Whooping Cough Cases Increase in Central Italy after COVID-19 Pandemic.

Pertussis continues to be a highly contagious respiratory infection, especially in children, with cyclical peaks of disease spread every three to five years. Here, we report relevant cases of B. pertussis infection between August 2023 and January 2024, and compare them with B. pertussis prevalence in pediatric patients admitted to the Reference Italian Pediatric Hospital, located in Rome, from January 2015 to July 2023. A total of 5464 tests for B. pertussis were performed during the study period, and 6.9% were positive. At the time of the COVID-19 pandemic, there was a sharp decrease in the presence of B. pertussis, which reappeared only in August 2023, recording five new cases. All five children presented with paroxysmal cough 5 to 10 days before admission. Four patients had other mild respiratory symptoms and moderate B. pertussis DNA levels (Ct mean: 26). Only one child, with very high B. pertussis DNA levels (Ct: 9), presented with severe respiratory failure. The patients with mild/moderate infection achieved clinical recovery while the patient with the severe manifestation died of cardiac arrest. These observations highlight the reemergence of pertussis even in vaccinated countries and its association with morbidity and mortality especially in young children. This emphasizes the importance of rapid diagnosis to immediately implement appropriate treatment and monitoring of immune status.

Use of an Orthodontic and Otolaryngological Approach in an Infant with Holoprosencephaly.

Holoprosencephaly is a complex human brain malformation resulting from incomplete cleavage of the prosencephalon into both hemispheres. Congenital nasal pyriform aperture stenosis (CNPAS) is sometimes found in patients with mild forms of holoprosencephaly. Surgical treatment is required. Low-invasive surgical approaches involve balloon dilation of the pyriform opening. We present the case of an 8-day-old girl diagnosed with holoprosencephaly, CNPAS, and the presence of a solitary median maxillary central incisor. Once examined by neonatologist, geneticist, pneumologist, otolaryngologist, and pediatric dentist, a combined otolaryngological-orthodontic approach was used. The obstruction of the right nasal cavity was treated by widening the nasal cavities and stabilizing them with a balloon dilation technique. After surgery, the respiratory space was increased by applying a neonatal palatal expander plate (NPEP) considering the palatal deformity: ogival shaped, anterior vertex growth direction, reduction of transverse diameters. The NPEP promoted distraction of the median palatine suture and assisted the nasal dilation. Therefore, after the insertion of NPEP, the physiological sucking-swallowing mechanism was activated. In infants with CNPAS, NPEP can be useful to ensure the safe stability of nasal dilation. A multidisciplinary approach is fundamental. In our experience, the close collaboration between an otolaryngologist and orthodontist is essential for the management of the patient with CNPAS.

Management of respiratory issues in patients with Rett syndrome: Italian experts' consensus using a delphi approach.

BACKGROUND: Despite the publication of the 2020 guidelines on how to manage Rett Syndrome (RS), some fundamental topics are still open, in particular respiratory problems. OBJECTIVE: Identification and reinforcement of current recommendations concerning the management of respiratory issues in RS patients. MATERIALS AND METHODS: Using a Delphi approach, the leading group reviewed the literature and formulated 14 statements. A multidisciplinary panel of 29 experts were invited to score, for each statement, their agreement on a 1-5 scale. The cut-off level for consensus was 75%, obtained through multiple rounds. RESULTS: The panel agreed that in all RS types, respiratory issues should be faced at an early stage, regardless of epilepsy onset. It is recommended to perform periodically sleep studies in all Congenital Rett Syndrome, and in selected cases with other RS types. Noninvasive ventilation should be considered in all RS subjects with sleep respiratory disorders and in those with hypotonia associated with hypercapnia. Chest physiotherapy should be performed in all RS patients with difficult management of the accumulation of respiratory secretions, using airway clearance techniques and devices (PEP-mask, AMBU bag, or cough machine), more appropriate and tolerated by the patients. The panel recommended individualized programs for the management of scoliosis, and to consider performing gastrostomy in patients at increased risk of ab ingestis pneumonia. CONCLUSIONS: This consensus could support everyday clinical practice on respiratory issues in RS patients, complementary to existing recommendations by regulatory agencies and guidelines.

Care Issues in Patients with Rett Syndrome: A Parental Perspective.

BACKGROUND: The purpose of this study is to better understand the way caregivers of patients with Rett syndrome perceive the quality of the health care services they receive and identify its main shortcomings. METHODS: A survey was distributed to all caregivers who are part of AIRETT (the Italian Association of Relatives of Patients with RS). The survey gathered information on the management of relatives of patients with Rett syndrome. RESULTS: The data refers to 52 patients, all females, with a median age of 15 years at the time of the survey. Concerning RS specificity, our data confirm the high complexity of this chronic, multifaceted condition, mainly characterized by the presence of epilepsy, apnea, severe scoliosis, and gastrointestinal symptoms. The specialists more frequently involved in the care of patients were general practitioners or family pediatricians (98%) and neurologists (92%), and more rarely physiatrists (71%). Only 15% of patients were followed by a pulmonologist, despite the fact that respiratory problems were frequent (apneas were present in 81% of patients, and 2% had a tracheostomy). Although 63.5% of patients presented with gastrointestinal symptoms and 2% had a gastrostomy, only 33% were followed by a gastroenterologist. Moreover, although orthopedic issues were present in 78.8% of patients, including severe scoliosis in 22% of them, only 25% were followed by an orthopedist. Furthermore, despite the fact that RS patients are fragile, about one quarter of them were not vaccinated. As far as organizational issues are concerned, several specialized centers are located in various regions throughout the country. As a consequence, the high mobility rate from one center to another resulted in non-homogeneous assistance. CONCLUSIONS: The study shows that caregivers of RS patients take over most obligations and burdens by increasing their perceived level of stress. For the majority of patients, the most frequent complications were not followed by the reference subspecialist, with the only exception of epilepsy. Moreover, improving vaccination strategies for these patients is necessary.

Sleep architecture and Nusinersen therapy in children with Spinal Muscular Atrophy type 1.

BACKGROUND: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder, the phenotype of the disease is caused by the mutation of the SMN1 (survival motor neuron 1) gene which encodes for the SMN protein. Innovative treatments for SMA have become available and the first molecule approved is Nusinersen, an antisense oligonucleotide that increases the production of SMN protein. Nusinersen has been shown to be associated with a significant motor improvement and an increase of the event-free survival. For these reasons the aim of the present study is to assess if Nusinersen is able modify sleep architecture and microstructure and to improve sleep structure in these patients. METHODS: Sixteen patients affected by SMA1 were enrolled in the study (4 boys, 12 girls; median age 72.5 months, intelligence quotient range 24-84). All patients underwent complete nocturnal PSG before the start of the treatment trough intrathecal injections with Nusinersen (T0) and after the fifth infusion (day 180, T180). PSG recordings were visually scored and interpreted according to the indications of the American Academy of Sleep Medicine (AASM) and and microstructure by means of the Cyclic Alternating Pattern (CAP). RESULTS: After 6 months therapy we found a significantly reduced sleep latency and a significantly increased sleep efficiency. Regarding sleep microstructure parameters (CAP), we did not find any significant change after therapy however, it is worth mentioning that a moderate effect size was observed for the increase in CAP A3 index. CONCLUSIONS: We observed short-term effects of Nusinersen on sleep with an improvement in sleep efficiency and reduction in sleep onset latency; regarding sleep microstructure, a moderate effect size was found for the number of CAP A3 subtypes that slightly increased, possibly indicating a slightly higher arousability. This finding points at a probably overall better sleep pattern organization associated with the treatment, but they need to be confirmed by larger studies with patients treated earlier in life and for a longer period.

Children with medical complexity and pediatric palliative care: Data by a respiratory intermediate care unit.

Pediatric palliative care (PPC) is an active and total approach to the care of children with life-limiting conditions and their families. PPC programs provide ongoing treatment for children with medical complexity (CMC), many of whom will reach adulthood. Aim of the study was to describe a population of CMC attendingin six preselected months the Respiratory Intermediate Care Unit of a tertiary referral hospital for southern and central Italy. We enrolled all CMC patients admitted to our unit in six preselected months and registered pathologies and different categories of childhood diseases, devices and needs, hospitalization and home care plan. Among the 275 children admitted to our unit, 130 CMC were included. Median age was 9.9 (0.1-40.0) years. The main pathologies recorded were neuromuscular, neurological, respiratory, metabolic and malformative diseases, genetic syndromes and outcomes of prematurity. Comorbidity due to respiratory, digestive, neurological, cardiac and urological involvement was present in a high percentage of cases. Among our patients, only 46 were not carriers of any medical device. The average length of hospitalization was 7.0 (1.0-270.0) days with 2 (1.0-7.0) admissions per year per patient. Home care activation was not required for 47 out of 130 patients. Children eligible for PPC are increasing and their survival results in a rise of comorbidities and special needs demanding multilevel interventions. Respiratory symptoms are the most recurrent ones observed, thus requiring an expert in PPC with expertise in the respiratory field. Sharing data and knowledge of CMC needs may help improve care coordination.

Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies.

BACKGROUND: X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from pathogenic variants in the MTM1 gene. Affected male subjects typically present with severe hypotonia and respiratory distress at birth and they often require intensive supportive care. Long-term survivors are often non-ambulant, ventilator and feeding tube-dependent and they generally show additional organ manifestations, indicating that myotubularin does play a vital role in tissues other than muscle. For XLMTM several therapeutic strategies are under investigation. For XLMTM several therapeutic strategies are under investigation including a study of intravenous MTM1 gene transfer using a recombinant AAV8 vector of which has some concerns arises due to hepatotoxicity. RESULTS: We report prospective and retrospective clinical data of 12 XLMTM patients collected over a period of up to 10 years. In particular, we carried out a thorough review of the data about incidence and the course of hepatobiliary disease in our case series. CONCLUSIONS: We demonstrate that hepatobiliary disease represents a common comorbidity of XLMTM that seems irrespective to age and diseases severity. We recommend to carefully explore and monitor the hepatobiliary function in XLMTM patients. We believe that a better understanding of the pathogenic mechanisms that induce hepatobiliary damage is essential to understand the fatal events that may occur in the gene therapy program.

How the Management of Children With Congenital Central Hypoventilation Syndrome Has Changed Over Time: Two Decades of Experience From an Italian Center.

Background: Congenital central hypoventilation syndrome (CCHS) is a rare disorder whose clinical phenotype is closely related to genotype. Methods: A retrospective analysis has been conducted on 22 patients with CCHS, who were referred to the Pediatric Pulmonology and Respiratory Intermediate Care Unit of Bambino Gesù Children's Hospital (Italy) for a multidisciplinary follow-up program between 2000 and 2020. Results: Apnea and cyanosis were the most frequent symptoms at onset (91%). Overall, 59% of patients required tracheostomy and invasive mechanical ventilation (IMV) in the first months of life. Thirty-two percent of patients had Hirschsprung disease (HSCR) that was associated with longer polyalanine repetitions or non-polyalanine repeat expansion mutations (NPARMs). Polyalanine repeat expansion mutations (PARMs) were more frequent and two novel NPARMs (c.780dupT and C.225-256delCT) were described in 14% of patients. Focal epilepsy was first described in 14% of patients and neurocognitive and neuromotor impairment involved 27% and 23% of children, respectively. Symptoms due to autonomic nervous system dysfunction/dysregulation (ANSD)-including strabismus (27%), dysphagia (27%), abnormal heart rhythm (10%), breath-holding spells (9%), and recurrent seizures due to hypoglycemia (9%)-were associated with an increased number of polyalanine repetitions of exon 3 or NPARMs of PHOX2B gene. Overall, the number of patients with moderate to severe phenotype initially treated with non-invasive ventilation (NIV) increased over time, and the decannulation program was concluded with 3 patients who started with IMV. Conclusions: Our study confirms that more severe phenotypes of CCHS are related to the number of polyalanine repetitions or to NPARMs. Although invasive ventilation is often required by patients with severe genotype/phenotype, gradual acquisition of specific skills in the management of patients with CCHS and technological improvements in mechanical ventilation allowed us to improve our therapeutic approach in this population.

A Novel, Portable MESH Nebulizer-An Alternative to Metered Dose Inhaler: Efficacy and Usability in Preschool Wheezers.

Introduction and Objectives: Wheezing episodes are the first causes of doctor's consultation in preschool age. Treatment is usually administered with a metered dose inhaler (MDI) spacer. At variance, many parents and doctors prefer to use a compressor nebulizer, which cannot be easily carried. The study is aimed at testing whether a pocket mesh nebulizer has similar efficacy and acceptability than a standard MDI device. Materials and Methods: The IPAC study was a randomized, controlled, non-inferiority trial (number: 1616/2018, Ospedale Pediatrico Bambino Gesu'-IRCCS). The study had two arms: cases, using MicroAIR U100, and controls, using MDI+spacer device. Both devices were adopted for long-term treatment and for exacerbations. Follow-up was organized with clinical visits and a daily e-diary connected to an application for mobile phone. Results: One hundred patients were enrolled. The frequency of asthmatic symptoms showed a non-inferiority for MicroAIR U100 group vs. MDI. Accordingly, no significant difference was found in the average % of days with cough, wheezing, breathlessness after exercise, days lost at school, and not-programmed visits. Considering only patients with >1 day with symptoms, no significant sdifferences were found in the number of exacerbations nor in the cumulative days with symptoms. The acceptance and usability of both devices have been favorable. However, the MDI+AeroChamber® device showed better acceptability. Conclusions: Our study shows that MicroAIR U-100, a mesh nebulizer, has similar clinical efficacy but lower acceptance and usability than an MDI plus Aerochamber® in delivering therapy in preschool wheezers. Therefore, MicroAIR U-100 might be a valuable second choice, when the delivery of medication with an MDI plus Aerochamber® is not accepted, or wrongly used by the parents.

Characteristics and outcomes in children on long-term mechanical ventilation: the experience of a pediatric tertiary center in Rome.

BACKGROUND: Children with chronic respiratory failure and/or sleep disordered breathing due to a broad range of diseases may require long-term ventilation to be managed at home. Advances in the use of long-term non-invasive ventilation has progressively leaded to a reduction of the need for invasive mechanical ventilation through tracheostomy. In this study, we sought to characterize a cohort of children using long-term NIV and IMV and to perform an analysis of those children who showed significant changes in ventilatory support management. METHODS: We performed a retrospective cohort study of pediatric (within 18 years old) patients using long-term, NIV and IMV, hospitalized in our center between January 1, 2000 and December 31, 2017. A total of 432 children were included in the study. Long Term Ventilation (LTV) was defined as IMV or NIV, performed on a daily basis, at least 6 h/day, for a period of at least 3 months. RESULTS: 315 (72.9%) received non-invasive ventilation (NIV); 117 (27.1%) received invasive mechanical ventilation (IMV). Children suffered mainly from neuromuscular (30.6%), upper airway (24.8%) and central nervous system diseases (22.7%). Children on IMV were significantly younger when they start LTV [NIV: 6.4 (1.2-12.8) years vs IMV 2.1 (0.8-7.8) years] (p < 0.001)]. IMV was likely associated with younger age at starting ventilatory support (aOR 0.9428; p = 0.0220), and being a child with home health care (aOR 11.4; p < 0.0001). Overtime 39 children improved (9%), 11 children on NIV (3.5%) received tracheostomy; 62 children died (14.3%); and 74 children (17.1%) were lost to follow-up (17.8% on NIV, 15.4% on IMV). CONCLUSIONS: Children on LTV suffered mainly from neuromuscular, upper airways, and central nervous system diseases. Children invasively ventilated usually started support younger and were more severely ills.

Effects of long-term non-invasive ventilation on sleep structure in children with Spinal Muscular Atrophy type 2.

OBJECTIVE: Changes of sleep architecture have been reported in children with Spinal Muscular Atrophy type 2 (SMA2), mainly represented by a decrease of arousability. No studies have evaluated the effect of long-term ventilation on sleep parameters in these children. The aim of this study was to evaluate the effects of long-term non-invasive positive pressure ventilation (LTNPPV) on sleep architecture and to assess the residual differences from normal controls. METHODS: Nine consecutive children with SMA2 underwent two distinct polysomnographic (PSG) studies, one in spontaneous breathing, and subsequently after LTNPPV. The results were then compared to 15 age-matched controls. RESULTS: SMA2 patients showed only slightly modified sleep architecture on LTNPPV: increased stage N2% and decreased number of awakenings, while several significant differences persisted between SMA2 patients on LTNPPV and controls (decreased total sleep time, number of awakenings, sleep efficiency, and percentage of REM sleep). Sleep microstructure, evaluated by means of the Cyclic alternating pattern (CAP) showed only marginal changes on LTNPPV (small shortening of CAP A1 subtype duration and small increase in CAP A3 index). Conversely, CAP parameters on LTNPPV showed significant differences between SMA2 patients vs. controls, with increased A1 subtype percentage and decreased percentage of A2 and A3 subtypes. CONCLUSIONS: This is the first study in children affected by SMA2 reporting data on sleep microstructure and their changes after LTNPPV. We found persisting, small but important changes in sleep microstructure during LTNPPV in these children, suggesting that this treatment only partially improves their arousability.

Sleep architecture in children with spinal muscular atrophy type 2.

OBJECTIVE: There have been few published reports on the sleep patterns of patients with spinal muscular atrophy (SMA) type 2, and none on sleep microstructure. The aim of this study was to analyze sleep architecture and microstructure in a group of children with SMA type 2, compared with age-matched and sex-matched controls. METHODS: Seventeen SMA type 2 children (seven males, mean age 4.2 years) and 12 controls (five males, mean age 5.0 years) underwent full polysomnography to evaluate sleep architecture and microstructure by means of the Cyclic Alternating Pattern (CAP). RESULTS: Compared with the control children, the SMA type 2 patients showed a mild increase in the apnea/hypopnea index. Sleep was characterized by a decrease in the number of sleep stage shifts per hour, of percentage of stage N3, of stage R, and of sleep efficiency. On the contrary, significant increases of awakenings per hour, wake after sleep onset, and percentage of stage N1 were found. The CAP analysis revealed a significant increase in the percentage of A1 CAP subtypes, a reduction of that of A3 subtypes, and of A2 and A3 indexes. CONCLUSIONS: The results indicated an abnormality of sleep macrostructure and microstructure in SMA type 2 patients, which was characterized by a reduction of A2 and A3 subtypes (low and high power arousals), supporting the concept of a decreased arousability in SMA type 2 patients. Similar to a previous report on SMA type 1, the findings might be additional proof of central nervous system involvement, although these alterations are less severe than those observed in infants with SMA type 1.

Survival of patients with spinal muscular atrophy type 1.

BACKGROUND: Spinal muscular atrophy type 1 (SMA1) is a progressive disease and is usually fatal in the first year of life. METHODS: A retrospective chart review was performed of SMA1 patients and their outcomes according to the following choices: letting nature take its course (NT); tracheostomy and invasive mechanical ventilation (TV); continuous noninvasive respiratory muscle aid (NRA), including noninvasive ventilation; and mechanically assisted cough. RESULTS: Of 194 consecutively referred patients enrolled in this study (103 males, 91 females), NT, TV, and NRA were chosen for 121 (62.3%), 42 (21.7%), and 31 (16%) patients, respectively. Survival at ages 24 and 48 months was higher in TV than NRA users: 95% (95% confidence interval: 81.8%-98.8%) and 67.7% (95% confidence interval: 46.7%-82%) at age 24 months (P < .001) and 89.43% and 45% at age 48 months in the TV and NRA groups, respectively (P < .001). The choice of TV decreased from 50% (1992-1998) to 12.7% (2005-2010) (P < .005) with a nonstatistically significant increase for NT from 50% to 65%. The choice of NRA increased from 8.1% (1999-2004) to 22.7% (2005-2010) (P < .001). CONCLUSIONS: Long-term survival outcome is determined by the choice of the treatment. NRA and TV can prolong survival, with NRA showing a lower survival probability at ages 24 and 48 months.