ABSTRACT
The identification of cystic fibrosis screening-positive, inconclusive diagnosis (CFSPID) in infants is a controversial outcome of newborn screening for cystic fibrosis (CF). Today, despite improvements in the knowledge of CFSPID and the description of several cohorts, little data are available on cohorts with a follow-up period of more than 6 years. In this study, we report the outcomes of an Italian cohort of CFSPID individuals with CFSPID or formerly CFTR-related disorders (CFTR-RD) (CFSPID > CFTR-RD) or diagnosed with CF (CFSPID > CF). This was an observational and multicentre Italian study collecting clinical data on CFSPID born between the period January 1, 2011, and December 13, 2019. A total of 268 participants were included: 243 with persistent CFSPID, 7 with CFSPID > CFTR-RD, and 18 with CFSPID > CF. The trend of sweat chloride (SC) values, percentage of definitive diagnoses, lung function in school-aged children, and development of CF-related complications were evaluated. At the end of the observation period, almost 80% of the individuals with CFSPID did not have a conclusive diagnosis. A total of 29 children (10.8%) transitioned to a diagnosis of CF for pathological SC values (≥ 60 mmol/L) or multi-organ involvement, and 18 (6.7%) to CFTR-RD. Children who were followed up for > 6 years (median age, 7.5 years; range, 6.04-10.5) had normal lung function and were pancreatic sufficient, and the evolution in CF was only present in two cases. CONCLUSION: Most Italian preschool and school-aged children with CFSPID did not have a conclusive diagnosis, and progression to CF was unlikely in children > 6 years of age. An annual follow-up could be indicated to identify early evolution in clinical features consistent with a CFTR-RD. WHAT IS KNOWN: ⢠Cystic Fibrosis newborn screening identifies also subjects with an inconclusive diagnosis (CFSPID). ⢠Over time a variable percentage of CFSPIDs will be diagnosed as CF. ⢠Little data is available on CFSPIDs with a follow-up period of more than six years. WHAT IS NEW: ⢠80% of Italian preschool and school-age CFSPIDs not have a conclusive diagnosis. ⢠Italian preschool and school-age CFSPIDs have normal lung function and are pancreatic sufficient. ⢠Annual follow-up after 6 years is recommended in CFSPID with abnormal LCI2.5 or with a CF-causing variant in trans with a VVCC.
Subject(s)
Cystic Fibrosis , Infant , Infant, Newborn , Child , Humans , Child, Preschool , Cystic Fibrosis/diagnosis , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Neonatal Screening , Genetic Testing , Italy/epidemiologySubject(s)
Cystic Fibrosis , Gilbert Disease , Humans , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , Cystic Fibrosis/genetics , Gilbert Disease/diagnosis , Gilbert Disease/drug therapy , Gilbert Disease/genetics , Hyperbilirubinemia , Aminophenols/adverse effects , Benzodioxoles/adverse effects , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Mutation , Chloride Channel Agonists/adverse effects , Drug CombinationsABSTRACT
To evaluate whether vertical HIV infection interferes with the expression of CD28 on T lymphocytes, 25 HIV-infected children and 29 seroreverted children born to HIV+ mothers were studied. The percentage of CD28- cells among CD8+ T lymphocytes was higher in HIV-infected children than in controls (P < 0.001). In fact, in HIV-infected children, this percentage was elevated from the first year of life, while in healthy seroreverted children, the proportion of CD28- cells among CD8+ cells rose progressively with age (r = 0.49; P = 0.008). In HIV+ children, the CD8+ CD28-, but not CD8+ CD28+ cell proportion was significantly correlated with immunological markers of disease progression, such as CD4+ cell loss (r = -0.65; P < 0.001) and the level of in vitro spontaneous lymphocyte apoptosis (r = 0.53; P = 0.03).
Subject(s)
CD28 Antigens/immunology , CD8-Positive T-Lymphocytes/immunology , HIV Infections/immunology , HIV Infections/transmission , Age Factors , Apoptosis , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , Child , Child, Preschool , HIV Seropositivity , Humans , Infant , Infectious Disease Transmission, Vertical , Lymphocyte CountABSTRACT
The inhalation of aerosolized drugs for therapeutic purpose has been used for many years in respiratory diseases as asthma, chronic bronchitis, cystic fibrosis. Therapeutic aerosols have the advantages to deliver active substances directly to the site of disease, without systemic side effects, to produce a more rapid clinical response, to avoid barriers to the absorption of drugs such as the gastrointestinal tract. We review the mechanisms and the site of lung deposition and the range of devices that can provide an effective aerosol such as metered dose-inhaler and spacers. Besides drugs as cromolyn, beta-2-agonists and topical steroids, recently new inhalation therapies were proposed using antiviral drugs (interferon), pentamidine for Pneumocystis carinii in immunocompromised host, inhalation of attenuated virus (measles) for active immunization. However there is a need for further work in this area.
