History Of Recurrent Respiratory Infections Research Articles

Congenital bilio-bronchial fistula in an adult: a review of literature and video demonstration of laparoscopic fistula tract excision.

This article presents a review of the literature on congenital bilio-bronchial fistula (BBF), a rare anomaly characterized by abnormal communication between the bile duct and respiratory tract. Congenital BBF often presents with bilioptysis in early neonates and infants; however, patients with no overt symptoms may occasionally present in adulthood. Our literature search in Medline from 1850 to 2023 revealed 42 reported cases of congenital BBF, primarily managed with thoracotomy and excision of the fistula tract. About one-third of these cases required multiple surgeries due to associated biliary anomalies. The review underscores the importance of diagnostic imaging, including bronchoscopy, in identifying and delineating the extent of the fistula. It also highlights the evolving surgical management, with recent cases showing the efficacy of minimally invasive approaches such as laparoscopy and thoracoscopy. In addition to the literature review, we report a young female patient with a history of recurrent respiratory infections presenting with bilioptysis and extensive left lung damage. Initial management included bronchoscopy-guided glue instillation, left thoracotomy, and pneumonectomy. Following the recurrence of symptoms, the patient was successfully treated with laparoscopic excision of the fistula tract. In recent times, minimally invasive approaches such as laparoscopy and thoracoscopy, with excision of the fistula tract are gaining popularity and have shown good results. We suggest biliary communication being the high-pressure end, tackling it transabdominal may prevent recurrent problems.

IMDDHH: A Contribution to the Understanding of the Disease

Inborn Errors of Immunity (IEI) is an extremely rare group of heterogenous disorders which are characterized by predisposition to severe unusual and recurrent infections, severe allergies, features suggestive of autoimmune conditions and sometimes malignancies. We report a two-year-old female child presented to our emergency department with complaints of a history of recurrent respiratory infections, recurrent skin infections and a recent history of purulent discharge from both ears. Clinical examination revealed acute otitis media, pneumonia, multiple healed skin lesions associated with soft non-tender hepatomegaly and normal cardiac findings. Elevated hepatic transaminases and hypogammaglobulinemia suggested the possibility of an inborn error of immunity. A whole exome sequencing study performed on the patient established a diagnosis of IMDDHH (Immunodeficiency, Developmental Delay, and Hypohomosyteinemia) by revealing a missense mutation in the NFE2L2 gene of chromosome 2q31. Diagnosing such conditions with inborn errors of immunity requires a high index of suspicion combined with a comprehensive knowledge of the structure and function of both innate and adaptive immune systems. Recurrent skin and respiratory infections in a growing child belonging to a low-and-middle-income country like India is a common clinical scenario encountered frequently in pediatric clinic practice and is often ignored after attributing it to poor hygienic conditions. However, with careful history taking and examination, a sub-group of such patients may be isolated with a high probability of an underlying IEI, which can later be confirmed by genetic work-up.

A rare pediatric neurometabolic disorder: Leigh syndrome

Subacute necrotizing encephalomyelopathy called Leigh Disease is a rare inherited pediatric neurological disorder generally involving infants. The condition primarily involves the central nervous system and the most involved structures are basal ganglia, thalamus, and brainstem. In this disorder, there is a progressive loss of mental and movement abilities associated with abnormal muscle tones, weakness, visual loss, respiratory failure, and strikingly, we got raised lactate levels in the blood, cerebral spinal fluid, and other body fluids. The prognosis of this condition is bad as there is no effective treatment and finally, the patient succumbs to death mostly due to respiratory failure. Here, we present a case of Leigh disease in an 8-month-old boy having chief complaints of delayed motor (weakness), and cognitive development with a previous history of recurrent respiratory infection. Upon recent radiological imaging, gross neurological abnormalities were seen which suggested the possibility of Leigh disease which was further confirmed by raised body fluid lactate levels.

The use of antibacterial drugs in the treatment of coronavirus infection in children in real outpatient clinic practice

Introduction. In light of the available data on the unjustified use of antibiotics in children with acute respiratory viral infections, the frequency of prescribing antibacterial drugs to children with a new coronavirus infection in real clinical practice is of great practical and scientific interest.The aim of the study was to study the frequency of antibiotic therapy and identify factors that increase the risk of needing antibiotics in children with coronavirus infection at the outpatient stage.Materials and methods. A retrospective cross-sectional study was conducted on the basis of children's polyclinics in Samara from November 2021 to July 2022, which included a survey of parents and an analysis of outpatient records of 100 children who were under outpatient observation and treatment for COVID-19. An analysis was made of the frequency of prescribing antibiotics to them and potential factors predisposing to their prescribing to children with COVID-19. The obtained data were subjected to statistical processing using the IBM SPSS Statistics 25 program and a comparative analysis.Results. The frequency of use of antibiotic therapy according to the results of the study was 11 % and did not exceed the Russian average data (14.3 %). When analyzing the factors influencing the doctor's decision to prescribe an antibiotic to a child with coronavirus infection, the most important were a history of recurrent respiratory infections (children from the FIC group), as well as the presence of concomitant diseases and background conditions in children, primarily chronic bronchopulmonary diseases. and nervous system.Discussion. The prescription of antibiotics for children with a new coronavirus infection at the outpatient stage remains empirical due to the limitations of the use of laboratory and instrumental methods for additional examination of the child, which objectifies the likelihood of a secondary bacterial infection. Despite this, the frequency of antibiotic use according to the results of the study was 11 % and did not exceed the Russian average data (14.3 %), as well as the average frequency of antibiotic use for acute respiratory viral infections in children in the Russian Federation (21.5-23.3 %).

Hemoptysis: unilateral pulmonary artery atresia? a case report

BackgroundAsymptomatic, isolated cases of unilateral pulmonary artery atresia may present in adulthood with symptoms such as recurrent respiratory infections, dyspnea, hemoptysis, and pulmonary hypertension. Unlike previously reported patients that underwent surgical management for this pathology, the patient in this report had no chronic history of recurrent respiratory infections, dyspnea, or pulmonary hypertension, making a diagnosis prior to extensive imaging difficult.Case presentationA 55-year-old male presented to our emergency department (ED) with a 3-day history of recurrent cough with 2–3 tablespoons of hemoptysis per episode, chills, and occasional wheezing. A computed tomography angiography (CTA) was performed, which identified a congenital absence of the left pulmonary artery and a right-sided aortic arch. Hypertrophied left intercostal and bronchial arteries were noted to be perfusing the left lung. V/Q scan confirmed a heterogeneous distribution of gas throughout both lung fields with 97% perfusion to the right lung, but no visualization of the left lung on the perfusion images. Given extensive collateral blood supply to the left lung, interventional radiology performed a GELFOAM® embolization of the hypertrophied left bronchial artery and two parasitized arteries from the left subclavian artery to minimize intra-operative blood loss. This was immediately followed by a left thoracotomy, pneumonectomy, intercostal muscle flap placement, and bronchoscopy. The procedure was 360 min long with a total of 1500 cc blood loss that was salvaged and re-infused. No additional blood products were administered. The patient remained intubated post-operatively and was transferred to the surgical intensive care unit. His postoperative course was complicated by troponin leak, rhabdomyolysis, delirium, and ileus, all of which resolved over time. He was discharged home on postoperative day seven and continues to do well one-year later.ConclusionsThe patient in this report presented with several episodes of isolated hemoptysis but unlike previously reported cases of unilateral pulmonary artery atresia, he had no history of recurrent respiratory infections, dyspnea, or pulmonary hypertension. Although unilateral pulmonary artery atresia is a rare diagnosis, in patients with unexplained, isolated hemoptysis, further examination of the vasculature may be warranted, and surgical management may be beneficial in appropriate, symptomatic patients.

STK36 splice site variant in an Australian Shepherd dog with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) represents a group of diseases characterized by impaired movement of cilia and subsequent health problems in diverse organ systems, notably the respiratory tract. Almost 50 candidate genes for PCD are known in humans. In this study, we investigated an Australian Shepherd dog with a history of recurrent respiratory infections and nasal discharge. A transmission electron microscopy investigation led to the diagnosis of PCD with central pair defect, in which the normal 9:2 arrangement of respiratory cilia was altered and reduced to a 9:0 arrangement. Whole genome sequencing data from the affected dog was obtained and searched for variants in PCD candidate genes that were not present in 918 control genomes from different breeds. This revealed a homozygous single base pair exchange at a splice site of STK36, XM_038585732.1:c.2868-1G>A. The mutant allele was absent from 281 additionally genotyped Australian Shepherd dogs. RT-PCR confirmed aberrant splicing in the affected dog with the skipping of exon 20 and the insertion of a cryptic exon, which is predicted to lead to a premature stop codon and truncation of 36% of the STK36 wild-type open reading frame, XP_038441660.1:(p.Met957Profs*11). STK36 variants were previously reported to cause PCD in humans and mice. The knowledge from other species together with the absence of the mutant allele in more than 1000 control dogs suggests STK36:c.2868-1G>A as the most likely candidate variant for PCD in the investigated case.

PROPHYLACTIC USE OF ALLOPATHIC, COMPLEMENTARY & ALTERNATIVE MEDICINE (CAM) FOR COVID-19: A CROSS SECTIONAL SURVEY AMONG MEDICAL POST-GRADUATES OF TERTIARY CARE TEACHING HOSPITALS, GUJARAT

Introduction: COVID-19 infection was declared a global pandemic and public health emergency by WHO. In order to avoid getting infected with the virus, various preventive measures were followed including prophylactic medicine, particularly among health care professional working with patients. The current study aimed to evaluate pattern of prophylactic medicines consumed by post graduate doctors for prevention of COVID-19 infection. Methodology: A prospective cross-sectional study was conducted among the post graduate resident doctors (1st year to 4th year) of various medical specialties working in COVID-19 at various tertiary care teaching hospitals across Gujarat. A questionnaire regarding prophylactic use of medicine was communicated through online tool. Results: Of 311 respondents, mean age was 28±2 years and male to female ratio was 0.94. 8% participants have history of recurrent respiratory infection. Out of 311 participants 233 (74.91%) consumed prophylaxis. Most commonly consumed prophylactic medicine was of allopathy (64%) followed by Complementary & alternative medicine and home remedies (63.02%). Vitamin C (56.27%), Multivitamins (33.11%), Zinc (27%), Azithromycin (21.86%), Hydroxychloroquine (16.72%) were most frequently consumed allopathic medicines. Turmeric (53.06%), Ayurvedic kadha (44.38%), lemon (43.36%) were frequently consumed CAM and home remedies. 20 participants reported Adverse Drug Reactions (ADRs) in which common ADRs nausea (65%) and Diarrhea (50%). 59.16 % participants developed COVID-19 out of 51.63 % participants had COVID-19 after taking prophylaxis. Occurrence of COVID-19 infection among post-Graduate doctors was not signicantly associated with prophylactic use of medicine. Conclusion: Vitamins, zinc, azithromycin and hydroxychloroquine (allopathic medicines) and turmeric and ayurvedic kadha (CAM) were commonly used prophylactic medicines. Occurrence of COVID-19 infection was not signicantly associated with intake of prophylactic medicine

Double Aortic Arch as a Rare Condition in a 10-year-old Boy with Recurrent Pneumonia: A Case Report Study

Introduction: A double aortic arch (DAA) is a congenital anomaly of the aortic arch, which is also the most common type of complete vascular ring. This vascular ring can compress the trachea and esophagus, as well as cause respiratory, gastrointestinal, and cardiac symptoms. Case Presentation: In the present case report, a 10-year-old boy with recurrent cough, fever, shortness of breath, chest pain, and a history of recurrent respiratory infections was examined. According to the results of bronchoscopic evaluation, he was found to have a localized tracheomalacia. DAA and dextrocardia condition were also confirmed for this patient by performing a computed tomography angiography of the thorax and the three-dimensional reconstruction of CT angiography. Conclusions: The diagnosis of double aortic arch may be confused with upper respiratory tract infections or foreign body aspiration. Therefore, it was recommended that a particular attention should be paid to the double aortic arch when evaluating cases of stridor in children with unknown causes or recurrent respiratory infections. CT angiography and cardiac MRI were the diagnostic methods of choice for examining vascular rings.

DILATATION DES BRONCHES REVELANT UN SYNDROME DE KARTAGENER : A PROPOS DUN CAS ET REVUE DE LA LITTERATURE

Primary ciliary dyskinesias (PCD) are rare genetic diseases with autosomal recessive transmission, affecting nearly 1/15000 births, due to a structural/functional defect of cilia. Kartagener syndrome (KS) represents 50% of PCDs and is characterised by the triad of bronchiectasis, chronic sinusitis and situs inversus. It is manifested by clinical signs of upper and lower respiratory infections or infertility. Situs inversus is often discovered incidentally. The diagnosis is confirmed by specialized centers and is based on analysis of ciliary ultrastructure by electron microscopy or ciliary beats by light microscopy/high speed video microscopy , measurement of nasal nitric oxide flow and genetic tests. Treatment is supportive and in line with recommendations for the management of cystic fibrosis or idiopathic adult bronchiectasies. It includes respiratory physiotherapy, antibiotic medication to treat infections, vaccinations and local treatment of the otorhinolaryngeal tract if necessary. We present here the case of a 23-year-old woman with a history of recurrent respiratory infections since her early age, who consulted for cough, chronic bronchorrhea and dyspnea. The evolution to respiratory failure is slowed by the early diagnosis and management of exacerbations.

Menke-Hennekam syndrome 1: A Case Report

IntroductionMenke-Hennekam syndrome (MHS) is a relatively new genetic condition characterized by intellectual disabilities, autistic behavior, auditory defects, recurrent upper respiratory tract infections, microcephaly and short stature. Facial characteristics include short palpebral fissures, telecanthus, depressed nasal bridge, short nose, anteverted nares, short columella, and long philtrum. The genetic defect is represented by missense variants of CREBBP gene, located on exons 30 or 31. There are only around 30 cases reported by now.ObjectivesThe aim of the paper is to report a new case of MHS.MethodsThe case is a 3-year-old boy admitted in our department for developmental delay. The clinical examination revealed dysmorphic features; severe speech delay, mild intellectual disability, autistic behaviour.The patient had a personal history of recurrent respiratory infections, visual defect and bilateral sensorineural hearing loss. Other investigations included EEG, abdominal echography, and cerebral MRI all were normal. The genetic studies included array CGH and WES.ResultsThe array CGH was normal. WES identified a pathogenic heterozygote variant c.5600G>A in the exon 31 of CREBBP gene, confirming MHS.ConclusionsOverall, the features of our patient are consistent with those reported in the previous reports, including developmental and speech delay, autistic behavior, dysmorphic features, recurrent upper way infections, sensorineural hearing loss, and visual defects. Other common features, such as growth delay and microcephaly were not present in our patient. Our case contributes to the clinical characterisation of the new syndrome. Funding: The research leading to these results has received funding from the EEA Grant 2014-2021, under the project contract No 6/2019.DisclosureNo significant relationships.

Diagnostic Errors in Initial Misdiagnosis of Foreign Body Aspiration in Children: A Retrospective Observational Study in a Tertiary Care Hospital in China.

Background: Foreign body aspiration (FBA) in children is a common emergency that can easily be missed, leading to delays in treatment. Few large cohort studies have focused on errors in diagnostic assessment. The main purpose of this study was to analyze factors contributing to the initial misdiagnosis of FBA in children.Methods: We retrospectively reviewed the charts of 226 children diagnosed with FBA at the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from January 2018 to November 2020. Cases were divided into two groups according to whether or not patients were initially misdiagnosed. The clinical characteristics of the two groups were then compared. The Diagnosis Error Evaluation and Research (DEER) taxonomy tool was applied to cases with initial misdiagnosis.Results: Of the 226 included children with a final diagnosis of FBA, 153 (67.7%) were boys. Ninety percent of patients were under 3 years old. More than half (61.9%) of the children were referred from primary institutions, and 38.1% visited tertiary hospitals directly. A total of 80 (35.4%) patients were initially misdiagnosed. More than half of misdiagnosed children received an alternative diagnosis of bronchiolitis (51.3%), the most common alternative diagnosis. Test failures (i.e., errors in test ordering, test performance, and clinician processing) were primarily responsible for the majority of initial diagnostic errors (76.3%), followed by failure or delay in eliciting critical case history information (20.0%). Characteristics significantly associated with initial misdiagnosis were: presentation over 24 h (OR 9.2, 95% CI 4.8–17.5), being referred from primary institutions (OR 8.8, 4.1–19.0), no witnessed aspiration crisis (OR 7.8, 3.0–20.3), (4) atypical signs or symptoms (OR 3.2, 1.8–5.7), foreign body not visible on CT (OR 36.2, 2.1–636.8), foreign body located in secondary bronchi (OR 4.8, 1.3–17.2), organic foreign body (OR 6.2, 1.4–27.2), and history of recurrent respiratory infections (OR 2.7, 1.4–5.3). Children with misdiagnosis tended to have a longer time from symptom onset to the definitive diagnosis of FBA (P < 0.001).Conclusions: More than one-third of children with FBA were missed at first presentation. Errors in diagnostic testing and history taking were the main reasons leading to initial misdiagnosis.

Joubert syndrome: a case report

BackgroundJoubert syndrome (JS) is a rare autosomal recessive genetic heterogeneously inherited disorder characterized by neurological features that include hypotonia, ataxia, developmental delay, intellectual disability, abnormal eye movements, and neonatal breathing dysregulation.Case presentationThe main purposes of the case report are to highlight the benefit of multidisciplinary rehabilitation team approach and describe the clinical features associated with Joubert syndrome. In this case report, we have discussed a 9-month-old girl who presented with developmental delay, impaired vision, and a history of recurrent respiratory infection with respiratory distress. On examination, she had facial dysmorphism, myopia, and hypotonia. Brain magnetic resonance imaging showed a thick, elongated, and abnormally oriented superior cerebellar peduncle showing molar tooth appearance with elongated bat-wing shaped 4th ventricle and hypoplasia of the vermis suggestive of JS. The patient has been treated at Garden Reach Institute for the Rehabilitation and Research (GRIRR), Kolkata, India, by a multidisciplinary team of physiotherapist, speech therapist, special educator, orthotist, medical officer, and social worker that shown excellent improvement in her condition, and she has achieved good sitting balance, able to sit without support, stand with wall support, and able to walk using bilateral AFO and reverse walker.ConclusionKnowledge of characteristic clinical and radiological findings in JS will help in early diagnosis and successful rehabilitation.

A Rare Case of Resistant Pigmentation

Introduction: Familial glucocorticoid deficiency (FGD) is characterised by ACTH resistance & isolated glucocorticoid deficiency, with typical biochemical findings of low serum cortisol & high plasma ACTH. Patients present with hyperpigmentation (due to stimulation of MC1R by POMC products) & hypoglycemia. Clinical presentation includes failure to thrive & susceptibility to infections. Case Report: A 14 year old girl presented to us with generalised hyperpigmentation of the skin and oral mucosa- it started when she was 4 years of age. There was history of recurrent respiratory infections around the same time the hyperpigmentation appeared - the patient required multiple hospitalisations for the same (she was admitted 3 times in 6 months). Her random serum cortisol was measured – it came out to be 8.27nmol/L. Her serum Na+ was 140 mEq/L & K+ was 3.5 mEq/L. She was also diagnosed with subclinical hypothyroidism at that time (TSH- 7.3 mIU/L, anti TPO antibodies positive). There was no history of alacrimia or achalasia. Her 17-OHP was 2.20 nmol/L. A probable diagnosis of autoimmune polyendocrine syndrome was made & oral hydrocortisone (@ 12 mg/m2) & levothyroxine (@25 mcg) was started. The patient was compliant with the treatment, but the mother complained that her hyperpigmentation improved only by 20–30 % despite continued treatment. There was no history of salt wasting crises or hospitalisations after the initiation of treatment. Her serum ACTH values were checked 2 times (2011 & 2015) and were > 2000 pg/ml on both the occasions. The hydrocortisone dose was increased to 20mg/m2 for 1 year in between, without any improvement in hyperpigmentation. Patient presented to us with persistent hyperpigmentation in 2019. She was a product of consanguineous marriage. Non-compliance was ruled out. She had attained menarche at the age of 12 years. There was history of delayed pubarche (started @ age of 13 years) & axillary hair was absent. Again, her serum ACTH was > 2000 pg/ml and electrolytes and BP were normal. In view of normal electrolytes with low cortisol at the time of diagnosis & persistent hyperpigmentation even on supraphysiological doses of hydrocortisone, Familial Glucocorticoid Deficiency was considered. Genetic analysis showed mutation in Thioredoxin Reductase (TXNRD2) Gene. This gene mutation has recently been reported in FGD. (Prasad R et al, JCEM Aug 2014.) Conclusion: In cases of primary adrenal insufficiency with normal electrolytes & resistant hyperpigmentation, familial glucocorticoid deficiency should be thought of. Treatment with standard glucocorticoid therapy should be given. Serum ACTH values should not be chased. The hyperpigmentation may not resolve completely. TXNRD2 deficiency leads to impaired redox homeostasis, highlights the important redox pathway in addition to defective ACTH signaling, giving us new insights in regard to steroidogenesis.

Clinical efficacy of a screening approach to the differentiated prescription of antibiotic therapy in children with acute tonsilopharyngitis

Aim. To assess the effectiveness of the screening approach by prescribing a streptotest to verify the etiological cause of tonsillopharyngitis in children.&#x0D; Methods. We observed 67 patients aged 7 to 11 with a history of recurrent respiratory infections. The incidence of acute respiratory infections varied from 8 to 12 times during the year preceding the examination. The main group consisted of 36 children who had tonsillopharyngitis with severe inflammation of the tonsils and plaque on the tonsils. The control group included 31 patients with acute tonsillopharyngitis with inflammatory changes in the tonsils and the absence of plaque. The observation and control groups were comparable and did not have statistically significant differences in gender and age. All patients underwent a common clinical, laboratory, and instrumental examination. Along with microbial culture, the special examinations included an express test (Dectra Pharm, France) for the presence of group A -hemolytic streptococcus.&#x0D; Results. All children underwent an etiological examination. The presence of a viral antigen was confirmed in 71.64% of children. 27.49% of patients in the control group and 30.72% of patients in the main group had positive results of the express test for group A -hemolytic streptococcus, taking into account the requirements for assessing this reaction. It was revealed a reliable direct relationship between the detected viral infection and the negative results of the streptatest test (r=0.86; p=0.03) for the control group, and a positive correlation of the confirmed presence of group A -hemolytic streptococcus in the main group as with both C-reactive protein (r=0.78; p=0.04) and with inflammatory markers in the general blood test. A combination of positive fluorescence of viral antigens based on the results of immunofluorescence and a positive enzyme-linked immunosorbent assay (ELISA) for group A -hemolytic streptococcus was recorded in 7.46% of all patients. Clinical examples are given the justification of practical implementation of the express test for the quick diagnostic information.&#x0D; Conclusion. Differentiated etiological diagnosis of acute tonsillopharyngitis based on clinical symptoms and the levels of markers of bacterial inflammation is extremely difficult therefore laboratory criteria should be the justification for prescribing antibiotic therapy; currently, the most accessible is the streptatest for the detection of group A -hemolytic streptococcus, which allows confirming or denying the presence of group A -hemolytic streptococcus within a few minutes, which means that it is correct to prescribe antibacterial drugs to patients.

Ligation of patent ductus venosus in a child with pulmonary arterial hypertension and hypersplenism

Introduction:Patent ductus venosus (PDV) is a rare and critical disease, and the majority of patients present with pulmonary arterial hypertension (PAH) or hepatopulmonary syndrome due to congenital portosystemic shunt. We reported that both PAH and hypersplenism were major complications of PDV in this case. This case report can assist the treatment and recovery of the patients with similar symptoms.Patient concerns:A 4-year-old male patient presented to our institution with a history of recurrent respiratory infections accompanied by leukocytopenia, thrombocytopenia and presented with tachypnoea. upon mild exertion.Diagnosis:A wide communication, 10 mm in diameter, between the portal vein and inferior vena cava was identified in the subcostal echocardiogram and computed tomography images. Echocardiography showed an estimated systolic pulmonary artery pressure of 106 mm Hg. Right-sided cardiac catheterization indicated a mean pulmonary arterial pressure of 30 mm Hg and a pulmonary vascular resistance of 3 Wood units. Chest X-ray revealed cardiomegaly with a prominent pulmonary segment.Interventions:The patient was treated with combination pharmacotherapy of bosentan and tadalafil and PDV ligation.Outcomes:A year later, the boy showed normal exercise tolerance and weight gain. Liver and spleen parameters, liver function, blood cells and the general condition of the boy improved.Conclusion:Initial combination therapy of bosentan and tadalafil is safe and effective in children with PAH associated with PDV. When PDV banding test shows normal portal pressure, PDV ligation is considered acceptable in children with PAH and hypersplenism associated with PDV.

Trained Immunity Based-Vaccines as a Prophylactic Strategy in Common Variable Immunodeficiency. A Proof of Concept Study.

Background. A major concern in the care of common variable immunodeficiency (CVID) patients is the persistence of subclinical or recurrent respiratory tract infections (RRTI) despite adequate trough IgG levels, which impacts the quality of life (QoL) and morbidity. Therefore, the development of new approaches to prevent and treat infection, especially RRTI, is necessary. Objectives. We conducted a clinical observational study from May, 2016 to December, 2017 in 20 CVID patients; ten of these patients had a history of RRTI and received the polybacterial preparation MV130, a trained immunity-based vaccine (TIbV) to assess its impact on their QoL and prognosis. Methods. Subjects with RRTI received MV130 for 3 months and were followed up to 12 months after initiation of the treatment. The primary endpoint was a reduction in RRTI at the end of the study. We analyzed the pharmacoeconomic impact on the RRTI group before and after immunotherapy by estimating the direct and indirect costs, and assessed CVID-QoL and cytokine profile. Specific antibody responses to the bacteria contained in MV130 were measured. Results. The RRTI-group treated with TIbV MV130 showed a significant decrease in infection rate (p = 0.006) throughout the 12 months after initiation of the treatment. A decrease in antibiotic use and unscheduled outpatient visits was observed (p = 0.005 and p = 0.002, respectively). Significant increases in anti-pneumococcus and anti-MV130 IgA antibodies (p = 0.039 both) were detected after 12 months of MV130. Regarding the CVID QoL questionnaire, an overall decrease in the score by more than 50% was observed (p < 0.05) which demonstrated that patients experienced an improvement in their QoL. The pharmacoeconomic analysis showed that the real annual direct costs decreased up to 4 times per patient with the prophylactic intervention (p = 0.005). Conclusion. The sublingual administration of the TIbV MV130 significantly reduced the rate of respiratory infections, antibiotic use and unscheduled visits, while increasing specific IgA responses in CVID patients. Additionally, the CVID population felt that their QoL was improved, and a decrease in expenses derived from health care was predicted.

OM-85 BV for primary prevention of recurrent airway infections: a pilot randomized, double-blind, placebo-controlled study.

ABSTRACTObjectiveTo compare the frequency of respiratory tract infections in children treated with OM-85 BV and placebo during the 3-month therapy period, and observation for a further 3 months after treatment.MethodsA randomized, double-blind, placebo-controlled trial was conducted with 54 children (6 months to 5 years old) with no past history of recurrent respiratory infections attending daycare center. Family members were instructed to administer one capsule per day for 10 consecutive days, for 3 months of OM-85 BV or placebo. Telephone interviews were conducted every 30 days.ResultsThere was no significant difference in the number of respiratory infections between the groups. The mean number of respiratory tract infection in the OM-85 BV Group in the first 3 months was 0.92±0.87, and in the Placebo Group was 0.74±1.02, and at 6 months it was 1.62±1.47 and 1.03±1.34, respectively.ConclusionOM-85 BV was not effective in the primary prevention of respiratory tract infections. Although most authors recommend the use of this immunostimulant in children with a history of recurrent respiratory infections, more studies are needed to define its usefulness in the primary prevention of respiratory infections in healthy children exposed to few risk factors.

Atypical Case of Chronic Granulomatous Disease: A Case Report

Background: Chronic Granulomatous Disease (CGD) is a heterogeneous clinical presentation immunodeficiency, whose origin can be autosomal recessive or X-linked. In this pathology there is a deficiency in the effector mechanisms of phagocytes. Case study: A review of the patient's medical records was performed, as well as the currently available bibliography. The case report presented is of an 8-year-old male patient, who had a history of recurrent respiratory infections and ICU admissions since 3 years old, being diagnosed with atypical presentation of CGD at 5 years old, and managed with standard prophylactic treatment based on sulfamethoxazole-trimethoprim (SMX-TMP). Conclusion: CGD has a wide range of symptoms, so treatment should be guided based on each patient. In the presented case, the patient is being treated with a prophylactic combination of Itraconazole and SMX-TMP. Besides, we are still awaiting judicial clearance by the Brazilian National Health System (SUS) for financial support for IFN-gamma (IFN-γ), which is recommended as prophylactic treatment.

Clinical, Immunological, and Genetic Features in Patients with Activated PI3Kδ Syndrome (APDS): a Systematic Review.

Activated phosphoinositide 3-kinase delta syndrome (APDS) is a novel primary immunodeficiency (PID) caused by heterozygous gain of function mutations in PI3Kδ catalytic p110δ (PIK3CD) or regulatory p85α (PIK3R1) subunits leading to APDS1 and APDS2, respectively. Patients with APDS present a spectrum of clinical manifestations, particularly recurrent respiratory infections and lymphoproliferation. We searched PubMed, Web of Science, and Scopus databases for APDS patients and screened for eligibility criteria. A total of 243 APDS patients were identified from 55 articles. For all patients, demographic, clinical, immunologic, and molecular data were collected. Overall, 179 APDS1 and 64 APDS2 patients were identified. The most common clinical manifestations were respiratory tract infections (pneumonia (43.6%), otitis media (28.8%), and sinusitis (25.9%)), lymphoproliferation (70.4%), autoimmunity (28%), enteropathy (26.7%), failure to thrive (20.6%), and malignancy (12.8%). The predominant immunologic phenotype was hyper-IgM syndrome (48.1%). Immunologic profiling showed decreased B cells in 74.8% and CD4+ T cells in 64.8% of APDS patients. The c.3061 G>A (p. E1021K) mutation in APDS1 with 85% frequency and c.1425+1 G> (A, C, T) (p.434-475del) mutation in APDS2 with 79% frequency were hotspot mutations. The majority of APDS patients were placed on long-term immunoglobulin replacement therapy. Immunosuppressive agents such as rituximab, tacrolimus, rapamycin, and leniolisib were also administered for autoimmunity and inflammatory complications. In addition, hematopoietic stem cell transplantation (HSCT) was used in 12.8% of patients. APDS has heterogynous clinical manifestations. It should be suspected in patients with history of recurrent respiratory infections, lymphoproliferation, and raised IgM levels. Moreover, HSCT should be considered in patients with severe and complicated clinical manifestations with no or insufficient response to the conventional therapies.

Impact of OM-85 Given during Two Consecutive Years to Children with a History of Recurrent Respiratory Tract Infections: A Retrospective Study.

In otherwise healthy infants and young children, respiratory tract infections (RTIs) are extremely common. Clinical data have shown that OM-85 could prevent respiratory recurrences in children. However, further studies are needed to explore the true importance of OM-85 in clinical practice. In addition, an unsolved problem is the efficacy of OM-85 when it is administered for two consecutive years. Moreover, another open question is the safety of OM-85 when co-administered with the influenza vaccine. In order to solve these unanswered issues, 200 children aged three to six years with a history of recurrent RTIs, defined as at least six documented episodes of acute RTI in a single year, who had received OM-85 (Broncho-Vaxom®; OM Pharma, a Vifor Pharma Group Company, Geneva, Switzerland) for two consecutive years (3.5 mg once a day for 10 days for 3 months of each year) were selected and matched based on age, sex, and period of evaluation with children with recurrent RTIs who did not receive OM-85. In the group of children treated with OM-85, the number of patients who did not experience any new episode of RTI, as well as the number of RTIs, wheezing episodes, medical visits, and prescribed antibiotic courses, were significantly lower than that in the group not treated with OM-85. The results were similar in the first and second year of OM-85 administration. A minority of patients showed mild adverse events, and the safety profile was overall good, including in the 49 children who received the influenza vaccination within one month from the beginning of the first cycle of OM-85. Our data suggest that OM-85 can effectively and safely reduce the risk of new infective episodes in children with recurrent RTIs and that a second yearly course of lysate administration can be useful to maintain protection, particularly when the diagnosis of recurrent RTIs is made in younger children for whom it is likely that definitive maturation of the immune system still requires a long time.