J Allergy Clin Immunol Pract. 2025 Mar;13(3):720. doi: 10.1016/j.jaip.2025.01.008.

NO ABSTRACT

PMID:40049792 | DOI:10.1016/j.jaip.2025.01.008

J Allergy Clin Immunol Pract. 2025 Mar;13(3):720-721. doi: 10.1016/j.jaip.2025.01.009.

NO ABSTRACT

PMID:40049791 | DOI:10.1016/j.jaip.2025.01.009

Langmuir. 2025 Mar 6. doi: 10.1021/acs.langmuir.4c04840. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa (P. aeruginosa) is a pathogen commonly associated with lung infections in cystic fibrosis (CF) patients, often developing a mucoid phenotype that overproduces alginate, a major component of the biofilm's extracellular polymeric substances (EPS) matrix, increasing tolerance to antibiotics. Past studies have shown that low-frequency ultrasound (LFU) increases the antibiotic susceptibility of P. aeruginosa in biofilms, but its effects on mucoid strains are unknown. In this study, we assessed the combined application of LFU and antibiotics on P. aeruginosa FRD1, a mucoid strain, and compared it to nonmucoid P. aeruginosa PAO1 biofilms. The mucoid biofilm exhibited greater stiffness, thickness, and density, with polysaccharides (likely alginate) comprising over 70% of the EPS matrix. Although LFU application led to a 50% increase in biofilm creep compliance, no synergistic effect was observed with tobramycin. However, the same LFU treatment significantly improved ciprofloxacin susceptibility. We implemented a one-dimensional model that estimated a 25-fold increase in the diffusion coefficient for ciprofloxacin following LFU, though higher intensities were needed to induce comparable effects in diffusivity and mechanical properties compared to the nonmucoid biofilm. The model also suggested that tobramycin likely sorbed to alginate, hindering diffusion to the biofilm interior, thereby reducing its inactivation efficiency. Our findings suggest that LFU can impact antibiotic diffusion through the biofilm and mechanical properties but not necessarily overcome antibiotic interactions with the EPS matrix. Additionally, variations in EPS matrix composition may require different LFU intensities for effective outcomes. These results may have significant implications for potential clinical applications, especially for CF patients.

PMID:40048555 | DOI:10.1021/acs.langmuir.4c04840

Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar 6. doi: 10.1007/s00210-025-03970-x. Online ahead of print.

ABSTRACT

Inflammatory lung diseases (ILDs) such as asthma, acute respiratory distress syndrome, bronchiectasis, chronic obstructive pulmonary disease, COVID-19, cystic fibrosis, and lung cancer impose a substantial worldwide healthcare impact. The pathophysiology of these disorders is primarily influenced by the involvement of neutrophils, which are crucial triggers in the natural immune reaction. Neutrophils participate in pulmonary inflammation and tissue destruction. When neutrophils are activated and recruited, they migrate to inflammatory lung tissues via the chemokine receptor CXCR2. This study explores how neutrophils, directed by CXCR2 signaling, participate in the inflammatory environment in the lung, inducing tissue injury and the development of illness. We investigate both the functional and structural features of CXCR2, emphasizing its relationship with ligands such as IL-8 (CXCL8) and GRO-α (CXCL1) and its involvement in ILDs. The article also explores novel treatment approaches that focus on CXCR2, such as the use of small molecule antagonists. These compounds can regulate neutrophil behavior and reduce signs of the illness. The study provides a detailed analysis of current clinical studies and the results of inhibiting CXCR2, specifically looking at the effectiveness and safety of these new medicines. This study seeks to deliver a thorough analysis of the important function of neutrophils and CXCR2 in ILDs, as well as the possibility of CXCR2-targeted therapeutics to enhance clinical outcomes.

PMID:40047857 | DOI:10.1007/s00210-025-03970-x

Int Forum Allergy Rhinol. 2025 Mar 6:e23557. doi: 10.1002/alr.23557. Online ahead of print.

ABSTRACT

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) is a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) therapy that improves pulmonary function and chronic rhinosinusitis (CRS) in cystic fibrosis (CF) adults with at least one copy of the F508del CFTR mutation. The purpose of this study is to evaluate the impact of ETI on CRS symptoms in children and adolescents with CF.

METHODS: The MODUL-CF observational study is a multicenter prospective cohort study enrolling CF children with at least 1 F508del mutation in France. Subjects answered a standardized questionnaire on nasal obstruction and smell and were invited to complete the Sinus and Nasal Quality of Life Survey (SN-5) questionnaire prior to ETI therapy and at 1, 3, 6, and 12 months ETI. Part of the cohort underwent sinus computerized tomography (CT) within an ancillary study, scored by the Lund-Mackay CT score (LMKS).

RESULTS: Of 391 subjects, 94 (24.0%) were aged between 6 and 12 years, and 297 were adolescents. Sixty-four (16.3%) reported nasal obstruction at baseline. One hundred and sixty-three completed the SN-5 questionnaire at M0, 181 at M12, and 123 at M0 and M12. Mean SN-5 global score baseline value was similar to that of a healthy pediatric control cohort. SN-5 global score, nasal obstruction, sinus infection, and emotion domain subscores improved significantly at 1 month and this was sustained over 12 months. LMKS improved significantly in 43 patients who underwent sinus CT at M0 and M12.

CONCLUSION: ETI improves sinonasal symptoms and related quality of life (QOL), including emotion domain, in children and adolescents with CF.

PMID:40047648 | DOI:10.1002/alr.23557

J Physiol. 2025 Mar 6. doi: 10.1113/JP287891. Online ahead of print.

ABSTRACT

Electrogenic transepithelial ion transport can be measured with the short-circuit current technique. Such experiments are frequently used to evaluate the activity of the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel that is defective in cystic fibrosis, one of the most frequent genetic diseases. Typically, CFTR activity is estimated from the effect of CFTRinh-172, a selective CFTR inhibitor. Unexpectedly, we found that CFTRinh-172, in addition to PPQ-102, another CFTR inhibitor, caused only partial inhibition of CFTR function, particularly in epithelia in pro-inflammatory conditions, which are characterized by abundant mucus secretion. We hypothesized that the mucus layer was responsible for the poor activity of CFTR inhibitors. Therefore, we treated the epithelial surface with the reducing agent dithiothreitol to remove mucus. Removal of mucus, confirmed by immunofluorescence, resulted in highly enhanced sensitivity of CFTR to pharmacological inhibition. Our results show that the mucus layer represents an important barrier whose presence limits the activity of pharmacological agents. This is particularly relevant for CFTR and the evaluation of therapeutic approaches for correction of the basic defect in cystic fibrosis. KEY POINTS: Activity of the cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel can be evaluated by measuring the inhibition elicited by the selective blockers CFTRinh-172 and PPQ-102. In short-circuit current recordings on human airway epithelia, CFTR inhibitors had only a partial effect on cAMP-dependent chloride secretion, suggesting the possible contribution of other ion channels. The mucus layer covering the epithelial surface was removed with the reducing agent dithiothreitol. Treatment of epithelia with dithiothreitol markedly improved the efficacy of CFTR inhibitors. The partial effect of CFTR inhibitors might be explained by the presence of the mucus layer acting as a barrier.

PMID:40047394 | DOI:10.1113/JP287891

Am J Physiol Cell Physiol. 2025 Mar 6. doi: 10.1152/ajpcell.00026.2025. Online ahead of print.

ABSTRACT

The intestine, as a critical interface between the external environment and the internal body, plays a central role in nutrient absorption, immune regulation, and maintaining homeostasis. The intestinal epithelium, composed of specialized epithelial cells, hosts apical anion transporters that primarily mediate the transport of chloride and bicarbonate ions, essential for maintaining electrolyte balance, pH homeostasis, and fluid absorption/secretion. Additionally, the intestine hosts a diverse population of gut microbiota that plays a pivotal role in various physiological processes including nutrient metabolism, immune regulation and maintenance of intestinal barrier integrity, all of which are critical for host gut homeostasis and health. The anion transporters and gut microbiome are intricately interconnected, where alterations in one can trigger changes in the other leading to compromised barrier integrity and increasing susceptibility to pathophysiological states including gut inflammation. This review focuses on the interplay of key apical anion transporters including Down Regulated in Adenoma (DRA, SLC26A3), Putative Anion Transporter-1 (PAT1, SLC26A6) and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR, ABCC7) with the gut microbiome, barrier integrity and their relationship to gut inflammation.

PMID:40047092 | DOI:10.1152/ajpcell.00026.2025

Cureus. 2025 Feb 3;17(2):e78441. doi: 10.7759/cureus.78441. eCollection 2025 Feb.

ABSTRACT

Spirometry is the most common and straightforward examination following the mandatory initial steps of personal history and physical examination when assessing chronic and/or recurrent lung symptoms in children, especially cough or specific conditions that can impact lung function. When dealing with a chronic cough (lasting more than four weeks), it is not uncommon to find that no specific clues regarding the cause of the cough can be deduced from the patient's history alone. Moreover, clinical examinations can be quite normal without any abnormal lung sounds. In the next step (spirometry), surprisingly, as the child forcefully expels the air from the lungs, you can hear secretions moving along the bronchi as the rapidly moving air drifts excessive sputum to the upper airways. Less commonly, forceful exhalation during spirometry may uncover a brassy or honking sound, indicating potential collapsibility of the tracheal walls. Secretions in the bronchi can imply specific conditions, such as protracted bacterial bronchitis or suppurative bronchitis. Additionally, forced exhalation may uncover sputum in other chronic lung conditions, such as cystic fibrosis or primary cilia dyskinesia. The presence of tracheomalacia is an important parameter, as it can precipitate several respiratory symptoms, ranging from prolonged cough in acute bronchitis to recurrent and/or chronic wet cough. In conclusion, forceful exhalation during spirometry has the potential to uncover secretions in the bronchi or even tracheomalacia that might otherwise go unnoticed. Before watching the flow-volume loop or interpreting the results of the spirometry parameters, we should first "hear" the spirometry.

PMID:40046377 | PMC:PMC11882152 | DOI:10.7759/cureus.78441

Cureus. 2025 Feb 3;17(2):e78408. doi: 10.7759/cureus.78408. eCollection 2025 Feb.

ABSTRACT

Cystic fibrosis liver disease (CFLD) is a common complication of cystic fibrosis (CF), typically emerging within the first two decades of life. It significantly impacts both short- and long-term prognosis, being the third leading cause of mortality in this population. We present the case of a child with a rare CF mutation who was diagnosed with CFLD, portal hypertension, esophageal varices, and early-onset CF-related diabetes at the age of 6. This case provides valuable insights into the early onset and progression of CF liver disease, highlighting the importance of timely diagnosis and management.

PMID:40046358 | PMC:PMC11880950 | DOI:10.7759/cureus.78408

Phage (New Rochelle). 2024 Dec 18;5(4):203-222. doi: 10.1089/phage.2024.0011. eCollection 2024 Dec.

ABSTRACT

Rising antibiotic resistance among bacterial pathogens has become a substantial health issue for human civilization. The emergence of these pathogens in high-risk diseases such as cystic fibrosis (CF) has led to financial and nonfinancial losses, necessitating alternative therapies. This study presents an overview of such approaches, including phage therapy, antimicrobial peptides (AMPs), nanotechnology, monoclonal antibodies (mAbs), microbial therapies (probiotic therapy), clustered regularly interspaced short palindromic repeats technology (CRISPR), and aptamers focusing on their mechanisms of action and exploring the impact of combining phage and phage derivatives with the mentioned approaches. Although alternative approaches and their combinations with phages show promise, the phage-antibiotic combination has been the subject of most studies, and It has been proven to be highly effective in combating antibiotic-resistant infections. Other combinations also appear promising, but further studies are needed to determine their effectiveness. This emphasizes the need for more thorough research into different phage combination treatments beyond the well-established phage-antibiotic strategy.

PMID:40045937 | PMC:PMC11876824 | DOI:10.1089/phage.2024.0011

J Pediatr Orthop. 2025 Mar 6. doi: 10.1097/BPO.0000000000002947. Online ahead of print.

ABSTRACT

BACKGROUND: Although cystic fibrosis (CF) mainly affects the respiratory and gastrointestinal systems, it may frequently present with musculoskeletal manifestations including bone fractures, low bone mineral density, and spinal pathologies. Assessment of spinal pathologies in CF patients is of vital importance because the effects on lung capacity and spinal posture are clearly defined.

QUESTIONS/PURPOSES: The frequency of vertebral pathologies in CF patients has yet to be determined. The aim of this study was to investigate the frequency of scoliosis and hyperkyphosis and the relationship of coronal, sagittal, and spinopelvic parameters with disease severity in CF patients.

METHODS: Patients were tested with forced expiratory volume in 1 second (FEV1), dual-energy x-ray absorptiometry (DEXA), and full spine radiographs. Measurements were taken of the major coronal curve in the coronal plane, cervical and lumber lordosis, thoracic kyphosis, and C7 plumb line values. Patients were categorized into 3 groups based on the FEV1 values (severity) from respiratory function tests (severe: group 1 FEV 1≤40, moderate: group 2 FEV1 40 to 80, mild: group).

RESULTS: This cross-sectional study included 208 CF patients aged 5 to 21 years. The rates of scoliosis and thoracic hyperkyphosis were 31% (n=64) and 24% (n=50), respectively. The highest rates of scoliosis (63%) and thoracic hyperkyphosis (56%) were found in the severe CF group (P=0.016 and P=0.006, respectively). FEV1 and thoracic kyphosis were weakly and inversely but significantly correlated (rho: -0.200 and P=0.004). There was no difference in BMD between patients with and without scoliosis and between patients with and without hyperkyphosis. There was no significant difference in DEXA Z-score between patients with and without hyperkyphosis. The L1-L4 DEXA Z-score of patients without scoliosis was significantly higher (P=0.017).

CONCLUSIONS: Scoliosis and hyperkyphosis were more prevalent in the severe CF patients group, although the proportion of patients requiring treatment was relatively low. Understanding the relationship between disease severity and coronal and sagittal spinal balance, and spinopelvic parameters is crucial, as it guides the early detection and management of scoliosis in CF patients.

LEVEL OF EVIDENCE: Level II.

PMID:40045563 | DOI:10.1097/BPO.0000000000002947

Nat Commun. 2025 Mar 5;16(1):2214. doi: 10.1038/s41467-025-57520-3.

ABSTRACT

Putting pancreatic adenocarcinoma (PAAD) screening into perspective for high-risk individuals could significantly reduce cancer morbidity and mortality. Previous studies have profiled somatic mutations in PAAD. In contrast, the prevalence of mutations in PAAD predisposition genes has not been defined, especially in the Asian population. Using a multi-tier cohort design and whole genome/exome sequencing, we create a comprehensive germline mutation map of PAAD in 1,123 Chinese cancer patients in comparison with 11 pan-ethnic studies. For well-known pathogenic/likely pathogenic germline variants, Chinese patients exhibit overlapping but distinct germline mutation patterns comparing with Western cohorts, highlighted by lower mutation rates in known PAAD genes including BRCA1, BRCA2, ATM, CDKN2A, and CHEK2, and distinct mutations in CFTR, RAD51D, FANCA, ERCC2, and GNAS exclusive to Chinese patients. CFTR emerges as a top candidate gene following loss of heterozygosity analysis. Using an integrative multi-omics and functional validation paradigm, we discover that deleterious variants of uncertain significance may compromise CFTR's tumor suppressor function, and demonstrate the clinical relevance by using patient derived organoids for drug screen. Our multifaceted approach not only deepens the knowledge of population differences in PAAD germline mutations but also unveils potential avenues for targeted therapeutic interventions.

PMID:40044664 | DOI:10.1038/s41467-025-57520-3

Int J Pharm. 2025 Mar 3:125424. doi: 10.1016/j.ijpharm.2025.125424. Online ahead of print.

ABSTRACT

Lipoplexes are non-viral lipid vectors that effectively form complexes with genetic material, positioning them as promising alternatives to viral vectors in gene therapy. Their advantages include lower toxicity, reduced immunogenicity, improved targetability, and ease of large-scale production. A typical lipoplex is composed of cationic lipids, neutral lipids, and anionic nucleic acids (e.g., DNA, mRNA, miRNA, siRNA, shRNA). Neutral lipids play an auxiliary role and are often used as transfection enhancers. Enhancing lipoplex efficiency often involves modifying the cationic lipid structure through functional groups like PEG polymers and targeting ligands. The assembly of lipoplexes occurs spontaneously. This process involves the binding of the positively charged polar head group of the cationic lipid to the negatively charged DNA spontaneously as a result of electrostatic interaction, then irreversible rearrangement and condensation of the lipoplex occurs to form either lamellar or hexagonal structures. The transfection process encompasses several steps: cellular entry, endosomal escape and cargo release, cytoplasmic trafficking, and nuclear entry. The physicochemical and biological properties of lipoplexes are influenced by factors such as lipid structure, charge ratio, and environmental conditions. Despite certain limitations like low gene transfer efficiency and rapid clearance by serum proteins, lipoplexes show promise for clinical applications. They can be administered through various routes, offering potential treatments for diseases such as cancer, bone damage, infection, and cystic fibrosis. The study aims to examine the potential of lipoplexes as a promising vehicle for delivering therapeutic agents and their progression from theoretical concepts to practical clinical applications.

PMID:40043964 | DOI:10.1016/j.ijpharm.2025.125424

Ann Am Thorac Soc. 2025 Jan;22(1):39-40. doi: 10.1513/AnnalsATS.202411-1148ED.

NO ABSTRACT

PMID:40043192 | DOI:10.1513/AnnalsATS.202411-1148ED

Ann Am Thorac Soc. 2025 Mar 5. doi: 10.1513/AnnalsATS.202408-831OC. Online ahead of print.

ABSTRACT

RATIONALE: Since the approval of elexacaftor/tezacaftor/ivacaftor (ETI), data suggests there have been changes in the management of pulmonary exacerbations (PEx) of Cystic Fibrosis (CF).

OBJECTIVE: Given the subjective nature of PEx diagnosis and management, we sought to characterize provider PEx management practices in people with CF (pwCF) prescribed highly effective modulator therapy (HEMT) and to identify practice changes that may impact clinical outcomes.

METHODS: We conducted semi-structured qualitative interviews amongst clinicians in the United States (US) in late 2021 to 2022 to investigate changes in the management of PEx in pwCF prescribed ETI. Inductive coding of transcripts was utilized in a thematic analysis.

RESULTS: We conducted 19 qualitative interviews with providers at 15 CF centers. Thematic analysis identified five themes regarding the presentation, diagnosis, and management of PEx in pwCF prescribed ETI: (1) PEx have changed in the era of HEMT to become a more subtle pathology that may result in providers questioning PEx diagnosis; (2) providers feel less anxious about clinical outcomes after PEx; (3) providers are expanding their assessment of PEx in the era of HEMT to identify more subtle PEx phenotypes; (4) pwCF are driving their care during PEx more than in the pre-HEMT era, with interviewees reporting that some "patients don't really contact us [with mild PEx symptoms]…we hear about it in retrospect." Interviewees expressed concern that this may result in more severe PEx; (5) provider management is less aggressive in the post-HEMT era, reflecting reduced PEx severity. Participants emphasized that their approach to PEx in general is unchanged and that "[providers] treat depending on severity…and the background of the patient." Interviewees reported they increasingly recommend maintenance therapies for PEx treatment before prescribing antibiotics.

CONCLUSIONS: Participants report that PEx in pwCF prescribed ETI appear milder, resulting in less anxiety about outcomes and a more conservative approach to management. Providers express uncertainty regarding the diagnosis of PEx given its evolving presentation and reduced in-person evaluation. Further research is necessary to identify sensitive markers of PEx and to assess the impact of conservative management on clinical outcomes.

PMID:40042492 | DOI:10.1513/AnnalsATS.202408-831OC

mBio. 2025 Mar 5:e0388324. doi: 10.1128/mbio.03883-24. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in CFTR protein dysfunction. CFTR dysfunction has multi-organ consequences, leading to dehydrated mucus that is adherent to epithelia. In the lungs, this leads to recalcitrant infections with bacteria such as Pseudomonas aeruginosa. In the gut, mucus-laden feces can adhere to the intestines, resulting in distal intestinal obstruction syndrome (DIOS). There is limited information on how lung colonization and DIOS are correlated in people with CF (pwCF). In this novel work, we describe the development of spontaneous lung colonization of CF pathogens in young (<3 months old) CF rats, preceding the development of DIOS. Once DIOS is established, the lung microbiome becomes predominated by taxa also observed in the feces. Induced infection with P. aeruginosa in the CF rats reflects data found in pwCF, as once CF rats are infected, they retain a higher relative abundance of P. aeruginosa than their healthy agemates. Finally, we found that ivacaftor treatment favors a healthier gut microbiome in CF rats, decreasing the relative abundance of Escherichia coli. These results indicate that the CF rat model is recapitulative of human CF disease with the spontaneous lung colonization of traditional CF pathogens and maintenance of P. aeruginosa after induced infection. Furthermore, these results indicate a possible role for the gut-lung axis in lung colonization and DIOS in CF.IMPORTANCEThese data describe for the first time the development of spontaneous lung colonization in the cystic fibrosis (CF) rat model, a hallmark aspect of human CF disease. We also find that CF rats infected with Pseudomonas aeruginosa maintain higher relative abundance following chronic infection as compared to healthy rats, similar to those is seen in people with CF. Additionally, we describe the possible contribution of the gut-lung axis linking lung health with distal intestinal obstruction syndrome, a relationship largely unexplored in the context of CF.

PMID:40042272 | DOI:10.1128/mbio.03883-24

Pediatr Pulmonol. 2025 Mar;60(3):e71035. doi: 10.1002/ppul.71035.

NO ABSTRACT

PMID:40042147 | DOI:10.1002/ppul.71035

Pediatr Pulmonol. 2025 Mar;60(3):e71024. doi: 10.1002/ppul.71024.

ABSTRACT

BACKGROUND: Systemic antibiotics can impact all microbes inhabiting patients, regardless of the intended target organism(s). We studied the simultaneous effects on respiratory and fecal microbiomes of β-lactam antibiotics administered for respiratory symptoms in infants with cystic fibrosis (IWCF).

OBJECTIVE: To compare the magnitude and duration of intended (respiratory) and unintended (fecal) antimicrobial action by analyzing oropharyngeal (OP) and fecal microbiota in IWCF.

DESIGN: Shotgun metagenomic sequencing and qPCR were performed on OP and fecal samples collected longitudinally from 14 IWCF (ages 1-17 months) during ("On Antibiotics") and after ("Off Antibiotics") β-lactam therapy, and from 5 IWCF (3-16 months) never treated with antibiotics.

RESULTS: Total bacterial loads (TBL) for On Antibiotics samples were lower than for both Never (OP and fecal) and Off Antibiotics samples (fecal only). α-diversities (within-sample) for OP On Antibiotics samples were lower than for Never and Off Antibiotics samples but did not differ between fecal sample groups. β-diversity (between-sample) differed between all OP sample groups and between fecal On and Never Antibiotics and Off and Never antibiotics samples; however, fecal On and Off Antibiotics sample β-diversities did not differ. Patterns of change in antibiotic resistance gene abundances reflected shifts in microbial community composition.

CONCLUSIONS: β-lactam antibiotic exposure was followed by marked alterations in both OP and fecal microbiota. While microbiota appeared to rebound after treatment in both sample types, our results suggest that fecal microbiota recovered less than OP. The clinical consequences of these findings should be studied in IWCF and other populations frequently treated with antibiotics.

PMID:40042126 | DOI:10.1002/ppul.71024

Afr J Thorac Crit Care Med. 2024 Dec 11;30(4):e1899. doi: 10.7196/AJTCCM.2024.v30i4.1899. eCollection 2024.

ABSTRACT

BACKGROUND: Bronchiectasis, a chronic suppurative lung condition, is a largely neglected disease, especially in low- to middle-income countries (LMICs), from which there is a paucity of data. Post-infectious causes are more common in LMICs, while in high-income countries, inborn errors of immunity (IEIs), recurrent aspiration, primary ciliary dyskinesia (PCD) and cystic fibrosis are more common. Children living with HIV (CLWH), especially those who are untreated, are at increased risk of bronchiectasis. Data on risk factors, diagnosis and follow-up of children with bronchiectasis are required to inform clinical practice and policy.

OBJECTIVES: To describe the demographics, medical history, aetiology, clinical characteristics and results of special investigations in children with bronchiectasis.

METHODS: We undertook a retrospective descriptive study of children aged <16 years with chest computed tomography (CT) scan-confirmed bronchiectasis in Johannesburg, South Africa, over a 10-year period. Demographics, medical history, aetiology, clinical characteristics and results of special investigations were described and compared according to HIV status.

RESULTS: A total of 91 participants (51% male, 98% black African) with a median (interquartile range) age of 7 (3 - 12) years were included in the study. Compared with HIV-uninfected children, CLWH were older at presentation (median 10 (6 - 13) years v. 4 (3 - 9) years; p<0.01), and more likely to be stunted (p<.01), to have clubbing (p<0.01) and hepatosplenomegaly (p=0.03), and to have multilobar involvement on the chest CT scan (p<0.01). All children had a cause identified, and the majority (86%) of these were presumed to be post-infectious, based on a previous history of a severe lower respiratory tract infection. This group included all 38 CLWH. Only a small proportion of the participants had IEIs, secondary immune deficiencies or PCD.

CONCLUSION: A post-infectious cause for bronchiectasis was the most common aetiology described in children from an LMIC in Africa, especially CLWH. With improved access to diagnostic techniques, the aetiology of bronchiectasis in LMICs is likely to change.

STUDY SYNOPSIS: What the study adds. In this retrospective descriptive study of children aged <16 years with chest computed tomography scan-confirmed bronchiectasis in Johannesburg, South Africa (SA), over a 10-year period, we report that a post-infectious cause for bronchiectasis was the most commonly described, and that HIV was an important contributor. A large proportion of children with bronchiectasis in low- and middle-income countries such as SA do not benefit from an extensive work-up for the non-infectious causes of bronchiectasis.Implications of the findings. With improved access to diagnostic techniques, including improvements in early diagnosis and access to treatment for children living with HIV, the aetiology of bronchiectasis is likely to change in the coming years.

PMID:40041419 | PMC:PMC11874181 | DOI:10.7196/AJTCCM.2024.v30i4.1899

Afr J Thorac Crit Care Med. 2024 Dec 11;30(4):e2884. doi: 10.7196/AJTCCM.2024.v30i4.2884. eCollection 2024.

NO ABSTRACT

PMID:40041417 | PMC:PMC11874178 | DOI:10.7196/AJTCCM.2024.v30i4.2884