Biochemical and genetic tools to predict the progression to Cystic Fibrosis in CRMS/CFSPID subjects: A systematic review.

OBJECTIVES: Aim of this study was to identify risk factors for a progression to cystic fibrosis (CF) in individuals detected as CF Screening Positive, Inconclusive Diagnosis (CFSPID). METHODS: This is a systematic review through literature databases (2015-2023). Blood immunoreactive trypsinogen (b-IRT) values, CFTR genotype, sweat chloride (SC) values, isolation of Pseudomonas aeruginosa (Pa) from respiratory samples, Lung Clearance Index (LCI) values in CFSPIDs who converted to CF (CFSPID > CF) and age at CF transition were assessed. RESULTS: Percentage of CFSPID > CF varies from 5.3 % to 44 %. Presence of one CF-causing CFTR variant in trans with a variant with variable clinical consequences (VVCC), an initial SC ≥ 40 mmol/L, an increase of SC > 2.5 mmol/L/year and recurrent isolation of pseudomonas aeruginosa (Pa) from airway samples could allow identification of subjects at risk of progression to CF. CONCLUSIONS: CFSPIDs with CF causing variant/VVCC genotype and first SC in the higher borderline range may require more frequent and prolonged clinical follow-up.

Sleep Respiratory Disorders in Children and Adolescents with Cystic Fibrosis and Primary Ciliary Dyskinesia.

Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are genetic respiratory diseases featured by chronic upper and lower airway inflammation and infection, mainly due to impaired mucociliary clearance due to genetic mutations. Sleep is crucial to healthy children's normal physical and psychological development and has an important value in chronic respiratory diseases. Impaired sleep quality, such as sleep deprivation or insufficient sleep during the night, and sleep respiratory disorders (SRDs) are common in 5% to 30% of the general population. Sleep disruption leads to attention deficits, daytime sleepiness, fatigue and mood disorders and correlates to a worsened quality of life. Furthermore, sleep respiratory disorders (SRSs) are under-recognized comorbidities in CF and PCD patients. SRSs include a spectrum of symptoms ranging from primary snoring through upper airway resistance to obstructive sleep apnea (OSA), nocturnal hypoventilation and hypoxemia occurring in people with moderate to severe lung disease and damaging the disease-related outcomes and quality of life. Effective screening during sleep with polysomnography is very important for the timely initiation of efficacious treatments and to prevent worsened respiratory, metabolic and cardiovascular outcomes. However, the impact of SRDs on health and quality of life is still underinvestigated.

Lung clearance index: A new measure of late lung complications of cancer therapy in children.

INTRODUCTION: Childhood cancer survivors (CSs) might face an increased lifelong risk of lung function impairment. The lung clearance index (LCI) has been described as being more sensitive than spirometry in the early stages of some lung diseases. The aim of this study was to evaluate this index in a cohort of patients with a history of childhood cancer for the first time. MATERIALS AND METHODS: We evaluated 57 off-treatment CSs aged 0-18 years old and 50 healthy controls (HCs). We used the multiple-breath washout method to study LCI and spirometry. RESULTS: CSs did not show any differences from the controls in ventilation homogeneity (LCI 6.78 ± 1.35 vs. 6.32 ± 0.44; p: not significant [ns]) or lung function (FEV1 99.9 ± 11.3% vs. 103.0 ± 5.9% of predicted; p: ns; FVC 98.2 ± 10.3% vs. 101.1 ± 3.3% of predicted). LCI significantly correlated with the number of years since the last chemotherapy (r = .35, p < .05). CONCLUSIONS: Our study describes the trend of LCI in a cohort of CSs and compares it with the results obtained from HCs. The results show that patients maintain both good values of respiratory function and good homogeneity of ventilation during childhood. Moreover, as LCI increases and worsens as the years pass after the end of the treatment could identify the tendency toward pulmonary fibrosis, which is typical of adult CSs, at an earlier time than spirometry.

Pidotimod in allergic diseases.

The rising incidence of allergic disease requires more specific, effective and safe therapeutic strategies. In this regard, several kinds of biologically active substances, commonly known as immunostimulants, have been introduced for the prevention and treatment of allergic diseases in pediatric population. Among the heterogeneous group of biologically active molecules to date available, pidotimod (Axil, Valeas S.p.A, Milan) is proved to be able to ameliorate both innate and adaptive immunity and enhances the immune system properties often impaired in patients with allergic disorders.

Gastroesophageal reflux and respiratory diseases: does a real link exist?

INTRODUCTION: Gastro-esophageal reflux disease (GERD) indicates a gastroesophageal reflux that causes symptoms such as pain, and needs medical therapy, and may result in complications such as erosive esophagitis, aspiration pneumonia. Here, we review if it exists a real link between clinical presentation of some respiratory diseases such as asthma, chronic cough, cystic fibrosis and laryngopharyngitis and GERD. EVIDENCE ACQUISITION: This review was conducted employing 2 databases: PubMed and Science Direct. EVIDENCE SYNTHESIS: Asthma may lead to reflux, and reflux could exacerbate asthma or cause asthma-like symptoms. Prevalence of GERD in children with asthma ranged from as low 32% to as high 80%. There are several studies where the use of proton pump inhibitors (PPIs) and histamine H2 receptor antagonists lead to inconclusive results. The relation of chronic unexplained cough to GERD remains controversial in children and pediatric guidelines do not currently recommend empirical GERD treatment trials for pediatric chronic cough. Gastroesophageal reflux is more frequent in patients with cystic fibrosis (CF) than general population. Although PPIs are regularly prescribed in approximately half of the patients with CF, there are no specific guidelines for treatment of reflux in CF and it was shown that chronic treatment with PPIs was correlated to possible increased risk of exacerbations. CONCLUSIONS: The pathogenesis of GER-related respiratory symptoms is multifactorial. The causal relationship between these two conditions may be difficult to prove also with the aid of supporting tests. Multichannel intraluminal impedance associated with pH-metry (pH/MII) detect all gastroesophageal reflux episodes accompanied with a bolus movement and classify GER episodes according to their content (liquid, gas and mixed), pH value and proximal extension. There are no consistent evidences confirming the validity of medical therapy in reflux with respiratory symptoms.