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Abstract Background Pneumocystis pneumonia (PCP) is a major cause of hospitalization and mortality in HIV-infected African children. Microbiologic diagnosis relies predominantly on silver or immunofluorescent staining of a lower respiratory tract (LRT) specimens which are difficult to obtain in children. Diagnosis on upper respiratory tract (URT) specimens using PCR has been reported useful in adults, but data in children are limited. The main objectives of the study was (1) to compare the diagnostic yield of PCR with immunofluorescence (IF) and (2) to investigate the usefulness of upper compared to lower respiratory tract samples for diagnosing PCP in children. Methods Children hospitalised at an academic hospital with suspected PCP were prospectively enrolled. An upper respiratory sample (nasopharyngeal aspirate, NPA) and a lower respiratory sample (induced sputum, IS or bronchoalveolar lavage, BAL) were submitted for real-time PCR and direct IF for the detection of Pneumocystis jirovecii. A control group of children with viral lower respiratory tract infections were investigated with PCR for PCP. Results 202 children (median age 3.3 [inter-quartile range, IQR 2.2 - 4.6] months) were enrolled. The overall detection rate by PCR was higher than by IF [180/349 (52%) vs. 26/349 (7%) respectively; p < 0.0001]. PCR detected more infections compared to IF in lower respiratory tract samples [93/166 (56%) vs. 22/166 (13%); p < 0.0001] and in NPAs [87/183 (48%) vs. 4/183 (2%); p < 0.0001]. Detection rates by PCR on upper (87/183; 48%) compared with lower respiratory tract samples (93/166; 56%) were similar (OR, 0.71; 95% CI, 0.46 - 1.11). Only 2/30 (6.6%) controls were PCR positive. Conclusion Real-time PCR is more sensitive than IF for the detection of P. jirovecii in children with PCP. NPA samples may be used for diagnostic purposes when PCR is utilised. Wider implementation of PCR on NPA samples is warranted for diagnosing PCP in children.

The article presents a case study of a seven-month-old, a HIV-unexposed male, was taken to the hospital due to increased work of breathing and progressive shortness of breath. It mentions the symptoms like fever, vomiting and pyrexia of the patient, and states that he was diagnosed with varicella pneumonia to stahphylococcus aureus with pneumatoceles. It also mentions the use of computed tomography (CT) that showed enlarged anterior mediastinal mass of the patient.

A 31-week gestation male infant with respiratory distress since day of delivery had lobectomy at 8 weeks of age for symptomatic, suspected congenital pulmonary airway malformation (CPAM). Histology of resected lung showed cytomegalovirus (CMV) inclusion bodies and emphysematous changes. The infant was treated with antiviral therapy with improvement in symptoms. CMV infection of the lung should be considered in any neonate presenting with lung cysts., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Background: Factors associated with severe COVID-19 infection have been identified; however, the impact of infection on longer-term outcomes is unclear. The objective of this study was to examine the impact of COVID-19 infection on the trajectory of lung function and nutritional status in people with cystic fibrosis (pwCF)., Methods: This is a retrospective global cohort study of pwCF who had confirmed COVID-19 infection diagnosed between January 1, 2020 and December 31, 2021. Forced expiratory volume in one second percent predicted (ppFEV 1 ) and body mass index (BMI) twelve months prior to and following a diagnosis of COVID-19 were recorded. Change in mean ppFEV 1 and BMI were compared using a t-test. A linear mixed-effects model was used to estimate change over time and to compare the rate of change before and after infection., Results: A total of 6,500 cases of COVID-19 in pwCF from 33 countries were included for analysis. The mean difference in ppFEV 1 pre- and post-infection was 1.4 %, (95 % CI 1.1, 1.7). In those not on modulators, the difference in rate of change pre- and post-infection was 1.34 %, (95 % CI -0.88, 3.56) per year (p = 0.24) and -0.74 % (-1.89, 0.41) per year (p = 0.21) for those on elexacaftor/tezacaftor/ivacaftor. No clinically significant change was noted in BMI or BMI percentile before and after COVID-19 infection., Conclusions: No clinically meaningful impact on lung function and BMI trajectory in the year following infection with COVID-19 was identified. This work highlights the ability of the global CF community to unify and address critical issues facing pwCF., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors of this manuscript receive funding in the form of consulting fees or honoraria from Vertex Pharmaceuticals, Chiesi Pharmaceuticals, Enterprise Therapeutics, Gilead Sciences, GSK, Astra-Zeneca, Insmed, MSD, Sanofi, Viartis, Zambon, Limbic, Effrx Pharmaceuticals and Omron. Additionally, there is an author who serves on the Novartis Data and Safety Monitoring Board. There are several authors who are employed by the Cystic Fibrosis Foundation (CFF). The CFF, to advance drug development and search for a cure, have contracts with several companies to help fund the development of potential treatments and/or cures for cystic fibrosis. Pursuant to these contracts, CFF may receive milestone-based payments, equity interests, royalties on the net sales of therapies, and/or other forms of consideration. Resulting revenue received by CFF is used in support of our mission. See “How Drugs Get on the Pipeline” on the CFF website for more information. Additionally, CFF may license CFF Patient Registry data to some companies to monitor drug safety as part of the U.S. Food and Drug Administration's required Phase 4 clinical trials process and to encourage research aimed at improving the care of people with CF, while maintaining our obligation and commitment to protect the privacy of Registry participants. In connection with these licenses, and upon request, CFF may also assist company researchers in interpreting CFF Patient Registry data to aid in designing, analyzing, and interpreting real world studies in CF., (Copyright © 2024. Published by Elsevier B.V.)

Primary ciliary dyskinesia (PCD) is an inherited ciliopathy that results in impaired mucous clearance and affects primarily the respiratory tract, causing upper airway disease, bronchial inflammation and bronchiectasis. The prevalence of PCD in low- and middle-income settings, including South Africa (SA), is unknown, largely owing to challenges with diagnosis, and identifying children or adults with PCD is challenging in a setting with a high prevalence of other infectious diseases, including lower respiratory tract infections and tuberculosis. No single test is diagnostic of PCD, and while some tests are costly, others are labour intensive and require highly specialised laboratory expertise. In the SA setting, awareness and opportunities for the diagnosis of PCD need to be created. In this commentary, we provide a pragmatic approach to identifying which children and adults require further investigations for PCD using a range of diagnostic tests or tools that are available. Furthermore, we recommend that designated centres of expertise for PCD diagnosis are created in SA. This would be an important step towards improving accessibility of diagnostic tests and developing local expertise to improving PCD diagnosis, especially in early childhood, to prevent long-term irreversible respiratory sequelae.

Long-term ventilation (LTV) in children at home, especially invasive ventilation, is not widely available nor practised in low-resource settings (LRS). Barriers to providing LTV include underdeveloped pediatric critical care services, limited expertise in pediatric LTV, limited capacity to screen for sleep-disordered breathing (SDB) and high cost of LTV equipment and consumables. Additional challenges encountered in LRS may be unreliable electricity supply and difficult socioeconomic conditions. Where LTV at home has been successfully implemented, caregivers and families in LRS must often take full responsibility for their child's care as professional home-based nursing care is scarce. Selecting suitable children and families to offer LTV in LRS may therefore face difficult ethical decisions when families are disempowered or incapable of providing 24-h care at home. Early caregiver participation and hands-on training in tracheostomy care and LTV equipment is key to success, irrespective of the caregiver's level of education. The use of overnight oximetry, mobile phone technology, spirometry, and clinical evaluation are simple tools that can aid recognition and monitoring of children needing LTV. As children survive longer supported by LTV, engaging with adult services at an early stage is important to ensure suitable pathways for transition to adult care are in place. Building capacity and expertise in pediatric LTV in LRS requires targeted training of health professionals in related disciplines and advocacy to policymakers and funders that LTV in appropriately selected circumstances is worthwhile, life-changing, and cost-saving., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Confirming the aetiology of pleural effusion in children may be difficult in TB-endemic settings. We investigated the role of polymerase chain reaction (PCR) and routine biochemical tests in discriminating pleural effusion caused by bacteria from other aetiologies.This is a cross-sectional post-hoc analysis among children with pleural effusion in a tertiary hospital in South Africa, incorporating new data from PCR testing of stored pleural fluid. Aetiological classification was defined by microbiological confirmation.Ninety-one children were enrolled; the median age 31 months (IQR 12-102). The aetiology of pleural effusion was 40% (36/91) bacteria, 11% (10/91) TB, 3% (3/91) viruses, 11% (10/91) polymicrobial and 35% (32/91) had no pathogen identified. The most common pathogen was Staphylococcus aureus (27/91, 30%) with similar yields on culture and PCR, followed by Streptococcus pneumoniae (12/91, 13%), detected more commonly by PCR. PCR reduced the number of children with unconfirmed aetiologies from 48 to 32. Characteristics of children with no pathogen most resembled those with TB. Pleural fluid lactate dehydrogenase ≥1,716 U/L best discriminated bacterial pleural effusion from other aetiologies (sensitivity of 86%; specificity 95%).PCR improved detection of pathogens and reduced number of children with unconfirmed aetiologies in presumed exudative pleural effusion..

Background: Outcomes of cystic fibrosis (CF) differ between low-middle income and high-income countries, but comparative data are lacking. We compared South African (SA) and Canadian CF outcomes to explore what disparities existed prior to access of CFTR modulators in Canada., Methods: A cross-sectional study of SA and Canadian CF registries data for period 1 January to 31 December 2018. CF registry data were harmonised between countries to compare lung function and nutrition outcomes. Poor nutrition was defined as BMIz-score < -1 in children and < 18.5 kg/m 2 in adults. Standardised mean difference (SMD) >10 was considered significant., Results: After excluding Canadians on CFTR modulators and lung transplant recipients, data on 4049 Canadian and 446 SA people was analysed. Compared to Canada, people in SA were younger (median age 15.8 years vs. 24.1 years: SMD 52) with fewer males (47.8% vs 54.2%; SMD 12.5) and White (70.9% vs. 93.3%; SMD 61.3). Class I-III CFTR mutation frequency was similar in SA (n = 384, 86.1%) and Canada (n = 3426, 84.9%). After adjusting for age, gender, diagnosis age, genotype, P.aeruginosa infection and pulmonary treatments, FEV1pp was 8.9% lower (95% CI 6.3% to 11.4%) and poor nutrition 1.7-fold more common (OR 1.70; 95% CI 1.19-2.41) in SA compared to Canada., Conclusion: Lung function and nutrition was significantly lower in SA compared to Canada. Global disparities in CF outcomes between high and low-middle income countries are likely to widen as CFTR modulators are rapidly scaled up in only high-income countries., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Medical advancement has enabled children to survive congenital airway anomalies, rare diseases and critical illnesses with medical technology including tracheostomies and long-term ventilation to support breathing. This study aimed to assess (1) the validity of the EQ-TIPS and EQ-5D-Y-3L in children dependent on technology and (2) the impact of caring for these children on the EQ-5D-5L and CarerQoL., Methods: Caregivers of children aged 1 month to 18 years completed the EQ-TIPS or EQ-5D-Y-3L, Pediatric Quality of Life Inventory (PedsQL) and Paediatric Tracheostomy Health Status Instrument (PTHSI) to reflect the child's health. In addition, caregivers self-completed the EQ-5D-5L and CarerQoL. Reports of problems on EQ dimensions were compared across age groups with the Fisher's exact test. Spearman and Pearson's correlation coefficients and Kruskal-Wallis H-test were used to explore the association between caregiver and child scores, concurrent validity, and known-group validity of the EQ-TIPS and EQ-5D-Y-3L., Results: Responses from 144 caregivers were collected, 66 for children aged 1 month to 4 years completing EQ-TIPS and 78 for children aged 5-18 years completing EQ-5D-Y-3L. The EQ-TIPS showed a higher report of no problems for social interaction for children aged 1-12 months (p = 0.040) than the older age groups, there were however no differences in the level sum score (LSS) or EQ Visual Analogue Scale scores between the age groups. The EQ-5D-Y-3L showed a significantly less report of problems for mobility (p = 0.013) and usual activities (p = 0.006) for children aged 5-7 years compared with children aged 8-12 and children aged 13-18 years. Similarly, the 5-7 years of age group had a significantly lower EQ-5D-Y-3L LSS compared with the older groups (H = 12.08, p = 0.002). The EQ-TIPS and EQ-5D-Y-3L showed moderate-to-strong associations with the PedsQL. EQ-TIPS median LSS was able to differentiate between groups on the clinical prognosis with a better health-related quality of life (HRQoL) in those where weaning from technology is possible compared with those where weaning is not possible (H = 18.98, p = 0.011). The EQ-5D-Y-3L can discriminate between breathing technology, where those with only a tracheostomy reported better HRQoL (H = 8.92, p = 0.012), and between mild and moderate clinical severity (H = 19.42, p < 0.001). Neither the PedsQL nor the PTHSI was able to discriminate between these groups across the age range. Caregiver and child HRQoL scores showed moderate-to-strong associations., Conclusions: The EQ-TIPS and EQ-5D-Y-3L showed good validity in children dependent on the technology for breathing. The EQ-TIPS and EQ-5D-Y-3L LSS were all able to differentiate between children with known clinical variables and outperformed both the PedsQL and PTHSI, making them preferable for intervention research. The caregiver scores are associated with the child HRQoL scores and thus a spill-over should be accounted for in any interventions targeting this cohort. It is recommended that future studies investigate the reliability and responsiveness of these measures in children dependent on technology for breathing., (© 2023. The Author(s).)

Mycobacterium abscessus is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Guérin (BCG) vaccination may impact NTM infection, using a murine model of Mycobacterium abscessus infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD4 + T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with M. abscessus afforded the highest level of protection against M. abscessus challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4 + T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for M. abscessus . This study provides evidence that routine BCG vaccination may reduce M. abscessus colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4 + T cells recognising M. abscessus in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF.

Objectives: Pulmonary hypertension (PH) secondary to obstructive sleep apnea (OSA) is an uncommon but serious perioperative risk factor in children undergoing surgery for adenotonsillar hypertrophy. Routine pre-operative echocardiography is commonly requested if severe OSA is suspected. We investigated the incidence of PH in children with suspected OSA and explored the association between PH and OSA severity., Methods: A prospective study of children aged 1-13 years with suspected OSA admitted for overnight oximetry (OO) and echocardiography at a pediatric referral hospital in Cape Town, South Africa from 2018 to 2019. OSA severity was defined by McGill Oximetry Score (MOS): MOS 1-2 (mild-moderate) and MOS 3-4 (severe). PH was defined as mean pulmonary arterial pressure (mPAP) ≥20 mmHg estimated on echocardiographic criteria. Children with congenital heart disease, underlying cardio-respiratory or genetic disorders, and severe obesity were excluded., Results: One hundred and seventy children median age 3.8 years (IQR 2.7-6.4) were enrolled and 103 (60%) were female. Twenty-two (14%) had a BMIz >1.0 and 99 (59%) had tonsillar enlargement grade 3/4. One hundred and twenty-two (71%) and 48 (28%) children had mild-moderate and severe OSA, respectively. Echocardiographic assessment for PH was successful in 160 (94%) children of which eight (5%) had PH with mPAP 20.8 mmHg (SD 0.9): six with mild-moderate OSA and two with severe OSA. No significant difference in mPAP and other echocardiographic indices was observed in children with mild-moderate (16.1 mmHg; SD 2.4) and severe OSA (15.7 mmHg; SD 2.1). Similarly, no clinical and OSA severity differences were observed in children with and without PH., Conclusion: PH is uncommon in children with uncomplicated OSA and there is no association of PH with severity of OSA measured by OO. Routine echocardiographic screening for PH in children with clinical symptoms of OSA without co-morbidity is unwarranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Investigating inconclusive cystic fibrosis (CF) diagnosis in children is difficult without advanced cystic fibrosis transmembrane conductance regulator (CFTR) function tests. This study investigated the utility of beta (β)-adrenergic sweat test to exclude CF in participants with inconclusive diagnosis (CF suspects) in South Africa., Methods: β-adrenergic sweat test and sweat chloride tests (SCT) were performed simultaneously in CF suspects and adult controls (healthy, CFTR heterozygotes and CF). Cholinergic and β-adrenergic induced sweat rate was measured by evaporimetry (transepithelial water loss [TEWL]: g H 2 O/m 2 /h) following intradermal injections. Next-generation sequencing of CFTR was performed in CF suspects. CF diagnosis was defined by genotype., Results: Thirty-seven controls (10 healthy, 14 CF, 13 CFTR heterozygotes) and 32 CF suspects (26 children; 6 adults) were enrolled. Six were excluded from formal analyses due to β-adrenergic sweat test failure. In adults, evaporimetry was superior to SCT for diagnosis of CF with β-adrenergic:cholinergic ratio TEWL ≤ 0.05 achieving 100% sensitivity and specificity. Twenty-two CF suspect children (age range: 3.4-15.6 years) completed β-adrenergic sweat testing of which none had CF confirmed by genotyping: β-adrenergic:cholinergic ratio > 0.05 successfully excluded CF in all but one child who was CFTR heterozygous. Median peak β-adrenergic TEWL and β-adrenergic:cholinergic ratio in CFTR negative and CFTR heterozygous children was significantly lower than adult controls., Conclusion: β-adrenergic sweat test is more accurate than SCT for excluding CF in children with inconclusive diagnosis. Established reference ranges for β-adrenergic sweat test may not be suitable for children due to lower β-adrenergic sweat secretion compared to adults., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Consensus on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) is lacking, and comparison between studies remains difficult due to a large variety in outcome measures. We aimed to define a core outcome set (COS) for pediatric patients with an asymptomatic CPAM. An online, three-round Delphi survey was conducted in two stakeholder groups of specialized caregivers (surgeons and non-surgeons) in various European centers. Proposed outcome parameters were scored according to level of importance, and the final COS was established through consensus. A total of 55 participants (33 surgeons, 22 non-surgeons) from 28 centers in 13 European countries completed the three rounds and rated 43 outcome parameters. The final COS comprises seven outcome parameters: respiratory insufficiency, surgical complications, mass effect/mediastinal shift (at three time-points) and multifocal disease (at two time-points) . The seven outcome parameters included in the final COS reflect the diversity in priorities among this large group of European participants. However, we recommend the incorporation of these outcome parameters in the design of future studies, as they describe measurable and validated outcomes as well as the accepted age at measurement.

Background: This international study aimed to characterise the impact of acute SARS-CoV-2 infection in people with cystic fibrosis and investigate factors associated with severe outcomes. Methods Data from 22 countries prior to 13 th December 2020 and the introduction of vaccines were included. It was de-identified and included patient demographics, clinical characteristics, treatments, outcomes and sequalae following SARS-CoV-2 infection. Multivariable logistic regression was used to investigate factors associated with clinical progression to severe COVID-19, using the primary outcome of hospitalisation with supplemental oxygen., Results: SARS-CoV-2 was reported in 1555 people with CF, 1452 were included in the analysis. One third were aged <18 years, and 9.4% were solid-organ transplant recipients. 74.5% were symptomatic and 22% were admitted to hospital. In the non-transplanted cohort, 39.5% of patients with ppFEV1<40% were hospitalised with oxygen verses 3.2% with ppFEV >70%: a 17-fold increase in odds. Worse outcomes were independently associated with older age, non-white race, underweight body mass index, and CF-related diabetes. Prescription of highly effective CFTR modulator therapies was associated with a significantly reduced odds of being hospitalised with oxygen (AOR 0.43 95%CI 0.31-0.60 p<0.001). Transplanted patients were hospitalised with supplemental oxygen therapy (21.9%) more often than non-transplanted (8.8%) and was independently associated with the primary outcome (Adjusted OR 2.45 95%CI 1.27-4.71 p=0.007)., Conclusions: This is the first study to show that there is a protective effect from the use of CFTR modulator therapy and that people with CF from an ethnic minority are at more risk of severe infection with SARS-CoV-2., Competing Interests: COI Statement All authors declare no conflicts of interest in relationship to this work. Outside of this work the following authors declare payments or honoraria to them or their institution for a combination of lectures, presentations, educational events, advisory boards, steering groups, grants or consultancy fees: SC-Vertex, Chiesi, Profile, Zambon. RC- Vertex, P-RB – Astra-Zeneca, Boehringer Ingelheim, GSK, Insmed, Chiesi, Pfizer, Vertex, Zambon. I deM – Vertex,LN – Vertex, Boehringer,LVS-F – Vertex, AS -Vertex., (Copyright © 2022. Published by Elsevier B.V.)