with Th2-dependent inflammation. Nasal obstruction is the most typical symptom in children with mite allergy. OBJECTIVES: The aim of this study was to evaluate the possible relationships among nasal symptoms, allergic inflammation, including inflammatory cells and cytokine pattern, and nasal airflow in children with persistent allergic rhinitis because of mite sensitization. METHODS: Twenty children (13 males and seven females, mean age 13.4 +/- 1.6 years) with persistent rhinitis because of mite allergy were evaluated. All of them had moderate-severe grade of nasal obstruction. Total symptom score (TSS), rhinomanometry, nasal lavage, and nasal scraping were obtained in all subjects. Inflammatory cells were counted by conventional staining; interleukin (IL)-5, and IL-8 were measured by immunoassay on fluids recovered from nasal lavage. RESULTS: Eosinophils were significantly associated with TSS (R = 74.4%, P = 0.0002), with IL-5 (R = 90.6%, P < 0.0001) and with nasal flow (R = -69%, P = 0.0007), but not with IL-8 (R = 0.1%, P = 0.995). Eosinophil levels were shown to independently predict nasal flow (P < 0.001), with flow decreasing linearly for increasing eosinophils, together with a significant effect of neutrophils (P = 0.016, linear increase in flow) and a borderline effect of IL-8 (P = 0.063, linear increase in flow). CONCLUSIONS: This study demonstrates the close association between IL-5 concentration and eosinophil infiltration. In addition, there is clear evidence concerning the relationship between eosinophil infiltration and nasal airflow. Thus, nasal eosinophils can be regarded as the most important predictor of upper airway function. These findings constitute first evidence of the relationship between nasal airflow impairment and Th2-related eosinophilic inflammation in children with persistent allergic rhinitis because of mite sensitization.     

Mucosal output of eotaxin in allergic rhinitis and its attenuation by topical glucocorticosteroid treatment

BACKGROUND: Eotaxin is a chemokine that attracts and activates eosinophils. The present study examines the occurrence of eotaxin in nasal mucosal surface liquids in patients with seasonal allergic rhinitis without allergen exposure and during repeat allergen challenge with and without topical glucocorticosteroid treatment. The number of subepithelial eosinophils and mucosal outputs of bulk plasma (alpha2-macroglobulin) and eosinophil cationic protein (ECP) are also examined. METHODS: Twelve patients underwent daily allergen challenges for 6 days. Separately, 14 patients, who were receiving budesonide and placebo in a parallel group design, also underwent allergen challenge for 6 days. Nasal biopsies were obtained before and 24 h after the allergen challenge series, and lavages were carried out before and 15 min after selected allergen challenges. RESULTS: At baseline nasal lavage fluid levels of eotaxin correlated to levels of alpha2-macroglobulin and ECP. After the first allergen challenge there was a correlation between nasal lavage fluid levels of eotaxin and ECP. Repeat allergen exposure increased the mucosal output of eotaxin (P <0.05) and ECP (P <0.01) as well as eosinophil numbers (P <0.01), but no correlation was found between increased eosinophil numbers and eotaxin. Budesonide reduced eotaxin levels during repeat allergen challenge (P <0.05). CONCLUSIONS: Repeat allergen exposure in allergic rhinitis is associated with increased mucosal output of eotaxin. Topical budesonide attenuates this effect, suggesting the possibility that inhibitory effects on mucosal eotaxin may contribute to anti-eosinophilic actions of topical glucocorticosteroids.     

Food allergy and non-allergic food hypersensitivity in children and adolescents

BACKGROUND: Previous studies have shown a 10-fold discrepancy of self-reported food-induced symptoms and physician-diagnosed food hypersensitivity. Little information is available on the prevalence of food hypersensitivity in unselected paediatric populations. No data were available for German children. OBJECTIVE: To study the perception of food-induced symptoms in the paediatric population, to investigate the allergens accused, to objectify patients' reports, and to identify subgroups at risk of having food-induced allergy (FA) or non-allergic food hypersensitivity (NAFH) reactions. METHODS: This paper presents the data of the paediatric group (0-17 years) of a representative, randomly sampled, cross-sectional population-based survey studying 13 300 inhabitants of the German capital city Berlin regarding food-related symptoms. Instruments included mailed questionnaires, structured telephone interviews, physical examination, skin-prick tests, specific serum IgE and standardized, controlled and blinded oral food challenges. RESULTS: Two thousand three hundred and fifty-four individuals were contacted by mailed questionnaire, 739 (31.4%) responses could be fully evaluated. Four hundred and fifty-five (61.5%) participants reported symptoms related to food ingestion, 284 (38.4%) affirmed reproducible symptoms in the standardized telephone interview. One hundred and eighty-four (24.8%) individuals were fully examined. Reproducible symptoms to food were found in 31 (4.2%) children and adolescents: 26 (3.5%) showed symptoms of FA and five (0.7%) of NAFH. The oral allergy syndrome was most often observed. Foods most commonly identified by oral challenges were apple, hazelnut, soy, kiwi, carrot and wheat. CONCLUSION: The perception of food-related symptoms is common among children and adolescents from the general population. Self-reports could be confirmed in around one out of 10 individuals, still resulting in 4.2% of proven clinical symptoms. However, most reactions were mild and mainly because of pollen-associated FA, while NAFH reactions were less common. Severe IgE-mediated FA was observed in individuals with pre-existing atopic disease, who should be fully investigated for clinically relevant FA.