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.

Focus on gastroesophageal reflux disease in patients with cystic fibrosis.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder in cystic fibrosis (CF), and based on various studies, its prevalence is elevated since childhood. There are several pathogenetic mechanisms on the basis of association between CF and GERD. However, there are no specific guidelines for GERD in CF patients, so diagnosis is based on guidelines performed on patients not affected by CF. The aim of this review is to provide the pathophysiology, diagnostic and therapeutic options, complications, and future directions in the management of GERD patients with CF.

Allergic bronchopulmonary aspergillosis in children.

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disease caused by Aspergillus induced hypersensitivity that occurs in immunocompetent but susceptible patients with asthma and/or cystic fibrosis (CF). In children, ABPA remains mostly undiagnosed resulting in one of the most common causes of poorly controlled asthma and highly significant morbidity in children with CF. Currently, no specific diagnostic criteria of ABPA for children are available. Corticosteroids and itraconazole are the mainstays of therapy although there is a lack of randomized clinical trials regarding their usefulness for ABPA in children. Several monoclonal antibodies, such as omalizumab and mepolizumab, may be potential therapies for refractory ABPA in pediatric patients; however, further data are required to clarify the optimal dose and duration of therapy as a routine treatment approach.