COVID-19 Lockdown Impacts Among Patients with Cystic Fibrosis: An Italian Regional Reference Centre Experience

Coronavirus pandemic has influenced our society with social distancing and management of chronic disease such as cystic fibrosis (CF). During the Italian lockdown from March to May 2020, CF patients reduced the number of outpatient visits, limited social interactions and spent more time at home. The aim of this study is to evaluate the impact of the lockdown on body mass index (BMI) and lung function tests on CF patients.We retrospectively reviewed clinical data about 111 CF patients followed in our Regional Cystic Fibrosis Reference Centre (Policlinico Umberto I, Rome) according to two periods: pre-lockdown (from October 2019-March 2020) and post-lockdown (from May 2020-October 2020). We collected data on nutritional (BMI and body weight) and lung function status; we chose the best values of the 'pre-lockdown' and 'post-lockdown' period for each patient. Patients were divided into 3 groups according to FEV1 value (Forced Expiratory Volume in the 1st second): group 1 (FEV140%), group 2 (FEV1 40-70%), group 3 (FEV170%). All patients received a telephone interview asking for the number of hours per week devoted to physical activity, number of pulmonary acute exacerbations and subjective evaluation of adherence to medical therapy, respiratory physiotherapy and diet, during the two periods.Comparing weight, BMI and respiratory function between pre and post lockdown periods, we noticed an increase in weight during among overall patients. Male patients improved weight, BMI, FEF 25-75% (Forced Expiratory flow between 25% and 75% of vital capacity) and Tiffenau index more than female patients. The most severely compromised patients (group 1), showed a significant loss of both weight and BMI. Instead, patients with moderate respiratory function (group 2) showed a significant increase of both weight and BMI and a slightly reduced CVF (Forced Vital capacity). We found no differences among patients with good respiratory function (group 3). Comparing each clinical sub-groups, we noticed a significative improvement of weight (Lockdown period had benefit among CF patients in terms of weight in particular in male patient. The greatest benefit on nutritional state was observed in patients with moderate reduction of respiratory function. In addition, we noted a stabilization and sometimes a slight improvement of lung function, instead of a continuous and steady decline that is normally observed in CF patients. These beneficial effects are slight but significative, bearing in mind the general worsening that CF patients experience annually

Usefulness of cyanide-nitroprusside test in detecting incomplete recessive heterozygotes for cystinuria: a standardized dilution procedure

We present the results of a cyanide-nitroprusside test (CNT) after a standardized dilution procedure of urine samples and report the efficiency of this method in detecting heterozygotes for cystinuria when applied on an open pediatric population. In the preliminary study we assayed by quantitative determination of amino acids 162 urine samples from a hospital population identifying 24 type III heterozygotes and 2 type II heterozygotes for cystinuria. The classic CNT gave 38 false positive results and 5 false negative results showing a sensitivity and specificity of 0.808 and 0.721, respectively. When progressively diluted, all samples of heterozygotes remained CNT positive up to a creatinine concentration of 90 mg/dl. At this level of dilution 31 out of 38 false positive turned to negative, thus obtaining a specificity of 0.922 without a lowering of the sensitivity in detecting heterozygotes. The standardized dilution at 90 mg/dl of creatinine concentration was applied to 74.7% of a population of 1024 schoolchildren. In this way 163 out of 210 positive results were eliminated and thus the specificity of CNT rose from 0.789 to 0.953. On the basis of these results, the method proposed can be regarded as reliable and useful for a screening program in detecting heterozygotes for cystinuria

Increased taurine content in esophageal mucosa of children affected by gastroesophageal reflux

We studied the possible involvement of mucosal amino acid metabolism in the pathogenesis of gastroesophageal reflux disease in children. Eighteen children with gastroesophageal reflux disease (8 with reflux esophagitis and 10 without) and 10 children with normal 24-h esophageal pH monitoring as a comparative group underwent esophagogastroduodenoscopy with biopsies. Plasma and esophageal mucosa amino acids were assayed by liquid chromatography. In children affected by gastroesophageal reflux disease we found an increase of mucosal taurine (P < 0.01) and a decrease of serine (P < 0.01). No differences were noted between patients with and without esophagitis. Significant positive correlations (P < 0.001; r = 0.626) were found between mucosal taurine content and reflux index. Plasma amino acid concentrations did not show any significant differences among groups. Our results indicate that biochemical alterations precede the histological findings of inflammation, likely reflecting the adaptive response of the esophageal mucosa to the gastric contents exposure

Gut microbiome response to a modern Paleolithic diet in a Western lifestyle context.

The modern Paleolithic diet (MPD), featured by the consumption of vegetables, fruit, nuts, seeds, eggs, fish and lean meat, while excluding grains, dairy products, salt and refined sugar, has gained substantial public attention in recent years because of its potential multiple health benefits. However, to date little is known about the actual impact of this dietary pattern on the gut microbiome (GM) and its implications for human health. In the current scenario where Western diets, low in fiber while rich in industrialized and processed foods, are considered one of the leading causes of maladaptive GM changes along human evolution, likely contributing to the increasing incidence of chronic non-communicable diseases, we hypothesize that the MPD could modulate the Western GM towards a more "ancestral" configuration. In an attempt to shed light on this, here we profiled the GM structure of urban Italian subjects adhering to the MPD, and compared data with other urban Italians following a Mediterranean Diet (MD), as well as worldwide traditional hunter-gatherer populations from previous publications. Notwithstanding a strong geography effect on the GM structure, our results show an unexpectedly high degree of biodiversity in MPD subjects, which well approximates that of traditional populations. The GM of MPD individuals also shows some peculiarities, including a high relative abundance of bile-tolerant and fat-loving microorganisms. The consumption of plant-based foods-albeit with the exclusion of grains and pulses-along with the minimization of the intake of processed foods, both hallmarks of the MPD, could therefore contribute to partially rewild the GM but caution should be taken in adhering to this dietary pattern in the long term

Effects of inhaled hypertonic (7%) saline on lung function test in preschool children with cystic fibrosis: results of a crossover, randomized clinical trial

Abstract Background This crossover, randomized, double-blind study (conducted over a 32-week period) was performed to determine, in clinically stable Cystic fibrosis (CF) preschool children: the effects of 7% inhaled hypertonic saline on spirometry and interrupter resistance technique (Rint), and the possible side effects. Methods Twelve CF children (6M, mean age ± SD: 5.7 ± 0.8 yrs) were enrolled and randomly assigned to receive hypertonic saline (HS-4 ml 7% sodium chloride), or normal saline (NS-0.9% sodium chloride) twice a day. After a 16 weeks period, therapy was exchanged to allow all the patients enrolled in the study to carry out both treatments. Monitoring visits, spirometry (COSMED Quark PFT4 ergo) and Rint were scheduled at 0,4,16,20,32 weeks. At T0, spirometric measurements and Rint were performed immediately before and 30 min after the inhalation therapy. Salbutamol (400 mcg) was administered before the drug at each visit. Results After a 16-weeks treatment with HS an improvement of FVC (p = 0.02) and a favorable trend of FEV1 were registered. A worsening of FEV1 (p < 0.0001) and of FEF25-75 (p = 0.019) were found in NS group. No differences were found in expiratory and inspiratory Rint in both groups. No serious adverse events occurred. Conclusions Seven percent hypertonic saline therapy proved to be a useful and safe treatment in young CF children with clinically stable conditions. Trial registration ISRCTN12345678

Migrainous Infarction in a Patient With Sporadic Hemiplegic Migraine and Cystic Fibrosis: A 99mTc-HMPAO Brain SPECT Study

Genetic mutations of sporadic hemiplegic migraine (SHM) are mostly unknown. SHM pathophysiology relies on cortical spreading depression (CSD), which might be responsible for ischemic brain infarction. Cystic fibrosis (CF) is caused by a monogenic mutation of the chlorine transmembrane conductance regulator (CFTR), possibly altering brain excitability. We describe the case of a patient with CF, who had a migrainous stroke during an SHM attack. A 32-year-old Caucasian male was diagnosed with CF, with heterozygotic delta F508/unknown CFTR mutation. The patient experiences bouts of coughing sometimes triggering SHM attacks with visual phosphenes, aphasia, right-sided paresthesia, and hemiparesis. He had a 48-hour hemiparesis triggered by a bout of coughing with hemoptysis, loss of consciousness, and severe hypoxia-hypercapnia. MRI demonstrated transient diffusion hyperintensity in the left frontal-parietal-occipital regions resulting in a permanent infarction in the primary motor area. Later, a brain perfusion SPECT showed persistent diffuse hypoperfusion in the territories involved in diffusion-weighted imaging alteration. Migrainous infarction, depending on the co-occurrence of 2 strictly related phenomena, CSD and hypoxia, appears to be the most plausible explanation. Brain SPECT hypoperfusion suggests a more extensive permanent neuronal loss in territories affected by aura. CF may be then a risk factor for hemiplegic migraine and stroke since bouts of coughing can facilitate brain hypoxia, triggering auras

Adult Patients Affected by Cystic Fibrosis in Therapy with Cystic Fibrosis Transmembrane Regulator Modulators and Lung Transplant: Renal Function, Metabolic and Nutritional Status

Background. Cystic fibrosis (CF) is one of the most frequent genetic diseases. The discovery and implementation of new therapies prolonged the survival of CF patients in the last years. Evaluation of long-term complications could be useful to improve the outcome of these patients. Aim of the Study. To evaluate renal function, metabolic, nutritional, and inflammatory status in CF patients on cystic fibrosis transmembrane regulator (CFTR) modulators therapy as well as lung transplant recipients (LRs) and patients on conservative therapy (control group). Materials and Methods. We performed a prospective, longitudinal study on 69 CF patients. Clinical and laboratory parameters (metabolic and nutritional indices and inflammatory markers) were evaluated in all patients before starting CFTR therapy or transplant (T0) and after 3 years (T1). Results. We enrolled 69 CF patients (42 males). Patients were distributed into three groups. The average age was 35.01 ± 10.57 years for the control group (group 0), 32.47 ± 9.40 years for patients on CFTR modulators therapy (group 1), and 38.93 ± 7.14 years for LRs (group 2). At T1, we showed a significant difference among the three groups in terms of renal function indices: creatinine, eGFR, serum nitrogen as well as serum uric acid, sodium, and potassium (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, and p<0.001, respectively), particularly in LRs patients. Significant differences were found in nutritional status parameters among the three groups: total protein, serum albumin, serum fibrinogen, serum transferrin, and white blood cell counts (p<0.001, p=0.037, p=0.04, p=0.003, and p=0.007, respectively), particularly in LRs compared with other groups. Moreover, we found significant differences in metabolic profile (HbA1c, p=0.026) and inflammatory status, with a significant difference in C-reactive protein values, neutrophil counts, and neutrophil-lymphocyte ratio (NLR) among the three groups (p<0.001, p=0.005, and p=0.026, respectively). Conclusions. Our study showed a reduced renal function and poor nutritional status in LRs, along with worse metabolic control. Moreover, we showed a lower inflammatory status in patients on CFTR modulators therapy. Therefore, we suggest early and careful monitoring of renal function, metabolic, and nutritional parameters in CF patients, whether they are on conservative therapy, CFTR modulators therapy, and LRs patients

Neutrophil glutamine deficiency in relation to genotype in children with cystic fibrosis

Pulmonary disease in cystic fibrosis (CF) is characterized by a chronic neutrophil-dominated inflammation of lung tissue. Inasmuch as some amino acids (AA) play a pivotal role in various aspects of neutrophil metabolism, the aim of this study was to investigate a possible alteration of neutrophil AA metabolism and to evaluate its relation (if any) with the genotype. We performed plasma and neutrophil AA analysis in 26 CF patients with known Genotype. 10 patients with non-CF bronchiectasis, and 20 normal subjects. The CF group showed a significant decrease of free intracellular neutrophil glutamine (Gin) content compared with controls and the non-CF bronchiectasis group. In the latter group, levels of neutrophil Gin were significantly lower compared with the controls. Amino acid plasma concentration in non-CF bronchiectasis showed a decrease of Gin and taurine compared with controls. Neutrophil Gin content showed values significantly lower in CF patients with severe mutations (class I, II and III mutations) compared with mild mutations (class IV and V mutations). Results of our study add further evidence for intrinsic neutrophil alterations that could play an important role in the pathogenesis of chronic pulmonary disease in CF patients