Recurrent Respiratory Infections Research Articles

STAT5B germline heterozygous variant presenting with lymphadenopathy, atopy, and short stature

Background: Signal Transducers and Activators of Transcription (STAT) proteins are fundamental for multiple cellular processes, including immunity. STAT5B serves as a signal transducer downstream of cytokine and growth factor-mediated activation. Aberrations in STAT5B are associated with the development of atopy, immunodeficiencies, autoimmunity, cancers, hematological disease, growth disorders, and lung disease. Biallelic STAT5B variants are associated with loss-of-function of the gene, and cause a recessive disorder characterized by growth hormone insensitivity and immune dysregulation. Clinically significant heterozygous variants result in either dominant negative or gain-of-function effects; these latter variants are rare and their impact on the immune system is less clearly delineated than those responsible for the recessive form of the condition. Aim: We describe the presentation, immune workup, and genetic findings in a pediatric patient with a novel STAT5B heterozygous variant. Methods: A thorough retrospective review of the patient’s chart was performed. Results: A four-year-old male presented with history of lymphadenopathy, eczema, asthma, food allergy, short stature, and recurrent upper and lower respiratory tract infections. Clinical trio whole exome sequencing identified a novel heterozygous variant (c.1A>G; p. Met1?) in STAT5B. His mother harbours the same heterozygous variant and has a history remarkable for atopy. Immune investigations on the child revealed persistent elevated IgE. The patient’s variant targets the STAT5B N-terminal domain, and represents the first case with a heterozygous variant affecting this region. Conclusion: We present a novel STAT5B variant associated with a dominantly-inherited growth and immune phenotype. This is the first report of a heterozygous variant affecting the N-terminal domain in association with a clinical phenotype, expanding the genotypic landscape of this disorder. Further investigations and follow up responses to growth hormone replacement are needed to better delineate the functional effect of the variant identified in this family. Statement of Novelty: We report a novel germline heterozygous STAT5B variant in a paediatric patient with lymphadenopathy, atopy, and short stature.

OGBN P06 Co-location of pulmonary abnormalities on high resolution CT imaging and pulmonary microaspiration reflux scan: Suggests a causative relationship

Abstract Background The relationship between micro-aspiration of refluxate as a form of gastro-oesophageal reflux disease (GORD) and pulmonary diseases including bronchiectasis and lung fibrosis has been circumstantially suggested but not proven. Clarification of the role of GORD and microaspiration in pulmonary disease may enable targeted therapies. This study aims to determine whether there is a relationship between anatomical location of aspiration of radiological tracer on scintigraphic imaging and changes associated with pulmonary disease on high resolution computed tomographic imaging of the lung (HRCT-L). Methods Data were obtained from a prospectively populated database of patients with treatment resistant typical and atypical GORD and suspected reflux pulmonary microaspiration. Patients who underwent microaspiration studies and had concurrent HRCT-L for chest symptoms were included. Modified novel digital technique of reflux pulmonary microaspiration scintigraphy using a previously validated technique was performed to evaluate the possibility of significant GORD or extra-oesophageal symptoms, including typical symptoms such as heartburn and reflux and atypical symptoms such as throat symptoms, cough, globus, mucous, throat clearing, dysphonia and recurrent respiratory infections. HRCT-L was obtained in clinically indicated patients and compared with scintigraphic findings. Results Pulmonary reflux microaspiration scanning was performed in 121 patients (75% female, 25% male). The mean age was 67 years (range: 31 – 91 years). All patients demonstrated reflux microaspiration on scintigraphy in the supine delayed phase and all had intermittent or continuous full column gastro-oesophageal reflux. Lung parenchymal changes were apparent in 66 of 73 patients who underwent HRCT-L. Fibrotic changes were demonstrated in 51% of patients and bronchiectactic changes in 46%. Correlation at anatomical lobar levels with areas of aspiration of isotope on scintigraphic imaging was seen in 97% of fibrosis patients and 85% of bronchiectasis patients. Conclusions Modified reflux pulmonary microaspiration scintigraphy demonstrated the presence of pulmonary aspiration on delayed imaging. This is the first imaging technique with the ability to confirm the presence of lung aspiration of gastric content. Given the large proportion of cases showing lobar co-location of pulmonary abnormality on HRCT-L, this study indicates a strong relationship between aspiration of refluxate and parenchymal lung changes associated with pulmonary diseases such as IPF and bronchiectasis. There may be a significant role for modified technique scintigraphy to accurately diagnose the presence of reflux aspiration, allowing further research into pathogenesis and management of pulmonary disease.

High oral carriage of multidrug resistant Gram-negative bacilli in adolescents: the SOPKARD-Junior study.

The colonization of the oral cavity by potentially pathogenic antimicrobial-resistant bacteria in adolescents and its consequences is very poorly understood. The present study focused on the occurrence of oral colonization by Gram-negative bacilli (GNB) and their multidrug resistance, including the production of extended-spectrum β-lactamases (ESBLs) and carbapenemases, among healthy adolescents and risk factors associated with GNB colonization. This study was conducted as part of "A program for the early detection of risk factors for lifestyle diseases SOPKARD-Junior" (SOPKARD-Junior). Oral samples were collected from 182 adolescents from four public elementary schools in Sopot, Poland, aged 13-14 years. Bacterial strains were identified by the MALDI-TOF MS method. Screening of antimicrobial resistance was performed using a disk diffusion method. The NG-Test® CARBA-5 was used to detect and differentiate the five most widely distributed carbapenemases. Demographic and clinical data were collected and statistical analysis of risk factors was performed. A total of 68 out of 182 (37.4%) healthy adolescents was documented oral colonization with Gram-negative bacilli, including 50/182 (27.5%) multidrug resistant (MDR-GNB) strains. Over 60% of oral carriage concerned three main genera Enterobacter spp., Pseudomonas spp., and Serratia spp., which were detected in 22.1%, 19.1%, and 19.1% of participants, respectively. Citrobacter spp., Escherichia coli, Klebsiella spp., Hafnia spp., Aeromonas spp., Acinetobacter spp., and Stenotrophomonas spp. were also isolated. The antimicrobial resistance to ampicillin (100%), ceftazidime (69.1%), meropenem (60.3%), gentamycin (60.3%), piperacillin/tazobactam (52.9%), and piperacillin (45.6%) were the most common. Among 73.5% GNB strains multidrug resistance was observed, including all Pseudomonas spp. strains. Among MDR-GNB, 30.4% were resistant to four groups of antibiotics, half of the MDR Pseudomonas spp. strains were resistant to 10 groups of antibiotics. Extended-spectrum β-lactamases were produced by Enterobacter cloacae, Klebsiella spp., and Serratia spp. (7.4%). Colonization by ESBLs-positive GNB strains was significantly associated with recurrent respiratory infections, nasal congestion, and bronchitis (p<0.05). Our study revealed high oral carriage of multi-drug resistant Gram-negative bacilli in healthy adolescents and the association of ESBL-producing strains with respiratory infections. Further studies on oral colonization with GNB are necessary due to the possibility of distinct infections and the acquisition of antibiotic resistance by resident microbiota.

Mycoplasma pneumoniae carriage in children with recurrent respiratory tract infections is associated with a less diverse and altered microbiota

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in recurrent respiratory tract infections is unclear. We studied the prevalence of M.pneumoniae carriage in children with recurrent respiratory infections and identified associated factors. We tested M.pneumoniae carriage by qPCR in children with recurrent infections and their healthy family members in a cross-sectional study. Serum and mucosal total and M.pneumoniae-specific antibody levels were measured by ELISA and nasopharyngeal microbiota composition was characterized by 16S-rRNA sequencing. Prevalence of M.pneumoniae carriage was higher in children with recurrent infections (68%) than their family members without infections (47% in siblings and 27% in parents). M.pneumoniae carriage among family members appeared to be associated with transmission within the household, likely originating from the affected child. In logistic regression corrected for age and multiple comparisons, IgA (OR 0.16 [0.06-0.37]) and total IgG deficiency (OR 0.15 [0.02-0.74]) were less prevalent in M.pneumoniae carriers (n=78) compared to non-carriers (n=36). In multivariable analysis, the nasopharyngeal microbiota of M.pneumoniae carriers had lower alpha diversity (OR 0.27 [0.09-0.67]) and a higher abundance of Haemophilus influenzae (OR 45.01 [2.74-1608.11]) compared to non-carriers. M.pneumoniae carriage is highly prevalent in children with recurrent infections and carriers have a less diverse microbiota with an overrepresentation of disease-associated microbiota members compared to non-carriers. Given the high prevalence of M.pneumoniae carriage and the strong association with H.influenzae, we recommend appropriate antibiotic coverage of M.pneumoniae and H.influenzae in case of suspected pneumonia in children with recurrent respiratory tract infections or their family members. Wilhelmina Children's Hospital Research Fund, 'Christine Bader Stichting Irene KinderZiekenhuis', Sophia Scientific Research Foundation, ESPID Fellowship funded by Seqirus, Hypatia Fellowship funded by Radboudumc and The Netherlands Organisation for Health Research and Development (ZonMW VENI grant to LM Verhagen).

Insights Into Cystic Fibrosis Gene Mutation Frequency, Clinical Findings, and Complications Among Pakistani Patients.

Background Cystic fibrosis (CF) is a genetic disorder with diverse symptoms. Understanding its genetic basis and prevalence is crucial for effective management and treatment. Objective The study aimed to provide comprehensive insights into the frequency of CF gene mutations, clinical presentations, and complications among the Pakistani population. Methodology A cohort comprising 892 patients, ranging in age from 18 to more than 40 years, was selected on the basis of clinical and genetic criteria for the diagnosis of CF. Polymerase chain reaction (PCR) was used to look for 34 variants in the CFTR gene in blood samples. Statistical analysis, which included figuring out the number of mutations, the average age of diagnosis, and the genetic diversity of the samples, was performed to analyze the percentage of patients with specific mutations, offering insights into the genetic diversity. Results In our comprehensive analysis of 892 patient samples, 77.47% (n=691) displayed consanguinity, indicating a family history. The prevailing symptoms included chronic cough (88.67%; n=791), recurrent respiratory infections (76.68%; n=684), and fatigue (73.76%; n=658). The major complications comprised pulmonary infections (22%; n=197), cystic fibrosis-related diabetes (21%; n=187), and malabsorption (20%: n=178). A paired t-test revealed a mean difference of 5.750 with a standard deviation of 9.147, a 95% confidence interval from -0.061 to 11.561, a t-value of 2.178 with 11 degrees of freedom, and a two-tailed p-value of 0.052, suggesting a potential trend towards significance. Nevertheless, the asymptotic significance values of 1.000 and 0.998 for both groups indicate no significant difference. Furthermore, the study identified 12 cystic fibrosis gene mutations, with F508del and N1303K being the most prevalent. Conclusion This research revealed significant consanguinity, confirmed typical CFsymptoms, and identified common complicationsand prevalent CFTR gene mutations (with F508del and N1303K being the most common), providing insights for genetic guidance and treatment in the Pakistani community.

Features of pyelonephritis course in adolescent females with co-existing anаemic syndrome

Background. Anaemic syndrome of complex origin is not uncommon in urinary tract infection, particularly in dietary non-adherence, menstrual cycle disorders, or concomitant digestive diseases, recurrent respiratory infections, etc. However, there is currently insufficient epidemiological data on this comorbidity in the literature. This study aims to establish the features of pyelonephritis course in its combination with anaemic syndrome in children. Materials and methods. We analysed the medical records of 200 children aged 0 to 17 years with acute non-complicated pyelonephritis, complicated and recurrent urinary tract infections for 2012–2017. In the second stage of our work, we comprehensively examined 85 girls aged 11 to 17 who underwent inpatient treatment between 2018 and March 2023. Thirty children of the same age and gender made up the comparison group. A paediatric gastroenterologist, a paediatric gynaecologist and/or urologist examined all patients. Immunochemical method with electrochemiluminescence immunoassay was used to assess ferritin content; also, serum iron and total iron-binding capacity were measured. Results. Anaemic syndrome is common in most girls with urinary tract infections (58.8 % of сases). Among the causes, the follo­wing are distinguished: menstrual cycle disorders with abnormal uterine bleeding (50.0 %), chronic digestive disorders, in particular malabsorption syndrome of unknown origin (25.0 %), recurrent bronchopulmonary disorders (15.0 %), and unbalanced diet (10.0 %). The features of urinary tract infections and concomitant iron deficiency in children include fatigue (55.0 % in acute non-complicated pyelonephritis vs. 40.0 % in complicated urinary tract infections, р &lt; 0.05), dizziness (35.0 % in acute non-complica­ted pyelonephritis vs. 15.0 % in recurrent urinary tract infections, χ2 = 48.6532, р &lt; 0.05), and pallor (25.0 % in complicated urinary tract infections vs. 10 % in recurrent urinary tract infections, χ2 = 0.7168, р &gt; 0.05). The ferritin level was the highest in patients with complicated urinary tract infections (18.2 µg/mL). In patients with recurrent urinary tract infections, this indicator was the lo­west — 5.0 µg/mL. Conclusions. Retrospective analysis of medical records confirmed the presence of anaemia in 30.0 % of girls with inflammatory kidney diseases. During the physical examination, 58.8 % of female adolescents with urinary tract infections had signs of anaemic syndrome.

Transcatheter closure of large ostium secundum atrial septal defects in symptomatic small children: A single-center retrospective study.

In general, the risks associated with transcatheter atrial septal defect (ASD) device closure are reported to be relatively low, but the evidence stems from trials involving adults and older children. Current guidelines do not recommend ASD device closure in children with defect sizes >20 mm due to limited data available in this group of patients. This retrospective study sought to determine the clinical and procedural characteristics of successful transcatheter ASD device closure in small children with large defects and assess the complication rates and reasons for unsuccessful device closure. We retrospectively reviewed the data of all patients who underwent elective transcatheter closure of ostium secundum ASD in our department between September 2013 and February 2022. All children weighing <20 kg, requiring a device of size 20 mm or greater, were included. Major and minor complications were predefined and indications for referral were evaluated. Echocardiogram reports were reviewed from the time of referral, postcatheterization day 1, and at 1-year follow-up. We identified 40 patients meeting inclusion criteria with a median (interquartile range [IQR]) procedural age of 5 (4-7) years and median (IQR) weight of 14 (12-18) kg. Successful device closure was achieved in 39 patients with a success rate of 97.5%. The total complication rate was 2.5% (95% confidence interval: 0.44%- I2.8%) with only 1 major complication. All children had right heart enlargement and exertional dyspnea, 30% of patients had recurrent lower respiratory tract infections, and 10% had failure to thrive. At 1-year follow-up, a transthoracic echocardiogram showed a well-endothelialized device in a stable position in all the patients, and none of the patients had a residual shunt. In experienced centers, percutaneous ASD closure of large defects in symptomatic small children can be done effectively and safely with a great degree of predictability and a low complication rate.

The Efficacy and Safety of Shashen-Maidong Decoction Combined with Western Medicine in the Treatment of Omicron Infected Individuals Over 85 Years Old: A Retrospective Study.

During the Omicron variant outbreak of COVID-19 (2022-2023), Chinese healthcare institutions combined traditional Chinese medicine (TCM) with Western medical practices to treat COVID-19 patients, especially the elderly. The efficacy and safety of this approach, especially for individuals aged over 85, need further investigation. In this retrospective study, a cohort of 62 patients aged over 85 years, diagnosed with COVID-19 infection, was examined. Among them, 34 patients were administered Shashen-Maidong decoction in conjunction with Western medicine (SMD+WM group), while the remaining 28 patients received only Western medicine (WM group). Comparative analysis was conducted between the two groups, encompassing parameters such as the duration for the nucleic acid test to turn negative, length of intensive care unit (ICU) stay, mortality rate, utilization of high-flow nasal cannula oxygen (HFNC), occurrence of endo-tracheal intubation, frequency of recurrent respiratory infections within three months, and various laboratory indicators. There were no significant differences observed between the two groups in terms of the duration for the nucleic acid test to turn negative, the length of ICU stay, mortality rate, utilization of HFNC, performance of endo-tracheal intubation, or the frequency of recurrent respiratory infections within three months (P > 0.05). However, in comparison to the WM group, the SMD+WM group exhibited notably lower growth rates in white blood cell (WBC) and neutrophil (NEUT) values. Additionally, the SMD+WM group demonstrated superior improvement in cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP) values. In contrast to the administration of Western medicine alone, the combined use of Shashen-Maidong decoction with Western medicine significantly suppresses the increase in WBC count, particularly in NEUT levels, in elderly patients diagnosed with COVID-19. Moreover, this combined treatment exhibits a protective effect on cardiac function and demonstrates a relatively safe profile.

Brief research report: OM-85 reduces SARS-COV-2 viral RNA expression in nasopharyngeal cells from COVID-19 patients

OM-85 is a bacterial lysate from common respiratory tract pathogens, with an excellent safety profile, widely used to prevent recurrent respiratory tract infections. Several studies have been reporting the immunomodulating properties and antiviral roles of OM-85. The COVID-19 pandemic, originating in 2019, has presented a significant global public health crisis. While effective vaccines have been developed, vaccination rates vary considerably, and numerous concerning viral variants continue to emerge. The challenge persists in creating early interventions to halt the progression of the disease to its severe stages. To examine the therapeutic effect of OM-85 after SARS-CoV-2 infection and compared to recombinant human (rhINF-β) we collected nasopharyngeal cells from COVID-19 patients. The cells were treated ex-vivo with OM-85 or hrINF-β and the response was analyzed after 24h for gene expression by real-time PCR. We found that OM-85 decreased the SARS-CoV-2 N1 gene expression and increased RIG-I (DDX58) in these cells. The expression of ACE2 was undetected in these samples. These data support the antiviral effect of OM-85 against SARS-CoV-2.

Persistent ciprofloxacin exposure induced the transformation of Klebsiella pneumoniae small colony variant into mucous phenotype

IntroductionSmall colony variant (SCV) is a bacterial phenotype closely related to persistent and recurrent infections. SCVs are mutations that occur within bacterial populations, resulting in a change in bacterial morphology and the formation of small colonies. This morphological change may enhance bacterial resistance to antibiotics and contribute to persistent and recurrent infections.MethodsWe isolated Klebsiella pneumoniae (KPN) and its SCV from a child with recurrent respiratory tract infections. KPN and SCV were treated with subinhibitory concentrations of antibiotics. growth curves, serum resistance experiments, macrophage phagocytosis experiments and whole genome sequencing were used to characterize KPN and SCV.ResultsAfter treating KPN and SCV with subinhibitory concentrations of antibiotics, we found that ciprofloxacin induced the SCV transition to the mucoid phenotype. We found that the growth of mucoid Klebsiella pneumoniae was significantly slower than maternal strain and SCV though growth curves. Serum resistance experiments showed that mucoid strains had significantly higher serum resistance compared to maternal strain and SCV. Macrophage phagocytosis experiments revealed that SCV had significantly higher intracellular survival rates compared to maternal strain and mucoid strains. Differential gene analysis of three strains revealed that the mucoid strain contained DNA polymerase V subunit UmuC gene on the plasmid, while the SCV strain had an additional IcmK family IV secretion protein on its plasmid.DiscussionOur study showed the SCV of KPN changed to a mucoid colony when exposed to subinhibitory concentrations of ciprofloxacin. The higher resistance of serum of mucoid colonies was possibly related to the UmuC gene, while the increased intracellular survival of SCV may be related to the IcmK family type IV secretion proteins.

Role of multi-strain probiotics in preventing severity and frequency of recurrent respiratory tract infections in children

BackgroundRespiratory tract infections are among the most common infections in the pediatric population throughout the globe. Globally around 20% of all deaths in children below 5 years of age are secondary to acute respiratory infections, mostly pneumonia. Probiotics are live microorganisms that when administered in adequate amounts confer a health benefit on the host. Their mechanism in preventing respiratory tract infections is not known but it is thought that probiotics act by modulating the immune system. This study was conducted to find out whether using probiotics is effective in decreasing the severity and frequency of recurrent respiratory tract infections or not.MethodsA Quasi-experimental study was conducted at the Pediatric Medicine Department of Abbassi Shaheed Hospital Karachi during 2021–2022. The study was approved by the institutional ethical review committee i.e. advanced studies and research board (ASRB). The sampling technique was non-probability consecutive sampling and the sample size was 70 patients with recurrent respiratory tract infections, aged six months to 12 years of age. All enrolled children were given probiotics containing Bifidobacterium, Lactobacillus Acidophilus for two weeks. Data were analyzed by using SPSS version 22. A p-value of < 0.05 was considered statistically significant.ResultsOut of 70 children with recurrent respiratory tract infections, 39 (55.71%) were male and 31 (44.29%) female. Around 75% of the children were below five years of age. The most common presenting complaint was fever (72.86%), followed by cough (68.57%), wheezes (45.71%) and nasal discharge/sneezing (32.86%), respectively. The most common RRTI was infectious rhinitis (30% of the cases), otitis media (24%) and pharyngitis/tonsillitis (21%). After giving probiotics for two weeks most significant decrease was found in recurrent infectious rhinitis (p-value 0.02), recurrent otitis media (p-value 0.03) and recurrent bronchiolitis (p-value 0.05) over the next six months.ConclusionThe results of our study indicate that the administration of probiotics reduces recurrent respiratory tract infections among children. This six months trial has demonstrated that there was a significant decline in respiratory symptoms among study participants. This study also observed a significant decrease in respiratory diseases during the follow-up.

The clinical and genotypic-phenotypic findings of mucopolysaccharidosis VI patients: an Iraqi single-study descriptive study.

Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI; MPS VI) is a chronic illness that causes progressive enlargement, inflammation, or scarring of several tissues and organs until their collapse. In most cases, an infant with MPS VI shows no symptoms. The early signs and symptoms of MPS VI in children often develop in the first few months of life. MPS VI affects various systems in the body, including the skeletal, cardiac, and respiratory systems. The authors aim in our study to describe the clinical and genotypic-phenotypic findings of MPS VI patients in 'children Welfare Teaching Hospital, Medical City Complex.' The single-center study was conducted at the 'children Welfare Teaching Hospital, Medical City Complex' from November 2016 to May 2022. The research recruited 72 MPS VI patients from Iraq, all under 20. The authors investigated the sociodemographic characteristics, hematological lab results, gene-phenotype findings, and clinical features and evaluated the severity and progression of the MPS 6 disease. Seventy-two Iraqi MPS VI patients were involved in the study, and the average age of the study sample was 6.38±3.4 (0.3-19). The consanguinity rate was 94.4%. In the research, females comprised 56.9% of the patients, and the Z-scores for body mass index and occipital-frontal head circumference were -2.66 and 1.2. The fascial features at diagnosis, 'coarse facies' (90.3%), dysostosis multiplex (93%), short stature (94.4%), and recurrent respiratory infections (91.6%), were the most common clinical features among the enrolled patients. The most frequent mutation was (complementary DNA: c.753C>G, protein effect: p.(Tyr2*) or p.(Tyr251Term), and the codon cross-tabulation: premature stop codon, or homozygous stop nonsense mutation/exon N.3) (33/69 (47.82%)). Furthermore, a statistically significant correlation existed between lower weight and height readings and the progressed and severe stages of the MPS VI illness. As the first research in Iraq with a sufficient sample size of MPS VI patients, the investigation presented important clinical and gene-phenotype findings and revealed the necessity for enhancing the diagnosis of MPS VI, including the updated molecular analysis and monitoring the multisystem parameters, aberrant comorbidities, and the progression and severity.

Cluster Analysis of Finnish Population-Based Adult-Onset Asthma Patients.

Phenotypes of adult asthma have been identified in previous studies but rarely in population-based settings. To identify clusters of adult-onset asthma in a Finnish population-based study on subjects born before1967. We used population-based data from 1350 asthmatics with adult-onset asthma (Adult Asthma in Finland) from Finnish national registers. Twenty-eight covariates were selected based on literature. The number of covariates was reduced by using factor analysis before cluster analysis. Five clusters (CLU1-CLU5) were identified, 3 clusters with late-onset adult asthma (onset ≥40 years) and 2 clusters with onset at earlier adulthood (<40 years). Subjects in CLU1 (n= 666) had late-onset asthma and were nonobese, symptomatic, and predominantly female with few respiratory infections during childhood. CLU2 (n= 36) consisted of subjects who had earlier-onset asthma, were predominantly female, obese with allergic asthma, and had recurrent respiratory infections. Subjects in CLU3 (n= 75) were nonobese, older, and predominantly men with late-onset asthma, smoking history, comorbidities, severe asthma, least allergic diseases, low education, many siblings, and childhood in rural areas. CLU4 (n= 218) was a late-onset cluster consisting of obese females with comorbidities, asthma symptoms, and low education level. Subjects in CLU5 (n= 260) had earlier onset asthma, were nonobese, and predominantly allergic females. Our population-based adult-onset asthma clusters take into account several critical factors such as obesity and smoking, and identified clusters that partially overlap with clusters identified in clinical settings. Results give us a more profound understanding of adult-onset asthma phenotypes and support personalized management.

Psycho-emotional portrait of primary school-age children with recurrent respiratory infections

Respiratory infections occupy a leading place in the structure of the population’s morbidity, especially among children. At the same time, recurrent respiratory infections (RRIs) impose the main burden on society and families. Most of the factors contributing to the manifestation of the RRI phenomenon have already been well-studied. However, the influence of psychological and emotional aspects on a child’s health has remained largely overlooked. Aim. to study the psychological characteristics of children aged 5–7 years in comparison to episodically ill peers and their correlation with local immunity indicators. Materials and Methods. The study involved 80 children, with 60 in the main group (children with recurrent respiratory infections) and 20 in the control group (episodically ill children). For psychological testing (psychometrics), the following methods were used: Blob Tree test (P. Wilson) to determine motivation and adaptation of children in a group setting. The projective „Family Sociogram‟ test (E.G. Aidemiller) to determine the place of the subject in the system of interpersonal relationships and to assess the nature of communication within the family. A modified version of A. Etkind’s Color Relations Test was used to determine individual typological personality characteristics and attitudes towards significant people and the surrounding environment on both a conscious and partially unconscious level. Clinical laboratory examination included measuring levels of secretory IgA and lysozyme in unstimulated saliva. Results. When analyzing the data obtained, a statistically significant difference was found between the results of children in the main and control groups. Conclusions. During color selection, children with RRIs more often associated themselves with the color red (40.7 %), their mothers with purple (40.7 %), and kindergarten or school with yellow (29.7 %) compared to episodically ill peers (p &lt; 0.05). Children with RRIs in the „Family Sociogram‟ test more often than episodically ill peers demonstrated reduced self-esteem (73 % vs. 30 %, p = 0.038). In the Blob Tree test, children with RRIs differ in their first choice (current position in the group) from episodically ill peers (p &lt; 0.0001). The level of sIgA and lysozyme in saliva in the group of children with RRIs correlates with the sensory choice of color for the mother (p &lt; 0.0001).

Risk factors of recurrent respiratory infections in early school-age children

Acute respiratory infections (ARIs) annually rank first in the structure of infectious diseases both in Ukraine and worldwide. ARIs are the leading cause of disability and death in preschool children, and with recurrent episodes, they can impact the physical and psychological aspects of children's health, imposing a significant medical burden on families, healthcare systems, and society as a whole. Preventing recurrent respiratory infections (RRIs) can only be achieved through timely intervention in risk factors.Aim: to determine the influence of risk factors on the development of recurrent episodes of acute respiratory infections in children aged 5 to 7 years and to develop preventive measures for their control in primary healthcare settings.Materials and Methods. The authors retrospectively analyzed medical records of 342 children aged 5 to 7 years. The main group included children with RRIs (264), and the control group consisted of children with sporadic illness episodes (78). Results: the incidence of RRIs in children has two peaks at ages 3 and 6, which is likely associated with the commencement of attendance in childcare settings (kindergarten and school). Key prenatal and postnatal, clinical-anamnestic, and social risk factors that increase the likelihood of recurrent respiratory infections in younger school-age children were identified.Conclusions. factors significantly increasing the likelihood of developing RRIs in a child include: ARI episode within the first 6 months of life (OR = 22, 95% CI 11.6 - 41.7), previous pneumonia (OR = 12, 95% CI 3.7 - 40), and the presence of chronic infection foci in the form of tonsillitis (OR = 8.2, 95% CI 4.3 - 15.6), p=0.0001. Primary healthcare practitioners should follow strategies to modify these risk factors and not wait for further depletion of the child's adaptive potential (sanitation of chronic infection foci, promotion of breastfeeding, and tobacco cessation).

Hematopoietic stem cell transplantation in patient with DOCK8 deficiency: Ukrainian experience

Dedicator of Cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency that exemplifies the broad clinical features of primary immunodeficiencies (PIDs), extending beyond recurrent infections including atopy, autoimmunity, and cancer. Purpose - to describe the natural course of hyper-IgE syndrome (HIES) disease in an 8-year-old boy and his path to diagnosis, as well as our first local history of conservative treatment for 6 months. In particular, we describe the effectiveness of omalizumab, and the application of allogeneic hematopoietic stem cell transplantation with follow-up. Clinical case. The 8-year-old boy presented with severe eczema and an involvement of the whole surface of the body. Infectious syndrome manifested from the age of 4 months in a form of recurrent respiratory infections. Over the next few years, the child suffered from life-threatening infections with high serum IgE (&gt;3000 IU/ml). The examination revealed a cushingoid constitution, flat-valgus feet, and dysmorphic features. Therefore, HIES was suspected. Genetic studies have confirmed the diagnosis by detecting a pathogenic homozygous mutation in the DOCK8 gene (Deletion Exons 2-46). We decided to use a humanized monoclonal anti-IgE antibody (off-label) to control the skin syndrome rather than systemic steroids. A significant improvement in skin condition, a decrease in eosinophils, and IgE were observed. Allogeneic stem cell transplantation of hematopoietic cells (HSCT) derived from peripheral blood of an human leukocyte antigen (HLA) - identical sibling donor was performed. The donor had a pathogenic mutation identical to the recipient in the DOCK8 gene but in a heterozygous state. Our data and treatment approach may be clinically useful as a diagnostic and treatment approach to HIES. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies No conflict of interests was declared by the authors.

Patient-reported outcomes in patients with primary immunodeficiency diseases in Japan: baseline results from a prospective observational study.

Primary immunodeficiency diseases (PIDs) are rare inherited diseases resulting in impaired immunity. People with PID experience lower health-related quality of life (HR-QOL) and disease-related burdens in daily activities. This ongoing, prospective observational study aims to evaluate disease activity, treatment status, treatment-related burden, daily activities, and HR-QOL in patients with PID in Japan over a 1-year period. In this interim report (database lock: July 29, 2022), we present baseline results. Participants were enrolled between November 2021 and May 2022; data were collected four times/year per participant until May 2023 using an online electronic patient-reported outcomes system. Patients with PID and healthy volunteers aged ≥12 years, residing in Japan, and with access to a smartphone were eligible. HR-QOL (primary endpoint) was assessed by the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Work productivity was assessed by the Work Productivity and Activity Impairment (WPAI) Questionnaire. Other aspects of PID and burden were assessed with a new questionnaire developed in-house. The study is registered at the University hospital Medical Information Network clinical trials registry (UMIN000045622). The full interim analysis set comprised 71 patients with PID and 47 healthy volunteers. The most common International Union of Immunological Societies PID category was primary antibody deficiency (56.3% of patients). Complications were common, especially recurrent respiratory tract infections (63.4%). Most patients with PID were treated with immunoglobulin replacement therapy (73.2%); 22.4% of these patients had serum immunoglobulin levels <700 mg/dL. Among patients who did not undergo hematopoietic cell transplantation, EQ-5D-5L (n=67) and SF-36 (n=59) Physical and Mental Component Summary scores were significantly lower than in healthy volunteers (p < 0.001). WPAI absenteeism, work productivity loss, and activity impairment scores were significantly lower in 42 working patients with PID than in 37 working healthy volunteers (p < 0.05). Other results indicated that patients with PID experience substantial burdens related to medical visits, expenses, work, and daily activities. This interim analysis confirms that patients with PID in Japan have lower HR-QOL and work productivity compared with healthy individuals and experience substantial limitations and burdens in their daily lives.

Can Scoliosis Help the Early Diagnosis of Congenital Myasthenic Syndrome?

Background Congenital myasthenic syndromes (CMS) are a group of hereditary diseases of the neuromuscular junction. CMS are extremely rare diseases that cause hypotonia; however, scoliosis may theoretically be helpful in early diagnosis of CMS. The objective of this studywas to emphasize the clinical features of the patients we followed up with the diagnosis of CMS and demonstrate that scoliosis is an important finding in the diagnosis of CMS in the presence of hypotonia/weakness. Materials and methods In this retrospective study, data were retrieved by examining the digital files of the patients who presented to Aydın Maternity and Children's Hospital and Elazığ Fethi Sekin City Hospital Pediatric Neurology Clinics between 2018 and 2023. The diagnosis of CMS was strongly supported by a combination of clinical characteristics, neurophysiological studies, genetic tests, AChR antibodies, and serum creatine kinase measurement. The presence of scoliosis was evaluated by an orthopedics and traumatology specialist. Results Eleven CMS patients with accompanying scoliosis were included in the study. The mean age of the patients was 69.4±39.28 months. The age of the patients at the time of diagnosis was 42.7±35.19 months. Among the patients, eight were males (72.7%), and three were females (27.2%). Seven patients (63.6%) had COLQ mutations. Electromyography was conducted on eight patients, with one of them showing no pathological findings, while seven exhibited decremental responses. All patients had ptosis, while six (54.5%) had bulbar signs. Ten patients (90.9%) had weakness. Nine patients (81.8%) experienced frequent recurrent lower respiratory tract infections. Both the patient with CHAT mutation and RAPSN mutation had arthrogryposis. Conclusion In this study, CMS stands out as an essential consideration in the differential diagnosis, particularly when scoliosis accompanies early-onset muscle weakness.

Two cases of successful sirolimus treatment for patients with activated phosphoinositide 3-kinase δ syndrome 1

BackgroundActivated phosphoinositide3-kinase (PI3K) δ syndrome 1 (APDS1) is a novel inborn errors of immunity (IEIs) caused by heterozygous gain of function mutations in PI3Kδ catalytic p110δ (PIK3CD). APDS1 has a spectrum of clinical manifestations. Recurrent respiratory infections, lymphoproliferation, hepatosplenomegaly, hyper-IgM syndrome and autoimmunity are the common symptoms of this disease.Case PresentationPatient 1 presented with recurrent respiratory infections, hepatosplenomegaly and hyper-IgM syndrome. Patient 2 developed early onset systemic lupus erythematosus (SLE)-like disease with resistant thrombocytopenia. c.3061 G > A and c.2314G > A variants in the PIK3CD gene were detected by whole exome sequencing in two patients respectively. c.2314G > A variant in PIK3CD gene of patient 2 is a newly report. After genetic diagnosis, two patients received sirolimus treatment and sirolimus alleviated clinical manifestations, including hepatosplenomegaly in patient 1 and thrombocytopenia in patient 2.ConclusionGenetics diagnosis should be considered in patients with complicated clinical manifestations with no or insufficient response to the conventional therapies. If whole exome sequencing suggests a variant in PIK3CD gene, sirolimus may relieve hepatosplenomegaly and resistant thrombocytopenia. This is the first report of c.2314G > A variant in PIK3CD gene.

Incidental Finding of Mounier-Kuhn Syndrome

Tracheobronchomegaly (TBM) or Mounier - Kuhn syndrome is a rare disorder of uncertain etiology characterized by marked dilatation of the trachea and bronchi and recurrent lower respiratory tract infection. We report the case of a 56-year-old male presenting with a chronic cough.