Recurrent Respiratory Infections Research Articles

Bronchiectasis in a patient with Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy: a case report

BackgroundThe rare monogenic syndrome Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) leads to multisystemic autoimmunity with possible lung involvement. Autoimmune pneumonitis is a rare manifestation, with bronchiectasis being the most frequent radiologic pattern, and may lead to fatal outcome. The Sardinian population in Italy has a high incidence of APECED, although no case of lung manifestation has been reported yet in this cohort. This is the case of a Sardinian APECED patient referred to a bronchiectasis clinic. Our aim is to raise awareness and screen these patients earlier for pulmonary involvement and to initiate multidisciplinary treatment for better outcome.Case presentationA 49-year-old female native of Sardinia from consanguineous parents was diagnosed with APECED in childhood and was referred to our bronchiectasis clinic in March 2023. In addition to typical APECED features, she reported recurrent respiratory infections since childhood, chronic purulent sputum and a hospitalization for pneumonia. She came to our attention with a recent isolation of P. aeruginosa on sputum culture and diffuse cylindrical and varicoid bronchiectasis on her first CT scan. She underwent aetiologic screening for bronchiectasis with no evidence of another cause of disease. Lung treatment was optimized according to bronchiectasis guidelines, and during follow-up the patient developed methicillin-resistant Staphylococcus aureus (MRSA) infection and M. intracellulare pulmonary disease. The patient was offered P. aeruginosa eradication treatment with intravenous antibiotics and initiation of antimycobacterial therapy.ConclusionThis is the first documented lung involvement case of APECED in a Sardinian patient, and the first patient reported to enter a bronchiectasis program. The patient was prescribed lung imaging late in time when bronchiectasis complications were already present. Our case report highlights the need for early pulmonary screening and multidisciplinary management in patients with APECED.

Risk factors of obstructive sleep apnea syndrome in the developmental age

Background: Obstructive Sleep Apnea Syndrome (OSAS) is a prevalent respiratory sleep disorder in children, associated with severe health consequences, including hypertension, cardiac dysfunction, and neurocognitive impairment. Despite extensive research on OSAS in adults, the risk factors for pediatric OSAS remain underexplored. Objective: This literature review aims to identify and present the key risk factors associated with pediatric OSAS based on contemporary studies. Methods: A systematic search of the PubMed and Scopus databases was conducted for literature published between 2016 and 2024. Search terms included “obstructive sleep apnea,” “children,” and “risk factors.” A total of 93 relevant studies were reviewed after excluding non-pediatric and irrelevant papers from an initial pool of 283. Results: The most commonly identified risk factors for pediatric OSAS include adenoid and tonsillar hypertrophy, obesity, craniofacial abnormalities, and asthma. Additional risk factors such as allergic rhinitis, recurrent upper respiratory infections, nasal stenosis, congenital diseases, low vitamin D levels, and preterm birth were also noted. Conclusion: Pediatric OSAS is influenced by multiple factors, including anatomical, physiological, and genetic components. Further research is required to explore emerging risk factors, such as role of vitamin D deficiency and microbiota, and to clarify the impact of variables like ethnicity and breastfeeding.

Cohen syndrome: Can early-onset recurrent infections and hypotonia provide early diagnosis and intervention for intellectual disability?

Cohen syndrome is a rare disease associated with neurodevelopmental disorders, especially intellectual disability (ID), neutropenia and recurrent infections are consistently reported in cases. Neutropenia is an important part of the syndrome, as well as ID. Homozygous variants in the VPS13B gene, located on chromosome 8q22 and containing 62 exons, have been found to cause Cohen syndrome. Cohen syndrome is commonly diagnosed when dysmorphological findings and developmental delay become more apparent. However, the identification of some findings with increasing age has caused the diagnosis of Cohen syndrome to be delayed. Cases diagnosed with ID were evaluated using whole-exome sequencing/clinical exome sequencing method. Family segregation analysis was performed using Sanger sequencing. We presented the clinical and genetic findings of three cases diagnosed with Cohen syndrome and their parents in detail. In this study, we presented the occurrence of symptoms in different age groups, and the prognosis of three cases carrying the VPS13B gene variants, including three different variant types: missense, frameshift and nonsense. Although our cases had different variant types, they shared important similarities on the onset period and prognosis of the symptoms. All cases presented hypotonia, difficulties in swallowing, recurrent respiratory tract infections, neutropenia, delay in motor development, ID and hyperactivity. Our cases did not have a diagnosis of autism spectrum disorder. All cases had increased willingness to engage in social communication. We emphasize the importance of early-onset recurrent infections and hypotonia for early diagnosis and preventive genetic counselling in Cohen syndrome.

Clinical features and genetic analysis of child with Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 due to variant of DNA2 gene

To explore the genetic etiology for a child with Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 (PEOA6). A child who had attended the Women and Children's Hospital Affiliated to Ningbo University on 7 August, 2023 was selected as the study subject. Clinical data of the child were analyzed retrospectively. The child and her parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Women and Children's Hospital Affiliated to Ningbo University (Ethics No. EC2020-048). The child, a 7-year-old female, had presented with limb muscle pain, amyosthenia, significantly increased creatine kinase, congenital diaphragmatic hernia and recurrent respiratory tract infections. WES revealed that the she has harbored a heterozygous c.1590G>C (p.L530F) variant of the DNA2 gene, which was verified to have a de novo origin by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1590G>C was rated as a likely pathogenic variant (PS2+PM2_Supporting+PP3). The c.1590G>C (p.L530F) variant of the DNA2 gene probably underlay the PEOA6 in this child.

“She mimicked the manipulations on my hand”: fostering embodied care among children with recurrent acute respiratory tract infections in Southern China

IntroductionWhen young children experience recurrent respiratory infections, caregivers face the challenge of preventing new episodes whilst maintaining close rapport with their children. Pediatric massage, such as pediatric Tuina, entails soft massage of the skin, administered by trained providers. This non-pharmaceutical measure is used to prevent new respiratory infections in China. The aim of this study is to deepen our understanding of caregivers’ experiences and perceptions of providing pediatric Tuina treatment to their children with recurrent respiratory tract infections.MethodsA qualitative study, based on semi-structured interviews, was conducted in accordance with the Consolidated Criteria for Reporting Qualitative Research checklist. Sixteen mothers from Southern China, whose children had received pediatric Tuina for recurrent respiratory tract infections, participated online. Analysis was conducted according to the principles of reflexive thematic analysis, using the NVivo qualitative research software.ResultsThe overarching theme was “Fostering embodied care with children”. Caregivers assessed pediatric Tuina by hearing others’ experiences of pediatric Tuina, as well as observing the manipulations on their child’s body and their bodily reactions during pediatric Tuina sessions. Caregivers also closely observed children’s bodily changes after pediatric Tuina sessions. Embodied attachment between children and adults was nurtured through the pediatric Tuina. Compared to other treatments or medical consultations, children were more relaxed and more involved in embodied care, which involved direct skin touching and verbal communication from the pediatric Tuina provider. Children also took the initiative to bring pediatric Tuina into their family life, by asking caregivers to perform it on them and mimicking the manipulations on the caregivers’ hand.ConclusionsPediatric Tuina served as a means of interaction between children and adults, fostering an embodied care on both a physical and emotional level. Beyond its potentially preventive effect on recurrent respiratory tract infections, pediatric Tuina could be a support for parents of children with recurrent or chronic disease at home.

Salivary polyreactive antibodies and Haemophilus influenzae are associated with respiratory infection severity in young children with recurrent respiratory infections.

Recurrent respiratory tract infections (rRTIs) are a common reason for immunodiagnostic testing in children, which relies on serum antibody level measurements. However, because RTIs predominantly affect the respiratory mucosa, serum antibodies may inaccurately reflect local immune defences. We investigated antibody responses in saliva and their interplay with the respiratory microbiota in relation to RTI severity and burden in young children with rRTIs. We conducted a prospective cohort study including 100 children aged <10 years with rRTIs, their family members and healthy healthcare professionals. Total and polyreactive antibody concentrations were determined in serum and saliva (ELISA); respiratory microbiota composition (16S rRNA sequencing) and respiratory viruses (quantitative PCR) were characterised in nasopharyngeal swabs. Proteomic analysis (Olink) was performed on saliva and serum samples. RTI symptoms were monitored with a daily mobile phone application and assessed using latent class analysis and negative binomial mixed models. Serum antibody levels were not associated with RTI severity. Strikingly, 28% of salivary antibodies and only 2% of serum antibodies displayed polyreactivity (p<0.001). Salivary polyreactive IgA was negatively associated with recurrent lower RTIs (adjusted OR 0.80, 95% CI 0.67-0.94) and detection of multiple respiratory viruses (adjusted OR 0.76, 95% CI 0.61-0.96). Haemophilus influenzae abundance was positively associated with RTI symptom burden (regression coefficient 0.05, 95% CI 0.02-0.08). These results highlight the importance of mucosal immunity in RTI severity and burden, and suggest that the level of salivary polyreactive IgA and H. influenzae abundance may serve as indicators of infection severity and burden in young children with rRTIs.

Traditional Chinese Medicine in the treatment of recurrent respiratory tract infections in children: an overview of systematic reviews and Meta-analyses.

To evaluate and summarise the evidence from published Meta-analyses/systematic reviews (MAs/SRs) of Traditional Chinese Medicine (TCM) in the treatment of recurrent respiratory tract infections (RRTIs) and to provide a scientific basis for the clinical treatment of RRTIs with TCM. Studies were retrieved from Chinese and English databases including the China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database, SinoMed, PubMed, Web of Science, the Cochrane Library and EMbase from their establishment date to March 2023. Involved studies were screened, extracted, and evaluated for quality by two researchers independently. The a measurement tool to assess systematic reviews (AMSTAR) 2 scale was used for methodological quality evaluation, as well as the preferred reporting items for systematic reviews and Meta-analyses (PRISMA) 2020 statement for report quality evaluation, the risk of bias in systematic reviews (ROBIS) tool for risk of bias, and the grading of recommendations, assessment, development and evaluation (GRADE) quality assessment tool for evidence quality. Twenty MAs/SRs studies were included, including analyses of 274 original studies involving 38 335 patients with RRTIs. The AMSTAR 2 scale evaluation results showed that 19 studies were of very low quality and one of moderate quality. The ROBIS evaluation results showed that 11 MAs/SRs were at high risk and nine at low risk of bias. The PRISMA 2020 report quality showed the included studies had scores between 23.5 and 35.5, among them one with high quality, 17 with moderate quality and two with low quality. The GRADE system results showed that among 126 outcome indicators, only 17 had moderate quality of evidence, 27 had low quality, 82 had very low quality, and none had high quality. The MAs/SRs methodological quality of using TCM for treatment RRTIs is generally poor, the quality of reports as well as of evidence is generally low, and the risk of bias is high; therefore we should treat these results with caution.

Oral Bacterial Lysate OM-85: Advances in Pharmacology and Therapeutics.

Bacterial lysates are known for having immunomodulatory properties and have been used mainly for the prevention and treatment of respiratory tract infections (RTIs). However, rigorous studies are needed to confirm the clinical efficacy of bacterial lysates with various bacterial antigen components, preparation methods, administration routes and course of treatment. OM-85, an oral standardized lysate prepared by alkaline lysis of 21 strains from 8 species of common respiratory tract pathogens, is indicated as immunotherapy for prevention of recurrent RTIs and acute infectious exacerbations of chronic bronchitis. OM-85 acts on multiple innate and adaptive immune targets and can restore type 1helper T (Th1)/Th2 balance. Sporadic studies have shown advances in pharmacology and therapeutics of OM-85, and thus an update review is necessary. Literature was retrieved by searching PubMed, Web of science, Embase, CNKI, and Full Text Database of Chinese Medical Journals. New roles of OM-85 were discovered in prevention and treatment of lung cancer, pulmonary tuberculosis, SARS-CoV-2 infection, allergic rhinitis, pulmonary fibrosis, atopic dermatitis, and nephrotic syndrome. Pharmacoeconomic values of OM-85 were demonstrated in prophylaxis and treatment of RTIs, chronic obstructive pulmonary disease, asthma, chronic bronchitis, rhinosinusitis and allergic rhinitis. Two consecutive courses of OM-85 (6 or 12 months apart) could prevent recurrent RTIs in children. Maternal OM-85 treatment could offer benefits for offspring. Product-specific response was observed. The efficacy of OM-85 may be associated with patient's characteristics (eg, severity of the disease, age, immune response pattern, malignancy risk stratification). OM-85 can improve effectiveness of standard care for some primary diseases, and carry significant pharmacoeconomic implications. The benefits shown by OM-85 in vitro and in vivo, when extrapolated to humans, are exciting but also require caution. Individualized treatment may need to be considered. It is necessary to compare the efficacy and safety of various bacterial lysate preparations.

Impact of SARS-CoV-2 viral load on restrictive spirometry patterns in mild COVID-19 recovered middle-aged individuals: a six-month prospective study

BackgroundLong term respiratory complications of Corona Virus Disease-2019 (COVID-19) are of great concern. Many studies have reported altered respiratory patterns in COVID-19 recovered individuals and most of them were from severe to critically ill patients. The association of viral load at the time of infection with symptoms of long COVID-19 specifically on pulmonary functions after months of recovery is still not known. This study was aimed to assess the impact of SARS-CoV-2 viral load during mild-moderate COVID-19 disease on pulmonary functions in middle-aged population after 6–8 months of acute infection.MethodsThis study included 300 (102 healthy controls and 198 COVID-19 recovered) individuals between age 30–60 of either gender. Mild-moderate COVID-19 recovered individuals were recruited between a period of 6–8 months post-acute infection. Spirometry was performed with MIR-Spirolab-III. The association of spirometry pattern was compared with SARS-CoV-2 viral loads during acute infection.ResultsWe observed up to 70% of the participants presented with either shortness of breath (11.5%), body aches (23.5%), recurrent cough (4.4%), recurrent respiratory infections (9.5%) and/or fatigue (33.3%) at follow up. In our study, 35.5% of COVID-19 recovered individuals had abnormal respiratory patterns (33.5% had restrictive and 2% had obstructive patterns). Viral load ≤ 20 CT value was associated with restrictive respiratory patterns (p = 0.004). No association was found between viral load and disease severity (p = 0.23).ConclusionIn this study, we found one third of mild-moderate COVID-19 recovered individuals have restrictive respiratory patterns after 6–8 months of recovery. These findings had a strong association with SARS-CoV-2 viral loads during acute infection which has been reported for the first time in our study. Studying the relationship between viral load and pulmonary functions can contribute to identifying potential risk factors for long COVID and developing preventive measures to mitigate the long-term impact on lung health.Clinical trial numberNot applicable.

The interplay of immunity and growth: A case of combined variable immunodeficiency and growth hormone deficiency

Introduction: Common Variable Immunodeficiency (CVID) is one of the more common immunodeficiencies seen in clinical practice with a complex disease pathology; while Growth Hormone Deficiency (GHD) is a disorder characterized by complete or relative absence of the human Growth Hormone. Case Presentation: This case report presents a 13-year-old female patient with a long history of recurrent respiratory tract and ear infections along with a notable failure to hit her developmental milestones early in the second decade of her life. The diagnosis was based on a thorough investigation of serum immunoglobulins for CVID and a GH stimulation test for GHD. For these, the patient was placed on a tailored regimen of IVIGs, somatropin therapy and antibiotics for the recurrent infections. Case Discussion: CVID patients characteristically present with recurrent respiratory and ear infections, showing a marked decrease in immunity. Often diagnosed in childhood, GHD typically presents as growth failure along with developmental delays in dentition. There has been a notable rise in the coexistence of immunodeficiency syndromes and endocrinopathies studied in the past few decades. The case highlights and discusses the complex underlying pathology at play that links the two conditions to each other, while also excluding the various differentials. Conclusion: The report highlights the various challenges faced by both clinicians and patients when dealing with dual health conditions that may have a relatively non-specific presentation. Some of which include the diagnostic difficulties, financial strains on the patient leading to poor follow-up, and in the long-term, the development of various complications. This emphasizes the importance of early disease diagnosis and strict management protocols for the said disease, for the overall betterment of the patient’s quality of life.

Lung Recruitment Before Surfactant Administration in Extremely Preterm Neonates

A multicenter randomized clinical trial (RCT) showed a lung recruitment maneuver using high-frequency oscillatory ventilation just before surfactant administration (ie, intubate-recruit-surfactant-extubate [IN-REC-SUR-E]) improved the efficacy of treatment compared with the standard intubate-surfactant-extubate (IN-SUR-E) technique without increasing the risk of adverse neonatal outcomes. To examine follow-up outcomes at corrected postnatal age (cPNA) 2 years of preterm infants previously enrolled in an RCT and treated with IN-REC-SUR-E or IN-SUR-E in 35 tertiary neonatal intensive care units. This was a follow-up study of infants recruited into the primary RCT from 2015 to 2018 at 35 tertiary neonatal intensive care units (NICUs) in Italy. Follow-up examinations included neurodevelopmental, growth, and respiratory outcomes of these children at cPNA 2 years. Participants included spontaneously breathing extremely preterm neonates (24 0/7 to 27 6/7 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 hours of life. Data were analyzed from April 2023 to January 2024. Infants were randomly assigned (1:1) to IN-REC-SUR-E or IN-SUR-E and then followed up. The primary outcome was the occurrence of death after discharge or major disability at cPNA 2 years. Secondary outcomes were neurodevelopmental outcomes (major disability, cerebral palsy, cognitive impairment, visual deficit, or auditory deficit), anthropometric measurements (weight, length, and head circumference), and recurrent respiratory infections and hospitalizations because of respiratory causes at 2y cPNA. A total of 137 extremely preterm infants (median [IQR] gestational age, 26.5 [25.3-27.5] weeks and 75 [54.7%] female), initially enrolled in the original RCT, were followed up at cPNA 2 years, including 64 infants in the IN-SUR-E group and 73 infants in the IN-REC-SUR-E group. There were no significant differences in the occurrence of death after discharge or major disability at cPNA 2 years (IN-SUR-E: 13 children [20.3%] vs IN-REC-SUR-E: 10 children [13.7%]; P = .36). There were no significant differences in incidence of disability, cerebral palsy, or cognitive impairment in the IN-REC-SUR-E group compared with the IN-SUR-E group. There were no significant differences in anthropometric measurements (weight, length, and head circumference) between groups. There were no significant differences in the incidence of recurrent respiratory infections or in hospitalizations because of respiratory causes between groups. In this RCT of lung recruitment before surfactant vs standard care there were no significant differences between the 2 groups in death, neurodevelopmental outcomes, anthropometric measurements, or recurrent respiratory infections at the 2-year follow-up. These findings can aid clinicians in decision-making for the best strategy to administer surfactant, considering long-term outcomes.

Pidotimod – Current Role and Evidence

ABSTRACT Recurrent respiratory infections (RRIs) are common in the pediatric age group and in patients with chronic respiratory disorders, leading to frequent hospitalization and poorer quality of life. Studies have shown that an immature immune system in childhood can predispose to RRIs, leading to adult life. Immunomodulators are drugs which modulate the immune system of the host to increase resistance against various infections. They interact with specific receptors and cellular components of innate and adaptive response to modulate the immune response. Pidotimod (PDT) is one such immunomodulator which has shown emerging evidence in the past 2 decades, to reduce the recurrence of lower respiratory tract infections and help in faster recovery from the same. This review highlights the evidence behind the potential role of PDT in the prevention and management of RRIs.

Primary ciliary dyskinesia: a case report of double DNAH11 mutant alleles

Primary ciliary dyskinesia (PCD), a rare disorder, is genetically varied. Mutations in proteins involved in the structure, function, or assembly of cilia are known to determine situs inversus, male infertility, and chronic destructive airway disease. PCD is inherited by an autosomal recessive pattern of inheritance in most cases. Nonetheless, patterns of autosomal dominant and X-linked inheritance have been mentioned. A history of recurrent upper and lower respiratory tract infections raised clinical suspicion of primary ciliary dyskinesia in a 10-year-old patient. Genetic tests were performed using next-generation sequencing technology (Illumina NextGen) with the multiplex ligation-dependent probe amplification technique for primary ciliopathies and syndromes subject to differential diagnosis. Genetic testing identified two pathogenic variants, not previously associated with a case report in the literature, c.7727A&gt;G (p.Asp2576Gly) and c.8578G&gt;A (p.Gly2860Ser), within the DNAH11 gene, which is associated with autosomal recessive PCD. The result also reported mutations in other genes involved in autosomal recessive PCD (DNAH8, DNAH9 and ZMYND10), which were classified as variants with uncertain clinical significance. Transmission electron microscopy of respiratory cilia and nasal nitric oxide measurement cannot be used to diagnose PCD in patients with DNAH11 mutations because the structure of cilia is normal, and the levels of NO are not constantly low. High-speed video microscopy analysis can be helpful because DNAH11 mutations cause a distinct phenotype of PCD. Nevertheless, the mutation analysis of various PCD-causing genes remains the easiest to conduct and with good results. Genetic research on PCD has identified a number of significant ciliary genes in recent years, offering fresh perspectives on the molecular processes underlying cilia assembly and function. This facilitates the development of new methods for the diagnosis, prevention, and treatment of PCD. However, because it is a highly complex and heterogeneous disease, the field of gene diagnosis and therapy in PCD is still in its infancy.

A new multicomponent nasal spray for managing children with recurrent upper respiratory infections.

A new multicomponent nasal spray for managing children with recurrent upper respiratory infections.

Clinical phenotype and genetic analysis of a rare case with 6p duplication and terminal deletion syndrome

To explore the genetic basis for a child with developmental delay and intellectual deficit (DD/ID). A child who was admitted to the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City on June 3, 2023 due to DD/ID, craniofacial malformations, and recurrent infections of upper respiratory tract was selected as the study subject. G-banded chromosomal karyotyping was carried out for the child and her parents. Low-depth genome-wide copy number variation sequencing (CNV-seq) and chromosomal microarray analysis (CMA) were used to screen for genome-wide copy number variations (CNV), and fluorescence in situ hybridization (FISH) was used to verify the origin of candidate CNV. The child, an 8-year-old girl, had featured unexplained growth and intellectual development delay, multiple craniofacial malformations, and recurrent infections of the upper respiratory tract. She was found to have a karyotype of 46,XX,der(6)add(6)(q23), while both of her parents were normal. Both CNV-seq and CMA showed that the child has harbored a 21.38 Mb interstitial duplication at 6p25.3p22.3 and a 0.78 Mb terminal deletion at 6p25. FISH verified that both the duplication and deletion had occurred de novo. The abnormal phenotype of the child may be attributed to the 6p duplication and terminal deletion.

Unilateral hyperlucent lung: Swyer James Macleod Syndrome

Swyer James Macleod Syndrome, also known as unilateral hyperlucent lung syndrome, is a rare lung condition characterized by the underdevelopment of one lung. This syndrome typically occurs in childhood and is often discovered incidentally during imaging studies for unrelated conditions.Individuals with Swyer James Macleod Syndrome may experience symptoms such as recurrent respiratory infections, shortness of breath, and decreased exercise tolerance. Diagnosis is typically made through imaging studies such as chest X-rays,computed tomography or ventilation-perfusion scans.

Parental smoking and respiratory outcomes in young childhood cancer survivors.

Passive exposure to cigarette smoke has negative effects on respiratory health. Childhood cancer survivors (CCS) are at increased risk for respiratory disease due to treatment regimens that may harm the respiratory system. The objective of this study was to assess the prevalence of parental smoking among CCS and investigate its association with respiratory outcomes. As part of the Swiss Childhood Cancer Survivor Study, between 2007 and 2022, we sent questionnaires to parents of children aged ≤16 years who had survived ≥5 years after a cancer diagnosis. Parents reported on their children's respiratory outcomes including recurrent upper respiratory tract infections (otitis media and sinusitis), asthma, and lower respiratory symptoms (chronic cough persisting>3 months, current and exercise wheeze), and on parental smoking. We used multivariable logistic regression to investigate associations between parental smoking and respiratory outcomes. Our study included 1037 CCS (response rate 66%). Median age at study was 12 years (interquartile range 10-14 years). Eighteen percent of mothers and 23% of fathers reported current smoking. CCS exposed to smoking mothers were more likely to have recurrent upper respiratory tract infections (OR 2.1; 95%CI 1.1-3.7) and lower respiratory symptoms (OR 2.0; 95%CI 1.1-3.7). We found no association with paternal smoking. A substantial proportion of CCS in Switzerland have parents who smoke. Exposure to maternal smoking was associated with higher prevalence of upper and lower respiratory problems. Healthcare providers can support families by addressing caregiver smoking behaviors and providing referrals to smoking cessation programs.

Mexican Delphi Consensus For Use Immunotherapy With MV130 Vaccine In Patients With Recurrent Respiratory Infectious Diseases (Expert Panel)

Background and objectives: recurrent respiratory infections are currently a public health problem due to their high costs and resistance to treatments as well increase morbidity and mortality. An imbalance in the homeostasis of progressive cellular and humoral immunity the application of immunotherapy with trained immunity vaccines (ivie) is currently a therapeutic option in all patients with recurrent respiratory infections by training innate and adaptive immunity by reducing episodes of respiratory exacerbations and improving the quality of life of patients. Methods: using delphi method and a panel of experts, a questionnaire was developed that included questions regarding the benefit and non-benefit of the treatment of patients with persistence of recurrent respiratory infections by specific criteria, from diagnosis, identification of risk factors and comorbidities, ideal candidate by consensus to receive the therapy, follow-up, and presentation of clinical data for reduction of recurrence of the conditions. There was a consensus on determining the use of immunotherapy mv130 vaccine in patients with specific criteria as long- and short-term use. Conclusion: immunotherapy with trained immunity vaccines (ivie) is currently a therapeutic option in all patients with recurrent respiratory infections and associated comorbidities in patients with chronic respiratory illnesses, autoimmune diseases, hematological malignancies for improvement clinical infections and improvement quality of life.

A single center experience on PI3K/AKT/MTOR signaling defects: Towards pathogenicity assessment for four novel defects.

Phosphoinositide 3 kinases (PI3K) are lipid kinases expressed in lymphocytes/myeloid cells. PI3K/AKT/mTOR signaling defects present with recurrent infections, autoimmunity, lymphoproliferation, and agammaglobulinemia. To characterize the PI3K/AKT/mTOR pathway defects and perform pathway analyses to assess novel variant pathogenicity. We included 12 patients (heterozygous PIK3CD (n = 9) and PIK3R1 (n = 1) (activated PI3K delta syndrome (APDS) with gain-of-function mutations) and homozygous PIK3R1 variant (n = 2)), performed clinical/laboratory/genetic evaluation, and flow cytometric PI3K/AKT/mTOR pathway analyses. Median age at onset of complaints was 17.5 months (3 months to 12 years) and at diagnosis was 15.7 years (2.5-37) in APDS. Median diagnostic delay was 12.9 years (1.6-27). Recurrent respiratory tract infections (90%), lymphoproliferation (70%), autoimmune/inflammatory findings (60%), and allergy (40%) were common in APDS. Recurrent viral infections were present in 4/10 and malignancy (non-Hodgkin lymphoma and testicular yolk sac tumor) was present in 2/10 in APDS. Low CD4+ T cells(5/8) with increased CD4+ effector memory (8/8) and CD4+ TEMRA cells (6/8) were present in the given number of APDS patients. We diagnosed tubulointerstitial nephritis, Langerhans cell histiocytosis, and late-onset congenital adrenal hyperplasia in APDS. Allergic findings, lymphoproliferation/malignancy, and high IgM were present in the APDS but not in PIK3R1 deficiency. Low IgM/IgG/CD19+ B cell counts were characteristic in patients with PIK3R1 homozygous loss-of function mutations. Differential diagnosis with combined immunodeficiency and diseases of immune dysregulation make molecular genetic analysis crucial for diagnosing mTOR pathway defects. It is easy to differentiate APDS and homozygous PIK3R1 defects with specific laboratory features. Additionally, mTOR pathway functional analysis is a definitive diagnostic and pathogenicity assessment tool for novel APDS mutations.

427. THE ROLE OF CROSS-SECTIONAL IMAGING IN PATIENTS WITH PULMONARY MICRO ASPIRATION

Abstract Background There is increasing evidence of a strong relationship between pulmonary microaspiration of refluxate and pulmonary diseases such as bronchiectasis and lung fibrosis. This group has demonstrated the presence of co-location of pulmonary aspiration on modified reflux scintigraphy with lobar parenchymal lung changes on high resolution computed tomographic imaging of the lung (HRCT-L) in patients with typical and atypical reflux symptoms. There is, however, a cohort of patients who demonstrate evidence of reflux aspiration without evidence of parenchymal changes on HRCT-L. This study aims to demonstrate a group of patients with confirmed reflux micro-aspiration without corresponding changes in lung parenchyma on HRCT. Methods Data were obtained from a prospectively populated database of patients with treatment resistant typical and atypical GORD and suspected reflux pulmonary microaspiration. 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. Patients who underwent microaspiration studies and had normal HRCT-L for chest symptoms were included. The group was compared to patients with lung changes on HRCT-L corresponding with micro-aspiration studies. Results Inclusion criteria were met by 14 patients (86% female, 14% male). The mean age was 54 years (range: 36 – 81 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 on HRCT-L corresponding to site of reflux micro-aspiration on scitigraphy were demonstrated in 66 out of 80 patients listed in the database. Amongst patients with normal HRCT-L typical reflux symptoms were reported in 1 patient, atypical symptoms in 6 patients, both in 5 patients and 2 did not report symptoms. Most common presenting symptom was cough. There was no difference in symptomatology of patients with or without HRCT-L pulmonary parenchymal changes. Patients with pulmonary changes on HRCT were on average 13 years older than patients without CT changes (mean age 67, range 31-91). Conclusion HRCT-L is an important additional investigation in patient with reflux micro-aspiration detected on scintigraphy to identify patients with reflux related lung parenchymal changes. Younger age of patients with normal HRCT-L suggests that parenchymal changes may be developing as a result of prolonged exposure to reflux micro-aspiration over time.