Cystic fibrosis (CF) is a genetic disease that causes absence or dysfunction of a protein named transmembrane conductance regulatory protein (CFTR) that works as an anion channel. As a result, the secretions of the organs where CFTR is expressed are very viscous, so their functionality is altered. The main cause of morbidity is due to the involvement of the respiratory system as a result of recurrent respiratory infections by different pathogens. In recent decades, survival has been increasing, rising by around age 50. This is due to the monitoring of patients in multidisciplinary units, early diagnosis with neonatal screening, and advances in treatments. In this chapter, we will approach the different therapies used in CF for the treatment of symptoms, obstruction, inflammation, and infection. Moreover, we will discuss specific and personalized treatments to correct the defective gene and repair the altered protein CFTR. The obstacle for personalized CF treatment is to predict the drug response of patients due to genetic complexity and heterogeneity of uncommon mutations.

Pulmonary exacerbation is one of the main risk factors for death in patients with cystic fibrosis. Several biomarkers have proven useful in the diagnosis and treatment of pulmonary exacerbations, although none has been associated with severity. The objective of the present study was to investigate whether C-reactive protein (CRP) level was associated with the severity of pulmonary exacerbation requiring admission to hospital in patients with cystic fibrosis. We designed a severity index for exacerbations based on 4 clinical parameters and determined whether there was an association between CRP levels and severity of the exacerbation. We also investigated the association between CRP and baseline functional and clinical variables. Twenty-seven patients with cystic fibrosis required 62 admissions to hospital. CRP levels were not significantly associated with the severity index, although they were associated with specific patient characteristics: colonization by Pseudomonas aeruginosa, allergic bronchopulmonary aspergillosis, treatment with oral corticosteroids, and number of severe exacerbations treated with intravenous antibiotics during the previous year. CRP level is not associated with the severity of pulmonary exacerbations, but it is associated with specific clinical characteristics. This simple scoring system (severity index) could prove very useful for evaluating the severity of exacerbations.

Introduction: Malnutrition has always been a problem in CF (cystic fibrosis) patients; however, new treatments with CFTR (cystic fibrosis transmembrane conductance regulator protein) modulators have led to weight gain, with some patients at risk of overweight and obesity. Objective: Our study aimed to analyze the evolution of BMI (body mass index) after one year of treatment with triple therapy and the factors associated with weight gain in CF patients undergoing treatment with triple therapy with CFTR protein modulators (ETI) (elexacaftor/tezacaftor/ivacaftor). Methods: We conducted a prospective, observational, longitudinal, multicenter study in patients diagnosed with cystic fibrosis, aged 18 years or older, with at least one F508del allele and who underwent ETI therapy for at least one year, from 2020 to 2023. One hundred and eight patients from two cystic fibrosis units in Spain, Princess University Hospital of Madrid (74 patients) and Central University Hospital of Asturias (HUCA) (34 patients), were included. Demographic data, anthropometric data, lung function, and exacerbations were collected, comparing the data in the previous year to the start of therapy with the results after one year of treatment. Multivariant models were developed to account for repeated weight and BMI measurements, using a mixed effects model approach and accounting for possible modifying factors Results: One hundred and eight patients were included in the study, 58 men (53.7%) and 50 women (46.3%) with a mean age of 29.5 ± 9.4 years (18–59). Patient weight and BMI were recorded at baseline and at 3-month intervals during the study period. The weight increased from 59.6 kg to 62.6 kg and BMI increased from 21.9 kg/m² to 23.0 kg/m² after one year of treatment (p < 0.0001 for both). The proportion of underweight individuals decreased after one year of ETI therapy, from 9.3% to 1.9%, while the proportion of overweight or obese individuals increased from 8.3% to 22.9 % at the same time (p < 0.001). In relation to exacerbations, there is a significant increase in the number of patients who did not have any exacerbations after one year of treatment, which increased from 10.2% to 46.2% (p < 0.001), while the number of patients who had >4 exacerbations decreased significantly, from 40.7% to 1.9% (p < 0.001). FEV1% (forced expiratory volume) increased from 63.9 ± 20.9 to 76.8 ± 21.4 (p < 0.001) and the VR/TLC (residual volume/total lung capacity) value decreased from 45.1 ± 10.9 to 34.9 ± 6.2 (p < 0.001). The proportion with FEV1% > 80% increased from 23.1% before ETI therapy to 49.1% one year after ETI therapy. We performed multivariate mixed models to evaluate the evolution of BMI changes with time, accounting for repeated measures and for possible modifying factors. After the introduction of the triple therapy, patients included in the study had significant weight gain during the 12 months, and when including different covariates in the multivariate mixed model, we found that lower baseline BMI, lower baseline FEV1 and FVC (forced vital capacity), and higher VR/TLC value and higher number of exacerbations were associated with higher BMI changes over the study period. Conclusions: CF patients treated with triple therapy experience significant weight gain, increasing the proportion of overweight patients. CF patients who experienced greater weight gain were those with worse BMI at the start of treatment, as well as patients with worse lung function and a greater number of exacerbations in the year before starting ETI therapy.

Introduction: Among the limited studies on physical exercise interventions in adults with cystic fibrosis (CF), few have specifically addressed the improvement of peripheral muscle strength and body fat‐free mass. The aim of this study was to examine the impacts of a remotely supervised, individualized 8‐week resistance training program of moderate to high intensity on strength and body composition in these subjects.Methods: This was a randomized controlled trial performed in adults with CF. The exercise group (EX) performed three 1‐h resistance training sessions per week over 8 weeks. The control group (CON) followed the physical activity recommendations of their physician. The main outcomes were muscle strength and body composition, with secondary measures including pulmonary function and quality of life. Two‐way repeated measures analysis was used.Results: In 23 participants (age 32.13 ± 7.72 years), the intervention showed a significant beneficial effect on leg press strength, with a large effect size, both in absolute (p = 0.011; = 0.281) and relative (p = 0.007; = 0.310) terms. Large intervention effects were observed on total fat mass (p < 0.001; = 0.415), body adiposity index (p < 0.001; = 0.436), and fat mass index (p < 0.001; = 0.445), all showing reduction in the EX group. In addition, significant large size effects were detected on total fat‐free mass (p = 0.046; = 0.177), trunk fat‐free mass (p = 0.039; = 0.188), and fat‐free mass index (p = 0.048; = 0.174), all favoring exercise. No significant effects were observed on pulmonary function and quality of life.Conclusions: An 8‐week remotely supervised resistance training program, with moderate to high intensity, effectively improved lower limb muscle strength and body composition.