L'identificazione della variante polimorfica Trp64Arg del recettore β3 adrenergico, nei pazienti affetti da Fibrosi Cistica, correla con la riduzione dei livelli linfomonocitari di sfingosina chinasi 1.

La Fibrosi Cistica (FC) è la malattia genetica a trasmissione autosomica recessiva più frequente nella popolazione caucasica. L’assenza di una netta correlazione genotipo-fenotipo e la grande variabilità genetica non consentono allo stato attuale di prevedere l’andamento clinico del singolo paziente con FC. Recenti studi hanno dimostrato che un ruolo rilevante nello sviluppo e nella progressione della FC è svolto dal lipide sfingosina 1-fosfato (S1P). Scopo del nostro studio è quello di dimostrare che la S1P rappresenti un marcatore predittivo di severità della malattia respiratoria ostruttiva nei pazienti affetti da FC e che la presenza di mutazioni genetiche a carico del recettore β3AR, come la variante polimorfica Trp64Arg (nota per ridurre la funzione del recettore), possa essere responsabile di peggiore “outcome” nei pazienti FC. In questo studio abbiamo presentato dati originali di 64 pazienti provenienti da un singolo centro FC raccolti tra il 2015 e il 2018 finalizzati a definire: - la frequenza della variante polimorfica Trp64Arg del gene codificante per il β3AR; - l’impatto di tale polimorfismo sulla produzione di S1P; - l’impatto del polimorfismo sulla severità della malattia respiratoria cronica. I nostri dati suggeriscono che la variante polimorfica ipofunzionante Trp64Arg è presente in un’alta percentuale di pazienti con FC ma in nessuno dei controlli. Inoltre, i pazienti con FC con la variante polimorfica presentava una ridotta espressione linfocitaria dei livelli di SphK1, l’enzima responsabile della formazione del S1P. Tali risultati supportano il coinvolgimento del β3AR sulla produzione di S1P e l’ipotesi di un effetto negativo esercitato dalla variante polimorfica Trp64Arg sul signaling della S1P

Lung disease assessment in primary ciliary dyskinesia: a comparison between chest high-field magnetic resonance imaging and high-resolution computed tomography findings

Abstract Background Primary ciliary dyskinesia (PCD) is associated with pulmonary involvement that requires periodical assessment. Chest high-resolution computed tomography (HRCT) has become the method of choice to evaluate chronic lung disease, but entails exposure to ionizing radiation. Magnetic resonance imaging (MRI) has been proposed as a potential radiation-free technique in several chest disorders. Aim of our study is to evaluate whether high-field MRI is as effective as HRCT in identifying PCD pulmonary abnormalities. We also analyzed the relationships between the severity and extension of lung disease, and functional data. Methods Thirteen PCD patients (8 children/5 adults; median age, 15.2 yrs) underwent chest HRCT and high-field 3T MRI, spirometry, and deep throat or sputum culture. Images were scored using a modified version of the Helbich system. Results HRCT and MRI total scores were 12 (range, 6–20) and 12 (range, 5–17), respectively. Agreement between HRCT and MRI scores was good or excellent (r > 0.8). HRCT and MRI total scores were significantly related to forced vital capacity (r = -0.5, p = 0.05; and r = -0.7, p = 0.009, respectively) and forced expiratory volume at 1 second (r = -0.6, p = 0.03; and r = -0.7, p = 0.009, respectively). Conclusion Chest high-field 3T MRI appears to be as effective as HRCT in assessing the extent and severity of lung abnormalities in PCD. MRI scores might be used for longitudinal assessment and be an outcome surrogate in future studies.</p

Lung structure and function similarities between primary ciliary dyskinesia and mild cystic fibrosis: a pilot study

BACKGROUND: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are increasingly compared. There are no chest magnetic resonance imaging (MRI) comparative studies of PCD and CF. We assessed clinical, functional, microbiological and MRI findings in PCD and mild CF patients in order to evaluate different expression of lung disease. METHODS: Twenty PCD (15.1 years) and 20 CF subjects with mild respiratory impairment (16 years, 70% with pancreatic insufficiency) underwent MRI, spirometry, and sputum cultures when clinically stable. MRI was scored using the modified Helbich system. RESULTS: PCD was diagnosed later than CF (9.9 versus 0.6 years, p = 0.03), despite earlier symptoms (0.1 versus 0.6 years, p = 0.02). In the year preceding the study, patients from both groups underwent two systemic antibiotic courses (p = 0.48). MRI total scores were 11.6 ± 0.7 and 9.1 ± 1 in PCD and CF, respectively. FEV1 and FVC Z-scores were -1.75 (range, -4.6-0.7) and -0.6 (-3.9-1.8) in PCD, and -0.9 (range, -5.4-2.3) and -0.3 (-3.4-2.5) in CF, respectively. No difference was found between lung function or structure, despite a higher MRI subscore of collapse/consolidation in PCD versus CF (1.6 ± 0.1 and 0.6 ± 0.2, p < 0.001). These findings were confirmed after data-control for diagnostic delay. Pseudomonas aeruginosa and Staphylococcus aureus were more frequent in CF than in PCD (p = 0.05 and p = 0.003, respectively). CONCLUSIONS: MRI is a valuable radiation-free tool for comparative PCD and CF lung disease assessment. Patients with PCD may exhibit similar MRI and lung function changes as CF subjects with mild pulmonary disease. Delay in PCD diagnosis is unlikely the only determinant of similarities

Autonomic dysfunction in Alzheimer's disease: tools for assessment and review of the literature

Autonomic dysfunction is very common in patients with dementia, and its presence might also help in differential diagnosis among dementia subtypes. Various central nervous system structures affected in Alzheimer's disease are also implicated in autonomic nervous system regulation, and it has been hypothesized that the deficit in central cholinergic function observed in Alzheimer's disease could likely lead to autonomic dysfunction. Several feasible tests can be used in clinical practice for the assessment of parasympathetic and sympathetic functions, especially in terms of cardiovascular autonomic modulation. In this review, we describe the different tests available and the evidence from the literature which indicate a definite presence of autonomic dysfunction in dementia at various degrees. Importantly, the recognition of dysautonomia, besides possibly being an early marker of dementia, would help prevent the disabling complications which increase the risk of morbidity, institutionalization, and mortality in these individuals

The role of nasal washes in CF patients affected by chronic rhinosinusitis

Cystic Fibrosis (CF) presents multiorgan manifestations that include chronic rhinosinusitis (CRS) with or without nasal polyposis. Nasal washes (NWs) are widely used in clinical practice especially in CF patients, although their effectiveness on Ear Nose Throat (ENT) symptoms is controversial. In this study we evaluate the performance and the safety of a NWs solution, with or without surfactant, to reduce symptoms and bacterial load. Materials and methods We enrolled 20 CF patients (mean age: 27,6 years) with CRS, confirmed by nasal endoscopy. All patients, colonized by Pseudomonas Aeruginosa, performed daily a NW by physiological solution or by saline solution with surfactant (Naridek). All patients, at the time of enrollment, filled out a sinonasal questionnaire (SANQ11) and they received instructions for proper washing. During follow-up, we evaluated the reduction of the bacterial load in the nasal lavage. We assess the nasal cavities by endoscopy (2.7 mm 30° rigid endoscope - Storz, Tuttlingen, Germany) according to a modified Lund Kennedy endoscopic scoring system: - rhinorrhea (present = 0, mild = 1, purulent = 2); - edema, and hyperemia (absent = 0, mild = 1 or severe =2) - nasal mucosa (eutrophic = 1; hyperemic = 2; dystrophic = 3); - left and right turbinate hypertrophy (none = 0; mild = 1; medium = 2; and serious = 3). All subjects underwent the Sniffin’Sticks to evaluate the olfactory performance. Results Twelve patients completed 4 months of treatment: 6 patients performed the treatment with Naridek and 6 patients with physiological solution. Due to the small sample size, the scores were added together to have an overall indication of the treatment. (Table1) Nasal endoscopy ENT signs score Olfactory performance SNAQ 11 Naridek V1 80 72* 169 197** Naridek V4 15* 15* 159 98** Physiological solution V1 68 61 151 166 Physiological solution V4 52 39 159 152 *P<0.05 ** p< 0,01 The bacterial colonization in NWs shows no statistically significant difference. However, in 2 patients, we detected a reduction of the bacterial load. While there was no difference in the saline-treated group. Conclusions Considering our small sample we can only draw some great deal to think about: - treatment with NWs allows an improvement of the ENT symptoms and is well tolerated by patients. These data are confirmed by the ENT signs score and by the reduction of the SNAQ11 score in both treatment arms; - the solution with surfactant (Naridek) significantly improves the ENT signs and decreases the nasal endoscopy and the SNAQ11 scores; - no benefit was detected at the evaluation of olfactory performance. In conclusion, even if further confirmations are necessary on broader cases, it seems to emerge as significant the role of surfactant in the therapeutic advantage of NWs

CHRONIC RHINOSINUSITIS IN CYSTIC FIBROSIS PATIENTS: SMELL EVALUATION

Cystic Fibrosis (CF) involves the upper airways with chronic rhinosinusitis (CRS) causing nasal congestion, rhinorrhea, mouth breathing, facial pain, and olfactory dysfunction. Twelve to 71% of CF patients report smelling alterations impacting nutrition and quality of life. The aim was to study olfaction performance in CF patients with CRS that worsens quality of life. One hundred and twenty-one subjects were enrolled in this study. Seventy-one had CF and underwent ear, nose, and throat evaluation with nasal endoscopy, SNOT-22, VAS and “Sniffin’ Sticks”. Fifty subjects were age-matched with healthy controls. All 71 CF patients were affected by CRS; 59/71 (83.1%) had CRS without nasal polyps and 12/71 (16.9%) had CRS with early nasal polyps. None of the 50 controls had CRS. Total SNOTT-22 mean values in the 71 CF patients was 38.10 ± 21.08 pts. If considering only the 59 CF patients without nasal polyps the SNOTT-22 mean value was 36.76 ± 21.52 pts. Moreover, based on the VAS scores, the degree of nasal symptoms was classified as mild for facial pain, smell alteration, nasal discharge, and sneezing and resulted in moderate symptoms for nasal blockage and headache. Among the CF patients, 55/71 (76.5%) declared normosmia while the smelling ability assessed by “Sniffin’ Sticks” showed that only 4/71 (5.63%) were normosmic, 58 (81.69%) were hyposmic, and 9 (12.68%) were anosmic. In the controls 41(82%) were normosmic, 9 (18%) were hyposmic, and none were reported anosmia (p < 0.001). The study confirms that most CF patients have a relevant olfactory impairment, although only a low percentage declare it. A careful evaluation with simple and rapid tests helps to select the patients that may benefit from specific therapies

Employment Status and Work Ability in Adults with Cystic Fibrosis

Improvements in the survival and clinical outcomes of cystic fibrosis (CF) patients raised questions about their workforce participation and capacity to work. One hundred and ninety-six outpatients, attending the Adult CF Center of an Italian University Hospital, were enrolled between May 2020 and March 2021. The patients’ personal and clinical characteristics, employment status, and profession were assessed. The Cystic Fibrosis Questionnaire—Revised and the work ability index (WAI) were employed to assess CF health-related quality of life and the employee’s perception of their ability to work, respectively. Among the enrolled patients, 98 (50%) were employed. The non-working subjects were significantly younger (mean age ± standard deviation: 30 ± 10 vs. 37 ± 10 years) and were diagnosed with CF significantly earlier (9 ± 13 vs. 17 ± 18 years) than the employed subjects. The vast majority of CF workers (82.6%) were employed in tertiary professions. A general good work ability perception was determined in the employed population. Aging and being employed for &gt;15 years could significantly predict a reduction in work ability, while a better quality of life was a positive predictor for its enhancement. Although further research is necessary, these results may introduce interdisciplinary CF healthcare management that includes a work function assessment, formal career counseling, and job guidance to support the personal, social and professional lives of CF patients

Lipidomic alterations in human saliva from cystic fibrosis patients

Abstract Cystic fibrosis is a hereditary metabolic disorder characterized by impaired traffic of chloride ions and water through membranes of the respiratory and gastrointestinal, that causes inadequate hydration of airway surfaces, dehydrated mucous secretions and a high-sodium chloride sweat. Although the classical presentation of the condition is well known, a better characterization of metabolic alterations related is need. In particular, the metabolic composition alterations of biological fluids may be influence by the disease state and could be captured as putative signature to set targeted therapeutic strategies. A targeted comprehensive mass spectrometry-based platform was employed to dissect the lipid content of saliva samples form CF patients, in order to investigate alterations in the lipid metabolic homeostasis related to the pathology, chronic obstructive pulmonary disease, Pseudomonas Aeruginosa infection, pancreatic insufficiency, liver disfunction and diabetes-related complications

Lipidomic alterations in human saliva from cystic fibrosis patients

: Cystic fibrosis is a hereditary metabolic disorder characterized by impaired traffic of chloride ions and water through membranes of the respiratory and gastrointestinal, that causes inadequate hydration of airway surfaces, dehydrated mucous secretions and a high-sodium chloride sweat. Although the classical presentation of the condition is well known, a better characterization of metabolic alterations related is need. In particular, the metabolic composition alterations of biological fluids may be influence by the disease state and could be captured as putative signature to set targeted therapeutic strategies. A targeted comprehensive mass spectrometry-based platform was employed to dissect the lipid content of saliva samples form CF patients, in order to investigate alterations in the lipid metabolic homeostasis related to the pathology, chronic obstructive pulmonary disease, Pseudomonas Aeruginosa infection, pancreatic insufficiency, liver disfunction and diabetes-related complications