Abstract Introduction Tracheobronchomegaly, also known as Mounier-Kuhn Syndrome, is a rare disorder characterized by marked dilation of the trachea and bronchi resulting from atrophy of the elastic fibers and muscularis propria in the airway wall. Patients typically exhibit nonspecific chronic respiratory symptoms, which often contribute to a delay in diagnosis. In this report, we describe a case presenting with hemoptysis and recurrent lower respiratory tract infections. The diagnosis of Mounier-Kuhn syndrome was established based on findings from high-resolution computed tomography (HRCT). Case presentation A 74-year-old male, a retired worker, was transferred to our hospital following episodes of hemoptysis and recurrent lower respiratory tract infections. He reported a previous smoking history of 5 years, with a consumption of approximately 10 cigarettes per day, but currently denies tobacco use. The laboratory data were as follows: white blood cell count 13.3 × 109/l, neutrophils 11.34 × 109/l, C-reactive protein 176.4 mg/L, and positive procalcitonin (PCT, 1.53 ng/mL). High-resolution computed tomography (HRCT) was performed, and coronal reconstruction demonstrated marked dilation of the trachea and main bronchi, with diameters measuring 30.2 mm in the trachea, 26.3 mm in the right main bronchus, and 23.7 mm in the left main bronchus (Figure 1 A). On the sagittal view, the tracheal diameter reached 33.32 mm (Figure 1 B). Three-dimensional reconstruction further revealed extensive tracheobronchial dilatation accompanied by multiple diverticula (indicated by arrows, Figure 1 C). Subsequent fibrobronchoscopy confirmed the presence of tracheomalacia with dynamic partial collapse during expiration (Figure 1D.E.F). Finally, he was diagnosed as Mounier-Kuhn syndrome. Discussion Tracheobronchomegaly (Mounier-Kuhn Syndrome) is a rare disorder that has been underdiagnosed since its first description in 1932. Computed tomography (CT) serves as the cornerstone for establishing the diagnosis and guiding comprehensive evaluation. The characteristic hallmarks—marked airway dilation, tracheobronchial diverticulosis, and related complications—should be recognized to facilitate accurate diagnosis, inform appropriate management, and avoid unnecessary interventions. In the management of Mounier-Kuhn syndrome, a symptom-driven approach is recommended. No specific treatment is indicated for asymptomatic patients, whereas tobacco cessation constitutes a cornerstone of care. For symptomatic individuals, the mainstay of management includes routine respiratory physiotherapy and the use of antibiotics to manage acute infectious exacerbations. This report aims to enhance awareness of the common complications and associated pulmonary conditions in these patients. This abstract is funded by: None

ResumoFundamento O edema pulmonar é uma complicação clinicamente significativa em crianças com cardiopatia congênita (CC). Ocorre com maior frequência em casos complexos e está associado a internações prolongadas. A identificação precoce é essencial devido ao seu impacto direto nos desfechos clínicos.Objetivos Avaliar a ultrassonografia pulmonar (USP) como ferramenta diagnóstica para edema pulmonar e identificar fatores clínicos e laboratoriais associados em crianças com CC.Métodos Foram incluídas crianças com CC submetidas à USP entre setembro de 2020 e setembro de 2023. Os achados da USP foram comparados com dados clínicos, resultados de radiografia de tórax e níveis de peptídeo natriurético tipo B (BNP). Os pacientes foram classificados de acordo com a categoria fisiopatológica (hiperfluxo pulmonar, hipertensão pulmonar ou outras).Resultados Foram avaliadas 62 crianças, com mediana de idade de 5,5 meses (intervalo interquartil, 4-10,1 meses). Hiperfluxo pulmonar foi identificado em 49 pacientes (79%), hipertensão pulmonar em sete (11,3%) e outras condições fisiopatológicas em seis (9,7%). O nível mediano de BNP foi 815,5 pg/mL. O edema pulmonar foi detectado em 36 pacientes (58%) pela radiografia de tórax e em 33 pacientes (53%) pela USP. Observou-se sobreposição significativa, uma vez que 79% dos pacientes com USP positiva também apresentaram edema na radiografia de tórax (p < 0,001). Em contraste, apenas 34,5% dos pacientes com USP negativa apresentaram evidência radiográfica de edema. O edema pulmonar esteve significativamente associado a infecções recorrentes do trato respiratório inferior, baixo peso, índice de massa corporal abaixo de –2 desvios-padrão e níveis elevados de BNP. A análise de regressão logística multivariada identificou falha no crescimento como preditor independente de edema pulmonar. Os achados da radiografia de tórax permaneceram como o principal fator associado ao edema pulmonar.Conclusão A USP é um método confiável e livre de radiação para a detecção de edema pulmonar em crianças com CC. A identificação de fatores de risco associados pode facilitar o reconhecimento precoce de pacientes vulneráveis e apoiar intervenções clínicas oportunas e adequadas.

The Genetics of Primary Ciliary Dyskinesia - Advances and Limitations.

Introduction: Primary immunodeficiency diseases (PIDs), also referred to as inborn errors of immunity, are a heterogeneous group of genetic disorders associated with recurrent infections, immune dysregulation, and increased morbidity and mortality when diagnosis is delayed. Primary care physicians (PCPs) play a critical role in early recognition; however, data on PCPs’ knowledge and preparedness regarding PID remain limited. This study aimed to evaluate PCPs’ knowledge, clinical approaches, and preparedness regarding PIDs across Türkiye. Methods: This nationwide, cross-sectional study included 385 PCPs – general practitioners (GPs), family medicine residents (FMRs), and family medicine specialists (FMSs) – working in Family Health Centers in Türkiye. Participants completed a structured online questionnaire assessing sociodemographic characteristics, educational background, clinical experience, self-perceived PID knowledge, and performance on 15 PID-related multiple-choice questions based on international guidelines. Total knowledge scores (range: 0–15) were calculated. Correct response rates for individual items and total scores were compared across professional groups and according to educational and clinical variables. Multivariable logistic regression analyses were performed to identify factors independently associated with higher knowledge scores. Results: The mean total knowledge score was 9.09 ± 2.46 (range 0–15). FMSs demonstrated significantly higher total scores than FMRs and GPs (GPs 8.67 ± 2.47; FMRs 8.82 ± 2.63; FMSs 9.83 ± 2.03; p < 0.001). In multivariable analysis, being an FMS was independently associated with scoring above the mean (OR = 2.02, 95% CI: 1.26–3.23; p = 0.004). Regular participation in general medical educational activities was associated with significantly higher total scores (9.74 ± 2.31 vs. 8.23 ± 2.38; p < 0.001). PCPs who participated in PID-related educational activities within the past 5 years were also associated with higher total scores (9.43 ± 2.58 vs. 8.87 ± 2.47; p = 0.027). PCPs who reported requesting immunoglobulin testing or referring patients with recurrent lower respiratory tract infections achieved significantly higher total scores (9.18 ± 2.43 vs. 7.52 ± 2.42; p = 0.001). PCPs who self-perceived their PID knowledge as moderate or good had substantially higher total knowledge scores compared to those who self-perceived their knowledge as low (low: 8.36 ± 2.55; moderate: 9.41 ± 2.26; good: 10.09 ± 2.50; p < 0.001). Conclusion: PID-related knowledge scores among PCPs differed across professional groups, with GPs demonstrating lower scores. Higher knowledge scores were significantly associated with being an FMS and with participation in regular general medical education and past 5-year PID-related education. Strengthening targeted educational strategies, particularly for GPs in primary care settings, may improve early recognition and management of PIDs.

Aspiration pneumonia is a clinically significant condition that may result from unrecognized structural or functional abnormalities of the upper gastrointestinal tract. Esophageal diverticula, although often asymptomatic, can predispose patients to recurrent aspiration and serious pulmonary complications. This case report describes a 59-year-old female patient admitted with recurrent lower respiratory tract infections of unclear etiology. Comprehensive clinical assessment, laboratory testing, and radiological imaging revealed aspiration pneumonia secondary to a large esophageal diverticulum. Targeted antibiotic therapy was initiated, and the patient was referred for definitive surgical treatment. This case highlights the importance of considering gastrointestinal causes in patients with recurrent pneumonia and emphasizes the role of an interdisciplinary diagnostic approach.

Kartagener's syndrome is a rare autosomal recessive genetic disorder, a subset of primary ciliary dyskinesia. It comprises the triad of situs inversus totalis, bronchiectasis, and chronic paranasal sinusitis. The incidence is 1:30,000 live births, while the male: female ratio is 1:1. Most patients of Kartagener's syndrome present in early childhood with common symptoms of frequent colds, chronic cough with excessive production of purulent sputum, and recurrent lower respiratory tract infections affecting respiratory functions. Kartagener's syndrome commonly presents as infertility in males and subfertility in females. We present the clinical and radiological findings in a patient of Kartagener's syndrome referred to us with recurrent lower respiratory tract infections.

Background.The association between major dental diseases and recurrent upper and lower respiratory tract infections is of interest due to their high prevalence in the child population. The aim of our study is to analyze the literature where this problem has been studied. Materials and methods.In accordance with the PRISMA 2020 protocol, a search was performed in four databases: PubMed (including Medline), Web of Science, eLibrary.Ru и Google Scholar. The search resulted in 526 publications from databases. After the identification and screening phases, eight articles were included in the qualitative analysis. Results. Studies presented in publications show that children with frequent respiratory infections have a deterioration of oral hygiene, impairment of the properties of the mouth fluid, increased activity of caries of temporary and permanent teeth. The results published in three articles show that the presence of early childhood caries increased the frequency of episodes of respiratory infection in children. However, one study did not reveal a significant association between caries, dental plaque and the number of episodes of acute respiratory viral infections in children. Conclusion.In the last 10 years, a small number of articles have been published on dental problems of children with recurrent respiratory infections. There is no information on the condition of periodontal tissue and mucosa of the mouth in this category of children. The association between tooth decay and children’s susceptibility to respiratory infections remains unclear.

ObjectivesCerebrospinal fluid (CSF) rhinorrhea involves drainage of CSF through the nasal cavity due to disruption of the skull base, and pneumonitis secondary to CSF aspiration is a lesser‐known complication reported. We present the case of a patient whose pulmonary symptoms and function improved after surgical CSF leak repair.MethodsThis is a case report with review of the electronic medical record and literature review.ResultsA 35‐year‐old female presented with 1 year of refractory right‐sided rhinorrhea and recurrent lower respiratory infections. Nasal drainage was positive for beta‐2‐transferrin. Sinus CT showed a possible leakage site at the right lateral lamella of the cribriform plate. Chest CT showed upper lobe predominant ground‐glass opacities. Following surgical CSF leak repair, chest CT showed resolution of ground‐glass opacities and pulmonary function testing showed an increase in spirometric lung volumes.ConclusionsAspiration pneumonitis from CSF leaks is rarely reported. Studies report resolution of ground‐glass opacities on chest CT as well as clinical improvement in symptoms such as cough following surgical leak repair. Proposed mechanisms leading to aspiration pneumonitis include nasopharyngeal bacterial transit; the mechanism of persistent leak may be related to cough‐induced increase in intracranial pressure leading to increased CSF flow. In patients with lower airway inflammation and obstruction as well as unexplained aspiration pneumonitis, a high index of suspicion for CSF rhinorrhea is warranted.

Elucidating the outpatient burden of lower respiratory tract infections due to RSV and other viruses in children under 2 years of age: Clinical presentation, medical treatment, and family impact (Germany, 11/2022-10/2024).

Predictors of Progression in Pre-COPD: The 3P Study Rationale and Design

Aicardi–Goutières syndrome (AGS) is a rare inherited disease predominantly affecting the brain, immune system, and skin. AGS is caused by a mutation in one or more of a small group of specific genes leading to the accumulation of calcium in the brain, which is thought to trigger the immune response that causes symptoms of AGS. A male neonate weighing 2760 g was delivered at 38 weeks of gestation by lower segment cesarean section to a 30-year-old mother in her third pregnancy. The antenatal period was uneventful except for the anomaly scan revealing enlarged cisterna magna. On examination, microcephaly was noted with sutural overriding. The neonate exhibited multiple dysmorphic features, including low-set ears, hypertelorism, a thin upper lip, a long philtrum, and microcephaly. Other findings include paucity of limb movements, lethargy, hepatosplenomegaly noted on the first day of life, generalized hypotonia, and a characteristic central pattern of breathing manifesting occasionally as labored breathing. The neonate was then transferred to the neonatal intensive care unit for further evaluation, where the neonate continues to be encephalopathic. The detailed neurological examination revealed generalized hypotonia with diminished level of consciousness and poor suck. The family history is significant for a similar clinical presentation in an older male sibling, who had exhibited intracranial calcifications, generalized hypotonia, and global developmental delay. However, the cause was not evaluated. This sibling had died at 1 year of age following recurrent lower respiratory tract infections and prolonged hospitalization. The cranial ultrasound revealed bilateral periventricular calcification, corpus callosal dysgenesis. The magnetic resonance imaging brain was done later which showed periventricular, subcortical white matter, and basal ganglia calcifications, thinning of corpus callosum with colpocephaly, mild flattening of pontine belly with enlargement of retrocerebellar space. TORCH evaluation was negative. Hence, whole exam sequencing was done which demonstrated the mutation of RNASEH2C gene revealing the diagnosis of AGS type 3. AGS can mimic congenital infections, making diagnosis challenging. A neonate presenting with microcephaly and hypotonia should be thoroughly evaluated once intrauterine infections are ruled out. Genetic testing can confirm the diagnosis.

Abnormalities in immune system development and function result in increased susceptibility to infection and reactivation of latent infections. Other immunodeficiencies can result in mild infections and may first be detected in adulthood. This literature review aims to discuss primary immunodeficiencies, including their definition, causes, treatment, and examples of the diseases they cause. This literature review was compiled through a literature search method by reviewing various scientific journals obtained from databases such as PubMed, Google Scholar, and ScienceDirect. The results Primary immunodeficiency disease (PID) results from immune system defects caused by mutations in the genetic code that codes for components of the body's immune system. PID is broadly classified as either a disorder of adaptive immunity (T-cell, B-cell, or combined immune deficiencies) or innate immunity (phagocyte and complement deficiencies). Patients with PID may experience a variety of lung problems, including recurrent lower respiratory tract infections, lung parenchymal abnormalities, asthma, ventilation abnormalities, and bronchiectasis (BE). In conclusion, primary immunodeficiency disease (PID) refers to a large, heterogeneous group of disorders characterized by abnormalities in the development and/or function of the immune system. These conditions result from immune system defects caused by mutations in the genetic code that codes for components of the body's immune system.

Cardiac tamponade is a life-threatening condition that requires urgent diagnosis and intervention. Its occurrence in patients with complex pulmonary histories, such as bronchial carcinoid and previous tuberculosis (TB) infection, is rare and clinically challenging. We report the case of a 76-year-old male with a prior history of endoscopically treated bronchial carcinoid and treated pulmonary TB (2016), who presented with acute breathlessness, restlessness, chest discomfort, and gastrointestinal symptoms. He had a background of chronic productive cough and recurrent lower respiratory tract infections. On admission, he was tachycardic, tachypnoeic, hypotensive, and hypoxic. Clinical examination and 2D echocardiography confirmed massive pericardial effusion causing cardiac tamponade. Emergency pericardiocentesis drained 300 mL of turbid yellow pericardial fluid, which showed lymphocytic predominance. Imaging revealed bilateral pleural effusion, atelectasis, and left lung collapse. The patient was managed with intravenous antibiotics (meropenem and Targocid), vasopressors, bronchodilators, supportive care, and empiric antitubercular therapy. His condition improved significantly, and follow-up echocardiography showed only mild residual effusion without tamponade. He was discharged in stable condition with a comprehensive treatment plan and scheduled follow-up.

Foreign body aspiration (FBA) in children is a common public health issue that can present as a clinical emergency. However, long-standing occult foreign bodies (FBs) in the airway pose a diagnostic challenge, often mimicking common respiratory illnesses. Despite regular education on child safety, such cases are frequently encountered in clinical practice. This paper emphasises the need for a high index of suspicion for FBA when evaluating children with chronic respiratory symptoms presented through three cases with varying clinical presentations and outcomes. Case 1, a 7-year-old girl presented with chronic cough, was misdiagnosed as pulmonary tuberculosis and was on antitubercular therapy for 3 months without any response to treatment before visiting our hospital. Case 2, a 2-year-old boy, presented as hyperreactive airway disease and was under regular treatment with bronchodilators and inhaled corticosteroids in the past 2 months. Case 3, a 9-year-old girl, presented with a chronic cough and was on oral antibiotics for recurrent lower respiratory tract infections for 1 month. All three cases underwent radiological evaluation followed by rigid bronchoscopy in view of a high index of suspicion of occult long-standing airway FB. Although organic FB (areca nut) was retrieved in the first two cases, we lost the first case to complications (hypoxic ischaemic injury) during the procedure. The second case improved well after the FB removal. The third case continued to experience a chronic cough, which was well-managed with bronchodilators on follow-up. A literature review was performed through the MEDLINE database using a few key terms: ‘Airway foreign body’, ‘long-standing foreign body airway’, ‘chronic cough’ and ‘rigid bronchoscopy in children’. We focused on presentation and management of occult long-standing airway FB in children, with practical aspects on prevention. The three cases presented here further emphasise the clinician to consider occult FB airway as a differential diagnosis in the evaluation of any child with chronic cough. This literature review aims to present the recent scientific literature and provide a clear practical guide on the approach towards long-standing airway FB in children.

Williams – Campbell syndrome (WCS) is a rare developmental defect characterized by deficiency or complete absence of cartilage mainly in the subsegmental bronchi. Inferiority of the cartilaginous apparatus creates favorable conditions for the development of recurrent lower respiratory tract infection and, as a consequence, the formation of bronchiectasis, which ultimately leads to the appearance and progression of respiratory failure, as well as to a decrease in the quality of life of patients. Insufficient awareness of this disease among doctors leads to later diagnosis, and complex conservative therapy in the absence of specific treatment for WCS entails a positive effect only in the short term.The aim. Demonstration of a clinical case of a rare respiratory disease – WCS in a 35-year-old man.Conclusion. This case illustrates the complexities of diagnosing and treating WCS and highlights the importance of raising awareness among healthcare workers regarding this disease.

Introduction: Vitamin D is a vital nutrient with immunomodulatory effects that may impact susceptibility to infections. Lower Respiratory Tract Infections (LRTI) are among the leading causes of morbidity and mortality in children. However, there is limited research exploring the relationship between vitamin D levels and LRTI in children in India. Aim: To find a correlation between vitamin D levels and recurrent LRTI in children aged 6 months to 5 years. Materials and Methods: A cross-sectional study was conducted in the Pediatric ward of Bokaro General Hospital in Jharkhand, India, between June 2019 and May 2020. A total of 222 children aged 6 months to 5 years diagnosed with recurrent LRTI were enrolled as cases (n=111), while other children in the same age group who were admitted with different diagnoses and required blood sampling were enrolled as controls (n=111) after obtaining parental consent. The blood levels of 25-hydroxy vitamin D [25(OH)D] were estimated and compared for both groups. Qualitative data were analysed using the chi-square test, while the Pearson’s correlation coefficient was used to compute the correlation between quantitative variables. Results: Among a total of 222 children, the majority 53 (47.7%), exhibited Vitamin D Deficiency (VDD), while most controls, 44 (39.6%) had normal vitamin D levels (p-value=0.03). The mean vitamin D level in the case group was significantly lower (p-value=0.022) compared to the control group. The VDD was found in 36 (39.13%) of the 92 cases with 2-3 episodes of LRTI, whereas it was observed in 17 (89.47%) of the 19 cases with 4-5 LRTI episodes (p-value=0.001). A significant inverse correlation was noted between the number of LRTI episodes and vitamin D levels (r-value=0.53, p-value&lt;0.01). Conclusion: The present study reinforces the role of VDD and insufficiency in the occurrence of recurrent LRTI in children. Therefore, all children diagnosed with recurrent LRTI should be checked for their vitamin D status and should receive repletion therapy in addition to antibiotic treatment if found to be vitamin D deficient.

Background: Lower respiratory tract infections (LRTIs) are one of the major causes of morbidity and mortality in children under five. Recurrent LRTIs which is defined as three or more episodes in one year or two or more in six months pose a significant health burden. Emerging evidence suggests that vitamin D deficiency in may increase susceptibility of children to such infections. Methods: This comparative observational study was conducted over one year (January 2024 to December 2024) in the pediatric department of Bidar Institute of Medical Sciences, Karnataka, India. The study was undertaken to assess the association between vitamin D status and recurrent LRTIs in children aged 6 months to 5 years. The study included 80 children with recurrent LRTIs (group A) and 80 age matched healthy controls (group B). Detailed demographic details, clinical findings and nutritional status of cases was collected using a structured questionnaire. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using chemiluminescent immunoassay and categorized as deficient (&lt;20 ng/ml), insufficient (20–30 ng/ml) or sufficient (&gt;30 ng/ml). Statistical analysis was performed using statistical package for the social sciences (SPSS) version 21.0 with significance set at p&lt;0.05. Results: No significant differences were noted between groups regarding age and gender distribution. Bronchiolitis and pneumonia were the most common types of LRTIs observed. The mean serum vitamin D level in group A (18.7±7.3 ng/ml) was significantly lower than in group B (26.1±8.5 ng/ml) (p&lt;0.0001). Vitamin D deficiency was observed in 47.5% of children with recurrent LRTIs compared to 27.5% in controls (p=0.0002). Conclusions: Children with recurrent LRTIs were found to have significantly lower serum vitamin D levels compared to healthy counterparts. These findings suggest that vitamin D deficiency may be a modifiable risk factor for recurrent respiratory infections.

Abstract Introduction: Good syndrome is a rare entity accounts for only 5% of parathymic syndromes and is characterized by the association of a thymoma, hypogammaglobulinemia, and recurrent infections, primarily bronchopulmonary, which can sometimes lead to bronchiectasis. Case report: A 71-year-old male patient, father of four, with a history of chronic smoking (30 pack-years, quit 20 years ago) and chronic bronchitis, as well as a history of treated pulmonary tuberculosis in 1980. His current symptoms began 4 years ago with recurrent bronchopulmonary infections, worsening over the past year with exacerbation of his chronic cough, increased mucopurulent sputum production, and episodes of minor, recurrent hemoptysis that resolved spontaneously. Pulmonary examination revealed a BMI of 23 kg/m², diffuse rhonchi, and bilateral basal crackles and rhonchi. The remainder of the physical exam, including cardiovascular, lymphatic, and abdominal assessments, was unremarkable. Among the tests performed, a complete blood count showed hemoglobin at 14 g/dl, white blood cell at 9930, with lymphocytes at 1972, and C-reactive protein (CRP) at 16 mg/l. HIV, hepatitis B, and C serologies were negative. Three sputum samples for acid-fast bacilli (AFB) and cultures were negative. Protein electrophoresis revealed hypogammaglobulinemia at 5 g/l. A thoracic CT scan revealed an anterior mediastinal mass, lateralized to the right, measuring 79 mm in its largest dimension. The mass was oval-shaped, well-defined, and of heterogeneous density, abutting the pericardium without signs of invasion. There were also a few mediastinal lymph nodes, with the largest measuring 12 mm in the pretracheal region. Additionally, bilateral moniliform and cystic bronchiectasis were noted, along with cystic fibrosis affecting the entire lower right lobe. A CT-guided biopsy of the mediastinal mass confirmed a type A thymoma. Bronchoscopic examination revealed abundant diffuse bronchorrhea without visible obstruction of the bronchial tree. The GeneXpert test, as well as bacteriological and parasitological analyses of the bronchial aspirate, were negative. The association of a thymoma with hypogammaglobulinemia, recurrent bronchopulmonary infections, and CT findings of diffuse cylindrical and cystic bronchiectasis led to the diagnosis of Good syndrome in our patient. However, the patient declined surgical resection and has since been lost to follow-up. DISCUSSION: Although rare, Good syndrome can be an underlying cause of bronchiectasis. Serum protein electrophoresis is a simple test that should be performed in patients with recurrent lower respiratory tract infections and/or bronchiectasis, particularly when a thymoma is present.

Air pollution is a significant global health concern, particularly for younger children who are especially susceptible to its adverse effects. Pollutants such as particulate matter (PM), nitrogen oxides (NO and NO₂), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO) are associated with increased risks of upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI). While this association is well-documented, there are critical gaps in understanding the magnitude of these risks, the roles of specific pollutants, and the influence of age, sex, and exposure duration. To confirm the relationship between air pollution and respiratory tract infections in children and to identify areas for further research on reducing pollution-related respiratory damage, a literature review was conducted using the MEDLINE/PubMed database for studies published from January 2000 to December 2024. Eligible studies included randomized controlled trials, cohort studies, and meta-analyses focusing on the relationship between air pollution and respiratory infections in children. Studies were grouped by pollutant type, exposure timing, and infection type. The literature analysis confirmed that pollution significantly increases the risk of URTI and LRTI in children, with infants and young children being the most vulnerable. Potential mechanisms for the development of respiratory tract pollution-related diseases include the promotion of oxidative stress, induction of inflammatory responses, deregulation of the immune system, and genetic alterations. Prenatal exposure significantly alters respiratory tract development, increasing the risk of LRTI and acute otitis media (AOM) early in life. Both short-term and long-term postnatal exposures can cause severe and recurrent LRTIs, reducing quality of life and leading to frequent hospitalizations and early death. However, the available data do not allow for precise definition of the magnitude of the risk, the individual and combined roles of specific pollutants, and the influence of factors such as age, sex, duration, and site of exposure on the development and severity of respiratory infections. Inconsistent findings on pollutant combinations and specific diseases like otitis media highlight the need for further research. Air pollution is a major risk factor for respiratory infections in children, both prenatal and postnatal exposure can have significant negative impact. However, present knowledge is inadequate to develop effective preventive and therapeutic measures. Further studies are needed to minimize these cultural limits. In particular, it is necessary to delve deeper into how the various pollutants circulate, how they interact with each other, and how they are influenced by climate change and other environmental drivers. Results of these key researches can be translate into clinical and public health practice capable to help protect and improve children's environmental health.

Exposure to bacterial respiratory pathogens is commonplace, but severe recurrent disease requiring hospitalization may suggest an underlying IEI. We studied a pair of siblings with decade-long histories of severe recurrent lower respiratory tract infections and positive cultures for Streptococcus pnuemoniae. These patients had normal total B cell counts but reduced generation of B cell memory and low antibody levels. CyTOF analysis showed all other immune cell subsets were present at normal frequencies. No mutations in known IEI-causal genes explained these patients’ phenotypes. By whole-exome sequencing, we identified a novel mutation in TANK, which segregated in an autosomal recessive manner. This mutation caused a frameshift and early truncation of the TANK protein, and complete TANK deficiency in the patients’ cells. TANK is an adaptor protein with poorly characterized roles in both canonical and noncanonical NF-kB signaling. Using an in vitro B cell differentiation assay, we know that TANK-deficient patients’ B cells seem “blocked” at the IgD-CD27- double-negative stage and proliferate poorly. Using scRNA-seq of patient and healthy control samples, we show an accumulation of intermediate B cells with a unique gene, including high SOX5 expression. Mechanistically, TANK suppresses the canonical NF-kB pathway and serves as a critical determinant of B cell proliferation and differentiation, antibody secretion, and protection from respiratory pathogens.