With the introduction of elexacaftor/tezacaftor/ivacaftor (ETI), more women with cystic fibrosis (CF) are likely to grow families. Hence, an understanding long-term safety and effects of CFTR modulators on fertile women and children while monitoring their concentrations is crucial. Here, we report on the development of an improved LC–MS/MS methodology to measure ETI concentrations in maternal and child blood and breastmilk, applied in one case of successful pregnancy of a 30-year-old woman with CF (F508del/R334W). We observed that ETI remains stable in breastmilk, is absorbed by the infant and can be detected in child plasma. Our results confirm accumulating evidence of a successful pregnancy in women treated with CFTR modulators without significant side effects on the child and provide valuable analytical procedures suitable for the post-marketing evaluation of CFTR modulators in pregnant and lactating women, as well as in their infants.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy effects on respiratory function, pulmonary exacerbations and quality of life have been well documented. However, CFTR modulator therapy effects on sinus disease have not been so well reported. A previous study reported that ivacaftor improves appearance of sinus disease on Computed Tomography (CT) in cystic fibrosis (CF) patients with G551D mutation. The aim of this study was to evaluate the effect of CFTR modulator therapy in sinus disease using CT scores in a wider CF patient population. Forty-eight adult patients with CF underwent at least one CT sinus examination before CFTR modulator therapy (ivacaftor, lumacaftor, ivacaftor/lumacaftor or elexcaftor/tezacaftor/ivacaftor) and one CT sinus examination one year after CFTR modulator therapy initiation. Two radiologists assessed the images in consensus. The Lund-Mackay score (LM score) and the Sheikh-Lind CT sinus disease severity scoring system (SL score) were used. The 22-item SinoNasal Outcome Test (SNOT-22) questionnaire was evaluated before CFTR modulator therapy and one year after CFTR modulator therapy initiation. CT sinus examination after CFTR modulator therapy showed statistically significant lower mean LM, SL and SNOT-22 scores than CT sinus examination before CFTR modulator therapy (p < 0.001). Evolution of imaging findings on CT during follow-up closely correlate with improved SNOT-22 score one year after CFTR modulator therapy initiation, indicating that CT may be a useful adjunct during follow-up of CF patients under this treatment as an objective measure of sinonasal disease improvement.

The aim of this article is to identify and illustrate the most used psychological techniques in the field of cystic fibrosis (CF) and to help clinicians choose the most appropriate strategy among various possibilities. The disease and its medical treatments can be difficult to tolerate and can cause anxiety about health status or feelings of hopelessness and stress. The prevalence of depression and anxiety is 2.3 times higher in adults with CF than in community samples. A strong correlation has been identified between elevated psychological distress and unfavorable health outcomes, including, among others, impaired lung function, reduced BMI, an increased incidence of pulmonary exacerbations, and an elevated risk of transplantation. The use of psychological interventions is useful in addressing these common distresses in CF patients. Aware of the necessity of identifying efficacious interventions for all levels of depression and anxiety in CF patients, this study presents an overview of the research on psychological interventions for patients with CF, in order to complement the treatments suggested by the international guidelines on mental health in CF cases. In fact, the aim of this study is to conduct a review and quantitative synthesis of the psychological intervention techniques that are currently available for individuals with CF.

The aim of the article is to identify and illustrate the most used psychological techniques in the field of cystic fibrosis (CF) and to help clinicians choosing the appropriate strategy among the various possibilities. The disease and its medical treatments can be difficult to tolerate and can cause anxiety about health status or feelings of hopelessness and stress. The prevalence of depression and anxiety is 2.3 times higher in adults with CF than in community samples. A strong correlation has been identified between elevated psychological distress and unfavorable health outcomes, including, among others, impaired lung function, reduced BMI, an increased incidence of pulmonary exacerbations, and an elevated risk of transplantation. The use of psychological interventions is useful in addressing these common distress in CF patients. Aware of the necessity to identify efficacious interventions for all levels of depression and anxiety in CF patients, this study presents an overview of the research on psychological interventions for patients with CF, in order to complement the treatments suggested by the international guidelines on mental health in CF cases. In fact, the aim of this study is to conduct a review and quantitative synthesis of the psychological intervention techniques that are currently available for individuals with CF.

Therapeutic drug monitoring (TDM) is becoming increasingly essential in cystic fibrosis (CF), as a growing number of children and adults are now eligible for elexacaftor/tezacaftor/ivacaftor (ETI) CF Transmembrane conductance Regulator (CFTR) modulator therapies. Although plasma remains the benchmark, its invasive nature limits practical use. Analytical approaches based on dried matrices currently available still rely on venipuncture and intensive workflows. To overcome these limitations, we developed an advanced, multidimensional TDM framework for ETI quantification that incorporates truly venipuncture-free, self-collected, and quantitative dried blood spot (DBS) sampling, along with non-invasive nasal airway swabs (NAS) and sweat. We also evaluated ETI in airway and sweat fluids, offering insight into drug distribution and activity at key target tissues. Selectivity, specificity, linearity, accuracy, precision, and inter/intraday stability of the methods applied to plasma, NAS, and sweat specimens were investigated according to ICH M10 guidelines and IATDMCT for DBS. Analytical performance of the methods in all tested matrices were demonstrated and met the acceptance criteria of ICH M10 guidelines for bioanalytical-method validation, with DBS additionally fulfilling the IATDMCT DBS-specific recommendations. DBS measurements were statistically equivalent to plasma concentrations, supporting their utility as a minimally invasive surrogate for TDM. ETI levels in NAS were significantly higher than in plasma or sweat, indicating localized accumulation of the drug on the airway surface, a key site of CFTR activity. Sweat samples, while showing lower analyte amounts, contained detectable levels in all analytes within their biologically active concentrations. This integrated analytical approach provides a holistic view of systemic and local ETI distribution, increasing the potential for personalized TDM, pharmacokinetics/pharmacodynamics study, and optimization of CFTR modulator therapy.

The prognosis for people with Cystic Fibrosis (CF) has significantly improved due to the introduction of CF Transmembrane Regulator (CFTR) modulators. This study aims to analyze pregnancies and related outcomes in Italian women with CF while also identifying current and potential future challenges. This retrospective study utilized data from the Italian cystic fibrosis Registry (ICFR), focusing on pregnancies occurring between 2016 and 2023. Key clinical variables assessed included genotype, age at conception, body mass index, percent predicted forced respiratory volume (ppFEV₁), presence of CF-related diabetes (CFRD), and CFTR modulator therapy. The outcomes analyzed were pulmonary function and BMI as a surrogate of nutritional status before and after pregnancy, as well as preterm birth rate, birthweight, and mode of delivery. Between 2016 and 2023, the ICFR reported 172 pregnancies, of which 148 (86.0 %) were carried to term. The median age at conception was 31.8 years (range: 17.0-43.9), median BMI 21.6 kg/m² (range: 16.5-38.9), and median ppFEV₁ 79.7 (range: 29.0-120.4). CFRD was present in 32 women (21.6 %), and 55 (37.2 %) were receiving CFTR modulator therapy. Better clinical status at the beginning of pregnancy was observed in 2016-23 period, with a higher mean ppFEV₁, in the mean age at conception and in the mean BMI value. In the present study, only a limited number of women were in severe clinical condition (<5 % had a severe ppFEV₁ value or a BMI showing a malnutrition status). The overall preterm birth (<37 weeks gestation) was 24.1 % (34 cases), higher in women with CFRD (40.6 %) and lowest in those receiving CFTRm (22.7 %). Median birthweight was 2,990 g (range: 800-4,155 g). The overall cesarean section rate was 54.9 %, peaking at 81.2 % in women with CFRD. Understanding national pregnancy trends and outcomes is essential for informing effective public health strategies and improving maternal-infant wellbeing. An increasing number of women with CF are achieving successful pregnancies and delivering healthy babies. It is essential to provide women treated with CFTR modulators with up-to-date information regarding the safety of these therapies during pregnancy and breastfeeding.