Effects of Elexacaftor/Tezacaftor/Ivacaftor on Cardiorespiratory Polygraphy Parameters and Respiratory Muscle Strength in Cystic Fibrosis Patients with Severe Lung Disease.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators represent targeted therapies directly acting on the CFTR channel. The triple therapy Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) has been demonstrated to improve lung function and quality of life in cystic fibrosis (CF) patients. However, the effects of ELX/TEZ/IVA on sleep-disordered breathing (SDB) and respiratory muscle strength are poorly studied. The aim of this study was to assess the effects of ELX/TEZ/IVA in patients with CF and severe lung disease on cardiorespiratory polygraphy parameters, maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) measures. METHODS: patients with CF aged ≥ 12 who started treatment in a compassionate use program were retrospectively studied through the evaluation of nocturnal cardiorespiratory polygraphy parameters, MIP and MEP; and six-minute walk test (6MWT) at baseline and at months 3, 6, and 12 of treatment. RESULTS: Nine patients (mean age 30.3 ± 6.5 years) with severe CF (mean baseline ppFEV1 34.6 ± 5.1%) were evaluated. A significant improvement in nocturnal oxygenation measured by mean SpO2 (92.4 vs. 96.4%, p < 0.05), time spent with SpO2 ≤ 90% (-12.6, -14.6, -15.2 min from baseline at months 3, 6, and 12, respectively, p < 0.05), and respiratory rate (RR) was shown, at month 12 and across the time points compared with baseline, as well as in respiratory muscle strength, although only the change in MEP was significant. CONCLUSIONS: We provide further evidence on the efficacy of the CFTR modulators ELX/TEZ/IVA, adding information about their effect on the respiratory muscles' performance and cardiorespiratory polygraphy parameters in CF patients with severe lung disease.

Safety of biologics in severe asthmatic patients with SARS-CoV-2 infection: A prospective study.

BACKGROUND: Asthma guidelines have recommended continuing treatment with biologics during coronavirus disease 2019 (COVID-19) pandemic. However, a continuation of treatment with biologics in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been little investigated. OBJECTIVE: To assess the safety of biologics in patients with SARS-CoV-2 infection. METHODS: A pilot, monocentric, prospective study. Patients aged 6 years old and older with severe asthma on treatment with biologics and confirmed SARS-CoV-2 infection were enrolled. Patients were followed-up with periodic calls at different time points up to 3 months to detect any adverse effect and its relationship with biologic treatment according to the Naranjo Adverse Probability Scale (NAPS). The severity of SARS-CoV-2 infection and clinical outcome were also assessed. RESULTS: Overall, we included 21 patients (10 on therapy with omalizumab, 9 with dupilumab, and 2 with mepolizumab). Only a patient-reported two local adverse events. No other adverse event was reported. Twenty out of 21 patients had a mild COVID-19 course, and no adverse outcome was observed. CONCLUSION: We showed that the scheduled dose of the biologic therapy can be administered safely on time in patients with SARS-CoV-2 infection, as the treatment did not result in adverse events or outcomes.

Biologic drugs in treating allergic bronchopulmonary aspergillosis in patients with cystic fibrosis: a systematic review.

BACKGROUND: Aspergillus fumigatus is a common saprophytic fungus causing allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF). The recommended first-line treatment for ABPA is oral steroids, followed by antifungal therapy. However, both treatments are not free from adverse effects; thus, efforts are being made to identify new drugs showing the same effectiveness but with fewer or no side-effects. Therein, biologic drugs have been significantly implemented in clinical practice in treating ABPA in patients with CF. OBJECTIVE: To systematically review the available literature, providing evidence for the administration of biologic drugs as a new potential treatment of ABPA in both the paediatric and adult populations with CF. METHODS: A systematic review of the literature published between January 2007 and July 2021 was performed, using a protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO CRD42021270932). RESULTS: A total of 21 studies focusing on the use of biologics in treating ABPA in CF patients was included. We highlighted a paucity of data providing evidence for biologic drug use in ABPA. CONCLUSION: Scientific evidence is insufficient to support firm conclusions and randomised clinical trials are urgently required to investigate the efficacy and safety of biologics for ABPA in CF patients.

Nocturnal non invasive ventilation in normocapnic cystic fibrosis patients: a pilot study.

BACKGROUND AND AIM: In patients with cystic fibrosis (CF) non-invasive ventilation (NIV) improves lung mechanics and gas exchange, and decreases the work of breathing. Domiciliary NIV is mainly used in hypercapnic patients with severe disease, because it counteracts the progression of lung functional impairment and it is often used as a useful "bridge" to lung transplantation. However, to date, there are no standardized criteria to indicate the effect of a precocious starting of NIV in patients with functional ventilation inhomogeneity without hypercapnia. In this pilot study we assessed whether an early NIV treatment might influence functional and clinical outcomes in CF patients. METHODS: Six normocapnic CF patients were treated for one year with NIV. At baseline and after 1 year of NIV treatment, arterial gas analysis, spirometry, MBW to derive LCI, nocturnal cardio-respiratory polygraphy (PG), and Pittsburgh Sleep Quality Index (PSQI) were perfomed in all enrolled patients. RESULTS: After one year, despite spirometric and LCI values remain statistically not modified, the number of infectious exacerbations was reduced by 50%. CONCLUSIONS: These results suggest that nocturnal NIV improves clinical conditions of stable CF patients. Finally, we suggest that this procedure can be useful to counteract the progression of lung disease even in normocapnic patients.

Looking beyond pulmonary disease in COVID-19: A lesson from patients with cystic fibrosis.

Coronavirus disease 2019 (COVID-19) caused more than 52.775.271 million confirmed cases, 1.293.106 deaths, globally, and afflicted 208 countries, areas, or territories; and almost three months have passed since the World Health Organisation (WHO) declared COVID-19 as a pandemic. Despite the dramatic and global impact of the Coronavirus, the knowledge about the SARS-CoV-2 infection has been improved remarkably. Herein, we provided the rationale for SARS-CoV-2 infection as endothelial dysfunction rather than respiratory disease. Accordingly, we strongly invited the researchers to look beyond pulmonary injury and shift their attention from respiratory disease to endothelial disorder. This strategy could be particularly relevant to identifying therapeutic weapons stabilizing the endothelium rather than the lungs.

Severe disease in Cystic Fibrosis and fecal calprotectin levels.

Fecal calprotectin (FC) is used to asses the presence of intestinal inflammation also in patients with Cystic Fibrosis (CF) and recent studies showed a correlation between bowel and lung disease in these patients. The aim of this study was to analyze the levels of FC in CF and correlate them with different phenotypes of disease. We enrolled a cohort of 54 CF patients and 50 healthy controls. In these patients, calprotectin has been assayed on a stools sample using an ELISA kit. In all patients we analyzed, FC levels were elevated above the cut-off value and significantly higher than in healthy controls. Among CF patients, FC was significantly higher in patients older than 18 years, with pancreatic insufficiency, underweight status, Pseudomonas Aeruginosa airways colonization, CF-related diabetes mellitus, reduced lung function, or high number of pulmonary exacerbations. These results suggest that in patients with CF, FC levels are not only influenced by the CF enteropathy but also by the severity of the genetic disease. Since we found higher FC levels in patients with a severe phenotype (P. Aeruginosa airways colonization, FEV1<50% of predicted, pancreatic insufficiency, underweight status,) we suggest that this marker could be useful to monitor longitudinally a clinical worsening.

Post-traumatic stress symptoms among mothers of children with leukemia undergoing treatment: a longitudinal study.

OBJECTIVE: To assess post-traumatic stress symptoms (PTSS) in mothers of children over 2 years of leukemia treatment, to identify possible early family and child predictors of this symptomatology and to indicate the temporal trajectory of PTSS. METHODS: Participants were 76 Italian mothers (mean age = 37.30 years; SD = 6.07) of children receiving treatment for acute lymphoblastic (n = 69) or myeloid (n = 7) leukemia. Mothers had 12.05 years of education (SD = 3.87), and their incomes were average (52.1%), high (26%) and low (21.9%) for Italian norms, never in poverty. The pediatric patients with leukemia were equally distributed by gender with their mean age of 7.10 years (SD = 4.18). Post-traumatic stress symptoms were measured by a 17-item checklist. Scales assessing anxiety, depression, physical (Brief Symptom Inventory 18) and cognitive functioning (Problem Scale), and life evaluation were also used. There were five assessment points: 1 week (T1), 1 month (T2), 6 months (T3), 12 months (T4) and 24 months post-diagnosis (T5). RESULTS: The main results indicated moderate presence of clinical PTSS (≥9 symptoms: 24% at T2, 18% at T3, 16% at T4 and 19% at T5) that remained stable across time points, whereas Brief Symptom Inventory 18 Global score decreased and life evaluation improved. A series of hierarchical regression models identified cognitive functioning early after the diagnosis as the best predictive factor of PTSS across time points. CONCLUSION: Specific psychological interventions could be devised for mothers at risk for short and long-term PTSS just after the diagnosis.