Diagnosis and management of food allergy-induced constipation in young children-An EAACI position paper.

The recognition of constipation as a possible non-Immunoglobulin E (IgE)-mediated allergic condition is challenging because functional constipation (unrelated to food allergies) is a common health problem with a reported worldwide prevalence rate of up to 32.2% in children. However, many studies in children report challenge proven cow's milk allergy and constipation as a primary symptom and have found that between 28% and 78% of children improve on a cow's milk elimination diet. Due to the paucity of data and a focus on IgE-mediated allergy, not all food allergy guidelines list constipation as a symptom of food allergy. Yet, it is included in all cow's milk allergy guidelines available in English language. The Exploring Non-IgE-Mediated Allergy (ENIGMA) Task Force (TF) of the European Academy for Allergy and Clinical Immunology (EAACI) considers in this paper constipation in the context of failure of standard treatment and discuss the role of food allergens as culprit in constipation in children. This position paper used the Delphi approach in reaching consensus on both diagnosis and management, as currently published data are insufficient to support a systematic review.

Impulse oscillometry assessment of respiratory function in pediatric patients with a history of COVID-19.

OBJECTIVE: While coronavirus disease 2019 (COVID-19) is generally considered to exhibit a less severe clinical course in children than in adults, studies have demonstrated that respiratory symptoms can endure for more than 3 months following infection in at least one-third of pediatric cases. The present study evaluates the respiratory functions of children aged 3-15 years within 3-6 months of their recovery from COVID-19 using impulse oscillometry (IOS) and compares them with the values of healthy children. METHODS: Included in this prospective cross-sectional study were 63 patients (patient group) aged 3-15 years who contracted COVID-19 between December 2021 and May 2022, as well as 57 healthy children as a control group, matched for age and sex. The demographic, clinical, and laboratory data of the patients were recorded, and respiratory function was assessed based on airway resistance (zR5, zR20, R5-20) and reactance (zX5, zX20, reactance area [AX], resonant frequency [Fres]) using an IOS device. RESULTS: There were no significant differences in the age, weight, height, and body weight z score values of the two groups (p > .05). While the zR5 and R5-20 levels of the patient group were higher (p = .008 and p < .001, respectively) than those of the controls, the zR20, AX, and Fres values did not differ significantly between the groups (p > .05). The parameters indicating the reactance, including zX5 and zX20, were significantly lower in the patient group than in the control group (p = .028 and p < .001, respectively). CONCLUSION: Total and peripheral airway resistances were found to be elevated in children who had recovered from COVID-19 in the preceding 3-6 months.

Beyond the Skin: Reduced Lung Function Associated With Atopic Dermatitis in Infants.

BACKGROUND: Very few studies have examined lung function parameters using tidal breath analysis (TBA) in atopic dermatitis (AD) with its high potential for progression to asthma. OBJECTIVE: To measure lung functions using TBA in infants with AD and in healthy controls (HCs), and to investigate the effects of disease severity, food sensitivity, and history of recurrent wheezing on TBA parameters in infants with AD. METHODS: Two hundred thirty infants were included in this prospective cross-sectional study, including an AD group (n = 150) and an HC group (n = 80). Food sensitivity was assessed by means of food-specific IgE or the skin prick test. The severity of the disease was evaluated using the SCORing Atopic Dermatitis. Lung function was assessed using TBA. RESULTS: The following TBA parameters were significantly lower in the AD group than in the HC group (P < .05): time to peak tidal expiratory flow, exhaled volume to peak tidal expiratory flow, ratio of time to peak tidal expiratory flow to expiratory time, ratio of exhaled volume to peak tidal expiratory flow to total expiratory volume, expiratory flow when 25% of tidal volume remains in the lungs, respiratory rate, and minute ventilation. No difference was observed in the AD group when TBA parameters were compared according to disease severity, food sensitivity, and history of recurrent wheezing (P > .05). The receiver-operating characteristic curve demonstrated by the ratio of time to peak tidal expiratory flow to expiratory time yielded an area under the curve of 0.826 (CI, 0.772-0.879), with a cutoff value of 31.65 or higher in differentiating AD, with a sensitivity of 78.7% and a specificity of 77.5%. CONCLUSIONS: TBA curves can be a useful tool for demonstrating expiratory airway obstruction in AD and for providing objective information for the clinician. Bronchial obstruction was detected in young children with AD irrespective of the severity of the disease, food sensitivity, and history of recurrent wheezing.

The effect of hydrochlorothiazide on the recurrence of nonmelanoma skin cancer: a 7-year retrospective study comprising 300 patients.

BACKGROUND: Hydrochlorothiazide (HCTZ) possesses well-described photosensitizing properties, and a causal association with nonmelanoma skin cancer (NMSC) was recently shown. However, previous studies have not shown whether HCTZ use is associated with the risk of recurrence of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). This study aims to investigate the association between HCTZ use and recurrence in patients with NMSC. METHODS: We identified cases with NMSC from our hospital archives during the period between 2013 and 2019. Patients were divided into groups according to the pathological diagnosis, HCTZ use, and recurrence. Multivariable analysis was performed to determine factors associated with recurrence in BCC and SCC. RESULTS: Recurrences of BCC were significantly higher in HCTZ users with ORs of 4.839221 (95% confidence interval [CI], 1.22-19.12).In HCTZ users, NMSC cases were associated with increased age (p < 0.001 for both BCC and SCC). BCC recurrences were statistically significant with age, longer follow-up, and positive margins after excision in HCTZ users (p = 0.048, 0.020, and, 0.003, respectively). SCC recurrences were not significantly associated with HCTZ use. DISCUSSION: HCTZ use is significantly associated with BCC recurrences. Especially in the elderly population, cases with a positive margin should be followed closely.

Does maternal fermented dairy products consumption protect against cow's milk protein allergy in toddlers?

BACKGROUND: Cow's milk protein allergy (CMPA) is the most common immunoglobulin E-mediated food allergy in childhood. OBJECTIVE: To investigate the potential impact on the disease of the frequency, amount, and diversity of maternal consumption of fermented dairy products (FDP) during pregnancy and lactation in children with immunoglobulin E-mediated CMPA. METHODS: One hundred sixty toddlers (80 with physician-diagnosed CMPA and 80 healthy controls) and their mothers participated in this case-control study. The data were collected using a structured questionnaire and were compared between the 2 groups. RESULTS: The most commonly consumed FDP were cheese, yogurt, and tarhana. The amounts of maternal yogurt, tarhana, and kefir consumed during pregnancy (P < .001, P < .001, and P = .04, respectively) in addition to yogurt and tarhana consumption during lactation (P < .001 and P = .001, respectively) were lower in toddlers with CMPA. The frequency of maternal consumption of yogurt, cheese, and tarhana during lactation (P = .001, P = .003, and P = .02, respectively) and the diversity of FDP were also lower in toddlers with CMPA (P = .001). At multivariate logistic regression analysis, maternal weight gain during pregnancy (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.04-1.18; P = .001), maternal age (OR, 1.20; 95% CI, 1.09-1.31; P < .001), and gestational age at birth (OR, 1.23; 95% CI, 1.03-1.48; P = .02) increased the odds of the baby having CMPA. The diversity of FDP consumed during lactation was protective against CMPA (OR, 0.439; 95% CI, 0.272-0.711; P = .001). CONCLUSION: Weekly maternal consumption of FDP was low during pregnancy and lactation in toddlers with CMPA. Although the diversity of FDP consumed during lactation may reduce the risk of CMPA, this effect was not observed during pregnancy.

The impact of adenoid hypertrophy on pulmonary functions measured using impulse oscillometry in preschool-age children.

PURPOSE: To assess pulmonary impedance [resistance (zR5, zR20, R5-20, Fres, and AX) and reactance (zX5 and zX20)] using impulse oscillometry (IOS) in children with adenoid hypertrophy (AH) and its association with the degree of AH, and to evaluate subsequent changes in pulmonary function 3 months after adenoidectomy. METHODS: This prospective cross-sectional study was conducted with 170 preschool-age children [110 with AH and 60 sex- and age-matched healthy controls (HCs)]. Pulmonary function was analyzed using IOS at baseline (1st visit) in all participants and 3 months after adenoidectomy (2nd visit) in patients who underwent the operation. RESULTS: The IOS parameters of zR5, zR20, R5-20, Fres, and AX were higher, but zX20 was lower, in children with AH compared to the HCs (p < 0.05 for all). The parameters of zR5, Fres, and AX were higher in children with grade IV AH than in those with grade I (p < 0.001). zR5, zR20, R5-20, Fres, and AX decreased, but zX20 increased, after adenoidectomy (2nd visit) compared to baseline (1st visit) (p < 0.05). Post-adenoidectomy (2nd visit) zR5, AX, Fres values were higher in children with AH compared to baseline values in the HCs (1st visit) (p < 0.05). The area under the ROC curve (AUC) value for estimating adenoidectomy was 0.741 for zX20 (CI 0.648-0.834, p < 0.001) with a cut-off value of  ≤ -3.21, sensitivity of 68.8%, and specificity of 70%. CONCLUSION: This study shows that IOS is a useful method for demonstrating subclinical bronchial obstruction in preschool-age children with AH with greater pulmonary impedance (resistance and reactance). Pulmonary impedance decreased 3 months after adenoidectomy, but remained higher than in the HCs. The IOS parameter of X20 may be predictive of adenoidectomy. This study evaluated the pulmonary functions of children with adenoid hypertrophy (AH) using impulse oscillometry (IOS) and the association with the scale of AH. Pulmonary functions were analyzed using IOS. The main IOS parameters include resistances (zR5 and zR20), reactance (zX5 and zX20), R5-20 (resistance at 5 Hz minus resistance at 20 Hz), resonant frequency (Fres), and AX. Fres is the point at which reactance is zero and is measured in Hz (1/s). The Reactance Area (AX - "Goldman Triangle") represents the integrated low-frequency respiratory reactance magnitude between 5 Hz and Fres. Faster frequencies of R (~ 20 Hz) reflect larger airways, regarded as resistance around the central airways. Lower frequencies of R (~ 5 Hz) providing information around the entire (small and large) airways. Peripheral (small) airway resistance is defined by R5-20. IOS parameters of zR5, zX20, Fres, and AX differed among AH grades I-IV and compared to the HCs (p < 0.001 for all).

Diagnosis and management of food allergy-associated gastroesophageal reflux disease in young children-EAACI position paper.

Gastro-oesophageal reflux (GOR) and food allergy (FA) are common conditions, especially during the first 12 months of life. When GOR leads to troublesome symptoms, that affect the daily functioning of the infant and family, it is referred to as GOR disease (GORD). The role of food allergens as a cause of GORD remains controversial. This European Academy of Allergy and Clinical Immunology (EAACI) position paper aims to review the evidence for FA-associated GORD in young children and translate this into clinical practice that guides healthcare professionals through the diagnosis of suspected FA-associated GORD and medical and dietary management. The task force (TF) on non-IgE mediated allergy consists of EAACI experts in paediatric gastroenterology, allergy, dietetics and psychology from Europe, United Kingdom, United States, Turkey and Brazil. Six clinical questions were formulated, amended and approved by the TF to guide this publication. A systematic literature search using PubMed, Cochrane and EMBASE databases (until June 2021) using predefined inclusion criteria based on the 6 questions was used. The TF also gained access to the database from the European Society of Paediatric Gastroenterology and Hepatology working group, who published guidelines on GORD and ensured that all publications used within that position paper were included. For each of the 6 questions, practice points were formulated, followed by a modified Delphi method consisting of anonymous web-based voting that was repeated with modified practice points where required, until at least 80% consensus for each practice point was achieved. This TF position paper shares the process, the discussion and consensus on all practice points on FA-associated GORD.

New-onset cutaneous nodule arising from hypertrichotic brownish patch in a 6-year-old girl.

A 6-year-old girl presented with an enlarging asymptomatic nodule within a hyperpigmented hypertrichotic patch on her left thigh. Histopathological examination revealed tumour cells with round to fusiform nuclei in a fine fibrillary collagenous stroma, along with increased cellularity. Most of the tumour cells were positive for S-100 and negative for HMB-45 and Melan-A.

The Low Maternal Consumption of Homemade Fermented Foods in Pregnancy Is an Additional Risk Factor for Food Protein-Induced Allergic Proctocolitis: A Case-Control Study.

INTRODUCTION: Food protein-induced allergic proctocolitis (FPIAP) is the most common non-IgE-mediated food allergy and it varies between 4% and 8% in infants. The aim of the study was to evaluate the potential association between FPIAP in infants and maternal daily consumption of homemade fermented foods (FFs) during pregnancy. METHODS: Two hundred and seven infants were included in this case-control study, 106 with physician-diagnosed FPIAP (FPIAP group) and 101 age- and gender-matched healthy infants (control group), together with their mothers. The frequency and diversity of the 8 most consumed homemade FFs in traditional Turkish cuisine and daily maternal consumption of these during pregnancy were evaluated retrospectively using a structured questionnaire. RESULTS: Rates of vaginal delivery, maternal smoking during pregnancy, educational status, and monthly household income were higher in the FPIAP group than the control group (p = 0.046, p = 0.014, p < 0.001, and p = 0.009, respectively). The 3 most common daily-consumed FFs during pregnancy were, in order, yogurt, cheese, and tarhana. The diversity of daily-consumed FFs during pregnancy (p = 0.004) and the consumption of the 3 most common FFs (p = 0.011) were lower in the FPIAP group than in the control group. Maternal smoking during pregnancy (odds ratio [OR]: 2.97, 95% confidence interval [CI]: 1.19-7.41, p = 0.019) and a higher maternal educational status (OR: 3.34, 95% CI: 1.63-6.84, p = 0.001) increased the risk of FPIAP at multivariate logistic regression, while the diversity of maternal FF consumption was protective against FPIAP (OR: 0.75, 95% CI: 0.58-0.96, p = 0.025). CONCLUSION: Daily maternal consumption of yogurt, cheese, and tarhana during pregnancy was less common in FPIAP. The diversity of traditional Turkish homemade FFs may reduce the risk of FPIAP, whereas maternal smoking and a higher maternal educational status were associated with an increased risk of FPIAP.

School-age obese asthmatic children have distinct lung function measures from lean asthmatics and obese children.

BACKGROUND: The lung functions of children with obese asthma seem to be distinct from those of obese children or lean asthmatics. AIM: To measure baseline lung function, exercise-induced bronchoconstriction (EIB), and bronchial hyperreactivity (BHR) in school-age obese asthmatics (OA group) and to compare the data with obese children (O group), lean asthmatics (A group), and healthy controls (H group). METHODS: One hundred seventy school-age children were enrolled in this prospective cross-sectional study. Baseline fractionated exhaled nitric oxide (FeNO), and baseline, post-exercise (post-E), and post-bronchodilation (post-BD) impulse oscillometry (IOS) and spirometry tests were performed. EIB and BHR were evaluated based on the difference (Δ) in post-E - baseline, and post-BD - baseline values. RESULTS: The mean FeNO level was higher in the OA group than in the other groups (p = 0.002). Baseline zR5 and R5-20 were higher (p = 0.013 and p = 0.044), but zFEF25-75 was lower (p < 0.01), in the OA group. ΔPost-E - baseline zFEV1 was lower in the A group (p = 0.003) but was higher in the OA group (p = 0.014) than the other groups. ΔPost-BD - baseline zFEV1 was lower in the H group compared to the other three groups (p = 0.004), but no significant difference was observed among the O, A, and OA groups (p > 0.05). CONCLUSION: Higher airway inflammation (high FeNO), peripheral airway resistance (high zR5 and zR5-20) and a lower peripheral airway flow (low FEF25-75) were observed at baseline measurement in school-age obese asthmatics compared to lean asthmatics and obese children. Obese asthmatics had no EIB but exhibited a similar BHR to that of asthmatics.

Evaluation of the thiol disulfide homeostasis in patients with traumatic hemorrhagic shock.

BACKGROUND: Traumatic hemorrhagic shock is a condition associated with a high mortality rate in the absence of timely diagnose and intervention. The class and severity of hemorrhagic shock are the key factors that guide the decisions in the management of these patients. This study aims to provide guidance for the timely administration of an appropriate treatment to patients with traumatic hemorrhagic shock, and thus, decrease morbidity and mortality, by determining shock severity and class more clearly with the use of the thiol disulfide homeostasis balance, which is an objective criterion. METHODS: This controlled, prospective, and clinical study was conducted in the Emergency Medicine Clinic at the University of Health Sciences, Ankara Numune Training and Research Hospital between October 1, 2018 and April 30, 2019. Thiol disulfide homeostasis was assessed in blood collected from patients and healthy volunteers. A total of one hundred two patients were included; of whom 52 were female and male volunteer patients aged 18 or older who presented to the emergency department with traumatic hemorrhagic bleeding and fifty were control subjects. RESULTS: Patient and control groups demonstrated significantly different native thiol, total thiol, disulfide, disulfide/native thiol, and disulfide/total thiol levels (P-values for native thiol, total thiol, disulfide, disulfide/native thiol, and disulfide/total thiol: 0.001>, 0.001>, 0.018, 0.002, and 0.002, respectively). According to pairwise comparisons; Class-3 hemorrhagic shock was associated with significantly lower native thiol and total thiol levels compared to Class-1 and Class-2 hemorrhagic shock (Comparison of Class-1 and Class-3 hemorrhagic shock: p-value for native thiol = 0.001, p-value for total thiol = 0.002) (Comparison of Class-2 and Class-3 hemorrhagic shock: p-value for native thiol = 0.009, p-value for total thiol = 0.006). Total thiol levels were found to be lower in patients who died compared to those who survived (p=0.040). CONCLUSION: Thiol disulfide homeostasis data were found to be correlated with the shock class and mortality. The assessment of thiol disulfide homeostasis can serve as a guide in the determination of the severity and classification of the disease, evaluation of the prognosis, and management of the treatment in traumatic hemorrhagic shock patients.

Food-induced anaphylaxis in early childhood and factors associated with its severity.

Background: Several factors that increase the risk of severe food-induced anaphylaxis have been identified. Objective: We aimed to determine the demographic, etiologic, and clinical features of food-induced anaphylaxis in early childhood and also any other factors associated with severe anaphylaxis. Methods: We carried out a medical chart review of anaphylaxis cases from 16 pediatric allergy and immunology centers in Turkey. Results: The data of 227 patients with 266 food-induced anaphylaxis episodes were included in the study. The median (interquartile range) age of the first anaphylaxis episode was 9 months (6-18 months); 160 of these patients were boys (70.5%). The anaphylaxis episodes were mild in 75 cases (28.2%), moderate in 154 cases (57.9%), and severe in 37 cases (13.9%). The most frequent food allergens involved were cow's milk (47.4%), nuts (16.7%), and hen's egg (15.8%). Epinephrine was administered in only 98 (36.8%) of these anaphylaxis episodes. A logistic regression analysis revealed two statistically significant factors that were independently associated with severe anaphylaxis: the presence of angioedema and hoarseness during the anaphylactic episode. Urticaria was observed less frequently in patients who developed hypotension. In addition, confusion and syncope were associated with 25.9- and 44.6-fold increases, respectively, in the risk of concomitant hypotension. Conclusion: Cow's milk, nuts, and hen's egg caused the majority of mild and moderate-to-severe anaphylaxis episodes. The presence of angioedema and hoarseness in any patient who presents with a history of food-induced anaphylaxis should alert clinicians that the reaction may be severe. In addition, the presence of confusion, syncope, or stridor probably indicates concomitant hypotension.

Proven Food-Induced Acute Urticaria and Predictive Factors for Definitive Diagnosis in Childhood.

BACKGROUND: Urticaria can be the only sign of a food allergy or can be seen together with other signs and symptoms of a food allergy. OBJECTIVE: To determine the demographic, etiologic, and clinical features of food-induced acute urticaria in childhood. METHODS: Patients suspected of food-induced acute urticaria were included in this prospective cross-sectional multicenter study. RESULTS: Two hundred twenty-nine urticaria cases were included in this study. Seventeen patients who did not meet the inclusion criteria of the study were excluded. Of the 212 included cases, 179 (84.4%) were diagnosed with definitive food-induced acute urticaria. The most common foods causing acute urticaria were cow's milk, hen's eggs, and nuts in 56.4, 35.2, and 19% of cases, respectively. The positive predictive value of a history of milk-induced acute urticaria together with a milk-specific IgE >5 kU/L for cow's milk-induced acute urticaria was 92% (95% CI: 81-96%). A history of cow's milk-induced and/or hen's egg-induced acute urticaria was consistent with a definitive diagnosis of food-induced urticaria (Chen's kappa: 0.664 and 0.627 for milk and eggs, respectively). Urticaria activity scores were higher in patients with food-induced acute urticaria (p = 0.002). CONCLUSION: Cow's milk, hen's eggs, and nuts were the most common allergens in the etiology of childhood food-induced acute urticaria. Although the urticaria activity score provides guidance for diagnosis, an oral food challenge is often essential for the definitive diagnosis of a patient with a history of food-induced acute urticaria.