Limitations of the apnea-hypopnea index in children and young adults with neuromuscular disorders.

There are no validated criteria to initiate noninvasive ventilation (NIV) in children and young adults with neuromuscular disease (NMD). In order to analyze NIV initiation criteria, we reviewed the polysomnography (PSG) criteria that led to the initiation of NIV in 61 consecutive patients with NMD, median age 4.1 (0.8-21) years, who had a PSG during their routine care. NIV was initiated on abnormal PSG data (apnea-hypopnea index (AHI) > 10 events/h and/or a transcutaneous carbon dioxide pressure > 50 mmHg and/or a pulse oximetry 〈 90%, both during at least 2% sleep time or 〉 5 consecutive minutes) in 11 (18%) patients. Six of these 11 patients had an AHI ≤ 10 events/h and would not have been ventilated if only AHI was retained. However, one of these 6 patients had isolated nocturnal hypoxemia, 3 isolated nocturnal hypercapnia and 2 abnormal respiratory events. Six (10%) patients with a normal PSG were started on NIV on clinical criteria. Our results show the limitation of the AHI when taken as the unique PSG criterion for NIV initiation in young patients with NMD and underline the need to include also abnormalities of overnight gas exchange into the NIV decision-making process.

Do not forget asthma comorbidities in pediatric severe asthma!

Asthma is the most common chronic respiratory disease in childhood. The long-term goals in managing asthma aim to control symptoms and prevent exacerbations, as well as to reduce side effects of therapy and mortality disease-related. Most of patients have mild to moderate asthma and respond well to standard therapies. However, a minor proportion of children with asthma has severe disease that remains uncontrolled despite optimal adherence to prescribed therapy and treatment of contributory factors, including trigger exposures and comorbidities, which can mimic or worsen asthma and contribute to exacerbations and poor quality of life. Evaluation of comorbidities is fundamental to optimize the management of the disease in a subgroup of patients with poor responder asthma. The overall aim of this article is to describe characteristics of main pediatric severe asthma comorbidities reported in literature, giving clinicians tools to recognize and manage properly these conditions.

CFTR Modulator Therapies: Potential Impact on Airway Infections in Cystic Fibrosis.

Cystic Fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding for the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein, expressed on the apical surface of epithelial cells. CFTR absence/dysfunction results in ion imbalance and airway surface dehydration that severely compromise the CF airway microenvironment, increasing infection susceptibility. Recently, novel therapies aimed at correcting the basic CFTR defect have become available, leading to substantial clinical improvement of CF patients. The restoration or increase of CFTR function affects the airway microenvironment, improving local defence mechanisms. CFTR modulator drugs might therefore affect the development of chronic airway infections and/or improve the status of existing infections in CF. Thus far, however, the full extent of these effects of CFTR-modulators, especially in the long-term remains still unknown. This review aims to provide an overview of current evidence on the potential impact of CFTR modulators on airway infections in CF. Their role in affecting CF microbiology, the susceptibility to infections as well as the potential efficacy of their use in preventing/decreasing the development of chronic lung infections and the recurrent acute exacerbations in CF will be critically analysed.

Clinical course and risk factors for severe COVID-19 among Italian patients with cystic fibrosis: a study within the Italian Cystic Fibrosis Society.

PURPOSE: To describe the clinical course of COVID-19 in patients with cystic fibrosis (CF) and to identify risk factors for severe COVID-19. METHODS: We conducted a prospective study within the Italian CF Society. CF centers collected baseline and follow-up data of patients with virologically confirmed SARS-CoV-2 infection between March 2020 and June 2021. Odds ratios (ORs) for severe SARS-CoV-2 (as defined by hospital admission) were estimated by logistic regression models. RESULTS: The study included 236 patients with positive molecular test for SARS-CoV-2. Six patients died, 43 patients were admitted to hospital, 4 admitted to intensive care unit. Pancreatic insufficiency was associated with increased risk of severe COVID-19 (OR 4.04, 95% CI 1.52; 10.8). After adjusting for age and pancreatic insufficiency, forced expiratory volume in one second (FEVp) < 40% (OR 4.54, 95% CI 1.56; 13.2), oxygen therapy (OR 12.3, 95% CI 2.91-51.7), underweight (OR 2.92, 95% CI 1.12; 7.57), organ transplantation (OR 7.31, 95% CI 2.59; 20.7), diabetes (OR 2.67, 95% CI 1.23; 5.80) and liver disease (OR 3.67, 95% CI 1.77; 7.59) were associated with increased risk of severe COVID-19, while use of dornase alfa was associated with a reduced risk (OR 0.34, 95% CI 0.13-0.88). No significant changes were observed in FEVp from baseline to a median follow-up of 2 months (median difference: 0, interquartile range: - 4; 5, P = 0.62). CONCLUSION: Clinical features indicative of severe form of CF are associated with increased risk of COVID-19 hospitalization. SARS-CoV-2 infected patients do not experience a deterioration of respiratory function.

ERS statement on paediatric long-term noninvasive respiratory support.

Long-term noninvasive respiratory support, comprising continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV), in children is expanding worldwide, with increasing complexities of children being considered for this type of ventilator support and expanding indications such as palliative care. There have been improvements in equipment and interfaces. Despite growing experience, there are still gaps in a significant number of areas: there is a lack of validated criteria for CPAP/NIV initiation, optimal follow-up and monitoring; weaning and long-term benefits have not been evaluated. Therapeutic education of the caregivers and the patient is of paramount importance, as well as continuous support and assistance, in order to achieve optimal adherence. The preservation or improvement of the quality of life of the patient and caregivers should be a concern for all children treated with long-term CPAP/NIV. As NIV is a highly specialised treatment, patients are usually managed by an experienced paediatric multidisciplinary team. This statement written by experts in the field of paediatric long-term CPAP/NIV aims to emphasise the most recent scientific input and should open up new perspectives and research areas.

SARS-CoV-2 infection in cystic fibrosis: A multicentre prospective study with a control group, Italy, February-July 2020.

OBJECTIVE: To describe the symptoms and clinical course of SARS-CoV-2 infection in patients with cystic fibrosis (CF). METHODS: We carried out a prospective multicentre cohort study based on 32 CF centres and 6597 patients. Centres were contacted to collect baseline and follow-up data of patients who reported symptoms suggestive of COVID-19 or who had contact with a positive/suspected case between the end of February and July 2020. Symptoms and clinical course of the infection were compared between patients who tested positive by molecular testing (cases) and those who tested negative (controls). RESULTS: Thirty patients were reported from the centres, 16 of them tested positive and 14 tested negative. No differences in symptoms and outcome of the disease were observed between groups. Fever, cough, asthenia and dyspnea were the most frequently reported symptoms. Eight cases (50%) were hospitalized but none required ICU admission. Two adults with a history of lung transplant required non-invasive ventilation, none required ICU admission and all patients fully recovered without short-term sequelae. CONCLUSIONS: The course of SARS-CoV-2 in our patients was relatively favorable. However, COVID-19 should not be considered a mild disease in CF patients, particularly for those with severely impaired respiratory function and organ transplant.

Barriers and incentives for Italian paediatricians to become smoking cessation promoters: a GARD-Italy Demonstration Project.

BACKGROUND: Paediatricians rarely devote any time to screening and treatment for parental tobacco use. The present project is part of a Global Alliance against Chronic Respiratory Diseases (GARD)-Italy Demonstration Project, aimed to increase the skills of primary care physicians and paediatricians as "promoter of smoking cessation". The aims of this study were: (I) to identify latent classes of barriers and incentives for smoking cessation counseling among paediatricians using latent class analysis (LCA); (II) to investigate risk factors for inclusion into the identified classes. METHODS: In 2018, 1,500 Italian paediatricians were invited to complete an online survey on passive smoke exposure in children. LCA was used to discover underlying response patterns, and to identify respondent groups with similar attitudes toward passive smoke exposure in children. Multinomial logistic regression helped investigate which explanatory variables influenced inclusion into a class. A P value <0.05 was considered significant. RESULTS: The overall response rate was 71% (n=1,071/1,500). Three classes were identified: Class 1 "passive" (n=226, 21.10%); Class 2 "unmotivated" (n=124, 11.58%); and Class 3 "proactive" (n=721, 67.32%). Assuming Class 3 as reference, ever having been a smoker was borderline associated (P=0.052) with increased probability of inclusion into Class 1 (OR =1.43, 95% CI, 1.00-2.06). Having 6-15 or ≥15 years of work experience versus having less than five years was associated with decreased probability of being in the "passive" class (OR =0.46, 95% CI, 0.22-0.96 and OR =0.49, 95% CI, 0.27-0.87, respectively), as was discussing parents' addiction to alcohol/drugs (OR =0.50, 95% CI, 0.33-0.76). CONCLUSIONS: We identified three profiles among Italian paediatricians related to barriers and incentives for smoking cessation promotion. Tailored educational interventions for paediatricians are required to promote smoking cessation programs.

Long Term Non-invasive Ventilation in Children With Central Hypoventilation.

Central hypoventilation (CH) is a quite rare disorder caused by some congenital or acquired conditions. It is featured by increased arterial concentration of serum carbon dioxide related to an impairment of respiratory drive. Patients affected by CH need to be treated by mechanical ventilation in order to achieve appropriate ventilation and oxygenation both in sleep and wakefulness. In fact, in severe form of Congenital Central Hypoventilation Syndrome (CCHS) hypercarbia can be present even during the day. Positive pressure ventilation via tracheostomy is the first therapeutic option in this clinical condition, especially in congenital forms. Non-Invasive ventilation is a an option that must be reserved for more stable clinical situations and that requires careful monitoring over time.

Ceftolozane/Tazobactam for Treating Children With Exacerbations of Cystic Fibrosis Due to Pseudomonas aeruginosa: A Review of Available Data.

Ceftolozane-tazobactam is a novel fifth-generation cephalosporin/ß-lactamase inhibitor combination recently approved for treatment of both complicated intra-abdominal and urinary tract infections in adults. Considering its potent bactericidal activity against Pseudomonas aeruginosa, it might represent an important option also for treating children with exacerbations of cystic fibrosis due to Pseudomonas aeruginosa when other alternative treatments have been exhausted. We hereby review available data on the use of ceftolozane-tazobactam in children, focusing on cystic fibrosis.

Italian pediatric respiratory society recommendations on pediatric pulmonary function testing during COVID-19 pandemic.

BACKGROUND: Effective prevention and control strategies are mandatory to prevent SARS-CoV-2 infection. MAIN TEXT: The Italian Pediatric Respiratory Society promotes a series of new recommendations that should be followed in pulmonary function testing laboratories during the COVID-19 pandemic. CONCLUSION: Pulmonary function testing should be performed in children with chronic lung disease only if it is needed to guide management and limited to the necessary tests, namely spirometry. When performed, strict infection control measures should be followed due to the potential risk of transmitting SARS-CoV-2.

European Cystic Fibrosis Society Standards of Care: Quality Management in cystic fibrosis.

Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful treatments and patient outcomes to be recognized and improvement programmes to be implemented in specialist CF centres. Over the past decades, the greater volumes of data becoming available through Centre databases and patient registries led to the possibility of making comparisons between different therapies, approaches to care and indeed data recording. The quality of care for individuals with CF has become a focus at several levels: patient, centre, regional, national and international. This paper reviews the quality management and improvement issues at each of these levels with particular reference to indicators of health, the role of CF Centres, regional networks, national health policy, and international data registration and comparisons.

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.

Oxidative stress in stable cystic fibrosis patients: do we need higher antioxidant plasma levels?

UNLABELLED: Oxidative stress plays an important role in cystic fibrosis (CF). However, there is a lack of validated biomarkers of oxidative damage that correlate with the antioxidant needs of patients with CF. OBJECTIVE: To investigate oxidative stress in stable pediatric CF patients and evaluate if vitamin supplementation may be tailored to individual needs and oxidative status. RESULTS: Lipid-adducts 4-hydroxynonenal (HNE-L) and malonaldehyde (MDA-L) (chromolipids) were elevated in the majority of patients despite normal plasma vitamin E, A and C. HNE-L and MDA-L increased with age, while plasma vitamins decreased. The most relevant correlation was identified between vitamin C and chromolipids. Patients with pancreatic insufficiency (PI) showed significantly higher plasma chromolipids despite no differences in plasma vitamins. CONCLUSIONS: The majority of patients showed elevated plasma chromolipids that increased with age. Antioxidant vitamin reference ranges provide incomplete information on the redox status. CF patients with PI showed excessive oxidative stress damage.

Two pediatric cases of multidrug-resistant tuberculosis treated with linezolid and moxifloxacin.

We report here 2 pediatric cases of multidrug-resistant (MDR) tuberculosis (TB) that were observed in Italy. Both families came from an Eastern European country, which is notably an area with a high prevalence of MDR TB. An increase of new cases of MDR TB in developed countries is expected over the next years because of migratory flow, and specific measures and strategies need to be taken to prevent the propagation and dissemination of MDR TB. An efficacious treatment including linezolid and moxifloxacin was administered for 13 months in 1 case. No adverse reactions were detected during close child monitoring. Linezolid and newer fluoroquinolones such as moxifloxacin have been reported to be effective for MDR-TB treatment in adults. On the contrary, there is limited available evidence regarding the effectiveness and safety of these drugs in infants and children with MDR TB. The use of second-line drugs not approved for use in children may be necessary to treat a life-threatening disease such as MDR TB, but it requires careful monitoring to quickly recognize the occurrence of dose- and duration-dependent adverse drug reactions.