Arianna Biffi

Background: The impact of COVID-19 on respiratory outcomes in people with cystic fibrosis (pwCF) has not been clearly characterized. We evaluated changes in respiratory function indicators derived from spirometry and pulmonary exacerbation rates 6 months after SARS-CoV-2 infection. Methods: This multicentre prospective study was based on pwCF enrolled between October, 2020 and June, 2021 in the DECO COVID-19 project. PwCF complaining of COVID-like symptoms were tested with real-time polymerase chain reaction (RT-PCR) for SARS-CoV-2 on nasopharyngeal swab. Mean changes in respiratory function indicators and time to first episode of pulmonary exacerbation were compared between RT-PCR-positive and RT-PCR-negative patients. Regression models were used to adjust for baseline percent predicted forced expiratory volume in one second (ppFEV1) values, number of comorbidities, and initiation of CFTR modulator therapy during the follow-up. Results: We enrolled 26 pwCF with RT-PCR-confirmed infection and 42 with a RT-PCR-negative test. After 6 months of follow-up, mean ppFEV1 changes were not significantly different between groups (+0.3% in positive vs. +0.2% in negative patients, p = 0.19). The 6-month cumulative probabilities of a first episode of pulmonary exacerbation were: 0.575 among RT-PCR-negative patients and 0.538 among those with a positive test (adjusted hazard ratio: 0.88, 95% CI: 0.44–1.75). Conclusions: COVID-19 did not appear to negatively affect respiratory outcomes of pwCF at 6 months from infection.

Objective: Diabetes is a frequent comorbidity in cystic fibrosis (CF), related to multiple unfavorable outcomes. During the progression of β-cell dysfunction to diabetes, insulin deficiency could possibly reduce the anabolic support to grow even in the absence of significant glycemic derangements. To test this hypothesis, we evaluated whether prepuberal insulin secretory indices are independent predictors of adult height. Design: Observational cohort study. Research design and methods: A longitudinal analysis of 66 CF patients (33 females) from an ongoing cohort received at prepuberal age (median age of 12 years) modified 3-h oral glucose tolerance tests with 30-min insulin and C-peptide sampling, modeling of insulin secretory and sensitivity parameters, anthropometric evaluation. The latter was repeated when adults after a median follow-up of 9 years. Results: In alternative models, we found a positive association with either basal insulin secretion (mean 0.22, 95% CI 0.01, 0.44 z-scores) or prepuberal β-cell glucose sensitivity (mean 0.23, 95% CI 0.00, 0.46 z-scores) and adult height, while total insulin secretion was negatively related to adult height (mean −0.36, 95% CI −0.57, −0.15 z-scores or mean −0.42, 95% CI −0.69, −0.16 z-scores, respectively). The high total insulin secretion of low adult height patients was mainly due to late (>60 min) secretion and was associated with a worse glucose response during OGTT. Conclusions: Abnormal insulin secretion associated with high glucose response during OGTT predicts a decrease in adult height z-score. Our results suggest that insulin secretory defects in CF affect growth prior to the development of fasting hyperglycemia.

Background: A wide range of frequency of azole‐resistance in A fumigatus in different patient populations worldwide was observed threatening to reduce therapeutic options.Objectives: Estimate the prevalence of azole‐resistance, investigate the molecular mechanisms of resistance, compare the genotypes of resistant clinical isolates with those from the surrounding environment.Methods: Aspergillus isolates were collected by seven Italian hospital microbiology laboratories. Strains were isolated from different clinical samples from unselected patients. The azole‐resistance was evaluated using screening test and microdilution EUCAST method. The molecular mechanism of resistance was performed sequencing the cyp51A gene. Resistant isolates were genotyped by microsatellite analysis and their profiles compared with those of azole‐resistant isolates from previous Italian studies.Results: 425 Aspergillus isolates from 367 patients were analysed. The azole‐resistance rates were 4.9% and 6.6% considering all Aspergillus spp. isolates and the A fumigatus sensu stricto, respectively. All resistant isolates except one were from a single hospital. Two rare azole‐resistant species were identified: A thermomutatus and A lentulus. The predominant resistance mechanism was TR₃₄/L98H. No correlation between the clinical resistant strains and environmental isolates from patients’ home/work/ward was observed. The analysis of the molecular correlation between the resistant clinical strains collected in the present study and those of environmental and clinical origin collected in previous Italian studies reveals a progressive diversification of azole‐resistant genotypes starting from a founder azole‐resistant genotype.Conclusions: This study confirms the trend of azole‐resistance rate in Italy, showing a geographical difference. Data reinforce the importance of surveillance programmes to monitor the local epidemiological situation.

Vitamin A is a fundamental micronutrient that regulates various cellular patterns. Vitamin A deficiency (VAT) is a worldwide problem and the primary cause of nocturnal blindness especially in low income countries. Cystic fibrosis (CF) is a known risk factor of VAD because of liposoluble vitamin malabsorption due to pancreatic insufficiency. We describe a case of a 9-year-old girl who experienced recurrent episodes of nocturnal blindness due to profound VAD. This little girl is paradigmatic for the explanation of the key role of the gut–liver axis in vitamin A metabolism. She presents with meconium ileus at birth, requiring intestinal resection that led to a transient intestinal failure with parenteral nutrition need. In addition, she suffered from cholestatic liver disease due to CF and intestinal failure-associated liver disease. The interaction of pancreatic function, intestinal absorption and liver storage is fundamental for the correct metabolism of vitamin A.

Bacteria from the Burkholderia cepacia complex (Bcc) are capable of causing severe infections in patients with cystic fibrosis (CF). Bcc infection is often extremely difficult to treat due to its intrinsic resistance to multiple antibiotics. In addition, it seems to speed up the decline of lung function and is considered a contraindication for lung transplantation in CF. This study investigates the species of the Bcc strains recovered from chronically infected CF subjects by means of: isolation, identification methods and complete recA nucleotide sequences of 151 samples. Molecular typing showed that B. cenocepacia III is the dominant strain found in the group of subjects being treated at the Milan CF Centre (Italy) and that the infection is chronically maintained by the same species. Defining species by means of molecular analysis yields important information for the clinician in order to establish the most appropriate therapy and implement correct measures for prevention of transmission among CF subjects.

Background: Hypertonic saline (HS) has been established as a therapy aimed at restoring the surface liquid of airways liquid and enhancing mucociliary clearance in patients with cystic fibrosis (CF). A formula containing 7% HS and 0.1% hyaluronic acid (HA) is also available, basing its use on the protective effects of HA against elastin injury and on its greater ease of administration (i.e., the perceived acceptability of inhalation). This study explores the effect of HA+HS in reducing the inflammation of airways, by measuring cytokine levels in sputum, its safety profile, and the prevalence of commonly reported symptoms like cough, throat irritation, and saltiness. Methods: In a pilot, double-blind, randomized controlled, parallel-group, 1:1 trial, clinically stable CF patients older than 6 years of age and with a FEV₁pred. >40% were randomized to one of the treatment arms, HS or HS+HA, to be administered twice a day at home. Clinical data, inflammatory markers (IL-1β, IL-6, IL-8, IL-10, TNF-α, VEGF) in sputum, and judgments on the tolerability and pleasantness were collected at the beginning and after 28 days. Results: HA+HS had no significant effect on inflammatory markers versus HS alone, as shown by broad confidence intervals. In the HS+HA group, the highest decrement from baseline values was observed for IL-1β (−58.8%) followed by VEGF (−49.9%), whereas in the HS group a significant increment of IL-10 levels (+83.0%; p = 0.011) was the only significant finding. Prevalence of unfavorable scores was 36.8% in HA+HS versus 55% in HS group (p = 0.207); no significant differences were detected in the prevalence of moderate/severe symptoms of cough, saltiness, and throat irritation in pulmonary functions tests after 28 days. Conclusions: HS+HA administration in CF patients does not show any significant effects on lung inflammation and function as compared to HS alone.