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Advances in the treatment and management of cystic fibrosis (CF) have led to a substantial increase in patient life expectancy, thus facilitating healthier lives and labour force participation. This review aimed to address the impact of CF on the occupational functioning of patients. A significant proportion of patients were reported to retain a job on a full- or part-time schedule. Less physically demanding occupations were most frequently performed, perhaps due to CF-related inability to sustain a heavy workload. Disease severity parameters (e.g., lung function measurements, or personal, psycho-social, or economic conditions) have been reported as determinant or co-determinant factors for the development of work-related disability. Although further research is necessary, our results may be useful to inform interdisciplinary CF healthcare management, including the assessment of work function, and to define career counselling plans and workplace risk assessment and management strategies to support the personal, social and professional lives of patients.

The aim of this study was to assess the long-term clinical impact of the application of e-health as part of a virtual model of care in patients with Cystic Fibrosis (CF).Digital care group (DCG) were deemed suitable for using the NuvoAir Home platform to monitor their disease at home as part of a virtual model of care project. The usual care group (UCG) remained on usual care. NuvoAir Home platform consists of a smartphone application, Bluetooth spirometer and a clinician portal. Data on pulmonary function, Cystic Fibrosis Questionnaire-Revised (CFQR) and pulmonary exacerbations were collected at baseline and after twelve months. A survey for the digital care group was emailed to evaluate their experience using the technology.Between February 2020 and May 2020 a cohort of 43 CF patients were recruited for the DCG (26 females; mean age 31.6 ± 6.8; 16 homozygous for delta F508; FEVThe application of digital technologies in the management of adults with CF showed an improvement in patients' quality of life. Using a virtual model of care was well accepted by CF patients and improved their understanding of their medical condition.

Elexacaftor/tezacaftor/ivacaftor (ETI) is the newest cystic fibrosis transmembrane conductance regulator (Retrospective observational study inppFEVIn

In recent years, patients with cystic fibrosis (CF) conductance regulator (CFTR) variant poly(T) sequences have been increasingly reported with a wide spectrum of clinical severity. We describe the long-term clinical outcomes and progression to a CF diagnosis over time in a large Italian cohort of patients carrying the CFTR F508del/5T;TG12 genotype.A retrospective analysis of subjects from 10 CF centres in Italy with the F508del/5T;TG12 genotype was performed. Demographic, clinical, microbiological, and biochemical data, as well as information about the follow-ups and complications of the enroled patients, were collected.A total of 129 subjects (54 females; median age: 15.0 years, range: 0-58 years; 59 older than 18 years) were included. In terms of initial diagnoses, 30 were CF (23.3%), 41 were CFTR-related disorder (CFTR-RD) (31.7%), and 58 were CF transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID) (45.0%). After a median follow-up of 6.7 years (range 0.2-25 years), 15 patients progressed to CF, bringing the total number of CF diagnoses to 45/129 (34.9%). Most of these patients had mild lung diseases with pancreatic sufficiency and a low prevalence of CF-related complications.At the end of the study, 34.9% of subjects with the CFTR F508del/5T;TG12 genotype were diagnosed with CF. We suggest including patients with the F508del/5T;TG12 genotype in long-term follow-ups.

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.

Background: Cystic fibrosis (CF) is one of the most common inherited diseases. It is characterised by a severe decline in pulmonary function associated with metabolic perturbations and an increased production of inflammatory cytokines. The key role of physical activity (PA) in improving the health status of CF patients and reducing lung function decline has recently been demonstrated. This study evaluated interleukin-6 (IL-6) and tumour necrosis factor α (TNFα) expression in two subgroups of CF patients classified based on PA. Methods: We selected 85 CF patients, half of them regularly undertook supervised PA in the three years leading up to the study and half of them were not physically active. Patients were analysed for serum IL-6 and TNFα levels using enzyme-linked immunosorbent assays. Results: We found that the expression levels of IL-6 and TNFα differed in terms of their regulation by PA. In particular, TNFα levels negatively correlated with FEV1% decrease/year and FEV1% decrease (p = 0.023 and p = 0.02, respectively), and positively correlated with serum fasting glucose (p = 0.019) in PA CF patients. In contrast, in the NPA subgroup, TNFα levels were positively correlated with IL-6 (p = 0.001) and negatively correlated with adiponectin (p = 0.000). In addition, multiple logistic regression analysis confirmed that PA is an independent modulator of the inflammatory state. Conclusions: PA modulates inflammatory processes in CF patients by regulating the secretion of pro-inflammatory cytokines and thus ameliorating lung function. Our data show that PA is a useful complementary strategy in the management of CF and that TNFα may be a marker of these effects of PA.

Impaired salivary non-esterified fatty acids (NEFA) levels have been previously observed in cystic fibrosis (CF). This study aimed to characterize the salivary NEFA profile in CF and to examine whether the alterations are related to the pancreatic status and/or lung disease severity. We analyzed salivary NEFA, cholesterol and interleukin-6 (IL-6) in CF patients (n = 66) and healthy subjects (n = 48). CF patients showed higher salivary levels of cholesterol, total NEFA (that was negatively correlated with serum triglycerides), unsaturated NEFA/saturated NEFA (U/S NEFA) ratio and IL-6 than controls. The U/S NEFA ratio was positively correlated with IL-6 in both patients and controls, suggesting an association between this parameter and local inflammation independently from the disease. No correlation between salivary lipids and pancreatic status was observed, while the U/S NEFA ratio was higher in patients with severe lung disease than mild/moderate severity and may represent a prognostic marker of lung disease in CF.

Background: A wide range of cystic fibrosis (CF)-related conditions are reported in CF carriers, but no study has explored the possibility that such subjects may be affected by cystic fibrosis transmembrane regulator-related disorders (CFTR-RD). No data are available so far on the occurrence of CFTR-RD among CF carriers. Methods: We studied 706 CF carriers—first- and second-degree relatives of CF patients that carried the parental mutation; such subjects were divided in two groups: a first group (353 subjects, group A) performed at first only the analysis of the CFTR proband mutation; we retrospectively evaluated the number of cases that had been diagnosed as CFTR-RD based on subsequent symptoms; a second group (353 subjects, group B) performed extensive CFTR molecular analysis in absence of any reported symptoms, followed by a clinical evaluation in cases that carry a second CFTR mutation; we evaluated the number of cases that prospectively were diagnosed as CFTR-RD. Results: We found seven (2.0%) out of 353 subjects of group A and 24 (6.8%) out of 353 subjects of group B as affected by CFTR-RD (chi square, p = 0.002). Conclusions: A percentage of CF carriers are affected by undiagnosed CFTR-RD. Genetic tasting scanning analysis helps to identify CFTR-RD, some of which may benefit from follow-up and specific therapies improving their outcome.

About 50% of patients with cystic fibrosis (CF) have sinonasal complications, which include inferior turbinate hypertrophy (NTH) and/or nasal polyposis (NP), and different degrees of lung disease, which represents the main cause of mortality. Monitoring of sinonasal disease requires complex instrumental procedures, while monitoring of lung inflammation requires invasive collection of bronchoalveolar lavage fluid. The aim of this study was to investigate the associations between salivary cytokines levels and CF-related airway diseases. Salivary biochemical parameters and cytokines, i.e., interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-&alpha, ), were analyzed in resting saliva from healthy subjects and patients with CF. Patients with CF showed significantly higher levels of salivary chloride, IL-6, IL-8, and TNF-&alpha, and lower calcium levels than healthy subjects. Among patients with CF, IL-6 and IL-8 were significantly higher in patients with NTH, while TNF-&alpha, was significantly lower in patients with NP. A decreasing trend of TNF-&alpha, in patients with severe lung disease was also observed. On the other hand, we did not find significant correlation between cytokine levels and Pseudomonas aeruginosa or Stenotrophomonas maltophilia colonization. These preliminary results suggest that salivary IL-6 and IL-8 levels increase during the acute phase of sinonasal disease (i.e., NTH), while the end stages of pulmonary disease and sinonasal disease (i.e., NP) show decreased TNF-&alpha, levels

The clinical manifestation of cystic fibrosis (CF) is heterogeneous also in patients with the same cystic fibrosis transmembrane regulator (CFTR) genotype and in affected sibling pairs. Other genes, inherited independently of CFTR, may modulate the clinical manifestation and complications of patients with CF, including the severity of chronic sinonasal disease and the occurrence of chronic Pseudomonas aeruginosa colonization. The T2R38 gene encodes a taste receptor and recently its functionality was related to the occurrence of sinonasal diseases and upper respiratory infections. We assessed the T2R38 genotype in 210 patients with CF and in 95 controls, relating the genotype to the severity of sinonasal disease and to the occurrence of P. aeruginosa pulmonary colonization. The frequency of the PAV allele i.e., the allele associated with the high functionality of the T2R38 protein, was significantly lower in i) CF patients with nasal polyposis requiring surgery, especially in patients who developed the complication before 14 years of age; and ii) in CF patients with chronic pulmonary colonization by P. aeruginosa, especially in patients who were colonized before 14 years of age, than in control subjects. These data suggest a role for T2R38 as a novel modifier gene of sinonasal disease severity and of pulmonary P. aeruginosa colonization in patients with CF.

BackgroundCystic fibrosis (CF) is a multisystem disease that involves the upper airways with chronic rhinosinusitis (CRS) causing nasal congestion, rhinorrhea, mouth breathing, facial pain, and olfactory dysfunction. Twelve percent to 71% of CF patients report smelling alterations with an impact on nutrition and quality of life.ObjectivesThe goal was to study olfaction performance in CF patients with CRS that worsens quality of life.MethodsA total of 121 subjects were enrolled in this study. Seventy-one had CF and underwent ear, nose, and throat evaluation with nasal endoscopy, sinonasal outcome test 22 (SNOT-22), visual analog scale (VAS), and “Sniffin’ Sticks.” Fifty subjects were age-matched with healthy controls.ResultsAll 71 CF patients were affected by CRS; 59 of 71 (83.1%) had CRS without nasal polyps and 12 of 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 were 38.10 ± 21.08 points. If considering only the 59 CF patients without nasal polyps, the SNOTT-22 mean value was 36.76 ± 21.52 points. 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 of 71 (76.5%) declared to be normosmic, while the smelling ability assessed by “Sniffin’ Sticks” showed that only 4 of 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 to be anosmic ( P ConclusionsWe confirm that most CF patients have a relevant olfactory impairment, although only a low percentage declares such alteration. A careful evaluation with simple and rapid tests helps to select the patients who may benefit from specific therapies.

Background Cystic fibrosis (CF) patients have reduced intestinal absorption of sterols and, despite enhanced endogenous synthesis, low plasma cholesterol. Lumacaftor/ivacaftor CFTR protein modulator therapy is used to improve the clinical outcome of CF patients homozygous for F508del mutation (homo-deltaF508). Aim of the study is to evaluate the cholesterol metabolism and hepatobiliary injury/function in adult homo-deltaF508 patients, before and after lumacaftor/ivacaftor treatment. Baseline parameters in homo-deltaF508 patients were compared to those in CF patients compound heterozygous for F508del mutation and another severe mutation (hetero-deltaF508). Methods Cholesterol metabolism was evaluated measuring plasma phytosterols and cholestanol, as intestinal absorption markers, and lathosterol, as liver biosynthesis marker. We quantified serum vitamin E, as nutritional marker. We evaluated liver injury by aspartate aminotransferase (AST) and alanine transaminase (ALT), biliary injury by γ-glutamyltransferase (γGT) and AP, and the liver function by bilirubin and albumin. Results Before the treatment, homo-deltaF508 patients (n = 20) had significantly lower cholesterol and vitamin E compared to hetero-deltaF508 (n = 20). Lumacaftor/ivacaftor treatment caused: 1) further reduction of cholesterol; 2) lathosterol reduction, suggesting a normalization of endogenous synthesis; 3) cholestanol and vitamin E increment, indicating an improvement of lipid digestion/absorption. Vitamin E difference (after-before treatment) was positively associated to treatment months. Alkaline phosphatase was also reduced. Conclusions These data suggest an effect of lumacaftor/ivacaftor on cholesterol metabolism and enterohepatic flux in CF patients. However, lumacaftor/ivacaftor does not promote the increase of cholesterol serum concentration that on the contrary declines. Further studies are needed to research the real mechanism causing this reduction.

Background Patients with cystic fibrosis (CF) have a reduced intestinal absorption of cholesterol and in a preliminary study we observed differences in plasma sterol profile between patients with pancreatic sufficiency (PS) and those with pancreatic insufficiency (PI). Therefore, we hypothesized that the sterol analysis may contribute to study the digestion and absorption state of lipids in patients with CF. To this aim we evaluated plasma sterols in a significant number of adult patients with CF in relation to the pancreatic status. Methods Beside cholesterol, we measured phytosterols and lathosterol as markers of intestinal absorption and hepatic biosynthesis, respectively, by gas-chromatography in plasma of adult CF patients with pancreatic sufficiency (PS-CF, n = 57), insufficiency (PI-CF, n = 97) and healthy subjects (control group, CT, n = 71). Results PI-CF patients had cholesterol and phytosterols levels significantly lower than PS-CF and CT (p −10) suggesting a reduced intestinal absorption of sterols related to PI. Instead, lathosterol was significantly higher in PI-CF patients than PS-CF and CT (p Conclusions A plasma sterols profile may be useful to evaluate the metabolic status of lipids in adult patients with CF and could help to manage the pancreatic enzyme supplementation therapy.

Background Elexacaftor/tezacaftor/ivacaftor (E/T/I) is a cystic fibrosis transmembrane conductance regulator (CFTR) triple combination therapy used for the treatment of cystic fibrosis (CF) in patients aged ≥12 years who have at least one copy of the Phe508del mutation (F) in the CFTR gene or another mutation that is responsive to treatment with E/T/I. This study determined the effectiveness and safety of E/T/I treatment in a cohort of CF patients. Methods This retrospective cohort study collected data from the first 6 months of treatment of patients with CF, compound heterozygotes for the F and a minimal function (MF) mutations, enrolled in an E/T/I compassionate use program only available to patients having ppFEV1 Results After 6 months of treatment, the mean (standard deviation (SD)) SCC decreased from 91.1 (19.3) mmol/L to 46.2 (24.2) mmol/L. The decrease of SCC was accompanied by improvement of lung function (mean (95% Confidence Interval (CI) absolute increase in ppFEV1 was 10.69 (8.05,13.33) after 1 month and 14.16 (11.43, 16.89) after 6 months of treatment), nutrition (mean (SD) BMI increased from 20.7 (3.0) kg/m2 at baseline to 22.6 (3.1) after 6 months), and QoL. No safety concerns were observed. Conclusions E/T/I was clinically effective and safe in patients with advanced CF lung disease with an F/MF genotype.

BACKGROUND: The effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies. OBJECTIVES: To describe the genotype-phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator (CFTR) complex alleles. METHODS: We studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p.[Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr;Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p.[Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p.Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele. RESULTS: The p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I-II mutation. Their CFTR activity on NEC was comparable with patients with two class I-II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p.Asp1270Asn have scarce functional effects, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I-II mutation in trans, or CFTR-related disorders (CFTR-RD) in three having in trans a class IV-V mutation. The p.[Arg74Trp;Val201Met;Asp1270Asn] causes significantly (pT] and a class I-II mutation had mild CF or CFTR-RD (gating activity: 18.5-19.0%). CONCLUSIONS: The effect of complex alleles partially depends on the mutation in trans. Although larger studies are necessary, the CFTR activity on NEC is a rapid contributory tool to classify patients with CFTR dysfunction.

BACKGROUND Ivacaftor is a significant innovation in the treatment of cystic fibrosis (CF) with gating mutations. A substantial percentage of patients with CF have severe lung involvement, but these patients are usually excluded from phase III clinical trials. Thus, the effectiveness of ivacaftor in this population has not been fully determined. METHODS Data were collected from Italian CF centers with patients enrolled in an ivacaftor compassionate use programme (percent predicted [pp] forced expiratory volume in 1 second [FEV1 ]

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.

Cystic fibrosis (CF) is a genetic disease characterized by progressive decline of lung function and chronic airway inflammation. Adipose tissue, through adiponectin and leptin, exerts several effects on energy metabolism and inflammatory processes. This study evaluated the levels of adiponectin and leptin in adult healthy subjects, in patients with CF and their correlation with long-term physical activity. CF patients were divided into two groups (sedentary versus active) based on their regular physical activity over 3 years. Anthropometric and serum biochemical profiles of CF patients and controls were evaluated and compared. Total serum adiponectin and leptin levels were measured by ELISA; adiponectin oligomeric profiles were analysed by western blot. Adiponectin levels were significantly higher while leptin levels were lower in patients with CF than in healthy controls. Furthermore, adiponectin was significantly lower in active compared to sedentary CF (p=0.047), while leptin was slightly increased in active compared to sedentary CF. In addition, C-reactive protein levels were significantly lower in active than in sedentary CF patients (p=0.048). Interestingly, only in the active group adiponectin levels were inversely correlated with forced expiratory volume (FEV) 1% decrease/year and FEV1% decrease. Moreover, adiponectin levels negatively correlated with lipid profiles. Our findings indicated that regular, long-term physical activity in CF improves respiratory function, metabolism, and inflammation status. These improvements in patients’ conditions are associated with immunometabolic processes involving adiponectin, leptin, and C-reactive protein. Therefore, we propose that both adipokines may be a useful biomarker in the evaluation of metabolic and inflammatory status in patients with CF.

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

Objective Cystic fibrosis (CF) is the most common inherited, life limiting condition among Caucasians. No healing therapy is currently available for patients with CF. The aim of the study was to define clinical, anthropometric and biochemical effects of regular, supervised physical exercise in a large cohort of patients with CF. Materials and methods Fifty-nine adult patients with CF that performed regularly supervised physical exercise in the last 3 years in comparison to 59 sex and age matched sedentary patients with CF were included in the study. Results Physical exercise had significantly beneficial effects on: (a) FEV1% decline; (b) anthropometric parameters (lower number of cases with altered BMI, waist and arm circumferences); (c) lipid and glucose metabolism; (d) vitamin D serum levels. Of course, some of this improvement may be because of the better adherence to therapy typical of patients with CF that perform physical activity. Conclusions Such clinical and metabolic effects make supervised physical activity one of the hubs in managing patients with CF.

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 followup, we evaluated the reduction of the bacterial load in the nasal lavage. We assessed 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

Introduction: 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. Aims and objectives: we assessed clinical, functional, microbiological and MRI findings in PCD and mild CF patients in order to evaluate different expression of lung disease. Methods: 20 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 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.

Background:Low cholesterol is typically observed in the plasma of patients with cystic fibrosis (CF) contrasting with the subcellular accumulation of cholesterol demonstrated in CF cells and in mice models. However, the homeostasis of cholesterol has not been well investigated in patients with CF.Methods:We studied the plasma of 26 patients with CF and 33 unaffected controls campesterol and β-sitosterol as markers of intestinal absorption and lathosterol as a marker of de novo cholesterol biosynthesis by gas chromatography (GC-FID and GC-MS).Results:Plasma campesterol and β-sitosterol results were significantly (p=0.01) lower while plasma lathosterol was significantly higher (p=0.001) in patients with CF as compared to control subjects. Plasma cholesterol results were significantly lower (p=0.01) in CF patients.Conclusions:Our data suggest that the impaired intestinal absorption of exogenous sterols in patients with CF stimulates the endogenous synthesis of cholesterol, but the levels of total cholesterol in plasma remain lower. This may be due to the CFTR dysfunction that reduces cholesterol blood excretion causing the accumulation of cholesterol in liver cells and in other tissues contributing to trigger CF chronic inflammation.

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.

patients with the G551Dmutation highlight opportunities to understand EOR in ‘real world’ people with CF. We aimed to evaluate symptoms of EOR in people with CF prior and during treatment with ivacaftor. Methods: We collected 52 week data from 12 adults with CF and the G551D mutation from a regional centre at baseline, and following 6, 26 and 52 weeks of treatment with ivacaftor (150mg bd). EOR was measured by questionnaire [reflux symptom index (RSI), Hull airway reflux questionnaire (HARQ) score >13 EOR symptomatic]. Sweat chloride (mmol/L), lung function (FEV1 and FVC % of predicted) and weight gain (kg and kg/m) were also measured. Results: See the table.

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.

Several studies reported low nasal nitric oxide (nNO) levels in subjects with primary ciliary dyskinesia (PCD) and proposed nNO measurement as a diagnostic tool to screen for the disease. All these reports used the aspiration nNO method. The goal of this study was to evaluate nNO in patients with PCD using different methods of NO measurement, including continuous aspiration, silent exhalation, and single-breath humming exhalation, which increases NO wash-out from the paranasal sinuses to the nose.Fourteen patients with established diagnosis of PCD and 14 healthy controls (HC) were examined. Oral and nasal NO levels were measured by chemiluminescence. Each subject performed NO measurement in triplicate during oral exhalation, nasal aspiration (nNOasp), nasal exhalation (nNOexh), and single-breath humming (nNOhum).The median nNOasp value (95% confidence interval) was 11.6 (7.2-19.1) ppb in PCD and 321.8 (270.6-510.6) ppb in HC (p0.001). The nNOexh value was 2.2 (1.3-3.1) in PCD and 31.8 (26.6-47.2) ppb in HC (p0.001). Patients with PCD had lower nNO than HC during the last 80% of the exhalation throughout humming, i.e. 2.8 (2.2-4.3) ppb vs. 212.4 (158.7-244.8) ppb (p0.001), and did not show a clear nNO peak. All nasal NO measurements had excellent specificity and sensitivity in detecting PCD compared with the healthy controls.nNO is consistently low in PCD with good specificity and sensitivity whatever the method used for NO measurement. The extremely low levels of nNO during humming support the notion that NO is defective in the paranasal sinuses in PCD.

Objectives: Magnetic resonance imaging (MRI) has been proposed as a radiation-free alternative to high resolution computed tomography (HRCT) for the assessment and follow-up of chest disorders. Thus far, no study has compared the efficacy of high-field MRI and HRCT in children and adults with noncystic fibrosis (CF) chronic lung disease. The aims of our study were: (1) to assess whether chest high-field MRI is as effective as chest HRCT in identifying pulmonary abnormalities; and (2) to investigate the relationships between the severity and extent of lung disease, and functional data in patients with non-CF chronic lung disease. Materials and Methods: Forty-one subjects (median age, 13.8 years; range, 5.9-29.3 years; 30 children/11 adults) with primary ciliary dyskinesia (n = 14), primary immunodeficiency (n = 14), or recurrent pneumonia (n = 13) underwent pulmonary function tests, chest HRCT (120 kV, dose-modulated mAs) and high-field 3.0-T MRI (HASTE; transversal orientation; repetition time/echo time/flip angle/acquisition time, infinite/92 milliseconds/150°/approximately 90 seconds). HRCT and MRI images were scored in consensus by 2 raters using a modified version of the Helbich scoring system. The maximal score was 25. Results: HRCT and high-field MRI total scores were 11 (range: 1-20) and 11 (range: 1-17), respectively. There was good agreement between the 2 techniques for all scores (r > 0.8). HRCT and MRI total scores, and extent of bronchiectasis scores were significantly related to pulmonary function tests (r = -0.4, P < 0.05). The MRI mucous plugging score was significantly related to pulmonary function tests (r = -0.4, P < 0.05). Conclusions: Chest high-field 3.0-T MRI appears to be as effective as HRCT in assessing the extent and severity of lung abnormalities in non-CF chronic lung diseases, and might be a reliable radiation-free option to HRCT.