The Impact of Age of Diagnosis in Children with Primary Ciliary Dyskinesia.

RATIONALE: The typical symptoms for primary ciliary dyskinesia (PCD) manifest after birth and in early infancy, however diagnosis is often not confirmed during infancy. There is currently a lack of evidence in PCD regarding the impact of the age of diagnosis on clinical outcomes. OBJECTIVE: To determine whether early diagnosis is related to improved long-term outcomes. METHOD: This was a retrospective study of patients diagnosed with PCD between 2000 to 2022. We divided our cohort to three groups according to the age of diagnosis. 1) early diagnosis (<1 year); typical diagnosis (1-7 years) and late diagnosis (8-14 years). We compared various clinical long-term outcomes between the groups. RESULTS: Over the study period, 110 patients were included in the analysis, with 41 patients in the early diagnosis group, 35 in the typical diagnosis group and 34 patients in the late diagnosis group. The presence of unexplained neonatal respiratory distress (NRDS) and organ laterality defect were higher in the early diagnosis group with rates between the early, typical, and late diagnosis groups for NRDS (80% vs 53% vs 61%, p=0.045) and laterality defect (64% vs 50% vs 18%, p<0.001). At the end of the first decade of life, patients in the early diagnosis and the typical age of diagnosis had better forced expiratory volume in 1 second (FEV1), compared to the late diagnosis group (93.5% and 93.1% vs 80.2%, P=0.002), respectively, but there was no significant change in the annual rate of decline between the groups once diagnosis was confirmed. Patient diagnosed late had significantly higher rates of pulmonary exacerbations (Pex) compared to typical age (1.95 vs 0.75 Pex/year, p<0.01) Conclusion: Late diagnosis (>8 years) was associated with lower FEV1 throughout childhood, although once diagnosed, the annual rate of decline was not different. These findings demonstrate the negative effect of delayed diagnosis in pediatric PCD.

Fighting to Breathe and Fighting for Health-Related Quality of Life: Measuring the Impact of Being Dependent on Technology for Breathing on the Child and Their Caregiver.

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.

Treatment response to pulmonary exacerbation in primary ciliary dyskinesia.

INTRODUCTION: Pulmonary exacerbation (Pex) are common in pediatric primary ciliary dyskinesia (PCD), however changes in forced expiratory volume in 1 s precent predicted (FEV1pp) during Pex are not well described. AIM: To assess the evolution of FEV1pp during Pex and to define factors associated with failure to return to baseline lung function. METHOD: This was a retrospective study of patients with PCD between 2010 and 2022. Pex were defined as the presence of increased respiratory symptoms treated with intravenous (IV) antibiotics. The main outcomes were the changes in FEV1 during therapy and the proportion of patients (responders) achieving ≥90% of baseline FEV1pp values at the end of admission. RESULTS: The study included 52 Pex events in 28 children with PCD. The rate of responders was 32/41 (78%) at the end of admission. Nonresponse was associated with lower median body mass index (BMI) Z-score (-2.4 vs. -0.4, p < .01) and with a history of IV treated Pex in the previous year (p = .06). For the 22 Pex with available FEV1pp measurements at mid admission, the median relative and absolute improvement from admission to Day 7 was 9.1% and 6.2%, respectively (p- .001), and from Days 7 to 14 was 4.4% and 2.8%, respectively (p = .08). CONCLUSION: In children with PCD treated with IV antibiotics, the majority of lung function recovery happens during the first week of IV therapy. Lower BMI was associated with nonresponse to therapy.

No decrease in annual risk of tuberculosis infection in endemic area in Cape Town, South Africa.

OBJECTIVE: To estimate the change in annual risk of tuberculosis infection (ARTI) in two neighbouring urban communities of Cape Town, South Africa with an HIV prevalence of approximately 2%, and to compare ARTI with notification rates and treatment outcomes in the tuberculosis (TB) programme. METHODS: In 1998-1999 and 2005, tuberculin skin test surveys were conducted to measure the prevalence of Mycobacterium tuberculosis infection and to calculate the ARTI. All 6 to 9-year-old children from all primary schools were included in the survey. Notification rates and treatment outcomes were obtained from the TB register. RESULTS: A total of 2067 children participated in the survey from 1998 to 1999 and a total of 1954 in 2005. Based on a tuberculin skin test cut-off point of 10 mm, the ARTI was 3.7% (3.4-4.0%) in the 1998-1999 survey and 4.1% (3.8-4.5%) in 2005. The notification rate for pulmonary TB increased significantly from 646 per 100 000 in 1998 to 784 per 100,000 in 2002. In Ravensmead, there was no significant change in ARTI [first survey: 3.5% (3.1-3.9%), second survey: 3.2% (2.9-3.6%)], but in Uitsig the ARTI increased significantly from 4.1% (3.6-4.6%) to 5.8% (5.2-6.5%). The difference in ARTI between the two areas was associated with differences in reported case rates and the proportion of previously treated cases. CONCLUSION: Tuberculosis transmission remains very high in these two communities and control measures to date have failed. Additional measures to control TB are needed.

Acute demyelinating encephalomyelitis (ADEM), cryptococcal reactivation and disseminated Herpes simplex in an HIV infected child following HAART.

Highly active antiretroviral treatment (HAART) is increasingly becoming available for HIV infected children in South Africa. We describe a 7-year-old HIV infected child (CD4=10, viral load =180,669copies/ml) who develops a cryptococcal meningitis, with raised intracranial pressure, complicated by ADEM and disseminated Herpes simplex infection following commencement of HAART.

Descriptive analysis of central sleep apnea in childhood at a single center.

UNLABELLED: Data on central sleep apnea (CSA) and its significance in children are limited. Our objectives were to describe the polysomnogram (PSG) characteristics and clinical features of children with significant CSA at a single pediatric sleep center. STUDY DESIGN AND METHODS: A retrospective chart review of children diagnosed with CSA on a PSG, from January 2007 to December 2008, was performed. All the PSG's were performed in the pediatric sleep laboratory at The Hospital for Sick Children in Toronto, Canada. All children diagnosed with significant CSA with a PSG was eligible for inclusion. Each PSG was conducted and scored according to the American Academy of Sleep Medicine standard. Significant CSA was defined as a central apnea index (CAI) of >5 events/hr. Outcome for each patient was defined by the percentage change in the CAI at follow up. RESULTS: 52/969 (5.4%) patients had a CAI > 5/hr on a baseline PSG. Of the 25/52 (13 males) patients who met inclusion criteria, the median age was 19 months (range 3-156 months) and their median BMI z score was +0.27 (range -2.95 to 3.02). The median CAI was 11 events/hr (range 6-198/hr). The mean oxygen saturations ranged from 92.8% to 98.5%, with a median of 97%. Six (24%) patients had associated sleep-related hypoventilation and none of the patients had periodic breathing. The commonest identifiable risk factor for CSA in the study population was a neurological disorder. CONCLUSIONS: This study confirms that CSA is an important finding in a significant number of young children referred for an evaluation for suspected sleep related disordered breathing. Any child diagnosed with CSA warrants full clinical assessment, including neuro-imaging. Future research should aim to evaluate the long term outcome of significant CSA.