Childhood interstitial lung disease in Turkey: first data from the national registry.

The childhood interstitial lung diseases (chILD) Turkey registry (chILD-TR) was established in November 2021 to increase awareness of disease, and in collaboration with the centers to improve the diagnostic and treatment standards. Here, the first results of the chILD registry system were presented. In this prospective cohort study, data were collected using a data-entry software system. The demographic characteristics, clinical, laboratory, radiologic findings, diagnoses, and treatment characteristics of the patients were evaluated. Clinical characteristics were compared between two main chILD groups ((A) diffuse parenchymal lung diseases (DPLD) disorders manifesting primarily in infancy [group1] and (B) DPLD disorders occurring at all ages [group 2]). There were 416 patients registered from 19 centers. Forty-six patients were excluded due to missing information. The median age of diagnosis of the patients was 6.05 (1.3-11.6) years. Across the study population (n = 370), 81 (21.8%) were in group 1, and 289 (78.1%) were in group 2. The median weight z-score was significantly lower in group 1 (- 2.0 [- 3.36 to - 0.81]) than in group 2 (- 0.80 [- 1.7 to 0.20]) (p < 0.001). When we compared the groups according to chest CT findings, ground-glass opacities were significantly more common in group 1, and nodular opacities, bronchiectasis, mosaic perfusion, and mediastinal lymphadenopathy were significantly more common in group 2. Out of the overall study population, 67.8% were undergoing some form of treatment. The use of oral steroids was significantly higher in group 2 than in group 1 (40.6% vs. 23.3%, respectively; p = 0.040).   Conclusion: This study showed that national registry allowed to obtain information about the frequency, types, and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. What is Known: • Childhood interstitial lung diseases comprise many diverse entities which are challenging to diagnose and manage. What is New: • This study showed that national registry allowed to obtain information about the frequency, types and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. Also, our findings reveal that nutrition should be considered in all patients with chILD, especially in A-DPLD disorders manifesting primarily in infancy.

Food oral immunotherapy: Any distinguishing factors predicting the need of anti-IgE?

Oral immunotherapy (OIT) has gained popularity recently for IgE-mediated food allergy. Omalizumab (OMZ) has been used in patients (10-20%) who have too severe/frequent allergic reactions (AR) to continue OIT, to reduce these reactions. In this study, it was aimed to compare two groups of patients who completed OIT with and without OMZ and to seek determinants predicting the need of this treatment. It was also aimed to share the clinical findings regarding the long-term use of OMZ and the withdrawal process. Forty-one patients were started OIT and 93% could be desensitized. Two groups were similar in means of demographic characteristics, and clinical and laboratory findings. The patients who needed OMZ during OIT had also lower reaction doses during oral challenge (p = 0.037). Higher AR rate in this group declined after starting OMZ (p < 0.001). The injection intervals of OMZ were gradually extended. Most patients were able to discontinue OMZ (81%). There were no severe reactions during drug withdrawal attempts. The low reaction thresholds during oral food challenge may give a clue about OMZ requirement during OIT. It may be an option to start the treatment before OIT if reaction was seen in the first few steps of the oral food challenge. For the sake of safety, extension of injection intervals should be preferred instead of abruptly stopping OMZ.

Immunologic changes during desensitization with cow's milk: How it differs from natural tolerance or nonallergic state?

BACKGROUND: Oral immunotherapy (OIT) is a novel allergen-specific treatment for food allergies. OBJECTIVE: To investigate the effect of OIT on blocking antibodies, T cell regulation, and cytokine response during immunoglobulin (Ig)E-mediated cow's milk allergy (CMA) treatment. METHODS: A total of 59 children with IgE-mediated CMA who were followed in pediatric allergy outpatient clinic and 18 healthy children were included. The children were evaluated in the following 4 groups: OIT group, elimination group (patients receiving dairy elimination diet), tolerance group (patients who developed tolerance), and healthy control group. Milk-specific IgE, IgG4, and IgA levels, cow's milk induration diameters in skin prick test, CD4 + CD25 + FoxP3 + Treg cell percentages, messenger RNA (mRNA) expressions, and interleukin (IL)-10, transforming growth factor-beta (TGF-ß), IL-2, IL-4, and IL-13 cytokine levels were compared between the groups. RESULTS: The mean age of the patients was 42.6 ± 39 (6-201) months, and 63.6% (n = 49) of the patients were girls. We observed an increase in total IgE levels (P = .02), a decrease in cow's milk sIgE (P = .08, NS), and an increase in cow's milk component (ß-lactoglobulin and casein) specific IgA (P < .05) and IgG4 (P < .001) levels at 2 months after the maintenance phase of OIT. In addition, the immune response after OIT treatment, which had a 100% clinical success rate, was notable for similar CD4 + CD25 + FoxP3 + cell percentages (P = .8), and increased IL-10 (P = .04) levels and increased but statistically nonsignificant TGF-ß levels (P = .17) compared with those before treatment. FoxP3 mRNA expression was similar to that of patients who developed natural tolerance. Pretreatment and post-treatment FoxP3 mRNA-FoxP3 flow cytometric expressions were positively correlated with TGF-ß concentrations in the OIT group. CONCLUSION: A successful immune response to OIT was found, possibly through the blockage of IgE-mediated allergen presentation by blocking antibodies, marked IL-10 cytokine response, and TGF-ß response. FoxP3 mRNA expression was similar to the natural tolerance mechanism, but more studies are needed.

Identifying wheezing phenotypes in a pediatric Turkish cohort.

OBJECTIVE: Characterization of wheezing phenotypes in children might help to identify the underlying mechanisms through which asthma occurs. In our study, we aimed to describe wheezing phenotypes in Turkish children and to identify risk factors according to phenotypes. METHODS: 651 wheezy children were evaluated and 5 wheezing phenotypes were described according to age of onset, atopy and persistence at 6 years of age and risk factors were identified. RESULTS: Distribution of wheezing phenotypes was transient early wheeze (TEW)(34.9%) non-atopic wheeze (NAW) (18%), atopic wheeze (AW) (22.3%), intermediate onset wheeze (IOW) (11.1%), late onset wheeze (LOW) (11.7%). LOW, AW, and IOW were associated with, father's, sibling's and family's atopy (p:0.001) whereas LOW and AW were associated with mother's asthma and atopy as well as family's asthma (p < 0.05). Atopic dermatitis and allergic rhinitis were common of patients with LOW, AW, and IOW (p < 0.05). Infection was the major trigger for TEW and NAW whereas multiple triggers were common of AW, LOW, and IOW. Allergens were mostly associated with AW, IOW and LOW. Aeroallergen-specific IgE positivity was mostly with AW, IOW, and LOW phenotype. Skin prick tests showed multiple allergen sensitivity in IOW, LOW groups and mostly single allergen in AW phenotype. Modified asthma predictive index (mAPI) positivity was high in all groups except TEW and NAW. CONCLUSIONS: With this study we classified five wheeze phenotypes and found that atopy and family's atopy history, maternal asthma were strongly associated with AW, LOW, and IOW phenotypes which were usually effected by allergens or multiple triggers.

Retrospective Cross-sectional Analysis of Factors Associated with Asthma in a Pediatric Cohort from Turkey.

BACKGROUND: It is difficult to identify young children at increased risk of developing asthma amongst those with recurrent wheezing. In this study, we aimed to determine factors associated with asthma in Turkish children. METHODS: We performed a retrospective cross-sectional analysis on factors associated with asthma in 651 children (200 girls, 451 boys) admitted for recurrent wheezing. RESULTS: Amongst all included children, asthma frequency was 57.7%. Maturity, consanguinity, family income, passive smoking, father's, siblings' asthma were not found to be associated with asthma. Factors associated with asthma were: family's, parents', siblings' atopy, family's, mother's asthma, allergic rhinitis and atopic dermatitis, respiratory symptoms between wheezing attacks. The sensitivity (SN) of the modified asthma predictive index (mAPI) was 59.2% with a specificity (SP) of 91.3%, positive predictive index (PPI) of 65.1% and negative predictive index (NPI) of 82.3%. The SN of the modified Prevention and Incidence of Asthma and Mite Allergy (PIAMA) score was 22.9% with a SP of 89.2%, PPI of 84.6%, and NPI of 42.2%. Adjusted odds ratio for mAPI was 12.9, and for the modified PIAMA score 4. CONCLUSION: Our analysis confirmed previously described factors associated with asthma. Although the SN is limited, the mAPI and PIAMA risk scores can be used to predict asthma in Turkish children. Differential diagnoses and overlaps with other chronic pediatric diseases such as immunodeficiencies need to be carefully excluded when confirming the diagnosis asthma.

Asthma-like symptom or "cystic fibrosis asthma"?

INTRODUCTION: The diagnosis of asthma is still a difficult problem in cystic fibrosis. There is no consensus on how to define "CF asthma". The aim of this study was to determine the role of bronchodilator response and laboratory evidence of allergy in "CF asthma". MATERIALS AND METHODS: Patients aged ≥6 years with evaluated bronchodilator response and characteristics of atopy were included in the study. Patients diagnosed with Allergic Bronchopulmonary Aspergillosis or pulmonary exacerbation were excluded. RESULT: A total of 204 CF patients were evaluated, and 40 who met the criteria were included. Asthma had been diagnosed in ten patients. A positive bronchodilator response was present in 47.3% of the patients tested. Aeroallergen sensitization was present in 52.5% of the patients. While the frequency of recurrent/history of wheezing, family history of atopy and elevated total immunoglobulin E were similar (p> 0.05), the frequencies of inhaled medication use and coexistence of asthma were statistically higher in the group with positive allergen sensitization (p<0.05). The frequencies of positive bronchodilator response (77.7% versus 37.9%) and a family history of asthma/atopy (40% versus. 23%) were found to be similar in CF asthma and CF. There were significant increases in total IgE and allergen-specific IgE and an increase in the frequency of aeroallergen sensitization in CF asthma compared to CF (p<0.05). CONCLUSIONS: Although not routinely used in the evaluation of patients, allergen specific-IgE and skin prick test for aeroallergen sensitization may be used as an adjunctive test in patients with suspected clinical findings. The recognition of CF asthma may facilitate the development of targeted therapies.

Prospective evaluation of vascular changes in acute respiratory infections in children with cystic fibrosis

Background/aim: Acute exacerbations and chronic inflammation are risk factors for cardiovascular disease (CVD) in cystic fibrosis (CF) patients. The aim of this study was to investigate the effects of acute exacerbation therapy on arterial stiffness in children with CF. Materials and methods: Augmentation index (Aix) and pulse wave velocity (PWV) were measured before and after treatment and 1 month after the end of treatment in patients with acute exacerbation. The relationship between hemodynamic measurements and c-reactive protein (CRP) and pulmonary function tests (PFTs) was investigated. Results: Measurements before and after treatment were evaluated in 27 patients and were repeated in 21 patients who were clinically stable 1 month following acute exacerbation. There was a significant decrease in CRP and an increase in spirometry parameters after treatment. While no significant difference was found between PWV (P = 0.33), a significant difference for Aix before (41.95 ± 12.96%) and after (30.95 ± 11.47%) treatment and before treatment and stable clinical condition (34.19 ± 14.36%) was obtained (P =0.00, and P =0.01, respectively). No significant difference in heart rate and other hemodynamic measurements was found. Pretreatment Aix is associated with poor clinical condition (PFTs, BMI, and clinical score) and systemic inflammation (CRP) (P <0.05). Conclusion: The decrease of arterial stiffness (Aix) with acute exacerbation treatment in children with CF has been demonstrated. This result shows that systemic inflammation in CF may cause an increase in arterial stiffness and recurrent exacerbations may increase the risk of CVD.

[The comparison of microscopy and real time polymerase chain reaction methods for the diagnosis of Pneumocystis Jirovecii pneumonia: evaluation of clinical parameters]. / Pneumocystis jirovecii pnömonisi tanisinda mikroskopi ve gerçek zamanli polimeraz zincir reaksiyonu yöntemlerinin karsilastirilmasi: Klinik bulgular ile yorumlanmasi.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PCP) causes serious infections, especially in patients with immunosuppressive diseases. In this study, it was aimed to evaluate the results of samples obtained from PCP suspected patients using two different methods together with clinical data. MATERIALS AND METHODS: Microscopy and real time polymerase chain reaction (real time PCR) methods were performed with bronchoalveolar lavage (BAL) samples sended to Ege University Medical Faculty Direct Parasitology Diagnostic Laboratory between March 2009 and June 2010. Demographic characteristics, clinical and laboratory data were also recorded retrospectively. The data were evaluated using the SPSS 16.0 program. RESULT: A total of 42 BAL samples collected from patients (24 males, mean age: 31.49 ± 26.14) were included. There were totally 16 P. jirovecii positives either one of the tests. Sixteen and three samples were detected positive by real time PCR and microscopy, respectively. Trimethoprim-sulfamethoxazole was prescribed in 11 PCP diagnosed cases and 6 of them died. CONCLUSIONS: Today, despite the growing opportunities in diagnosis and treatment, PCP pneumonia is associated with high mortality. Careful examination of clinical data and immune status of the patients are important. Multidisciplinary approach is required for early PCP diagnosis.

A successful desensitization protocol for horse-derived antithymocyte globulin in severe aplastic anemia.

BACKGROUND: Horse antithymocyte globulin (h-ATG) (ATGAM(®) ) is the first choice of treatment in very severe patients with aplastic anemia who do not have any HLA matched sibling donor. h-ATG is a heterologous serum that may cause anaphylaxis. Alternative treatment strategies must be planned in case of hypersensitivity. Desensitization must be considered in patients without an alternative treatment of choice. We aimed to present the h-ATG desensitization protocol and consider its effectiveness in patients with aplastic anemia who are hypersensitized with h-ATG and do not have an alternative treatment of choice. METHODS: Skin prick tests were performed with non-diluted solution in eight very severe patients with aplastic anemia who are followed up in Ege University Children's Hospital. Although skin prick test was found negative in these eight patients, different dilution h-ATG intradermal tests were performed and found positive in all patients. h-ATG desensitization program was started to these hypersensitized patients. RESULTS: Desensitization program was started to six male and two female very severe patients with aplastic anemia whose ages were between seven and 19 yr (median: 12.9 yr). All of the patients completed the desensitization program. While local reaction was seen in two patients, systemic reaction was seen in one patient and late reaction was seen in one patient during and after desensitization program. CONCLUSION: A successful desensitization program with h-ATG in children with aplastic anemia is presented. Even though there is not an exposure before to such high allergy potential heterologous serum, skin tests should be performed and desensitization must be started to patients who are hypersensitized to h-ATG. As the expected effectiveness of the treatment is so much, the desensitization protocol can be carried out safely and effectively with trained stuff although allergic reactions can be seen.

[Simultaneous detection of respiratory viruses and influenza A virus subtypes using multiplex PCR]. / Solunum viruslari ve influenza A virus alt tiplerinin multipleks PCR yöntemi ile ayni anda saptanmasi

This study was conducted to investigate the respiratory viruses and subtyping of influenza A virus when positive by multiplex PCR in patients with flu-like symptoms, after the pandemic caused by influenza A (H1N1)pdm09. Nasopharyngeal swab samples collected from 700 patients (313 female, 387 male; age range: 24 days-94 yrs, median age: 1 yr) between December 2010 - January 2013 with flu-like symptoms including fever, headache, sore throat, rhinitis, cough, myalgia as defined by the World Health Organization were included in the study. Nucleic acid extractions (Viral DNA/RNA Extraction Kit, iNtRON, South Korea) and cDNA synthesis (RevertAid First Strand cDNA Synthesis Kits, Fermentas, USA) were performed according to the manufacturer's protocol. Multiplex amplification of nucleic acids was performed using DPO (dual priming oligonucleotide) primers and RV5 ACE Screening Kit (Seegene, South Korea) in terms of the presence of influenza A (INF-A) virus, influenza B (INF-B) virus, respiratory syncytial virus (RSV), and the other respiratory viruses. PCR products were detected by automated polyacrylamide gel electrophoresis using Screen Tape multiple detection system. Specimens which were positive for viral nucleic acids have been further studied by using specific DPO primers, FluA ACE Subtyping and RV15 Screening (Seegene, South Korea) kits. Four INF-A virus subtypes [human H1 (hH1), human H3 (hH3), swine H1 (sH1), avian H5 (aH5)] and 11 other respiratory viruses [Adenovirus, parainfluenza virus (PIV) types 1-4, human bocavirus (HBoV), human metapneumovirus (HMPV), rhinovirus types A and B, human coronaviruses (HCoV) OC43, 229E/NL63] were investigated with those tests. In the study, 53.6% (375/700) of the patients were found to be infected with at least one virus and multiple respiratory virus infections were detected in 15.7% (59/375) of the positive cases, which were mostly (49/59, 83%) in pediatric patients. RSV and rhinovirus coinfections were the most prevalent (18/29, 62.7%) dual infections. The distribution of 436 respiratory viruses identified from 375 patients were as follows; 189 (43.3%) RSV, 93 (21.4%) rhinovirus, 86 (19.8%) INF-A, seven (1.6%) INF-B, 22 (5%) PIV types 1-3, 14 (3.2%) HMPV, 11 (2.5%) HCoV, nine (2%) HBoV, and five (1.2%) adenovirus. Fifty-five (64%) out of 86 INF-A viruses were subtyped as hH3, 24 (27.9%) were sH1 and seven (8.1%) were hH1. Avian H5 was not detected in any samples. The overall prevalence rates of INF-A, INF-B, RSV and other respiratory viruses were 12%, 1%, 27%, and 14.6%, respectively. RSV was the most prevalent respiratory agent in pediatric (161/313, 51%) cases, while INF-A virus in adult (24/62, 38.7%) patients. Influenza viruses were detected as responsible pathogens in 13.3% (93/700) of the patients with flu-like symptoms. Among the cases, a 1-month-old baby was infected with three virus strains (INF-A hH1+INF-A sH1+HCoV OC43) and a 82-year-old patient was infected with two INF-A virus subtypes (hH3 + sH1). INF-A viruses were mostly detected (79/86) in winter period, from December to March. INF-A virus sH1, was the most prevalent subtype in flu cases till February 2011 (22/86), after replaced by INF-A virus hH3. Beginning from February 2012, a significant increase observed in the cases infected with INF-A virus subtype hH3 (39/86). In conclusion, the identification and surveillance of influenza virus types and subtypes circulating in populations have importance both for epidemiological data and selection of vaccine strains.

[Mold hypersensitivity in children with frequent respiratory tract infection and prolonged cough attacks]. / Sik solunum yolu enfeksiyonu ve uzamis öksürük ataklari olan çocuklarda küf duyarliligi

OBJECTIVES: This study aims to investigate pollen, mite and mold sensitivities among children with frequent respiratory tract infection living in damp apartments and to evaluate the effects of separated parents, education status, ethnicity, the presence of siblings, and their atopy status on the development of atopy. PATIENTS AND METHODS: Between June 2012 and September 2013, 63 children (28 girls, 35 boys; mean age 80.2 years; range 24 to 97 years) who were admitted to Acibadem Bodrum Hospital with at least six respiratory tract infection per year with mold exposure and prolonged cough attacks and underwent skin prick test (SPT) were included. Skin prick test-positive patients were further divided into groups according to the upper respiratory tract (URT) or lower respiratory tract (LRT) involvement and were assessed for mold, mite and pollen sensitivities. RESULTS: One-third of the patients were SPT positive. The parents of these patients had physician-diagnosed allergy (p<0.05). Most patients with mite sensitivity presented with URT and LRT findings (p<0.05). Pollen-sensitive patients had predominantly URT findings (p<0.05). All children with mold sensitivity presented with LRT findings (p<0.05). CONCLUSION: Atopic children may experience more frequent LRT symptoms when exposed to molds than non-atopic children. Mold exposure may also cause inflammation at LRT without causing immunoglobulin E-dependent sensitization.

Comparison of Clinical Presentations and Disease Severity of Children Hospitalized with Influenza A and B.

This study compared the clinical presentations and disease severity between influenza A and B (FLUA and FLUB). The study included children hospitalized with virologically confirmed influenza between 2010 and 2020. The severity of the disease was evaluated based on admission to the pediatric intensive care unit (PICU), mechanical ventilation requirement, length of hospital stay, length of stay in the PICU, and death. Influenza viruses were compared within predefined age groups (0-2, 3-9, and 10-18 years) and in all age groups. Of 343 patients, FLUA and FLUB were detected in 75.8% and 24.2% of children, respectively. FLUB was associated with a higher incidence of headache and abdominal pain (P < .001 and P = .01). Children with FLUB were prescribed antibiotics and antivirals 0.56 and 0.58- fold fewer than those with FLUA. Headache and abdominal pain rates were higher in patients between 3 and 9 years with FLUB. Children between 0 and 2 years with FLUA were more frequently admitted to the PICU than those with FLUB (23.6% vs. 4.0%; P < .004). Eight patients with FLUA died, while only 1 with FLUB died (P = .69). The clinical presentation of FLUA and FLUB appeared similar, except for headache and abdominal pain, which were more prevalent in older patients with FLUB. Our study revealed that children between 0 and 2 years with FLUA were at a significantly higher risk for admission to the PICU. As a result, greater attention and awareness should be paid to children under 2 years old with FLUA.

Experience of flexible bronchoscopy in the pediatric pulmonary diseases clinic.

Introduction: Flexible bronchoscopy is a valuable method in the diagnosis and treatment of respiratory tract diseases in children. This study aimed to examine the indications for and results of flexible bronchoscopy in children. Materials and Methods: The study included patients aged 0-18 years who underwent flexible bronchoscopy between 1 January 2017 and 31 December 2022. The patients were evaluated for demographic characteristics, indications for bronchoscopy, comorbidities, bronchoscopy findings, and the results of bronchoalveolar lavage. Result: During the defined study period, a total of 410 flexible bronchoscopy procedures were performed. 51.9% of the patient population were male, and 48.1% were female, with a mean age of 96.93 ± 63.45 months. The most common indication for flexible bronchoscopy was recurrent lower respiratory tract infection (26.8%), followed by chronic cough (19.1%). The bronchoalveolar lavage culture results showed that the most commonly isolated microorganisms were H. influenzae non-type b (7.8%) followed by M. catarrhalis (7.3%). Mucus obstruction and secretion (33.0%) constituted the most common bronchoscopic findings, while the flexible bronchoscopy examination was normal in 27% of patients. No serious complications occurred in any patient during or after the procedure. Conclusions: The results of this study demonstrated that the most common indication for flexible bronchoscopy was recurrent lower respiratory tract infection and the most common bronchoscopy finding was purulent secretion with mucus obstruction. Flexible bronchoscopy is an important diagnostic and treatment tool for patients with recurrent respiratory symptoms. It is a highly valuable method as it enables direct visualization of the airways and facilitates the collection of bronchoalveolar lavage samples.

Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. METHODS: This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex® website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. RESULTS: Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. CONCLUSION: The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.

Successful treatment of post-pericardiotomy syndrome via C1 inhibitor replacement therapy in a hereditary angioedema patient with Marfan syndrome.

BACKGROUND: Hereditary angioedema with C1 inhibitor deficiency (HAE-C1INH) is caused by dysfunctional C1-INH protein due to mutations in the SERPING1 gene encoding C1-INH. Marfan syndrome is a genetic connective tissue disease that affects the cardiovascular and ocular systems along with the skeletal system. In this case, we present the successful treatment of post-pericardiotomy syndrome unresponsive to classical therapy, which has not been described in the literature. The syndrome developed in a patient with hereditary angioedema (HAE) who underwent open heart surgery due to cardiac involvement in Marfan syndrome. CASE: A nine-year-old male HAE-C1INH patient underwent open heart surgery secondary to cardiac involvement caused by Marfan syndrome. To prevent HAE attacks, 1000 units of C1 inhibitor concentrate therapy were given 2 hours before and 24 hours after the operation. Post-pericardiotomy syndrome was diagnosed on the postoperative second day and ibuprofen 15 mg/kg/day (3 weeks) was started. Since there was no response to classical treatment on the 21st postoperative day, C1 inhibitor concentrate treatment was planned as 1000 units/ dose for 2 days a week considering a prolonged hereditary angioedema attack. In the second week of treatment, complete recovery was achieved for pericardial effusion with a total of 4 doses. CONCLUSIONS: We emphasize that in patients with hereditary angioedema undergoing this treatment, care should be taken in terms of complications that may be associated with the disease even if short-term prophylaxis is given before operations and that longer-term use of C1 inhibitor concentrate has a place in treatment.

Effectiveness and adverse reactions to subcutaneous immunotherapy in children with allergic rhinitis/asthma.

OBJECTIVE: Adverse reactions, which are mostly local and rarely systemic, can be seen during subcutaneous immunotherapy (SCIT). It was not possible to continue SCIT at times due to systemic reactions. The purpose of the present study was to identify the incidence and risk factors associated with adverse reactions during subcutaneous allergen-specific immunotherapy (AIT). METHODS: A total number of 344 patients under 18 years old with allergic rhinitis and/or asthma who underwent SCIT between 2005 and 2021 were included in the study. Demographic characteristics of the patients, laboratory findings [Total Immunglobulin E(IgE), aeroallergen prick test, inhaler, and allergen specific IgE(sIgE) and eosinophil counts], and adverse events observed during AIT were recorded retrospectively. Descriptive and univariate/multivariate logistic regression analyses were used to identify risk factors for adverse events. RESULTS: Among 344 patients, 33.4% (n = 115) were female, mean age was 133.1 ± 41.0 months, and 42.2% (n = 145) were >12 years old. One hundred-thirty eight (40.1%) of the patients were mono-sensitized, 47 (13.7%) had asthma, 207 (60.2%) allergic rhinitis, and 90 (26.2%) asthma and allergic rhinitis. Single allergen content was administered to 187 (54.4%) patients (62 mite, 114 grass mix, 11 olea), and multiple allergens to 157 (45.6%) patients (121 pollen mix, 36 other (mite/alternaria)]. A total number of 33.008 injections were administered. 840 adverse reactions (262 (31.1%) at up-dosing phase, 578 (68.8%) at maintenance phase) in 195 (56.7%) patients were observed. Among the adverse reactions, 632 (75.2%) were local, 160 (19%) large local, and 48 (5.7%) (39 at maintenance, 9 at up-dosing) (in 31 patients) were systemic (28 Grade 1, 12 Grade 2, 8 Grade 3). Adrenalin was administered to 8 patients with Grade 3 systemic reaction (8/33008; %0.024). Adverse reactions, especially local ones, were seen more frequently in children under 12 years old (p < 0.001). Patients sensitized with grass pollen (p:0.01) and mite (p:0.004), and those who had received SCIT with pollen mixture had more adverse reactions than the others. More adverse reactions were observed in SCIT containing calcium-phosphate as adjuvant (p: 0.01). Local reactions were risk factors for large local (OR = 3.591, %95 CI:2.064-6.247, p < 0.001) and systemic (OR = 2.190, %95 CI:1.005-4.722 p = 0.046) reactions at univariate analyses. Total nasal symptom scores, Visual Analog Scale and asthma symptom control test decreased after one year of treatment (p < 0.01). CONCLUSION: SCIT is a safe and effective treatment method in childhood that leads to improvements in all nasal symptoms and asthma after one year of treatment.

Investigation of dynamic hyperinflation and its relationship with exercise capacity in children with bronchiectasis.

BACKGROUND AND AIM: Dynamic hyperinflation (DH) is a major contributor to exercise intolerance in patients with obstructive lung diseases. However, it has not been investigated in children with bronchiectasis (BE). We aimed to investigate dynamic ventilatory responses and their influence on functional exercise capacity in children with BE. METHODS: Forty children with BE (mean forced expiratory volume in 1 s [FEV1 ] = 78 ± 19%pred) were included. Six-minute walk test (6MWT) was conducted using Spiropalm 6MWT® for evaluating dynamic ventilatory responses including inspiratory capacity (IC), minute ventilation (VE), breathing reserve (BR) and respiratory rate (RR). A decrease of ≥100 ml in IC during exertion was defined as DH. Also, spirometry was performed, and peripheral muscle strength were measured. RESULTS: Twenty patients (50%) developed DH, and four patients (10%) were ventilatory limited (BR < %30) during 6MWT. There was a 176 [100-590] ml decrease in IC after exertion in patients with DH. DH did not correlate to clinical or functional indicators of the disease, except for an increase in RR (∆RR) during exertion. High ∆RR was associated with presence of DH (rpb = 0.390; p < 0.05). Clinical features, peripheral muscle strength, and Spiropalm 6MWT metrics including 6MWT distance did not differ between patients with and without DH. Univariate analysis revealed FVC% (R = 0.340), VEpeak (R = 0.565), quadriceps strength (R = 0.698) and handgrip strength (R = 0.711) were the only predictors of 6MWT distance (p < 0.05). CONCLUSION: Although DH is common in children with BE, the severity of DH is rather low and may not seem to affect functional exercise capacity. However, peripheral muscle strength was a major contributor to functional exercise capacity.

High-flow nasal cannula oxygen in children with bronchiolitis: A randomized controlled trial.

OBJECTIVE: To determine whether high-flow nasal cannula oxygen (HFNCO) provided enhanced respiratory support in bronchiolitis than low-flow oxygen (LFO). METHODS: We conducted a prospective, randomized controlled trial in children between 1 and 24 months diagnosed with moderate-to-severe bronchiolitis requiring oxygen therapy. Participants received LFO via face mask (6-10 L/min) or HFNCO (2 L/kg/min). Primary outcomes were the time that heart rate (HR) and respiratory rate (RR) return to their normal range for age and the time that baseline clinical respiratory score (CRS) regress to a lower severity score. Secondary outcomes were changes in HR, RR, and CRS over time, length of stay (LOS), duration of oxygen requirement, treatment failure, and adverse event (AE). RESULTS: Eighty-seven children were enrolled (48 in LFO; 39 in HFNCO). The time that HR and RR baseline values reached their normal range for age was shorter in HFNCO therapy (2.0 h [1.0-4.0] vs. 12.0 h [2.0-24.0], and 4.0 h [2.0-12.0] vs. 24.0 h [4.0-48.0], respectively; p < 0.001); additionally, the improvement in CRS emerged more quickly in children treated with HFNCO (2.0 h [1.0-4.0] vs. 4.0 h [2.0-24.0]; p = 0.003). While the duration of oxygen requirement (19.0 h [4.0-30.0] vs. 29.5 h [14.0-45.7]; p = 0.009) and treatment failure (3% vs. 21%) was statistically lower in children who received HFNCO, there were no differences in LOS and AE between groups. CONCLUSION: HFNCO may provide enhanced respiratory support with a notable improvement in HR, RR, and CRS than LFO. Comprehensive studies are needed to assess the clinical efficacy of HFNCO therapy.

Cut-Off Values of Specific IgE and Skin Prick Test to Predict Oral Food Challenge Positivity in Children with Cow's Milk Allergy.

OBJECTIVE: The cut-off values for the skin prick test diameters and cow's milk-specific IgE measurements are used to predict the result of the oral food challenge test for the diagnosis of cow's milk allergy. This study aimed to determine the diagnostic values of skin prick test and cow's milk-specific IgE according to age groups and compare the diagnostic powers of these 2 methods. MATERIALS AND METHODS: In total, 153 children who had a preliminary diagnosis of cow's milk allergy were evaluated. Group A (n = 90) consisted of cow's milk allergy patients whose diagnosis was confirmed by a positive oral food challenge or a history of anaphylaxis. Group B (n = 63) was composed of patients with a negative oral food challenge. The demographic, clinical, and laboratory findings of 2 groups were compared. RESULTS: The cut-off points for cow's milk-specific IgE and cow's milk-skin prick test were determined as >2.12 kUA/L and >5 mm, respectively. The area under the curve was 0.844 for cow's milk-skin prick test (sensitivity 73%, specificity 84%) and 0.745 for cow's milk-specific IgE (sensitivity 67%, specificity 86%). The diagnostic power of skin prick test was determined to be higher when compared to cow's milk-specific IgE (P = .02). According to the predicted probability curves, decision points for cow's milk-specific IgE and cow's milk-skin prick test with 95% probability were determined as follows, respectively: for ≤24 months: 22 kUA/L, 11.3 mm; for >24 months: 44.1 kUA/, 15.1 mm. The lowest cut-off value with a positive predictive value of 95% and a specificity of 96% was found in patients 3.3 kUA/L) Conclusion: The use of high probability diagnostic values of communities for specific IgE and skin prick test along with a significant clinical history may provide accurate and rapid diagnosis of cow's milk allergy and facilitate patient follow-up.

Could Age and Oral Challenge Outcomes Identify High-Risk Patients During Cow's Milk Oral Immunotherapy?

Objective: Severe immunglobuline E (IgE)-mediated reactions during oral immunotherapy (OIT) are major obstacles to treatment. The present study aimed to evaluate and identify clinical and laboratory biomarkers of adverse events during OIT among children with cow's milk (CM) allergy. Study Design: Eighty-six children older than 36 months who had undergone OIT with milk were enrolled. Clinical data, oral food challenge (OFC) test results, and laboratory data were recorded retrospectively. Results: The median duration of the build-up phase of OIT was 19 weeks (min 10-max 40) and the duration of the maintenance phase was 86.5 (min 1-max 132) months. A total of 11,767 CM doses were administered during the build-up phase and adverse reactions were seen in 62 (73.8%) patients with reactions registered for 157 doses among 11,767 (1/75 doses). The number of reactions during the maintenance phase was 41 (47.6%) in 24 (27.9%) patients. There was a significant reduction in the number of reactions (P = 0.000) between the build-up phase and maintenance phase. Adverse reactions and anaphylaxis were higher for patients who had cough during OFC (P = 0.003, P = 0.002, respectively) during the build-up phase and also during the maintenance phase too (P = 0.000). Evaluation for all reactions and anaphylaxis (during build-up and maintenance) with Kaplan-Meier and Cox regression analysis showed class IV-VI of CM-specific immunoglobulin E (sIgE), casein-sIgE and cough during OFC were significantly associated with increased probability of reaction and anaphylaxis. Younger age at onset of OIT was associated with risk reduction (0.017). Conclusion: Laboratory data and reactions during the OFC (especially cough) can help to identify high-risk patients during OIT.