In this prospective study, it was found that the outcomes FFM and FFMI had a significant improvement between the beginning of hospitalization and the 14th day. The predictors of this improvement for FFM were sex and FVC. For the FFMI, the predictive variable of this improvement was sex only. The analysis showed that the male individuals obtained a higher increase in FFM and a higher improvement in FFMI than the female individuals.
The significant increase in FFM between the beginning and the end of a hospital stay was also evidenced by Bell et al.24, which revealed an average FFM of 42.9Kg on the 1st day, and 43.7Kg (p < 0.001) at the end of hospitalization. These values were very similar to the findings in our study: 41.8 kg at the beginning of hospitalization, and 43.0 kg at the end.
The influence of gender on body composition was evident in the study. Gender was identified as one of the independent variables that were significantly associated with FFM and was the only independent variable significantly associated with FFMI. Our results are in accordance with the findings of Alvarez et al.10 who studied 32 clinically stable individuals with CF and a control group without CF, and found better nutritional status in males. Sheikh et al.25 concluded that FFMI is more strongly associated with pulmonary function compared to BMI, especially in men. Still, Alicandro et al.5 studied 85 young adults with CF retrospectively. Body composition data were compared between two groups, exacerbators and infrequent exacerbators. Male patients classified as frequent exacerbators had lower FFMI (mean of 18.0 kg/m2) compared to infrequent exacerbators (mean of 19.3 kg/m2, p = 0.024). Among the frequent exacerbators, male patients had lower FFM compared to patients who had a lower exacerbation rate.
Significant pulmonary functional improvement was also demonstrated after the treatment of infectious pulmonary exacerbation: FEV1 at hospital admission of 40.0% of the predicted, and 45.0% (p < 0.001) on the 14th day of hospitalization. In the study by Bell et al.24, the functionality was more severely compromised than in our study, but a significant increase in FEV1 was also identified, from 28.5% of predicted to 34.7% of predicted (p < 0.001), between hospital admission and the 15th day after antibiotic treatment. Another study19 also verified the variation in FEV1 values from 47.7% of predicted at admission to 54.2% of predicted (p < 0.0001) at the end of treatment.
The dimension of pulmonary functional improvement in our study also involved FVC (from 63.3–69.5% of predicted, p < 0.001). These findings were similar to those identified in the study by Bell et al.24 (improvement of 38.8–46.9%, p < 0.001) in the 15th day after antibiotic treatment.
Although cortisol is a stress response hormone, our values did not get a significant improvement when we compared it at the beginning and on the 14th day. In contrast, the study by Ionescu et al.7 showed a decrease in its values from 453 to 347, p < 0.05.
In our research, FVC was one of the independent variables significantly associated with FFM. Charatsi et al.8 also observed in their sample that patients with FFM depletion had a lower FVC, median of 57%, interquartile interval (IQ) (51;61), versus those with normal FFM, with median FVC of 93%, IQ (82;101.5) and p = 0.001. The study by Sheikh et al.25 observed that only in women, after adjusting for age, the FFM - Z score was positively associated with FVC % of predicted β = 5.5, p = 0.004. In another study26, the FVC % of the predicted was reduced both in the group of normal BMI and low FFMI, group of hidden depletion of FFM, p < 0.05 and in the group of low BMI and low FFMI p < 0,01.
Although studies show a positive relationship between FEV, FFM and FFMI7,8,9,11,26−28, in our sample, FEV1 was not identified as an independent variable significantly associated with FFM, after multivariate linear regression analysis, as well as in King et al.12 during the evaluation of 58 adult patients with CF within 4 years. Nutritional status, including FFM, was generally preserved, despite the increased severity of lung disease. Two factors were associated with loss of FFM: the highest serum levels of interleukin 6, and the presence of the F508del mutation for CF. In this study, the correlation between the change in FFM and the change in FEV1% of the predicted did not reach statistical significance. Alicandro et al.4 after including FEV1 in the multiple linear regression model, observed that no significant association with full-body FFMI β= −0.03, p = 0.80 in men remained.
Several blood biomarkers have been studied against the background of acute infectious pulmonary exacerbation of CF, although none of them are exclusively related to inflammation. CRP is a non-specific acute phase protein that can be easily measured in laboratory. Several studies have shown that CRP is elevated at the onset of pulmonary infectious exacerbation of CF, and decreases significantly until the end of treatment, in proportion to the clinical and functional pulmonary improvement. Despite this response to treatment of exacerbation, no study has shown that CRP is useful in predicting the clinical course of exacerbation29. In the present study, CRP decreased from admission until the 14th day with treatment. However, it was not associated with FFM and FFMI on the 14th day after treatment. Sharma et al.29, as well as our research, compared CRP values at the beginning and at the end of treatment, and a reduction in CRP values was found at the beginning of treatment with an average CRP of 125 (± 69) for an average CRP of 56 (± 51) p < 0.0001 at the end of treatment.
Severe pulmonary infectious exacerbation in CF has a negative impact on the prognosis of the disease. Partly due to the effect of the inflammatory process of exacerbation on muscle catabolism, leading to the depletion of FFM. Thus, the evaluation of the FFMI at the end of hospitalization and the analysis of possible factors associated with this process, could contribute to a better understanding and management of this clinical situation12. Body composition and FFB in the context of severe pulmonary exacerbation of CF have scarce data in the literature, and a knowledge gap on this topic remains. A better understanding about this process would be of paramount importance for the development of new strategies of nutritional interventions in this population8. Nutritional interventions to treat malnutrition should probably be early and not postponed until nutritional deficits are severe enough to be detected using weight-only criteria27.
One of the main limitations of this study was the small sample size and the performance in a single center, restricting the generalization of the data. Secondly, food intake and physical activity were disregarded, influenced by the improvement of muscle mass. Thirdly, tetrapolar electrical bioimpedance was used to evaluate FFM, and not dual-energy x-ray absorptiometry (DXA), which is a method with greater precision. The evaluation of body composition by bioimpedance is usually responsible for overestimating FFM when compared with the gold standard – DXA30. Although our population was compared with itself, avoiding overestimating FFM.
In conclusion, this study found that FFM and FFMI had significant improvement after the treatment of exacerbation. The predictor parameters of this improvement for FFM were gender and FVC percent of predicted. For the FFMI, the predictive variable of this improvement was only gender. Males obtained a higher increase in FFM and a superior improvement in FFMI.