Preterm infants (PI) are particularly vulnerable to respiratory viral infections (RVI), which may affect their lung development and immune responses, increasing the risk of recurrent wheezing (RW) and asthma. This study aimed to evaluate the cytokine immune profile in PI admitted to neonatal intensive care units (NICUs) and to explore its association with RVI and subsequent respiratory outcomes during the first year of life. A prospective cohort of 118 PI (<32 weeks gestational age) was studied in 2 NICUs. Nasopharyngeal aspirates were collected at birth and discharge for virological and immunological analyses. Infants were classified into 4 groups based on RVI and RW presence. Cytokine levels were measured using Luminex and ELISA. Infants with RVI and/or RW showed higher rates of BPD and respiratory readmissions. Distinct cytokine patterns were observed: V-/W+ infants showed elevated baseline TNF-α and reduced IL-13 and TGF-β over time. V+/W- infants had increasing TNF-α levels during hospitalization. Notably, immune profiles at birth differed even in the absence of RVI, suggesting innate predispositions. Correlation analyses revealed significant associations between cytokines and clinical factors like birth weight and oxygen need. Preterm infants without RVI who developed RW appeared to exhibit a distinct pro-inflammatory cytokine profile early in life. This cytokine pattern may be associated with respiratory outcomes later in infancy, although predictive value cannot be inferred from this study and requires confirmation in larger, more representative cohorts.

A man in his 80s with small cell lung cancer (SCLC) was admitted to hospital with suspected neutropaenic sepsis after a single cycle of chemotherapy. He failed to improve with broad-spectrum antibiotics and was noted to be lymphopaenic and recurrently hypokalaemic. Serum cortisol level was markedly elevated, suggesting SCLC-related paraneoplastic Ectopic Cushing's Syndrome (ECS). Induced sputum revealed Pneumocystis jirovecii Despite high-dose co-trimoxazole, he died from respiratory failure due to progressive multilobar pneumonia. We suggest that immunosuppression due to occult SCLC-related hypercortisolaemia resulted in death from P. jirovecii pneumoniae infection and that ECS should be considered as a cause of hypokalaemia and lymphopaenia in patients with SCLC.

Immunoglobulin G subclass deficiencies (IgGSD) are associated with recurrent respiratory tract infections. Tools to identify patients with IgGSD who benefit from immunoglobulin G replacement therapy (IgGRT) are lacking. This crossover study evaluated the number of antibiotic-demanding infections on and after up to 18 mo off IgGRT in 28 patients with IgGSD. Pneumococcal antibodies against 21 serotypes were assessed using a multiplex assay. After 12 mo on IgGRT, the frequency of infections was reduced during the following 6 mo compared with the last 6 mo without IgGRT, indicating a delayed therapeutic effect. Low levels of pneumococcal serotype-specific antibodies and lower IgG2 levels were associated with the need to restart IgGRT. In conclusion, IgGRT effectively reduces bacterial infections in IgGSD, but the benefits may take at least a year to manifest. Pneumococcal antibody profiling and IgG2 levels may help identify patients needing long-term IgGRT.

Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal storage metabolic disorder caused by pathogenic mutations in the iduronate-2-sulfatase (IDS) gene. Herein, we report the case of a 2-year-old male patient diagnosed with concurrent Evans syndrome (ES) and MPS II, who presented with severe anemia, thrombocytopenia, recurrent respiratory tract infections, and typical clinical manifestations of MPS II. Laboratory examinations showed decreased hemoglobin (Hb) and platelet (PLT) counts, a positive direct Coombs test, presence of anti-platelet antibodies, elevated urinary glycosaminoglycan levels, and complete absence of IDS enzyme activity. Whole exome sequencing identified a novel compound heterozygous nonsense mutation in the IDS gene: c.380_383dup GCTA, p.Y128X. The patient received hematopoietic stem cell transplantation (HSCT) and underwent long-term follow-up. During the follow-up period, the patient's IDS enzyme activity returned to normal levels, and no further recurrence of ES was observed. This study reports a novel pathogenic mutation of the IDS gene, and represents the first documented case of concurrent ES and MPS II in a toddler. HSCT has been confirmed to be an effective therapeutic strategy for this extremely rare comorbid condition. Additionally, we discuss the potential pathogenic association between mucopolysaccharidosis (MPS) and ES, and present a systematic summary of the clinical management of this patient, to provide a reference for improved identification and treatment of similar clinical cases in the future.

Objective: To investigate the association between recurrent childhood and adolescent antibiotic exposure and the risk of adult-onset pneumonia in individuals aged 40 and over, using data from the United Kingdom Biobank (UKB). Methods: A total of 170 496 UKB participants without a history of pneumonia at baseline were included. Based on a baseline questionnaire, participants were categorized into an exposed group (recurrent early-life antibiotic use), a non-exposed group, or an unknown-exposure group. Cox proportional hazards regression models were applied to calculate HRs and their 95%CIs for pneumonia incidence, with the non-exposed group as the reference. Subgroup analyses were conducted to test for effect modification and heterogeneity, and the robustness of the findings was assessed through multiple sensitivity analyses. Results: During a median follow-up of 13.8 years, 6 041 incident pneumonia cases were recorded. After adjusting for major sociodemographic and lifestyle factors, a significantly increased risk of pneumonia was observed in both the exposed group (HR=1.42, 95%CI: 1.32-1.52) and the unknown-exposure group (HR=1.21, 95%CI: 1.11-1.31) compared with the non-exposed group. Subgroup analysis revealed that this association was stronger in individuals with baseline cancer but weaker in those with chronic obstructive pulmonary disease (COPD) (both P for interaction <0.05). The results remained robust across multiple sensitivity analyses, and the association varied with increasing age at pneumonia onset. Conclusions: Recurrent childhood and adolescent antibiotic exposure is associated with a significantly increased risk of adult-onset pneumonia in individuals aged 40 and older. Baseline health status, such as the presence of cancer or COPD, may act as an effect modifier for this association, and its strength appears to be influenced by age of onset.

&lt;b&gt;Introduction:&lt;/b&gt; Non-specific orbital inflammation (NSOI), or orbital pseudotumor, is the third most common orbital disease, yet its pathogenesis remains poorly understood. A dysregulated immune response to infections or trauma, including surgery, has been proposed as a contributing factor. However, reports of NSOI coexisting with sinusitis are scarce and mostly limited to isolated case reports.&lt;b&gt;Aim:&lt;/b&gt; This study examines a subset of NSOI patients with coexisting chronic rhinosinusitis with nasal polyps (CRSwNP), aiming to explore potential pathophysiological links and evaluate treatment outcomes.&lt;b&gt;Materials and methods:&lt;/b&gt; Between 2014 and 2024, 34 patients with NSOI were assessed at the Medical University of Bialystok. In 7 cases (20%), NSOI was associated with CRSwNP. Diagnosis was confirmed through orbital tissue biopsy and exclusion of systemic diseases.&lt;b&gt;Results:&lt;/b&gt; Orbital symptoms - diplopia, proptosis, and pain - developed after sinonasal symptoms and surgical intervention in all cases. Early bacteriological cultures showed various pathogens, but intraoperative cultures during remission were sterile. Tissue or blood eosinophilia, along with recurrent exacerbations and signs of bacterial infection, suggested a mixed type 2/type 3 inflammatory endotype. Imaging revealed orbital wall defects with new bone formation (osteogenesis), and histopathology showed marked fibrosis. Treatment with corticosteroids led to partial stabilization in four patients; two required immunosuppressants and two underwent radiotherapy. None achieved complete remission.&lt;b&gt;Conclusions:&lt;/b&gt; These findings suggest that chronic rhinosinusitis may trigger or worsen NSOI in susceptible individuals, particularly those with underlying immune dysregulation. Standard treatments are often ineffective in advanced fibrotic stages, highlighting the need for tailored, multidisciplinary approaches and further research into the underlying mechanisms.

The respiratory tract (i.e., airways and alveoli) is in close contact with the milieu that is outside the human body and thus, in addition to its role in exchange of gases, it is needed to protect the human being from outside threats such as microbes and pollution. Respiratory tract diseases can have major detrimental effects on human health with increased risks for morbidity and mortality. An example of this dilemma is the orphan disease, primary ciliary dyskinesia (PCD), a complex genetic disorder linked with myriad genetic mutations involving over 50 genes and over 2000 pathogenic variants that lead to dysfunction of vital human components including the respiratory tract, auditory system, mechanisms of fertility and others. The core defect involves abnormal function and motion of microscopic organelles called cilia found throughout the human body with abnormal mucociliary clearance (i.e., aberrant mucociliary escalator). The regulation of motile cilia that are involved in various aspects of physiology such as respiration and reproduction is via thousands of genes. PCD pathophysiology, genetic underpinnings, diagnosis and principles of treatment are considered in this review of primary ciliary dyskinesia in pediatric persons (i.e., newborns, children and adolescents). Primary ciliary dyskinesia (PCD) is one of many ciliopathies that is identified as a condition with remarkable phenotypic and genetic variability. In this fluid fluctuation phenomenon, some PCD patients exhibit classic features such as chronic respiratory disease, situs abnormalities, and infertility, while others may present with milder or atypical disease. In certain cases, ultrastructural analysis of cilia may appear normal despite underlying dysfunction. Disease severity can range from early-onset bronchiectasis to relatively preserved pulmonary function into adulthood, reflecting perplexing genotype-phenotype diversity. Testing for PCD requires an experienced team with expertise in sophisticated technology that includes nasal nitric oxide (nNO) analysis, transmission electron microscopy (TEM), immunofluorescence analysis (IFA), high-speed video-microscopy analysis (HSVMA), three-dimensional explant spheroid formation (3D-E; ex vivo technique), genetic studies and others. Genetic testing is recommended for those suspected of having PCD, as for example in certain neonates (i.e., persistent respiratory distress, unexplained rhinorrhea with chronic cough, situs inversus), at-risk children (i.e., having persistent wet cough, chronic sinusitis, unexplained bronchiectasis, recurrent otitis media with airway symptomatology) and adults with early childhood respiratory symptoms often associated with infertility. The medical evaluation is complicated by various factors including the absence of a gold standard for a precise diagnosis. Also, as the clinician or clinical team considers a patient with possible PCD, the testing that is done should keep in mind the differential diagnoses of PCD; these conditions include cystic fibrosis (CF), various immune disorders, numerous infections (i.e., tuberculosis, aspergillosis, others), alpha-1-antitrypsin deficiency (AATD) and others as noted in this article. As emerging cutting-edge 21st century research seeks treatment of PCD via gene therapy, current management involves intense therapy of upper and lower respiratory tract infections (i.e., rhinosinusitis, otitis media, pneumonia) as well as bronchiectasis with focused efforts at dealing with impaired mucus clearance. Primary ciliary dyskinesia is a classic example of how microscopic (electron microscopic) maladies can lead to major macroscopic maladies in newborns, children, adolescents and adults.